PubMed Health⌕ Search

Biomedical subjects

Fernando C Fervenza

Publications and source records attributed to Fernando C Fervenza.

13 recordsLinked to original sources
PubMed2026

Obinutuzumab or Tacrolimus in Primary Membranous Nephropathy.

BACKGROUND: Studies of obinutuzumab, a type II anti-CD20 antibody, have shown efficacy in the treatment of hematologic cancers and autoimmune diseases. An evaluation of the efficacy and safety of obinutuzumab in patients with primary membranous nephropathy is needed. METHODS: In a phase 3 trial, we randomly assigned adults with primary membranous nephropathy in a 1:1 ratio to receive intravenous obinutuzumab or oral tacrolimus. The primary end point was complete remission (defined as a urinary protein-to-creatinine ratio of 0.3 or lower and a stable estimated glomerular filtration rate [eGFR]) at week 104. Key secondary end points were complete or partial remission at week 104, complete remission at week 76, a sustained reduction in the eGFR of at least 30%, duration of complete remission, and change in the Patient-Reported Outcomes Measurement Information System Fatigue T score from baseline to week 104. Fixed-sequence hierarchical testing was performed. Safety was assessed. RESULTS: A total of 142 patients underwent randomization. At week 104, complete remission was observed in 26 of 71 patients in the obinutuzumab group and in 4 of 70 patients in the tacrolimus group (37% vs. 6% with multiple imputation for missing data; adjusted difference, 31 percentage points; 95% CI, 18 to 44; P<0.001). The analyses of complete or partial remission at week 104 and complete remission at week 76 also showed a significant treatment effect. The analysis of a sustained eGFR reduction did not show a significant treatment effect; thus, subsequent end points in the hierarchy were not formally tested for significance. Adverse events of grade 3 or higher were reported in 16 patients (22%) in the obinutuzumab group and in 13 patients (19%) in the tacrolimus group; serious adverse events occurred in 12 (17%) and 10 (14%), respectively. There were 61 and 57 infections per 100 patient-years in the obinutuzumab and tacrolimus groups, respectively; 3 and 4 serious infections per 100 patient-years; and 11 and 14 serious adverse events per 100 patient-years. Adverse drug reactions with obinutuzumab included infusion-related reactions, respiratory tract infections, and neutropenia. One patient in each group died during escape therapy. CONCLUSIONS: Obinutuzumab was superior to tacrolimus in inducing complete remission in patients with primary membranous nephropathy. (Funded by F. Hoffmann-La Roche; MAJESTY ClinicalTrials.gov number, NCT04629248.).

Adult↗
PubMed2006

A proliferative glomerulonephritis secondary to a monoclonal IgA.

A distinct entity mimicking immune-complex-mediated glomerulonephritis characterized by a proliferative glomerulonephritis with monoclonal immunoglobulin G (IgG) deposits recently was described. We now report a case of a 35-year-old woman who presented with sudden onset of edema, proteinuria, hematuria, and hypertension. Renal biopsy showed diffuse endocapillary proliferation, mesangial cellularity, and amorphous material in the mesangium. Immunofluorescence examination showed mesangial and capillary wall staining for IgA (2+), C3 (2+), fibrinogen (2+), and lambda (2+). Congo red stain was negative. Electron microscopy showed mesangial and subendothelial deposits with a paracrystalline lattice-like substructure forming parallel linear arrays. Extensive laboratory evaluation showed a small population of monoclonal plasma cells with lambda restriction. The present case suggests that monoclonal IgA deposits also can cause proliferative glomerulonephritis. However, the presence of paracrystalline deposits in association with monoclonal IgA deposits has not been described previously.

Adult↗
PubMed2006

Microscopic polyangiitis associated with thymoma, exacerbating after thymectomy.

A variety of autoimmune diseases has been associated with thymoma, and thymectomy does not always induce remission of these disorders. This case report describes a 50-year-old man who presented with migratory polyarthritis and an anterior mediastinal mass that proved to be a thymoma. Five months after thymectomy, the patient presented with worsening polyarthritis, hematuria, and azotemia. Based on elevated titers of antineutrophil cytoplasmic antibodies directed against myeloperoxidase and renal biopsy showing crescentic necrotizing glomerulonephritis, microscopic polyangiitis was diagnosed. After remission-induction therapy with prednisone and cyclophosphamide, articular symptoms and renal manifestations resolved. Microscopic polyangiitis was not associated previously with thymoma, and this case broadens the spectrum of autoimmune disorders seen with this tumor. Progressive disease seen after thymectomy in this patient has potential implications regarding the pathophysiological characteristics of microscopic polyangiitis and management of patients with this clinical association.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2005

Rituximab for refractory Wegener's granulomatosis: report of a prospective, open-label pilot trial.

RATIONALE: Standard therapy for Wegener's granulomatosis is fraught with substantial toxicity and not always effective. B lymphocytes have been implicated in the pathogenesis of Wegener's granulomatosis. Their depletion has been proposed as salvage therapy for refractory disease. Earlier encouraging reports are confounded by concomitant immunosuppressive medications and include only limited available biomarker data. OBJECTIVES: To evaluate the efficacy and safety of rituximab for remission induction in refractory Wegener's granulomatosis. METHODS: A prospective open-label pilot trial was conducted with 10 patients monitored for 1 yr. Included were patients with active severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, ANCA positivity, and resistance to (or intolerance of) cyclophosphamide. The remission induction regimen consisted of oral prednisone (1 mg/kg/d) and four weekly infusions of rituximab (375 mg/m(2)). Prednisone was tapered and discontinued over 5 mo. Failure to achieve remission, a clinical flare in the absence of B lymphocytes, and inability to complete the glucocorticoid taper were considered treatment failures. MAIN RESULTS: Three women and seven men (median age, 57 yr; range, 25-72 yr) were enrolled. All had ANCA reacting with proteinase-3. The median activity score at enrollment was 6 (range, 5-10). All patients tolerated rituximab well, achieved swift B-lymphocyte depletion and complete clinical remission (activity score, 0) by 3 mo, and were tapered off glucocorticoids by 6 mo. Five patients were retreated with rituximab alone for recurring/rising ANCA titers according to protocol. One patient experienced a clinical flare after B lymphocyte reconstitution. CONCLUSION: In this cohort, rituximab was a well-tolerated and effective remission induction agent for severe refractory Wegener's granulomatosis.

Adult↗
PubMed2005

Recurrent Goodpasture's disease secondary to a monoclonal IgA1-kappa antibody autoreactive with the alpha1/alpha2 chains of type IV collagen.

Goodpasture's disease is characterized by crescentic glomerulonephritis and lung hemorrhage in the presence of anti-glomerular basement membrane (anti-GBM) antibodies. This disease usually is mediated by IgG autoantibodies directed against the noncollagenous domain of the alpha3(IV) collagen chain, the Goodpasture autoantigen. In rare cases, anti-GBM antibodies of IgA or IgM class are involved, but their specificity has not been determined, and their target antigen remains unknown. The authors present the case of a 62-year-old man with anti-GBM disease mediated by a monoclonal IgA-kappa antibody, which progressed to end-stage renal disease despite intensive immunosuppression. The patient underwent living-related kidney transplantation, but lung hemorrhage and crescentic glomerulonephritis recurred, causing the loss of the allograft 2 years later. Indirect immunofluorescence found the presence of circulating IgA antibodies reactive with a basement membrane component, identified by enzyme-linked immunoabsorbent assay and Western blot as the alpha1/alpha2(IV) collagen chains. Sensitivity to digestion with collagenase indicated that IgA bound to epitopes located in the collagenous domain. This is the first case of recurrent Goodpasture's disease secondary to an autoreactive IgA antibody. The specificity of an IgA antibody implicated in the pathogenesis of anti-GBM disease has been investigated for the first time, identifying the alpha1/alpha2(IV) collagen chains as a novel target for nephritogenic antibodies.

Anti-Glomerular Basement Membrane Disease↗
PubMed2005

Renal response after high-dose melphalan and stem cell transplantation is a favorable marker in patients with primary systemic amyloidosis.

BACKGROUND: Primary systemic (AL) amyloidosis is a rare plasma cell disorder characterized by soft-tissue deposition of monoclonal light chain fragments. High-dose melphalan followed by autologous stem cell transplantation currently has become the treatment of choice. Favorable outcome is ensured with achievement of hematologic response, but little is known about organ response. This study was undertaken to determine the prognostic importance of renal response after high-dose melphalan and stem cell transplantation. METHODS: All patients with AL amyloidosis who underwent autologous stem cell transplantation between 1996 and December 2002 were selected for study. Renal response is defined as a 50% or greater reduction in proteinuria with less than 25% decline in renal function. Exclusion criteria included pretransplantation dialysis therapy or dialysis dependence posttransplantation, treatment mortality, lack of proteinuria assessment posttransplantation, and baseline proteinuria with protein less than 1 g/d. RESULTS: Of 105 patients, 47 were excluded for stated reasons. Renal response was achieved in 60.3% of evaluated patients. Proteinuria was reduced by greater than 90% in 37.9% and returned to normal in 15.5%. Median response time was 12 months. Renal response was associated with a greater increase in serum albumin level (P = 0.001), maintenance of renal function (P < 0.001), and better survival (P = 0.0003). Renal responders had better survival regardless of hematologic response (P = 0.01 to 0.05). CONCLUSION: Currently, high-dose melphalan followed by stem cell transplantation is the most effective treatment for AL amyloidosis for those who are eligible. Our data show that renal response after high-dose melphalan followed by stem cell transplantation is associated with improved survival. Renal response is an independent marker of treatment success and can be used in cases in which determination of hematologic response is difficult.

Adult↗
PubMed2005

Acute granulomatous interstitial nephritis secondary to bisphosphonate alendronate sodium.

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world and is characterized by a progressive accumulation of functionally incompetent monoclonal lymphocytes. Renal involvement has been described in CLL but is uncommon. Granulomatous interstitial nephritis is a rare but characteristic hallmark of certain diseases such as sarcoidosis and tuberculosis. These epithelial reactions have also been reported with medications, infections, inflammation, Wegener's granulomatosis, and jejunoileal bypass. We present a 74-year-old woman with a stage 0 chronic lymphocytic leukemia who developed acute renal failure following the initiation of alendronate. The renal biopsy revealed an acute granulomatous interstitial nephritis. Infectious and inflammatory etiologies were ruled out. Hemodialysis was required despite discontinuation of all medications. Partial recovery of renal function occurred after 6 weeks of prednisone therapy and cyclophosphamide. This report describes a unique case of acute granulomatous interstitial nephritis and leukemic cell kidney infiltration by CLL.

Acute Disease↗
PubMed2004

Acute rapamycin nephrotoxicity in native kidneys of patients with chronic glomerulopathies.

BACKGROUND: Based on its success as a transplant immunosuppressor, there is intense interest in using rapamycin in the treatment of progressive glomerulopathies involving native kidneys. However, we call attention to the potential toxicity associated with the use of rapamycin in this setting. METHODS: We conducted a study to examine the efficacy and safety of rapamycin in patients with progressive chronic renal failure. Eleven patients with either focal segmental glomerulosclerosis, immunoglobulin A nephropathy, membranous nephropathy or membrano-proliferative glomerulonephritis and progressive renal failure (defined as an increase in >25% of baseline serum creatinine over the last year or loss of glomerular filtration rate > or =5 ml/min/year as determined by the Cockcroft-Gault formula), proteinuria > or =1.0 g/24 h and with a creatinine clearance of > or 20 ml/min/1.73 m(2) were entered into a 12 month study. Patients were treated with rapamycin, starting at 5 mg/day, orally, aiming for target blood levels of 7-10 ng/dl. All patients were on treatment with an angiotensin-converting enzyme inhibitor and/or an angiotensin receptor blocker, aiming to control blood pressure < or =145/90 mmHg. RESULTS: Six patients developed acute renal failure, defined as an increase in serum creatinine > or =0.5 mg/dl (baseline: 3.2+/-0.9 mg/dl; peak: 5.6+/-1.6 mg/dl; P<0.01, paired t-test). In four patients, discontinuation of the drug resulted in improvement of renal function close to baseline levels. One patient required haemodialysis and had no subsequent recovery of renal function. In another patient, renal function recovered after discontinuation of the drug and then rapamycin was resumed at a lower dose when creatinine returned to baseline. This resulted in a second acute increase in serum creatinine that failed to return to baseline when the medication was discontinued. Four other patients had the following adverse events: skin rash, severe hypertriglyceridaemia, diarrhoea and hyperkalaemia. In none of the subjects were rapamycin levels >15 ng/dl. CONCLUSIONS: Rapamycin can cause nephrotoxicity in some patients with chronic glomerulopathies. Whether the toxicity is solely related to rapamycin, due to the combination of proteinuria and rapamycin, or other unknown factor use is presently undetermined.

Acute Kidney Injury↗
PubMed2004

Long-term outcome of renal transplantation in light-chain deposition disease.

BACKGROUND: Light-chain deposition disease (LCDD) is a monoclonal gammopathy characterized by nonamyloid deposition of light chain in various organs. A small number of kidney transplantations have been performed on LCDD patients in whom end-stage renal disease (ESRD) developed. METHODS: The authors retrospectively reviewed the clinical and histologic findings and outcome of 7 patients with LCDD who underwent kidney transplantation at our institution. RESULTS: Renal insufficiency, hypertension, and proteinuria were present in all 7 patients. Proteinuria level was greater than 3.5 g/24 h in 3 patients. Three patients had microscopic hematuria. Monoclonal protein was detected in the serum in 3 patients, urine in 5, and was undetectable in 2. Median age at presentation was 42.7 (range, 33 to 58) years. The most common renal biopsy findings were mesangial expansion, mesangial nodules, tubular basement membrane thickening, and tubular atrophy. Kappa light chain was detected in all 7 renal biopsy results. Five patients were on dialysis before transplantation. LCDD recurred after a median of 33.3 (range, 2 to 45) months in 5 of the 7 patients. One patient remains on dialysis, whereas the other 4 have died. One patient died of progression of multiple myeloma 3 months after kidney transplantation without evidence of recurrence. Only 1 patient remains recurrence free after 13 years with normal renal allograft function. CONCLUSION: Although long-term benefits are occasionally seen, renal allograft survival is reduced significantly in LCDD patients. Kidney transplantation should not be an option for LCDD patients unless measures have been taken to reduce light chain production.

Adult↗
PubMed2004

A novel alpha-galactosidase a mutant (M42L) identified in a renal variant of Fabry disease.

A 65-year-old man presented to our institution for workup of proteinuria. His serum creatinine level was 1.7 mg/dL (130 micromol/L), and he had proteinuria with protein of almost 5 g/24 h. Fabry disease was diagnosed by means of kidney biopsy and low serum and leukocyte levels of alpha-galactosidase A. Review of his history, family history, physical examinations, and diagnostic studies did not show other findings typical of this disease. His renal function continued to decline, and he eventually underwent a living unrelated renal transplantation 5 years later. Three years after transplantation, his creatinine level is 1.7 mg/dL (130 micromol/L), and corrected iothalamate clearance is 53 mL/min/1.73 m2 . Genetic studies showed that he has a novel missense mutation (M42L) in exon 1. Methionine at codon 42 is highly conserved in eukaryotic alpha-galactosidase A orthologues. This genotype predicts a minor misfolding of alpha-galactosidase A because of a small difference in hydrophobicity between methionine and leucine. His mutation resulted in a very low, but detectable, serum level of alpha-galactosidase A (0.002 U/L; normal range, 0.016 to 0.2 U/L). Cases of Fabry disease that present with predominantly renal manifestations are rare and require a high index of suspicion for diagnosis. Because treatment for Fabry disease recently has become available, it is important for clinicians to be aware of this disease and pursue the diagnosis in cases of otherwise unexplained renal dysfunction.

Aged↗
PubMed2002

The role of growth factors and ammonia in the genesis of hypokalemic nephropathy.

Hypokalemia is a common electrolyte abnormality encountered in clinical practice. It can be identified in an asymptomatic patient undergoing routine electrolyte screening or can manifest itself as part of a number of functional abnormalities in a variety of organs and systems. Among the most commonly recognized complications are profound effects on the cardiovascular and neuromuscular systems, together with abnormalities in acid-base regulation. In humans, hypokalemia contributes to the development of hypertension and predisposes patients to a variety of ventricular arrhythmias, including ventricular fibrillation. Commonly recognized neuromuscular complications include weakness, cramping, and myalgia. Hypokalemia also affects systemic acid-base homeostasis by interfering with multiple components of the renal acid-base regulation and is a frequent cause of metabolic alkalosis. Less known, however, is the role of potassium deficiency in causing progressive renal failure. In animals, potassium deficiency stimulates renal enlargement because of cellular hypertrophy and hyperplasia. If potassium deficiency persists, interstitial infiltrates appear in the renal interstitial compartment, and eventually tubulointerstitial fibrosis develops. In humans, longstanding hypokalemia is associated with the development of renal cysts, chronic interstitial nephritis, and progressive loss of renal function, the so-called hypokalemic nephropathy. This review focuses on the potential mechanisms involved in the development of the hypokalemic nephropathy with emphasis on the role of ammonia and growth factors in its pathogenesis.

Acid-Base Equilibrium↗