Gender- and disease-specific urinary thioredoxin in chronic kidney disease patients with or without type 2 diabetic nephropathy.

AIM: The role of urinary (U-) thioredoxin (Trx), a class of small redox proteins, in physiological and pathological conditions, in addition to its gender specificity, has been insufficiently determined in chronic kidney disease (CKD) patients, especially in diabetes mellitus (DM) nephropathy. METHODS: U-Trx was measured cross-sectionally in 110 CKD outpatients with estimated glomerular filtration rate (eGFR) of >15 mL/min per 1.73 m(2) , namely, in 57 type 2 DM patients (male: n = 41, female: n = 16) and 53 non-DM patients (M: n = 33, F: n = 20), as well as 30 healthy controls (M: n = 11, F: n = 19). Comparisons were made among controls, DM and non-DM, and between M and F, with clinical parameters compared in each group. In addition, a comparison between average U-Trx level and the changes of renal function during a one-year period was performed. RESULTS: U-Trx was significantly higher in females than in males in controls (P < 0.05) and in non-DM patients (P < 0.05). Multiple regression analysis revealed that urinary protein (UP)/creatinine (Cr) ratio, female sex and HbA1c were independent factors affecting U-Trx among all subjects (adjusted R(2) = 0.468). In DM patients, U-Trx was negatively correlated with eGFR, especially in males, and positively correlated with UP/Cr and NAG in both sexes (all P < 0.01), as well as with systolic blood pressure in all (P < 0.05). Average U-Trx was positively correlated with the rate of annual eGFR decline of male (P < 0.01) but not female DM patients. CONCLUSION: U-Trx might have a gender-specific physiological and pathological role and be a potent marker of renal damage in DM nephropathy.

Evaluation of the newly proposed simplified histological classification in Japanese cohorts of myeloperoxidase-anti-neutrophil cytoplasmic antibody-associated glomerulonephritis in comparison with other Asian and European cohorts.

The prognostic value of renal biopsy in anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis is widely recognized; however, there is no consensus regarding its pathological classification. Berden et al. proposed a new classification of glomerulonephritis in ANCA-associated vasculitis (AAV) categorized into focal, crescentic, mixed, and sclerotic classes and showed its prognostic value in 100 international multicenter cohorts for 1- and 5-year renal outcomes. In order to evaluate whether this new classification has predictive value and reproducibility in Japanese AAV cases, 87 cohorts with only microscopic polyangiitis in 3 limited centers in Japan were analyzed. In addition, those from Japan, Europe (Berden's cohorts) and China were compared in a recent report.

Income and Employment of Patients at the Start of and During Follow-up After Palliative Radiation Therapy for Bone Metastasis.

Purpose: The aim of this study was to understand the income and employment status of patients at the start of and during follow-up after palliative radiation therapy for bone metastasis. Methods and Materials: From December 2020 to March 2021, a prospective multi-institutional observational study was conducted to investigate income and employment of patients at the start of administration of radiation therapy for bone metastasis and at 2 and 6 months after treatment. Of 333 patients referred to radiation therapy for bone metastasis, 101 were not registered, mainly because of their poor general condition, and another 8 were excluded from the follow-up analysis owing to ineligibility. Results: In 224 patients analyzed, 108 had retired for reasons unrelated to cancer, 43 had retired for reasons related to cancer, 31 were taking leave, and 2 had lost their jobs at the time of registration. The number of patients who were in the working group was 40 (30 with no change in income and 10 with decreased income) at registration, 35 at 2 months, and 24 at 6 months. Younger patients (P = 0), patients with better performance status (P = 0), patients who were ambulatory (P = .008), and patients with lower scores on a numerical rating scale of pain (P = 0) were significantly more likely to be in the working group at registration. There were 9 patients who experienced improvements in their working status or income at least once in the follow-up after radiation therapy. Conclusions: The majority of patients with bone metastasis were not working at the start of or after radiation therapy, but the number of patients who were working was not negligible. Radiation oncologists should be aware of the working status of patients and provide appropriate support for each patient. The benefit of radiation therapy to support patients continuing their work and returning to work should be investigated further in prospective studies.

Impact of obesity on IgA nephropathy: comparative ultrastructural study between obese and non-obese patients.

BACKGROUND: The pathological role of obesity in the progression of glomerular lesions has rarely been studied in primary glomerular diseases. The purpose of this study is to investigate the influence of non-diabetic obesity on clinicopathological findings in IgA nephropathy. METHODS: 74 patients with biopsy-proven IgA nephropathy were retrospectively divided into two groups according to the criteria for obesity in Japan: non-obese group (group N: n = 50) with BMI <25 kg/m(2), and obese group (group O: n = 24) with BMI > or =25 kg/m(2). Clinical and pathological data at the time of renal biopsy were analyzed. Moreover, the outcome of proteinuria in patients treated with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin II receptor blockers (ARB) was evaluated in different groups after a 1-year follow-up. RESULTS: Urinary protein excretion was significantly greater in the obese group compared to normal-weight patients (p < 0.05). There was no significant difference in the prevalence of hypertension and hyperlipidemia. By light microscopy, the obese group showed significantly larger glomerular size (p < 0.0001). On the other hand, the severity of mesangial matrix expansion and crescent formation revealed no difference between the two groups. By electron microscopy, glomerular basement membrane (GBM) thickness was significantly increased in obese patients (p < 0.001). Among 61 patients who were followed up for 1 year in our institute, 15 patients were treated with ACE-I or ARB without steroids. ACE-I or ARB treatment without steroids tended to reduce proteinuria in the obese patients, but this change did not achieve statistical significance. CONCLUSIONS: In IgA nephropathy, obesity induces not only glomerular enlargement but also ultrastructural modification of GBM, which would contribute to increase proteinuria.

IFI27 Is a Useful Genetic Marker for Diagnosis of Immunoglobulin A Nephropathy and Membranous Nephropathy Using Peripheral Blood.

Diagnosis of chronic glomerulonephritis (CGN) depends primarily on renal biopsy, which is expensive and requires hospitalization, creating a demand for noninvasive diagnostic method for this disease. We used DNA microarray analysis to search for genes whose expression levels in peripheral blood mononuclear cells (PBMCs) could distinguish between patients with CGN and healthy volunteers (HVs). We selected immunoglobulin A nephropathy (IgAN) and membranous nephropathy (MN) as typical forms of CGN. The mRNA level of the gene encoding interferon (IFN)-alpha-inducible protein 27, IFI27, which is preferentially expressed in podocytes of glomeruli, was lower in PBMCs of IgAN and MN patients than in those of HVs. This result was confirmed by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Moreover, qRT-PCR analysis revealed that the IFI27 mRNA level was reduced in PBMCs of patients with other types of chronic glomerulonephritis. IFI27 immunohistochemical staining of biopsied specimens also confirmed reduced expression of IFI27 protein in IgAN and MN patients. Based on these results, we propose that IFI27 could serve as a noninvasive diagnostic marker for CGNs using peripheral blood.

Ficolin-1 is up-regulated in leukocytes and glomeruli from microscopic polyangiitis patients.

Microscopic polyangiitis (MPA) is a systemic autoimmune disease that often has a fatal outcome. Although delineating the molecular pathogenesis is essential for its remedy, an understanding of its molecular mechanism has remained elusive. To search for new markers of active lesions that might help better understand the molecular basis of MPA and aid in its diagnosis, we here performed DNA microarray analysis with peripheral blood mononuclear cells (PBMCs). Compared to normal control, several genes were up- or down-regulated in MPA patients, including up-regulation of the mRNA level of ficolin-1 (FCN1 or M-ficolin), an innate pattern recognition complement molecule. The amount of ficolin-1, as detected by immunohistochemistry, was higher in the glomeruli of another group of MPA patients than in the glomeruli of control patients who harbored almost normal glomeruli. Many of the ficolin-1 dots were also positive for CD68, suggesting that the ficolin-1-positive cells were monocytes, such as macrophages or dendritic cells. This is not due to the difference in the number of neutrophil or monocytes in the blood samples of MPA and control patients. Taken together, we conclude that increased ficolin-1 expression could serve as a new marker for the characterization of MPA, especially when it is associated with local active lesions.

Clinicopathological influence of obesity in IgA nephropathy: comparative study of 74 patients.

The pathological role of obesity has rarely been studied in primary glomerular diseases. The purpose of this study is to examine the clinicopathological influence of obesity in IgA nephropathy (IgAN). 74 patients with IgA nephropathy in our institution from October 2000 to January 2004 were retrospectively divided into two groups according to body mass index (BMI): the non-obese group (group N) with BMI < 25 kg/m(2), and the obese group (group O) with BMI > or = 25 kg/m(2). There were 50 patients in group N and 24 patients in group O. Clinical analysis showed no significant difference between these two groups in blood pressure, serum cholesterol, creatinine clearances or grade of hematuria. However, urinary protein excretion and serum creatinine were significantly greater in group O than in group N. Although semiquantitative analysis of light-microscopical findings showed no significant differences in the severity of mesangial proliferation, matrix expansion, glomerulosclerosis or crescent formation, image analysis showed that total glomerular area and tuft area were significantly larger in group O. In addition, ultrastructural study revealed significantly higher glomerular basement membrane thickness in group O. 62 patients (46 patients, group N; 16 patients, group O) were followed in our institution for one year. Urinary protein was significantly decreased only in patients who received steroid in both groups. Although administration of ACE inhibitor or ARB tended to decrease urinary protein in group O, the change was not statistically significant. Our findings indicate that obesity may accelerate the increase of proteinuria in IgAN through ultrastructural modification of the glomerular basement membrane.