Promotion, prediction and prevention of progression of nephropathy in Type 1 diabetes mellitus

Abstract

The scope of the present review is to discuss the prognosis of diabetic renal disease, putative progression promoters and the possibilities for treatment and prediction of treatment efficacy. The recent changes in the incidence of diabetic nephropathy in Type 1 diabetes mellitus are discussed. Promoters of progression in diabetic nephropathy are evaluated, in particular arterial blood pressure, glycaemic control, albuminuria and cholesterol levels. Potential treatment modalities are discussed, with special focus on antihypertensive therapy, including a discussion of a specific renoprotective action of certain antihypertensive agents. Furthermore putative predictors of treatment efficacy are evaluated, demonstrating that the ability to lower the urinary albumin excretion rate after onset of treatment heralds a slow progression of the renal disease. The prognosis in diabetic renal disease has improved with an increase in median survival after onset of nephropathy from 6 to 15 years. This has exposed the importance of cardiovascular morbidity and mortality. The identification and treatment of cardiovascular risk factors has become essential. Although the prognosis has improved remarkably, the primary goal should be prevention of diabetic nephropathy, as it is unlikely that the increased risks associated with this complication can be eliminated.

Kidney injury molecule (KIM)-1 is associated with insulin resistance: Results from two community-based studies of elderly individuals

“…Tubulointerstitial injury is present in all forms of chronic kidney disease and is thought to be a better predictor of disease progression and long-term prognosis than is the severity of damage to glomeruli [7,16]. By measuring KIM-1, this "tubular phase" of renal damage could be detected before the development of albuminuria, the currently used marker of early diabetic nephropathy [18]. However, the clinical relevance of such an approach remains to be evaluated.…”

“…Early renal tubular damage biomarker levels (including urinary KIM-1 levels) are elevated in patients with diabetes, even in those with normoalbuminuria [4,18]. Interestingly, regression of diabetic nephropathy has been shown to be associated with reduced levels of urinary KIM-1 as well [23].…”

Pregnancy and progression of diabetic nephropathy

“…The patients benefited from improved prognosis as compared to the natural history of the diabetic nephropathy as discussed below [17±19]. The two groups were well matched at baseline and during follow-up regarding the major risk factors for losing filtration power i. e. arterial blood pressure, albuminuria, glycaemic control and lipids [20]. Aggressive antihypertensive treatment is thought to play a major role for the observed improvement in the progression of diabetic nephropathy.…”

Are glomerular volume differences between type 1 and type 2 diabetic patients pathologically significant?

“…However, the reported rate of progress varies, particularly in type 2 diabetic patients, where the decline in GFR can range from +3.1 to −22.0 ml min −1 year −1 [2,[7][8][9]. In type 1 diabetic patients, the average rate of decline is 10 ml min −1 year −1 in those with poorly controlled blood pressure and 4.8 ml min −1 year −1 in those with good blood pressure control [10].…”