Kai Rönnholm

Management of congenital nephrotic syndrome of the Finnish type

Congenital nephrotic syndrome of the Finnish type (CNF) is a rare autosomal recessively inherited disease characterised by intrauterine onset of massive urinary loss of proteins, 90% of which is albumin. The CNF gene has been localised to the long arm of chromosome 19, but the pathogenesis remains unclear. Historically, all CNF patients died, usually within the first 6 months of life. Today, a normal life can be achieved for a child with CNF by correcting the protein deficiency and normalising nutrition. This is accomplished by early intravenous albumin supplementation, nutritional support, aggressive treatment of complications and early renal transplantation, after bilateral nephrectomy and peritoneal dialysis. In the present article current treatment strategies are reviewed, and our own experience with 43 CNF patients during the last 10 years is presented.

Neurodevelopmental outcome in high-risk patients after renal transplantation in early childhood

Abstract: Patient and graft survival rates of pediatric renal transplant recipients are currently excellent, but there are few reports regarding the long‐term neurodevelopmental outcome after renal transplantation (Tx) in early childhood. Children with renal failure from infancy would be expected to have a less favorable developmental prognosis. We report the neurodevelopmental outcome in 33 school‐age children transplanted between 1987 and 1995 when < 5 yr of age. We prospectively performed a neurological examination, magnetic resonance imaging (MRI) of the brain, electroencephalograms (EEGs), audiometry, and neuropsychological tests (NEPSY), and measured cognitive performance (WISC‐R); we related these results to school performance and to retrospective risk factors prior to Tx. Twenty‐six (79%) children attended normal school and 76% had normal motor performance. Six of the seven children attending a special school had brain infarcts on MRI. The EEG was abnormal in 11 (35%), and five (15%) received anti‐convulsive treatment after Tx. Sensorineural hearing loss was documented in six patients. The mean intelligence quotient (IQ) was 87, and 6–24% showed impairment in neuropsychological tests. The children attending a special school had been more premature, but had not had a greater number of pre‐ or neonatal complications. They had experienced a greater number of hypertensive crises (p = 0.002) and seizures (p = 0.03), mainly during dialysis, but the number of septic infections and the mean serum aluminum levels were not significantly greater than in the children with normal school performance. In these previously lethal diseases, the overall neurodevelopmental outcome is reassuring. However, it is of crucial importance to further minimize the risk factors prior to Tx.

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.

Psychosocial adjustment and quality of life after renal transplantation in early childhood

Abstract:   Psychosocial adjustment and quality of life has been reported good in children after a successful renal transplantation (Tx). There are, however, few reports of using standardized methods in evaluating these issues, particularly in small children. We investigated the psychosocial adjustment in 32 children at school age (mean 9.6 ± 1.6), who had received a renal Tx under the age of 5 yr, using the Achenbach Child Behavior Checklist with data collected from both parents (CBCL) and teachers (CBCL–TRF). Health‐related quality of life (HRQOL) was assessed by interviewing the children using a 17‐dimensional (17D) health‐related measure and compared to HRQOL of 244 normal school children. The effect of additional diseases and comorbidity on psychosocial adjustment and HRQOL was assessed. The total scores on the CBCL did not differ from normative samples of healthy children. However, somatic complaints and social problems were reported more frequently in boys, and attention problems in both boys and girls. Patients with pathological scores had significantly more comorbidity (p = 0.03) and were more often attending a special school (p = 0.007) than patients with normal scores. The global 17D HRQOL index was significantly lower than measured in healthy controls (94 ± 5 for controls and 85 ± 7 for patients, p < 0.0001). It is of crucial importance to further minimize the risk factors leading to comorbidity in children after Tx. HRQOL assessment by the children themselves can be used to direct interventions and support the childrens psychosocial adjustment.

Clinical outcome of pediatric patients on peritoneal dialysis under adequacy control

Abstract Clinical outcome under adequacy control was studied in 10 pediatric patients under 5 years and 11 patients over 5 years of age on continuous peritoneal dialysis (PD). Outcome was compared between the age groups and with our previous results in patients under 5 years of age. Peritoneal equilibration test and 24-h dialysate collection were performed. Laboratory data, clinical status, and diet were recorded. PD prescription was adjusted for these parameters. The mean weekly urea Kt/V was similar and stable in the two age groups (3.1±0.6 vs. 3.2±0.4 at baseline). The mean weekly creatinine clearance (CCr) was at baseline significantly lower in the younger age group (58.7±11.9 vs. 78.0±14.9 l/week per 1.73 m2, P=0.004), but later similar. Urea Kt/V and CCr correlated significantly. Hematological and biochemical parameters were stable, and catch-up growth was observed in 62% of the patients during 9 months of follow-up. The outcome for children under and over 5 years of age did not differ significantly. The clinical outcome in patients under 5 years of age improved under adequacy control, when compared with our previous results in patients of the same age. This suggests a positive effect of adequacy control on clinical outcome.

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.

Graft function 5-7 years after renal transplantation in early childhood.

BACKGROUND Low recipient age is still a risk factor for graft failure after kidney transplantation (Tx). Detailed prospective reports on long-term graft function in small children after renal Tx are still lacking. METHODS Forty-nine kidney allograft recipients who received transplants before the age of 5 years were followed prospectively. The most common disease was congenital nephrotic syndrome of the Finnish type. Twenty patients were recipients of living related donors (LRD), and 29 were cadaveric kidney (CAD) recipients. All patients received triple immunosuppression. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), sodium, urate, and potassium handling, and concentrating capacity were studied for up to 7 years after Tx. RESULTS Patient survival 7 years after Tx was 100% for LRD and 96% for CAD recipients. Graft survival was 94% for LRD and 79% for CAD recipients (P=NS) and 89% and 83% for children >2 years and <2 years of age at Tx, respectively (P=NS). Five years after Tx, GFR was 70 vs. 64 and ERPF was 380 vs. 310 ml/min/1.73 m2 for LRD and CAD recipients, respectively (P=NS). Mean absolute GFR remained stable. GFR was lower in children who received transplants at <2 years than in children who received transplants at >2 years of age, 54 vs. 75 ml/min/1.73 m2 (P=0.02). Sodium handling remained intact, but hyperuricemia was seen in 43-67%; 17-33% showed abnormal handling of potassium; and most patients had a subnormal concentrating capacity. CONCLUSIONS Excellent long-term graft survival and good graft function can be achieved with triple immunosuppression, even in young CAD kidney recipients.

Growth after renal transplantation in infancy or early childhood.

Abstract Forty-one children <5 years of age at kidney transplantation (TX) were investigated for growth, bone age, and renal function up to 7 years (n=26) after TX. All children received triple immunosuppression, including alternate-day corticosteroid treatment. Catch-up growth was seen in 81% of 30 children without growth hormone (GH) treatment. Children <2 years of age without GH had a mean height standard deviation score (hSDS) of –1.1±0.8 at TX and –1.1±0.5 at 7 years; children between 2 and 5 years improved their hSDS from –1.9±0.9 to –0.4±0.8 (P<0.0001). The hSDS at TX correlated inversely with the ΔhSDS from TX to 7 years (r=–0.80, P=0.0002). Glomerular filtrations rate (GFR) at 5 years post TX correlated with the subsequent growth rate from 5 to 7 years TX (r=0.58, P=0.01). Catch-up growth was seen in all 11 children receiving GH. Their mean hSDS improved from –2.5±0.9 to –1.1±0.9 (P<0.0001). In the majority of children receiving a kidney graft in early life, triple immunosuppression with alternate-day steroids can ensure catch-up growth. In children <5 years of age at TX, growth is predicted better by the degree of stunting than by age.

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.

Bone Health in Children and Adolescents After Renal Transplantation

The basis for lifelong bone health is established in childhood and adolescence. Whereas pediatric renal transplant (RTx) patients are at risk for impaired bone mass gain and fractures, scarce data on this subject are available. We performed a cross‐sectional and longitudinal study of bone health in a national cohort of 106 pediatric RTx patients (median age, 12.6 yr; median follow‐up, 5.1 yr after RTx). The patients underwent clinical evaluation, DXA for BMD, and spinal imaging for vertebral fractures. In longitudinal analysis, the median lumbar spine BMD Z‐score was lowest (median, −1.0) at 1 yr postoperatively but increased to a peak value of −0.2 at 5 yr. In boys, the lumbar spine BMD Z‐score increased also during puberty but decreased in girls. In cross‐sectional analysis, the lumbar spine, hip, and whole body BMD Z‐scores were < −2 SD in 4%, 6%, and 6% of the patients, respectively. Sixteen percent had sustained peripheral fractures, and 8% had vertebral fractures. Female sex and age >15 yr (OR, 56.26; 95% CI, 5.17–611.82; p = 0.0007) as well as high plasma PTH levels (OR, 4.03; 95% CI, 1.37–11.85; p = 0.009) were significant predictors for low BMD. Three‐year cumulative glucocorticoid dose, outside the immediate post‐RTx years, was not associated with BMD parameters. The observed BMD results were satisfactory. However, the high (8%) prevalence of vertebral fractures warrants careful evaluation of bone health in these patients.