Marja Ala-Houhala

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.

Reference intervals for cystatin C in pre- and full-term infants and children.

Abstract Cystatin C is a non-glycated, 13-kDa basic protein produced by all nucleated cells. Recent studies have indicated that the plasma concentration of cystatin C is a better marker for glomerular filtration rate (GFR) than plasma creatinine, which is most commonly used for this purpose. We established reference values for plasma cystatin C in pre- or full-term infants and children. For comparison we also measured the creatinine concentration in the same samples. Cystatin C was measured by a commercially available immunoturbidimetric method with a Hitachi 704 analyzer in sera obtained from 58 pre-term infants, 50 full-term infants and 299 older children (132 girls, 167 boys, median age 4.17 years, range 8 days to 16 years). No sex differences were found. The pre-term infants had higher cystatin C concentrations (mean 1.88 mg/l, SD 0.36 mg/l) than the full-term (mean 1.70 mg/l, SD 0.26 mg/l, P=0.0145). The reference interval for pre-term infants calculated non-parametrically was 1.34–2.57 mg/l and for full-term infants 1.36–2.23 mg/l. The cystatin C concentration decreased rapidly after birth, and above 3 years of age did not depend on age. The reference interval for children 3–16 years of age calculated non-parametrically was 0.51–1.31 mg/l. Younger children (<1 year: 0.75–1.87 mg/l; 1–3 years: 0.68 –1.60 mg/l) had slightly, but significantly, higher plasma cystatin C levels.

Maternal compared with infant vitamin D supplementation.

Vitamin D metabolites were studied in mother-infant pairs at delivery and eight and 15 weeks after that to evaluate the possibility of vitamin D supplementation of infant through the mother. Healthy mothers (n = 49) delivering in January received daily either 2000 IU (group 1), 1000 IU (group 2), or no (group 3) vitamin D. Their infants were exclusively breast fed, and those in group 3 received 400 IU of vitamin D a day. After eight weeks of lactation the infantile vitamin D concentrations were similar in groups 1 and 3 but significantly lower in group 2. The serum 24,25-dihydroxyvitamin D and 1,25-dihydroxyvitamin D concentrations were also lower in group 2. The mean mineral, parathyroid hormone, and alkaline phosphatase values showed no intergroup differences at any point. No infants showed any clinical or biochemical signs of rickets, and their growth was equal. In conclusion, a daily postpartum maternal supplementation with 2000 IU of vitamin D, but not with 1000 IU, seems to normalise the vitamin D metabolites of breast fed infants in winter. Maternal safety with such supplementation over prolonged periods, however, should be examined.

Cystatin C as a marker for glomerular filtration rate in pediatric patients

Abstract Cystatin C is a non-glycated 13-kilodalton basic protein produced by all nucleated cells. The low molecular mass and the basic nature of cystatin C, in combination with its stable production rate, suggest that the glomerular filtration rate (GFR) is the major determinant of cystatin C concentration in the peripheral circulation. Recently published studies have shown that cystatin C correlates more strongly than creatinine with GFR measured using the 51Cr-EDTA clearance. The aim of this study was to evaluate serum cystatin C as a marker for GFR in children. GFR was determined on medical indications using the 51Cr-EDTA technique in pediatric patients (2–16 years) in our renal unit. Simultaneously their cystatin C and creatinine concentrations were also measured. Of our 52 patients, 19 had a reduced renal function (<GFR 89 ml/min per 1.73 m2) based on the 51Cr-EDTA clearance. The correlation of cystatin C with the isotopic measurement of GFR tended to be stronger (r=0.89, P=0.073) than that of creatinine (r=0.80). Receiver operating characteristic analysis showed that the diagnostic accuracy of cystatin C was better (P=0.037) than that of creatinine in discriminating between subjects with normal renal function and those with reduced GFR. This study demonstrates that serum cystatin C has an increased diagnostic accuracy for reduced GFR when compared with serum creatinine. Hence, cystatin C seems to be an attractive alternative for the estimation of GFR in children.

Renal manifestations of Henoch–Schönlein purpura in a 6-month prospective study of 223 children

Objective To assess the risk factors for developing Henoch–Schönlein purpura nephritis (HSN) and to determine the time period when renal involvement is unlikely after the initial disease onset. Design A prospective study of 223 paediatric patients to examine renal manifestations of Henoch–Schönlein purpura (HSP). The patients condition was monitored with five outpatient visits to the research centre and urine dipstick testing at home. Results HSN occurred in 102/223 (46%) patients, consisting of isolated haematuria in 14%, isolated proteinuria in 9%, both haematuria and proteinuria in 56%, nephrotic-range proteinuria in 20% and nephrotic-nephritic syndrome in 1%. The patients who developed HSN were significantly older than those who did not (8.2±3.8 vs 6.2±3.0 years, p<0.001, CI for the difference 1.1 to 2.9). Nephritis occurred a mean of 14 days after HSP diagnosis, and within 1 month in the majority of cases. The risk of developing HSN after 2 months was 2%. Prednisone prophylaxis did not affect the timing of the appearance of nephritis. The risk factors for developing nephritis were age over 8 years at onset (OR 2.7, p=0.002, CI 1.4 to 5.1), abdominal pain (OR 2.1, p=0.017, CI 1.1 to 3.7) and recurrence of HSP disease (OR 3.1, p=0.002, CI 1.5 to 6.3). Patients with two or three risk factors developed nephritis in 63% and 87% of cases, respectively. Laboratory tests or blood pressure measurement at onset did not predict the occurrence of nephritis. Conclusion The authors recommend weekly home urine dipstick analyses for the first 2 months for patients with HSP. Patients with nephritis should be followed up for more than 6 months as well as the patients with HSP recurrence.

Clinical course of extrarenal symptoms in Henoch–Schönlein purpura: a 6-month prospective study

Objective To describe the extrarenal symptoms and clinical course of Henoch–Schönlein purpura (HSP). Design A prospective national multicentre trial with 6-month follow-up. Patients A total of 223 newly diagnosed paediatric HSP patients. Results Purpura was the initial symptom in 73% of the patients and was preceded by joint or gastrointestinal manifestations in the rest by a mean of 4 days. Joint symptoms, abdominal pain, melena, nephritis and recurrences occurred in 90%, 57%, 8%, 46% and 25% of the patients, respectively. Orchitis affected 17/122 (14%) of the boys. Seven patients developed protein-losing enteropathy characterised by abdominal pain, oedema and serum albumin under 30 g/l, and an additional 49 patients had subnormal albumin levels without any proteinuria. Positive fecal occult blood (26/117, 22%) and α1-antitrypsin (7/77, 9%) suggested mucosal injury even in the patients without gastrointestinal symptoms. HSP was often preceded by various bacterial, especially streptococcal (36%) and viral infections. Previous streptococcal infection did not induce changes in the level of complement component C3. Recurrences were more frequent in patients >8 years of age (OR 3.7, CI 2.0 to 7.0, p<0.001) and in patients with nephritis (OR 4.6, CI 2.3 to 8.9, p<0.001). Patients with severe HSP nephritis had more extrarenal symptoms up to 6 months. There was no difference in the clinical course between the prednisone-treated and non-treated patients during the 6-month follow-up. Conclusions Serum albumin is often low in HSP patients without proteinuria, due to protein loss via the intestine. Although corticosteroids alleviate the symptoms, they seem not to alter the clinical course of HSP during 6 months of follow-up.

Double blind study on the need for vitamin D supplementation in prepubertal children.

ABSTRACT. Fifty‐one healthy prepubertal schoolchildren were followed for 13 months in a double blind study. Twenty‐four of them were supplemented with 400 IU of vitamin D2 5–7 times weekly, while 27 received a placebo. The children were examined in winter both at the beginning and at the end of the study, and in the middle of the study in autumn. Mean 25‐hydroxyvitamin D levels in the supplemented group were significantly higher than those in the placebo group both in autumn and in winter, when the study ended. The vitamin D supplementation did not, however, affect other vitamin D metabolites, serum calcium, albumin, inorganic phosphorus, parathyroid hormone concentrations or alkaline phosphatase activity. Moreover, the supplementation caused no alterations in the weight or height gain or bone mineral content of the distal radius of the children, and thus subclinical rickets could not be shown.

Risk of renal scarring in vesicoureteral reflux detected either antenatally or during the neonatal period

OBJECTIVES To evaluate both the demographic features and the renal outcome of fetal vesicoureteral reflux (VUR), two well-defined populations were analyzed: those with hydronephrosis detected by obstetric ultrasonography, and neonates diagnosed after developing their first urinary tract infection within the first 4 postnatal weeks. METHODS Twenty-one neonates with antenatally detected VUR were compared with 30 patients with neonatally detected symptomatic disease. The mode of presentation, fate of reflux, and renal outcome were analyzed. RESULTS Significantly more bilateral dilating VUR was found in postnatally versus antenatally diagnosed patients (53% versus 29%; P = 0.05). Fourteen percent presented with congenital renal dysplasia. No difference was found in the incidence of congenital dysplasia between the two groups. Focal renal scars developed during follow-up in 19% of renal units. New scars were observed in dilating VUR only, especially in grades 4 and 5 (P <0.05), and these were exclusively in the postnatal patient group (P <0.005). CONCLUSIONS Several demographic features of fetal VUR differ, depending on whether detected antenatally or postnatally. The incidence of bilateral dilating VUR was greater in postnatally detected cases, suggesting a more severe manifestation of the disease. Renal injury occurred in an appreciable number of renal units. The damage may be of congenital origin or may be acquired secondary to urinary tract infection. The risk of acquired renal scarring is particularly significant if dilating VUR is not detected until neonatally after the first urinary tract infection.

Predictive factors associated with significant urinary tract abnormalities in infants with pyelonephritis.

BACKGROUND Major urinary tract abnormalities are detected in 20 to 40% of infants with acute pyelonephritis (APN). Early detection of structural defects is essential for protecting the kidneys from reinfection and subsequent scarring. The purpose of this study was to investigate whether any factors present during the acute phase of infection could predict the presence of existing significant urinary tract abnormalities in infants. METHODS A prospective study of 180 infants, aged 1 to 24 months, with APN was conducted. Blood and urine samples were collected. Renal ultrasound (US) was performed within 0 to 6 days from admission. Final diagnosis of the urinary tract anatomy was elucidated using the results of two or more radiologic imaging studies. RESULTS Risk factors for the presence of significant urinary tract abnormalities in infants were pathogens other than Escherichia coli in urine [relative risk (RR) 3.4, 95% confidence interval (CI) 2.2 to 5.3; P = 0.001], positive blood culture (RR 2.3, 95% CI 1.3 to 4.0; P = 0.039), young age (1 to 6 months) (RR 2.2, 95% CI 1.3 to 3.9; P = 0.004), lack of papG adhesin genes of E. coli in urine (RR 2.1, 95% CI 1.2 to 3.9; P = 0.016) and abnormal renal US (RR 2.0, 95% CI 1.2 to 3.4; P = 0.008). CONCLUSIONS Infants 1 to 6 months of age with APN caused by bacteria other than E. coli or by papG-negative E. coli strain, positive blood culture and abnormal renal US carry an increased risk for significant urinary tract abnormalities and need enforced follow-up.

Serum 25‐Hydroxyvitamin D Levels in Finnish Children Aged 2 to 17 Years

ABSTRACT. Serum levels of 25‐hydroxyvitamin D (25‐OHD) in summer and winter were studied in 564 children aged 2–17 years living in the northern, central or southern parts of Finland. The mean levels of 25‐OHD were significantly lower in winter (13.3 ± 10.8 ng/ml) than in summer (27.2 ± 10.3 ng/ml) in all age groups (p < 0.001). The mean 25‐OHD levels in the northern part of the country did not differ significantly from the others. In both seasons the levels of 25‐OHD were lower in the 11–17 year age group than in younger children. In that age group 22.4 % of the children had serum levels of 25‐OHD below 5 ng/ml (the limit of risk for rickets), compared to 16.8 % of children 6–10 years old and 7.5 % of children 2–5 years old, but none of the children showed any laboratory evidence of rickets.