[Clinical significance of urinary cholesterol/total protein ratio as a marker of selectivity of proteinuria: comparison with selectivity index].

Selectivity index (SI) has been reported to reflect the selectivity of proteinuria, and it has a relationship with tubulointerstitial damage. Moreover it has a predictive value on functional outcome. However, it is necessary to measure serum IgG, serum transferrin, urinary IgG, and urinary transferrin to calculate SI. We measured urinary micro-cholesterol (mCHO) levels in sixty-three patients with proteinuria (urinary total protein > or = g/gCr) and compared urinary mCHO/total protein(uTP) ratio and SI. The patients' diseases were minimal change nephrotic syndrome (MCNS, n = 12), focal and segmental glomerular sclerosis (FSGS, n = 12), membranous nephropathy (MN, n = 17), and diabetic nephropathy (DMN, n = 22). Urinary mCHO levels were measured by the ECC method using cholesterol ester hydrolase (CEH) and cholesterol dehydrogenase, and this method was performed conveniently by automatic analyzer. No correlation was observed between urinary mCHO/gCr and serum lipid levels. There was no difference of urinary protein levels among each disease group. We found urinary mCHO/uTP ratio has a good positive correlation with SI(R = 0.722, p < 0.001). Although the difference between ROC curves of SI and urinary mCHO/uTP ratio in distinguishing MCNS from other diseases (FSGS+MN+DMN) did not reach the statistical significance, the area under the curve was larger for mCHO/uTP ratio. These results suggest that measurement of urinary mCHO by ECC method can be a simple and useful tool for predicting selectivity of proteinuria and lipoprotein-loading tubulopathy.

[Soluble fibrin is not excreted in urine and its plasma level is elevated in nephrotic syndrome].

Soluble fibrin (SF) is produced by activated blood coagulation reaction and is useful to diagnose thrombotic diseases. We measured plasma and urine SF levels in nephritic patients to assess the hypercoagulability state associated with the disease. Before they received anti-coagulation or anti-platelet therapies, 60 patients underwent measurement of plasma SF and D-dimer levels by Latex agglutination turbidimetric immnoassay (LA). Urinary SF levels were also measured by LA. Plasma and urinary thrombin antithrombin III complex (TAT) levels were measured by enzyme immunoassay (EIA). Plasma SF levels showed a good correlation with plasma TAT levels but only weak positive correlations were observed between plasma D-dimer and SF or TAT levels. Plasma SF and D-dimer levels were significantly higher in the Iatients with nephrotic-range hypoalbuminemia (< or =3 g/dL) than those without it. Contrarily there was no significant difference in plasma TAT levels between these two groups of patients. In almost all patients, urinary SF levels were under the detection limit. However, TAT was excreted into urine more frequently in patients showing the nephrotic range of hypoalbuminemia at 38.2% than in non-nephrotic patients at 8.0%. Thus, plasma SF levels more precisely indicate activated blood coagulation reaction than plasma TAT levels in nephrotic patients, probably because the plasma SF is not excreted into urine, while plasma TAT is.

Efficacy of statin on vascular access patency in diabetic hemodialysis patients.

INTRODUCTION: An effective approach to prevent hemodialysis vascular access dysfunction is still unclear despite previous studies, which have shown conflicting results of several drugs on vascular access outcomes. In this study, we focused on diabetic hemodialysis patients with native arteriovenous fistula and evaluated the impact of statin treatment on vascular access patency. METHODS: A retrospective cohort study of 268 consecutive patients who newly started hemodialysis due to diabetic nephropathy between January 2011 and December 2013 at Japan Community Health Care Organization Sendai Hospital was performed and the patients were followed for two years. The primary outcome was vascular access dysfunction. Effect of statin treatment was examined using Kaplan Meier analysis and Cox proportional hazard, after adjusting for covariates. RESULTS: The mean follow-up period was 426.7 days, and 117 (52.2%) patients developed vascular access dysfunction. The two-year patency rate was 55.0% among statin users and 36.1% in non-users. Vascular access survival period was significantly longer among statin users (log-rank test, p = 0.004). In multivariable analysis, statin treatment is significantly associated with better vascular access outcomes, in which the hazard ratio was 0.71 (95% CI, 0.52 to 0.97; p = 0.028) in the unadjusted model and 0.63 (95% CI, 0.45 to 0.88; p = 0.007) after adjustment for covariates. CONCLUSIONS: Statin treatment could be associated with improved vascular access dysfunction among diabetic hemodialysis patients.

Predictive value of urinary micro-cholesterol (mCHO) levels in patients with progressive glomerular disease.

BACKGROUND: Trace amounts of lipids are present in the urine of patients with glomerular disease, raising the possibility that the excess lipids reabsorbed by tubule cells may be toxic to these cells. In the present study, we assessed the prognostic value of micro-cholesterol (mCHO) levels in patients with chronic glomerular disease. METHODS: The urinary mCHO levels of healthy subjects and patients with chronic kidney disease were measured by the enzymatic cholesterol cycling (ECC) method with a minimum detection level of 0.10 x 10(-3) mmol/L. First, the urinary mCHO levels of healthy subjects and 320 patients with various glomerular diseases with proteinuria >1000 mg/gCr were measured. Second, correlations of urinary mCHO levels with those of various other molecules, including albumin, IgG, IgM, transferrin, phospholipid, alpha1-microglobulin (alpha1MG), Apo A1, Apo A2, and Apo B, and urinary fatty body counts, were determined. Third, urinary mCHO, total protein (TP), albumin, and N-acetyl-beta-D-glucosaminidase (NAG) levels were measured longitudinally over 12 months (20.5 +/- 5.8 months) in 68 nondiabetic patients with impaired renal function [serum creatinine (Cr) > or = 1.5 mg/dL]. Correlations of the concentrations of urinary parameters in the initial 3-month period with the slopes of the reciprocal of creatinine versus time for the entire follow-up period were assessed by the ROC method and multiple regression analysis. RESULTS: Urinary mCHO levels of the healthy subjects were 0.06 to 0.72 mg/gCr for males and 0.16 to 2.34 mg/gCr for females. Urinary mCHO levels in subjects with minimal change nephrotic syndrome were significantly lower than those in the patients with other glomerular diseases with massive proteinuria. Urinary mCHO levels correlated significantly with Apo A1 and Apo A2 levels, but not with urinary Apo B levels, in the latter subjects. The correlation coefficient of urinary fatty body counts (a marker of lipoprotein loading tubulopathy) with mCHO was higher than those with TP, albumin, IgG, IgM, and alpha1MG. The urinary mCHO elevation was significantly greater in patients who had a nonselective index of proteinuria than in those with a highly or moderately selective index. In nondiabetic patients with impaired renal function, the urinary mCHO level had a higher predictive value for rapid decline of renal function than TP, albumin, or NAG. CONCLUSION: The urinary cholesterol level corresponds to the magnitude of urinary HDL excretion, and correlates with the degree of lipoprotein loading tubulopathy. Measurement of urinary mCHO by the ECC method is a simple and useful tool for predicting progression of chronic glomerular disease.

Enhanced expression of C chemokine lymphotactin in IgA nephropathy.

Leukocyte accumulation in the kidney is observed in patients with IgA nephropathy. Chemokines are a large family of cytokines chemotactic for leukocytes and have been shown to be upregulated in renal diseases. We previously reported that the gene expression of lymphotactin, a sole member of C chemokine subfamily, is enhanced in an animal model of crescentic glomerulonephritis, but its expression in human renal diseases is totally unknown. In the present study, we investigated the expression of mRNAs of lymphotactin and some other chemokines in IgA nephropathy. The expression of mRNAs for three chemokines, lymphotactin, MCP-1, and MIP-1beta, in renal cortex was increased and the levels of lymphotactin and MCP-1 mRNAs were statistically higher in patients with glomerular crescents than in those without crescents. These levels also correlated with tubulointerstitial changes and urinary protein excretion. Glomerular levels of mRNAs for lymphotactin and MCP-1, but not MIP-1beta, were higher in IgA nephropathy than controls. By immunohistochemical analysis, lymphotactin was detected in tryptase-positive cells (putative mast cells) in the interstitial space. These results suggest that lymphotactin, as well as MCP-1, may contribute to leukocyte infiltration and disease progression in IgA nephropathy.