Diabetes – Effects on Kidneys
Diabetes – Effects on kidneys. (Diabetic nephropathy)
Advanced kidney disease is seen 30 – 40% of type 1 diabetics and 20 – 30% of type 2 diabetics.
What causes glomerulosclerosis?
- Metabolic defects – like insulin deficiency, hyperglycemia are responsible for alterations in glomerular basement membrane causing its thickening.
- Advanced glycosylation end products – AGEs have effects like altering endothelial, mesangial and macrophage cellular functions, modifying LDL cholesterol so it oxidized and deposited within vessel walls causing atheromas, generation of reactive oxygen species.
- Hemodynamic changes – Early stages of diabetes, there is increased glomerular capillary pressure and glomerular hypertrophy with slowly developing glomerulosclerosis.
- Cytokines like TGF-beta causes hypertrophy of the mesangial cells and deposition of the collagen in the glomerulus.
Lesions in kidney :
Basement membrane thickening – BM of the glomeruli becomes thick. This can be diagnosed electron microscopy.
Cells in between the glomeruli (mesangial cells) increase in number and deposition of pink substance leading to mesangial thickening.
Glomerular lesions – Called Kimmelstiel Wilson disease. Consists of ball like deposits at the periphery of the glomerulus. These contain mesangial cells and PAS postive substance and surrounded by patent capillary loops. As disease advances whole glomerulus become sclerosed.
Renal afferent and efferent arterioles become thickened as a part of macrovascular disease.
Pyelonephritis is infection of the kidneys. Both acute and chronic types can be seen. These are also seen in general population, but more common in diabetics.
How diabetic kidney manifests in clinical practice?
Microalbuminuria – Urinary excretion of 30 – 300 mg per day of albumin. Slowly frank nephrotic syndrome develops. Diagnosed by overnight collection of urine. This can be done 3 times in 3 – 6 months period. Two of three values are abnormal, then it is said that patient has microalbuminuria.
Frank nephrotic syndrome – develops overtime with hypoalbuminemia, edema, increased circulating cholesterol. As renal failure progresses, glucose appears in urine. Protein will be more than 3.5 g/d. There will be rising blooad urea nitrogen and creatinine ratio.
Management of nephropathy includes -
Strict control of glucose has been shown that intensive therapy can partially reverse glomerular hypertrophy and hyperfiltration, delay the development of microalbuminuria.
Angiotensin converting enzyme inhibitors – Decrease progress of diabetic glomerulopathy. Also decreases mean arterial pressure and microalbuminuria. Usually combined with diuretics in long term.
In end stage disease dialysis and renal transplantation are considered.