Glomerular hyperfiltration and increased glomerular filtration surface are associated with renal function decline in normo- and microalbuminuric type 2 diabetes

Abstract

The prevalence of glomerular hyperfiltration in type 2 diabetic patients varies widely. Here we studied whether glomerular hyperfiltration in diabetic nephropathy in type 2 patients is related to renal structural changes and predicts the functional development of diabetic nephropathy. Thirty normo- or microalbuminuric type 2 diabetic patients having a renal biopsy were followed every 6 months for a mean of 6.2 years. The glomerular filtration rate (GFR) at the time of biopsy, determined by iohexol clearance, correlated with filtration surface per glomerulus, but no other quantitative microscopic morphometric parameter. The filtration surface was positively associated with the decrease in GFR during the first year but not associated in subsequent years following the renal biopsy. The GFR showed a statistically significant linear decrease in 9 of the 30 patients; however, slopes of the regression lines were almost zero in 11 patients. The GFR increased and decreased in a parabolic manner in two patients. Seven of the nine patients with a statistically significant decline in renal function did not show any appreciable worsening of albuminuria, while two patients developed persistent proteinuria. Thus, in renal biopsy-proven normo- or microalbuminuric type 2 diabetic patients, glomerular hyperfiltration is closely associated with an increased glomerular filtration surface. An elevated GFR predicts its subsequent decline, which may occur without worsening of albuminuria.

Prediabetes and Risk of Glomerular Hyperfiltration and Albuminuria in the General Nondiabetic Population: A Prospective Cohort Study

“…12 Glomerular hyperfiltration has been established as an early manifestation of diabetic nephropathy and has been shown to predict albuminuria and GFR decline in diabetes. 13,14 Hyperfiltration is also a possible common causal pathway for other causes of CKD; however, the longitudinal association between prediabetes and hyperfiltration remains to be established. Previous longitudinal studies assessing the association between prediabetes and kidney function used estimated GFR (eGFR) to assess changes in GFR.…”

“…7 In contrast, we found that prediabetes predicted higher mGFR and hyperfiltration after almost six years of follow up. If hyperfiltration in prediabetes represents a maladaptive response to metabolic changes, as indicated by animal models and in studies of patients with diabetes, 13,14,30 the process of kidney damage is likely to start early in the course of chronic hyperglycemia. The current finding of an increased risk of developing elevated ACR for those with a higher baseline FG or prediabetesR IEC R after excluding persons with diabetes at baseline and follow-up supports this theory.…”

Gastric Bypass Surgery and Measured and Estimated GFR in Women

“…Obesity (body mass index (BMI) greater than 30 kg/m 2 ) is associated with glomerular hyperfiltration, glomerular hypertrophy, and proteinuria, all potentially harmful 1 . Although bariatric surgery can achieve sustained long-term weight loss, is recommended by consensus guidelines 2 , and is associated with overall decreased mortality 3 , the renal effects of this acute weight loss on glomerular hyperfiltration are not clearly established, and the accuracy of the equations that are used to estimate GFR (eGFR) before and after the procedure is unclear.…”

Kidney Disease in Obesity and Metabolic Syndrome

“…While there is some conflicting data concerning early intervention in diabetic patients with evidence of glomerular hyperfiltration and its effect on the progression of CKD and diabetic nephropathy, the majority of recent evidence suggests considerable benefit (Magee et al 2009;Moriya et al 2012;Ruggenenti et al 2012). Given this promising evidence, numerous clinical trials have been designed to test that SGLT-2 inhibitors can improve hyperglycemia, glomerular hyperfiltration/hypertrophy, and the downstream renal consequences.…”