A specific biomarker that can separate active renal vasculitis from other causes of renal dysfunction is lacking, with a kidney biopsy often being required. Soluble CD163 (sCD163), shed by monocytes and macrophages, has been reported as a potential biomarker in diseases associated with excessive macrophage activation. Thus, we hypothesized that urinary sCD163 shed by crescent macrophages correlates with active glomerular inflammation. We detected sCD163 in rat urine early in the disease course of experimental vasculitis. Moreover, microdissected glomeruli from patients with small vessel vasculitis (SVV) had markedly higher levels of CD163 mRNA than did those from patients with lupus nephritis, diabetic nephropathy, or nephrotic syndrome. Both glomeruli and interstitium of patients with SVV strongly expressed CD163 protein. In 479 individuals, including patients with SVV, disease controls, and healthy controls, serum levels of sCD163 did not differ between the groups. However, in an inception cohort, including 177 patients with SVV, patients with active renal vasculitis had markedly higher urinary sCD163 levels than did patients in remission, disease controls, or healthy controls. Analyses in both internal and external validation cohorts confirmed these results. Setting a derived optimum cutoff for urinary sCD163 of 0.3 ng/mmol creatinine for detection of active renal vasculitis resulted in a sensitivity of 83%, specificity of 96%, and a positive likelihood ratio of 20.8. These data indicate that urinary sCD163 level associates very tightly with active renal vasculitis, and assessing this level may be a noninvasive method for diagnosing renal flare in the setting of a known diagnosis of SVV.
High field 1H NMR spectroscopy was used for the rapid multicomponent analysis of low molecular wt compounds in urine in order to investigate the patterns of metabolic changes associated with early renal allograft dysfunction. Urine samples were collected daily for 14 days from 33 patients who underwent primary renal allograft transplantation, and analyzed by 500 and/or 600 MHz 1H NMR spectroscopy. All patients received 20 mg prednisolone and 5 mg/kg b.d. oral cyclosporin A (CsA) solution. In this study no patient showed clinical or histopathological evidence of CsA nephrotoxicity. For each patient the NMR-generated metabolite data were correlated with the clinical observations, graft biopsy pathology, and data from conventional laboratory techniques for assessing renal function. The NMR spectra of urine from patients with immediate functioning grafts were similar with respect to their patterns of amino acids, organic acids and organic amines, whereas the patients with delayed or non-functioning grafts showed significantly different metabolite excretion patterns. In longitudinal studies on individual patients there were increased urinary levels of trimethylamine-N-oxide (TMAO), dimethylamine (DMA), lactate, acetate, succinate, glycine and alanine during episodes of graft dysfunction. However, only the urinary concentration of TMAO was statistically significantly higher (P < 0.025) in the urine collected from patients during episodes of graft dysfunction (410 +/- 102 microM TMAO/mM creatinine) than in patients with good graft function (91 +/- 18 microM TMAO/mM creatinine) or healthy control subjects (100 +/- 50 microM TMAO/mM creatinine). These findings suggest that graft dysfunction is associated with damage to the renal medulla which causes the release of TMAO into the urine from the damaged renal medullary cells. This provides a possible novel urinary marker for post-transplant graft dysfunction. This study shows that NMR spectroscopy of biofluids, when used in combination with conventional laboratory techniques, is a valuable aid to renal transplant monitoring.
♦ Background: The percutaneous Seldinger method of peritoneal dialysis catheter (PDC) insertion has gained favor over recent years whereas traditionally it was reserved for patients considered not fit for general anesthesia. This blind technique is believed to be less safe, and is hence avoided in patients with previous laparotomy incisions. Reports on the success of this method may therefore be criticized for selection bias. In those with no prior abdominal surgery the optimal method of insertion has not been established. ♦ Methods: We retrospectively reviewed the outcomes of first-time PDC placements comparing the percutaneous (group P) and surgical (group S) insertion techniques in patients without a history of previous abdominal surgery in a single center between January 2003 and June 2010. We assessed catheter survival at 3 and 12 months postinsertion and compared complication rates between the two groups. ♦ Results: A total of 63 percutaneous and 64 surgical catheter insertions were analyzed. No significant difference was noted in catheter survival rates between group P and group S (86.2% vs 80% at 3 months, p = 0.37; and 78.3% vs 71.2% at 12 months, p = 0.42 respectively). Early and overall peritonitis rates were similar (5% vs 5.3%; p = 1, and 3.5 vs 4.9 episodes per 100 patient-months; p = 0.13 for group P and group S respectively). There were also no significant differences between the two groups in exit site leaks (15.9% in group P vs 6.3% in group S; p = 0.15), poor initial drainage (9.5% in group P vs 10.9% in group S, p = 0.34) or secondary drainage failure (7.9% in group P vs 18.8% in group S, p = 0.09).
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