PubMed · 8855878
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M Virdee, J Collinson, R H Stables. 1996-10-12. Ticlopidine and renal function.. https://doi.org/10.1016/s0140-6736(05)64958-6
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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.
Systemic sclerosis is a rare connective tissue disorder, potentially affecting several internal organs. Renal disease is seen in 10-40% of the cases, while autopsy studies have shown interstitial renal changes in as many as 80%. Renal involvement is clinically divided into two separate forms; chronic and acute nephritis. Acute nephritis in a patient suffering from systemic sclerosis is termed renal chrisis, and is associated with high morbidity and mortality. Renal crisis in systemic sclerosis is discussed based on a case report and a review of the literature. Treatment with ACE-inhibitors has dramatically improved the prognosis of this complication. Careful surveillance of patients at risk, especially patients with the diffuse type of systemic sclerosis and showing antibodies against RNA-polymerase, as well as early treatment is considered important for the outcome.
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