Early Renal Function Decline in Type 2 Diabetes

Centers for Disease Control and Prevention, 4770 Buford Hwy, NE MS-K10, Atlanta, GA 30341-3724, USA.
Clinical Journal of the American Society of Nephrology (Impact Factor: 4.61). 11/2011; 7(1):78-84. DOI: 10.2215/CJN.07610711
Source: PubMed


Early decline in GFR may reflect progressive kidney disease in type 1 diabetes, but its predictive value in type 2 diabetes is uncertain.
In this longitudinal study, GFR was measured serially over approximately 4.0 years in 195 Pima Indians with type 2 diabetes. Renal function decline (RFD) was defined during this initial period by an average GFR loss ≥3.3%/yr, as defined previously in type 1 diabetes. Subsequently, participants were followed for up to 17.8 years to ESRD onset, death, or December 31, 2010, whichever came first.
RFD prevalence during the initial period was 32% in 68 participants with normal baseline albuminuria (albumin/creatinine ratio [ACR] < 30 mg/g), 42% in 88 with microalbuminuria (ACR 30 to <300 mg/g), and 74% in 39 with macroalbuminuria (ACR ≥300 mg/g; P<0.001). The cumulative incidence of ESRD 10 years after the initial period was 41% in those with RFD and 15% in those without (P<0.001); 41 of the 49 ESRD cases (83.7%) occurred in participants who had or developed macroalbuminuria during the initial period. When adjusted for age, sex, diabetes duration, and hemoglobin A1c, the ESRD hazard rate was 4.78 times (95% confidence interval, 2.39-9.58) as high in those with RFD as in those without; further adjustment for albuminuria attenuated this association (hazard ratio, 1.79; 95% confidence interval, 0.82-3.91).
In type 2 diabetes, loss of GFR often occurs before the onset of macroalbuminuria, but a decline predictive of ESRD is strongly dependent on progression to macroalbuminuria.

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    • "m2/yr, and only 2.2 ml/min/1.73 m2/yr in the high risk group, which is lower than other DN trials [9]. "
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    ABSTRACT: Background Diabetic nephropathy is a growing clinical problem, and the cause for >40% of incident ESRD cases. Unfortunately, few modifiable risk factors are known. The objective is to examine if albuminuria and history of diabetic nephropathy (DN) in a sibling are associated with early DN progression or mortality. Methods In this longitudinal study of adults >18 yrs with diabetes monitored for up to 9 yrs (mean 4.6 ± 1.7 yrs), 435 subjects at high risk (DN family history) and 400 at low risk (diabetes >10 yrs, normoalbuminuria, no DN family history) for DN progression were evaluated for rate of eGFR change using the linear mixed effects model and progression to ESRD. All-cause mortality was evaluated by Kaplan-Meier analyses while controlling for baseline covariates in a Cox proportional hazards model. Covariates included baseline eGFR, age, gender, race, diabetes duration, blood pressure, hemoglobin A1c and urine albumin:creatinine ratio. Propensity score matching was used to identify high and low risk group pairs with balanced covariates. Sensitivity analyses were employed to test for residual confounding. Results Mean baseline eGFR was 74 ml/min/1.73 m2 (86% of cohort >60 ml/min/1.73 m2). Thirty high risk and no low risk subjects developed ESRD. eGFR decline was significantly greater in high compared to low risk subjects. After controlling for confounders, change in eGFR remained significantly different between groups, suggesting that DN family history independently regulates GFR progression. Mortality was also significantly greater in high versus low risk subjects, but after controlling for baseline covariates, no significant difference was observed between groups, indicating that factors other than DN family history more strongly affect mortality. Analyses of the matched pairs confirmed change in eGFR and mortality findings. Sensitivity analyses demonstrated that the eGFR results were not due to residual confounding by unmeasured covariates of a moderate effect size in the propensity matching. Conclusions Diabetic subjects with albuminuria and family history of DN are vulnerable for early GFR decline, whereas subjects with diabetes for longer than 10 years, normoalbuminuria and negative family history, experience slower eGFR decline, and are extremely unlikely to require dialysis. Although we would not recommend that patients with low risk characteristics be neglected, scarce resources would be more sensibly devoted to vulnerable patients, such as the high risk cases in our study, and preferably prior to the onset of albuminuria or GFR decline.
    BMC Nephrology 06/2013; 14(1):124. DOI:10.1186/1471-2369-14-124 · 1.69 Impact Factor
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    • "Although a decline in GFR may indicate progressive kidney disease, it is not sufficiently sensitive to be a useful surrogate end point in clinical trials of early diabetic kidney disease. We reported previously that decline in GFR in early diabetic kidney disease did not predict progression to ESRD unless it was accompanied by progression to macroalbuminuria (19). These findings may support superiority of structural over functional outcomes in clinical trials involving patients with early diabetic kidney disease. "
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    Diabetes 04/2013; 62(9). DOI:10.2337/db12-1512 · 8.10 Impact Factor
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    ABSTRACT: Depending on age, duration of diabetes and glycaemic control, 20–40% of patients with type 2 diabetes will incur a moderate or severe deterioration of renal function. This will impact the choice of blood glucose-lowering therapy and require more frequent monitoring of both renal function and glycaemic control. Moderate renal impairment (glomerular filtration rate 30 – < 60 ml/min) requires consideration of dose reduction or treatment cessation for metformin, glucagon-like peptide-1 receptor agonists, some sulphonylureas and some dipeptidyl peptidase-4 inhibitors. At lower rates of glomerular filtration down to about 15 ml/min it may be appropriate to use a meglitinide, pioglitazone or certain sulphonylureas with careful consideration of dose and co-morbidities. Dipeptidyl peptidase-4 inhibitors can be used at reduced dose in patients with very low rates of glomerular filtration, and linagliptin can be used without dose reduction, and has been used in patients on dialysis. Insulin can be used at any stage of renal impairment, but the regimen and the dose must be suitably adjusted and accompanied by adequate monitoring.
    The British Journal of Diabetes & Vascular Disease 09/2012; 12(4):167-171. DOI:10.1177/1474651412458811
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