Kidney outcomes in children with primary focal segmental glomerulosclerosis from a low- and middle- income country.

BACKGROUND: Limited data exists regarding the clinical course and outcomes of children with primary focal segmental glomerulosclerosis (FSGS) from low- and middle- income countries. METHODS: Children aged 1-18 years with biopsy-proven primary FSGS followed from January 2010-June 2023 in a tertiary-care center were enrolled and their clinical profile, histological characteristics, kidney outcomes, and predictors of adverse outcomes were determined. RESULTS: Over 13 years, 73 (54.8% boys) children with median (IQR) age at FSGS diagnosis 6.7 (3,10) years were recruited and followed up for median 4 (2.5,8) years. FSGS-not otherwise specified (NOS) was the most common histological subtype, in 64 (87.6%) children, followed by collapsing variant in 5 (6.8%) children. At last follow-up, 43 (58.9%), 2 (2.7%) and 28 (38.3%) children were in complete remission (CR), partial remission (PR), and no remission (NR) respectively. Calcineurin inhibitors led to CR or PR in 39 (62%) children. Overall, 21 (28.7%) children progressed to chronic kidney disease (CKD) stage 2-5 (19 from NR vs. 2 from PR group; p = 0.03); with 41% of those NR at 12 months progressing to CKD 4-5 by last follow-up. On multivariable analysis, collapsing variant [adjusted HR 2.5 (95%CI 1.5, 4.17), p = 0.001] and segmental sclerosis > 25% [aHR 9.9 (95%CI 2.2, 45.2), p = 0.003] predicted kidney disease progression. CONCLUSIONS: In children with FSGS, response to immunosuppression predicts kidney survival as evidenced by nil to lower progression to CKD 2-5 by median follow-up of 4 (2.5,8) years in children with CR and PR, compared to those with no remission at 12 months from diagnosis. Segmental sclerosis > 25% and collapsing variant predicted progression to advanced CKD.

Congenital nephrotic syndrome with diffuse mesangial sclerosis caused by compound heterozygous mutation in LAMA5 gene.

A two-and-a-half-month-old female infant presented with generalized edema for 10 days. At presentation, she had periorbital puffiness, moderate ascites, and pedal edema. Laboratory investigations revealed serum albumin 1.3 g/dL, spot urine protein to creatinine ratio (Up:Uc) 20.87 mg/mg, total cholesterol 380 mg/dL, and serum creatinine 0.31 mg/dL. Exome sequencing revealed compound heterozygous variants in LAMA5 gene (NM_005560.6). There was a heterozygous likely pathogenic missense variant in exon 2: LAMA5: c.385C > A (depth 195 ×) and another heterozygous pathogenic variant in exon 31: LAMA5: c.3932_3936dup; parental segregation by Sanger sequencing proved that the variants were in trans. Kidney biopsy showed diffuse mesangial sclerosis (DMS). Our case adds LAMA5 gene to the constellation of genes causing DMS, in addition to the classically described WT1, LAMB2, and PLCE1 genes and to the list of genes causing congenital nephrotic syndrome (CNS).

Etiology, Comorbidities, and Rate of Progression of Pediatric Chronic Kidney Disease: A Cohort Study.

OBJECTIVES: To evaluate the etiology of pediatric chronic kidney disease (CKD), assess comorbidities, and identify rate of progression of CKD and its risk factors. METHODS: Children aged 2-18 y with the Kidney Disease Improving Global Outcome (KDIGO) CKD stages 2-4 were enrolled. The etiology of CKD and its comorbidities were recorded. Kaplan-Meier survival curves were used to analyze the time to progression of CKD. RESULTS: Of the 131 patients enrolled, CKD stages 2, 3a, 3b, and 4 constituted 62 (47.3%), 17 (13%), 26 (19.8%), and 26 (19.8%), respectively. At the last follow-up [at median (IQR) 24 (12, 30) mo], the number of children in CKD stages 2, 3a, 3b, 4 and 5 were 48 (36.6%), 16 (12.2%), 23 (17.6%), 28 (21.4%), and 16 (12.2%), respectively. Etiologies of CKD included obstructive uropathy [48 (36.6%)], chronic glomerular disease [19 (14.5%)], reflux nephropathy [14 (10.7%)] and cystic renal disease [11 (8.3%)]. Comorbidities during follow-up included CKD-MBD [87 (66.4%)], metabolic acidosis [95 (72.5%)], hypertension [88 (67.1%)], growth retardation [69 (52.6%)], and anemia [63 (48.1%)]. The number of patients with metabolic acidosis, hypertension, MBD and anemia in CKD stage 2 were 27 (56%), 26 (54.2%), 24 (50%), 15 (30%), respectively. The median (IQR) rate of decline in eGFR was 3.3 (2, 4.6) mL/min/1.73 m2/y. On multivariable analysis, proteinuria [hazard ratio 3.5 (95% CI 1.4, 8.8) p = 0.01] and hyperphosphatemia [hazard ratio 2.2 (95% CI 1.1, 4.3) p = 0.03] were significant predictors for progression of CKD. CONCLUSIONS: Even the earlier stages of CKD had significant comorbidities. The median decline in eGFR was 3.3 mL/min/1.73 m2/y. Proteinuria and hyperphosphatemia were the risk factors for progression of CKD.

Atypical manifestations of infantile-onset nephropathic cystinosis: a diagnostic challenge.

A 7-month-old male infant was referred to us for evaluation of hypercalcemia and failure to thrive. He was the second-born child to third-degree consanguineous parents with a birth weight of 3.5 kg. The index child was severely underweight. Initial laboratory investigations showed hypercalcemia (13.6 mg/dL), hypophosphatemia, hyponatremia, hypokalemia and hypochloremia. The initial serum bicarbonate level was 20.9 mEq/L. The urine calcium: creatinine ratio (0.05) was normal. He was noted to have polyuria (6 mL/kg/hr) and required intravenous fluids to maintain intravascular volume and manage hypercalcemia, along with potassium chloride supplements. The serum calcium decreased to 9.7 mg/dL after hydration for 48 h. At this juncture, the child was noted to exhibit metabolic acidosis (serum bicarbonate 16 mEq/L) for the first time. Thereafter, fractional excretion of bicarbonate was estimated to be 16.5% while the tubular threshold maximum for phosphorus per glomerular filtration rate was 1.2 mg/dL; indicating bicarbonaturia and phosphaturia, respectively. Glycosuria with aminoaciduria were also noted. Clinical exome sequencing revealed a NM_004937.3:c.809_811del in exon 10 of the CTNS gene that resulted in in-frame deletion of amino acids [NP_004928.2:p.Ser270del] at the protein level. The child is now growing well on oral potassium citrate, neutral phosphate and sodium bicarbonate supplements. This case was notable for absence of metabolic acidosis at admission. Instead, severe hypercalcemia was a striking presenting manifestation, that has not been reported previously in literature. Cystinosis has been earlier described in association with metabolic acidosis, hypocalcemia and hypomagnesemia. However, typical features like metabolic acidosis were masked in early stages of the disease in our case posing a diagnostic challenge. This atypical initial presentation adds to the constellation of clinical features in this condition.

Assessment of Causality in Hospitalized Children With Aminoglycoside-Related Nephrotoxicity.

OBJECTIVE: To evaluate the incidence of aminoglycoside-related nephrotoxicity and ascertain drug causality and its risk factors. METHODS: This prospective study was conducted from January, 2019 to January, 2021, and recruited 110 consecutively admitted children aged 1 month to 12 years, receiving aminoglycosides for ≥4 days. Drug causality was assessed using Liverpool adverse drug reaction causality assessment tool. RESULTS: 42 (38.2%) children developed acute kidney injury (AKI), with 71 (64.5%) having composite nephrotoxicity (AKI and/or tubular-dysfunction). Only 17 (15.5%) had AKI definitively attributable to aminoglycosides. Hypotension [OR 0.016 (95% CI 0.01-0.71), P=0.03], PRISM-III score 20-29% [OR 55.48 (95% CI 3.66-840.53), P=0.004] and post-surgery patients [OR 3.2 (95% CI 1.01-10.1), P=0.047] were independent predictors of AKI. Conclusions: Only a small proportion of children receiving aminoglycosides had AKI definitively attributable to the drug.

Calyx to Parenchymal Ratio (CPR): An unexplored tool and its utility in the follow-up of pyeloplasty.

INTRODUCTION: Antero-posterior trans pelvic diameter (APD) and renal scintigraphy play a significant role in the diagnosis of pelvi-ureteric junction (PUJ) obstruction and postoperative follow-up following pyeloplasty. However, the APD varies irrespective of improvement, deterioration, or preserved function in a hydronephrotic kidney and is not a reliable parameter due to various factors (hydration status, compliance, and reduction pyeloplasty). Calyx to Parenchymal Ratio (CPR) is the ratio of the depth of the calyx and parenchymal thickness measured on ultrasound (USG) in coronal image. We assessed the utility of CPR in the follow up of pyeloplasty and compared it with the commonly used APD of the pelvis and renal scintigraphy. MATERIAL AND METHODS: A prospective cohort study was done from July 2016 to October 2017. During this period 73 pyeloplasties were done, and 62 cases meeting the inclusion criteria were enrolled. All the children underwent ultrasound and Technetium-99 m Ethylene dicysteine isotope renogram (EC) scan before and after pyeloplasty. APD and CPR values were measured on USG and compared with isotope renogram outcomes in these children in the preoperative versus postoperative period. Two defined objective variables ΔAPD, percent ΔAPD and ΔCPR, percent ΔCPR were compared with categorical variables that would predict the surgical outcome as - failed, successful or equivocal. Multinomial logistic regression analysis and receiver operating curve (ROC) analysis was used to identify predictive accuracy. RESULTS: The mean (range) APD value recorded in the preoperative period was 3.67 cm (1.40-8.00 cm), which decreased to 1.67 cm (0.40-6.50) postoperatively, which was 54.2% lower (P=<0.001). The mean (range) CPR value decreased from 5.96 (1.20-20.00) in the preoperative period to 2.57 (0.43-10.90) postoperatively, which was 56.8% lower (P=<0.001). On multinomial logistic regression analysis, ΔCPR was found to be a significant predictor of outcome with an overall accuracy of 95.1%, change in CPR was a better predictor of success after pyeloplasty as compared to change in APD, which had an overall accuracy of 85.2% (p = 0.01). Further, on ROC curve analysis, we observed that ΔCPR and %ΔCPR can strongly predict successful pyeloplasty with a sensitivity of each with 96% and 98% respectively and AUC of 0.897 and 0.799 respectively. DISCUSSION: USG (APD) and renogram are the most widely used investigation in follow-up of pyeloplasty; however, APD has its own limitations like operator variability and slower improvement. CPR has the advantages that neither calyceal depth nor parenchymal thickness is directly altered during the surgery, and early resolution of calyceal dilatation and rapid parenchymal growth following pyeloplasty and thus a surgeon independent parameter. Our results have shown that ΔCPR can identify successful pyeloplasty with strong prediction than ΔAPD and thus renal scans can be avoided if there is visible improvement in CPR on follow-up. CONCLUSIONS: Our study identified a change in CPR, i.e., ΔCPR as a strong predictor of surgical outcome, as it is not influenced by extent of pelvis reduction during pyeloplasty and early to change. Using this parameter, we can avoid unnecessary repeated nuclear scans based on persistent high APD values and optimize resource utilization. We recommend the use of CPR in routine practice in the preoperative and postoperative follow-up of PUJ obstruction following pyeloplasty.

Incidence, Risk Factors, the Role of Plasma NGAL and Outcome of Contrast-Induced Acute Kidney Injury in Critically Ill Children.

OBJECTIVES: To study the incidence of contrast-induced acute kidney injury (CI-AKI), evaluate its risk factors, study the role of plasma neutrophil gelatinase-associated lipocalin (NGAL) and evaluate the outcome of CI-AKI in critically ill children. METHODS: In this prospective cohort study, children aged 1 mo to 12 y who underwent contrast computed tomography (CECT) for various medical indications were included. Patients without renal function test before contrast administration, children with chronic kidney disease, children admitted for less than 48 h, and those with serum bilirubin more than 5 mg per dL were excluded. Serum creatinine and estimated-Glomerular filtration rate (e-GFR) were measured at admission, immediately before, and at 6, 24, 48 h after contrast. Plasma neutrophil gelatinase-associated lipocalin (NGAL) was measured before and 6 h after contrast. The incidence of CI-AKI by p-RIFLE (Pediatric Risk, Injury, Failure, Loss, End Stage Renal Disease) criteria, its risk factors, the diagnostic role of NGAL in CI-AKI, and outcomes [30 d unfavorable outcome (death, readmission) and renal recovery] were studied. RESULTS: One hundred children were enrolled. The indications for CECT were brain (58%) and respiratory pathology (20%). Incidence of CI-AKI was 35% (95% CI 26.4% to 44.8%); 71% in 'Risk,' and 29% in the 'Injury' stage. After multivariate logistic regression, age younger than 2 y was independently associated with CI-AKI. There was no significant difference in NGAL before (ROC-AUC 0.38, 95% CI 0.26 to 0.50) and 6 h after CECT scan (AUC 0.41, 95% CI 0.29 to 0.54) to predict CI-AKI. There were 7% deaths but no readmission at 30 d. Among 33 CI-AKI patients who survived, the operational definition of renal recovery was achieved in 51.5% (n = 17), complete renal recovery was achieved in 97% (n = 32), and partial renal recovery was achieved in 3% (n = 1) of patients at discharge, while none received renal supportive therapy. CONCLUSIONS: The incidence of contrast-induced acute kidney injury was 35% with age younger than two year being independently associated with CI-AKI. NGAL did not predict the CI-AKI.

Metabolic and Clinical Characteristics of Children with Urolithiasis from Southern India.

OBJECTIVE: To study the etiological profile and patterns of clinical presentations of urolithiasis (UL) in children. METHODS: This observational study included patients <18 y with UL, who were referred to the pediatric nephrology clinic. Clinical features, family history, consanguinity and estimated glomerular filtration rate (eGFR) at presentation and follow-up were recorded. The children were evaluated using relevant blood and urine investigations. RESULTS: A total of 72 children with UL were evaluated for the study. The etiology of UL (n = 72) included hyperoxaluria (n = 25; 34.7%), idiopathic hypercalciuria (n = 21; 29.2%), idiopathic hyperuricosuria (n = 3; 4.2%), cystinuria (n = 3; 4.2%), urate transporter defect (n = 2; 2.8%) and mixed stones (predominant component calcium oxalate) (n = 9; 12.5%). No etiology was detected in 4 cases (5.5%). Common presenting complaints included flank pain (n = 41; 56.7%), hematuria (n = 29; 40.3%), urinary tract infection (UTI) (n = 29; 40.3%) and vomiting (n = 11; 15.3%). The median age of presentation was 60 (36, 96) mo. Family history and consanguinity were present in 30 cases (41.7%) and 28 cases (38.9%) respectively. Stone analysis was done in 20 cases, of which 9 cases were mixed stones (predominant calcium oxalate) and 6 were calcium oxalate stones. CONCLUSIONS: Among children with urolithiasis, hyperoxaluria, idiopathic hypercalciuria, idiopathic hyperuricosuria, and cystinuria were the predominant identifiable entities, together accounting for 72% of cases; and renal colic, hematuria and UTI were the commonest clinical complaints.

Association of Urinary Vitamin D Binding Protein and Neutrophil Gelatinase-Associated Lipocalin with Steroid Responsiveness in Idiopathic Nephrotic Syndrome of Childhood.

Idiopathic nephrotic syndrome (NS) is one of the most common kidney diseases of childhood. In this study, we assessed urine Vitamin-D binding protein (VDBP) and neutrophil gelatinase-associated lipocalin (NGAL) levels as a predictor of steroid responsiveness in idiopathic NS. This cross-sectional study included children with steroid-resistant NS (SRNS) (n = 28), steroid-sensitive NS (SSNS) (n = 28), and healthy controls (n = 28). Urine levels of VDBP and NGAL were measured using a commercially available ELISA kit and normalized to urine creatinine (Cr). Urine microalbumin (MALB) was measured using nephelometer, and MALB/Cr was calculated. Urine Vitamin-D binding protein (uVDBP) and urine neutrophil gelatinase-associated lipocalin (uNGAL) levels were statistically significantly higher (P < 0.001) in patients with SRNS (701.12 ± 371.64 ng/mL and 28.42 ± 15.40 ng/mL, respectively) than in patients with SSNS (252.87 ± 66.34 ng/mL and 8.86 ± 5.54 ng/mL, respectively) and normal controls (34.74 ± 14.10 ng/mL and 6.79 ± 1.32 ng/mL, respectively). Estimated glomerular filtration rate shows a significant negative correlation with MALB/Cr, uVDBP, and uNGAL. However, uVDBP and uNGAL showed a much higher discriminatory ability for differentiating SRNS from MALB/Cr. uVDBP and uNGAL at the cutoff value of 303.81 and 13.1 ng/mL, respectively, yielded the optimal sensitivity (82% and 86%) and specificity (78% and 89%) to distinguish SRNS from SSNS. Urine levels of VDBP and NGAL can predict steroid responsiveness in patients with idiopathic NS.

Screening for Renal and Urinary Tract Anomalies in Asymptomatic First Degree Relatives of Children with Congenital Anomalies of the Kidney and Urinary Tract (CAKUT).

OBJECTIVE: To estimate the frequency of renal and urinary tract anomalies in first-degree relatives of children with Congenital anomalies of kidney and urinary tract (CAKUT). METHODS: This descriptive study was conducted on parents and siblings of 138 children with CAKUT. Renal ultrasonogram, radionuclide diuretic renogram and micturating cysturethrogram were the tools used for screening these family members. RESULTS: Asymptomatic first-degree relatives of 138 children [total of 270 first-degree relatives (95 fathers, 97 mothers and 78 siblings)] were screened, with new anomalies detected in 11 first-degree relatives (4% out of 270 first-degree relatives screened) from 11 families (7.9% out of 138 families screened). The anomalies detected were vesicoureteric reflux (VUR) (n = 2), non-obstructive non-refluxing hydronephrosis (n = 2), pelviureteral junction obstruction (PUJO) (n = 3), Duplex collecting system (n = 1), hypodysplastic kidney (n = 1), single kidney (n = 1) and horseshoe kidney (n = 1). Most of the anomalies were discordant to the index anomaly (66.6%). Among 95 fathers screened, 5 (5.2%) had renal anomalies. Among 97 mothers screened, 2 (2.1%) had renal anomalies. Among the 78 siblings screened, 4 (5.1%) had renal anomalies. CONCLUSIONS: Familial clustering was noted in 7.9% of the 138 families (of the index cases) screened. The anomalies detected were mostly discordant to the index anomaly.

Etiological Profile of Nephrocalcinosis in Children from Southern India.

OBJECTIVE: To study the etiological profile and patterns of clinical presentation of nephrocalcinosis. METHODS: In this observational study, patients 18 years or younger, referred to the pediatric nephrology clinic with nephrocalcinosis were evaluated for etiology. Symptoms/signs at presentation, estimated glomerular filtration rate (eGFR) at presentation and follow-up, and growth parameters were recorded. RESULTS: The etiology of nephrocalcinosis (n=54) included distal renal tubular acidosis (n=18; 33.3%), primary hyperoxaluria (n=9; 16.7%), Bartter syndrome (n=7; 13%), Dent disease (n=4; 7.4%), cystinosis, familial hypomagnesemia with hypercalciuria and idiopathic hypercalcemia of infancy (2 each). Idiopathic nephrocalcinosis was seen in 5 (9.3%) children. Clinical features included failure to thrive (53.7%), polyuria (44.4%), bony deformities (31.5%) and hypokalemic paralysis (11.1%). At a median (IQR) follow-up of 24 (8, 56) months, the mean (SD) eGFR had improved from 59 (25.5) to 77 (31.48) mL/min/1.73m2 (P<0.01). Consanguinity was present in 50% (27/54). Genetic analysis in 5 primary hyperoxaluria cases confirmed AGXT mutations in 4; and GRHPR mutation in 1 child. CONCLUSIONS: Distal RTA, primary hyperoxaluria and Bartter syndrome were the common etiologies of nephrocalcinosis in our patient population.

Clinical Spectrum of Congenital Anomalies of Kidney and Urinary Tract in Children.

OBJECTIVES: To evaluate the clinical spectrum and patterns of clinical presentation in congenital anomalies of kidney and urinary tract. METHODS: We enrolled 307 consecutively presenting children with congenital anomalies of kidney and urinary tract at the pediatric nephrology clinic. Patients were evaluated clinically, with serum biochemistry, appropriate imaging and radionuclide scans. RESULTS: The most common anomaly was primary vesicoureteric reflux (VUR) (87, 27.3%), followed by pelviureteral junction obstruction (PUJO) (62,20.1%), multicystic dysplastic kidney (51 16.6%), non-obstructive hydronephrosis (32, 10.4%) and posterior urethral valves (PUV) (23, 7.4%). 247 (80.4%) anomalies had been identified during the antenatal period. Another 33 (10.7%) were diagnosed during evaluation of urinary tract infection, and 21 (6.8%) during evaluation for hypertension at presentation. Obstructive anomalies presented earlier than non-obstructive (7 (3, 22.5) vs 10 (4, 24) mo: (P=0.01)). The median (IQR) ages of presentation for children with PUV (n=23), VUR (n=87) and PUJO (n=62) were 4 (2, 14) mo, 10 (5, 27) mo, and 7 (3, 22.5) mo, respectively. Nine (2.9%) children had extrarenal manifestations. CONCLUSIONS: The median age at clinical presentation for various subgroups of anomalies indicates delayed referral. We emphasize the need for prompt referral in order to initiate appropriate therapeutic strategies in children with congenital anomalies of kidney and urinary tract.

Wilson disease and lupus nephritis: is it coincidence or a true association?

A 12-year-old girl born to third-degree consanguineous parents presented with recurrent episodes of haematuria for 8 months in association with peri-orbital and lower limb oedema for 20 days. There was no jaundice, hepatomegaly or neurological abnormality at presentation. An older brother had died following jaundice at 10 years of age. Urinalysis showed multiple dysmorphic erythrocytes without proteinuria and there was leucopenia, thrombocytopenia and hypo-albuminaemia (23 g/L). C3 component of complementaemia was low and anti-nuclear antibodies and anti-double-stranded DNA antibodies were strongly positive by immunofluorescence. Systemic lupus erythematosus (SLE) was considered but the severe hypo-albuminaemia was unexplained. During the pre-renal biopsy work-up, a deranged coagulation profile with raised transaminases prompted evaluation for chronic liver disease which culminated in the diagnosis of Wilson disease. Treatment with penicillamine and immunosuppressants was initiated, but there was neurological deterioration on Day 30 of admission and she died owing to worsening liver failure on the Day 41. Post-mortem liver biopsy demonstrated cirrhosis and post-mortem renal biopsy showed features of class-II lupus nephritis. Auto-immune antibodies and autoimmune disorders have been reported in Wilson disease and there are anecdotal reports of an association of SLE with Wilson disease. However, this case is unique in that lupus nephritis was the presenting manifestation before Wilson disease was diagnosed. The underlying pathophysiological mechanisms of this association requires further research.

Validation of pneumococcal iron acquisition (piaA) gene for accurate identification of Streptococcus pneumoniae.

PURPOSE: The pneumococcal iron acquisition (piaA) gene is found to be highly specific and hence proposed as a diagnostic marker for identification of pneumococci. The objective of the present study was to evaluate the piaA gene as a genetic marker for the identification of pneumococci. METHODS: Twenty isolates were initially sequenced for lytA gene using published primers. PiaA-PCR (piaA polymerase chain reaction) was performed using in-house primers and protocol. Based on the sensitivity and specificity results, a final sample of 30 pneumococcal isolates and 11 non-pneumococcal isolates confirmed with lytA- sequencing were selected. Statistical analyses were performed using OpenEpi v3.01 and GraphPad Quickcalc at P < 0.05 as the level of statistical significance. RESULTS: Of the initial 20 samples tested, piaA PCR was positive in only 71.43% (10/14) of the pneumococcal isolates but was 100% specific (0/6 non-pneumococcal isolates) P = 0.011. When the PCR was performed on 41 samples, the sensitivity increased to 73.33% (95% of confidence interval [CI] = 55.55-85.82) and specificity remained the same P < 0.001. The level of agreement between the PCR and lytA-sequencing was found to be moderate (κ = 0.694; 95% CI = 0.432-0.955). CONCLUSIONS: PiaA-PCR can be used as a specific marker for the identification of pneumococcus, though it is less sensitive. As the level of agreement was moderate, further analyses on a large number of samples can give conclusive evidence for its use as a diagnostic marker for pneumococcus.

Effect of two prophylactic bolus vitamin D dosing regimens (1000 IU/day vs. 400 IU/day) on bone mineral content in new-onset and infrequently-relapsing nephrotic syndrome: a randomised clinical trial.

OBJECTIVES: To examine the efficacy of two vitamin D dosages (1000 vs. 400 IU/day) for osteoprotection in children with new-onset and infrequently-relapsing nephrotic syndrome (IFRNS) receiving corticosteroids. METHODS: This parallel-group, open label, randomised clinical trial enrolled 92 children with new-onset nephrotic syndrome (NS) (n = 28) or IFRNS (n = 64) to receive 1000 IU/day (Group A, n = 46) or 400 IU/day (Group B, n = 46) vitamin D (administered as a single bolus initial supplemental dose) by block randomisation in a 1:1 allocation ratio. In Group A, vitamin D (cholecalciferol in a Calcirol® sachet) was administered in a single stat dose of 84,000 IU on Day 1 of steroid therapy (for new-onset NS), calculated for a period of 12 weeks@1000 IU/day) and 42,000 IU on Day 1 of steroid therapy (for IFRNS, calculated for a period of 6 weeks@1000 IU/day). In Group B, vitamin D (cholecalciferol in a Calcirol® sachet) was administered as a single stat dose of 33,600 IU on Day 1 of steroid therapy (for new-onset NS, calculated for a period of 12 weeks@400 IU/day) and 16,800 IU on Day 1 of steroid therapy (for IFRNS, calculated for a period of 6 weeks@400 IU/day). The proportionate change in bone mineral content (BMC) was analysed in both groups after vitamin D supplementation. RESULTS: Of the 92 children enrolled, 84 (n = 42 new onset, n = 42 IFRNS) completed the study and were included in the final analysis. Baseline characteristics including initial BMC, bone mineral density, cumulative prednisolone dosage and serum 25-hydroxycholecalciferol levels were comparable in the two groups. There was a greater median proportionate change in BMC in the children who received 1000 IU/day vitamin D (3.25%, IQR -1.2 to 12.4) than in those who received 400 IU/day vitamin D (1.2%, IQR -2.5 to 3.8, p = 0.048). The difference in proportionate change in BMC was only statistically significant in the combined new-onset and IFRNS, but not for IFRNS alone. There was a greater median proportionate change in serum 25-hydroxycholecalciferol, in the children who received 1000 IU/day vitamin D (20.6%, IQR 14.9-36.75) than in those who received 400 IU/day vitamin D (7.7%, IQR 3.5-18.5, p < 0.01). There was a greater median proportionate change in serum calcium in the children who received 1000 IU/day vitamin D (20%, IQR 13.1-29.0) than in those who received 400 IU/day vitamin D (11.3%, IQR 2.8-25.0, p = 0.03). Despite vitamin D therapy, BMC decreased from the baseline in 15 (32.6%) children receiving 1000 IU/day vitamin D and in 17 (36.9%) children receiving 400 IU/day vitamin D. There were no adverse effects attributable to vitamin D. CONCLUSION: The 1000 IU/day dose is marginally more effective than 400 IU/day and it is likely than an even larger dose is required. Further research is required to assess the efficacy and safety of vitamin D doses higher than 1000 IU/day.

Basidiobolomycosis complicated by hydronephrosis and a perinephric abscess presenting as a hypertensive emergency in a 7-year-old boy.

A 7-year-old boy presented with a chronic, indurated, tender left thigh swelling in association with a hypertensive emergency. He had a bilateral moderate degree of hydronephrosis and a left perinephric abscess, and MRI features of posterior reversible encephalopathy syndrome. Histopathological examination of the biopsy specimen demonstrated eosinophilic fasciitis with filamentous fungi. Basidiobolus ranarum was isolated from the culture. The fungus was also isolated from a perinephric fluid aspirate. Computerised tomography of the abdomen demonstrated features consistent with fungal invasion of the pelvic floor muscles and urinary bladder, leading to bilateral hydronephrosis. He required multiple antihypertensive drug therapy and was treated with intravenous amphotericin B, oral itraconazole and potassium iodide. Antihypertensive agents were discontinued after 2 weeks of antifungal therapy. At 6-months follow-up, the hydronephrosis had resolved completely. Perinephric abscess associated with basidiobolomycosis has not been reported previously.