Development Of Nephrotic Syndrome Research Articles

Podocytopathy and Nephrotic Syndrome in Smpdl3b Gene Knockout Mice

Recent clinical studies have shown that downregulation of sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b) in podocytes is a hallmark of idiopathic nephrotic syndrome in children. Meanwhile, there is increasing evidence suggesting that changes of SMPDL3b level in podocytes determine the phenotypes of podocyte injury in glomerular diseases. However, it remains unknown whether SMPDL3b exclusively plays a crucial role in the pathogenesis of podocytopathy and nephrotic syndrome without any other pathogenic stimuli. In the present study, we tested whether Smpdl3b gene knockout induces podocyte injury and nephrotic syndrome in mice. By immunohistochemistry and confocal microscopy, we first confirmed that SMPDL3b was highly expressed in podocytes of wild type (WT) mice but undetectable in these cells of Smpdl3b knockout (KO) mice. Also, Western blot analysis showed that SMPDL3b was not detected in podocytes isolated from Smpdl3b KO mice compared to podocytes of WT mice. Although no significant morphologic changes in glomeruli were observed in Smpdl3b KO mice under light microscope, severe proteinuria and albuminuria were found in Smpdl3b KO mice compared to control littermates. Transmission electron microscopy showed that podocytes of Smpdl3b KO mice had distinctive foot process effacement and moderate microvillus formation and vacuolation. These functional and morphologic changes indicate the development of nephrotic syndrome in mice lacking Smpdl3b gene. In vitro, Smpdl3b gene silencing induced remarkable decrease in podocin levels in podocytes compared to control cells. Phalloidin staining of F-actin showed elevation of cortical actin and reduction of stress fiber in podocytes transfected with Smpdl3b shRNA. Such actin cytoskeleton rearrangement induced by Smpdl3b gene silencing was significantly attenuated by choline but exaggerated by CDP-choline, which are product and substrate of SMPDL3b, respectively. Furthermore, atom force microscopy was used to study mechanical properties of podocytes lacking Smpdl3b gene as the outcome of actin cytoskeleton reorganization. Smpdl3b gene deletion was found to increase podocyte height but decrease cortical elasticity in these cells. Moreover, these pathological changes were markedly inhibited by choline. Taken together, our findings suggest that SMPDL3b is essential for the maintenance of functional and structural integrity of podocytes and that Smpdl3b gene knockout may induce podocytopathy and nephrotic syndrome in mice. This study was supported by NIH grants DK054927 and DK120491. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The interplay of oxidative stress and inflammation in pediatric patients with nephrotic syndrome

Summary 
 Background: The pathophysiological mechanisms crucial in the development of nephrotic syndrome (NS) in the pediatric population are still not fully understood. This study aims to investigate the synergistic interaction of oxidative stress and inflammation in the pathogenesis of NS. Additionally, one of the objectives of this study is to examine the relationship between hypertension and the degree of oxidative stress and inflammation in patients during the acute phase of the disease. 
 Methods: The study included 33 children, aged 2 to 9 years, with NS. Blood samples were collected during the acute phase and remission. Parameters of oxidative status were determined, including total oxidative status (TOS), advanced oxidation protein products (AOPP), prooxidant-antioxidant balance (PAB), sulfhydryl groups (-SH), paraoxonase 1 (PON1), and total antioxidant status (TAS) in serum, measured spectrophotometrically. Inflammatory parameters such as pentraxin 3 (PTX3), leptin, programmed cell death ligand 1 (PD-L1), and E-cadherin were determined using enzyme-linked immunosorbent assay (ELISA).
 Results: Patients with NS and hypertension had significantly higher levels of AOPP and TOS (p=0.029 and p=0.003, respectively). During the acute phase of the disease, lower activity of -SH and PON1 was observed compared to remission (p<0.001, for both). PTX3 levels were higher, while leptin levels were lower during the acute phase (p<0.001, for both). PTX3 correlated with AOPP and TAS during the acute phase but not in remission (rs=0.42, p=0.027 and rs=0.43, p=0.025, respectively). A negative correlation between AOPP and leptin was observed during the acute phase, which disappeared in remission (rs=-0.42, p=0.028).
 
 Conclusions: Results of this study show that hypertension influences oxidative stress markers, and decreased antioxidant capacity may contribute to NS development. PTX 3 appears as a potential disease activity marker, indicating a dynamic connection between inflammation and oxidative stress. Leptin may also play a role in oxidative stress in NS. 
 List of abbreviations: AOPP, advanced oxidation protein products; BMI, body mass index; DBP, diastolic blood pressure; ELISA, enzyme-linked immunosorbent assay; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; total antioxidant status; PAB, prooxidant-antioxidant balance; -SH, sulfhydryl group; SBP, systolic blood pressure; PON 1, paraoxonase; PTX 3, pentraxin 3; PD-L1, programmed cell death ligand 1; TC, total cholesterol; TG, triglyceride; TAS, total antioxidant status; TOS, total oxidation status.

Atypical form of Goodpasture's disease.

Goodpasture's disease and anti-glomerular basement membrane nephritis (anti-GBM nephritis) are rare autoimmune small vessel vasculitis predominantly affecting young men. Goodpasture's disease plays an important part in differential diagnosis of pulmonary - renal syndrome. The evidence of circulating autoantibodies, a typical histological appearance of the kidney biopsy with finding of the crescent glomerulonephritis and clinical presentation of nephritic syndrome play an important role in diagnosis. Our case report describes a case of a young male with anti-GBM nephritis that presents as rapidly progressive glomerulonephritis (RPGN) with progression to dialysis-dependent renal failure. The atypical sign of the case was development of nephrotic syndrome with volume-dependent hypertension. The case was complicated by heparin-induced thrombocytopenia. During combined immunosuppressive therapy with plasmapheresis, the condition of the patient has stabilized. However, renal function did not recover. This previously fatal disease has nowadays a very good survival rate because of immunosuppresion therapy, plasmapheresis and hemodialysis.

Nephrotic Syndrome in Adult Patients With COVID-19 Infection or Post COVID-19 Vaccine: A Systematic Review.

Nephrotic syndrome is a condition characterized by damage to podocytes that results in significant proteinuria, edema, hyperlipidemia, and hypercoagulability. Infections and malignancies are frequently associated with nephrotic syndrome. The COVID-19 virus has been associated with several atypical presentations of upper respiratory infections and acute kidney injury. Considering that COVID-19 causes systemic inflammatory changes, it seems plausible that it may also lead to nephrotic syndrome. This study aimed to investigate if an association between COVID-19 and the different types of nephrotic syndromes exists. Data were extracted into a spreadsheet. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS, IBM Corp., Armonk, NY, USA).We performed a systematic search of PubMed/Medline and Embase databases using both medical subject headings (MeSH) and regular keywords associated with COVID-19 and nephrotic syndrome, including different types of nephrotic syndromes. The search was performed on 17th December 2021. We included case reports and case series about adult patients who developed findings suggestive of nephrotic syndrome shortly after infection or vaccination. We excluded cases involving children, pregnant women, articles written in languages other than English, and those that were not retrievable. The relevance and quality of identified articles were assessed.We included 32 articles in the study, primarily case reports and case series. In our study, COVID-19 and the COVID-19 vaccine have been associated with the development of nephrotic syndrome, primarily a collapsing form of focal segmental glomerulosclerosis, although other forms have been observed as well. There was little consistency in patient histories, clinical presentations, clinical courses, or treatment regimens, although it appeared that most cases eventually resolved. More cases need to be reported and analyzed before more definitive conclusions can be reached.In conclusion, nephrotic syndrome is a possible complication of both COVID-19 infection and the COVD-19 vaccine and should be considered in patients exhibiting sudden onset edemas or deterioration in kidney function. While the majority of cases respond to standard treatment, clearer guidelines will need to be developed once more data is available.

VERRUCOUS CARCINOMA IN POSTTRANSPLANTED PATIENT WITH DECH

A male patient, 30 years old, diagnosed with severe aplastic anemia in 2005, underwent a hematopoietic stem cell transplantation in the same year. The patient developed graft-versus-host disease (GVHD), and underwent prolonged immunosuppression, which resulted in the development of nephrotic syndrome and immune thrombocytopenic purpura. The patient came to the dentistry clinic complaining of an oral lesion. We observed the presence of a 2 cm exophytic and ulcerated lesion with hardened edges, slightly bleeding to the touch, on the side of the tongue. In view of the suspicious aspect of the lesion, an incisional biopsy was performed and, after histopathologic analysis, the diagnosis of verrucous squamous cell carcinoma with ulceration was confirmed, and angiolymphatic and perineural invasions were not identified. The patient was referred to the head and neck surgery service for treatment. GVHD is a condition with the potential for malignant transformation, and such oral lesions must be monitored.

Difficulties of biological therapy in the patient with active rheumatoid arthritis and secondary renal amyloidosis: A report of clinical case

A clinical case of a patient with active rheumatoid arthritis (RA) resistant to standard basic therapy is presented, which served as the reason for the appointment of the target drug – Janus kinase, tofacitinib (Jaquinus) and then biological therapy using anti-IL6 receptor antibody tocilizumab (Actemra). This clinical example demonstrates the patient with the presence of several complications, both the course of the disease – amyloid nephropathy with the development of nephrotic syndrome (NS) as a manifestation of secondary amyloidosis with kidney damage, as well as basic therapy – the presence of comorbid infections with hospital pneumonia and infectious (septic) knee arthritis.An additional contribution of NS to the development of infectious complications in patients with RA receiving immunosuppressive therapy is supposed. Current treatment options for resistant RA and the feasibility of early use of biologics before the development of irreversible complications, as well as the difficulties of therapy and the complications associated with immunosuppression are discussed. Preventive measures for immunization with the anti-pneumococcal vaccine and the need to correct hemostatic disorders in patients with RA and NS are important.

Podocytes: The Role of Lysosomes in the Development of Nephrotic Syndrome

This commentary highlights the article by Li etal that links ceramide accumulation in podocytes to cellular damage and nephrotic syndrome.

Absence of Long Noncoding RNA H19 Promotes Childhood Nephrotic Syndrome through Inhibiting ADCK4 Signal.

BackgroundNephrotic syndrome (NS) is a common chronic kidney disease in children characterized by a group of clinical symptoms such as massive proteinuria, hypoproteinemia, high edema, and hyperlipidemia. Despite the tremendous efforts already made, the diagnosis for nephrotic syndrome still remains poor in children.Material/MethodsThe blood samples from 30 healthy children and 30 children with nephrotic syndrome were collected. The expression of H19 and ADCK4 (which are genes recently identified to play key roles in the development of nephrotic syndrome) in peripheral blood mononuclear cells (PBMCs), were detected by real-time quantitative polymerase chain reaction (RT-qPCR). The expression of ADCK4 was also detected by RT-qPCR or western blot when H19 was overexpressed or knocked down in human primary renal podocytes. Luciferase activity analysis was performed to measure whether H19 could regulate the promoter activity of ADCK4. RNA pull-down. In addition, mass spectrometry assay was used to find the transcription factor which could bind with H19, and RNA immunoprecipitation assay (RIPA) analysis was done to further confirm the interaction between H19 and candidate transcription factor.ResultsLong noncoding RNA H19 (lncRNA H19) expression was downregulated in PBMCs of children with nephrotic syndrome. ADCK4 was also downregulated. In human primary renal podocytes, overexpression of H19 promoted the expression of ADCK4, while H19 knockdown inhibited it. Furthermore, our study demonstrated that H19 could regulate the promoter activity of ADCK4. Using RNA pull-down and mass spectrometry technology, we found the transcription factor-THAP1 could bind with H19, and the interaction between them was further confirmed by RIPA analysis.ConclusionsH19 expression in blood samples may be a novel marker of the diagnosis of nephrotic syndrome in children.

Podocytopathy and Nephrotic Syndrome in Mice with Podocyte-Specific Deletion of the Asah1 Gene: Role of Ceramide Accumulation in Glomeruli

Lysosomal acid ceramidase (Ac) has been shown to be critical for ceramide hydrolysis and regulation of lysosome function and cellular homeostasis. In the present study, we generated a knockout mouse strain (Asah1fl/fl/PodoCre) with a podocyte-specific deletion of the α subunit (main catalytic subunit) of Ac. Although no significant morphologic changes in glomeruli were observed in these mice under light microscope, severe proteinuria and albuminuria were found in these podocyte-specific knockout mice compared with control genotype littermates. Transmission electron microscopic analysis showed that podocytes of the knockout mice had distinctive foot process effacement and microvillus formation. These functional and morphologic changes indicate the development of nephrotic syndrome in mice bearing the Asah1 podocyte-specific gene deletion. Ceramide accumulation determined by liquid chromatography-tandem mass spectrometry was demonstrated in isolated glomeruli of Asah1fl/fl/PodoCre mice compared with their littermates. By crossbreeding Asah1fl/fl/PodoCre mice with Smpd1-/- mice, we also produced a double knockout strain, Smpd1-/-/Asah1fl/fl/PodoCre, that also lacks Smpd1, the acid sphingomyelinase that hydrolyzes sphingomyelin to ceramide. These mice exhibited significantly lower levels of glomerular ceramide with decreased podocyte injury compared with Asah1fl/fl/PodoCre mice. These results strongly suggest that lysosomal Ac in podocytes is essential for themaintenance of the structural and functional integrity of podocytes.

Minimal change disease after hematopoietic stem cell transplant: Manifestation of chronic graft-versus-host disease

Chronic graft-versus-host disease is a potentially life-threatening immunological complication which can occur any time after hematopoietic stem cell transplant. Many organ systems can be affected; however, kidneys are normally not and development of nephrotic syndrome is particularly rare. In our report, a 64 year old who was diagnosed with acute myelogenous leukemia developed acute kidney injury and nephrotic syndrome secondary to minimal change disease. The patient responded well to treatment with steroids and rituximab therapy. Our goal is to communicate that nephrotic syndrome should be suspected in patients with significant hypoalbuminemia after graft-versus-host disease and withdrawing immunosuppression.

TRPC6 and NPHS2 gene variants in adult patients with steroid-resistant nephrotic syndrome in North-West of Iran.

Podocyte gene mutations and their role in the development of nephrotic syndrome (NS) have been reported in some ethnic groups. The aim of this study was to evaluate the presence of possible variants in TRCP6 and NPHS2 (podocin) genes and their association with clinical manifestations in a group of adult patients with steroid resistant nephrotic syndrome (SRNS). All participants including 36 patients with SRNS and 71 healthy volunteers were genotyped using polymerase chain reaction (PCR) and direct sequencing. Whole exons of NPHS2 gene and -254 C > G, -218 C > T, and -361 A > T polymorphisms in the promoter of TRPC6 gene were studied. There were no significant differences in the allele and genotype frequencies of aforementioned TRCP6 polymorphisms between cases and controls (P > 0.05). However, four novel polymorphisms including - 257 T > C, - 266 G > A, - 293 G > C, and - 21 G > A found in the promoter region of TRPC6 gene that may be involved in SRNS in our cohort. In NPHS2 gene, three different polymorphisms in the NPHS2 gene were found in 7 patients with FSGS and none of the previously reported risk polymorphisms was detected in our patients. Podocin related mutations are not too much associated with SRNS in adults, but we should consider the possibility of TRPC6 gene mutation in this population.

Acute Kidney Injury Following Methimazole Initiation: A Case Report

Objective: Nephritis has been rarely associated with methimazole, primarily in the development of nephrotic syndrome. We describe a case of acute kidney injury without evidence of nephrotic syndrome following methimazole initiation. Methods: We present the relevant history, laboratory data, and nuclear medicine data and review relevant documentation from the literature. Results: A 72-year-old male recently diagnosed with new-onset atrial fibrillation was found to have suppressed thyroid-stimulating hormone (TSH) levels; elevated free T3, T4, and thyroid-stimulating immunoglobulin (TSI) levels; and a nonnodular thyroid gland with normal iodine uptake. He was diagnosed with Graves’ disease and treated with propylthiouracil (PTU) for 5 years. When his poor compliance with PTU was impeding his antithyroid treatment, he was converted to methimazole. Within 1 month following methimazole initiation, his serum creatinine (SCr) had risen to 1.6× baseline in the absence of other contributing nephrotoxins. SCr returned to baseline within 2 weeks of methimazole discontinuation, and the patient was subsequently managed on PTU. Conclusion: Acute kidney injury with or without the presence of nephrotic syndrome may occur during treatment with methimazole. Renal function should be closely monitored after the initiation of methimazole to prevent progressive renal dysfunction.

Minimal change disease associated with anti-PD1 immunotherapy: a case report

BackgroundOncologic immunotherapy is a form of therapy intended to reactivate the immune response to tumor cells using agents that modulate immune checkpoints, such as programmed cell death protein 1 and its ligand (PD-1/PD-L), and cytotoxic T-lymphocyte-associated antigen 4. Along with activation of the immune system to tumors, immune-mediated kidney side effects have been reported, most of which are cases of interstitial nephritis. Glomerular disease, however, appears rare.Case presentationHerein, we describe a patient with nephrotic syndrome related to treatment with an anti-PD1 antibody for Hodgkin lymphoma. Following the third dose of anti-PD1 antibody, the patient developed massive proteinuria and nephrotic syndrome. Kidney biopsy showed diffuse podocyte foot process effacement upon electron microscopy, which was consistent with minimal change disease. Corticosteroid treatment yielded full and rapid remission of nephrotic syndrome in 1 month.ConclusionThe present case suggests an association between anti-PD1 therapeutic immune activation and the development of nephrotic syndrome. Given the increasing prevalence of oncologic immunotherapy, patients should be routinely monitored for kidney side effects associated with these agents.

EFFICACY AND SAFETY OF ENZYME REPLACEMENT THERAPY IN CHILDREN WITH MUCOPOLYSACCHARIDOSIS TYPE I, II, AND VI: A SINGLE-CENTER COHORT STUDY

Background. There are limited data on the efficacy of long-term enzyme replacement therapy (ERT) in children with mucopolysaccharidosis (MPS). Objective. Our aim was to study the efficacy and safety of long-term ERT in children with MPS type I, II, and VI. Methods. We analyzed the results of ERT with laronidase, idursulfase, and galsulfase in children with MPS type I, II, and VI admitted to the federal research center from January 2007 to November 2016. The response rate was assessed by the level of normalized urinary excretion of glycosaminoglycans (GAGs) (the ratio of GAGs concentration to urine creatinine) recalculated in percent (%) exceedance of the upper limit of normal for the corresponding age. Data on the administered therapy and its results, including adverse events, is extracted from the medical records of in-patients. Results. The results of treatment (intravenous infusions, intervals between administrations from 4 to 10 days) were studied in 33 children (5 of them were girls) with MPS type I (n = 4; laronidase at a dose of 0.58 mg/kg), II (n = 26; idursulfase at a dose of 0.5 mg/kg), and VI (n = 3; galsulfase at a dose of 1 mg/kg). A decrease in the normalized urinary excretion of GAGs from 376% (172; 791) to 54% (0; 146) exceedance of the upper limit of normal for the age (p < 0.001) was noted in the course of ERT lasting (median) 27 (14; 41) months. A decrease in the normalized GAGs excretion below the upper limit of normal for the age was established in 12/33 (36%) patients. ERT-associated adverse events were identified in 12 patients; one case required a two-fold therapy interruption. The development of nephrotic syndrome in the course of ERT in patients with severe MPS II was first described. Conclusion. Long-term ERT in children with MPS type I, II, and VI is characterized by acceptable efficacy and safety. Key words: children, mucopolysaccharidosis, enzyme replacement therapy, laronidase, idursulfase, galsulfase, glycosaminoglycans.

An unusual association between hemophagocytic lymphohistiocytosis, mixed connective tissue disease, and autoimmune hemolytic anemia

Rationale:In the adult patient, hemophagocytic lymphohistiocytosis (HLH) is uncommon and frequently difficult to diagnose due to its nonspecific presentation and numerous complications.Patient concerns:Herein, we present the case of a 25-year-old female who initially presented for evaluation of persistent fevers and fatigue. She was found to have splenomegaly, generalized lymphadenopathy, pancytopenia, and acute hepatic failure.Diagnoses, Interventions, and Outcomes:Her course was further complicated by the development of nephrotic syndrome and autoimmune hemolytic anemia (AIHA). Antinuclear antibody and ribonucleoprotein were positive, with concurrent physical examination findings, indicating underlying mixed connective tissue disease (MCTD). Ferritin was greater than 40,000 ng/dL. Viral studies, including hepatitis A, B, and C, cytomegalovirus, and Epstein–Barr virus were negative. On the basis of her clinical presentation, a diagnosis of HLH secondary to MCTD was made. This was later confirmed on liver biopsy. She was started on high-dose prednisone and her symptoms completely resolved. She was then transitioned to azathioprine, hydroxychloroquine, prophylactic antibiotics, and a prednisone taper for long-term management.Lessons:This case is notable for the association of both AIHA and MCTD with HLH, providing support for a possible relationship between these 3 conditions.

Secondary (AA) Amyloidosis with Development of Nephrotic Syndrome

A 25-year-old Caucasian female with a history of irritable bowel syndrome, presented to the emergency room with worsening upper bilateral abdominal pain and fatigue that began two days before arrival. The patient described having mild intermittent lower back pain and worsening bilateral edema of her ankles that began several months prior. Blood and urine specimens were tested, with results indicating the presence of systemic inflammation and nephrotic syndrome. The patient was admitted to the hospital for further testing and observation. An ultrasound of the kidneys was negative for renal calculus. A gallium scan indicated localization of leukocytes in the kidneys, liver and spleen. A CT urogram indicated renal damage and a SAP scan indicated amyloid deposits in the kidneys, liver and spleen. The patient was diagnosed with amyloidosis and nephrotic syndrome. Corticosteroids were prescribed and testing to determine the underlining cause of amyloidosis was initiated. ABBREVIATIONS:BUN - blood urea nitrogen, CBC - complete blood count, CRP - C-reactive protein, ECM - extracellular matrix, ESR - erythrocyte sedimentation rate, HLA - human leukocyte antigen, RBC - red blood cell, SAA - serum amyloid A, SAP - serum amyloid P, TNF - tumor necrosis factor, WBC - white blood cell

The glomerular permeability factors in idiopathic nephrotic syndrome.

It is currently postulated that steroid-sensitive idiopathic nephrotic syndrome (SSNS) and steroid-resistant idiopathic nephrotic syndrome (SRNS), which are not related to the mutation of a gene coding for podocyte structures or for glomerular basement membrane proteins, result from a circulating factor affecting podocyte shape and function. T lymphocytes have for a long time been suspected to be involved in the pathophysiology of these diseases. The successful treatment of steroid-dependant nephrotic syndrome with rituximab suggests a potential role for B lymphocytes. Clinical and experimental data indicate roles for cytokines IL-13, TNFα, circulating cardiotrophin-like cytokine factor 1 (member of the IL-6 family), circulating hemopexin, radical oxygen species, and the soluble urokinase-type plasminogen activator receptor (suPAR) in the development of nephrotic syndrome. Podocyte metabolism modifications—leading to the overexpression of the podocyte B7-1antigen (CD 80), hypoactivity of the podocyte enzyme sphingomyelin phosphodiesterase acid-like 3 b (SMPDL3b), and to the podocyte production of a hyposialylated form of the angiopoietin-like 4 (Angptl4)—are mechanisms possibly involved in the changes in the podocyte cytoskeleton leading to SSNS and or SRNS. Different multifactorial pathophysiological mechanisms can be advocated for SSNS and SRNS. The present paper reviews the experimental and clinical data upon which the different hypotheses are based and reports their possible clinical applications.

Albumin-associated free fatty acids induce macropinocytosis in podocytes.

Podocytes are specialized epithelial cells in the kidney glomerulus that play important structural and functional roles in maintaining the filtration barrier. Nephrotic syndrome results from a breakdown of the kidney filtration barrier and is associated with proteinuria, hyperlipidemia, and edema. Additionally, podocytes undergo changes in morphology and internalize plasma proteins in response to this disorder. Here, we used fluid-phase tracers in murine models and determined that podocytes actively internalize fluid from the plasma and that the rate of internalization is increased when the filtration barrier is disrupted. In cultured podocytes, the presence of free fatty acids (FFAs) associated with serum albumin stimulated macropinocytosis through a pathway that involves FFA receptors, the Gβ/Gγ complex, and RAC1. Moreover, mice with elevated levels of plasma FFAs as the result of a high-fat diet were more susceptible to Adriamycin-induced proteinuria than were animals on standard chow. Together, these results support a model in which podocytes sense the disruption of the filtration barrier via FFAs bound to albumin and respond by enhancing fluid-phase uptake. The response to FFAs may function in the development of nephrotic syndrome by amplifying the effects of proteinuria.

Nephrotic syndrome with a nephritic component associated with toxoplasmosis in an immunocompetent young man

Introduction: Although the association of infection by toxoplasmosis with the development of nephrotic syndrome is uncommon, cases of this association have nevertheless been reported in the literature for more than two decades, not only for congenital toxoplasmosis, but also in acquired cases, and occasionally in immunocompetent patients.Results: A case is presented of an immunocompetent patient aged 15 with clinical and laboratory indications of nephrotic/nephritic syndrome, in whom serological tests showed toxoplasma infection.Conclusion: The presentation of nephrotic syndrome in ages where it is not commonly seen, leads to clinical suspicion of secondary causes. Active search for possible causes should include common tropical infections.

Membranous nephropathy in an HIV-positive patient complicated with hepatitis B virus infection

In ordinary settings, human immunodeficiency virus (HIV)-associated nephropathy should be considered when HIV infection is associated with heavy proteinuria. On the other hand, hepatitis B virus (HBV) may also play a role in the development of glomerular injury among patients with HIV infection, since HIV and HBV infections commonly occur together due to shared modes of transmission. We present here a case of nephrotic syndrome in an HIV-positive patient complicated with HBV infection. A renal biopsy revealed sparse granular deposits of immunoglobulin G in the subepithelial region, consistent with membranous nephropathy (MN) stage I. Moreover, immunostaining exhibited weak anti-hepatitis B core activity within glomeruli. These results led us to consider that HBV-associated MN might play a role in the development of nephrotic syndrome. Although anti-viral treatment for patients with HBV-associated MN has been suggested to be clinically effective, the use of two anti-HIV agents (tenofovir and emtricitabine), both of which have anti-HBV activities, was not effective for the patient's nephrotic syndrome, despite obtaining a decrease in the serum HBV-DNA levels. A lack of prospective data suggests that many decisions on the treatment of glomerulopathies with HIV infections are potentially empirical. Obviously, further studies and accumulated clinical experience are required to better determine the pathogenesis and management of HBV-associated MN among patients with HIV infections.