Title:Histological Manifestations of Diabetic Kidney Disease and its Relationship
with Insulin Resistance
Volume: 19
Issue: 1
Author(s): María M. Adeva-Andany*, Lucía Adeva-Contreras, Carlos Fernández-Fernández, Natalia Carneiro-Freire and Alberto Domínguez-Montero
Affiliation:
- Internal Medicine Department, Nephrology Division, Hospital General Juan Cardona c/ Pardo Bazán s/n, 15406 Ferrol,
Spain
Keywords:
Diabetes, focal glomerulosclerosis, C3 glomerulopathy, herparan sulfate, factor H, aging, obesity, lipodystrophy, HIV, cystic fibrosis, insulin receptor, Alström syndrome.
Abstract: Histological manifestations of diabetic kidney disease (DKD) include mesangiolysis,
mesangial matrix expansion, mesangial cell proliferation, thickening of the glomerular basement
membrane, podocyte loss, foot process effacement, and hyalinosis of the glomerular arterioles, interstitial
fibrosis, and tubular atrophy. Glomerulomegaly is a typical finding. Histological features
of DKD may occur in the absence of clinical manifestations, having been documented in patients
with normal urinary albumin excretion and normal glomerular filtration rate. Furthermore, the histological
picture progresses over time, while clinical data may remain normal. Conversely, histological
lesions of DKD improve with metabolic normalization following effective pancreas transplantation.
Insulin resistance has been associated with the clinical manifestations of DKD
(nephromegaly, glomerular hyperfiltration, albuminuria, and kidney failure). Likewise, insulin resistance
may underlie the histological manifestations of DKD. Morphological changes of DKD are
absent in newly diagnosed type 1 diabetes patients (with no insulin resistance) but appear afterward
when insulin resistance develops. In contrast, structural lesions of DKD are typically present before
the clinical diagnosis of type 2 diabetes. Several heterogeneous conditions that share the occurrence
of insulin resistance, such as aging, obesity, acromegaly, lipodystrophy, cystic fibrosis,
insulin receptor dysfunction, and Alström syndrome, also share both clinical and structural manifestations
of kidney disease, including glomerulomegaly and other features of DKD, focal segmental
glomerulosclerosis, and C3 glomerulopathy, which might be ascribed to the reduction in the
synthesis of factor H binding sites (such as heparan sulfate) that leads to uncontrolled complement
activation. Alström syndrome patients show systemic interstitial fibrosis markedly similar to that
present in diabetes.
