Monday , November 20 2017
Home / Conditions / MODY/LADA / Handbook of Diabetes, 4th Ed., Excerpt #15: Diabetic Nephropathy

Handbook of Diabetes, 4th Ed., Excerpt #15: Diabetic Nephropathy

Epidemiology
Reported prevalence and incidence of microalbuminuria and clinical nephropathy vary according to the population under study (type 1 versus type 2; age range; population or hospital clinic base; ethnicity; year of reporting; type of test). In population-based studies the prevalence of microalbuminuria ranged from 12.3% to 27.2% for type 1 and 19.4% to 42.1% for type 2 diabetes. For clinical nephropathy, the figures were 0.3 – 24% and 9.2 – 32.9% for type 1 and type 2 diabetes population-based studies respectively.
The incidence of persistent microalbuminuria is around 2% per annum for both type 1 and type 2 diabetes with normoalbuminuria. For microalbuminuric patients, the incidence of clinical nephropathy is around 3% per annum.
Rates for ESRD are more difficult to interpret because they are not linear with time and vary according to duration of diabetes. For type 1 diabetes, the latest Finnish National Data reports rates of 2.2% at 20 years’ and 7.8% at 30 years’ duration; for the UKPDS the rate of renal replacement therapy or death from renal failure was 0.6% at 10.4 years.
Pathology and pathophysiology
The classic pathological lesions of nodular glomerulosclerosis were first described in 1936. The earliest pathological feature is thickening of the glomerular capillary basement membrane due to an accumulation of matrix material, which is detectable within 5 years of diabetes onset in patients with type 1 diabetes (Figures 16.2 – 16.4).
Increasing proteinuria is preceded and accompanied by further accumulations of matrix material (mostly type IV collagen and laminin) in the mesangium (called diffuse glomerulosclerosis), due to both overproduction and reduced breakdown and clearance. Ultimately this process obliterates the capillary and reduces filtration, leading to renal failure.
Arteriolar hyalinosis leading to glomerular ischemia, glomerular epithelial cell (podocyte) loss and tubulointerstitial inflammation and fibrosis are also features of advanced nephropathy.
The pathophysiology of these changes has been partly covered in Chapter 14. Essentially, metabolic and hemodynamic factors combine to stimulate the release of profibrogenic cytokines such as transforming growth factor ß (TGF-ß) and connected tissue growth factor, as well as decreasing matrix degradation by inhibition of enzymes such as metalloproteinases. In experimental and human diabetes, renal blood flow is increased and there is a relative dilatation of the afferent compared to the efferent glomerular arteriole. This leads to an increase in glomerular capillary pressure which has been closely related to the development of glomerulosclerosis in diabetic animals. Angiotensin II blockade relaxes the efferent arteriole and lowers intra-glomerular capillary pressure (Figure 16.5).
These changes in structure and capillary pressure underpin the development of albuminuria. The glomerular capillary has an inherent size and molecular charge selectivity. In structural terms the endothelium lining the capillary is fenestrated and has a complex glycocalyx of proteins on its surface. The glomerular basement membrane (GBM) is a meshwork of mainly type IV collagen which is cross-linked in a lattice formation. Finally the epithelial surface comprises the podocytes which have a series of interdigitating foot processes (Figure 16.6).