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Background: Tacrolimus has been reported to be effective in refractory nephrotic syndrome, such as focal segmental glomerulosclerosis and membranous nephropathy. Some IgA nephropathy (IgAN) patients with massive proteinuria showed resistance to steroids and/or cytotoxic immunosuppressants based on the supportive therapy with renin- angiotensin system blockade. The efficacy and safety of tacrolimus in such refractory IgAN patients are extremely ambiguous, and the mechanism of tacrolimus improving proteinuria remission needs to be investigated. Methods: 14 refractory IgAN patients were enrolled. The patients received tacrolimus (0.05-0.1 mg/kg/day) and prednisone (0.5 mg/kg/day) for at least 6 months. Synaptopodin and calcineurin expression were detected in renal tissues of patients who received re-biopsy. A puromycin aminonucleoside (PAN)-induced human podocyte injury model was applied to investigate the possible role of tacrolimus in proteinuria remission. Results: Of the 14 patients enrolled, 3 were withdrawn because serum creatinine increased over 30% baseline. In 11 patients treated with tacrolimus over 6 months, 9 showed complete or partial remission and 7 achieved remission within 1 month. In renal tissues, the expression of calcineurin increased while synaptopodin decreased and recovered partially after tacrolimus therapy. In an in vitro study, F-actin disrupted in human podocytes after stimulation of PAN, while calcineurin increased and synaptopodin decreased. After co-treatment with tacrolimus the reorganization of F-actin and the expression of calcineurin and synaptopodin recovered. Conclusions: Tacrolimus showed a rapid proteinuria remission in refractory IgAN patients. The possible mechanism of tacrolimus to proteinuria remission might be podocyte cytoskeleton stabilization through inhibition of calcineurin expression. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background. Massive proteinuria is often associated with hypoalbuminaemia in glomerulopathy. However, patients may have normal levels of serum albumin despite heavy proteinuria in many circumstances. This study analysed factors affecting serum levels of albumin in primary glomerulopathy patients with nephrotic-range proteinuria.Methods. The renal histopathological data of 780 consecutive adult patients (age ≥ 18 years old) with primary glomerulopathy and nephrotic-range proteinuria, who received native renal biopsies in Peking University First Hospital from 1998 to 2007, were retrospectively analysed.Results. Compared with patients with hypoalbuminaemia (serum albumin < 30 g/L), patients without hypoalbuminaemia were significantly younger (P < 0.001) and had significantly lower levels of proteinuria (P < 0.001). Patients without hypoalbuminaemia had a significantly higher proportion of IgA nephropathy (66.0% vs. 17.2%, P < 0.001). The independent predictors of hypoalbuminaemia in nephrotic-range proteinuria patients included age, gender, interval between onset of the disease and renal biopsy, proteinuria level, and pathological type of glomerulopathy. A serum level of albumin ≥ 35 g/L could predict IgA nephropathy with a specificity of 95.8%, and specificity increased with age.Conclusions. Among patients with primary glomerulopathy and nephrotic-range proteinuria, normoalbuminaemia is associated with IgA nephropathy. [ABSTRACT FROM AUTHOR]

Abstract: Aberrant glycosylation of serum IgA1 was considered as an initial event and involvement in the pathogenesis of IgAN. We previously demonstrated that aberrant glycosylation of serum IgA1 was associated with pathologic phenotype of IgAN. The present study is to investigate if abnormal sialylation of IgA1 affects renal survival of IgAN. 127 patients with biopsy-proven IgAN were enrolled and followed up to 8 years. Seventy-nine healthy and 75 patients with non-IgAN renal diseases were selected as controls. Alpha 2, 6 sialic acid (SA) of serum IgA1 was measured by sandwich-ELISA. Renal survival rate was estimated by Kaplan–Meier method. Alpha 2, 6 SA level in patients with IgAN was lower than that in healthy controls (0.92±0.14 vs. 0.98±0.12, P =0.001) and non-IgAN glomerulonephritis (0.92±0.14 vs. 1.00±0.18, n =53, P =0.001). Patients with IgAN in Low SA Group were no significant differences compared with patients in Normal SA Group in age, gender, hypertension, serum creatinine, and excretion of proteinuria. Renal cumulative survival rate was 53.3% in patients in Low SA Group and 83.5% in Normal SA Group (P =0.0008). The lower the alpha 2, 6 SA level of serum IgA1 in patients with IgAN was, the worse their renal survival rate was. Although patients in Low SA Group had worse renal function evaluated by eGFR, there was no significant difference in various CKD stages in non-IgAN renal function controls (n =42, P =0.352). Alpha 2, 6 SA level of serum IgA1 was associated with the prognosis of patients with IgAN and could serve as a predictor of poor prognosis in IgAN. [Copyright &y& Elsevier]