Individual and regional factors of access to the renal transplant waiting list in france in a cohort of dialyzed patients.

Several studies have investigated geographical variations in access to renal transplant waiting lists, but none has assessed the impact on these variations of factors at both the patient and geographic levels. The objective of our study was to identify medical and non-medical factors at both these levels associated with these geographical variations in waiting-list placement in France. We included all incident patients aged 18-80 years in 11 French regions who started dialysis between January 1, 2006, and December 31, 2008. Both a multilevel Cox model with shared frailty and a competing risks model were used for the analyses. At the patient level, old age, comorbidities, diabetic nephropathy, non-autonomous first dialysis, and female gender were the major determinants of a lower probability of being waitlisted. At the regional level, the only factor associated with this probability was an increase in the number of patients on the waiting list from 2005 to 2009. This finding supports a slight but significant impact of a regional organ shortage on waitlisting practices. Our findings demonstrate that patients' age has a major impact on waitlisting practices, even for patients with no comorbidity or disability, whose survival would likely be improved by transplantation compared with dialysis.

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.

[Evolution of the access to the kidney transplantation in France of foreign patients and French patients living in overseas territories]. / Évolution de l'accès à la greffe rénale en France des patients étrangers ou résidant outre-mer.

In France, foreign patients, whether resident or not in France, can register on the national waiting list under administrative and financial conditions. We performed a retrospective analysis to evaluate the access to kidney transplantation on a cohort 2004-2008, using the national registry. Among the 14,732 patients registered during this period, 15.3% are of non-French nationality (3.4% other European, 5.9% North African, 3.9% sub-Saharan African, 2.9% other). Among the 84.6% of French nationality, 3.3% are living in French overseas territories. Compared to the 17.6-month median waiting time of the cohort, median waiting time differs significantly between groups, from 15.7 months for mainland French patients to 36 months for sub-Saharan African patients. Despite the regular development of the allocation rules, these disparities in access to transplantation are mainly, but not completely, explained by blood group or HLA matching difficulties. After adjustment for the other factors known to be significantly linked to a difficult access to transplantation, North and sub-Saharan African patients have the worst difficulties. Future research should consider nonmedical factors, such as socio-economic or socio-cultural factors, potentially relevant to avoid disparities in access to transplantation and should aim at developing specific interventions.

Laparoscopic retroperitoneal nephrectomy in high risk children.

PURPOSE: Nephrectomy may be indicated in children with end stage renal disease before transplantation. We studied the feasibility and results of nephrectomy performed via a retroperitoneal laparoscopic approach in these high risk children. MATERIALS AND METHODS: We performed 12 nephrectomies in 9 children with end stage renal disease and a mean age of 7 years (range 7 months to 13 years) through a 3 trocar retroperitoneal laparoscopic approach. Cases were classified as American Society of Anesthesiologists grade III and presented with end stage renal disease, hypertension, thrombocytopenia and/or the nephrotic syndrome. The renal artery and vein were ligated separately with endocorporeal knots and clips. Mean size of the kidney was 8 cm. (range 5 to 12). Bilateral nephrectomy was performed simultaneously in 2 patients 7 and 12 months old, respectively. Cardiorespiratory changes related to retroperitoneal gas insufflation were assessed prospectively. To compare laparoscopic versus open nephrectomy we retrospectively analyzed the data of 12 open nephrectomies performed in 9 children with similar nephrological indications. RESULTS: The procedure was feasible in all cases without conversion to open surgery, and no intraoperative incident occurred. Mean operative time of laparoscopic nephrectomy was 2 hours (range 1 hour 20 minutes to 3 hours 10 minutes). After retroperitoneal carbon dioxide insufflation systolic arterial pressure and end-tidal carbon dioxide were significantly increased without the need for specific measure to correct these modifications. Hemodialysis began 1 day postoperatively and feeding began 2 days postoperatively. Mean hospital stay was 5.2 days (range 3 to 7). The comparative study of the open nephrectomy group showed no significant difference in mean operating time (p = 0.07), and hospital stay was significantly shorter for the laparoscopic group (p <0.001). CONCLUSIONS: Retroperitoneal laparoscopic nephrectomy is safe and feasible for high risk children. The relatively long operating time is necessary for hemostasis in these children at risk for hemorrhagic complications.

Outcome of posterior urethral valves: to what extent is it improved by prenatal diagnosis?

PURPOSE: To assess the impact of prenatal diagnosis and evaluation on the outcome of posterior urethral valves we studied all cases of valves detected prenatally, including cases of pregnancy termination due to posterior urethral valves. MATERIALS AND METHODS: Between 1989 and 1996, 30 neonates with prenatally detected posterior urethral valves were treated at our hospital. The prenatal parameters analyzed were age of gestation at diagnosis, ultrasonographic appearance of renal parenchyma and amniotic fluid volume. Fetal urine was analyzed in 9 cases. We reviewed the outcome of 10 neonates treated for posterior urethral valves which were not diagnosed prenatally during the same period. RESULTS: Of the 30 neonatal survivors 6 (20%) had renal failure, including end stage renal disease in 2, after a mean followup of 4 years. Renal failure developed in 2 of 5 cases detected before 24 weeks of gestation, in 1 of 6 with oligohydramnios and in 2 of 5 with abnormal parenchymal renal ultrasound. Normal parenchymal ultrasound and amniotic volume could not predict for good outcome. Renal failure developed in 2 of 7 cases predicted by fetal urinalysis as good prognosis and in 1 of 2 cases predicted as poor prognosis. Pregnancy was terminated for posterior urethral valves in 5 cases based on prenatal criteria of severe renal impairment. Considering these cases as poor outcome, the rate of poor prognosis increased from 20 to 31%. Among the 10 neonates without a prenatal diagnosis of posterior urethral valves renal failure developed in 2 (20%), including end stage renal disease in 1. CONCLUSIONS: When negative parameters were absent and/or fetal urine predicted good outcome there were no cases of end stage renal disease in early infancy, which was a significant help in parent counseling. The predictive value of the currently available prenatal parameters needs to be updated with larger series specifically dealing with posterior urethral valves. According to the current data, the outcome of posterior urethral valves is not yet significantly improved by prenatal diagnosis.

Pharmacokinetics of the S(+) and R(-) enantiomers of vigabatrin during chronic dosing in a patient with renal failure.

AIMS: To study the pharmacokinetics of vigabatrin in a patient affected with tuberous sclerosis who developed major agitation and aggression, while receiving vigabatrin orally (1.5 g every 12 h) and in whom impaired renal function was diagnosed. METHODS: The patient received vigabatrin (0.5 g day(-1)). A pharmacokinetic study of the S(+) and R(-) enantiomers of vigabatrin was performed before and during dialysis. Plasma concentrations were measured at 0, 1, 2, 3, 4, 6, 12, 18 and 24 h by a specific GCMS assay. RESULTS: Before dialysis, the maximum and minimun plasma concentrations of vigabatrin at steady-state were lower for the S(+) than for the R(-) enantiomer, while the apparent oral clearance was higher for the S(+) than for the R(-) enantiomer (2.97 vs 0.48 l h(-1)). In addition, the haemodialysis clearance was similar for the two enantiomers (4.96 vs 5.15 l h(-1)). CONCLUSIONS: Vigabatrin is an irreversible inhibitor of GABA-transaminase, effective in the treatment of drug-resistant epilepsy and reported to be eliminated unchanged by renal excretion. Although vigabatrin is known to have stereoselective kinetics, the difference in plasma dry concentrations and pharmacokinetics of the S(+) and R(-) enantiomers that we observed during long term administration at high doses in a patient with impaired renal function, has not been reported before. The question remains of the potential toxicity of the high levels of the R(-) enantiomer.

Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP).

Mutations in the PEX gene at Xp22.1 (phosphate-regulating gene with homologies to endopeptidases, on the X-chromosome), are responsible for X-linked hypophosphataemic rickets (HYP). Homology of PEX to the M13 family of Zn2+ metallopeptidases which include neprilysin (NEP) as prototype, has raised important questions regarding PEX function at the molecular level. The aim of this study was to analyse 99 HYP families for PEX gene mutations, and to correlate predicted changes in the protein structure with Zn2+ metallopeptidase gene function. Primers flanking 22 characterised exons were used to amplify DNA by PCR, and SSCP was then used to screen for mutations. Deletions, insertions, nonsense mutations, stop codons and splice mutations occurred in 83% of families screened for in all 22 exons, and 51% of a separate set of families screened in 17 PEX gene exons. Missense mutations in four regions of the gene were informative regarding function, with one mutation in the Zn2+-binding site predicted to alter substrate enzyme interaction and catalysis. Computer analysis of the remaining mutations predicted changes in secondary structure, N-glycosylation, protein phosphorylation and catalytic site molecular structure. The wide range of mutations that align with regions required for protease activity in NEP suggests that PEX also functions as a protease, and may act by processing factor(s) involved in bone mineral metabolism.

[Vitamin A poisoning revealed by hypercalcemia in a child with kidney failure]. / Intoxication à la vitamine A révélée par une hypercalcémie chez un enfant insuffisant rénal.

BACKGROUND: Patients with chronic renal failure are at risk of vitamin A intoxication, a risk that must be evoked when unexplained hypercalcemia occurs. CASE REPORT: An 8 year-old boy with Alagille syndrome and chronic renal failure was admitted because of general deterioration, and bone pain. Severe hypercalcemia (3.9 mmol/L) was present. Serum phosphate, parathyroid hormone and 25 OH D3 levels were normal; 1-25 (OH)2 D3 levels were undetectable. Hypercalcemia was attributed to vitamin A intoxication, due to the administration of a mean daily dose of 12000 IU of vitamin A for at least 2 years. The diagnosis was confirmed by high plasma levels of retinol (1475 micrograms/L). Hypercalcemia only partially responded to treatment with bisphosphonates, calcitonin and dialysis with low calcium dialysate. Serum vitamin A levels remained elevated one month after vitamin A withdrawal. The boy died two months after admission from atrioventricular block. CONCLUSION: Vitamin A administration induces a high risk of intoxication in patients with chronic renal failure. Serum vitamin A concentrations are elevated in these patients, because of decreased renal metabolism of retinol, and vitamin A supplements must be avoided.

Pharmacokinetics of ganciclovir in renal transplant children.

Three cytomegalovirus (CMV)-seronegative children received renal transplants from CMV-seropositive donors and developed clinical symptoms of CMV infection between days 20 and 34 post transplantation. Ganciclovir (DHPG) was administered in a 1-h infusion, and the doses and dose intervals were adapted to the degree of renal insufficiency, according to the manufacturer's recommendations for adults. Individual pharmacokinetic parameters of DHPG were determined and were markedly altered. Plasma clearances were 0.4, 1.1 and 2.2 ml/min per kg and were related to individual creatinine clearances (20, 45 and 60 ml/min per 1.73 m2); the corresponding elimination half-lives were 23.7, 9.9 and 3.9 h. In two patients, the doses had to be further reduced in order to maintain plasma levels within the recommended values for peak and trough plasma concentrations. Therefore, monitoring of DHPG appears essential in adjusting dosage for optimal efficacy and minimal toxicity.

[Prognosis of prune belly syndrome]. / Pronostic du syndrome d'aplasie des muscles de la paroi abdominale.

The Prune Belly syndrome (PBS) is unfrequent. Fourteen cases have been followed in our unit during the last 20 years. Four infants (29%) died during the first months of life, because of neonatal sepsis (2 cases) or end-stage renal failure (2 cases). Among the other 10 cases, 6 (43%) had normal glomerular filtration rate at a mean age of 10 years 6 months (6 months to 15 years), 4 had chronic renal failure, including 3 cases who developed end-stage renal failure at 8, 8 years 8 months and 17 years respectively. Resection of an urethral obstruction was performed in 2 cases. This surgical indication remains widely accepted, while the current tendency is to limit ureteral surgery in PBS. Orchidopexy was performed in 4 children, 3 of them less than 6 years 6 months of age. Fertility of these early operated children remains to be established, as all adults reported in the literature remain sterile when orchidopexy was not performed or was performed after age 6.

[The intellectual development of children with severe early kidney insufficiency]. / Développement intellectuel des enfants atteints d'insuffisance rénale grave précoce.

Recent studies have suggested that patients with neonatal onset of severe renal failure may be at risk for mental retardation. We studied the intellectual development of 13 pediatric patients with neonatal onset of severe renal failure who immediately received active medical therapy. The verbal, performance, and overall intelligence quotient (IQ) was determined using the Weschler-PPSI and the WISC-R at a mean age of 7 years and 4 months (4 years 5 months to 15 years 8 months). Mean overall IQ was 89 (73 to 106), mean verbal IQ was 94.7 (79 to 124) and mean performance IQ was 85.6 (69 to 112). Overall IQ was greater than 100 (101 to 106) in three patients (23%), and under 100 in ten patients (77%), with values of 87 to 92 in six cases (46%) and 73 to 84 in four cases (31%). A significant negative correlation (p less than 0.05) was found between the IQ and the length of hospital or medical institution stays during the first year of life. We found no significant correlation either between IQ and severity of renal failure, quality of growth or nutritional status before the age of two, or between IQ and dose of aluminum ingested. Our results suggest that early severe renal failure does not induce severe mental retardation. However, in 77% of studied children the IQ was within the lower portion of the normal range or under this normal range. This proportion is greater than that seen in normal children from similar socioeconomic backgrounds. Reducing hospital stays and separations from home, as well as even more active nutritional management, may help to improve these children's mental abilities.

Hickman catheter for haemodialysis in paediatric patients.

Twelve Hickman catheters were inserted in nine children in order to establish access for haemodialysis or plasmapheresis. Catheters were implanted either through the external or internal jugular vein and the tip located in the right atrium or superior vena cava. Mean blood flow was 25-55 ml/min with single lumen catheters and 83-100 ml/min with double lumen catheters. Three catheters had to be removed because of obstruction, whilst seven remained in situ until an arteriovenous fistula had matured or renal function was restored. Infection in two cases was successfully treated with antibiotics and transient obstruction by urokinase instillation. Following catheter removal, angiographic studies showed that with one exception all catheterized vessels were obstructed, but this did not prevent from ipsilateral arteriovenous fistulas to mature satisfactorily.

[Acute kidney failure caused by hyperphosphoremia in tumor lysis]. / Insuffisance rénale aiguë par hyperphosphorémie au cours des lyses tumorales.

We report the cases of two children presenting with tumor lysis syndrome responsible for major hyperphosphatemia, hypocalcemia and acute renal failure and treated by hemodialysis. Twenty similar cases have been reported in the literature. Hyperphosphatemia responsible for hypocalcemia and renal failure occurs within 24 to 48 hours after the onset of chemotherapy, is maximal on the 2nd or 3rd day and is, on the average, of 7 days duration. Short-term functional renal prognosis is good but long-term studies are lacking. The usual preventive measures are not always sufficient to prevent these accidents. A dialysis is appropriate when phosphatemia rises rapidly and exceeds 5 mmol/l, when the creatinine plasma level exceeds 200 mumol/l and kaliemia 6 mmol/l and when hyperphosphatemia is associated with severe clinical signs.

[Chronic renal insufficiency in the child. Etiology, development and prognosis]. / Insuffisance rénale chronique chez l'enfant. Etiologie, évolution et pronostic.

Our study concerned 147 children with chronic renal failure (CRF) (creatinine clearance less than 50 ml/min/1.73 m2). Its goal was to analyse the distribution of primary renal diseases, natural history of renal failure (RF) according to etiology, and long term survival. Renal diseases responsible for RF were: malformations of the urinary tract (38%), glomerular pathology (26%), hereditary renal diseases (20%), isolated renal hypoplasias (11%), and miscellaneous (5%). Corticoresistant nephrosis accounted for 34% of glomerular diseases and nephronophtisis 63% of hereditary renal diseases. On the whole, RF was related with an uropathy or renal hypoplasia in half of cases and with congenital renal disease in almost 3/4 of cases. The natural history varied according to primary renal disease: slow deterioration after a period of relative stability for uropathy or renal hypoplasias, slow and regular deterioration for nephronophtisis, rapid deterioration for glomerular diseases.

Sequential echocardiographic study prior and during antihypertensive therapy in children with severe hypertension.

This study was performed to assess myocardial involvement in 18 children with severe hypertension (HT), using two dimensional (2D) guided M mode echocardiography, prior and during therapy. All patients but 2 had renal or renovascular disease. Septal diastolic thickness (SDT) was utilized as a serial marker. Except for one case, all patients had increased SDT initially (1.03 +/- .26 cm/m2, p less than .01 vs normal). Evolution under therapy allowed subdivision of patients: Group I: 12 patients showed left ventricular (LV) hypertrophy regression, within a follow-up period of 20 +/- 9 months (final SDT: .78 +/- .12 cm/m2 vs initial 1.09 +/- .28, p less than .01). Blood pressure (BP) was normalized in 9 patients, and borderline in 3. Therapy consisted on acebutolol (n = 10), captopril (n = 1), and renal artery surgery (n = 1). Group II: LV hypertrophy was unchanged (n = 3) or increased (n = 3), within a follow-up period of 19 +/- 8 months, with persistent severe (n = 3) or mild (n = 3) HT, under acebutolol (n = 5). Treatment was changed to captopril with subsequent normal BP and echocardiogram improvement (n = 3). In the overall population, final SDT was significantly correlated to the final BP (r = .69, p less than .01). In conclusion, echocardiographic follow-up allowed serial non invasive assessment of LV hypertrophy in our severely hypertensive pediatric population. At first echocardiogram, LV hypertrophy was present in all patients but one. Antihypertensive therapy allowed simultaneous decrease of BP and LV hypertrophy in 12 patients, 10 under acebutolol.

[Value of chlormethine in children with corticoid-dependent or partially corticoid-sensitive nephrosis, in steroid poisoning]. / Intérêt de la chlorméthine chez les enfants atteints de néphrose corticodépendante ou partiellement corticosensible, en intoxication stéroïdienne.

Mechlorethamine was administered at a low dose (0.8 mg/kg) to 27 children presenting with steroid dependent or partially responsive nephrotic syndrome, with signs of steroid toxicity. This drug induced a fast decrease of proteinuria (average delay: 7 days). It led to long lasting remission (average follow-up 34 months) in 16 cases (59%). Relapse occurred in 11 children (41%) most often (9 of 11 cases) in the first 7 months. However the evolutive pattern was clearly improved in 5 of these cases. Altogether, mechlorethamine allowed to stop corticosteroid therapy or, at least, to reduce the given dose, with a decrease of the signs of steroid toxicity, in 78% of the cases. In 6 cases (22%) evolution was almost not improved. One may hope that this dosage of mechlorethamine will not be gonadotoxic. This should be checked later on.