Effect of different modes of dialysis on serum erythropoietin levels in pediatric patients

The relative importance of erythropoietin (Ep) and inhibitors of erythropoiesis in the development of anemia in pediatric patients with end-stage renal disease (ESRD) was assessed in 82 patients: 41 treated with peritoneal dialysis (PD) and 41 with hemodialysis (HD). Serum Ep was determined with a sensitive radioimmunoassay. Potential serum inhibition of erythroid (CFU-E) and granulocytic (CFU-GM) progenitor cell growth was assessed using human bone marrow cell cultures. The mean Ep level for all 82 patients was 33.1±3.1 mU/ml, which was significantly higher (P<0.05) than the values obtained in 29 normal children (26.2±2.4 mU/ml). Serum Ep in the PD group (41.6±5.6 mU/ml) was significantly higher (P=0.007) than that of the HD group (24.6±2.1 mU/ml). The mean hematocrit in the PD group (25.2±0.8%) was also significantly higher (P<0.002) than that of the HD group (22.2±0.5%). The mean serum parathyroid hormone (PTH) level as measured by a mid-terminal radioimmunoassay was not significantly different (P=0.79) in the HD group (17,298±3,998 pg/ml) from that of the PD group (15,747±4,227 pg/ml). Neither serum Ep nor PTH concentration correlated with hematocrit or degree of inhibition of erythroid progenitor cell colony (CFU-E) formation in either group of dialysis patients, nor did the hematocrit correlate, with the degree of serum inhibition of CFU-E formation. The higher level of Ep in the PD group may indicate more effective removal by PD of some enzymatic substance which reduces the immunologic and biologic activities of Ep. The higher hematocrit in the PD group may be due to the higher serum level of biologically active Ep in the PD patients. The lack of any difference in PTH level in the HD and PD groups suggests that differences in PTH activity are not responsible for the higher hematocrit in PD patients. Southwest Pediatric Nephrology Study Group (SPNSG Central Office, Baylor University Medical Center at Dallas, Tex. USA): Director, Ronald J. Hogg; Statistician, Joan S. Reisch; Administrative Assistant, Kaye Green. SPNSG Centers and Clinicians participating in this study: Baylor College of Medicine, Houston, Tex, Phillip L. Berry, L. Leighton Hill, Sami A. Sanjad: Tulane University Medical Center, New Orleans, La., Frank Boineau, John E. Lewy, Radhakrishna Baliga; University of Arkansas, Little Rock, Watson Arnold, Eileen Ellis; University of Colorado Health Science Center, Denver, Gary M. Lum; University of Oklahoma Medical Center, Oklahoma City, James Wenzl, James Matson; University of Tennessee Center for the Health Sciences, Memphis, F. Bruder Stapleton, Shane Roy, III, Robert J. Wyatt, Charles McKay; University of Texas Health Science Center at Dallas, Billy S. Arant, Jr.; University of Texas Medical School, Houston, Susan B. Conley, Ann Ince; University of Texas Health Science Center at San Antonio, Michael Foulds, Fred A. McCurdy; University of Texas Medical Branch, Galveston, Ben H. Brouhard, Alok Kalia, Luther B. Travis, Lisa Hollander; University of Utah Medical Center, Salt Lake City, Eileen Brewer, Richard Siegler. Offprint requests to: R. J. Hogg, Department of Pediatrics, Baylor University Medical Center, 3500 Gaston Avenue, Dallas TX, 75246, USA     

Endothelin-1 in children with chronic renal failure

Endothelin-1 (ET-1) was meansured after extraction from plasma of normal adults (5.9±1.9 pg/ml,n=22), normal children (7.1±1.86 pg/ml,n=29), nonhaemodialysed children with chronic renal failure (CRF) (11.1±1.8 pg/ml),n=10), renal graft recipients (9.5±3.4 pg/ml,n=37), haemodialysed children 24 h after a haemodialysis session (20.02±10.9 pg/ml,n=26) and haemodialysed children before and after a haemodialysis session (15.31±10.6 and 13.8±8.5 respectively,n=14). A sensitive and specific radioimmunoassay was used. ET-1 was significantly higher in non-haemodialysed CRF children and in renal graft recipients than in normal children (P<0.001 andP<0.01, respectively) and significantly higher in haemodialysed children when compared with normal children, non-haemodialysed CRF children and renal graft recipients (P<0.001). ET-1 concentrations were similar in normal children and normal adults. ET-1 was inversely correlated with glomerular filtration rate in non-haemodialysed CRF children (r=–0.39,P<0.01) and positively correlated with extracellular volume in haemodialysed children (r=0.435,P<0.03). After haemodialysis, ET-1 increased in 6 and decreased in 8 of the 14 children studied before and after a haemodialysis session.     

Growth of children following the initiation of dialysis: a comparison of three dialysis modalities

Maintenance dialysis usually serves as an interim treatment for children with end-stage renal disease (ESRD) until transplantation can take place. Some children, however, may require dialytic support for an extended period of time. Although dialysis improves some of the problems associated with growth failure in ESRD (acidosis, uremia, calcium, and phosphorus imbalance), many children continue to grow poorly. Therefore, three different dialysis modalities, continuous ambulatory peritoneal dialysis (CAPD), cycler/intermittent peritoneal dialysis (CPD), and hemodialysis (HD), were evaluated with regard to their effects on the growth of children initiating dialysis and remaining on that modality for 6–12 months. Growth was best for children undergoing CAPD when compared with the other two modalities with regard to the following growth parameters: incremental height standard deviation score for chronological age [–0.55±2.06 vs. –1.69±1.22 for CPD (P<0.05) and –1.80±1.13 for HD (P<0.05)]; incremental height standard deviation score for bone age [–1.68±1.71 vs. –2.45±1.43 for CPD (P=NS) and –2.03±1.28 for HD (P=NS)]; change in height standard deviation score during the dialysis period [0.00±0.67 vs. –0.15±.29 for CPD (P=NS) and –0.23±.23 for HD (P=NS)]. The reasons why growth appears to be best in children receiving CAPD may be related to its metabolic benefits: lower levels of uremia, as reflected by the blood urea nitrogen [50±12 vs. 69±16 mg/dl for CPD (P<0.5) and 89±17 for HD (P<0.05)], improved metabolic acidosis, as indicated by a higher serum bicarbonate concentration [24±2 mEq/l vs. 22±2 for CPD (P<0.05) and 21±2 for HD (P<0.05)]. In addition, children undergoing CAPD receive significant supplemental calories from the glucose absorbed during dialysis. CAPD, and possibly, other types of prolonged-dwell daily peritoneal dialysis appear to be most beneficial for growth, which may be of particular importance for the smaller child undergoing dialysis while awaiting transplantation.     

Effects of growth hormone on kidney function in pediatric transplant recipients

Recent evidence suggests that treatment with recombinant human growth hormone (rhGH) after a successful kidney transplant improves the growth rate of children with short stature. We prospectively investigated eight children (6 boys, 2 girls), focusing on acute rejection episodes and changes in serum creatinine levels during rhGH treatment. The children (mean age 11.6±3.4 years) received rhGH daily (0.04–0.05 mg/kg subcutaneously). Seven patients completed at least 12 months (20±8 months) of rhGH treatment. Their mean serum creatinine level was 1.3±0.7 mg/dl 12 months before, and increased to 3.4±4.2 mg/dl after 12 months of rhGH treatment, but did not achieve statistical significance (P=0.06). Their mean calculated glomerular filtration rate was 58±20 ml/min per 1.73 m² 12 months before, and decreased to 38±21 ml/min per 1.73 m² 12 months before, and decreased to 38±21 ml/min per 1.73 m² after 12 months of rhGH treatment, but did not achieve statistical significance (P=0.08). Of the seven patients, two developed acute rejection after 5 and 6 rejection-free years; three lost their grafts and returned to dialysis. These preliminary observations describe untoward renal events in children receiving rhGH treatment after a kidney transplant.     

Sevelamer hydrochloride: an effective phosphate binder in dialyzed children

This pilot study was designed to evaluate the efficacy and acceptability of sevelamer hydrochloride as a phosphate binder in pediatric patients treated with dialysis. A 6-month open-label trial of sevelamer hydrochloride (Renagel) was initiated in 17 patients, aged 11.8±3.7 years, undergoing hemodialysis (n=3) or peritoneal dialysis (n=14). Following a 2-week washout period of the phosphate binders, serum phosphorus increased from 5.2±1.3 mg/dl to 7.5±2.2 mg/dl (P<0.0002). After initiation of therapy with sevelamer hydrochloride, serum phosphorus levels decreased to 6.2±1.2 mg/dl (P<0.01) during the first 8 weeks and final values were 6.3±1.5 mg/dl. Serum calcium concentration decreased during the washout period from 9.4±0.9 mg/dl to 8.9±1.5 mg/dl (P<0.01); values remained unchanged thereafter. The serum calcium-phosphorus ion product decreased during the first 8 weeks and values did not change subsequently. Serum bicarbonate, parathyroid hormone, total cholesterol, low-density lipoprotein and high-density lipoprotein cholesterol, and triglyceride levels did not change. The initial prescribed dose of sevelamer hydrochloride was 121±50 mg/kg (4.5±5 g/day) and the final prescribed dose was 163±46 mg/kg (6.7±2.4 g/day). Sevelamer hydrochloride was well tolerated and without adverse effects related to the drug.     

Atrial natriuretic peptide and cyclic 3′5′-guanosine monophosphate as indicators of fluid volume overload in children with chronic renal failure

Plasma atrial natriuretic peptide (ANP) and cyclic 35-guanosine monophosphate (cGMP) were investigated as indicators of fluid volume overload in children and adolescents with chronic renal failure. Plasma ANP and cGMP were measured in both paediatric patients with chronic renal failure (n=17, mean serum creatinine 371±242 mol/l) and those with end-stage renal disease on haemodialysis (n=18). cGMP was higher in children with chronic renal failure than in 45 healthy controls (1.0±0.4 vs 2.1±0.8 nmol/l,P<0.01), whereas plasma ANP was similar (26.9±9.7 vs 34.0±12.3 pmol/l). Both ANP and cGMP were markedly elevated in children with end-stage renal disease before haemodialysis and fell significantly during dialysis. During dialysis body weight decreased by 1.6±0.7 kg, corresponding to 4.5±2.1% of body weight. Plasma ANP correlated positively with plasma cGMP in haemodialysed patients (r=0.43,P<0.05). Reduction in body weight and in mean arterial pressure correlated more closely with plasma ANP than with cGMP. Therefore, elevation of plasma ANP appears to indicate volume overload in children undergoing haemodialysis, but whether it can be used also in children with chronic renal failure requires further investigation     

Vitamin D status and its relationship with bone mineral density in healthy Asian Indians

Synthesis of vitamin D takes place in the skin under the effect of sunlight. The Indian subcontinent is situated between 8.4° N and 37.6° N latitudes and has adequate sunshine throughout the year. Thus, it has been presumed that Indians are vitamin D sufficient. We measured serum 25-hydroxy vitamin D [25(OH)D] (n=92) and 1,25-dihydroxy vitamin D [1, 25(OH)₂D] (n=65) levels in healthy hospital staff, using ¹²⁵I radioimmunoassay. Serum intact parathyroid hormone (PTH) concentration was estimated by immunoradiometric assay. Bone mineral density was estimated using a dual energy X-ray absorptiometer (Hologic^R QDR 4500A). Using a serum 25(OH)D level of 15 ng/ml as a cutoff, 66.3% (61/92) of the subjects were found to be vitamin D deficient. Of these, 20.6% (19/92) subjects had severe vitamin D deficiency (<5 ng/ml), 27.2% (25/92) had moderate vitamin D deficiency (5–9.9 ng/ml), while 18.5% (17/92) had mild vitamin D deficiency (10–14.9 ng/ml). When a serum 25(OH)D level of 20 ng/ml was used as a cutoff, 78.3% subjects were diagnosed to be vitamin D deficient/insufficient. The serum 1,25(OH)₂D level was within the normal range (40.6±20.1 pg/ml; mean ± SD). Mean (±SD) serum intact PTH, estimated in a limited number of subjects (n=15), was 72.3 (±21.0) pg/ml (range 36–100 pg/ml). There was a significant correlation between daily sun exposure and 25(OH)D levels (r=0.731, P<0.001). The serum 25(OH)D level correlated with BMD at the femoral neck and Ward's triangle (r=0.50, P=0.020 and r=0.46, P=0.037, respectively). Our findings show that vitamin D deficiency is common in urban north Indian hospital staff. The possible reasons include inadequate sunlight exposure and skin pigmentation in Indians. The serum 1,25(OH)₂D level is not a good indicator of vitamin D deficiency. A low serum 25(OH)D level is possibly one of the reasons for lower bone mineral density among Indians.     

Interleukin-6 and granulocytic elastase levels following laparoscopic cholecystectomy

Interleukin-6 (IL-6) levels have been shown to correlate well with the magnitude of surgical stress. Serum IL-6 and plasma granulocytic elastase levels, 24 h after surgery, were determined in 12 patients who underwent open major surgery [MS group; esophageal carcinoma (n=5), gastric carcinoma (n=3), colorectal carcinoma (n=4) 5 patients who had open cholecystectomy [OC group] and 17 patients who had laparoscopic cholecystectomy [LC group]. IL-6 levels correlated significantly with the duration of surgery (r=0.685,P < 0.01) and with intraoperative blood loss (r=0.583,P < 0.02). However, there was no significant correlation between granulocytic elastase and the duration of surgery or blood loss. Plasma IL-6 levels in the LC group (21±3 pg/ml) were significantly lower than those in the OC group (47±5 pg/ml) and the MS group (186±36pg/ml) (P<0.05;P<0.01). However, there was no significant difference in granulocytic elastase levels between the LC group (318±8g/l), the OC group (360±130 gmg/ml), and the MS group (701±344 g/l). Increased IL-6 levels correlated well with increased duration of surgery. The lower IL-6 levels following laparoscopic cholecystectomy may therefore be indicative of lower surgical stress associated with laparoscopic cholecystectomy.     

Increase in Serum Magnesium Level in Haemodialysis Patients Receiving Sevelamer Hydrochloride

Background: Clinical studies have shown that sevelamer hydrochloride improves lipid profiles and attenuates the progression of the cardiovascular calcifications in haemodialysis patients. It is known that both of these properties are associated with increased magnesium levels. The effect of sevelamer on serum magnesium level is not well documented. The aim of this study was to determine the effects of sevelamer treatment on serum magnesium in haemodialysis patients and to assess the association of magnesium levels with lipid profiles and intact parathyroid hormone (iPTH). Methods: Phosphate binders were discontinued during a two week washout period. Forty-seven patients, whose serum phosphate was greater than 6.0 mg/dl at the end of washout, received sevelamer hydrochloride for eight weeks. The patients were then washed off sevelamer for another two weeks. Results: Mean serum phosphorus concentration declined from 7.5 ± 1.3 to 6.4 ± 1.2 mg/dl (P < 0.001), mean serum magnesium levels increased from 2.75 ± 0.35 to 2.90 ± 0.41 mg/dl (P < 0.001) and median serum iPTH levels decreased from 297 to 213 pg/ml (P=0.001) during the eight weeks of sevelamer treatment. After the two week post-treatment washout phosphorus levels increased to 7.3 ± 1.3 mg/dl (P < 0.001), magnesium levels were reduced to 2.77 ± 0.39 mg/dl (P < 0.001) and iPTH levels increased to 240 pg/ml (P=0.012). No change was observed in serum calcium levels during the sevelamer treatment period and the subsequent washout period. The mean decline in total and low density lipoprotein (LDL) cholesterol during sevelamer treatment was 16.3 and 28.3 (P < 0.001), respectively. The mean increase in high density lipoprotein (HDL) cholesterol and in apolipoprotein A1 was 2.9 ± 5.8 mg/dl (P=0.004) and 6.8 ± 11.1 mg/dl (P=0.001), respectively. Multivariate analysis showed that the rise in serum magnesium concentration significantly correlated with reductions in iPTH levels (r=−0.40, P=0.016), but did not have any significant correlation with the changes in lipid profiles. Conclusions: Our findings indicate that patients on haemodialysis receiving sevelamer have a significant increase in serum magnesium concentrations. This increase in serum magnesium is associated with reduction in iPTH levels. The changes in lipid profiles of these patients however are not related to changes in serum magnesium levels.     

The immune status of uraemic children/adolescents with chronic renal failure and renal replacement therapy

In adults with chronic renal failure (CRF) and/or renal replacement therapy (RRT) various immunological abnormalities have been described, but few data are available for the paediatric age group. We performed basic in vitro immunological studies in 26 patients 10 months–19 years of age with advanced renal failure, 11 with CRF (creatinine clearance 16.8±5.2 ml/min per 1.73 m²), 15 on RRT with haemodialysis (HD;n=9) and continuous ambulatory peritoneal dialysis (CAPD;n=6) as well as in 16 healthy controls. None had clinical evidence of deranged immune function. No significant differences were found in the percentages of B- and T-cells, T-cell subsets CD3, CD4, CD8 and mitogenic responses to phytohaemagglutinin and concanavalin A (Con A) between RRT patients (HD=CAPD) and control children. Most parameters in CRF patients were also normal, although they had a low percentage of B-cells (12.1±4.1; RRT: 19.7±6.5; controls: 18.5±7.1;P<0.01), relatively low levels of serum immunoglobulin G (948.4±209.4 mg/dl; HD: 1374.7±235.2 mg/dl;P<0.01; CAPD: 966.3±430.2 mg/dl, NS) and a high normal response to Con A (34.3±13.6 cpm ×10^–3; RRT: 34.5±11.3 cpm ×10^–3; controls: 23.4±9.9 cpm ×10^–3,P<0.01). All these values were, however, well within the normal accepted range. These data indicate that children/adolescents with CRF and/or RRT have no significant basic in vitro immunological defects. This study did not test the functional immune status of the young uraemic patients.     

Acute and long-term changes in plasma levels of atrial natriuretic factor in patients with renal replacement therapy

In 14 patients on hemodialysis who received kidney grafts from living related donors, plasma levels of immunoreactive atrial natriuretic factor (Ir-ANF) were determined in a sequence covering the last hemodialysis treatment, the day of transplantation, and a follow-up period of 6–12 months. The geometric mean value before dialysis was 196 pg/ml, the range 32–634. Weight loss during dialysis was 1.5±1.1 kg (mean±SD), but only a nonsignificant reduction in Ir-ANF levels occurred. On the day of transplantation, plasma Ir-ANF levels increased from 143 pg/ml before to 391 post-transplantation (P=0.02, n=12), probably in response to deliberate volume expansion. Post-transplant Ir-ANF levels correlated significantly to diuresis during the first 24 h, which ranged from 3.7 to 17.81 (mean 6.6; r=0.65, P=0.02). On day 2, mean 24 h diuresis decreased to 3.3±1.41. Most patients had reached their true dry weight by day 5, but Ir-ANF levels remained high, the geometric mean being 180 pg/ml. During further follow-up and preserved graft function (GFR range 34–88 ml/min per 1.73 m² body surface area), Ir-ANF levels declined to a geometric mean of 63 pg/ml by 2–6 months and to 36 at 12 months post-transplant. We conclude that plasma Ir-ANF levels are chronically elevated in patients with chronic renal failure but may be further stimulated by acute overhydration. Transplanted kidneys initially respond to the increased levels but adapt within a day. Even with good graft function, normalization of plasma Ir-ANF requires several weeks or months.     

Abnormal left ventricular mass and aortic distensibility in pediatric dialysis patients

There is ample evidence that the same pathophysiological processes that affect cardiovascular function in adults with end-stage renal disease (ESRD) also operate in children with ESRD. In adults undergoing hemodialysis (HD), a good correlation has been established between left ventricular mass (LVM) and aortic distensibility (AD) as markers of cardiovascular disease progression; however, this correlation has not been established in children. Therefore, in this retrospective study we investigated some aspects of cardiovascular damage (i.e., LVM, LVMI, and AD) in children with ESRD undergoing HD ( n =9) or peritoneal dialysis (PD, n =9), and analyzed the relationship between AD, LVM, LVMI, pre-dialysis, post-dialysis blood pressure (BP), and demographic factors in children and adolescents with ESRD. Both LVM and AD were significantly greater in the dialysis population than in a control population derived from our institutional files ( P =0.015, P =0.001). LVM and LVMI in children undergoing HD (92.9±83.7 g, 80.1±31.1 g/cm) were not statistically different from the values in children on PD (130.0±89.2 g, 89.6±35.9 g/cm), ( P =0.3, P =0.5). AD in children on HD (2.2±0.55 cm² * dynes^–1*10–6) was significantly lower than in children on PD (2.7±0.54 cm² * dynes^–1*10–6), ( P =0.01). The findings in this study confirm earlier studies that demonstrated that LVMI is greater in children on dialysis. This study also demonstrates that abnormal vascular stiffness, as defined by AD, is present in these children. The degree of vascular stiffness in children receiving HD is greater than in children receiving PD. However, further study is needed to address how control of BP, uremia, and other factors may affect these abnormalities in children with ESRD.     

Sequential changes of biochemical bone parameters after kidney transplantation

Background. Persistant hyperparathyroidism after renal transplantation (Rtx) has been reported in several studies. However these studies evaluated biochemical bone parameters either only during a short time period (up to 6 months) or for a longer time period, but with long intervals in between. Therefore, we prospectively evaluated biochemical bone parameters of kidney transplant recipients at short intervals for 2 years after surgery. Methods. Biochemical bone parameters were prospectively investigated in 129 patients 2, 3, 5, 8, 12, 18 and 24 months after Rtx. All patients received prednisone and cyclosporin A as immunsuppressive therapy, and 75 patients was treated with calcium, phosphorus, or vitamin D preparations. Results. Serum creatinine levels decreased from 166.8±5.4 &mgr;mol/l to 140.0±4.9 two years after Rtx; (data are expressed as mean±s.e.m.). Serum phosphorus levels increased slightly from 0.9±0.022 mmol/l to 0.98±0.025 (12m), but remained within the lower normal range. We observed a rise in total and albumin adjusted calcium concentrations 3 months after Rtx. 52% of all patients had serum calcium levels above 2.62 mmol/l (upper normal limit in our laboratory) 3 months after renal transplantation with a gradual decrease thereafter. There was no correlation of calcium and PTH levels. We observed a significant rise in biochemical bone parameters from 2 to 5 months after renal transplantation (P<0.001): alkaline phosphatase (AP) increased from 164.3±9.4 to 236±12.7 U/l (normal 50-180), bone specific alkaline phosphatase (BAP) rose from 17.7±1.36 to 23.2±1.7 ng/ml (normal:4-20) and osteocalcin (OC) increased from 20.2±1.5 to 26.7±1.9 ng/ml (normal 4-12). AP and BAP levels values normalized 12 months after renal transplantation, whereas OC was still above normal throughout the study period. Patients were subdivided into two groups: those with good and those with impaired graft functions. Patients with good graft function had stable serum creatinine levels (⩽132 &mgr;mol/l or ⩽1.5 mg/dl) well below the mean serum creatinine concentration during the study period. The significant changes in AP, BAP, and OC occurred irrespective of renal function. However, patients with impaired graft function (n=65) had significantly higher PTH-levels (70 pg/ml higher) than patients with good graft function (n=64), P<0.01. PTH was positively correlated with serum creatinine (r=0.0.001). Moreover, patients with low 25(OH) vitamin D levels (n=63) had significantly higher PTH concentrations (between 40 and 80pg/ml, P<0.01) throughout the sudy period compared to patients (n=66) with a sufficient 25(OH)D supply irrespective of graft function. There was a negative correlation of 25(OH)D levels and PTH; (r=-0.49, P<).001). 1,25(OH)2D3 (evaluated in 24 patients) levels increased from 46.5±6.6 to 76.9±7.6pg/ml (normal: 35-90) at 12 months. Conclusion: Hypercalcaemia is a common phenomenon in the early period after kidney transplantation and occurs in the presence of low normal phosphorus levels. It is most probably related to improved PTH action and 1-hydroxylation of vitamin D. The rise in biochemical bone parameters between 3 and 5 months occurs irrespective of graft function and normalization is only achieved 1 year after transplantation. PTH is constantly elevated for up to 2 years after kidney transplantation and is most probably related (a)to impaired graft function and (b) to suboptimal 25 OH vitamin D supply. Keywords: hypercalcaemia; biochemical bone parameters; renal transplantatiom; secondary hyperparathyroidism; vitamin D      

Serum erythropoietin levels and hematocrit in end-stage renal disease: influence of the mode of dialysis

Serum erythropoietin (Ep) levels were measured by radioimmunoassay in 70 patients with end-stage renal disease (ESRD) to evaluate the influence of the mode of dialysis on the relationship between serum Ep levels and the severity of anemia. Thirty-five patients were on hemodialysis (HD), seven were on intermittent peritoneal dialysis (IPD), and 28 were on continuous ambulatory peritoneal dialysis (CAPD). Compared to HD, CAPD patients had higher serum Ep (CAPD), 46.1 +/- 13.4 v HD, 16.9 +/- 2.2 mU/mL) and hematocrit (CAPD, 33.9 +/- 2.5 v HD, 24.8 +/- 1.4%; P less than 0.05). The Ep and Hct values for IPD patients were intermediate between the other two groups. Serum Ep levels were higher in CAPD patients in the first 4 weeks of initiation of CAPD (144 +/- 35 mU/mL, n = 6) than later (39 +/- 6.4 mU/mL, n = 24). A significant fluctuation in serum Ep and Hct values was noted in patients on all three modes of dialysis, when multiple samples were obtained at different time intervals. There was a weak correlation between serum Ep and Hct in the three groups of dialysis patients; r = 0.36, P less than 0.005. The data suggest that CAPD provides a better biochemical milieu for Ep production and responsiveness than HD treatment of ESRD.     

Plasma and urinary adrenomedullin levels in children with renal parenchymal scar and vesicoureteral reflux

Adrenomedullin (AM) is a strong vasodilator peptide with proven antimitogenic and antiproliferative effects in renal mesangial cells, as well as diuretic and natriuretic actions. Its gene expression is stimulated by endotoxins (lipopolysacharides) and cytokines. Consequently, its plasma and urinary levels are known to deviate from normal levels in many renal diseases. The purpose of this study is to determine plasma and urinary AM levels in children with renal parenchymal scar (RPS) and vesicoureteral reflux (VUR). The study was carried out on 74 children with recurrent urinary tract infections, arranged in groups: 25 patients with RPS with VUR (group I), 16 patients with RPS without VUR (group II), 12 patients with VUR without RPS (group III) and 21 healthy children as the control group. Plasma and urinary AM concentrations were both determined by high performance liquid chromotography (HPLC). Plasma AM was measured as picomoles per milliliter (pM/ml) and urinary AM as pM/mg urinary creatinine. In addition, serum creatinine, creatinine clearance and fractional sodium excretion (FE_Na) were measured. All cases with RPS and VUR had normal blood pressure levels. The plasma AM levels were higher, although not significantly, in the control group (56.2±14.0 pM/ml) than in group I (50.6±4.2 pM/ml), group II (49.6±3.7 pM/ml) and group III (50.6±3.6 pM/ml) ( P =0.162). The urinary AM levels were higher in the control group (80.1±33.9 pM/mg) than in the three study groups (52±7.6 pM/mg, 58.6±7.5 pM/mg and 44.2±6.4 pM/mg; P =0.003, P =0.002 and P =0.002, respectively). There were no differences among the 4 groups (group I, group II, group III and the control group) in terms of FE_Na and creatinine clearance ( P >0.05 and P >0.05, respectively). The finding that diminished urinary AM levels in patients with RPS and VUR implies that AM can be a prognostic factor in the long-term follow-up of cases with these diseases.     

Serum insulin-like growth factor binding protein (IGFBP)-4 and IGFBP-5 in children with chronic renal failure: relationship to growth and glomerular filtration rate

Growth retardation in children with chronic renal failure (CRF) is partly due to an inhibition of insulin-like growth factor (IGF) activity by an excess of high-affinity IGF-binding proteins (IGFBPs). The aim of this study was to analyze the serum levels and forms of IGFBP-4 and IGFBP-5 in CRF patients using specific, recently developed radioimmunoassays (RIAs) and immunoblot analysis. We examined 89 children [age 11.5 (2.8–19.0) years] with CRF [glomerular filtration rate 26.6 (7.0–67.4) ml/min per 1.73 m²], nine of them with end-stage renal disease undergoing peritoneal dialysis. Serum-immunoreactive IGFBP-4 levels were fourfold increased in CRF (prepubertal 1080±268 ng/ml; pubertal 989±299 ng/ml) compared to healthy prepubertal controls (265±73 ng/ml). In contrast, serum IGFBP-5 levels were not significantly increased neither in prepubertal (361±120 ng/ml vs 282±75 ng/ml in controls) nor pubertal CRF children (478±165 ng/ml vs 491±80 ng/ml in controls). Immunoblot analysis showed the presence of intact as well as fragmented IGFBP-4 and IGFBP-5. Serum IGFBP-4, but not IGFBP-5, levels were inversely correlated with GFR (r=–0.39, P<0.001). In prepuber- tal children, IGFBP-4 levels were inversely correlated with standardized height (r=–0.40; P<0.005). In contrast, IGFBP-5 levels were positively correlated both with standardized height (r=0.32, P<0.02) and baseline height velocity (r=0.45, P<0.005). A 3-month therapy with rhGH stimulated serum IGFBP-5 levels by 43% (P<0.01); there was no consistent effect on IGFBP-4 levels. There was a positive correlation between IGFBP-4 and IGFBP-2 (r=0.46, P<0.001); IGFBP-5 was positively correlated with IGF-I (r=0.59, P<0.001), IGF-II (r=0.42, P<0.001) and IGFBP-3 (r=0.47, P<0.001) and inversely correlated with IGFBP-1 (r=–0.41, P<0.001). In summary, serum IGFBP-4 is fourfold elevated in children with CRF in relation to the degree of renal dysfunction and contributes to the marked increase in IGF-binding capacity in CRF serum. The inverse correlation of serum IGFBP-4 with standardized height is consistent with its role as another inhibitor of the biological action of the IGFs on growth plate cartilage. In contrast, serum IGFBP-5 is not elevated in CRF serum and circulates mainly as proteolysed fragments. The positive correlation of serum IGFBP-5 with growth and its increase during GH therapy indicate that IGFBP-5 is a stimulatory IGFBP in patients with CRF, either by enhancing IGF activity through better presentation of IGF to its receptor or by an IGF-independent effect through activation of a specific, recently described putative IGFBP-5-receptor. Received: 24 September 1999 / Revised: 6 January 2000 / Accepted: 13 January 2000 / Accepted: 13 January 2000     

Urinary excretion of endothelin-1 in children with absorptive idiopathic hypercalciuria

Urinary excretion of endothelin-1 (ET-1) and plasma ET-1 were measured in 21 children with absorptive idiopathic hypercalciuria (AIH) and 22 controls. The absorptive type of idiopathic hypercalciuria was determined by a calcium loading test. Daily urinary excretion of ET-1 and urinary ET-1/creatinine ratio were significantly increased (P=0.005 and P=0.007, respectively) in patients with AIH (9,274±6,444 pg/24 h and 14.04±9.52 pg/mg, respectively) compared with controls (4,699±2,120 pg/24 h and 7.36±4.71 pg/mg, respectively). Plasma ET-1 levels were significantly lower in patients with AIH (0.84±0.64 pg/ml) than in controls (1.54±0.54 pg/ml, P=0.0001). In conclusion, patients with AIH had increased urinary ET-1 excretion and decreased plasma ET-1 levels. This is most likely due to the decreased reabsorption of ET-1 in the renal tubule and increased renal production.     

Urinary neutrophil gelatinase-associated lipocalcin in D+HUS: a novel marker of renal injury

Background: Diarrhea-associated hemolytic uremic syndrome (D+HUS) causes acute renal failure. Neutrophil gelatinase-associated lipocalcin (NGAL) is an early indicator of kidney injury. Objective: To determine if urinary NGAL excretion is a biomarker of severe renal injury and predicts the need for dialysis in D+HUS. Methods: Patients were randomly selected from among participants in the SYNSORB Pk trial. Urine samples were collected daily if available during the first week of hospitalization. NGAL levels were determined by ELISA. Results: 34 children, age 5.9±3.9 yr, were studied; ten (29%) required dialysis. Patients were categorized based on urinary NGAL concentration within five days of hospitalization - <200 ng/ml and ≥200 ng/ml. Twenty patients (58%) had increased urinary NGAL excretion. The severity of D+HUS at enrollment was similar in the two groups. However, children with increased urinary NGAL levels had higher peak BUN and creatinine concentrations (P<0.01) and required dialysis more often, 9/20 versus 1/14 (P=0.024) compared to children with normal excretion. Conclusion: The majority of patients with D+HUS have renal tubular epithelial injury, as evidenced by elevated urinary NGAL excretion. Urinary NGAL levels below 200 ng/ml within five days of hospitalization may be an adjunctive marker that defines less severe renal involvement.     

Relationship of leptin and insulin-like growth factor I to nutritional status in hemodialyzed children

Malnutrition is prevalent in patients with end-stage renal disease (ESRD). Elevated serum leptin levels were thought to contribute to the anorexia and poor nutrition in renal failure. However, studies of the relationship between nutritional status and leptin concentration in chronic renal failure have yielded conflicting results. Plasma insulin-like growth factor I (IGF-I) level has been used as an indicator of nutritional status in patients with renal failure. The relationship between leptin and IGF-I is controversial. The present study was conducted with the aim of assessing the relationship between nutritional status, hyperleptinemia, and serum IGF-I. Seventeen ESRD patients (8 male, 9 female), aged 8–18 years (mean 15.3±3.3 years) and undergoing standard hemodialysis for 58.8±23.1 months were enrolled. Nine age-matched healthy children served as controls. In all patients, energy and protein intakes were 40–70 kcal/kg per day and 1–1.54 g/kg per day, respectively. Predialysis serum leptin and IGF-I levels were measured by radioimmunoassay. Body mass index was decreased in 13 (76%) patients. Triceps skinfold thickness (TST) was reduced (below the 5th percentile) in 7 (41%), whereas mid arm circumference and mid arm muscle circumference were reduced in 14 (82.5%) and 13 (76.5%), respectively. The median serum leptin level was significantly higher in patients than in controls [13.7 interquartile range (IQR) 30.50 pg/ml vs. 6.50 IQR 8.65 pg/ml, P=0.01]. The median serum IGF-I level was lower in the patients (205.1 ng/ml IQR 194.4 ng/l) than controls (418.0 ng/l IQR 310.5 ng/ml) (P=0.01). IGF-I levels were more decreased in patients with severe malnutrition, defined according to TST (145.0 ng/ml IQR 125.5 ng/l) than patients without malnutrition (301.2 ng/l IQR 218.8 ng/ml) (P=0.03) and healthy children (P=0.002). Although statistically not significant, IGF-I levels tended to be decreased, while leptin levels were increased. The median plasma insulin concentration was 15 U/ml (1.63–45.80) and did not correlate with leptin and IGF-I levels. In conclusion, the results of this study confirm the presence of high circulating plasma leptin levels, which may be one of the many factors involved in the pathogenesis of the malnutrition in children on hemodialysis.     

Psychosocial adjustment to end-stage renal failure: comparing haemodialysis,continuous ambulatory peritoneal dialysis and transplantation

Seventy-three children and adolescents in end-stage renal failure (ESRF) undergoing haemodialysis (n=32), continuous ambulatory peritoneal dialysis (CAPD) (n=28) or with a functioning transplant (n=13), were assessed, with their parents, on adjustment to dialysis and psychological functioning. Quantitative assessment techniques were used; the three treatment groups were compared using the Mann-Whitney U test. Findings showed a number of advantages of transplantation over dialysis, and of CAPD over haemodialysis. Children with transplants suffered less functional impairment (P=0.007), less social impairment (P=0.001) and fewer practical difficulties associated with treatment (P=0.000) than children undergoing dialysis. Parents of children with transplants also reported fewer practical difficulties than parents of children on dialysis (P=0.002). Dialysis and transplant groups did not differ on children's or parents' reports of psychological stress associated with treatment, parents' reports of marital strain, children's and parents' levels of anxiety and depression or children's behavioural disturbance. Compared with children undergoing hospital haemodialysis, those using CAPD suffered less social impairment (P=0.004), reported better adjustment to dialysis (P=0.031) and fewer practical problems associated with treatment (P=0.005), had lower depression scores (P=0.054), and showed less behavioural disturbance (P=0.013). Parents of children undergoing either CAPD or hospital haemodialysis reported similar practical difficulties, psychological stress or marital strain associated with treatment, but mean depression and anxiety scores were lower in the parents of children undergoing CAPD (P=0.042 andP=0.054). The findings have clear implications for clinical practice and may help to choose the most appropriate renal replacement therapy for children in ESRF.