Two successful pregnancies in a membranous nephropathy patient: Case report and literature review.

BACKGROUND: Pregnancy in patients with nephrotic syndrome presents enormous challenges to both the mother and fetus, and there are no treatment guidelines for these patients. METHODS: We show a case of a woman with anti-PLA2R antibody-positive membranous nephropathy who did not have a kidney biopsy. Her clinical course during both pregnancies was closely followed and her medications were guided. RESULTS: She gave birth to 2 healthy babies and her condition was very well controlled with the help of medication. CONCLUSION: Patients with nephrotic syndrome can have successful pregnancies after drug treatment. In addition, similar to the non-pregnant population, percutaneous kidney biopsy is not required for the diagnosis of idiopathic membranous nephropathy (IMN) in pregnant nephrotic syndrome patients with anti-PLA2R antibody positive, but the etiology of secondary MN should be excluded.

Nephrotic syndrome due to focal segmental glomerulosclerosis complicating scleroderma: a case report.

BACKGROUND: Systemic scleroderma (SSc) is an insidious autoimmune connective tissue disorder with multiorgan involvement. Renal involvement is one of the important causes of morbidity and mortality in scleroderma; however, nephrotic syndrome is reported rarely in association with SSc. We present a patient with SSc who developed focal segmental glomerulosclerosis (FSGS) as a complication of scleroderma. CASE PRESENTATION: A 59 year old Caucasian female patient, with a known history of diffuse systemic sclerosis from 8 years, presented to our clinic with symptoms of anasarca and weight gain. Her physical examination was unremarkable except for periorbital and extremity edema. Her biochemistry assessment revealed decreased serum albumin levels and elevated serum creatinine levels. A renal biopsy was performed, which showed histopathological patterns of FSGS type of nephrotic syndrome. After administration of high doses of steroid and rituximab in the course of her treatment for 6 months, her symptoms and proteinuria were improved without the occurrence of scleroderma renal crises. CONCLUSION: SSc is a complex multisystemic autoimmune disorder. SRC is the most prominent renal involvement in SSc, but other renal pathologies may also occur. Each patient should be precisely investigated since managing these renal conditions can differ significantly. Nephrotic syndrome is a rare complication of SSc, which could be managed with prompt diagnosis and steroid administration.

Post-transplant recurrence of focal segmental glomerular sclerosis: consensus statements.

Focal segmental glomerular sclerosis (FSGS) is 1 of the primary causes of nephrotic syndrome in both pediatric and adult patients, which can lead to end-stage kidney disease. Recurrence of FSGS after kidney transplantation significantly increases allograft loss, leading to morbidity and mortality. Currently, there are no consensus guidelines for identifying those patients who are at risk for recurrence or for the management of recurrent FSGS. Our work group performed a literature search on PubMed/Medline, Embase, and Cochrane, and recommendations were proposed and graded for strength of evidence. Of the 614 initially identified studies, 221 were found suitable to formulate consensus guidelines for recurrent FSGS. These guidelines focus on the definition, epidemiology, risk factors, pathogenesis, and management of recurrent FSGS. We conclude that additional studies are required to strengthen the recommendations proposed in this review.

Patients with primary focal segmental glomerulosclerosis with detectable urinary CD80 are more similar to patients with minimal change disease in clinicopathological features.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is an important cause of refractory nephrotic syndrome (NS) in children and adults. Urinary CD80 is elevated in some patients with primary FSGS, however, its clinical value is not fully clarified. This study aims to evaluate the clinical and pathological significance of urinary CD80 in patients with primary FSGS. METHODS: Sixty-one adult patients with biopsy-proven primary FSGS, with standard treatment and long-term follow up, were enrolled retrospectively. Urinary CD80, on the day of kidney biopsy, was measured using commercial ELISA kits and adjusted by urinary creatinine excretion. Their associations with clinical and pathological parameters were investigated. RESULTS: Urinary CD80 was detectable in 30/61 (49.2%) patients, who presented with a higher level of proteinuria (10.7 vs. 5.8 g/24h; p = 0.01), a lower level of serum albumin (19.3 ± 3.9 vs. 24.2 ± 8.2 g/L; p = 0.005), a higher prevalence of hematuria (70.0 vs. 38.7%; p = 0.01), and showed a lower percentage of segmental glomerulosclerosis lesion [4.8 (3.7-14.0) vs. 9.1 (5.6-21.1) %; p = 0.06]. The cumulative relapse rate was remarkably high in these patients (log-rank, p = 0.001). Multivariate analysis identified that the elevated urinary CD80 was an independent risk factor for steroid-dependent NS (OR 8.81, 95% CI 1.41-54.89; p = 0.02) and relapse (HR, 2.87; 95% CI 1.29-6.38; p = 0.01). CONCLUSIONS: The elevated urinary CD80 is associated with mild pathological change and steroid-dependent cases of primary FSGS adults, which indicates these patients are more similar to minimal change disease (MCD) in clinicopathological features.

Cell-type-specific molecular characterization of cells from circulation and kidney in IgA nephropathy with nephrotic syndrome.

Nephrotic syndrome (NS) is a relatively rare and serious presentation of IgA nephropathy (IgAN) (NS-IgAN). Previous research has suggested that the pathogenesis of NS-IgAN may involve circulating immune imbalance and kidney injury; however, this has yet to be fully elucidated. To investigate the cellular and molecular status of NS-IgAN, we performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) and kidney cells from pediatric patients diagnosed with NS-IgAN by renal biopsy. Consistently, the proportion of intermediate monocytes (IMs) in NS-IgAN patients was higher than in healthy controls. Furthermore, flow cytometry confirmed that IMs were significantly increased in pediatric patients with NS. The characteristic expression of VSIG4 and MHC class II molecules and an increase in oxidative phosphorylation may be important features of IMs in NS-IgAN. Notably, we found that the expression level of CCR2 was significantly increased in the CMs, IMs, and NCMs of patients with NS-IgAN. This may be related to kidney injury. Regulatory T cells (Tregs) are classified into two subsets of cells: Treg1 (CCR7 high, TCF7 high, and HLA-DR low) and Treg2 (CCR7 low, TCF7 low, and HLA-DR high). We found that the levels of Treg2 cells expressed significant levels of CCR4 and GATA3, which may be related to the recovery of kidney injury. The state of NS in patients was closely related to podocyte injury. The expression levels of CCL2, PRSS23, and genes related to epithelial-mesenchymal transition were significantly increased in podocytes from NS-IgAN patients. These represent key features of podocyte injury. Our analysis suggests that PTGDS is significantly downregulated following injury and may represent a new marker for podocytes. In this study, we systematically analyzed molecular events in the circulatory system and kidney tissue of pediatric patients with NS-IgAN, which provides new insights for targeted therapy in the future.

A Hematopoietic Stem Cell Transplant Recipient with Nephrotic Syndrome and Immune Complex Deposits in Tubular Basement Membrane: A Rare Case Report.

Following allogenic hematopoietic stem cell transplantation (HSCT), graft-versus-host disease (GVHD) may develop which may affect several organs. Although the presence of nephrotic syndrome after HSCT is rare, sometimes it occurs in the setting of GVHD. The most common histological finding on kidney biopsy of patients with proteinuria owing to GVHD is membranous glomerulonephritis (MGN). However, reports of immune complex deposition in the tubular basement membrane (TBM) and glomerular basement membrane (GBM) are extremely rare. Herein we present a 65-year-old female with a history of HSCT at six years ago who was referred to Dr.Shariati Hospital in Tehran with nephrotic syndrome. Secondary serologic laboratory tests were all normal. The histopathologic study indicated diffuse GBM and TBM thickening, spike formation, infiltration of inflammatory mononuclear cells in tubulointerstitial area and acute tubular injury in light microscopy. Immunofluorescence staining showed immune complex deposits in GBM, mesangial cells, and TBM.  DOI: 10.52547/ijkd.7550.

Mild mesangial proliferative IgA nephropathy with and without minimal change disease.

Mild mesangial proliferative IgA nephropathy with minimal change disease (MCD-IgAN) and mild mesangial proliferative IgA nephropathy without minimal change disease (Non-MCD-IgAN) have similar characteristics on light microscopy. Nevertheless, their discrepancies in clinicopathological features and prognosis remain unknown. A total of 589 patients with biopsy-proven mild mesangial proliferative IgA nephropathy (M-IgAN) combined with light microscopy and immunofluorescence were enrolled. Firstly, the diagnoses of the patients by electron microscopy were recorded and used as the gold standard. We calculated the sensitivity and specificity using nephrotic syndrome (NS) as the diagnostic criteria to identify MCD-IgAN. Then, excluding patients with a 24-h urinary total protein less than 0.5 g/day, incomplete clinical data, or less than the six-month follow-up, we included 184 cases of non-MCD-IgAN and 98 cases of MCD-IgAN. The patients' clinicopathological and outcome data were collected and compared. Among the 589 patients, according to electron microscopy, 381 were diagnosed with non-MCD-IgAN, 167 with MCD-IgAN, and 41 with M-IgAN complicated by other glomerular diseases. Using NS as the diagnostic criteria to distinguish non-MCD-IgAN and MCD-IgAN, the sensitivity and specificity were 83.8% and 99.5%, respectively. The patients in the MCD-IgAN group tended to be younger, hypotensive, with lower urinary erythrocytes, and more likely to achieve complete remission, and fewer patients progressed to the endpoint than those in the non-MCD-IgAN group (all P < 0 .05). NS appears to be an objective indicator for differentiating MCD-IgAN from non-MCD-IgAN. Non-MCD-IgAN varies greatly from MCD-IgAN in clinicopathology and treatment response, with a poorer prognosis.

Membranous nephropathy.

Membranous nephropathy is a glomerulopathy, which main affected target is the podocyte, and has consequences on the glomerular basement membrane. It is more common in adults, especially over 50 years of age. The clinical presentation is nephrotic syndrome, but many cases can evolve with asymptomatic non-nephrotic proteinuria. The mechanism consists of the deposition of immune complexes in the subepithelial space of the glomerular capillary loop with subsequent activation of the complement system. Great advances in the identification of potential target antigens have occurred in the last twenty years, and the main one is the protein "M-type phospholipase-A2 receptor" (PLA2R) with the circulating anti-PLA2R antibody, which makes it possible to evaluate the activity and prognosis of this nephropathy. This route of injury corresponds to approximately 70% to 80% of cases of membranous nephropathy characterized as primary. In the last 10 years, several other potential target antigens have been identified. This review proposes to present clinical, etiopathogenic and therapeutic aspects of membranous nephropathy in a didactic manner, including cases that occur during kidney transplantation.

Nephrotic syndrome following COVID-19 vaccination: a systematic review.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 infection has caused significant morbidity and mortality. Vaccines produced against this virus have proven highly effective. However, adverse events following vaccination have also been reported. One of them is nephrotic syndrome, that can be associated with different pathologic pictures. This review aims to provide a wider understanding of incidence, etiopathogenesis, and management of nephrotic syndrome following vaccination against SARS-CoV-2. METHODS AND RESULTS: A literature search was undertaken using appropriate keywords in various databases like PubMed, Google Scholar, Europe PMC, and Science Direct. Twenty-one articles were included following qualitative assessment. Data of 74 patients from these articles were included. DISCUSSION: The pathogenesis of nephrotic syndrome following COVID vaccination has been widely attributed to the activation of angiotensin-converting enzyme-2 receptors, leading to podocyte effacement. Relapses have also been reported in patients with prior history of nephrotic syndrome following COVID-19 vaccination. A renal biopsy is necessary to identify the histopathological picture. Management of COVID-19 vaccine-induced nephrotic syndrome was mainly reported as successfully attainable with corticosteroids and supportive management. CONCLUSION: Further investigations will help in establishing an early diagnosis and salvaging kidney function.

Nephrotic syndrome: pathophysiology and consequences.

In patients with kidney disease, nephrotic syndrome can lead to several complications including progressive kidney dysfunction. Proteinuria may lead to the formation of cellular or fibrous crescents with reciprocal development of rapidly progressive glomerulonephritis or focal glomerulosclerosis. Proteinuria may also cause overload and dysfunction of tubular epithelial cells, eventually resulting in tubular atrophy and interstitial fibrosis. Hypoalbuminemia is usually associated with increased risk of mortality and kidney dysfunction. Dyslipidemia may increase the risk of atherosclerotic complications, cause podocyte dysfunction and contribute to vascular thrombosis. Urinary loss of anticoagulants and overproduction of coagulation factors may facilitate a hypercoagulable state. Edema, hypogammaglobulinemia, loss of complement factors, and immunosuppressive therapy can favor infection. Treatment of these complications may reduce their impact on the severity of NS. Nephrotic syndrome is a kidney disorder that can worsen the quality of life and increase the risk of kidney disease progression.

Pulmonary hypertension, nephrotic syndrome, and polymyositis due to hepatitis C virus infection: A case report.

BACKGROUND: Hepatitis C infection not only damages the liver but also often accompanies many extrahepatic manifestations. Incidences of pulmonary hypertension (PH) caused by hepatitis C are rare, and incidences of concurrent nephrotic syndrome and polymyositis are even rarer. CASE SUMMARY: Herein we describe the case of a 57-year-old woman who was admitted to our department for intermittent chest tightness upon exertion for 5 years, aggravated with dyspnea for 10 d. After relevant examinations she was diagnosed with PH, nephrotic syndrome, and polymyositis due to chronic hepatitis C infection. A multi-disciplinary recommendation was that the patient should be treated with sildenafil and macitentan in combination and methylprednisolone. During treatment autoimmune symptoms, liver function, hepatitis C RNA levels, and cardiac parameters of right heart catheterization were monitored closely. The patient showed significant improvement in 6-min walking distance from 100 to 300 m at 3-mo follow-up and pulmonary artery pressure drops to 50 mmHg. Long-term follow-up is needed to confirm further efficacy and safety. CONCLUSION: Increasing evidence supports a relationship between hepatitis C infection and diverse extrahepatic manifestations, but it is very rare to have PH, nephrotic syndrome, and polymyositis in a single patient. We conducted a literature review on the management of several specific extrahepatic manifestations of hepatitis C.

Nephrotic Syndrome for the Internist.

Nephrotic syndrome (NS) is a key clinical entity for the internist to recognize and understand. A wide range of infectious, metabolic, malignant, and autoimmune processes drive nephrosis, leading to a syndrome defined by proteinuria, edema, and hypoalbuminemia. NS occurs due to increased permeability to proteins at the level of the glomerulus, which allows for passage of albumin and other proteins into the urine. Proteinuria leads to a cascade of clinical complications characterized by fluid accumulation, kidney inflammation, and dysregulation of coagulation and immunity. In this article, the authors review the clinically important etiologies of NS that should inform an initial clinical evaluation.

Pediatric glomerulopathy after COVID-19 vaccination: A case series and review of the literature.

BACKGROUND: Cases of glomerulopathy after COVID-19 vaccination have been reported in the adult population, while only a few cases have been reported in children and adolescents. For better understanding of this association in pediatric population, we aimed to describe clinical course of patients with glomerulopathy within 60 days of COVID-19 vaccination who were under followed up in the pediatric nephrology department of National Taiwan University Children's Hospital. METHODS: We reviewed the clinical characteristics, vaccine types, and outcomes of patients with newly diagnosed glomerular diseases or relapse of underlying glomerulopathy within 60 days after COVID-19 vaccination at our facility between January 2021 and July 2022. RESULTS: Thirteen pediatric patients were found to have newly diagnosed glomerular diseases or relapse from their underlying glomerulopathy after receiving their first, second, or third COVID-19 vaccines in our facility. Of the five pediatric patients with newly diagnosed glomerulopathy after vaccination, thin basement membrane nephropathy, idiopathic nephrotic syndrome, and hematuria have been identified. Seven patients had relapse episodes of underlying nephrotic syndrome and one patient with underlying isolated microscopic hematuria developed subnephrotic proteinuria after COVID-19 vaccination. All patients experienced remission or improvement with either immunosuppressive or conservative treatment during the follow-up period. CONCLUSIONS: This is the largest case series to date of pediatric glomerulopathy after COVID-19 vaccination. From our report, patients with either newly diagnosed or relapse of glomerulopathy after vaccination had good outcomes, and receiving vaccination to prevent COVID-19 infection or complications should be encouraged in pandemic era under close monitoring kidney manifestations.

A child diagnosed with severe hemophilia A presenting with nephrotic syndrome: a case report.

BACKGROUND: Nephrotic syndrome occurring as a complication of immune tolerance therapy for inhibitors in hemophilia B is well recognized. It is also known to occur in association with factor borne infections, especially hepatitis C. This is the first case report of nephrotic syndrome occurring in a child receiving prophylactic factor VIII in the absence of inhibitors of hepatitis infection. However, the pathophysiology of this phenomenon is poorly understood. CASE PRESENTATION: A 7-year Sri Lankan boy diagnosed with severe hemophilia A on weekly factor VIII prophylaxis was diagnosed with three episodes of nephrotic syndrome, a condition in which there is leakage of plasma protein into urine. He had three episodes of nephrotic syndrome, all of which responded well to 60 mg/m2 daily dose of oral steroids, achieving remission within 2 weeks of starting daily prednisolone. He has not developed inhibitors for factor VIII. His hepatitis screening remained negative. CONCLUSIONS: There is a possible link between factor therapy for hemophilia A and nephrotic syndrome, which can be a T-cell-mediated immune response. This case also highlights the importance of monitoring for renal involvement in patients treated with factor replacement.

Nephrotic syndrome and acute coronary syndrome in children, teenagers and young adults: Systematic literature review.

Myocardial infarction is rare in children, teenagers and young adults (aged<20 years). The most common aetiologies identified include Kawasaki disease, familial hypercholesterolaemia, collagen vascular disease-induced coronary arteritis, substance abuse (cocaine, glue sniffing), trauma, complications of congenital heart disease surgery, genetic disorders (such as progeria), coronary artery embolism, occult malignancy and several other rare conditions. Nephrotic syndrome is a very rare cause of myocardial infarction, but it is probably underestimated. The purpose of this review was to determine the current state of knowledge on acute coronary syndrome related to nephrotic syndrome. We thus performed a comprehensive structured literature search of the Medline database for articles published between January 1st, 1969 and December 31st, 2021. Myocardial infarction in young adults can be broadly divided into two groups: cases of angiographically normal coronary arteries; and cases of coronary artery disease of varying aetiology. There are several possible mechanisms underlying the association between acute coronary syndrome and nephrotic syndrome: (1) coronary thrombosis related to hypercoagulability and/or platelet hyperactivity; (2) atherosclerosis related to hyperlipidaemia; and (3) drug treatment. All of these mechanisms must be evaluated systematically in the acute phase of disease because they evolve rapidly with the treatment of nephrotic syndrome. In this review, we propose a decision algorithm for the management of acute coronary syndrome in the context of nephrotic syndrome. The final part of the review presents the short- and medium-term therapeutic strategies available. Thromboembolism related to nephrotic syndrome is a rare non-atherosclerotic cause of acute coronary syndrome, and prospective studies are needed to evaluate a systematic approach with personalized therapeutic strategies.

Complete remission of primary membranous nephropathy following hepatitis E infection.

Primary membranous nephropathy (PMN) is a major cause of nephrotic syndrome in adults. Studies have shown that one-third of PMN cases undergo spontaneous remission, among which are some cases of infection-related complete remission. Herein, we report the case of a 57-year-old man who achieved complete remission of PMN shortly after the onset of acute hepatitis E infection. At the age of 55 years, the patient developed a nephrotic syndrome, and renal biopsy revealed membranous nephropathy, Ehrenreich-Churg stage 1. Treatment with prednisolone (PSL) reduced urinary protein from 7.8 g/gCre to approximately 1 g/gCre but did not lead to complete remission. However, 7 months after starting treatment, he developed an acute hepatitis E infection after consuming wild boar meat. Immediately after the onset of acute hepatitis E, the patient's urinary protein levels decreased to < 0.3 g/gCre. The PSL dose was subsequently reduced and discontinued after 2 years and 8 months, and complete remission was maintained thereafter. We considered that an increase in the number of regulatory T cells (Tregs) caused by acute hepatitis E infection was associated with PMN remission in this patient.