Diagnostic and prognostic value of proteinuria in chronic renal diseases

Abstract: To the extent that increased urinary protein excretion is an indicator of alterations of the glomerular capillary wall (GCW) and appearance of tubulointerstitial damage, proteinuria can be a good marker of the overall severity of the glomerular and tubulointerstitial damage, and therefore, the prognosis of glomerular diseases. Studies I, II, and III show that it is the type of proteinuria, rather than the degree of albuminuria, that predicts the progression in renal, proteinuric diseases. For instance, we found that the quantity of urinary IgM correlated to the decrease of glomerular filtration rate (GFR) in primary glomerular diseases,irrespective of the degree of albuminuria. 21% of patients with initial proteinuria with high IgM content developed end-stage renal failure compared to none of the patients with proteinuria with low IgM content. Patients who maintained high urinary IgM excretion during the course of glomerular disease showed a more rapid GFR decline over time compared to patients with maintained low IgM excretion despite persistent high degree of albuminuria. Changes in urinary IgG, but not in albumin excretion, during the course of the glomerular disease, correlated to changes in urinary protein HC excretion. Protein HC is a marker of impairment of the proximal tubular function. In study IV, we observed that patients with type 2 DN had a higher urinary excretion of high molecular weight proteins (IgG and IgM) than patients with type 1 DN, despite similar degree of albuminuria. This suggests partly different patho-physiological mechanisms in diabetic nephropathy (DN) in type 1 and type 2 diabetes mellitus. Patients with type 2 DN have a better preserved ratio of urinary excretion of IgG2/IgG4 than type 1 DN patients, indicating that the charge selectivity is less impaired in type 2 DN. Finally, old but not young hypertensive rats (study V) develop proteinuria as a result of a dysfunction of the glomerular capillary filter, affecting primarily its size-selectivity. The changes are functionally compatible with the appearance in the glomerular barrier of an increased number of unselective pores. Conclusions: During the course of glomerular diseases a maintained low urinary excretion of IgG or IgM indicates a salutary prognosis. Different patho-physiological mechanisms of albuminuria in type 1 and type 2 diabetes have been found, and hypertension induced proteinuria is primarily a size-selective disorder.