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Nephrotic syndrome in patients with cancer may be related to the primary malignancy or chemotherapeutic therapy. Solid organ cancers may cause membranous glomerulonephritis manifesting with nephrotic syndrome; other less common histologic presentations include focal and segmental glomerulosclerosis and minimal change disease. In addition, chemotherapy agents can cause renal toxicity by affecting the small blood vessels, glomeruli, tubules, and interstitium. Tyrosine kinase inhibitors such as sunitinib may cause endothelial and podocyte damage leading to renal limited thrombotic microangiopathy, manifested by proteinuria and hypertension. We report a case of an elderly man with gastrointestinal stromal tumor (GIST) on treatment with sunitinib who had as a complication of a thrombotic microangiopathy manifested with nephrotic syndrome and difficult-to-control hypertension, which was controlled by stopping this drug but with a fatal outcome due to its malignant neoplasm.

Tyrosine kinase inhibitors (TKI) are anticancer agents widely used for a variety of malignancies including gastrointestinal stromal tumours (GIST). Although generally well-tolerated, TKIs have been associated with a number of adverse events including hypertension, proteinuria and nephrotic syndrome. We present the case of a 70-year-old patient with metastatic GIST on long-standing sunitinib who developed hypertension, oedema and hypoalbuminemia with a rising serum creatinine and was found to have nephrotic syndrome. Workup revealed elevated antiphospholipase A2 receptor (PLA2R) antibody IgG titres and a kidney biopsy confirmed PLA2R-positive membranous nephropathy without findings of thrombotic microangiopathy. Cessation of sunitinib led to reduction in anti-PLA2R antibody IgG titres while resumption, due to concern for cancer progression, led to worsening symptoms. Treatment with rituximab led to undetectable anti-PLA2R IgG titres. We highlight the importance of maintaining a systematic approach for evaluating nephrotic syndrome and provide a case showing that TKIs can exacerbate underlying nephrotic syndrome.

Background Nephrotic syndrome (NS) is associated with an increased risk of thromboembolic events (TEs), due to hemostatic derangements. The use of direct oral anticoagulants (DOACs) in the prevention of TE has not been studied intensively in patients suffering from NS. Methods The method included retrospective analysis of consecutive incident patients with NS due to glomerular disease, receiving apixaban for thromboprophylaxis. It is an uncontrolled, single-center study. Results We identified 27 patients treated with apixaban for the prevention of TEs, in the context of NS. During follow-up, apixaban minimal blood concentration (trough level; Cmin) and maximum blood concentration (Cmax) levels were measured. The mean duration of the anticoagulant treatment was 153 days (±132). Patients were followed for a mean of 14.7 months (±8.4) since the introduction of apixaban. Three patients had a TE at the time of NS diagnosis. Two patients had pulmonary embolism (PE) and one patient presented a stroke in a lupus membranous nephropathy context. One patient developed PE approximately 2 months after the introduction of apixaban treatment. No minor or major bleeding events were noticed. Conclusion The present study shows that patients, suffering from severe NS under anticoagulant therapy with apixaban had a reduced risk of venous and arterial TEs compared with patients previously described in the literature, without increased risk of bleeding.

Several novel antigens have recently been characterized in membranous nephropathy (MN), but those involved in the rare cases of MN associated with inflammatory neuropathies (IN) remain elusive. Although several antibody specificities were identified in the serum, there is no evidence so far for their deposition in glomeruli. We report the case of a 73 y/o woman who was referred because of subacute onset of proximal asymmetric lower limb weakness together with ataxic gait. She was diagnosed with IN. Blood tests showed an eGFR of 73 ml/min/1.73m2, hypoalbuminemia (2.89 g/dl) and proteinuria (3.6 g/24h). Autoantibodies (ANA, ENA, DNA, LAC, anti-cardiolipin, ANCA) were undetectable. Serum Ig and complement levels were normal. A kidney biopsy with electron microscopy examination showed a classical picture of MN. Anti-PLA2R antibody was negative in the serum and PLA2R and THSD7A antigens were not detected in kidney tissue. Anti-contactin1 (CNTN1) antibody was found by ELISA at 1:100 serum dilution and shown to be mostly of IgG4 subclass by Western blot. CNTN1 antigen was co-localized with IgG4 within immune deposits by confocal microscopy. This observation suggests a pathophysiological link between IN and MN. CNTN1 should be considered as a potential candidate antigen involved in MN and tested in PLA2R negative forms associated with IN.

Chylothorax is an uncommon and serious clinical condition, typically induced by trauma, either postsurgical or accidental injury, but the mechanism of chylothorax caused by nephrotic syndrome is still unclear. Here, we report a case of primary nephrotic syndrome with membranous nephropathy (MN) in a 66-year-old man who presented with severe chylothorax. The chylothorax was managed by intercostal chest tube drainage, subcutaneous injection of enoxaparin, and treatment with anti-inflammatory agents and diuretics. After treatment, the patient's pleural effusion decreased, and the chyle gradually became clear. We discuss the causes of MN with chylothorax. We considered that the hypoproteinemia changed the permeability of mucous membranes and lymphatic vessels, leading to leakage of chylous particles and chylous pleural effusion formation. Chylothorax may also have been caused by severe tissue edema, edema of the lymphatic walls, and increased pressure, resulting in increased permeability or rupture of the lymphatic wall, and leakage of chylous fluid into the thoracic cavity. Because of its rarity, we hope this case report will improve clinicians' understanding of MN complications in primary nephrotic syndrome and provide suitable treatment options for future clinical reference.

Calciphylaxis is commonly associated with end-stage renal disease (ESRD) and renal transplant. We present a rare case of early onset calciphylaxis in a patient presenting with acute kidney injury (AKI) secondary to anti-glomerular basement membrane (anti-GBM) antibody disease. A 65-year-old obese Caucasian woman with type 2 diabetes mellitus and hypertension presented with a 1-month history of painless gross haematuria and worsening lower extremity oedema. Laboratory results indicated AKI and nephrotic-range proteinuria. Anti-glomerular antibodies were elevated. Renal biopsy revealed focal crescentic glomerulonephritis with linear capillary immunoglobulin G staining consistent with anti-GBM antibody disease. She was treated with haemodialysis, plasmapheresis, steroids, bumetanide and cyclophosphamide. Two months later, she developed necrotic lesions on bilateral thighs. Wound biopsy was consistent with calciphylaxis. This case highlights that calciphylaxis, usually seen in patients with chronic kidney disease or ESRD, can manifest in patients with AKI as well.

A 39-year-old woman was hospitalized for nephrotic syndrome. Laboratory test results showed increased serum creatinine levels and urinary excretions of beta-2-microglobulin, and N-acetyl-beta-D-glucosaminidase. A renal biopsy revealed collapsing focal segmental glomerulosclerosis (FSGS) and acute interstitial nephritis. Despite treatment with pulse steroid followed by oral high-dose glucocorticoids and cyclosporines, heavy proteinuria persisted. After low-density lipoprotein apheresis (LDL-A) therapy was initiated, her proteinuria gradually decreased, leading to complete remission. A repeat renal biopsy after treatment revealed no collapsing glomeruli. Immediate LDL-A should be performed to treat cases of collapsing FSGS poorly responding to other treatments.

Tubular basement membrane (TBM) deposits are very uncommon in non-lupus membranous nephropathy. We report 5 patients with membranous nephropathy and extensive TBM deposits following allogeneic hematopoietic cell transplant. Patients presented with nephrotic syndrome (3 also had acute kidney injury) late post-transplant in association with chronic graft-versus-host disease (cGVHD). Kidney biopsies revealed global subepithelial and extensive TBM immune complex deposits, accompanied by acute tubular injury (n = 4) and tubulointerstitial inflammation (n = 4). Proteomic analysis of glomeruli in 4 cases identified PLA2R in 1, with no significant protein spectra for PLA2R, THSD7A, EX1/2, NELL-1, PCDH7, NCAM1, or SEMA3B detected in the remaining 3. On follow-up (for a mean 42 months), 4 patients had complete and 1 partial remission following prednisone and/or rituximab therapy. We propose that membranous nephropathy with extensive TBM deposits is a distinctive clinicopathologic lesion associated with allogeneic hematopoietic cell transplant. Pathogenesis likely involves cGVHD-driven antibodies against glomerular and TBM components, the identity of which remains to be elucidated.

Systemic mastocytosis is characterised by tissular infiltration and a cytokine storm due to mast cells excessive proliferation and activation. Herein, we report an extraordinary case of AH1N1 influenza post-viral glomerulonephritis occurring in the course of an aggressive systemic mastocytosis with an associated hematological neoplasm. Because of a multisystemic involvement including the liver and lungs, we treated mastocytosis with midostaurin (multiple inhibitor of kinase protein), anti H1/H2 blockers and dexamethasone as first line treatment. One month later and despite vaccination, he developed a severe acute lung injury with respiratory distress due to AH1N1 influenza in association with the nephrotic syndrome. Kidney biopsy disclosed a membranoproliferative glomerulonephritis that was successfully treated with mycophenolate mofetil. Only a few cases of influenza post-viral or post-vaccination glomerulonephritis are documented in the medical literature. This is an exceptional association of uncommon conditions occurring within only a few months in the same patient.

Background Sixty percent of children with nephrotic syndrome have frequently relapsing or steroid-dependent course. Serious infections like peritonitis, cellulitis, pneumonia etc. and anasarca with reduced urine output and complications there of including acute kidney injury and thromboembolism contribute significantly to morbidity and mortality in these children. Methods Questionnaire-based module to study infectious complications in children with nephrotic syndrome was circulated through survey monkey portal to paediatric nephrologists in our country. Twenty-two responded. Forty percent said that they saw patients with severe infections once a month. Fish bone analysis conducted on such patients reporting to our centre over next 3 months revealed that only 22% regularly monitored urine protein by dipstick. We proposed that reduction in time to report relapse by regularly monitoring urine protein could reduce complications in these children. Six urine protein dipsticks were handed over to patients who presented >7 days since relapse or with severe infection or anasarca in the last 1 year. These children were followed up for the next 1 year and given six more urine dipsticks every 3 months. Results Twenty-three patients were given urine protein dipsticks. Nine of them had 12 severe complications in the previous 6 months. None had any serious infections/anasarca on follow-up. Sixteen new patients had 14 serious complications in this time. Conclusions Early detection of relapse by home monitoring of urine protein by dipsticks was effective in significantly reducing the number of patients with severe infections and anasarca with reduced urine output.

We herein report a 43-year-old woman with Buerger's disease who presented with nephrotic syndrome, renal dysfunction, and mild hypertension. A kidney biopsy revealed focal segmental glomerulosclerosis (FSGS), but there were no findings associated with frequent secondary FSGS or a history of long-term hypertension. A small focal renal infarction was seen on 99mTc-dimercaptosuccinic acid renal scintigraphy, suggesting that FSGS was due to renal microinfarction associated with Buerger's disease. After the commencement of angiotensin-converting enzyme inhibitor therapy, the hypertension immediately improved, along with significant attenuation of proteinuria. Renal ischemia by vasoconstriction of the glomerular efferent arterioles in association with Buerger's disease may result in glomerular hyperfiltration followed by FSGS.

Antineutrophil cytoplasmic antibodies (ANCAs) are associated with small vessel vasculitis but their prevalence is not rare in other immune diseases. In lupus nephritis (LN), their pathological role and clinical relevance have been the target of controversial views. We present a case of acute kidney injury and nephrotic syndrome in a young woman with diffuse global proliferative and membranous nephritis on her kidney biopsy, showing a full-house immunofluorescence pattern, very allusive of class IV + V LN, but lacking associated clinical criteria and laboratory findings to support the diagnosis of systemic lupus erythematosus (SLE). Furthermore, the patient presented with high titers of ANCA, steadily decreasing alongside the renal function and proteinuria improvements, with mycophenolate mofetil (MMF) and steroid treatment. The authors believe this is a case of lupus-like nephritis, in which ANCAs are immunological markers, although they are not directly involved in the pathogenesis.

Nephrotic syndrome is characterized by severe proteinuria, hypoalbuminaemia, edema and hyperlipidaemia. Genetic studies of nephrotic syndrome have led to the identification of proteins playing a crucial role in slit diaphragm signaling, regulation of actin cytoskeleton dynamics and cell-matrix interactions. The laminin α5 chain is essential for embryonic development and, in association with laminin β2 and laminin γ1, is a major component of the glomerular basement membrane, a critical component of the glomerular filtration barrier. Mutations in LAMA5 were recently identified in children with nephrotic syndrome. Here, we have identified a novel missense mutation (E884G) in the uncharacterized L4a domain of LAMA5 where homozygous mice develop nephrotic syndrome with severe proteinuria with histological and ultrastructural changes in the glomerulus mimicking the progression seen in most patients. The levels of LAMA5 are reduced in vivo and the assembly of the laminin 521 heterotrimer significantly reduced in vitro. Proteomic analysis of the glomerular extracellular fraction revealed changes in the matrix composition. Importantly, the genetic background of the mice had a significant effect on aspects of disease progression from proteinuria to changes in podocyte morphology. Thus, our novel model will provide insights into pathologic mechanisms of nephrotic syndrome and pathways that influence the response to a dysfunctional glomerular basement membrane that may be important in a range of kidney diseases.

Amyloidosis is a rare group of diseases characterized by abnormal folding of proteins and extracellular deposition of insoluble fibrils. It can be localized to one organ system or can have systemic involvement. The kidney is the most common organ to be involved in systemic amyloidosis often leading to renal failure and the nephrotic syndrome. The two most common types of renal amyloidosis are immunoglobulin light chain-derived amyloidosis (AL) and reactive amyloidosis (AA). A novel form of amyloidosis (ALECT2) derived from leukocyte chemotactic factor 2 (LECT-2) and primarily involving the kidneys was first described by Benson et al in 2008. The liver was subsequently identified as the second most common organ involved in ALECT2 amyloidosis. LECT-2 is a unique protein that can form amyloid deposits even in its unmutated form. Patients with ALECT2 present with minimal proteinuria in contrast to other forms of amyloidosis especially AL and AA. They may present with slightly elevated serum creatinine. Nephrotic syndrome and hematuria are rare. ALECT2 can be found in association with other types of amyloidosis as well as malignancies or autoimmune diseases. ALECT2 may be confused with amyloidosis associated with light and heavy chain monoclonal gammopathy if the immunofluorescence is positive with anti-light chain and anti-AA sera. The other organs involved are the duodenum, adrenal gland, spleen, prostate, gall bladder, pancreas, small bowel, parathyroid gland, heart, and pulmonary alveolar septa, but consistently uninvolved organs included brain and fibroadipose tissue. A renal biopsy along with characteristic features found on immunohistochemistry and mass spectrometry is diagnostic of ALECT2. ALECT2 should be suspected when all markers for AL and AA are negative. Proper diagnosis of ALECT2 can determine need for supportive care versus more aggressive interventions.

Objective The existing cyclosporine (CsA) population pharmacokinetic (PPK) model does not apply well to children. The aim of the study was to establish a CsA PPK model for Chinese children with nephrotic syndrome (NS) and conduct a dosage simulation to provide drug-dosing guidance. Materials and methods A total of 311 drug monitoring data points were collected from 165 children. Blood samples were collected before dosing. Non-linear mixed-effects model was applied to develop the PPK model. Covariate analysis was applied to select candidate factors associated with pharmacokinetic (PK) parameters. A model-based simulation was then performed to estimate the optimal initial dose for different patient subgroups. Results A one-compartment model with first-order absorption and elimination was chosen to describe the drug trajectory in vivo. The typical values for apparent clearance/absorption fraction (CL/F) and apparent volume of distribution/absorption fraction (V/F) were 40.1/h and 2.32 ×103 L, respectively. The covariate analysis revealed that weight and total cholesterol were strongly associated with CL/F and V/F. Goodness-of-fit and model evaluation suggested that the proposed model was acceptable. A dosage regimen table was created for specific pediatric groups to facilitate clinical application. Conclusion A PPK model of CsA in Chinese pediatrics was successfully established, allowing the development of individualized dosing regimens for Chinese pediatric NS patients.

The pathogenesis of primary focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) remains unknown to date. Some circulating permeability factors are being discussed. This work assessed molecule candidates for permeability in serum samples of patients with nephrotic syndrome (NS). MATERIALS AND METHODS 41 patients with chronic glomerulonephritis (CGN) were included in our study. 17 patients had FSGS, 7 patients had MCD, 5 patients had membranoproliferative glomerulonephritis (MPGN), 6 patients had IgA nephropathy, and 6 patients had membranous nephropathy (MN). The laboratory data were compared with the clinical and histological features of nephritis. Serum levels of plasminogen activator urokinase receptor (uPAR) and cardiotrophin-like cytokine factor 1 (CLCF-1)were measured by ELISA. RESULTS The serum levels of uPAR were higher in FSGS patients before treatment than in patients with other morphological forms (MCD, IgA nephropathy, MN, and MPGN). The levels of uPAR in serum did not correlate with daily proteinuria, serum creatinine/eGFR, arterial hypertension, the number of sclerosed glomeruli, or tubulointerstitial fibrosis. No correlations were found between the levels of CLCF-1 in serum and creatinine levels/glomerular filtration rate, the percentage of sclerosed glomeruli, or the severity of tubulointerstitial fibrosis. There were no significant differences between the histological variants of nephritis. However, we found correlations between CLCF-1 levels and proteinuria and lipid levels. CONCLUSION The data indicate an increase in the serum uPAR levels of FSGS before treatment. CLCF-1 levels in serum do not depend on histological forms of CGN, kidney function, or immunosuppressive treatment, but they correlate with proteinuria and serum lipids in patients with NS.

We herein report two cases in which add-on acetazolamide to furosemide was effective for diuretic-resistant volume overload and hypercapnia. Case 1 was a woman in her 40s presenting with volume overload due to the nephrotic syndrome with diabetes mellitus. Case 2 was a man in his 60s with fluid overload and non-nephrotic proteinuria and sepsis. In both cases, although fluid overload was resistant to high-dose loop diuretics and complicated with hypercapnia due to pulmonary effusion, add-on acetazolamide administration resulted in symptom resolution. The additional effect of acetazolamide occurred regardless of the degree of proteinuria and kidney function.

Background Nephrotic syndrome (NS) is the most frequent glomerular disease among children. Renal biopsy is the most precise procedure for diagnosing and following childhood NS; however, it is an invasive procedure with potential complications. As a result, early non-invasive diagnostic and prognostic indicators and new treatment targets are urgently needed for this disease. Purpose To assess the miR-142-5p expression in peripheral blood as an indicator of the autoimmune processes in children with NS and the role of differential microRNAs (miR) expression and expression panels in diagnosing and predicting the response to steroid treatment in children with NS. Methods Eighty (80) children with NS and 100 subjects matched for age and gender used as controls constitute the study sample in this case-control study. MiR-142-5p, miR-191, miR-181-5p, miR-30a-5p and miR-50a-5p expression are measured in all enrolled children by real-time PCR. We assessed the sensitivity and accuracy of different MicroRNAs panels. Results miR-142-5p, miR-191, miR-181-5p, miR-30a-5p and miR-150a-5p expressions were significantly increased in the children with NS than controls. There was a significant difference in the five mRNAs differential expressions between steroid-resistant and steroid-sensitive children with NS. Of the selected five microRNAs, miR-142a-5p was the best to allow very good discrimination of the children with NS and predict steroid resistance (AUC = 0.965 and 1.00, respectively), suggesting the possible autoimmunity processes' role in the pathogenesis of NS and the resistance to steroids. The (miR-142a-5p with miR-181a-5p and miR-30a-5p) was the best expression panel to diagnose new NS cases and predict steroid resistance. Conclusions microRNAs expressions, either differential or as a panel, are important for early diagnosing childhood NS and may provide a non-invasive clue for the response to steroid treatment in these patients. The (miR-142a-5p, miR-181-5p, and miR-30a-5p) panel was the best one to cover both the diagnosis of the new cases and prediction of response to steroid treatment. Autoimmunity has an important role in NS pathogenesis and resistance to steroid treatment.

Aim The prevalence of kidney disease and the number of renal biopsies performed in the elderly are increasing with aging of the population. We aimed to analyze the clinicopathological findings of kidney diseases in the elderly (≥ 65 years), in comparison with their younger counterparts (aged 16 - 64 years). Materials and methods The data at the time of renal biopsy were obtained by reviewing medical records and the biopsy reports of the patients retrospectively. The data at the time of renal biopsy were obtained by reviewing medical records and the biopsy reports of the patients who underwent renal biopsy at Bakirkoy Dr. Sadi Konuk Education and Research Hospital. Demographic characteristics, clinical syndrome at presentation, and histopathological diagnosis of all patients were recorded. Results Among the 750 renal biopsies, 93 were performed in elderly patients, which constitutes 12.4% of the biopsies. The mean age of the patients was 71.7 ± 5.4 years, and 62.4% were male. The most common indication for renal biopsy was nephrotic syndrome (NS) in elderly and younger age groups (45.2% vs. 40%). The most frequent histopathological diagnosis was membranous glomerulonephritis (MGN). According to the clinical presentation, MGN (42.8%) was the leading cause of NS, and almost 1/3 of the patients with acute or rapidly progressive renal failure were found to have pauci-immune glomerulonephritis (GN). In comparison with renal biopsy results of younger patients, MGN and pauci-immune GN were more prevalent, but IgA nephropathy, lupus nephritis, and acute tubular necrosis were less common in elderly patients. Conclusion Clinical presentation and the frequency of certain renal pathologies differ with age. The relatively high prevalence of potentially curative kidney diseases in the elderly indicates the importance of renal biopsy in these patients.

Nephrotic syndrome (NS) is characterized by massive urinary protein leakage and associated hypoproteinemia due to increased protein permeability caused by impaired renal glomerular connections. Although there have been several sporadic reports regarding the relationship between NS and thyroid dysfunction, a consensus has yet to be reached. The mechanism of hypothyroidism in NS is attributed to the loss of protein-bound thyroid hormones, such as thyroxine-binding globulin, transthyretin, and albumin, into the urine. Herein, we report four adults with hypothyroidism that developed or worsened due to the onset of NS. The patients' underlying thyroid status was post-total thyroidectomy with supplemental levothyroxine (L-T4) in two patients, hypothyroidism with supplemental L-T4 due to Hashimoto's disease in one patient, and Hashimoto's disease with normal thyroid function in one patient. Our results suggest that the presence of a reduced thyroid reserve may predispose patients to hypothyroidism in NS. We conclude that NS may cause or exacerbate hypothyroidism. In such cases, an NS assessment, including a urine test, is required.

We report a 64-year-old caucasian woman diagnosed with membranous nephropathy secondary to alpha-1 antitrypsin deficiency (AATD). AATD is a rare autosomal codominant genetic disorder. Its clinical manifestations are mostly observed in the lungs, with early-onset emphysema. Nephropathy due to AATD is still very rare and only a few cohort studies have been reported. It has been recognised that alpha-1 antitrypsin has a protective role in the kidneys which enhances the possibility of development of kidney failure, such as nephrotic syndrome, in cases of AATD. Further clinical investigation is needed to understand the relationship between the development of nephropathy, namely membranous nephropathy, and AATD.

The association between Takayasu’s arteritis and membranous nephropathy is uncommon. We present the case of a 46-year-old man with Takayasu’s arteritis treated over 10 years by a multidisciplinary medical team. He had an atrophic left kidney due to arterial stenosis, with a basal creatinine of 1.59 mg/dL (140.55 µmol/l). Three years ago, he presented with full nephrotic syndrome, uncontrolled blood pressure, creatinine increases to 4.5 mg/dL (basal: 1.59 mg/dL), severe hypoalbuminaemia (1.4 g/dL) and albuminuria of 24.6 g per day. He underwent percutaneous biopsy of the right kidney that showed membranous nephropathy with negative PLA2R1 and positive IgG 1, 3 and 4 subclasses. After therapy with oral prednisone and cyclophosphamide, the patient’s kidney function improved, without recurrence of disease after 3 years of follow-up. Here, we present this extremely uncommon association of Takayasu’s arteritis and membranous nephropathy.

Unlike patients with congestive heart failure (CHF) and cirrhosis, patients with nephrotic syndrome have some underlying renal disease. Also, effective circulating volume (ECV) is not decreased in all patients with nephrotic syndrome. This syndrome is characterized by proteinuria in excess of 3.5 g/day, hypoalbuminemia, hyperlipidemia, edema, and lipiduria. The mechanism for salt and water retention is not clear. The traditional (“underfill”) theory implies that loss of protein in the urine causes hypoalbuminemia and decreased plasma oncotic pressure. These factors favor fluid movement into the interstitium, resulting in intravascular hypovolemia and activation of salt-retaining mechanisms (Fig. 9.1). Two lines of evidence, however, argue against this traditional theory. First, not all patients with congenital deficiency of albumin (analbuminemia) develop edema. Second, some patients with nephrotic syndrome have either normal or increased intravascular volume despite hypoalbuminemia. This evidence suggests that mechanisms other than hypoalbuminemia and decreased intravascular volume play a role in renal retention of Na+ in nephrotic syndrome.

AIM This meta-analysis comprehensively investigated the ef?cacy and safety of rituximab (RTX) in patients with idiopathic membranous nephropathy (IMN). METHODS We searched the MEDLINE, EMBASE and Cochrane Registry of Controlled Trials databases from January 2000 to January 2020. Studies evaluating the efficacy and safety of RTX in the treatment of IMN with nephrotic syndrome (NS) were included. RESULTS Nine studies (total of 357 patients) were included in the meta-analysis. The pooled complete response and overall response (OR) rates at 12 months were 13.2% (95% confidence interval [CI], 0.09?0.18) and 60% (95% CI, 0.48?0.72), and those at 24 months were 27.8% (95% CI, 0.22?0.34) and 66% (95% CI, 0.6?0.72), respectively. The pooled OR rates for the low-, standard-, and high-dose groups were 39.3%, 64%, and 60%, respectively, and those for the first-line and second-line groups were 58% and 54%, respectively. CONCLUSIONS Treatment of IMN with RTX has comparable efficacy to other immunosuppressive treatments (ISTs). RTX has the advantages of no requirement for steroids and lower rates adverse event and relapse rates. Patients who relapse or are resistant to other IST agents also respond to RTX. RTX-based regimens and other B-cell-targeted therapies may represent the future of IMN therapy.

Nephrotic syndrome (NS) might be caused by a kidney disorder or it can be a secondary disease. Untreated or resistant to treatment, NS stimulates glomerular damage that reduces the kidney function. This reduction leads to the end stage of renal failure. Therefore, it is very important to diagnose NS early, with the aim of inhibiting or lessening its associated morbidity and mortality.Gene polymorphism analysis for the three genes eNOS 27 bp VNTR, GSTP1 and IL-10(1082 G/A) were checked in 98 children with NS and 101 control subjects.eNOS 27 bp VNTR genotypes and alleles are significantly different in the group of 98 children with NS compared to the 101 control subjects. The frequencies of ab and bb genotypes are significantly lower in patients than in the control group (ab: 17.2% vs. 22.8%; OR: 0.19; 95% CI: 0.06-0.58; p = 0.0026bb: 54.7% vs. 70.3%; OR: 0.19; 95% CI: 0.07-0.5; p = 0.0004). However, neither GSTP1 nor IL-10(1082 G/A) genotypes showed any significant difference in both groups.eNOS 27 bp VNTR gene might be considered as an independent risk factor in the early prediction of nephrotic syndrome incidence, which may help prevent/reduce the occurrence of other complications associated with the late diagnosis and treatment of the disease.

International audience; Primary focal and segmental glomerulosclerosis (FSGS) frequently recurs after transplantation and is associated with a poor prognosis. We describe here the successful kidney graft reuse in an adult recipient, 8 months after early primary FSGS recurrence resistant to all available therapeutics. Patient 1, a 23-year-old man, followed for kidney failure secondary to primary FSGS, was first transplanted in 2018 with a deceased donor graft. Unfortunately, we observed an immediate recurrence of biopsy-proven primary FSGS. After 4 lines of treatment (intravenous cyclosporine + corticosteroids, plasma exchanges, immunoadsorption, and rituximab), the patient was still highly nephrotic and kidney function was slowly deteriorating. After approval from both the patient and the health authority (Biomedicine Agency), the graft was detransplanted 8 months after transplantation and reimplanted in patient 2, a 78-year-old nonimmunized and anephric recipient (bi-nephrectomy 2 years previously for bilateral renal carcinoma). We observed immediate kidney function and progressive resolution of proteinuria (serum creatinine of 1.2 mg/dL and proteinuria of 0.1 g/d 1 year later). Biopsies performed after surgery showed persistent FSGS lesions with a decrease in overall foot-process effacement. To our knowledge, this is the first reported case showing that kidney graft transfer may still be a viable option for refractory primary FSGS several months after transplantation.

A 78-year-old man presented with nephrotic syndrome and new-onset disorientation. Plasma D-dimer level was increased, and a lower leg deep vein thrombosis was identified on ultrasound. Histopathologic analysis of percutaneous renal biopsy samples confirmed the diagnosis of minimal change disease. Treatment with prednisone (20 mg/day), cyclosporine (50 mg/day), and anticoagulant therapy with edoxaban tosylate hydrate led to the complete resolution of nephrotic syndrome after 4 weeks. Despite this, his disorientation persisted. Head CT and MRI have revealed cerebral venous sinus thrombosis and dural arteriovenous fistula, which was considered a possible complication of nephrotic syndrome. Embolization dramatically improved his disorientation. This paper highlights that cerebral venous sinus thrombosis and dural arteriovenous fistula should always be considered in patients with nephrotic syndrome and new-onset disorientation.

BACKGROUND: Variation in dose and duration of corticosteroids for childhood-onset steroid-sensitive nephrotic syndrome occurs worldwide, likely reflecting the evolving evidence on optimal dosing and variable severity of the disease observed between patients. We conducted a study to determine the associations between site, physician, and patient factors, and average daily corticosteroid dose and duration of therapy. METHODS: Data were derived from the Canadian Childhood Nephrotic Syndrome (CHILDNEPH) Project, an observational longitudinal study from 2013 to 2019 of children with nephrotic syndrome involving pediatric nephrologists in 11 sites across Canada. The primary outcome was average daily corticosteroid dose prescribed per episode of proteinuria, reported as mg/m(2) prednisone equivalents. Secondary outcome was duration of treatment for each episode of proteinuria in days. Exposure variables were categorized into site-, physician-, and patient-level variables. RESULTS: In total, 328 children, median age at enrollment of 4.3 years old (interquartile range [IQR], 3.6), participated and were followed for a median time of 2.62 years (IQR, 2.6). The observed variability in average daily corticosteroid dose and in duration of therapy was mostly attributed to the site where the patient was treated. Accounting for between patient, physician, and site differences, average daily corticosteroid dose decreased with increasing age (beta coefficient, −0.07; 95% confidence interval [95% CI], −0.09 to −0.05], P

Galloway-Mowat syndrome (GAMOS) is an extremely rare clinically heterogeneous autosomal or X-linked inherited recessive disease characterized by early-onset steroid-resistant nephrotic syndrome (SRNS), microcephaly and neurological impairment. In this study, two siblings mainly presenting with decreased head circumference, hypotonia, gross motor delay, and dysmorphic features were initially detected without pathogenic variants by karyotyping, SNP-array and WES. After a 3 year’s follow-up, the proband manifested additional proteinuria, hematuria and “deeper sulci” with a sign of brain atrophy. By reanalysis on the proband’s previous WES data, two novel compound heterozygous variants of OSGEP (c.133dupA; c.608C > T) were identified. Furthermore, functional studies showed that the variants reduced the expression of OSGEP protein and activated the DNA damage response (DDR) signaling in the lymphoblastoid cell lines (LCLs) obtained from the patient. The analysis of protein localization with confocal microscopy revealed that the EGFP-tagged/HA-tagged mutant OSGEP proteins were abnormal aggregation or retained inside the cytosol, respectively. Our study not only expanded the pathogenic variant spectrum of OSGEP but also carried on regular follow-up for kidney involvement and established a strategy for evaluation on the function of mutant OSGFP by subcellular localization assay.

Background: Primary nephrotic syndromes are rare diseases which impedes adequate sample size for observational patient-oriented research and clinical trial enrollment. A computable phenotype may be powerful in identifying patients with these diseases for research across multiple institutions. Methods: A comprehensive algorithm of inclusion and exclusion ICD-9 and ICD-10 codes to identify patients with primary nephrotic syndrome was developed. The algorithm was executed against the PCORnet® CDM at 3 institutions from Jan 1, 2009 to Jan 1, 2018, where a random selection of 50 cases and 50 non-cases (individuals not meeting case criteria seen within the same calendar year and within five years of age of a case) were reviewed by a nephrologist, for a total of 150 cases and 150 non-cases reviewed. The classification accuracy (sensitivity, specificity, positive and negative predictive value, F1 score) of the computable phenotype was determined. Results: The algorithm identified a total of 2,708 patients with nephrotic syndrome from 4,305,092 distinct patients in the CDM at all sites from 2009-2018. For all sites, the sensitivity, specificity, and area under the curve of the algorithm were 99% (95% CI: 97-99%), 79% (95% CI: 74-85%), and 0.9 (0.84-0.97), respectively. The most common causes of false positive classification were secondary FSGS (9/39) and lupus nephritis (9/39). Conclusion: This computable phenotype had good classification in identifying both children and adults with primary nephrotic syndrome utilizing only ICD-9 and ICD-10 codes, which are available across institutions in the United States. This may facilitate future screening and enrollment for research studies and enable comparative effectiveness research. Further refinements to the algorithm including use of laboratory data or addition of natural language processing may help better distinguish primary and secondary causes of nephrotic syndrome.

Objective: Children with nephrotic syndrome (NS) have a stressful condition, and oxidative damage may impair their treatment response. This study aims to gain a better understanding of the relationship between oxidative stress and NS to lay the basis for further research into improved diagnostic options, treatment, and prevention of the disease. Methods: We took a blood sample from 100 Indian patients aged 2-14 y. Each patient was tested for oxidative stress. The buege method was used to assess MDA levels in patients. The pyrogallol method was used to measure SOD activity in blood serum, and the jollow method was used to measure glutathione levels. Results: The levels of oxidative stress markers (MDA, SOD, and GSH) were compared between NS patients and the control. SOD and GSH concentrations were significantly decreased in the NS group when compared to the control. In contrast, MDA level was significantly higher in the NS group than in the control. In the correlation analysis, we found that the serum SOD activity was significantly positively correlated with serum albumin and creatinine level in patients with NS. Thus, oxidative stress in children with NS is indicated by reduced antioxidant potential because of low albumin. Therefore, it is thought that oxidative stress is implicated in the development of NS in Indian children. Conclusion: We concluded that oxidative stress was intensified in children with NS due to decreased antioxidant levels caused by hypoalbuminemia.

We sought to investigate the utility of anti-PLA2R antibody as a non-invasive screening method for the diagnosis of primary MN in patients with nephrotic syndrome (NS). All consecutive patients with NS admitted in our department, between 01.01.2015 and 31.12.2019 were screened for anti-PLA2R antibodies by an ELISA assay (EUROIMMUN, Lubeck, DE). A positive anti-PLA2R serology was defined as an ELISA value over 2 RU/ml. Subsequently, all patients underwent kidney biopsy to confirm the histological diagnosis. Of the 203 patients with NS, we identified 67 patients with “high” titer of anti-PLA2R antibodies (> 20 RU/ml) and 47 patients with “intermediate” titer (2–20 RU/ml). In the entire cohort, the area under the curve (AUC) was 0.83 (95% CI 0.78–0.89; p

A 17-year-old lady was diagnosed with proteinuria and microscopic hematuria within the prior 2 years to this presentation. Further tests revealed nephrotic syndrome with hematuria and hypocomplementemia. Renal histopathology showed membranoproliferative glomerulonephritis. Immunostaining and electron microscopy, suggested C3 glomerulonephritis (C3GN). Nephritis-associated plasmin receptor (NAPlr) and plasmin activity (PA), markers of infection-related glomerulonephritis, were identified in the aforementioned pathology specimens. There are several reports suggesting a causal relationship between group A streptococcal infection and C3 glomerulopathy (C3G). There are many intractable cases, whereas some have responded to immunosuppressive therapy, as did our case. However, there is currently no established gold standard treatment for this disease. We herein report a case of C3G with glomerular positive NAPlr and PA despite the absence of a streptococcal infection. Accumulation of cases such as this may help advance treatment by clarifying the etiology and pathogenic mechanism of C3G and future prognosis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13730-021-00662-2.

Background. To investigate the clinical effects of Chinese medicine decoction combined with glucocorticoid in treating children with primary nephrotic syndrome. Methods. A total of 70 children with pediatric nephritis nephrotic syndrome treated at Weifang People’s Hospital from January 2019 to December 2019 were randomly allocated to the therapy group and the control group, each with 35 cases. The control group was treated with conventional Western medicine, and the therapy group received Western medicine and Chinese medicine. After 12 weeks of treatment, the therapeutic effect of the two groups was compared. Results. After receiving the treatment, the levels of urine protein (UPro), triglyceride, and cholesterol were significantly decreased in the two groups ( p < 0.05 ), and these levels in the therapy group were much lower than those of the control group ( p < 0.05 ). However, the level of albumin (ALB) was predominantly increased in the two groups after treatment ( p < 0.05 ), and this level in the therapy group was much higher than that of the control group ( p < 0.05 ). Moreover, the immune indicators, coagulation function, and recurrence rate were noticeably improved after treatment ( p < 0.05 ), and the therapy group was better than the control group ( p < 0.05 ). Furthermore, the comparison of renal function indexes, liver function indexes, and blood routine between the two groups showed no statistical significance in the incidence of adverse reactions between the two groups ( p > 0.05 ). Conclusions. For the treatment of refractory nephrotic syndrome in children, based on conventional shock therapy, the addition of traditional Chinese medicine (Liuwei Dihuang pill decoction) remedy can significantly improve the disease symptoms in children and improve the efficacy, and the incidence of adverse reactions is low.

Introduction: Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults and can be primary or secondary. The antigenic target of antibodies in 70% of primary cases is phospholipase A2 receptor (PLA2R). The presence or absence of mesangial electron-dense deposits has been used to distinguish between primary and secondary MN. Mesangial deposits suggest MN due to lupus, infection, or other causes, though they are reported to occur in approximately 10% of primary MN. Staining for PLA2R is now frequently used for confirming a diagnosis of primary MN. If mesangial deposits predict a secondary cause, they should be more frequent in PLA2R-negative biopsies. Methods: A review of institutional kidney biopsies between March 2017 and June 2020 identified all cases of MN. Cases with a diagnosis of lupus or near “full-house” staining by immunofluorescence microscopy (IF) were excluded. Light microscopy, IF, and electron microscopy (EM) were performed. PLA2R staining was performed by IF. EM for all cases was reviewed and electron-dense deposit location, distribution, and size were determined. Results: Ninety-three cases of MN were identified, of which 86 had both PLA2R staining and EM performed. Of these, 51 cases (59%) were positive for PLA2R and 35 (41%) were negative. Mesangial electron-dense deposits were present in 22 (25.6%) of the 86 cases, including 27.5% (14/51) of PLA2R-positive cases and 22.8% (8/35) of PLA2R-negative cases. No difference was seen in size or distribution of deposits, or other features considered suggestive of secondary MN. Conclusion: PLA2R-negative cases were not more likely to have mesangial deposits than PLA2R-positive cases. Mesangial deposits should not be used as an indicator of secondary MN.

Pediatric patients with nephrotic syndrome take medications long-term with significant toxicity and complex regimens, yet data on medication adherence are limited.In a multicenter observational study of patients with nephrotic syndrome, NEPTUNE (NCT01209000), we surveyed caregivers of patients19 years old and adolescent patients on medication adherence during longitudinal follow-up beginning in June 2015. Data extraction was in October 2020. We described the proportion of nonadherent patients at first survey. Participant social and economic factors, condition-related factors, therapy-related factors, and patient-related factors were examined for relationships with nonadherence by generalized linear mixed models using the longitudinal data. In exploratory fashion, we assessed the relationship between adherence and subsequent steroid response classification by binary logistic regression and adherence with healthcare utilization by Poisson regression.A total of 225 participants completed a median of 3 surveys during follow-up (IQR, 2-5), with a total of 743 surveys. Overall, 80 (36%) reported nonadherence with medications. In adjusted analysis, older age (per 1 year; OR 1.08; 95% CI, 1.03 1.12), lower maternal educational level (≥ high school vs.high school; OR 0.47; 95% CI 0.25 to 0.89), and increased parent and self-identification of medications barriers (per 1 point; OR 1.57; 95% CI, 1.15-2.15) were significantly associated with nonadherence. No relationship between nonadherence and subsequent frequency of healthcare utilization was observed. A trend toward increased subsequent steroid resistance classification was seen with nonadherence, though not statistically significant.Medication nonadherence is common in pediatric nephrotic syndrome. Investigations into the use of surveys in the clinic setting to identify at-risk patients and ways to support families over time are needed. A higher resolution version of the Graphical abstract is available as Supplementary information.

Objective: To evaluate and compare the effectiveness of zinc and B-Complex supplementation to prevent the recurrence of nephrotic syndrome in the cases priory responsive to corticosteroid therapy. Methodology It is a randomized controlled trial conducted at OPD Pediatric medicine, Shaheed Zulfiqar Ali Bhutto University, PIMS Children Hospital Islamabad from October 3, 2016 to April 2, 2017. 192 patients (96 in each group) were included in the study after obtaining informed consent from parents or guardians taken before determining the population. Patients were randomly assigned to two groups (Group 1: Zinc and Group 2: B-Complex) to receive oral zinc sulphate (10 mg / day) or B-Complex using a random number table. The patients were followed up after 4 months. All data were collected by the researchers themselves in a structured form. Results: The age of 192 participants of the trial averaged 6.38±3.42 years of age ranging from 1-12 years. There were 88 (45.8%) men and 104 (54.2%) women cases. In group 1, there were 22 (22.9%) and in group 2, there were 47 (49%) cases that had been pardoned. The recurrence of nephrotic syndrome was significantly higher in group 1 than group 2 (p =

Long-term steroid treatment in children is known to cause obesity and negatively affect growth. The objective of this study was to determine the prevalence of obesity and overweight and analyze linear growth in children with nephrotic syndrome. The study involved 265 children treated with glucocorticoids for nephrotic syndrome for a mean duration of 43 months (range: 6–167, IQR: 17, 63.3). Height, weight, and BMI SDS were recorded at each visit. Rate of change between the final and initial height, weight, and BMI was calculated (Δ score). The cumulative steroid dose (mg/kg/day) during follow-up was calculated. Relapses without significant edema were treated with low-dose steroids and steroid-sparing drugs were used in children with steroid dependency/frequent relapses. Mean first BMI SDS was + 1.40 ± 1.30 and final + 0.79 ± 1.30. At initial assessment, 41.4% of the patients were obese (BMI ≥ 95th percentile) and 19.5% were overweight (BMI 85th–95th percentile). At the last clinical visit, 24% were obese and 17% overweight. The children had lower BMI SDS at last clinical visit compared to initial assessment. Mean first height SDS of the cohort was − 0.11 ± 1.22 and final score 0.078 ± 1.14 (p

Membranous nephropathy associated with anti-PLA2 R autoantibody is a significant cause of nephrotic syndrome worldwide. Treatment remains empiric with a significant side-effect burden despite an increase in our understanding of the disease. We studied the effect of selectively removing this pathogenic autoantibody using immunoadsorption in adult patients with biopsy proven anti-PLA2 R membranous nephropathy. This was a multicenter, single-arm prospective clinical trial carried out in the United Kingdom. Twelve patients underwent five consecutive sessions of peptide GAM immunoadsorption with 12 months follow-up. Primary outcome was anti-PLA2 R titer at week 2. Secondary outcomes were safety and tolerability of therapy, antibody profile, and change in proteinuria, renal excretory function, serum albumin, total immunoglobulin, and quality of life at weeks 12, 24, and 52. Patients were also stratified by the presence or absence of the high-risk allele (heterozygous or homozygous for HLA-DQA1*05). Median pretreatment anti-PLA2 R was 702.50 U/mL, 1045.00 U/mL at week 2 (P-value .023) and 165.00 U/mL at week 52 (P-value .017). The treatment was well tolerated and safe. Two patients required rescue immunosuppression during the follow-up period. There was a significant improvement in serum albumin with a median at baseline of 20.50 g/L rising to 25.00 g/L at week 52 (P-value

Purpose of review Nearly 20 years ago, vascular endothelial growth factor (VEGF)inhibitors (VEGFi) were adapted from systemic use from antiangiogenesis roles to intravitreal uses. Initially bevacizumab a murine immunoglobulin was injected 'off label' as a treatment for diabetic macular edema and age-related macular degeneration. Throughout the following decade aflibercept and finally ranibizumab were adapted and obtained Food and Drug Administration approval for intravitreal use. Initially systemic absorption was thought to be quite low after intravitreal injections and was quoted as being 200-fold lower than levels postulated to induce significant VEGF inhibition. Pharmacodynamic studies obtained in 2014 and again in 2017 revealed significant systemic absorption and detectable VEGF inhibition, this has since been confirmed in multiple subsequent studies. Recent findings A few case reports of renal dysfunction and glomerular disease related to VEGFi were initially identified. Mixed findings on effects on blood pressure were noted in studies. More recently, 32 cases of de-novo glomerular disease and/or proteinuria exacerbation were identified. New studies have corroborated increased blood pressure, proteinuria exacerbation in patients with pre-existing nephrotic syndrome, and systemic VEGF depletion. Further, the most common lesion of systemic VEGFi nephrotoxicity, thrombotic microangiopathy, has recently been reported by our group. Summary We will review the pharmacokinetic, translational, and epidemiological data that year upon year establish the finite-yet real risk of intravitreal VEGFi.

Chimeric antigen receptor T (CAR-T) cell treatment is a rapidly emerging therapy for relapsed/refractory hematologic malignancies. Although cytokine release syndrome is a common complication, a concomitant development of biopsy-proven collapsing glomerulopathy and acute kidney injury (AKI) has not been described with CAR-T cell therapy. We report a man in his early 20s with relapsed/refractory pre–B-cell acute lymphoblastic leukemia and compensated liver cirrhosis who received 3 courses of CD19-directed CAR-T cells. After the third CAR-T cell therapy, he developed severe cytokine release syndrome accompanied by new onset of nephrotic syndrome and AKI. Cytokine release syndrome was treated with tocilizumab. His kidney biopsy showed collapsing glomerulopathy, glomerulitis, and interstitial nephritis along with complete podocyte foot-process effacement. Due to disease progression, he was subsequently treated with bispecific CD19-directed CD3 T-cell engager antibody, blinatumomab, during which he developed another episode of cytokine release syndrome with exacerbation of nephrotic-range proteinuria and his AKI progressed to stage 3 chronic kidney disease. Excess cytokine-induced podocyte and renal tubulointerstitial injury and/or “on-target off-tumor” direct renal cell toxicity are the probable mechanisms of kidney injury. Further such reports will increase our understanding of the pathophysiologic basis of kidney injury with CAR-T treatment.

BACKGROUND: The long-term outcome of COVID-19–associated collapsing glomerulopathy is unknown. METHODS: We retrospectively identified 76 native kidney biopsies from patients with history of COVID-19 between March 2020 and April 2021. Presenting and outcome data were obtained for all 23 patients with collapsing glomerulopathy and for seven patients with noncollapsing podocytopathies. We performed APOL1 genotyping by Sanger sequencing, immunostaining for spike and nucleocapsid proteins, and in situ hybridization for SARS-CoV-2. RESULTS: The 23 patients with COVID-19–associated collapsing glomerulopathy were median age 57 years (range, 35–72), included 16 men, and were predominantly (91%) Black. Severity of COVID-19 was mild or moderate in most (77%) patients. All but one patient presented with AKI, 17 had nephrotic-range proteinuria, and six had nephrotic syndrome. Fourteen (61%) patients required dialysis at presentation. Among 17 patients genotyped, 16 (94%) were high-risk APOL1. Among 22 (96%) patients with median follow-up at 155 days (range, 30–412), 11 (50%) received treatment for COVID-19, and eight (36%) received glucocorticoid therapy for podocytopathy. At follow-up, 19 (86%) patients were alive, and 15 (68%) were dialysis free, including seven of 14 who initially required dialysis. The dialysis-free patients included 64% (seven of 11) of those treated for COVID-19 and 75% (six of eight) of those treated with glucocorticoids for podocytopathy. Overall, 36% achieved partial remission of proteinuria, 32% had no remission, and 32% reached combined end points of ESKD or death. Viral infection of the kidney was not detected. CONCLUSIONS: Half of 14 patients with COVID-19–associated collapsing glomerulopathy requiring dialysis achieved dialysis independence, but the long-term prognosis of residual proteinuric CKD remains guarded, indicating a need for more effective therapy.

Primary focal segmental glomerulosclerosis (FSGS) is a podocytopathy with an irregular response to immunosuppressive therapies. FSGS relapse occurs in 30% to 80% of kidney grafts, and poor survival outcomes include large proteinuria and the nephrotic syndrome's cardinal clinical features. Thrombotic microangiopathy (TMA) is caused by endothelial injury due to complement dysregulation including acute kidney injury, proteinuria, and severe hypertension common renal presentations. Both pathologies have well-described genetic forms, but their relationship remains uncertain. FSGS lesions can be found in kidney biopsy specimens in patients with TMA, and TMA has been reported in patients with collapsing glomerulopathy. However, this combination has not been clearly described in renal transplant recipients. We present the case of a 22-year-old man who received his second kidney allograft and developed an early graft disfunction with nephrotic syndrome and clinical TMA. His background was remarkable for primary, biopsy-confirmed FSGS in childhood, and he started hemodialysis in 2006 and received a living donor kidney graft the same year. He presented with a FSGS relapse with malignant hypertension and seizures in the first posttransplant month and had an irregular response to plasma exchange and rituximab, and dialysis was reinitiated 10 years later. A total of 3 biopsies were performed after his second kidney transplant showing the evolution of a FSGS relapse with histologic and clinical TMA in the absence of identified genetic mutations. Partial responses to treatments with plasma exchange, eculizumab, and rituximab were obtained, but the allograft was lost after 26 months. This case is the first report of concomitant FSGS and TMA in a renal transplant recipient.

Since previous research suggests a role of a circulating factor in the pathogenesis of steroid-sensitive nephrotic syndrome (NS), we speculated that circulating plasma extracellular vesicles (EVs) are a candidate source of such a soluble mediator. Here, we aimed to characterize and try to delineate the effects of these EVs in vitro. Plasma EVs from 20 children with steroid-sensitive NS in relapse and remission, 10 healthy controls, and 6 disease controls were obtained by serial ultracentrifugation. Characterization of these EVs was performed by electron microscopy, flow cytometry, and Western blot analysis. Major proteins from plasma EVs were identified via mass spectrometry. Gene Ontology classification analysis and Ingenuity Pathway Analysis were performed on selectively expressed EV proteins during relapse. Immortalized human podocyte culture was used to detect the effects of EVs on podocytes. The protein content and particle number of plasma EVs were significantly increased during NS relapse. Relapse NS EVs selectively expressed proteins that involved actin cytoskeleton rearrangement. Among these, the level of RAC-GTP was significantly increased in relapse EVs compared with remission and disease control EVs. Relapse EVs were efficiently internalized by podocytes and induced significantly enhanced motility and albumin permeability. Moreover, relapse EVs induced significantly higher levels of RAC-GTP and phospho-p38 and decreased the levels of synaptopodin in podocytes. Circulating relapse EVs are biologically active molecules that carry active RAC1 as cargo and induce recapitulation of the NS phenotype in podocytes in vitro.

Left ventricular hypertrophy, atrial fibrillation and chronic heart failure are often in the practice of a cardiologist. The etiology of these conditions is very important because the correct early treatment. We are presenting a case of a late diagnosis of amyloidosis in a 53-year-old man. Despite the complex therapy, the course of the disease was complicated by the development of bilateral pneumonia, sepsis, disseminated intravascular coagulation and the patient died. Autopsy confirmed the diagnosis of systemic AL-amyloidosis (type Kappa) with massive damage to the heart, kidneys, lungs, liver, spleen, adrenal glands, thyroid gland, pancreas, gastrointestinal tract, subcutaneous fatty tissue and arterial vessels of the bone marrow. Thus, screening for amyloidosis is necessary in idiopathic LV thickening, atrial fibrillation, and heart failure for timely intravital diagnosis and therapy.

Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults. Idiopathic MN (IMN), one of the forms of MN, usually has an unknown etiology. IMN is described as an autoimmune disease, and its pathogenesis is quite complex. The discovery of the M-type phospholipase A2 receptor (PLA2R) plays an important role in promoting our understanding of IMN, although the exact mechanisms of its occurrence and development are still not completely clear. Other target antigens have been discovered one after another, as considerable progress has been made in the molecular pathomechanisms of IMN. Here, we review the findings about the target antigens associated with IMN in recent years. It is hoped that this article can provide researchers with some scientific issues or innovative ideas for future studies of IMN, which will provide clinicians with more knowledge about further improving their abilities to provide better medical care for IMN patients.

Graphical abstract, Introduction Nephrotic syndrome is a common pediatric kidney disease. Investigations on several genetic polymorphisms revealed an inconsistent influence on the resistance of patients to steroids. Objectives This study aimed to identify the association of ABCB1 (1236C > T, 2677G > T, 3435C > T), NR3C1 (rs10482634, rs6877893), and CYP3A5 (CYP3A5*3) gene polymorphism as well as sociodemographic and clinicopathological parameters with the risk of developing prednisolone resistance in pediatric patients with nephrotic syndrome. Methods A case-control analysis was performed on 180 nephrotic syndrome patients. Among them, 30 patients were classified as prednisolone resistant group, and 150 were classified as prednisolone sensitive group. Genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results No significant association of 1236C > T polymorphism with the risk of prednisolone resistance (p > 0.05) was found. The GT heterozygous of 2677G > T was found to be significantly associated with the development of prednisolone resistance (OR = 3.9, p = 0.034). In the case of 3435C > T, a statistically significant association was observed in TC heterozygous and TT mutant homozygous genotypes (OR = 0.38, p = 0.047; OR = 3.06, p = 0.038, respectively) with prednisolone resistance. For rs10482634 polymorphism, the AG heterozygous and AG+GG genotypes were significantly linked with prednisolone resistance (OR = 2.40, p = 0.033; OR = 2.36, p = 0.034, respectively). We found no association with the risk of prednisolone resistance with rs6877893 and CYP3A5*3 polymorphism (p > 0.05). CTC and TGT haplotypes of ABCB1 and GA haplotype of NR3C1 were also associated with the increased risk of pediatric prednisolone resistance (OR = 4.47, p = 0.0003; OR = 2.71, p = 0.03; and OR = 4.22, p = 0.022, consecutively). We also observed the correlation of different sociodemographic and clinicopathological factors with prednisolone resistance in pediatric nephrotic syndrome. Conclusion Our findings showed a significant association of ABCB1 and NR3C1 gene polymorphisms with prednisolone resistant pediatric nephrotic syndrome.

Background Up to 70% of patients with ANCA-associated vasculitis (AAV) develop GN, with 26% progressing to ESKD. Diagnostic-grade and noninvasive tools to detect active renal inflammation are needed. Urinary soluble CD163 (usCD163) is a promising biomarker of active renal vasculitis, but a diagnostic-grade assay, assessment of its utility in prospective diagnosis of renal vasculitis flares, and evaluation of its utility in proteinuric states are needed. Methods We assessed a diagnostic-grade usCD163 assay in (1) a real-world cohort of 405 patients with AAV and 121 healthy and 488 non-AAV disease controls; (2) a prospective multicenter study of 84 patients with potential renal vasculitis flare; (3) a longitudinal multicenter cohort of 65 patients with podocytopathy; and (4) a cohort of 29 patients with AAV (with or without proteinuria) and ten controls. Results We established a diagnostic reference range, with a cutoff of 250 ng/mmol for active renal vasculitis (area under the curve [AUC], 0.978). Using this cutoff, usCD163 was elevated in renal vasculitis flare (AUC, 0.95) but remained low in flare mimics, such as nonvasculitic AKI. usCD163's specificity declined in patients with AAV who had nephrotic-range proteinuria and in those with primary podocytopathy, with 62% of patients with nephrotic syndrome displaying a "positive" usCD163. In patients with AAV and significant proteinuria, usCD163 normalization to total urine protein rather than creatinine provided the greatest clinical utility for diagnosing active renal vasculitis. Conclusions usCD163 is elevated in renal vasculitis flare and remains low in flare mimics. Nonspecific protein leakage in nephrotic syndrome elevates usCD163 in the absence of glomerular macrophage infiltration, resulting in false-positive results; this can be corrected with urine protein normalization.