Arife Uslu Gokceoglu

Assessment of left ventricular function by tissue Doppler echocardiography in pediatric chronic kidney disease

Abstract Background: Cardiovascular (CV) disease remains the most common cause of mortality in chronic kidney disease (CKD). Methods: In this cross-sectional study, 43 pediatric patients with CKD were divided into two groups according to their estimated glomerular filtration rate (eGFR): groups 1 and 2 (eGR; 29–75 and 15–29 mL/min/1.73 m2, respectively). M – mode, conventional pulsed wave Doppler (cPWD) echocardiography and tissue Doppler imaging (TDI) were performed in all patients and 16 healthy controls. Maximal early (E wave) and late (A wave) diastolic flow velocities were assessed by cPWD. Using TDI, the early (E′) and late (A′) diastolic filling velocities were recorded. Early and late diastoles were evaluated using E′ values and E/E′ ratios, respectively. Results: Left ventricular hypertrophy (LVH) was determined in 19/43 (44.2%) patients. The E/E′ ratio was significantly higher in group 2 than in group 1 and controls. E/E′ was found to be positively correlated with left ventricular mass (LVM) index, and negatively with hemoglobin (Hb) levels. Low Hb levels were only independent predictor of E/E′ (p = 0.001, β: −0.470, 95% CI: −0.764; −0.196). E′ ratio was significantly lower in both patient groups compared to the controls. Conclusions: LVH and diastolic dysfunction are already present in early stages of CKD. Treatment of risk factors, such as anemia, is important to improve the clinical outcome.

Epstein-Barr virus infection in children with renal transplantation: 17 years experience at a single center

Abstract Objectives: The aim of this study was to detect the frequency, time of occurrence, management and outcome of Epstein–Barr virus (EBV) infection and related complications in pediatric renal transplant recipients. Methods: Pediatric renal allograft recipients transplanted between August 1994 and December 2011 at our hospital was evaluated retrospectively. The patients were divided into two groups; Groups 1 and 2 were composed of patients transplanted before and after November 2007, respectively, when plasma EBV DNA levels were periodically measured. Results: The study included 166 children, 89 (53.6%) boys, with a mean age of 12.2 ± 3.8 years. Prior to transplantation, 144 patients (86.7%) were EBV seropositive. Within a median follow-up period of 36 months, 11 of 22 seronegative children (50%) developed primary EBV infection. EBV reactivation was observed in 23 of 144 children (15.9%). Two patients with primary infection developed post-transplant lymphoproliferative disorder, one of whom died. Elevated serum creatinine levels or graft loss were not observed in any patient with EBV reactivation. Conclusions: EBV DNA monitoring by PCR in high-risk pediatric renal transplant recipients will provide early diagnosis and treatment of EBV infections.

Magnesium excretion and hypomagnesemia in pediatric renal transplant recipients

Abstract Background: We investigated magnesium excretion and rate of hypomagnesemia in pediatric renal transplant recipients. Method: The medical records of 114 pediatric renal transplant recipients were retrospectively evaluated. After exclusion of 23 patients, 91 patients were included in the study. We recorded serum magnesium levels at the time of measurement of urine magnesium wasting. Results: Mean serum magnesium levels were 1.73 ± 0.22 mg/dL and 38 of the patients (41%) had hypomagnesemia. There was a negative correlation between serum magnesium levels and estimated glomerular filtration rate and serum tacrolimus trough level (r = −0.215, p = 0.040 and r = −0.409, p = 0.000, respectively). Also, there was a statistically significant positive correlation between serum magnesium levels and transplantation duration (r = 0.249, p = 0.017). Mean fractional magnesium excretion was 5.9 ± 3.7% and 59 patients (65%) had high magnesium excretion. There was a significant negative correlation between fractional magnesium excretion and estimated glomerular filtration rate (r = −0.432, p = 0.001). There was a significant positive correlation between fractional magnesium excretion and serum creatinine (r = 0.379 p = 0.003). Conclusion: Patients with higher tacrolimus trough blood levels, lower glomerular filtration rate and at early posttransplant period had risk of hypomagnesemia.

A case report: hepatic posttransplant lymphoproliferative disorder in a non-liver transplant patient.

Posttransplant lymphoproliferative disorder (PTLD) is the most common malignancy in children after solid organ transplantation. We present a patient, who developed Epstein-Barr virus (EBV)-related PTLD in the liver after renal transplantation. A 10-year-old EBV-seronegative boy with cystinosis underwent a living related preemptive renal transplantation. He received antiviral prophylaxis with valacyclovir. At 5.5 months posttransplantation he displayed a primary EBV infection with an high fever, hepatosplenomegaly, monocytosis, and positive EBV DNA levels. Two months there after, a hypoechoic nodular 20-mm lesion in the left lobe of liver was detected on abdominal ultrasonography, performed because of anorexia and weight loss. EBV-DNA copy number was 7820 copies per milliliter. Liver biopsy showed a diffuse large B-cell lymphoma that was compatible with PTLD. We stopped all immunosupressive agents other than prednisolone. Chemotherapy consisting of two courses of cyclophosphamide, vincristine, prednisolone, and adriamycin was followed by rituximab. Within 2 months, the lesion resolved and within 18 months, he was free of disease.

An infant with hypercalcemia and hyperammonia: inborn error of metabolism or not? Answers

Pathological findings of this patient were mild dehydration, oral intolerance, andmetabolic acidosiswith alkaline urine and normal anion gap, hyperammonia, hypercalcemia, hypokalemia, positive urine anion gap, nephrolithiasis, and hypercalciuria. These findings were consistent with a diagnosis of distal renal tubular acidosis (dRTA). Intravenous fluid supply and oral sodium bicarbonate replacement therapy at 2 mEq/kg/day improved the metabolic acidosis, hyperammonemia, and dehydration in a few days. Potassium citrate was added for hypokalemia and prevention of urinary calculi. The serum ammonia level reduced to 97 mg/dL on the seventh day of treatment and the patient was discharged after an 18-day hospitalization. Ultimately, whole exome sequencing demonstrated a novel homozygote mutation in ATP6VOA4 gene, c.474delGinsTC (p.E158Dfs*29) (p.Glu158Asp*29). Our patient had weight gain with medication. Plasma ammonia level should be obtained for any child with unexplained vomiting, lethargy, or other evidence of an encephalopathy. Significant hyperammonia is observed in a limited number of conditions. Inborn errors of metabolism like urea cycle defect and many of the organic acidemia are at the top of list. Newborn transient hyperammonemia in differential diagnosis of newborn, and fatty acid oxidation defects may be considered in older infants. Urine organic acid analysis should be done for organic acidemia. Metabolic acidosis is not a typical feature of the urea cycle defect. Plasma amino acid analysis is helpful in the differentiation of the specific defects in this group [1]. Differential diagnosis of hyperammonia with less significant elevation in infants other than inborn errors of metabolism is transient hyperammonia of newborn, severe infection, liver failure, and urinary tract infection associated with congenital ureteral obstruction [2]. In our patient, we detected slight hyperammonia and analyzed plasma amino acid and urine organic acid tests which were found normal. Hypercalcemia is rarely seen in children and is a much less common problem than hypocalcemia. The cause of hypercalcemia is age-related with many cases underlying genetic origin. In order to provide the most appropriate treatment, the most important point is to establish the correct diagnosis promptly [3]. Causes of hypercalcemia in infants with elevated parathyroid hormone (PTH) levels include neonatal hyperparathyroidism, mucolipidosis type II, parathyroid-related pathologies, and phosphate depletion in prematurity. Causes of hypercalcemia in infants with low or suppressed PTH levels are malignancy, drug-induced, acute immobilization, genetic diseases likeWilliams and Down syndrome, idiopathic hypercalcemia of infancy, granulomatous disease like subcutaneous fat necrosis, sarcoidosis, tuberculosis, and endocrine causes like hyperthyroidism, Addison’s disease, pheochromocytoma, congenital hypothyroidism, diabetic ketoacidosis; inborn errors of metabolism like congenital lactase deficiency, Bartter syndrome, blue diaper syndrome, disaccharidase intolerance; renal causes like distal renal tubular acidosis, multicystic dysplasia, ketotic diet. Conditions with normal PTH levels are familial hypocalciuric hypercalcemia and types I, II, and III and early-onset primary hyperparathyroidism [4]. Ammonia (NH3 and NH4) is vital in maintaining the acid base status. Most NH4 is synthesized in proximal tubules. In the loop of Henle, NH4 goes into the interstitium, gets converted into NH3, and is accumulated in the medullary interstitium. Finally, NH3 diffuses into acidified urine as a buffer in the distal tubule. Both chronic metabolic acidosis and hypokalemia act as stimuli for renal ammoniagenesis and ammonia reabsorption. Because dRTA manifests as both hypokalemia and acidosis, it is reasonable that the abovementioned mechanism leads to high medullary ammonia concentration and subsequent serum hyperammonemia. This association was This article refers to the article that can be found at (https://doi.org/10. 1007/s00467-018-4018-z).

Circulating endothelial cells in pediatric renal transplant recipients

BackgroundAn increase in the number of circulating endothelial cells (CEC) indicates endothelial damage and the risk of cardiovascular disease. The aim of our study was to investigate the association of CEC with various clinical parameters in pediatric renal transplant recipients.MethodsCEC, defined as CD45−CD146+, were enumerated by flow cytometry from the peripheral blood of 50 pediatric renal transplant recipients and 20 healthy controls. Clinical parameters, including renal function tests, fasting blood glucose, serum cholesterol and triglyceride, cyclosporine A (CsA) (trough and 2nd-hour) and tacrolimus (tac) trough blood levels and their association with CEC numbers were analyzed.ResultsCEC numbers of patients were higher than those of controls (respectively, 128 ± 89 cells/ml (42–468 cells/ml), 82 ± 33 cells/ml (32–137 cells/ml), p = 0.024). There was a statistically significant negative correlation between CEC numbers and glomerular filtration rate (GFR) (r = −0.300, p = 0.012). There was also a statistically positive association between CEC numbers and transplant duration as well as cyclosporine trough level (respectively, r = 0.397, p = 0.004, r = 0.714, p = 0.004). CEC numbers in patients on tac and CsA were similar (p = 0.716).ConclusionsOur results demonstrate that renal transplant recipients with high CsA trough blood level, longer transplant duration, and lower GFR, are at greater risk of developing endothelial damage.

Effect of renal graft on longitudinal growth in prepubertal children.

OBJECTIVES Linear growth impairment frequently accompanies chronic kidney disease in children. Despite successful renal transplant, growth retardation may persist in renal allograft recipients. MATERIALS AND METHODS We recorded the longitudinal growth and biochemical data of prepubertal children during the first 2 years after renal transplant in 34 children (18 boys [52.9%]; mean age at renal transplant, 7.3 ± 2.5 y; range, 1.4 to 9.8 y). Height standard deviation scores were calculated. The patients were divided into 2 groups according to the increase in height standard deviation scores over the first 2 years after renal transplant: group 1 (increases in height standard deviation scores < 1) and group 2 (increases in height standard deviation scores > 1). RESULTS Increases in height standard deviation scores were 0.12 ± 0.34 and 1.62 ± 0.52 for group 1 and group 2 (P < .001). The number of acute rejection episodes was significantly different between groups (P = .04). At renal transplant, increases in height standard deviation scores were negatively correlated with mean age (r: -0.354; P = .04) and height standard deviation scores (r: -0.353; P = .04). In the multivariate model, mean age and height standard deviation scores at renal transplant remained significantly associated with increases in height standard deviation scores (P = .018; β coefficient: -0.341, 95% CI: -0.17; -0.002; and P = .005; β coefficient: -0.431, 95% CI: -0.519; -0.101). CONCLUSIONS Renal transplant improves linear growth by providing moderate or accelerated growth in prepubertal children.