WDR35 variants in a cranioectodermal dysplasia patient with early onset end-stage renal disease and retinal dystrophy.

Cranioectodermal dysplasia (CED) is rare heterogeneous condition. It belongs to a group of disorders defined as ciliopathies and is associated with defective cilia function and structure. To date six genes have been associated with CED. Here we describe a 4-year-old male CED patient whose features include dolichocephaly, multi-suture craniosynostosis, epicanthus, frontal bossing, narrow thorax, limb shortening, and brachydactyly. The patient presented early-onset chronic kidney disease and was transplanted at the age of 2 years and 5 months. At the age of 3.5 years a retinal degeneration was diagnosed. Targeted sequencing by NGS revealed the presence of compound heterozygous variants in the WDR35 gene. The variants are a novel missense change in exon 9 p.(Gly303Arg) and a previously described nonsense variant in exon 18 p.(Leu641*). Our findings suggest that patients with WDR35 defects may be at risk to develop early-onset retinal degeneration. Therefore, CED patients with pathogenic variation in this gene should be assessed at least once by the ophthalmologist before the age of 4 years to detect early signs of retinal degeneration.

Evaluation of Cumulative Effect of Standard Triple Immunosuppression on Prevention of De Novo Donor Specific Antibodies (dnDSA) Production in Children after Kidney Transplantation-A Retrospective and Prospective Study.

De novo Donor Specific Antibodies (dnDSA) are associated with inferior graft outcomes. Standard immunosuppression is expected to prevent dnDSA production in low-risk patients. We have evaluated a cumulative effect of a triple immunosuppression (CNI/MMF/Pred), as well as TAC concentration and coefficient of variation on the incidence of dnDSA production. Overall, 67 transplanted patients were evaluated in retrospective (dnDSA for-cause; n = 29) and prospective (dnDSA by protocol; n = 38) groups. In the retrospective group, the eGFR value at first dnDSA detection (median interval-4.0 years post-transplant) was 41 mL/min/1.73 m2; 55% of patients presented biopsy-proven cAMR, and 41% lost the graft within next 2.4 years. Patients from the prospective group presented 97% graft survival and eGFR of 76 mL/min/1.73 m2 at 2 years follow-up, an overall incidence of 21% of dnDSA and 18% of acute (T cell) rejection. None of the patients from the prospective group developed cAMR. Median value of Vasudev score within 2 years of follow-up was not significantly higher in dsDSA negative patients, while median value of TAC C0 > 1-24 months post-transplant was 7.9 in dnDSA negative vs. 7.1 ng/mL in dnDSA positive patients (p = 0.008). Conclusion: dnDSA-negative patients presented a higher exposure to tacrolimus, while not to the combined immunosuppression.

Gastroesophageal Reflux Disease in Children with Cystic Fibrosis.

Previously published studies have indicated that gastroesophageal reflux (GER) disease is common in pediatric patients with cystic fibrosis. The aim of the present study was to get insight into the incidence of GER and to characterize the nature of reflux episodes in children with cystic fibrosis. This was a multicenter, prospective study of children with cystic fibrosis older than 18 months. Forty four consecutive patients (22 boys, mean age 10.4 ± 3.6, range 3.0-17.8 years) were enrolled into the study. All patients underwent 24 h pH-impedance monitoring. GER were classified according to the widely recognized criteria as an acid, weakly acid, weakly alkaline, or proximal. The pH-impedance trace was considered abnormal when acid exposure was >6 %. GER was diagnosed in 24/44 (54.5 %) children. A total of 1585 (median 35, range 7-128) reflux episodes were detected; 1199 (75.6 %) were acidic, 382 (24.1 %) weakly acidic, and 4 (0.3 %) weakly alkaline. Six hundred and ninety-one (43.6 %) reflux episodes reached the proximal esophagus. In 14/44 patients typical GER symptoms were present. We conclude that the incidence of GER in children with cystic fibrosis is very high. In the majority of patients typical GER symptoms are absent. Therefore, diagnostic procedures should be considered, regardless of lacking symptoms. Although acid reflux episodes predominate in children with cystic fibrosis, classical pH-metry may not constitute a sufficient diagnostic method in this population because of a relatively high number of proximal reflux episodes. Such episodes also indicate an increased risk for aspiration. The pH-impedance diagnostic measurement is advocated when suspecting GER in children with cystic fibrosis.

Renal assessment in teenage patients with cystic fibrosis - preliminary report.

BACKGROUND: Together with increasing life expectancy of patients with cystic fibrosis *CF*, there is a growing need to deal with unforeseen problems and complications. Among others renal dysfunction has become of great concern. AIM: Evaluation of renal function in CF children. MATERIAL AND METHODS: We performed cross-sectional study on a group of 11 teenage inpatients with CF. Physical examination, past medical history analysis, renal function measurements and analysis were conducted in all of them. Renal assessment included: serum cystatin C and creatinine levels, measured and estimated creatinine clearance, estimated cystatin C clearance, urine indicators of crystallization risk and renal ultrasonography. RESULTS: One patient had elevated serum cystatin C level and diminished McIsaac equation. Renal ultrasound revealed non-congenital anomaly in 1 case - it was nephrolithiasis. All the individuals had elevated at least 1 urine indicator of crystallization risk. CONCLUSION: There is a great need of good, standardized test of renal function in cystic fibrosis patients. The focus of research should turn towards finding a tool similar to faecal elastase, which is cheap, easy to perform, sensitive and specific, and can be used to confirm the diagnosis.

Management of anemia in children receiving chronic peritoneal dialysis.

Little information exists regarding the efficacy, modifiers, and outcomes of anemia management in children with CKD or ESRD. We assessed practices, effectors, and outcomes of anemia management in 1394 pediatric patients undergoing peritoneal dialysis (PD) who were prospectively followed in 30 countries. We noted that 25% of patients had hemoglobin levels below target (<10 g/dl or <9.5 g/dl in children older or younger than 2 years, respectively), with significant regional variation; levels were highest in North America and Europe and lowest in Asia and Turkey. Low hemoglobin levels were associated with low urine output, low serum albumin, high parathyroid hormone, high ferritin, and the use of bioincompatible PD fluid. Erythropoiesis-stimulating agents (ESAs) were prescribed to 92% of patients, and neither the type of ESA nor the dosing interval appeared to affect efficacy. The weekly ESA dose inversely correlated with age when scaled to weight but did not correlate with age when normalized to body surface area. ESA sensitivity was positively associated with residual diuresis and serum albumin and inversely associated with serum parathyroid hormone and ferritin. The prevalence of hypertension and left ventricular hypertrophy increased with the degree of anemia. Patient survival was positively associated with achieved hemoglobin and serum albumin and was inversely associated with ESA dose. In conclusion, control of anemia in children receiving long-term PD varies by region. ESA requirements are independent of age when dose is scaled to body surface area, and ESA resistance is associated with inflammation, fluid retention, and hyperparathyroidism. Anemia and high ESA dose requirements independently predict mortality.