Post-transplant diabetes mellitus in children following renal transplantation.

PTDM plays a role in chronic allograft nephropathy and decreases graft and patient survival. Considering the serious outcome of chronic hyperglycemia, the importance of early recognition and the few data in children, in this retrospective analysis we studied the characteristics and risk factors of PTDM in 45 pediatric renal transplant recipients receiving Tac or CyA-based immunosuppression. Fasting blood sampling and OGTT were performed. PTDM has been developed in six patients (13%), while seven children (16%) had IGT, with the overall incidence of a glucose metabolic disorder of 29% in pediatric renal transplants. Patients in the PTDM + IGT group were younger and had higher systolic blood pressure and serum triglyceride level than children with normal glucose tolerance. Multivariate analysis identified Tac treatment, Tac trough level, steroid pulse therapy and family history of diabetes to be associated with the onset of PTDM. In pediatric renal transplants, OGTT and frequent assessment of blood glucose levels might be essential not only in the post-transplant management, but also prior to transplantation, particularly with family history of diabetes. Careful monitoring and modified protocols help to minimize the side effects of Tac and corticosteroids.

Effect of propranolol on heart rate variability in patients with end-stage renal disease: a double-blind, placebo-controlled, randomized crossover pilot trial.

BACKGROUND: Low heart rate variability (HRV) is an independent risk factor of cardiac mortality in patients with end-stage renal disease (ESRD). It has been explained by uremic parasympathetic neuropathy. Sympathetic overactivity can also reduce HRV. Our aim was to determine whether there is vagal activity in ESRD patients that is masked by sympathetic activity. METHODS: The effect of propranolol on HRV was examined in 13 patients with ESRD, aged 20.1 +/- 7.6 years without diabetes. All patients were given intravenous propranolol (0.05 mg/kg) once and placebo once in a randomized, double-blind way, with an interval of 6.6 days (mean, range: 2-9). Propranolol was administered before hemodialysis treatment, after 40 minutes supine resting period. HRV was registered for 10 minutes, during supine, before and after the injection. Patients' HRV data were compared to that of 29 age-matched healthy controls. RESULTS: Initially, both high-(HFV) and low-frequency (LFV) bands of heart rate variability were lower in ESRD patients compared to controls (p < 0.001 for both). Propranolol resulted in a significant increase of HFV (propranolol: AlgHFV = 0.182 (0.027 - 0.337), placebo: deltalgHFV = -0.029 (-0.128 - +0.070); p = 0.032). Elevation of LFV was not significant. Six patients had an elevated plasma norepinephrine and/or epinephrine level. Plasma dopamine level was elevated in all but 1 patient (mean: 432 pmol/l, 95% CI: 320-543) and showed an inverse relationship with the increase of IgHFV secondary to propranolol (r = -0.66, p = 0.014). CONCLUSIONS: Low HFV of ESRD patients can be improved by beta-adrenergic blockade. It demonstrates that there is some vagal activity in ESRD that is masked by sympathetic activity. Therefore, altered sympathovagal balance of ESRD patients should be taken into consideration in the assessment of vagal uremic neuropathy.

Prevalence of obesity and metabolic changes after kidney transplantation: Hungarian pediatric cohort study.

BACKGROUND: Cardiovascular mortality rate in patients with end-stage renal disease is 3 magnitudes higher than in the general population; it remains 10-fold higher after successful renal transplantation (Tx). Among others, obesity and hypertension can exert deleterious effects on vascular structure and function after Tx. Successful kidney transplantation may induce excessive weight gain in part because of the effects of steroid treatment. METHODS: The purpose of this study was to evaluate the presence of obesity in Tx children, their obesity-related metabolic disturbances, and to assess their blood pressure and arterial stiffness in relation to obesity. Forty-one transplant children (age, 15.7 [3.5] years; 28 males) were studied. Body composition was assessed by body mass index (BMI), waist circumference, skin-fold measurements, and multifrequence bioimpedance analysis. Glucose metabolism, blood pressure, and arterial stiffness (with the use of pulse wave velocity) were studied. Age- and sex-dependent parameters were expressed as standard deviation scores (SDS). RESULTS: The prevalence of overweight (BMI >85%) increased from 3.2% to 24.4% at 49 months (3-183) (median, range); the BMI SDS increased from -0.27 (0.79) to 0.67 (1.35) after Tx. There was a close correlation between BMI SDS and the percentage of body fat and body fat mass in the Tx group (r = 0.80; r = 0.94, P = .0001). Children with disturbed glycemic control (n = 14) had higher percentage of body fat and higher blood pressure compared with those with normal glucose metabolism (P < .05). There was no difference in pulse wave velocity between the lean and obese patients. CONCLUSIONS: The prevalence of overweight or obese patients in the Hungarian pediatric renal cohort is low at transplantation and rises subsequently. Overweight is associated with disturbed glycemic control and increased blood pressure; however, these disturbances are not yet reflected by stiffening of the arteries. Strategies are needed to prevent obesity, its impact on hypertension, and cardiovascular disease in pediatric transplantation.

Complement activation in thrombotic thrombocytopenic purpura.

BACKGROUND: Ultra-large von Willebrand factor and deficiency of its cleaving protease are important factors in the events leading to thrombotic microangiopathy; however, the mechanisms involved are only partly understood. Whereas pathological activation of the alternative complement pathway is linked to atypical hemolytic uremic syndrome, the role of complement activation in thrombotic thrombocytopenic purpura (TTP) is unknown. The aim of this study was to investigate whether signs of complement activation are characteristic of TTP. PATIENTS AND METHODS: Twenty-three patients with TTP (18 women, median age 38 years) and 17 healthy controls (13 women, median age 38 years) were included. Complement parameters (C3, Factors H, I, B and total alternative pathway activity) together with complement activation fragments (C3a) or complexes (C1rs-INH, C3bBbP, sC5b9) were measured by ELISA or RID. ADAMTS13 activity and anti-ADAMTS13 inhibitory antibodies were measured by the VWF-FRET73 assay. RESULTS: Increased levels of C3a, and SC5b9 were observed in TTP during acute episodes, as compared with healthy controls. Decreased complement C3 levels indicative of complement consumption occurred in 15% of acute TTP patients. Significant decrease of complement activation products C3a and SC5b9 was observed during plasma exchange (PEX). The sustained presence of anti-ADAMTS13 inhibitory antibodies in complete remission was associated with increased complement activation. CONCLUSION: These data document in an observational study the presence of complement activation in TTP. Further investigation is needed to determine its potential pathogenetic significance.

Diagnosis and classification of hemolytic uremic syndrome: the Hungarian experience.

BACKGROUND: Hemolytic uremic syndrome (HUS) is a rare disease with various etiologies, making the identification of the specific forms and appropriate treatment difficult. Therefore, clinical and laboratory data from these patients need to be analyzed in national and international registries. Herein we have described 47 Hungarian HUS patients with detailed laboratory and clinical data obtained between 2008 and 2010. METHODS: Blood samples and clinical data of 47 patients with HUS diagnosed according to characteristic clinical signs were submitted for diagnostic evaluation, including complement protein and genetic analysis, measurement of ADAMTS13 activity and antibody analysis against O157LPS and factor H. RESULTS: There were 8 patients with typical diarrhea-positive HUS; 13 with atypical HUS (aHUS) and 26 with secondary HUS/thrombotic thrombocytopenic purpura group characterized by signs of complement consumption and decreased ADAMTS13 activity. Thus, decreased total alternative pathway activity is a promising diagnostic parameter with good sensitivity for aHUS. CONCLUSIONS: These observations highlight the requirement for multiple diagnostic tests together with clinical data to identify the specific cause of HUS. Because the long-term prognosis of aHUS, eg, graft survival after renal transplantation, may vary according to the molecular etiology, it is important for all affected patients to undergo a detailed molecular diagnosis of the disease. There is a clear clinical need for the development and application of novel assay in this field to allow more rapid efficient diagnosis of patients who undergo a first episode of HUS.

Heat shock protein polymorphism predisposes to urinary tract malformations and renal transplantation in children.

BACKGROUND: Anatomical malformations of the kidney and urinary tract account for 17% of pediatric renal transplantation procedures. Heat shock proteins (HSPs) are molecular chaperones with a protective function that promotes cell survival. HSP72 is an endogenous ligand for toll-like receptor TLR4, thereby stimulating innate immunity. Both in adults and children, decreased expression of HSP70s is associated with a number of kidney diseases. OBJECTIVE: To assess the prevalence of HSPA1A G(190)C, HSPA1B A(1267)G, and TLR4 A(896)G polymorphisms in children who had undergone kidney transplantation. PATIENTS AND METHODS: Genotypes were analyzed using allele-specific polymerase chain reaction in 41 pediatric recipients. Allelic prevalence was related to reference values in 65 age- and sex-matched healthy children. RESULTS: Clinical data did not reveal a difference between any of the groups. HSPA1B (1267)GG genotype and HSPA1B (1267)G allele were observed more frequently in the transplant recipients compared with the control group: AA vs AG: odds ratio [OR], 12.6; 95% confidence interval [CI], 1.58-100.0; P = .004; AA vs GG: OR, 20.80; 95% CI, 2.32-187.00; P = .01; and A vs G: OR, 2.10; 95% CI, 1.19-3.07; P = .01. Furthermore, the prevalence of the HSPA1B (1267)GG genotype was greater in transplant recipients with vs without urinary tract malformations: AG vs GG: OR, 0.10; 95% CI, 0.09-0.48; P = .007. No differences were observed in the other studied polymorphisms. CONCLUSION: Our findings suggest an association between the carrier status of HSPA1B (1267)G with urinary tract malformations, leading to end-stage renal disease requiring kidney transplantation. This observation raises further questions about the clinical and therapeutic relevance of this polymorphism to pediatric nephrology.

Determinants of baroreflex function in juvenile end-stage renal disease.

Arterial baroreflex sensitivity (BRS) is markedly reduced in middle-aged patients with end-stage renal disease (ESRD), due to the combined effects of aging, arterial stiffening, and autonomic neuropathy. Much less is known about the effects of ESRD on arterial baroreflex in juvenile patients. Therefore, we investigated baroreflex function and its relation to carotid artery elasticity and heart rate variability in children and young adults with ESRD. We studied 42 subjects (9-30 years): 14 patients on maintenance hemodialysis (HD), 14 renal transplant recipients (RT), and 14 healthy control subjects (C). Baroreflex function was determined by pharmacological (BRS) and spontaneous (sequence and spectral indices) techniques. Carotid artery elasticity was characterized by stiffness index beta. Heart rate variability was assessed using time and frequency domain measures. Data are expressed as mean+/-s.d. BRS was markedly reduced in HD as compared to C (10.0+/-4.2 vs 25.7+/-5.9 ms/mm Hg); spontaneous indices were reduced to similar extent. Carotid artery stiffness was approximately 50% higher in HD than in C and was inversely related to BRS. Heart rate variability was also compromised in HD, and was directly related to spontaneous indices. No significant differences existed in any of these variables between RT and C. Decreased baroreflex function in juvenile HD is partly due to loss of carotid artery elasticity and partly due to impaired heart rate variability. Renal transplantation may partly prevent impairment or improve compromised baroreflex function in young patients with ESRD.

Guide-lines to the treatment of patients with X-linked hypophosphatemic rickets.

The causes of the development of nephrocalcinosis in familial hypophosphatemic rickets (FHR) are reviewed. The treatment combines vitamin D or 1,25 dihydroxyvitamin D and oral phosphate supplementation. Hypercalcaemia and hypercalciuria were thought to cause the renal calcification. On the basis of the data of eighteen patients with familiar hypophosphatemic rickets we have found that the main difference between the treatment of patients having nephrocalcinosis and those with normal renal morphology consisted in the dose of oral phosphate intake. Patients with nephrocalcinosis received significantly higher doses of oral phosphate (130 mg/kg/day versus 70 mg/kg/day, p < 0.01). Correspondingly, their urinary phosphate excretion was also significantly higher (p < 0.01). There was no difference between the two groups with respect of the doses of vitamin D and urinary calcium excretion. It can be concluded, that high concentrations of urinary phosphate can lead to nephrocalcinosis even if urinary calcium concentration is normal. In order to prevent nephrocalcinosis in patients with X-linked hypophosphatemia, the following guide-lines could be recommended: 1) urinary calcium excretion should be kept lower, than the usually allowed < 4 mg/kg/day; 2) oral phosphate supplementation should not exceed 100 mg/kg/day, 3) patients should be encouraged to drink large amounts of water, 4) regular ultrasound controls should be part of the routine follow-up.

Hydrochlorothiazide treatment of children with hypercalciuria: effects and side effects.

Urinary excretion of calcium and the changes in serum cholesterol fractions were investigated in 15 children with renal hypercalciuria, following 3-month hydrochlorothiazide (HCT) treatment (daily dose 1 mg/kg). Urinary calcium excretion (expressed as the ratio of calcium to creatinine) reached its lowest value after 2 weeks. It was still below the initial value at the end of the 3rd month of treatment (0.84 +/- 0.06, 0.29 +/- 0.03 and 0.6 +/- 0.09 mmol/mmol, respectively). A significant rise in the total serum cholesterol level (4.64 +/- 0.23 vs. 4.25 +/- 0.18 mmol/l before treatment, P < 0.01) and the low-density lipoprotein (LDL)-cholesterol fraction (2.6 +/- 0.24 vs. 2.31 +/- 0.31 before treatment, P < 0.01) was observed at the end of the 3rd month, while high-density lipoprotein (HDL)-cholesterol was slightly decreased. A significant elevation of the LDL/HDL ratio was also observed (from 1.76 +/- 0.17 to 2.2 +/- 0.17, P < 0.001), indicating an increase in the atherogenic cholesterol fractions. The risks and benefits of the thiazide therapy should be considered before starting long-term treatment of children with hypercalciuria and haematuria or renal stone disease.

Data on the degree of saturation of urine with respect to calcium hydrogen phosphate in hypercalciuric children and renal stone formers.

Calcium hydrogen phosphate (CaHPO4) was considered as one of the main factors governing renal calculus formation. The degree of saturation with respect to this phase was therefore calculated in urines of 36 hypercalciuric children (20 absorptive, 16 renal subtype) with isolated hematuria, 10 renal stone patients, and 30 healthy controls. The effects of low calcium diet and hydrochlorothiazide treatment were also investigated in the patient groups. The results were compared to the widely used indicator of hypercalciuria (Ca/Cr ratio). Urines of both the hypercalciuric and the normocalciuric renal stone patients were saturated on basal conditions. On low calcium diet, 12 children of the absorptive hypercalciuric, 13 of the renal hypercalciuric and 7 of the renal stone-forming children had their urines in the saturated zone - irrespective of the evolution of Ca/Cr ratio. Thiazide normalized the activity product of CaHPO4 in all groups. The use of the Ca/Cr ratio as the sole parameter in the investigation of children with isolated hematuria and hypercalciuria or calcium nephrolithiasis seems to be insufficient; simultaneous determinations of the state of saturation of urines is recommended. This technique should also allow a quantitative assessment of the various therapeutic regimens recommended.

Effect of thiazide on urinary calcium excretion and hematuria in children with postglomerular hematuria.

The effect of short term hydrochlorothiazide therapy on urinary calcium excretion was compared to that of low calcium and a combined low calcium and low sodium diet in 30 children with postglomerular hematuria. On basal conditions 9 children were normocalciuric, 11 had absorptive, 10 renal hypercalciuria. The effect of thiazide treatment on the haematuria was also evaluated. Thiazide revealed to be more effective in reducing calcium excretion than low calcium diet alone in all groups (p less than 0.001 in normocalciuria; p less than 0.01 in both hypercalciuric groups). Combined low calcium--low sodium diet and thiazide treatment were equally effective in reducing calcium excretion in the hypercalciuric groups. On the first 3 days of thiazide treatment a slight increase of hematuria was observed; in the following period a significant decrease in the occurrence (p less than 0.01 in both hypercalciuric groups) and degree (p less than 0.01 in absorptive; p less than 0.02 in renal hypercalciuria) of hematuria was noted. These data furnish further evidence on the relation of hypercalciuria and post-glomerular hematuria.

Higher osteocalcin levels and cross-links excretion in young men born with low birth weight.

As the result of accelerated growth, the final height of infants born with low birth weight (LBW) is near to the normal. Limited data are available about the bone density and bone turnover just after completion of skeletal development. We have investigated the bone turnover and bone density in 49 apparently healthy young LBW men (age 19-21 years; 21 born small for gestational age (SGA) and 28 appropriate for gestational age (AGA)) and in 16 age-matched controls. Bone mineral density of lumbar spine, femoral neck, and radius midshaft, the markers of calcium homeostasis, biochemical parameters of bone turnover as serum osteocalcin (OC), and urinary pyridinoline (PYD) and deoxypyridinoline (DPD) levels were measured. Bone mineral densities of LBW subjects were not altered. Serum calcium (SGA: 2.44+/-0.15; AGA:2.41+/-0.17, control: 2.25+/-0.09 mmol/liter, P < 0.05), OC (SGA:23.4+/-9.9; AGA:20.8+/-7.6; control:13.3+/-4.6 ng/ml, P < 0.01), total alkaline phosphatase (AP) (SGA:201+/-61; AGA:193+/-81, control: 117+/-34 IU/liter, P < 0.01), and urinary DPD/creat (ln.values: SGA:3.10+/-0.48; AGA:3.17+/-0.46; control:2.58+/-0.57 nmol/mmol, P < 0.05) were higher, whereas fractional excretion of calcium (SGA:0.94+/-0.470; AGA: 1.03+/-0.51, control:1.31+/-0.75%, P < 0.05) was lower in both SGA and AGA groups. PTH and 25OHD were not different. Significant correlation was obtained between seCa, OC, AP, DPD and birth weight of the subjects, but feCa correlated inversely to the birth weight. It was concluded that the bone turnover of LBW men is accelerated, but well balanced in young adulthood. Further investigation is needed to describe the possible link between accelerated bone turnover and hormonal homeostasis of LBW subjects.

Studies on the urinary calcium excretion in children with hematuria of postglomerular origin: effects of the variation of dietary calcium and sodium intake.

The effect of different dietary regimens and of an oral calcium (Ca) load was studied in 30 children with postglomerular hematuria, 8 of whom were renal stone formers. In addition we investigated the urinary inorganic phosphate complex composition in 12 of them, based on the principles of complex equilibria. Twenty-one of the 30 hematuric children with a urinary Ca/creatinine (Ca/cr) ratio of greater than or equal to 0.6 (mmol/mmol) were regarded as hypercalciuric. Low calcium intake normalised the ratio in 11 patients, fulfilling the definition of absorptive hypercalciuria, but not in the other 10 patients with renal hypercalciuria. Sodium restriction combined with low calcium diet induced a further significant decrease of the urinary Ca/cr ratio to a normal range in both forms of hypercalciuria (mean +/- SD: 0.325 +/- 0.112 in absorptive hypercalciuria; 0.533 +/- 235 in renal hypercalciuria). There was a significant difference in the composition of phosphate complexes between the 6 normocalciuric patients and the 6 children with renal hypercalciuria investigated. Lithogenic urinary phosphate complexes (CaHPO4, MgHPO4) were excreted by the latter group in a significantly higher amount under basal conditions. On the basis of these data sodium restriction added to low calcium diet could represent a dietary approach in preventing excessive calcium excretion in idiopathic hypercalciuria, and therefore renal stone formation.

Urinary calcium and oxalate excretion in children.

We have established normal values for calcium/creatinine (Ca/Cr) and oxalate/creatinine (Ox/Cr) ratios in 25 infants (aged 1-7 days) and 391 children (aged 1 month to 14.5 years) and compared these with values obtained in 137 children with post-glomerular haematuria and 27 with nephrolithiasis. Oxalate was measured by ion chromatography. Nomograms of Marshall and Robertson were used to calculate urine saturation to calcium oxalate. The Ca/Cr ratio was normally distributed whereas the Ox/Cr ratio had a log-normal distribution. The molar ratio of Ca/Cr was the lowest in the first days of life and the highest between 7 month and 1.5 years (mean +/- SD = 0.39 +/- 0.28 mmol/mmol). Following a slight decrease it stabilised by the age of 6 years (0.34 +/- 0.19 mmol/mmol). The highest Ox/Cr values were measured during the 1st month of life [geometric mean 133 (range 61-280) mumol/mmol], followed by a gradual decrease until 11 years of age [mean 24 (range 6-82) mumol/mmol]. Thirty-six haematuric children had hypercalciuria (26%), 23 had absorptive hypercalciuria, 13 renal type. Children with absorptive hypercalciuria on a calcium-restricted diet had significantly higher oxalate excretion than those with renal hypercalciuria and the control group [38 (range 28-49) vs. 22 (range 16-29) and 23 (range 22-27) mumol/mol respectively, P < 0.01]. Calcium oxalate urine saturation of stone patients was higher than that of patients with haematuria and the normal population (1.18 +/- 0.05 vs. 1.06 +/- 0.03, P < 0.03 and 0.84 +/- 0.03, P < 0.001 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Normal kidney function and elevated natriuresis in young men born with low birth weight.

The aim of our study was to characterize renal function and its relationship to blood pressure in healthy young Caucasian men born with a birth weight under 2,500 g (LBW). Urinary protein patterns, N-acetylglucosamine and gamma-glutamyltransferase activities, fractional sodium and potassium excretions, glomerular filtration rate, blood pressure, and erythrocyte Na+/K+-ATPase activities were determined in 65 subjects, of whom 49 were born with LBW. Signs of glomerular or tubular damage were not detected in the LBW population. However, the blood pressure and the renal sodium excretion were inversely correlated to the subjects' birth weight and were higher in LBW subjects than in controls. In contrast, the erythrocyte Na+/K+-ATPase activities were lower in LBW subjects. An inverse correlation was detected between the subjects' Na+/K+-ATPase activities and the renal sodium excretion or blood pressure. In summary, our results suggest that: (1) in young LBW Caucasian males signs of early glomerular and tubular impairment are not present; (2) the elevated renal sodium excretion may be a result of higher blood pressure; (3) the alteration of Na+/K+-ATPase activity might play a role either in the elevation of blood pressure and/or in the enhanced natriuresis of LBW subjects.

24 hour blood pressure monitoring in healthy and hypertensive children.

24 Hour ambulatory blood pressure monitoring (ABPM) was performed to provide data on the normal daily blood pressure of healthy schoolchildren and on patients with hypertension. The subjects studied were 123 healthy schoolchildren with a mean (SD) age of 12.5 (1.6) years (range 9.5-14.5 years), 24 children with borderline or mild hypertension, 17 with renal hypertension and normal renal function, 10 with chronic renal failure, and six with a renal allograft. In eight children with definite renal disease a second measurement was performed after treatment modification. The monitor used for ABPM was validated with a mercury column manometer. The mean (SD) of the signed differences of the blood pressure measured by the two methods was -0.19 (1.75) mmHg for the systolic and -0.21 (2.11) mmHg for the diastolic blood pressure (n = 60). Normal values for daytime and night time blood pressure were determined for those aged 10-14 years. The mean (SD) blood pressure of the 123 children was 109 (7)/66 (8) mmHg (systolic/diastolic) for the daytime and 96 (8)/52 (7) mmHg at night time. Of the 24 children with borderline or mild hypertension 14 had a raised blood pressure on ABPM. The circadian rhythm was disturbed in three children of this group. Even children with normal daytime blood pressure had significantly higher systolic blood pressure in the night when compared with the controls. The incidence of disturbed circadian rhythm was higher in the groups with renal hypertension (4/17 in the subgroup with normal renal function, 5/16 in the group with renal failure and/or transplantation). All children undergoing a second ABPM measurement had a lower average blood pressure after treatment adjustment. ABPM measurements were reproducible and accurate. The method provided new data on the physiological circadian variation of blood pressure in healthy children. It proved to be a helpful tool in the diagnosis of hypertension, particularly in the detection of cases of disturbance of the circadian rhythm of blood pressure pattern and individual adjustment of treatment.

Signs of autonomic neuropathy in childhood uremia.

To evaluate the presence of autonomic neuropathy in childhood uremia, cardiovascular autonomic reflexes were examined in children with chronic renal failure. Cardiovascular autonomic reflexes of 10 uremic patients on chronic dialysis and 10 transplanted patients were compared to assess the effect of transplantation on autonomic neuropathy. Resting heart rate, heart rate changes induced by deep breathing, by Valsalva maneuver, and following standing up, and blood pressure change induced by handgrip test were examined. Of the 10 uremic children, 4 showed early involvement and 2 had definite involvement of autonomic neuropathy. Only 1 of the 10 transplanted patients showed early signs of autonomic neuropathy. Autonomic tests demonstrated predominantly parasympathetic dysfunction. In conclusion, cardiovascular autonomic neuropathy is not rare in children and adolescents and young adults with chronic renal failure. In contrast, the prevalence is very low in transplanted patients with similar uremic precedents. Efforts should be made to prevent or delay this uremia-related complication.

Determination of oxalate excretion in spot urines of healthy children by ion chromatography.

Evidence for the suitability of spot urines for selective screening in children was obtained by comparing the 24-hour urinary oxalate excretion with the ratio of urinary oxalate to creatinine [mmol/mol] in spontaneously voided urine samples. Spot urines of 169 healthy children aged 1 day to 13 years were analysed in order to establish reference values for the urinary oxalate/creatinine ratio in relation to age and body surface area. Oxalate was measured by automated ion chromatography. Results showed an inverse relationship between the oxalate/creatinine ratio and age. The highest ratios, 131 +/- 57 mmol/mol (mean +/- 2 SD), were found in infants. At age two years, the ratio was 84 +/- 55, at age five years 56 +/- 35, and for children older than ten years 42 +/- 31. This finding can be explained by the gain of muscle mass and hence increased creatinine production with increasing age. Data for the urinary oxalate/creatinine ratio are presented according to body surface area for the assessment of children with abnormal growth. In 19 urine samples from nine patients with primary hyperoxaluria, the oxalate/creatinine ratio greatly exceeded (286-2022 mmol/mol) the above reference ranges. We therefore propose the determination of the oxalate/creatinine ratio in spot urines for the selective screening for hyperoxaluria in children with nephrocalcinosis or urolithiasis.

X-linked hypophosphatemia: effects of treatment with recombinant human growth hormone.

The impact of recombinant human growth hormone (rhGH) treatment on growth, bone mineral metabolism, and bone mineral density (BMD) was evaluated in six children (3 girls, 3 boys) with familial hypophosphatemic rickets (XLH). Five were prepubertal (aged 6-8.8 years), one 15.3-year-old boy had combined XLH and GH deficiency, but had not been treated with rhGH previously. rhGH was administered daily for 1 year, at a dose of 1 IU/kg per week, combined with 1,25-dihydroxyvitamin D3 and oral phosphate therapy. Z scores for growth velocity and height improved significantly (-2.9 vs. 2.5, P < 0.01, and -2.2 vs. -1.5, P < 0.01, respectively). However, the ratio of Z score for height to that of subischial leg length decreased significantly (0.65 vs. 0.43, P < 0.01), indicating disproportionate growth in favor of the trunk. The height-corrected BMD Z increased slightly (-0.99 vs. -0.94, P < 0.05). A slight increase in serum phosphate occurred (0.78 vs. 0.88 mmol/l, P < 0.02). Tubular reabsorption of phosphate/glomerular filtration rate increased from 0.45 mmol/l to 0.55 mmol at 6 months (P < 0.02), but returned to the initial level at 12 months. These results indicate that children with XLH can benefit from the positive effect of rhGH on growth, however treatment could aggravate the already existing tendency to disproportionate growth. GH production should be evaluated in poorly growing patients with XLH, because it can mask GH deficiency. rhGH can be safely combined with conventional treatment in XLH. Further studies are needed to determine the effect of treatment on final height and maximal BMD.

Sodium-lithium countertransport in children with nephrotic syndrome.

The mechanisms of sodium retention in edema-forming minimal change nephrotic syndrome (MCNS) have not been completely evaluated. The aim of this study was to characterize the transmembrane sodium transport in nephrotic syndrome by measuring the erythrocyte sodium-lithium countertransport (SLC) in vitro. Eighteen children with MCNS were studied in the edema-forming state, and subsequently at the beginning of remission. Nephrotic children with edema retained sodium (10+/-12 micromol/day) and had a higher SLC [426+/-118 vs. 281+/-60 micromol/l red blood cells (RBC) per hour, P=0.003). The intracellular sodium concentration of nephrotics was 6.1+/-2.1 mmol/l RBC, which did not differ from that of controls (6.42+/-2.24, n=13). In remission sodium balance became negative (-30+/-21 mmol/day), and the SLC decreased but still differed significantly from control values (P=0.009). The intracellular sodium content decreased to 4.4+/-0.9 mmol/l RBC (P=0.002). There was a negative correlation between erythrocyte SLC and plasma albumin concentration (r=0.48, P=0.003), and urinary sodium excretion rate (r=0.66, P=0.001). In conclusion, erythrocyte SLC is high in the edema-forming state of childhood nephrotic syndrome and decreases with the onset of remission. A role for the SLC in the altered sodium homeostasis of nephrotic syndrome is suggested.