Manejo de glomerulonefritis membranoproliferativa secundaria a infección por virus de hepatitis C / Management of membranoproliferative glomerulonephritis secondary to infection by hepatitis C virus

Las glomerulonefritis membranoproliferativas son ne-fropatías glomerulares poco frecuentes cuya prevalencia ha disminuido en nuestro medio. Presentan una histología característica y pueden asociarse a diferentes enfermeda-des. La presentación clínica es variada y su diagnóstico de-finitivo requiere realizar una biopsia renal. El tratamiento viene condicionado por la enfermedad de base, tratándose con inmunosupresores cuando existe una disminución del filtrado glomerular.Presentamos el caso de una mujer de 47 años con glo-merulonefritis membranoproliferativa secundaria a infec-ción por de virus de hepatitis C para describir el manejo de este tipo de pacientes, dado que se trata de una patología con una baja prevalencia (AU)

Membranoproliferative glomerulonephritis is an un-common condition that affects the glomeruli of the kid-neys; its prevalence has decreased in our environment. Membranoproliferative glomerulonephritis has a charac-teristic histology that can be associated to different diseas-es. The clinical presentation varies, and to achieve a defin-itive diagnosis a renal biopsy must be done. Treatment is based on the underlying disease; when a drop in glomer-ular filtration rate is detected, immunosuppressants are prescribed.We describe the management of a 47-year-old female with membranoproliferative glomerulonephritis second-ary to hepatitis C virus infection, a condition with very low prevalence (AU)

Parvovirus B19 infection and kidney injury: report of 4 cases and analysis of immunization and viremia in an adult cohort of 100 patients undergoing a kidney biopsy.

BACKGROUND: The seroprevalence of human Parvovirus B19 (PVB19) is 70-85% in adults worldwide. PVB19 is the etiologic agent of the fifth disease, is a cause of aplastic anemia, and can be associated with kidney injury. We aimed to describe the cases of 4 patients with kidney injury related to PVB19 primary infection, and to evaluate the seroprevalence of PVB19 and the incidence of PVB19 primary infection in patients undergoing a native kidney biopsy. METHODS: Cases of PVB19 infection with kidney injury were reviewed from the archives of the department of Nephrology. A systematic screening of anti-PVB19 IgG and IgM antibodies and viral DNA was performed in sera from 100 consecutive patients with a kidney biopsy in 2017-2018. RESULTS: The 4 patients with PVB19 infection-associated kidney disease displayed: one lupus-like glomerulonephritis (GN) without lupus auto-antibodies, one minimal change disease with tubular necrosis, one secondary hemolytic and uremic syndrome and one membrano-proliferative GN. In the 100 patients biopsied, 67 had elevated anti-PVB19 IgG, among whom 8 had elevated IgM, without circulating viral DNA, without any particular renal pathological pattern. One additional patient showed a seroconversion at the time of kidney biopsy, which revealed a class V lupus nephritis. CONCLUSION: PVB19 primary infection can be associated with different kidney diseases. The seroprevalence of PVB19 among patients with a kidney biopsy is similar to the overall population, and primary infection is rarely documented (1%) after systematic screening. Whether PV19 is nephrotoxic, or triggers renal endothelial injury and immune activation, remains to be elucidated.

Rare case of post-varicella membranoproliferative glomerulonephritis presenting with massive proteinuria.

Chicken pox caused by varicella zoster virus is usually a self-limiting disease causing rare life-threatening complications. Involvement of the kidneys is infrequent during the course of the illness. Literature shows rare reports of acute glomerulonephritis following varicella infection. We report a case of 16-year-old boy presenting with anasarca with characteristic healed rashes of chicken pox. His urinalysis revealed a 'massive' nephrotic range proteinuria (16 g/24 hours), gross hematuria and pyuria. A percutaneous renal biopsy showed membranoproliferative glomerulonephritis. Most cases of post-varicella glomerulonephritis have been described in children, massive proteinuria of this range in an immunocompetent adolescent, being an extremely rare entity. Acute proliferative glomerulonephritis in such cases is usually an immune complex hypocomplementaemic glomerulonephritis in response to the zoster infection. Proteinuria in most patients is benign and self-limiting with few fatal reports of crescentic glomerulonephritis progressing to acute renal failure.

Parvoviral infection with systemic impact and renal consequences.

Parvovirus infection is usually asymptomatic especially in immunocompetent adults. When symptomatic it can range from mild to life threatening depending on the patient's age and comorbidities. We report a case of a 40-year-old male patient with parvovirus infection who presented a purpuric rash in distal extremities, acute kidney injury, type II mixed cryoglobulinaemia and hypocomplementaemia. His renal biopsy showed a mesangioproliferative glomerulonephritis with positive immunoreactivity to C3, IgM and C1q. Parvovirus B19 was detected in the biopsy tissue by PCR. He was treated with prednisolone with total remission after 1 month. We discuss the diagnosis of kidney lesion due to parvovirus in an immunocompetent person, which is a very rare condition and its association with the cryoglobulinaemia diagnosis.

Successful entecavir plus prednisolone treatment for hepatitis B virus-associated membranoproliferative glomerulonephritis: A case report.

RATIONALE: Adult-onset hepatitis B virus-associated membranoproliferative glomerulonephritis (HBV-MPGN) is generally refractory, and an effective treatment for this condition has not been established. The indications for steroids in HBV-MPGN are an important clinical concern. PATIENT CONCERNS: A 28-year-old woman with a chronic hepatitis B virus infection developed nephrotic syndrome in her second month of pregnancy, with urinary protein levels of 3 to 10 g/d that continued into her postpartum period. She was a carrier of HBV with HBeAg seroconversion. As her renal impairment could have been a result of pregnancy, we observed her for 10 months postpartum without any intervention. However, spontaneous remission after childbirth was not achieved and urine protein levels were sustained at 1 to 3 g/d. About 10 months after delivery, elevated serum liver enzyme levels were observed. DIAGNOSIS: Biopsies showed MPGN, with deposition of hepatitis B antigen in the glomeruli, and chronic B-type hepatitis with a severity grade of A1F0. She was diagnosed with HBV-MPGN. INTERVENTIONS: The patient was started on entecavir 0.5 mg/d in March 2008. Within 1 month, serum HBV DNA became undetectable; within 3 months, her alanine aminotransferase levels normalized. However, urinary protein excretion did not decrease to <2 g/d. On a second renal biopsy, performed 7 months after entecavir treatment, proliferative lesions of the glomeruli were observed; therefore, prednisolone was started at an initial dose of 30 mg/d. OUTCOMES: Her proteinuria improved immediately and prednisolone was tapered over 10 months. A third renal biopsy showed a remarkable resolution of HBV-MPGN, with a significant decrease in mesangial proliferation and immune complex deposition. HBV reactivation was not observed during the prednisolone treatment. LESSONS: Additional prednisolone therapy in combination with antiviral therapy should be considered for refractory HBV-MPGN, with sufficient care taken regarding HBV reactivation.

Membranoproliferative glomerulonephritis and interstitial nephritis in the setting of Epstein-Barr virus-related hemophagocytic syndrome
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BACKGROUND: Hemophagocytic syndrome (HPS) is a rare, aggressive disorder characterized by dysregulation of lymphocyte and macrophage activity, which culminates in tissue infiltration with hemophagocytosis and ultimately organ failure. Renal involvement frequently ensues and usually results in acute tubular necrosis with associated interstitial inflammation. Less frequently, glomerulopathy can also be found. CASE: We report a case of a 24-year-old Caucasian woman with previous asymptomatic hematuria, mild proteinuria, and normal renal function who presented to us with fever. Laboratory findings revealed pancytopenia, elevated lactate dehydrogenase, and ferritin as well as liver and kidney failure. Renal biopsy showed a tubulointerstitial nephritis superimposed in a membranoproliferative glomerulonephritis with crescents. Extensive etiologic investigation was negative except for Epstein-Barr virus (EBV) viral load. EBV-DNA was then identified by in situ hybridization in the renal biopsy. HPS could be diagnosed with the presence of six criteria: fever, splenomegaly, bicytopenia, high ferritin, hypertriglyceridemia, and high levels of soluble CD25. Steroid therapy was initiated with resolution of HPS as well as complete recovery of renal and liver function. CONCLUSION: In this case, we believe that EBV triggered both HPS and tubulointerstitial nephritis. Steroid therapy successfully treated the inflammatory syndrome, allowing renal function recovery without compromising EBV infection resolution.
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Sofosbuvir and Daclatsvir in Treatment of Hepatitis C Virus-related Membranoproliferative Glomerulonephritis With Cryoglobulinemia in a Patient With Hepatitis C Genotype 4.

Direct antivirals showed dramatic response in hepatitis C virus (HCV) eradication, but their effect on extrahepatic manifestations is still unclear. A 49-year-old woman was referred to us suffering from lower limb edema and frothy urine. Renal biopsy was done and she was diagnosed with HCV-related membranoproliferative glomerulonephritis with cryoglobulinemia. Treatment with interferon plus ribavirin, steroid, and cyclophosphamide was tried but failed. After introduction of a sofosbuvir-based regimen to the treatment, sustained virologic response was achieved and nephrotic syndrome remission was induced successfully. We could conclude that HCV-related membranoproliferative glomerulonephritis with cryoglobulinemia could be treated successfully with immunosuppressive drugs plus sofosbuvir and dacalatasvir.

Profile of glomerular diseases associated with hepatitis B and C: A single-center experience from India.

Hepatitis B and C are known to affect kidneys in a number of ways. Glomerular diseases associated with hepatitis B and C include membranous nephropathy (MN), membranoproliferative glomerulonephritis (MPGN), focal segmental glomerulosclerosis, immunoglobulin A nephropathy, rarely amyloidosis, and fibrillary and immunotactoid glomerulopathy. In a retrospective analysis of kidney biopsy of 534 patients, we found 16 (2.9%) patients of hepatitis B and 11 (2.05%) patients of hepatitis C with glomerular disease. The most common form of glomerulonephritis in hepatitis B patient was MN and in hepatitis C patient was MPGN.

Hepatitis E Virus-Induced Cryoglobulinemic Glomerulonephritis in a Nonimmunocompromised Person.

Hepatitis E virus (HEV)-related kidney disease and symptomatic cryoglobulinemia have been observed in solid-organ transplant recipients. However, HEV RNA in the cryoprecipitate has not yet been assessed. We report what to our knowledge is the first documented case of autochthonous HEV-induced cryoglobulinemic crescentic and membranoproliferative glomerulonephritis in an immunocompetent man with no notable medical history. He presented with edema, hypertension, increased serum creatinine level, and nephrotic syndrome. Type II cryoglobulinemia with monoclonal immunoglobulin G (IgG) κ light chain was detected. Anti-HEV IgG and IgM, as well as HEV RNA, were detected in serum and cryoprecipitate. Histologic analysis of a kidney biopsy specimen revealed features of crescentic and membranoproliferative glomerulonephritis. After HEV clearance, kidney and liver parameters improved and HEV RNA and cryoglobulinemia were undetectable. Hence, we conclude that HEV can cause severe kidney disease and should be considered in cases of unexplained glomerular disease.

Hepatitis C virus-related mixed cryoglobulinemic endocapillary proliferative glomerulonephritis and B-cell non-Hodgkin lymphoma: a case report and literature review.

OBJECTIVE: Chronic HCV (hepatitis C virus) infection is recognized as the major cause of mixed cryoglobulinemia. Cryoglobulins continually precipitate and form deposits on the vascular endothelium of small to medium-sized blood vessels, which may progress to vasculitic syndrome. CASE REPORT: A 44-year-old female patient with chronic HCV infection presented with purpuras, edema and proteinuria. Her renal findings included microscopic hematuria, moderate proteinuria and endocapillary proliferative glomerulonephritis (EnPGN) on renal biopsy. Serum cryoglobulins comprised mixed monoclonal cryoglobulins characterized by IgM kappa. The serum protein electrophoresis revealed a monoclonal M protein (9.0%). CD19 and CD20-positive B-cell oligo-monoclonal expansion in the bone marrow was revealed. Rapid relief of the clinical symptoms, the disappearance of proteinuria and a sharp decrease in the HCV viral load were observed in our case after one year of interferon therapy. CONCLUSIONS: HCV infection-associated extrahepatic manifestations are diverse, which may lead to misdiagnosis. This is the first report of HCV-associated cryoglobulinemic EnPGN and B-NHL, which rapidly responded to interferon.

A Case of Cryoglobulinemic Membranoproliferative Glomerulonephritis Induced by Hepatitis C Virus.

A 61-year-old man with bilateral purpura of the lower limbs and subsequent edema, was hospitalization after renal dysfunction developed. The presence of hepatitis C virus (HCV) RNA and cryoglobulin and the finding of membranoproliferative glomerulonephritis on renal biopsy led to a diagnosis of HCV-related glomerulonephritis due to cryoglobulinemia. Because of the pre-existence of nephrotic syndrome and the continuously increasing serum level of creatinine, treatment with cryofiltration, interferon, and steroids was started. After 5 cryofiltration sessions, the cryocrit level had decreased to 1% and the levels of serum creatinine and proteinuria had also decreased. However, 3 weeks after the start of treatment, nephrotic syndrome developed again and was accompanied by lower-extremity mononeuropathy and renal dysfunction. Thereafter, the patient showed disorientation, an affective disorder, and delirium, and his condition gradually deteriorated. Radiological examination of the head and examination of the cerebrospinal fluid showed no abnormalities. Despite the withdrawal of the interferon therapy and the reduction of the steroid dose, the patient's conditions remained unchanged, and the level of consciousness deteriorated. Although cryofiltration had beneficial effects and plasma exchange was continuously performed, the patient died on the 74th hospital day. Because of the significant changes due to ventilatory support and hemorrhage associated with disseminated intravascular coagulation, the autopsy findings did not allow us to definitively determine whether the symptoms had been caused by the HCV-related membranoproliferative glomerulonephritis or the interferon therapy or both. We have reported this case to provide insight into whether interferon therapy should be administered for HCV-related membranoproliferative glomerulonephritis with marked neurological symptoms due to cryoglobulinemia.

Efficacy and safety of pegylated interferon plus ribavirin for the treatment of hepatitis C virus-positive cryoglobulinemic glomerulonephritis.

BACKGROUND: The most frequent form of renal involvement in patients with hepatitis C infection is cryoglobulinemic membrano-proliferative glomerulonephritis. Nonetheless, some reports indicate that the eradication of the hepatitis C virus may also lead to the remission of this renal disease. METHODS: The virological, immunological and nephrological response to pegylated interferon α plus ribavirin (48 weeks in patients infected with genotype 1, and 24 weeks for patients infected with genotypes 2 and 3) was evaluated retrospectively in 10 patients with cryoglobulinemic glomerulonephritis. RESULTS: 6 patients obtained end of treatment virological response (60%); during follow-up, 2 relapsed, and 4 patients maintained a sustained virological response (40%). At the end of follow-up, three patients obtained a significant nephrological response and decrease in cryoglobulin levels (p<0.05). No significant changes in clinical and biological parameters were observed in non-responders/relapsers. CONCLUSIONS: Eradication of hepatitis C may be associated with the regression of cryoglobulinemic glomerulonephritis.

Successful treatment of hepatitis E virus-associated cryoglobulinemic membranoproliferative glomerulonephritis with ribavirin.

Hepatitis E virus genotype-3 (HEV3) infection can cause chronic hepatitis in immunosuppressed patients and induce extra-hepatic manifestations, such as neurological symptoms, kidney injuries, and immune-mediated thrombocytopenia. Very few cases of HEV-induced kidney manifestations have been reported. Herein, we report, for the first time, a case of de novo membranoproliferative glomerulonephritis that occurred in a kidney transplant patient who developed a chronic HEV3 infection, which was successfully treated with ribavirin.

Hepatitis C virus associated glomerulopathies.

Hepatitis C virus (HCV) infection is a systemic disorder which is often associated with a number of extrahepatic manifestations including glomerulopathies. Patients with HCV infection were found to have a higher risk of end-stage renal disease. HCV positivity has also been linked to lower graft and patient survivals after kidney transplantation. Various histological types of renal diseases are reported in association with HCV infection including membranoproliferative glomerulonephritis (MPGN), membranous nephropathy, focal segmental glomerulosclerosis, fibrillary glomerulonephritis, immunotactoid glomerulopathy, IgA nephropathy, renal thrombotic microangiopathy, vasculitic renal involvement and interstitial nephritis. The most common type of HCV associated glomerulopathy is type I MPGN associated with type II mixed cryoglobulinemia. Clinically, typical renal manifestations in HCV-infected patients include proteinuria, microscopic hematuria, hypertension, acute nephritis and nephrotic syndrome. Three approaches may be suggested for the treatment of HCV-associated glomerulopathies and cryoglobulinemic renal disease: (1) antiviral therapy to prevent the further direct damage of HCV on kidneys and synthesis of immune-complexes; (2) B-cell depletion therapy to prevent formation of immune-complexes and cryoglobulins; and (3) nonspecific immunosuppressive therapy targeting inflammatory cells to prevent the synthesis of immune-complexes and to treat cryoglobulin associated vasculitis. In patients with moderate proteinuria and stable renal functions, anti-HCV therapy is advised to be started as pegylated interferon-α plus ribavirin. However in patients with nephrotic-range proteinuria and/or progressive kidney injury and other serious extra-renal manifestations, immunosuppressive therapy with cyclophosphamide, rituximab, steroid pulses and plasmapheresis should be administrated.

Membranoproliferative glomerulonephritis in a calf with nephrotic syndrome.

A 2-month-old Japanese black calf was presented with a history of weight loss, exophthalmos and subcutaneous oedema of the brisket. Urinalysis and serum biochemistry showed proteinuria and hypoproteinaemia suggestive of nephrotic syndrome. Microscopically, lesions in the kidney were characterized by proliferation of mesangial cells and diffuse thickening of the glomerular basement membranes with the appearance of double contours. Immune complex deposits were confirmed by electron microscopy and immunofluorescence using reagents specific for bovine immunoglobulin G, complement factor C3 and bovine viral diarrhoea virus (BVDV). Consequently, the glomerular lesion in this case was diagnosed as membranoproliferative glomerulonephritis. BVDV type 1 was detected in serum by nested reverse transcriptase polymerase chain reaction. Viral antigen was also identified in the glomeruli by immunofluorescence. These results suggest that BVDV may have been the cause of immune complex glomerulonephritis in this calf.

Transition from endocapillary proliferative glomerulonephritis to membranoproliferative glomerulonephritis in a patient with a prolonged human parvovirus B19 infection.

We report a case in which renal biopsies were performed 4 years apart in a woman with a prolonged human parvovirus B19 (HPB19) infection. When she was 29 years old the first biopsy, performed because of microscopic hematuria and mild proteinuria, showed endocapillary and mesangial proliferative glomerulonephritis in light microscopy as well as deposits of immunoglobulins (Igs) and complement C3 on capillary walls. Mesangial, intramembranous, and subepithelial hump-like electron dense deposits were seen in electron microscopy. The principal differential diagnoses, acute poststreptococcal glomerulonephritis and lupus nephritis, were unlikely, and her serological positivity for IgM antibody for HPB19 made us diagnose acute glomerulonephritis associated with HPB19 infection. The second biopsy, performed 4 years later because of persistent proteinuria and prolonged positivity for IgM antibody for HPB19, showed membranoproliferative glomerulonephritis (MPGN) with mesangial interposition and with thickening and double contours of glomerular basement membrane. In tissues obtained in both biopsies, HPB19 DNA was detected by polymerase chain reaction. HPB19 infection has been widely known to cause various glomerular diseases. This case reveals that acute endocapillary proliferative glomerulonephritis can change into MPGN during prolonged HPB19 infection.

Membranoproliferative glomerulonephritis and circulating cryoglobulins.

BACKGROUND: Previous studies on membranoproliferative glomerulonephritis (MPGN) and cryoglobulinemic glomerulopathy (CG) were based upon case series that were performed before hepatitis C virus (HCV) infection was routinely investigated. Therefore, it remains unknown how far HCV contributes to MPGN or CG, and there have only been a few reports about HCV-negative idiopathic MPGN. PATIENTS AND METHODS: Thirty-five patients with MPGN diagnosed by renal biopsy who underwent examination for HCV infection at our institute between 1990 and 2008 were recruited for this study. Patients with HCV infection at presentation were included, but patients with complications such as underlying lymphoproliferative disorders, autoimmune diseases like lupus nephritis, infection, and liver disease due to hepatitis B virus or alcohol abuse were excluded. A total of 35 patients were enrolled and they were divided into two groups according to the presence/absence of circulating cryoglobulins (cryo). The 23 patients who had cryo-negative and HCV-negative idiopathic MPGN were divided into subgroups with type 1 and type 3 disease. RESULTS: In the cryo-positive group (n = 9), 7 patients were positive for HCV infection, while 2 patients were negative. In the cryo-negative group (n = 26), 3 patients were positive for HCV infection, while 23 patients were negative (idiopathic MPGN). Compared with the cryo-negative group, the cryo-positive group had several characteristics such as more severe thrombocytopenia, higher serum immunoglobulin (Ig)G and IgM levels, lower levels of hemolytic complement (CH50) and complement component (C)4, predominant IgM staining, and type 1 histology. Patients with cryo-negative and HCV-negative 'idiopathic' MPGN showed predominant staining for IgG in both type 1 and type 3 cases, unlike the predominant staining for IgM in the cryo-positive group. Compared with type 3 cases, type 1 cases had a younger age, lower levels of CH50, C3 and C4, and less proteinuria. In the cryo-positive group, 4 patients (44.4 %) died, with death from B cell lymphoma and liver failure in 2 patients each, while 1 patient (8 %) developed end-stage renal failure requiring dialysis. In contrast, all patients in the cryo-negative group remained alive during follow-up, although 4 patients (2 type 1 cases and 2 type 3 cases) required dialysis. CONCLUSION: Cryo-positive MPGN shows a close relationship with HCV infection and IgM, resulting in a poor prognosis. Cryo-negative and HCV-negative idiopathic MPGN has a close relationship with IgG staining, and type 1 cases feature characteristics such as a younger age, more severe hypocomplementemia, and less proteinuria than in type 3 cases.

Recombinant Human Erythropoietin (RHuEpo) and Granular Colony Stimulating Factor (G-CSF) in hepatitis C virus (HCV) related to mixed cryoglobulinaemia associated to membranoproliferative glomerulonephritis type I: a case report description.

HCV infection is related to hepatic disease and mixed cryoglobulinaemia (MC). Renal involvement is reported in one third of cryoglobulinaemic patients. The combination of HCV related MC with renal involvement has been associated with poor survival and identified as Hepatitis C Virus Risk Syndrome (HCV RS). Here we describe antiviral treatment and management of side effects (anaemia and neutropenia) with RHuEpo and G CSF in a rare case of HCV RS.