Hyperfiltration may affect renal function, nephropathy in type 2 diabetes

Hyperfiltration may lead to renal function loss and onset or progression of nephropathy in some patients with type 2 diabetes, a new study has found.

European researchers performed a longitudinal cohort study to examine hyperfiltration (defined as a glomerular filtration rate [GFR] ≥120 mL/min/1.73 m²) and its relation to GFR decreases and nephropathy in patients with type 2 diabetes and normo- or microalbuminuria. Six hundred patients from two randomized trials examining the effect of angiotensin-converting enzyme inhibitors on nephropathy in hypertensive patients with type 2 diabetes and normo- or microalbuminuria (albuminuria <200 µg/min) were included. Predefined study end points were rate of GFR decline over time and time to persistent micro- or macroalbuminuria (≥20 µg/min and <200 µg/min or ≥200 µg/min, respectively). The study results were published online July 6 by Diabetes Care.

Patients were followed for a median of 4.0 years (range, 1.7 to 8.1 years). Ninety study patients (15%) had hyperfiltration at baseline. Of the 47 with persistent hyperfiltration, 11 (23.4%) developed micro- or macroalbuminuria compared with 53 of 502 patients (10.6%) who had ameliorated hyperfiltration (defined as a GFR reduction of 10%) at six months or who never developed hyperfiltration (hazard ratio, 2.16; 95% CI, 1.13 to 4.14). Over the study period, GFR decreased by 3.37 mL/min/1.73 m² per year. Change in GFR from baseline to six months was the best predictor of subsequent slope; a large change during this period indicated a higher likelihood of a slower slope later. Patients with persistent hyperfiltration tended to have faster GFR decline than those with ameliorated hyperfiltration or those who never developed hyperfiltration (4.19 vs. 3.23 mL/min/1.73 m²; P=0.09). Hyperfiltration amelioration did not appear to be related to baseline characteristics or angiotensin-converting enzyme inhibitor treatment but was significantly associated with improved blood pressure and improved metabolic control, amelioration of glucose disposal rate and slower long-term decline of GFR during follow-up.

The authors acknowledged that the post hoc observational nature of the study limited their findings and that their results are hypothesis-generating. However, they concluded that persistent hyperfiltration may be an independent risk factor for faster renal loss and nephropathy in patients with type 2 diabetes and hypertension who have normo- or microalbuminuria, and that ameliorating hyperfiltration may be renoprotective in such patients. “Prospective ad hoc studies are needed to unravel the mechanisms underlying persistent hyperfiltration despite optimized metabolic and [blood pressure] control and to assess whether and to what extent glomerular hyperfiltration can be a specific treatment target for novel interventions aimed to limit renal function loss in this population,” they wrote.