Membranoproliferative Glomerulonephritis Type Research Articles

Membranoproliferative glomerulonephritis type II-induced extensive retinal drusen with choroidal neovascularization – A rare case report

A 34-year-old female presented with complaints of decreased and distorted vision in the right eye (RE) for 3 months. She had hypertension and membranoproliferative glomerulonephritis (MPGN) type II for 5 years. Her best corrected visual acuity was 6/12, N24 and 6/6, N6 in the right and left eye, respectively. The diagnosis of bilateral MPGN type II-induced retinal drusen was made with active choroidal neovascularization (CNV) in the RE and confirmed by optical coherence tomography. The CNV was treated with antivascular endothelial growth factor injection. After the treatment, her visual acuity improved and metamorphopsia reduced. There have been a handful of case reports about retinal drusen with CNV secondary to MPGN type II across the globe. However, to the best of our knowledge, this is the first case report from India.

Atypical Hemolytic Uremic Syndrome: A Nationwide Colombian Pediatric Series.

Objectives. Atypical hemolytic uremic syndrome (aHUS) is a rare complement-mediated kidney disease with genetic predisposition and represents up to 10% of pediatric hemolytic uremic syndrome (HUS) cases. Few studies have evaluated aHUS in Latin American population. We studied a Colombian pediatric cohort to delineate disease presentation and outcomes. Methods. A multicenter cohort of 27 Colombian children with aHUS were included. Patients were grouped by age at onset. Clinical features were compared using analysis of variance (ANOVA) and Fisher exact tests. Renal biopsy was performed on 6 patients who were suspected of having other renal diseases before aHUS diagnosis. Results. Most patients were male (70%). The onset of aHUS occurred frequently before age 4 years (60%) and followed gastroenteritis as the main triggering event (52%). Age groups showed comparable clinical presentation, disease severity, treatment, and outcomes. Pulmonary involvement (67%) was the main extrarenal manifestation, particularly in the 1 to 7 age group (P = .01). Renal biopsies were as follows: 3 had membranoproliferative glomerulonephritis (MPGN) type I, one MPGN type III, one C3-glomerulonephritis, and one rapidly progressive GN. Genetic screening was available in 6 patients and identified 2xCFHR5, 2xMCP, 1xADAMTS13/THBD, and 1xDGKE mutations. A total of 15 relapses were seen, of which 8 (72%) occurred in the 1 to 7 age group. The renal outcome was not significantly different regardless of age group. Conclusion. In our cohort, we observed a relatively high frequency of extrarenal involvement at first presentation represented by pulmonary manifestations. The renal prognosis at initial presentation was worse than in previous reports.

Recurrent Membranoproliferative Glomerulonephritis After Kidney Transplantation: Risk Factors and Impact on Graft Survival.

BACKGROUND Membranoproliferative glomerulonephritis (MPGN) is an uncommon cause of end-stage renal disease (ESRD). Recurrence rates after transplantation range from 11.8% to 18.9% after 5 and 15 years, respectively. This study aimed to assess the risk factors of MPGN recurrence after kidney transplantation and its impact on graft survival. MATERIAL AND METHODS This was a single-center retrospective cohort, including renal transplant recipients older than 18 years, with a diagnosis of MPGN in native kidneys. Data were obtained from medical records during the first 5-year post-transplant follow-up. Primary endpoints were graft function and survival. Secondary endpoints were MPGN recurrence risk factors and these cases' clinical, laboratory, and histological features. RESULTS Twenty-eight patients were included; the majority male (60.7%), with a mean age of 24.0±9.4 years. At MPGN native diagnosis, all patients presented proteinuria, with C3 consumption in 42.9%. Histological analysis showed 13 (42.9%) MPGN type I and 5 (17.9%) type II, with no cases of type III. MPGN recurrence occurred in 7 (25.0%) patients; 85.7% were male, 57.1% were recipients from a living donor, all presenting nephrotic syndrome and hematuria, with C3 consumption in 71.4%. The graft function was similar between the groups. Two (28.6%) patients progressed to graft failure in the recurrence group, and 1 died with a functioning graft. CONCLUSIONS The MPGN recurrence rate was 25%, most of them recipients of kidneys from living donors. Nephrotic syndrome and C3 consumption were frequent at recurrence. The graft function was similar between the groups, and the 5-year graft survival rate in the recurrence group was higher than in other studies.

Hepatitis C associated membranoproliferative glomerulonephritis treated with directly acting antivirals for hepatitis C

Hepatitis C virus (HCV) infection affects kidneys with different histopathological patterns on kidney biopsy, which commonly include membranoproliferative glomerulonephritis (MPGN) pattern with mixed cryoglobulinemia (CG), thrombotic microangiopathy, membranous nephropathy and small to medium vessel vasculitis. Type 1 MPGN associated with type II mixed CG is the most common glomerulopathy associated with hepatitis C infection. Treatment of these glomerulopathies and cryoglobulinemic renal disease associated with HCV infection includes antiviral therapy for HCV, B-cell depletion therapy for prevention of immune complexes and cryoglobulins or nonspecific immunosuppressive therapy. We describe a patient who presented to us with HCV associated MPGN type 1 with cryogloblinemia and detectable HCV RNA, who recovered completely with directly acting antiviral agents (DAA) alone without immunosuppression.

Demographic, clinical characteristics and treatment outcomes of immune-complex membranoproliferative glomerulonephritis and C3 glomerulonephritis in Japan: A retrospective analysis of data from the Japan Renal Biopsy Registry.

The reclassification of membranoproliferative glomerulonephritis (MPGN) into immune-complex MPGN (IC-MPGN) and C3 glomerulopathy (C3G) based on immunofluorescence findings in kidney biopsies has provided insights into these two distinct diseases. C3G is further classified into dense deposit disease and C3 glomerulonephritis (C3GN) based on electron micrographic findings. Although these diseases have poor outcomes, limited Japanese literature confined to small, single-center cohorts exist on these diseases. We retrospectively analyzed 81 patients with MPGN type I and III from 15 hospitals in the Japan Renal Biopsy Registry to compare demographic, clinical characteristics and treatment outcomes of patients with IC-MPGN to those with C3GN. Of the 81 patients reviewed by immunofluorescence findings in kidney biopsies, 67 patients had IC-MPGN and 14 patients had C3GN. Age at diagnosis and systolic and diastolic pressure were higher and proteinuria and impaired renal function were significantly more prevalent in patients with IC-MPGN than those with C3GN. About 80% of the patients in both groups were treated with immunosuppressive therapy. At last follow-up (median 4.8 years), complete remission rate of proteinuria was significantly higher in patients with C3GN (64.3%) than in those with IC-MPGN (29.9%; P = 0.015). The renal survival rate was lower in patients with IC-MPGN when compared to C3GN (73.1% vs. 100%; log-rank, P = 0.031). Systolic blood pressure and renal function at baseline were independent predictors of progression to end-stage kidney disease. The overall prognosis of patients with C3GN is more favorable than for patients with IC-MPGN.

Autoimmune Hypophysitis with Late Renal Involvement: A Case Report

We report a case of a 50-year-old male admitted to the Endocrinology Unit because of persistent headaches, nausea, feeling tired, sudden weight loss, cold intolerance, decreased appetite, and lack of sex interest. Diagnostic workup showed a 6-millimeter pituitary tumor without signs of compression, and a condition of progressive panhypopituitarism. After 12 months of hormone replacement therapy, the patient was hospitalized because of sudden weight gain, periorbital-peripheral edema, severe dyslipidemia, hypertension, and proteinuria. Corticosteroid therapy was shifted from oral to continuous intravenous infusion, and once the diagnosis of “immune complex-mediated glomerulonephritis with mesangial deposits suggestive for membranoproliferative glomerulonephritis type IIIIgG4-positive” was made, the immunosuppressant mycophenolate (1500 mg/day) was started. After a 6-month follow-up, the complete resolution of renal symptoms was accompanied by the disappearance of a pituitary lesion and the patient was back to prior hormone replacement therapy. Autoimmune hypophysitis (AH) is a rare autoimmune inflammatory disease of the pituitary gland that can impair hormone secretion and function. IgG4-hypophysitis is rare and is usually associated with other IgG4-related diseases. Herein, we describe a rare case of AH associated with late renal disease, and without any other organ involvement.

Spectrum of Kidney Involvement in Patients with Myelodysplastic Syndromes

IntroductionMyelodysplastic syndromes (MDS) are characterized by a high prevalence of associated autoimmune manifestations. Kidney involvement has been rarely reported in MDS patients. We report on the spectrum of kidney pathological findings in MDS patients.MethodsWe retrospectively identified MDS patients who had undergone a kidney biopsy between 2001 and 2019 in nine Swiss and French nephrology centres.ResultsNineteen patients (median age 74 years [63-83]) were included. At the time of kidney biopsy, eleven (58%) patients had extra-renal auto-immune manifestations and sixteen (84%) presented with acute kidney injury. Median serum creatinine at diagnosis was 2.8 mg/dL [0.6-8.3] and median urinary protein to creatinine ratio was 1.2 g/g [0.2-11]. Acute tubulo-interstitial nephritis (TIN) was present in seven (37%) patients. Immunofluorescence study in one patient with acute TIN disclosed intense IgG deposits along the tubular basement membrane and Bowman’s capsule. Other kidney pathological features included ANCA-negative pauci-immune necrotizing and crescentic glomerulonephritis (n = 3), membranous nephropathy (n = 2), IgA nephropathy (n = 1), IgA vasculitis (n = 1), immunoglobulin-associated membrano-proliferative glomerulonephritis type I (n=1), crescentic C3 glomerulopathy (n = 1), fibrillary glomerulonephritis (n = 1) and minimal change disease (n = 1). Eleven (58%) patients received immunosuppressive treatments, among whom one developed a severe infectious complication. After a median follow-up of 7 month [1-96], nine (47%) patients had chronic kidney disease stage 3 (n = 6) or 4 (n = 3) and five (26%) progressed to end-stage kidney disease. Three patients died.ConclusionsMDS are associated to several autoimmune kidney manifestations, predominantly acute TIN. MDS are to be listed among the potential causes of autoimmune TIN.

Rare Glomerular Presentation of Essential Cryoglobulinemia without HCV Infection

Membranoproliferative glomerulonephritis (MPGN) is characterized by mesangial cell proliferation and structural changes in glomerular capillary walls and double-contoured glomerular basement membrane (GBM). Usually, it is connected with cryoglobulinemia which is defined by the presence of a circulating, a cold-precipitating immunoglobulin. The chemical and immunological features of the cryoglobulins are used to define three types of cryoglobulinemia. In this report we describe the third case of MPGN type II with essential cryoglobulinemia without HCV infection, which is usually defined in the literature as MPGN type II. Here, we present 61-years old woman previously diagnosed with MPGN in 2012 at another institution. At that time, she was not examined in terms of cryoglobulinemia. Initially she was treated with pulses of methylprednisolone, then oral corticosteroids until cessation when complete remission was achieved. Meanwhile, she had two relapses of the disease. In October 2020 we re-evaluated her and found out positive cryoglobulins in repeating testing. Serological studies for anti-neutrophil cytoplasmic antibodies (ANCA), myeloperoxidase and proteinase 3, anti-double stranded DNA antibodies, anti-hepatitis C antibodies, anti-HIV antibodies and anti-hepatitis B surface antibodies were all negative. Serum M protein or monoclonal IgM were not detected. Percutaneous renal biopsy was compatible with the diagnosis of MPGN. Based on clinical, laboratory and histological evaluation, it was concluded that the patient had a MPGN with essential cryoglobulinemia. Therapy with mycophenolate mofetil had a beneficial effect on the course of disease and the patient achieved partial remission and stabile renal function for the last 3 months of follow-up. Since the therapy for MPGN with essential cryoglobulinemia is not standardized, further research in the field is needed.

Design, Synthesis, and Preclinical Characterization of Selective Factor D Inhibitors Targeting the Alternative Complement Pathway.

Complement factor D (FD), a highly specific S1 serine protease, plays a central role in the amplification of the alternative complement pathway (AP) of the innate immune system. Dysregulation of AP activity predisposes individuals to diverse disorders such as age-related macular degeneration, atypical hemolytic uremic syndrome, membranoproliferative glomerulonephritis type II, and paroxysmal nocturnal hemoglobinuria. Previously, we have reported the screening efforts and identification of reversible benzylamine-based FD inhibitors (1 and 2) binding to the open active conformation of FD. In continuation of our drug discovery program, we designed compounds applying structure-based approaches to improve interactions with FD and gain selectivity against S1 serine proteases. We report herein the design, synthesis, and medicinal chemistry optimization of the benzylamine series culminating in the discovery of 12, an orally bioavailable and selective FD inhibitor. 12 demonstrated systemic suppression of AP activation in a lipopolysaccharide-induced AP activation model as well as local ocular suppression in intravitreal injection-induced AP activation model in mice expressing human FD.

MON-257 A Case of Primary Hyperparathyroidism Complicated by Vitamin D Deficiency

Background: Primary hyperparathyroidism is a relatively common disorder caused by the inappropriate autonomous secretion of parathyroid hormone which subsequently leads to hypercalcemia. There is increased prevalence of vitamin D deficiency in patients with primary hyperparathyroidism. As these patients are already hypercalcemic, there is reluctance within the medical community to provide vitamin D supplementation due to fear of exacerbating hypercalcemia. Clinical Case: A 17 year old African American male was referred to the pediatric endocrinology clinic for hypercalcemia (total serum calcium level 11.2 mg/dL, 8.6-10.6). His past medical history was significant for a diagnosis of membranoproliferative glomerulonephritis type 2 which was in remission. His most recent blood tests showed normal renal function. A review of his hospital chart showed that his calcium levels had been on the upper end of the reference range or above it for at least a year prior to his presentation to the clinic. He had no signs or symptoms concerning for hypercalcemia. He was not taking any calcium supplements or other medications which are known to be associated with elevated calcium levels. There was no known family history of hypercalcemia. He denied any history of renal stones, adrenal disease, weight loss, or osteoporosis but did report a wrist and knee fracture both of which occurred during competitive wrestling matches. His vital signs and physical exam were unremarkable. On laboratory analysis his serum calcium was 11.0 mg/dL, intact PTH 112 pg/mL (ref range 12-88), 25 hydroxyvitamin D was 10 ng/mL (ref range 20-80), Alk Phos 145 U/L (ref range 100-300), Albumin 4.8 g/dL (3.4-5.0), TSH 1.97 mcIU/mL (0.35-4.0), Free T4 0.8 ng/dL (0.6-1.7), Cr 0.94 mg/dL (0.5-1.3), 24 hour urine calcium excretion was 228 mg and calculated calcium to creatinine ratio was 0.07. Ultrasound of the neck and nuclear parathyroid scan and did not definitively show a parathyroid adenoma but could also not rule out the presence of an adenoma. Given patient’s low 25 OH vitamin D level he was given a 4 week course of supplemental vitamin D (1,000 units daily) with resultant 25 OH vitamin D level of 21 ng/mL. His serum calcium and intact PTH level remained elevated at 10.9 mg/dL and 108 pg/mL respectively. The patient was sent to otolaryngology for evaluation should the need arise in the future for surgical intervention and genetic testing to definitively rule out familial hypocalciuric hypercalcemia was sent. As he is asymptomatic with mild hypercalcemia currently, we will continue to monitor yearly per guideline recommendations. Conclusion: Supplementation with modest doses of vitamin D did not significantly raise our patient’s calcium level and led to an improvement in the 25 hydroxyvitamin D level. Vitamin D repletion should be considered in cases of asymptomatic primary hyperparathyroidism associated with mild hypercalcemia.

Complete biopsy-proven resolution of deposits in recurrent proliferative glomerulonephritis with monoclonal IgG deposits (PGNMIGD) following rituximab treatment in renal allograft

BackgroundProliferative glomerulonephritis with monoclonal IgG deposits (PGNMIGD) is a disease entity classified under the group of “Monoclonal gammopathy-related kidney diseases”, and can recur after transplant. Clinical remission of proteinuria in patients with PGNMIGD has been previously shown following anti-B cell and/or anti-plasma cell therapies. Our case is the first to show complete histologic resolution of the glomerular monoclonal IgG kappa deposits in a case of recurrent PGNMIGD in renal allograft after rituximab and steroid treatment. This is a novel finding and it shows that the deposits are amenable to therapy. This case also highlights the importance of IgG subclass staining in the recognition of the monoclonal nature of the deposits. It is particularly important in PGNMIGD because only 20 to 30% of patients with this disease are reported to have detectable monoclonal gammopathy, and the deposits do not have any organized substructure on electron microscopic examination. Morphologically, they resemble polyclonal immune-type deposits seen in other immune complex glomerulonephritides such as lupus nephritis, infection-associated glomerulonephritis, and membranoproliferative glomerulonephritis (MPGN type I).Case presentationThe patient is a 44 year old Caucasian male who received a living unrelated donor kidney transplant for end-stage renal disease diagnosed 7 years before transplant. The reported native kidney biopsy diagnosis was membranoproliferative glomerulonephritis (MPGN) with IgG, C3 and kappa restricted deposits. Fourteen months post-transplant, he presented with abrupt worsening of graft function, proteinuria and serum IgG kappa monoclonal spike. Allograft biopsy was consistent with recurrent PGNMIGD, considering the native kidney diagnosis and interval post-transplant. He underwent plasmapheresis, IV pooled immune globulin, steroid pulse and taper, and anti-CD-20 Rituximab therapy. Patient had gradual decline in proteinuria and complete resolution of the immune deposits on repeat biopsy 3 months later. Unfortunately he subsequently developed chronic antibody-mediated rejection and transplant glomerulopathy and graft failure 34 months post-transplant.ConclusionsIn a transplant setting, repeat allograft biopsies are frequently performed for graft dysfunction. This provides a good opportunity to study the evolution of the immune deposits following treatment. Our case shows complete histologic resolution of the deposits in allograft PGNMIGD.

Diseases associated with complement system dysregulation and the prospects of their treatment

The lack of pharmaceutical agents that could modulate complement activation is one of the most serious problems in modern medical practice. Meanwhile, the complement system plays a significant role in the pathogenesis of numerous diseases such as age-related macular degeneration (degenerative eye disease, which is the main cause of blindness in the elderly), kidney diseases such as atypical hemolytic-uremic syndrome and membranoproliferative glomerulonephritis type II, paroxysmal nocturnal hemoglobinuria (Marchiafava-Micheli disease), and hereditary angioedema. The complement and its components are involved in the development and progression of autoimmune pathological processes, such as systemic lupus erythematosus, rheumatoid arthritis, and autoimmune hemolytic anemia; neurodegenerative and neoplastic diseases; and complications after heart attacks, strokes, and transplants. This review considers the involvement of complements in the pathological processes, existing methods of treatment, and the prospects for the development of drugs that can correct the work of complement - the most important component of innate immunity.

A large, international study on post-transplant glomerular diseases: the TANGO project

BackgroundLong-term outcomes in kidney transplantation (KT) have not significantly improved during the past twenty years. Despite being a leading cause of graft failure, glomerular disease (GD) recurrence remains poorly understood, due to heterogeneity in disease pathogenesis and clinical presentation, reliance on histopathology to confirm disease recurrence, and the low incidence of individual GD subtypes. Large, international cohorts of patients with GD are urgently needed to better understand the disease pathophysiology, predictors of recurrence, and response to therapy.MethodsThe Post-TrANsplant GlOmerular Disease (TANGO) study is an observational, multicenter cohort study initiated in January 2017 that aims to: 1) characterize the natural history of GD after KT, 2) create a biorepository of saliva, blood, urine, stools and kidney tissue samples, and 3) establish a network of patients and centers to support novel therapeutic trials. The study includes 15 centers in America and Europe. Enrollment is open to patients with biopsy-proven GD prior to transplantation, including IgA nephropathy, membranous nephropathy, focal and segmental glomerulosclerosis, atypical hemolytic uremic syndrome, dense-deposit disease, C3 glomerulopathy, complement- and IgG-positive membranoproliferative glomerulonephritis or membranoproliferative glomerulonephritis type I-III (old classification). During phase 1, patient data will be collected in an online database. The biorepository (phase 2) will involve collection of samples from patients for identification of predictors of recurrence, biomarkers of disease activity or response to therapy, and novel pathogenic mechanisms. Finally, through phase 3, we will use our multicenter network of patients and centers to launch interventional studies.DiscussionMost prior studies of post-transplant GD recurrence are single-center and retrospective, or rely upon registry data that frequently misclassify the cause of kidney disease. Systematically determining GD recurrence rates and predictors of clinical outcomes is essential to improving post-transplant outcomes. Furthermore, accurate molecular phenotyping and biomarker development will allow better understanding of individual GD pathogenesis, and potentially identify novel drug targets for GD in both native and transplanted kidneys. The TANGO study has the potential to tackle GD recurrence through a multicenter design and a comprehensive biorepository.

Management and outcome of multifetal gestation in a 35-year-old woman with childhood-onset membranoproliferative glomerulonephritis type I

A 35-year-old woman with membranoproliferative glomerulonephritis type I had quintuplet gestation after induced ovulation. Her serum creatinine level and estimated glomerular filtration rate were 0.86 mg/dL and 61.5 mL/min/1.73 m2 before pregnancy. Blood pressure was normal and urinary protein to creatinine ratio was 0.2 g/gCr. Prednisolone 10 mg on alternate-day administration was continued during pregnancy. At 10 weeks of gestation transvaginal selective embryo reduction was performed and five embryos were reduced to twins. Hypertension occurred at 20 weeks of gestation. She developed nephrotic syndrome and serum creatinine level increased to 1.29 mg/dL. Elective cesarean section was performed at 28 weeks of gestation and dichorionic diamniotic twins were born. After delivery blood pressure, serum creatinine level, estimated glomerular filtration rate and serum albumin level in their mother returned to baseline. Her twin infants were well at discharge from neonatal-intensive-care-unit. Incidence of multifetal pregnancies due to the improvement of assisted reproduction technologies and ovulation-inducing hormones has been increasing. Management for multifetal pregnancy in women with chronic kidney disease will be needed further.

Respuesta a la farmacoterapia en pacientes con glomerulonefritis membranoproliferativa en una clínica de Barranquilla, Colombia. 2007-2014

Introducción. La glomerulonefritis membranoproliferativa (GnMP) es un patrón de lesión glomerular hipercelular mesangial con adelgazamiento de la membrana basal glomerular y proliferación endocapilar que está mediado por las inmunoglobulinas o el sistema del complemento en el mesangio y endotelio capilar.Objetivo. Evaluar la respuesta a la farmacoterapia en pacientes diagnosticados con GnMP en una clínica de Barranquilla entre los años 2007 y 2014.Materiales y métodos. Estudio de cohorte retrospectivo en el que se evaluaron 58 pacientes con diagnóstico de GnMP por biopsia renal, quienes se clasificaron como respondedores y no respondedores. Se realizó una evaluación de tratamiento estándar según tipo de GnMP: mediado por complemento y mediado por inmunocomplejos e inmunofluorescencia negativa a los 6 y 12 meses de tratamiento.Resultados. La edad promedio de los participantes fue de 35±13 años. De 58 pacientes, 52% eran mujeres, 63% desarrolló enfermedad renal crónica (ERC) al año de evaluación, 25.8% logró remisión (22.4% completa y 3.4% parcial) y 74.2% no logró entrar en remisión.Conclusión. La GnMP es una causa importante de ERC entre la población estudiada. La respuesta al tratamiento inmunosupresor no demostró beneficios estadísticamente significativos, independiente del tipo de GnMP.

Key role of renal biopsy in management of progressive chronic kidney disease in liver graft recipients.

Chronic kidney disease (CKD) is a common complication after liver transplantation (LT). The etiology of CKD is broad and may only be assessed accurately by renal histology. The current study aimed to analyze the safety of renal biopsy in daily clinical practice as well as its usefulness regarding management of CKD after LT. We performed a retrospective analysis of clinical data and renal biopsies obtained from patients with severe renal impairment (overt proteinuria, progressive deterioration of renal function) after LT with respect to safety, etiology of renal disease, and therapeutic consequences. Renal biopsies were obtained from 14 patients at median (minimum-maximum) 3 (0.2-12) years after LT. No major complications associated with renal biopsy were observed. Histomorphological alterations were varied (nephrosclerosis, n = 5; IgA-glomerulonephritis, n = 4; tenofovir-associated nephropathy, membranoproliferative glomerulonephritis type 1, membranous glomerulonephritis, amyloid A amyloidosis, and calcineurin inhibitor nephropathy, n = 1, respectively). The diagnosis of specific renal diseases other than calcineurin-inhibitor nephrotoxicity facilitated specific treaments and avoided unnecessary modification of immunosuppression in the majority of patients. Renal biopsy in patients with CKD after LT seems safe and may offer specific therapeutic options. Furthermore, unnecessary changes of immunosuppression can be avoided in a considerable number of patients.

Treatment of Subretinal Neovascular Membranes in a Patient with Membranoproliferative Glomerulonephritis Type II: A Longitudinal Case Report

A 38-year-old woman with membranoproliferative glomerulonephritis type II (MPGN II), previously treated successfully for choroidal neovascular membrane (CNV) in the left eye with injections of anti-vascular endothelial growth factor (VEGF) therapy, subsequently developed blurry vision due to new CNV in her right eye. She was treated with a total of 6 intravitreal injections of ranibizumab, with improvement in acuity and imaging findings. At her most recent follow up visit prior to the writing of this paper, nearly 10 years after her initial presentation with left eye CNV and 7.5 years after developing right eye CNV, she remains recurrence-free.

Dense deposit disease: An ultra-rare c3 glomerulopathy in children

Dense deposit disease (DDD), previously known as membranoproliferative glomerulonephritis type 2, is an extremely rare disease affecting two to three people per million. The rarity of this disease makes it difficult for clinicians to establish evidence-based clinical practices for its management. Here, we report a case of DDD who presented with features of acute nephritic syndrome and did not respond to most of the treatment options available in literature.

A haplotype in CFH family genes confers high risk of rare glomerular nephropathies

Despite distinct renal lesions, a series of rare glomerular nephropathies are reportedly mediated by complement overactivation. Genetic variations in complement genes contribute to disease risk, but the relationship of genotype to phenotype has not been straightforward. Here, we screened 11 complement genes from 91 patients with atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy (C3G) and membranoproliferative glomerulonephritis type I (MPGN I), and identified the concomitant presence of three missense variations located within the human complement Factor H (CFH) gene cluster. The three variations, rs55807605, rs61737525 and rs57960694, have strong linkage disequilibrium; subsequent haplotype analysis indicated that ATA increased the susceptibility of these renal diseases. In silico analysis, the CFHR3 rs61737525-T risk allele altered the physical and structural properties and generated a reduction in binding affinity of the CFHR3/C3b complex. Surface plasmon resonance (SPR) binding analysis further demonstrated the substitution induced a decrease of two orders of magnitude in C3b-binding properties, with a declined cofactor activity in fluid phase. These data suggest that the haplotype carrying the causative allele behaves as a partial C3 convertase deficiency, predisposing individuals to diverse pathologic lesions underlying complement overactivation. Such genotype-phenotype discrepancies allow better understanding about these nephropathies mediated by genetic complement disorders.

A case of rapid amelioration of hepatitis C virus-associated cryoglobulinemic membranoproliferative glomerulonephritis treated by interferon-free directly acting antivirals for HCV in the absence of immunosuppressant.

Mixed cryoglobulinemic syndrome, which is a systemic vasculitis characterized by the immune complex deposition in small- and medium-sized arteries and most often due to chronic hepatitis C virus (HCV) infection, sometimes clinically manifests as refractory glomerulonephritis or nephritic syndrome. Patients with mixed cryoglobulinemic nephropathy who have a rapidly progressive glomerulonephritis should receive immunosuppressive therapy. After disease stabilization, patients should receive concurrent therapy for the underlying HCV infection. The standard therapy of a chronic HCV infection is IFN monotherapy or IFN combined with ribavirin; however, after the introduction of direct-acting antivirals (DAAs), the standard therapy for patients with HCV genotype 1 has dramatically changed. We report a case of HCV-associated cryoglobulinemic membranoproliferative glomerulonephritis (MPGN) successfully treated by daclatasvir and asunaprevir, which are IFN-free DAAs for HCV, in combination with angiotensin II receptor blocker without immunosuppressive therapy. The patient developed severe nephrotic syndrome with progressive kidney dysfunction. Blood examination revealed a high copy number of HCV-RNA (6.4 log IU/mL, type 1), cryoglobulinemia, paraproteinemia of IgM-κ, and hypocomplementemia. Histological analysis showed MPGN type 1. These findings were compatible with those observed in HCV-associated cryoglobulinemic MPGN. This case offers original evidence for the application of newer generation of IFN-free DAAs in the treatment of HCV-associated cryoglobulinemic nephropathy.