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Acute kidney injury (AKI) is common in critically ill patients, affecting 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 fluid 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 significant 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., (© 2023. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Objectives: To examine the feasibility, efficacy, and safety of sustained low-efficiency dialysis (SLED) in hemodynamically unstable, critically ill children., Methods: Critically ill patients, 1-18 y old with hemodynamic instability (≥ 1 vasoactive drugs) and severe acute kidney injury (AKI) requiring kidney replacement therapy (KRT) in a tertiary care pediatric intensive care unit were prospectively enrolled. Patients weighing ≤ 8 kg or with mean arterial pressure < 5 th percentile despite > 3 vasoactive drugs, were excluded. Patients underwent SLED until hemodynamically stable and off vasoactive drugs, or lack of need for dialysis. The primary outcome was the proportion of patients in whom the first session of SLED was initiated within 12 h of its indication and completed without premature (< 6 h) termination. Efficacy was estimated by ultrafiltration, urea reduction ratio (URR), and equilibrated Kt/V. Other outcomes included: changes in hemodynamic scores, circuit clotting, adverse events, and changes in indices on point-of-care ultrasonography and echocardiography., Results: Between November 2018 and March 2020, 18 patients with median age 8.6 y and vasopressor dependency index of 83.2, underwent 41 sessions of SLED. In 16 patients, SLED was feasible within 12 h of indication. No session was terminated prematurely. Ultrafiltration achieved was 4.0 ± 2.2 mL/kg/h, while URR was 57.7 ± 16.2% and eKt/V 1.17 ± 0.56. Hemodynamic scores did not change significantly. Asymptomatic hypokalemia was the chief adverse effect. Sessions were associated with a significant improvement in indices on ultrasound and left ventricular function. Fourteen patients died., Conclusions: SLED is feasible, safe, and effective in enabling KRT in hemodynamically unstable children with severe AKI., (© 2022. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Guidelines recommend initiating supplemental enteral feeding through a nasogastric (NG) or gastrostomy tube (G-tube) in patients with chronic kidney disease who have inadequate oral intake despite repeated nutritional counseling. While G-tube placement is shown to improve both nutritional status and anthropometric indices of children with CKD in developed regions, information from developing countries is lacking. This retrospective report reviewed the impact of G-tube feeding on nutritional intakes and anthropometric parameters over a 1-y follow-up in 5 children with CKD-5D managed at one tertiary care center in India. Gastrostomy feeding facilitated significant increments in caloric and protein intake and was easy and safe. However, G-tube feeding led to additional expenses, and the changes in growth parameters were variable in the short term. A longer follow-up appears necessary to understand its impact on wasting, growth velocity, and stature., (© 2023. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

The present paper reports 10 patients (9 families) with Fanconi-Bickel syndrome managed during 2010-2021. Patients presented with polyuria, polydipsia, hepatomegaly, rickets, and stunting at a median of 5 (3, 7.3) mo; one had transient neonatal diabetes. Glucosuria, generalized aminoaciduria, β 2 -microglobinuria, urinary phosphate wasting, and hypercalciuria were present in all patients; 3 patients had nephrocalcinosis. Other metabolic abnormalities included hypertriglyceridemia (n = 5/6), fasting hypoglycemia (n = 5/8), and postprandial hyperglycemia (n = 3/6). Genetic analysis showed 7 homozygous or compound heterozygous variants in SLC2A2. A pathogenic variant c.952G>A, common to 4 patients (3 families), might be a potential hotspot. At a median follow-up of 43 mo, 4 patients died at a median of 25 mo; short stature persisted in all except one patient who showed catch-up growth with uncooked corn-starch diet. The present findings suggest that the Fanconi-Bickel syndrome has a severe phenotype with an unsatisfactory outcome. A high index of suspicion for diagnosis and efforts for facilitation of dietary therapy are necessary., (© 2022. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Objective: To evaluate metabolic and genetic abnormalities in children with nephrolithiasis attending a referral center in North India., Methods: The patients aged 1-18 y old with nephrolithiasis underwent biochemical evaluation and whole-exome sequencing. The authors evaluated for monogenic variants in 56 genes and compared allele frequency of 39 reported polymorphisms between patients and 1739 controls from the GenomeAsia 100 K database., Results: Fifty-four patients, aged 9.1 ± 3.7 y were included. Stones were bilateral in 42.6%, familial in 33.3%, and recurrent in 25.9%. The most common metabolic abnormalities were hypercalciuria (35.2%), hyperoxaluria (24.1%), or both (11.1%), while xanthinuria (n = 3), cystinuria (n = 1), and hyperuricosuria (n = 1) were rare. Exome sequencing identified an etiology in 6 (11.1%) patients with pathogenic/likely pathogenic causative variants. Three variants in MOCOS and one in ATP7B were pathogenic; likely pathogenic variants included MOCOS (n = 2), AGXT, and SLC7A9 (n = 1, each). Causality was not attributed to two SLC34A1 likely pathogenic variants, due to lack of matching phenotype and dominant family history. Compared to controls, allele frequency of the polymorphism TRPV5 rs4252402 was significantly higher in familial stone disease (allele frequency 0.47 versus 0.53; OR 3.2, p = 0.0001)., Conclusion: The chief metabolic abnormalities were hypercalciuria and hyperoxaluria. A monogenic etiology was identified in 11% with pathogenic or likely pathogenic variants using a gene panel for nephrolithiasis. Heterozygous missense variants in the sodium-phosphate cotransporter SLC34A1 were common and required evaluation for attributing pathogenicity. Rare polymorphisms in TRPV5 might increase the risk of familial stones. These findings suggest that a combination of metabolic and genetic evaluation is useful for determining the etiology of nephrolithiasis., (© 2022. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Data on the effect of vitamin D supplementation on fibroblast growth factor 23 (FGF23), in chronic kidney disease (CKD) are scarce. In a prospective interventional study, the effect of vitamin D supplementation on cFGF23 (C-terminal FGF23) levels in children with CKD stages 2-4 was examined. Forty-one children with CKD and vitamin D insufficiency were administered 600,000 units of cholecalciferol over 3 d; 88% of patients achieved sufficiency at 8 wk. Significant increase in serum cFGF23 and phosphate levels was observed in CKD stage 2 after supplementation, but not in CKD stages 3 and 4. There was no correlation of the change in cFGF23 level with baseline or change in bone health parameters (calcium, phosphate, parathormone or alkaline phosphatase) or with change in flow-mediated dilatation (FMD) of the brachial artery. It is concluded that cholecalciferol supplementation increases serum calcium and reduces PTH, but does not adversely affect FGF23 levels in CKD., (© 2022. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Objective: Severe edema in children with nephrotic syndrome is often refractory to conventional diuretics. Tolvaptan has been used satisfactorily for managing edema in patients with heart failure and cirrhosis. The safety and efficacy of combination therapy with oral tolvaptan and intravenous (IV) furosemide was assessed in patients with furosemide refractory edema., Methods: Patients, aged 5-18 y with nephrotic syndrome and severe edema, were screened for eligibility. After excluding hypovolemia, patients received IV furosemide (3-4 mg/kg/d) for 48 h. Those refractory to IV furosemide (weight loss < 3%) received tolvaptan (0.5-1 mg/kg once daily) and IV furosemide for the next 48 h. Parameters were compared between 48 h of furosemide alone and combination therapy., Results: A total of 24 patients (18 boys) with mean age of 8.0 ± 3.0 y were enrolled. Urine volume significantly increased with combination therapy as compared to furosemide therapy (mean difference: 1.2 mL/kg/h; 95% CI: 0.8-1.65 mL/kg/h) (p < 0.001). Compared to therapy with furosemide alone, combination therapy resulted in significant reduction in body weight from 26.9 ± 10.3 kg to 24.8 ± 9.7 kg (p < 0.001). Estimated glomerular filtration rate did not change (p = 0.81) but serum sodium increased from 135.7 ± 3.3 mEq/L to 140.4 ± 4.8 mEq/L (p < 0.001) with combination therapy; 2 patients showed asymptomatic hypernatremia., Conclusion: The combination of oral tolvaptan and IV furosemide is effective in augmenting diuresis and reducing weight in patients with furosemide refractory edema but requires monitoring of electrolytes and volume status., (© 2021. Dr. K C Chaudhuri Foundation.)

Mycoplasma-induced rash and mucositis (MIRM), has been recently distinguished as an entity distinct from the spectrum of Steven-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). It is characterized by a younger age of onset, predominant mucosal lesions and sparse skin involvement, in contrast to widespread cutaneous lesions in TEN/SJS. While therapy with azithromycin and a short course of corticosteroids suffices in the majority of cases, intravenous immunoglobulin and cyclosporine may be useful in refractory cases. The authors report a 6-y-old girl with mucopurulent conjunctivitis, hemorrhagic oral mucosal crusting, maculopapular skin rash, and positive serology for Mycoplasma pneumoniae. The girl recovered following therapy with azithromycin and oral prednisolone. The index case is instructive in highlighting a rare complication of a common infection, and delineates the importance of clinical suspicion and a systematic approach to evaluation and management of MIRM in patients with unusual mucosal lesions and skin rash., (© 2021. Dr. K C Chaudhuri Foundation.)

Monogenic defects in tubular sodium handling contribute a small proportion to hypertension in childhood. Presentation varies from severe hypertension manifesting at birth to asymptomatic hypertension and hypokalemic metabolic alkalosis detected incidentally in adulthood. A 12-y-old girl presenting with polyuria, polydipsia, severe hypertension and seizures, was found to have hypokalemia, renal medullary cysts and nephrocalcinosis. Clinical exome revealed a homozygous variation of unknown significance in exon 5 of the HSD11B2 gene, indicating the diagnosis of apparent mineralocorticoid excess. Therapy with spironolactone was associated with resolution of hypokalemia and normal blood pressure during two-year follow up.

Renal tubular acidosis (RTA) comprises a group of disorders characterized by low capacity for net acid excretion and persistent hyperchloremic metabolic acidosis, despite preserved glomerular filtration rate. RTA are classified into chiefly three types (1, 2 and 4) based on pathophysiology and clinical and laboratory characteristics. Most patients have primary RTA that presents in infancy with polyuria, growth retardation, rickets and/or hypotonia. Diagnosis requires careful evaluation, including exclusion of other entities that can cause acidosis. A variety of tests, administered stepwise, are useful for the diagnosis and characterization of RTA. A genetic or acquired basis can be determined in majority of patients through focused evaluation. Management involves correction of acidosis and dyselectrolytemia; patients with proximal RTA with Fanconi syndrome and rickets require additional supplements of phosphate and vitamin D.

Fibroblast growth factor-23 (FGF23) is central to phosphate homeostasis. The author examined if blood levels of FGF23 allow discrimination of classic hypophosphatemic rickets from other causes of non-nutritional rickets with hypophosphatemia. Forty-two children (median age: 102 mo) with non-nutritional rickets and hypophosphatemia were clinically classified as having distal renal tubular acidosis (RTA, n = 12), Fanconi syndrome (n = 8), classic hypophosphatemic rickets (n = 11), vitamin D dependent rickets (n = 7) and Dent disease (n = 4). Median blood FGF23 (measured by C-terminal ELISA) concentrations were similar in all groups (P = 0.24). These levels did not correlate with phosphate, tubular maximum for phosphate, calcium, 25-hydroxyvitamin D, creatinine, and parathormone levels. Patients with distal RTA showed variable degree of proximal tubular dysfunction that resolved following alkali supplements. Blood FGF23 levels did not satisfactorily differentiate classic hypophosphatemic rickets from other causes of hypophosphatemic rickets.

Objectives: To screen patients with frequently relapsing nephrotic syndrome (FRNS) for the presence of ambulatory hypertension and left ventricular hypertrophy., Methods: Following ethical and parental approvals, consecutive patients with FRNS of ≥2 y duration were enrolled. Those with estimated glomerular filtration rate <60 ml/min/1.73 m 2 and known familial hypercholesterolemia or diabetes mellitus were excluded. Clinic blood pressure was measured by oscillometry and 24-h ambulatory blood pressure was recorded by Spacelab 90207; echocardiography was done for left ventricular mass. Ambulatory hypertension was defined as the presence of clinic blood pressure >95th centile for age, sex and height, and systolic blood pressure load exceeding 25 %., Results: Of 99 patients, 73 were boys; their median (IQR) age was 120 (84-156) mo. Clinic blood pressure was >95th percentile in 63 (63.6 %) patients. Ambulatory hypertension was present in 33 (33.3 %), including 14 patients with severe hypertension; 16 (16.1 %) had masked hypertension and 30 (30.3 %) had white coat hypertension. Non-dipping was seen in 72 and 55 patients had high nocturnal systolic blood pressure load. Of 21 patients with increased left ventricular mass index, 9 (42.9 %) had ambulatory hypertension, 3 (14.3 %) had masked hypertension and 6 (28.6 %) patients had white coat hypertension. Compared to those with normal blood pressure, patients with ambulatory hypertension were younger at onset of nephrotic syndrome (odds ratio, OR 0.94; 95 % CI 0.91-0.98; P = 0.002), longer duration of frequently relapsing disease (OR 1.05; 95 % CI 1.00-1.10; P = 0.034) and higher body mass index (BMI) (OR 1.61; 95 % CI 1.07-4.40; P = 0.020). BMI was positively correlated with 24-h systolic blood pressure load (r = 0.23; P = 0.002) and with the left ventricular mass index (r = 0. 57; P = 0.001)., Conclusions: Many patients with FRNS showed high prevalence of clinic, ambulatory and white coat hypertension, emphasizing the need to carefully screen these patients in order to ensure their appropriate management. While clinic blood pressure monitoring detects most patients with hypertension, it misses a significant proportion with masked hypertension, underscoring the need for ambulatory blood pressure monitoring and screening for end organ damage. High BMI was the chief risk factor for hypertension, suggesting that control of overweight and hypertension might improve cardiovascular outcomes.

The authors report a case of congenital chloride diarrhea with molecular confirmation of diagnosis. A 10-mo-old boy presented with failure to thrive, voluminous diarrhea, dehydration, hyponatremia, hypokalemia, metabolic alkalosis and history of maternal polyhydramnios. The diagnosis of congenital chloride diarrhea was based on high fecal and low urinary chloride excretion, in addition to biochemical abnormalities. Genetic testing revealed a novel homozygous mutation in exon 4 of the SLC26A3 gene that encodes the protein regulating chloride bicarbonate absorption in distal ileum and colon. Therapy with oral fluids and electrolytes led to decrease in stool frequency and improvement in growth parameters.

Information on provision of continuous renal replacement therapy (CRRT) in critically ill children from developing countries is limited. The authors describe their experience in 17 children with hypotension and acute kidney injury (AKI) with fluid overload or electrolyte imbalance managed by 20 sessions of CRRT. The median (range) age and weight were 6 y (0.75-18) and 20 kg (6.2-42), respectively. All patients were receiving inotropic agents; nine had fluid overload (19 %, range 11-34.1 %) and ten had severe AKI. Median clearance and filter-life were 2171.4 ml/1.73 m(2)/h (1730.6-4405.8) and 69.7 h (2.8-98.3), respectively. Complications were catheter flow related (n = 1), filter clotting (n = 3), hemorrhage (n = 3), hypokalemia (n = 16) and hypophosphatemia (n = 11). Eight patients (47.1 %) survived; the median PRISM III score of survivors was significantly lower than non survivors (10.5 vs.17.0; P 0.02). Renal function recovered in the survivors emphasizing the role of this modality in managing critically ill patients.

The pathogenetic basis of idiopathic nephrotic syndrome, a common childhood glomerulopathy, is being explored. While initial evidence supported an imbalance of T helper responses, recent studies suggest alterations in both innate and adaptive immune responses, including evidence for impaired T regulatory function. The central role of the podocyte in causing proteinuria is confirmed by the observation of mutations in key podocyte proteins in steroid resistant nephrotic syndrome and experimental evidence of altered podocyte signaling and cytoskeletal organization. The outcome and management of idiopathic nephrotic syndrome in children is determined by the response to corticosteroids and the frequency of relapses. While patients with steroid sensitive nephrotic syndrome have a favorable long term outcome, almost half of them relapse frequently and are at risk of adverse effects of corticosteroids. Although various non-corticosteroid immunosuppressive agents are used to prolong disease remission, careful monitoring is required for the potential adverse effects. Calcineurin inhibitors have emerged as the choice of therapy in patients with steroid resistant nephrotic syndrome. However, the management of this form of the disease is particularly challenging because of the variable response to immunosuppression, therapy-related significant adverse effects and high rates of disease progression to end stage renal disease. Patients with both corticosteroid sensitive and resistant forms of the disease are at risk of complications of disease, and require close monitoring and repeated counseling.

The authors present their experience with therapeutic plasmapheresis (TPE) using membrane filters at the pediatric dialysis unit of a referral center. Between January 2006 and December 2010, 486 sessions of TPE were performed in 39 patients (range 6-17 y), chiefly for atypical hemolytic uremic syndrome (HUS, n = 22), crescentic glomerulonephritis (n = 8) and focal segmental glomerulosclerosis (n = 5). Satisfactory response was noted in 32 patients, particularly with HUS (n = 22) or crescentic glomerulonephritis (n = 6). Adverse effects included chills or urticaria (n = 8 sessions), hypocalcemia (n = 6) and hypotension (n = 5). The present findings highlight the safety, efficacy and feasibility of TPE using membrane filtration.

Hypertensive emergencies, though uncommon in children, are potentially life threatening. While targeting blood pressure reduction to below the 90th percentile for age, gender and height, mean arterial blood pressure should be gradually lowered by one-fourth of the planned reduction over 8-12 h, a further fourth over the next 8-12 h, and the final 50% over the 24 h after that. Frequent invasive or non-invasive blood pressure monitoring is essential, as is monitoring for sensorial alteration and loss of papillary reflexes. Few antihypertensive agents have been examined in children. Continuous intravenous infusions of short acting drugs such as nitroprusside, labetalol and nicardipine are preferred to intravenous boluses of hydralazine or diazoxide. If severe symptoms are absent, oral agents such as nifedipine, clonidine, minoxidil, hydralazine, labetalol, captopril, and prazosin may be used. Nicardipine and labetalol are particularly suited in emergencies with intracranial bleeding or ischemic stroke, while furosemide, sodium nitroprusside and nitroglycerine are useful in congestive cardiac failure. Therapy with oral antihypertensive drugs should be instituted within 6-12 h of parenteral therapy, and the latter gradually withdrawn over the next 12-48 h. Oral agents have limited application as primary therapy, except when administration of intravenous infusion is likely to be delayed. This article provides a summary of the clinical approach to evaluation and management of severe symptomatic hypertension in children.

Diabetic ketoacidosis (DKA), a life-threatening complication of diabetes mellitus (DM), occurs more commonly in children with type 1 DM than type 2 DM. Hyperglycemia, metabolic acidosis, ketonemia, dehydration and various electrolyte abnormalities result from a relative or absolute deficiency of insulin with or without an excess of counter-regulatory hormones. Management requires careful replacement of fluid and electrolyte deficits, intravenous administration of insulin, and close monitoring of clinical and biochemical parameters directed towards timely detection of complications, including hypokalemia, hypoglycemia and cerebral edema. Cerebral edema may be life threatening and is managed with fluid restriction, administration of mannitol and ventilatory support as required. Factors precipitating the episode of DKA should be identified and rectified. Following resolution of ketoacidosis, intravenous insulin is transitioned to subcutaneous route, titrating dose to achieve normoglycemia.

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.

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.

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.

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.