PubMed · 5763706
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E P Maynard. 1969-02-27. Renal function and cephalothin.. https://pubmed.ncbi.nlm.nih.gov/5763706/
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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.
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To assess long-term hematologic and renal effects associated with a solitary kidney, 16 healthy cats undergoing uninephrectomy for kidney donation between May 1987 and January 1991 were evaluated by use of physical examination, CBC, serum biochemical analysis, urinalysis, and urine protein:creatinine ratio. Results of preoperative CBC, serum biochemical analysis, and urinalysis were within reference limits in all donors. Median age at surgery and at follow-up evaluation was 34 and 72 months, respectively. Mean (+/- SEM) interval between follow-up and uninephrectomy was 39.3 +/- 14.6 months. Postuninephrectomy hematocrit and RBC indices were within reference limits in 15 donors. One cat with chronic renal insufficiency had normocytic, normochromic, nonregenerative anemia. In 15 clinically normal donor cats, mean (+/- SEM) serum creatinine concentrations pre- and post-uninephrectomy were 1.36 +/- 0.20 and 1.71 +/- 0.33 mg/dl, respectively (P = 0.0002); however, the clinical relevance of this statistical difference in serum creatinine is uncertain, because all values were within reference limits. In addition, urine-concentrating ability was maintained in 14 donors, with urine specific gravity > or = 1.040. Two donors, including the cat with chronic renal insufficiency, produced dilute urine (specific gravity < or = 1.020) and had substantial proteinuria, with urine protein:creatinine ratios of 2.16 and 3.62, respectively. Mean urine protein:creatinine ratio in donor cats was not significantly different from that in an age- and sex-matched comparison group. Renal and erythropoetic function was clinically preserved in the group of donor cats within 2 to 5 years after uninephrectomy.(ABSTRACT TRUNCATED AT 250 WORDS)