Kostić M

Disparities in Policies, Practices and Rates of Pediatric Kidney Transplantation in Europe

We aimed to provide an overview of kidney allocation policies related to children and pediatric kidney transplantation (KTx) practices and rates in Europe, and to study factors associated with KTx rates. A survey was distributed among renal registry representatives in 38 European countries. Additional data were obtained from the ESPN/ERA‐EDTA and ERA‐EDTA registries. Thirty‐two countries (84%) responded. The median incidence rate of pediatric KTx was 5.7 (range 0−13.5) per million children (pmc). A median proportion of 17% (interquartile range 2−29) of KTx was performed preemptively, while the median proportion of living donor KTx was 43% (interquartile range 10−52). The median percentage of children on renal replacement therapy (RRT) with a functioning graft was 62%. The level of pediatric prioritization was associated with a decreased waiting time for deceased donor KTx, an increased pediatric KTx rate, and a lower proportion of living donor KTx. The rates of pediatric KTx, distribution of donor source and time on waiting list vary considerably between European countries. The lack of harmonization in kidney allocation to children raises medical and ethical issues. Harmonization of pediatric allocation policies should be prioritized.

Medium- and Long-Term Prognosis of Patients with Acute Poststreptococcal Glomerulonephritis

The prognosis of acute poststreptococcal glomerulonephritis (APSGN) is still a matter of considerable debate. In an attempt to elucidate this controversy, the medium-term prognosis was evaluated in 40 patients 5-9 years after the onset of the disease, and the long-term prognosis in 88 patients 10-17 years after the onset of the disease. All were sporadic cases. In the medium-term follow-up study, abnormalities were revealed in 5.0% (2/40) of the patients. Hypertension and proteinuria were the only abnormalities detected. In the long-term follow-up study, abnormalities were revealed in 6.8% (6/88) of the patients. Hypertension was found in 3.4, proteinuria in 2.3, and microhaematuria in 2.3% of the patients. In both studies, all patients had normal creatinine clearance. We conclude that the medium- and long-term outcome of patients with APSGN is excellent.

Hyperlipidemia, oxidative stress, and intima media thickness in children with chronic kidney disease.

BackgroundThe roles of dyslipidemia and oxidative stress in the early phases of atherosclerosis were tested in children with chronic kidney disease (CKD). Intima media thickness of common carotid arteries (cIMT) is used as a measure of early atherosclerosis.MethodsFifty-two pediatric CKD patients were enrolled in the study (10 with chronic renal failure [CRF], 22 with a renal transplant [RT], 20 with chronic hemodialysis (cHD) patients, and 36 healthy children (control group, CG). Lipid status, oxidative stress, and paraoxonase 1 (PON1) status were assessed. cIMT was measured by ultrasound, adjusted for age and sex, and presented as standard deviation scores (SDS).ResultsChildren with CKD had disturbed lipid content, which was most pronounced in cHD children, with higher free cholesterol and triglycerides compared with healthy children. Oxidative stress was markedly increased (malodialdehyde [MDA, μmol/L]: CRF 1.50 ± 0.26, RT 1.55 ± 0.40, cHD 1.77 ± 0.34, CG 0.97 ± 0.33, p < 0.001) and antioxidative defense was compromised (superoxide dismutase [SOD, U/L]: CG 120 ± 21, CRF 84 ± 25, RT 93 ± 12, cHD 119 ± 37, p < 0.001). Multiple linear regression analysis showed that a model that included disease duration, blood pressure, urea, lipid, and oxidative status parameters accounted for more than 90% of the variability of cIMT-SDS.ConclusionsEarly atherosclerosis in CKD children is caused, at least in part, by dyslipidemia and oxidative stress. Monitoring of vessel wall changes, along with assessment of oxidative stress status and high density lipoprotein (HDL) functionality is necessary to ensure better therapeutic strategies for delaying atherosclerotic changes in their asymptomatic phase.

Clinical characteristics of haemorrhagic fever with renal syndrome in children

From January 1988 to September 1989, seven patients (4 girls and 3 boys, aged 3–12 years) with haemorrhagic fever with renal syndrome (HFRS) were hospitalised at the University Childrens Hospital in Belgrade. In four patients the disease appeared as a family outbreak, the others were sporadic cases. In six patients the clinical presentation was suggestive of HFRS, as they had fever with headache, myalgia, sore throat and gastrointestinal illness followed by renal abnormalities. However, severe haemorrhagic syndrome with petechia, haematoma, haematemesis and melaena was present in one patient only. Renal disease presented as nephritic syndrome and/or acute renal failure. Five patients recovered after 2–3 weeks without sequellae, one patient had decreased renal function 17 months after the start of the disease and the remaining patient died. In six patients the diagnosis of HFRS was confirmed serologically by a significant rise in antibody titres against hantaviruses, while in the patient with the fatal and fulminant course of the disease, the diagnosis was established on the basis of epidemiological and autopsy findings. We suggest that children living in endemic areas who develop an ill-defined, febrile and gastrointestinal disease with renal dysfunction should be evaluated for HFRS.

Hyponatremic hypertensive syndrome

Abstract We report on a 4-year-old girl with hyponatremic-hypertensive syndrome (HHS), a rare entity in childhood. The girl was referred to us from a local hospital with a history of recurrent fever, vomiting, and seizures. On admission she was markedly dehydrated. Initial investigations revealed severe hyponatremia (serum Na 120 mmol/l), hypochloremia (serum Cl 68 mmol/l), and mild hypokalemia (serum K 3.3 mmol/l), while serum calcium and magnesium were normal. Serum urea was 5 mmol/l and serum creatinine was 62 µmol/l. Despite hyponatremic dehydration, her urine output was high (2050 ml/24 h), as was her urinary sodium (168 mmol/24 h). She had massive transient proteinuria (maximal 1642 mg/24 h) while being severely hypertensive (blood pressure 210/160 mmHg). Further investigations revealed right kidney scarring, hyper-reflexive bladder dysfunction, massive brain infarcts, and myocardial left ventricular hypertrophy. Renal arteries were normal on arteriography. Blood pressure control resulted in normalization of serum and urinary electrolytes and decrease of proteinuria. Hyponatremia and transient massive proteinuria in this patient seem to be caused by high-pressure-forced diuresis due to malignant renoparenchymal hypertension.

Expression profiling of the AT2R mRNA in affected tissue from children with CAKUT

OBJECTIVES Congenital anomalies of the kidney and urinary tract (CAKUT) are common causes of chronic renal failure in children. The angiotensin II receptor type 2 (AT2R) is one of proposed candidate genes for CAKUT, but the expression was never explored in humans. The aim was to establish the AT2R gene expression in human CAKUT concerning -1332A/G polymorphism, which might affect alternative splicing. DESIGN AND METHODS Forty-eight patients with CAKUT constitute the basis of this study. Genotyping for -1332A/G, RT-PCR for AT2R gene expression and confirmation sequencing were performed. RESULTS The expression of Ex 1/2/3 and Ex 1/3 transcript splice variants of the AT2R mRNA were detected in human CAKUT tissue. The pattern was observed independently of A to G transition. CONCLUSIONS The expression of AT2R mRNA in human CAKUT was established for the first time and was not affected by -1332A/G polymorphism in children with CAKUT.

Characteristics of low-density and high-density lipoprotein subclasses in pediatric renal transplant recipients

Renal transplant recipients often suffer from dyslipidemia which is one of the principal risk factors for cardiovascular disease. This study sought to determine characteristics of high‐density lipoprotein (HDL) and low‐density lipoprotein (LDL) particles and their associations with carotid intima‐media thickness (cIMT) in a group of pediatric renal transplant recipients. We also examined the influence of immunosuppressive therapy on measured LDL and HDL particle characteristics. HDL size and subclass distribution were determined using gradient gel electrophoresis, while concentrations of small, dense LDL (sdLDL)‐cholesterol (sdLDL‐C) and sdLDL‐apolipoprotein B (sdLDL‐apoB) using heparin‐magnesium precipitation method in 21 renal transplant recipients and 32 controls. Renal transplant recipients had less HDL 2b (P < 0.001), but more HDL 3a (P < 0.01) and 3b (P < 0.001) subclasses. They also had increased sdLDL‐C (P < 0.01) and sdLDL‐apoB (P < 0.05) levels. The proportion of the HDL 3b subclasses was a significant predictor of increased cIMT (P < 0.05). Patients treated with cyclosporine had significantly higher sdLDL‐C and sdLDL‐apoB concentrations (P < 0.05) when compared with those on tacrolimus therapy. Pediatric renal transplant recipients have impaired distribution of HDL and LDL particles. Changes in the proportion of small‐sized HDL particles are significantly associated with cIMT. Advanced lipid testing might be useful in evaluating the effects of immunosuppressive therapy.

Progressive tubulointerstitial nephritis and chronic cholestatic liver disease

We report the clinical and morphological features of a distinctive hepatorenal disorder in four patients and review the five similar patients in the literature. The main clinical characteristics were early onset of cholestatic liver disease and progressive tubulointerstitial nephritis leading to renal death in early childhood. Liver histology showed disturbed architecture with nodular and acinar formations and portal fibrosis and bile duct proliferation. Histological abnormalities in the kidney were severe interstitial fibrosis and tubular atrophy and dilatation, while the typical features of nephronophthisis were lacking. These clinical and morphological characteristics distinguish our patients from the majority described, as having nephronophthisis and congenital hepatic fibrosis or any other known syndrome with concomitant hepatorenel involvement. We suggest that the association of cholestatic liver disease and progressive tubulointerstitial nephritis represents a new syndrome.

Prevalence and predictors of the sub-target Hb level in children on dialysis

BACKGROUND Anaemia is a common and potentially treatable co-morbidity of end-stage renal disease. We aimed to determine the prevalence of the sub-target haemoglobin (Hb) level among European children on dialysis and to identify factors associated with a low Hb level. METHODS From the European Society for Paediatric Nephrology (ESPN)/European Renal Association-European Dialysis Transplant Association (ERA-EDTA) registry, data were available on 2351 children between 1 month and 18 years of age, totalling 5546 measurements from 19 countries. RESULTS The mean Hb level was 10.8 g/dL (5th-95th percentiles, 7.4-13.9). Among those above 2 years of age, the mean Hb level was 10.9 g/dL (11.4% below 8.5 g/dL), while it was 10.3 g/dL among those below 2 years (11.2% below 8.0 g/dL). A total of 91.2% of the patients were on an erythropoiesis-stimulating agent (ESA). Hb levels increased with age and were higher in peritoneal dialysis compared with haemodialysis patients. Patients with congenital anomalies of the kidney and urinary tract showed the highest Hb levels, and those with cystic kidney diseases or metabolic disorders the lowest ones. Ferritin levels between 25 and 50 ng/mL were associated with the highest Hb levels. We found a weak inverse association between parathyroid hormone (PTH) and Hb. Whereas standardized blood pressure (BP) was not elevated in patients with above-target Hb, elevated systolic BP z-score was noted in those with sub-target Hb levels. CONCLUSIONS Sub-target Hb levels remain common in children on dialysis, in spite of virtually all children being treated with ESA; although we cannot exclude under-dosing. Optimal ferritin levels seemed to be slightly lower in children (25-50 ng/mL) than those in adults. Other risk factors for sub-target Hb are dialysis modality and a high PTH level.

Ambulatory Blood Pressure Monitoring in Chronic Haemodialysis Children with End-Stage Renal Failure

Dr. Amira Peco-Antić, Nephrology Department, University Children’s Hospital, Tiršova 10, 11000 Belgrade (Serbia) Dear Sir, According to the data from the literature, there are different opinions about predialy-sis (PreD) and postdialysis (PostD) blood pressures (BPs) [1,2] and the direct effect of hypervolaemia on PreD and PostD BPs [3]. To clarify these controversial opinions, ambulatory blood pressure monitoring (ABPM) was performed in two groups of patients: group A consisted of 13 children with end-stage renal failure, aged 15.15 ± 5.58 years, on chronic haemodialysis from 2 to 156 (mean 45.3) months, of whom 4 where hypertensive and 9 normotensive; group B consisted of 19 children with chronic mild hypertension (essential or renal) and normal global renal function, aged 15.28 ± 2.27 years. BP was measured with an oscillometer, model 90206 (SpaceLabs, Inc., Redmond, Wash., USA). Blunted circa-dian BP rhythm (nocturnal decrease of BP to less than 10% of daytime values) was observed in 84.62% of children from group A and 31.58% from group B (p = 0.0037). PreD and PostD systolic, diastolic and mean arterial BPs did not differ significantly and were correlated with InterD BP (r = 0.9; p < 0.01) (fig. 1). This is probably due to the fact