Evidence-based clinical practice guideline for management of urinary tract infection and primary vesicoureteric reflux.

We present updated, evidence-based clinical practice guidelines from the Indian Society of Pediatric Nephrology (ISPN) for the management of urinary tract infection (UTI) and primary vesicoureteric reflux (VUR) in children. These guidelines conform to international standards; Institute of Medicine and AGREE checklists were used to ensure transparency, rigor, and thoroughness in the guideline development. In view of the robust methodology, these guidelines are applicable globally for the management of UTI and VUR. Seventeen recommendations and 18 clinical practice points have been formulated. Some of the key recommendations and practice points are as follows. Urine culture with > 104 colony forming units/mL is considered significant for the diagnosis of UTI in an infant if the clinical suspicion is strong. Urine leukocyte esterase and nitrite can be used as an alternative screening test to urine microscopy in a child with suspected UTI. Acute pyelonephritis can be treated with oral antibiotics in a non-toxic infant for 7-10 days. An acute-phase DMSA scan is not recommended in the evaluation of UTI. Micturating cystourethrography (MCU) is indicated in children with recurrent UTI, abnormal kidney ultrasound, and in patients below 2 years of age with non-E. coli UTI. Dimercaptosuccinic acid scan (DMSA scan) is indicated only in children with recurrent UTI and high-grade (3-5) VUR. Antibiotic prophylaxis is not indicated in children with a normal urinary tract after UTI. Prophylaxis is recommended to prevent UTI in children with bladder bowel dysfunction (BBD) and those with high-grade VUR. In children with VUR, prophylaxis should be stopped if the child is toilet trained, free of BBD, and has not had a UTI in the last 1 year. Surgical intervention in high-grade VUR can be considered for parental preference over antibiotic prophylaxis or in children developing recurrent breakthrough febrile UTIs on antibiotic prophylaxis.

Consensus Guidelines on Management of Steroid-Resistant Nephrotic Syndrome.

JUSTIFICATION: The management of steroid resistant nephrotic syndrome (SRNS) is challenging. These guidelines update existing 2009 Indian Society of Pediatric Nephrology recommendations on its management. OBJECTIVE: To frame revised guidelines on diagnosis and evaluation, treatment and follow up, and supportive care of patients with the illness. PROCESS: The guidelines combine evidence-based recommendations and expert opinion. Formulation of key questions was followed by systematic review of literature, evaluation of evidence by experts and two face-to-face meetings. RECOMMENDATIONS: Fourteen statements provide updated advice for managing steroid resistance, and underscore the importance of estimating proteinuria and baseline kidney function, and the need for kidney biopsy and genetic screening. Calcineurin inhibitors are recommended as most effective in inducing remission of proteinuria, the chief factor associated with long-term renal survival. Advice on managing allograft recurrence, congenital nephrotic syndrome, and monitoring and supportive care, including transition of care, are described. This revised practice guideline is intended to improve management and patient outcomes, and provide direction for future research.

Enuresis, Lower Urinary Tract Dysfunction and Teachers' Perceptions: A School-based Survey.

OBJECTIVE: To determine the prevalence of enuresis and lower urinary tract dysfunction among Indian school children, and describe teachers' perceptions regarding toilet requests. METHODS: Anonymous survey of students of a secondary school in Visakhapatnam, India by a modified version of the Dysfunctional voiding and incontinence scoring system (DVISS) in 2518 parents. Two questionnaires - the Bathroom behaviour scale and Teachers' hassle scale for toilet requests were designed, validated and administered to 138 teachers. RESULTS: We received 1911 (75.9%) modified DVISS questionnaires with response; 1790 (93.7%) were valid. History was compatible with enuresis in 85 (4.7%), non-monosymptomatic enuresis in 38 (2.1%), overactive bladder in 46 children (2.6%), dysfunctional voiding syndrome in 14 children (0.8%) and both overactive bladder as well as dysfunctional voiding syndrome in 4 (0.2%). Responses of 43 (31.2%) teachers indicated refusal of toilet requests; medical cause underlying frequent toilet requests was understood by 82 (59.4%) teachers. At least one aspect of toilet requests was a frequent or intense hassle in 43 (39.8%) and 29 (28.7%) teachers, respectively. CONCLUSIONS: Toilet requests are misunderstood by and present a stressor to a sizeable minority of teachers.

Current Management of Urinary Tract Infection and Vesicoureteral Reflux.

Urinary tract infection (UTI) is defined as the growth of a significant number of microorganisms of a single species in the urine, in the presence of symptoms. Symptoms in young children are non-specific such as fever without focus; young infants may manifest with irritability, failure to thrive, jaundice, vomiting and diarrhea. Older children usually have symptoms of cystitis or pyelonephritis. Symptoms of cystitis are dysuria, frequency, new onset incontinence and malodorous urine while symptoms of pyelonephritis are high grade fever, flank pain and vomiting. Rapid urine testing by microscopy for pus cells, dipstick testing for leukocyte esterase and nitrite, and enhanced urinalysis are supportive tests. Urine culture samples should be collected with proper technique and results interpreted for significant growth accordingly. Antibiotic therapy for 7-14 d for complicated UTI and 3-4 d for uncomplicated UTI is adequate. Further evaluation is recommended clinically for bladder-bowel dysfunction and obvious anatomical defects and by imaging for vesicoureteral reflux (VUR), usually by micturating cystourethrography (MCU). Since MCU involves exposure to radiation and urethral catheterization, it is now reserved for children with parenchymal involvement or recurrent UTI. VUR is the backward flow of urine into one or both ureters. Clinical manifestations other than UTI include incidental diagnosis on antenatal ultrasonography. Reflux nephropathy, the renal scarring associated with VUR may manifest clinically as hypertension, proteinuria and renal failure. The management of VUR is primarily with antibiotic prophylaxis. Anatomical correction is indicated in case of breakthrough febrile UTI. No intervention has been shown to reduce renal scarring.

Hemolytic uremic syndrome in a developing country: Consensus guidelines.

BACKGROUND: Hemolytic uremic syndrome (HUS) is a leading cause of acute kidney injury in children. Although international guidelines emphasize comprehensive evaluation and treatment with eculizumab, access to diagnostic and therapeutic facilities is limited in most developing countries. The burden of Shiga toxin-associated HUS in India is unclear; school-going children show high prevalence of anti-factor H (FH) antibodies. The aim of the consensus meeting was to formulate guidelines for the diagnosis and management of HUS in children, specific to the needs of the country. METHODS: Four workgroups performed literature review and graded research studies addressing (i) investigations, biopsy, genetics, and differential diagnosis; (ii) Shiga toxin, pneumococcal, and infection-associated HUS; (iii) atypical HUS; and (iv) complement blockade. Consensus statements developed by the workgroups were discussed during a consensus meeting in March 2017. RESULTS: An algorithm for classification and evaluation was developed. The management of Shiga toxin-associated HUS is supportive; prompt plasma exchanges (PEX) is the chief therapy in patients with atypical HUS. Experts recommend that patients with anti-FH-associated HUS be managed with a combination of PEX and immunosuppressive medications. Indications for eculizumab include incomplete remission with plasma therapy, life-threatening features, complications of PEX or vascular access, inherited defects in complement regulation, and recurrence of HUS in allografts. Priorities for capacity building in regional and national laboratories are highlighted. CONCLUSIONS: Limited diagnostic capabilities and lack of access to eculizumab prevent the implementation of international guidelines for HUS in most developing countries. We propose practice guidelines for India, which will perhaps be applicable to other developing countries.

Effect of atorvastatin on dyslipidemia and carotid intima-media thickness in children with refractory nephrotic syndrome: a randomized controlled trial.

BACKGROUND: Dyslipidemia is an important cardiovascular risk factor in steroid-resistant nephrotic syndrome (SRNS). Efficacy of statins for treatment of hyperlipidemia in children with SRNS is unclear. METHODS: This prospective, randomized, double-blind, placebo-controlled, parallel-group clinical trial enrolled 30 patients with SRNS, aged 5-18 years, with serum low-density lipoprotein cholesterol (LDL-C) levels between 130 and 300 mg/dl, to receive a fixed dose of atorvastatin (n = 15, 10 mg/d) or placebo (n = 15) by block randomization in a 1:1 ratio. Primary outcome was change in serum LDL-C at 12 months. Change in levels of other lipid fractions, carotid intima-media thickness (cIMT), flow-mediated dilation (FMD) of the brachial artery, and adverse events were also evaluated. RESULTS: At the end of 12 months, atorvastatin was not superior to placebo in reducing plasma LDL-C levels, median percentage reduction 15.8% and 9.5% respectively, in atorvastatin and placebo arms (n = 14 in each; P = 0.40). Apolipoprotein B levels significantly declined with atorvastatin in modified intention-to-treat analysis (P = 0.01) but not in the per-protocol analysis. There was no significant effect on other lipid fractions, cIMT and FMD. Adverse events were similar between groups. Change in serum albumin was negatively associated with change in serum LDL-C, very low-density lipoprotein cholesterol, total cholesterol, triglyceride, and apolipoprotein B (P < 0.001), irrespective of receiving atorvastatin, age, gender, body mass index, and serum creatinine. CONCLUSIONS: Atorvastatin, administered at a fixed daily dose of 10 mg, was not beneficial in lowering lipid levels in children with SRNS; rise in serum albumin was associated with improvement in dyslipidemia.

Phenotype of Dent Disease in a Cohort of Indian Children.

OBJECTIVE: To describe the clinical and genotypic features of Dent disease in children diagnosed at our center over a period of 10 years. DESIGN: Case series. SETTING: Pediatric Nephrology Clinic at a referral center in Northern India. METHODS: The medical records of patients with Dent disease diagnosed and followed up at this hospital from June 2005 to April 2015 were reviewed. The diagnosis of Dent disease was based on presence of all three of the following: (i) low molecular weight proteinuria, (ii) hypercalciuria and (iii) one of the following: nephrolithiasis, hematuria, hypophosphatemia or renal insufficiency, with or without mutation in CLCN5 or OCRL1 genes. RESULTS: The phenotype in 18 patients diagnosed with Dent disease during this period was characterized by early age at onset (median 1.8 y), and polyuria, polydipsia, salt craving, hypophosphatemic rickets and night blindness. Rickets was associated with severe deformities, fractures or loss of ambulation in six patients. Nephrocalcinosis was present in three patients, while none had nephrolithiasis. Generalized aminoaciduria was seen in 13 patients, two had glucosuria alone, and one had features of Fanconi syndrome. Over a median follow up of 2.7 years, one patient developed renal failure. Genetic testing (n=15) revealed 5 missense mutations and 3 nonsense mutations in CLCN5 in 13 patients. Five of these variations (p.Met504Lys, p.Trp58Cys, p.Leu729X, p.Glu527Gln and p.Gly57Arg) have not been reported outside the Indian subcontinent. CONCLUSION: Our findings suggest a severe phenotype in a cohort of Indian patients with Dent disease.