First Cryptosporidium outbreak in Hungary, linked to a treated recreational water venue in 2015.

In June 2015, an outbreak of cryptosporidiosis with 35 cases (23 probable and 12 laboratory-confirmed) occurred among 191 attendees of a residential rehabilitation holiday for paediatric organ transplant patients (n = 49) and their families at a hotel in Somogy county, Hungary. The overall attack rate was 18%. Most of the cases were transplanted children who experienced severe acute disease and required adjustment to their tacrolimus immunosuppression. A retrospective case-control study suggested an association between recreational water exposures and illness: cases were seven times more likely than controls to have swum in the children's pool (odds ratio 7.17; 95% confidence interval 2.9-17.2; P < 0.0001) and five times more likely to have used the jetted whirlpool (odds ratio 5.25; 95% confidence interval 2.1-13.1; P < 0.0001). This was the first outbreak of cryptosporidiosis in Hungary and it is especially unfortunate that it affected vulnerable children who experienced severe symptoms. Cryptosporidium presents specific infection control difficulties in treated recreational water venues; the link to a whirlpool is unusual and highlights the importance of the age-appropriate use of these facilities and reminding users not to immerse their heads or swallow the water. Cryptosporidiosis is more commonly linked to children' pools where improved bather hygiene and promoting exclusion of diarrhoea cases could help to avoid similar outbreaks.

Considerable variations in growth hormone policy and prescription in paediatric end-stage renal disease across European countries-a report from the ESPN/ERA-EDTA registry.

BACKGROUND: Growth retardation in paediatric end-stage renal disease (ESRD) has a serious impact on adult life. It is potentially treatable with recombinant growth hormone (rGH). In this study, we aimed to quantify the variation in rGH policies and actual provided care in these patients across Europe. METHODS: Renal registry representatives of 38 European countries received a structured questionnaire on rGH policy. Cross-sectional data on height and actual use of rGH on children with ESRD aged <18 years were retrieved from the ESPN/ERA-EDTA Registry. RESULTS: In 21 (75%) of 28 responding countries, rGH is reimbursed for children with ESRD. The specific conditions for reimbursement (minimum age, maximum age and chronic kidney disease stage) vary considerably. Mean height standard deviation scores (SDS) at renal replacement therapy (RRT) [95% confidence interval (CI)] were significantly higher in countries where rGH was reimbursed -1.80 (-2.06; -1.53) compared with countries in which it was not reimbursed [-2.34 (-2.49;-2.18), P < 0.001]. Comparison of the mean height SDS at onset of RRT and final height SDS yielded similar results. Among the 13 countries for which both data on actual rGH use between 2007 and 2011 and data from the questionnaire were available, 30.1% of dialysis and 42.3% of transplanted patients had a short stature, while only 24.1 and 7.6% of those short children used rGH, respectively. CONCLUSION: Reimbursement of rGH associates with a less compromised final stature of ESRD children. In many countries with full rGH reimbursement, the actual rGH prescription in growth-retarded ESRD children is low and obviously more determined by the doctor's and patients' attitude towards rGH therapy than by financial hurdles.

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.

Needle-related ultrasound artifacts and their importance in anaesthetic practice.

Real-time ultrasound guidance for any intervention relies on visualization of needle advancement towards a target. Unfortunately, correct identification of the needle tip is not straightforward, as artifacts always distort the image. The ultrasonic appearance of the needle is often degraded by reverberation, comet tail, side-lobe, beam-width, or bayonet artifacts, which can easily confuse an unprepared operator. Furthermore, the typical needle image, that is, a dot or a straight line (out-of-plane and in-plane approaches, respectively), is also a result of artifacts that hide the real dimensions of the needle. Knowledge and correct interpretation of these artifacts is important for safe practice and is paramount to success when precise needle manipulation is mandatory, for example, when the target is small. In this review, authors discuss the most important needle-related artifacts and provide a physical explanation focusing on implications for everyday practice. Recent advances that allow increased needle visualization and reduction of artifacts are also discussed.

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.

The importance of different immunosuppressive regimens in the development of posttransplant diabetes mellitus.

Solid-organ transplantation is the optimal long-term treatment for most patients with end-stage organ failure. After solid-organ transplantation, short-term graft survival significantly improved (1). However, due to chronic allograft nephropathy and death with functioning graft, long-term survival has not prolonged remarkably (2). Posttransplant immunosuppressive medications consist of one of the calcineurin inhibitors in combination with mycophenolate mofetil (MMF) or azathioprine (Aza) and steroids. All of them have different adverse effects, among which posttransplant diabetes mellitus (PTDM) is an independent risk factor for cardiovascular (CV) events and infections causing the death of many transplant patients and it may directly contribute to graft failure (3). According to the criteria of the American Diabetes Association (4), diabetes mellitus (DM) is defined by symptoms of diabetes (polyuria and polydipsia and weight loss) plus casual plasma glucose concentration ≥ 11.1 mmol/L or fasting plasma glucose (FPG) ≥ 7.0 mmol/L or 2-h plasma glucose level ≥ 11.1 mmol/L following oral glucose tolerance test (OGTT). This metabolic disorder occurring as a complication of organ transplantation has been recognized for many years. PTDM, which is a combination of decreased insulin secretion and increased insulin resistance, develops in 4.9/15.9% of liver transplant patients, in 4.7/11.5% of kidney recipients, and in 15/17.5% of heart and lung transplants [cyclosporine A (CyA)/tacrolimus (Tac)-based regimen, respectively] (5). Risk factors of PTDM can be divided into non-modifiable and modifiable ones (6), among which the most prominent is the immunosuppressive therapy being responsible for 74% of PTDM development (7). Emphasizing the importance of the PTDM, numerous studies have determined the long-term outcome. On the basis of these studies, graft and patient survival is tendentiously (8) or significantly (9, 10) decreased for those developing PTDM.

H1N1 vaccination in pediatric renal transplant patients.

BACKGROUND: Solid organ transplant recipients undergoing immunosuppressive therapy are considered to be at high risk of serious infectious complications. In 2009, a new influenza pandemic caused serious infections and deaths, especially among children and immunocompromised patients. Herein we have reported the safety and efficacy of a single-shot monovalent whole-virus vaccine against H1N1 infection in the pediatric renal transplant population. METHODS: In November and December 2009, we vaccinated 37 renal transplant children and adolescents and measured their antibody responses. Seroprotection, seroconversion, and seroconversion factors were analyzed at 21 days after vaccination. RESULTS: None of the vaccinated patients experienced vaccine-related side effects. None of the patients had an H1N1 influenza infection after vaccination. All of the patients showed elevations in antibody titer at 21 days after vaccination. In contrast, only 29.72% of the patients achieved a safe seroprotection level and only 18.75% a safe seroconversion rate. More intense immunosuppressive treatment displayed negative effect on seroprotection and seroconversion, and antibody production significantly increased with age. No other factor was observed to influence seroprotection. CONCLUSIONS: We recommend vaccination of children and adolescent renal transplant recipients against H1N1 virus. However, a single shot of vaccine may not be sufficient; to achieve seroprotection, a booster vaccination and measurement of the antibody response are needed to assure protection of our patients.

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.

A single-center experience with kidney transplantation in the verteberal, anal, cardiac, tracheoesophageal, renal, and limb birth detects (VACTERL) association.

VACTERL association is a nonrandom association of birth defects in vertebral, anal, cardiac, tracheoesophageal, renal, and limb structures. Renal anomalies are observed in ∼60%-90% of VACTERL patients. We present 3 cases to demonstrate the clinical and surgical challenges that these patients present for renal transplantation. One pediatric and 2 adult patients with the VACTERL association were transplanted at a single center; their follow-up times were 6 years, 4 years, and 3 months. Only 1 of them had a suitable native bladder to receive the kidney graft; the other 2 required bladder augmentation, 1 of which was performed after the loss of the first graft. None of these patients had an uneventful posttransplantation course. Two patients had acute rejection episodes, and 2 had reoperations for urologic complications. One patient needed a surgical intervention owing to a sigmoid prolapse. All 3 grafts worked at last examination. The 2 patients with bladder reconstructions and longer follow-ups suffered recurrent pulmonary and urinary infections and had been hospitalized several times during each posttransplantation year. In conclusion, multiorgan involvement in VACTERL patients greatly complicates medical care after transplantation; urinary tract reconstruction seems to be essential before transplantation.

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.

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.

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.

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.

Abundance and activity of Ca2+-ATPase in hypercalciuric children.

The plasma membrane Ca2+-ATPase (PMCA) is one of the main regulators of cell Ca2+ homeostasis. The aim of our study was to determine whether the abundance and activity of PMCA are altered in erythrocytes of children with idiopathic hypercalciuria. Twenty-four children with idiopathic hypercalciuria (13 girls and 11 boys, mean age 10.6+/-4.8 years; mean urinary calcium concentration 0.85+/-0.20 mmol/mmol creatinine) and 30 healthy age-matched children were enrolled. PMCA protein abundance was determined by Western blot analysis. Enzyme activity was determined spectrophotometrically. The abundance of PMCA did not differ in hypercalciuric patients from that of control subjects (98+/-22% vs 100+/-18%). Moreover, the activity was not different between the studied groups (3141+/-1494 vs 2953+/-780 nmol ATP/mg protein/h). The extent of hypercalciuria did not correlate with enzyme abundance or activity. Assuming that erythrocytes may reflect the renal tubular transporting processes, our data suggest that other Ca2+-transport mechanisms than PMCA might be involved in the development of idiopathic hypercalciuria in children.

Hyperhomocysteinaemia and MTHFR C677T gene polymorphism in renal transplant recipients.

AIM: To study the effect of folate treatment on hyperhomocysteinaemia and the effect of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism on total homocysteine and folate concentrations after renal transplantation. METHODS: A total of 30 transplanted children and adolescents were investigated for total homocysteine and folate serum concentrations before and after folate treatment, as well as for the presence of the MTHFR C677T polymorphism. RESULTS: The allele frequency of C677T polymorphism in the MTHFR gene in the study population (0.33) was not different to that in controls (0.38). Before folate treatment the homocysteine concentration was raised in all groups; following folate supplementation it was significantly decreased in the CC and CT groups, but not in the TT group. In patients with CC genotype, serum homocysteine correlated with serum creatinine and cholesterol, and time since transplantation before treatment. CONCLUSION: Folate supplementation appears to be an effective strategy to normalise total homocysteine concentration in renal transplanted children and adolescents.

Monitoring cardiovascular changes during hemodialysis in children.

Hemodialysis (HD) causes rapid volume shifts and circulatory changes. In chronic renal failure (CRF) Na+/K+ATP-ase is depressed, whereas endogenous digoxin-like factor (EDLF) is elevated. Our aim was to characterize HD-induced cardiovascular adaptation and its possible links to Na+/K+ATP-ase and EDLF. Eleven children with CRF on HD (aged 14.7 +/- 3.7 years) and 11 healthy children were investigated for basic circulatory parameters. Thoracic impedance (Zo) and circulatory parameters were monitored by impedance cardiography (ICG) during HD. Erythrocyte Na+/K+ATP-ase and EDLF were measured before and after HD. Up to the loss of 6% of total body weight, Zo rose linearly with fluid removal, above this no further increase occurred. Heart rate and mean arterial pressure (MAP) were inversely related (r = -0.97); MAP rose in the first and decreased in the second part of HD. Systemic vascular resistance paralleled MAP, whereas stroke volume rapidly decreased, but stabilized in the second part of HD. The ratio of preejection period/ventricular ejection time (PEP/VET) correlated positively with HD duration (r = 0.92), suggesting diminished cardiac filling. Cardiac index (CI) remained stable. EDLF was high in uremia accompanied by depressed Na+/K+ATP-ase (P < 0.05 and P < 0.01, respectively). Following HD Na+/K+ATP-ase normalized. Correlation between Na+/K+ATP-ase activity and MAP was linear (r = 0.85). In conclusion, ICG during HD provides detailed information concerning circulatory adaptation resulting in stable CI, suggesting that the dialysis-induced hypovolemia is compensated by the centralization of the blood volume. Changes of Na+/K+ATP-ase indicate that dialyzable blood pressure-regulating substance(s) inhibit(s) the pump. However, lack of further correlation between Na+/K+ATP-ase, EDLF, and cardiovascular parameters indicates the complexity of the regulatory processes.

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.

[Familial hypophosphatemic rickets]. / Familiaris hypophosphataemiás rachitis.

Familiar hypophosphatemic rickets (FHR) is characterized by isolated defect of renal phosphate reabsorption, hypophosphataemia, rickets and poor growth. In untreated cases parathyroid hormone and calcitriol levels are normal. FHR is caused by mutations of the PHEX gene encoding a zinc-binding metalloprotease enzyme. PHEX is expressed in bones and the parathyroid gland but not in the kidney. The gene product is involved in the inactivation of a phosphate regulating hormone (phosphatonin). The presence of this hormone through unknown mechanisms decreases the sodium-dependent phosphate cotransporter in the kidney resulting in impaired phosphate transport. In addition the PHEX gene product exerts autocrine and paracrine effects on the bone. Despite recent advances in the understanding of the pathomechanism, treatment of FHR is still symptomatic. It consists of active vitamin D analogues and oral phosphate supplementation. Nephrocalcinosis is a well-known, usually non-progressive side effect of the conventional therapy. As shown by pilot studies, poorly growing children with FHR may benefit from the positive effect of human recombinant growth hormone (rhGH). However, rhGH treatment could aggravate the already existing tendency to disproportionate growth resulting in the overgrowth of the trunk. The disturbed phosphate homeostasis persists during the whole life span of the FHR patients. It is therefore essential to provide lifelong care, to prevent late skeletal and dental consequences or to treat them if already established. That care should be done by the teamwork of the pediatrician, internist, orthopedist, dentist and the psychologist.

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.