Minimal change disease (MCD) is the most common cause of idiopathic nephrotic syndrome in children, and it is well known for its multifactorial causes which are the manifestation of the disease. Proteinuria is an early consequence of podocyte injury and a typical sign of kidney disease. Steroid-sensitive patients react well with glucocorticoids, but there is a high chance of multiple relapses. CD80, also known as B7-1, is generally expressed on antigen-presenting cells (APCs) in steroid-sensitive MCD patients. Various glomerular disease models associated with proteinuria demonstrated that the detection of CD80 with the increase of urinary CD80 was strongly associated closely with frequent-relapse MCD patients. The role of CD80 in MCD became controversial because one contradicts finding. This review covers the treatment alternatives for MCD with the insight of CD80 as a potential therapeutic target. The promising effectiveness of CD20 (rituximab) antibody and CD80 inhibitor (abatacept) encourages further investigation of CD80 as a therapeutic target in frequent-relapse MCD patients. Therapeutic-based antibody towards CD80 (galiximab) had never been investigated in MCD or any kidney-related disease; hence, the role of CD80 is still undetermined. A new therapeutic approach towards MCD is essential to provide broader effective treatment options besides the general immunosuppressive agents with gruesome adverse effects.
Objective: To describe the effect of mycophenolate mofetil in Pakistani children with steroid dependent and steroid resistant nephrotic syndrome. Methods: This is cross sectional retrospective review of 16 patients; 9 boys and 7 girls (11 SD/FRNS and 5 SRNS) for a period of 4.8 years. This study was conducted in Mayo hospital and Fatima Memorial hospital specialist care centre, Lahore involving urban and suburban population. Results: The median age of the group was 4 years (1.6 to 12.6 years). Seven patients had histological diagnosis of MCN, 3 had diffuse mesangial proliferation, one of membranoproliferative glomerulonephritis and 4 had FSGS. Out of 5 SRNS 4 were found to have FSGS and 1 had membranoproliferative glomerulonephritis (MPGN). A total of three patients were completely off steroids and in two patients MMF was also successfully stopped. Number of relapses /patient /year calculated by applying Wilcoxan signed rank test was found to be 4.31 + 0.87(3.00-6.00 /patient/year) before starting MMF, which dropped to 1.12 + 0.718 (0.00- 2.000 /patient/year) after starting MMF, p=0.0001. Reduction in steroid dose from mean of 0.85 + 0.18 mg/kg/day to 0.3mg/kg/day + 1.56 was achieved in 12 months, p
Steroid-resistant nephrotic syndrome (SRNS) causes 15% of chronic kidney disease (CKD). Here we show that recessive mutations in FAT1 cause a distinct renal disease entity in four families with a combination of SRNS, tubular ectasia, haematuria and facultative neurological involvement. Loss of FAT1 results in decreased cell adhesion and migration in fibroblasts and podocytes and the decreased migration is partially reversed by a RAC1/CDC42 activator. Podocyte-specific deletion of Fat1 in mice induces abnormal glomerular filtration barrier development, leading to podocyte foot process effacement. Knockdown of Fat1 in renal tubular cells reduces migration, decreases active RAC1 and CDC42, and induces defects in lumen formation. Knockdown of fat1 in zebrafish causes pronephric cysts, which is partially rescued by RAC1/CDC42 activators, confirming a role of the two small GTPases in the pathogenesis. These findings provide new insights into the pathogenesis of SRNS and tubulopathy, linking FAT1 and RAC1/CDC42 to podocyte and tubular cell function.
We report a 14 year old Indian-Muslim girl who developed a fulminant, disseminated and fatal varicella infection while receiving steroids for nephrotic syndrome. The terminal phase of her illness was complicated by a bleeding dyscrasia and circulatory collapse. Varicella infection in healthy children is a benign disease. However in neonates and immunosuppressed patients it may be severe and often fatal. There are many reports of fatalities occurring in cancer patients receiving chemotherapy, patients on immunosuppressives for asthma, haemolytic anaemia, rheumatic fever, and renal and bone marrow transplantation. Patients with nephrotic syndrome receiving cyclophosphamide treatment are at particular risk of developing severe chickenpox infection. To our knowledge, there has been only one report of fatal chickenpox infection in a child who received steroids for nephrotic syndrome. We report here a case of fatal haemorrhagic chickenpox complicating nephrotic syndrome.
Renal biopsy is essential in the management of renal parenchymal diseases. Thus far there is no publish report on the pattern of glomerulonephritis in Kelantan. We decided to establish the pattern of glomerulonephritis in Kelantan and use this information as our reference in future studies. Records of patients who had proven glomerulonephritis histologically were analysed. Their biological data, clinical presentation, etiology and clinicopathological pattern were studied. Where appropriate mean and standard deviation were calculated. A total of 74 biopsies were performed during the study period (between January 1991 and December 1993), out of which 72 biopsies (97.3%) were considered suitable for analysis. The male to female ratio was 1:1.1. Mean age at presentation was 27.6 +/- 12.2 years. Nephrotic syndrome was the commonest clinical presentation (65.3%). The main underlying cause was systemic lupus erythematosus (50%) followed by primary glomerulonephritis. Histologically, IgA nephropathy and minimal change disease were the main patterns among patients with primary glomerulonephritis while diffuse proliferative glomerulonephritis was the commonest pattern among patients with lupus nephritis. Hence the pattern of glomerulonephritis is similar to other reported series. The procedure is considered safe and has a high success rate.
Nephrotic syndrome is often associated with a hypercoagulable state and thrombotic complications. Thrombosis may be due to a number of abnormalities in blood, including AT III deficiency, increased concentrations of fibrinogen, factors V and VIII, and platelet hyperaggregability. The therapeutic approach to thrombosis in nephrotic syndrome is the use of anticoagulants as a preventive measure or an attempt at thrombolysis with streptokinase, urokinase, or stanozolol.
Idiopathic nephrotic syndrome newly affects 1-3 per 100,000 children per year. Approximately 85% of cases show complete remission of proteinuria following glucocorticoid treatment. Patients who do not achieve complete remission within 4-6 weeks of glucocorticoid treatment have steroid-resistant nephrotic syndrome (SRNS). In 10-30% of steroid-resistant patients, mutations in podocyte-associated genes can be detected, whereas an undefined circulating factor of immune origin is assumed in the remaining ones. Diagnosis and management of SRNS is a great challenge due to its heterogeneous etiology, frequent lack of remission by further immunosuppressive treatment, and severe complications including the development of end-stage kidney disease and recurrence after renal transplantation. A team of experts including pediatric nephrologists and renal geneticists from the International Pediatric Nephrology Association (IPNA), a renal pathologist, and an adult nephrologist have now developed comprehensive clinical practice recommendations on the diagnosis and management of SRNS in children. The team performed a systematic literature review on 9 clinically relevant PICO (Patient or Population covered, Intervention, Comparator, Outcome) questions, formulated recommendations and formally graded them at a consensus meeting, with input from patient representatives and a dietician acting as external advisors and a voting panel of pediatric nephrologists. Research recommendations are also given.
A 31-year-old Malay female presented with nephrotic syndrome without renal impairment. Renal biopsy features were in keeping with immunotactoid glomerulopathy (ITG). Non-Congophilic deposits were seen causing thickening of the glomerular capillary basement membrane with segmental accentuation, and widening of the mesangium. Immunofluorescence examination showed moderate amounts of IgG and C3 in the glomerular capillary walls with some in the mesangium. Ultrastructurally, 20-nm thick fibrils with microtubular organisation were present predominantly in the subendothelial region with similar fibrils in the mesangium. Although immunotactoid glomerulopathy and fibrillary glomerulonephritis (FG) have been recognised as entities with extracellular fibrillary material in the kidney, to date much remains to be clarified regarding these 2 conditions. While the renal biopsy findings in this patient are consistent with ITG, her clinical presentation is unlike that of usual ITG in that she is of a much younger age and has no associated haemopoietic disorder. Response to initial treatment of 8 weeks of prednisolone therapy was poor.
Chronic hepatitis C manifests with many extrahepatic features including renal involvement. However, less commonly, interferon therapy for chronic hepatitis C can also result in renal involvement and we describe a case when interferon therapy resulted in minimal change glomerulopathy, a form of involvement which, carries a good prognosis. Our patient developed nephrotic syndrome while on interferon therapy and HCV RNA levels were undetectable at that time. The disease showed excellent response to steroid therapy.
Managing primary or even secondary glomerulonephritis remains a challenge to many nephrologists. In primary focal segmental glomerulosclerosis (FSGS) with heavy proteinuria, renin aldosterone system blockade and high dose of oral prednisolone is the mainstay of treatment. Other immunosuppressive medications like Cyclophosphamide, Cyclosporine A and Mycophenolate Mofetil (MMF) are warranted if a complete remission is not achieved. We illustrate a case of 21 year old gentleman with primary FSGS that was difficult to achieve remission despite on high dose steroid and oral Cyclophosphamide. He was also not responsive to a combination of MMF and Cyclosporine A (CSA) and even throughout the therapy he developed significant steroid and CSA toxicity. He presented to our center with severe nephrotic syndrome and acute kidney injury requiring acute haemodialysis. Despite re-challenged him again on high dose prednisolone, total of 2.4g of intravenous Cyclophosphamide, and MMF, he failed to achieve remission. He was subsequently given intravenous Rituximab 500mg/weekly for 4 doses and able to attained remission for 1 year. He relapsed again and a second course of Rituximab 500mg/weekly for 6 doses were given to attain remission. This case demonstrates the difficulty in managing refractory steroid dependent FSGS and we found that Rituximab is proven beneficial in this case to induce remission.
We report a case of a 21-year-old man with underlying nephrotic syndrome (NS) secondary to minimal change disease, who developed an ischemic stroke with left hemiparesis. He received intravenous thrombolysis followed by a mechanical thrombectomy. After mechanical thrombectomy, he developed acute kidney injury which subsequently required haemodialysis. Further workup revealed that he had concomitant antiphospholipid syndrome (APS) and NS. He was started on vitamin K antagonist anticoagulant. This case report illustrates the importance of workup in identifying causes of ischemic stroke in a young patient.
Kimura's disease is a rare condition and typically presents as non-tender subcutaneous swellings in the head and neck region, usually in the pre-auricular and submandibular areas. It is associated with lymphadenopathy (both local and distal), marked peripheral eosinophilia, and an elevated IgE level. It can easily be mistaken for a malignant disorder. Fine needle aspiration can be misleading, and a diagnosis is established only by histopathological examination. Renal involvement, which may affect up to 60% of patients, is the only systemic manifestation. We report a case of Kimura's disease in a Malay patient who was associated with steroid-responsive nephrotic syndrome.
Adequately biopsied renal tissue received in the Department of Pathology, University Hospital, Kuala Lumpur from 1,000 consecutive Malaysian patients during an eleven year period between 1970 and 1981 was reviewed. The youngest patient was 6 days old and the oldest 80 years. Both sexes were equally represented. The majority of the patients were Chinese (71%) with Malays and Indians comprising most of the remainder. Over half the patients (50.4%) presented with the nephrotic syndrome. Other modes of presentation included systemic lupus erythematosus, proteinuria and haematuria separately or in combination and hypertension. Minimal change (25.7%) and proliferative glomerulonephritis (24.8%) were present in about equal numbers and together accounted for over half of the cases (50.5%). Lupus nephritis was the third most common diagnosis (18.4%). In addition, there were patients with focal glomerulonephritis (5.4%), membranous glomerulonephritis (5.5%), Berger's disease (5.8%), amyloidosis (0.6%) and end stage renal disease (4.0%).
Galloway-Mowat syndrome (GAMOS) is an autosomal-recessive disease characterized by the combination of early-onset nephrotic syndrome (SRNS) and microcephaly with brain anomalies. Here we identified recessive mutations in OSGEP, TP53RK, TPRKB, and LAGE3, genes encoding the four subunits of the KEOPS complex, in 37 individuals from 32 families with GAMOS. CRISPR-Cas9 knockout in zebrafish and mice recapitulated the human phenotype of primary microcephaly and resulted in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibited cell proliferation, which human mutations did not rescue. Furthermore, knockdown of these genes impaired protein translation, caused endoplasmic reticulum stress, activated DNA-damage-response signaling, and ultimately induced apoptosis. Knockdown of OSGEP or TP53RK induced defects in the actin cytoskeleton and decreased the migration rate of human podocytes, an established intermediate phenotype of SRNS. We thus identified four new monogenic causes of GAMOS, describe a link between KEOPS function and human disease, and delineate potential pathogenic mechanisms.
Multiple myeloma is a blood dyscrasias that accounts of almost 10% of all hematological malignancy. The presentation of myeloma kidney is highly variable and it often presents as renal insufficiency, renal tubular dysfunction and proteinuria of various types. In Malaysia the true incidence of myeloma kidney is unknown. Often the diagnosis of myeloma kidney was missed out despite the patient has sought medical treatment early. A high index of suspicion is required when the middle to elderly age patients present with unexplained renal impairment and enlarged kidneys. We present here the presentation of a rare subtype of myeloma in a relatively young patient whereby the patient presented with nephrotic syndrome and aoztemia.
Nephrotic syndrome (NS) is a well documented complication after allogeneic peripheral blood stem cell transplantation. It is usually due to autoimmune glomerulonephritis and thought to be a clinical manifestation of graft versus host disease. NS has also been reported to be associated with other hematological malignancies. We report a case of nephrotic syndrome in a patient who relapsed after allogeneic peripheral blood stem cell transplantation (PBSCT) for chronic myeloid leukemia (CML). The renal biopsy was suggestive of minimal change disease. There was no other evidence of graft versus host disease. He was treated with high dose prednisolone, with no response and finally succumbed to the underlying disease.