Is hyperfiltration associated with the future risk of developing diabetic nephropathy? A meta-analysis

Abstract

Aims/hypothesis Glomerular hyperfiltration is a wellestablished phenomenon occurring early in some patients with type 1 diabetes. However, there is no consistent answer regarding whether hyperfiltration predicts later development of nephropathy. We performed a systematic review and meta-analysis of observational studies that compared the risk of developing diabetic nephropathy in patients with and without glomerular hyperfiltration and also explored the impact of baseline GFR. Methods A systematic review and meta-analysis was carried out. Cohort studies in type 1 diabetic participants were included if they contained data on the development of incipient or overt nephropathy with baseline measurement of GFR and presence or absence of hyperfiltration. Results We included ten cohort studies following 780 patients. After a study median follow-up of 11.2 years, 130 patients had developed nephropathy. Using a random effects model, the pooled odds of progression to a minimum of microalbuminuria in patients with hyperfiltration was 2.71 (95% CI 1.20-6.11) times that of patients with normofiltration. There was moderate heterogeneity (heterogeneity test p=0.05, measure of degree of inconsistency= 48%) and some evidence of funnel plot asymmetry, possibly due to publication bias. The pooled weighted mean difference in baseline GFR was 13.8 ml min −1 1.73 m −2 (95% CI 5.0-22.7) greater in the group progressing to nephropathy than in those not progressing (heterogeneity test p<0.01). Conclusions/interpretation In published studies, individuals with glomerular hyperfiltration were at increased risk of progression to diabetic nephropathy using study level data. Further larger studies are required to explore this relationship and the role of potential confounding variables.

The clinical significance of hyperfiltration in diabetes

“…There are several possible explanations for the divergent results reported in the meta-analysis [7] compared with those found in the Joslin clinic study [8]. Apart from the differences in mean HbA 1c levels mentioned above, it is possible that differences in the definition of progression of albuminuria may have influenced the results ( Table 2).…”

“…Three of these four studies [3,11,16] reported a significant odds ratio for the association between baseline hyperfiltration and subsequent progression to at least microalbuminuria [7]. By contrast none of the remaining six studies [2,4,9,10,15,72] in the meta-analysis that used the conventional definition of microalbuminuria demonstrated a significant odds ratio.…”

“…The first was a study-level metaanalysis of ten cohort studies of 780 normoalbuminuric patients with a mean follow-up of 11.2 years [7]. The pooled odds of progression were significantly higher in patients with hyperfiltration at baseline.…”

“…However, it may not exclude the b Proportion of studies with significant OR (95% CI >1.0) for association between hyperfiltration and progression to at least microalbuminuria [7] c This is the correct reference for the data shown in the meta-analysis (another study [62] by Mogensen was incorrectly cited in the meta-analysis) possibility of hyperfiltration preceding the diagnosis of type 2 diabetes, since the onset of type 2 diabetes may occur up to 7 years prior to diagnosis [77]. Several additional aspects need to be considered when interpreting rates of change of GFR (Fig.…”

“…It does this with special emphasis on longitudinal studies of progression of AER and rates of decline of GFR. In particular, it examines the evidence linking hyperfiltration to the onset of microalbuminuria and seeks to rationalise apparently divergent results obtained in several studies [7,8]. Initial hyperfiltration has also been associated with an increased rate of decline of GFR in some studies, and the onset and duration of this decline are also reviewed [9,10].…”