Denis F. Geary

Intensive Hemodialysis Associates with Improved Survival Compared with Conventional Hemodialysis

Patients undergoing conventional maintenance hemodialysis typically receive three sessions per week, each lasting 2.5-5.5 hours. Recently, the use of more intensive hemodialysis (>5.5 hours, three to seven times per week) has increased, but the effects of these regimens on survival are uncertain. We conducted a retrospective cohort study to examine whether intensive hemodialysis associates with better survival than conventional hemodialysis. We identified 420 patients in the International Quotidian Dialysis Registry who received intensive home hemodialysis in France, the United States, and Canada between January 2000 and August 2010. We matched 338 of these patients to 1388 patients in the Dialysis Outcomes and Practice Patterns Study who received in-center conventional hemodialysis during the same time period by country, ESRD duration, and propensity score. The intensive hemodialysis group received a mean (SD) 4.8 (1.1) sessions per week with a mean treatment time of 7.4 (0.87) hours per session; the conventional group received three sessions per week with a mean treatment time of 3.9 (0.32) hours per session. During 3008 patient-years of follow-up, 45 (13%) of 338 patients receiving intensive hemodialysis died compared with 293 (21%) of 1388 patients receiving conventional hemodialysis (6.1 versus 10.5 deaths per 100 person-years; hazard ratio, 0.55 [95% confidence interval, 0.34-0.87]). The strength and direction of the observed association between intensive hemodialysis and improved survival were consistent across all prespecified subgroups and sensitivity analyses. In conclusion, there is a strong association between intensive home hemodialysis and improved survival, but whether this relationship is causal remains unknown.

Rituximab in refractory nephrotic syndrome

The aim of this study was to establish the efficacy and safety of rituximab in refractory nephrotic syndrome (NS). Members of the International Paediatric Nephrology Association were asked to retrospectively fill in a questionnaire with details on the use of rituximab in their centres. We divided the data into three groups: group 1, patients with steroid-dependent and frequently relapsing NS; group 2, with steroid-resistant NS; group 3, with post-transplant recurrence of NS. Seventy questionnaires from 25 centres described the outcome of 28, 27 and 15 patients in groups 1, 2 and 3, respectively. Of these, 82% of patients in group 1, 44% of patients in group 2 and 60% of patients in group 3 had a good initial response. Side effects were observed in 27% of the patients, and these were mostly acute reactions. We present a large multicentre series of children with refractory NS. Children in group 1 showed the best response. The good initial response in group 3 can be biased by the accompanying treatments that were administered at the same time as rituximab. Controlled prospective trials are required to establish the value of rituximab in idiopathic NS.

Attitudes of pediatric nephrologists to management of end-stage renal disease in infants

A multinational survey of pediatric nephrologists found no intercountry difference in the rate at which renal replacement therapy is offered to infants with end-stage renal disease. Overall, renal replacement therapy is offered by 41% to all infants < 1 month old and by 53% to all infants between 1 and 12 months.

Ultrasound findings in juvenile nephronophthisis

The ultrasound finding of renal medullary cysts associated with increased echogenicity has been suggested to be diagnostic of juvenile nephronophthisis. The lack of cysts in several of our patients with juvenile nephronophthisis lead us to review the ultrasound findings at presentation in our patient population. Of 11 children with the diagnosis of juvenile nephronophthisis. 10 demonstrated increased echogenicity with loss of corticomedullary differentiation on initial ultrasound. Only 2 children had a single cyst each. On follow-up ultrasound, 2, 4.5, and 7 years later, 3 patients developed visible renal cysts. We conclude that at presentation the ultrasound finding consistent with the diagnosis of juvenile nephronophthisis is most often that of hyperechogenic kidneys without cysts; namely the lack of cysts does not rule out the diagnosis of juvenile nephronophthisis.

Platelet-associated complement factor H in healthy persons and patients with atypical HUS

Atypical hemolytic uremic syndrome (aHUS) is associated with complement system dysregulation, and more than 25% of pediatric aHUS cases are linked to mutations in complement factor H (CFH) or CFH autoantibodies. The observation of thrombocytopenia and platelet-rich thrombi in the glomerular microvasculature indicates that platelets are intimately involved in aHUS pathogenesis. It has been reported that a releasable pool of platelet CFH originates from alpha-granules. We observed that platelet CFH can arise from endogenous synthesis in megakaryocytes and that platelets constitutively lacking alpha-granules contain CFH. Electron and high-resolution laser fluorescence confocal microscopy revealed that CFH was present throughout the cytoplasm and on the surface of normal resting platelets with no evident concentration in alpha-granules, lysosomes, or dense granules. Therapeutic plasma transfusion in a CFH-null aHUS patient revealed that circulating platelets take up CFH with similar persistence of CFH in platelets and plasma in vivo. Washed normal platelets were also observed to take up labeled CFH in vitro. Exposure of washed normal platelets to plasma of an aHUS patient with CFH autoantibodies produced partial platelet aggregation or agglutination, which was prevented by preincubation of platelets with purified CFH. This CFH-dependent response did not involve P-selectin mobilization, indicating a complement-induced platelet response distinct from alpha-granule secretion.

Anemia in children with chronic kidney disease

Anemia is a common feature of chronic kidney disease, but the management of anemia in children is complex. Erythropoietin and supplemental iron are used to maintain hemoglobin levels. The National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) clinical practice guidelines for the management of anemia specifically in children were recently published. Pediatric nephrologists are encouraged to use current clinical practice guidelines and best evidence in conjunction with their clinical experience to optimally manage patients with anemia.

Complications of gastrostomy feeding in children receiving peritoneal dialysis

Abstract Gastrostomy tube (g-tube) feeding is recognized to improve the nutritional delivery to children with end-stage renal disease. A retrospective study was undertaken assessing the complications of g-tube feeding in children receiving peritoneal dialysis (PD). Twenty-three patients, mean age 3.8±3.2 years received PD and g-tube feeding for 758 patient-months, with 127 patients receiving PD for 1,969 patient-months used as controls. Peritonitis occurred every 18.4 patient-months in controls and 7.8 patient-months in those with a g-tube. Peritonitis occurred every 6.0 patient-months before and 8.1 patient-months after g-tube insertion in those undergoing g-tube insertion on PD. PD catheter exit site infection (PDESI) occurred every 18.7 patient-months in controls and 16.8 patient-months in those with a g-tube. PDESI occurred every 126 patient-months before and 16.2 patient-months following g-tube insertion. PD catheter replacement secondary to infection occurred every 109.4 patient-months in controls and 39.9 patient-months in those with a g-tube. It did not occur before g-tube insertion and occurred every 32.5 patient-months following insertion. Thirty-four episodes of g-tube exit site infection occurred, in 10 the same organism caused concurrent peritonitis. G-tube replacement occurred on 37 occasions. Hemodynamically significant gastrointestinal bleeding occurred in 3 patients, being terminal in 1. We conclude that, although not without risk, g-tube feeding in patients receiving PD is not contraindicated.

A Broader Spectrum of Abnormalities in the Prune Belly Syndrome

The clinical course of 25 children with the prune belly syndrome was reviewed retrospectively to assess the over-all morbidity associated with this disorder. There were 3 neonatal deaths of renal or pulmonary disease. Chronic renal insufficiency or end stage renal disease developed in 5 survivors, all of whom had impaired kidney function in early infancy. An additional 17 patients survived with only mild renal insufficiency. Growth retardation, which correlated poorly with renal function, was present in a third of the patients. Clinically significant pulmonary and orthopedic problems were noted in 55 per cent of the survivors. Chronic constipation was another common, although less serious, feature. This report emphasizes the severity of the extrarenal problems associated with the prune belly syndrome.

Linear growth and anthropometric and nutritional measurements in children with mild to moderate renal insufficiency: A report of the growth failure in children with renal diseases study

During the control period of the Growth Failure in Children With Renal Diseases Study, investigators at 23 centers were able to observe and characterize growth and to make anthropometric and nutritional measurements in 82 children with mild to moderate renal insufficiency. As a multicenter, controlled clinical trial designed to study the relative efficacy of 1,25-dihydroxyvitamin D3 and dihydrotachysterol in the treatment of renal osteodystrophy, no prior vitamin D exposure and a creatinine clearance of 25 to 75 ml/min/1.73 m2 were criteria for entrance into the clinical trial. Ages ranged from 18 months to 11 years (mean 5.6 +/- 3.1 years), and distribution by age category was as follows: 38%, 1 to 3 years; 28%, 4 to 6 years; and 34%, 7 to 10 years. There was a 3:1 male/female ratio; 72% of the patients had congenital disease by the International Classification of Diseases (ninth revision). Mean creatinine clearance was 49.5 +/- 20 ml/min/1.73 m2. The C-terminal parathyroid hormone values (1121 +/- 1562 pg/ml) were well above 2 SD of the mean of a normal growing population of similar age. Parathyroid hormone values correlated with degree of renal insufficiency (r = -0.57) and with height by bone age but not with chronologic height or growth velocity. The bone age/height age ratio, a predictor of growth potential in normal children, was low for the entire series of patients (0.88 +/- 0.35) but failed to correlate with growth velocity and was negatively correlated with rising parathyroid hormone levels. Average values for height, weight, triceps skin fold, mid-arm muscle circumference, and body mass index were within 2 SD of the mean of the normal population, although measurements for the 1- to 3-year age group were significantly less than those of the older patients. Total energy intake averaged less than 86% of the recommended dietary allowances; total protein intake was more than 161% of the allowance. Nitrogen balance in 23 patients was positive and correlated most significantly with increasing energy intake (r = 0.6). Growth velocity, calculated from the interval gain during the month control period, averaged +0.3 SD, with the highest growth velocity z scores recorded for those with acquired disease. A growth velocity index, expressed as the slope of the regression between change in height SD and growth velocity z score, was used to describe the growth accomplished in the control period by age category.(ABSTRACT TRUNCATED AT 400 WORDS)

ATTITUDES OF CAREGIVERS TO MANAGEMENT OF END-STAGE RENAL DISEASE IN INFANTS

♦ Objectives: To characterize the attitudes of pediatric nephrologists caring for infants with end-stage renal disease (ESRD) compared with attitudes from a survey published in 1998. Nephrology nurses and social workers were included. ♦ Methods: An e-mail survey was distributed to pediatric nephrology teams in Canada, Germany, Japan, the United Kingdom, and the United States. ♦ Results: Survey responders totaled 270. Renal replacement therapy (RRT) is offered by all nephrologists to some children 1 – 12 months, and by 98% to some less than 1 month of age (93% in 1998). Of responding nephrologists, 30% offer RRT to all children less than 1 month of age (41% in 1998), and 50%, to all children 1 – 12 months. Among respondents, 50% indicated that parents can never refuse RRT for children aged 1 – 12 months, compared with 27% for younger infants. The most influential factor in rejecting RRT for infants was the presence of a co-existing abnormality. Nurses were more likely to believe that parents have the right to refuse RRT for infants. ♦ Conclusions: Attitudes of pediatric nephrologists have changed since 1998. Also, nurses have opinions that are different from those of the nephrologists on some issues, and a consensus should be reached before speaking to families.