Etiological spectrum of acute kidney injury and adverse outcome: A single-center observation

ABSTRACT

Background:

The present study aims to evaluate the etiological spectrum with clinicopathological parameters and adverse outcomes of acute kidney injury (AKI).

Methods:

A hospital-based prospective observational study was conducted for a spectrum of AKI in 103 AKI patients and their AKI-associated adverse outcomes. The AKI patients were included as per the KDIGO definition. The patients with a known chronic kidney disease (CKD) were excluded from the study population. A clinicopathological association with AKI was observed. Adverse outcomes and the need for renal biopsy were recorded in 3 weeks followed up to 6 months.

Results:

A single-center study recorded that the incidence of AKI was 8.6% with a mean age of 34 ± 16 years. The cause of AKI due to medical reasons was maximum (70.8%), followed by obstetric (21.3%) and surgery (7.7%). The AKI mortality rate was 16% (P < 0.05). Renal biopsy in 34 cases showed that acute tubular necrosis was higher (38%), followed by acute cortical necrosis (23%). The spectrum of AKI was very diverse. In the 6-month follow-up, the adverse outcome was observed in 27.2% of patients, where the mortality rate was 16.5% and 10.7% of patients progressed to CKD.

Conclusion:

The spectrum of AKI was diverse among the population, and most of the etiologies are preventable. This alarms the need for better preventive strategies with a better referral system. The obstetric population with AKI, which majorly leads to either mortality or progression to CKD, is the section that seeks more attention.

Introduction

Acute kidney injury (AKI) is a major health concern worldwide, and the International Society of Nephrology has aimed to reduce the mortality associated with AKI to zero by 2025. Thus, the knowledge of AKI incidences and risk factors is crucial for early detection and treatment. A significant difference in the AKI incidence exists in developed and developing countries because of underreporting.[1] As per KDIGO guidelines, AKI syndrome is characterized by a rapid decline in the glomerular filtration rate (GFR) and retention of nitrogenous waste products such as blood urea nitrogen and creatinine (Cr). The data on AKI etiology and clinical outcome are limited in the Indian population, especially from eastern India. AKI is majorly associated with a high rate of comorbidity, mortality, and consumption of healthcare resources in hospitalized patients. Nephrological care in India has impressive advancements over 2 decades, but despite improvements in diagnosis and prevention, community-acquired AKI (CAAKI) remains a major reason for hospitalization in India.[2,3,4,5,6]

Most common factors such as frequent infection, obstetric complications, poor hygiene, low socioeconomic status, overuse of the drug, infections due to malaria, and leptospirosis contribute to the varied etiology of CAAKI in the younger age of the Indian population.[7,8,9,10,11,12,13] The incidence of acute cortical necrosis has shown a reduction, whereas the incidence of drug-induced, surgical, and sepsis-related AKI has been seen to be increased.[12,13,14,15,16] These changes direct the need for frequent epidemiological studies to devise preventive and therapeutic strategies. Thus, the present study evaluated the etiological spectrum of AKI and risk factors associated with AKI. Further, the clinicopathological association and the prognostics related to adverse outcomes were also evaluated.

Materials and Methods

A hospital-based prospective study was conducted on 103 AKI patients admitted to the Nephrology department over a year with ethical approval (No. Inst/IEC/252) for the AKI spectrum and AKI-associated adverse outcomes. As per inclusion criteria, all consecutive patients (age >1 year) who met the diagnostic criteria of AKI as per the KDIGO 2012 definition [Table 1] were included during the study period of 1 year. Patients having eGFR <60 ml/min/1.73 m² diagnosed with defined chronic kidney disease (CKD), terminal malignancy, multisystem disease, and hospital-acquired AKI were excluded from the study[Figure 1].

Table 1.

Stages of AKI as per KDIGO guidelines

Stage of AKI	Serum creatinine	Urine output
1	1.5–1.9 times baseline or ≥0.3 mg/dl (≥26.5 mcmol/l) increase	<0.5 ml/kg/h for 6–12 h
2	2.0–2.9 times baseline	<0.5 ml/kg/h for >12 h
3	3.0 times baseline or	<0.3 ml/kg/h for >24 h OR
	An increase in serum creatinine to ≥4.0 mg/dl (≥353.6 mcmol/l)	Anuria for >12 h
	OR Initiation of renal replacement therapy
	OR, In patients <18 years, a decrease in eGFR to <35 ml/min per 1.73 m2

Figure 1.

A Flow chart of the methodology

KDIGO 2012 defines AKI as any of the following

1. An increase in serum creatinine by ≥0.3 mg/dl (26.5 micro mol/l) within 48 hours or

2. An increase in serum creatinine to ≥1.5 times baseline, which is known or presumed to have occurred within the prior 7 days or

3. Urine volume <0.5 ml/kg/h for 6 hours.

AKI commonly precedes or aggravates CKD.[10,11,12,13,14,15,16] A complete follow-up study was conducted prospectively at 3 weeks, 1 month, 3 months, and 6 months. All patients had undergone the standard AKI treatment after taking a detailed history to evaluate the etiology of AKI. The patient’s old records and treatment history were recorded. The need for renal replacement therapy was based on the patient’s symptomatology and the discretion of the unit’s consultant Nephrology. Renal biopsy was conducted if the patient failed to show the improvement in renal parameters and clinically even after 3 weeks of suspected renal injury. Patients were followed up to 6 months at the abovementioned intervals to know their natural history.

Primary outcome was measured for

1. Complete Recovery: as evidenced by serum creatinine, attainment of baseline eGFR, normalization of urinary parameters, and absence of significant protinuria or imaging abnormalities.

2. Progression to CKD: as defined by CKD KDIGO 2012, that is, eGFR <60 ml/min/1.73 m² of BSA or renal abnormalities as evidenced by biochemical, urine, histopathology, or imaging studies.

3. Dialysis-Dependent CKD

4. Mortality.

Secondary outcomes were measured for the need of renal replacement therapy and renal biopsy.

A descriptive analysis was performed by using IBM SPSS Statistics for Windows version 20.0 (IBM Corp., Armonk, NY, USA). Mean and standard deviation data were presented for continuous data, and percentage data were for categorical data. The significance of variance level (P-value <0.05) was detected at a 95% confidence interval.

Results

A total of 1326 patients were admitted to the nephrology unit, out of which 115 (8.6%) patients were diagnosed with AKI, and 103 patients were included in the study with consent. The prevalence of AKI in the present study was found to be 8.6%. The mean age of the patients was 34 ± 16 years. Among the AKI patients, 51% patients were male and 48.5% were females. The mean duration of hospital stay among the AKI patients was 16.7 ± 10.4 days. Out of 103 AKI patients, 73 patients (70.8%) had AKI due to medical causes, 22 (21.3%) from obstetric, and 8 (7.7%) from surgery [Table 2].

Table 2.

Clinicodemographic features of the AKI

Demographic feature	Details
Age in years (Mean±SD)	34±16
Gender distribution (%)
Male	51
Female	48.5
Duration of hospital stay in days (Mean±SD)	16.7±10.4
Cause of AKI
Medical AKI (%)	70.8
Surgical AKI (%)	7.7
Obstretic AKI (%)	21.3
Type of AKI
Prerenal (%)	10.6
Intrinsic renal (%)	85.40
Postrenal (%)	5.8

The etiology of AKI was diverse, which included medical causes like cases of envenomation due to snake bite, wasp bite, leptospirosis, AIN (acute interstitial nephritis), UTI, sepsis secondary to UTI, pneumonia, acute gastroenteritis, post-blood transfusion reaction AKI, poisoning like Paraquat, zinc phosphide, D-HUS/TTP, postsurgical sepsis and nephrolithiasis; obstetric causes like puerperal sepsis (including post-LUCS) and APH (antepartum hemorrhage); and postsurgery causes like postpartum TMA (thrombotic microangiopathy), septic abortion, and PPH (postpartum hemorrhage) [Figures 2 and 3]. In the pediatric cohort, the AKI patients were diagnosed in 15 cases with varied etiology [Figure 4].

Figure 2.

AKI spectrum in adult patients

Figure 3.

AKI spectrum in pediatric patients (n = 15). PIGN: postinfectious glomerulonephritis, TTP: Thrombotic thrombocytopenia purpura, D + HUS: Diarrhea-associated hemolytic uremic syndrome DCM: Dilated cardiomyopathy, AIN: Allergic interstitial nephritis

Figure 4.

Clinical outcome of AKI through renal biopsy in 34 cases. ATN: Acute tubular necrosis, PIGN: Postinfectious glomerulo nephritis, ACN: Acute cortical necrosis, AIN: Acute interstitial nephritis, TMA: Thrombotic microangiopathy

Among the AKI patients, 67.90% required RRT (renal replacement therapy) and infections were associated with 58% of AKI episodes. Nephrotoxic drugs contributed to 13.6% of AKI patients. Drugs that contributed to AKI were aminoglycosides in 4 cases, ACE inhibitors, NSAIDs, and antibiotics causing suspected AKI in 12 cases. The mortality in the whole year was 103 (8.82%). The mortality among those with AKI was 14.8% (17) versus 7.76% among those without AKI, and it was found to be significant (P < 0.05).

Renal biopsy was done in 34 AKI patients [Figure 4]. The most common biopsy diagnosis was ATN (acute tubular necrosis), which was found in 13 cases (38%), followed by ACN (acute cortical necrosis), accounting for 8 cases (23%). ACN was mainly associated with postpartum TMA as observed in 4 cases, post-LUCS sepsis (1 case), severe PPH with sepsis (2 cases), and ante-partial hemorrhage (1 case). In the present study, the obstetric cases accounted for 100% of ACN in biopsy-proven cases. Thrombotic microangiopathy (TMA) was a biopsy diagnosis as observed in 6 cases (18%). Acute interstitial nephritis was found in 4 cases, and glomerulonephritis, mainly postinfectious glomerulonephritis, was found in 3 cases [Figure 4].

Clinical outcome revealed that 87.5% CKD patients were recovered in surgery cases [Figure 5]. AKI-associated mortality was observed in the total study population, where 16% (17/103) of mortality was associated with AKI. Out of 17 death cases, 6 deaths were caused due to snake bite [Figure 6]. Rest all are due to different causes.

Figure 5.

Clinical outcome (recovered, CKD progression, and mortality) at the end of 6 months follow-up in all AKI groups

Figure 6.

The AKI etiologies associated with mortality at the end of 6 months follow-up. DCM: Dilated cardiomyopathy, ATN: Acute tubular necrosis, TTP: Thrombotic thrombocytopenic purpura, HTN: Hypertension, ACS: Acute coronary syndrome, IWMI: Inferior wall myocardial infarction, PPH: Postpartum hemorrhage, LUCS: Lower uterine cesarean section

Factors that showed a significant association with mortality in univariate analysis are oliguria, sepsis, hypotension at presentation, thrombocytopenia, encephalopathy, more than one organ (except) kidney failure, and requirement of renal replacement therapy at presentation. Factors that showed significant association with progression to CKD in univariate analysis were AKI due to obstetric causes, need for renal biopsy, that is nonrecovering renal failure after 3 weeks, abnormal serum creatinine, and 24 hours urine protein at 1 month and 3 months. Further, the mortality in AKI patients in the presence of other organ dysfunction was 64.7% versus 35.3% in the absence of it.

Discussion

AKI is recognized as the most commonly encountered community-acquired renal emergency in tropical countries.[17,18] There are areas with a high prevalence of community-acquired AKI as a result of infection or ingestion of toxins in different parts of the tropics. The major population of AKI patients in developing tropical countries is younger (mean age 37–47 years) than that reported in developed temperate countries (mean age 68 years).[17,18,19,20] The mean age of patients in our study was 34 years, found to be similar to that of other developing countries.

Males and females (53 male patients and 50 female patients) are almost equally affected. Most patients with AKI in developing tropical countries do not have pre-existing comorbidities, such as hypertension, diabetes, or CKD, which are characteristically found in patients with AKI in the hospitals of temperate countries. The majority of patients in our AKI cohort were nondiabetic (only 4.8% were diabetic) and had no history of hypertension (only 6.7% were hypertensive). Advancements in health care and socioeconomic development have eliminated pregnancy-related AKI in developed countries.[21] The incidence of obstetric AKI shows a bimodal distribution; the first peak is accounted for by hyperemesis gravidarum or septic abortion in women late in their first trimester of pregnancy, whereas preeclampsia, eclampsia, placental abruption, postpartum hemorrhage, and puerperal sepsis in women in their third trimester account for the second peak.

The comparative frequencies of AKI in this study were found to be 73 patients (70.8%) with medical causes, 22 (21.3%) with obstetric causes, and 8 (7.7%) with surgical causes of AKI. The present study had more obstetric AKI cases as compared to surgical AKI cases. Moreover, if we analyze the spectrum of obstetric AKI, we find a declining trend in first-trimester obstetric AKI like AKI induced by septic abortion. Puerperal sepsis is the leading cause, followed by postpartum TMA, APH, and PPH. TMA is still a not-so-uncommon disorder that has a very poor outcome, and it is not as rare an entity as reported in other parts of India.[22]

Infections remain the major culprit in most cases of AKI, with high mortality rates. In our study, infection was associated with 58%. When we categorize the AKI by type, prerenal AKI contributed in 10.60%, intrinsic renal causes predominated in 85.40%, and postrenal only contributed in 5.8% of cases. The most probable explanation for this might be that prerenal AKI is being successfully dealt with in peripheral and secondary centers and only those patients who land up in stage 3 AKI are being referred to our center. Drugs have been contributory causes associated in 13.4% of cases which are prevalent in the community drugs that contributed to AKI with aminoglycosides (in 4 cases), ACE inhibitors, NSAIDs, and antibiotics (causing suspected AIN in 12 cases). This figure is different from two hospital-based AKI studies in which NSAIDS and rifampicin[22] are most common causes. In another study from SGPGI of hospital-acquired AKI, NSAIDs, Amphotericin B, aminoglycosides, Cisplatin 2, and vancomycin were implicated.[22] Hence, it can be seen that the causes of drug-induced community-acquired AKI are different from hospital-acquired AKI. In this study, the mortality caused in 1 year was 103 (8.82%). The mortality among those with AKI was 14.8% versus 7.76% among those without AKI, and it is statistically significant. This is comparable to other studies in India, where the mortality varies between 10% and 27%.[22]

In those patients who underwent renal biopsy, 34 cases showed ATN to be the predominant cause, followed by ACN at 8 cases (25% of all biopsies), TMA at 6 cases (19.3%), and AIN and postinfectious glomerulonephritis. This finding is similar to a study by Prakash et al., whose study showed postpartum AKI incidence to be around 3.59% and ACN at 18%,[22] which is in contrast to the finding in previous studies which stated a decline in ACN due to obstetric causes.[14] In our study, the predominant cause of ACN is obstetric AKI-pregnancy-related TMA (4 cases), post-LUCS sepsis (1 case), severe PPH with sepsis (2 cases), and ante-partial hemorrhage (1 case).

In six 6-month follow-ups, a total of 28 (27.2%) patients had adverse outcomes; that is 17 (16.5%) patients died mostly within the first month and 11 (10.7%) patients progressed to CKD. This is comparable to other studies which show mortality of 26% in CAAKI[8] and 18% in the HAAKI.[22] The mortality and CKD progression are significant in these young AKI patients (mean age 34), most of whom do not have many pre-existing comorbidities like pre-existing CKD, diabetes, and hypertension. The strength of the study was its prospective design and close follow-up till outcome analysis; this was not meant to be a prevalence study. The main weakness of the study was it was a single-center study done in a Government hospital, and most of the study participants belonged to rural backgrounds with middle to low economic status. The referred case had a more advanced stage of AKI and a more adverse outcome. This study points to the need for large state and central registries and multicenter studies to assess the prevalence of AKI in the community and its impact on health resources.

Conclusion

AKI not only is a major cause of mortality but also contributes to morbidity in terms of increasing CKD and dialysis burden on the health care system. There are areas with a high prevalence of community-acquired AKI as a result of infection or ingestion of toxins in different parts of the tropics. The spectrum of AKI varies among the population, the affected population is rather young, and most of the etiologies are preventable and alarm a need for better preventive strategies better referral system. In our study, we noted that obstetric AKI patients are subjected to adverse outcomes. Puerperal sepsis is the leading cause of AKI, followed by postpartum TMA, APH, and PPH.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.