Management of Acute Kidney Injury in Critically Ill Children

Acute kidney injury (AKI) is common in critically ill patients, afecting almost one in four critically ill children and one in three neonates. Higher stages of AKI portend worse outcomes. Identifying AKI timely and instituting appropriate measures to prevent and manage severe AKI is important, since it is independently associated with mortality. Methods to predict severe AKI should be applied to all critically ill patients. Assessment of volume status to prevent the development of fuid overload is useful to prevent adverse outcomes. Patients with metabolic or clinical complications of AKI need prompt kidney replacement therapy (KRT). Various modes of KRT are available, and the choice of modality depends most on the technical competence of the center, patient size, and hemodynamic stability. Given the signifcant risk of chronic kidney disease, patients with AKI require long-term follow-up. It is important to focus on improving awareness about AKI, incorporate AKI prevention as a quality initiative, and improve detection, prevention, and management of AKI with the aim of reducing acute and long-term morbidity and mortality

Assessment of Prevalence and Pattern of Mandibular 3rd Molar Impaction: A Cross-Sectional Study

Background: Impacted teeth, if left untreated, have a potentialto induce various complications. The mandibular third molar isthe most frequently impacted tooth with incidence varies from9.5% to 68% in different populations. The aim of the presentcross-sectional study was to assess the prevalence andpattern of mandibular 3rd molar impaction.Materials and Methods: A retrospective cross-sectional studywas conducted over the period of 1 year in which 270 cases ofpatients aged between 20 and 50 years were selected for thestudy. Parameters studied into the study were an age group,gender, location of the impacted third molar, angulation,position, and level of the impacted tooth. The data analysiswas done using the Statistical Package SPSS version 22.0.Results: In the present study total patients were 270 in which61.48% were males and 38.51% were females. Impacted teethwere maximum in both males and females in the age group 20-30 years. Mesioangular kind of impaction was maximum inboth males and females. According to Pell and Gregoryclassification at level B impactions were maximum (66.3%) andclass II impactions were maximum (51%).Conclusion: Our study concluded that the prevalence ofmandibular impactions were common in males than females.The study also noted that mesioangular impactions were themost common type of impaction. The least common form ofimpactions was the transverse types.

Lupus Nephritis in Indian Children: Flares and Refractory Illness

Objective: To evaluate the incidence of flares and treatment resistance in children with lupusnephritis and their association with renal outcomes. Methods: We retrospectively reviewedthe case records of 34 children treated for lupus nephritis (Class II-IV) at a single center.Patients were followed for a minimum of five years to evaluate treatment response, onset offlares, and renal survival. Regression analyses were performed to identify the factorsassociated with treatment refractoriness, incidence of flares and renal survival. Results: Theincidence of flares was 0.16 episodes/person/year. Eight patients (23.5%) were refractory totreatment. The five-year renal survival was 79%. Multiple episodes of flares (P=0.028) andtherapy refractoriness (P=0.003) were associated with poor renal survival. Conclusions:Prevention and aggressive management of renal flares is expected to prevent progression toend stage renal disease in lupus nephritis.

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.

Plasma Exchanges and Immunosuppression for Anti-complement Factor H Associated Hemolytic Uremic Syndrome.

Background: Atypical hemolytic uremic syndrome associated with autoantibodies to complement factor H is an important cause of acute kidney injury; most patients require dialysis and are at risk of progressive renal failure. Case Characteristics: 7 patients with gastrointestinal symptoms, acute kidney injury, thrombotic microangiopathy and elevated levels of anti-complement factor H antibodies. Intervention: Prompt initiation of plasma exchanges and immunosuppression. Outcome: Remission of hematological and kidney functions. Message: Prompt and specific management of antibody associated hemolytic uremic syndrome is associated with favorable outcome.

Effect of Enalapril on Glomerular Filtration Rate and Proteinuria in Children with Chronic Kidney Disease: A Randomized Controlled Trial.

Objective: To evaluate the efficacy of enalapril treatment on decline in glomerular filtration rate and reduction in proteinuria in children with chronic kidney disease (CKD). Design: Open-label, randomized controlled trial. Setting: Pediatric nephrology clinic at a tertiary-care referral hospital. Intervention: Children with GFR between 15-60 mL/min/1.73 m2 were randomized to receive either enalapril at 0.4 mg/kg /day or no enalapril for 1 year. Outcome measures: Change in GFR using 99mTc-DTPA and urine protein to creatinine ratio. Secondary outcomes included occurrence of composite outcome (30% decline in GFR or end stage renal disease) and systolic and diastolic blood pressure SDS during the study period. Results: 41 children were randomized into two groups; 20 received enalapril while 21 did not receive enalapril. During 1 year, GFR decline was not different in the two groups (regression coefficient (r) 0.40, 95% CI -4.29 to 5.09, P=0.86). The mean proteinuria reduction was 65% in the enalapril group, significantly higher than control group. The difference was significant even after adjustment for blood pressure was 198.5 (CI 97.5, 299.3; P<0.001). 3 (17.6%) patients in enalapril and 7 (36.8%) in nonenalapril group attained the composite outcome. Conclusions: Enalapril is effective in reducing proteinuria in children with CKD and might be renoprotective in proteinuric CKD.

Etiology and Outcome of Crescentic Glomerulonephritis.

Objective: To determine the etiology, course and predictors of outcome in children with crescentic glomerulonephritis (GN). Study design: Retrospective, descriptive study. Setting: Pediatric Nephrology Clinic at a referral center in Northern India. Methods: Clinic records of patients aged <18 year with crescentic GN diagnosed from 2001-2010 and followed at least 12-months were reviewed. Crescentic GN, defined as crescents in ≥50% glomeruli, was classified based on immunofluorescence findings and serology. Risk factors for renal loss (chronic kidney disease stage 4-5) were determined. Results: Of 36 patients, (median age 10 yr) 17 had immune complex GN and 19 had pauci-immune crescentic GN. The etiologies of the former were lupus nephritis (n=4), postinfectious GN (3), and IgA nephropathy, Henoch Schonlein purpura and membranoproliferative GN type II (2 each). Three patients with pauci-immune GN showed antineutrophil cytoplasmic antibodies (ANCA). Rapidly progressive GN was present in 33 patients, and required dialysis in 12. At median 34 (19-72) months, 2 patients with immune complex GN and 8 with pauci-immune GN showed renal loss. Renal survival was 94.1% at 3 yr, and 75.3% at 8 yr in immune complex GN; in pauci-immune GN survival was 63.2% and 54.1%, respectively (P=0.054). Risk factors for renal loss were oliguria at presentation (hazards ratio, HR 10.50; P=0.037) and need for dialysis (HR 6.33; P=0.024); there was inverse association with proportion of normal glomeruli (HR 0.91; P=0.042). Conclusions: Pauci-immune GN constitutes one-half of patients with crescentic GN at this center. Patients with pauci-immune GN, chiefly ANCA negative, show higher risk of disease progression. Renal loss is related to severity of initial presentation and extent of glomerular involvement.

Revised Guidelines on Management of Antenatal Hydronephrosis.

Widespread antenatal screening has resulted in increased detection of anomalies of the kidneys and urinary tract. The present guidelines update the recommendations published in 2000. Antenatal hydronephrosis (ANH) is transient and resolves by the third trimester in almost one-half cases. The presence of oligohydramnios and additional renal or extrarenal anomalies suggests significant pathology. All patients with ANH should undergo postnatal ultrasonography; the intensity of subsequent evaluation depends on anteroposterior diameter (APD) of the renal pelvis and/or Society for Fetal Urology (SFU) grading. Patients with postnatal APD exceeding 10 mm and/or SFU grade 3-4 should be screened for upper or lower urinary tract obstruction and vesicoureteric reflux. Infants with vesicoureteric reflux should receive antibiotic prophylaxis through the first year of life, and their parents counseled regarding the risk of urinary tract infections. The management of patients with pelviureteric junction or vesicoureteric junction obstruction depends on clinical features and results of sequential ultrasonography and radionuclide renography. Surgery is considered in patients with increasing renal pelvic APD and/or an obstructed renogram with differential renal function <35-40% or its subsequent decline. Further studies are necessary to clarify the role of prenatal intervention, frequency of follow up investigations and indications for surgery in these patients.

Disease Course in Steroid Sensitive Nephrotic Syndrome.

Objective: To review the disease course in patients with steroid sensitive nephrotic syndrome (SSNS) and the factors that determine outcome Design: Retrospective, analytical Setting: Pediatric Nephrology Clinic at referral center in North India Participants/patients: All patients with SSNS evaluated between 1990 and 2005 Intervention: None Main outcome measures: Disease course, in patients with at least 1-yr follow up, was categorized as none or infrequent relapses (IFR), frequent relapses or steroid dependence (FR), and late resistance. Details on complications and therapy with alternative agents were recorded. Results: Records of 2603 patients (74.8% boys) were reviewed. The mean age at onset of illness and at evaluation was 49.7±34.6 R E S E A R C H P A P E R INDIAN PEDIATRICS 881 VOLUME 49__NOVEMBER 16, 2012 and 67.5±37.9 months respectively. The disease course at 1-yr (n=1071) was categorized as IFR in 37.4%, FR in 56.8% and late resistance in 5.9%. During follow up, 224 patients had 249 episodes of serious infections. Alternative medications for frequent relapses (n=501; 46.8%) were chiefly cyclophosphamide and levamisole. Compared to IFR, patients with FR were younger (54.9±36.0 vs. 43.3±31.4 months), fewer had received adequate (≥8 weeks) initial treatment (86.8% vs. 81.7%) and had shorter initial remission (7.5±8.6 vs. 3.1±4.8 months) (all P<0.001). At follow up of 56.0±42.6 months, 77.3% patients were in remission or had IFR, and 17.3% had FR. Conclusions: A high proportion of patients with SSNS show frequent relapses, risk factors for which were an early age at onset, inadequate initial therapy and an early relapse.

Novel Mutations causing Hyperimmunoglobulin D and Periodic Fever Syndrome.

Hyperimmunoglobulin D and periodic fever syndrome (HIDS) is a rare, hereditary autoinflammatory condition characterized by recurrent inflammatory episodes. We report a 9-year-old boy, diagnosed with HIDS due to two novel mutations, c.62C>T (p.Ala21Val) and c.372-6T>C (probable splicing defect), in the mevalonate kinase (MVK) gene. The pathogenicity of these mutations was confirmed by measurement of low MVK enzyme activity in cultured primary skin fibroblasts of the patient. The symptoms have been refractory to therapy with steroids and non steroidal anti inflammatory drugs. This report expands the genetic and ethnic spectrum of HIDS.

Incidence of Acute Kidney Injury in Hospitalized Children.

Objective: To determine the incidence and outcome of acute kidney injury (AKI) in hospitalized patients. Design: Prospective, observational. Setting: Tertiary care center in North India. Participants/patients: Inpatients, 1 month to 18-yr-old. Intervention: None. Main Outcome Measures: Incidence of AKI based on the serum creatinine criteria proposed by the AKI Network. Results: During February to September 2008, thirty nine of 108 (36.1%) critically ill patients and 34 of 378 (9.0%) patients who were not critically ill developed AKI (P <0.001); the respective incidence densities were 45.1 and 11.7 cases/1000 patient days, respectively. The maximal stage of AKI was stage 1 in 48 (65.8%) patients, stage 2 in 13 (17.8%) and stage 3 in 12 (16.4%) patients; 11 (15.1%) required dialysis. Patients with AKI had a significantly longer duration of hospital stay (9 days vs 7 days, P<0.02) and higher mortality (37% vs 8.7%; hazard ratio, HR 2.73; 95% CI 1.64, 4.54). Independent risk factors for AKI were young age (HR 0.89; 95% CI 0.83, 0.95), shock (HR 2.65; 95% CI 1.32, 5.31), sepsis (HR 3.64; 95% CI 2.20, 6.01), and need for mechanical ventilation (2.18; 95% CI 1.12, 4.26). Compared to patients without AKI, the mortality was higher for AKI stage 2 (HR 5.18; 95% CI 2.59, 10.38) and stage 3 (HR 4.34; 95% CI 2.06, 9.16). Shock was an independent risk factor for mortality (HR 10.7; 95% CI 4.96, 22.98). Conclusions: AKI is common in critically ill children, especially younger patients with septicemia and shock, and results in increased hospital stay and high mortality.

Vitamin D deficiency in healthy breastfed term infants at 3 months & their mothers in India: Seasonal variation & determinants.

Background & objectives: Vitamin D deficiency with a resurgence of rickets and tetany are increasingly being reported in young infants from temperate regions, African Americans and also from India. The data on vitamin D status of healthy term breastfed Indian infants and mothers are scant. Therefore, we undertook this study to determine the prevalence of vitamin D deficiency and insufficiency [serum 25 hydroxyvitamin D (25OHD) ≤ 15 ng/ml and 15-20 ng/ml, respectively] among healthy term breastfed 3 month old infants and their mothers, evaluate for clinical and radiological rickets in those infants having 25OHD < 10 ng/ml, and check for seasonal variation and predictors of infants’ vitamin D status. Methods: A total of 98 infants aged 2.5 to 3.5 months, born at term with appropriate weight and their mothers were enrolled; 47 in winter (November- January) and 51 in summer (April-June). Details of infants’ feeding, vitamin D supplementation, sunlight exposure and mothers’ calcium and vitamin D intake were recorded. Serum calcium, phosphate, alkaline phosphatase, 25 hydroxyvitamin D (25OHD) and parathormone were estimated. Results: Vitamin D deficiency was found in 66.7 per cent of infants and 81.1 per cent of mothers; and insufficiency in an additional 19.8 per cent of infants and 11.6 per cent of mothers. Radiological rickets was present in 30.3 per cent of infants with 25OHD < 10 ng/ml. 25OHD did not show seasonal variation in infants but maternal concentrations were higher in summer [11.3 (2.5 - 31) ng/ml] compared to winter [5.9 (2.5-25) ng/ml, P=0.003]. Intake of vitamin supplement, sunlight exposure and mother’s 25OHD were predictors of infants’ 25OHD levels. Interpretation & conclusions: Prevalence of vitamin D deficiency and insufficiency was found to be high in breastfed infants and their mothers, with radiological rickets in a third of infants with 25OHD < 10 ng/ml in this study. Studies with large sample need to be done in different parts of the country to confirm these findings.

Post obstructive pulmonary edema in a child who attempted suicidal hanging.

Postobstructive pulmonary edema occurs rarely in children. We describe here a child who attempted suicide by hanging and developed postobstructive pulmonary edema and was successfully managed. There was a rapid response to management with morphine and supportive care, enabling extubation by 30 hours of ventilatory support. The case highlights an unusual cause of postobstructive pulmonary edema.

Pulse steroid therapy.

Intravenous supra-pharmacological doses of corticosteroids are used in various inflammatory and autoimmune conditions because they are cumulatively less toxic than sustained steroid treatment at lower quantitative dosage. Their action is supposed to be mediated through non-genomic actions within the cell. Common indications for use in children include steroid resistant and steroid dependent nephrotic syndrome, rapidly progressive glomerulonephritis, systemic vasculitis, systemic lupus erythematosus, acute renal allograft rejection, juvenile rheumatoid arthritis, juvenile dermatomyositis, pemphigus, optic neuritis, multiple sclerosis and acute disseminated encephalomyelitis. Methylprednisolone and dexamethasone show similar efficacy in most conditions. Therapy is associated with significant side effects including worsening of hypertension, infections, dyselectrolytemia and behavioral effects. Adequate monitoring is essential during usage.

Evaluation of renal tubular acidosis.

Renal tubular acidoses (RTA) comprises of a group of disorders characterized by a low capacity for net acid excretion and persistent hyperchloremic, metabolic acidosis. The RTAs are classified into chiefly three types (types 1,2 and 4) based on clinical and laboratory characteristics. Correct diagnosis involves careful evaluation, including exclusion of other entities causing acidosis. A variety of tests are required to be administered in a stepwise fashion for the diagnosis and characterization of RTA.

Bruck syndrome.

The combination of arthrogryposis multiplex congenita and osteogenesis imperfecta is extremely rare. This combination is named Bruck syndrome. A 34 week male baby weighing 1.7 kg at birth was noted to have multiple flexion contractures and pterygia at elbows, wrists and knees, in addition to right foot talipes equinovarus deformity. Postnatally the child developed multiple swellings involving both the upper and lower limbs. A plain radiograph revealed the presence of fractures involving the long bones of the upper and lower limbs. A diagnosis of osteogenesis imperfecta with arthrogryposis multiplex congenita was made, and the patient was labeled as a case of Bruck Syndrome. The aim of this report is to make the readers aware regarding this rare entity and to specifically look for presence of features suggestive of osteogenesis imperfecta when encountered with a neonate born with arthrogryposis multiplex congenita.