Short-term protein restriction in healthy volunteers: effects on renal hemodynamics and renal response to a meat meal

We have studied the renal hemodynamic effects of short-term protein restriction and short-term protein loading in 12 healthy volunteers, who adhered to a low protein diet (0.6 g/kg/day) for three weeks and then switched to a high protein diet (1.8 g/kg/day) for another three weeks. Baseline glomerular filtration rate (GFR) was not influenced by dietary protein intake. Effective renal plasma flow (ERPF), however, was significantly lower on the low protein diet (491 +/- 23 ml/min; mean +/- SEM) as compared to values on the high protein diet (538 +/- 19 ml/min; p less than 0.01). The increase of GFR after a meat meal (providing 1.8 g protein/kg body weight) was higher on the high protein diet (GFR: +23.6 +/- 5.1 ml/min) than on the low protein diet (GFR: +13.0 +/- 2.4 ml/min; p less than 0.05). We conclude that three weeks of dietary protein restriction do not decrease glomerular filtration rate and do not enhance the renal response to a meat meal. Therefore, it seems doubtful that dietary protein restriction decreases glomerular capillary pressure through vasoconstriction of the afferent glomerular arteriole. Furthermore, measurement of the renal hemodynamic response to an acute protein load seems of doubtful physiological significance.     

Paraoxonase, anti-oxidant response and oxidative stress in children with chronic renal failure

Increased oxidative stress is believed to contribute to an increased risk of cardiovascular disease in uraemia. In children with chronic renal failure (CRF), an anti-oxidant enzyme, paraoxonase (PON), that inhibits oxidation of LDL-cholesterol, has not been previously investigated. In this study we aimed to investigate PON activity, total anti-oxidant response (TAR), total peroxide (TPX), oxidative stress index (OSI) and some pro-oxidant cytokines in 29 children with CRF [mean age 10.2±3.5 years; 19 pre-dialysis, ten on continuous ambulatory peritoneal dialysis (CAPD)] and in 25 control subjects. Children with CRF had lower PON and TAR and higher TPX and OSI values than did controls (P<0.05). Except for lower TAR and serum albumin levels of the CAPD subgroup (P<0.05), other parameters were similar in non-dialysis and CAPD patients (P>0.05). Patients had significant positive correlation between TAR and serum albumin (P<0.05). Serum urea had significant positive correlation with TPX and OSI (P<0.05). Increased oxidative stress and decreased anti-oxidants measured by serum PON activity and TAR were found in children with CRF. We can hypothesize, on the basis of statistical correlations, that low levels of serum albumin and high levels of uraemic metabolites might be responsible for increased oxidative stress in children with CRF. Further studies with larger sample sizes are needed to verify these results.     

Parathyroidectomy in children with chronic renal failure

Severe bone disease complicates chronic renal failure in children more frequently than in adults. The bony changes of renal origin are regularly reversed by successful renal transplantation. When a renal transplant cannot be accomplished at an early date, this osteodystrophy may become disabling. Under these circumstances bony changes are not arrested by medical therapy and subtotal parathyroidectomy is indicated.     

Immunization in children with chronic renal failure

Infections jeopardize children on immunosuppression after organ transplantation. Immunization is protective in healthy children. The aims of this study were to analyze the rate and efficacy of immunization in 62 children undergoing dialysis and renal transplantation (RTPL) between 1987 and 2000. The analysis was based on clinical findings, vaccination certificates, and measurement of specific serum antibodies. A member of the renal unit administered vaccinations. All 62 patients were immunized against diphtheria, tetanus, pertussis, poliomyelitis, measles, mumps, rubella, and hepatitis B. Since introduction in 1991 and 1995, 44 and 42 children were also vaccinated against influenza and Hemophilus influenzae type b, respectively. Of 16 patients with a negative history, 14 were given varicella vaccine; 16 children on peritoneal dialysis (PD) or with nephrotic syndrome were immunized against Streptococcus pneumoniae. All vaccinated patients had detectable serum antibodies against measles, mumps, rubella, varicella, hepatitis B, H. influenzae, and S. pneumoniae. There were 3 infections despite vaccination; 1 patient developed varicella after RTPL and 1 patient on PD had 2 episodes of peritonitis caused by H. influenzae and S. pneumoniae. In conclusion, monitoring and administration of the vaccines by the renal team enabled a high immunization rate. Whether vaccines, as documented by antibody titers, or by the low prevalence in the general population promoted the low prevalence of infections remains open, as there were at least a few vaccination failures.     

Growth in children with chronic renal failure and after renal transplantation

Growth retardation is a major problem for many children with chronic renal failure (CRF) and transplantation. The aim of this study is to assess the relation between height, glomerular filtration rate (GFR), hormonal alterations in children with CRF on regular haemodialysis (HD), and the impact of functioning graft after kidney transplantation. Thirty-six hemodialysed children were included in the study beside 32 pediatric transplants. Mean duration on HD was 14.72 ± 7.73 months for the CRF group, while the mean interval after transplantation was 1.97 ± 0.9 years for the second group. Moreover, twenty healthy children of matched age and sex served as controls. Assessment of growth parameters included height, expressed as standard deviation scores (Ht SDS) for chronological age, serum levels of growth hormone (hGH), and parathormone (PTH). Growth performance was evaluated twice: at the start of the study and one year later. Children with CRF and transplantation had significantly higher levels of both serum hGH and PTH compared to their controls, while CRF children experienced significantly higher serum levels of both hGH and PTH compared to those with functioning graft. Furthermore, analysis of our results by non-parametric Kendall’s correlation at the start and one year later revealed negative correlation concerning dialysis duration, serum creatinine, and PTH. On the other hand, positive correlation was achieved for serum calcium and GFR.     

Electrocardiographic monitoring in children with chronic renal failure

Continuous electrocardiographic (ECG) monitoring was performed over 24 h in 44 children at various stages of chronic renal failure in order to determine the incidence and nature of cardiac dysrhythmias. In addition the ECG was followed during haemodialysis sessions and during dialysate exchanges in continuous ambulatory peritoneal dialysis (CAPD) patients. In contrast to adult patients on haemodialysis life-threatening dysrhythmias were not observed. The proportion of children with premature ventricular complexes (41%) was at the upper limit of that in healthy children. A relatively high heart rate was found in children on CAPD, which varied during the exchange procedure. In 57% of all patients a transient marked prolongation of the QT interval up to 40% greater than normal was observed without obvious changes in the serum electrolyte levels. Continuous ECG monitoring is a useful tool for detecting alterations of cardiac rhythm and conduction in at-risk children with renal failure.     

Growth in young children with chronic renal failure

Statural growth and its relation to growth potential, renal function, blood urea nitrogen (BUN), mineral metabolism hormones and dietary intake were studied in 17 prepubertal children (aged 1.6–9.3 years) on conservative treatment for chronic renal failure due to tubulo-interstitial nephropathy. Statural growth (height SDS) was related to the degree of renal failure, was more retarded than ossification, and was independent of the chronological age of the patients. We observed that the lower the glomerular filtration rate (GRF), the lower was the growth potential (increased bone age/statural age ratio). Growth velocity may be normal regardless of statural and bone maturation delay and the degree of renal insufficiency. Impaired growth rate correlated with parathyroid hormone levels, caloric intake and increased blood urea nitrogen during the year of observation. These data show that comprehensive monitoring and suitable treatment must be performed in order to prevent growth retardation at any GFR level.     

QTc interval in children with chronic renal failure and with renal transplants

Prolongation of the QTc interval, a risk factor for cardiac arrhythmias, has been observed in adult hemodialysis patients; there are few data on the QTc interval in children with chronic renal failure (CRF) and following renal transplantation (Tx). The purpose of our study was to determine the QTc interval in children with CRF and post renal Tx. Twenty children with CRF and 16 children with renal Tx who were followed at the University of California, Davis, underwent prospective EKG monitoring. The mean QTc interval in the CRF and post-Tx cohorts was normal at 407.9 ms and 408.2 ms, respectively. None of the children with CRF had QTc prolongation. Two Tx recipients had QTc prolongation; both had cardiac dilatation on echocardiography (ECHO). There was no correlation between the QTc interval and the creatinine clearance in either group. However, a significant correlation was noted between QTc prolongation and cardiac dilatation on ECHO in the Tx group (P=0.02, Fisher’s exact test). In conclusion, QTc prolongation is uncommon in children with CRF and following Tx, in the absence of cardiac dilatation. However, caution is still needed before prescribing medications known to cause QTc prolongation. Received: 7 March 2001 / Revised: 17 July 2001 / Accepted: 23 July 2001     

Aluminum loading in children with chronic renal failure

Plasma aluminum levels were measured in 17 children with chronic renal failure who were receiving aluminum containing antacids for the control of hyperphosphatemia. Seven children were on hemodialysis, five on peritoneal dialysis, and five were awaiting dialysis with creatinine clearances between 10 to 20 cc/min/1.73 m2. Plasma aluminum levels correlated directly with oral aluminum dosage; extremely high levels were documented in small, nondialyzed children. Bone aluminum levels were measured in four children with high plasma levels and confirmed significant aluminum loading. Other factors such as the level of aluminum in dialysate and tap water were measured and were not contributory. All patients with plasma aluminum levels greater than 100 micrograms/liter had signs of aluminum toxicity and were receiving greater than 75 mg/kg/day of elemental aluminum orally. We concluded that children who require greater than 30 mg/kg/day of elemental aluminum to control hyperphosphatemia should have plasma aluminum levels monitored and/or be considered for other forms of therapy including more restricted diets and earlier or more aggressive dialysis.     

Psychiatric disorders in children with chronic renal failure

Psychiatric assessment was done according to the DSM-IV TR criteria in 19 children with predialysis chronic renal failure (CRF) and 19 children with end-stage renal disease on regular hemodialysis. The prevalence rate of psychiatric disorders in all the studied patients was 52.6%. Adjustment disorders were the most common disorders (18.4%), followed by depression (10.3%) and neurocognitive disorders (7.7%). Anxiety and elimination disorders were reported in 5.1 and 2.6%, respectively. The disorders were more prevalent (P=0.05) in dialysis (68.4%) than in predialysis patients (36.8%). The presence of psychiatric disorders was not significantly correlated with sex, severity of anemia, duration of CRF or the efficiency or the duration of hemodialysis. In conclusion, psychiatric disorders were prevalent in our patients, especially in those on hemodialysis. Both adjustments with depression and depressive disorders were the most common psychiatric disorders. This array of disorders was more likely explained by the difficulties encountered in living with CRF rather than by demographic or physical factors.     

Varicella vaccination in children with chronic renal failure

Children with kidney disease are at risk for serious varicella-related complications. To evaluate the safety and immunogenicity of a two-dose regimen of varicella vaccine in children (aged 1-19 years) with chronic renal insufficiency and on dialysis, the Southwest Pediatric Nephrology Study Group (SPNSG) undertook an open-label, multi-center, prospective 3-year clinical trial. Ninety-six patients without history of varicella were enrolled. Fifty (mean age 4.2 years) had no detectable varicella zoster virus (VZV) antibody; 98% seroconverted after the two-dose regimen. At 1, 2, and 3 years' follow-up, all patients studied maintained VZV antibody, including 16 who received a transplant. No significant vaccine-associated adverse events were seen. One subject developed mild varicella (10-50 maculopapular lesions) 16 months post transplant. In multivariate regression analysis, patients vaccinated after age 6 years had VZV antibody levels 73% (95% confidence interval 33%-89%) lower than patients vaccinated before age 6 years after controlling for gender, estimated glomerular filtration rate, and dialysis treatment. Adjusted analysis also showed that VZV antibody levels were lower after kidney transplantation, but this appeared to be a transient phenomenon. In this study, varicella vaccination with a two-dose regimen of varicella vaccine was generally well tolerated and highly immunogenic in children with chronic kidney disease.     

Immunization in children with chronic renal failure: a practical approach

The prevention of systemic viral and bacterial infections by effective vaccination represents an essential task of pediatric nephrologists caring for children with chronic renal failure (CRF) undergoing renal transplantation (RTPL) with life-long immunosuppression. This review addresses three issues: risk of vaccine-preventable diseases, safety, immunogenicity, and clinical efficacy of available vaccines, and implementation of immunization guidelines. Infections (including vaccine-preventable infections) represent the leading cause of morbidity and mortality in children on dialysis and after RTPL. Vaccination in children with CRF and after RTPL is safe and does not cause reactivation of an immune-related renal disease or rejection after RTPL. Children with CRF generally produce protective serum antibodies to primary vaccinations with killed or component vaccines and live virus vaccines; some children on dialysis and after RTPL may not respond optimally, requiring repeated vaccination. Proof of vaccine efficacy is absence of disease, which can only be confirmed in large cohort studies. A few observational studies provide evidence that vaccination has contributed significantly, at least in the western hemisphere, to the low prevalence of vaccine-preventable diseases among children with CRF. Close cooperation between the local pediatrician/practitioner and the pediatric nephrologist is essential for successful implementation of the vaccination schedule.     

Enalapril attenuates glomerular hyperfiltration following a meat meal

It has been shown that the glomerular filtration rate increases after a meat meal. We examined in humans whether enalapril, which has been shown to decrease glomerular capillary pressure in rats with chronic renal failure, could attenuate the renal response to a meat meal. Twelve healthy volunteers were studied after an oral protein load, 1.5 g/kg body weight, as lean cooked beef meat, and on a separate day, after eating the same meal with prior oral intake of enalapril. On the control day, creatinine clearance increased from 114.3 +/- 4.7 before the meal to 137.1 +/- 4.7 ml/min/1.73 m2 after the meal (p less than 0.001). On the enalapril intake day, creatinine clearance increased from 113.7 +/- 5.6 before the meal to 128.3 +/- 5.8 ml/min/1.73 m2 after the meal (p less than 0.01). However, the mean increase in creatinine clearance was lower on the enalapril intake than on the control day (14.0 +/- 4.3 vs. 21.0 +/- 4.1%, p less than 0.05). Mean arterial pressure before the meal was lower on the enalapril intake day than on the control day (76.2 +/- 3.5 vs. 84.2 +/- 3.6, p less than 0.01). Likewise, postprandial mean arterial pressure was lower on the enalapril day compared with the control day (69.9 +/- 2.8 vs. 78.5 +/- 3.7, p less than 0.01). We conclude that enalapril blunts the hyperfiltration which follows a meat meal.     

Unresolved lytic lesions following parathyroidectomy in a patient with chronic renal failure

With advances in the treatment of patients with chronic renal failure, their life expectancy has increased. In turn, the prevalence of osteitis fibrosa cystica, a manifestation of secondary hyperparathyroidism, and beta2 microglobulin amyloidosis, a result of long-term haemodialysis, has risen. While both conditions share similar radiological features, their management is very different. We present the case of a patient with renal failure who had been receiving haemodialysis for over 20 years. Lytic lesions had been observed in the proximal part of both femurs for ten years. A presumptive diagnosis of osteitis fibrosa cystica was made. However, no regression of the lesions occurred after parathyroidectomy. The patient subsequently developed sequential pathological fractures through the lesions, for which bilateral total hip replacements were performed. Histology of the lesions revealed that the patient was in fact suffering from amyloidosis. In patients with chronic renal failure, osseous amyloidosis is a highly probable differential diagnosis, especially if no regression of a lytic lesion is observed after parathyroidectomy.     

Plasma homocysteine concentration in children with chronic renal failure

Hyperhomocysteinemia, a risk factor for vascular disease, is commonly found in adult patients with end-stage renal disease. Major determinants of elevated plasma homocysteine levels in these patients include deficiencies in folate and vitamin B₁₂, methylenetetrahydrofolate reductase (MTHFR) genotype and renal function. Little information is available for children with chronic renal failure (CRF). The prevalence and the factors that affect plasma homocysteine concentration were determined in children. Twenty-nine children with various degrees of CRF (15 were dialyzed, 14 were not dialyzed) were compared with 57 age- and sex-matched healthy children. Homocysteine concentrations were higher in patients than controls (17.3 μmol/l vs 6.8 μmol/l, P<0.0001) and hyperhomocysteinemia (>95th percentile for controls: 14.0 μmol/l) was seen in 62.0% of patients and 5.2% of controls. Folate concentrations were lower in patients (9.9 nmol/l) than controls (13.5 nmol/l), P<0.01. Vitamin B₁₂ was similar in patients (322 pmol/l) and controls (284 pmol/l). Dialyzed patients have a higher prevalence of hyperhomocysteinemia than nondialyzed patients (87% vs 35%). Dialyzed patients with MTHFR mutation have higher plasma homocysteine (28.5 μmol/l) than nondialyzed patients with the mutation (10.7 μmol/l), P<0.002. In our study, differences between controls and patients in plasma homocysteine concentrations are observed when age is greater then 92 months, folate less than 21.6 nmol/l and vitamin B₁₂ less than 522 pmol/l.Our study shows that hyperhomocysteinemia is common in children with CRF and is associated with low folate and normal vitamin B₁₂ status, compared to normal children. Among the patients, the dialyzed patients with the MTHFR mutation are particularly at risk for hyperhomocysteinemia. Further studies are needed to investigate therapeutic interventions and the potential link with vascular complications in these patients. Received: 26 January 2001 / Revised: 16 April 2001 / Accepted: 17 April 2001     

Parathyroid hormone and growth in children with chronic renal failure

BACKGROUND: In pediatric chronic renal failure (CRF) optimal parathyroid hormone (PTH) concentrations that minimize renal osteodystrophy and maximize growth are unknown. The search for optimum concentrations has been complicated as currently used "intact" PTH (iPTH) assays cross-react with long carboxyl-terminal PTH fragments (C-PTH), which antagonize the biologic actions of 1-84 PTH. The purpose of this study was to investigate the relationship between PTH, the 1-84 PTH:C-PTH ratio and growth rate in children with CRF. METHODS: A total of 162 patients, median (range) age 9.9 years (0.3 to 17.1 years), were recruited: 136 with a glomerular filtration rate (GFR) <60 mL/min/1.73 m(2)[96 managed conservatively (CRF group) and 40 transplanted patients], and 26 dialysis patients. Over a median (range) period of 1.1 years (0.5 to 1.7 years), children attended five (three to 15) clinics at which iPTH, cyclase-activating PTH (CAP-PTH), and height were measured. RESULTS: Mean PTH concentrations were within the normal range for both assays for the CRF group and up to twice the upper limit of normal for the dialysis group; CAP-PTH 24.8 pg/mL and 59.9 pg/mL (normal range 5 to 39 pg/mL), iPTH 37.1 pg/mL, and 102.6 pg/mL, respectively (normal range 14 to 66 pg/mL). The patients grew normally (change in height standard deviation score per year (DeltaHtSDS) =-0.01). There was no relationship between PTH concentrations and DeltaHtSDS in any patient group. The 1-84 PTH:C-PTH ratio was lower in dialyzed patients (P= 0.003), with worsening renal function (P= 0.047) and with PTH concentrations outside the normal range (P= 0.01). There was a weak correlation between the 1-84 PTH:C-PTH ratio and the DeltaHtSDS (r= 0.2, P= 0.01). CONCLUSION: Normal range PTH concentrations are appropriate, allowing normal growth in children with CRF managed conservatively. C-PTH may be of clinical significance.     

Hemolysis and blood loss in children with chronic renal failure

Erythrocyte life span was determined in 19 children with chronic renal failure on conservative treatment and in 12 children on regular hemodialysis. Erythrocytes were labeled with 111Indium. Blood loss was measured using a special counting chamber. Erythrocyte life span decreased with increasing blood urea nitrogen. Blood loss into the intestine and into the dialysis equipment was found to be a major cause for anemia of children with chronic renal failure. Daily intestinal blood loss amounted to 6 ml/m2 BSA on conservative treatment and 11 ml/m2 on hemodialysis. Mean blood loss in the dialysis equipment was 8 ml/m2 per dialysis, almost half being lost in the connecting tubing systems.