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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

Anemia and low-grade inflammation are reported to be associated with impaired long-term graft outcome in renal transplant (RTx) recipients. In this study, hemoglobin (Hb) and inflammation marker levels were correlated with measured glomerular filtration rate (GFR) in 128 pediatric RTx recipients over a median follow-up period of 10 years. Serum levels of erythropoietin (EPO), hepcidin-25, high-sensitivity C-reactive protein (CRP) (hsCRP) and interleukin-6 (IL-6) were analyzed by enzyme-linked immunosorbent assays, and GFR was analyzed by Cr-51-EDTA clearance. The median levels of Hb (115 g/L), hsCRP (0.4 mg/L) and IL-6 (1.4 pg/mL) and the median erythrocyte sedimentation rate (ESR; 19 mm/h) remained stable after the first post-operative year. However, approximately half of the patients had a normocytic, normochromic anemia, and one-third had elevated levels of hsCRP (> 1 mg/L) and ESR (> 25 mm/h), indicating continuous low-grade inflammation. Low Hb levels preceded increased fibrosis in protocol biopsies taken at 1.5 and 3 years after transplantation and preceded decreased GFR by several years. Hb levels showed an inverse correlation with EPO levels (r = -0.206, p = 0.038) and ESR (r = -0.369, p

Acute idiopathic tubulointerstitial nephritis (TIN) is considered a condition with a good long-term prognosis. However, there is evidence that some patients develop permanent renal impairment. The aim of this study was to evaluate the clinical characteristics of TIN at the time of diagnosis in children and determine whether the findings upon presentation predict renal outcome. The clinical data and biopsy findings from 26 children with idiopathic TIN admitted to four Finnish university hospitals were analyzed retrospectively. Twenty-five patients (96%) manifested renal insufficiency. After the mean follow-up time of 2.75 years (SD 2.5; 0.9-13.5), 4 patients (15%) had permanent renal insufficiency and 8 patients (31%) had persistent low-molecular weight proteinuria. Uveitis was found in 12 patients (46%). Four of these patients (33%) developed chronic uveitis. Our analysis showed that none of the laboratory or biopsy findings upon presentation prognosticated renal outcome. No correlation between renal disease and uveitis could be found either. The occurrence of uveitis among TIN patients was higher than previously reported. Uveitis may develop late and without recurrence of renal dysfunction. Therefore, follow-up by a pediatrician and by an ophthalmologist is warranted in children with acute TIN for at least 12 months from diagnosis.

The original publication contained an erroneous version of Table 3 with incorrect data regarding ureteral visibility. The authors apologize for any inconvenience caused by their mistake and are pleased to present the corrected table here.

Evaluation of renal function should be performed as part of the follow-up during and after chemotherapy in pediatric cancer patients. The aim of this study was to compare an isotope clearance method [isotope glomerular filtration rate (iGFR)] with alternative methods to determine GFR in such patients. Isotope GFR [(99m)Tc-labeled diethylene triaminopentoacetic acid (DTPA) or (51)Cr-labeled ethylenediaminetetra-acetate (EDTA)] was measured in 36 children (112 studies) and compared with simultaneously measured creatinine clearance (CrCl), serum creatinine (SCr), and cystatin C (CysC) concentrations, as well as the results of Schwartz, Counahan-Barratt, and Cockroft-Gault formulae, using general linear mixed models. Our results showed a significant association between iGFR and CysC concentrations (p0.001). No linear relationship was observed between CrCl and iGFR (p = 0.7). As expected, the results of height-based formulae (Counahan-Barratt and Schwartz) had significantly (p = 0.004) better correlation to iGFR than the results of a formula based on weight (Cockroft-Gault) (p = 0.19). Despite significant linear correlation, intraclass correlation coefficients showed poor agreement. Tests of similarity between iGFR estimates showed differences between average values of GFR. Therefore, determination of iGFR remains the method of choice in estimation of GFR in cancer patients. In our study population, assay of serum CysC was the most reliable alternative method to measure glomerular function.

We evaluated the natural long-term outcome after childhood IgA nephritis. Altogether 55 patients with biopsy-proven IgA nephritis were identified, 37 (67%) responded to the health questionnaire and 31 (56%) participated in the medical examination after a mean follow-up of 18.7 years (SD 6.2; range 8.5-29.8). The results of medical examination, onset data and the re-analysis of original biopsies of 31 participants were used when analyzing the predictive factors for persistent nephropathy, i.e. constant proteinuria/hematuria or end-stage renal disease (ESRD). All patients' medical history data were obtained from regional hospitals and renal survival data from the national kidney register. Six (11%) of the 55 identified patients had developed ESRD. Sixteen (52%) of the 31 participants were not attending for regular follow-up visits after the acute phase. Twenty-two (71%) had renal symptoms and 12 (39%) were receiving drugs for hypertension/proteinuria at their latest follow-up visit. The chronicity index and total biopsy score in the first renal biopsy were higher in patients with persistent nephropathy or ESRD than in those without (p=0.022 and p=0.014, respectively). Nine (69%) of the 13 subjects who had been over 16 years of age at diagnosis had persistent nephropathy or ESRD, compared with 4 (22%) of the 18 subjects who had been under 16 years of age (relative risk 3.1, 95% CI 1.2-8.0). Pregnancy complications were common: 12 (55%) of the 22 pregnancies had been complicated by proteinuria and/or hypertension, and the prematurity rate was 30%. Long-term follow-up during adulthood is needed even after mild childhood IgA nephritis, especially in women during and after pregnancy.

Sirs,Dr. Lava and his colleagues present the interesting case of apatient with idiopathic tubulointerstitial nephritis (TIN) andlate-onset uveitis [1]. The authors highlight the importanceof ophthalmologic follow-up in TIN patients, and their casedemonstrates that uveitis may develop in a patient evenduring ongoing corticosteroid therapy. In our study [2],uveitis was diagnosed in five patients between 3 and15 months after onset of nephritis, i.e., in 42% of the patientswith TIN and uveitis. Two of these patients were not receivingany medication at the time uveitis was diagnosed, threepatients were on corticosteroids (0.15 –0.65 mg/kg/day), withone also on cyclosporin A.The case report by Dr. Lava et al. as well as our ownexperience suggest that uveitis may develop in TIN patientsduring the weaning of systemic corticosteroid treatment.Uveitis may be asymptomatic and, therefore, ophthalmologicslit lamp examination should be performed before thecorticosteroid dose is reduced. If necessary, topical treatmentshould be started in order to avoid long-term eye complica-tions.Theophthalmologicalfollow-upofbothTINandTINUpatients for at least 12 months is motivated by three factors:(1) uveitis may develop late and be asymptomatic; (2) uveitismay relapse afterapparenthealing;(3)uveitis may turnout tobe chronic.References