Membranous nephropathy and lupus-like syndrome after hematopoietic cell transplantation: a case report

<p>Abstract</p> <p>Introduction</p> <p>The kidney is increasingly recognised as a target organ of chronic graft-versus-host disease after hematopoietic cell transplantation in the context of the development of the nephrotic syndrome. Chronic graft-versus-host disease is associated with autoimmune phenomena similar, but not identical, to those observed in various rheumatologic disorders, implicating autoimmunity as an important component of the disease.</p> <p>Case presentation</p> <p>We report the case of a 57-year-old Caucasian man who developed the nephrotic syndrome due to membranous nephropathy in association with recurrent chronic graft-versus-host disease, along with a lupus-like syndrome manifested with pancytopenia, hair loss, positive anti-DNA antibodies and sub-epithelial and mesangial immune deposits. To the best of our knowledge, this is the first case reported in the literature. The nephrotic syndrome subsided soon after he was treated with a short course of cyclosporin with steroids. Unfortunately he died seven months later due to a relapse of leukemia.</p> <p>Conclusions</p> <p>Our case report confirms the notion that chronic graft-versus-host disease is characterized by the appearance of autoimmune phenomena similar, but not identical, to those seen in autoimmune diseases. The decision for more immunosuppression has to be weighed against the need for preservation of the graft versus leukemia phenomenon.</p

Blocking glomerular immunoglobulin deposits in a mouse model of lupus nephritis on indirect immunofluorescence with the use of Fab fragments

One of the most characterized models of murine lupus nephritis is the [NZB x NZW] F1 female hybrid. Extended glomerular IgG deposits may pose an obstacle in studying molecules of interest via indirect immunofluorescence due to secondary antibodies non-specific binding to deposited IgG molecules. Application of Fab fragments may mitigate non-specific interactions in this mouse model. Specifically we provide evidence that blocking paratopic interactions of secondary antibodies with indigenous glomerular IgG deposits is possible. However the blocking effect seems to be related to the species used for secondary antibody production. Increased secondary antibody host species homology with the mouse could make blocking of non-specific binding via the use of Fab fragments impossible in this mouse model. (c) 2011 Elsevier B.V. All rights reserved

The role of serum magnesium and calcium on the association between adiponectin levels and all-cause mortality in end-stage renal disease patients.

BACKGROUND: Adiponectin (ADPN) is the most abundant adipocyte-specific cytokine that plays an important role in energy homeostasis by regulating lipid and glucose metabolism. Studies of the impact of ADPN on clinical outcomes have yielded contradictory results so far. Here, we examined the association of ADPN with serum magnesium (s-Mg) and calcium (s-Ca) levels and explored the possibility whether these two factors could modify the relationship between ADPN and all-cause mortality in patients with end-stage renal disease. METHODOLOGY/PRINCIPAL FINDINGS: After baseline assessment, 47 hemodialysis and 27 peritoneal dialysis patients were followed- up for a median period of 50 months. S-Mg and s-Ca levels emerged as positive and negative predictors of ADPN levels, respectively. During the follow-up period 18 deaths occurred. There was a significant 4% increased risk for all-cause mortality for each 1-µg/ml increment of ADPN (crude HR, 1.04; 95% CI, 1.01-1.07), even after adjustment for s-Mg and s-Ca levels, dialysis mode, age, albumin and C-reactive protein. Cox analysis stratified by s-Mg levels (below and above the median value of 2.45 mg/dl) and s-Ca levels (below and above the median value of 9.3 mg/dl), revealed ADPN as an independent predictor of total mortality only in the low s-Mg and high s-Ca groups. Furthermore, low s-Mg and high s-Ca levels were independently associated with malnutrition, inflammation, arterial stiffening and risk of death. CONCLUSIONS/SIGNIFICANCE: The predictive value of ADPN in all-cause mortality in end-stage renal disease patients appears to be critically dependent on s-Mg and s-Ca levels. Conversely, s-Mg and s-Ca may impact on clinical outcomes by directly modifying the ADPN's bioactivity

Rapamycin Ameliorates Proteinuria and Restores Nephrin and Podocin Expression in Experimental Membranous Nephropathy

Objective. Recent studies have shown a beneficial effect of rapamycin in passive and active Heymann Nephritis (HN). However, the mechanisms underlying this beneficial effect have not been elucidated. Methods. Passive Heymann Nephritis (PHN) was induced by a single intravenous infusion of anti-Fx1 in 12 Sprague-Dawley male rats. One week later, six of these rats were commenced on daily treatment with subcutaneous rapamycin 0.5 mgr/kg (PHN-Rapa). The remaining six rats were used as the proteinuric control group (PHN) while six more rats without PHN were given the rapamycin solvent and served as the healthy control group (HC). All rats were sacrificed at the end of the 7th week. Results. Rapamycin significantly reduced proteinuria during the autologous phase of PHN. Histological lesions were markedly improved by rapamycin. Immunofluorescence revealed attenuated deposits of autologous alloantibodies in treated rats. Untreated rats showed decreased glomerular content of both nephrin and podocin whereas rapamycin restored their expression. Conclusions. Rapamycin monotherapy significantly improves proteinuria and histological lesions in experimental membranous nephropathy. This beneficial effect may be mediated by inhibition of the alloimmune response during the autologous phase of PHN and by restoration of the normal expression of the podocyte proteins nephrin and podocin

Prognostic Utility of Impedance Cardiography Measurements in Elderly Hemodialysis Patients with Coronary Artery Disease

Aim: We evaluated the utility of impedance cardiography (IC) in elderly hemodialysis (HD) patients with coronary artery disease (CAD). Patients and Methods: Seventy-five HD patients (30 with CAD) participated. IC cardiac output (ICCO), systemic vascular resistance and pulse pressure (PP) were calculated at baseline, and 30 and 180 days after study entry. ICCO was compared to echocardiography cardiac output (ECO). Relationships of IC measurements and cardiovascular mortality were assessed. Patients were followed up for 6 years after study entry or until death due to cardiovascular events. Results: ICCO and ECO were strongly correlated (r = 0.94, p &lt; 0.001). ICCO correlated inversely with PP (r = -0.61; p &lt; 0.001). Thirty fatal cardiovascular events were recorded. Using the bayesian’ information criterion, multivariate Cox regression models revealed that increased PP and New York Heart Association (NYHA) class as well as decreased diastolic blood pressure (DBP) were predictors of cardiovascular mortality. Having a DBP &lt; 60 mm Hg (adjusted for NYHA) yielded a hazard ratio of 2.8 (95% confidence interval = 1.2-6.7). Conclusion: IC accurately estimates the hemodynamic status in HD patients with CAD. Deterioration of cardiovascular performance expressed by decreased DBP values, adjusted for NYHA, may help to predict outcome. Copyright (c) 2008 S. Karger AG, Base

Androgen deficiency and endothelial dysfunction in men with end-stage kidney disease receiving maintenance hemodialysis

Two thirds of men with end-stage kidney disease (ESKD) have serum testosterone levels in the hypogonadal range. We examined if low serum testosterone levels were correlated with measures of endothelial dysfunction in ESKD. Bilateral common carotid artery (CCA) intima-media thickness (IMT) and atherosclerotic plaque occurrence, left ventricular mass index, flow- (FMD) and nitrate-mediated vasodilatation (NMD) of the brachial artery were determined by ultrasound imaging in 100 nondiabetic men with ESKD (50 men exhibited androgen deficiency; serum testosterone concentrations <300 ng/dl). Left-ventricular mass index, CCA diameter, CCA-IMT and atherosclerotic plaque occurrence were all significantly increased in ESKD patients with androgen deficiency compared with patients without androgen deficiency (p < 0.05). Also, FMD and NMD measurements were significantly reduced in the former compared with the latter (p < 0.05). Testosterone levels were inversely correlated with age and duration of hemodialysis therapy (r = -0.44 and r = -0.55; p < 0.001). Testosterone levels were negatively correlated to CCA-IMT and atherosclerotic plaque occurrence in patients with androgen deficiency (r = -0.32, p < 0.003, and r = -0.23, p < 0.04, respectively). FMD and NMD measurements were positively correlated to total (r = 0.65 and r = 0.61; both p < 0.0001) and free (r = 0.52 and r = 0.48; both p < 0.001) testosterone levels in patients with low androgenicity. The present results indicated that ESKD patients with androgen deficiency had increased CCA-IMT, atherosclerotic plaque occurrence and reduced FMD and NMD compared with patients without androgen deficiency. Testosterone serum levels were negatively correlated to CCA-IMT and positively correlated to endothelium-dependent vasodilatation in ESKD patients with androgen deficienc