Proximal-tubule molecular relay from early Protein diaphanous homolog 1 to late Rho-associated protein kinase 1 regulates kidney function in obesity-induced kidney damage.

The small GTPase protein RhoA has two effectors, ROCK (Rho-associated protein kinase 1) and mDIA1 (protein diaphanous homolog 1), which cooperate reciprocally. However, temporal regulation of RhoA and its effectors in obesity-induced kidney damage remains unclear. Here, we investigated the role of RhoA activation in the proximal tubules at the early and late stages of obesity-induced kidney damage.

Diagnosis of monoclonal immunotactoid glomerulopathy with positive λ chain by immunoelectron microscopy.

We report the case of a 73-year-old-man who developed immunotactoid glomerulopathy (ITG). ITG is a rare disease characterized by proliferative glomerulonephritis and capillary wall deposits with a 10-60 nm diameter microtubular substructure. In monoclonal ITG, immunofluorescence analysis typically exhibits IgG with light chain restriction.

The significance of NAD + metabolites and nicotinamide N-methyltransferase in chronic kidney disease.

Dysregulation of nicotinamide adenine dinucleotide (NAD +) metabolism contributes to the initiation and progression of age-associated diseases, including chronic kidney disease (CKD). Nicotinamide N-methyltransferase (NNMT), a nicotinamide (NAM) metabolizing enzyme, regulates both NAD + and methionine metabolism. Although NNMT is expressed abundantly in the kidney, its role in CKD and renal fibrosis remains unclear.

Home-based aerobic exercise and resistance training for severe chronic kidney disease: a randomized controlled trial.

Background: The potential effects of aerobic and resistance training in patients with severe chronic kidney disease (CKD) are not fully elucidated. This study investigated the effects of a home-based exercise programme on physical functioning and health-related quality of life (HRQOL) in patients with Stage 4 CKD, equivalent to estimated glomerular filtration rate of 15-30 mL/min/1.73 m .

Fabry disease associated with multiple myeloma: a case report.

Fabry disease (FD) is an X-linked genetic lysosomal disorder caused by alpha-galactosidase A (GLA) deficiency. Multiple myeloma (MM) predominately affects older adults, which ranks as the second commonest hematological malignancy. Their overlap has rarely been reported.

Pre-emptive Short-term Nicotinamide Mononucleotide Treatment in a Mouse Model of Diabetic Nephropathy.

Background: The activation of NAD-dependent deacetylase, Sirt1, by the administration of nicotinamide mononucleotide (NMN) ameliorates various aging-related diseases.

Methods: Diabetic mice were treated with NMN transiently for 2 weeks and observed for effects on diabetic nephropathy (DN).

Results: At 14 weeks after the treatment period, NMN attenuated the increases in urinary albumin excretion in mice without ameliorating hemoglobin A1c levels.

Development of nephropathy in an adult patient after Fontan palliation for cyanotic congenital heart disease.

Cyanotic congenital heart disease is occasionally associated with kidney dysfunction, which is known as cyanotic nephropathy or cyanotic glomerulopathy. The clinical presentation of cyanotic nephropathy includes proteinuria, decreased estimated glomerular filtration rate, hyperuricemia, thrombocytopenia, or polycythemia. Although advances in surgical procedures have improved the prognosis of cyanotic congenital heart diseases, adult cases of cyanotic nephropathy are still rare, and there are few reports of kidney biopsy in adults with cyanotic nephropathy.

Diabetic condition induces hypertrophy and vacuolization in glomerular parietal epithelial cells.

Diabetic nephropathy (DN) is accompanied by characteristic changes in the glomerulus, but little is known about the effect of diabetes on parietal epithelial cells (PECs). In this study, a descriptive analysis of PECs was undertaken in diabetic db/db mice and in diabetic patients. PEC hypertrophy was significantly more prominent in diabetic mice than in nondiabetic mice, and this was evident even at the early stage.

Malignancy-associated membranous nephropathy with PLA2R double-positive for glomeruli and carcinoma.

Phospholipase A2 receptor (PLA2R) is the most common primary target antigen of idiopathic membranous nephropathy (MN) although PLA2R antibodies are also reported to be present in malignancy-associated MN. However, a case of PLA2R-positive MN secondary to PLA2R-positive carcinoma has not been reported. A 26-year-old Japanese woman presented with general fatigue, fever, and nonproductive cough.

The effect of aldosterone and aldosterone blockade on the progression of chronic kidney disease: a randomized placebo-controlled clinical trial.

The progression of chronic kidney disease (CKD) cannot be completely inhibited. We first explored factors contributing to CKD progression in patients with CKD in a prospective observational study. In the next phase, we focused on the effects of aldosterone, conducting a single-blinded placebo-controlled study using the selective mineralocorticoid receptor antagonist (MRA), eplerenone (25 mg/day).

Difficulty in managing nephrotic syndrome-associated cerebral venous thrombosis.

Thromboembolism is one of the most serious complications of nephrotic syndrome (NS). Although the occurrence of renal vein thrombosis or deep vein thrombosis is well recognized in NS patients, they rarely develop cerebral venous thrombosis (CVT). The mortality rate of CVT patients is still approximately 10%, and 6-10% of patients who survive have a severe and permanent disability.

A case of cerebral infarction caused by painless acute aortic dissection in autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder, characterized by the progressive formation of renal cysts. Although ADPKD is strongly associated with cerebral and cardiovascular complications, cerebral ischemia caused by dissection of thoracic and carotid arteries has rarely been reported. We report the case of a 71-year-old Japanese woman who complained of hemiparesis.

Association of glomerular DNA damage and DNA methylation with one-year eGFR decline in IgA nephropathy.

Accumulation of DNA double-strand breaks (DSBs) is linked to aging and age-related diseases. We recently reported the possible association of DNA DSBs with altered DNA methylation in murine models of kidney disease. However, DSBs and DNA methylation in human kidneys was not adequately investigated.

Low birth weight is associated with decline in renal function in Japanese male and female adolescents.

Background: Low birth weight (LBW) is a risk factor for chronic kidney disease (CKD) in later life and is becoming increasingly common in developed countries, including Japan. Furthermore, a serial decrease in birth weight has been associated with an increasing prevalence of CKD stage 2 in male Japanese adolescents. Sex-specific differences affect CKD susceptibility, and the association between birth weight and CKD in women, has not been elucidated.

Acute Interstitial Nephritis With Karyomegalic Epithelial Cells After Nivolumab Treatment-Two Case Reports.

Clinical application of immune checkpoint inhibitors (CPIs) including nivolumab is expanding in the field of oncology treatment. Nivolumab is an anti-programmed death 1 protein (PD-1) antibody designed to augment an immunologic reaction against cancer cells. On the contrary, CPIs are known to cause a unique variety of side effects termed as immune-related adverse events, which can affect any organ including kidney.

A Case Report of Autosomal Dominant Polycystic Kidney Disease Under Peritoneal Dialysis With Cyst Infection and Culture-Positive Peritoneal Fluid.

Background: Cyst infection is a complication sometimes seen in patients with autosomal dominant polycystic kidney disease (ADPKD) and often shows through a positive blood culture. However, there have been no reports of ADPKD patients whose cyst infection propagate to peritoneal fluid leading to positive peritoneal fluid culture.

Case Presentation: A 74-year-old Japanese man with ADPKD under peritoneal dialysis (PD) was presented with left flank pain, fever, and chills at our hospital.

Role of Nampt-Sirt6 Axis in Renal Proximal Tubules in Extracellular Matrix Deposition in Diabetic Nephropathy.

Nicotinamide adenine dinucleotide (NAD) metabolism plays a critical role in kidneys. We previously reported that decreased secretion of a NAD precursor, nicotinamide mononucleotide (NMN), from proximal tubules (PTs) can trigger diabetic albuminuria. In the present study, we investigated the role of NMN-producing enzyme nicotinamide phosphoribosyltransferase (Nampt) in diabetic nephropathy.

β-hydroxybutyrate attenuates renal ischemia-reperfusion injury through its anti-pyroptotic effects.

Ketone bodies including β-hydroxybutyrate (β-OHB) have been shown to protect against ischemic tissue injury when present at low concentrations. We evaluated the impact of β-OHB on renal ischemia/reperfusion injury (IRI). Mice were treated with a continuous infusion of β-OHB using an osmotic mini-pump before and after IRI.

NNMT activation can contribute to the development of fatty liver disease by modulating the NAD metabolism.

Nicotinamide N-methyltransferase (NNMT) catalyses the reaction between nicotinamide (NAM) and S-adenosylmethionine to produce 1-methylnicotinamide and S-adenosylhomocysteine. Recently, this enzyme has also been reported to modulate hepatic nutrient metabolism, but its role in the liver has not been fully elucidated. We developed transgenic mice overexpressing NNMT to elucidate its role in hepatic nutrient metabolism.

High Basolateral Glucose Increases Sodium-Glucose Cotransporter 2 and Reduces Sirtuin-1 in Renal Tubules through Glucose Transporter-2 Detection.

Under diabetic conditions, sodium-glucose cotransporter 2 (SGLT2) for glucose uptake in proximal tubules (PTs) increases, whereas NAD-dependent protein deacetylase silent mating type information regulation 2 homolog 1 (Sirtuin-1; SIRT1) for PT survival decreases. Therefore, we hypothesized that increased glucose influx by SGLT2 reduces SIRT1 expression. To test this hypothesis, db/db mice with diabetes and high-glucose (HG)-cultured porcine PT LLC-PK1 cells in a two-chamber system were treated with the SGLT2 inhibitor canagliflozin.

Oral adsorbent AST-120 ameliorates gut environment and protects against the progression of renal impairment in CKD rats.

Background: Oral charcoal adsorbent AST-120 (AST) is reported to ameliorate renal dysfunction by the absorption of toxic substance in the gut. Recent study revealed that, in CKD, gut environment is disturbed including the decrease in tight junctions and Lactobacillus (Lact). In this study, we examined whether AST improves the renal dysfunction through gut environment.

Penile calciphylaxis in a patient on combined peritoneal dialysis and hemodialysis.

Calciphylaxis presents with painful purpura and intractable skin ulcers on the trunk and particularly the distal extremities, and it mainly occurs in patients on chronic dialysis. A 66-year-old man with renal failure due to diabetic nephropathy was on peritoneal dialysis alone for 1 year, followed by peritoneal dialysis combined with hemodialysis for 3 years. He developed calciphylaxis of the penis, which was diagnosed from the skin biopsy findings and clinical observation.

Non-Tuberculous Mycobacterial Infections Related to Peritoneal Dialysis.

Most infections related to peritoneal dialysis (PD) are caused by common bacteria, and non-tuberculous mycobacteria are rare. The clinical characteristics and prognosis of PD patients with non-tuberculous mycobacterial infections were investigated at our hospital. Non-tuberculous mycobacteria were detected in 11 patients (exit-site infection, tunnel infection, and peritonitis in 3, 5, and 3 patients, respectively).

Persistent fever and destructive arthritis caused by dialysis-related amyloidosis: A case report.

Rationale: Dialysis-related amyloidosis (DRA) can present rheumatic manifestations in patients on long-term hemodialysis. Typical articular symptoms with DRA involve carpal-tunnel syndrome, effusion in large joints, spondyloarthropathy, or cystic bone lesions, which are usually with non-inflammatory processes.

Patient Concerns: A 64-year-old man on hemodialysis for >30 years was admitted because of intermittent fever, polyarthritis, and elevated serum C-reactive protein (CRP) level, which was continuous for 2 years.