Clinical and Histological Correlations of Decline in Renal Function in Diabetic Patients With Proteinuria

Abstract

In 47 patients with diabetic nephropathy (29 type I, 18 type II) renal function and blood pressure (BP) (treated with or without an angiotensin-converting enzyme [ACE] inhibitor, enalapril [10 mg], in 38 hypertensive patients) were followed over 4 years. A percutaneous renal biopsy was performed in all patients initially and repeated in a representative 19 patients with treated hypertension after 4 years. Mean glomerular volume (MGV), interstitial fibrosis (IF), capillary volume, and sclerosed glomeruli (GS) were measured histomorphometrically. Mean fall in creatinine clearance (CCr) was 11.8% after 4 years with no difference between treatment groups or type of diabetes. BP both initially and during treatment correlated with initial and final serum creatinine and CCr (P < 0.01). There were no histomorphometric differences between type I and type II patients or hypertension treatment groups. Initial IF correlated with initial and final serum creatinine and CCr (P < 0.05) in all patients and type I patients alone, MGV correlated inversely with CCr in type I patients (P < 0.05). After 4 years, IF (24.8 vs. 30.0%, P < 0.01) and GS (26 vs. 37%, P < 0.05) increased significantly, and increase in IF correlated with fall in CCr (P < 0.01). Proteinuria and HbA1 did not correlate with indexes of function or structure. In this longitudinal study of patients with diabetic nephropathy, there was a close relation between BP and renal function but no difference between treatment with enalapril and other hypertensive agents. The correlations between renal function and histology at entry and after 4 years suggest that IF is a co-determinant of renal function in diabetic nephropathy.

Comparison of renal morphology in the Streptozotocin and the SHR/N-cp models of diabetes

“…[29][30][31] The number of the mesangial cells was significantly higher in STZ and SHR/N-cp rats, but the mean mesangial cell volume was considerably higher in the SHR/N-cp compared to the STZ rats. It is thought that the mesangial cell matrix production in culture correspond to a 'wound healing' phenotype.…”

Effect of Ruboxistaurin on Urinary Transforming Growth Factor-β in Patients With Diabetic Nephropathy and Type 2 Diabetes

“…Indeed, by stimulating fibrogenesis in epithelial cells, the tubular passage of TGF-␤ has also been implicated in the development of the tubulointerstitial fibrosis characterizing proteinuric renal diseases (14). This may be particularly important in the context of human diabetes, where the extent of tubulointerstitial disease is a close correlate of declining renal function (16,17) and therapeutic response (18). Among placebo patients in the ruboxistaurin study (11), ACR remained stable with good blood pressure control and blockade of the RAS.…”

Predictors of Estimated GFR Decline in Patients with Type 2 Diabetes and Preserved Kidney Function

“…The estimated GFR (eGFR) is the most widely used parameter for the evaluation of changes in kidney function in clinical practice. However, the course of GFR is very complex and heterogeneous in type 2 diabetes, mainly depending on individual, ethnic, and diseasespecific conditions (8)(9)(10)(11)(12)(13)(14). For instance, it was recently reported that albuminuria is the strongest risk factor of faster annual eGFR decline in 153 Caucasian patients with type 2 diabetes with a baseline eGFR ,50 ml/min per 1.73 m 2 during a 2.5-year follow-up (15).…”