Persistent Renal Hypertrophy and Faster Decline of Glomerular Filtration Rate Precede the Development of Microalbuminuria in Type 1 Diabetes

Abstract

Soon after the onset of type 1 diabetes, renal hypertrophy and hyperfiltration become manifest, particularly among patients who will subsequently develop diabetic nephropathy. Whether these early renal dysfunctions are involved in the pathogenesis of diabetic nephropathy is currently unclear. We evaluated, during the same day, kidney volume and glomerular filtration rate (GFR) in 146 patients with type 1 diabetes and normal renal function. All the individuals were then monitored for a mean of 9.5 ؎ 4.4 years for the development of microalbuminuria. Kidney volume and GFR were reevaluated in a subset of 68 patients 4 years after baseline. During follow-up, microalbuminuria developed in 27 of 146 diabetic patients. At baseline, kidney volume (312.8 ؎ 52.6 vs. 281.4 ؎ 46.1 vs. 236.8 ؎ 41.6 ml/1.73 m 2 , P < 0.05) but not GFR was increased in patients predisposed to microalbuminuria. Risk of progression was higher in patients with increased kidney volume (P ‫؍‬ 0.0058). Patients predisposed to microalbuminuria showed a stable increase in kidney volume (P ‫؍‬ 0.003), along with a faster decline of GFR (P ‫؍‬ 0.01). Persistent renal hypertrophy and faster decline of GFR precede the development of microalbuminuria in type 1 diabetes. These findings support the hypothesis that renal hypertrophy precedes hyperfiltration during the development of diabetic nephropathy. Diabetes

The clinical significance of hyperfiltration in diabetes

“…However, baseline AER was not recorded and the retrospective design of these studies made it difficult to compare them with other studies. In the three subsequent studies [10,15,63], final GFR was in the high normal range in participants with or without progression of AER, despite similar study duration. Whether this indicates that the early decline in GFR observed in hyperfiltering patients represents resolution of hyperfiltration or an early stage of progressive decline in GFR to the subnormal range cannot be answered by the available data.…”

“…In a longitudinal study of 146 normoalbuminuric patients with mean duration of type 1 diabetes of 9.5 years, increased kidney volume at baseline, but not hyperfiltration, was a predictor of progression to microalbuminuria in 27 patients [10]. Patients predisposed to microalbuminuria showed a stable increase in kidney volume along with a faster initial decline in GFR.…”

“…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. It is, therefore, possible that differences in the definition of microalbuminuria contributed to the significant relationship between hyperfiltration and progression of AER in the meta-analysis.…”

“…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].…”

Therapeutic Modalities in Diabetic Nephropathy: Standard and Emerging Approaches

“…5,6 Perhaps more worrisome is the realization that some diabetic patients develop DN in the absence of microalbuminuria. 7 In newly diagnosed diabetics, Zerbini et al 8 found that GFR began to decrease prior to the appearance of microalbuminuria. Thus, urinary albumin lacks both sensitivity and specificity to detect early DN.…”