Refining Incidence and Characteristics of Inflammatory Myopathies: A Quadruple-Source Capture-Recapture Survey Using the 2017 European League Against Rheumatism/American College of Rheumatology Classification Criteria.

OBJECTIVE: Inflammatory myopathies (IM), characterized by muscle inflammation and weakness, are rare systemic diseases. Our previous study estimated an IM incidence rate of 7.98 cases per million people per year (95% confidence interval 7.38-8.66) and highlighted important variations that were likely because of methodologic issues rather than true epidemiologic differences. In this study, we aimed to refine the incidence of IM, using the 2017 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for IM and a quadruple-source capture-recapture method during a 6-year period in Alsace, France, a region with a population of 2 million having benefits of good access to health care and accredited IM referral centers. METHODS: Clinical data of potential IM patients were obtained from 4 sources (general practitioners and community specialists, public and private hospital records, public and private laboratories, and archives from the pathology department). Patients residing in Alsace and who fulfilled the 2017 EULAR/ACR criteria for IM between January 1, 2006, and January 1, 2013, were included. We corrected potentially incomplete ascertainment of cases with capture-recapture analyses. We studied both spatial and temporal distributions of incidence of IM. We also assessed systemic manifestations of the disease. RESULTS: Our review of 1,742 potential cases identified 106 patients with IM. No spatial or temporal heterogeneity was observed. Use of log-linear models showed an estimated 14.9 additional missed cases. Thus, the incidence rate of IM was 8.22 new cases per million inhabitants per year (95% confidence interval 6.76-9.69). Extramuscular manifestations other than dermatomyositis rash were frequently recorded. CONCLUSION: The stringent methodology used in our study provides an accurate estimation of the incidence of IM. This study also demonstrates, in a population-based cohort, the systemic nature of IM.

Risk Factors Leading to Anti-TNF Alpha Therapies in Pediatric Severe Uveitis.

Purpose: Pediatric uveitis is the leading cause of acquired child blindness, due to unremitting inflammation and long-term steroid exposition. Biotherapies with anti-tumor necrosis factor alpha (anti-TNFα) are effective in controlling inflammation for severe pediatric uveitis in recent studies. Major concern of anti-TNFα prescription is the balance between the severity of the disease and side effects of the drug. The aim of the present study is to describe a cohort of children with severe uveitis and to highlight the risk factors for a pejorative development that led to the prescription of anti-TNFα drugs. Method: A retrospective case-control study was carried out on children with uveitis associated with systemic inflammatory disease or idiopathic uveitis, with a minimum follow-up of 5 years. Anti-TNFα-treated patients (case) were studied and compared with patients who were not requiring anti-TNFα (control). Univariate logistic regression analyses were performed to compare both groups and determine the risk factors for anti-TNFα therapy. Results: Seventy-three cases of pediatric uveitis were included, 13 cases and 60 controls. The risk factors associated with increased odds of anti-TNFα therapy were initial systemic disorder associated with uveitis [OR = 11.22 (1.37-91.85), p = 0.0241), family history of autoimmune diseases [OR = 9.43 (2.27-39.15), p = 0.0020], uveitis diagnosis before the age of 6 [OR = 4.05 (1.16-14.13), p = 0.0284], eye surgery [OR = 26.22 (2.63-261.77), p = 0.0054], ocular complications at the first slit lamp exam [OR = 67.11 (3.78-1191.69), p = 0.0042], low visual acuity at diagnosis (≥0.3 logMAR) [OR = 11.76 (2.91-47.62), p = 0.0005] and especially low binocular acuity at diagnosis (≥0.3 logMAR) [OR = 8.75 (1.93-39.57), p = 0.0048], panuveitis [OR = 9.17 (2.23-37.60), p = 0.0021], having positive ANA [OR = 3.89 (1.07-14.11), p = 0.0391], and positive HLA B27 [OR = 9.43 (2.27-39.16), p = 0.0020]. Conclusion: Those risk factors could be used to establish a new follow-up and treatment schedule for severe uncontrolled uveitis. This could help to better predict the best time to start anti-TNF therapy.

Benign and malignant proliferation in idiopathic nephrotic syndrome: a French cohort study.

BACKGROUND: There seems to be a possible link between nephrotic syndrome (NS) and lymphoproliferative syndrome, but it remains poorly understood. METHODS: This multicentric and retrospective study focuses on children, who developed idiopathic NS and malignant or benign proliferation between 2000 and 2021. RESULTS: Eleven patients were included, with a median age of 4 years. Only one had a steroid-resistant nephrotic syndrome (SRNS). The maintenance therapy before the proliferation was in majority tacrolimus or mycophenolate mofetil (MMF), but three patients did not receive treatments. The proliferation was mainly a Hodgkin's lymphoma (45%) or a lymphoproliferative disease (36%), in a median time after the NS of two years. Viruses were found in seven cases (EBV in five cases and HHV-8 in two). CONCLUSION: The association between proliferative syndrome and idiopathic NS may not be fortuitous, possibly with a common lymphocytic disturbance. Genetic analyses could improve the comprehension of these manifestations in the future. A higher resolution version of the Graphical abstract is available as Supplementary information.

Bi-allelic mutations in renin-angiotensin system genes, associated with renal tubular dysgenesis, can also present as a progressive chronic kidney disease.

BACKGROUND: Bi-allelic loss of function variations in genes encoding proteins of the renin-angiotensin system (AGT, ACE, REN, AGTR1) are associated with autosomal recessive renal tubular dysgenesis, a severe disease characterized by the absence of differentiated proximal tubules leading to fetal anuria and neonatal end-stage renal disease. CASE-DIAGNOSIS/TREATMENT: We identified bi-allelic loss of function mutations in ACE, the gene encoding angiotensin-converting enzyme, in 3 unrelated cases displaying progressive chronic renal failure, whose DNAs had been sent for suspicion of juvenile hyperuricemic nephropathy, nephronophthisis, and cystic renal disease, respectively. In all cases, patients were affected with anemia whose severity was unexpected regarding the level of renal failure and with important polyuro-polydipsia. CONCLUSIONS: Bi-allelic loss of function mutation of ACE can have atypical and sometimes late presentation with chronic renal failure, anemia (out of proportion with the level of renal failure), and polyuro-polydipsia. These data illustrate the usefulness of next generation sequencing and "agnostic" approaches to elucidate cases with chronic kidney disease of unknown etiology and to broaden the spectrum of phenotypes of monogenic renal diseases. It also raises the question of genetic modifiers involved in the variation of the phenotypes associated with these mutations.

Patient and transplant outcome in infants starting renal replacement therapy before 2 years of age.

Background: Despite major technical improvements in the care of children requiring renal replacement therapy (RRT) before 2 years of age, the management of those patients remains challenging and transplantation is generally delayed until the child weighs 10 kg or is 2 years old. In this national cohort study, we studied patient and graft survival in children starting RRT before 2 years of age to help clinicians and parents when deciding on RRT initiation and transplantation management. Methods: All children starting RRT before 24 months of age between 1992 and 2012 in France were included through the national Renal Epidemiology and Information Network (REIN) registry. The primary endpoints were patient survival on dialysis and 10-year graft survival. Results: A total of 224 patients were included {62% boys, median age 10.5 months [interquartile range (IQR) 5.8-15.6]}. The 10-year survival rate was 84% (IQR 77-89). Suffering from extrarenal comorbidities was the only factor significantly associated with both an increased risk of death on dialysis [hazard ratio 5.9 (95% confidence interval 1.8-19.3)] and a decreased probability of being transplanted. During follow-up, 174 renal transplantations were performed in 171 patients [median age at first transplantation 30.2 (IQR 21.8-40.7) months]. The 10-year graft survival was 74% (IQR 67-81). Factors associated with graft loss in multivariate analysis were the time spent on dialysis before transplantation, donor/recipient height ratio with an increased risk for both small and tall donors and presenting two human leucocyte antigen-antigen D-related mismatches. Conclusions: This study confirms the good outcome of children starting RRT before 2 years of age. The main question remains when and how to transplant those children. Our study provides data on the optimal morphological and immunological matching in order to help clinicians in their decisions.

[Peritoneal equilibration test: Conventional versus adapted. Preliminary study]. / Tests d'équilibration péritonéaux : conventionnel versus adapté. Étude de faisabilité.

Conventional automated peritoneal dialysis (APD) is prescribed as a repetition of cycles with the same dwell time and the same fill volume. Water and sodium balance remains a common problem among patients on peritoneal dialysis. More recently, adapted automated peritoneal dialysis was described, as a combination of short dwells with a low volume, in order to enhance ultrafiltration, followed by long dwells with a large fill volume to favor solute removal. We performed a preliminary crossover study on 4 patients. The total amount of dialysate was the same, i.e. 2L/m2 as well as the total duration of the test, i.e. 150 minutes. The conventional test was made with two identical cycles, each cycle had a fill volume of 1L/m2 and a duration of 75 minutes, while the adapted test was performed with one short cycle, i.e. 30 minutes with a low fill volume, i.e. 0.6L/m2, followed by a long cycle, i.e. 120 minutes, with a large fill volume, i.e. 1.4L/m2. Sodium extraction was improved by 29.3mmol/m2 (169%) in the adapted test in comparison to the conventional test. Ultrafiltration was enhanced by 159mL/m2 (128%) in the adapted test compared to the conventional one. Glucose absorption was decreased by 35% in the adapted test in comparison to the conventional test and osmotic conductance was also improved. In conclusion, adapted dialysis may allow for a better volume and sodium balance, since we observed an improvement in sodium extraction and ultrafiltration. This pre-study authorizes an improvement of the European Pediatric Study's protocol on Adapted APD, already started and which will continue in the next months.

Long term follow up of two independent patients with Schinzel-Giedion carrying SETBP1 mutations.

Schinzel-Giedion syndrome (SGS, MIM #269150) is a rare syndrome characterized by severe intellectual disability, typical facial gestalt, hypertrichosis and multiple congenital malformations including skeletal, genitourinary, renal and cardiac abnormalities. The prognosis of SGS is very severe and death occurs generally within a few years after birth. In 2002, we reported 2 children with SGS with a follow-up of 3 years. They presented a very similar and particular phenotype associating distinctive facial gestalt, severe developmental delay, megacalycosis, progressive neurodegeneration, alacrimi, corneal hypoesthesia and deafness. Furthermore, temporal bone imaging revealed a tuning-fork malformation of the stapes. In 2010, Hoischen et al. identified in SGS patients pathogenic heterozygous de novo mutations in SETBP1. We sequenced SETBP1 in our patients and found the previously reported c.2608G>A (p.Gly870Ser) mutation in both children. Since 2002, one of our patients died at 6 years old and the other patient is still alive at 15 years old. Such a life expectancy has never been reported so far. We describe herein the follow up of the 2 children during 6 and 15 years respectively. This article gives further evidence of the implication of SETBP1 as the major gene of SGS, and reports the previously unseen natural evolution of the disease in a 15 years old patient.

Spectrum of steroid-resistant and congenital nephrotic syndrome in children: the PodoNet registry cohort.

BACKGROUND AND OBJECTIVES: Steroid-resistant nephrotic syndrome is a rare kidney disease involving either immune-mediated or genetic alterations of podocyte structure and function. The rare nature, heterogeneity, and slow evolution of the disorder are major obstacles to systematic genotype-phenotype, intervention, and outcome studies, hampering the development of evidence-based diagnostic and therapeutic concepts. To overcome these limitations, the PodoNet Consortium has created an international registry for congenital nephrotic syndrome and childhood-onset steroid-resistant nephrotic syndrome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Since August of 2009, clinical, biochemical, genetic, and histopathologic information was collected both retrospectively and prospectively from 1655 patients with childhood-onset steroid-resistant nephrotic syndrome, congenital nephrotic syndrome, or persistent subnephrotic proteinuria of likely genetic origin at 67 centers in 21 countries through an online portal. RESULTS: Steroid-resistant nephrotic syndrome manifested in the first 5 years of life in 64% of the patients. Congenital nephrotic syndrome accounted for 6% of all patients. Extrarenal abnormalities were reported in 17% of patients. The most common histopathologic diagnoses were FSGS (56%), minimal change nephropathy (21%), and mesangioproliferative GN (12%). Mutation screening was performed in 1174 patients, and a genetic disease cause was identified in 23.6% of the screened patients. Among 14 genes with reported mutations, abnormalities in NPHS2 (n=138), WT1 (n=48), and NPHS1 (n=41) were most commonly identified. The proportion of patients with a genetic disease cause decreased with increasing manifestation age: from 66% in congenital nephrotic syndrome to 15%-16% in schoolchildren and adolescents. Among various intensified immunosuppressive therapy protocols, calcineurin inhibitors and rituximab yielded consistently high response rates, with 40%-45% of patients achieving complete remission. Confirmation of a genetic diagnosis but not the histopathologic disease type was strongly predictive of intensified immunosuppressive therapy responsiveness. Post-transplant disease recurrence was noted in 25.8% of patients without compared with 4.5% (n=4) of patients with a genetic diagnosis. CONCLUSIONS: The PodoNet cohort may serve as a source of reference for future clinical and genetic research in this rare but significant kidney disease.

Why does three times per week hemodialysis provide inadequate dialysis for children?

The duration of chronic conventional dialysis is a risk factor in children, both in terms of growth retardation and cardiovascular morbidity and mortality. Therefore, we need to develop alternative strategies, such as preemptive kidney transplantation and/or more intensive dialysis prescription. Indeed, conventional hemodialysis could be improved in all children by the use of high permeable membrane and ultrapure dialysis fluids (having very low endotoxin levels); by the addition of a convective dialysis dose to the urea diffusion dialysis dose (Kt/Vurea), i.e., hemodiafiltration; moreover, by the preservation of cardiovascular morphology and function (optimized blood pressure control); and also by the prescription of more frequent/longer dialysis sessions.

Intensified daily dialysis: the best chronic dialysis option for children?

Children receiving chronic hemodialysis (HD) three times a week have many obstacles to overcome. Not only do they have to endure dietary restrictions, but they also need to take various medications on a daily basis, which contribute to anorexia. Children on such conventional dialysis programs often have poorly controlled blood pressure (which can lead to left ventricular hypertrophy and/or left ventricular dysfunction) and impaired statural growth. Therefore, the need for more frequent and/or intensive dialysis is recognized. Nevertheless despite limited center experience, daily dialysis is currently most often limited as a rescue treatment. When performed, daily intensified HD provides a modality for preserving cardiovascular health and promoting normal growth in children. Therefore, the time spent on chronic dialysis preserves their chances of the best possible outcome.

Endoscopic Mic-Key button placement for continent vesicostomy.

INTRODUCTION: The use of a gastrostomy button for intermittent emptying of the bladder has been already proposed. The aim of this study was to describe a percutaneous button placement under endoscopic control as a safe, minimally invasive technique. MATERIALS AND METHODS: The percutaneous gastrostomy kit, according to the Russell gastrostomy tray (Cook; Cook, Bloomington, IN), was used under cystoscopic control. The U-stitche technique, according to Georgeson, allowed us to secure the bladder to the abdominal anterior wall. A guide was introduced into the bladder through a needle. Three dilatators, respectively 12, 14, and 16 FR, allowed the path for a probe or, immediately, the gastrostomy button (Mic-Key; Ballard Medical Products, Draper, UT). RESULTS: Over 2 years, 10 percutaneous continent vesicostomies were performed for patients with a neurogenic bladder. Patients were from 5 months to 19 years old. The procedure was safe. No major complication was observed except for only minor ones. DISCUSSION: When intermittent urethral catheterization cannot be established, Mitrofanoff continent urinary diversion seems to be a major surgery for patients and their parents. In addition, for some patients, intermittent bladder emptying may be required for a transitory period. For all these reasons, there is a place for a reversible vesicostomy with a minimally invasive procedure. Button vesicostomy seems to be a good alternative. In this article, we propose a percutaneous technique with an endoscopic control. If this kind of treatment is effective, it may avoid further major surgery. CONCLUSIONS: Percutaneous button vesicostomy placement under endoscopic control is safe and feasible and must be evaluated with large series.

Daily on line haemodiafiltration promotes catch-up growth in children on chronic dialysis.

BACKGROUND: In children, growth can be used as a measurable parameter of adequate nutrition and dialysis dose. Despite daily administration of recombinant human growth hormone (rhGH), growth retardation remains a frequent problem in children on chronic dialysis. Therefore, we performed an observational prospective non-randomized study of children on in-centre daily on line haemodiafiltration (D-OL-HDF) dialysis with the aim of promoting growth. PATIENTS AND METHODS: Mean age at the start of the study was 8 years and 3 months, and all children had been receiving rhGH treatment for >12 months before enrolment. Mean follow-up time on D-OL-HDF was 20.5 +/- 8 months (range, 11-39 months). Renal residual function was either <3 mL/min/1.73 m(2) or anuric. Vascular access was a fistula (13/15) or a central venous catheter (2/15). Dialysis was delivered daily, six days a week in 3 hourly sessions (18 h/week), in a predilution OL-HDF mode, allowing a high convective volume (18 to 27 L/m(2) body surface area per session), Kt/V(urea) on line measured at least 1.4 per session. RESULTS: Mean growth velocity increased from 3.8 +/- 1.1 cm/year at inclusion to 14.3 +/- 3.8 cm/year during the first year of D-OL-HDF, resulting in a change in height standard deviation score (SDS) over the follow-up period from -1.5 +/- 0.3 SDS to +0.2 +/- 1.1 SDS. Increase in body mass was also noted without impaired control of blood pressure. Time-average deviation for urea (TAD(urea)) was low at 2.5 +/- 0.4 as was TAD(bicarbonate) due to the normal pre and post dialysis bicarbonate levels, respectively, 23.6 +/- 0.5 mmol/L and 26.6 +/- 0.5 mmol/L. The absence of any dietary restrictions permitted a mean protein diet intake (PDI) of 2.5 +/- 0.2 g/kg/day (PDI measured from a 3-day diet survey), contrasting with a mean normalized protein nitrogen appearance (nPNA) of 1.53 +/- 0.12 g/kg/day (nPNA calculated from urea dialytic kinetic). A low C-reactive protein was noted in 13/15 children, and mean beta(2) microglobulin was low, 15.3 +/- 0.3.3 mg/L. CONCLUSIONS: Daily OL-HDF promotes catch-up growth in children despite on chronic dialysis. This catch-up growth if continued, should allow the children to reach their mid-parental target height in the future. It could be speculated that the improved response to rhGH is the result of several combined factors conducting to less malnutrition and to less cachexia.

Importance of the curve shape for interpretation of blood volume monitor changes during haemodiafiltration.

In children, the prescribed ultrafiltration needed to achieve the fixed end session dry weight can induce hypotensive episodes. A variety of on-line devices based on the direct measurement of the hematocrit are available, but these devices nearly always only measure the quantitative variation in the blood volume as the means of identifying a hypotensive occurrence risk. In February 2002, our unit began using an on-line hematocrit measurement available even with infants' blood lines. Since January 2004, this blood volume monitor (BVM) has been used routinely in all dialysis sessions, and 2240 BVM data sets have been recorded and analysed during the last 4 years. Based on our analysis of these data sets, we have determined that, in addition to the described threshold points, which provide a quantitative analysis of the BVM, the qualitative analysis of the BVM, the so-called curve shape, is also of clinical importance. In 91% of the sessions analysed, a very similar "symptom-free" curve shape was noted that consisted of an initial decrease, followed by the BV reaching a "stable" plateau. Additional curve shapes were identified: one with no BV decrease, presumably indicating an overload risk state, and one with a continuous BV decrease, presumably indicating an hypovolemic risk state. In our experience, only 2% of the patients had relevant clinical symptoms that were not visible by BVM.

Immunosuppressants used in a steroid-sparing strategy for childhood uveitis.

PURPOSE: To review, with respect to etiology, the efficacy and complications of different immunosuppressants used in a steroid-sparing strategy for children with uveitis. PATIENTS AND METHODS: Forty children with uveitis were observed during a 5-year period, from 1997 to 2002. After complete ocular and physical assessment, routine and specific laboratory investigations were conducted along with radiologic examination. All cases underwent local therapy. Systemic corticosteroids were necessary in 75% of cases. Pediatric staff determined the need for initial association or sequential relay with immunosuppressants, depending on the severity of the uveitis. A steroid-sparing strategy was developed. RESULTS: The average age was 6.5 years (range, 3 months to 14 years), with a male-to-female ratio of 23 to 17. Uveitis was anterior in 55% of cases, intermediate in 2.5%, posterior in 42.5%, and bilateral in 62.5%. A positive etiology was found in 47.5% of cases, and articular symptoms were present in 25%. Overall, the improvement in visual acuity was 62.2%. Where corticotherapy was associated with azathioprine, a 61% improvement was achieved. Corticosteroid therapy associated with mycophenolate mofetil resulted in a 94% improvement. No complications were present in 42.5% of cases. Ocular complications were present in 57.5% of cases and systemic complications were present in 12.5% of cases, none being directly related to the use of steroids. CONCLUSION: The association of systemic corticotherapy and immunosuppressants in pediatric relapsing or steroid-dependent uveitis allows good recovery of visual acuity, fewer complications, and a minimization of side effects, especially those related to systemic corticosteroids. It requires close collaboration between the ophthalmologist and a fully involved pediatrician.

Intensified and daily hemodialysis in children might improve statural growth.

In children conventional hemodialysis does not often improve growth. We determined linear growth in five children on in-center intensified and daily hemodialysis (IDd) regimen, with a mean age of 8 years 7 months at enrollment. Four of five were on growth hormone started for a median of 28.5 months before IDd. IDd was delivered 5 to 6 times weekly, for three hours each session. Mean follow up of IDd was 18.6 months. Dropout from IDd was kidney transplantation (n=4) or transfer to another center (n=1). IDd and free diet improved appetite, thereby protein intake, was above 2 g/kg/BW. Median weekly Kt/V(urea) was 9.1 (8.7 to 10.4). Predialysis phosphorus blood levels were higher at the start (2.04+/-0.34 mmol/L) than at end of IDd (1.39+/-0.41 mmol/L) without need for carbonate of calcium in four of five cases. During conventional dialysis ht SDS decreased from -0.8 to -1.44, which occurred predominantly before rhGH start. Conversion to IDd significantly increased growth velocity to a mean of 13 cm/year (10.3-18) with a mean change of +1.84 ht SDS/year (0.4 to 2.7). This preliminary report suggests the potential efficacy of IDd regimen in promising growth velocity, either directly from a higher dialysis dose or indirectly through an improved nutritional status.

Epidemiology of juvenile idiopathic arthritis in Alsace, France.

OBJECTIVE: To determine the incidence, prevalence, and principal characteristics of the different forms of juvenile idiopathic arthritis (JIA) in the region of Alsace, northeastern France, using the new classification of the International League of Associations for Rheumatology (ILAR). METHODS: In 2002 we performed a retrospective epidemiologic study pertaining to the year 2001. The pediatricians, rheumatologists, ophthalmologists, orthopedic surgeons, and physicians involved in functional reeducation in the Alsace region were interviewed, and all patients were classified according to the new ILAR classification using the criteria revised in Durban in 1997. RESULTS: Among the 361 clinicians contacted, the participation rate was 97.8%. The study identified 67 children followed for JIA in Alsace in 2001, from a total population of 1.8 million inhabitants including 339,095 children under age 16 years. The incidence was calculated to be 3.2 cases/100,000/year and the prevalence 19.8 cases/100,000 children under age 16 years. Among these 67 cases of JIA, the most frequent forms were oligoarthritis (n = 27, 40.3%), polyarthritis without rheumatoid factor (RF; n = 15, 22.4%), and enthesitis related arthritis (n = 12, 17.9%). Other forms, notably systemic arthritis (n = 6, 8.9%) and psoriatic arthritis (n = 3, 4.5%), were more rare and in this study there was no case of polyarthritis with RF. Only 4 patients (6%) were classified in the undifferentiated arthritis group using the new classification. Antinuclear antibodies (ANA; by indirect immunofluorescence, HEp >/= 1/80) were detected in patients with oligoarthritis (81%) and polyarthritis without RF (79%). Uveitis occurred in 41% of children with oligoarthritis and in 14% of those with polyarthritis without RF. CONCLUSION: Our results are comparable to those of other studies carried out in Caucasian populations with regard to incidence and prevalence. This work also highlights the frequent presence of ANA and uveitis in patients with oligoarthritis or polyarthritis without RF.

The influence of peritoneal surface area on dialysis adequacy.

In children, the prescription of peritoneal dialysis is based mainly on the choice of the peritoneal dialysis fluid, the intraperitoneal fill volume (mL/m2 body surface area (BSA)], and the contact time. The working mode of the peritoneal membrane as a dialysis membrane is more related to a dynamic complex structure than to a static hemodialyzer. Thus, the peritoneal surface area impacts on dialysis adequacy. In fact, the peritoneal surface area may be viewed as composed of three exchange entities: the anatomic area, the contact area, and the vascular area. First, in infants, the anatomic area appears to be two-fold larger than in adults when expressed per kilogram body weight. On the other hand, the anatomic area becomes independent of age when expressed per square meter BSA. Therefore, scaling of the intraperitoneal fill volume by BSA (m2) is necessary to prevent a too low ratio of fill volume to exchange area, which would result in a functional "hyperpermeable" peritoneal exchange. Second, the contact area, also called the wetted membrane, is only a portion of the anatomic area, representing 30% to 60% of this area in humans, as measured by computed tomography. Both posture and fill volume may affect the extent of recruitment of contact area. Finally, the vascular area is influenced by the availability of both the anatomic area and the recruited contact area. This surface is governed essentially by both peritonealvascular perfusion, represented by the mesenteric vascular flow and, hence, by the number of perfused capillaries available for exchange. This vascular area is dynamically affected by different factors, such as composition of the peritoneal fluid, the fill volume, and the production of inflammatory agents. Peritoneal dialysis fluids that will be developed in the future for children should allow an optimization of the fill volume owing to a better tolerance in terms of lower achieved intraperitoneal pressure for a given fill volume. Moreover, future peritoneal dialysis fluids should protect the peritoneal membrane from hyperperfusion (lower glucose degradation products).

Daily on-line haemodiafiltration: a pilot trial in children.

BACKGROUND: Despite major improvements in paediatric dialysis over the last two decades, cardiovascular outcome is often poor. As France gives priority to kidney transplantation over dialysis, children in chronic haemodialysis are generally pre-adolescents or adolescents with long medical histories and low compliance. In them, the usual weekly schedule of dialysis is often unsuitable. We conducted a study of conversion to daily dialysis, which allowed an enhanced dialysis dose, a gentle ultrafiltration rate and achievement of dry body weight. METHODS: In this single-centre, observational, prospective, non-randomized study, five oligoanuric dialysis patients (mean age: 13.8 +/- 3.2 years) were converted from standard on-line haemodiafiltration (S-OL-HDF) (4 h, three times/week) to daily on-line haemodiafiltration (D-OL-HDF) (3 h, six times/week). Patient selection was based on both the presence of uraemic cardiomyopathy (left ventricular hypertrophy and reduced fractional shortening) and their reduced therapeutic compliance. The D-OL-HDF parameters were the same as for the S-OL-HDF. RESULTS: Increasing the number of sessions from three to six weekly positively impacted the weekly dialysis dose. On D-OL-HDF, mean arterial blood pressure decreased significantly (from 95 +/- 15 to 82 +/- 13 and 87 +/- 9 mmHg at 6 and 12 months, respectively). Left ventricular hypertrophy decreased and its fractional shortening improved markedly (from 26.6 +/- 17% to 31 +/- 14% and 46.6 +/- 15% at 6 and 12 months, respectively). Pre-dialytic plasma phosphorus also decreased markedly (from 1.87 +/- 0.23 to 1.43 +/- 0.22 and 1.28 +/- 0.29 mmol/l at 6 and 12 months, respectively), as did the calcium-phosphorus product. The post-dialytic recovery time disappeared and so did perception of fatigue. Fasting the day before dialysis to avoid excess weight gain (necessitating longer dialysis) disappeared. Combined with an improved appetite, these changes resulted in higher caloric and protein intake (nPCR), from 1.28 +/- 0.23 to 1.43 +/- 0.24 g/kg at 6 months, and school attendance became regular. The only pre-pubertal child included showed catch-up growth. CONCLUSIONS: Increasing dialysis frequency to daily sessions without shortening the durations of sessions excessively allowed us to overcome the "free diet" imposed on these paediatric, very uncompliant patients. This strategy led to a reduction in blood pressure and an improvement of left ventricular size and function, normalization of pre-dialytic plasma phosphorus and improvements in general well-being and dialysis acceptance. Long-term, however, this protocol is only acceptable for the children if associated with the potential of clinical recovery allowing inscription on the kidney transplantation waiting list.