Abstract
Background
Cordyceps sinensis (Cordyceps, Dong Chong Xia Cao), a herbal medicine also known as Chinese caterpillar fungus, is one of the most commonly used ingredients in traditional Chinese medicine for the treatment of people with chronic kidney disease (CKD).
Objectives
This review aimed to evaluate the therapeutic effects and potential adverse effects of Cordyceps sinensis for the treatment of people with CKD.
Search methods
We searched the Cochrane Renal Group's Specialised Register to 14 April 2014 through contact with the Trials' Search Co‐ordinator using search terms relevant to this review. We also searched CINAHL, AMED, Current Controlled Trials, OpenSIGLE, and Chinese databases including CBM, CMCC, TCMLARS, Chinese Dissertation Database, CMAC and Index to Chinese Periodical Literature.
Selection criteria
Randomised and quasi‐randomised trials comparing Cordyceps or its products with placebo, no treatment, or conventional treatment were considered for inclusion in the review.
Data collection and analysis
Two authors independently assessed data quality and extracted data. Statistical analyses were performed using the random‐effects model and the results expressed as risk ratio (RR) for dichotomous outcomes or mean difference (MD) for continuous data with 95% confidence intervals (CI).
Main results
We included 22 studies that involved 1746 participants. Among people with CKD who were not receiving dialysis, Cordyceps preparations were found to significantly decrease serum creatinine (14 studies, 987 participants): MD ‐60.76 μmol/L, 95% CI ‐85.82 to ‐35.71); increase creatinine clearance (6 studies, 362 participants): MD 9.22 mL/min, 95% CI 3.10 to 15.34) and reduce 24 hour proteinuria (4 studies, 211 participants: MD ‐0.15 g/24 h, 95% CI ‐0.24 to ‐0.05). However, suboptimal reporting and flawed methodological approaches meant that risk of bias was assessed as high in four studies and unclear in 18 studies, and hence, these results need to be interpreted with caution.
Authors' conclusions
We found that Cordyceps preparation, as an adjuvant therapy to conventional medicine, showed potential promise to decrease serum creatinine, increase creatine clearance, reduce proteinuria and alleviate CKD‐associated complications, such as increased haemoglobin and serum albumin. However, definitive conclusions could not be made because of the low quality of evidence.
Plain language summary
Cordyceps sinensis (a Chinese medicinal herb) for treating chronic kidney disease
People with chronic kidney disease (CKD) experience gradual worsening of kidney function. Cordyceps (Cordyceps sinensis), which is sometimes known as Chinese caterpillar fungus, is widely used in traditional Chinese medicine to treat people with CKD. We conducted this review to investigate if Cordyceps was a safe and effective treatment for people with CKD.
We searched the literature published up to April 2014 and assessed evidence from 22 studies conducted in China that involved 1746 people with CKD who received Cordyceps as part of their treatment.
We found some evidence to indicate that Cordyceps preparations given in addition to conventional Western medicine may be beneficial in improving kidney function and addressing some complications. However, evidence quality was poor, and no definitive conclusions could be made about Cordyceps for people with CKD.
Background
Description of the condition
Chronic kidney disease (CKD) is a common condition in which kidney function progressively deteriorates, which may be asymptomatic until the disease is advanced. CKD aetiology has been associated with both non‐communicable diseases, such as diabetes and hypertension, and infectious diseases including malaria, HIV, and hepatitis B (Nugent 2011). CKD is defined by the Kidney Disease Outcomes Quality Initiative (KDOQI) in terms of either kidney damage (indicated by markers such as abnormalities in urine or blood tests, or on imaging), or decreased glomerular filtration rate (GFR) (< 60 mL/min/1.73 m²) with or without evidence of kidney damage, for three or more months, regardless of cause (Levey 2003; NKF 2008). People with CKD whose kidney function continues to deteriorate may require renal replacement therapy (RRT) (dialysis or kidney transplantation). Adverse effects such as high blood pressure (hypertension), too few red blood cells (anaemia), malnutrition, bone diseases, nerve damage (neuropathy), and decreased quality of life may occur concurrently with gradual loss of kidney function (NKF 2008).
CKD incidence and prevalence is increasing and is associated with escalating rates of hypertension and diabetes mellitus. Together, these diseases pose a major global healthcare challenge (Nugent 2011). In India, where incidence of diabetes and hypertension is high, it has been estimated that between 25% and 40% of the population are at risk of developing CKD (Srinath Reddy 2005). A recent systematic review reported that impaired kidney function prevalence, defined as reduced GFR (< 60 mL/min/1.73 m²), creatinine clearance (CrCl) (< 60 mL/min) or elevated serum creatinine (SCr), ranged from 1.7% in a Chinese study to 8.1% in a US study (McCullough 2012). The high cost of RRT imposes significant economic burden on society, especially in the developing world (Nugent 2011).
Description of the intervention
Laboratory and clinical studies have demonstrated that medicinal herbs traditionally used to treat people with kidney disease may offer potential therapeutic benefits for people with CKD (Wojcikowski 2006). Cordyceps sinensis (Cordyceps) is one of the most commonly used ingredients in traditional Chinese medicine for people with CKD (Deng 2001). Cordyceps, a unique blade‐shaped fungus that grows on caterpillars, is valued as a tonic herb in traditional Chinese medicine to treat a wide range of disorders, including respiratory, kidney, liver and cardiovascular diseases, low libido and impotence, and hyperlipidaemia. Because naturally‐occurring Cordyceps sinensis is in limited supply, various cultured and fermented mycelial products that have similar pharmacologically active components are now used in clinical practice (Zhu 1998a; Zhu 1998b).
How the intervention might work
Clinical studies investigating the use of Cordyceps for treating people with CKD have demonstrated potential beneficial effects in decreasing progression of end‐stage kidney disease (ESKD) (Jin 2004), reducing SCr levels (Yu 2003); and increasing CrCl (Wu 2007), serum albumin and haemoglobin (Jin 2004; Yang 1999b); and improving lipid metabolism (Jin 2004; Quan 2004).
Studies investigating the active mechanisms of Cordyceps for CKD have found that its observed benefits may be related to its antioxidant and immunostimulation properties (Shin 2001; Yamaguchi 2000), inhibition of mesangial proliferation (Yang 1999a; Yang 2003; Zhao 2000), anti‐inflammatory effects (Liu 2005; Shahed 2001; Yin 2007), ability to decrease accumulation of extracellular matrix in the renal cortex (Ma 2008), and in reducing renal interstitial fibrosis (Min 2008).
Why it is important to do this review
Previous clinical experience and studies investigating Cordyceps have suggested that it is a promising natural substance for the treatment of people with CKD. Although a previous systematic review that investigated the therapeutic benefits of Cordyceps for people with CKD reported favourable effects, this analysis was methodologically flawed by reliance on a limited literature search, inclusion of inappropriate outcome measures, and poor quality reporting (Xu 2006). Therefore, a systematic review applying appropriate, rigorous scientific methodology will not only provide reliable evidence on the therapeutic effect of Cordyceps for people with CKD, but also identify areas for improvement if future clinical studies are to be undertaken.
Objectives
This review aimed to evaluate the therapeutic effects and potential adverse effects of Cordyceps sinensis for the treatment of people with CKD.
Methods
Criteria for considering studies for this review
Types of studies
All randomised controlled trials (RCTs) and quasi‐RCTs (RCTs in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth or other predictable methods) evaluating the benefits and potential side effects of Cordyceps sinensis for CKD were included in the review.
Types of participants
Inclusion criteria
We included adults and children with CKD at all stages. Where possible, we applied the KDOQI definition for CKD (NKF 2008). However, we anticipated that most studies were likely to have been conducted in countries where the KDOQI definition was not applied, so we also accepted CKD definitions described by the studies.
Exclusion criteria
Participants with kidney impairment where baseline GFR or creatinine concentration data could be obtained from the report or through author contact
Kidney transplant recipients
Participants with diabetic nephropathy and primary nephrotic syndrome. These issues have been investigated in (Feng 2013; Liu 2007)
Types of interventions
Treatment group participants received Cordyceps or its products as the single treatment drug, regardless of the formulation and route of administration. These could include extracts of Cordyceps (any part of Cordyceps); or any derived, cultured, fermented mycelial products that contain pharmacologically‐active components similar to wild Cordyceps
Control group participants received placebo, no treatment, or conventional treatment. Other herbal or complementary medicines without validated efficacy were not accepted as the control intervention
Studies involving Cordyceps as one of several active components in a compound or as part of a combined treatment regimen were not included in the review
Co‐interventions were permitted where participants in all randomised arms received the same co‐interventions.
Types of outcome measures
Primary outcomes
Time to requirement for RRT or initiation of dialysis
All‐cause mortality
CKD progression, defined as increased CrCl or decreased SCr > 20% from baseline (Zheng 2002).
Secondary outcomes
Kidney function, measured by GFR, CrCl, or SCr levels
Quality of life measured by a validated scale
Proteinuria measured by 24 hour urinary protein excretion, protein/creatinine ratio or albumin/creatinine ratio
Blood pressure (systolic and diastolic)
Anaemia measured by haemoglobin or haematocrit levels
Nutritional status assessed by serum albumin, serum total cholesterol, oedema‐free actual body weight, per cent standard (NHANES II) body weight, normalised protein nitrogen appearance or dietary interviews and diaries
Bone disease measured by serum calcium and phosphorus or bone mineral density
Symptoms including skin pruritus, vomiting, measured by visual analogue or other scales
Adverse effects.
Primary and secondary outcome measures were collected immediately after treatment and at the end of follow‐up.
Search methods for identification of studies
Electronic searches
We searched the Cochrane Renal Group's Specialised Register to 14 April 2014 through contact with the Trials' Search Co‐ordinator using search terms relevant to this review. The Cochrane Renal Group’s Specialised Register contains studies identified from the following sources.
Monthly searches of the Cochrane Central Register of Controlled Trials (CENTRAL)
Weekly searches of MEDLINE OVID SP
Handsearching of renal‐related journals and the proceedings of major renal conferences
Searching of the current year of EMBASE OVID SP
Weekly current awareness alerts for selected renal journals
Searches of the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
Studies contained in the Specialised Register are identified through search strategies for CENTRAL, MEDLINE, and EMBASE based on the scope of the Cochrane Renal Group. Details of these strategies, as well as a list of handsearched journals, conference proceedings and current awareness alerts, are available in the specialised register section of information about the Cochrane Renal Group.
See Appendix 1 for search terms used in strategies for this review.
We also searched the following electronic databases to July 2012.
CINAHL, AMED (Allied and Complementary Medicine Database), and CISCOM (Centralised Information Service for Complementary Medicine). Search strategies were adapted from the approach described for MEDLINE
OpenSIGLE (System for Information on Grey Literature in Europe)
-
Chinese language databases were also searched to January 2011:
CBM (Chinese BioMedical Literature Database)
CMCC (Chinese Medical Current Contents)
TCMLARS (Traditional Chinese Medical Literature Analysis and Retrieval System)
Chinese Dissertation Database
CMAC (China Medical Academic Conference)
Index to Chinese Periodical Literature.
The search strategies for Chinese language databases are also shown in Appendix 1.
Index to Theses and ProQuest Dissertations and Theses were also searched for relevant studies.
Searching other resources
Reference lists of nephrology textbooks, review articles and relevant studies were also checked.
Data collection and analysis
Selection of studies
The search strategies described were used to obtain titles and abstracts of studies possibly relevant to this review. Titles and abstracts were screened independently by two authors who discarded studies that were not applicable; however, studies and reviews thought to potentially include relevant data or information on studies were retained initially. Two authors independently assessed the retrieved abstracts, and if necessary the full text, to determine which satisfied the inclusion criteria.
Data extraction and management
Data extraction was carried out independently by the same authors using a pre‐tested data extraction form. Where more than one publication of one study existed, only the publication with the most recent complete data was used. When further information was required, we wrote to the first author of the article concerned. Disagreements between authors were discussed and resolved by consensus.
Assessment of risk of bias in included studies
Two authors independently assessed the risk of bias of the included studies. Any discrepancies were resolved by discussion and conclusions made by consensus.
To detect potential selection bias, performance bias, attrition bias, detection and reporting bias, the following items were assessed using the Cochrane risk of bias assessment tool (Higgins 2011) (see Appendix 2).
Was there adequate sequence generation (selection bias)?
Was allocation adequately concealed (selection bias)?
-
Was knowledge of the allocated interventions adequately prevented during the study (detection bias)?
Participants and personnel
Outcome assessors
Were incomplete outcome data adequately addressed (attrition bias)?
Are reports of the study free of suggestion of selective outcome reporting (reporting bias)?
Was the study apparently free of other problems that could put it at a risk of bias?
Baseline comparability was considered as one of the other sources of bias.
We categorised the risk of bias for each outcome within and across the included studies into three levels, i.e. low, unclear and high risk of bias. Based on this, we also used the GRADE system (Higgins 2011) for evaluating the quality of evidence for each individual outcome, which involved not consideration of risk of bias (methodological quality), and directness of evidence, heterogeneity, precision of effect estimates and risk of publication bias.
Measures of treatment effect
For dichotomous outcomes (all‐cause mortality, CKD progression), results were expressed as risk ratio (RR) with 95% confidence intervals (CI). Where continuous scales of measurement were used to assess the effects of treatment (kidney function, quality of life, proteinuria, blood pressure, anaemia, nutritional status, bone disease) the mean difference (MD) was calculated.
Unit of analysis issues
Analysis of outcomes was based on randomised individuals. In the case of multiple intervention groups within a study, we chose pair‐wise comparisons relevant to the study objective. We did not identify any cluster RCTs, cross‐over studies, or studies reporting repeated measures on the same participants.
Dealing with missing data
Available case analysis was conducted. The potential impact of missing data was considered in the risk of bias assessment and interpretation of results. Because the imbalance of missing data on treatment and control groups is suggestive of high risk of bias, two studies were excluded from our meta‐analysis (Guo 2009; Yu 2003).
Assessment of heterogeneity
Heterogeneity was analysed using a Chi² test on N‐1 degrees of freedom, with an alpha of 0.1 used for statistical significance and with the I² test (Higgins 2003). I² values of 25%, 50% and 75% correspond to low, medium and high levels of heterogeneity, respectively.
Assessment of reporting biases
Reporting biases were investigated on a funnel plot (Higgins 2011). Possible reasons other than publication bias, such as poor methodological quality and true heterogeneity, were explored.
Data synthesis
Data were pooled using the random‐effects model but the fixed‐effect model was also analysed to ensure robustness of the model chosen and susceptibility to outliers. Data synthesis was restricted to studies assessed as low or unclear risk of bias. For studies at high risk of bias, results were displayed on a forest plot without pooling. A narrative, qualitative summary is also presented.
Subgroup analysis and investigation of heterogeneity
If sufficient evidence was available, we planned to conduct the following subgroup analyses to explore potential sources of heterogeneity.
CKD stage
CKD definition (KDOQI or other)
Risk of bias (low or unclear)
Cordyceps source (wild or cultivated) and preparation (whole plant or extract)
Cordyceps use (combined with or without other treatment).
Adverse effects were to be tabulated and assessed using descriptive techniques, because they were likely to be different for the various agents used. Where possible, the risk difference (RD) with 95% CI was to be calculated for each adverse effect, either compared to no treatment or to another agent.
We were able to undertake subgroup analyses on levels of risk of bias only. There were insufficient reported data to define CKD stage; CKD definition; use, source and preparation of Cordyceps, to enable subgroup analyses to be undertaken.
Adverse effects were analysed qualitatively. There were insufficient data in the included studies to calculate risk differences (RD) with 95% CI for adverse effects.
Sensitivity analysis
There were insufficient data to conduct sensitivity analyses to explore the influence of risk of bias factors on effect estimates for adequacy of sequence generation and blinding. Likewise, sensitivity analyses were not undertaken to examine if limiting the definition of CKD to the KDOQI standard had an impact on results.
Results
Description of studies
Results of the search
The search of English and Chinese language databases resulted in identification of 1168 citations (Figure 1). Two authors independently screened titles and abstracts and identified 245 studies as potentially relevant. Assessment of full‐text articles resulted in identification of 25 potential studies. Three studies are awaiting assessment (Chai 2009; Jin 2006; Lin 2003). As a result, 22 studies were included in this review (Chen 2003; Chen 2006a; Fu 2009; Gao 2007; Guo 2009; Hu 2008; Huang 2008; Jin 2004; Liu 2006a; Liu 2007a; Pan 2007; Shi 2009; Sun 1999; Wang 2005a; Wei 2004; Wu 2007; Xu 2004; Yan 2005a; Yang 1999b; Yu 2002; Yu 2003; Zhang 2009).
1.
Study flow diagram showing the search process and study selection
Included studies
This review included 22 studies, all published in Chinese, that were conducted in hospital settings in China involving 1746 participants (958 males (54.9%); 788 females (45.1%)). Study sample size ranged from 27 to 212 participants.
Participants in 18 studies had reported baseline SCr ranging from 135 to 820 µmol/L. Primary causes of CKD varied, but included chronic glomerulonephritis, diabetic nephropathy, arteriosclerosis of the kidney, chronic pyelonephritis, and hypertension nephropathy. Two studies dealt with aristolochic acid nephropathy (Gao 2007; Zhang 2009), and one investigated participants with hypertension nephropathy (Fu 2009).
Three studies compared Cordyceps plus conventional treatment with Western medicine plus the same conventional treatment (Gao 2007; Huang 2008; Jin 2004), and one compared Cordyceps plus traditional Chinese medicine to the same traditional Chinese medicine (Yan 2005a). The remaining 18 studies compared Cordyceps plus conventional treatment with the same conventional treatment; of these, three studies administered haemodialysis as the co‐intervention (Guo 2009; Sun 1999; Yu 2002).
All studies investigated mycelial fermentation products of Cordyceps sinensis. Of the 22 included studies, 13 studied Jin Shui Bao capsule and nine investigated Bai Ling capsule. Jin Shui Bao capsules contain 0.33 g fermented Cordyceps and Bai Ling capsules contain 0.2 g Cordyceps. Both capsules were administered orally, and doses ranged from three to six capsules, taken three times daily. Treatment duration ranged from one to six months.
All studies included co‐interventions in all treatment arms. Aside from dietary interventions, the most common co‐interventions were symptomatic and supportive treatments including maintaining water, electrolyte and acid‐base balance; controlling blood pressure; treating anaemia; and controlling infection when necessary. Yan 2005a reported that the compounded traditional Chinese herbal medicines administered as co‐intervention to treat CKD included Cangzhu (Rhizoma Atractylodis), Baizhu (Rhizoma Atractylodis Macrocephalae), Yiyiren (Semen Coicis), Fulingpi (Poria), Zelan (Herba Lycopi), Gouqizi (Fructus Lycii), Sangjisheng (Herba Taxilli), Huainiuxi (Radix Cyathulae), Dahuang (Radix et Rhizoma Rhei), and Baihuasheshecao (Herba Hedyotidis Diffusae).
Excluded studies
The most common reasons for study exclusion were lack of control arm; no randomisation; Cordyceps was one of many components in the traditional Chinese medicine treatment; and absence of targeted outcomes. See Characteristics of excluded studies.
Studies awaiting classification
Risk of bias in included studies
Figure 2 and Figure 3 present graphical presentations of assessments of risk of bias in the included studies.
2.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
3.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study
Allocation
In most studies, random allocation was briefly mentioned, and detailed methodologies were not provided. One study used a random number table to generate allocation sequence (Wei 2004); and another used entry sequence (Huang 2008). None of the included studies reported allocation concealment.
Blinding
Blinding was unclear in three studies (Liu 2006a; Liu 2007a; Yan 2005a) and not reported in the remaining 19 studies.
Incomplete outcome data
Two studies reported on missing data. Guo 2009 and Yu 2003 reported attrition rates of 21.9% and 2.5% respectively, but reasons were not provided. Yu 2003 did not report data relating to four control arm participants; and although 34 and 30 participants respectively were enrolled into the intervention and control arms, Guo 2009 included data from 25 participants only from each arm in the analysis.
Selective reporting
Because study protocols were not available, and measurement outcomes for assessing the treatment effect were not reported consistently in the included studies, it was not possible to assess for selective reporting.
Other potential sources of bias
We considered that blinding may not have substantially influenced objective outcome measures. Our assessment found that risk of bias was unclear in most studies, except for four that were at high risk of bias (Chen 2003; Chen 2006a; Guo 2009; Yu 2003). Participant numbers did not balance after randomisation in Chen 2003 and Chen 2006a; and there were missing data from the treatment phase in Guo 2009 and Yu 2003. These four studies were therefore excluded from our quantitative analysis.
Effects of interventions
Cordyceps + conventional medicine versus conventional medicine
Kidney function measures (CKD progression, SCr, CrCl)
Overall, in studies judged to have unclear risk of bias, Cordyceps preparations did not confer significant benefits for people with CKD (defined as CrCl increase or SCr decrease greater than 20% over baseline) (Analysis 1.1.1 (5 studies, 368 participants): RR 1.09, 95% CI 0.99 to 1.21; I² = 23%). However, effects were significant in studies assessed as being at high risk of bias for this outcome (Analysis 1.1.2 (2 studies, 227 participants): RR 1.36, 95% CI 1.17 to 1.58; I² = 0%).
1.1. Analysis.
Comparison 1 Cordyceps + conventional treatment versus conventional treatment, Outcome 1 CKD progression (%).
Overall, Cordyceps preparations significantly decreased SCr levels (Analysis 1.2 (15 studies, 1047 participants): MD ‐53.50 μmol/L, 95% CI ‐84.17 to ‐22.83; I² = 93%) in people with CKD. This was seen in both patients not on dialysis (Analysis 1.2.2 and Analysis 1.2.3 (14 studies, 987 participants): MD ‐60.76 μmol/L, 95% CI ‐85.82 to ‐35.71; I² = 82%) and in one study by Sun 1999 in patients on dialysis (Analysis 1.2.1 (1 study, 60 participants): MD ‐32.88 μmol, 95% CI ‐44.23 to ‐21.53). Differences in participants' CKD stages may explain some heterogeneity in treatment effects on SCr levels. Pooled SCr results also indicated greater effects in studies assessed at high risk of bias for this outcome (Analysis 1.2.3 (3 studies, 273 participants): MD ‐118.77 μmol, 95% CI ‐148.81 to ‐88.74). There were some differences in the pooled result for SCr between the fixed‐effect model (MD ‐39.27 μmol, 95% CI ‐48.13 to ‐30.40) and random‐effects model. There was no apparent publication bias (Figure 4).
1.2. Analysis.
Comparison 1 Cordyceps + conventional treatment versus conventional treatment, Outcome 2 Serum creatinine.
4.
Funnel plot of comparison: 1 Cordyceps + conventional treatment versus conventional treatment, outcome: 1.2 SCr
CrCl was significantly increased in participants who received Cordyceps preparations (Analysis 1.3 (6 studies, 362 participants): MD 9.22 mL/min, 95% CI 3.10 to 15.34; I² = 81%). A study in patients with hypertensive nephrology (Fu 2009), whose kidney function was better than participants in other studies, contributes all of the heterogeneity in this analysis. Removing this study from the analysis did not change the significance of the results (MD 6.16 mL/min, 95% CI 3.78 to 8.54). Chen 2006a, judged to be at high risk of bias for this outcome, also showed a significant increase in CrCl in patients receiving Cordyceps (Analysis 1.3.2 (1 study, 67 participants): MD 5.09 mL/min, 95% CI 0.56 to 9.62), but did not affect the significance of the result when removed (MD 6.57 mL/min, 95% CI 3.77 to 9.37).
1.3. Analysis.
Comparison 1 Cordyceps + conventional treatment versus conventional treatment, Outcome 3 Creatinine clearance.
Proteinuria
Cordyceps preparations significantly reduced 24 hour proteinuria (Analysis 1.4 (4 studies, 211 participants): MD ‐0.15 g/24 h, 95% CI ‐0.24 to ‐0.05; I² = 9%).
1.4. Analysis.
Comparison 1 Cordyceps + conventional treatment versus conventional treatment, Outcome 4 Proteinuria.
Blood pressure
In a study that considered treatment for people with hypertension nephrology (Fu 2009), no significant effects observed in reducing systolic or diastolic blood pressure in relation to Cordyceps (Analysis 1.5 (systolic, 1 study, 75 participants): ‐1.40 mm Hg, 95% CI ‐5.90 to 3.10); (Analysis 1.6 (diastolic, 1 study, 75 participants): 0.80 mm Hg, 95% CI ‐3.19 to 4.79).
1.5. Analysis.
Comparison 1 Cordyceps + conventional treatment versus conventional treatment, Outcome 5 Systolic BP.
1.6. Analysis.
Comparison 1 Cordyceps + conventional treatment versus conventional treatment, Outcome 6 Diastolic BP.
Anaemia
Cordyceps significantly increased haemoglobin levels in people with CKD regardless of their haemodialysis status (Analysis 1.7 (5 studies, 283 participants): MD 10.40 g/L, 95% CI 6.22, 14.58: I² = 81%). The pooled results of three studies of non‐dialysis patients indicated improvement in anaemia (Analysis 1.7.2 (3 studies, 173 participants): MD 8.20 g/L, 95% CI 2.39 to 14.01; I² = 79%).
1.7. Analysis.
Comparison 1 Cordyceps + conventional treatment versus conventional treatment, Outcome 7 Haemoglobin.
Wei 2004 reported that Cordyceps significantly increased haematocrit levels (Analysis 1.8 (1 study, 60 participants): MD 3.49%, 95% CI 1.42 to 5.56).
1.8. Analysis.
Comparison 1 Cordyceps + conventional treatment versus conventional treatment, Outcome 8 Haematocrit.
Nutritional status (albumin, cholesterol)
Serum albumin levels were increased among Cordyceps recipients (Analysis 1.9 (4 studies, 323 participants): MD 3.52 g/L, 95% CI 2.79 to 4.24; I² = 0%), but there was no significant improvement in total cholesterol (Analysis 1.10 (2 studies, 198 participants): MD 0.41 mmol/L, 95% CI 0 to 0.82; I² = 0%).
1.9. Analysis.
Comparison 1 Cordyceps + conventional treatment versus conventional treatment, Outcome 9 Serum albumin.
1.10. Analysis.
Comparison 1 Cordyceps + conventional treatment versus conventional treatment, Outcome 10 Total cholesterol.
Bone disease (calcium, phosphorus)
Liu 2006a reported a significant increase in serum calcium (Analysis 1.11 (1 study, 66 participants): MD 0.15 mmol/L, 95% CI 0.04 to 0.26) and a significant decrease serum phosphorus (Analysis 1.12 (1 study, 66 participants): MD ‐0.11 mmol/L, 95% CI ‐0.18 to ‐0.04) among Cordyceps recipients.
1.11. Analysis.
Comparison 1 Cordyceps + conventional treatment versus conventional treatment, Outcome 11 Calcium.
1.12. Analysis.
Comparison 1 Cordyceps + conventional treatment versus conventional treatment, Outcome 12 Phosphorus.
Cordyceps + conventional medicine versus Western medicine + conventional medicine
Three studies compared Cordyceps preparations with Western medicine interventions. In consideration of the differing Western medicines used the results have not been pooled.
In a comparison of prednisone and Cordyceps for treatment of aristolochic acid nephropathy, Gao 2007 (27 participants) reported Cordyceps significantly reduced SCr (Analysis 2.2: MD ‐116.07 μmol/L, 95% CI ‐209.13 to ‐23.01) and significantly increased CrCl (Analysis 2.3: MD 8.07 mL/min, 95% CI 5.22 to 10.92).
2.2. Analysis.
Comparison 2 Cordyceps + conventional treatment versus Western medicine + conventional treatment, Outcome 2 Serum creatinine.
2.3. Analysis.
Comparison 2 Cordyceps + conventional treatment versus Western medicine + conventional treatment, Outcome 3 Creatinine clearance.
In comparison to coated aldehyde oxystarch, Jin 2004 (82 participants) reported Cordyceps significantly reduced SCr (Analysis 2.2: MD ‐41.72 μmol/L, 95% CI ‐77.99 to ‐5.45); and increased CrCl (Analysis 2.3: MD 7.25 mL/min, 95% CI 2.29 to 12.21), haemoglobin (Analysis 2.5: MD 21.3 g/L, 95% CI 14.2 to 28.4), haematocrit (Analysis 2.6: MD 3.6%, 95% CI 1.56 to 5.64), and albumin (Analysis 2.7: MD 4.35 g/L, 95% CI 2.89 to 5.81).
2.5. Analysis.
Comparison 2 Cordyceps + conventional treatment versus Western medicine + conventional treatment, Outcome 5 Haemoglobin.
2.6. Analysis.
Comparison 2 Cordyceps + conventional treatment versus Western medicine + conventional treatment, Outcome 6 Haematocrit.
2.7. Analysis.
Comparison 2 Cordyceps + conventional treatment versus Western medicine + conventional treatment, Outcome 7 Serum albumin.
Huang 2008 (86 participants) reported no significant differences between Lipo PGE1 and Cordyceps preparation on CKD progression (Analysis 2.1: RR 0.92, 95% CI 0.76 to 1.12), SCr (Analysis 2.2: MD 25.14 µmol/L, 95% CI ‐38.55 to 88.83), CrCl (Analysis 2.3: MD 1.61 mL/min 95% CI ‐3.64 to 0.42) or 24 hour proteinuria (Analysis 2.4: MD 0.31 g/24 h, 95% CI ‐0.06 to 0.68) in CKD patients.
2.1. Analysis.
Comparison 2 Cordyceps + conventional treatment versus Western medicine + conventional treatment, Outcome 1 CKD progression (%).
2.4. Analysis.
Comparison 2 Cordyceps + conventional treatment versus Western medicine + conventional treatment, Outcome 4 Proteinuria.
Cordyceps + traditional Chinese medicine versus traditional Chinese medicine alone
Yan 2005a (65 participants) reported no significant differences when Cordyceps was administered as a co‐intervention with traditional Chinese herbal medicine for the treatment of CKD for SCr (Analysis 3.1: MD ‐24.00 µmol/L, 95% CI ‐49.91 to 1.91), but significantly reduced 24 hour proteinuria (Analysis 3.2: MD ‐0.59 g/24 h, 95% CI ‐0.99 to ‐0.19) and significantly increased haemoglobin levels (Analysis 3.3: MD 24.00 g/L, 95% CI 16.62 to 31.38).
3.1. Analysis.
Comparison 3 Cordyceps + TCM versus TCM, Outcome 1 Serum creatinine.
3.2. Analysis.
Comparison 3 Cordyceps + TCM versus TCM, Outcome 2 Proteinuria.
3.3. Analysis.
Comparison 3 Cordyceps + TCM versus TCM, Outcome 3 Haemoglobin.
Adverse effects
Four studies reported that no obvious adverse effects were associated with Cordyceps preparations (Chen 2006a; Fu 2009; Sun 1999; Yan 2005a).
Hu 2008 (30 participants) reported that test results for blood chemistry, liver function, cardiographic studies and electrolytes were normal after administration of Jin Shui Bao capsule (Cordyceps 0.33 g) over two months.
Liu 2006a (66 participants) reported that two intervention arm participants (5.9%) had diarrhoea and six (17.6%) experienced constipation; three control arm participants (9.3%) developed nausea, three (9.3%) had abdominal distention, and six (18.8%) became constipated.
Huang 2008 (86 participants) reported that four (4.7%) of 86 participants experienced discomfort after taking Jin Shui Bao capsule. Symptoms were minimised when the capsule was taken after eating.
The remaining 15 included studies did not report adverse events. Therefore definitive associations between adverse effects and Cordyceps could not be derived with certainty.
Other outcomes
Several outcomes were not reported in the included studies.
Time to requirement for RRT or initiation of dialysis (primary outcome)
All‐cause mortality (primary outcome)
Quality of life measured by a validated scale (secondary outcome)
Symptoms including skin pruritus, vomiting, measured by visual analogue or other scales (secondary outcome).
Discussion
Summary of main results
This review included 22 studies that involved 1746 participants with CKD; all studies were undertaken in hospitals in China. Different stages of CKD were represented in the studies; baseline SCr ranged from 135 to 820 µmol/L. All studies investigated mycelial fermentation products of Cordyceps sinensis.
Cordyceps was administered as a co‐intervention in all studies: 18/22 studies compared Cordyceps plus conventional treatment with the same conventional treatment, and of these three administered haemodialysis as the co‐intervention. Three studies compared Cordyceps plus conventional treatment with Western medicine plus the same conventional treatment; and one study compared Cordyceps plus traditional Chinese medicine to the same traditional Chinese medicine.
As an adjunctive treatment to conventional medicine, Cordyceps preparation had promising effects on decreasing SCr, increasing CrCl, reducing proteinuria and alleviating CKD‐associated complications such as reduced haemoglobin and serum albumin levels. However, low methodological quality and under‐reporting among the included studies meant that definitive conclusions could not be made about the possible effects of Cordyceps preparation for people with CKD.
Overall completeness and applicability of evidence
Although we intended to explore potential benefits of Cordyceps for people with CKD on aspects including CKD progression and complications, none of the included studies reported outcome data on time to requirement for RRT or initiation of dialysis, or all‐cause mortality. Data on the effects of Cordyceps preparations on SCr and CrCl were reported. It is noteworthy that CrCl tends to overestimate GFR (Shemesh 1985). Lack of GFR data meant that it was difficult to clearly define degree of kidney function damage and the CKD stage.
Because all included studies were undertaken in China questions about applicability of the evidence to other settings exist. Co‐interventions explored in the included studies for CKD management in China are likely to differ from other settings. It is uncertain if this aspect influenced assessment of the effects and safety of Cordyceps for people with CKD.
Quality of the evidence
Evidence quality of included studies in the review was suboptimal. Risk of bias was assessed as high in four and unclear in 18/22 included studies. Methodological flaws related to lack of clear descriptions of randomisation, allocation concealment, and binding. There was marked heterogeneity in the conventional treatment as co‐interventions in some included studies. Because of no masking during the study, the possible difference in the multiple co‐interventions between treatment and control group would likely introduce bias to the results.
Potential biases in the review process
Four studies were excluded from our quantitative analysis because of the absence of some essential data. However, we believe that exclusion of these studies did not bias review results because they represented similar study populations and results to the body of included studies.
Agreements and disagreements with other studies or reviews
In an earlier review that included six studies, statistically significant treatment effects were reported for Cordyceps compared with control (Xu 2006). Because information about control interventions and definitions of outcome measures were not clearly stated in Xu 2006, we did not compare our results with findings from this review.
Authors' conclusions
Implications for practice.
The current evidence indicated that when used with conventional treatment, Cordyceps may offer some benefits for people with CKD by improving kidney function and alleviating complications such as anaemia and malnutrition. However, methodological quality was suboptimal, and further clinical studies are required to ascertain the potential benefits of Cordyceps for people with CKD.
Implications for research.
Based on the methodological deficits identified in the available studies, we suggest that future clinical studies investigating Cordyceps for people with CKD consider the following:
Randomisation and allocation concealment methodology need to be undertaken and clearly reported.
Efforts should be made to develop placebo controls that mimic Cordyceps products to clarify its efficacy for CKD. Blinding intervention assignment to participants, clinicians and outcomes assessors needs to be undertaken and reported. In settings where it is not possible or feasible to blind participants and clinicians, outcomes assessors should be blinded, especially when subjective outcomes are involved.
Sample sizes should be calculated to ensure that studies have sufficient power to detect possible differences between groups.
Incorporating long‐term outcome measures, such as need for RRT, all‐cause mortality, or quality of life measures may help to confirm beneficial outcomes associated with Cordyceps for CKD.
Record and report all in‐study adverse effects.
The elaborated CONSORT statement for reporting RCTs of herbal medicines is strongly recommended when designing and reporting clinical studies (Gagnier 2006).
Acknowledgements
We would like to thank Fan Cheung and Yi Fong Ho who assisted with study selection, data extraction and data entry.
We would also like to thank the referees for their editorial advice, and Narelle Willis and Gail Higgins of the Cochrane Renal Group for their kind assistance in preparing this review.
Appendices
Appendix 1. Electronic search strategies
| Database | Search terms |
| CENTRAL |
|
| MEDLINE |
|
| EMBASE |
|
| CBM |
|
| CMCC |
|
| TCMLARS |
|
| Chinese Dissertation Database |
|
| CMAC |
|
| Index to Chinese Periodical Literature |
|
Appendix 2. Risk of bias assessment tool
| Potential source of bias | Assessment criteria |
|
Random sequence generation Selection bias (biased allocation to interventions) due to inadequate generation of a randomised sequence |
Low risk of bias: Random number table; computer random number generator; coin tossing; shuffling cards or envelopes; throwing dice; drawing of lots; minimization (minimization may be implemented without a random element, and this is considered to be equivalent to being random). |
| High risk of bias: Sequence generated by odd or even date of birth; date (or day) of admission; sequence generated by hospital or clinic record number; allocation by judgement of the clinician; by preference of the participant; based on the results of a laboratory test or a series of tests; by availability of the intervention. | |
| Unclear: Insufficient information about the sequence generation process to permit judgement. | |
|
Allocation concealment Selection bias (biased allocation to interventions) due to inadequate concealment of allocations prior to assignment |
Low risk of bias: Randomisation method described that would not allow investigator/participant to know or influence intervention group before eligible participant entered in the study (e.g. central allocation, including telephone, web‐based, and pharmacy‐controlled, randomisation; sequentially numbered drug containers of identical appearance; sequentially numbered, opaque, sealed envelopes). |
| High risk of bias: Using an open random allocation schedule (e.g. a list of random numbers); assignment envelopes were used without appropriate safeguards (e.g. if envelopes were unsealed or non‐opaque or not sequentially numbered); alternation or rotation; date of birth; case record number; any other explicitly unconcealed procedure. | |
| Unclear: Randomisation stated but no information on method used is available. | |
|
Blinding of participants and personnel Performance bias due to knowledge of the allocated interventions by participants and personnel during the study |
Low risk of bias: No blinding or incomplete blinding, but the review authors judge that the outcome is not likely to be influenced by lack of blinding; blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken. |
| High risk of bias: No blinding or incomplete blinding, and the outcome is likely to be influenced by lack of blinding; blinding of key study participants and personnel attempted, but likely that the blinding could have been broken, and the outcome is likely to be influenced by lack of blinding. | |
| Unclear: Insufficient information to permit judgement | |
|
Blinding of outcome assessment Detection bias due to knowledge of the allocated interventions by outcome assessors. |
Low risk of bias: No blinding of outcome assessment, but the review authors judge that the outcome measurement is not likely to be influenced by lack of blinding; blinding of outcome assessment ensured, and unlikely that the blinding could have been broken. |
| High risk of bias: No blinding of outcome assessment, and the outcome measurement is likely to be influenced by lack of blinding; blinding of outcome assessment, but likely that the blinding could have been broken, and the outcome measurement is likely to be influenced by lack of blinding. | |
| Unclear: Insufficient information to permit judgement | |
|
Incomplete outcome data Attrition bias due to amount, nature or handling of incomplete outcome data. |
Low risk of bias: No missing outcome data; reasons for missing outcome data unlikely to be related to true outcome (for survival data, censoring unlikely to be introducing bias); missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups; for dichotomous outcome data, the proportion of missing outcomes compared with observed event risk not enough to have a clinically relevant impact on the intervention effect estimate; for continuous outcome data, plausible effect size (difference in means or standardized difference in means) among missing outcomes not enough to have a clinically relevant impact on observed effect size; missing data have been imputed using appropriate methods. |
| High risk of bias: Reason for missing outcome data likely to be related to true outcome, with either imbalance in numbers or reasons for missing data across intervention groups; for dichotomous outcome data, the proportion of missing outcomes compared with observed event risk enough to induce clinically relevant bias in intervention effect estimate; for continuous outcome data, plausible effect size (difference in means or standardized difference in means) among missing outcomes enough to induce clinically relevant bias in observed effect size; ‘as‐treated’ analysis done with substantial departure of the intervention received from that assigned at randomisation; potentially inappropriate application of simple imputation. | |
| Unclear: Insufficient information to permit judgement | |
|
Selective reporting Reporting bias due to selective outcome reporting |
Low risk of bias: The study protocol is available and all of the study’s pre‐specified (primary and secondary) outcomes that are of interest in the review have been reported in the pre‐specified way; the study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre‐specified (convincing text of this nature may be uncommon). |
| High risk of bias: Not all of the study’s pre‐specified primary outcomes have been reported; one or more primary outcomes is reported using measurements, analysis methods or subsets of the data (e.g. subscales) that were not pre‐specified; one or more reported primary outcomes were not pre‐specified (unless clear justification for their reporting is provided, such as an unexpected adverse effect); one or more outcomes of interest in the review are reported incompletely so that they cannot be entered in a meta‐analysis; the study report fails to include results for a key outcome that would be expected to have been reported for such a study. | |
| Unclear: Insufficient information to permit judgement | |
|
Other bias Bias due to problems not covered elsewhere in the table |
Low risk of bias: The study appears to be free of other sources of bias. |
| High risk of bias: Had a potential source of bias related to the specific study design used; stopped early due to some data‐dependent process (including a formal‐stopping rule); had extreme baseline imbalance; has been claimed to have been fraudulent; had some other problem. | |
| Unclear: Insufficient information to assess whether an important risk of bias exists; insufficient rationale or evidence that an identified problem will introduce bias. |
Data and analyses
Comparison 1. Cordyceps + conventional treatment versus conventional treatment.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 CKD progression (%) | 8 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 1.1 Unclear risk of bias subgroup | 6 | 418 | Risk Ratio (M‐H, Random, 95% CI) | 1.09 [0.99, 1.21] |
| 1.2 High risk of bias subgroup | 2 | 227 | Risk Ratio (M‐H, Random, 95% CI) | 1.36 [1.17, 1.58] |
| 2 Serum creatinine | 15 | 1047 | Mean Difference (IV, Random, 95% CI) | ‐53.50 [‐84.17, ‐22.83] |
| 2.1 Dialysis | 1 | 60 | Mean Difference (IV, Random, 95% CI) | 32.88 [21.53, 44.23] |
| 2.2 Non‐dialysis (unclear risk of bias) | 11 | 714 | Mean Difference (IV, Random, 95% CI) | ‐44.43 [‐69.04, ‐19.83] |
| 2.3 Non‐dialysis (high risk of bias group) | 3 | 273 | Mean Difference (IV, Random, 95% CI) | ‐118.77 [‐148.81, ‐88.74] |
| 3 Creatinine clearance | 6 | 362 | Mean Difference (IV, Random, 95% CI) | 9.22 [3.10, 15.34] |
| 3.1 Unclear risk of bias subgroup | 5 | 295 | Mean Difference (IV, Random, 95% CI) | 10.78 [2.54, 19.02] |
| 3.2 High risk of bias subgroup | 1 | 67 | Mean Difference (IV, Random, 95% CI) | 5.09 [0.56, 9.62] |
| 4 Proteinuria | 4 | 211 | Mean Difference (IV, Random, 95% CI) | ‐0.15 [‐0.24, ‐0.05] |
| 5 Systolic BP | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 6 Diastolic BP | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 7 Haemoglobin | 5 | 283 | Mean Difference (IV, Random, 95% CI) | 10.40 [6.22, 14.58] |
| 7.1 Dialysis | 1 | 60 | Mean Difference (IV, Random, 95% CI) | 19.0 [14.44, 23.56] |
| 7.2 Non‐dialysis (unclear risk of bias) | 3 | 173 | Mean Difference (IV, Random, 95% CI) | 8.20 [2.39, 14.01] |
| 7.3 Non‐dialysis (high risk of bias) | 1 | 50 | Mean Difference (IV, Random, 95% CI) | 7.70 [2.61, 12.79] |
| 8 Haematocrit | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 9 Serum albumin | 4 | 323 | Mean Difference (IV, Random, 95% CI) | 3.52 [2.79, 4.24] |
| 9.1 Dialysis | 1 | 65 | Mean Difference (IV, Random, 95% CI) | 3.08 [1.44, 4.72] |
| 9.2 Non‐dialysis | 3 | 258 | Mean Difference (IV, Random, 95% CI) | 3.62 [2.81, 4.43] |
| 10 Total cholesterol | 2 | 198 | Mean Difference (IV, Random, 95% CI) | ‐0.41 [‐0.82, 0.00] |
| 11 Calcium | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 12 Phosphorus | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected |
Comparison 2. Cordyceps + conventional treatment versus Western medicine + conventional treatment.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 CKD progression (%) | 1 | Risk Ratio (M‐H, Random, 95% CI) | Totals not selected | |
| 2 Serum creatinine | 3 | 195 | Mean Difference (IV, Random, 95% CI) | ‐37.49 [‐101.43, 26.44] |
| 3 Creatinine clearance | 3 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 4 Proteinuria | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 5 Haemoglobin | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 6 Haematocrit | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 7 Serum albumin | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 8 Total cholesterol | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected |
2.8. Analysis.
Comparison 2 Cordyceps + conventional treatment versus Western medicine + conventional treatment, Outcome 8 Total cholesterol.
Comparison 3. Cordyceps + TCM versus TCM.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Serum creatinine | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 2 Proteinuria | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 3 Haemoglobin | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected |
Characteristics of studies
Characteristics of included studies [ordered by study ID]
Chen 2003.
| Methods |
|
|
| Participants |
|
|
| Interventions | Treatment group
Control group
Conventional treatment
|
|
| Outcomes |
|
|
| Notes |
|
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | High risk | Randomisation claimed, but there were 164 participants in treatment group and 48 in the control group |
| Allocation concealment (selection bias) | High risk | Not reported |
| Blinding (performance bias and detection bias) All outcomes | High risk | No placebo control and no description of blinding |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | No losses to follow‐up. All participants included in the analysis |
| Selective reporting (reporting bias) | Unclear risk | Limited outcome measures were reported |
| Other bias | High risk | Imbalance in the patient numbers in the treatment and control group |
Chen 2006a.
| Methods |
|
|
| Participants |
|
|
| Interventions | Treatment group
Control group
Conventional treatment
|
|
| Outcomes |
|
|
| Notes |
|
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomisation methodology not reported |
| Allocation concealment (selection bias) | Unclear risk | Not reported |
| Blinding (performance bias and detection bias) All outcomes | High risk | No placebo control and no description of blinding |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | No losses to follow‐up. All participants included in the analysis |
| Selective reporting (reporting bias) | Unclear risk | Limited outcome measures reported |
| Other bias | High risk | Imbalance in participant numbers in treatment and control groups |
Fu 2009.
| Methods |
|
|
| Participants |
|
|
| Interventions | Treatment group
Control group
Conventional treatment
|
|
| Outcomes |
|
|
| Notes |
|
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomisation methodology not reported |
| Allocation concealment (selection bias) | Unclear risk | Not reported |
| Blinding (performance bias and detection bias) All outcomes | High risk | No placebo control and no description of blinding |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | No losses to follow‐up. All participants included in the analyses |
| Selective reporting (reporting bias) | Unclear risk | Limited outcome measures were reported |
| Other bias | Unclear risk | Conventional treatment may differ between arms |
Gao 2007.
| Methods |
|
|
| Participants |
|
|
| Interventions | Treatment group
Control group
Conventional treatment
|
|
| Outcomes |
|
|
| Notes |
|
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | High risk | Randomisation methodology not reported. Sequencing according to presentation at hospital |
| Allocation concealment (selection bias) | High risk | Possibly quasi‐randomised, based on sequencing at presentation |
| Blinding (performance bias and detection bias) All outcomes | High risk | Different interventions in two groups; unlikely to be blinded |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | No losses to follow‐up. All participants included in the analysis |
| Selective reporting (reporting bias) | Unclear risk | Limited outcome measures were reported |
| Other bias | Unclear risk | Conventional treatment may differ between arms |
Guo 2009.
| Methods |
|
|
| Participants |
|
|
| Interventions | Treatment group
Control group
Conventional treatment
|
|
| Outcomes |
|
|
| Notes |
|
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomisation method not reported |
| Allocation concealment (selection bias) | Unclear risk | Not reported |
| Blinding (performance bias and detection bias) All outcomes | High risk | No placebo control and no description of blinding |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Data from 9 and 5 participants respectively in the treatment and control arms not reported |
| Selective reporting (reporting bias) | Unclear risk | Limited outcome measures were reported |
| Other bias | Unclear risk | Conventional treatment may differ between arms |
Hu 2008.
| Methods |
|
|
| Participants |
|
|
| Interventions | Treatment group
Control group
Conventional treatment
|
|
| Outcomes |
|
|
| Notes |
|
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomisation method not reported |
| Allocation concealment (selection bias) | Unclear risk | Not reported |
| Blinding (performance bias and detection bias) All outcomes | High risk | No placebo control and no description of blinding |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | No losses to follow‐up. All participants included in the analysis |
| Selective reporting (reporting bias) | Unclear risk | Limited outcome measures were reported |
| Other bias | Unclear risk | Conventional treatment may differ between arms |
Huang 2008.
| Methods |
|
|
| Participants |
|
|
| Interventions | Treatment group
Control group 1
Control group 2
Conventional treatment
|
|
| Outcomes |
|
|
| Notes |
|
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | High risk | Entry sequencing used for allocation to treatment or control arms |
| Allocation concealment (selection bias) | High risk | Entry sequencing |
| Blinding (performance bias and detection bias) All outcomes | High risk | Three groups received different interventions; no placebo control |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | No missing data |
| Selective reporting (reporting bias) | Unclear risk | Limited outcome measures were reported |
| Other bias | Unclear risk | Conventional treatment may differ between arms |
Jin 2004.
| Methods | Design: parallel RCT Setting: 2 hospitals in China Power calculation: no |
|
| Participants |
|
|
| Interventions | Treatment group
Control group 1
Control group 2
Conventional treatment
|
|
| Outcomes |
|
|
| Notes |
|
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Randomised block design |
| Allocation concealment (selection bias) | High risk | The random code may easily be broken in randomised block design |
| Blinding (performance bias and detection bias) All outcomes | High risk | No placebo was designed for comparisons between different interventions |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | No losses to follow‐up. All participants included in the analysis |
| Selective reporting (reporting bias) | Low risk | Some commonly used outcomes for study on CKD were reported. All results in three groups were reported |
| Other bias | Unclear risk | Conventional treatment may differ between arms |
Liu 2006a.
| Methods |
|
|
| Participants |
|
|
| Interventions | Treatment group
Control group
Conventional treatment
|
|
| Outcomes |
|
|
| Notes |
|
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomisation method not reported |
| Allocation concealment (selection bias) | Unclear risk | Not reported |
| Blinding (performance bias and detection bias) All outcomes | Unclear risk | No placebo control and no description of blinding |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | No losses to follow‐up. All participants included in the analysis |
| Selective reporting (reporting bias) | Unclear risk | Limited outcome measures were reported |
| Other bias | Unclear risk | Conventional treatment may differ between arms |
Liu 2007a.
| Methods |
|
|
| Participants |
|
|
| Interventions | Treatment group
Control group
Conventional treatment
|
|
| Outcomes |
|
|
| Notes |
|
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomisation method not reported |
| Allocation concealment (selection bias) | Unclear risk | Not reported |
| Blinding (performance bias and detection bias) All outcomes | Unclear risk | No placebo control and no description of blinding |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | No losses to follow‐up. All participants included in the analysis |
| Selective reporting (reporting bias) | Unclear risk | Limited outcome measures were reported |
| Other bias | Unclear risk | Conventional treatment may differ between arms |
Pan 2007.
| Methods |
|
|
| Participants |
|
|
| Interventions | Treatment group
Control group
Conventional treatment
|
|
| Outcomes |
|
|
| Notes |
|
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomisation method not reported |
| Allocation concealment (selection bias) | Unclear risk | Not reported |
| Blinding (performance bias and detection bias) All outcomes | High risk | No placebo control and no description of blinding |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | No losses to follow‐up. All participants included in the analysis |
| Selective reporting (reporting bias) | Unclear risk | Limited outcome measures were reported |
| Other bias | Unclear risk | Conventional treatment may differ between arms |
Shi 2009.
| Methods |
|
|
| Participants |
|
|
| Interventions | Treatment group
Control group
Conventional treatment
|
|
| Outcomes |
|
|
| Notes |
|
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomisation method not reported |
| Allocation concealment (selection bias) | Unclear risk | Not reported |
| Blinding (performance bias and detection bias) All outcomes | High risk | No placebo control and no description of blinding |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | No losses to follow‐up. All participants included in the analysis |
| Selective reporting (reporting bias) | Unclear risk | Limited outcome measures were reported |
| Other bias | Unclear risk | Conventional treatment may differ between arms |
Sun 1999.
| Methods |
|
|
| Participants |
|
|
| Interventions | Treatment group
Control group
Conventional treatment
|
|
| Outcomes |
|
|
| Notes |
|
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomisation method not reported |
| Allocation concealment (selection bias) | Unclear risk | Not reported |
| Blinding (performance bias and detection bias) All outcomes | High risk | No placebo control and no description of blinding |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | No losses to follow‐up. All participants included in the analysis |
| Selective reporting (reporting bias) | Unclear risk | Limited outcome measures were reported |
| Other bias | Unclear risk | Conventional treatment not clearly stated |
Wang 2005a.
| Methods |
|
|
| Participants |
|
|
| Interventions | Treatment group
Control group
Conventional treatment
|
|
| Outcomes |
|
|
| Notes |
|
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomisation method not reported |
| Allocation concealment (selection bias) | Unclear risk | Not reported |
| Blinding (performance bias and detection bias) All outcomes | High risk | No placebo control and no description of blinding |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | No losses to follow‐up. All participants included in the analysis |
| Selective reporting (reporting bias) | Unclear risk | Limited outcome measures were reported |
| Other bias | Unclear risk | Conventional treatment may differ between arms |
Wei 2004.
| Methods |
|
|
| Participants |
|
|
| Interventions | Treatment group
Control group
Conventional treatment
|
|
| Outcomes |
|
|
| Notes |
|
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Random number table used |
| Allocation concealment (selection bias) | Unclear risk | Not reported |
| Blinding (performance bias and detection bias) All outcomes | High risk | No placebo control and no description of blinding |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | No losses to follow‐up. All participants included in the analysis |
| Selective reporting (reporting bias) | Low risk | Some commonly used outcomes for studying CKD were reported |
| Other bias | Unclear risk | Conventional treatment may differ between arms |
Wu 2007.
| Methods |
|
|
| Participants |
|
|
| Interventions | Treatment group
Control group
Conventional treatment
|
|
| Outcomes |
|
|
| Notes |
|
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomisation method not reported |
| Allocation concealment (selection bias) | Unclear risk | Not reported |
| Blinding (performance bias and detection bias) All outcomes | High risk | No placebo control and no description of blinding |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | No losses to follow‐up. All participants included in the analysis |
| Selective reporting (reporting bias) | Unclear risk | Limited outcome measures were reported |
| Other bias | Unclear risk | Conventional treatment may differ between arms |
Xu 2004.
| Methods |
|
|
| Participants |
|
|
| Interventions | Treatment group
Control group
Conventional treatment
|
|
| Outcomes |
|
|
| Notes |
|
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomisation method not reported |
| Allocation concealment (selection bias) | Unclear risk | Not reported |
| Blinding (performance bias and detection bias) All outcomes | High risk | No placebo control and no description of blinding |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | No losses to follow‐up. All participants included in the analysis |
| Selective reporting (reporting bias) | Unclear risk | Limited outcome measures were reported |
| Other bias | Unclear risk | Conventional treatment may differ between arms |
Yan 2005a.
| Methods |
|
|
| Participants |
|
|
| Interventions | Treatment group
Control group
TCM treatment
|
|
| Outcomes |
|
|
| Notes |
|
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomisation method not reported |
| Allocation concealment (selection bias) | Unclear risk | Not reported |
| Blinding (performance bias and detection bias) All outcomes | Unclear risk | No placebo control and no description of blinding |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | No losses to follow up. All participants included in the analysis |
| Selective reporting (reporting bias) | Unclear risk | Limited outcome measures reported |
| Other bias | Unclear risk | TCM treatments may differ between arms |
Yang 1999b.
| Methods |
|
|
| Participants |
|
|
| Interventions | Treatment group
Control group
Conventional treatment
|
|
| Outcomes |
|
|
| Notes |
|
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomisation method not reported |
| Allocation concealment (selection bias) | Unclear risk | Not reported |
| Blinding (performance bias and detection bias) All outcomes | High risk | No placebo control and no description of blinding |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | No losses to follow‐up. All participants were included in the analysis |
| Selective reporting (reporting bias) | Unclear risk | Limited outcome measures were reported |
| Other bias | Unclear risk | Conventional treatment differed between arms |
Yu 2002.
| Methods |
|
|
| Participants |
|
|
| Interventions | Treatment group
Control group
|
|
| Outcomes |
|
|
| Notes |
|
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomisation method not reported |
| Allocation concealment (selection bias) | Unclear risk | Not reported |
| Blinding (performance bias and detection bias) All outcomes | High risk | No placebo control and no description of blinding |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | No losses to follow‐up. All participants included in the analysis |
| Selective reporting (reporting bias) | Unclear risk | Limited outcome measures were reported |
| Other bias | Unclear risk | Conventional treatment may differ between arms |
Yu 2003.
| Methods |
|
|
| Participants |
|
|
| Interventions | Treatment group
Control group
Conventional treatment
|
|
| Outcomes |
|
|
| Notes |
|
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomisation method not reported |
| Allocation concealment (selection bias) | Unclear risk | Not reported |
| Blinding (performance bias and detection bias) All outcomes | High risk | No placebo control and no description of blinding |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Data from 4 control arm participants were not reported; no reason for data omission provided |
| Selective reporting (reporting bias) | Unclear risk | Limited outcome measures were reported |
| Other bias | Unclear risk | Conventional treatment administered not identical in both arms |
Zhang 2009.
| Methods |
|
|
| Participants |
|
|
| Interventions | Treatment group
Control group
Conventional treatment
|
|
| Outcomes |
|
|
| Notes |
|
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomisation method not reported |
| Allocation concealment (selection bias) | Unclear risk | Not reported |
| Blinding (performance bias and detection bias) All outcomes | High risk | No placebo control and no description of blinding |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | No losses to follow‐up. All participants included in the analysis |
| Selective reporting (reporting bias) | Unclear risk | Limited outcome measures were reported |
| Other bias | Unclear risk | Conventional treatment may differ between arms |
AKD ‐ acute kidney injury; BP ‐ blood pressure; CKD ‐ chronic kidney disease; CrCl ‐ creatinine clearance; ESKD ‐ end‐stage kidney disease; Hb ‐ haemoglobin; HCT ‐ haematocrit; NR ‐ not reported; SCr ‐ serum creatinine; TCM ‐ traditional Chinese medicine; UPE ‐ urinary protein electrophoresis
Characteristics of excluded studies [ordered by study ID]
| Study | Reason for exclusion |
|---|---|
| Bao 1994 | Information about the duration of aminoglycoside nephrotoxicity was not available |
| Huang 2008b | Ginkgo leaf tablet was used with Cordyceps preparation in the treatment group |
| Jiang 2008 | Did not include outcomes relevant to the review |
| Li 1992 | Wrong population: participants had respiratory infection or febrile diseases, normal kidney function, and absence of history of kidney disease |
| Quan 2004 | Follow up periods differed for individual participants |
| Wu 2005 | Participant allocation was not randomised |
| Xu 2009 | Did not include outcomes relevant to the review |
| Yan 2005b | Participant allocation was not randomised |
| Yan 2007 | The wording and data were similar to those in Liu 2007a to some degree, possibly duplicate report |
| Yang 2001 | Did not include outcomes relevant to the review |
| Yin 2001 | Did not include outcomes relevant to the review |
| Zhou 2002 | Did not include outcomes relevant to the review |
Characteristics of studies awaiting assessment [ordered by study ID]
Chai 2009.
| Methods |
|
| Participants |
|
| Interventions |
|
| Outcomes |
|
| Notes |
|
Jin 2006.
| Methods |
|
| Participants |
|
| Interventions |
|
| Outcomes |
|
| Notes |
|
Lin 2003.
| Methods |
|
| Participants |
|
| Interventions |
|
| Outcomes |
|
| Notes |
|
CKD ‐ chronic kidney disease; CrCl ‐ creatinine clearance; Hb ‐ haemoglobin; HCT ‐ haematocrit; RCT ‐ randomised controlled trial; SCr ‐ serum creatinine
Differences between protocol and review
Diabetic nephropathy and primary nephrotic syndrome, which will be covered in other reviews (Feng 2013; Liu 2007), were excluded from this review after discussion with the Cochrane Renal Group.
Contributions of authors
Draft protocol: HWZ, ZXL
Study selection: HWZ, FC, YFH
Extract data from studies: HWZ, FC, YFH
Enter data into RevMan/check data entry: HWZ, FC
Carry out the analysis: HWZ
Interpret the analysis: HWZ, ZXL, CL, LSC
Draft the final review: HWZ, ZXL
Disagreement resolution: ZXL,
Update the review: HWZ, ZXL
Sources of support
Internal sources
School of Chinese Medicine, The Chinese University of Hong Kong, China.
Yan Oi Tong, Hong Kong, China.
External sources
No sources of support supplied
Declarations of interest
None known.
New
References
References to studies included in this review
Chen 2003 {published data only}
- Chen QK, Zhou J, Luo LM, Li QY, E Y. The treatment of 164 cases of chronic kidney failure by Jin Shui Bao capsule [Jin shui bao jiao nang zhi liao man xing shen gong neng shuai jie 164 li]. Zhongguo Zhongyiyao Xinxi Zazhi [Chinese Journal of Information on Traditional Chinese Medicine] 2003;10(5):43. [Google Scholar]
Chen 2006a {published data only}
- Chen QZ. Clinical observation on the treatment of 36 cases of chronic kidney insufficiency with Jin Shui Bao capsule [Jin shui bao jiao nang zhi liao man xing shen gong neng bu quan 36 li lin chuang guan cha]. Zhongguo Yi Xue Wen Zhai Nei Ke Xue [China Medical Abstracts Internal Medicine] 2006;27(5):459‐60. [Google Scholar]
Fu 2009 {published data only}
- Fu GS. Clinical observation on the treatment of Jin Shui Bao capsule combined with anti‐hypertensive on 35 cases of hypertensive nephrology [Jin shui bao jiao nang lian he jiang ya yao zhi liao gao xue ya shen bing 35 cases lin chuang guan cha]. Zhongyiyao Daobao [Guiding Journal of Traditional Chinese Medicine] 2009;15(9):14‐6. [Google Scholar]
Gao 2007 {published data only}
- Gao Z, Ku BQ, Qin YF, Guo ZD. Efficacy of Corbrin capsule in treatment of chronic aristolochic acid nephropathy [Bai ling jiao nang zhi liao man xing ma dou ling suan shen bing de lin chuang guan cha]. Zhongguo Yaoshi [China Pharmacist] 2007;10(9):851‐2. [Google Scholar]
Guo 2009 {published data only}
- Guo XL. The influence of Jin Shui Bao capsule on the kidney function of patients receiving maintaining hemodialysis [Jin shui bao jiao nang dui wei chi xing xue ye tou xi huan zhe shen gong neng de ying xiang]. Hebei Zhongyi [Hebei Journal of Traditional Chinese Medicine] 2009;31(7):1063‐4. [Google Scholar]
Hu 2008 {published data only}
- Hu WX. Observation of the effects of Jinshuibao Capsules on chronic renal failure [Jin shui bao jiao nang zhi liao man xing shen gong neng bu quan de liao xiao guan cha]. Zhongguo Yiyao Daobao [China Medical Herald] 2008;5(5):59‐60. [Google Scholar]
Huang 2008 {published data only}
- Huang YY, Huang P. Clinical observation on the treatment effect of integrated Chinese and Western medicine for chronic kidney failure [Zhong xi yi jie he zhi liao man xing shen gong neng bu quan lin chuang liao xiao guan cha]. Shiyong Yixue Zazhi [Journal of Practical Medicine] 2008;24(14):2516‐7. [Google Scholar]
Jin 2004 {published data only}
- Jin ZH, Chen YP. Clinical study on the effect of Cordyceps sinensis mycelium on delaying progression of chronic kidney failure [Chong cao jun si yan huan man xing shen gong neng shuai jie jin zhan de lin chuang yan jiu]. Nanjing Zhongyiyao Daxue Xuebao (Ziran Kexue Ban) [Journal of Nanjing University of Traditional Chinese Medicine] 2004;20(3):155‐7. [Google Scholar]
Liu 2006a {published data only}
- Liu T, Li JF, Wang LP, Liu HH, Cheng GF. Clinical observation on the treatment of Bai Ling capsule combined with medicinal charcoal capsules on chronic kidney failure [Bai ling jiao nang lian he ai xi te zhi liao man xing shen shuai jie de lin chuang guan cha]. Zhongguo Zhongxiyi Jiehe Shenbing Zazhi [Chinese Journal of Integrated Traditional and Western Nephrology] 2006;7(10):603‐4. [Google Scholar]
Liu 2007a {published data only}
- Liu Z, Luo S, Quan X. Study on the treatment of chronic renal failure using shen shuai ning capsule combined with zymolysis cordyceps sinensis powder [Shen shuai ning jiao nang lian he fa xiao chong cao jun fen zhi liao man xing shen shuai jie de lin chuang guan cha]. Lin Chuang Shen Zang Bing Za Zhi [Journal of Clinical Nephrology] 2007;7(2):84‐5. [Google Scholar]
Pan 2007 {published data only}
- Pan HJ. Clinical observation on the treatment of Bai Ling Capsule on chronic kidney failure [Bai ling jiao nang zhi liao man xing shen shuai jie lin chuang guan cha]. Xian Dai Yi Yao Wei Sheng [Modern Medicine Health] 2007;23(3):345‐6. [Google Scholar]
Shi 2009 {published data only}
- Shi XH, Li H. Therapeutic evaluation of valsartan combined with bailing capsule on proteinuria in nephropathy [Jie sha tan lian he bai ling jiao nang zhi liao shen xing dan bai niao de liao xiao guan cha]. Zhongguo Shiyong Yiyao Zazhi [Chinese Journal of Practical Medicine] 2009;36(3):30‐31,3. [Google Scholar]
Sun 1999 {published data only}
- Sun JH, Sun JD, Ye RG. Clinical observation on the treatment of 30 cases of chronic kidney failure by the hemodialysis combined with Jinshuibao [Xue ye tou xi pei he jin shui bao zhi liao man xing shen shuai 30 li lin chuang guan cha]. Xuzhou Yixueyuan Xuebao [Acta Academiae Medicinae Xuzhou] 1999;19(1):73‐5. [Google Scholar]
Wang 2005a {published data only}
- Wang FL. Clinical observation on the treatment of integrated Chinese and Western medicine on chronic kidney failure [Zhong xi yi jie he zhi liao man xing shen shuai jie de lin chuang guan cha]. Zhongguo Zhongxiyi Jiehe Shenbing Zazhi [Chinese Journal of Integrated Traditional and Western Nephrology] 2005;6(9):546. [Google Scholar]
Wei 2004 {published data only}
- Wei R, Ma L, Wang XL. Clinical observation on the treatment of the chronic kidney failure with Bai Ling capsule [Bai ling jiao nang zhi liao man xing shen gong shuai jie de lin chuang guan cha]. Xinjiang Zhong Yi Yao [Xinjiang Journal of Traditional Chinese Medicine] 2004;22(4):19‐20. [Google Scholar]
Wu 2007 {published data only}
- Wu WC, Meng T. Clinical observation on the treatment effect of Jin Shui Bao Capsule for chronic kidney failure as a complementary approach [Jin shui bao jiang nang fu zhu zhi liao man xing shen gong neng shuai jie liao xiao guan cha]. Zhongguo Zhongyi Jizhen [Journal of Emergency in Traditional Chinese Medicine] 2007;16(12):1473. [Google Scholar]
Xu 2004 {published data only}
- Xu HH, Zhang DY. Therapeutic evaluation of Bailing Capsule on chronic renal failure [Bai ling jiao nang zhi liao man xing shen shuai jie 42 li liao xiao guan cha]. Zhongcheng Yao [Chinese Traditional Patent Medicine] 2004;26(7):559‐560. [Google Scholar]
Yan 2005a {published data only}
- Yan ZL. Observation on the treatment effect of Jin Shui Bao capsule on the chronic kidney disease [Jin shui bao jiao nang zhi liao man xing shen bing liao xiao guan cha]. Liaoning Zhongyi Xueyuan Xuebao [Journal of Liaoning University of Traditional Chinese Medicine] 2005;7(4):372. [Google Scholar]
Yang 1999b {published data only}
- Yang HR, Zhang CM, Ma JC, Liu XQ, Hou ML. Influences of artificial cordyceps sinensis on renal functions and immune functions in patients with chronic renal failure [Ren gong chong cao dui man xing shen gong neng shuai jie huan zhe shen gong neng ji mian yi gong neng de ying xiang]. Zhongguo Zhongxiyi Jiehe Jijiu Zazhi [Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care] 1999;6(4):168‐9. [Google Scholar]
Yu 2002 {published data only}
- Yu W, Peng LJ, Zheng HW. The influence of Cordyceps preparation on the plasma protein in the elderly patients with uremia receiving hemodialysis [Chong cao zhi ji dui lao nian niao du zheng xue ye tou xi huan zhe xue jiang dan bai de ying xiang]. Zhongguo Zhongxiyi Jiehe Shenbing Zazhi [Chinese Journal of Integrated Traditional and Western Nephrology] 2002;3(8):471‐2. [Google Scholar]
Yu 2003 {published data only}
- Yu XM, Tan SF. Clinical study on the treatment of chronic renal failure with Bailing capsule [Chong cao zhi ji zhi liao man xing shen gong neng shuai jie lin chuang guan cha]. Redai Yixue Zazhi [Journal of Tropical Medicine] 2003;3(2):203‐4. [Google Scholar]
Zhang 2009 {published data only}
- Zhang M, Gao X, Yang LM. Observation on the treatment effect of Jin Shui Bao capsule combined with prednisone on the aristolochic acid nephrology at early stage [Jin shui bao jiao nang lian he qiang di song zhi liao zao qi ma dou ling suan shen bing de liao xiao guan cha]. Shoudu Yiyao [Capital Medicine] 2009;8:46‐7. [Google Scholar]
References to studies excluded from this review
Bao 1994 {published data only}
- Bao ZD, Wu ZG, Zheng F. Amelioration of aminoglycoside nephrotoxicity by Cordyceps sinensis in old patients [Dong chong xia cao dui lao nian ren an ji tang dai shen du xing sun shang de bao hu zuo yong]. Zhongguo Zhongxiyi Jiehe Zazhi [Chinese Journal of Integrated Traditional and Western Medicine] 1994;14(5):271‐3, 259. [MEDLINE: ] [PubMed] [Google Scholar]
Huang 2008b {published data only}
- Huang JC, Li JH, Liu TX. Effect of combined therapy with hypha Cordyceps and ginkgo leaf tablet on micro‐inflammation in patients undergoing maintenance hemodialysis [Chong cao jun si lian he yin xing ye pian dui xue ye tou xi huan zhe wei yan zheng de ying xiang]. Zhongguo Zhongxiyi Jiehe Zazhi [Chinese Journal of Integrated Traditional and Western Medicine] 2008;28(6):502‐4. [MEDLINE: ] [PubMed] [Google Scholar]
Jiang 2008 {published data only}
- Jiang WF. The influence of the treatment of integrated Chinese and western medicine on the HPA axis of patients with PNS [Zhong xi yi jie he zhi liao PNS dui huan zhe HPA zhou de ying xiang]. Yi Xue Chuang Xin Yan Jiu [Medicine Innovation Research] 2008;5(20):58‐9. [Google Scholar]
Li 1992 {published data only}
- Li LS, Zheng F, et al. Clinical protection of aminoglycoside nephrotoxicity by cordyceps sinensis (cs) [abstract]. Journal of the American Society of Nephrology 1992;3(3):726. [CENTRAL: CN‐00461168] [Google Scholar]
Quan 2004 {published data only}
- Quan YH, Xu L. Clinical study on the Cordyceps preparation for the treatment of chronic kidney failure [Chong cao zhi ji zhi liao man xing shen gong neng shuai jie de lin chuang yan jiu]. Hubei Zhongyi Zazhi [Hubei Journal of Traditional Chinese Medicine] 2004;26(5):11‐2. [Google Scholar]
Wu 2005 {published data only}
- Wu ZL, Zhu HL, Wang GB, Deng HT, Zhu Q. Treatment of 53 cases of chronic kidney failure through Da Huang Zhe Chong Pill combined with Jin Shui Bao capsule [Da huang zhe chong wan lian he jin shui bao jiao nang zhi liao man xing shen gong neng shuai jie 53 li]. Zhongguo Zhongyiyao Xinxi Zazhi [Chinese Journal of Information on Traditional Chinese Medicine] 2005;12(2):68‐9. [Google Scholar]
Xu 2009 {published data only}
- Xu ZX, Nong YQ. The influence of Bai ling capsule on the microinflammation reactions on the uremia patients not receiving dialysis treatment [Bai ling jiao nang dui niao du zheng fei tou xi huan zhe wei yan zheng fan ying de ying xiang]. Zhongguo Shequ Yishi (Zongheban) [Chinese Community Doctors] 2009;11(215):159. [Google Scholar]
Yan 2005b {published data only}
- Yan Y, Wang ZQ. Observation on the treatment effect of Bai ling capsule for diabetic nephrology at early stage [Bai ling jiao nang zhi liao zao qi tang niao bing shen bing liao xiao guan cha]. Zhongguo Zhongxiyi Jiehe Shenbing Zazhi [Chinese Journal of Integrated Traditional and Western Nephrology] 2005;6(1):46‐7. [Google Scholar]
Yan 2007 {published data only}
- Yan JH, Wang YY. Clinical observation on the treatment of Shen Kang Ning Capsule combined with Jin Shui Bao Capsule on 58 cases of chronic kidney failure at the early and middle stage [Shen kang ning jiao nang lian he jin shui bao jiao nang zhi liao man xing shen gong neng shuai jie zao zhong qi 58 li lin chuang guan cha]. Xinzhongyi [Journal of New Chinese Medicine] 2007;39(11):78‐9. [Google Scholar]
Yang 2001 {published data only}
- Yang XH, Chen JL, Huang YH, et al. The exploration of the effects of cordyceps sinensis on human immunology. Zhongguo Zhongxiyi Jiehe Shenbing Zazhi [Chinese Journal of Integrated Traditional and Western Nephrology] 2001;2:28. [Google Scholar]
Yin 2001 {published data only}
- Yin JM, Fang JX, Xu JZ, liao WY, Jiang XS. Flollow‐up two years observation of Chinese herb Cordyceps in treating simple hematuria [Dong chong xia cao zhi liao dan chun xing xue niao de liao xiao guan cha]. Zhongguo Zhongxiyi Jiehe Shenbing Zazhi [Chinese Journal of Integrated Traditional and Western Nephrology] 2001;2(5):269‐70. [Google Scholar]
Zhou 2002 {published data only}
- Zhou HX. Observation on the treatment effect of Bai ling capsule on the IgA nephrology [Bai ling jiao nang zhi liao IgA shen bing xue niao de liao xiao guan cha]. Zhongyi Yanjiu [Traditional Chinese Medicinal Research] 2002;15(4):26‐7. [Google Scholar]
References to studies awaiting assessment
Chai 2009 {published data only}
- Chai WH, Yan SZ, Liu H. The effect of Cordyceps Sinenesis on renal function of patients with CRF [Dong chong xia cao zhi ji dui man xing shen gong neng shuai jie huan zhe shen gong neng de ying xiang]. Zhongguo Dang Dai Yi Yao [China Modern Medicine] 2009;16(17):28‐9,31. [Google Scholar]
Jin 2006 {published data only}
- Jin ZH, Chen YP. Clinical observation on the effect of Chan Hua Tang to delay the progress of chronic kidney failure [Chan hua tang yan huan man xing shen gong neng shuai jie jin zhan de lin chuang guan cha]. Zhongyiyao Xuekan [Chinese Archives of Traditional Chinese Medicine] 2006;24(8):1457‐9. [Google Scholar]
Lin 2003 {published data only}
- Lin JX. The influence of cordyceps mycelium on the metabolism of protein and lipid and the function of immunology in patients with chronic kidney disease [Chong cao jun si dui man xing shen gong neng shuai jie huan zhe dan bai zhi zhi zhi dai xie ji mian yi gong neng de ying xiang]. Anhui Yixue [Anhui Medical Journal] 2003;24(5):73‐4. [Google Scholar]
Additional references
Deng 2001
- Deng YY, Chen YP, He XL, Li L. Study of Cordyceps on mechanism in delaying chronic renal failure [Dong chong xia cao zhi ji yan huan man xing shen shuai jie de ji li yan jiu]. Zhongguo Zhongxiyi Jiehe Shenbing Zazhi [Chinese Journal of Integrated Traditional and Western Nephrology] 2001;2(7):381‐3. [Google Scholar]
Feng 2013
- Feng M, Yuan W, Zhang R, Fu P, Wu T. Chinese herbal medicine Huangqi type formulations for nephrotic syndrome. Cochrane Database of Systematic Reviews 2013, Issue 6. [DOI: 10.1002/14651858.CD006335.pub3] [DOI] [PMC free article] [PubMed] [Google Scholar]
Gagnier 2006
- Gagnier JJ, Boon H, Rochon P, Moher D, Barnes J, Bombardier C, et al. Reporting randomized, controlled trials of herbal interventions: an elaborated CONSORT statement. Annals of Internal Medicine 2006;144(5):364‐7. [MEDLINE: ] [DOI] [PubMed] [Google Scholar]
Higgins 2003
- Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analyses. BMJ 2003;327(7414):557‐60. [MEDLINE: ] [DOI] [PMC free article] [PubMed] [Google Scholar]
Higgins 2011
- Higgins JP, Green S [editors]. Cochrane Handbook for Systematic Reviews of Interventions 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Levey 2003
- Levey AS, Coresh J, Balk E, Kausz AT, Levin A, Steffes MW, et al. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Annals of Internal Medicine 2003;139(2):137‐47. [MEDLINE: ] [DOI] [PubMed] [Google Scholar]
Liu 2005
- Liu H, Ren Q, Zhou XJ. Clinical experiment on the effect of dong chong xia cao on the nephritis [Dong chong xia cao dui shen yan de lin chuang shi yan yan jiu]. Shiyong Zhongyi Neike Zazhi [Journal of Practical Traditional Chinese Internal Medicine] 2005;19(5):421‐2. [Google Scholar]
Liu 2007
- Liu J, Ai Y, Wan X, Zhang HW, Fei Y. Chinese medicinal herbs for diabetic kidney disease. Cochrane Database of Systematic Reviews 2007, Issue 1. [DOI: 10.1002/14651858.CD006336] [DOI] [Google Scholar]
Ma 2008
- Ma RX, Liu LQ, Zhou LM. The influence of dong chong xia cao on the accumulation of cellular matrix in renal cortex of 5/ 6 nephrectomized mouse kidney [Dong chong xia cao dui 5/6 shen qie chu da shu shen zang pi zhi xi bao wai ji zhi ji ju de ying xiang]. Zhongguo Laonianxue Zazhi [Chinese Journal of Gerontology] 2008;28(6):542‐4. [Google Scholar]
McCullough 2012
- McCullough K, Sharma P, Ali T, Khan I, Smith WC, MacLeod A, et al. Measuring the population burden of chronic kidney disease: a systematic literature review of the estimated prevalence of impaired kidney function. Nephrology Dialysis Transplantation 2012;27(5):1812‐21. [MEDLINE: ] [DOI] [PubMed] [Google Scholar]
Min 2008
- Min YL, Yu Q, Xiao J. The effect of dong chong xia cao on the renal interstitial fibrosis rat model and its influence on TGF‐β1 and α‐SMA [Dong chong xia cao zai shen jian zhi xian wei hua da shu mo xing zhong de zuo yong ji qi dui TGF‐β1he α‐SMA de ying xiang]. Zhongguo Zhongxiyi Jiehe Shenbing Zazhi [Chinese Journal of Integrated Traditional and Western Nephrology] 2008;8(2):92‐3. [Google Scholar]
NKF 2008
- National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification. http://www.kidney.org/professionals/kdoqi/guidelines_ckd/toc.htm (accessed 15 July 2014).
Nugent 2011
- Nugent RA, Fathima SF, Feigl AB, Chyung D. The burden of chronic kidney disease on developing nations: a 21st century challenge in global health. Nephron 2011;118(3):c269‐77. [MEDLINE: ] [DOI] [PubMed] [Google Scholar]
Shahed 2001
- Shahed AR, Kim SI, Shoskes DA. Down‐regulation of apoptotic and inflammatory genes by Cordyceps sinensis extract in rat kidney following ischemia/reperfusion. Transplantation Proceedings 2001;33(6):2986‐7. [MEDLINE: ] [DOI] [PubMed] [Google Scholar]
Shemesh 1985
- Shemesh O, Golbetz H, Kriss JP, Myers BD. Limitations of creatinine as a filtration marker in glomerulopathic patients. Kidney International 1985;25(5):830‐8. [MEDLINE: ] [DOI] [PubMed] [Google Scholar]
Shin 2001
- Shin KH, Lim SS, Lee SH, Lee YS, Cho SY. Antioxidant and immunostimulating activities of the fruiting bodies of Paecilomyces japonica, a new type of Cordyceps sp. Annals of the New York Academy of Sciences 2001;928:261‐73. [MEDLINE: ] [DOI] [PubMed] [Google Scholar]
Srinath Reddy 2005
- Srinath Reddy K, Shah B, Varghese C, Ramadoss A. Responding to the threat of chronic diseases in India. Lancet 2005;366(9498):1744‐9. [MEDLINE: ] [DOI] [PubMed] [Google Scholar]
Wojcikowski 2006
- Wojcikowski K, Johnson DW, Gobe G. Herbs or natural substances as complementary therapies for chronic kidney disease: ideas for future studies. Journal of Laboratory & Clinical Medicine 2006;147(4):160‐6. [MEDLINE: ] [DOI] [PubMed] [Google Scholar]
Xu 2006
- Xu FL, Huang WY, Wu TX, Qiu X, Zhang H, Liu XH. Clinical efficacy of Cordyceps sinensis for chronic kidney diseases: a systematic review [Dong chong xia cao zhi liao man xing shen bing lin chuang liao xiao de xi tong ping jia]. Zhongguo Xunzheng Yixue Zazhi [Chinese Journal of Evidence‐Based Medicine] 2006;6(11):804‐8. [EMBASE: 2006595391] [Google Scholar]
Yamaguchi 2000
- Yamaguchi Y, Kagota S, Nakamura K, Shinozuka K, Kunitomo M. Inhibitory effects of water extracts from fruiting bodies of cultured Cordyceps sinensis on raised serum lipid peroxide levels and aortic cholesterol deposition in atherosclerotic mice. Phytotherapy Research 2000;14(8):650‐2. [MEDLINE: ] [DOI] [PubMed] [Google Scholar]
Yang 1999a
- Yang LY, Chen A, Kuo YC, Lin CY. Efficacy of a pure compound H1‐A extracted from Cordyceps sinensis on autoimmune disease of MRL lpr/lpr mice. Journal of Laboratory & Clinical Medicine 1999;134(5):492‐500. [MEDLINE: ] [DOI] [PubMed] [Google Scholar]
Yang 2003
- Yang LY, Huang WJ, Hsieh HG, Lin CY. H1‐A extracted from Cordyceps sinensis suppresses the proliferation of human mesangial cells and promotes apoptosis, probably by inhibiting the tyrosine phosphorylation of Bcl‐2 and Bcl‐XL. Journal of Laboratory & Clinical Medicine 2003;141(1):74‐83. [MEDLINE: ] [DOI] [PubMed] [Google Scholar]
Yin 2007
- Yin HP, Lv XB, Chen T. Therapeutic effects of Cordyceps polysaccharide on adenine‐induced chronic renal failure in rats [Chong cao duo tang dui xian piao ling yiu fa man xing shen shuai da shu de zhi liao zuo yong]. Zhongyao Xinyao Yu Linchuang Yaoli [Traditional Chinese Drug Research & Clinical Pharmacology] 2007;18(6):451‐3. [Google Scholar]
Zhao 2000
- Zhao LW, Xiao XW, Wei YC. Inhibitory effect of Cordyceps sinensis and Cordyceps militaris on human glomerular mesangial cell proliferation induced by native LDL. Cell Biochemistry & Function 2000;18(2):93‐7. [MEDLINE: ] [DOI] [PubMed] [Google Scholar]
Zheng 2002
- Zheng XY (editor). Guidelines for clinical research on Chinese new herbal medicine for the treatment of chronic renal failure [Zhong Yao Xin Yao Zhi Liao Man Xing Shen Gong Neng Shuai Jie De Lin Chuang Yan Jiu Zhi Dao Yuan Ze]. Zhong Yao Xin Yao Lin Chuang Yan Jiu Zhi Dao Yuan Ze [Guidelines for clinical research on Chinese new herbal medicines (trial implementation)]. Beijing: China Medico‐Pharmaceutical Science & Technology Publishing House, 2002:163‐8. [Google Scholar]
Zhu 1998a
- Zhu JS, Halpern GM, Jones K. The scientific rediscovery of an ancient Chinese herbal medicine: Cordyceps sinensis: part I. Journal of Alternative & Complementary Medicine 1998;4(3):289‐303. [MEDLINE: ] [DOI] [PubMed] [Google Scholar]
Zhu 1998b
- Zhu JS, Halpern GM, Jones K. The scientific rediscovery of a precious ancient Chinese herbal regimen: Cordyceps sinensis: part II. Journal of Alternative & Complementary Medicine 1998;4(4):429‐57. [MEDLINE: ] [DOI] [PubMed] [Google Scholar]
References to other published versions of this review
Zhang 2010
- Zhang HW, Ho YF, Lin ZX, Tung YS, Kwan TH, Mok CK, et al. Cordyceps sinensis (a Chinese medicinal herb) for treating chronic kidney disease. Cochrane Database of Systematic Reviews 2010, Issue 2. [DOI: 10.1002/14651858.CD008353] [DOI] [PMC free article] [PubMed] [Google Scholar]