PubMed · 8808237
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S Bhandari, P Johnston, R C Fowler, A Joyce, J H Turney. 1995. Non-dilated bilateral ureteric obstruction.. https://doi.org/10.1093/ndt%2F10.12.2337
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Early transplant dysfunction and failure because of immunological and nonimmunological factors still presents a significant clinical problem for transplant recipients. A critical unmet need is the noninvasive detection and prediction of immune injury such that acute injury can be reversed by proactive immunosuppression titration. In this study, we used iTRAQ -based proteomic discovery and targeted ELISA validation to discover and validate candidate urine protein biomarkers from 262 renal allograft recipients with biopsy-confirmed allograft injury. Urine samples were randomly split into a training set of 108 patients and an independent validation set of 154 patients, which comprised the clinical biopsy-confirmed phenotypes of acute rejection (AR) (n = 74), stable graft (STA) (n = 74), chronic allograft injury (CAI) (n = 58), BK virus nephritis (BKVN) (n = 38), nephrotic syndrome (NS) (n = 8), and healthy, normal control (HC) (n = 10). A total of 389 proteins were measured that displayed differential abundances across urine specimens of the injury types (p < 0.05) with a significant finding that SUMO2 (small ubiquitin-related modifier 2) was identified as a "hub" protein for graft injury irrespective of causation. Sixty-nine urine proteins had differences in abundance (p < 0.01) in AR compared with stable graft, of which 12 proteins were up-regulated in AR with a mean fold increase of 2.8. Nine urine proteins were highly specific for AR because of their significant differences (p < 0.01; fold increase >1.5) from all other transplant categories (HLA class II protein HLA-DRB1, KRT14, HIST1H4B, FGG, ACTB, FGB, FGA, KRT7, DPP4). Increased levels of three of these proteins, fibrinogen beta (FGB; p = 0.04), fibrinogen gamma (FGG; p = 0.03), and HLA DRB1 (p = 0.003) were validated by ELISA in AR using an independent sample set. The fibrinogen proteins further segregated AR from BK virus nephritis (FGB p = 0.03, FGG p = 0.02), a finding that supports the utility of monitoring these urinary proteins for the specific and sensitive noninvasive diagnosis of acute renal allograft rejection.
PURPOSE: Neither serum creatinine concentration nor creatinine clearance assess renal function accurately. Serum creatinine concentration is affected by muscle mass, and the creatinine clearance overestimates the glomerular filtration rate because of tubular secretion of creatinine. The present study was designed to determine whether serum concentrations of 2-(alpha-mannopyranosyl)-L-tryptophan (MPT), a tryptophan glycoconjugate, can be used as a marker of renal function. METHODS: Clearances of MPT and of inulin were compared in normal rats and in rats with cisplatin-induced acute renal failure. We also compared the clearances of MPT and of creatinine with inulin clearance in 25 patients with chronic renal disease. Serum concentrations of MPT and creatinine as a function of MPT clearance were determined in 108 patients with chronic renal disease. RESULTS: There was strong linear correlation between clearances of MPT and inulin in rats (r = 0.97) and humans (r = 0.87), indicating that renal handling of MPT is similar to that of inulin. In humans, linear regression analyses indicated that MPT was a better indicator of inulin clearance than was creatinine clearance. At the same level of renal function, serum creatinine concentrations tended to be lower in patients with less muscle mass (as indicated by a urinary creatinine excretion <1,000 mg in 24 hours) than in those who excreted >1,000 mg in 24 hours, whereas serum MPT concentrations were not affected by creatinine excretion. CONCLUSION: MPT clearance can replace inulin clearance in the clinical setting. The serum MPT concentration is an accurate measure of renal function even in patients with diminished muscle mass, and thus is a better indicator of renal function than is the serum creatinine concentration.
Revascularization of renal artery stenosis for the treatment of hypertension is an established procedure. In selected clinical scenarios, successful revascularization procedures may preserve or restore renal function. We present a 31-year-old man who underwent successful renal revascularization of a solitary functioning kidney after being dialysis dependent for approximately 190 days. He had dramatic improvement of renal function and has remained off dialysis since his surgery 18 months ago. He continues to have severe but controllable hypertension.