Longitudinal FGF23 and Klotho axis characterization in children treated with chronic peritoneal dialysis.

BACKGROUND: Fibroblast Growth Factor-23 (FGF23) and cofactor Klotho are key regulators of mineral metabolism in chronic kidney disease (CKD), but little is known about the mechanisms that regulate their production. This study evaluates longitudinal changes of FGF23 and Klotho levels and their regulatory factors in children on chronic peritoneal dialysis (PD). METHODS: FGF23, Klotho, 25(OH) vitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone (PTH) plasma concentrations were measured during 1 year of follow-up in PD children. Anthropometric and dialytical parameters were evaluated in addition to mineral metabolism variables. RESULTS: Thirty-one patients under chronic PD were followed for 12 months. FGF23 mean plasma levels at Month 1 were significantly increased compared with controls, 215.1 ± 303.6 versus 9.4 ± 5.7 pg/mL, respectively (P < 0.001). Baseline Klotho levels were 41% lower in patients compared with controls, 132.1 ± 58 versus 320 ± 119.4 pg/mL, respectively (P < 0.001), and did not correlate with FGF23 and phosphorus levels. At Month 12, FGF23 (195 ± 300 pg/mL) and Klotho levels (130 ± 34 pg/mL) remained similar to baseline values. Log-FGF23 correlated significantly with height/age Z score (r= -0.38) and residual renal function (r = -0.44), but no correlation was found with serum phosphorus, phosphate intake, PTH and vitamin D levels. The log-FGF23 strongly correlated with calcium levels at Months 1, 6 and 12, however, this relationship was blunted if serum phosphorus was >6 mg/dL. By multiple regression analysis, calcium was the strongest variable determining FGF23 levels. CONCLUSIONS: In this longitudinal study, FGF23 levels are markedly increased, and Klotho levels are reduced in PD children compared with controls. FGF23 levels appeared to be regulated primarily by serum calcium, showing a significant correlation at each time of measurement. This relationship was lost in patients with phosphorus >6 mg/dL. These observations may have important consequences to the therapeutic management of phosphate homeostasis in CKD patients.

Twenty-five years of infant dialysis: a single center experience.

OBJECTIVE: To perform a retrospective analysis of the long-term outcome of infants with end-stage kidney disease (ESKD) treated at our center during the past 25 years. STUDY DESIGN: The total cohort (n = 52) was divided into era 1 (1983-1995; n = 23) and era 2 (1996-2008; n = 29). Dialysis morbidity, transplantation, and long-term survival rates were assessed and compared between the 2 eras. RESULTS: Average age at initiation of dialysis was 4.4 +/- 5.3 months (range, 0.5-18 months), with 96% begun on peritoneal dialysis. The predominant diagnoses were dysplasia/obstructive uropathy and autosomal recessive polycystic kidney disease. The overall survival rate is 46%, with current age of survivors ranging from 1.5 to 25 years. Mortality rates in the 2 eras were not significantly different. The predominant mortality occurred within the first year. Twenty-four patients received an initial renal transplant at 2.6 +/- 1.7 years of age. Six patients (25%) required a second renal allograft. Increased risk for mortality included African-American ethnicity, oligoanuria, autosomal recessive polycystic kidney disease, and co-morbid diagnoses. CONCLUSIONS: Long-term survival is possible in infants with ESKD, although mortality and morbidity remain high. Technical innovations are needed to accommodate smaller infants undergoing dialysis. Early initiation of dialysis treatment is preferable because prognostic indicators remain poorly defined.

Vitamin D insufficiency and deficiency in children with early chronic kidney disease.

OBJECTIVE: To assess the prevalence of abnormal vitamin D status in children and adolescents with chronic kidney disease (CKD). STUDY DESIGN: This was an outpatient cross-sectional, retrospective study of 258 patients, mean age 12.3 +/- 5.2 years, with an average estimated glomerular filtration rate (eGFR) of 106 +/- 51 mL/min/1.73 m2 (range, 0 to 220 mL/min/1.73 m2). Serum 25-hydroxy-vitamin D [25(OH)D], calcium, phosphorus, and parathyroid hormone levels, as well as selected anthropometric variables, were analyzed. RESULTS: Reduced 25(OH)D concentrations (< 30 ng/mL) were found in 60% of the patients. In 28%, the concentration was < 20 ng/mL, indicating vitamin D deficiency. Patients with more advanced CKD were more likely to have vitamin D deficiency compared with those with incipient CKD or normal GFR (42% vs 26%; P = .03) and displayed more prominent hyperparathyroidism. Suboptimal vitamin D status was similar in males and females, but was significantly more prevalent in older (P < .01), non-Caucasian (P < .01), and overweight (P = .02) patients. Patients with early-stage CKD (eGFR > 60 mL/min/1.73 m2) and with vitamin D deficiency were significantly shorter than their counterparts with 25(OH)D levels > 20 ng/mL (P = .02). CONCLUSIONS: Vitamin D insufficiency and deficiency are very prevalent in pediatric patients across all stages of CKD, particularly in non-Caucasian and obese patients, and may contribute to growth deficits during the earliest stages of CKD.

Bone mineral content and mineral metabolism during cyclosporine treatment of nephrotic Syndrome.

OBJECTIVE: Although cyclosporine (Cy) has been associated with bone loss following transplantation, its effects on bone in growing children are largely unknown. STUDY DESIGN: Thirty-seven patients (2-16 years of age) with remitting nephrotic syndrome (NS), n = 16 receiving Cy for 39 +/- 27 months and n = 21 without Cy, underwent mineral metabolism and bone turnover assessment. In 28 of 37 patients, bone mineral density (BMD) was obtained while off corticosteroid therapy (Rx). RESULTS: Urinary calcium (Ca), phosphate (PO(4)), and magnesium (Mg) excretion was normal, but serum Mg was lower in patients receiving Cy (1.8 +/- 0.1 v 1.95 +/- 0.2 mg/dL, P < .05). BMD Z scores were similar at the spine (-0.45 +/- 0.74 v 0.04 +/- 0.9) and femur (-0.17 +/- 0.52 v 0.38 +/- 1.28) with no Z score <-2. Serum bone-specific alkaline phosphatase was normal, and N-telopeptide of type I collagen also normal, was higher on Cy (P < .05). Cumulative prednisone exposure was similar and had no significant effect on height and BMD Z scores. Length of Cy-Rx and time elapsed from onset of NS did not correlate with BMD, height Z score, or markers of bone turnover. CONCLUSIONS: In growing children with NS, during long-term Cy-Rx urinary wasting of Ca and Mg was absent and bone density was preserved.

Síndrome de epstein primer caso en la literatura nacional / Syndrome of epstein first case in of literature national

Presentamos el primer caso descrito en la literatura nacional de Síndrome de Epstein; el cual está caracterizado por la presencia de trombocitopatía de plaquetas gigantes, glomerulonefritis proliferativa (con hallazgos idénticos a la microscopia electrónica al Sindrome de Aiport) y sordera neurosensorial