scholarly journals Long-term prospective observation suggests that glomerular hyperfiltration is associated with rapid decline in renal filtration function: A multiethnic study

2018 ◽  
Vol 15 (5) ◽  
pp. 417-423 ◽  
Author(s):  
Serena Low ◽  
Xiao Zhang ◽  
Jiexun Wang ◽  
Lee Ying Yeoh ◽  
Yan Lun Liu ◽  
...  

Aim: Glomerular hyperfiltration usually occurs early in development of kidney complications in diabetes. To understand hyperfiltration as a marker of renal disease progression in type 2 diabetes mellitus, we aimed to examine association between glomerular hyperfiltration (estimated glomerular filtration rate ⩾ 120 mL/min/1.73 m2) and rapid renal decline (annual estimated glomerular filtration rate loss ⩾ 3 mL/min/1.73 m2). Methods: This was a prospective cohort comprising 1014 patients with type 2 diabetes mellitus attending a Diabetes Centre of a regional hospital in 2002–2014. A separate prospective cohort, comprising 491 patients who attended Diabetes Centre or primary-care polyclinics, was used for validation. We performed binary mediation analysis to examine role of hyperfiltration on relationship between baseline haemoglobin A1c and rapid renal decline. Results: Among patients in discovery cohort, 5.2% had baseline hyperfiltration. Over mean follow-up of 6 years, 22.9% had rapid glomerular filtration rate decline. Baseline hyperfiltration was significantly associated with greater odds of rapid renal decline after adjusting for demographics, diabetes duration and clinical covariates (odds ratio: 2.57; 95% confidence interval: 1.21–5.46; p = 0.014). Similar finding was found in validation cohort (odds ratio: 2.98; 95% confidence interval: 1.06–8.42; p = 0.034). Hyperfiltration significantly accounted for 35.3% of association between increasing baseline haemoglobin A1c and rapid renal decline. Conclusion: Glomerular hyperfiltration is an independent risk factor of rapid renal decline. It mediates the association between increasing haemoglobin A1c and rapid renal decline.

Stroke ◽  
2021 ◽  
Author(s):  
Zien Zhou ◽  
Meg J. Jardine ◽  
Qiang Li ◽  
Brendon L. Neuen ◽  
Christopher P. Cannon ◽  
...  

Background and Purpose: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. Methods: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-analysis. Results: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55–1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61–1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19–1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20–1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53–1.10]; n=115). The overall effects in the 4 CVOTs combined were: total stroke (HR pooled , 0.96 [95% CI, 0.82–1.12]), ischemic stroke (HR pooled , 1.01 [95% CI, 0.89–1.14]), hemorrhagic stroke (HR pooled , 0.50 [95% CI, 0.30–0.83]), undetermined stroke (HR pooled , 0.86 [95% CI, 0.49–1.51]), and AF/AFL (HR pooled , 0.81 [95% CI, 0.71–0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate ( P =0.01), with protection in the lowest estimated glomerular filtration rate (<45 mL/min/1.73 m 2 ]) subgroup (HR pooled , 0.50 [95% CI, 0.31–0.79]). Conclusions: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02065791.


Author(s):  
Tadarro L. Richardson ◽  
Amber J. Hackstadt ◽  
Adriana M. Hung ◽  
Robert A. Greevy ◽  
Carlos G. Grijalva ◽  
...  

Background Metformin and sulfonylurea are commonly prescribed oral medications for type 2 diabetes mellitus. The association of metformin and sulfonylureas on heart failure outcomes in patients with reduced estimated glomerular filtration rate remains poorly understood. Methods and Results This retrospective cohort combined data from National Veterans Health Administration, Medicare, Medicaid, and the National Death Index. New users of metformin or sulfonylurea who reached an estimated glomerular filtration rate of 60 mL/min per 1.73 m 2 or serum creatinine of 1.5 mg/dL and continued metformin or sulfonylurea were included. The primary outcome was hospitalization for heart failure. Echocardiogram reports were obtained to determine each patient's ejection fraction (EF) (reduced EF <40%; midrange EF 40%–49%; ≥50%). The primary analysis estimated the cause‐specific hazard ratios for metformin versus sulfonylurea and estimated the cumulative incidence functions for heart failure hospitalization and competing events. The weighted cohort included 24 685 metformin users and 24 805 sulfonylurea users with reduced kidney function (median age 70 years, estimated glomerular filtration rate 55.8 mL/min per 1.73 m 2 ). The prevalence of underlying heart failure (12.1%) and cardiovascular disease (31.7%) was similar between groups. There were 16.9 (95% CI, 15.8–18.1) versus 20.7 (95% CI, 19.5–22.0) heart failure hospitalizations per 1000 person‐years for metformin and sulfonylurea users, respectively, yielding a cause‐specific hazard of 0.85 (95% CI, 0.78–0.93). Among heart failure hospitalizations, 44.5% did not have echocardiogram information available; 29.3% were categorized as reduced EF, 8.9% as midrange EF, and 17.2% as preserved EF. Heart failure hospitalization with reduced EF (hazard ratio, 0.79; 95% CI, 0.67–0.93) and unknown EF (hazard ratio, 0.84; 95% CI 0.74–96) were significantly lower in metformin versus sulfonylurea users. Conclusions Among patients with type 2 diabetes mellitus who developed worsening kidney function, persistent metformin compared with sulfonylurea use was associated with reduced heart failure hospitalization.


2018 ◽  
Vol 127 (07) ◽  
pp. 455-460 ◽  
Author(s):  
Karel Kostev ◽  
Alexander Lucas ◽  
Louis Jacob

Abstract Background The goal of this study was to analyze the frequency of blood pressure (BP) and estimated glomerular filtration rate (eGFR) testing in type 2 diabetes mellitus (T2DM) patients followed in general and diabetological practices in Germany. Methods The study included individuals who had at least two concultations due to T2DM diagnosis (ICD-10: E11) between January and December 2016. Patients were followed in 557 general and diabetological practices. The primary outcome was the frequency of BP and eGFR testing in T2DM patients in 2016. The association between several demographic and clinical variables and the odds of receiving≥2 BP and≥1 eGFR tests in the year 2016 was analyzed using multivariate logistic regression models. Results A total of 43,509 individuals were available for analysis. The mean age of the population was 68.6 years (SD=12.4 years). The mean number of measurements was 2.9 (SD=3.5) for BP and 0.4 (SD=1.1) for eGFR. 52.3% of patients were tested at least twice for BP and 15.3% of them at least once for eGFR in 2016. Older patients, individuals followed in diabetological practices, people receiving antihyperglycemic medications, and those affected by chronic conditions (i. e. hypertension, renal complications, or neuropathy) displayed higher odds of receiving≥2 BP and≥1 eGFR tests, whereas patients with a diabetes duration of>1 year displayed lower odds. Conclusions The frequency of BP and eGFR testing was low in T2DM patients in Germany in 2016. Several demographic and clinical variables were associated with this frequency.


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