[Normal kidney function and acute and chronic kidney function disorders].

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.

Acute Kidney Injury↗

PubMed1998

Twin zygosity testing for medical purposes.

After being poisoned by eating the mushroom species Cortinarius speciosissimus, a twin developed interstitial nephritis with acute renal failure. He received a renal transplant from his living twin brother, who was presumed dizygotic on phenotypic grounds. Fifteen years later, the twins were zygosity tested by DNA "fingerprint analysis" and found to be monozygotic, despite important phenotypic discordances. The recipient has discontinued immunosuppression therapy and remains well after 9 months. We suggest that, for medical and other reasons, zygosity should be determined at birth on all like-sexed twins.

Acute Kidney Injury↗

PubMed1998

Hepatocyte growth factor protects renal epithelial cells from apoptotic cell death.

Hepatocyte growth factor (HGF) is a pleiotropic factor that plays an essential role in renal tubular repair and regeneration following injury. Studies indicate that administration of exogenous HGF to animals stimulates renal epithelial cell DNA synthesis and accelerates recovery from acute renal failure (ARF). However, whether increased cell proliferation accounts for all of the beneficial effects of HGF in ARF is unknown. In this study, we demonstrate that HGF protects renal epithelial cells from undergoing apoptotic cell death. Treatment of renal epithelial mIMCD-3 cells with 25 microM cisplatin in the serum-free medium induced significant apoptosis, as assessed by fluorescent Dye H-33342 staining, TUNEL staining, light and electron microscopy, and DNA laddering analysis. However, constitutive expression of HGF by transfection in mIMCD-3 cells resulted in resistance to cisplatin-induced apoptotic death. The survival rate of HGF-producing C1 cells was more than 2-fold greater as compared to control, mIMCD-3 cells following treatment with 25 microM cisplatin for 2 days. These results suggest that HGF may not only activate tubular repair processes but also ameliorate the initial injury by protecting renal epithelial cells from undergoing apoptosis.

Acute Kidney Injury↗