Association between Exclusive Breastfeeding and the Incidence of Childhood Nephrotic Syndrome.

OBJECTIVE: To assess the relationship between breastfeeding and the risk of developing nephrotic syndrome using a population-based nationwide birth cohort in Korea. STUDY DESIGN: This nationwide cohort study utilized data from the Korean National Health Information Database and the Korean National Health Screening Program for Infants and Children. The study included all children born between January 1, 2010, and December 31, 2018, who underwent their first health screening, which included a specific questionnaire on breastfeeding between 4 and 6 months of age. Associations between nephrotic syndrome and exclusive breastfeeding were estimated using adjusted hazard ratios (aHR) derived from Cox proportional hazards models, adjusted for sociodemographic variables, with follow-up until the occurrence of nephrotic syndrome, eight years post-index date, death, or December 31, 2022, whichever was first. RESULTS: The study population comprised 1,787,774 children (median follow-up: 7.96 years; IQR: 6.31-8.00 years), including 612,556 exclusively breastfed and 1,175,218 formula-fed children. Exclusive breastfeeding was associated with a decreased risk of developing nephrotic syndrome (aHR: 0.80; 95% CI: 0.69 - 0.93). Subgroup analysis stratified by sex mirrored the overall findings, although statistical significance was not observed in girls (boys: aHR, 0.75; 95% CI, 0.62-0.92; girls: aHR, 0.87; 95% CI, 0.70 - 1.09). Sensitivity analysis confirmed these results. CONCLUSION: Exclusive breastfeeding was associated with a 20% reduced risk of developing nephrotic syndrome up to 8 years of age.

Timing of relapse as a key indicator of steroid-sparing requirements in childhood idiopathic nephrotic syndrome.

BACKGROUND: Managing children with frequent relapses or steroid-dependent nephrotic syndrome poses challenges due to recurrent relapses necessitating prolonged steroid exposure, thus increasing susceptibility to long-term complications. Identifying those at risk of poor response to steroid therapy may be helpful to guide timely intervention with steroid-sparing agents. This study aimed to identify factors associated with steroid-sparing agent needs in children with frequent relapses or steroid-dependent nephrotic syndrome. METHODS: A retrospective multicenter cohort study was conducted by reviewing the medical records of children with idiopathic nephrotic syndrome treated between 2006 and 2023. Cox proportional regression analyzed prognostic factors for steroid-sparing agent requirements in children with frequent relapses or steroid-dependent nephrotic syndrome. The time-to-event analysis utilizing the Kaplan-Meier estimate examined the proportion of children needing steroid-sparing agents after diagnosis. RESULTS: Medical records of 121 children (85 males) diagnosed with idiopathic nephrotic syndrome at a median age of 4.5 years (range 1.3-12.8) were reviewed over a median follow-up of 3.7 years (range 1.0-15.0). Time to subsequent relapse post-frequent relapses or steroid-dependent nephrotic syndrome diagnosis (at 3-month threshold) emerged as the sole significant predictor of steroid-sparing agent requirement, adjusted hazard ratio (aHR) = 2.26, 95% confidence interval (CI) 1.26-4.05. Kaplan-Meier analysis indicated that an earlier first relapse (< 3 months) led to earlier steroid-sparing agent requirement (log-rank p = 0.005). Children who relapsed within 3 months post-frequent relapses or steroid-dependent nephrotic syndrome diagnosis exhibited a higher frequency of relapses, a greater incidence of steroid-related adverse events, and were more likely to develop steroid dependency. CONCLUSIONS: Early subsequent relapse following diagnosis of frequent relapses or steroid-dependent nephrotic syndrome was linked to earlier requirement of steroid-sparing agent therapy. Further prospective research is necessary to confirm this observation.

Novel mutation patterns in children with steroid-resistant nephrotic syndrome.

Background: Idiopathic nephrotic syndrome (NS) in children poses treatment challenges, with a subset developing steroid-resistant nephrotic syndrome (SRNS). Genetic factors play a role, yet data on paediatric SRNS genetics in India are scarce. We conducted a prospective study using whole-exome sequencing to explore genetic variants and their clinical correlations. Methods: A single-centre prospective study (October 2018-April 2023) enrolled children with SRNS, undergoing renal biopsy and genetic testing per institutional protocol. Clinical, histological, and genetic data were recorded. DNA isolation and next-generation sequencing were conducted for genetic analysis. Data collection included demographics, clinical parameters, and kidney biopsy findings. Syndromic features were evaluated, with second-line immunosuppressive therapy administered. Patient and renal outcomes are presented for patients with and without genetic variants. Results: A total of 680 paediatric NS patients were analysed, with 121 (17.8%) having SRNS and 96 consent to genetic analysis. 69 (71.9%) had early SRNS, 27 (28.1%) late. Among participants, 62 (64.58%) had reportable genetic variants. The most common were in COL4A genes, with 20 (31.7%) positive. Renal biopsy showed focal segmental glomerulosclerosis in 31/42 (74%) with variants, 16/28 (57.1%) without variants. Second-line immunosuppressions varied, with CNIs the most common. Outcomes varied, with partial or complete remission achieved in some while others progressed to ESRD. Conclusion: The study underscores the importance of genetic analysis in paediatric SRNS, revealing variants in 65.7% of cases. COL4A variants were predominant. Variants correlated with varied renal outcomes, highlighting potential prognostic implications. These findings emphasize the value of personalized approaches and further research in managing paediatric SRNS.

National Unified Renal Translational Research Enterprise: Idiopathic Nephrotic Syndrome (NURTuRE-INS) study.

Background: Idiopathic nephrotic syndrome (INS) is a heterogenous disease and current classification is based on observational responses to therapies or kidney histology. The National Unified Renal Translational Research Enterprise (NURTuRE)-INS cohort aims to facilitate novel ways of stratifying INS patients to improve disease understanding, therapeutics and design of clinical trials. Methods: NURTuRE-INS is a prospective cohort study of children and adults with INS in a linked biorepository. All recruits had at least one sampling visit collecting serum, plasma, urine and blood for RNA and DNA extraction, frozen within 2 hours of collection. Clinical histology slides and biopsy tissue blocks were also collected. Results: A total of 739 participants were recruited from 23 centres to NURTuRE-INS, half of whom were diagnosed in childhood [n = 365 (49%)]. The majority were white [n = 525 (71%)] and the median age at recruitment was 32 years (interquartile range 12-54). Steroid-sensitive nephrotic syndrome (SSNS) was the most common clinical diagnosis [n = 518 (70%)]. Of patients diagnosed in childhood who underwent a kidney biopsy, for SSNS (n =103), 76 demonstrated minimal change disease (MCD), whereas for steroid-resistant nephrotic syndrome (n =80), 21 had MCD. Almost all patients diagnosed in adulthood had a kidney biopsy [n = 352 (94%)]; 187 had MCD and 162 had focal segmental glomerulosclerosis. Conclusions: NURTuRE-INS is a prospective cohort study with high-quality biosamples and longitudinal data that will assist research into the mechanistic stratification of INS. Samples and data will be available through a Strategic Access and Oversight Committee.

Pediatric nephrotic syndrome: The interplay of oxidative stress and inflammation.

Background: The pathophysiological mechanisms crucial in the development of nephrotic syndrome (NS) in the pediatric population are still not fully understood. This study aimed to investigate the relationship between hypertension, oxidative stress, and inflammation in pediatric patients during the acute phase of the disease. Methods: The study included 33 children, aged 2 to 9 years, with nephrotic syndrome. Blood samples were collected during the acute phase and remission. Parameters of oxidative status were determined, including total oxidative status (TOS), advanced oxidation protein products (AOPP), prooxidant-antioxidant balance (PAB), sulfhydryl groups (-SH), paraoxonase 1 (PON1), and total antioxidant status (TAS) in serum, measured spectrophotometrically. Inflam - matory parameters such as pentraxin 3 (PTX3), leptin, program med cell death ligand 1 (PD-L1), and E-cadherin were determined using enzyme-linked immunosorbent assay (ELISA). Results: Patients with nephrotic syndrome and hypertension had significantly higher levels of advanced oxidation protein products and total antioxidant status (p=0.029 and p=0.003, respectively). During the acute phase of the disease, lower activity of sulfhydryl groups and paraoxonase 1 was observed compared to remission (p<0.001, for both). Pentraxin 3 levels were higher, while leptin levels were lower during the acute phase (p<0.001, for both). Pentraxin 3 correlated with advanced oxidation protein products and total antioxidant status during the acute phase but not in remission (rs=0.42, p=0.027 and rs=0.43, p=0.025, respectively). A negative correlation between Advanced oxidation protein products and leptin was observed during the acute phase, which disappeared in remission (rs=-0.42, p=0.028). Conclusions: Results of this study show that hypertension influences oxidative stress markers, and decreased antioxidant capacity may contribute to nephrotic syndrome development. Pentraxin 3 appears as a potential disease activity marker, indicating a dynamic connection between inflammation and oxidative stress. Leptin may also play a role in oxidative stress in nephrotic syndrome.

Association between hypothyroidism and nephrotic syndrome: a bidirectional two-sample Mendelian randomization analysis.

BACKGROUND: There is a close clinical association between hypothyroidism and nephrotic syndrome (NS) was close, but whether there is genetic causality between the two is not known. OBJECTIVE: Using pooled data from a genome-wide association study (GWAS), the association between hypothyroidism and NS was explored via Mendelian randomization (MR) analysis. METHODS: Single-nucleotide polymorphisms (SNPs) associated with hypothyroidism (or NS) were screened as genetic instrumental variables (IVs) from pooled GWAS data, and inverse-variance weighting (IVW) was used for the main analysis to estimate causal effects, with MR-Egger, weighted median, and weighted mode used as complementary methods. Sensitivity analyses, including Cochran's Q test, MR-Egger intercept, MR-PRESSO and leave-one-out, were also conducted to assess the robustness of the results. RESULTS: Genetically predicted hypothyroidism was positively associated with the risk of developing NS (IVW: OR = 1.18, 95% CI: 1.07-1.30, p = 0.00; MR-Egger: OR = 1.36, 95% CI: 1.10-1.68, p = 0.01), and the MR-Egger intercept (intercept = -0.02, p = 0.14), MR-PRESSO test (p = 0.14), Cochran's Q test (p = 0.15) and leave-one-out test results supported the robustness of the results. Genetically predicted NS status might not be associated with an increased risk of developing hypothyroidism (IVW: OR = 1.01, 95% CI: 1.00-1.03, p = 0.08; MR-Egger: OR = 1.01, 95% CI: 0.98-1.04, p = 0.43), and the MR-Egger intercept (intercept < 0.01, p = 0.69), MR-PRESSO test (p = 0.64), Cochran's Q test (p = 0.61) and leave-one-out test results supported the robustness of the results. CONCLUSION: Hypothyroidism status could increase the risk of developing NS.

Urine-derived podocytes from steroid resistant nephrotic syndrome patients as a model for renal-progenitor derived extracellular vesicles effect and drug screening.

BACKGROUND: Personalized disease models are crucial for evaluating how diseased cells respond to treatments, especially in case of innovative biological therapeutics. Extracellular vesicles (EVs), nanosized vesicles released by cells for intercellular communication, have gained therapeutic interest due to their ability to reprogram target cells. We here utilized urinary podocytes obtained from children affected by steroid-resistant nephrotic syndrome with characterized genetic mutations as a model to test the therapeutic potential of EVs derived from kidney progenitor cells (nKPCs). METHODS: EVs were isolated from nKPCs derived from the urine of a preterm neonate. Three lines of urinary podocytes obtained from nephrotic patients' urine and a line of Alport syndrome patient podocytes were characterized and used to assess albumin permeability in response to nKPC-EVs or various drugs. RNA sequencing was conducted to identify commonly modulated pathways after nKPC-EV treatment. siRNA transfection was used to demonstrate the involvement of SUMO1 and SENP2 in the modulation of permeability. RESULTS: Treatment with the nKPC-EVs significantly reduced permeability across all the steroid-resistant patients-derived and Alport syndrome-derived podocytes. At variance, podocytes appeared unresponsive to standard pharmacological treatments, with the exception of one line, in alignment with the patient's clinical response at 48 months. By RNA sequencing, only two genes were commonly upregulated in nKPC-EV-treated genetically altered podocytes: small ubiquitin-related modifier 1 (SUMO1) and Sentrin-specific protease 2 (SENP2). SUMO1 and SENP2 downregulation increased podocyte permeability confirming the role of the SUMOylation pathway. CONCLUSIONS: nKPCs emerge as a promising non-invasive source of EVs with potential therapeutic effects on podocytes with genetic dysfunction, through modulation of SUMOylation, an important pathway for the stability of podocyte slit diaphragm proteins. Our findings also suggest the feasibility of developing a non-invasive in vitro model for screening regenerative compounds on patient-derived podocytes.

Long-Term Rehabilitation Therapy Is Effective for Physical Function in a Patient With Amyloid Light Chain Amyloidosis Complicated by Nephrotic Syndrome: A Case Report and Literature Review.

We report on the rehabilitation of a patient with amyloid light chain (AL) amyloidosis complicated by nephrotic syndrome. Various symptoms produced by AL amyloidosis, including nephrotic syndrome, complicate rehabilitation therapy. In this case report, long-term physical therapy was initiated prior to autologous peripheral blood stem cell transplantation owing to the risk of further decline in physical function due to decreased mobility and physical activity. Patients were instructed on how to perform home exercise therapy. Furthermore, compliance was monitored using a checklist and regular face-to-face feedback. There was no increase in skeletal muscle mass, but improvements in grip strength, lower extremity muscle strength, and phase angle were observed after 24 weeks of physical therapy. Despite the absence of partial remission (urinary protein level of 3.5 g/gCre or higher), nephrotic syndrome demonstrated a trend toward improvement. Since the effectiveness of physical therapy in such patients has not yet been fully established, this report suggests that long-term rehabilitation therapy for physical function in patients with nephrotic syndrome complicated by persistent proteinuria may be effective.

Filariasis-Associated Secondary Membranous Nephropathy: A Rare Presentation.

Parasitic infections like filariasis are uncommon causes of secondary membranous nephropathy (MN) which requires serological tests to detect circulating Wuchereria bancrofti antigens for its diagnosis or the identification of microfilariae in the capillary lumen on kidney biopsy. The immunochromatographic card tests is simple, non invasive and has high sensitivity and specificity. We report a case of 30 year old lady who presented to us with nephrotic syndrome which on kidney biopsy showed features of membranous nephropathy with negative staining for Anti PLA2R, THSD7A and exostosin. A thorough workup was done to find out any secondary cause of MN where she was found positive with filiarial antibody test. Hence, a diagnosis of secondary membranous pattern nephropathy was considered for which she was treated with diethylcarbamazine (DEC) and other supportive medications which on follow up showed marked resolution of proteinuria.

Exposure to Mycophenolic Acid and Its Clinical Response in an Indian Pediatric Population with Nephrotic Syndrome.

Background: Children with nephrotic syndrome experience many side effects and frequent relapses when treated with steroids and other drugs. Mycophenolic acid (MPA) is one of the effective and least toxic drug for the treatment of nephrotic syndrome. This drug needs to be monitored for maximal efficacy and minimal toxicity. The therapeutic reference range for this drug is not established for the aforementioned patient population of Indian origin. Materials and Methods: In this observational study, children with nephrotic syndrome on mycophenolate mofetil were followed up for a minimum duration of three months. Following this, their clinical status (relapse/remission) was determined and the mycophenolate exposure was measured for over 12 hours. Results: A total of 34 participants were included, with 17 (50%) in relapse. Median MPA Area under the curve over 12 hours (AUC0-12h) (36.5 µg·h/ml) in the remission group differed significantly compared to that in the relapse group (17.2 µg·h/ml). Conclusion: Higher exposure to MPA AUC0-12h is associated with clinical remission of pediatric nephrotic syndrome.

Rituximab in Steroid-Dependent Podocytopathies.

Introduction: Rituximab (RTX) has been reported as an effective treatment alternative in primary forms of minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) associated with steroid dependence and frequent relapses. However, the optimal RTX regimen and the outcomes of further doses of RTX remain unclear. This study aimed to evaluate the use of induction and maintenance RTX therapy for adults with primary podocytopathies. Methods: We performed a retrospective case series on adult patients with steroid-dependent podocytopathies who received an induction RTX therapy. Maintenance therapy was performed at physician's discretion. Remission and relapse rates, concomitant corticosteroids and immunosuppressants use, B-cell depletion and adverse events were analyzed. Results: Fourteen patients (mean age at start of RTX 29.1 ± 21.9 years) with MCD (n = 7) or FSGS (n = 7) were treated with 2 doses of 1,000 mg 2 weeks apart (n = 13) or four doses of 375 mg/m2 (n = 1) of RTX. At last follow-up (mean 47.3 ± 101.7 months), 10 patients were in complete remission and two remained in partial remission. A reduction in the number of relapses, number of patients under corticosteroids and immunosuppressants, and dose of prednisolone was observed when compared to baseline (14 [100%] vs. 5 [35.7%]; 8/14 [57.1%] vs. 4/12 [33.3%]; 13/14 [92.9%] vs. 7/12 [58.3%]; 20 mg/day vs. 5.25 mg/day, respectively). Maintenance RTX therapy was used in 6 patients, with sustained complete remission. Infusion reactions were observed in 4 patients (one required treatment withdrawal). Conclusions: Our findings support the use of RTX for a steroid-free remission in podocytopathies and suggest that maintenance RTX is well-tolerated and associated with prolonged remission. Further studies are needed to confirm its efficacy and safety and establish the optimal induction and maintenance RTX regimen in steroid-dependent podocytopathies.

Rituximab (RTX) seems to be an effective treatment alternative in primary forms of MCD and FSGS, particularly in cases of steroid dependence and frequent relapses. Our findings support the use of RTX for a steroid-free remission in podocytopathies and suggest that maintenance RTX is well-tolerated and associated with prolonged remission. Further studies are needed to confirm its efficacy and safety and establish the optimal induction and maintenance RTX regimen in steroid-dependent podocytopathies.

Analyzing three pedigrees in X-linked Alport syndrome with the presentation of nephrotic syndrome.

Background: Alport syndrome (AS) is a common cause of end-stage renal disease (ESRD) with various clinical symptoms and incomplete manifestation. Patients with AS and other renal disorders are often misdiagnosed. This study reported three X-linked dominant Alport syndrome (XLAS) pedigrees with nephrotic syndrome (NS) as the predominant phenotype and analyzed COL4A5 gene alterations. Methods: Three Han Chinese XLAS pedigrees were recruited, and clinical phenotypes were obtained. The pre-certified individuals' peripheral blood DNA was taken, and whole-genome next-generation sequencing (NGS) was performed for candidate genes and mutation screening, followed by NGS or Sanger sequencing of suspected mutant types in participating family members. Results: Both probands A and B were diagnosed with NS through biochemical tests, and X-linked Alport syndrome-associated renal injury was diagnosed by renal biopsy. The biopsy revealed focal foamy cells in the renal interstitium, tearing and delamination changes in the glomerular basement membrane, and negative α3 and α5 chains of type IV collagen. Proband C, who was earlier diagnosed with NS, has now advanced to ESRD, along with his mother and proband A's mother. Genetic sequencing of all three pedigrees identified three mutations, namely, c.5020C>T, c.4435_4445del, and c.1584_1587+6del in the X-linked dominant gene COL4A5 (NM_000495.5). These mutations lead to the production of shortened proteins, potentially impacting the function of COL4A5 and causing pathogenic effects. Conclusion: The novel c.4435_4445del and c.1584_1587+6del mutations not only enrich the spectrum of mutations in the COL4A5 gene but also indicate that carriers of both mutation sites and those with mutation c.5020C>T may present NS as their primary clinical manifestation.

Vascular Threads and Nephron Nests: Exploring the Association Between Takayasu Arteritis and Membranous Nephropathy.

Takayasu arteritis (TA) primarily causes ischaemic nephrosclerosis but can occasionally be associated with glomerulopathy. We report a case of a female in her twenties with PLA2-negative, THSD7A-positive membranous nephropathy (MN) refractory to rituximab, who presented with neck pain and new-onset hypertension. Blood work showed elevated inflammatory markers. Imaging of the head and neck revealed focal dilation and irregularity of the vertebral arteries, consistent with TA. The patient was started on treatment with steroids, followed by mycophenolate mofetil, which led to the resolution of symptoms and nephrotic syndrome. This case highlights an uncommon sequence of events, with MN presenting before TA, underscoring the need to consider TA in differentials for patients with MN. Notably, this is the first reported case in a young female, emphasising the need for further understanding of TA-associated glomerular diseases. Additionally, the presence of THSD7A in MN, despite negative malignancy workup, is also noteworthy. LEARNING POINTS: Membranous nephropathy (MN) and Takayasu arteritis (TA) have distinct clinical presentations; therefore, diagnosing coexisting MN and TA is challenging, which may lead to delayed diagnoses.A multidisciplinary approach with tailored treatments is essential for prompt diagnosis and optimal management.Comprehensive follow-up studies are vital to understand the pathogenesis of this rare amalgamation, refine targeted treatment strategies and potentially improve overall prognosis.

Short segment myelitis as a dominant manifestation of cryptococcal infection: a case report.

Cryptococcal infection of central nervous system commonly involves meningitis or meningoencephalitis, but rarely mimics inflammatory myelitis. We present short segment myelitis as a dominant manifestation caused by Cryptococcus neoformans in a patient with nephrotic syndrome under immunosuppressive therapy. This case report highlights Cryptococcus neoformans as a potential etiological factor for short segment myelitis in immunocompromised hosts.

In steroid-resistant nephrotic syndrome that meets the strict definition, monogenic variants are less common than expected.

BACKGROUND: In patients with steroid-resistant nephrotic syndrome (SRNS), the presence of monogenic variants influences therapeutic strategies. Large cohort studies reported the detection of monogenic variants in approximately 30% of patients with SRNS. However, these cohorts included many patients, such as those with symptomatic proteinuria, who did not meet the strict diagnostic criteria for pediatric nephrotic syndrome (NS). Therefore, we investigated the proportion of causative monogenic variants detected in patients who strictly met the diagnostic criteria of SRNS and explored their clinical characteristics. METHODS: We examined pediatric SRNS cases with genetic analysis conducted in our hospital. Cases satisfying all of the following criteria were included: (1) age at onset 1-18 years, (2) serum albumin at onset ≤ 2.5 g/dl, (3) persistent heavy proteinuria, and (4) no complete remission after 4 weeks of steroid monotherapy. RESULTS: The proportion of detected monogenic variants was 12% (22/185) among all patients. The proportion was only 7% (9/129) in patients with edema at disease onset compared with 38% (9/24) in those without (p < 0.0001). Monogenic variants were rare in patients with acute kidney injury associated with NS (1% (1/11)) or a history of complete remission (4% (2/51)). CONCLUSIONS: Our study revealed a monogenic cause in 12% of individuals with strictly defined SRNS, a much smaller proportion than previously reported. The presence or absence of edema at the onset was an important factor to distinguish SRNS with monogenic cause from SRNS without. Our results provide further evidence of the SRNS types attributable to monogenic causes.

Case report: Successful treatment of renal-limited thrombotic microangiopathy secondary to chronic lymphocytic leukemia.

Thrombotic microangiopathy (TMA) is a rare renal complication of patients with chronic lymphocytic leukemia (CLL) and is often associated with peripheral features. We present the first case of CLL patients with renal-limited TMA. A 70-year-old female patient with a history of well-controlled type 2 diabetes and baseline albuminuria of 87.2 mg/g 1 year prior and CLL was on active surveillance only. Her baseline white blood cell (WBC) was 202.6 x 103/µl. She presented with nephrotic syndrome with proteinuria of 10 g/g and a subsequent unremarkable serologic work-up. A kidney biopsy revealed diabetic glomerulosclerosis and chronic TMA. Initially, she was treated conservatively with angiotensin receptor blockade and sodium glucose cotransporter-2 inhibition but progressed with increased proteinuria of 17 g/g. Complement functional panel testing was pursued and showed dysregulation of the classical and alternative complement pathways. We decided to treat CLL which was suspected to be the culprit. At 9 months post-ibrutinib initiation, there was a 90% reduction in the WBC as well as a 94% reduction in proteinuria (17 g/g to 0.97 g/g). This case emphasizes the role of complement dysregulation in the pathogenesis of TMA in CLL patients. Treatment of CLL can restore complement dysregulation and improve renal outcomes.

Histopathologic Characteristics of Childhood Nephrotic Syndrome in a Tertiary Health Facility in Nigeria.

BACKGROUND: Globally, the predominant histopathologic characteristic of childhood nephrotic syndrome has been minimal change nephropathy (MCN). However, some studies from Africa and Nigeria have revealed otherwise. It is imperative that this pattern is re-examined from time to time given changing disease and environmental dynamics from place to place. OBJECTIVE: This study aimed to determine the histopathological characteristics of childhood nephrotic syndrome in Ilorin, northcentral Nigeria. METHODS: A prospective study of all new patients aged 2-14 years who presented with clinical features of nephrotic syndrome between January 2010 to December 2023 at the University of Ilorin Teaching Hospital, Ilorin was carried out. All eligible patients underwent renal biopsy. RESULTS: A total of 47 children with nephrotic syndrome were biopsied comprising of 21 males and 26 females making an M: F ratio of 1:1.2. The age range of subjects was 2-14 years with a mean of 7.8 ±3.6 years. The most common histological type of nephrotic syndrome was minimal change nephrotic syndrome (MCNS) which occurred in 35(74.5%) children followed by membranoproliferative glomerulonephritis (MPGN) in 5(10.6%) and focal segmental glomerulosclerosis (FSGS) in 2(4.3%). Of the 35 MCNS patients, 31(88.6%) were steroid sensitive while 4(11.4%) were steroid resistant. CONCLUSION: The predominant histopathological characteristic of childhood nephrotic syndrome was minimal change nephrotic syndrome, which was mostly steroid-sensitive.

CONTEXTE: Au niveau mondial, la principale caractéristique histopathologique du syndrome néphrotique de l'enfant a été la néphropathie à lésions minimales (NLM). Cependant, certaines études en Afrique et au Nigeria ont montré des résultats différents. Il est essentiel de réévaluer ce modèle régulièrement en raison de l'évolution des maladies et de l'environnement d'un endroit à l'autre. OBJECTIF: Cette étude visait à déterminer les caractéristiques histopathologiques du syndrome néphrotique de l'enfant à Ilorin, dans le nord-centre du Nigeria. MÉTHODES: Une étude prospective de tous les nouveaux patients âgés de 2 à 14 ans présentant des signes cliniques de syndrome néphrotique entre janvier 2010 et décembre 2023 à l'hôpital universitaire d'Ilorin, à Ilorin, a été réalisée. Tous les patients éligibles ont subi une biopsie rénale. RÉSULTATS: Au total, 47 enfants atteints du syndrome néphrotique ont été biopsiés, dont 21 garçons et 26 filles, soit un ratio H/F de 1/1,2. La tranche d'âge des sujets était de 2 à 14 ans avec une moyenne de 7,8 ± 3,6 ans. Le type histologique le plus fréquent du syndrome néphrotique était la néphropathie à lésions minimales (NLM), obser vée chez 35 (74,5 %) enfants, suivie de la glomérulonéphrite membranoproliférative (GMPN) chez 5 (10,6 %) et du sclérose segmentaire et focale (SSF) chez 2 (4,3 %). Parmi les 35 patients atteints de NLM, 31 (88,6 %) étaient cortico-sensibles et 4 (11,4 %) cortico-résistants. CONCLUSION: La principale caractéristique histopathologique du syndrome néphrotique de l'enfant était la néphropathie à lésions minimales, qui était principalement cortico-sensible. MOTS-CLÉS: Syndrome néphrotique, Enfant, Histopathologie, Nigeria.

Nephrotic Syndrome Without Nephrotic Range Proteinuria.

Nephrotic syndrome in adults is defined as nephrotic-range (≥3.5g/24h) proteinuria with low serum albumin, usually associated with edema, hyperlipidemia, and lipiduria. The 3.5g/24h threshold was selected arbitrarily and might not be reached in certain cases despite severe defects in glomerular permeability. We describe the case of a 57-year-old male who presented with progressively worsening swelling involving his limbs and abdomen. He also reported decreased urine output and fatigue. Physical examination was notable for severe pitting edema over legs, arms, and abdomen, in addition to peri-orbital puffiness. Labs revealed low serum albumin (1.3 g/dL), moderate proteinuria (2.3g/24h), and elevated total cholesterol (334 mg/dL). Renal biopsy showed amyloid light chain (AL) amyloidosis and bone marrow biopsy confirmed the presence of lambda-restricted plasma cells. Computed tomography, ultrasound, elastography, and laboratory findings were congruent with those seen in hepatic amyloidosis. A diagnosis of nephrotic syndrome caused by systemic AL amyloidosis was made despite the absence of nephrotic range proteinuria. The primary abnormality in nephrotic syndrome is increased glomerular permeability, leading to severe proteinuria causing low serum albumin, decreased oncotic pressure, and increased water retention by kidneys due to activation of the epithelial sodium channel (ENaC). The amount of albuminuria is influenced by both the extent of glomerular permeability and the rates of glomerular filtration and albumin synthesis. In cases where albumin synthesis is decreased secondary to concurrent liver disease, as in our case, a steady state of renal protein excretion may be reached at a lower threshold than 3.5g/24h despite severe defects in glomerular permeability.