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PubMed · 13857672

[WAR surgery].

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1959-09-17. [WAR surgery].. https://pubmed.ncbi.nlm.nih.gov/13857672/

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The identification of novel potential injury mechanisms and candidate biomarkers in renal allograft rejection by quantitative proteomics.

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↗

[A rare case of birenal malacoplakia with renal failure].

HISTORY AND ADMISSION FINDINGS: A 45 year old man was admitted to our hospital because of fever, loss of appetite, and deterioration of general health. For two weeks the patient suffered from diarrhea which had resulted in moderate volume depletion. In addition, he complained of bilateral flank pain at the time of admission. Furthermore, the patient had a history of heavily drinking alcohol as well as cigarette smoking for many years. He had never attended a medical doctor before. INVESTIGATIONS: The patient presented with the clinical picture of acute renal failure and urosepticaemia which was caused by Escherichia coli. The kidneys were found to be at the upper limit of normal by sonography. Magnetic resonance imaging revealed signal-alterations in both kidneys with hyper- and hypointense zones in the renal parenchyma. DIAGNOSIS: To clarify the cause of rapid deterioration of renal function, we performed a renal biopsy. The histology of the renal specimen revealed an unusual type acute bacterial interstitial nephritis most likely due to an infection with E. coli. The clinical picture, the laboratory findings and renal histology, lead to the diagnosis of birenal malakoplakia. TREATMENT AND COURSE: After intravenous and subsequent oral antibiotic therapy the fever and the clinical signs of urosepticaemia subsided and renal function gradually improved. Antibiotic therapy and supplementation with vitamins were continued for 20 weeks. Five years after initial diagnosis, renal function was stable at a glomerular filtration rate of approximately 45 ml/min. CONCLUSIONS: Malakoplakia of the kidney is a rare form of bacterial interstitial nephritis and requires long-term antibiotic therapy.

Acute Kidney Injury↗

Use of i.v. immune globulin and occurrence of associated acute renal failure and thrombosis.

PURPOSE: The use trends of i.v. immune globulin (IGIV) and the frequency of acute renal failure (ARF) and thrombosis at one institution were studied. METHODS: A retrospective chart review on the indications and dosages of IGIV was conducted with inpatients and outpatients at a Veterans Affairs medical center between May 1, 1998, and June 30, 2003. Patients under 18 years of age were excluded from the study. Patient data were obtained through the center's computerized patient record system and included patient demographics, comorbidities, frequency of ARF, concomitant therapies, and IGIV therapy courses. ARF was defined as an increase in serum creatinine of >/=0.5 mg/dL within 10 days from the initiation of IGIV therapy. RESULTS: Forty-six patients were identified as receiving at least one cycle of IGIV therapy between May 1, 1998, and June 30, 2003. The three main indications for IGIV therapy were hypogammaglobulinemia, idiopathic thrombocytopenic purpura (ITP), and chronic inflammatory demyelinating polyneuropathy (CIDP). No new cases of thrombosis were found. Six patients (13%) developed ARF after IGIV administration, but none required dialysis. A greater percentage of patients with ARF were 65 years or older, had chronic renal insufficiency or diabetes mellitus, and used nephrotoxic agents, compared with patients who did not develop ARF. No association was observed between ARF and underlying primary disease. CONCLUSION: A retrospective review of 46 courses of IGIV therapy showed that the therapy was most often used for hematologic, neurologic, and immunologic indications, and the most common diagnoses for which it was used were hypogammaglobulinemia, ITP, and CIDP. ARF developed in 13% of patients, but no case of thrombosis was reported.

Acute Kidney Injury↗