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.

Intraperitoneal calcitriol in infants on peritoneal dialysis.

BACKGROUND: Calcitriol has long been used as the main therapy in renal osteodystrophy, but the efficacy of the oral route is not always as high as expected. OBJECTIVE: To asses the safety and efficacy of intraperitoneal calcitriol in infants undergoing peritoneal dialysis (PD). PATIENTS AND METHODS: PD patients on oral calcitriol therapy, with serum parathyroid hormone (PTH) >1000 pg/mL during the previous 3 months of treatment, were switched to intraperitoneal calcitriol therapy, 1 microg twice per week. Dose was increased to 1 microg three times per week if PTH remained >1000 pg/mL, and was later readjusted. Target PTH was 200-300 pg/mL according DOQI guidelines. STATISTICS: All results are expressed as mean +/- SE. The Wilcoxon signed rank test was used to evaluate differences in measurements for each pair of values. The confidence interval for differences between population medians was 96.9%. A p value less than 0.05 was considered significant. RESULTS: Six male children, mean age 17 +/- 3.86 months, completed a 12-month follow-up. Mean pretreatment PTH was 1654 +/- 209 pg/mL. Mean PTH at months 0, 3, 6, 9, and 12 was 1448 +/- 439*, 1277 +/- 723, 910 +/- 704, 582 +/- 282*, and 465 +/- 224* pg/mL, respectively (*p < 0.05). Twelve hypercalcemic and 10 hyperphosphatemic episodes were successfully treated. CONCLUSION: Infants on PD who fail to respond to oral calcitriol therapy can be safely treated with intraperitoneal administration of active vitamin D.

Body composition in children on peritoneal dialysis.

Dual-energy X-ray absorptiometry (DEXA) can be used to evaluate total-body bone mineral content (BMC), bone mineral density (BMD), fat-free mass (FFM), and fat body mass (FBM), which are all frequently affected in patients (PD) on peritoneal dialysis. We used DEXA to evaluate body composition in children on PD and to establish whether relationships existed with nutrition status, dialytic parameters, and biochemical data. We evaluated 20 PD patients (12 boys, 8 girls). The mean age of the patients was 5.84 years (range: 0.16- 14.66 years). We carried out DEXA, anthropometry (weight/age, height/age, and body mass index), and measurements of dietary intake (protein, energy, calcium, and phosphorus), nitrogen balance (NB), dialysis dose (Kt/V), peritoneal equilibrium test (PET), and plasma calcium, phosphorus, and bicarbonate at months 1 and 6 of the study. Energy intake was prescribed according to the United States Recommended Dietary Allowances, and Kt/V and daily protein intake (DPI) according to the Dialysis Outcomes Quality Initiative (DOQI) guidelines. In the patients, BMD increased to 0.769 +/- 0.174 g/ cm2 from 0.747 +/- 0.166 g/cm2 (p < 0.05), and BMC increased to 680.3 +/- 666.1 g from 632.6 +/- 597.5 g (p < 0.01). The mean BMD Z score for patients older than 4 years (n = 11) was -0.69 at month 1, with a significant increase to -0.35 at month 6. The FBM and FFM increased, but without reaching statistical significance. At months 1 and 6, the DPI was 144.3% and 129.9% respectively (p = nonsignificant) and showed a negative correlation with BMD, BMC, and FFM (p < 0.05). Comparing DPI to plasma bicarbonate showed a negative correlation at month 1 (p < 0.05). Negative correlations were also found between NB and the parameters BMD, FBM, and FFM (p < 0.05). be content All patients showed a positive NB. No correlation was found between DEXA and anthropometric measurements, energy intake, serum calcium, serum phosphorus, or Kt/V Dialysate-to-plasma creatinine from the PET showed a negative correlation with BMD and FFM (p < 0.05). In terms of positive NB and controlled Kt/V we observed an increase in bone mineralization within the 6 months offollow-up. A high protein intake seems to negatively affect acid-base status, bone mineralization, and FFM.

Renal osteodystrophy in pediatric patients on peritoneal dialysis.

Renal osteodystrophy (ROD) is one of the mostfrequent complications in pediatric uremic patients on peritoneal dialysis (PD), and each case requires a different therapeutic approach. In the present study, we characterized ROD in pediatric patients on chronic PD. We studied 20 patients (12 boys, 8 girls) for a 12-month period. The mean age of the patients was 5.82 +/- 5 years. We allocated each patient to one of three groups according to intact parathormone (iPTH) value: group 1, iPTH < or = 150 pg/mL, n = 12; group 2, iPTH 151 - 400 pg/mL, n = 2; and group 3, iPTH > or = 401 pg/mL, n = 6. Monthly, we recorded plasma calcium, phosphorus, and alkaline phosphatase; Kt/V; normalized protein equivalent of total nitrogen appearance (nPNA); and calcitriol dose. Growth was registered as the Z height/age. Student t-test and analysis of variance for repeated measures were used for the statistical analyses. A value of p < 0.05 was considered significant. All 20 patients completed 6 months of follow-up; 9 patients completed 12 months. At months 1, 6, and 12, vitamin D doses for groups 1 and 3 were significantly different (p < 0.05), as expected. Mean values of iPTH for groups 1 and 3 were 52 +/- 47 pg/mL and 1239 +/- 718 pg/mL respectively, p < 0.05. At 6 months' follow-up, iPTH values had changed to 163 +/- 177 pg/mL for group 1 and 544 +/- 249 pg/mL for group 3 (p < 0.05), butfor group 3 that trend was lost at 12 months' follow-up, when their mean iPTH value rose to 972 +/- 420 pg/mL. Patients who had been started on PD less than 6 months before entering the study (60% of patients) showed a mean iPTH value of 629.13 pg/mL. Patients with more than 6 months on dialysis before entering the study showed an iPTH value of 115.53 pg/mL (p < 0.05). At 6 months' follow-up, iPTH values in groups 1 and 3 both showed a change toward the value range for group 2. At month 12, iPTH values in group 1 continued to show the same tendency, but iPTH values in group 3 showed a tendency to return to their initial levels. Low-turnover ROD was highly prevalent in the study, correlating strongly with time on dialysis.

Nitrogen balance studies and Kt/V urea in children undergoing chronic peritoneal dialysis.

Currently, urea kinetic modeling has been accepted for the routine evaluation of peritoneal dialysis (PD) through the calculation of Kt/V (normalized whole body urea clearance) and nPNA (normalized protein equivalent of total nitrogen appearance). In pediatric dialysis, the exact meaning of and target values for, those parameters is still under debate. We evaluated the mean values and correlations between Kt/V urea and parameters of nutrition. During a 12-month period, we prospectively performed 186 nitrogen balance studies in pediatric patients on chronic PD. We also assessed daily protein intake (DPI) by nutritional evaluation. Protein, albumin, urea, and creatinine were analyzed in dialysate and urine, collected once monthly. Dialysis adequacy was evaluated using monthly measurements of Kt/V urea and creatinine clearance (CCr) in urine and dialysate. All statistical comparisons were performed using the paired t-test. Two-way analysis of variance for repeated measures was used to calculate correlations. A p value less than 0.05 was considered significant. We studied 20 patients (15 boys, 5 girls) of mean age 5.1 +/- 4.7 years (range: 3 months - 14.8 years). Mean DPI in these patients was 3.52 +/- 1.1 g/kg/day. Weekly total Kt/V urea was 3.41 +/- 1.35, and residual Kt/V urea was 1.69 +/- 1.46. Weekly total and residual CCr were 72.4 +/- 70 L and 45 +/- 44 L respectively. Mean protein catabolic rate (PCR) was 0.84 +/- 0.33 g/ kg/day, showing a net nitrogen balance (NB = DPI - PCR) of +1.37 +/- 0.4 g/kg/day. The mean nPNA was 1.38 +/- 0.40 g/kg/day, with positive correlations with DPI, PCR, and total Kt/V (p < 0.001). Total Kt/V showed significant positive correlations with PCR (p < 0.001) and nPNA (p < 0.001), but not with NB (p = 0.23) and DPI (p = 0.21). A negative correlation was found between all urea kinetic parameters and plasma bicarbonate (p < 0.001). The values of Kt/V urea and nPNA in our patients were higher than those recommended in the adult literature. The positive correlations seen between Kt/V urea and nPCR and nPNA could not be demonstrated between Kt/V and DPI or NB, suggesting that the correlations could be the result of a mathematical association. The negative correlations between plasma bicarbonate and urea kinetic variables suggest a negative impact of acidosis on nutrition status in our patients.

Adequacy and nutrition in pediatric peritoneal dialysis.

Outcomes for pediatric peritoneal dialysis (PD) patients are closely related to dialysis adequacy and nutrition, which need to be measured frequently using a number of laboratory parameters. Although the critical meaning of adequacy and nutrition in the long-term prognosis of dialyzed children is well-documented, PD prescriptions are still largely empirical. Our objective was to evaluate nutritional and dialytic parameters in PD children (urea, creatinine, and albumin excretion in dialysate and urine, and daily protein intake); to measure peritoneal equilibration test (PET) results, Kt/V, normalized equivalent of protein nitrogen appearance (nPNA) and nitrogen balance; and to study the correlations between those variables. We performed 59 prospective laboratory measurements in 15 stable PD patients (7 boys; mean age: 6.7 years; age range: 1.1-14.8 years) during 6 months of follow-up. Creatinine, urea, total protein, and albumin were measured in plasma, urine, and dialysate. We calculated PET, Kt/V, daily dietary protein intake (DPI), protein catabolic rate (PCR), and nPNA. All statistical comparisons used the paired t-test, and correlations were calculated by two-way analysis of variance for repeated measures. A value of p < 0.05 was considered significant. The mean 4-hour dialysate-to-plasma ratio (D/P) of creatinine was 0.78 +/- 0.02 at month 0 and 0.74 +/- 0.13 at month 6 [p = nonsignificant (NS)]. The mean final-dialysate-to-initial-dialysate ratio (D/D0) of glucose was 0.35 +/- 0.11 and 0.34 +/- 0.08 at the same intervals (p = NS). The D/P creatinine showed an inverse correlation with patient age and body surface area, and the D/D0 glucose ratio showed a positive correlation with both of those parameters (p < 0.05). Weekly total and residual Kt/V urea were 3.41 +/- 0.86 and 1.49 +/- 1 respectively. The daily DPI was 3.32 +/- 1.05 g/kg, and the daily PCR was 1.32 +/- 0.47 g/kg, showing a positive net protein balance (DPI-PCR = +2 g/kg daily), which was negatively correlated with age and body surface area (p < 0.001). The mean daily nPNA was 0.94 +/- 0.33 g/kg, which was negatively correlated with age and body surface area (p < 0.05, r = -0.51), and positively correlated with daily DPI and total and residual Kt/V (p < 0.0001). Our patients could be classified as high-average transporters, with low-average ultrafiltration. The high transport state was associated with greater peritoneal albumin losses, a point of concern at younger ages. Total Kt/V and nPNA were higher for the youngest patients, suggesting a favorable nutrition status, but more studies are needed to determine the best value for both parameters in clinical practice.