Abstract
The study aimed to determine the different status of hypertension and diabetes on the risk of new‐onset chronic kidney disease (CKD) events in Kailuan Study. A total of 21 905 individuals were enrolled in the study. The new‐onset incidents of CKD, hypertension, and diabetes were collected in the follow‐ups. All the individuals were divided into five groups according to baseline and follow‐up hypertension and diabetes status: baseline hypertension (BH), baseline hypertension and incidence of diabetes (BHID), baseline diabetes (BD), baseline diabetes and incidence of hypertension (BDIH), and baseline hypertension and diabetes (BHD). The risk of new‐onset CKD of the five groups was calculated using the Cox regression analysis. In the median follow‐up of 7.05 ± 2.59 years, the prevalence of new‐onset CKD in the group of BH, BHID, BD, BDIH, and BHD were 27.1, 43.79, 25.4, 36.6, and 45.1 per 1000 years, respectively. When adjusted possible confounders, the hazard ratios (HRs) and 95% confidence intervals (CIs) of new‐onset CKD were 1.50 (95% CI: 1.38‐1.63), 1.25(95% CI: 1.07‐1.47), and 1.52 (95% CI: 1.35‐1.7) in the group of BHID, BDIH, and BHD, respectively, as referred to the BH group (P < .001). No obvious difference was observed in the group of BH and BD for the incidence of new‐onset CKD. Sensitivity analysis still showed the similar results among the five groups. The study showed that the effect of simple hypertension or simple diabetes on new‐onset CKD was not significantly different, but the incidence of new‐onset hypertension or diabetes increased the risk of new‐onset CKD. Hypertension and diabetes had a synergistic influence on the risk of new‐onset CKD.
Keywords: chronic kidney disease, diabetes, hypertension
1. INTRODUCTION
Chronic kidney disease (CKD) has become a public common disease over the last two decades. Epidemiologic study showed that the prevalence of CKD worldwide had increased to approximately 275 millions in 2016, with about 86.95% increase compared with that in 1990.1 Meanwhile, CKD played a considerable role for cardiovascular diseases, end‐stage renal disease (ESRD), and all‐cause mortality,2, 3, 4, 5, 6 and the number of deaths or disabled caused by CKD also increased, seen from the Global Burden of Disease Study that CKD was the 11th death reason globally, which was an absolute shift compared with the 18th death cause in 1990.7 Chronic kidney disease had become an important public health problem globally.
Diabetes mellitus and hypertension had been recognized to be the two leading drivers of CKD,5 which was reported to contribute 50.62% and 23.26% to CKD worldwide, respectively.1 Previous studies showed that for diabetic patients the prevalence of CKD was 19%‐66%,8, 9 and the prevalence of CKD was about 30%‐51% in hypertensive patients.9 It was recognized that hypertension and diabetes were both related to a high prevalence of CKD, but there was a lacking of information how hypertension interacted with hyperglycemia in the progress of CKD. A latest animal study indicated that diabetes mellitus and hypertension had a synergistic effect for kidney dysfunction and injury,10 but there was still limited clinical studies to support the relationship.
In China, previous studies showed that the prevalence of hypertension and diabetes were 44.7%11 and 10.9%,12 respectively, and the prevalence of CKD was 10.8%, among whom 42.9% had diabetes and 61% had hypertension.13 However, up to now, the effect of different status of hypertension and diabetes on new‐onset CKD is rarely known. Therefore, our study focused on investigating the inner relationship between hypertension and diabetes status and the risk of new‐onset CKD events prospectively in Kailuan Study in northern China.
2. MATERIALS AND METHODS
2.1. Study population
All the participants were from Kailuan Study, which had been described previously.14 Kailuan Study was registered on August 24, 2011, and the registration number was ChiCTR‐TNRC‐11001489. Briefly, it was a prospective and community‐based cohort study in northern China and all the baseline characteristics of the participants were recorded through the eleven community hospitals of Kailuan Community from June 2006 to October 2007. We included the individuals who met the following criteria: (a) were aged ≥18 years; (b) were diagnosed with hypertension or diabetes in Kailuan Community Hospitals before; (c) wrote informed consent; and (d) had health physical examination biennially. We excluded 7 837 cases lacking data of blood pressure or fast blood glucose at any health examinations and 129 cases lacking CKD data in the follow‐ups. We also excluded 16 066 participants who had chronic kidney diseases and 2197 participants who were diagnosed cancer or had cardio‐cerebrovascular diseases at baseline. Ultimately, a total of 21 905 individuals with hypertension or diabetes were included in the study. The follow‐up was carried out every 2 years, and the evaluations included standardized questionnaires, physical examination, laboratory parameters, and recording of hypertension and diabetes status and new‐onset kidney diseases. The study was approved by the ethics committees of Kailuan General Hospital.
2.2. Questionnaire assessments and laboratory assessments
Information of the participants about demographic and socioeconomic details was obtained face to face by the standardized questionnaire, including age, sex, income level, physical activity, smoking status, alcohol consumption, and the medicine use condition of antihypertensive drugs or hypoglycemic drugs. Income level (RMB/month) was divided into three groups: <600, 600‐1000, and >1000. Physical activity (≥20 minutes each time) was evaluated based on the frequency and was classified as “never,” “sometimes,” and “frequent.” Both smoking status and alcohol consumption were classified as “never,” “past,” and “current” according to self‐report. The use of antihypertensive drugs and hypoglycemic drugs were also collected by self‐report.
For all the participants, blood samples were collected in the morning from the median cubital vein after fasting overnight and were reserved in the vacuum tubes containing ethylenediaminetetraacetic acid (EDTA). The level of fasting blood glucose (FBG), total cholesterol (TG), high‐density lipoprotein cholesterol (HDL‐C), and low‐density lipoprotein cholesterol (LDL‐C) were detected by the autoanalyzer (Hitachi 747; Hitachi). Height and weight were measured by the training doctors in Kailuan Community Hospital. Body mass index (BMI) was calculated as weight (kg)/height2 (m2). Blood pressure was measured at the participant's right upper arm by professional doctors using a calibrated mercury sphygmomanometer with appropriate cuff circumference after at least 5 minutes of rest in the sitting position. We made at least two measurements of blood pressure for more than two office visits, and the mean measurement was calculated for the analysis. Hypertension was defined according to the 7th edition report of the US Joint National Committee on Prevention, Detection, Evaluation and Treatment of Hypertension15: SBP (systolic blood pressure) ≥140 mm Hg and/or DBP (diastolic blood pressure) ≥90 mm Hg. And incidence of hypertension was defined as the occurrence of hypertension during the follow‐ups according to the JNC7 Guideline in Kailuan Community Hospitals. Similarly, diabetes mellitus was defined as fasting blood glucose level ≥7.0 mmol/L for at least two times, or using of hypoglycemic drugs or insulin, and incidence of diabetes was defined as the occurrence of diabetes during anytime in the follow‐ups. Based on baseline and follow‐up status of the hypertension and diabetes, all the participants were divided into five groups: baseline hypertension (BH), baseline hypertension and incidence of diabetes (BHID), baseline diabetes (BD), baseline diabetes and incidence of hypertension (BDIH), and baseline hypertension and diabetes (BHD).
2.3. New‐onset chronic kidney diseases
The estimated glomerular filtration rate (eGFR) was calculated with the use of Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) formula16: for males, eGFR = 141 × (Scr/0.9)−0.411 × (0.993)age as serum creatinine (Scr) ≤80 mmol/L and eGFR = 141 × (Scr/0.9)−1.209 × (0.993)age as serum creatinine >80 mmol/L; for females, eGFR = 144 × (Scr/0.7)−0.329 × (0.993)age as serum creatinine ≤62 mmol/L and eGFR = 144 × (Scr/0.7)−1.209 × (0.993)age as serum creatinine >62 mmol/L. New‐onset chronic kidney disease was defined as the occurrence of eGFR <60 mL/min/1.73 m2 in the follow‐ups.
2.4. Follow‐up
The follow‐up was carried out during 2008‐2009, 2010‐2011, and 2012‐2013, and during the follow‐up, the incidence of hypertension or diabetes was recorded, as well as the new‐onset CKD.
2.5. Statistical analysis
Statistical analysis was performed with the use of SAS 9.3 (SAS Institute). Continuous variables were exhibited as means ± standard deviation (SD). Categorical variables were presented as frequencies and percentages. Student's t test or analysis of variance (ANOVA) was applied for comparison of normally distributed parameters. The chi‐square test was performed for the comparison of categorical variables. The incidence of CKD per 1000 years was calculated using the Kaplan‐Meier analysis. Multivariate Cox regression was applied to evaluate the effect of hypertension and diabetes status on the risk of new‐onset CKD. To avoid the effects of the underlying CKD at baseline to the result, we used sensitivity analysis to evaluate the effect of different hypertension and diabetes status on the risk of new‐onset CKD again by excluding participants with new occurrence of eGFR <60 mL/min/1.73 m2 (new‐onset CKD) in the 2008‐2009 follow‐up. More sensitivity analysis excluding participants with new‐onset hypertension or new‐onset diabetes in 2008‐2009 were also made to eliminate the effect of potential hypertension or diabetes to the results. P‐values <.05 was considered statistically significant.
3. RESULTS
A total of 21 905 individuals with hypertension or diabetes were included in the study. At baseline, 81.87% (17 933) of the participants were men, 82.86% (18 151) of them had simple hypertension, and 9.91% (2 171) of them had both hypertension and diabetes. The mean blood pressure was 145.1 ± 16.24/92.61 ± 9.44 mm Hg for baseline hypertension participants, and the average fast blood glucose level was 9.26 ± 3.37 mmol/L for participants with baseline diabetes, while for participants with baseline hypertension and diabetes, the mean blood pressure was 148.41 ± 17.25/91.99 ± 10.51 mm Hg and the average fast blood glucose level was 9.01 ± 2.8 mmol/L. There were 27.7% of the patients with diabetes receiving hypoglycemia drugs and 14.8% of the hypertensive participants having antihypertensive drugs at baseline. The blood levels of TC, LDL‐C, and HDL‐C showed significant statistical differences for all the participants (P < .001; Table 1).
Table 1.
The baseline characteristics of the study population according to hypertension and diabetes status
| BH | BHID | BD | BDIH | BHD | P‐trend | ||
|---|---|---|---|---|---|---|---|
| N | 14 702 | 3449 | 517 | 1066 | 2171 | ||
| Age, y | 60.0 ± 10.84 | 61.1 ± 9.85 | 57.5 ± 10.1 | 61.2 ± 9.12 | 62.8 ± 9.39 | <.001 | |
| Man, % | 12 156 (82.7) | 2856 (82.8) | 375 (72.5) | 839 (78.7) | 1707 (78.6) | <.001 | |
| Income level (RMB/month), % | <600 | 4135 (28.1) | 961 (27.9) | 155 (30.0) | 295 (27.7) | 575 (26.5) | <.001 |
| 600‐1000 | 9595 (65.3) | 2231 (64.7) | 315 (60.9) | 658 (61.7) | 1411 (65.0) | ||
| >1000 | 695 (4.7) | 159 (4.6) | 39 (7.5) | 91 (8.5) | 136 (6.3) | ||
| Missing data | 277 (1.9) | 98 (2.8) | 8 (1.6) | 22 (2.1) | 49 (2.3) | ||
| Physical activity (each time more than 20 min), % | Never | 1136 (7.7) | 252 (7.3) | 41 (7.9) | 61 (5.7) | 137 (6.3) | <.001 |
| <4 times/week | 10 864 (73.9) | 2529 (73.3) | 379 (73.3) | 794 (74.5) | 1539 (70.9) | ||
| ≥4 times/week | 2407 (16.4) | 567 (16.4) | 90 (17.4) | 189 (17.7) | 444 (20.5) | ||
| Missing data | 295 (2.0) | 101 (2.9) | 7 (1.4) | 22 (2.1) | 51 (2.4) | ||
| Smoking status, % | Never | 8847 (60.2) | 2097 (60.8) | 319 (61.7) | 625 (58.6) | 1320 (60.8) | <.001 |
| Past smoker | 764 (5.2) | 172 (5.0) | 22 (4.3) | 58 (5.4) | 139 (6.4) | ||
| Current smoker | 4805 (32.7) | 1085 (31.5) | 169 (32.7) | 363 (34.1) | 664 (30.6) | ||
| Missing data | 286 (2.0) | 95 (2.8) | 7 (1.4) | 20 (1.9) | 48 (2.2) | ||
| Alcohol consumption, % | Never | 8560 (58.2) | 2017 (58.5) | 313 (60.5) | 631 (59.2) | 1325 (61.0) | <.001 |
| Past drinker | 418 (2.8) | 101 (2.9) | 16 (3.1) | 51 (4.8) | 97 (4.5) | ||
| Current drinker | 5449 (37.1) | 1237 (35.9) | 180 (34.8) | 364 (34.2) | 701 (32.3) | ||
| Missing data | 275 (1.9) | 94 (2.7) | 8 (1.6) | 20 (1.9) | 48 (2.2) | ||
| SBP, mm Hg | 145.1 ± 16.24 | 148.0 ± 16.88 | 115.8 ± 10.67 | 122.4 ± 9.22 | 148.4 ± 17.25 | <.001 | |
| DBP, mm Hg | 92.6 ± 9.44 | 93.7 ± 10.21 | 75.5 ± 7.02 | 78.4 ± 5.62 | 92.0 ± 10.51 | <.001 | |
| FBG, mmol/L | 5.03 ± 0.66 | 5.57 ± 0.76 | 9.26 ± 3.37 | 9.21 ± 2.84 | 9.01 ± 2.8 | <.001 | |
| eGFR, mL/min/1.73 m2 | 75.81 ± 20.18 | 74.19 ± 19.93 | 79.61 ± 20.87 | 79.48 ± 20.19 | 73.05 ± 20.14 | <.001 | |
| LDL‐C, mmol/L | 2.41 ± 0.94 | 2.43 ± 0.95 | 2.42 ± 0.89 | 2.41 ± 0.88 | 2.48 ± 1.0 | <.001 | |
| HDL‐C, mmol/L | 1.58 ± 0.4 | 1.58 ± 0.42 | 1.51 ± 0.37 | 1.55 ± 0.43 | 1.56 ± 0.41 | <.001 | |
| TC, mmol/L | 4.98 ± 1.2 | 5.09 ± 1.24 | 5.06 ± 1.18 | 5.21 ± 1.21 | 5.23 ± 1.31 | <.001 | |
| Body mass index (BMI, kg/m2) | 25.8 ± 3.34 | 27.0 ± 3.44 | 24.8 ± 3.22 | 25.8 ± 3.16 | 26.8 ± 3.44 | <.001 | |
| Use of antihypertensive drugs, % | 1955 (14.3) | 549 (17.4) | 0 (0) | 0 (0) | 509 (25.8) | <.001 | |
| Use of hypoglycemic drugs, % | 0 (0) | 0 (0) | 131 (34.0) | 344 (42.8) | 566 (35.9) | <.001 |
Abbreviations: BD, baseline diabetes; BDIH, baseline diabetes and incidence of hypertension; BH, baseline hypertension; BHD, baseline hypertension and diabetes; BHID, baseline hypertension and incidence of diabetes; DBP, diastolic blood pressure; FBG, fasting blood glucose; HDL‐C, high‐density lipoprotein cholesterol; LDL‐C, low‐density lipoprotein cholesterol; SBP, systolic blood pressure; TC, total cholesterol.
During the median 7.05 ± 2.59 follow‐up years, a total of 3449 hypertensive individuals had incidence of diabetes and 1066 of the diabetic individuals had incidence of hypertension. In general, the participants in the BHD group had the highest incidence of CKD and participants in the BD group had the lowest incidence of CKD, showing in Table 2 that the prevalence of new‐onset CKD in the group of BH, BHID, BD, BDIH, and BHD were 27.1, 43.79, 25.4, 36.6, and 45.1 per 1000 years, respectively. Female participants had the similar results on the incidence of new‐onset CKD for the five groups, but for males, the lowest incidence of new‐onset CKD was in the BH group and the highest incidence of new‐onset CKD was identified in the BHID group.
Table 2.
The incidence of new‐onset chronic kidney disease among different hypertension and diabetes status
| BH | BHID | BD | BDIH | BHD | Total | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Case/n |
New‐onset CKD (Per 1000 y) |
Case/n |
New‐onset CKD (Per 1000 y) |
Case/n |
New‐onset CKD (Per 1000 y) |
Case/n |
New‐onset CKD (Per 1000 y) |
Case/n |
New‐onset CKD (Per 1000 y) |
Case/n |
New‐onset CKD (Per 1000 y) |
|
| Total | 2873/14702 | 27.1 | 1005/3449 | 43.79 | 95/517 | 25.4 | 269/1066 | 36.6 | 650/2171 | 45.1 | 4892/21905 | 31.68 |
| Male | 2407/12156 | 24.9 | 843/2856 | 39.99 | 68/375 | 26.3 | 220/839 | 29.8 | 532/1707 | 36.25 | 4070/17933 | 28.64 |
| Female | 466/2546 | 27.6 | 162/593 | 44.6 | 27/142 | 25.09 | 49/227 | 38.6 | 118/464 | 47.7 | 822/3972 | 32.38 |
Abbreviations: BD, baseline diabetes; BDIH, baseline diabetes and incidence of hypertension; BH, baseline hypertension; BHD, baseline hypertension and diabetes; BHID, baseline hypertension and incidence of diabetes; CKD, chronic kidney disease.
Multivariate Cox regression evaluated the effect of different hypertension and diabetes status on the risk of new‐onset CKD (Table 3). When adjusted for age, sex, income level, physical activity, smoking status, alcohol consumption, use of antihypertensive drugs, use of hypoglycemic drugs, SBP, DBP, BMI, TC, LDL‐C, HDL‐C and FBG, the hazard ratios (HRs) and 95% confidence intervals (CIs) of new‐onset CKD were 1.50 (95% CI: 1.38‐1.63), 0.93 (95% CI: 0.73‐1.18), 1.25 (95% CI: 1.07‐1.47), and 1.52 (95% CI: 1.35‐1.7) in the group of BHID, BD, BDIH, and BHD, respectively (P < .001), compared with the BH group, demonstrating the incidence of hypertension or diabetes increased the risk of new‐onset CKD, but no statistical difference was found in the BH or BD group on the risk of new‐onset CKD. Similarly, there was the semblable HRs for the risk of new‐onset CKD for men in the five groups. But, the HRs of new‐onset CKD events for women were 1.60(95% CI: 1.30‐1.98), 0.90(95% CI: 0.56‐1.44), 1.06(95% CI: 0.72‐1.55), and 1.37(95% CI: 1.02‐1.83) in the group of BHID, BD, BDIH, and BHD, respectively (P < .001).
Table 3.
The hazard ratios (HRs) and 95% confidence intervals (95% CIs) of new‐onset chronic kidney disease among different hypertension and diabetes status
| Baseline/incidence of hypertension and diabetes status | Total | Male | Female | |
|---|---|---|---|---|
| HR (95% CI) | HR (95% CI) | HR (95% CI) | ||
| Model 1 | BH | Ref | Ref | Ref |
| BHID | 1.57 (1.46‐1.68) | 1.57 (1.45‐1.7) | 1.56 (1.31‐1.87) | |
| BD | 0.94 (0.77‐1.16) | 0.91 (0.72‐1.16) | 1.07 (0.73‐1.58) | |
| BDIH | 1.31 (1.16‐1.49) | 1.35 (1.18‐1.55) | 1.18 (0.88‐1.59) | |
| BHD | 1.60 (1.47‐1.74) | 1.66 (1.51‐1.82) | 1.41 (1.15‐1.73) | |
| P‐trend | <.001 | <.001 | <.001 | |
| Model 2 | BH | Ref | Ref | Ref |
| BHID | 1.59 (1.48‐1.71) | 1.59 (1.47‐1.72) | 1.59 (1.33‐1.9) | |
| BD | 0.93 (0.76‐1.15) | 0.90 (0.71‐1.14) | 0.99 (0.67‐1.47) | |
| BDIH | 1.34 (1.18‐1.51) | 1.37 (1.2‐1.58) | 1.18 (0.88‐1.58) | |
| BHD | 1.65 (1.52‐1.8) | 1.69 (1.54‐1.86) | 1.50 (1.22‐1.84) | |
| P‐trend | <.001 | <.001 | <.001 | |
| Model 3 | BH | Ref | Ref | Ref |
| BHID | 1.50 (1.38‐1.63) | 1.49 (1.36‐1.63) | 1.60 (1.30‐1.98) | |
| BD | 0.93 (0.73‐1.18) | 0.91 (0.69‐1.2) | 0.90 (0.56‐1.44) | |
| BDIH | 1.25 (1.07‐1.47) | 1.29 (1.08‐1.53) | 1.06 (0.72‐1.55) | |
| BHD | 1.52 (1.35‐1.7) | 1.53 (1.35‐1.74) | 1.37 (1.02‐1.83) | |
| P‐trend | <.001 | <.001 | <.001 |
Model 1, single‐factor analysis; Model 2, adjusted for Model 1 and age and sex; Model 3, adjusted for Model 2 and income level (<600 RMB/month, 600‐1000 RMB/month, >1000 RMB/month), physical activity (never, <4 times/week, ≥4 times/week), smoking status (never, past smoker, current smoker), alcohol consumption (never, past drinker, current drinker), use of antihypertensive drugs (no, yes), use of hypoglycemic drugs (no, yes), SBP (mm Hg), DBP (mm Hg), BMI (body mass index, kg/m2), TC (total cholesterol, mmol/L), LDL‐C (low‐density lipoprotein, mmol/L), HDL‐C (high‐density lipoprotein, mmol/L), and FBG (fasting blood glucose, mmol/L).
Abbreviations: BD, baseline diabetes; BDIH, baseline diabetes and incidence of hypertension; BH, baseline hypertension; BHD, baseline hypertension and diabetes; BHID, baseline hypertension and incidence of diabetes.
To exclude the influence of underlying hypertension, diabetes, or CKD at baseline to the results, we made sensitivity analysis by eliminating participants with new‐onset CKD (Model 1), new‐onset hypertension (Model 2), and new‐onset diabetes (Model 3) in 2008‐2009 and the HRs value of new‐onset CKD in the five groups were calculated again (Table 4). Similarly, the BHID and BDIH group still had higher HRs as compared to the BH group when we adjusted new‐onset CKD and new‐onset hypertension in 2008‐2009 and there was no statistical difference between the BH group and BD group for new‐onset CKD.
Table 4.
The sensitivity analysis of hazard ratios (HRs) and 95% confidence intervals (95% CIs) of new‐onset chronic kidney disease among different hypertension and diabetes status
| Baseline/incidence of hypertension and diabetes status | Model 1 | Model 2 | Model 3 | |
|---|---|---|---|---|
| HR (95% CI) | HR (95% CI) | HR (95% CI) | ||
| Full‐adjusted model a | BH | Ref | Ref | Ref |
| BHID | 1.65 (1.45‐1.88) | 1.40 (1.18‐1.67) | 1.48 (1.35‐1.63) | |
| BD | 0.90 (0.62‐1.32) | 1.13 (0.88‐1.46) | 1.04 (0.72‐1.49) | |
| BDIH | 1.43 (1.13‐1.82) | 1.37 (1.07‐1.76) | 1.17 (0.86‐1.57) | |
| BHD | 1.46 (1.21‐1.76) | 1.49 (1.18‐1.88) | 1.45 (1.21‐1.74) | |
| P‐trend | <.001 | <.001 | <.001 |
Model 1 excluded the participants who had new‐onset chronic kidney disease in the 2008‐2009 follow‐up; Model 2 excluded the participants who had new‐onset hypertension in the 2008‐2009 follow‐up; Model 3 excluded the participants who had new‐onset diabetes in the 2008‐2009 follow‐up.
Abbreviations: BD, baseline diabetes; BDIH, baseline diabetes and incidence of hypertension; BH, baseline hypertension; BHD, baseline hypertension and diabetes; BHID, baseline hypertension and incidence of diabetes.
Adjusted for baseline hypertension and diabetes status, age, sex, income level (<600 RMB/month, 600‐1000 RMB/month, >1000 RMB/month), physical activity (never, <4 times/week, ≥4 times/week), smoking status (never, past smoker, current smoker), alcohol consumption (never, past drinker, current drinker), use of antihypertensive drugs (no, yes), use of hypoglycemic drugs (no, yes), SBP (mm Hg), DBP (mm Hg), BMI (body mass index, kg/m2), TC (total cholesterol, mmol/L), LDL‐C (low‐density lipoprotein, mmol/L), HDL‐C (high‐density lipoprotein, mmol/L), and FBG (fasting blood glucose, mmol/L).
4. DISCUSSION
In our prospective study, we found that the incidence of new‐onset hypertension or diabetes increased the risk of new‐onset CKD, but the effect of simple hypertension or simple diabetes on new‐onset CKD was no different. The study indicated that hypertension and diabetes had a synergistic effect on the risk of new‐onset CKD.
Previous studies reported that high blood pressure or hyperglycemia17, 18, 19 was associated with a renal dysfunction or ESRD, respectively. And patients with hypertension and diabetes had higher risk for nephropathy than those with simple hypertension or diabetes.20 Similar findings from a mild type 2 diabetes model, the Goto‐Kakizaki rat, combined with hypertension also reported diabetes and hypertension interacted synergistically in promoting the progress of kidney dysfunction and injury.10 Some clinical studies had suggested that adequate blood pressure control was as important as glycemic control in delaying progression of chronic kidney disease, and hypertension may be a precondition in the progression of diabetic nephropathy. Inconsistent findings showed that for diabetic patients with normal renal function, the achievement of blood pressure control was not related to worse renal dysfunction in the 4‐year follow‐up, which indicated that glycemic control may remain the major target in the process of diabetic nephropathy.21
In our prospective study, we also found the increased new‐onset CKD risk with the incidence of new‐onset hypertension and new‐onset diabetes, while no difference was found on the effect of simple hypertension or simple diabetes on new‐onset CKD, indicating the synergistic effect of hypertension and diabetes on the risk of new‐onset CKD. Meanwhile, our study showed that the incidence of diabetes had higher risk of new‐onset CKD than the incidence of hypertension, suggesting that diabetes status may play a more important role in the progression of kidney diseases. However, we could not determine whether hypertension was required in the progression of diabetic nephropathy. In addition, hypertension and diabetes often coexisted,8, 10, 22, 23, 24 and in our study, nearly 70% of diabetic patients had incidence of hypertension in the follow‐ups, which demonstrated the strong bond of the two diseases. As hypertension and diabetes had a synergistic effect on the risk of new‐onset CKD, good management of both blood pressure and blood glucose was required to prevent the progression of kidney injury.
Some potential mechanisms may explain the synergetic effect of hypertension and diabetes on new‐onset CKD. Firstly, participants with hypertension or diabetes were more likely to complicate with underlying health problems, such as metabolic diseases and obesity, which were also observed in our study, contributing to the progress of nephropathy.24, 25, 26, 27 It was also reported that diabetic patients with hypertension were more likely to have a peripheral arterial resistance21 and the resistant hypertension increased the risk of end‐stage renal diseases by at least 2.6‐fold.28 Moreover, the upregulation of the renin‐angiotensin‐aldosterone system and the sodium transporters for hypertension and diabetes patients could promote to destroy the glomerular structure,29 eventually lead to albuminuria and reduce nephron function.30 Recent studies indicated the reactive oxygen metabolites played an important part in the process of diabetic kidney disease, through the regulation of nuclear factor erythroid 2p45–related factor 2 (Nrf2)31 or endoplasmic reticulum stress,10 but further molecular mechanisms needed to be investigated.
Our study had several strengths. Firstly, it was a large population and a long‐term follow‐up study with many outcome events. Secondly, we excluded the potential influence of underlying hypertension, diabetes, or CKD at baseline to the results. Thirdly, the prospective cohort study design and the long follow‐up period helped to determine the effect of different hypertension and diabetes status on the new‐onset CKD. However, some limitations should be considered. Firstly, the duration of hypertension or diabetes, and detailed information about medication use were not taken into consideration, particularly antihypertensive drugs and hypoglycemic agents, which may affect the statistical power. But some cohort study found that the duration of diabetes and the HbAlc level were not related to the renal outcome in the 4‐year follow‐up for patients with diabetes.21 Secondly, the new‐onset CKD was based on the new occurrence of eGFR <60 mL/min/1.73 m2 in the follow‐ups so participants with acute kidney injury were also included in our study. However, there were only a small part of participants with acute kidney injury. Finally, our study population had more males than females, but it represented the whole population of employees in Kailuan Community, and there were roughly similar results in male than female population, respectively.
5. CONCLUSIONS
In conclusion, the incidence of new‐onset hypertension or diabetes increased the risk of new‐onset CKD. Hypertension and diabetes had a synergetic influence on new‐onset CKD event, while simple hypertension and simple diabetes had no difference on the risk of new‐onset CKD. Good management of blood pressure and blood glucose were both crucial for hypertension or diabetic individuals to prevent CKD. Further researches are required to investigate the mechanism of that synergetic effect, and more clinical trials are required to evaluate the proper blood pressure and glucose level to prevent the development of kidney diseases.
CONFLICT OF INTEREST
The authors have no conflict of interest to declare.
AUTHOR CONTRIBUTIONS
M W. and J‐j L contributed equally to this work. M W. searched the literature, analyzed data, and wrote the manuscript. J‐j L. searched the literature, and collected and analyzed data. Y L., S‐y Y., C W., and M‐x Z. contributed to the discussion. H X. designed the study, contributed to the discussion, and reviewed and edited the manuscript. S‐l W. contributed to discussion and edited the manuscript. H X. and S‐l W. are the guarantor of this work and, as such, have full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors read and approved the final manuscript.
ACKNOWLEDGMENTS
We thank all the staff of Kailuan Community Hospitals for their contributions to this work.
Wang M, Li J, Li Y, et al. The effects of hypertension and diabetes on new‐onset chronic kidney disease: A prospective cohort study. J Clin Hypertens. 2020;22:39–46. 10.1111/jch.13768
Miao Wang and Junjuan Li contributed equally to this work.
Funding information
This work was supported by the National Natural Science Foundation of China (Grant No. 81570383).
Contributor Information
Shouling Wu, Email: drwusl@163.com.
Hao Xue, Email: xuehaoxh301@163.com.
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