Short stature and growth hormone use in pediatric hemodialysis patients

End-stage renal disease (ESRD) causes growth retardation in children, and poor growth has been linked to worse outcomes. Recombinant human growth hormone (rhGH) can increase growth velocity and final adult height in pediatric ESRD patients. We aimed to identify clinical predictors of short stature (height standard deviation score (Ht SDS) <-1.88) and rhGH use in short stature pediatric hemodialysis patients. In 2002, the Centers for Medicare & Medicaid Services (CMS) Clinical Performances Measures (CPM) ESRD Project collected demographic, clinical and laboratory data as well as rhGH use on all in-center hemodialysis patients in the US aged <18 years. The odds ratios (OR) of short stature and rhGH use for individual predictors were determined by multivariate logistic regression modeling. Six-hundred and fifty-one (92%) of 710 eligible patients were included for analysis. Of these, 266 (41%) had Ht SDS <-1.88. After adjustment, short stature was predicted by congenital/urologic causes of ESRD ((OR 5.4; 95% confidence interval [CI], 2.1-13.8; p <0.001) in patients aged 10-14 years; (OR 2.8; 95% CI, 1.5-5.4; p <0.01) in patients aged 15-18 years) and increasing years on dialysis ((OR 1.2; 95% CI, 1.1-1.4; p <0.01) in patients aged 10-14 years; (OR 1.2; 95% CI, 1.1-1.4; p <0.001) in patients aged 15-18 years). Of 266 short stature patients, 214 (80.5%) had data on rhGH use. Of these, 80 (37%) had been prescribed rhGH. After adjustment, use of rhGH in short-stature patients was predicted by white race (OR 2.1; 95% CI, 1.1-4.0; p <0.05), increasing years on dialysis (OR 1.13; 95% CI, 1.05-1.22; p <0.01) and patients with BMI <16.6 kg/m(2) (OR 3.1; 95% CI, 1.2-8.4; p <0.05). Increasing age and level of intact parathyroid hormone were not associated with rhGH use among short stature patients. A significant proportion of pediatric hemodialysis patients have short stature. The majority of short-stature patients are not receiving rhGH. Patients with short stature who are white, have longer durations on dialysis and have lower BMI are more likely to receive rhGH.     

Longitudinal analysis of intermediate outcomes in adolescent hemodialysis patients

In 2000 and 2001, The Centers for Medicare & Medicaid Services (CMS) End-Stage Renal Disease (ESRD) Clinical Performance Measures (CPM) project collected data on all in-center hemodialysis (HD) patients in the United States aged >or=12 and <18 years. There were 433 of 486 (89%) patients and 435 of 516 (84%) patients who had the minimum required data submitted and were included in the 2000 and 2001 study years, respectively. There were 188 patients (43%) who had data submitted in both study years, providing longitudinal data on this cohort. A comparison of clinical parameters on these 188 patients in the 2000 and 2001 study years reveals significant improvement in mean calculated spKt/V (1.50+/-0.36 vs. 1.58+/-0.30, P<0.01), mean hemoglobin (11.0+/-1.6 g/dl vs. 11.5+/-1.3 g/dl, P<0.001), mean ferritin (286+/-278 ng/ml vs. 460+/-353 ng/ml, P<0.001), mean transferrin saturation (27.8+/-15.1% vs. 31.3+/-15.0%, P<0.05), mean serum albumin as measured by the bromocresol green method (3.83+/-0.54 g/dl vs. 3.95+/-0.42 g/dl, P<0.01), and mean height standard deviation score (-1.814+/-1.756 vs. -1.699+/-1.657, P<0.05). In addition, 20 of 29 (69%) patients who had a spKt/V <1.2 in the 2000 study year had a spKt/V >1.2 in the 2001 study year. Of 68 (44%) patients who had a catheter as their HD access in the 2000 study year, 30 had an arteriovenous fistula or graft in the 2001 study year and 49 of 80 (61%) patients who had a mean hemoglobin <11 g/dl in the 2000 study year had a hemoglobin >11 g/dl in the 2001 study year. In summary, these longitudinal data demonstrate significant improvements in nearly all clinical parameters studied in these adolescent HD patients.     

Growth hormone treatment in hemodialysis patients--a randomized, double-blind, placebo-controlled study

OBJECTIVE: Renal failure and hemodialysis (HD) affect the anabolic growth hormone (GH)-insulin-like growth factor (IGF) axis. A positive correlation between serum IGF-I and normalized protein catabolic rate (PCRn) in HD patients has been reported, and the aim of this study was to assess the metabolic impact of recombinant human (rh)GH in these patients. MATERIAL AND METHODS: In a randomized, double-blind, placebo-controlled study, rhGH was given to 35 HD patients for 8 weeks: 0.025 IU/kg/day for 1 week, increasing to 0.05 IU/kg/day. Patients with diabetes, malignancy or clinical signs of infection and those receiving steroid treatment were excluded. RESULTS: All patients completed the study. Side-effects were rare and equally distributed between the two groups. Post-treatment, serum IGF-I and IGF-I standard deviation score (IGF-I SD) increased in the rhGH group compared to the placebo group: 283+/-33 vs 151+/-16 mg/l (p = 0.001) and 1.8+/-0.6 vs -0.2+/-0.6 (p = 0.002), respectively. IGF binding protein-3 was higher in the rhGH group compared to the placebo group: 5859+/-285 vs 4369+/-321 mg/l (p = 0.002). PCRn was significantly higher in the rhGH group compared to the placebo group: 1.09+/-0.06 vs 0.90+/-0.06 g/kg/day (p = 0.029). No differences were found in body weight, serum albumin or leptin between the two groups. There was no change in C-reactive protein (CRP) in the rhGH group compared to the placebo group: 17.4+/-9.0 vs 12.3+/-4.6 mg/l (p = NS). When the patients were subgrouped according to the CRP level (< or > 10 mg/1), the effect on PCRn persisted only in rhGH-treated subjects with a normal CRP level: 1.10+/-0.08 vs 0.81+/-0.09 g/kg/day (p = 0.025). CONCLUSION: Treatment of HD patients with rhGH at a moderate dose causes augmentation of PCRn which is considered to indicate a higher dietary protein intake. The anabolic effect of rhGH seems to be abolished by subclinical inflammation.     

The effects of sevelamer and calcium acetate on proxies of atherosclerotic and arteriosclerotic vascular disease in hemodialysis patients

BACKGROUND: We recently determined that in hemodialysis patients, the use of calcium salts to correct hyperphosphatemia led to progressive coronary artery and aortic calcification as determined by sequential electron beam tomography (EBT) while the use of the non-calcium-containing binder sevelamer did not. Whether the specific calcium preparation (acetate vs. carbonate) might influence the likelihood of progressive calcification was debated. METHODS: To determine whether treatment with calcium acetate was specifically associated with hypercalcemia and progressive vascular calcification, we conducted an analysis restricted to 108 hemodialysis patients randomized to calcium acetate or sevelamer and followed for one year. RESULTS: The reduction in serum phosphorus was roughly equivalent with both agents (calcium acetate -2.5 +/- 1.8 mg/dl vs. sevelamer -2.8 +/- 2.0 mg/dl, p = 0.53). Subjects given calcium acetate were more likely to develop hypercalcemia (defined as an albumin-corrected serum calcium > or =10.5 mg/dl) (36 vs. 13%, p = 0.015). Treatment with calcium acetate (mean 4.6 +/- 2.1 g/day - equivalent to 1.2 +/- 0.5 g of elemental calcium) led to a significant increase in EBT-determined calcification of the coronary arteries (mean change 182 +/- 350, median change +20, p = 0.002) and aorta (mean change 181 +/- 855, median change +73, p < 0.0001). These changes were similar in magnitude to those seen with calcium carbonate. There were no significant changes in calcification among sevelamer-treated subjects. CONCLUSION: Despite purported differences in safety and efficacy relative to calcium carbonate, calcium acetate led to hypercalcemia and progressive vascular calcification in hemodialysis patients.     

Insomnia in diabetic hemodialysis patients. Prevalence and risk factors by a multicenter study

BACKGROUND: Insomnia is one of the most common problems in dialysis patients, and likely to contribute impairment in quality of life, which has a positive correlation with patients' survival. In diabetic patients, morbidity and mortality are substantially higher than in the nondiabetic counterparts, and also the incidence of sleep disturbances. However, there is no means to predict sleep disturbance in the dialysis patients especially in diabetics. To define the prevalence and risk factors for insomnia in diabetic patients on hemodialysis, we undertook a cross-sectional multicenter study. METHODS: Eighty-two diabetic patients (50 men/32 women, aged 58.7 +/- 9.23 years) on maintenance hemodialysis for more than 6 months from 12 different hospitals were enrolled. The demographic data, subjective symptoms, depression scale, and insomnia were assessed by questionnaires, and lean body mass, BMI, Kt/V, subjective global assessment, nursing assessment score (NAS), and biochemical parameters were examined. RESULTS: The number of patients with and without insomnia were 56 and 26, respectively, which amounted to 68.2% for insomnia. NAS (28.1 +/- 3.81 vs. 30.8 +/- 2.88, p = 0.002), serum albumin concentration (3.82 +/- 0.44 vs. 4.09 +/- 0.36 g/dl, p = 0.008), and depression scale (25.2 +/- 12.1 vs. 18.9 +/- 10.3, p = 0.025) were significantly different between them. Patients with insomnia were older (60.5 +/- 9.0 vs. 56. 1 +/- 9.60 years, p = 0.053) and felt pain (38.5 vs. 15.3%, p = 0.06) more frequently than those without insomnia. The scale of depression was correlated with NAS (r = -0.455, p < 0.001) and the serum albumin concentration was correlated with NAS (r = 0.337, p = 0.002). NAS, age, and serum albumin concentration were the major risk factors for insomnia in logistic regression analysis. CONCLUSION: The prevalence of insomnia in diabetic hemodialysis patients was 68.2%. Age, nutritional status, and depression were the major risk factors for sleep disturbance in diabetic patients.     

Differential effects of growth hormone therapy in malnourished hemodialysis patients

BACKGROUND: Malnutrition is common in chronic hemodialysis patients and is associated with increased morbidity and mortality. Several factors such as metabolic acidosis, hyperparathyroidism, and insulin as well as growth hormone (GH) resistance may lead to enhanced protein catabolism. Recombinant human growth hormone (rhGH) has been proposed as treatment of malnutrition because of its anabolic effects. METHODS: In the present placebo-controlled, double blind study, the effects of three months of rhGH therapy on nutritional and anthropometric parameters, on bone metabolism and bone mineral density (BMD), as well as on polymorphonuclear leukocyte (PMNL) function and quality of life (QoL) were evaluated in 19 malnourished hemodialysis patients (10 females and 9 males) with a mean age of 59.3 +/- 13.4 years. RhGH (0.125 IU/kg) was given three times a week during the first four weeks and 0.25 IU/kg thereafter three times a week after each dialysis session. RESULTS: Insulin-like growth factor I (IGF-I) concentration rose significantly from 169.2 +/- 95.6 ng/mL to 262.9 +/- 144.4 ng/mL (p< 0.01) in the group receiving rhGH. Albumin, prealbumin, transferrin, cholesterol, high-density lipoprotein (HDL) cholesterol, cholinesterase, predialytic creatinine, and blood urea nitrogen showed no significant changes during the three months in both groups. Total body fat (%TBF) was slightly reduced after three months (P = NS) in the patients receiving GH, whereas lean body mass (LBM) remained stable during therapy. Procollagen I carboxy terminal peptide (PICP), a marker of bone formation, increased significantly after three months from 250.1 +/- 112.6 to 478.5 +/- 235.2 microg/L (P < 0.01) in the GH-treated patients, whereas parameters of bone resorption like telopeptide ICTP showed only a slight increase (50.3 +/- 18.5 vs. 70.0 +/- 39.5 microg/L, P = NS). BMD at the lumbar spine decreased significantly after three months in the treatment group (0.8 +/- 0.17 vs. 0.77 +/- 0.16 g/cm2, P < 0.01), whereas BMD at the femoral neck remained stable in both groups. Phagocytic activity of PMNLs increased significantly after three months of therapy with rhGH, whereas other parameters of PMNL function were not affected by GH. QoL was slightly improved in the GH treated group, but decreased markedly in the placebo group. CONCLUSIONS: Three months of treatment with rhGH in malnourished patients on chronic hemodialysis causes a significant increase in IGF-I levels without significant changes in nutritional and anthropometric parameters. In contrast, bone turnover was enhanced with an initial decrease in BMD at the lumbar spine, and phagocytic activity of PMNLs was increased.     

Effects of optimized heart failure therapy and anemia correction with epoetin beta on left ventricular mass in hemodialysis patients

BACKGROUND: In chronic hemodialysis (HD) patients, the presence and degree of left ventricular hypertrophy (LVH) correlates with mortality. Previous studies have shown that interventions, such as anemia correction or treatment of hypertension and/or chronic heart failure (CHF), can result in moderate regression of LVH. The primary objective of our study was to investigate the effects of a multi-interventional treatment strategy on LVH in HD patients. METHODS AND RESULTS: In a series of 202 consecutive HD patients, we combined optimized CHF therapy, including beta-blockers (BB), ACE inhibitors and angiotensin receptor blockers (ARBs), to target doses with full anemia correction by epoetin beta (hemoglobin (Hb) target males 14.5 g/dl, females 13.5 g/dl). Serial echocardiograms were recorded every 3-6 months. Mean follow-up was 3.4 +/- 1.2 years. Mean Hb at baseline was 11.4 +/- 1.4 vs. 14.6 +/- 1.6 g/dl (p < 0.001) at study end. There was a significant reduction in left ventricular mass index (LVMI, 159 +/- 65 vs. 132 +/- 46 g/m2 (p < 0.001)), an improvement in left ventricular ejection fraction (LVEF, 60 +/- 15 vs. 66 +/- 12% (p < 0.01)) and in NYHA class (2.8 +/- 0.76 vs. 1.96 +/- 0.76 (p < 0.01)) from baseline to follow-up in the overall study population. In a subgroup of 70 patients, LVMI returned to normal (169 +/- 33 vs. 114 +/- 14 g/m2 (p < 0.001)) after 1.4 +/- 1 years. CONCLUSIONS: Our study shows that optimized CHF therapy, in combination with anemia correction to normal Hb targets, results in a significant reduction of LVH, an increase in LVEF and an improvement in NYHA class. Moreover, in contrast to previous studies, our data also demonstrate that complete regression and prevention of LVH in HD patients is possible.     

Linear growth in pediatric hemodialysis patients

Growth is an important outcome in pediatric kidney disease. We aimed to identify factors associated with growth in pediatric hemodialysis (HD) patients. Height standard deviation scores (Ht SDS) of pediatric HD patients with consecutive height measurements in the ESRD Clinical Performance Measures Project were calculated. Multiple linear regression determined the effect of factors on Ht SDS change/year. Four hundred and seven patients were included. Median age was 15.2 years (interquartile range 13.2-16.5 years); 44% were girls, and 27% were black. Of patients observed, 66% had growth hormone (GH) data, and of those, 29% were prescribed GH. Mean change in Ht SDS/year was -0.10+/-0.71. After adjustment, decreasing Ht SDS was associated with younger age (-0.2/year for <13 vs. >or=13 years; p<0.0001), longer duration on dialysis (-0.03/year for >or=6 months vs. <6 months; p<0.01), and higher normalized protein catabolic rate (nPCR) (-0.02/year per 0.1; p<0.05). Improved growth was seen in girls (0.10/year; p<0.01) and in those with lower Ht SDS (0.03/year per 0.5 decrease; p<0.001). Hemoglobin, GH use, and adequacy were associated with neither positive nor negative changes in Ht SDS. Growth retardation while on HD was most pronounced in patients who were young, male, had longer durations on HD, had higher nPCR, and had higher baseline Ht SDS.     

Clinical characteristics associated to atrial fibrillation in chronic hemodialysis patients

BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia diagnosed in non-uremic patients and its prevalence increases in older subjects, however, information concerning AF in dialysis patients is scarce. Therefore, we carried out a prospective cross-sectional study from September 1996 to December 1996 in order to evaluate the prevalence and some of the clinical characteristics associated to AF in hemodialysis (HD) patients. SUBJECTS AND METHODS: 316 HD patients (age 63 +/- 12 years, dialysis duration 69 +/- 71 months) treated in three different hospital-based units were studied. Standard 12-lead electrocardiograms (ECGs) carried out in the interdialytic day during the study period were reviewed. Data concerning age, history of ischemic heart disease (IHD), cerebrovascular disease (CVD), peripheral vascular disease (PVD), presence of diabetes, smoking history and antihypertensive therapy were collected. Systolic and diastolic blood pressure, fasting cholesterol and triglycerides, albumin and hemoglobin were also derived from the clinical records. Performance status was assessed by Karnofsky index (Ki). RESULTS: 74 patients (23.4%) had persistent AF, i.e. presence of AF in all (at least two) ECGs performed in the study time. Patients with AF were older (age 69 +/- 10 vs 62 +/- 12 years, p < 0.001), had lower Ki (54 +/- 20 vs 68 +/- 17, p < 0.01), cholesterol (182 +/- 46 vs 198 +/- 52 mg/dl, p < 0.01) and albumin (3.9 +/- 0.5 vs 4.1 +/- 0.5 g/dl, p < 0.001) compared to those with no AF. Prevalence of IHD (44.5% vs 19%, p < 0.05) and PVD (23% vs 11%, p < 0.05) was higher among AF patients. Logistic regression analysis showed that IHD (p < 0.001) and Ki (p < 0.01) were independently associated to AF. CONCLUSION: We conclude that AF is a frequent arrhythmia in HD patients treated in hospital-based dialysis units, especially in those with low performance status. It appears to be associated to the atherosclerotic damage of coronary arterial tree. Prospective studies are necessary to assess whether it could contribute to cardiovascular morbidity and mortality in end-stage renal disease.     

Lipoprotein lipid abnormalities in healthy renal transplant recipients: persistence of low HDL2 cholesterol

There is disagreement about the prevalence and character of lipoprotein lipid abnormalities in renal transplant patients. To test the hypothesis that these abnormalities may be related to the coexistence of medical conditions and medications which affect lipoprotein metabolism in these patients, triglyceride (TG), cholesterol (C), high-density lipoprotein (HDL) and HDL-C subfractions were measured in 26 transplanted patients (10 F/16 M), control subjects matched for age, sex, weight and race and uremic patients being treated with hemodialysis. Female transplant recipients had higher TG (181 +/- 47 vs. 68 +/- 6 mg/dl; p less than 0.001), C (242 +/- 19 vs. 165 +/- 9 mg/dl; p less than 0.01), and low-density lipoprotein (LDL)-C (155 +/- 15 vs. 93 +/- 8 mg/dl; p less than 0.01) than controls. Levels of HDL-C were similar, but HDL2 was significantly lower in the transplanted patients (9 +/- 2 vs. 19 +/- 2 mg/dl; p less than 0.01). Compared to the uremic patients, female transplanted patients had higher C (242 +/- 19 vs. 178 +/- 22 mg/dl; p less than 0.01), LDL-C (155 +/- 15 vs. 94 +/- 18 mg/dl; p less than 0.01), HDL-C (51 +/- 5 vs. 32 +/- 4 mg/dl; p less than 0.001) and HDL3-C (42 +/- 4 vs. 26 +/- 2 mg/dl; p less than 0.001); however, HDL2-C levels were not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)     

Growth hormone therapy and lipid profile in children on chronic peritoneal dialysis

The aim of the study was to assess the effect of recombinant human growth hormone (rhGH) on serum lipids in children treated with chronic peritoneal dialysis. We studied 26 patients aged 5-18 years, including 13 patients treated with rhGH at a dose of 1-1.1 IU/kg per week for 6 months and a control group of 13 patients. Serum total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), HDL-C, triglycerides (TG), apolipoproteins A-I and B-100 (apoA and apoB), lipoprotein (a) [Lp(a)], total protein, albumin, urea, and creatinine levels were measured in all children at baseline and at 1, 3, and 6 months of follow-up. We found a significant increase in the TG level after 1 month of administration of rhGH in the treatment group compared with both baseline (218.8+/-49.2 mg/dl vs. 175.9+/-71.9 mg/dl, respectively, P<0.05) and the control group at 1 month of follow-up (146.5+/-44.3 mg/dl, P<0.001). We found no change in TC, LDL-C, HDL-C, apoA, and Lp(a) levels during treatment with rhGH. These data suggest that administration of rhGH to children treated with peritoneal dialysis results in only a transient increase of serum TG level and has no effect on TC, LDL-C, HDL-C, apoA, and Lp(a) levels.     

Erythropoietin requirements increase following hospitalization in end-stage renal disease patients.

The effect of hospitalization on an ESRD patient's hemoglobin (Hgb) level and erythropoietin (Epo) requirement has not been investigated. We postulated patients with end stage renal disease required an increased Epo dose to maintain stable Hgb during hospitalization and for a period following discharge. To evaluate this hypothesis, we conducted a retrospective chart review on 65 hemodialysis patients. All hemodialysis patients admitted for more than 2 days who did not have more than the index hospitalizations for 2 months prior to and following discharge were included. Multiple parameters including Hgb, Epo dose, intravenous iron dose, serum iron, TIBC, and ferritin during the 2 months before and the two months after hospitalization, Hgb at admission and discharge, Hgb trough, surgery, blood transfusions and co-morbid factors were evaluated. Statistical significance was evaluated using ANOVA or rank-sum testing, as appropriate. In 65 hemodialysis patients (24 M/41 F, age 58 +/- 2.2 years, mean +/- SEM), Hgb levels following discharge and for 2 subsequent months were significantly lower than 2 months prior to admission (11.4 +/- 0.25 vs. 10.7 +/- 0.22 g/dl, p < 0.01). This occurred in spite of an increase in Epo dose (128 +/- 14 vs. 185 +/- 21 U/kg/week, p < 0.0001) over this 2-month period. There was no difference in the iron saturation before and after hospitalization (22 vs. 23%,p > 0.05). There were also no apparent effects of comorbid factors, including surgery, or discharge diagnosis on the changes in Hgb or Epo requirements. However, patients who required a blood transfusion during the hospitalization had lower Hgb levels and higher Epo doses both prior to and after hospitalization, as well as lower Hgb trough levels. In addition, females had lower Hgb levels than males both prior to and after hospitalization, and were receiving a higher Epo dose 191 +/- 18 vs. 129 +/- 20 U/kg/week at 1 month and 215 +/- 18 U/kg/week vs. 134 +/- 22, p < 0.005 at 2 months after hospitalization. CONCLUSION: This study points out that hemodialysis patients experience a significant and prolonged decrease in Hgb levels after hospitalization, even despite a moderate increase in Epo dosing.     

Recombinant human growth hormone treatment of children on hemodialysis

Forty-two children, aged 2–21.5 years on hemodialysis with a height below –2.0 standard deviation score (SDS) for age, were selected to receive recombinant human growth hormone (rhGH) therapy at 17 French centers. Of the 42 children, 36 were prepubertal and 8 were in early puberty (testicular volume between 4 and 8 ml for boys, breast development B2 or B3 in girls). All received 1 IU/kg per week by daily subcutaneous injection for 1–5 years. The year before rhGH therapy served as a control period. During the 1st year of treatment, mean growth velocity increased from 3.5 to 7.0 cm/year (P <0.0001) and was always over 2.5 cm/year. This velocity allowed a catch-up growth of +0.5 height SDS. Neither weight nor the body mass index varied compared with the pretreatment year. No change was observed in urea, creatinine, or glucose tolerance. The mean increment in bone age was 0.9 years. The mean growth velocity decreased over subsequent years (P <0.0001), but remained higher than the prestudy velocity. A significant negative correlation was observed during the 1st year between the increase in growth velocity and the prestudy velocity (P <0.0001), with the least gain in patients who had the best spontaneous velocity. Pubertal status had no influence on response to rhGH. No significant side effects were observed during the 103 treatment-years. Five patients developed secondary hyperparathyroidism and 1 suffered from acute pancreatitis, but the relationship with rhGH therapy remains uncertain. rhGH therapy appears indicated for children on hemodialysis, even though the potential benefits appear somewhat lower for those with a spontaneous growth velocity over 6 cm/year. Received April 18, 1997; received in revised form October 23, 1997; accepted October 28, 1997     

Rise in serum albumin and creatinine in the first half year on hemodialysis

Rise in serum albumin and creatinine in the first half year on hemodialysis. BACKGROUND: Serum albumin and creatinine have been reported to rise in new hemodialysis patients; however, these trends have not been quantitated in a stable cohort, and their determinants and prognostic value are unknown. METHODS: This study examined the changes in monthly values of serum albumin and creatinine over the first half year of hemodialysis in 115 patients who survived to the start of the sixth month. After verifying that the trends were approximately linear, we calculated the rates of rise (slope) of six predialysis values of serum albumin (months 1 through 6) and of creatinine (months 2 through 7) and examined their associations with age, diabetes, race, baseline 24-hour urine protein and creatinine excretion, and survival during the latter half of the first year. RESULTS: Serum albumin rose by 13% over months 1 through 6 [0.08 +/- 0.12 (SD) g/dl/month, P < 10-9 vs. zero slope]. Patients who survived the entire year had higher mean values for both serum albumin (month 1, P < 0.003; months 3 through 6, P < 10-3) and rate of rise of albumin (0.09 +/- 0.11 g/dl/month vs. 0.01 +/- 0.13 g/dl/month, P < 0.005) than patients who died during months 6 through 12, but the slope was not an independent predictor of survival after adjusting for serum albumin concentration. Baseline proteinuria correlated inversely with serum albumin measured at the first and second months (P < 0.005) and directly with the albumin slope (r = 0.49, P < 10-5). Serum creatinine rose by 12% between months 2 through 7 (0.12 +/- 0.47 mg/dl/month, P < 0.02). Survivors had a significantly higher mean baseline creatinine excretion (P < 0. 03) and serum creatinine (month 2, P < 0.03; months 3 through 7, P < 0.01) but only a marginally higher rate of rise of serum creatinine (0.16 +/- 0.47 mg/dl/month vs. -0.07 +/- 0.48 mg/dl/month, P < 0.06) than patients who died during the second half of the year. Baseline urinary creatinine excretion correlated directly with serum creatinine at month 2 (P < 0.01) and more strongly at months 3 through 7 (P < 10-3), as well as correlating with the creatinine slope (r = 0.26, P < 0.03). CONCLUSIONS: Serum albumin and creatinine rose by 12 to 13% during the first half year of hemodialysis in a stable cohort. The slope of serum albumin versus time predicted survival, but it was not as predictive as the absolute albumin concentration. The pattern of correlations of baseline urinary protein and creatinine excretion with the respective monthly serum values of albumin and creatinine and their slopes is consistent with the hypothesis that as residual renal function declines, progressive retention of protein and creatinine contributes to the respective rises in serum albumin and creatinine.     

Final height in children with chronic renal failure who have not received growth hormone

Final height (FH), growth velocity after 16 and 18 years of age, and factors predictive for FH were assessed in 60 patients (21-36 years old), whose chronic renal failure (CRF) started before the age of 16 years (28 girls and 32 boys). At 16 years of age, 22 had conservative treatment (CT, group A) and 38 end-stage renal failure [ESRF, group B, which includes 19 receiving hemodialysis (HD) and 19 with a functional renal transplant (RTx)]. None received recombinant human growth hormone (rhGH) treatment. FH was lower than in a normal population: 161.6+/-8 cm for males [-2.06+/-1.3 standard deviation score (SDS)] and 154.3+/-8.1 cm for females (-1.4+/-1.4 SDS). FH in group A (-1.15+/-1.4 SDS) was significantly higher than in group B (-2.1+/-1.3 SDS); 45% of all patients (56% of males and 23% of females) had a final height below -2 SDS (41% in group A and 47% in group B). FH was reached at 20.2+/-1.8 years in males and 18.8+/-2 years in females. A continuation of growth after 18 years of age was observed in 23 males (71.8%): +5.2 cm (+0.87 SDS) and in 14 females (50%): +1.75 cm (+0.3 SDS). However, this partial recovery concerned mainly patients with an important growth deficiency. A higher height at enrolment or at ESRF was significantly associated with a higher FH, whereas a longer period of ESRF had a significantly negative effect. In conclusion, all efforts should be made to diagnose CRF as early as possible and to try to improve growth before ESRF and RTx. Early institution of rhGH therapy should improve FH and improve the chance of achieving near-normal adult height in most patients.     

Significant association between the presence of peripheral vascular calcification and lower serum magnesium in hemodialysis patients

AIM: Vascular calcification, which significantly increases cardiovascular and other causes of mortality, is highly prevalent in hemodialysis patients. The aim of the present study was to examine the association between serum magnesium levels and vascular calcification in hemodialysis patients. METHODS: 390 nondiabetic patients on maintenance hemodialysis (226 males and 164 females, 59 +/- 13 years) were examined. Hand roentgenography was performed in each patient, and visible vascular calcification of the hand arteries was evaluated. Blood was drawn to measure serum calcium, phosphate, magnesium and intact parathyroid hormone levels. RESULTS: There were 52 patients (38 males and 14 females) with vascular calcification, and 338 (188 males and 150 females) without. Serum phosphate was significantly higher in the former compared with the latter group (p < 0.005); serum intact parathyroid hormone was significantly higher (p < 0.05), whereas serum calcium was not statistically different between the two groups. Serum magnesium was significantly lower in patients with vascular calcification than in those without (2.69 +/- 0.28 vs. 2.78 +/- 0.33 mg/dl, p < 0.05). Multivariate logistic regression analysis revealed that serum magnesium concentration was a significant independent factor associated with the presence of vascular calcification in hemodialysis patients (odds ratio 0.28, 95% CI 0.09 - 0.92/1 mg/dl increase in serum magnesium, p = 0.036) after adjustment for age, gender, duration of hemodialysis, calcium, phosphate and intact parathyroid hormone concentrations. CONCLUSION: Hypomagnesemia is significantly associated with the presence of vascular calcification of the hand arteries, independent of serum calcium and phosphate levels. These results suggest that higher serum magnesium concentrations may play an important protective role in the development of vascular calcification in hemodialysis patients, and that magnesium concentration of dialysis fluid may be reconsidered in view of preventing vascular calcification in hemodialysis patients.     

Continuous intravenous sodium ferric gluconate improves efficacy in the maintenance phase of EPOrHu administration in hemodialysis patients

Although intravenous iron has proved to optimize the efficacy of EPOrHu in hemodialysis patients, hitherto no consensus exists with respect to the best regimen of intravenous iron administration. We started a prospective randomized study in 26 patients undergoing chronic hemodialysis who had adequate iron metabolism indices (serum ferritin >100 microg/l; %TSAT >20%; %HypoE <10% and CHr >26 pg) and were in the maintenance phase of EPOrHu administration (target hemoglobin obtained >10 g/dl). All patients were receiving sodium ferric gluconate (Ferrlecit) intermittently prior to the study and after a 1-month wash-out period where iron was not administered patients were randomized to receive the same previous dose of intravenous iron either in a continuous (6.25-21.3 mg in every hemodialysis session) or an intermittent regimen (62.5 mg every 1-4 weeks, not modifying the previous schedule of administration). At 16 weeks, the continuous group showed a significant increment in serum Hb (11.83 +/- 1.12 g/dl) with respect to baseline (10.96 +/- 1.31 g/dl) (p < 0.05), whereas no differences were obtained in intermittent group (baseline: 11.16 +/- 1.03 g/dl; 16 weeks: 11.14 +/- 0.90 g/dl, NS). In contrast with the intermittent group, serum ferritin increased significantly in the continuous group (16 weeks: 508 +/- 157 microg/l; baseline: 368 +/- 56 microg/l; p < 0.05), whereas %TSAT and CHr did not modified during the study in both groups. %HypoE increased significantly with respect to baseline values in the continuous group (p < 0.05) and close to significantly different in the intermittent group (p = 0.06). Our study suggests that hemodialysis patients in the maintenance phase of EPOrHu administration would obtain further benefit in terms of serum hemoglobin level with a continuous intravenous serum ferric gluconate regimen, at least in the short term.     

Subjective quality of life assessment in hemodialysis patients at different levels of hemoglobin following use of recombinant human erythropoietin.

The quality of life of 12 hemodialysis (HD) patients was assessed in a prospective, blinded, cross-over fashion before treatment with recombinant human erythropoietin (r-HuEPO) and at two different levels of hemoglobin (Hb, 9 and 12 g/dl) by means of an interviewer-based questionnaire, the sickness impact profile (SIP). Patients were matched into two groups with no significant difference for age, weight, Hb (6.3 +/- 0.5, mean +/- SEM, group A, vs. 6.4 +/- 0.9 group B), length of hemodialysis or number of years of prior transplantation. SIP was assessed prior to treatment, after reaching the first target Hb (Hb 9 g/dl group A, 12 g/dl group B), after 4 months at that target Hb and after 4 months at the alternative target Hb for each group. For all patients, there was a highly significant improvement in quality of life as assessed by lower SIP scores between the initial and second assessments. This was evident for the physical (8.9 +/- 1.4 vs. 2.8 +/- 1.0; p less than 0.001) and psychosocial (14.9 +/- 3.9 vs. 4.4 +/- 1.1; p less than 0.01) dimensions. Total scores (16.3 +/- 2.4 vs. 5.7 +/- 0.9; p less than 0.001) showed similar changes, reflecting significant improvement in 10 of 12 possible categories between the first two assessments (p less than 0.05 to p less than 0.001). Improved scores were maintained but did not change appreciably after the 2nd assessment. There was no significant difference in any score (category, dimensional or total) obtained after 4 months at Hb 9 g/dl compared to those after the same period at Hb 12 g/dl.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intensified and daily hemodialysis in children might improve statural growth

In children conventional hemodialysis does not often improve growth. We determined linear growth in five children on in-center intensified and daily hemodialysis (IDd) regimen, with a mean age of 8 years 7 months at enrolment. Four of five were on growth hormone started for a median of 28.5 months before IDd. IDd was delivered 5 to 6 times weekly, for three hours each session. Mean follow up of IDd was 18.6 months. Dropout from IDd was kidney transplantation (n=4) or transfer to another center (n=1). IDd and free diet improved appetite, thereby protein intake, was above 2 g/kg/BW. Median weekly Kt/V_urea was 9.1 (8.7 to 10.4). Predialysis phosphorus blood levels were higher at the start (2.04±0.34 mmol/L) than at end of IDd (1.39±0.41 mmol/L) without need for carbonate of calcium in four of five cases. During conventional dialysis ht SDS decreased from −0.8 to −1.44, which occurred predominantly before rhGH start. Conversion to IDd significantly increased growth velocity to a mean of 13 cm/year (10.3–18) with a mean change of +1.84 ht SDS/year (0.4 to 2.7). This preliminary report suggests the potential efficacy of IDd regimen in promising growth velocity, either directly from a higher dialysis dose or indirectly through an improved nutritional status.