Uremic syndrome with newly diagnosed HIV infection: reflections on a particular case.

INTRODUCTION: Diagnosis with Western blot test (WB) may not provide clear results for certain patients, including those who are not infected with human immunodeficiency virus (HIV) but produce non-specific reactions, individuals in the HIV window period (WP), those with acute HIV infection, and advanced acquired immunodeficiency syndrome (AIDS) patients. HIV-positive individuals face an elevated risk of developing kidney disease. HIV peritoneal dialysis patients may be more susceptible to catheter-related infections. This study reports a case of HIV detected during early development of a nephrotic syndrome into uremic syndrome. CASE PRESENTATION: A 46-year-old male individual diagnosed with stage 5 chronic kidney disease was admitted to the hospital in preparation for his first renal replacement therapy. During routine check-ups, the patient was identified as having a reactive response to the HIV antigen/antibody test. The rapid detection results exhibited a weak reaction across all manufacturers, while the enzyme-linked immunosorbent assay (ELISA) test (Bio-Rad, Hercules, USA) showed a reactive response. Nonetheless, the third and fourth generation tests did not yield a response, suggesting that the patient`s internal concentration of HIV antigen or antibody was relatively low at the time. However, the confirmation test did not provide conclusive results, leading the patient to decline further renal replacement therapy. Two months later, the patient`s HIV antigen/antibody levels were measured as 95.23 in the outpatient department of our hospital. CONCLUSIONS: This case underscores the importance of actively exploring various detection strategies to enhance the efficiency of detecting acute phase HIV infection during the testing process.

Gluconephrotic Syndrome: A Comprehensive Review.

This article provides an overview of the diabetic kidney disease paradigm, explaining important aspects such as prognostic markers, clinical assessments, and therapeutic options. The importance of the term gluconephrotic syndrome (GlucoNS) is emphasized, highlighting its significant influence on clinical evaluations, research procedures, screening techniques, and patient care. This term encapsulates nephrotic syndrome (NS) within the diabetic milieu, shedding light on the intricate relationship between renal complications and diabetes. GlucoNS necessitates a refined approach, considering the unique challenges posed by diabetes in the context of NS. With this review, we want to highlight how important it is to assess diabetes in every case of NS and how important it is to assess albuminuria in every diabetic patient.

Clinical relevance of proteinuria selectivity index and fractional excretion of sodium in patients with nephrotic syndrome.

Proteinuria selectivity index (PSI) is a potential tool for histological classification and prediction of treatment response in nephrotic syndrome, but evidence is insufficient. Clinical relevance of fractional excretion of sodium (FENa) in nephrotic syndrome remains largely unexplored. This multicenter retrospective study included patients with nephrotic syndrome who underwent kidney biopsy between January 2012 and June 2022. Optimal cutoffs for predicting complete remission based on PSI and FENa were determined using receiver operating characteristic curves. Patients were divided into two groups using these cutoffs and followed until complete remission. Of the 611 patients included, 177 had minimal change disease (MCD), 52 had focal segmental glomerulosclerosis (FSGS), and 149 had membranous nephropathy (MN). Median (interquartile range) PSI were 0.14 (0.09-0.19) for MCD, 0.33 (0.23-0.40) for FSGS, and 0.20 (0.14-0.30) for MN. FENa were 0.24 (0.09-0.68), 1.03 (0.50-2.14), and 0.78 (0.41-1.28). Patients with low PSI and FENa had a higher incidence of complete remission. Cox regression analyses demonstrated that both parameters were associated with achieving complete remission (HR 2.73 [95% CI 1.97-3.81] and HR 1.93 [95% CI 1.46-2.55], respectively). PSI and FENa may be useful for histological classification and predicting remission in nephrotic syndrome.

Rare presentation of May-Thurner syndrome in childhood with lower abdominal ectopic kidney.

We report a case of a child who presented clinically with features of nephrotic syndrome and May-Thurner syndrome consecutively in the first decade of life. Initially, the nephrotic syndrome was diagnosed and treated. May-Thurner syndrome was suspected clinically in later childhood when there was remission of nephrotic syndrome with persistent left lower leg swelling. The specific imaging modalities are used to document the mechanical compression of the left common iliac vein by the lower abdominal ectopic left kidney before definite management. Our discussion highlights the role of various imaging modalities in the diagnosis of May-Thurner syndrome.

Modeling a biofluid-derived extracellular vesicle surface signature to differentiate pediatric idiopathic nephrotic syndrome clinical subgroups.

Idiopathic Nephrotic Syndrome (INS) is a common childhood glomerular disease requiring intense immunosuppressive drug treatments. Prediction of treatment response and the occurrence of relapses remains challenging. Biofluid-derived extracellular vesicles (EVs) may serve as novel liquid biopsies for INS classification and monitoring. Our cohort was composed of 105 INS children at different clinical time points (onset, relapse, and persistent proteinuria, remission, respectively), and 19 healthy controls. The expression of 37 surface EV surface markers was evaluated by flow cytometry in serum (n = 83) and urine (n = 74) from INS children (mean age = 10.1, 58% males) at different time points. Urine EVs (n = 7) and serum EVs (n = 11) from age-matched healthy children (mean age = 7.8, 94% males) were also analyzed. Tetraspanin expression in urine EVs was enhanced during active disease phase in respect to the remission group and positively correlates with proteinuria levels. Unsupervised clustering analysis identified an INS signature of 8 markers related to immunity and angiogenesis/adhesion processes. The CD41b, CD29, and CD105 showed the best diagnostic scores separating the INS active phase from the healthy condition. Interestingly, combining urinary and serum EV markers from the same patient improved the precision of clinical staging separation. Three urinary biomarkers (CD19, CD44, and CD8) were able to classify INS based on steroid sensitivity. Biofluid EVs offer a non-invasive tool for INS clinical subclassification and "personalized" interventions.

An Alternative Diagnostic Test rather than 24 hours Urinary Protein to Detect Massive Proteinuria in Nephrotic Syndrome in Mymensingh Medical College Hospital, Bangladesh.

This cross-sectional study was conducted in Department of Paediatrics, Mymensingh Medical College Hospital (MMCH), Bangladesh from February 2016 to December 2016 to detect massive proteinuria by spot urinary protein creatinine ratio as an alternative diagnostic test to 24 hrs urinary total protein in nephrotic syndrome. Fifty one (51) children aged 2 to 12 years admitted with 1st episode of nephrotic syndrome in the pediatric department of MMCH were included in this by purposive sampling technique. All the patients were asked to give a 24 hours urine sample. After this collection the next spot urine samples were collected for protein and creatinine estimation. Among 51 patients 33 were male and 18 were female. The mean age was 5.5+2.3 years. The entire patient had normal renal function. The mean 24 hours urinary protein level was 3.8±1.7 gm/m²/24 hours, the mean spot urinary protein-creatinine ratio was 5.4±2.5. Mean serum albumin was 1.8±0.6 gm/dl and the mean serum cholesterol was 357.6±74.7 mg/dl. The spot urinary protein creatinine ratio was increased with the increase in the amount of 24 hours urinary total protein and a strong positive Pearson correlation (r=0.805) was found. In all the cases of nephrotic syndrome spot urinary protein creatinine ratio were found more than 2. Based on this study, it can be concluded that the determination of the spot urinary protein-creatinine ratio can replace the 24 hours urine collection in the quantitation of proteinuria in nephrotic syndrome.

Case report: Nephrotic syndrome and portal hypertensive ascites after allogeneic hematopoietic stem cell transplantation: a rare manifestation of chronic graft-versus-host disease.

Chronic graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (HSCT). Chronic GVHD may have atypical manifestations affecting non-classical organs. The diagnosis in patients with atypical manifestations of chronic GVHD is particullarly challenging, and there is a lack of knowledge regarding their pathogenesis and treatment. We reported a case who developed post-HSCT nephrotic syndrome and portal hypertensive ascites, which are both rare and atypical manifestations of chronic GVHD. Kidney biopsy revealed membranous nephropathy and renal thrombotic microangiopathy with glomerular immune deposits, suggesting antibody-mediated kidney injury. Treatment with ruxolitinib resulted in remission of both nephrotic syndrome and ascites, suggesting a role of cytokines in the pathogenesis. This case highlighted the awareness of nephrotic syndrome and portal hypertensive ascites as atypical manifestations of chronic GVHD, and the efficacy of ruxolitinib for the two manifestations.

Renal and Urinary Conditions: Nephrotic Syndrome.

Patients with nephrotic syndrome (NS) present with edema, proteinuria, hypoalbuminemia, and hyperlipidemia. In children, the most common causes are idiopathic minimal change disease and focal segmental glomerulosclerosis (FSGS). In adults, FSGS and membranous nephropathy (MN) are the most common primary causes. There are numerous secondary causes, including diabetes, amyloidosis, systemic lupus erythematosus, hematologic malignancies, and infections. In addition to confirming the diagnosis of NS by measuring proteinuria and serum albumin and lipid levels, evaluation should assess for secondary causes. In children, most cases are due to minimal change disease, which is responsive to steroid treatment. A glucocorticoid should be prescribed for children younger than 12 years. If the patient improves with steroid treatment, no biopsy is needed. If the patient does not improve, genetic testing and kidney biopsy are warranted to determine the diagnosis. In adults, biopsy typically is indicated for diagnosis, except in patients with positive test results for serum anti-phospholipase A2 receptor antibodies. This is diagnostic of MN. For patients with NS, management of initial and infrequent recurrences involves reduction of proteinuria with glucocorticoids. Frequent recurrences and/or the inability to discontinue glucocorticoids requires alternative therapies. Steroid-resistant NS also requires use of alternative therapies. Long-term NS management includes dietary sodium restriction, edema management, and blood pressure control. Thromboembolism prophylaxis should be considered for patients with NS and high risk of thromboembolism, particularly those with MN.

[Comparison of thrombodynamic methods and routine hemostasis tests in the evaluation of hypercoagulable syndrome in chronic glomerulonephritis].

BACKGROUND: Nephrotic syndrome (NS) is associated with a high risk of thrombotic complications. In this group of patients, routine local tests for assessing hemostasis do not accurately reflect hypercoagulable state. Global functional tests for assessing hemostasis, including thrombodynamics (TD), are considered promising for assessing disorders in the blood coagulation system of these patients. AIM: To compare the rate of hypercoagulability according to routine hemostatic tests and TD and to evaluate the factors associated with increased risk of thrombotic complications in patients with chronic glomerulonephritis (CGN). MATERIALS AND METHODS: The study included 94 patients with active CGN who were not receiving anticoagulant therapy; 63 (80.3%) patients had NS, and 31 (19.7%) had active CGN without NS. Hemostasis parameters were assessed using local coagulation tests and TD test. Using logistic regression analysis, factors associated with the risk of thrombosis were assessed. RESULTS: Of the 94 patients with active CGN in 63 without preventive anticoagulant therapy, hypercoagulability according to routine tests was detected in 6 (9.5%) patients with NS and in 3 (9.7%) patients without NS (p<0.05). Hypercoagulability according to the TD test was detected in 24 (53.9%) patients with NS and in 5 (32.2%) without NS (p<0.05). The formation of spontaneous clots was observed in 29 (30.9%) of patients with CGN, most of them 24 (83%) with NS. 10.6% of patients in our cohort experienced thromboembolic events. The risk of thromboembolic events according to the univariate regression analysis was associated with older age, higher lipid levels, use of glucocorticosteroids and detection of spontaneous clots by the TD test. No association of thromboembolic events with abnormalities in routine hemostasis tests was obtained. CONCLUSION: In patients with CGN with nephrotic syndrome, hypercoagulability is detected in 9.5% of cases with routine coagulation tests and in 53.9% of cases with TD test. Detection of spontaneous clots by TD test is associated with a risk of thromboembolic events.

Membranoproliferative glomerulonephritis in a child with congenital portosystemic shunt.

Congenital portosystemic shunts (CPSS) are rare congenital vascular anomalies characterized by abnormal connections between the portal vein and systemic circulation, bypassing the liver. They can lead to complications such as recurrent encephalopathy, liver nodules, portopulmonary hypertension, and neurocognitive issues due to hyperammonemia and rarely kidney involvement. Hepatic hemodynamic changes can lead to liver nodules and hepatocellular carcinoma, particularly in extrahepatic shunts. We describe here an 11-year-old girl with type 1 intrahepatic portosystemic shunt with focal nodular hyperplasia in the liver, presenting with nephrotic syndrome that was diagnosed as membranoproliferative glomerulonephritis on kidney biopsy and that responded partially to therapy with immunosuppressants.

Nephrotic syndrome and adrenoleukodystrophy in a 5-year-old boy.

Nephrotic syndrome is a common condition characterized by filtration of large amounts of protein, hypoalbuminemia, reduced plasma oncotic pressure, sodium retention, and edema. The mechanism responsible for sodium retention in this condition is still controversial. Two different pathophysiological pathways have been proposed to explain edema formation: activation of neurohumoral effector mechanisms, including the renin-angiotensin-aldosterone system, or abnormal intrinsic/primary renal sodium retention. A 5-year-old boy with X-linked adrenoleukodystrophy presented with bilateral leg swelling, massive proteinuria, and hypoalbuminemia. Minimal change disease was diagnosed. The patient was initially treated with corticosteroids and experienced several relapses. The progression of fractional excretion of sodium correlated with proteinuria and undetectable aldosterone levels. This unusual finding suggests that the mechanism of tubular sodium avidity in this child with mineralocorticoid insufficiency was independent of the renin-angiotensin-aldosterone system.

Case presentation: a severe case of cobalamin c deficiency presenting with nephrotic syndrome, malignant hypertension and hemolytic anemia.

BACKGROUND: The etiology of nephrotic syndrome can vary, with underlying metabolic diseases being a potential factor. Cobalamin C (cblC) defect is an autosomal recessive inborn error of metabolism caused by mutations in the MMACHC gene, resulting in impaired vitamin B12 processing. While cblC defect typically manifests with hematological and neurological symptoms, renal involvement is increasingly recognized but remains rare. CASE PRESENTATION: We describe a 7-month-old male patient presenting with fatigue and edema. His first laboratory findings showed anemia, thrombocytopenia, hypoalbuminemia and proteinuria and further examinations reveals hemolysis in peripheric blood smear. During his follow up respiratory distress due to pleural effusion in the right hemithorax was noticed. And fluid leakage to the third spaces supported nephrotic syndrome diagnosis. The patient's condition deteriorated, leading to intensive care admission due to, hypertensive crisis, and respiratory distress. High total plasma homocysteine and low methionine levels raised suspicion of cobalamin metabolism disorders. Genetic testing confirmed biallelic MMACHC gene mutations, establishing the diagnosis of cblC defect. Treatment with hydroxycobalamin, folic acid, and betaine led to remarkable clinical improvement. DISCUSSION/CONCLUSION: This case underscores the significance of recognizing metabolic disorders like cblC defect in atypical presentations of nephrotic syndrome. Early diagnosis and comprehensive management are vital to prevent irreversible renal damage. While cblC defects are more commonly associated with atypical hemolytic uremic syndrome, this case highlights the importance of considering cobalamin defects in the differential diagnosis of nephrotic syndrome, especially when associated with accompanying findings such as hemolysis. Our case, which has one of the highest homocysteine levels reported in the literature, emphasizes this situation again.

[The 508th case: recurrent edema of bilateral lower extremities with proteinuria].

A 31-year-old man sought medical evaluation for a 2-year history of edema and proteinuria, with prior pathology suggesting atypical membranous nephropathy (MN). Despite treatment with a combination of steroids, calcineurin inhibitors, and four courses of rituximab (1 g, intravenous injection), the patient's nephrotic syndrome showed no relief (24 h urine protein peaked at 31.18 g/d), indicating refractory nephrotic syndrome. Later in the disease course, a sudden surge of creatinine level (322.5 µmol/L) prompted a renal biopsy, which revealed concurrent acute interstitial nephritis. Further treatment involving steroids, cyclophosphamide, and a fifth rituximab infusion (1 g, intravenous injection) resulted in improvement in renal function (serum creatinine: 322.5➝147 µmol/L), but the MN failed to achieve partial relief. Subsequent treatment with the novel humanized CD20 monoclonal antibody obinutuzumab (1 g, intravenous injection) was initiated. In the latest follow-up, anti-phospholipase-A2-receptor antibody (PLA2R) antibody were negative, B cells were eliminated, serum albumin was 36 g/L, urine protein-to-creatinine ratio was 4 810 mg/g, and serum creatinine was 162 µmol/L. This case underscores the potential efficacy of obinutuzumab in refractory MN. For advanced MN cases, prompt identification of the cause of acute kidney injury is crucial, emphasizing the need for targeted interventions to potentially stall renal function decline.

Genetic Causes of Nephrotic Syndrome and Focal and Segmental Glomerulosclerosis.

The field of nephrology has a long-standing interest in deciphering the genetic basis of nephrotic syndrome (NS), motivated by the mechanistic insights it provides in chronic kidney disease. The initial era of genetic studies solidified NS and the focal segmental glomerulosclerosis lesion as podocyte disorders. The likelihood of identifying a single gene (called monogenic) cause is higher if certain factors are present such as positive family history. Obtaining a monogenic diagnosis enables reproductive counseling and screening of family members. Now, with a new era of genomic studies facilitated by technological advances and the emergence of large genetically characterized cohorts, more insights are apparent. This includes the phenotypic breadth associated with disease genes, as evidenced in Alport syndrome and congenital NS of the Finnish type. Moreover, the underlying genetic architecture is more complex than previously appreciated, as shown by genome-wide association studies, suggesting that variants in multiple genes collectively influence risk. Achieving molecularly informed diagnoses also holds substantial potential for personalizing medicine, including the development of targeted therapeutics. Illustrative examples include coenzyme Q10 for ADCK4-associated NS and inaxaplin, a small molecule that inhibits apolipoprotein L1 channel activity, though larger studies are required to confirm benefit.

Diagnosis and treatment of secondary nephrotic syndrome with rash as the first symptom: a case report.

BACKGROUND: Membranous nephropathy (MN) is a common type of nephrotic syndrome (NS) in adults, accounting for about 20-30% of cases. Although secondary to specific factors, the coexistence of MN and mantle cell lymphoma (MCL) has been scarcely reported in clinical literature. CASE PRESENTATION: A 59-year-old Chinese male was admitted to the hospital with a generalized pruritic rash with bilateral lower extremity edema, which did not improve significantly after symptomatic treatment. He had undergone renal biopsy, and the diagnosis was thought to be secondary MN (SMN), therefore, we did a lymph node biopsy on the patient and found that MN was complicated with MCL. Soon after, the patient was admitted to the hematology department for a BR chemotherapy regimen (composed of bendamustine 90 mg/m2 BSA (body surface area), rituximab 375 mg/m2 BSA and dexamethasone 5 mg), and during the post-treatment follow-up, both his symptoms and renal function improved. CONCLUSIONS: The mechanism underlying the combination of SMN and MCL remains elusive and exceedingly rare, consequently often overlooked in clinical practice. This case serves to offer valuable clinical insights for diagnosis and treatment, while emphasizing the pivotal role of renal pathology in clinical assessment.

The different serum albumin assays influence the prescriptions in children with primary nephrotic syndrome.

The differences between the serum albumin determined by bromocresol green (BCG) and immunonephelometry (IN) were inconsistent in past studies, and the samples were all adults. We sought to determine the differences in children and reveal the impacts of these differences on the clinical diagnosis and treatments of primary nephrotic syndrome (PNS). Repeated measurements from 576 PNS children showed that albumin measured by BCG and IN (ALB-B and ALB-I) were 19.95 (11.15) g/L and 15.30 (11.05) g/L, respectively, and the mean difference was 4.68 g/L (P < 0.001). The cut-offs we calculated for hypoalbuminemia and severe hypoalbuminemia based on the IN were 25 and 15 g/L, which were 5 g/L lower than the cut-offs recommended by KIDGO, respectively. A pair of historical control samples (206 vs. 216) with ALB-B or ALB-I showed that the proportion of severe hypoalbuminemia was 14.60% greater in IN group (75.20% vs. 60.60%, P < 0.001). The misdiagnosis rate of severe hypoalbuminemia by IN was 33.77% when 20 g/L rather than 15 g/L was used as the cut-off. Furthermore, the proportion of patients receiving albumin injections increased by 10.20%, and the average consumption increased by 97.06% (P = 0.01) along with the use of IN. So, our results suggested that the difference between ALB-B and ALB-I led to misdiagnosis and prescription abuse in PNS children.

Update on C3 Glomerulopathy.

C3 glomerulopathy (C3G) is a rare disorder marked by deposition of C3 in the glomerulus, resulting in damage to the glomerular filtration unit and presenting with features of the nephritic and nephrotic syndromes. Fundamentally, C3G is caused by dysregulation of the alternative pathway of the complement cascade, either due to genetic variants or acquired humoral factors. Despite significant advances in recent years in the understanding of the underlying mechanisms and culprit lesions that result in the development of C3G, treatment options remain severely limited, and the prognosis is often poor. Fortunately, a number of anticomplement therapies are emerging from the drug development pipeline, with several in late-stage testing in patients with C3G, and there is hope that we will soon have more targeted options for managing patients with this devastating disease. In this review, we provide an overview of C3G, as well as summarizing the evidence for current treatments and detailing the clinical trials that are currently underway.

Clinical characteristics and favorable treatment responses of recurrent focal segmental glomerulosclerosis or steroid-resistant nephrotic syndrome in children after kidney transplantation.

BACKGROUND: Recurrence of focal segmental glomerulosclerosis (FSGS) or steroid-resistant nephrotic syndrome (SRNS) after kidney transplant leads to significant morbidity and potentially earlier allograft loss. To date however, reported rates, risk factors and treatment outcomes have varied widely. METHODS: We applied computational phenotypes to a multicenter aggregation of electronic health records data from 7 large pediatric health systems in the USA, to identify recurrence rates, risk factors, and treatment outcomes. We refined the data collection by chart review. RESULTS: From > 7 million patients, we compared children with primary FSGS/SRNS who received a kidney transplant between 2009 and 2020 and who either developed recurrence (n = 67/165; 40.6%) or did not (n = 98/165). Serum albumin level at time of transplant was significantly lower and recipient HLA DR7 presence was significantly higher in the recurrence group. By 36 months post-transplant, complete remission occurred in 58.2% and partial remission in 17.9%. Through 6 years post-transplant, no remission after recurrence was associated with an increased risk of allograft loss over time (p < 0.0001), but any remission showed similar allograft survival and function decline to those with no recurrence. Since treatments were used in non-random fashion, using spline curves and multivariable non-linear analyses, complete + partial remission chance was significantly higher with greater plasmapheresis sessions, CTLA4-Ig doses or LDL-apheresis sessions. Only treatment with anti-CD20, CTLA4-Ig agents, or LDL-apheresis sessions were associated with complete remission. Excluding 25 patients with mutations did not significantly change our results. CONCLUSIONS: Our contemporary high-risk cohort had higher favorable response rates than most prior reports, from combinations of agents.