Identification of renal cyst cells of type I Nephronophthisis by single-nucleus RNA sequencing.

Background: Nephronophthisis (NPH) is the most common genetic cause of end-stage renal disease (ESRD) in childhood, and NPHP1 is the major pathogenic gene. Cyst formation at the corticomedullary junction is a pathological feature of NPH, but the mechanism underlying cystogenesis is not well understood. The isolation and identification of cystic cell subpopulation could help to identify their origins and provide vital clues to the mechanisms underlying cystogenesis in NPH. Methods: Single-nucleus RNA sequencing (snRNA-seq) was performed to produce an atlas of NPHP1 renal cells. Kidney samples were collected from WT (Nphp1 +/+) mice and NPHP1 (Nphp1 del2-20/del2-20) model mice. Results: A comprehensive atlas of the renal cellular landscape in NPHP1 was generated, consisting of 14 basic renal cell types as well as a subpopulation of DCT cells that was overrepresented in NPHP1 kidneys compared to WT kidneys. GO analysis revealed significant downregulation of genes associated with tubular development and kidney morphogenesis in this subpopulation. Furthermore, the reconstruction of differentiation trajectories of individual cells within this subpopulation confirmed that a specific group of cells in NPHP1 mice become arrested at an early stage of differentiation and proliferate to form cysts. We demonstrate that Niban1 is a specific molecular marker of cystic cells in both mice and human NPHP1. Conclusion: In summary, we report a novel subpopulation of DCT cells, marked by Niban1, that are classified as cystic cells in the NPHP1 mice kidney. These results offer fresh insights into the cellular and molecular basis of cystogenesis in NPH.

Direct, indirect, and vicarious nature experiences collectively predict preadolescents' self-reported nature connectedness and conservation behaviors.

Background: The quantity and context of children's nature experiences are undergoing significant changes, exacerbating a pervasive negative cycle that could impact future conservation efforts. Therefore, it is essential to conduct further studies on the potential impacts of these changes on children's willingness to engage in conservation practices. Methods: We surveyed 2,175 preadolescents (aged 9-12) from rural and city schools in Hangzhou, Kunming, and Xishuangbanna, China, regarding their nature experiences (direct, indirect, and vicarious) and self-reported nature connectedness and conservation behaviors. Results: We found that children in urban areas have higher frequencies of indirect and vicarious experiences than those in rural areas, with some direct nature experiences seldom reported among city respondents. Direct, indirect, and vicarious nature experiences significantly predicted children's conservation behavior and collectively provided the highest predictive power for conservation behavior. Direct and vicarious experiences were strongly correlated with pro-nature behavior, and the latter with pro-environmental behavior. Emotional and cognitive connection with nature positively predicted conservation behavior, influenced by location and residence type. Discussion: This study reveals that different types of nature experiences shape children's current conservation behaviors in China.

Reducing GEF-H1 Expression Inhibits Renal Cyst Formation, Inflammation, and Fibrosis via RhoA Signaling in Nephronophthisis.

Nephronophthisis (NPHP) is the most prevalent monogenic disease leading to end-stage renal failure in childhood. RhoA activation is involved in NPHP pathogenesis. This study explored the role of the RhoA activator guanine nucleotide exchange factor (GEF)-H1 in NPHP pathogenesis. We analyzed the expression and distribution of GEF-H1 in NPHP1 knockout (NPHP1KO) mice using Western blotting and immunofluorescence, followed by GEF-H1 knockdown. Immunofluorescence and renal histology were used to examine the cysts, inflammation, and fibrosis. A RhoA GTPase activation assay and Western blotting were used to detect the expression of downstream GTP-RhoA and p-MLC2, respectively. In NPHP1 knockdown (NPHP1KD) human kidney proximal tubular cells (HK2 cells), we detected the expressions of E-cadherin and α-smooth muscle actin (α-SMA). In vivo, increased expression and redistribution of GEF-H1, and higher levels of GTP-RhoA and p-MLC2 in renal tissue of NPHP1KO mice were observed, together with renal cysts, fibrosis, and inflammation. These changes were alleviated by GEF-H1 knockdown. In vitro, the expression of GEF-H1 and activation of RhoA were also increased, with increased expression of α-SMA and decreased E-cadherin. GEF-H1 knockdown reversed these changes in NPHP1KD HK2 cells. Thus, the GEF-H1/RhoA/MLC2 axis is activated in NPHP1 defects and may play a pivotal role in NPHP pathogenesis.

A novel ITGA3 homozygous splice mutation in an ILNEB syndrome child with slow progression.

BACKGROUND AND AIMS: ILNEB (interstitial lung disease, nephrotic syndrome, epidermolysis bullosa) syndrome is caused by ITGA3 mutations. Demises usually happened at infancy. This study reports a complete ILNEB syndrome child with slow disease progression. MATERIALS AND METHODS: Clinical data and related specimens were collected. Genomic DNA was extracted for genetic sequencing. Integrin α3 expression was detected by western blotting and immunofluorescence staining. RESULTS: The patient was male. He experienced recurrent rashes shortly after birth. His sparse eyebrows and eyelashes gradually lost. The patient was vulnerable to respiratory infections and had recurrent fever after vaccine immunization after 4 years. He was found with nephrotic syndrome and polycystic renal dysplasia at 8 years and progressed to end-stage renal disease at 12 years. A chest Computed Tomography revealed intestinal lung disease at 8 years. Continuous oxygen supplementation was needed at 13 years. Counts of lymphocyte subsets revealed elevated percentage of double-negative T cells and activated T cells. Next-generation sequencing revealed a novel homozygous splice mutation c.2219 + 4A > Cin ITGA3 that was predicted to be deleterious. The mutation resulted in exon17 skipping with the loss of 80 bp in the mRNA. The aberrant integrin α3 mRNA level was lower compared to the healthy control. Integrin α3 protein was not detected in urine epithelial cells and skin of the patient. CONCLUSIONS: We report a patient harboring a novel ITGA3 homozygous splice mutation who presented with complete ILNEB syndrome but slow disease progression. Immune disorders were suspected.

Overexpression of smad7 inhibits the TGF-ß/Smad signaling pathway and EMT in NPHP1-defective MDCK cells.

BACKGROUND: Nephronophthisis (NPHP) is a kind of ciliopathy. Interstitial fibrosis occurs at the early stage of the disease. TGF-ß/Smad is a key signaling pathway in regulating interstitial fibrosis and epithelial-mesenchymal transition (EMT). In this study, we explored the activation of the TGF-ß/Smad signaling pathway and EMT in NPHP1-defective MDCK cells to further understand the pathogenesis of NPHP. METHODS: NPHP1-knockdown (NPHP1KD) MDCK cells were constructed by recombinant lentiviral short hairpin RNA, and NPHP1-knockout (NPHP1KO) MDCK cells were constructed by using the CRISPR/Cas9 technique. The morphology and migration ability were observed under a microscope. Western blotting was used to detect the expression of E-cadherin, ß-catenin, α-smooth muscle actin (α-SMA), fibroblast-specific protein-1(FSP1), TGF-ß1, Smad2, Smad3, p-Smad3, Smad4 and Smad7. The localization of Smad3 was determined by immunofluorescence assay. RESULTS: NPHP1KD and NPHP1KO MDCK cells were spindle-shaped and presented EMT-like changes. E-cadherin and ß-catenin expression decreased, while α-SMA and FSP1 expression increased; the TGF-ß/Smad signaling pathway was activated, Smad2, Smad3, p-Smad3 and Smad4 expression increased, Smad3 translocated to nuclear and Smad7 expression decreased compared with those in wild type MDCK cells. Overexpression of Smad7 reversed these changes to different degrees. CONCLUSIONS: Our results indicate that NPHP1 defects induce the activation of the TGF-ß/Smad signaling pathway and EMT in MDCK cells. These factors may be implicated in the pathogenesis of interstitial fibrosis in NPHP.

An Nphp1 knockout mouse model targeting exon 2-20 demonstrates characteristic phenotypes of human nephronophthisis.

Nephronophthisis (NPH) is the most prevalent monogenetic disorder leading to end-stage renal failure (ESRD) in childhood. Mutations in Nphp1, encoding a cilia-localized protein, account for the majority of NPH cases. Despite its identification many years ago, Nphp1 deletions targeting exon 4 or exon 20 have not reproduced the histological features of human NPH in murine models. In this study, we deleted exon 2-20 of Nphp1 by CRISPR/Cas9 gene editing to create a near-total knockout (KO) mouse model (Nphp1del2-20/del2-20). Nphp1del2-20/del2-20 mice faithfully reproduced the renal and extrarenal phenotypes associated with human NPH, including renal cyst development, tubular basement membrane thickening, retinal degeneration and abnormal spermatogenesis. Importantly, Nphp1 re-expression using an adenoviral-associated-virus-9 vector could partially rescue both renal and retinal phenotypes in Nphp1del2-20/del2-20 mice. Our results reported the first relevant Nphp1 mouse model with renal phenotypes for human disease. It will be a valuable model for future studies of Nphp1 function and to develop novel treatments for this common childhood disease.

COQ2 mutation associated isolated nephropathy in two siblings from a Chinese pedigree.

BACKGROUD: Coenzyme Q10 (CoQ10) is involved in the biosynthesis of adenosine triphosphate (ATP), and is most abundant in the mitochondrial membrane. The primary CoQ10 deficiency caused by COQ2 defect is mostly manifested as encephalopathy, encephalopathy with nephropathy, and rarely as an isolated nephrotic syndrome. METHODS: Clinical and pathological data and peripheral blood samples of 2 siblings with steroid-resistant nephrotic syndrome (SRNS) and their family members of a Chinese pedigree were collected. DNA was extracted and subjected to next-generation sequencing of target genes of hereditary nephropathy. RESULTS: Compound heterozygous mutations of COQ2 (c.1058A > G, p.Y353C, paternal and c.973A > G, p.T325A, maternal)were identified in both siblings of the pedigree. Mutation of p.Y353C was novel. The proband was a girl, who presented with SRNS at the age of 7 months. CoQ10 was administered after the gene sequencing results came out. Proteinuria decreased gradually to 1+, occasionally negative. The child was normal in growth and intelligence. She is now 4 years old. The second patient was her elder brother. He was found to have SRNS at the age of 2 years old. Renal pathology indicated focal segmental glomerulosclerosis (FSGS). Electronic microcopy revealed that a large quantity of mitochondria with normal contour was accumulated within the podocytes. Both patients were in normal intelligence without convulsion. CONCLUSION: The 2 cases harboring COQ2compound heterozygous mutations presented with isolated SRNS, with a renal pathology of FSGS and a large quantity of mitochondria with normal contour accumulated within the podocytes. CoQ10 was efficacy in eliminating proteinuria.

Early diagnosis and successful treatment of cytomegalovirus peritonitis in children with primary nephrotic syndrome: case series and literature review.

Cytomegalovirus (CMV) is a major pathogen in immunocompromised population and CMV infections in immunocompromised patients cause substantial morbidity and mortality. The common clinical manifestations of CMV infection are pneumonia, hepatitis, colitis and so on, while CMV peritonitis without gut perforation is rare. Reviewing the literature, CMV peritonitis in patients with nephrotic syndrome (NS) had not been reported. Only four cases of CMV peritonitis without gut perforation were reported in adults with other diseases. Two cases were diagnosed by reverse-transcription polymerase chain reaction (RT-PCR) of ascites while the other two cases by histopathological examination of peritoneal tissue. We report four cases of primary nephrotic syndrome complicated with CMV peritonitis. Four cases all diagnosed by RT-PCR of ascites (659-455 000 copies/mL). We mainly discusses the diagnosis and treatment of CMV peritonitis without gut perforation.

Clinical and pathological features and varied mutational spectra of pathogenic genes in 55 Chinese patients with nephronophthisis.

BACKGROUND: Nephronophthisis (NPHP) is the most common genetic cause of end-stage renal disease (ESRD) in children. This study was performed to explore the pathogenic gene mutations and clinical and pathological features of Chinese patients with NPHP. METHODS: Patients for whom causative mutations were not identified in our previous study, as well as those recruited later, were subjected to whole-exome next-generation sequencing (NGS) or the exome of 63 primary cilia disease genes. RESULTS: We recruited 55 patients (27 boys and 28 girls) from 48 families, mainly from South China. We subjected 35 patients to NGS. Disease-causing mutations were revealed in seven more families (nine patients) by NGS. In total, disease-causing mutations were identified in 25 patients from 19 families, accounting for 39.6% (19/48) of all families, and novel mutation rate was 77.8% (35/45). NPHP1 and NPHP3 mutations were identified in 14.6% (7/48) and 12.5% (6/48) of all families, respectively. The patient with CEP83 mutations presented with prominent glomerular cysts and glomeruli dysplasia without extrarenal involvement. CONCLUSION: A high novel mutation rate was identified, and disease-causing mutations of NPHP3 prevailed in this group of Chinese NPHP patients. This is the second report of a patient with CEP83 mutations.

Lupus Nephritis With Mild Asymptomatic Hypercalcemia in Children: A Case Report and Literature Review.

Lupus nephritis (LN) in Children is caused by Kidney involvement in systemic lupus erythematosus (SLE). SLE is a chronic, multi-systemic, paroxysmal autoimmune disease with a wide spectrum of autoantibodies. Hypercalcemia is a common manifestation of primary hyperparathyroidism and other malignant tumors. LN or SLE with hypercalcemia is rare. We report a case of LN with hypercalcemia and review the literature. It suggests that the pathogenesis of SLE complicated with hypercalcemia complicates the response of drug therapy.

Two Chinese nephronophthisis pedigrees harbored a compound heterozygous deletion with a point mutation in NPHP1.

NPHP1 is the most prevalent genetic factor in the development of juvenile nephronophthisis (NPHP). In our previous study, NPHP1 homozygous point mutations were detected by Sanger sequencing in three cases from two nonconsanguineous pedigrees. However, mutant sites were detected in only one parent from each respective pedigree. To investigate whether other disease-causing mutations were present, targeted exome sequencing (TES) of 63 ciliopathy genes was performed in the probands of the two pedigrees. In addition to the previously detected point mutations, a complete heterozygous deletion of NPHP1 (1-20 exons) in the other allele was found in each of the three patients. The deletions were inherited from one parent of each pedigree. These is the first report of Chinese NPHP patients harboring a complete heterozygous deletion of NPHP1 in one allele and a point mutation in the other one. The study demonstrated that TES is helpful in identifying complicated mutations in patients with NPHP.

[Clinical and pathological features and the misdiagnosis of childhood Alport syndrome: a retrospective analysis of 91 cases].

OBJECTIVE: To explore the clinical and pathological features and the diagnosis of childhood Alport syndrome (AS). METHODS: A retrospective analysis was performed on clinical data of 91 children with AS. RESULTS: Hematuria was observed in all 91 patients, of whom 86 were accompanied with proteinuria. Sixty-one children with X-Linked AS (XL-AS) had positive family history. Renal biopsy was performed on 82 children. Mild to moderate mesangial proliferation was observed in 74 cases. Small amounts of immune complexes deposits in the glomerular mesangial area were observed in 48 cases. Glomerular basement membrane (GBM) attenuation, thickening and layering were observed in 53 cases by electron microscopy (EM). In 63 cases receiving renal tissue type IV collagen α3 and α5 chain immunofluorescence detection, 58 were diagnosed with AS, including 53 cases of XL-AS and 5 cases of autosomal recessive AS. In 91 cases of AS, 58 were diagnosed as AS by renal tissue type IV collagen α3 and α5 chain immunofluorescence, 21 were diagnosed by EM, one was diagnosed by skin biopsy, and 12 were diagnosed by gene detection. Six novel mutations of COL4A5 gene were found. Forty-five cases were misdiagnosed before the diagnosis of AS. Forty-one of the 45 cases received steroids and/or immunosuppressant therapy. CONCLUSIONS: The clinical manifestations and pathological changes are not specific in children with AS, resulting in a higher rate of misdiagnosis. Typical lesions of GBM under EM are only observed in a part of patients. There is a high novel mutation rate of COL4A5 in the detected AS children.

WT1 mutation-associated nephropathy: a single-center experience
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This study explored Wilms' tumor 1 (WT1) mutations in children with, or suspected of having, steroid-resistant nephrotic syndrome (SRNS), referred to or treated in our hospital in the past 6 years as well as the correlation between genotype and phenotype in WT1 mutation-associated nephropathy in Chinese patients. In total, 76 patients participated in the study. WT1 mutations were identified in 15 patients, 5 of whom harbored splice-site mutations in intron 9. Four of these 5 patients exhibited early onset of nephropathy and rapid deterioration of renal function. Missense mutations were detected in 8 patients, 4 of whom harbored hot-site mutations and had early-onset proteinuria. Of these 4 patients, rapid progression to end-stage renal disease was only observed in 1. Nonsense mutations were identified in 2 patients; both had a large number of immature glomeruli in the kidney cortex. Calcineurin inhibitors (CNI) were administered in 8 patients. Two patients with missense mutations and 1 patient with a nonsense mutation achieved complete remission. Two patients with missense mutations and 2 with splice-site mutations showed an improvement. One patient with a splice-site mutation showed no changes. In conclusion, a high WT1 mutation rate was observed in this group of SRNS patients. Patients with splice-site mutations experienced a rapid disease progression, and patients harboring nonsense mutations showed a prominent glomerular developmental delay. CNI therapy was effective in patients with WT1 missense mutations and nonsense mutations.
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Dent Disease in Chinese Children and Findings from Heterozygous Mothers: Phenotypic Heterogeneity, Fetal Growth, and 10 Novel Mutations.

OBJECTIVE: To characterize the phenotypes of Dent disease in Chinese children and their heterozygous mothers and to establish genetic diagnoses. STUDY DESIGN: Using a modified protocol, we screened 1288 individuals with proteinuria. A diagnosis of Dent disease was established in 19 boys from 16 families by the presence of loss of function/deleterious mutations in CLCN5 or OCRL1. We also analyzed 16 available patients' mothers and examined their pregnancy records. RESULTS: We detected 14 loss of function/deleterious mutations of CLCN5 in 15 boys and 2 mutations of OCRL1 in 4 boys. Of the patients, 16 of 19 had been wrongly diagnosed with other diseases and 11 of 19 had incorrect or unnecessary treatment. None of the patients, but 6 of 14 mothers, had nephrocalcinosis or nephrolithiasis at diagnosis. Of the patients, 8 of 14 with Dent disease 1 were large for gestational age (>90th percentile); 8 of 15 (53.3%) had rickets. We also present predicted structural changes for 4 mutant proteins. CONCLUSIONS: Pediatric Dent disease often is misdiagnosed; genetic testing achieves a correct diagnosis. Nephrocalcinosis or nephrolithiasis may not be sensitive diagnostic criteria. We identified 10 novel mutations in CLCN5 and OCRL1. The possibility that altered CLCN5 function could affect fetal growth and a possible link between a high rate of rickets and low calcium intake are discussed.

High mutation rate of NPHP3 in 18 Chinese infantile nephronophthisis patients.

AIM: The present study was designed to explore mutations of NPHP2 and NPHP3 and clinical features in 18 Chinese infantile nephronophthisis (NPHP) patients. METHODS: Patients were subjected to screen for mutations in both NPHP2 and NPHP3, and clinical data were collected. RESULTS: Eighteen patients from 17 families were included in this study. Eight of 17 (47.1%) patients detected were identified to have mutations in NPHP3, but none had a mutation in NPHP2. Of the patients with NPHP3 mutations, four had compound heterozygous mutations, and the other four harboured single heterozygous mutations. Ten of the NPHP3 mutations were novel. Low molecular weight proteinuria was observed in all 16 detected patients. Renal histology were available in seven children, five patients showed infantile type NPHP features, and the other two patients from the same family showed juvenile type NPHP features. Liver involvement was observed in all patients with NPHP3 mutations and congenital heart disease in two patients harbouring NPHP3 mutation of c.2369 T > C (p.L790P). CONCLUSIONS: In this group of infantile NPHP patients, mutations of NPHP3 were prevalent, whereas mutation of NPHP2 was absent. Genotype to phenotype correlations were observed in patients with NPHP3 mutations and all patients with NPHP3 mutations showed renal-hepatic phenotype.

The Accumulation of VEGFA in the Glomerular Basement Membrane and Its Relationship with Podocyte Injury and Proteinuria in Alport Syndrome.

The pathogenesis of proteinuria in Alport syndrome (AS) remains unclear. Vascular endothelial growth factor A (VEGFA) is a key regulator of the glomerular filtration barrier (GFB). This study explored the expression of VEGFA in the glomeruli and its accumulation in the glomerular basement membrane (GBM) and their relationship with podocyte injury and proteinuria in Alport syndrome (AS). Clinical data and renal tissues of control patients (11 cases) and AS patients (25 cases) were included. AS patients were further divided into 2 groups according to the quantities of their urinary protein: mild to moderate proteinuria group (proteinuria <50 mg/kg/d, 15 cases) and heavy proteinuria group (proteinuria ≥50 mg/kg/d, 10 cases). The expression and distribution of VEGFA and VEGF receptor 2 (VEGFR2) in the GFB, the phosphorylation of VEGFR2 (p-VEGFR2) and nephrin (p-nephrin), and the expression of synaptopodin and nephrin in the glomeruli were detected by immune electron microscopy and/or immunofluorescence, and their relationships to proteinuria in AS patients were analyzed. The accumulation of VEGFA in the GBM was increased in AS patients. The expression of VEGFA and the levels of p-VEGFR2 and p-nephrin in glomeruli were increased and were positively correlated with the degree of proteinuria in AS patients. The expression of synaptopodin and nephrin were decreased and were negatively correlated with the degree of proteinuria in AS patients. The over expressed VEGFA in the glomeruli and its accumulation in the GBM may activate the VEGFA-VEGFR2 and nephrin signaling pathways and lead to podocyte injury and occurrence of proteinuria in AS.

Clinical and pathological characteristics of 5 children with HBV surface antigen (HBsAg)-negative hepatitis B virus-associated glomerulonephritis.

BACKGROUND: Hepatitis B virus-associated glomerulonephritis (HBV-GN) mainly occurs in children. Patients with HBV-GN are frequently positive for serum HBV surface antigen (HBsAg), but they are rarely negative. OBJECTIVE: To explore the clinical and pathological characteristics of patients with HBV-GN who are serum HBsAg negative. STUDY DESIGN: Five children with HBV-GN who are negative for HBsAg were included in this study. Their clinical and pathological characteristics were collected and analyzed. RESULTS: All 5 children presented with different levels of proteinuria and microscopic hematuria. Renal biopsies showed membranous nephropathy accompanied by HBsAg and/or HBcAg deposits in glomeruli in all of the children. Steroids and/or other immunosuppressants were administered in all cases without antiviral therapy during the early stages of treatment. Two children achieved complete remission but relapsed after the drugs were tapered down. The other 3 children were initially non-responsive but achieved remission after lamivudine was added. CONCLUSIONS: Treatment of HBsAg-negative HBV-GN patients with immunosuppressants alone could not achieve satisfactory effects. Antiviral treatment is effective and may be necessary in this type of patient.

Novel mutation of OCRL1 in Lowe syndrome.

Lowe syndrome is a rare, X-linked recessive genetic disease with multi-organ involvement. The pathogenic gene is OCRL1. The authors analyzed the OCRL1 mutation and summarized the clinical features of a Chinese child with Lowe syndrome. The patient is a 3 year 7 mo-old boy. He presented with hypotonia at birth and gradually presented with bilateral congenital cataracts, psychomotor retardation, hypophosphatemic rickets and renal tubular function disorder. Sequence analysis of OCRL1 revealed a novel insertion mutation, c.2367insA (p. Ala813X), in exon 22. This mutation was suspected to cause a premature stop codon of OCRL1 and truncation of the OCRL1 protein. His mother, who carried a heterozygous mutation, had no sign of abnormality.

Clinical and pathological features of microscopic polyangiitis in 20 children.

OBJECTIVE: To explore the clinical and pathological features of microscopic polyangiitis (MPA) in children. METHODS: A retrospective analysis was performed of patients with pediatric MPA in our hospital over 10 years. RESULTS: Data for 20 patients were collected; 16 patients had primary MPA (4 boys, 12 girls), with a median age of 8.9 years at the time of disease onset; 4 patients, all female, had antithyroid drug (ATD)-associated MPA, with an age range of 12.5 to 16.2 years at the time of disease onset. All patients exhibited renal involvement. Renal biopsies were performed in 14 patients. Fibrinoid exudation and necrosis of the glomerular capillaries were observed in all biopsy specimens. Crescents and scleroses were noted in 92.9% and 85.7% of these cases, respectively. The most frequent extrarenal organs involved were lungs, followed by the central nervous system (CNS), skin, and digestive system. Ninety percent of patients were positive for perinuclear antineutrophil cytoplasmic antibody, 94.1% were positive for myeloperoxidase, and 88.2% were positive for both. Forty-five percent of the patients had received steroid plus cyclophosphamide (CTX) pulse therapy for more than 3 months, and varying degrees of remission had been achieved in 88.9% of the patients. CONCLUSION: Both primary and ATD-associated MPA showed a female predisposition. Renal involvement was the most frequently observed condition, followed by involvement of lungs. CNS involvement was not rare in these pediatric patients. The efficacy of steroid plus CTX as induction therapy was evident in these patients.