Kidney Podocyte Zebra Bodies after Lung Transplantation for Lymphangioleiomyomatosis.

A 55-year-old woman showed progressive renal dysfunction after unilateral deceased-donor lung transplantation for lymphangioleiomyomatosis. A kidney biopsy showed a striped pattern of interstitial fibrosis, suggesting calcineurin inhibitor toxicity, and zebra body accumulation predominantly in the podocytes, characteristics of Fabry disease. Nevertheless, she had no extra-renal symptoms of the disease, and gene testing identified no known pathogenic variant or exon deletion.

Renal-limited ANCA-associated vasculitis during erlotinib treatment for lung carcinoma.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) had clinical success in the treatment of non-small cell lung carcinoma (NSCLC). An effect of this drug on kidney has not been clarified and the occurrence of glomerulonephritis related to EGFR-TKI has rarely been reported. We present the case of a 71-year-old man with NSCLC who developed proteinuria and microscopic hematuria with the rise in a titer of MPO-ANCA, when 2 years and 3 months passed since the initiation of erlotinib, one of oral EGFR-TKI.

Clinical usefulness of multigene screening with phenotype-driven bioinformatics analysis for the diagnosis of patients with monogenic diabetes or severe insulin resistance.

Aims: Monogenic diabetes is clinically heterogeneous and differs from common forms of diabetes (type 1 and 2). We aimed to investigate the clinical usefulness of a comprehensive genetic testing system, comprised of targeted next-generation sequencing (NGS) with phenotype-driven bioinformatics analysis in patients with monogenic diabetes, which uses patient genotypic and phenotypic data to prioritize potentially causal variants.

Methods: We performed targeted NGS of 383 genes associated with monogenic diabetes or common forms of diabetes in 13 Japanese patients with suspected (n = 10) or previously diagnosed (n = 3) monogenic diabetes or severe insulin resistance.

Regional Variance of the Early Use of Tolvaptan for Autosomal Dominant Polycystic Kidney Disease.

Background: The development and prompt dissemination of the first drug against a particular disease can contribute to improvements in national health status and medical economy end points and are assumedly affected by socioeconomic factors that have yet to be analyzed. Tolvaptan, a vasopressin receptor 2 antagonist, was developed to treat hyponatremia, congestive heart failure, and cirrhosis ascites, although the approved indications may differ among countries. In Japan, high-dose tolvaptan tablets were approved as the first drug for autosomal dominant polycystic kidney disease (ADPKD) in 2014.

Renal Effects after Pembrolizumab Treatment for Non-small Cell Lung Carcinoma.

Immune checkpoint inhibitors (CPIs), including pembrolizumab, are becoming common oncological treatments. CPIs have been associated with a significant risk of developing immune-related adverse events (irAEs), such as nephritis and interstitial nephritis. However, the occurrence of glomerulonephritis has only rarely been reported.

Renal thrombotic microangiopathy during nintedanib treatment for idiopathic pulmonary fibrosis .

Agents that block vascular endothelial growth factor (VEGF) and its downstream pathway have been reported to be associated with nephrotoxicity including hypertension, proteinuria, and renal dysfunction. Bevacizumab, a monoclonal antibody against VEGF, is known to cause thrombotic microangiopathy (TMA), while tyrosine kinase inhibitors (TKIs) that block VEGF downstream are mainly associated with minimal change disease or focal segmental glomerulosclerosis. The question regarding the source of the diverse phenotypes of nephrotoxicity associated with these agents remains enigmatic.

Identification of a two-SNP PLA2R1 Haplotype and HLA-DRB1 Alleles as Primary Risk Associations in Idiopathic Membranous Nephropathy.

The associations of single nucleotide polymorphisms (SNPs) in PLA2R1 and HLA-DQA1, as well as HLA-DRB1*15:01-DQB1*06:02 haplotype with idiopathic membranous nephropathy (IMN) is well known. However, the primary associations of these loci still need to be determined. We used Japanese-specific SNP genotyping array and imputation using 2,048 sequenced Japanese samples to fine-map PLA2R1 region in 98 patients and 413 controls.

Prognostic factors of Erdheim-Chester disease: a nationwide survey in Japan.

Erdheim-Chester disease is a rare histiocytosis with insufficient clinical data. To clarify the clinical features and prognostic factors of Erdheim-Chester disease, we conducted a nationwide survey to collect the detailed data of 44 patients with Erdheim-Chester disease in Japan. The median age of onset of the participants was 51 (range: 23-76) years, and the median number of involved organs per patient was 4 (range: 1-11).

The Longitudinal Study of Liver Cysts in Patients With Autosomal Dominant Polycystic Kidney Disease and Polycystic Liver Disease.

Introduction: Although polycystic liver disease (PCLD) is one of the extrarenal complications in patients with autosomal dominant polycystic kidney disease (ADPKD), longitudinal changes and the association with total liver volume (TLV) have not been clearly elucidated yet.

Methods: Patients with ADPKD were chosen who underwent computed tomography or magnetic resonance imaging twice or more during August 2003 through December 2015. TLV, each cyst volume, and the proportion of parenchyma were measured.

Mitochondrial Abnormality Facilitates Cyst Formation in Autosomal Dominant Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) constitutes the most inherited kidney disease. Mutations in the and genes, encoding the polycystin 1 and polycystin 2 Ca ion channels, respectively, result in tubular epithelial cell-derived renal cysts. Recent clinical studies demonstrate oxidative stress to be present early in ADPKD.

High-density Association Mapping and Interaction Analysis of PLA2R1 and HLA Regions with Idiopathic Membranous Nephropathy in Japanese.

Although recent studies showed anti-PLA2R antibody plays a crucial role in idiopathic membranous nephropathy (IMN), detailed HLA mapping and interaction between the HLA genes and PLA2R1 have not been investigated in IMN. We genotyped across the PLA2R1 gene and the HLA region, using 183 IMN patients and 811 healthy controls. Five SNPs around the PLA2R1 gene were significantly associated with IMN.

The impact of PNPLA3 and JAZF1 on hepatocellular carcinoma in non-viral hepatitis patients with type 2 diabetes mellitus.

Background: Type 2 diabetes mellitus (T2DM) is an established independent risk factor for hepatocellular carcinoma (HCC). T2DM is associated with non-alcoholic steatohepatitis (NASH), which is a major cause of non-HBV and non-HCV-related HCC; nevertheless, it has been difficult to identify those patients with T2DM who have a high risk of developing HCC. The aim of this study was to identify genetic determinants that predispose T2DM patients to HCC by genotyping T2DM susceptibility loci and PNPLA3.

Glypican-5 Increases Susceptibility to Nephrotic Damage in Diabetic Kidney.

Type 2 diabetes mellitus is a leading health issue worldwide. Among cases of diabetes mellitus nephropathy (DN), the major complication of type 2 diabetes mellitus, the nephrotic phenotype is often intractable to clinical intervention and demonstrates the rapid decline of renal function to end-stage renal disease. We recently identified the gene for glypican-5 (GPC5), a cell-surface heparan sulfate proteoglycan, as conferring susceptibility for acquired nephrotic syndrome and additionally identified an association through a genome-wide association study between a variant in GPC5 and DN of type 2 diabetes mellitus.

High-throughput screening identified disease-causing mutants and functional variants of α-galactosidase A gene in Japanese male hemodialysis patients.

Fabry disease is a genetic disorder caused by deficient activity of lysosomal enzyme α-galactosidase A (GLA) and end-stage renal disease (ESRD) will be present after accumulation of glycosphingolipids within the kidney. Undiagnosed atypical variants of Fabry disease, which are limited to renal involvement, were found in several ESRD patient populations. On the other hand, unexpectedly high frequencies of male subjects having the c.

Cardiovascular protective effects of on-line hemodiafiltration: comparison with conventional hemodialysis.

Atherosclerotic complications have a significant effect on mortality in patients undergoing hemodialysis (HD) therapy. However, anti-atherosclerotic and cardioprotective effects of on-line hemodiafiltration (HDF) remain to be elucidated. We prospectively compared the anti-atherosclerotic and cardioprotective effects in two randomly divided groups, i.

Combination of two urinary biomarkers predicts acute kidney injury after adult cardiac surgery.

Background: Urinary L-type fatty acid-binding protein (L-FABP) has not been evaluated for adult post-cardiac surgery acute kidney injury (AKI) to date. This study was undertaken to evaluate a biomarker panel consisting of urinary L-FABP and N-acetyl-β-D-glucosaminidase (NAG), a more established urinary marker of kidney injury, for AKI diagnosis in adult post-cardiac surgery patients.

Methods: This study prospectively evaluated 77 adult patients who underwent cardiac surgery at 2 general hospitals.

A novel mechanism in maggot debridement therapy: protease in excretion/secretion promotes hepatocyte growth factor production.

Maggot debridement therapy (MDT) is effective for treating intractable wounds, but its precise molecular mechanism, including the association between MDT and growth factors, remains unknown. We administered MDT to nine patients (66.3 ± 11.

Beraprost sodium, an orally active prostaglandin I(2) analog, improves renal anemia in hemodialysis patients with peripheral arterial disease.

Beraprost sodium (BPS) is a stable, orally active prostaglandin I(2) (PGI(2) ) analog with antiplatelet and vasodilating properties. It has been reported that PGI(2) has pleiotropic effects that are anti-inflammatory and anti-atherogenic. In this study, we aim to determine the relationship between PGI(2) and renal anemia.

Differences in associated factors between aortic and mitral valve calcification in hemodialysis.

Increased prevalence of aortic and mitral valve calcification has been reported in patients on hemodialysis, but it remains unknown whether aortic and mitral valve calcification arise from similar pathogenesis. We detected heart valve calcification using two-dimensional echocardiography, and we related valve calcification to various clinical parameters in patients treated with hemodialysis three times a week for more than 1 year. In 112 patients (77 men and 35 women, age 67+/-10 years, duration on hemodialysis 95+/-67 months), aortic and mitral valve calcification were observed in 84 (75.

Impact of coronary artery calcification in hemodialysis patients: Risk factors and associations with prognosis.

The risk factors of coronary artery calcification (CAC) and the impact of CAC on cardiovascular events, cardiovascular deaths, and all-cause deaths in hemodialysis (HD) patients have not been fully elucidated. We examined the CAC score (CACS) in 74 HD patients using electron-beam computed tomography. Fifty-six patients underwent a second electron-beam computed tomography after a 15-month interval to evaluate CAC progression.

Postprandial hyperglycemia and hyperinsulinemia associated with renal arterio-arteriolosclerosis in chronic kidney disease.

Hypertension has an important function in the formation of renal arterio-arteriolosclerosis. However, renal arterio-arteriolosclerosis is sometimes found in biopsy specimens of normotensive patients, which indicates unknown factors may contribute to renal arterio-arteriolosclerosis. In this study, we aimed to evaluate the effects of glucose metabolism/insulin resistance on renal arterio-arteriolosclerosis.