Elisa Ylinen

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.

Outcome of patients with antenatally detected pelviureteric junction obstruction

We investigated the outcome of patients with antenatally detected pelviureteric junction (PUJ) obstruction treated either conservatively or surgically. The series comprised 68 such patients, 54 with unilateral obstruction. Of the unilateral cases, 22 units were treated conservatively, 21 underwent early and 11 late surgery. Of the bilateral cases, 18 units were treated conservatively, 9 underwent early pyeloplasty, whereas 1 underwent later surgery. Among the conservatively treated unilateral cases, none of the patients’ good renal function deteriorated during follow-up. In the group with early surgery, the primary good function remained unchanged in all. In some patients, moderate function improved after early pyeloplasty, but in patients with poor function no improvement occurred. Of patients who underwent late pyeloplasty, primary good renal function remained unchanged in all except 1, although it had deteriorated to moderate function in some before surgery. In all except 1 patient with bilateral obstruction treated conservatively, both the grade of hydronephrosis and split function remained unchanged. In most patients the outcome of antenatally detected unilateral PUJ obstruction with initially good renal function, whether treated conservatively or surgically, seems favorable. Some patients with moderate function might benefit from pyeloplasty. In kidneys with poor function, recovery may be minimal despite pyeloplasty.

Assessment of renal function during high-dose methotrexate treatment in children with acute lymphoblastic leukemia

High‐dose methotrexate (HD‐MTX) is potentially nephrotoxic. The feasibility of novel biomarkers to indicate renal injury due to HD‐MTX infusion was studied in children with acute lymphoblastic leukemia (ALL).

Increased risk of multicystic dysplastic kidney among babies of both pre-gestational and gestational diabetic mothers

Pre-gestational maternal diabetes mellitus (DM) is a well-established risk factor for congenital malformations in the offspring [1]. Recent epidemiological studies have shown a significant increase of anomalies also in the offspring of gestational diabetic mothers [3, 5]. Certain malformations have been recognised to be overrepresented, namely cardiovascular, CNS, and musculoskeletal defects, caudal regression in particular [1, 3, 4]. An association between maternal DM and renal and urinary tract malformations has been postulated as well, but reported cases have been mostly anecdotal and rather nonspecific [1, 3, 4]. Multicystic dysplastic kidney (MDK) is generally considered to represent a sporadic form of congenital cystic renal disease. It is thought to arise early (at about 5 to 6 weeks of gestation) due to obstruction of the ureteric bud. Thus MDK is an ideal malformation for studying the possible effects of the imbalance of maternal glucose metabolism on embryonic development of the kidneys and the urinary tract. In the present study the relationship between both pregestational and gestational DM, and MDK in the offspring was investigated in a well-defined population. The study population comprised all infants born with MDK between 1990 and 2001 in the Greater Helsinki area, Finland. During the study period, altogether 209,125 live infants were born in the same area (population data, Greater Helsinki area, Finland). An ultrasound examination was performed routinely in all mothers. Of the mothers studied, 0.38% had pre-gestational DM and 0.50% had gestational DM [2]. Gestational DM was diagnosed using a 75 g 2 h oral glucose tolerance test (OGTT) at 28–32 gestational weeks. For pathological thresholds, mean glucose values +2SD were chosen and at least two out of three had to be abnormal (fasting 4.4 mmol/l, 1 h 9.1 mmol/ l, 2 h 7.4 mmol/l, venous whole blood). An OGTT was performed in all women with any known risk factor for gestational DM. Maternity clinic and obstetric records of all women with MDK in the offspring were carefully reviewed, including not only maternal DM but also other common teratogenic factors (e.g. teratogenic medications, reproductive hormones, alcohol, narcotics, teratogenic infections). None of the infants with MDK had been exposed to any of these other common teratogenic factors during gestation. MDK was defined as a renal tissue conglomerate consisting ultrasonographically of cysts of variable size, with scanty or no identifiable renal parenchyma in between, and with no uptake in the renal isotope scan. For statistical evaluation, the relative risk (RR) was calculated and the Chi squared test used to estimate the statistical significance. In the study population, 51 infants were born with MDK. The prevalence of MDK was thus 1 in 4100 live births. Eight babies with MDK were born to diabetic mothers, comprising 16% of the total. Three mothers had insulin-dependent pre-gestational DM and five had gestational DM. The overall RR for MDK among infants of mothers with pre-gestational (n=795) or gestational (n=1046) DM was as high as 20.95 (P<0.0001) (Table 1). Improved preconceptional, gestational and postnatal care has significantly decreased the incidence of spontaneous abortions and stillbirths in offspring of diabetic mothers. The frequency of congenital malformations has, interestingly, remained constant. Careful examination for congenital anomalies, including the urinary tract and the kidneys in particular, of infants born to diabetic mothers, is recommended. Eur J Pediatr (2002) 161: 634–635 DOI 10.1007/s00431-002-1043-4

Human herpes virus 6 infection in pediatric organ transplant patients

Transplant patients need lifelong immunosuppressive medication, but this reduces their defense mechanisms, making them prone to viral infections and reactivations. We aimed to clarify the prevalence and clinical manifestations of the human herpes virus 6 (HHV‐6) infection in children after pediatric solid organ transplants. Clinical findings and viral loads were compared between primary HHV‐6 infections and reactivations. The study comprised 47 kidney, 25 liver, and 12 heart transplant patients who underwent surgery from 2009 to 2014. HHV‐6 antibodies were analyzed before surgery, and HHV‐6 DNAemia tests were regularly carried out after the transplant using a real‐time quantitative polymerase chain reaction method. We found the primary HHV‐6 infection in 19 of 22 (86%) seronegative patients, and it was more common in patients under 3 years of age (79%) than over 3 (38%, P=.0002). Post‐transplant HHV‐6 DNAemia affected 48 of 84 (57%) patients and was significantly higher in primary infections than reactivations (P=.001), and 17 of 48 (35%) patients had symptoms when it was detected at a median of 2 weeks post‐transplant. The HHV‐6 infection was common after solid organ transplants, especially under 3 years of age, and it typically started 2 weeks after surgery. Testing for HHV‐6 DNAemia is recommended shortly after transplantation, especially in patients with fever, diarrhea, rash, seizures, or abnormal liver enzyme tests.

Management of children with congenital nephrotic syndrome: challenging treatment paradigms

Background Management of children with congenital nephrotic syndrome (CNS) is challenging. Bilateral nephrectomies followed by dialysis and transplantation are practiced in most centres, but conservative treatment may also be effective. Methods We conducted a 6-year review across members of the European Society for Paediatric Nephrology Dialysis Working Group to compare management strategies and their outcomes in children with CNS. Results Eighty children (50% male) across 17 tertiary nephrology units in Europe were included (mutations in NPHS1, n = 55; NPHS2, n = 1; WT1, n = 9; others, n = 15). Excluding patients with mutations in WT1, antiproteinuric treatment was given in 42 (59%) with an increase in S-albumin in 70% by median 6 (interquartile range: 3-8) g/L (P < 0.001). Following unilateral nephrectomy, S-albumin increased by 4 (1-8) g/L (P = 0.03) with a reduction in albumin infusion dose by 5 (2-9) g/kg/week (P = 0.02). Median age at bilateral nephrectomies (n = 29) was 9 (7-16) months. Outcomes were compared between two groups of NPHS1 patients: those who underwent bilateral nephrectomies (n = 25) versus those on conservative management (n = 17). The number of septic or thrombotic episodes and growth were comparable between the groups. The response to antiproteinuric treatment, as well as renal and patient survival, was independent of NPHS1 mutation type. At final follow-up (median age 34 months) 20 (80%) children in the nephrectomy group were transplanted and 1 died. In the conservative group, 9 (53%) remained without dialysis, 4 (24%; P < 0.001) were transplanted and 2 died. Conclusion An individualized, stepwise approach with prolonged conservative management may be a reasonable alternative to early bilateral nephrectomies and dialysis in children with CNS and NPHS1 mutations. Further prospective studies are needed to define indications for unilateral nephrectomy.

Pediatric Intestinal Failure: The Key Outcomes for the First 100 Patients Treated in a National Tertiary Referral Center During 1984-2017: Original Communication

BACKGROUND Pediatric-onset intestinal failure (IF) remains a severe illness with life-threatening consequences. In this study, we analyzed a single centers outcomes of IF over 3 decades. METHODS All children with IF who required parenteral nutrition (PN) >2 months or small-intestinal resection ≥50% managed since 1984 were included for retrospective outcome analyses. RESULTS In total, 100 patients with median PN duration of 1.2 (interquartile range, 0.4-3.5) years were identified. Causes of IF were short bowel syndrome (SBS; n = 78), primary intestinal motility disorders (n = 14), and congenital intestinopathies (n = 8). Patients with SBS had median 40 (25-60) cm of small bowel remaining. Overall, Kaplan-Meier 5- and 10-year weaning-off estimates were 67% (95% CI, 57-77) and 73% (95% CI, 63-84), respectively. Weaning off PN was predicted by remaining bowel anatomy, multidisciplinary treatment era, and absence of immune deficiency. Catheter-related bloodstream infections decreased from 1.4 to 0.6/1000 PN days (P = .0003) with systematic use of taurolidine locks. None had progressive liver disease. Thirty-one percent of patients with SBS underwent autologous intestinal reconstructive surgery. Five patients received and 2 were listed for isolated intestinal transplantation. Eight patients died, and overall 15-year survival rate estimate was 91% (95% CI, 85-98). CONCLUSIONS Despite reassuring rates of survival and weaning off PN, long-term PN failed in 14% of patients solely because of catheter complications in the recent era. Achievement of enteral autonomy in those with the shortest remaining small bowel and functional cause of IF remains challenging.