Good long-term renal graft survival and low incidence of cardiac pathology in adults after short dialysis period and renal transplantation in early childhood - a cohort study.

Over the past 30 years, there has been an improvement in both patient and graft survival after pediatric renal transplantation (RTX). Despite this success, these patients still carry an elevated risk for untimely death, partly through premature aging of the vasculature. The aim of this study was thus to investigate the long-term outcome of individuals with RTX in childhood, as well as to explore the cardiovascular health of these adults more than a decade later. We studied 131 individuals who had undergone a RTX between the years 1979 and 2005. Furthermore, left ventricular hypertrophy (LVH), coronary artery calcifications (CAC), and related metabolic factors were investigated in a cross-sectional study including 52 individuals as part of the initial cohort. The mortality rate (n = 131) was 12.2%. The median estimated graft survival was 17.5 years (95% CI 13.6-21.3), being significantly better in children transplanted below the age of 5 years (18.6 vs. 14.3 years, P < 0.01) compared with older ones. CAC were found in 9.8% and LVH in 13% of the patients. Those with cardiac calcifications had longer dialysis vintage and higher values of parathyroid hormone (PTH) during dialysis. Left ventricular mass correlated positively with systolic blood pressure, PTH, and phosphate measured at the time of the study.

Implementation of a transition model to adult care may not be enough to improve results: National study of kidney transplant recipients.

Adolescents with a kidney transplant (KT) require special attention during the transition of care. Few longitudinal studies have assessed the effect of transition models (TM) on patient outcomes. Between 1986 and 2013, 239 pediatric patients underwent KT in Finland, of whom 132 have been transferred to adult care. In 2005, a TM was developed following international recommendations. We compared patient (PS) and graft survival (GS) rates before and after the introduction of the TM. PS and GS at 10 years were similar before and after the implementation of the TM (PS 85% and 90% respectively, P = 0.626; GS 60% and 58%, respectively, P = 0.656). GS was lower in patients transplanted at age 10-18 than in patients transplanted at a younger age in the TM cohort (79% vs 95%, P < 0.001). During the first five years after transfer, 63% of patients had stable KT function, 13% had deteriorating function and 24% lost their KT. Altogether 32 out of 132 patients lost their kidney allograft within five years after transfer to adult care (13 before and 19 after TM implementation, P = 0.566). The implementation of this TM had no effect on PS or GS. Further measures to improve our TM are in progress.

Outcomes of renal replacement therapy in boys with prune belly syndrome: findings from the ESPN/ERA-EDTA Registry.

BACKGROUND: As outcome data for prune belly syndrome (PBS) complicated by end-stage renal disease are scarce, we analyzed characteristics and outcomes of children with PBS using the European Society for Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association (ESPN/ERA-EDTA) Registry data. METHODS: Data were available for 88 male PBS patients aged <20 years who started renal replacement therapy (RRT) between 1990 and 2013 in 35 European countries. Patient characteristics, survival, and transplantation outcomes were compared with those of male patients requiring RRT due to congenital obstructive uropathy (COU) and renal hypoplasia or dysplasia (RHD). RESULTS: Median age at onset of RRT in PBS was lower [7.0; interquartile range (IQR) 0.9-12.2 years] than in COU (9.6; IQR: 3.0-14.1 years) and RHD (9.4; IQR: 2.7-14.2 years). Unadjusted 10-year patient survival was 85% for PBS, 94% for COU, and 91% for RHD. After adjustment for country, period, and age, PBS mortality was similar to that of RHD but higher compared with COU [hazard ratio (HR) 1.96, 95% confidence interval (CI) 1.03-3.74]. Seventy-four PBS patients (84%) received a first kidney transplant after a median time on dialysis of 8.4 (IQR 0.0-21.1) months. Outcomes with respect to time on dialysis before transplantation, chance of receiving a first transplant within 2 years after commencing RRT, and death-censored, adjusted risk of graft loss were similar for all groups. CONCLUSIONS: This study in the largest cohort of male patients with PBS receiving RRT to date demonstrates that outcomes are comparable with other congenital anomalies of the kidney and urinary tract, except for a slightly higher mortality risk compared with patients with COU.

Survival and clinical outcomes of children starting renal replacement therapy in the neonatal period.

End-stage renal disease requiring renal replacement therapy (RRT) during the neonatal period is a very rare condition, and little information is available regarding long-term RRT and outcomes. To gain more information, we performed a collaborative study on patient characteristics and treatment outcomes in children who started RRT as neonates during their first month of life between 2000 and 2011 who were prospectively registered in the ESPN/ERA-EDTA, the IPPN (since 2007), the Japanese registry, or the Australian and New Zealand Dialysis and Transplant (ANZDATA) registry. During the first month of life, 264 patients from 32 countries started RRT and were followed for a median of 29 months (interquartile range 11-60 months). Most neonates (242) started on peritoneal dialysis, 21 started on hemodialysis, and 1 patient with a transplant. The most important causes of renal failure were congenital anomalies of the kidney and urinary tract in 141, cystic kidneys in 35, and cortical necrosis in 30. Within 2 years after the start of RRT, 69 children changed dialysis modality and 53 received a renal transplant. After a median of 7 months, 45 children had died, mainly because of infection, resulting in an estimated 2-year survival of 81%, and 5-year survival of 76%. Growth retardation (63%), anemia (55%), and hypertension (57%) were still major problems after 2 years. Thus, relatively good medium-term patient survival may be achieved with RRT started during the neonatal period, but specific therapeutic challenges continue to exist in this age group.

Parent-child and spousal relationships in families with a young child with end-stage renal disease.

BACKGROUND: End-stage renal disease (ESRD) leads to the need for dialysis and renal transplantation (Tx). Peritoneal dialysis (PD) of young children is normally performed at home by the parents and affects the whole family. We studied the coping of families with a young child with ESRD by interviewing the parents of 19 children. METHODS: The spousal and parent-child relationships were assessed by using the Psychosocial Assessment of Childhood Experiences (PACE) and the Brief Measure of Expressed Emotion, respectively. A control group of 22 families with a healthy child was used for the parent-child relationship evaluation. RESULTS: The spousal relationship at the start of PD was good or fairly good in most of the families and remained good in half of the families following renal Tx. Lack of support from close relatives and renal Tx were associated with a poorer relationship quality. Almost all parents expressed much or fairly much emotional warmth towards the child throughout the study, but there was a trend towards increased criticism over time. No differences in the degree of expressed warmth or criticism were noted between the index parents and controls. CONCLUSIONS: Overall, the study families appeared to cope well despite the serious illness of their child and the demands of the treatments.

Tubulointerstitial nephritis and uveitis syndrome in children: a prospective multicenter study.

PURPOSE: To evaluate the occurrence and characteristics of uveitis related to tubulointerstitial nephritis (TIN) in children. DESIGN: Prospective, observational, multicenter, partly placebo-controlled treatment trial. PARTICIPANTS: Nineteen children with a biopsy-proven TIN. METHODS: Patients were treated with prednisone or followed without treatment. In addition to the nephrologic evaluations, the prospective follow-up included structured ophthalmological examinations at the onset of TIN and at 3 and 6 months after the diagnosis. MAIN OUTCOME MEASURES: Occurrence, clinical features, and outcome of uveitis. RESULTS: Some 84% (16/19) of the patients had uveitis, 83% (5/6) in the nontreatment group and 82% (9/11) in the prednisone-treated group. The remaining 2 patients, originally in the nontreatment group, were switched to the prednisone group after 2 weeks. Both of them developed uveitis. Altogether, 3 patients developed uveitis during prednisone treatment and 2 patients showed worsening of uveitis despite the systemic corticosteroid. Some 50% (8/16) of the patients with uveitis presented with no ocular symptoms; 88% (14/16) of the patients had a chronic course of uveitis. Two patients were diagnosed with uveitis before nephritis; nephritis and uveitis were diagnosed within 1 week from each other in 7 patients, and uveitis developed 1 to 6 months after the diagnosis of TIN in 7 patients. CONCLUSIONS: There was no statistically significant difference in the occurrence of uveitis in patients with TIN in the prednisone and nontreatment groups. In this study, the occurrence of uveitis associated with TIN was considerably higher than previously reported. Uveitis related to TIN may develop late and is often asymptomatic. The ophthalmological follow-up of all patients with TIN is warranted for at least 12 months starting with 3-month intervals. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any material discussed in this article.

The association of adult kidney size with childhood vesicoureteral reflux.

BACKGROUND: We used ultrasound to measure kidney volumes in adults with a history of childhood vesicoureteral reflux (VUR) and assessed whether total renal volume, small kidney size or the thickness of the upper pole correlated with renal function or hypertension. METHODS: The kidneys of 123 adults were studied by ultrasound, calculating their volumes using an ellipsoid formula normalised to body surface area (Vol(N)). The thickness of the upper pole parenchyma and the number of small kidneys (<80% of normal volume) were recorded. Blood pressure measurements and laboratory tests were also performed. RESULTS: Kidneys with a history of VUR were 12% smaller than those without known VUR (p < 0.05), and those with prior dilating VUR were 16% smaller than those with non-dilating VUR (p < 0.05). There was a moderate correlation (r = 0.42, p < 0.05) between total Vol(N) and GFR values in the total patient series. Thirteen percent of the patients had a moderate decrease in kidney function. The occurrence of hypertension and proteinuria was not affected by either kidney size or a thin upper pole. CONCLUSIONS: Total Vol(N) in ultrasound in early adulthood could probably predict possible renal deterioration in later life. The occurrence of one small kidney was a common finding and seemed not to affect the prevalence of proteinuria or hypertension.

Prednisone in the treatment of tubulointerstitial nephritis in children.

BACKGROUND: Patients with tubulointerstitial nephritis (TIN) may develop permanent renal impairment. However, there are no prospective studies available on the treatment of TIN. METHODS: The effect of prednisone in the treatment of TIN was evaluated in a total of 17 patients who received prednisone or who were followed up without medication. The patient group was subdivided based on the initial plasma creatinine (PCr), below or above 150 µmol/l. RESULTS: All prednisone-treated patients had normal plasma creatinine (PCr) after 1 month of treatment (median 59.1 [45-85] µmol/l) whereas only 50 % of patients in the non-treatment group had normal creatinine (median 81.0 [42-123] µmol/l) at the same time point (p = 0.025). During 6 months' follow-up, PCr decreased in all patient groups; however, it decreased significantly only in prednisone-treated patients with baseline PCr >150 µmol/l (p < 0.001). At the end of follow-up, no difference in PCr, glomerular filtration rate (GFR), or low molecular weight (LMW) proteinuria could be found between the study groups. A considerable number of patients in both groups had subnormal GFR and/or persistent LMW proteinuria at the 6-month follow-up visit. Eighty-two percent of the patients had uveitis. CONCLUSIONS: Prednisone speeds up the recovery from renal symptoms of TIN, especially in patients with severe nephritis. The renal function did not differ significantly between prednisone and control patients after 6 months' follow-up.

Shiga toxin-producing Escherichia coli serotype O78:H(-) in family, Finland, 2009.

Shiga toxin-producing Escherichia coli (STEC) is a pathogen that causes gastroenteritis and bloody diarrhea but can lead to severe disease, such as hemolytic uremic syndrome (HUS). STEC serotype O78:H(-) is rare among humans, and infections are often asymptomatic. We detected a sorbitol-fermenting STEC O78:H(-):stx(1c):hlyA in blood and fecal samples of a 2-week-old boy who had bacteremia and HUS and in fecal samples of his asymptomatic family members. The phenotypic and genotypic characteristics and the virulence properties of this invasive STEC were investigated. Our findings demonstrate that contrary to earlier suggestions, STEC under certain conditions can invade the human bloodstream. Moreover, this study highlights the need to implement appropriate diagnostic methods for identifying the whole spectrum of STEC strains associated with HUS.

Growth in very young children undergoing chronic peritoneal dialysis.

Very young children with chronic kidney disease often have difficulty maintaining adequate nutrition, which contributes to the high prevalence of short stature in this population. Characteristics of the dialysis prescription and supplemental feeding via a nasogastric (NG) tube or gastrostomy may improve growth, but this is not well understood. Here, we analyzed data from 153 children in 18 countries who commenced chronic peritoneal dialysis at <24 months of age. From diagnosis to last observation, 57 patients were fed on demand, 54 by NG tube, and 10 by gastrostomy; 26 switched from NG to gastrostomy; and 6 returned from NG to demand feeding. North American and European centers accounted for nearly all feeding by gastrostomy. Standardized body mass index (BMI) uniformly decreased during periods of demand feeding and increased during NG and gastrostomy feeding. Changes in BMI demonstrated significant regional variation: 26% of North American children were obese and 50% of Turkish children were malnourished at last observation (P < 0.005). Body length decreased sharply during the first 6 to 12 months of life and then tended to stabilize. Time fed by gastrostomy significantly associated with higher lengths over time (P < 0.001), but adjustment for baseline length attenuated this effect. In addition, the use of biocompatible peritoneal dialysate and administration of growth hormone independently associated with improved length, even after adjusting for regional factors. In summary, growth and nutritional status vary regionally in very young children treated with chronic peritoneal dialysis. The use of gastrostomy feeding, biocompatible dialysis fluid, and growth hormone therapy associate with improved linear growth.

Neurological development in 21 children on peritoneal dialysis in infancy.

Few studies have focused on the neurodevelopment of infants on peritoneal dialysis (PD). Infants are the most demanding patient group on PD and thus are vulnerable to neurological sequelae. We studied 21 patients <2 years of age (mean 0.59 years) at onset of PD. They were evaluated by a neurologist, otologist, physiotherapist, and occupational therapist during PD. Neuropsychological tests were collected from all patients at least 5 years old, and the brain images were reviewed. Eleven patients (52%) had a pre- or neonatal problem or comorbidity as risk factor for their development at onset of PD. All infants tolerated PD well. At the end of the study, 71% had some neurological abnormality, 29% a major impairment (all with predialysis risk factors), and 43% a minor one. Brain infarcts were detected in four patients (19%) and other ischemic lesions in three (14%). Three patients (14%) developed hearing defect. Mortality rate was 5%. PD is a safe treatment modality for end-stage renal failure in infants. Some patients had risk factors for development, but their neurological problems did not progress during PD. Patients without risk factors tolerated PD well without major neurological sequelae.

Normal growth and intravascular volume status with good metabolic control during peritoneal dialysis in infancy.

The most demanding patient population on peritoneal dialysis (PD) consists of children under 2 years of age. Their growth is inferior to that of older children and maintaining euvolemia is difficult, especially in anuric patients. In this prospective study reported here, we enrolled 21 patients <2 years of age (mean 0.59 years) at onset of PD and monitored their uremia parameters and evaluated their nutrition. Since no good instrument currently exists for estimating intravascular volume status, we used traditional blood pressure measurements, echocardiography, and N-terminal atrial natriuretic peptide measurements. Growth was compared with midparental height. Metabolic control was good. Long-term hypertension was seen in 43% of the patients, but left ventricular hypertrophy decreased during the study period. Mean weekly urea Kt/V was 3.38 +/- 0.66 and creatinine clearance was 49 +/- 20 L/week per 1.73 m(2). Catch-up growth was documented in 57% of the patients during PD. However, these children did not attain their midparental height at the end of PD at a mean age of 1.71 years. Although favorable metabolic control and good growth were achieved during PD, these children lagged in term of their midparental height. We conclude that several instruments are needed for determining the management of intravascular volume status and that the control of calcium-phosphorus status is demanding.

Characteristics and survival of young adults who started renal replacement therapy during childhood.

BACKGROUND: Little is known about the group of children on renal replacement therapy (RRT) who reach the age of 18 years and are transferred from paediatric to adult nephrology services. The aim of this study was to describe patient demographics, primary renal diseases, treatment history and determine the risk factors for mortality of these young adults who started RRT in childhood. METHODS: We included 1777 young adults who had started RRT during childhood and turned 18 between 1985 and 2004 from nine European renal registries submitting data to the ERA-EDTA Registry. The chi-square test was used to test differences between patient groups and Cox regression analysis to examine patient survival. RESULTS: Young adults who began RRT during childhood increased the total number of adult patients starting RRT by 1.5% per annum. The annual number of children on RRT turning 18, per million persons (Pmarp) reaching the age of 18 years, increased between 1985 and 2004 from 71 to 116. Over time, there was an increase in the percentage of young adults who started RRT at a very young age, a greater number of children with hypoplasia/dysplasia and cystic kidneys and more young adults who started RRT with peritoneal dialysis or pre-emptive transplantation. The unadjusted 5-year patient survival from the 18th birthday was 95.1% (95% CI 93.9-96.0). The average life expectancy was 63 years for young adults with a functioning graft and 38 years for those remaining on dialysis. CONCLUSIONS: The number Pmarp of young adults on RRT has increased over time. Their characteristics and treatment history changed. Their survival prospects are good; however, transplant recipients have an expected remaining lifetime that is at least twice as high as for young adults on dialysis.

Peritoneal dialysis in children under two years of age.

BACKGROUND: Although results of peritoneal dialysis (PD) in small children have improved during recent years, the youngest children have poorer growth, more infections and higher mortality than do older children. METHODS: In this retrospective study, we analysed patient records of all children under age 2 treated with continuous peritoneal dialysis (CPD) between 1995 and 2000 in Finland. Diagnoses leading to renal failure in these 23 children were congenital nephrotic syndrome of the Finnish type (13), polycystic kidney disease (4), a urethral valve (3), renal insufficiency due to neonatal asphyxia (2) and Prune-Belly syndrome (1). Of these 23, 17 (74%) were anuric. RESULTS: The mean age at the onset of PD was 0.4 years and the mean time on dialysis 1.4 years. Hernias were diagnosed in 57%. The peritonitis rate was 1:14.5 patient-months, and 30% were peritonitis-free. Hypertension was common, and 70% had at least one period on antihypertensive medication. None of the patients had pulmonary oedema or dialysis-related seizures. The mean height standard deviation score (hSDS) at the start of PD (n = 16) was -2.0 and after 9 months -1.6. Catch-up growth was documented in 64% of the patients during dialysis. Hospitalization time was 124 days/patient-year. Two patients (9%) died. CONCLUSIONS: Our results are reassuring. Mortality was low, laboratory parameters were acceptable and growth was good. Peritonitis rate was comparable to that in older children. Correction of inguinal hernia should be routinely performed; high blood pressure is still a problem.

Plasma exchange and retransplantation in recurrent nephrosis of patients with congenital nephrotic syndrome of the Finnish type (NPHS1).

BACKGROUND: Recurrent nephrotic syndrome (NS) is a severe problem after renal transplantation in patients with congenital nephrotic syndrome of the Finnish type (NPHS1). The NPHS1 kidneys do not express nephrin, and antibodies against this major glomerular filter protein have been observed in NPHS1 children with recurrent NS. We evaluated here the use of plasma exchange (PE) therapy and kidney retransplantation in NPHS1 patients with recurrent NS and extended our studies on the pathogenesis of the recurrence. METHODS: Clinical data on 65 NPHS1 patients who received 77 kidney transplants between the years 1986 and 2006 was collected. Serum anti-nephrin antibodies were assayed with an enzyme-linked immunosorbent assay method, and the kidney biopsy samples were evaluated by light microscopy and immunohistochemistry. RESULTS: Twenty-three episodes of recurrent NS occurred in 19 grafts of 13 NPSH1 patients homozygous for Fin-major mutation. Six retransplantations were performed to four NPHS1 patients, who lost their graft because of recurrent NS, and heavy proteinuria developed immediately in all cases. Although 73% of the patients had detectable serum anti-nephrin antibodies, the kidney biopsy findings were minimal. Introduction of PE alongside cyclophosphamide proved effective in the treatment of the proteinuric episodes (one graft loss out of nine). If remission was achieved, recurrent NS did not significantly deteriorate the long term graft function. CONCLUSIONS: The clinical and pathological data suggest that anti-nephrin antibodies effectively impair the glomerular function in kidney grafts of NPHS1 patients homozygous for Fin-major mutation. Plasma exchange is a useful adjunct to the treatment of the recurrent NS.

BIOKID: randomized controlled trial comparing bicarbonate and lactate buffer in biocompatible peritoneal dialysis solutions in children [ISRCTN81137991].

BACKGROUND: Peritoneal dialysis (PD) is the preferred dialysis modality in children. Its major drawback is the limited technique survival due to infections and progressive ultrafiltration failure. Conventional PD solutions exert marked acute and chronic toxicity to local tissues. Prolonged exposure is associated with severe histopathological alterations including vasculopathy, neoangiogenesis, submesothelial fibrosis and a gradual loss of the mesothelial cell layer. Recently, more biocompatible PD solutions containing reduced amounts of toxic glucose degradation products (GDPs) and buffered at neutral pH have been introduced into clinical practice. These solutions contain lactate, bicarbonate or a combination of both as buffer substance. Increasing evidence from clinical trials in adults and children suggests that the new PD fluids may allow for better long-term preservation of peritoneal morphology and function. However, the relative importance of the buffer in neutral-pH, low-GDP fluids is still unclear. In vitro, lactate is cytotoxic and vasoactive at the concentrations used in PD fluids. The BIOKID trial is designed to clarify the clinical significance of the buffer choice in biocompatible PD fluids. METHODS/DESIGN: The objective of the study is to test the hypothesis that bicarbonate based PD solutions may allow for a better preservation of peritoneal transport characteristics in children than solutions containing lactate buffer. Secondary objectives are to assess any impact of the buffer system on acid-base status, peritoneal tissue integrity and the incidence and severity of peritonitis. After a run-in period of 2 months during which a targeted cohort of 60 patients is treated with a conventional, lactate buffered, acidic, GDP containing PD fluid, patients will be stratified according to residual renal function and type of phosphate binding medication and randomized to receive either the lactate-containing Balance solution or the bicarbonate-buffered Bicavera solution for a period of 10 months. Patients will be monitored by monthly physical and laboratory examinations. Peritoneal equilibration tests, 24-h dialysate and urine collections will be performed 4 times. Peritoneal biopsies will be obtained on occasion of intraabdominal surgery. Changes in small solute transport rates, markers of peritoneal tissue turnover in the effluent, acid-base status and peritonitis rates and severity will be analyzed.

Recombinant human growth hormone treatment, using two dose regimens in children with chronic renal failure--a report on linear growth and adverse effects.

The aim of this study was to study the efficiency and the adverse effects of 2 or 4 IU/m2/day of growth hormone (GH) in the first year and 4 IU/m2/day in the second. Of 29 growth-retarded children with chronic renal failure (CRF) (aged 3.4-15.1 years), 23 completed the first year of therapy, and 16 completed the second year. Height velocity SDS (HVSDS) increased in the first year in the low-dose group with 3.0, and 3.8 in the high-dose group. In the second year, HVSDS increased by 1.3 in the low-dose group and by 2.1 in high-dose group (p < 0.05). The IGF-I/IGFBP-3 ratio rose identically during the first year (p < 0.01). The retarded bone age did not advance inappropriately. The integrated insulin levels (AUC) increased significantly after 1 year of therapy in both groups. HbA1c, levels did not change. The number of adverse events was highest in the low-dose group, in which one patient developed overt insulin dependent diabetes mellitus. In conclusion, glucose metabolism should be monitored in children with CRF during rhGH-treatment. GH therapy in our patients resulted in a significant increase in height velocity with no inappropriate bone age progression and few serious adverse effects, all without relation to the dose of rhGH. The low start dose (2 IU/m2/ day) was of no advantage compared to the high dose.