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Arvind Bagga

Publications and source records attributed to Arvind Bagga.

At least 19 recordsLinked to original sources
PubMed2025

Polygenic Risk Scores and HLA Class II Variants are Biomarkers of Corticosteroid Response in Childhood Nephrotic Syndrome.

INTRODUCTION: Nephrotic syndrome (NS), a common glomerular disease in children, is classified based on response to corticosteroid therapy as either steroid-sensitive nephrotic syndrome (SSNS), or steroid-resistant nephrotic syndrome (SRNS). However, there are currently no reliable predictors of therapy response at initial clinical presentation. METHODS: We conducted genome-wide association studies, developed polygenic risk scores (PRS) for therapy response and analyzed classical HLA alleles in 1,997 (994 discovery and 1,003 replication/validation cohorts) previously unstudied children with NS and 3,558 ancestry-matched controls. RESULTS: A significant association with HLA loci defined by variants in HLA-DQB1, HLA-DRB1, and HLA-DQA1 were found for SSNS (but not SRNS), along with a second immune-related SSNS locus: CLEC16A. A PRS that discriminates between SSNS and SRNS was validated in two independent cohorts. The HLA haplotype HLA- DRB1*07:01~DQA1*02:01~DQB1*02:02 was associated with ~4 times the risk of developing SSNS. A model incorporating HLA haplotype, PRS score, and age at onset of the disease was the best predictor of steroid responsiveness with an AUC of 0.68-0.70 and an overall classification accuracy of SSNS versus SRNS of 67-71%. CONCLUSIONS: Our findings confirm that SSNS (unlike SRNS) is an immune-mediated HLA-associated disorder. The PRS for therapy response and HLA haplotype can serve as biomarkers and provide a foundation for more accurate diagnoses and tailored and individualized treatment.

HLA haplotype↗
PubMed2006

Steroid-responsive nephrotic syndrome in a patient with nail-patella syndrome.

Nail-patella syndrome (NPS) is a rare disorder with autosomal dominant mode of inheritance. We report a child with NPS and steroid-responsive, frequently relapsing nephrotic syndrome. The child had dystrophic nails, flexion contractures of both elbows and normal renal functions. X-rays of the knees and pelvis showed hypoplastic patellae and iliac horns. Renal histology was unremarkable with mild focal increase in mesangial cellularity compatible with minimal change disease. Ultrastructural features of NPS including thickening of the glomerular basement membrane with electron-lucent areas were not found.

Child↗
PubMed2005

Mycophenolate mofetil therapy in frequently relapsing steroid-dependent and steroid-resistant nephrotic syndrome of childhood: current status and future directions.

Clinicians are often faced with therapeutic dilemmas and challenges while treating children with frequently relapsing steroid-dependent nephrotic syndrome (SDNS) and steroid-resistant nephrotic syndrome (SRNS). In the past, children with SDNS have been treated with long-term alternate day steroids cyclophosphamide, cyclosporine (CSA), chlorambucil, levamisole, and azathioprine. The essential aim of these therapies is to maintain remission while limiting exposure to steroids. These medications have variable efficacy and undesirable toxicity profiles. Recently, mycophenolate mofetil (MMF) has emerged as a new therapeutic option for the management of SDNS in a few uncontrolled clinical trials. Preliminary data are encouraging. MMF was found to be useful in maintaining remission and has a steroid-sparing effect. Clearly, more data are needed to further characterize the safety and efficacy of MMF, define adequate length of treatment, and optimize drug exposure and monitoring. The management of SRNS is primarily aimed at decreasing proteinuria and inducing remission, if possible. By doing so, one would aim to preserve renal function. CSA therapy is known to be useful in this regard but has undesirable side effects, the most concerning being nephrotoxicity. MMF in combination with steroids and angiotensin-converting enzyme-inhibitor drugs is known to have some efficacy in the management of SRNS. These preliminary data have prompted the National Institutes of Health to sponsor a multicentric controlled trial to compare the safety and efficacy of MMF with that of CSA in the treatment of steroid-resistant focal segmental glomerulosclerosis (FSGS). If MMF therapy is found to be efficacious, it would help obviate the need for CSA and its associated nephrotoxicity. Clearly, MMF has emerged as an important new therapeutic option for the treatment of childhood nephrotic syndrome and FSGS. Further data are required to assess those conditions most likely to respond.

Drug Resistance↗
PubMed2005

Training in pediatric nephrology for developing countries.

During recent years, there has been an increasing demand for specialized care for children with kidney diseases, even in developing countries with limited resources. It is imperative to provide suitable facilities for appropriate and relevant training in pediatric nephrology to promote growth of pediatric nephrology in these areas. The training should give emphasis on preventive aspects, early diagnosis of common diseases and their optimum management with available resources. It should focus on locally prevalent renal diseases. The training programs should take into consideration the socioeconomic and cultural framework of the local community when designing curricula. To overcome the shortage of pediatric nephrology health professionals in the developing countries, the International Pediatric Nephrology Association has taken initiatives to support development of such training programs.

Developing Countries↗
PubMed2005

Refractory isosporiasis.

The authors describe a case of severe debilitating diarrhea due to isosporiasis in a two year old child, a known case of systemic vasculitis receiving prolonged corticosteroids therapy, an association rarely reported previously. It was refractory to treatment with dihydrofolate reductase inhibitor combined with sulfonamide such as cotrimoxazole to which isosporiasis usually responds well and is being described here for clinical interest and uniqueness of its presentation and laboratory findings.

Animals↗
PubMed2005

Approach to renal tubular disorders.

The renal tubule plays an important role in fluid and electrolyte homeostasis. Renal tubular disorders may affect multiple ( e.g., Fanconi syndrome) or specific (e.g., nephrogenic diabetes insipidus, renal glucosuria) tubular functions. Most conditions are primary and monogenic but occasionally are secondary to other disorders (focal segmental glomerulosclerosis, cystinosis, Lowe syndrome). Tubular dysfunction should be considered in all children with failure to thrive, polyuria, refractory rickets, hypokalemia and metabolic acidosis. Careful clinical and laboratory evaluation is essential for appropriate diagnosis and specific management of these conditions.

Acid-Base Equilibrium↗
PubMed2005

Non-azotemic refractory rickets in Indian children.

In order to examine the etiology of refractory rickets, we evaluated the case records of patients presenting between 1990 and 2002. Subjects with impaired renal functions were excluded. Of 131 patients, 25.9 % each had hypophosphatemic rickets and distal renal tubular acidosis (RTA), 19.6 %vitamin D dependent rickets (VDDR), 11.3 % proximal RTA, 9.1 % liver disease and 6.1 % malabsorption. A significant proportion of patients with VDDR and proximal RTA showed deformities in the first year of life, whereas those with distal RTA and hypophosphatemic rickets presented later. Patients with hypophosphatemic rickets had predominant involvement of lower limbs; hypercalciuria was found in 4. Distal RTA was associated with marked rickets and normal levels of alkaline phosphatase. Hypophosphatemia and low tubular reabsorption of phosphate, though characteristic of hypophosphatemic rickets, was also seen in patients with VDDR (19.2%) and distal RTA (17.6 %). Our findings suggest that application and interpretation of appropriate investigations are useful in determining the cause of non-azotemic refractory rickets allowing initiation of specific therapy.

Acidosis, Renal Tubular↗
PubMed2005

Long-term outcome in children with primary distal renal tubular acidosis.

OBJECTIVE: To evaluate complications in adequately treated children with distal renal tubular acidosis (RTA) and to identify factors influencing their development. DESIGN: Records of patients with primary distal RTA followed for 2 or more years at this hospital were reviewed. Case records were examined for age at onset of symptoms and at initiation of treatment, treatment details, follow-up and complications. Height, weight and growth velocity were expressed as standard deviation score (SDS) during different periods of follow-up. Regression analysis was performed to evaluate factors influencing increase in height and weight SDS. P value of less than 0.05 was considered significant. RESULTS: Of 18 patients (eleven boys), the diagnosis was established at the median (range) age of 6 yr (1.5-13 yr). These patients were followed up for a median (range) period of 4 yr (2-18.5 yr). Short stature (height SDS <-2) was noted in all patients at the time of diagnosis with median (range) height SDS of -5.2(-7.5 - -0.4). All patients had failure to thrive with median (range) weight SDS of -3(-5.7 - -1.5). Height SDS increased by median (range) of 2 (1.2-5.5) to become -2.7(-4.8 - -1.1) at last follow-up. Weight SDS increased by median (range) of 0.9 (-0.6 - 2.8) to become -2.4 (-4 - -0.5). Median (range) growth velocity SDS decreased from 3 (1-16) during first year of treatment to 1(-0.3 - 7) at four years with an increase in mean height SDS by 1.3 during the first two years of treatment. Height SDS at last follow-up was not influenced by the age at initiation of treatment, follow-up duration, initial height SDS or severity of acidosis at diagnosis. Increase in height SDS correlated negatively with base excess and height SDS at diagnosis, and positively with follow-up duration on univariate analyses. Initial height SDS was the only factor that influenced increase in height SDS on multivariate analyses. Increase in weight SDS was negatively correlated with base excess and initial weight SDS with significant association with initial weight SDS, on multivariate analyses. All patients had rickets at the time of diagnosis with pathological fractures in four. Rickets resolved without treatment with vitamin D in seventeen patients after a median (range) period of 4 mo (1-12 mo). Eight patients (44.4%) had nephrocalcinosis at diagnosis. Twenty-four hour urine calcium excretion was higher in those with nephrocalcinosis (p = 0.01). Creatinine clearance remained normal in all except one who progressed to renal failure. CONCLUSION: There is a need for early diagnosis, appropriate treatment and regular follow-up of patients with distal RTA for improving outcome.

Acidosis, Renal Tubular↗
PubMed2005

Nephrotic syndrome in children.

Nephrotic syndrome is an important chronic disease in children, characterized by minimal change disease in the majority. Research on pathogenesis has emphasized the importance of T lymphocyte dysregulation and vascular permeability factors that might alter podocyte function and permselectivity. While mutations in genes that encode important podocyte proteins have also been identified, a hypothesis unifying available evidence on pathogenesis is yet to be proposed. Patients with nephrotic syndrome are at risk for life threatening infections and thromboembolic episodes. Long-term effects of persistent hyperlipidaemia and prolonged steroid therapy are increasingly recognized. Remission of proteinuria following corticosteroid therapy has greater prognostic value, in relation to long-term outcome, than the precise renal histology. Prospective studies show that prolonged duration of therapy for the initial episode results in sustained remission and reduced frequency of relapses. Treatment with levamisole, cyclophosphamide, cyclosporine and mycophenolate mofetil is beneficial in a variable proportion of patients with frequent relapses or steroid dependence. The management of steroid-resistant nephrotic syndrome is difficult; most patients failing to achieve remission show progressive renal damage. Calcineurin inhibitors (cyclosporine, tacrolimus) are capable of inducing remission in a significant proportion of patients, but at risk of nephrotoxicity. Reduction of proteinuria is also possible, in children, using angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers. Prospective trials are necessary to identify effective and safe therapies for patients with frequent relapses, steroid dependence and resistance.

Child↗
PubMed2004

Pseudohypoparathyroidism presenting with bony deformities resembling rickets.

Pseudohypoparathyroidism (PHP), characterized by hypocalcemia, hyperphosphatemia and elevated parathormone level, may rarely be associated with bony deformities resembling rickets. The authors report two siblings with clinical and radiological features suggestive of rickets unresponsive to treatment with vitamin D. Low serum calcium, elevated serum phosphate, normal renal functions, raised tubular maximum of phosphate and high serum parathormone were suggestive of PHP. Treatment with 1-hydroxyvitamin D and calcium carbonate led to decrease in bone pain, increase in height and weight and resolution of radiological features. PHP should be suspected in patients with bony deformities, hypocalcemia, elevated blood phosphate levels and normal renal functions.

Bone Diseases↗
PubMed2004

Patients with mutations in NPHS2 (podocin) do not respond to standard steroid treatment of nephrotic syndrome.

Nephrotic syndrome (NS) represents the association of proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Steroid-resistant NS (SRNS) is defined by primary resistance to standard steroid therapy. It remains one of the most intractable causes of ESRD in the first two decades of life. Mutations in the NPHS2 gene represent a frequent cause of SRNS, occurring in approximately 20 to 30% of sporadic cases of SRNS. On the basis of a very small number of patients, it was suspected that children with homozygous or compound heterozygous mutations in NPHS2 might exhibit primary steroid resistance and a decreased risk of FSGS recurrence after kidney transplantation. To test this hypothesis, NPHS2 mutational analysis was performed with direct sequencing for 190 patients with SRNS from 165 different families and, as a control sample, 124 patients with steroid-sensitive NS from 120 families. Homozygous or compound heterozygous mutations in NPHS2 were detected for 43 of 165 SRNS families (26%). Conversely, no homozygous or compound heterozygous mutations in NPHS2 were observed for the 120 steroid-sensitive NS families. Recurrence of FSGS in a renal transplant was noted for seven of 20 patients with SRNS (35%) without NPHS2 mutations, whereas it occurred for only two of 24 patients with SRNS (8%) with homozygous or compound heterozygous mutations in NPHS2. None of 29 patients with homozygous or compound heterozygous mutations in NPHS2 who were treated with cyclosporine A or cyclophosphamide demonstrated complete remission of NS. It was concluded that patients with SRNS with homozygous or compound heterozygous mutations in NPHS2 do not respond to standard steroid treatment and have a reduced risk for recurrence of FSGS in a renal transplant. Because these findings might affect the treatment plan for childhood SRNS, it might be advisable to perform mutational analysis of NPHS2, if the patient consents, in parallel with the start of the first course of standard steroid therapy.

Adolescent↗
PubMed2004

Idiopathic granulomatous hepatitis.

A 12-year-old male child reported with history of fever for last seven years. Hepatosplenomegaly, hepatic and bone marrow granulomas were the main features. Idiopathic Granulomatous Hepatitis (IGH), a rare syndrome amenable to immunosuppressive therapy was diagnosed.

Child↗
PubMed2004

Management of edema in nephrotic syndrome.

Nephrotic syndrome is a recurrent or chronic disorder characterized by heavy proteinuria, hypoalbuminemia and edema. In most patients, the edema can be managed satisfactorily with judicious oral administration of loop diuretics, most often frusemide. The treatment of patients with intractable edema is more difficult and comprises a series of measures including salt restriction, treatment with intravenous frusemide, additional use of thiazide and potassium sparing diuretics, and intravenous albumin. Ultrafiltration and head out water immersion are beneficial for treatment of patients with edema, which is unresponsive to the above measures.

Edema↗
PubMed2004

Short term efficacy of intravenous dexamethasone and methylprednisolone therapy in steroid resistant nephrotic syndrome.

OBJECTIVE: To compare the short term efficacy of intravenous pulses of methylprednisolone and dexamethasone in treatment of steroid resistant nephrotic syndrome in children. METHOD: We prospectively treated 81 children with idiopathic steroid resistant nephrotic syndrome with six alternate-day pulses of intravenous dexamethasone (5 mg/kg) or methylprednisolone (30 mg/kg). Fifty-nine patients received dexamethasone and 22 were treated with methylprednisolone. Two patients in dexamethasone and one in methylprednisolone group developed serious infection during administration of alternate-day pulses and could not complete the therapy. RESULTS: The median age at treatment was 38 (36-74.7) months. Of patients who completed therapy, 20 (35.1 percent) (95 PERCNT CI 22.9-48.9) and 7 (33.1 percent) (95 percent CI 14.6-56.9) patients in dexamethasone and methylprednisolone group, respectively achieved complete remission. Following alternate day pu1ses the median urinary albumin to creatinine ratio decreased from 9.2 to 1.5 (P less tha 0.005) in dexamethasone group and from 12.1 to 0.7 (P less than 0.005) in methylprednisolone group. The median reduction in urinary albumin to creatinine ratio was 54.1 PERCNT (95 percent CI 32.7- 83.9) and 63.2 percent (95 percent CI 23.5- 100) in dexamethasone and methylprednisolone group respectively. The chief side effects of therapy were transient hypertension or worsening of preexisting hypertension, which occurred in 31 (54.4 percent) patients in dexamethasone group and 10 (47.6 percent) in the methylprednisolone group. The hypertension was satisfactorily controlled on antihypertensive drugs. One or more side effects were observed in 66.7 percent (95 percent CI 52.9-78.6) children receiving dexamethasone therapy and 61.9percent (95 percent CI 38.4-81.9) receiving methylprednisolone, which was comparable. CONCLUSIONS: We conclude that intravenous dexamethasone is as effective as methylprednisolone in inducing remission in patients with steroid resistant nephrotic syndrome.

Adolescent↗
PubMed2003

Enalapril dosage in steroid-resistant nephrotic syndrome.

We have examined, in a randomized crossover trial, the antiproteinuric effect of treatment with low- (0.2 mg/kg daily) and high-dose (0.6 mg/kg daily) enalapril in 25 consecutive patients with steroid-resistant nephrotic syndrome (SRNS). Patients in group A ( n=11) received enalapril at low doses for 8 weeks, followed by 2 weeks of washout and then at high doses for 8 weeks. Those in group B ( n=14) initially received enalapril at high and then low doses. Patients continued to receive treatment with tapering doses of prednisolone; none received concomitant therapy with daily oral or intravenous steroids, alkylating agents, cyclosporine, non-steroidal anti-inflammatory drugs, and other antihypertensive medications. The urine albumin-to-creatinine (Ua/Uc) ratio and the percentage reduction were determined for each phase of therapy. Baseline clinical, biochemical, and histological features were comparable in the two groups. In the first phase, treatment with low-dose enalapril (group A) resulted in median 34.8% Ua/Uc reduction compared with 62.9% with high doses (group B) ( P<0.01). High-dose enalapril was associated with a significant reduction in Ua/Uc ratio in both groups. The combined median Ua/Uc (95% confidence interval) reduction in the low-dose phase was 33% (-10.3% to 72.4%) and in the high-dose 52% (15.4%-70.4%) ( P<0.05). The median Ua/Uc ratio at the end of 20 weeks was 1.1 and 1.8 in groups A and B, respectively ( P>0.05). Systolic and diastolic blood pressure reductions were similar in both groups. No period or carry-over effect was found. Prolonged treatment with enalapril thus resulted in a dose-related reduction in nephrotic-range proteinuria. Titration of the dose of enalapril may be a useful strategy for achieving substantial reduction of proteinuria in children with SRNS.

Adolescent↗