Introduction Recently serum soluble urokinase receptor (suPAR) has been proposed as a cause of two thirds of cases of focal segmental glomerulosclerosis (FSGS). It was noted to be uniquely elevated in cases of primary FSGS with higher levels noted in cases that recurred post-transplant. It is also suggested as a possible target and marker of therapy. Methods We studied serum and urine suPAR from pre-transplant banked samples from 86 well characterized kidney transplant recipients and 10 healthy controls to determine its prognostic utility. Causes of native kidney disease were; primary focal segmental glomerulosclerosis, diabetic nephropathy, membranous nephropathy, immunoglobulin A nephropathy, and autosomal dominant polycystic kidney disease. suPAR was measured using a commercially available enzyme-linked immunosorbent assay kit. Urinary suPAR was indexed to creatinine. Results Both serum and urine suPAR correlated with proteinuria and albuminuria. Serum suPAR was found to be elevated in all transplant candidates with advanced renal disease compared to healthy controls and could not differentiate disease diagnosis. Urine suPAR was elevated in cases of recurrent focal segmental glomerulosclerosis compared to all other causes of end stage renal disease. Recurrent focal segmental glomerulosclerosis cases had substantially higher proteinuria compared to all other cases. However, elevated urinary suPAR showed a trend in providing additional prognostic information beyond proteinuria in the small cohort of recurrent FSGS cases. Conclusion In advanced renal disease, elevated serum suPAR is not unique to FSGS cases. Urinary suPAR appears to be higher in cases of focal segmental glomerulosclerosis destined for recurrence and merits further evaluation.
Increased urinary protein excretion is common after renal transplantation and portends worse outcome. In this study we assessed the prognostic contribution of several urinary proteins. Urinary total protein, albumin, retinol binding protein (RBP), α-1-microglobulin, IgG and IgM, were measured in banked urine samples from 221 individuals one-year after renal transplantation (age 52 ± 13 years, 55% male, 93 % Caucasian and 82 % living donor). Levels of all proteins measured were higher than in normal non-transplant populations. Patients with glomerular lesions had higher urinary albumin than those with normal histology, while those with Interstitial Fibrosis and Tubular Atrophy plus Inflammation (ci>0, cg=0, i>0) had higher levels of IgG, IgM, α-1-microglobulin and RBP. Concomitant normal levels of urinary albumin, IgM and RBP identified normal histology (specificity 91%, sensitivity 15 %,). Urinary levels of the specific proteins were highly correlated, could not differentiate among the histologic groups, and appeared to result from tubulointerstitial damage. Increased urinary excretion of the low molecular weight protein RBP was a sensitive marker of allografts at risk, predicting long-term graft loss independent of histology and urinary albumin. This study highlights the prognostic importance of tubulointerstitial disease for long-term graft loss.
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