The Oxford Classification of IgA nephropathy (IgAN) includes the following four histologic components: mesangial (M) and endocapillary (E) hypercellularity, segmental sclerosis (S) and interstitial fibrosis/tubular atrophy (T). These combine to form the MEST score and are independently associated with renal outcome. Current prediction and risk stratification in IgAN requires clinical data over 2 years of follow-up. Using modern prediction tools, we examined whether combining MEST with cross-sectional clinical data at biopsy provides earlier risk prediction in IgAN than current best methods that use 2 years of follow-up data. We used a cohort of 901 adults with IgAN from the Oxford derivation and North American validation studies and the VALIGA study followed for a median of 5.6 years to analyze the primary outcome (50% decrease in eGFR or ESRD) using Cox regression models. Covariates of clinical data at biopsy (eGFR, proteinuria, MAP) with or without MEST, and then 2-year clinical data alone (2-year average of proteinuria/MAP, eGFR at biopsy) were considered. There was significant improvement in prediction by adding MEST to clinical data at biopsy. The combination predicted the outcome as well as the 2-year clinical data alone, with comparable calibration curves. This effect did not change in subgroups treated or not with RAS blockade or immunosuppression. Thus, combining the MEST score with cross-sectional clinical data at biopsy provides earlier risk prediction in IgAN than our current best methods.

BackgroundThe gut microbiota is interlinked with obesity, but direct evidence of effects of its modulation on body fat mass is still scarce. We investigated the possible effects of Bifidobacterium animalisssp. lactis 420 (B420) and the dietary fiber Litesse® Ultra polydextrose (LU) on body fat mass and other obesity-related parameters.Methods225 healthy volunteers (healthy, BMI 28–34.9) were randomized into four groups (1:1:1:1), using a computer-generated sequence, for 6 months of double-blind, parallel treatment: 1) Placebo, microcrystalline cellulose, 12 g/d; 2) LU, 12 g/d; 3) B420, 1010 CFU/d in microcrystalline cellulose, 12 g/d; 4) LU + B420, 12 g + 1010 CFU/d. Body composition was monitored with dual-energy X-ray absorptiometry, and the primary outcome was relative change in body fat mass, comparing treatment groups to Placebo. Other outcomes included anthropometric measurements, food intake and blood and fecal biomarkers. The study was registered in Clinicaltrials.gov (NCT01978691).FindingsThere were marked differences in the results of the Intention-To-Treat (ITT; n = 209) and Per Protocol (PP; n = 134) study populations. The PP analysis included only those participants who completed the intervention with > 80% product compliance and no antibiotic use. In addition, three participants were excluded from DXA analyses for PP due to a long delay between the end of intervention and the last DXA measurement. There were no significant differences between groups in body fat mass in the ITT population. However, LU + B420 and B420 seemed to improve weight management in the PP population. For relative change in body fat mass, LU + B420 showed a − 4.5% (− 1.4 kg, P = 0.02, N = 37) difference to the Placebo group, whereas LU (+ 0.3%, P = 1.00, N = 35) and B420 (− 3.0%, P = 0.28, N = 24) alone had no effect (overall ANOVA P = 0.095, Placebo N = 35). A post-hoc factorial analysis was significant for B420 (− 4.0%, P = 0.002 vs. Placebo). Changes in fat mass were most pronounced in the abdominal region, and were reflected by similar changes in waist circumference. B420 and LU + B420 also significantly reduced energy intake compared to Placebo. Changes in blood zonulin levels and hsCRP were associated with corresponding changes in trunk fat mass in the LU + B420 group and in the overall population. There were no differences between groups in the incidence of adverse events.DiscussionThis clinical trial demonstrates that a probiotic product with or without dietary fiber controls body fat mass. B420 and LU + B420 also reduced waist circumference and food intake, whereas LU alone had no effect on the measured outcomes.

In the present pilot study, enteric budesonide targeted to the ileocecal region had a significant effect on urine albumin excretion, accompanied by a minor reduction of serum creatinine and a modest increase of eGFR calculated by the MDRD equation, while eGFR calculated from Cockcroft-Gault equation and cystatin C was not changed. Enteric budesonide may represent a new treatment of IgAN warranting further investigation.

This new statistical approach has identified clinical and histological risk factors associated with outcome in children and young adults with IgAN.

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