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.

Molecular aspects of ABCB1 and ABCG2 in Gallbladder cancer and its clinical relevance.

The function of ABC transporters in the body is manifold; such as maintenance of homeostasis, effect on multi-drug resistance and their role in tumor initiation & progression. Evidence pointing towards the direct or indirect role of ABC transporter genes in particular; ABCB1 and ABCG2 in cancer genesis is increasing. However, their role in gallbladder cancer is unexplored. Therefore, we investigated the methylation status and expression pattern of ABCB1 and ABCG2in gallbladder carcinogenesis. The methylation and expression study of ABCB1/MDR1 and ABCG2/BCRP was performed in tumour and normal fresh tissue samples collected from 61 histopathologically diagnosed gallbladder cancer patients. The methylation status was analysed by Methylation-Specific PCR and expression was determined by Real-Time PCR and Immunohistochemistry. Hypomethylation of ABCB1 and ABCG2 was found in 44 (72.13%) and 48 (78.6%) cases, respectively. ABCB1 hypomethylation pattern showed association with female patients (p = 0.040) and GradeII tumors (p = 0.036) while, ABCG2 hypomethylation was more frequent in early tumors (T1-T2). The mRNA expression ofABCB1 and ABCG2 was up-regulated in 33 (54.10%) and 41 (67.21%) patients with fold change of 4.7 and 5.5, respectively. The mRNA expression of both genes showed association with Grade II tumours and the increased fold change of ABCG2 was higher in (T1-T2) depth of invasion (p = 0.02) and Stage I-II disease (p = 0.08). The protein expression on IHC was strongly positive for ABCB1/MDR1and ABCG2/BCRP in 32 (52.46%) and 45 (73.77%) patients, respectively. The protein expression in ABCG2 showed association with patients age > 50 years (p = 0.04) and GradeII differentiation (p = 0.07). Interestingly, the hypomethylation of both the genes showed significant correlation with increased expression. ABCB1/MDR1 and ABCG2/BCRP hypomethylation and overexpression could have a potential role in gallbladder cancer tumorigenesis especially in early stages. The epigenetic change might be a plausible factor for altered gene expression of ABCB1 and ABCG2 in gallbladder cancer.

Differential regulation of miR-21-5p delays wound healing of melanocyte-deprived vitiligo skin by modulating the expression of tumor-suppressors PDCD4 and Maspin.

The loss of melanocytes in vitiligo is associated with architectural, transcriptional, and cellular perturbations of keratinocytes and manifests as a reduced proliferation potential in vitro and delayed re-epithelialization in vivo. To understand the molecular mechanisms underlying this delay, microRNA (miRNA) profiling was performed on split skin biopsies collected on Day 1 (basal level) and Day 14 (wound re-epithelialization) from nonlesional (NL) and lesional (L) skin of five subjects with stable nonsegmental vitiligo and 129 miRNAs were found to be differentially regulated between the NL and L healed epidermis. miR-21-5p, expressed at comparable levels on NL and L Day 1 samples, demonstrated significant upregulation during re-epithelialization. However, the extent of its upregulation was relatively lower in L (10 times compared to Day 1) as compared to NL skin (17 times compared to Day 1). The overexpression of miR-21 in keratinocytes led to a significant increase in the expression of proliferation markers (Ki67 and MCM6 messenger RNA, Ki67 positivity), along with an increase in keratinocyte migration. Using a small interfering RNA mediated knockdown approach, we further demonstrated that miR-21-5p mediates its effects by suppressing the expression of programmed cell death 4 (PDCD4) and mammary serine protease inhibitor (Maspin), both tumor-suppressor genes. Investigation of clinical samples corroborated the lower miR-21 levels and a higher expression of PDCD4 and Maspin in L Day 14 compared to the NL Day 14 epidermis. In conclusion, this study revealed that a relatively lower upregulation of miR-21-5p in L skin leads to significantly higher levels of PDCD4 and Maspin, delaying wound re-epithelialization by reducing the proliferation and migration of keratinocytes.

Lesional skin in vitiligo exhibits delayed in vivo reepithelialization compared to the nonlesional skin.

Vitiligo, a common skin disorder, is characterized by the loss of functional melanocytes resulting in the depigmentation of skin. Previous studies have demonstrated molecular and architectural alterations in the epidermal keratinocytes upon loss of melanocytes. The physiological implications of these "altered" keratinocytes are yet not known. We investigated the wound healing efficiency of lesional vs nonlesional skin in 12 subjects with stable nonsegmental vitiligo using histological and ultrastructural evaluation of partial-thickness wounds. The wounds were examined 12 days postinjury, coinciding with the reepithelialization phase of healing marked primarily by keratinocyte migration and proliferation. This study demonstrated a significant difference in the reepithelialization potential between the lesional and nonlesional skin. While all 12 nonlesional wounds demonstrated considerable neoepidermis formation on the 12th day post wound, only four of the corresponding lesional samples showed comparable reepithelialization; the rest remaining in the inflammatory phase. Ultrastructural studies using transmission electron microscopy as well as immunohistochemical staining revealed a reduced number of desmosomes, shorter keratin tonofilaments and an increase in myofibroblast population in the dermis of lesional reepithelialized tissue compared to the nonlesional reepithelialized samples. This study implicates gross functional perturbations in the lesional skin during physiological wound healing in vitiligo, suggesting that the breakdown of keratinocyte-melanocyte network results in delayed wound repair kinetics in the lesional skin when compared to patient-matched nonlesional skin.

Cytopreparation of duodenal biopsy fixative improves detection rate of giardia in clinically suspected cases.

INTRODUCTION: Giardia intestinalis is a flagellated protozoan, frequently documented as an agent for enteric illness worldwide. Laboratory procedures for diagnosis include stool examination, antigenic detection assays and, at times, mucosal biopsy. We hypothesised that the formalin fixative used as a preservative for mucosal biopsy can be a good diagnostic sample for detecting surface mucosal and luminal infective agents such as giardia. The aim of the study was to find out the utility of processing the remaining formalin fixative as a complementary diagnostic method for detecting giardia. METHODS: This study included 200 cases of duodenal biopsies sampled over 6 months. The biopsies were picked up using clean forceps and the remaining fixative was processed using standard cytospin protocol. The cytospin preparation and formalin-fixed paraffin-embedded tissue sections were examined by two pathologists independently blinded to each others findings. RESULTS: On cytology, trophozoites of giardia were detected in 23 out of 200 cases (11.50%). The cytomorphology of pear-shaped organism with paired flagella and nuclei is very diagnostic. One case also showed presence of cryptosporidium spores. No other intestinal parasite was seen. Out of the 23 positive cytology samples, only 12 (6%) corresponding formalin-fixed paraffin-embedded tissue sections showed presence of giardia. CONCLUSION: Concurrent examination of duodenal biopsy and the formalin fixative cytopreparation in cases with high index of clinical suspicion of giardiasis proved to be a useful adjunct to biopsy diagnosis of giardiasis, which was statistically significant (P < .0001). This approach adds negligible cost and effort but with good diagnostic yield. We recommend that the formalin cytopreparation be used as a complementary technique to biopsy for cases suspected of intestinal parasitic infection.

Is spindle cell oncocytoma a true entity or a variant of pituicytoma? A case report with review of literature.

Spindle cell oncocytoma (SCO) is a newly described rare entity simulating clinicoradiological features of a nonfunctional pituitary adenoma and is corresponding to the category of World Health Organization grade I tumor. However, because of the reported incidence of recurrence and invasive presentation in some cases, its categorization as a low grade tumor is questionable. Earlier, it was thought to arise from the folliculostellate cells of adenohypophysis. Recently, few reports have described expression of thyroid transcription factor-1 [TTF-1], which is a specific marker for pituicytes of neurohypophysis, suggesting this tumor to be a variant of pituicytoma. We describe a case of SCO in a 28-year-old young female patient with TTF-1 immunopositivity, and ultra-structurally showing abundant mitochondria along with few neurosecretory granules.

Toll-like receptor 3 (TLR-3), TLR-4 and CD80 expression in peripheral blood mononuclear cells and urinary CD80 levels in children with idiopathic nephrotic syndrome.

BACKGROUND: The aims of this study were (1) to detect toll-like receptor (TLR)-3, TLR-4 and CD80 expression in peripheral blood mononuclear cells (PBMCs) and estimate urinary CD80 levels in children with idiopathic nephrotic syndrome and (2) to investigate the utility of these markers to differentiate between biopsy-proven minimal change disease (MCD) and focal segmental glomeruloscelerosis (FSGS). METHODS: The study included 70 patients with idiopathic nephrotic syndrome (NS), of whom 40 had steroid-sensitive NS (SSNS; 25 with active NS, 15 in remission) and 30 had steroid-resistant NS (SRNS) patients, and 23 healthy controls. TLR-3, TLR- 4 and CD80 mRNA expression levels in PBMCs were determined and the urinary CD80 level estimated. RESULTS: Median TLR-3, TLR-4 and CD80 mRNA expression levels were higher in patients with active SSNS than in those with SRNS, and the latter patient group also had significantly lower expression levels than the controls. The expression levels of these markers were associated with reductions in remission. Patients with biopsy-proven MCD had higher median expression levels of these markers than those with FSGS, but the differences were not statistically significant. Median urinary CD80/creatinine values were significantly higher in patients with SSNS and SRNS than in the controls and steroid-sensitive patients in remission (p < 0.001). CD80 levels were also significantly higher in patients with MCD than in those with FSGS (p = 0.002). A cut-off level of >914.5 ng/g had a sensitivity of 86.6%, specificity 71.4% and area under the curve of 0.828 (95% confidence interval 0.678-0.978, p = 0.002) for the diagnosis of MCD. CONCLUSIONS: Increased expressions of TLR-3, TLR-4 and CD80 mRNA and the level of urinary CD80/creatinine could be useful markers to differentiate patients of SSNS in relapse from those with SRNS. Further these markers can also distinguish biopsy proven MCD from FSGS in SRNS patients.

Intraventricular Tuberculoma in a Child: A Rare Location.

Intracranial tuberculoma is an uncommon presentation of tuberculosis, and its occurrence in an intraventricular location is very rare. It is usually confused with glioma, parasitic cyst, and craniopharyngioma. Few case reports exist in the literature on this entity. We report a case of tuberculoma at the foramen of Monro in a 7-year-old child and review the literature in terms of diagnostic dilemma.

Differentially expressed urinary biomarkers in children with idiopathic nephrotic syndrome.

BACKGROUND: We performed a discovery phase of urinary proteomic profile in children with idiopathic nephrotic syndrome and validated selected biomarkers. METHODS: Urinary proteomic profile was performed using isobaric tags for relative and absolute quantitation labeling, coupled with liquid chromatography-matrix assisted laser desorption and ionization analysis. Validation of biomarkers apolipoprotein A1, alpha 2 macroglobulin, orosomucoid 2, retinol binding protein 4 and leucine-rich alpha 2-glycoprotein 1 was done by enzyme-linked immunosorbent assay. RESULTS: Apolipoprotein A1 levels of <0.48 µg/mg of creatinine-differentiated steroid-resistant nephrotic syndrome (SRNS) from first episode nephrotic syndrome, area under curve (AUC) [0.99 (CI 0.9-1.0), 100 % sensitivity and 100 % specificity] and a value of <0.24 µg/mg of creatinine could differentiate SRNS from frequently relapsing nephrotic syndrome/steroid dependent nephrotic syndrome [AUC 0.99 (CI 0.9-1.0), 100 % sensitivity and 100 % specificity]. Alpha 2 macroglobulin could differentiate children with SRNS-focal segmental glomerulosclerosis (FSGS) from SRNS-minimal change disease (MCD) at values >3.3 µg/mg of creatinine [AUC 0.84 (CI 0.62-1.0), 90 % sensitivity and 85 % specificity]. Orosomucoid 2 >1.81 µg/mg of creatinine could distinguish SRNS-FSGS from SRNS-MCD [AUC 0.84 (CI 0.62-1.0), sensitivity 90 % and specificity 85.5 %]. RBP 4 value of >1.54 µg/mg of creatinine differentiated SRNS-FSGS from SRNS-MCD [AUC 0.87 (CI 0.68-1.0), sensitivity 90 % and specificity 85.7 %]. CONCLUSIONS: Lower level of apolipoprotein A1 in urine is suggestive of SRNS. Alpha 2 macroglobulin, retinol binding protein 4 and orosomucoid 2 are markers associated with FSGS, with alpha 2 macroglobulin being most predictive.

NPHS2 R229Q polymorphism in steroid resistant nephrotic syndrome: is it responsive to immunosuppressive therapy?

Steroid-resistant nephrotic syndrome (SRNS) patients with NPHS2 gene mutations have been reported as non-responsive to immunosuppressive therapy. Inter-ethnic differences can have influence over the frequency of mutations. The present study was undertaken to find out the incidence and treatment response. Mutational analysis of NPHS2 gene was performed in 20 sporadic idiopathic SRNS, 90 steroid-sensitive nephrotic syndrome (SSNS) and 50 normal controls. NPHS2 gene analysis showed R229Q polymorphism in six SRNS (30%), four SSNS (4.4%) and 13 controls (26%). The polymorphism (G→A) showed Hardy-Weinberg distribution and risk allele (G) had strong association with the disease (odds ratio 3.14, 95% CI 1.33-7.43) than controls. Five cases of SRNS having polymorphism showed partial remission to cyclosporine and prednisolone. Overall, partial remission was achieved in 14(70%), complete remission in four (20%), one(5%) patient had no response and one(5%) died. Thus, NPHS2 gene showed R229Q polymorphism and patients achieved partial remission to therapy.

Aplasia cutis congenita: a rare case with extensive symmetrically distributed lesions.

Aplasia cutis congenita is a rare developmental disorder of the skin of neonates, usually presenting as a solitary lesion over the scalp. We report an interesting presentation of AC along with the histopathological features in a neonate with extensive lesions over scalp as well as in bilaterally symmetrical areas over trunk and thighs; such symmetrical distributions being rarely reported.

Embryonal tumor with abundant neuropil and true rosettes with melanotic (retinal) differentiation.

Embryonal tumor with abundant neuropil and true rosettes (ETANTR) is a rare variant of central nervous system primitive neuroectodermal tumor occurring exclusively in the pediatric population. We report a unique case of a 6-month male child presenting with a large intraventricular lesion. Histological examination revealed a tumor composed of primitive neuroectodermal cells in dense aggregates, interspersed by hypocellular areas containing small round cells widely dispersed in neuropil-like material. Few ependymal and occasional ependymoblastic rosettes were appreciated. Focal melanotic neuroepithelium recapitulating retinal differentiation was also seen. Documentation of such cases may expand the neuroectodermal differentiation spectrum of ETANTR.

Metanephric stromal tumor: An unusual pediatric renal neoplasm.

A renal tumor in a 14-month- old child, who was initially diagnosed as mesoblastic nephroma, but on review post surgery was diagnosed as hyper-differentiated metanephric stromal tumor, with its excellent prognostic outcome. An attempt is made to document imaging features that may enable one to suspect this rare condition. The literature is reviewed with emphasis on its distinction from its look-alikes in the pediatric age group.

Pigmented skin exhibits accelerated wound healing compared to the nonpigmented skin in Guinea pig model.

This study investigated and compared the wound healing kinetics of pigmented (PG) and non-pigmented (NP) skin in guinea pigs, focusing on histological and transcriptional changes. Full-thickness wounds created on PG and NP skin were evaluated at various time points post-injury. Fontana-Masson staining and ultrastructural analysis suggested the presence of melanin and melanosomes in PG skin, which coincided with an upregulation of melanogenic genes cKIT, TYR, and DCT. On day 9 post-wound, PG skin exhibited a rapid transition from the inflammatory to proliferative phase, which correlated with the reappearance of epidermal pigmentation whereas the NP skin exhibited a delayed neo-epidermis formation. Furthermore, the study revealed that melanocyte-derived growth factors (conditioned media) positively regulated keratinocyte migration while inhibiting fibroblast differentiation. These effects were more prominent in tyrosine-treated (hyperpigmented) melanocyte-CM as was TGF- ß expression. These findings provide valuable insights into the mechanisms underlying skin repair and pigmentation.

Outcomes of children with idiopathic steroid resistant nephrotic syndrome: a single centre observational study.

INTRODUCTION: Idiopathic steroid resistant nephrotic syndrome (SRNS) has variable outcomes in children. The primary objective of the present study was to assess the cumulative remission rate and the secondary objectives were to assess factors affecting the remission status, kidney function survival, and adverse effects of medications. METHODS: One hundred fourteen patients with SRNS were included. Calcineurin inhibitor-based treatment protocol along with prednisolone and angiotensin-converting enzyme inhibitor were used, and patients were followed over 5 years. RESULTS: Median age was 4.5 years; 53.5% of cases were between 1 to 5 years of age. Sixty-two patients (54.4%) were at initial stage and 52 (45.6%) were at a late SRNS stage. Median eGFRcr was 83.5 mL/min/1.73m2 at presentation. Of the 110 patients, 63 (57.3%) achieved remission [complete remission 30 (27.3%), partial remission 33 (30%)], and 47 (42.7%) had no remission. Kidney function survival was 87.3% and 14 cases (12.7%) had progression to CKD (G3-8, G4-3, G5-1, and G5D-2). Median duration of follow up was 36 months (IQR 24, 60). Age of onset, cyclosporine/tacrolimus, eGFRcr, and histopathology (MCD/FSGS) did not affect remission. Similarly, remission status in addition to age of onset, drug protocol, and histopathology did not significantly affect kidney function during a period of 5 years. Hypertension, cushingoid facies, short stature, cataract, and obesity were observed in 37.7, 29.8, 25.5, 17.5, and 0.7% of cases, respectively. CONCLUSION: About half of the cases achieved remission. Age of onset of disease, cyclosporine/tacrolimus use, and histopathological lesion neither affected remission status nor short-term kidney function survival in SRNS.

Classification of endoscopic ultrasound guided fine needle aspiration cytology of pancreatic space occupying lesions by Papanicolaou Society of Cytopathology System: A five year study.

BACKGROUND: Majority of the pancreatic cancer patients present at an advanced stage and have poor 5 year survival rate. Thus, there is a need for early detection of pancreatic cancer with the initiation of the therapy. MATERIALS & METHODS: This is a retrospective study including all the endoscopic ultrasound guided (EUS) guided pancreatic FNAs from 2016 to 2020. The aspirate smears were analyzed and classified according to The Papanicolaou Society of Cytopathology System for Reporting Pancreaticobiliary Cytology (PSCPC). RESULTS: A total of 245 EUS guided FNAs from pancreatic lesions were included. Cyto-histological correlation was done wherever available. Category I (non diagnostic) accounted for 40 cases (16%) cases, Category II (negative) comprised of 44 cases (18%); and Category III (Atypical) had 5 cases (2%). Category IV neoplastic-benign category included 3 cases of serous cystadenoma, while neoplastic-others category included pancreatic neuroendocrine tumors (n = 21), solid pseudo-papillary neoplasms (SPEN) (n = 12) and mucinous cystic neoplasms (n = 4). A total of 7 cases (2.8%) were reported in Category V (Suspicious). A diagnosis of adenocarcinoma (Category VI) was rendered in 105 cases (42.8%) cases. Rarer types included non Hodgkins lymphoma (n = 3) and one case of primary undifferentiated carcinoma with osteoclastic giant cells. Cyto-histological correlation in all categories was available in 58 cases with 8 false negative cases. Thus overall sensitivity of EUS guided FNAC was found to be 87.8% with a diagnostic yield of 83.6% while sensitivity in diagnosing adenocarcinoma was 96.9%. CONCLUSION: The present study highlights the spectrum of EUS guided FNA of pancreatic lesions in a subset of North Indian population and classified them according to PSCPC. EUS guided FNAC is a sensitive investigation which plays a crucial role in confirming the diagnosis of pancreatic space occupying lesions (SOLs) in advanced stage.

Urinary Apolipoprotein A1 and Neutrophil Gelatinase-associated Lipocalin in Children with Idiopathic Nephrotic Syndrome.

Urinary biomarkers are a promising diagnostic modality whose role was explored in nephrotic syndrome (NS). We estimated urinary apolipoprotein A1 (Apo A1) and neutrophil gelatinase-associated lipocalin (NGAL) in children with first-episode NS (FENS) and controls with a longitudinal follow-up to see the serial changes during remission. The study groups comprised 35 children with FENS and an equal number of age- and sex-matched controls. Patients were followed up at regular intervals, and 32 patients were classified as having steroid-sensitive NS (SSNS) and 3 as having steroid-resistant NS (SRNS). The mean follow-up period was 8.7 ± 4.2 months. Three patients in the SSNS group were labeled as having frequent relapses or steroid-dependent disease during follow-up. Of the three children with SRNS, two had minimal changes in the disease and one had idiopathic membranous nephropathy. The levels of Apo A1:creatinine, NGAL:creatinine, and spot urinary protein:urinary creatinine ratios were significantly higher in children with FENS compared with controls. The levels of the urine biomarkers decreased significantly at subsequent follow-up with remission. The Apo A1 and NGAL levels in SSNS patients were significantly high compared with both the controls and FENS patients. Urinary Apo A1 levels in SRNS patients were lower at initial presentation. This longitudinal study revealed changes in the urinary Apo A1 and NGAL in NS over the course of the disease.

Steroid-resistant nephrotic syndrome associated with steroid sulfatase deficiency-x-linked recessive ichthyosis: a case report and review of literature.

UNLABELLED: Nephrotic syndrome associated with X-linked recessive ichthyosis due to steroid sulfatase deficiency has rarely been reported in English literature. We describe a 4 and a half-year-old boy presenting with steroid-resistant nephrotic syndrome (SRNS) with an underlying ichthyotic skin present since birth. Renal biopsy revealed minimal change disease. As many of the male members of the family also showed similar skin manifestations, genetic analysis was done on the patient, which revealed deletion of the steroid sulfatase (STS) gene spanning both the 3' as well as the 5'ends. The patient was thus diagnosed with SRNS associated with X-linked recessive ichthyosis. He was started on cyclosporine regimen, and remission was achieved in 5 weeks. We speculate that the deficiency of STS resulting in increased cholesterol sulfate accumulation interferes with the integrity of adherens junctions present between glomerular epithelial cells of the slit diaphragm, and this results in proteinuria and nephrotic syndrome. The nephrotic syndrome remitted with a calcineurin inhibitor medication. CONCLUSION: We suggest that the deficiency of STS is another one in an increasing list of genetic causes of podocytopathy and nephrotic syndrome. Remission of proteinuria in such a case may be achieved with immunosuppressive medication.

Childhood Steroid-resistant Nephrotic Syndrome: Long-term Outcomes from a Tertiary Care Center.

Introduction: Steroid-resistant nephrotic syndrome (SRNS) is a rare condition that accounts for about 10% to 20% of all nephrotic syndromes in children. While calcineurin inhibitors induce remission in the majority, the data on long-term outcomes are limited. This retrospective study aimed to look at the clinical profile, biopsy findings, and long-term treatment outcomes in children with SRNS. Methods: The records of all children (1-18 years) with SRNS with biopsy findings of minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), or mesangioproliferative glomerulonephritis, who received treatment for a minimum period of 12 months and were in follow-up during the years 2007-2018 at a tertiary care teaching hospital were retrieved. The clinical, histopathological, and biochemical factors and treatment outcomes were recorded and analyzed. Results: Ninety-one (72 boys) children with a median (interquartile range [IQR]) age of onset of nephrotic syndrome as 48 (24-87) months were included. MCD and FSGS were the most common histopathological types (57.1% and 36.3%, respectively) and 62 (68.1%) patients had late steroid resistance. Calcineurin inhibitors (CNIs) were used in 86.8% of the children, and response rates with cyclosporine and tacrolimus for complete remission (CR) were 80% and 73.7%, respectively, with median (IQR) time to response being 3 (2-4) months. The presence of MCD on histology and the use of CNIs were significantly associated with CR (P < 0.01). At a median (IQR) follow-up of 5 (3-7) years, 76 (83.5%) children had either CR or partial remission, four (4.4%) developed chronic kidney disease and five (5.5%) died (three due to end-stage renal disease and two of infective complications). Conclusion: SRNS children with MCD on biopsy, late resistance, and response to CNIs have better long-term outcomes. Most patients respond to CNIs within the first 6 months of use and need therapy for at least 24 to 36 months.