BACKGROUND: International practice guidelines advocate for the use of anti-phospholipase A2 receptor (PLA2R) antibody testing to diagnose primary membranous nephropathy (pMN). This study aimed to clarify the current status of anti-PLA2R antibody testing in the diagnosis of pMN in Japan and to scrutinize the factors associated with the implementation of this antibody test.
METHODS: Utilizing a web-based questionnaire for nephrologists, responses were collected from 306 facilities and 427 nephrologists between November 2021 and December 2021. Preference for anti-PLA2R antibody testing was also investigated. Factors related to the experience of quantifying anti-PLA2R antibodies were estimated by generalized estimating equations using a robust analysis of variance with clusters of facilities of affiliation.
RESULTS: Of the 427 respondents, 140 (32.8%) had previous measurement experience at their current workplace and 165 (38.6%) had previous measurement experience overall. In pMN-suspected cases without contraindications to renal biopsy, 147 (34.4%) of the respondents opted to request anti-PLA2R antibody testing. The respondents\' experience with anti-PLA2R antibody quantification at their current place of work was generally higher in university hospitals and increased with the annual number of kidney biopsies and the number of years since graduation.
CONCLUSIONS: The results of this study suggest that a significant proportion of nephrologists in Japan have no experience in performing anti-PLA2R antibody assays, and that the assays may be hampered by the limited capabilities of the current workplace and the financial burden on facilities and patients.

To examine the prevalence and health correlates of depressive and anxiety symptoms among adults living in Guangdong province of China with a large population and rapid urbanization.
The Guangdong Sleep and Psychosomatic Health Survey was conducted from September to November in 2019, which was a population-based study with a representative sample of adults aged 18-85 years. Multistage stratified cluster sampling was used. A total of 13,768 inhabitants were included and face-to-face interviewed using standardized assessment tools. Depressive and anxiety symptoms were evaluated using the Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder Scale (GAD-7), respectively.
The weighted prevalence rates of depressive and anxiety symptoms were 8.6% (95% confidence interval [CI]: 8.0%-9.3%) and 6.0% (95%CI, 5.4%-6.5%) respectively. People who have never married, irregular diet rhythm, hardly exercise, poorer sleep, alcohol consumption, chronic diseases and being unemployment and retirement were more likely to suffer depressive and anxiety symptoms. Moreover, the prevalence of depressive symptoms was significantly higher in those suffering from cardiovascular disease (Odds ratio[OR]:3.89, 95%CI: 1.77-8.54), chronic nephrosis (OR:3.89, 95%CI: 1.52-9.94), hyperlipidemia (OR:2.68, 95%CI: 1.57-4.59), anemia (OR:1.96, 95%CI: 1.33-2.89) and arthritis (OR:1.93, 95%CI: 1.17-3.16). The prevalence of anxiety symptoms was evidently greater within patients with cardiovascular disease (OR:3.15, 95%CI: 1.39-7.14), chronic nephrosis (OR: 2.89, 95%CI: 1.22-6.83), hyperlipidemia (OR:2.27, 95%CI: 1.20-4.29) and diabetes (OR:1.99, 95%CI: 1.15-3.44).
Depressive and anxiety symptoms are commonly found in patients with chronic diseases. Given these adverse outcomes on health, health professionals should pay more attention to depressive and anxiety problems in health care for high-risk population.

OBJECTIVE: The aim of the study is to do a clinicopathologic study of post mortem kidney biopsies with significant deposition of bilirubin pigment within tubular epithelial cells and in the lumen of distal tubules as a bile cast.
METHODS: All post mortem specimens with acute tubular necrosis, with the presence of bile casts in tubules or bile pigment deposition in the tubular epithelium during the period 2015-2018 were examined for gross and histopathology along with biochemical parameters and viral markers.
RESULTS: Bile casts with sloughed renal tubular epithelial cells and occasional macrophages were present in the distal convoluted tubule in 78.6% of biopsies (11/14). The plugging of distal convoluted tubule with casts was similar to that seen in myeloma and myoglobin cast nephropathies. Bilirubin pigment deposition was present in 35.7% (5/14) of cases. The frequency of bile casts in each biopsy was variable and it did not have any association with serum bilirubin levels or etiology of liver dysfunction. A striking difference from earlier studies is the high number of toxin-induced liver damage including six cases of paraquat and 2 cases of yellow phosphorus poisoning.
CONCLUSIONS: This study proves importance of the bile cast nephropathy as a reason for kidney injury, especially with varied hepatotoxic etiologies, especially paraquat and yellow phosphorus.

OBJECTIVE: To explore proteinuria components in preeclampsia (PE) and pregnancies complicated with chronic nephrosis (PCCN).
METHODS: A case-control study was conducted with 81 PE and 95 PCCN patients and 192 normal pregnancies from April 2016 to March 2018. The results of a 24 h proteinuria test and a proteinuria component analysis (PCA) of all enrolled patients were collected. Statistical analyses of variance and SNK-q were conducted to identify the difference between PE and PCCN in urinary protein components using SPSS 23.0 software. A Pearson test and linear regression were conducted to explore the association between 24 h proteinuria and PCA.
RESULTS: Among the PE, PCCN and control groups, the average values of mAlb(2868.5 ± 3119.3 vs 1586.2 ± 3627.0 vs 21.6 ± 23.6), TRF(252.0 ± 280.5 vs 112.9 ± 164.5 vs 3.1 ± 2.7), α1-MG(40.4 ± 40.7 vs 34.0 ± 38.6 vs 10.3 ± 8.0), β2-MG(1.9 ± 5.1 vs 6.8 ± 15.8 vs 0.9 ± 2.3), and RBP(0.9 ± 1.7 vs 3.1 ± 4.5 vs 0.4 ± 0.7) were significantly different (P＜0.001). According to the SNK-q test, the average value of mAlb and TRF in the PCCN group is lower than that in the PE group, but higher than the control group (P < 0.05). The average value of RBP and β2-MG in the PCCN group was higher than the PE and control groups (P < 0.05). The mAlb, TRF, and α1-MG values separately had a significant correlation with the 24 h proteinuria value in PE. The linear regression equation was 24 h proteinuria value = 0.891*mAlb + 5.969*TRF + 1742.378. The mAlb, TRF, α1-MG, β2-MG, and RBP values separately had a significant correlation with the 24 h proteinuria value in PCCN and a linear regression equation of PCCN was as follows: 24 h proteinuria value = 15.148*TRF + 0.571*mAlb.
CONCLUSIONS: The proteinuria components of PE and PCCN patients were different in the elevated β2-MG and RBP. The PCA could be a suitable test for qualitative analysis and an antidiastole for PE and PCCN.

We have previously reported that co-transplantation of the kidney with vascularized donor thymus from α-1,3-galactosyltransferase gene knockout pigs with an anti-CD154 with rituximab-based regimen led to improved xenograft survival in baboons with donor-specific unresponsiveness. However, nephrotic syndrome emerged as a complication in which the glomeruli showed mild mesangial expansion with similarities to minimal change disease (MCD) in humans. Since MCD is associated with CD80 expression in glomeruli and elevated urinary excretion, we evaluated a potential role for CD80 in xenograft nephropathy. Study 1 confirmed high urinary CD80 excretion in nephrotic animals with renal xenografts showing CD80 expression in glomeruli. In Study 2, baboons receiving xenografts received CTLA4-Ig once a week from the second postoperative week or no CTLA4-Ig. The non-CTLA4-Ig group developed severe proteinuria with modest mesangial expansion with high urinary excretion of CD80 and documented CD80 expression in glomerular podocytes. All of the recipients in non-CTLA4-Ig groups had to be euthanized before POD 60. In contrast, CTLA4-Ig group showed a marked reduction in proteinuria and survived significantly longer, up to 193 days. These results demonstrate that anti-CD80 targeted therapy represents a promising strategy for reduction of proteinuria following renal xeno-transplantation with improved survival.

Puromycin aminonucleoside (PA) has been generally utilized as model of podocyte injury followed by massive proteinuria, severe damage on endocytotic activity of epithelial cells and postmodification of endocytosed compounds. However, total PA nephrosis (PAN) mechanism cannot be understood. We aimed to study glomerular function, foot process degeneration and transport pathways of podocytes in pre-proteinuria and acute PAN rats. Eighteen male Wistar albino rats were divided into three groups: control, pre-proteinuria and acute nephrosis groups (n=6). PA was injected into pre-proteinuria group for three times and acute group for nine times. Proteinuria levels in urine, creatinine and albumin levels in blood were detected 24 hours after PA injections. Renal cortex samples were prepared for transmission electron microscopy. Proteinuria levels in acute group significantly elevated, whereas creatinine clearance, serum albumin levels and urine volumes diminished compared to control and pre-proteinuria groups. In pre-proteinuria group, hypertrophy and structurally rich cytoplasm were detected only within podocytes. Acute group had various protein absorption granules secreted from podocyte cytoplasm to the urinary space through exocytosis after lysosomal digestion; but not observed in pre-proteinuria group. The number of slit pores in pre-proteinuria group decreased, particularly related to fusion of foot processes, subsequently leading to proteinuria. We concluded that foot process fusion begins prior to development of proteinuria although their serum albumin and creatinine clearance levels do not differ significantly. Additionally, we suggested that in acute PAN, first affected glomerular cells could be podocytes and there could be a correlation between glomerular function and number of slit pores.

There was performed a study of carcinogenicity of benzidinsulfon (4.4\'-diaminodiphenil sulfone) in rats and mice. Experimental animals (99 mice and 99 rats, approximately equally divided by sex) received the drug throughout the life by subcutaneous injections (once a week) or addition to food (5 times a week). A single dose per animal in rats was: subcutaneous administration--50 mg (in females it was reduced due to the toxicity after beginning of the experiment to 25 mg) in 0.5 ml of oil, while feeding--20 mg in 0 5 ml of oil; in mice--respectively 5 mg in 0.2 ml of oil, and 2 mg in 0, 2 ml of oil. The maximum amount of a substance when administered subcutaneously to male rats was 5.65 g, to female rats--2, 68 g, when fed to rats 12.44 g, when injected subcutaneously in mice--380 mg, when fed--737 mg. The survival of experimental animals was significantly reduced as compared to the intact control because of the toxic effect of the drug, preferably chronic nephrosis with nephritic component and secondary nephrosclerosis and as well as miocardiosclerosis and aortic sclerosis. Frequency and timing of detection of tumors in experimental animals was not significantly different from that observed in the control that indicated the absence of carcinogenic features of benzidinsulfon.

BACKGROUND: Several studies have suggested that the exposure to cadmium (Cd) increased mortalities from renal diseases, cardiovascular diseases and malignant neoplasm, including lung cancer and prostate cancer among inhabitants living in Cd-polluted areas and factory workers. This study aimed to assess the influence of environmental exposure to Cd on long term outcome of inhabitants living in an area polluted by Cd.
METHODS: A 22-year follow-up study was conducted with 3119 inhabitants (1403 men and 1716 women) living in the Cd polluted Kakehashi River basin in Japan. The subjects were divided into 4 groups according to the amount of urinary Cd level (< 3.0 µg/g creatinine (Cr), 3.0 - 4.9 µg/g Cr, 5.0 - 9.9 µg/g Cr, and ≥ 10.0 µg/g Cr). Mortality was calculated by the person-years method. Hazards ratios (HR) and 95% confidence intervals (CI) were assessed by the Cox\'s proportional hazard model.
RESULTS: Compared with urinary Cd < 3.0 µg/g Cr group, the HR of 5.0 - 9.9 µg/g Cr and ≥ 10.0 µg/g Cr groups were significantly increased after adjustment for age in both sexes: 1.24 (95%CI 1.01 - 1.51) and 1.48 (95%CI 1.17 - 1.90) for men; 1.64 (95%CI 1.17 - 2.28) and 1.78 (95%CI 1.27 - 2.50) for women. The most frequent cause of death was malignant neoplasm in men and cardiovascular diseases in women. The significant increase in mortality risk for cardiovascular diseases was observed in the subjects with ≥ 10 µg/g Cr in both sexes: 1.79 for men (95%CI 1.02 - 3.12) and 2.38 for women (95%CI 1.11 - 5.07). When the subjects were divided into 2 categories (< 20 µg/g Cr and ≥ 20 µg/g Cr), the HR of the urinary Cd ≥ 20 µg/g Cr group for nephritis and nephrosis were 4.82 (95%CI 1.07 - 21.61) in men and 7.92 (95%CI 1.77 - 35.33) in women, respectively. The significant increase was not observed for malignant neoplasm.
CONCLUSIONS: These results suggest a dose-response relationship between Cd body burden and mortality for cardiovascular diseases, cerebrovascular diseases and nephritis and nephrosis.

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