Clinicopathologic features of infection-related glomerulonephritis with IgA deposits: a French Nationwide study.

BACKGROUND: Infection-related glomerulonephritis with IgA deposits (IRGN-IgA) is a rare disease but it is increasingly reported in the literature. Data regarding epidemiology and outcome are lacking, especially in Europe. We aimed to assess the clinical, pathologic and outcome data of IRGN-IgA. METHODS: Clinical and outcome data from patients from 11 French centers over the 2007-2017 period were collected retrospectively. We reviewed pathologic patterns and immunofluorescence of renal biopsies and evaluated C4d expression in IRGN-IgA. We analyzed the correlation between histological presentation and outcome. RESULTS: Twenty-seven patients (23 men, mean age: 62 ± 15 years) were included. Twenty-one (78%) had Staphylococcus aureus infection and twelve (44%) were diabetic. At the time of biopsy, 95.2% had haematuria, 48.1% had a serum creatinine level of > 4 mg/dL, and 16% had hypocomplementemia. The most common pathologic presentation included mesangial (88.9%) and endocapillary proliferative glomerulonephritis (88.9%) with interstitial fibrosis and tubular atrophy (IF/TA) (85.1%). Diffuse and global glomerular C4d expression was found in 17.8%, mostly in biopsies with acute or subacute patterns, and was associated with a short delay between infection and renal biopsy compared to segmental and focal staining. After median follow-up of 13.2 months, 23.1% died, 46.2% had persistent renal dysfunction and 15.4% reached end-stage renal disease. Renal outcome was correlated to IF/TA severity. CONCLUSIONS: Infection-related glomerulonephritis with IgA deposits is usually associated with Staphylococcus infections and mainly affects adult men. This entity has a poor prognosis which is correlated to interstitial fibrosis and tubular atrophy severity.

Bilateral renal cortical necrosis with end-stage renal failure following envenoming by Proatheris superciliaris: a case report.

Acute bilateral renal cortical necrosis (BRCN) has been reported following envenoming by exotic venomous snakes. Proatheris superciliaris is a rare viper with restricted distribution in east Africa. Very little information is available on envenoming by this species. We herein describe the case of a 60-year-old professional wildlife photographer who was bitten on his thumb while photographing an adult specimen of P. superciliaris that he held at home in France. On admission, physical examination revealed severe hypertension and bruising with edema at the bite site. Within the following 24 h, he developed vomiting, diarrhea, acute lumbar pain and anuria. Laboratory tests showed acute kidney injury (serum creatinine 4.6 mg/dL), with thrombocytopenia, anemia and severe coagulopathy. Contrast-enhanced computed tomography scan revealed hypodense areas in the cortex of both kidneys consistent with diffuse BRCN. As no appropriate antivenom existed, only symptomatic care was given to the patient. Coagulation tests returned to normal within 48 h. The patient was placed on chronic hemodialysis, until he underwent successful kidney transplantation 18 months later. In developed countries, severe complications provoked by snake bites tend to be more frequent with the number of trendy exotic pets. Acute kidney injury, including BRCN, is a classic complication of viper bites. The present case of end-stage renal failure related to diffuse BRCN illustrates the potentially devastating effects of envenoming by P. superciliaris. Clinicians in developed countries should be informed about renal disorders and other potentially fatal complications of venomous snake bites and seek urgent expert advice for optimizing clinical management. Education and coaching of envenomed patients and exotic snake owners is mandatory to prevent dramatic accidents.

[Renal disorders associated with monoclonal gammopathies: diagnostic and therapeutic progress]. / Atteintes rénales des dysglobulinémies: avancées diagnostiques et thérapeutiques.

Various renal disorders are associated with monoclonal gammopathies, secondary to tissue deposition or precipitation of a monoclonal immunoglobulin (Ig) or a fragment thereof (isolated Ig light chain or heavy chain). They are classified according to the localization of renal lesions, either glomerular or tubular and to the pattern of ultrastructural organization of Ig deposits. Renal disease in monoclonal gammopathies may be isolated, or associated with various systemic symptoms particularly in AL amyloidosis, Randall-type monoclonal Ig deposition disease and monoclonal cryoglobulinemias. Except for myeloma cast nephropathy, which occurs in the setting of high-mass myeloma and is recognized after electrophoretic analysis of proteinuria and AL amyloidosis, which diagnosis is usually made after pathological examination of non-invasive tissue specimens (i.e. abdominal fat or minor salivary glands), a kidney biopsy is required to identify the other types of renal disorders associated with monoclonal gammopathies and to estimate renal prognosis. Renal pathological diagnosis is difficult and relies on careful examination of kidney biopsy samples, by light microscopy, immunofluorescence studies using conjugates specific for Ig light and heavy chains, IgG sub-classes and heavy chain constant domains and by electron microscopy. In some cases, additional studies are required to identify the nature of deposits, such as immuno-electron microscopy or mass spectrometric-based proteomic analysis after laser dissection. In patients with renal disorders related to Ig light chain precipitation or deposition (myeloma cast nephropathy, AL amyloidosis, Randall-type light chain deposition disease), measurement of serum free light chains at baseline and throughout follow-up is mandatory to evaluate clonal response to chemotherapy. A more than or equal to 50% decrease in serum free light chain levels is associated with increased renal and patient survival. In AL amyloidosis, serum levels of markers of cardiac disease (NT-proBNP and troponin) are also closely associated with prognosis. Efficient chemotherapy, tailored to the underlying plasma cell or lymphoproliferative disorder and adapted to renal function, should be promptly introduced, even in the absence of overt malignant haematological disease. Renal prognosis and patient survival (particularly in AL amyloidosis and cast nephropathy) are closely associated with the rapid achievement of an haematological response. The combination of melphalan plus dexamethasone (MDex) is currently used as first-line chemotherapy in systemic AL amyloidosis. Bortezomib-based regimens are commonly employed as first-line treatment in myeloma cast nephropathy and Randall-type monoclonal Ig deposition disease and as second line therapy in AL amyloidosis patients with advanced cardiomyopathy or refractory to previous chemotherapy. Solid organ transplantation (heart and kidney) should be considered in patients with AL amyloidosis or Randall-type monoclonal Ig deposition disease and advanced cardiac or renal failure. Prolonged graft and patient survival may be obtained, providing that recipients do not have other severe organ involvement or symptomatic myeloma and that haematological remission has been achieved with chemotherapy before or after organ transplantation.

Cyclophosphamide therapy for corticoresistant drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome in a patient with severe kidney and eye involvement and Epstein-Barr virus reactivation.

DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome is a severe adverse drug reaction with significant mortality, characterized by erythroderma, fever, lymphadenopathy, and visceral involvement. We report a case of multivisceral DRESS syndrome with posterior multifocal placoid pigment epitheliopathy and acute tubulointerstitial nephritis responsible for dialysis-dependent acute kidney failure in the context of reactivation of Epstein-Barr virus infection. Because of resistance of the skin and kidney manifestations to prolonged corticosteroid therapy, a 6-month course of oral cyclophosphamide resulted in complete recovery of all symptoms. To our knowledge, this is the first case showing the efficacy of cyclophosphamide in severe DRESS syndrome.