Proteinuria: clinical signficance and basis for therapy

Proteinuria is the hallmark of renal disease and proteinuria exceeding 1 gm a day in patients with renal disease augers a poorer prognosis. Proteinuria has been shown to be tubulotoxic and directly contributes to renal deterioration. Patients with non-selective proteinuria are more likely to have progressive renal disease. Diabetic patients with persistent microhaematuria have about 20 times the risk of developing diabetic nephropathy. In essential hypertension, the onset of de novo proteinuria after years of adequate BP control is a marker of subsequent decline in renal function. In glomerulonephritis, more severe proteinuria is associated with faster rate of progression. Even though the initial phase of proteinuria in patients with glomerulonephritis is usually of immunological origin, in the vast majority of patients with established disease, the latter progressive phase of proteinuric glomerulopathy is the result of glomerular hyperfiltration which shifts glomerular non-selective pores to larger dimensions resulting in excessive leakage of protein in the urine. Endothelial injury resulting from glomerular hyperfiltration causes increase in local generation of Angiotensin II in the kidney as part of the hemodynamic response. ACE inhibitors and angiotensin II receptor antagonists (ATRA) can improve glomerular pore-selectivity by remodelling the glomerular basement membrane. In addition, these agents also have beneficial effects by decreasing TGF-beta production therapy decreasing mesangial cell proliferation, hence ameliorating disease progression in patients with diabetic nephropathy and IgA nephropathy. A number of recent clinical trials have shown that ACEI and ATRA therapy can retard the progression of renal deterioration in patients with NIDDM and those with IgA nephropathy and even restore normal renal function in those with mild renal impairment. Treatment and control of proteinuria in patients with renal disease should be regarded as important as treatment of hypertension as it can prevent renal failure.