Low molecular weight proteinuria in Chinese herbs nephropathy

Abstract

Urinary excretion of five low molecular weight proteins (LMWP) [β2-microglobulin (β2m), cystatin C (cyst C), Clara cell protein (CC16), retinol-binding protein (REP) and alpha1-microglobulin (α1m)], albumin and N-acetyl-β-D-glucosaminidase (NAG) were quantified in 16 patients who followed a weight reduction program which included Chinese herbs, which have been incriminated in the genesis of Chinese herbs nephropathy (CHN). An additional group of four patients transplanted for CHN were investigated. Urinary data were obtained for comparison purpose in five groups of proteinuric patients: two groups with normal serum creatinine (S(Cr)) and glomerular albuminuria [12 patients with diabetes mellitus and microalbuminuria (DN), 10 patients with primary nephrotic syndrome (NS)]; two groups with normal S(Cr) and toxic nephropathy [6 patients with analgesic (AN), 9 patients with cadmium nephropathy (CdN)]; and one group of seven patients with glomerular diseases and increased S(Cr) (GN). Patients were classified according to serum level S(β2m) to take into account the possibility of overflow proteinuria at S(β2m) ≥ 5 mg/liter. Three patients (CHNO) with a S(β2m) < 5 mg/liter, had a normal urinary protein pattern including NAG and a normal S(β2m). Eight patients (CHN1) with a S(β2m) < 5 mg/liter had various abnormalities of their urinary protein pattern. In four of them (CHN1a) only β2m, REP and CC16 were increased while total proteinuria and S(Cr) were normal. In the other four (CHN1b and c) albumin, cyst C, α1m and NAG were also elevated, while total proteinuria and S(Cr) were moderately raised. Five patients (CHN2) with a S(β2m) ≥ 5 mg/liter had a markedly increased excretion of all LMWP, albumin and NAG (CHN1 vs. CHN2, P < 0.05) as well as a further increase in total proteinuria and S(Cr). The urinary LMWP/albumin concentration ratio was strikingly higher in CHN patients than in patients with glomerular albuminuria (CHN1 vs. DN and NS, P < 0.01) or moderate renal failure with elevated S(β2m) level (CHN2 vs. GN, P < 0.01), confirming the existence of a tubular proteinuria independent of glomerular albuminuria or overflow proteinuria, a similar proteinuria pattern was present in the two toxic nephropathies (CdN and AN). This pattern was no longer recognizable after transplantation. In conclusion, CHN exhibits various profiles of tubular proteinuria which are the hallmarks of the disease. This pattern is still detectable in patients with renal failure and/or glomerular albuminuria. It is identical to that observed in cadmium and analgesic nephropathies. It does not recur after transplantation. Its most sensitive and reliable marker is a raised urinary level of CC16 or REP.