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BackgroundHemolytic 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.MethodsThe 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.ResultsFifty-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.ConclusionsAge 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.

BackgroundIn Henoch–Schönlein nephritis (HSN), a risk factor for unfavorable outcome is prolonged proteinuria, but the value of renal biopsies in prognosis assessment is debatable.MethodsWe 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.ResultsBetween 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).ConclusionsOur results suggest that follow-up biopsies provide limited additional information to clinical symptoms in HSN outcome prediction.

BackgroundThe 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.MethodsThe 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.ResultsGWAS 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.ConclusionsOur 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.

Objective: The aim of this study was to explore the factors associated with the survival of root canal treated teeth in a practise-based study setting in a 5-year period. Material and methods: This retrospective study used data from the electronic patient registration system of the public dental services of the City of Oulu, Finland. The inclusion criteria for this study were patients aged > 20 years who had root canal treatment (RCT) that was initiated in 2014. One RCT per patient was included in the study. A total of 713 patients met the inclusion criteria. The outcome variable for this study was the extraction of the RCT tooth during the 5-year period. Explanatory variables included age, diagnosis, tooth type (incisive, canine, premolar, molar), RCT technique (manual, motorized), time from RCT initiation to final restoration and type of final restoration (composite, glass ionomer, fixed dental prosthesis). To evaluate the association between the outcome variable and explanatory variables, Cox regression analyses were performed. Results: The overall survival rate was 91%. The middle-aged (40-59-years-old) and the oldest (60 and older) patients had a two-fold risk of extraction compared to younger (20-40-years-old) patients. Similarly, a short length of time from RCT initiation to final restoration (0-14 days) resulted in a nearly three times higher risk of extraction compared to a longer period (> 90 days). Conclusions: The 5-year survival rate of RCTs seems high. Extractions were more common among patients over 40 years of age and if the RCT was completed shortly after its initiation.

Background Histological findings from primary kidney biopsies were correlated with patient outcomes in a national cohort of paediatric Henoch–Schönlein nephritis (HSN) patients. Methods 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. Results 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]. Conclusions Our results suggest that the modified SQC is more sensitive than ISKDC classification for predicting the outcome in HSN cases.

Tubulointerstitial nephritis (TIN) and uveitis syndrome (TINU) are likely to be autoimmune diseases. Based on previous studies, adults with isolated idiopathic uveitis have polymorphisms in interleukin 10 (IL-10) and tumor necrosis factor α (TNF-α) genes. We aimed to evaluate the presence of IL-10 and TNF-α polymorphisms in a nationwide cohort of pediatric TIN/TINU patients. Single nucleotide polymorphisms in IL-10 (+434T/C, +504G/T, -1082G/A, -2849C/T) and in TNFα (-308G/A, -238G/A, -857C/T) genes were genotyped in 30 well-defined pediatric patients with idiopathic TIN/TINU syndrome. Control group frequencies for these SNPs were obtained from 393 independent Finnish subjects. The homozygous minor allele in IL-10 +434T (rs2222202) and IL-10+504G (rs3024490) was found in all patients with TIN or TINU syndrome while the frequency of these minor alleles in the control population was 44% and 23%, respectively (p <0.001). In IL-10 SNP -2849 (rs6703630) a significant difference was found with genotype TT in all patients (p = 0.004) and in subgroups with TINU syndrome (p = 0.017) and TINU syndrome with chronic uveitis (p = 0.01) compared to reference population. There were no statistical differences in any of the studied TNF-α genotypes between TIN/TINU patients and control population. A significant difference in the frequency of IL-10+434T and +504G alleles was found between TIN/TINU patients and control population. Genotype -2849TT was more frequently present in patients with TINU syndrome than in the reference subjects. Genetic variation in the inflammatory mediators may predispose to autoimmune nephritis and uveitis.

BackgroundOptimal treatment of Henoch-Schönlein 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.MethodsOutcome 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.ResultsMean 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 < 60 mL/min/1.73m2), both initially treated with MP (3%). Six patients (5 MP, 1 CyA) had eGFR between 60 and 89 mL/min/1.73m2 (10%). Eighteen patients (13 MP, 5 CyA) had proteinuria and/or hematuria (29%) and four of them had proteinuria > 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.ConclusionsLong-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.

BackgroundOnly a few studies reporting the long-term outcome of children with idiopathic tubulointerstitial nephritis (TIN) and uveitis syndrome (TINU) are available. We studied the long-term kidney and ocular outcome in a nationwide cohort of children with TIN or TINU.MethodsAll patients followed up for a minimum of 1 year by a paediatrician and an ophthalmologist were enrolled. The data on plasma creatinine (P-Cr), estimated glomerular filtration rate (eGFR), proteinuria, hypertension and uveitis were collected retrospectively.ResultsFifty-two patients were studied. Median age at time of diagnosis was 13.1 (1.8–16.9) years and median follow-up time was 5.7 (1.1–21.2) years. Forty-five (87%) patients were initially treated with glucocorticoids. The median of the maximum P-Cr was 162 μmol/l (47–1,016) and that of eGFR 47 ml/min/1.73m2 (8–124). Uveitis was diagnosed in 33 patients (63%) and 21 (40%) patients developed chronic uveitis. P-Cr normalised in a median of 2 months. Eleven (21%) patients had nephritis recurrence during or after discontinuation of glucocorticoids. At the latest follow-up, 13 (25%) patients had eGFR < 90 ml/min/1.73m2 (median 83; 61–89 ml/min/1.73m2). Six patients had tubular proteinuria; all presented with TIN without uveitis. Seven (13%) patients were hypertensive. Eleven (21%) patients had uveitis. One patient developed uraemia and was later transplanted.ConclusionsOur study questions the previously reported good long-term kidney and ocular outcome of patients with TIN/TINU. Decreased kidney function and/or ocular co-morbidities may persist for several years; thus, both kidney and ocular follow-up for at least 1 year is warranted.A higher resolution version of the Graphical abstract is available as Supplementary information

Henoch-Schönlein purpura arising in childhood could cause renal impairment or even an end-stage renal disease later in life. We aimed to assess long-term outcome of childhood Henoch-Schönlein purpura after 24 years. We studied a cohort of 26 boys and 26 girls who were treated for Henoch-Schönlein purpura at Helsinki University Hospital during 1964–83. Mean follow-up was 24·1 years (SD 6·0; 16·4–36·5). All participants were asked about their state of health in a questionnaire, and 47 (90%) were examined by a doctor. Patients' medical history data were obtained from health-care centres and regional hospitals. Seven (35%) of 20 adults who had severe Henoch-Schönlein purpura and glomerulonephritis at onset had renal impairment as adults, compared with two (7%) of 27 with mild or no renal symptoms at onset (relative risk 4·7, 95% CI 1·3–18·7). Relative risk for a poor outcome was 5·0 in women (1·1–32·5) and 2·0 in men (0·2–17·5). All patients with no renal symptoms at onset had a good outcome after 24 years of follow-up. Severity of first kidney biopsy finding did not correlate with risk of a poor outcome. 16 (70%) of 23 pregnancies had been complicated by hypertension, proteinuria, or both. Five (56%) of the nine women with complicated pregnancies had a poor renal outcome. Long-term follow-up of all patients who had Henoch-Schönlein purpura with severe renal symptoms at onset is needed during adulthood. All women who had even mild renal symptoms at onset of Henoch-Schönlein purpura should be carefully observed during and after pregnancy.

Background Patients with tubulointerstitial nephritis (TIN) may develop permanent renal impairment. However, there are no prospective studies available on the treatment of TIN. Methods 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. Results 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 PCr >150 μmol/l ( p  < 0.001). 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. Conclusions 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.