An autopsy study suggests that diabetic nephropathy is underdiagnosed

Although pathologic classifications exist for several renal diseases, including IgA nephropathy, focal segmental glomerulosclerosis, and lupus nephritis, a uniform classification for diabetic nephropathy is lacking. Our aim, commissioned by the Research Committee of the Renal Pathology Society, was to develop a consensus classification combining type1 and type 2 diabetic nephropathies. Such a classification should discriminate lesions by various degrees of severity that would be easy to use internationally in clinical practice. We divide diabetic nephropathy into four hierarchical glomerular lesions with a separate evaluation for degrees of interstitial and vascular involvement. Biopsies diagnosed as diabetic nephropathy are classified as follows: Class I, glomerular basement membrane thickening: isolated glomerular basement membrane thickening and only mild, nonspecific changes by light microscopy that do not meet the criteria of classes II through IV. Class II, mesangial expansion, mild (IIa) or severe (IIb): glomeruli classified as mild or severe mesangial expansion but without nodular sclerosis (Kimmelstiel-Wilson lesions) or global glomerulosclerosis in more than 50% of glomeruli. Class III, nodular sclerosis (Kimmelstiel-Wilson lesions): at least one glomerulus with nodular increase in mesangial matrix (Kimmelstiel-Wilson) without changes described in class IV. Class IV, advanced diabetic glomerulosclerosis: more than 50% global glomerulosclerosis with other clinical or pathologic evidence that sclerosis is attributable to diabetic nephropathy. A good interobserver reproducibility for the four classes of DN was shown (intraclass correlation coefficient = 0.84) in a test of this classification.

Kidney disease in type 2 diabetes mellitus (DM) is more heterogeneous than in type 1 DM. Reduced glomerular filtration rate (GFR) among individuals with type 2 DM may not always be due to classic diabetic glomerulosclerosis, which is associated with albuminuria and retinopathy. To determine the prevalence of chronic renal insufficiency (CRI), defined as a GFR less than 60 mL/min per 1.73 m2 body surface area (BSA) in the absence of microalbuminuria or macroalbuminuria and diabetic retinopathy among adults with type 2 DM. Cross-sectional analysis of adults aged 40 years or older with type 2 DM in the Third National Health and Nutrition Examination Survey, a probability sample of the total civilian US noninstitutionalized population conducted from 1988-1994. The GFR per 1.73 m2 BSA, calculated with serum creatinine, urea nitrogen, and serum albumin levels using the Modification of Diet in Renal Disease Study prediction equation; albuminuria, assessed using spot urine albumin/creatinine ratio; and presence of retinopathy, determined with fundus photography. Overall, 13% (sampled n = 171) of adults with type 2 DM (n = 1197) had CRI with a population estimate of 1.1 million. Among these adults with CRI, diabetic retinopathy was noted in 28% (n = 58), while the frequencies of microalbuminuria and macroalbuminuria were 45% (n = 64) and 19% (n = 47), respectively. Retinopathy and albuminuria (microalbuminuria or macroalbuminuria) were both absent in 30% (n = 51) of adults with type 2 DM and CRI. The population estimate of adults with type 2 DM and CRI in the absence of diabetic retinopathy or albuminuria was approximately 0.3 million. A substantial burden of CRI among persons with type 2 DM in the United States is likely due to renal parenchymal disease other than classic diabetic glomerulosclerosis. Approaches to screening renal disease in the type 2 DM population should incorporate assessment of GFR in addition to monitoring urine albumin excretion and funduscopic changes to ensure that individuals with type 2 DM and CRI not due to diabetic glomerulosclerosis will receive appropriate intervention.

In patients with type I diabetes mellitus who do not have uremia and have not received a kidney transplant, pancreas transplantation does not ameliorate established lesions of diabetic nephropathy within five years after transplantation, but the effects of longer periods of normoglycemia are unknown. We studied kidney function and performed renal biopsies before pancreas transplantation and 5 and 10 years thereafter in eight patients with type I diabetes but without uremia who had mild to advanced lesions of diabetic nephropathy at the time of transplantation. The biopsy samples were analyzed morphometrically. All patients had persistently normal glycosylated hemoglobin values after transplantation. The median urinary albumin excretion rate was 103 mg per day before transplantation, 30 mg per day 5 years after transplantation, and 20 mg per day 10 years after transplantation (P=0.07 for the comparison of values at base line and at 5 years; P=0.11 for the comparison between base line and 10 years). The mean (+/-SD) creatinine clearance rate declined from 108+/-20 ml per minute per 1.73 m2 of body-surface area at base line to 74+/-16 ml per minute per 1.73 m2 at 5 years (P<0.001) and 74+/-14 ml per minute per 1.73 m2 at 10 years (P<0.001). The thickness of the glomerular and tubular basement membranes was similar at 5 years (570+/-64 and 928+/-173 nm, respectively) and at base line (594+/-81 and 911+/-133 nm, respectively) but had decreased by 10 years (to 404+/-38 and 690+/-111 nm, respectively; P<0.001 and P=0.004 for the comparisons with the base-line values). The mesangial fractional volume (the proportion of the glomerulus occupied by the mesangium) increased from base line (0.33+/-0.07) to 5 years (0.39+/-0.10, P=0.02) but had decreased at 10 years (0.27+/-0.02, P=0.05 for the comparison with the baseline value and P=0.006 for the comparison with the value at 5 years), mostly because of a reduction in mesangial matrix. Pancreas transplantation can reverse the lesions of diabetic nephropathy, but reversal requires more than five years of normoglycemia.