The TNF family member a proliferation-inducing ligand (APRIL; also known as TNFSF13), produced by myeloid cells, participates in the generation and survival of antibody-producing plasma cells. We studied the potential role of APRIL in the pathogenesis of IgA nephropathy (IgAN). We found that a significant proportion of germinal centers (GCs) in tonsils of patients with IgAN contained cells aberrantly producing APRIL, contributing to an overall upregulation of tonsillar APRIL expression compared with that in tonsils of control patients with tonsillitis. In IgAN GC, antigen-experienced IgD+ B cells expressing a switched IgG/IgA B cell receptor produced APRIL. Notably, these GC B cells expressed mRNA encoding the common cleavable APRIL-a but also, the less frequent APRIL-d/z mRNA, which encodes a protein that lacks a furin cleavage site and is, thus, the uncleavable membrane-bound form. Significant correlation between TLR9 and APRIL expression levels existed in tonsils from patients with IgAN. In vitro, repeated TLR9 stimulation induced APRIL expression in tonsillar B cells from control patients with tonsillitis. Clinically, aberrant APRIL expression in tonsillar GC correlated with greater proteinuria, and patients with IgAN and aberrant APRIL overexpression in tonsillar GC responded well to tonsillectomy, with parallel decreases in serum levels of galactose-deficient IgA1. Taken together, our data indicate that antibody disorders in IgAN associate with TLR9-induced aberrant expression of APRIL in tonsillar GC B cells.

We conclude that a high titre of anti-Ascaris IgE is associated with an increased risk of asthma symptoms among 5-year-old rural Bangladeshi children with a high helminthic infectious load.

The significance of the finding of focal glomerulosclerosis (FGS) in idiopathic membranous glomerulonephritis (MGN) is uncertain. Twenty-seven patients with mixed FGS and MGN (MGN-FGS) were compared to 25 patients with MGN alone (generally matched for age, sex and stage of glomerular lesion) with respect to pathology, presenting clinical and laboratory features, and course of disease. Biopsies from the MGN-FGS patients showed significantly more extensive tubulointerstitial disease (P less than 0.001) than did those with MGN alone. At the time of biopsy, the MGN-FGS group had a significantly higher proportion of patients with hypertension (P = 0.006) and microhematuria (P = 0.006), a marginally higher percentage of patients with the nephrotic syndrome (P = 0.051), and a greater mean 24-hour urinary protein excretion (P = 0.004). A similar proportion of patients in each group were treated with either prednisone alone or prednisone with an immunosuppressive. Forty-eight percent of MGN-FGS patients and 13% of the MGN patients developed established renal failure in the follow-up period (P = 0.008). The renal survival rate for the MGN-FGS group was significantly lower at 24 months (0.61 vs. 0.93, P less than 0.05), 60 months (0.48 vs. 0.88, P less than 0.025), and over the entire follow-up period (P less than 0.05). The results indicate that FGS in MGN is associated with a significantly poorer prognosis than MGN without this lesion.

Background: Despite improvements in dialysis treatment, mortality rates remain high, especially among older hemodialysis patients. Quality of life (QOL) among hemodialysis patients is strongly associated with higher risk of death. This study aimed to describe the health-related QOL and its change in older maintenance hemodialysis patients and to demonstrate characteristics associated with health-related QOL. Methods: Data on 892 maintenance hemodialysis patients aged 60 years or older who were surveyed using the Kidney Disease Quality of Life Short Form at baseline and 2 years after study enrollment in phases 4 (2009-2011) and 5 (2012-2014) of the Japanese Dialysis Outcomes and Practice Patterns Study were analyzed. We categorized participants into 3 age groups (60-69, 70-79, and ≥80 years) and described baseline physical component summary (PCS) and mental component summary (MCS) scores, as well as their distribution of changes after 2 years across each category. Results: Hemodialysis patients aged 70-79 years and ≥80 years had lower PCS scores than those aged 60-69 years (median: 70-79 years = 43.1; interquartile range [IQR], 35.2-49.4; ≥80 years = 38.8; IQR, 31.6-43.8; 60-69 years = 45.4; IQR, 37.5-51.4; p < 0.001). In contrast, MCS scores did not significantly differ by age category (70-79 years = 45.6; IQR, 38.4-53.7; ≥80 years = 45.4; IQR, 36.9-55.1; 60-69 years = 46.8; IQR, 39.5-55.7; p = 0.1). As dialysis vintage lengthened, the PCS score significantly became lower, whereas no association was found with change in the MCS score. The MCS score declined over time in older patients, especially among those aged 80 years and older after 2 years' follow-up. Conclusions: Physical QOL became worse as dialysis vintage lengthened. In contrast, mental QOL declined over time within a relatively short period among older maintenance hemodialysis patients.

BackgroundWhether to perform a renal biopsy for isolated hematuria remains a matter of controversy. We performed renal biopsy in hematuria without overt proteinuria patients and reported the proportion of glomerulonephritis, pathological activities, and statistical analysis of indicators associated with glomerulonephritis.MethodsAmong 203 patients who underwent renal biopsy in Okubo Hospital, Japan, between January 2008 and October 2013, we identified 56 patients who fulfilled the criteria: (1) urine dipstick examination shows equal to or greater than ± blood on three or more visits, (2) proteinuria <0.3 g/day (g/g Cr), (3) eGFR ≧60 ml/min/1.73 m2, and (4) no current medication for renal disease. We investigated biopsy findings and compared the clinical indicators in the IgA nephropathy (IgAN) and non-IgAN group.ResultsThe pathological diagnosis was IgAN in 35 cases (62 %), thin basement membrane disease (TBMD) in 7 (13 %), minor glomerular abnormality (MGA) in 6 (11 %), glomerular basement membrane (GBM) abnormality in 5 (9 %), and others in 3 (5 %). The histological grade of IgAN was I in 90 % and II in 10; 31 % of patients had some crescentic lesions. Comparisons between the IgAN and non-IgAN group revealed significant differences in age of onset (26 ± 13 vs. 34 ± 17 years, p = 0.04), serum IgA (340 ± 114 vs. 220 ± 101 mg/dl, p < 0.01), proteinuria (0.08 [0–0.25] vs. 0 [0–0.23] g/day [g/gCr], p < 0.01), and the presence of poikilocytes (40 vs. 10 %, p = 0.02).ConclusionsThe proportion of IgAN in hematuria without overt proteinuria was high and the pathological activities were variable. Patients with hematuria without overt proteinuria should continue their medical follow-up and the best timing of biopsy may be controversial for these patients who have multiple risk factors of IgAN.

No abstract

The results indicated that PCAR was an independent risk factor for allograft loss. PCAR presented with all types of rejection in the Banff 2015 criteria, and AMR/sAMR was associated with poor allograft survival.

The difference of the protocol of TSP therapy may have some effect on the CR of IgAN, though the histological bias was observed in this study. The appropriate protocol and indication of TSP therapy must be analyzed and determined in the randomized controlled trial.