Abhishek Abhinay

Urinary Infections in Children

Urinary tract infection (UTI) is a common infection in infants and children. During infancy, boys are more commonly affected than girls and thereafter, female preponderance is found. Presentation varies among different age groups. Clinical features in neonates and young infants are non-specific, manifest as septicemia where a high index of suspicion is needed. Older children typically present as simple or complicated UTI. Rapid diagnosis, institution of early treatment and further evaluation by imaging modalities are of utmost importance. The prevention of recurrent UTI and detection of congenital anomalies of kidney and urinary tract are major objectives in the management. Use of ultrasound is required to detect underlying congenital abnormalities, whereas voiding cystourethrogram and dimercaptosuccinic acid (DMSA) scan are useful in the diagnosis of obstructive uropathy and vesicoureteric reflux and renal scar, respectively. The children requiring surgical interventions are to be recognised early to prevent recurrent UTI. The treatment of vesicoureteric reflux by chemoprophylaxis in lower grades and surgical treatment in higher grades are important consideration in prevention of recurrent UTI. This is required to prevent renal parenchymal damage and scarring that can cause hypertension and progressive renal insufficiency in later life.

Can We Predict Relapses in Children with Idiopathic Steroid-Sensitive Nephrotic Syndrome?

The objective of the present study was to find out the predictors of relapse. One hundred fifty children with a first episode of idiopathic nephrotic syndrome were followed for 12 months after initial treatment. Sixty-one (40.7%) children had no relapse, and 89 (59.3%) had relapses. A significantly higher proportion of children with disease onset between 1 and 3 years were relapsers in comparison with those with disease onset at 4-6 (p < 0.03) and 7-13 (p < 0.001) years. Risk of relapse was 2.99 times higher in this 1-3 year age-group as compared with patients aged >6 years (p = 0.001). Children responding between 1 and 2 weeks after start of treatment had a 0.423 times lesser risk of relapse than those who responded after 4 weeks (p = 0.023). Relapsers had significantly higher incidence of infection at relapse than at other time points (p < 0.001). Onset of disease in younger age and delayed response to prednisolone therapy were found as significant predictors for relapse.

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.

Serum Immunoglobulin E and Interleukin-13 Levels in Children with Idiopathic Nephrotic Syndrome

Serum IgE and IL-13 levels were estimated in 40 idiopathic nephrotic syndrome and 16 controls. There were 15 first episode nephrotic syndrome (FENS), 15 infrequent relapsing nephrotic syndrome (IRNS) and 10 patients belonged to frequent relapsing nephrotic syndrome (FRNS). Serum IgE and IL-13 levels were significantly increased in active nephrotic syndrome and its sub-groups as compared to controls and remission (p < 0.001). IgE levels did not differ significantly among different subgroups, while Il-13 was significantly higher in FRNS in comparison with FENS (p = 0.041). Both IgE and IL-13 levels were comparable in nephrotic patients with and without bronchial asthma. Serum IL-13 had significant positive correlation with IgE (r = 0.605, p < 0.001). Thus, raised levels of IgE and IL-13 are found in nephrotic syndrome and could have a role in the pathogenesis of disease.

Cytotoxic T- Lymphocyte Antigen-4 (CTLA4) Gene Expression and Urinary CTLA4 Levels in Idiopathic Nephrotic Syndrome

ObjectivesTo detect Cytotoxic T- Lymphocyte Antigen-4 (CTLA4) single nucleotide polymorphisms (SNPs) at +49A/G (rs231775) and -318C/T (rs5742909) positions in children with idiopathic nephrotic syndrome (INS) and also assay urinary soluble CTLA4 (sCTLA4) levels in children with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS) and steroid sensitive nephrotic syndrome (SSNS) in remission.MethodsThe study included 59 patients of INS (MCD-23, FSGS-15 and SSNS in remission-21) and 35 healthy controls. The CTLA4 SNPs profiling was done in peripheral blood mononuclear cells and urinary sCTLA4 level was assayed by ELISA kit.ResultsAlthough frequency of homozygous +49 GG (rs4553808) genotype (26.3% vs. 11.4%; p = 0.231) and G allele (52.6% vs. 40%; p = 0.216) were found to be higher in INS as compared to controls, the differences were statistically non-significant. Genotypes GG, AG, AA and alleles A and G frequencies were comparable among MCD, FSGS and controls. SNP at −318 C/T (rs5742909) did not show homozygous TT genotype both in INS as well as controls. Median urinary sCTLA4/creatinine level was significantly higher in MCD as compared to FSGS (p = 0.027), SSNS in remission (p = 0.001) and controls (p = 0.003).ConclusionsThe positive associations of +49 GG genotype and G allele in patients with nephrotic syndrome were not observed. The frequencies did not differ significantly among MCD, FSGS and controls. Urinary sCTLA4 level was significantly increased in MCD; suggesting its possible role in the pathogenesis of disease.

Urinary Neutrophil Gelatinase- Associated Lipocalin in Children with Idiopathic Nephrotic Syndrome: A Biomarker to Differentiate Between Steroid Sensitive and Resistant Forms of Disease

Background: Objectives of the study were to find out the ability of urinary neutrophil gelatinase- associated lipocalin (NGAL) as a biomarker to differentiate between steroid resistant nephrotic syndrome (SRNS) and steroid sensitive nephrotic syndrome (SSNS), and also to observe variation in levels, if any, between focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) in SRNS patients.Methods: The study included 63 patients of idiopathic nephrotic syndrome (19 SSNS in relapse, 19 SSNS in remission and 25 SRNS), aged 2.5-16 years, along with 17 controls. Urinary NGAL was measured by ELISA and the values were normalised with urinary creatinine.Results: Median urinary NGAL/creatinine level was significantly raised in SRNS as compared to SSNS relapse, SSNS remission and controls (p 18.3 ng/mg had sensitivity of 84%, specificity of 97.4% and area under the curve of 0.935 (p< 0.001, 95% confidence interval 0.871-0.998) to differentiate SRNS from SSNS patients. Median urinary NGAL/creatinine value was significantly raised in children with FSGS as compared to MCD (p=0.003) in SRNS patients. It had significant positive correlations with duration of illness (r=0.342, p=0.006), urine protein creatinine ratio (r=0.594, p< 0.001) and negative correlation with serum albumin (r=0.470, p<0.001).Conclusion: Urinary NGAL/creatinine level correlated with activity of the disease and it can distinguish not only SRNS from SSNS but also FSGS and MCD histopathological sub-types of SRNS in children.

Validation of Predictors of Relapse in Steroid Sensitive Idiopathic Nephrotic Syndrome

To the Editor: About 70% of the patients of idiopathic nephrotic syndrome in children experience relapse after treatment of first episode [1]. We found younger age at onset of disease and longer time to response as predictors of relapse and derived formulae using discriminant function analysis tool [2]; however, it needed validation for their prediction. The objectives of the present study were to validate the previously derived formulae on newly prospectively enrolled patients, and also re-derive new formulae by combining previous retrospectively and prospectively enrolled patients’ data and assess their predictive ability for relapses. One hundred patients of first episode of steroid sensitive idiopathic nephrotic syndrome, aged 1–13 y, were enrolled and followed for next 12 mo period after completion of treatment with prednisolone (2 mg/kg/d single dose for 6 wk, followed by 1.5 mg/kg/d single dose every alternate day for 6 wk). The protocol of the study was approved by Institute Ethical Committee. Initially patients were categorised into relapser and non-relapser groups by substituting the age at onset of disease and time to response scores in the following previously derived formulae [2] (for non-relapser, −6.965 + 3.558 age group score + 3.256 time to response score and for relapser, −6.559 + 2.817 age group score + 3.842 time to response score). The scores assigned for age group and time to response were 1 for 1–3 y and 1–2 wk, 2 for 4–6 y and 3–4 wk and 3 for 7–13 y and 5–8 wk, respectively. The formula yielding the higher value indicated the category of patient (non-relapser or relapser). It had 58.5% sensitivity, 89.4% specificity and 73% accuracy for predicting the relapses. Further, the data of 100 cases were combined with previously recorded 150 cases and new formulae (for non-relapser, −7.145 + 3.881 age group score + 3.881 time to response score and for relapser, −6.134 + 2.920 age group score + 3.566 time to response score) were derived, and applied on these total 250 cases. It had modest sensitivity (66.4%), specificity (70.1%) and accuracy (68%) in predicting relapses. Further, out of total of 100 new cases, 64 were predicted as non-relapsers and 36 as relapsers by both the old and new formulae. Constantinescu et al. [3] found that patients who achieved remission within the first week were more likely to be infrequent relapsers. Kabuki et al. [4] observed longer duration of time to response in younger age group of patients. Time to response has been also emphasized as a future prognostic factor by Vivarelli et al. [5]. In our study, old formulae had lower sensitivity but higher specificity and new formulae showed better sensitivity, but relatively lower specificity and almost similar accuracy. This difference could be because of sample size. However, no deviation between the two formulae was observed as regard to their predictive ability. Thus, any of these formulae can be used for prediction of relapses in these patients. This may help the families for better compliance in treatment and follow-up.

Askin tumor: A rare neoplasm of thoracopulmonary region.

Askin tumor is a rare neoplasm of thoracopulmonary region. But it mimics other common pediatric disorders, such as empyema, lymphoma, and tuberculosis, posing a great diagnostic and therapeutic challenge to the treating clinicians. So it is of utmost importance to make an early diagnosis and proper referral/treatment in such cases. We highlighted diagnostic challenge, treatment, and favorable outcome of a case that presented to us.

Neonatal brain abscess: Clinical report and review of Indian cases

Septicemia, pneumonia, meningitis are common problems in neonatal age group in developing countries. Epidemiology of meningitis differs in developed and developing countries with Group B streptococci, being more common in developed countries and Klebsiella pneumoniae in developing countries. In some of the cases, meningitis can lead to complications such as abscess, ventriculitis, and communication with ventricles. Proteus is the most common organism reported for brain abscess in neonatal age group in western literature. We found more cases of K. pneumoniae from the Indian subcontinent. Hence, we collected data from all published cases of Indian origin to highlight the etiology, any risk factor, most common site, complication, and outcome. We concluded that: K. pneumoniae is the most common organisms for neonatal brain abscess with fatal outcome in cases with ventricular perforation. Frontal lobe was the most common site of abscess. Minimum 6 weeks of antibiotic therapy was mentioned in 7 of 15 cases. Survival and discharge were reported in 13 of 15 cases, suggesting good immediate outcome in such cases.

Gerbode Defect of Congenital Variety in an Infant: A Case Report

Gerbode defect is a rare communication from left ventricle to right atrium. It is of two types: congenital versus acquired OR Direct (type I) versus Indirect (type II). Acquired forms are more common and increasingly reported than congenital. We report a second Indian case of such a rare defect and highlight the salient points of all such previously reported cases to make aware the clinicians and paediatricians of need of early diagnosis and timely surgery/ referral for successful outcome.