The natural history of diabetic nephropathy in type I diabetes and the role of metabolic control in its prevention, reversibility and clinical course

Abstract

The authors present a contemporary picture of the pathogenesis and clinical course of diabetic nephropathy in type I diabetics describing the stages of the disease and the possible evidence for reversibility of the kidney damage with tight metabolic control. During the so-called latency period, which is clinically non-detectable, the predominant functional abnormalities (increase in GFR with sub-clinical glomerular proteinuria) can be corrected by strict control although there is no evidence for the regression of the associated anatomical changes such as the enlarged filtration area. As for the described increase in thickness of the glomerular basement membrane, from experimental data and pancreatic transplants in man, delay in its development and to some extent regression of the glomerular lesions can be expected. The problem of how the renal lesions in experimental diabetes mirror the changes in the human kidney is discussed. During the symptomatic period, with intermittent and subsequently constant proteinuria and progressive decline in renal function, which are observed in only about 30% of type I diabetics, the role of arterial hypertension and its effective control is emphasized. Finally, the renal failure period is indicative of irreversible damage to the kidneys. The progression from its early to its late stages is variable between different patients but each individual patient shows a constant rate of deterioration. The evidence for the efficacy of medical treatment in slowing down its progression is very limited at present but much can be done to improve the quality of life by dietary measures, treatment of fluid overload and hypertension. When the end-stage diabetic kidney disease is reached, with serum creatinine above 8 mg/dl, renal transplantation from a living donor offers a good chance for a relatively acceptable quality of life for years. In conclusion, it is stressed that the morbidity of diabetic nephropathy could eventually be reduced through effective control of the metabolic abnormalities of diabetes with the methods presently available.