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Background Associations between anthropometric measures and patient outcomes in children are inconsistent and mainly based on data at kidney replacement therapy (KRT) initiation. We studied associations of height and body mass index (BMI) with access to kidney transplantation, graft failure, and death during childhood KRT. Methods We included patients 1.88. Underweight, overweight and obesity were calculated using age and sex-specific BMI for height-age criteria. Associations with outcomes were assessed using multivariable Cox models with time-dependent covariates. Results We included 11,873 patients. Likelihood of transplantation was lower for short (aHR: 0.82, 95% CI: 0.78–0.86), tall (aHR: 0.65, 95% CI: 0.56–0.75), and underweight patients (aHR: 0.79, 95%CI: 0.71–0.87). Compared with normal height, patients with short and tall statures showed higher graft failure risk. All-cause mortality risk was higher in short (aHR: 2.30, 95% CI: 1.92–2.74), but not in tall stature. Underweight (aHR: 1.76, 95% CI: 1.38–2.23) and obese (aHR: 1.49, 95% CI: 1.11–1.99) patients showed higher all-cause mortality risk than normal weight subjects. Conclusions Short and tall stature and being underweight were associated with a lower likelihood of receiving a kidney allograft. Mortality risk was higher among pediatric KRT patients with a short stature or those being underweight or obese. Our results highlight the need for careful nutritional management and multidisciplinary approach for these patients. Graphical abstract

Gastrointestinal symptoms are common among solid organ transplant (SOT) recipients. Information about colonoscopy findings after pediatric SOT is limited. This retrospective study reports endoscopy findings in a nationwide pediatric transplant recipient cohort.All pediatric recipients (kidney, liver, or heart) transplanted between 2010 and 2020 at our institution (n = 193) who had undergone ileocolonoscopy and upper gastrointestinal endoscopy after SOT were enrolled. Sixteen patients were identified. A meticulous search on clinical data including transplantation, gastrointestinal symptoms, endoscopy findings, and follow-up data was performed.Endoscopy was performed at a median of 2.6 years (0.4-13.3) after the first transplantation (median age at SOT 1.2 years). Gastrointestinal symptoms leading to endoscopy did not differ between the different transplant groups. The leading endoscopy indications were prolonged diarrhea and anemia. PTLD was found in 8 (50%) patients. Five were histologically early PTLD lesions and three were monomorphic large B-cell PTLDs (two EBV-positive and one EBV-negative), one having previously been diagnosed with autoimmune enteropathy. One patient had EBV enteritis. De novo inflammatory bowel disease was found in one patient, eosinophilic gastroenteritis in another, and in one patient with several episodes of watery diarrhea, the histological finding was mild non-specific colitis. In four patients, the endoscopy finding remained unclear and the symptoms were suspected to be caused by infectious agents or mycophenolate.PTDL with various stages is a common finding after pediatric SOT in patients with gastrointestinal symptoms. Endoscopy should be considered in transplant recipients with prolonged diarrhea, anemia, and/or abdominal pain.

Contains fulltext : 251790.pdf (Publisher’s version ) (Closed access) Fetal lower urinary tract obstruction (LUTO) is associated with high mortality and postnatal morbidity caused by lung hypoplasia and impaired kidney function. Specific diagnostic features that can guide clinical approach and decisions are lacking; thus, the European Reference Network for Rare Kidney Diseases established a work group to develop recommendations regarding the clinical definition, diagnosis and management of prenatally detected LUTO. The work group recommends the use of antero-posterior diameter of renal pelvis as the most reliable parameter for suspecting obstructive uropathies and for suspecting prenatal LUTO in the presence of fetal megacystis. Regarding prenatal and postnatal prognosis of fetuses with LUTO, the risk of fetal and neonatal death depends on the presence of oligohydramnios or anhydramnios before 20 weeks' gestation, whereas the risk of kidney replacement therapy cannot be reliably foreseen before birth. Parents of fetuses with LUTO must be referred to a tertiary obstetric centre with multidisciplinary expertise in prenatal and postnatal management of obstructive uropathies, and vesico-amniotic shunt placement should be offered in selected instances, as it increases perinatal survival of fetuses with LUTO.

BACKGROUND: Improved management of growth impairment might have resulted in less growth retardation after pediatric kidney transplantation (KT) over time. We aimed to analyze recent longitudinal growth data after KT in comparison to previous eras, its determinants, and the association with transplant outcome in a large cohort of transplanted children using data from the European Society for Paediatric Nephrology/European Renal Association and European Dialysis and Transplant Association Registry. METHODS: A total of 3492 patients transplanted before 18 years from 1990 to 2012 were included. Height SD scores (SDS) were calculated using recent national or European growth charts. We used generalized equation models to estimate the prevalence of growth deficit and linear mixed models to calculate adjusted mean height SDS. RESULTS: Mean adjusted height post-KT was -1.77 SDS. Height SDS was within normal range in 55%, whereas 28% showed moderate, and 17% severe growth deficit. Girls were significantly shorter than boys, but catch-up growth by 5 years post-KT was observed in both boys and girls. Children 12. CONCLUSIONS: Catch-up growth post-KT remains limited, height SDS did not improve over time, resulting in short stature in nearly half of transplanted children in Europe.

Background: The appearance of human leukocyte antigen (HLA) antibodies after solid organ transplantation predisposes recipients to graft dysfunction. In theory, vascular homografts, which are widely used in children with congenital heart defects, may cause allosensitization. Material/Methods: In this single-center retrospective study, the presence of pre-existing HLA antibodies in pediatric heart trans- plant (HTx) recipients with a vascular homograft was evaluated in a cohort of 12 patients. HLA antibodies were screened before and after HTx and positive screening results were confirmed and identified using the Luminex (R) single antigen bead method. Endomyocardial biopsies (EMB) and coronary angiography studies were re-evaluated to assess the prevalence of acute rejections and coronary artery change in these patients. Results: At the time of HTx, 8 patients (67%) had HLA antibodies detected by the Luminex assay, none of which were heart donor specific (DSA). All patients had negative leukocyte crossmatch. One patient developed DSAs against homograft donor prior to HTx. After the HTx, 5 patients (42%) developed DSAs against the heart donor and 4 patients (40%) against the homograft donor. In 2 patients (17%), the antibodies were against both heart and homograft donors. The rejection rate or prevalence of coronary artery vasculopathy did not differ significantly between the homograft cohort and our historical controls. Conclusions: Our results suggest that the prevalence of DSAs against homograft donor prior to HTx is relatively rare. However, almost half of the patients developed DSAs against homograft post-HTx. The clinical importance of these antibodies warrants further studies.

Background The pathophysiology of Henoch-Schönlein purpura (HSP) is still unclear, but several findings suggest that genetic factors may influence disease susceptibility. We aimed to perform a genome-wide association study (GWAS) in pediatric HSP patients with an emphasis on severe HSP nephritis. Methods The study included 46 HSP patients, 42 of whom had undergone kidney biopsy. Forty-nine pediatric patients with an inflammatory bowel disease (IBD) served as an autoimmune disease control group while Finnish bone marrow and blood donors represented the general reference population (n = 18,757). GWAS was performed for HSP and IBD samples in a case-control manner against the reference population. The analysis also included imputation of human leukocyte antigen (HLA) alleles. Results GWAS analysis in HSP revealed several polymorphisms from the HLA region that surpassed the genome-wide significance level. Three HLA class II alleles were also significantly more frequent in HSP than in the reference population: DQA1*01:01, DQB1*05:01, and DRB1*01:01. Haplotype DQA1*01:01/DQB1*05:01/DRB1*01:01 occurred in 43.5% of HSP patients, whereas its frequency was 8.2% in IBD patients and 15.0% in the reference population. HSP patients with this haplotype showed similar baseline clinical findings and outcome as HSP patients negative for the haplotype. In IBD patients, no polymorphism or HLA allele appeared significant at the genome-wide level. Conclusions Our results suggest that haplotype DQA1*01:01/DQB1*05:01/DRB1*01:01 is associated with susceptibility to HSP, but not with the severity of the kidney involvement. These HLA associations did not occur in IBD patients, suggesting that they are specific to HSP and not related to susceptibility to autoimmune diseases in general. Graphical abstract

Background Hemolytic uremic syndrome (HUS) is a multisystemic disease. In a nationwide study, we characterized the incidence, clinical course, and prognosis of HUS caused by Shiga toxin (Stx)–producing Escherichia coli (STEC) strains with emphasis on risk factors, disease severity, and long-term outcome. Methods The data on pediatric HUS patients from 2000 to 2016 were collected from the medical records. STEC isolates from fecal cultures of HUS and non-HUS patients were collected from the same time period and characterized by whole genome sequencing analysis. Results Fifty-eight out of 262 culture-positive cases developed verified (n = 58, 22%) STEC-HUS. Another 29 cases had probable STEC-HUS, the annual incidence of STEC-HUS being 0.5 per 100,000 children. Eleven different serogroups were detected, O157 being the most common (n = 37, 66%). Age under 3 years (OR 2.4), stx2 (OR 9.7), and stx2a (OR 16.6) were found to be risk factors for HUS. Fifty-five patients (63%) needed dialysis. Twenty-nine patients (33%) developed major neurological symptoms. Complete renal recovery was observed in 57 patients after a median 4.0 years of follow-up. Age under 3 years, leukocyte count over 20 × 109/L, and need for dialysis were predictive factors for poor renal outcome. Conclusions Age under 3 years, stx2, and stx2a were risk factors for HUS in STEC-positive children. However, serogroup or stx types did not predict the renal outcome or major CNS symptoms.

Background Pediatric-onset intestinal failure (IF) remains a severe illness with life-threatening consequences. In this study, we analyzed a single center's 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.

Background In Henoch–Schönlein nephritis (HSN), a risk factor for unfavorable outcome is prolonged proteinuria, but the value of renal biopsies in prognosis assessment is debatable. Methods We evaluated serial renal biopsies from 26 HSN patients. Follow-up biopsy occurred at median 2.1 years after diagnostic biopsy. Patients formed two groups at the follow-up biopsy: patients without proteinuria (group I; n = 11) and with proteinuria (group II; n = 15). Biopsies underwent evaluation according to three classifications: International Study of Kidney Disease in Children (ISKDC), Oxford (MEST-C), and semiquantitative classification (SQC) including an activity and chronicity score. Analysis also included expression of pro-fibrotic (alpha-smooth muscle actin and vimentin) and inflammatory (P-selectin glycoprotein ligand-1) molecules in the diagnostic biopsy specimens. Definition of unfavorable outcome was active renal disease or reduced renal function at last follow-up. Results Between the biopsies, SQC chronicity score increased in 22 (85%) patients, whereas activity score and ISKDC grade decreased in 21 (81%) and 17 (65%), respectively. Of the MEST-C parameters, endocapillary proliferation (from 83 to 13%; p < 0.001) and crescents (from 63 to 25%; p = 0.022) showed significant reduction, and segmental glomerulosclerosis (from 38 to 79%; p = 0.006) significant increment. These changes occurred similarly in groups I and II. Expression of the pro-fibrotic and inflammatory molecules showed no clinically significant differences between groups I and II. None in group I and five (33%) patients in group II had unfavorable outcome (p = 0.053). Conclusions Our results suggest that follow-up biopsies provide limited additional information to clinical symptoms in HSN outcome prediction.

BKPyV is widely recognized in KTRs, but little is known about rates of primary and secondary JCPyV exposure in pediatric KTRs. We evaluated JCPyV exposure in pediatric KTRs using antibody responses in the first 12 months post-transplant. Of 46 children transplanted between 2009 and 2014, 6 lacked any samples for serologic testing, leaving 40 KTRs for study. JCPyV-specific IgG and IgM antibodies were measured using a normalized VLP ELISA. Significant JCPyV exposure was defined as IgG seroconversion, increasing IgG levels of >0.5 nOD units, or IgM detection. Of 40 recipients (median age 3.2 years), 11 (27.5%) were seropositive, 20 (50%) seronegative for JCPyV-IgG, while 9 (22.5%) had no specimen at the time of transplantation, but were confirmed as seronegative in post-transplant samples. Of 29 (72.5%) at risk, JCPyV-IgG seroconversion occurred in 15/29 (51.7%) including JCPyV-IgM in 6 patients (20.7%). Two patients (6.9%) developed only JCPyV-IgM. Among JCPyV-IgG-positive KTRs, six (12.5%) had significant IgG increases. Altogether 23 of 40 patients (57.5%) had serological evidence of primary or secondary JCPyV exposure. In these patients, kidney function tended to be lower during the 2 years of follow-up, but only one patient lost the graft due to JCPyV nephropathy. Thus, JCPyV exposure is common in pediatric KTR and may present serologically as primary or secondary infection. Although only one case of JC-PyVAN occurred, a trend toward lower renal function was seen. Dedicated studies of larger cohorts are warranted to define impact of JCPyV in pediatric KTR.

Aim The human leukocyte antigen (HLA) allele and haplotype frequencies of the Finnish population are unique because of the restricted and homogenous gene population. There are no published data on HLA genotype associations in paediatric autoimmune liver diseases in Scandinavia. This study characterised the HLA genotypes of children with autoimmune liver or biliary disease in Finland. Methods The study cohort comprised 19 paediatric patients (13 female) aged 3-15 years treated for autoimmune liver or biliary disease at the Children's Hospital, Helsinki University Hospital, between 2000 and 2011 and followed up for 4.3 to 14.6 years. We genotyped HLA-B and HLA-DRB1 in the children and the HLA antigen frequencies were compared with 19,807 records from the Finnish Bone Marrow Donor Registry. Results All paediatric patients with autoimmune liver or biliary disease had either autoimmune HLA haplotype B*08;DRB1*03 or DRB1*13. These were significantly more common among patients with autoimmune hepatitis, primary sclerosing cholangitis and autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome than the Finnish control population. HLA RB1*04 was not found in the study cohort. Conclusion Our study found that B*08, DRB1*03 and DRB1*13 were significantly associated with autoimmune liver and biliary diseases in Finnish paediatric patients. This article is protected by copyright. All rights reserved.

Optimal treatment of Henoch-Schonlein purpura nephritis (HSN) remains unclear. We evaluated outcome of pediatric HSN patients treated initially with either methylprednisolone (MP) or cyclosporine A (CyA) in Finland between 1996 and 2011. Outcome of 62 HSN patients was evaluated by screening urine and blood samples (n = 51) or by collecting clinical parameters from medical charts until last follow-up visit (n = 11). Sixty (97%) patients had nephrotic-range proteinuria and/or ISKDC grade ≥ III before initial treatment. Patients were initially treated with either MP pulses (n = 42) followed by oral prednisone or with CyA (n = 20). Fifty-nine (95%) patients received angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers. Mean follow-up time was 10.8 years (range 3.2–21.2 years). One patient developed end-stage renal disease and another had decreased renal function (eGFR 0.5 g/day at end of follow-up. Sixteen (38%) MP-treated and two (10%) CyA-treated patients needed additional immunosuppressive treatment (RR 3.81, 95% CI 1.16–14.3, p = 0.035). Late initiation of treatment was associated with an increased risk for persistent proteinuria. Long-term outcome was relatively good in both treatment groups. However, since urinary abnormalities may persist or develop, long-term follow-up of HSN patients is mandatory. Early initiation of treatment had a favorable effect on proteinuria.

BackgroundNeonatal autosomal-recessive polycystic kidney disease (ARPKD) is associated with pulmonary hypoplasia and severe respiratory distress. There is no published information on long-term lung function in ARPKD survivors.MethodsPulmonary function tests, including spirometry and diffusion capacity, were performed in a nationwide cohort of Finnish paediatric patients with ARPKD. The annual incidence of respiratory infections and the need for permanent asthma medication were also evaluated in this population.ResultsPulmonary function in 11 children surviving the neonatal period was good when measured after a median follow-up time of 10.4 years (range 5.4–16.1 years). None of the patients required oxygen supplementation, and only one patient had asthma. Patients who had received ventilator therapy during infancy had significantly lower maximal instantaneous forced expiratory flow (MEF%) (66%; 43–93% vs 105%; 63–110%; p=0.048) and forced expiratory volume/forced vital capacity (0.76; 0.7–0.81 vs 0.89; 0.77–0.91; p=0.03) than patients without a history of mechanical ventilation, suggesting tendency for airway obstruction in the former group of patients. The frequency of respiratory infections did not differ from Finnish paediatric population in general.ConclusionsThe results of pulmonary function tests were within reference values for most patients with ARPKD, which suggested good long-term lung prognosis. Lung function tests should be considered for patients with ARPKD with a history of mechanical ventilation during infancy.

Pediatric-onset intestinal failure (IF) remains a severe illness with life-threatening consequences. In this study, we analyzed a single center's outcomes of IF over 3 decades.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.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).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.

Objective: Although impaired renal function has been a frequent finding among adults with intestinal failure (IF), the data on children is scarce. The aim of this study was to assess renal function in pediatric-onset IF. Methods: Medical records of 70 patients (38 boys) with pediatric-onset IF due to either short bowel syndrome (n = 59) or primary motility disorder (n = 11) and a history of parenteral nutrition (PN) dependency for >= 1 mo were evaluated. Renal function at the most recent follow-up was studied using plasma creatinine, cystatin C, and urea concentrations and estimated glomerular filtration rate (eGFR). Results: At a median age of 5.7 y and after PN duration of 3.2 y, 20 patients (29%) had decreased eGFR and higher cystatin C and urea concentrations. Patients with decreased renal function had significantly longer duration of PN (3.2 versus 0.9 y; P = 0.030) and shorter percentage of age adjusted small bowel length remaining (22 versus 32%; P = 0.041) compared with patients with preserved renal function. No other predisposing factors for decreased eGFR were identified. Conclusions: Patients with pediatric-onset IF are at significant risk for impaired renal function, which is associated with the duration of PN and the length of the remaining small bowel. In the present study, no other predisposing factors for decreased eGFR were found. Further studies using measured GFR are needed. (C) 2017 Elsevier Inc. All rights reserved.

WOS: 000493307500019 PubMed ID: 30215773 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 34months) 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. National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children National Health Service (NHS) Foundation Trust and University College, London; National Institute for Health Research (NIHR)National Institute for Health Research (NIHR) This work was supported by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children National Health Service (NHS) Foundation Trust and University College, London. R.S. holds a Career Development Fellowship with the National Institute for Health Research (NIHR).

Background 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). Procedure Markers for glomerular and tubular injury were evaluated prospectively after HD-MTX infusion in 20 children with ALL. Plasma creatinine, cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL) were measured 24–48 hr before MTX-infusion and 24, 36, 48, and 72 hr after starting the HD-MTX treatment, and thereafter daily until the MTX concentration was below 0.1 µmol/L. Urine NGAL, β2-microglobulin, and creatinine concentrations as well as dipstick and urinalysis were performed at the same time points. Results In children with ALL, HD-MTX treatment at 5 g/m2 over 24 hr was well tolerated and none of the patients developed significant glomerular or tubular dysfunction. The mean plasma cystatin C level increased significantly (P

Histological findings from primary kidney biopsies were correlated with patient outcomes in a national cohort of paediatric Henoch-Schonlein nephritis (HSN) patients. Primary kidney biopsies from 53 HSN patients were re-evaluated using the ISKDC (International Study of Kidney Disease in Children) classification and a modified semiquantitative classification (SQC) that scores renal findings and also takes into account activity, chronicity and tubulointerstitial indices. The ISKDC and SQC classifications were evaluated comparatively in four outcome groups: no signs of renal disease (outcome A, n = 27), minor urinary abnormalities (outcome B, n = 18), active renal disease (outcome C, n = 3) and renal insufficiency, end-stage renal disease or succumbed due to HSN (outcome D, n = 5). For the receiver operating characteristic and logistic regression analyses, outcomes A and B were considered to be favourable and outcomes C and D to be unfavourable. The median follow-up time was 7.3 years. The patients with an unfavourable outcome (C and D), considered together due to low patient numbers, had significantly higher total biopsy SQC scores and activity indices than those who had a favourable one (groups A and B). The chronicity and tubulointerstitial indices differed significantly only between group C + D and group A. The difference in areas under the curve between the total biopsy SQC scores and ISKDC findings was 0.15 [p = 0.04, normal-based 95% confidence interval (CI) 0.007-0.29, bias-controlled 95% CI -0.004 to 0.28]. Our results suggest that the modified SQC is more sensitive than ISKDC classification for predicting the outcome in HSN cases.

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.

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.

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).Markers for glomerular and tubular injury were evaluated prospectively after HD-MTX infusion in 20 children with ALL. Plasma creatinine, cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL) were measured 24-48 hr before MTX-infusion and 24, 36, 48, and 72 hr after starting the HD-MTX treatment, and thereafter daily until the MTX concentration was below 0.1 µmol/L. Urine NGAL, β2 -microglobulin, and creatinine concentrations as well as dipstick and urinalysis were performed at the same time points.In children with ALL, HD-MTX treatment at 5 g/m(2) over 24 hr was well tolerated and none of the patients developed significant glomerular or tubular dysfunction. The mean plasma cystatin C level increased significantly (P 0.001) from 0.83 mg/L at baseline to 0.94 mg/L at 36 hr after starting the HD-MTX treatment. The cystatin C concentration remained within reference range in all but two patients (10%). There was no significant change in plasma creatinine level during or after HD-MTX treatment, the values being normal in all patients. Plasma and urea NGAL did not increase during or after the HD-MTX treatment.Our results suggest that plasma cystatin C concentration alone is a sensitive marker to monitor renal function during and after HD-MTX infusion in pediatric ALL patients. Plasma or urine NGAL do not provide any further advantage in the follow-up of these patients.

Patients with tubulointerstitial nephritis (TIN) may develop permanent renal impairment. However, there are no prospective studies available on the treatment of TIN.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.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 PCr150 μmol/l (p0.001). 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.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.

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.

The aim of the study was to investigate the significance of different prognostic factors and long-term renal outcome in boys with posterior urethral valves (PUVs) detected either antenatally or during infancy. A total of 46 cases of PUVs, 23 antenatal and 23 postnatal, were followed prospectively from 1983 to 2003. The mean follow-up time was 12.5 years. The impact of vesicoureteral reflux (VUR), urinary tract infections (UTIs), urinary continence, and renal parenchymal damage on patient outcome was evaluated. Long-term renal outcome was defined as favorable if renal function was either normal or moderately impaired (glomerular filtration rateor = 60 ml/min per 1.73 m(2)) and poor if the patient had either chronic renal failure or end-stage renal disease. The outcome was poor in 14 (30%) of the 46 boys and was associated with a significantly higher nadir serum creatinine concentration (mean 157 micromol/l) during the 1st year of life ( P0.001), with bilateral VUR ( P0.05) and breakthrough UTIs ( P0.05). In our patients, age at achieving urinary continence, and the presence of renal parenchymal damage did not have a statistically significant association with long-term renal outcome. The long-term outcome among boys with antenatally detected PUVs did not differ from that among those cases detected postnatally after developing symptoms ( P=0.25).

To evaluate the criteria for conservative versus surgical treatment of multicystic dysplastic kidneys and to attempt to specify the optimal timing for surgery, when considered indicated.The study population comprised 48 antenatally or neonatally detected consecutive patients with unilateral multicystic dysplastic kidney. The fate of the affected renal conglomerate was regularly analyzed by ultrasonography. All cases were primarily followed up conservatively. In the patients who eventually underwent nephrectomy, the decision to operate was made after a minimum of 18 months (median 25).Ultrasound follow-up showed complete involution in 13 cases (27%); in 35 cases (73%), the renal conglomerate persisted throughout the study period (mean 46 months). Of the 48 patients, 32 (67%) eventually underwent nephrectomy. The size of the affected mass among the involuted cases was significantly smaller throughout the study period than in those requiring nephrectomy. The difference between the two groups continuously increased during follow-up, with a mean involution rate of 2.5 cm/yr versus 0.6 cm/yr (up to 18 months) for the involuted versus noninvoluted cases, respectively (P0.0001). From 18 months on, no statistically significant involution was observed in those who eventually underwent nephrectomy.Patients with antenatally or neonatally detected multicystic dysplastic kidney can primarily be followed up conservatively. Involution occurs in approximately one fourth of the cases, usually within about 14 months. In our experience, no significant involution can be expected to occur after 18 months. If surgery is decided on, we recommend an age of about 2 years. Late complications (eg, Wilms' tumor and renovascular hypertension) are rare.

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

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 (

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 (