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

Comparison of methods for the diagnosis of renal artery stenosis and study of outcomes following restoration of stenosis with angioplasty

AbstractBackgroundWe evaluated the effectiveness of percutaneous renal revascularization (PRR) with stenting for the treatment of atherosclerotic renal artery stenosis (ARAS) in patients with coronary artery disease (CAD) and the usefulness of captopril renal scintigraphy (CRS) for predicting clinical outcomes after PRR. Methods. Sixty four consecutive patients, referred for evaluation of suspected ARAS, after aortography obtained during coronary angiography, underwent baseline CRS followed by renal angiography. Forty four patients (68.7 %) were diagnosed with a significant ARAS ≥60% and were treated with PRR plus medical treatment. CAD was confirmed in 75% (48/64) of our patients. Outcome assessments were undertaken at baseline and 3 and 24 months after PRR. Results. At the end of the study, 86.4% (38/44) of PRR patients showed a hypertension benefit (cure or improvement) and 73.3% (34/44) a renal benefit (improvement or stabilization). CRS had a moderate ability to diagnose ARAS (sensitivity 57% and specificity 75%), but the combination of CRS with the extent of CAD and the number of antihypertensive drugs achieved a significantly higher diagnostic accuracy for identifying ARAS (sensitivity 87% and specificity 75%). CRS positivity had a sensitivity and specificity of 66% and 100%, respectively, for predicting a hypertension benefit, and 71% and 90% respectively for predicting a renal function benefit. In 13 patients with ARAS ≥70%, the sensitivity and specificity were 100% for both a hypertension and renal function benefit. Conclusions. PRR for ARAS conferred a substantial hypertension and renal benefit in patients with a high CAD burden. CRS was highly accurate in predicting clinical outcomes after PRR in patients with ARAS ≥ 70% and efficient in those with ARAS ≥ 60%.Μελετήσαμε την αποτελεσματικότητα της διαδερμικής νεφρικής επαναιμάτωσης (ΔΝΕ) με τοποθέτηση ενδοπρόθεσης (stent), για την αντιμετώπιση της αθηρωματικής στένωσης της νεφρικής αρτηρίας (ΑΣΝΑ), σε ασθενείς με στεφανιαία νόσο (ΣΝ), και τη χρησιμότητα του σπινθηρογραφήματος νεφρών με καπτοπρίλη (ΣΝΚ) όχι απλά για τη διάγνωση της ΑΣΝΑ όπως γίνεται στις περισσότερες μελέτες, αλλά κυρίως για την πρόβλεψη της κλινικής έκβασης μετά τη ΔΝΕ. Συνολικά παραπέμφθηκαν για εκτίμηση 64 ασθενείς με υποψία ΑΣΝΑ, μετά από στεφανιογραφικό έλεγχο. Όλοι υποβλήθηκαν σε ΣΝΚ βάσεως και στη συνέχεια σε ψηφιακή αφαιρετική αγγειογραφία νεφρικών αρτηριών.Σε 44 ασθενείς (68.7%) διαγνώστηκε σημαντική ΑΣΝΑ με στένωση αυλού ≥60% που ακολούθως αντιμετωπίστηκαν με διαδερμική νεφρική επαναιμάτωση και βέλτιστη φαρμακευτική αγωγή. Εικοσιτέσσερις μήνες μετά τη ΔΝΕ, το 86,4% και 73,3% των ασθενών είχαν όφελος αναφορικά με τη βελτίωση της ΑΥ και της νεφρικής λειτουργίας, αντιστοίχως.Το θετικό ΣΝΚ είχε μέτρια ευαισθησία και υψηλή ειδικότητα για την πρόβλεψη οφέλους στην ΑΠ και στη νεφρική λειτουργία. Όμως, σε ασθενείς με μεγαλύτερη στένωση (≥70%), η ευαισθησία και η ειδικότητα ήταν 100%, στην πρόβλεψη οφέλους τόσο για την ΑΠ, όσο και για τη νεφρική λειτουργία. Η ΔΝΕ παρέχει σημαντικό όφελος σε ασθενείς με σημαντικού βαθμού ΑΣΝΑ. Το ΣΝΚ προβλέπει με υψηλή ακρίβεια τα κλινικά αποτελέσματα

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

The P274S Mutation of Lecithin-Cholesterol Acyltransferase (LCAT) and Its Clinical Manifestations in a Large Kindred

Rationale & Objective: Lecithin-cholesterol acyltransferase (LCAT) catalyzes the maturation of high-density lipoprotein. Homozygosity for loss-of-function mutations causes familial LCAT deficiency (FLD), characterized by corneal opacities, anemia, and renal involvement. This study sought to characterize kidney biopsy findings and clinical outcomes in a family with FLD. Study Design: Prospective observational study. Setting & Participants: 2 (related) index patients with clinically apparent FLD were initially identified. 110 of 122 family members who consented to genetic analysis were also studied. Predictors: Demographic and laboratory parameters (including lipid profiles and LCAT activity) and full sequence analysis of the LCAT gene. Kidney histologic examination was performed with samples from 6 participants. Outcomes: Cardiovascular and renal events during a median follow-up of 12 years. Estimation of annual rate of decline in glomerular filtration rate. Analytical Approach: Analysis of variance, linear regression analysis, and Fine-Gray competing-risk survival analysis. Results: 9 homozygous, 57 heterozygous, and 44 unaffected family members were identified. In all affected individuals, full sequence analysis of the LCAT gene revealed a mutation (c.820C>T) predicted to cause a proline to serine substitution at amino acid 274 (P274S). Homozygosity caused a complete loss of LCAT activity. Kidney biopsy findings demonstrated lipid deposition causing glomerular basement membrane thickening, mesangial expansion, and “foam-cell” infiltration of kidney tissue. Tubular atrophy, glomerular sclerosis, and complement fixation were associated with worse kidney outcomes. Estimated glomerular filtration rate deteriorated among homozygous family members at an average annual rate of 3.56 mL/min/1.73 m 2 . The incidence of cardiovascular and renal complications was higher among homozygous family members compared with heterozygous and unaffected members. Mild thrombocytopenia was a common finding among homozygous participants. Limitations: The presence of cardiovascular disease was mainly based on medical history. Conclusions: The P274S LCAT mutation was found to cause FLD with renal involvement. Tubular atrophy, glomerular sclerosis, and complement fixation were associated with a worse renal prognosis