Renal structural changes in type 1 and 2 diabetes mellitus: Pathology, pathogenesis, and clinical correlations

Abstract

Diabetes mellitus represents an increasing health problem worldwide. Renal involvement in diabetic patients occurs in a subset of these patients, often playing a key role in morbidity and mortality. Diabetic nephropathy is the major cause of chronic renal disease and end-stage renal disease in the United States, accounting for about half of the patients entering dialysis each year. Diabetic nephropathy occurs in only approximately one third (20-40 %) of patients with diabetes mellitus, generally 15-20 years after diagnosis. A significant genetic component must be at least part of the explanation as to why only some patients with diabetes mellitus develop nephropathy. Characteristic lesions can be seen in glomeruli but there are also concomitant vascular alterations and secondary tubular interstitial alterations, all combining to lead to renal failure in many of these patients. Morphological findings in diabetes mellitus can be pathognomonic or rather nonspecific. The latter most typically happens in early cases but can also occur in situations where diabetic changes are found concomitantly with morphological manifestations of other superimposed disorders, mostly glomerulopathies. The differential diagnosis of nodular glomerulosclerosis, the classical glomerular lesion seen in well-established diabetic nephropathy, includes a number of other similar glomerulopathies that share similar pathogenetic molecular mechanisms, though their etiology is completely different. Recognition of these entities is imperative to avoid making the wrong assessment and/or delaying diagnosis. The present chapter addresses the morphological expressions of type 1 and 2 diabetes mellitus in the renal parenchyma with emphasis on structural changes that take place, pathology, differential diagnosis, pathogenesis, and clinical correlations. It also emphasizes underlying molecular events responsible for the pathological abnormalities to be able to understand why other totally different disorders may share morphological similarities. Future therapeutic interventions will likely take advantage of our more sophisticated understanding of the pathogenesis of diabetic nephropathy. Finally, the chapter attempts to correlate pathological findings with clinical manifestations, progression, and ultimately, prognosis. Other disorders that may exist concomitantly in a given case that may alter the morphological and clinical manifestations will also be discussed to provide a rather comprehensive view of the subject.