Kidney function and glomerulopathy over 8 years in young patients with Type I (insulin-dependent) diabetes mellitus and microalbuminuria

Abstract

Since the term microalbuminuria was coined and was shown to predict clinical nephropathy in Type-I (insulin-dependent) diabetes mellitus in the early 1980 s [1±3], the research has focused on the putative risk factors in the early stages of nephropathy and their relative importance for the decline in renal function. The present knowledge of these factors and the development of the ultrastructural changes in the glomeruli, i. e. basement membrane thickening and mesangial expansion, are scarce and primarily based on cross-sectional studies [4±8]. Long-term studies on homogeneous groups of Type I diabetic patients have not been carried out.Hyperglycaemia has been shown to be associated with the degree of glomerulopathy in incipient nephr- Diabetologia (2002) Abstract Aims/hypothesis. We aimed to investigate prospectively the interrelation between kidney function and glomerular morphological changes over 8 years in young patients with Type I (insulin-dependent) diabetes mellitus and microalbuminuria. Methods. Kidney biopsies were taken at baseline and after 8 years in 18 subjects who were 20 years of age (19±29 mean and range), had duration of diabetes for 11 years (7±18), and who had an albumin excretion rate of 45 mg/min (15±194). The glomerular ultrastructural parameters were analysed using stereological methods. Results. At the end of the study three patients had an increased albumin excretion rate of more than 25 % a year, two of whom developed overt nephropathy. Glomerular filtration rate declined 2.3 ml/min´1.73 m ±2´y r ±1 . Glomerular volume, volume fractions of matrix and mesangium, and basement membrane thickness showed an increase over the 8 years. Multiple regression analysis showed that mean 8-years HbA 1 c , matrix volume fraction baseline and basement membrane thickness BMT baseline accounted for 70 % of the variation in AER at the end of the study. Mesangial volume fraction baseline, glomerular filtration fraction baseline, and mean 8-year HbA 1 c accounted for 73 % of the change in glomerular filtration rate from baseline. Smoking was strongly associated with the glomerular filtration rate at baseline (r = 0.65). When glomerular filtration rate baseline was omitted from the equation, smoking was the only significant parameter linked to the change in glomerular filtration rate from the baseline. Conclusion/interpretation. In patients who had diabetes for 20 years, long-term hyperglycaemia and glomerulopathy found 8 years prior to the study, and possibly smoking, affected renal function (i. e. albumin excretion rate and glomerular filtration rate). [Diabetologia (2002) 45: 253±261]

Isolate diffuse thickening of glomerular capillary basement membrane: a renal lesion in prediabetes?

“…Of 23 patients with TGCBM, 17 were identified in 1999, 4 2000, 6 and 2001, 7 while only one patient in each of the 6 previous years was diagnosed, and indication of biopsy for proteinuria of 1 g/day or more was unchanged. The clinical features of all groups at the time of biopsy are shown in Table 1.…”

“…8,15 However, TGCBM in this series was not correlated with age, body weight, smoking or hypertension, and these patients with isolated TGCBM appeared to be related to a form of chronic renal disease, substantiated by persistent proteinuria, and possibly associated with early diabetes mellitus or prediabetes. 5,6,8 While patients with TGCBM and Figure 2 Normal appearing glomeruli in light microscopy not exhibiting the diffuse thickening of capillary basement membrane, detectable only in electron microscopy. PASM with H&E counterstain, Â 240.…”

“…5,6 Initially, however, many patients clearly did not demonstrate any supporting evidence for diabetes and a few still did not after a median follow-up of 46 months. Nonetheless, a majority of patients developed consistent abnormal blood tests in the course of followup, establishing the diagnosis of diabetes, and ascribing TGCBM to a prediabetic state.…”

“…One may argue that the coexistence of TGCBM and diabetes is merely coincidental, but whether such an argument is legitimate or refutable, the recognition of an isolated TGCBM denotes a close and important link with early diabetes or prediabetes in most of these cases. 5,6,16 In fact, the mechanisms involved in the development of diabetic lesions or thickening of basement membrane are poorly understood, but many processes induced by hyperglycemia have been implicated, including a deranged sorbitol pathway, excessive production of advanced glycosylation end products, and synthesis of glucoaminoglycans. 2,10 As most of our patients showed no hyperglycemia at the time of biopsy, these processes unlikely contributed to the development of TGCBM.…”

“…[1][2][3][4] However, many studies from Bangstad, Osterby and Hanssen had described TGCBM in young patients with type I insulin-dependent diabetes, associated with increased mesangial matrix or mesangial volume fraction, and ascribed TGCBM as the early glomerular lesion in these young diabetic patients. 5,6 Nevertheless, early renal lesions in diabetic patients, especially in type II diabetes remain poorly described, because of the policy to withhold biopsy, unless atypical presentation raises the suspicion of nondiabetic lesions, which may affect both the management and prognosis. 2,3,4,7 Moreover, TGCBM has been described in nondiabetic patients, associated with hypertension and smoking, but the correlation of TGCBM to these factors remains to be established.…”