Dataset Information

The Familiality of Rapid Renal Decline in Diabetes.

ABSTRACT: Sustained and rapid loss of glomerular filtration rate (GFR) is the predominant clinical feature of diabetic kidney disease and a requisite for the development of end-stage renal disease. Although GFR trajectories have been studied in several cohorts with diabetes and without diabetes, whether rapid renal decline clusters in families with diabetes has not been examined. To determine this, we estimated GFR (eGFR) from serum creatinine measurements obtained from 15,612 patients with diabetes at the University of Utah Health Sciences Center and established their renal function trajectories. Patients with rapid renal decline (eGFR slope < -5 mL/min/1.73 m²/year) were then mapped to pedigrees using extensive genealogical records from the Utah Population Database to identify high-risk rapid renal decline pedigrees. We identified 2,127 (13.6%) rapid decliners with a median eGFR slope of -8.0 mL/min/1.73 m²/year and 51 high-risk pedigrees (ranging in size from 1,450 to 24,501 members) with excess clustering of rapid renal decline. Familial analysis showed that rapid renal decline aggregates in these families and is associated with its increased risk among first-degree relatives. Further study of these families is necessary to understand the magnitude of the influence of shared familial factors, including environmental and genetic factors, on rapid renal decline in diabetes.

SUBMITTER: Frodsham SG

PROVIDER: S-EPMC6341306 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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The Familiality of Rapid Renal Decline in Diabetes.

Frodsham Scott G SG Yu Zhe Z Lyons Ann M AM Agarwal Adhish A Pezzolesi Melissa H MH Dong Li L Srinivas Titte R TR Ying Jian J Greene Tom T Raphael Kalani L KL Smith Ken R KR Pezzolesi Marcus G MG

Diabetes 20181113 2

Sustained and rapid loss of glomerular filtration rate (GFR) is the predominant clinical feature of diabetic kidney disease and a requisite for the development of end-stage renal disease. Although GFR trajectories have been studied in several cohorts with diabetes and without diabetes, whether rapid renal decline clusters in families with diabetes has not been examined. To determine this, we estimated GFR (eGFR) from serum creatinine measurements obtained from 15,612 patients with diabetes at th ...[more]

PMID: 30425064

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Project description:Introduction:Diabetic nephropathy remains a highly prevalent microvascular complication in individuals with type 2 diabetes mellitus (T2DM). Hispanic individuals are at increased risk of metabolic and cardiovascular complications compared with non-Hispanic white individuals. We described the long-term kidney outcomes using a culturally based approach to diabetes management in Hispanic patients implemented by the Joslin Diabetes Center's Latino Diabetes Initiative. Methods:Our retrospective study included 594 Hispanic patients evaluated at the Joslin Diabetes Center from July 2002 to July 2015. Demographic and clinical data were collected from the outpatient visits. Results:Uncontrolled high blood pressure (hazard ratio [HR]: 1.72; 95% confidence interval [CI]:1.18-2.51; P = 0.005), overweight (HR: 2.68; 95% CI: 1.13-6.38; P = 0.026), and longstanding T2DM duration (HR: 1.11; 95% CI: 1.08-1.14; P < 0.0001) at baseline were significantly associated with increased risk of chronic kidney disease (CKD). Although poor glycemic control (HR: 1.18; 95% CI: 1.099-1.258; P < 0.0001), systolic blood pressure (SBP) >140 (HR: 1.01; 95% CI: 1.006-1.02; P = 0.0002), and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use (HR: 1.53; 95% CI: 1.03-2.29; P = 0.04) were significantly associated with increased CKD incidence during follow-up. Interestingly, statin use was associated with lower CKD incidence during the follow-up (HR: 0.52; 95% CI: 0.42-0.65; P < 0.0001). The annual rate of renal function decline in our cohort was estimated to be -1.39 ml/min per 1.73 m2. Conclusion:Renal function decline in Latinos is associated with expected but modifiable variables, such as uncontrolled diabetes, uncontrolled hypertension, and being overweight. However, the annual rate of renal function decline in our cohort was estimated to be comparatively higher than previous reports in Hispanic individuals without T2DM, and the general US population with T2DM, but lower than expected for this high-risk group. We highlight the importance of a culturally based patient-centered therapeutic approach to improve long-term outcomes in Hispanic patients at high risk of CKD.

Project description:Diabetes mellitus is associated with increased risk of cognitive impairment. This study examines whether microvascular disease, as measured by albuminuria and decline in estimated GFR (eGFR), is associated with cognitive decline during 3.3 years of follow-up in individuals with diabetes with a normal baseline eGFR (approximately 90 ml/min per 1.73 m(2)).Participants were from the Action to Control Cardiovascular Risk in Diabetes Memory in Diabetes study (N=2977; mean age 62.5 ± 5.8 years; recruitment from August 2003 to December 2005, followed through June 2009), which examined the association of intensive versus standard glucose control on cognitive function. Participants underwent three neuropsychologic tests at baseline, 20 months, and 40 months. Tests included information processing speed, verbal memory, and executive function. Mixed-effects models were used to assess the association of albuminuria and eGFR on the percentage decline in each test.Participants with albuminuria at baseline and follow-up (persistent albuminuria) (-5.8% [95% confidence interval (CI), -7.3 to -4.2]) and participants with albuminuria at follow-up but none at baseline (progressive albuminuria) (-4.1% [95% CI, -5.6 to -2.7]) had greater percentage declines on information processing speed than participants without albuminuria at baseline and at follow-up (no albuminuria) (-2.6% [95% CI, -3.4 to -1.9]) (P=0.001 and P=0.10, respectively). There were borderline percentage changes in the test of verbal memory (4.8% [95% CI, 2.4 to 7.1] and 4.7% [95% CI, 2.5 to 7.0] versus 7.1% [95% CI, 6.0 to 8.3]; P=0.11 and P=0.08, respectively). On logistic regression analysis, persistent albuminuria (odds ratio, 1.37 [95% CI, 1.09 to 1.72]) and progressive albuminuria (odds ratio, 1.25 [95% CI, 1.02 to 1.56]) were associated with a ? 5% decline in information processing speed scores but not with verbal memory or executive function performance. A 1 ml/min per 1.73 m(2) per year eGFR decline had a borderline association with decline in tests of cognitive function.Persistent albuminuria and progressive albuminuria are associated with a decline in cognitive function in relatively young individuals with diabetes with unimpaired eGFR. These findings do not rule out the possibility of other processes causing cognitive decline.

Dataset Information

The Familiality of Rapid Renal Decline in Diabetes.

Publications

The Familiality of Rapid Renal Decline in Diabetes.

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