Kanika Kapoor

Endothelial dysfuntion in children with idiopathic nephrotic syndrome

BACKGROUND Impaired endothelial function is the initial step in atherogenesis, which is largely responsible for ischaemic heart disease and thrombotic strokes decades later. METHODS Fourty two children with first episode nephrotic syndrome (FENS) aged 1-16 years and 40 controls were enrolled. Soluble thrombomodulin (sTM), tissue plasminogen activator (t-PA), plasminogen activator inhibitor -1 (PAI-1) and von-willebrand factor (vWF) levels were measured in plasma in FENS, at 12 weeks of drug induced remission and in steroid resistant nephrotic syndrome (SRNS) patients at diagnosis. RESULTS PAI-1, sTM, vWF and t-PA were significantly raised at the onset of nephrotic syndrome (p<0.0001). All the markers had a fall after 12 weeks of steroid treatment, but were still raised. Children with SRNS had higher levels of sTM, tPA, vWF as compared to infrequent relapsers, at onset and at 4 weeks of steroid treatment. CONCLUSION Children with idiopathic nephrotic syndrome have endothelial dysfunction which is largely dependent upon disease activity.

Kawasaki shock syndrome presenting as toxic shock syndrome

Dear Editor, Kawasaki disease (KD) is an acute self-limiting vasculitis of childhood and is misdiagnosed very frequently as toxic shock syndrome (TSS) due to its varied presentation. We report a child presenting as TSS but with saccular aneurysms in the coronaries, later confirmed as Kawasaki shock syndrome. A 13-year-old girl presented to us with high-grade fever of 6 days, swelling at the right side of the neck and redness of the eyes of 3 days and vomiting and rash over the body over the last day. On examination, the child was febrile, had tachycardia (pulse rate 164/min) with low volume pulse; tachypnea (respiratory rate 28/min) and hypotension (blood pressure 82/46 mmHg). The child had generalized edema with a confluent erythematous rash over the neck, trunk and upper extremities, involving the palms. A firm, non-tender and erythematous swelling was noticed in the right anterior cervical triangle measuring 2.0 9 2.0 cm. Bilateral non-exudative bulbar conjunctivitis was present with dry and cracked lips and diffuse non-exudative injection of oral and pharyngeal mucosa. The child had meningeal signs with the rest of the systems being unremarkable. There was presence of neutrophilic leukocytosis (total leukocyte count 12 600/mm with 90% neutrophils). Erythrocyte sedimentation rate (ESR) was raised and the child had a positive C-reactive protein (10 mg/dL) and a normal blood culture. The liver function, electrolytes, kidney function tests and lumbar puncture were all unremarkable. A provisional diagnosis of septic shock was made and fluid resuscitation and antibiotics were started. In view of fluid-resistant shock, dopamine was started at 10 lg/kg/min. Electrocardiogram showed sinus tachycardia with short QRS complexes and non-specific ST segment depression. Urgent echocardiography showed diffusely hypokinetic myocardium with ejection fraction of 48% and minimal pericardial effusion (0.73 cm posteriorly). In view of echocardiography suggesting myocarditis, dobutamine was also started (10 lg/kg/min). The child was further investigated with contrast-enhanced computed tomography (CECT) neck showing unilateral multiple enlarged lymph nodes with the largest being 2.0 9 1.5 cm, along with inflamed subcutaneous tissue. Repeat echocardiography after 10 days showed a saccular aneurysm of 6.0 mm in the right coronary artery (RCA) with an internal diameter of artery of 4.0 mm and left anterior descending artery of 3.5 mm (Fig. 1). There was impairment in relaxation as evidenced by the depressed E wave velocity/A wave velocity. Based on the clinical and laboratory evaluation, a final diagnosis of Kawasaki disease shock syndrome (KDSS) was made, although the clinical presentation initially mimicked staphylococcal TSS. The presence of saccular aneurysm in the RCA in this case strongly pointed out the diagnosis. Intravenous immunoglobulin (IVIG) was given at 0.4 g/kg for 5 days along with high-dose aspirin at 80–100 mg/kg/day every 6 h until 14 days of illness, followed by 3–5 mg/kg/day for 6–8 weeks. The patient responded to the treatment and was discharged on day 16 post-onset. Follow-up echocardiography after 6 weeks showed resolution of coronary aneurysms with internal diameter of RCA of 3.6 mm and left anterior descending artery of 2.3 mm along with normal E wave velocity/A wave velocity. Kawasaki disease is an important cause of childhood morbidity. It was recently recognized that up to 20% of patients with KD have incomplete disease (fever with less than four of the required diagnostic criteria) and present without fulfilling the clinical criteria. KDSS is defined on the basis of systolic hypotension for age, a sustained decrease in systolic blood pressure from baseline of ≥ 20%, or clinical signs of poor perfusion. Features like myocarditis (40%), systolic dysfunction (20%) and aseptic meningitis (5–10%) were seen in our child. G amez-Gonz alez et al. recently reported higher incidence of gastrointestinal manifestations, incomplete presentation, IVIG resistance, and worse cardiac outcomes in patients with KDSS.

Proteinuria in HIV-infected Indian children.

Chronic kidney disease (CKD) is a major cause of morbidity and mortality among individuals with HIV infection. Screening for proteinuria in HIV-infected children will help in early detection and treatment, and thus prevention and progression to CKD to end-stage kidney disease (ESRD). We screened 139 HIV-infected children aged 18 months to 18 years for proteinuria by urinary dipstick and confirmed by spot urine protein-to-creatinine ratio. If proteinuria was absent by the above methods, patients were screened for microalbuminuria by urinary albumin to creatinine ratio. We found proteinuria in 11.5% and microalbuminuria in 10.6% of our study population. The prevalence of proteinuria was higher in the advanced stages; 8.05% in stage 1, 12.12% in stage 2 and 26.32% in stages 3 + 4.

Mycophenolate sodium for children with frequently relapsing or steroid dependent nephrotic syndrome

In this retrospective study, patients with idiopathic frequentlyrelapsing nephrotic syndrome (FRNS) (n=27) and steroid dependent nephrotic syndrome (SDNS) (n=13) who received enteric coated mycophenolate sodium (ECMS) for at least 6 months, were included for analysis. Primary outcome was response to ECMS, which was defined as complete if there were no relapses, partial response if there was 1 relapse and no response if there were 2 or more relapses within 6 months of initiation. The mean (SD) dose of ECMS was 985.24 (190.82) mg/m2/day. Thirty patients(75%) had complete response, eight (20%) had partial and two (5%) patients did not respond at 6 months. ECMS seems to be a safe and effective as steroid sparing agent in children with FRNS/SDNS.

Meningitis and intracranial bleed in a child with steroid-resistant nephrotic syndrome

Meningitis and associated intracranial bleeding have been rarely reported in patients with steroid-resistant nephrotic syndrome. We present such a case with raised intracranial tension in a 13-year-old child and discuss the management issues. Prompt recognition and appropriate treatment of these complications can be life saving in a child with nephrotic syndrome.

Hypercalcemic crisis in the pediatric emergency department: Answers

A 13-month-old boy presented to the emergency department with failure to thrive, excessive irritability, recent onset polyuria, polydipsia and severe hypercalcemia of uncertain etiology. The child was evaluated for causes of hypercalcemia. Undetectable parathyroid hormone (PTH) and normal serum phosphorus levels ruled out a diagnosis of primary hyperparathyroidism. Despite there being a history of failure to gain weight for last 3 months, counts were normal, and there was no lymphadenopathy or hepatosplenomegaly. Hence, malignancy as a cause of hypercalcemia was less likely. Alkaline phosphatase levels were at the upper limit of normal and a history of failure to gain weight prompted us to consider pa raneop las t i c syndromes l ike neurob las toma , hepatoblastoma, among others. No abdominal mass was detected during the clinical examination, and ultrasonography of the abdomen also did not reveal any such abnormality. Moreover, 1,25(OH)-vitamin D and parathyroid hormone-related protein (PTHrP) levels were subsequently reported to be normal. There was no contact history of tuberculosis, and a chest X-ray did not reveal any evidence of sarcoidosis or tuberculosis. There was no family history of kidney stones or disease. The patient had hypercalciuria and low PTH levels, thereby eliminating the possibility of familial hypocalciuric hypercalcemia as this is an autosomal dominant condition with a mutation in the calcium-sensing receptor gene (CASR) and the patients were found to have normal or increased PTHwith a low urine calcium:creatinine ratio [1]. Within 4 days of admission, laboratory test results for vitaminD, A and E levels became available. Vitamin A and E levels were normal, but 25(OH)-vitamin D levels were markedly elevated (>450 ng/ml), suggesting that the child had probably received intramuscular vitamin D injections followed by oral calcium and vitamin D supplements, which was confirmed later. Based on the medical history and clinical and biochemical evidence, the child was diagnosed with hypervitaminosis D. The parents were instructed to restrict dairy products and use sunscreen. Intravenous hydrocortisone was replaced by oral prednisolone at a dose of 1.5 mg/kg/day. The dose was tapered gradually and stopped after 3 weeks of treatment. At discharge, his 25(OH)-vitamin D level was 454 ng/mL and his total calcium concentration was 10.8 mg/dl.

Soft‐tissue calcinosis in an infant

A 4-month-old female child presented with generalised swelling and decreased urine output for 5 days. On examination, she was hypertensive and had firm non-tender swelling of left elbow. X-ray of the left upper extremity showed soft-tissue calcifications (Fig. 1). Laboratory investigations were suggestive of renal failure. Ultrasound examination revealed increased echogenicity in bilateral kidneys. The child was started on peritoneal dialysis; however, uraemia persisted. Urinary oxalate levels were 340 mg/1.73 m per 24 h (normal <40 mg/1.73 m/ 24 h). Percutaneous renal biopsy was done, which revealed tubules with extensive injury in the form of lowering of epithelium and deposition of highly polarisable retractile crystals lying within the tubular epithelial cells (Fig. 2). What is the diagnosis? (Answer on page 563)

Should all nephrotics with thyroid dysfunction be treated with levothyroxine

Sirs, We read with interest the recently published study in Pediatric Nephrology titled “Steroids combined with levothyroxine to treat children with idiopathic nephrotic syndrome (NS): a retrospective single-centre study,” by Guo et al. [1]. In their retrospective study, 73 of 164 nephrotic children had thyroid dysfunction, of who 40 were treated with steroids and levothyroxine. First, the authors observed that time to proteinuria remission was significantly shorter in the levothyroxine plussteroid group than in the group treated with steroids alone (21.05±11.00 vs 26.67±11.82, p<0.05). However, the mean time to remission in either group was much longer than that observed in most studies. This was probably due to the inclusion of both steroid-sensitive NS (SSNS) and steroid-resistant NS (SRNS) patients in a single group in the present study. Second, subclinical hypothyroidism is defined as a state of increased serum thyroid-stimulating hormone (TSH) concentration, with circulating thyroxine and triiodothyronine (TT3) within the population reference range [2]. Forty-four percent of patients were reported to have subclinical hypothyroidism. In groups A and B, there were 25 cases of low T3 syndrome (low TT3 and normal TSH), 11 cases of low T4 syndrome [low total thyroxine (TT4) and normal TSH], 27 cases of hypothyroxinemia (low TT3 and TT4 but normal TSH), and ten cases of hypothyroidism [low free thyroxine/free triiodothyronine (FT3/FT4) and high TSH]. None of the categories of thyroid dysfunction had increased TSH and normal T3/T4. Third, subclinical hypothyroidism is known to be due to reduced glomerular filtration rate (GFR), and as GFR decreases, there is further decrease of thyroid hormones levels. Guo et al. did not mention estimated GFR (eGFR) of the patients in their study, whichmay confound their results [1]. Finally, decrease in thyroid hormones and increase in TSH is transient in patients with SSNS, and they return to normal on remission; however, this may be persistent in patients with congenital NS and those with SRNS due to massive prolonged proteinuria [3]. We studied thyroid functions in 20 children with SRNS (14 in complete remission and six in partial remission) and found six of them to have nonautoimmune subclinical hypothyroidism [3]. Four of six children with grade 2–3 subclinical hypothyroidism received thyroid hormone replacement therapy, and levels of TSH normalized in all patients on therapy. In conclusion, thyroxine replacement therapy in children with SSNS who have proteinuria for a short duration (i.e., 2– 3 weeks) may not prove beneficial in terms of the transient nature of thyroid dysfunction. The final answer would come from a double-blind placebo-controlled trial on carefully selected patient groups.

Hypercalcemic crisis in the pediatric emergency department: Questions

A 13-month-old boy presented to our pediatric emergency department with failure to gain weight for the past 3 months. He had had excessive irritability, anorexia, polyuria, and polydipsia for the last 20 days. His mother also complained that the child cries excessively during micturition. He had not passed stools for 3 days and had several episodes of nonbilious vomiting 6 h before admission. He was born at term by caesarean section (indication—oligohydramnios). Infantile course was uneventful. He had received intramuscular injections weekly along with oral medications daily for the past 10 weeks prescribed by a general physician with no documentation of the treatment received.

Percutaneous renal biopsy in children: Are British Association of Pediatric Nephrology standards achievable?

1. Meulen ST, van Donselaar‐van der Pant KA, Bemelman FJ, Idu MM. Chylous ascites after laparoscopic hand‐assisted donor nephrectomy: Is it specific for the left‐side? Urol Ann 2013;5:45‐6. 2. Bachmann A, Ruszat R, Dickenmann M, Giannini O, Mayr M, Steiger J, et al. Chyloretroperitoneum with secondary chylothorax after retroperitoneoscopic donor nephrectomy. Urology 2005;66:881. 3. Aerts J, Matas A, Sutherland D, Kandaswamy R. Chylous ascites requiring surgical intervention after donor nephrectomy: Case series and single center experience. Am J Transplant 2010;10:124‐8. 4. Chan EH, Russell JL, Williams WG, Van Arsdell GS, Coles JG, McCrindle BW. Postoperative chylothorax after cardiothoracic surgery in children. Ann Thorac Surg 2005;80:1864‐70.