Penehyclidine hydrochloride (PHC) has been shown to be effective in the treatment of rhabdomyolysis (RM)-induced acute kidney injury (AKI). Our research sought to investigate the pharmacological effects and mechanisms of PHC on RM-induced AKI. RM-induced AKI models were established by FeG treatment and glycerol injection. Cell viability was analyzed by CCK-8 assay. ROS levels were examined by Flow cytometry. The LDH, Fe2+, MPO, MDA and GSH levels were measured using the corresponding kits. The interaction between HIF-1α and MT1G was analyzed by dual luciferase reporter gene and ChIP assays. The kidney pathological alterations were examined by HE staining. The levels of Scr, UA and BUN were examined using ELISA. Ferroptosis-related proteins (SLC7A11, GPX4 and ACSL4) were analyzed by western blot. PHC administration increased FeG-treated HK-2 cell viability, reduced ROS, LDH, Fe2+, MPO, MDA and ACSL4 levels, and raised GSH, SLC7A11 and GPX4 levels in cells, suggesting that PHC improved FeG-induced HK-2 cell ferroptosis and injury. PHC protected against AKI primarily by suppressing ferroptosis. HIF-1α blocked the SLC7A11/GPX4 pathway by transcriptionally activating MT1G. PHC alleviated glycerol-induced kidney injury in rats by inhibiting ferroptosis. PHC improved RM-mediated AKI by inhibiting ferroptosis through the HIF-1α/MT1G/ SLC7A11/GPX4 axis.

Blood coagulation is associated with glomerulonephritis (GN) pathophysiology. Using whole-blood-based rotational thromboelastometry, we recently reported that the degree of hypercoagulability in pediatric patients with immunoglobulin A nephropathy (IgAN), a GN, might be associated with pathological severity. To further clarify the coagulation status of mesangial proliferative glomerulonephritis (MesPGN), we assessed the platelet thrombus formation (PTF) under high-shear flow using a microchip-based flow chamber system (T-TAS®). Thirty-four pediatric patients definitively diagnosed with MesPGN by renal biopsy at Nara Medical University Hospital between 2015 and 2022 were enrolled, and 29 patients (case group; median age, 8.0 years) were assessed. Microchips coated with collagen (PL-chip) were used to assess PTF at high-shear in whole blood. The times to increase by 10 and 30 kPa (T10 and T30) from baseline were calculated and compared with those of the pediatric controls. Changes in the parameters during the treatment course and the relationship between pathological severity and the parameters were evaluated. T10 and T30 parameters in the PL-chip were significantly shorter and the area under the curves were greater in the case group than those in the control group (both p <0.05). Each parameter was enhanced during the 3-week treatment but improved after the end of treatment. No significant relationship was observed between pathological severity and these parameters. Little PTF difference was observed between IgAN and Henoch-Schönlein purpura nephritis. Pediatric MesPGN increased the potential for PTF under high-shear flow conditions.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors exert a kidney protective effect in patients with diabetic kidney disease. Several mechanisms have been proposed but why precisely SGLT2 inhibition has a kidney protective effect is incompletely understood. Clinical trials using SGLT2 inhibitors have found them to induce a rapid weight loss likely due to loss of sodium and subsequently fluid. While SGLT2 inhibitors are reported to increase hematocrit, it remains unknown whether the natriuretic and aquaretic effect reduces patient's blood volume and whether this could partly explain its kidney protective effects. A blood volume reduction could induce several beneficial effects with reduction in arterial and venous blood pressure as two central mechanisms. The aim of this paper is to review current techniques for assessing patient blood volume that could enhance our understanding of SGLT2 inhibitors' physiological effects. Measuring changes, induced by SGLT2 inhibitors, on erythrocyte volume and plasma volume can be assessed by tracer dilution techniques that includes radioisotopes, indocyanine green (ICG) dye or carbon monoxide. Techniques with radioisotopes can provide direct estimates of both erythrocyte volume and plasma volume but are cumbersome procedures and the radiation exposure is a limitation for repeated measures in clinical studies. Methods more suitable for repeated assessment of erythrocyte and plasma volume include dilution of injected ICG dye or dilution of inhaled carbon monoxide. ICG dye requires higher precision with timed blood samples and provides only a direct estimate of plasma volume wherefrom erythrocyte volume is estimated. Inhalation of carbon monoxide is a time-effective and automated method that provides measure of the total hemoglobin mass wherefrom erythrocyte and plasma volumes are estimated. - A kidney protective effect has been observed in clinical trials with SGLT2 inhibitors, but the underlying mechanisms are not fully understood. - Significant weight loss within weeks has been reported in the SGLT2 inhibitor trials and could be related to a reduction in blood volume secondary to increased natriuresis and aquaresis. - Alterations in blood volume compartments can be quantified by tracer dilution techniques and further improve our understanding of kidney protection from SGLT2 inhibitors.

Introduction: The regional variation in the use of percutaneous kidney biopsy in Japan remains unknown. There are several large datasets of kidney biopsies in Japan, but an exhaustive survey of kidney biopsies is lacking. Methods: We analyzed insurance claims for percutaneous kidney biopsies registered in the National Database of Health Insurance Claims and Specific Health Checkups of Japan, which is the closest to a complete dataset of kidney biopsies performed in Japan. In combination with other nationwide survey results, the number of inpatient percutaneous kidney biopsies per population in each prefecture was calculated. Factors associated with the frequency of percutaneous kidney biopsies were also explored. Results: The database contained 22,419 health insurance claims for percutaneous kidney biopsy in the fiscal year 2020. The frequency of inpatient percutaneous kidney biopsies could be up to 4.8 times as frequent in one prefecture than in another, even after adjusting for age and sex. The frequency of inpatient percutaneous kidney biopsies showed a positive correlation with the number of annual kidney transplants and patients on peritoneal dialysis per population and a weak negative correlation with the prevalence of reduced kidney function in the population aged 40–74 years. Conclusion: We found a large regional variation in the frequency of inpatient percutaneous kidney biopsies. Kidney transplants and peritoneal dialysis might be offered more frequently in regions with a higher frequency of kidney biopsy. This is the first dataset that shows more than 20,000 kidney biopsies were performed per year in Japan, as of 2020.

Continuous renal replacement therapy (CRRT) is frequently used for fluid management of critically ill patients with acute or chronic kidney failure. There is significant practice variation worldwide in fluid management during CRRT. Multiple clinical studies have suggested that both the magnitude and duration of fluid overload are associated with morbidity and mortality in critically ill patients. Therefore, timely and effective fluid management with CRRT is paramount in managing critically ill patients with fluid overload. While the optimal method of fluid management during CRRT is still unclear and warrants further investigation, observational data have suggested a U-shape relationship between net ultrafiltration rate and mortality. Furthermore, recent clinical data have underpinned a significant gap in prescribed vs. achieved fluid balance during CRRT, which is also associated with mortality. This review uses a case-based approach to discuss two fluid management strategies based on net ultrafiltration rate and fluid balance goals during CRRT and harmonizes operational definitions.

Living kidney donors (LKD) may experience some untoward consequences following donation such as development of chronic kidney disease (CKD). In this study, we aimed to investigate the rate of development of CKD and factors affecting the development of CKD in LKDs during long-term follow-up from a center in Turkey. This study was a retrospective analysis of LKDs followed between January 2000 and December 2017. Pre-transplant and post-transplant clinical data of the 338 LKDs were recorded and compared. Factors affecting the development of stage 3 and later stages of CKD were analyzed. Majority of the donors were females (64.2%) and the median age of all donors was 47 (39-54) years. Stage 3 CKD developed in 50 donors during the median follow-up of 71 months. Older age at the time of transplantation and low pre-transplant estimated glomerular filtration rate (eGFR) were determined as the factors affecting the development of stage 3 CKD (p<0.001, p<0.001). The receiver operating characteristic analysis showed that the cut-off age for the development of stage 3 CKD was 50.5 years. Newly-diagnosed hypertension was detected in 57 patients (16.8%) after the transplantation. While hypertension was seen at a rate of 42% in those with a eGFR<60ml/min/1.73m2, it was detected as 19.4% in the group with eGFR>60ml/min/1.73m2 (p<0.001). These results reveal that being a LKD is associated with the development of CKD and hypertension. Age and eGFR values at the time of transplantation were the determinants for the development of CKD.

NCAM1 is a recently identified new antigen of membranous nephropathy (MN) mostly secondary to systemic lupus erythematosus (SLE) with a low positive rate of 6.6%, and its corresponding antibody was detected in patients' sera. Here, we reported a case of NCAM1-positive lupus nephritis (class Ⅴ+Ⅲ) developed from MN. The patient was refractory to multiple immunosuppressive regimens, but achieved remission after the application of rituximab as an add-on therapy and showed a reduction of anti-NCAM1 antibody and proteinuria.

Acute kidney injury (AKI) is a highly prevalent condition with multiple acute and chronic consequences. Survivors of AKI are at risk of AKI-to-chronic kidney disease (CKD) transition, which carries significant morbidity and mortality. One retrospective analysis showed increased risk of bone fracture post-AKI in humans, which was independent of CKD development. While there are several theoretical reasons for late disturbances of bone health post-AKI, no definitive data are available to date. An important question is whether there are bone sequelae from AKI that are independent of CKD, meaning bone disease prior to the onset, or in the absence of CKD - a form of "post-AKI osteopathy". While pre-clinical studies examining bone health after acute stressors have focused mostly on sepsis models, multiple experimental AKI models are readily available for longitudinal bone health interrogation. Future research should be tailored to define whether AKI is a risk factor, independent of CKD, for bone disease and if present, the time course and type of bone disease. This review summarizes a fraction of the existing data to provide some guidance in future research efforts.

In phenylketonuria (PKU) toxic phenylalanine (Phe) can harm other organs beyond the brain. Furthermore, the lifelong therapy of PKU consists of consumption of increased amounts of amino acid mixture that provoke hyperfiltration in glomeruli. Therefore, the adherence to therapy in PKU might influence the long-term kidney function in PKU patients. Data from 41 adult, early treated PKU patients were analyzed in this 10-year, retrospective, monocentric study. Two subgroups were created according to their therapy-adherence: one with long-term blood Phe levels in the therapeutic range (<600 µmol/l), and one with suboptimal blood Phe levels. Renal function and metabolic parameters were collected over 10 years. Kidney function parameters were compared between the two groups and associations between blood Phe levels and kidney function were tested. After 10 years, serum creatinine levels (p=0,369) and estimated glomerular filtration rate (eGFR) (p=0,723) did not change significantly from baseline in the good therapeutic group. The suboptimal therapeutic group's eGFR decreased in the same period (from 110.4 ± 14 ml/min/1,73 m2 to 94.2 ± 16 ml/min/1.73 m2, p=0.017). At 10 years the suboptimal therapeutic group had an increased serum creatinine level (81 ± 14.4 μmol/L vs. 71.5 ± 13 μmol/L vs., p=0.038), and a decreased eGFR (94.2 ± 16 ml/min/1.73 m2 vs. 103.3 ± 13 ml/min/1.73 m2 p=0.031) compared to the good adhering group. Significant negative correlation between Phe levels and eGFR (r=-0.41, p=0.008) was observed. Long-term suboptimal therapy adherence in PKU patients with high blood Phe levels may lead to deteriorations in kidney function.