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The increasing number of patients undergoing dialysis due to diabetes mellitus (DM) is causing serious economic problems, and its reduction is an urgent policy issue in developed countries, including Japan. We aimed to assess the association between the annual rapid decline in renal function and health checkup measures, including blood pressure, to identify health guidance targets for preventing diabetic nephropathy (DN) and diabetic kidney disease (DKD) among individuals in a medical checkup system (“Tokuteikenshin” program) in 2018. This longitudinal analysis included 3,673,829 individuals who participated in the “Tokuteikenshin” program in 2018, had hemoglobin A1c (HbA1c) levels ≥5.6%, were available for follow-up, and underwent estimated glomerular filtration rate (eGFR) evaluation. We estimated the incidence of the relative annual decrease in eGFR ≥10% per 1000 person-years and odds ratios to evaluate the rapid decline in renal function and determine health guidance goals and their role in preventing DN and DKD. Overall, 20.83% of patients with DM had a rapid decline in renal function within the observation period. A rapid decline in renal function was associated with high systolic blood pressure, poor or strict DM control, increased urinary protein excretion, and decreased blood hemoglobin levels. The incidence of rapid decline in renal function is higher in DM, and appropriate systolic blood pressure and glycemic control are important to prevent the progression to DN or DKD. Our findings will be useful for researchers, clinicians, and other public health care members in establishing effective health guidance and guidelines for CKD prevention.

Background Recent clinical reports indicate a correlation between gross hematuria after the coronavirus 2019 (COVID-19) vaccination in patients with glomerulonephritis, especially immunoglobulin A nephropathy (IgAN). Furthermore, healthcare workers in Japan were initially vaccinated with an mRNA vaccine from February 17, 2021, and some of them experienced gross hematuria after receiving the vaccination. Methods We conducted a web-based survey of the councilor members of the Japanese Society of Nephrology (581 members, 382 facilities) to elucidate the relationship between gross hematuria and COVID-19 vaccination. Results In the first survey, 27 cases (female: 22, 81.5%) of gross hematuria were reported after receiving a COVID-19 vaccination. Of them, 19 (70.4%) patients were already diagnosed with IgAN at the occurrence of gross hematuria. Proteinuria appeared in eight of the 14 (57.1%) cases with no proteinuria before vaccination and hematuria in five of the seven (71.4%) cases with no hematuria before vaccination. The second survey revealed that a renal biopsy was performed after vaccination in four cases, all of whom were diagnosed with IgAN. Only one case showed a slightly increased serum creatinine level, and no patients progressed to severe renal dysfunction. Conclusion This study clarified the clinical features of gross hematuria after a COVID-19 vaccination. Because there was no obvious progression to severe renal dysfunction, safety of the COVID-19 vaccination is warranted at least in the protocol of inoculation twice.

Background Esaxerenone has potential renoprotective effects and reduces the urinary albumin-to-creatinine ratio (UACR) in patients with diabetic kidney disease and overt nephropathy. We investigated the efficacy and safety of esaxerenone in Japanese patients with type 2 diabetes (T2D) and macroalbuminuria (UACR ≥ 300 mg/g creatinine). Methods We conducted a multicenter, single-arm, open-label phase III study in 56 patients with T2D and UACR ≥ 300 mg/g creatinine with estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 and treated with a renin–angiotensin system inhibitor. Patients received esaxerenone for 28 weeks at 1.25 mg/day initially with titration to 2.5 mg/day based on serum potassium (K+) monitoring. Efficacy was evaluated as the change in UACR from baseline to week 28. Safety endpoints included adverse events (AEs), incidence of serum K+ increase, and change in eGFR from baseline. Results UACR decreased by 54.6% (95% CI 46.9%, 61.3%) on average from baseline (544.1 mg/g creatinine) to the end of treatment (246.8 mg/g creatinine); 51.8% of patients showed improvement to early nephropathy. AE incidence was 69.6%. Three patients (5.4%) had serum K+ levels ≥ 6.0 mEq/L or ≥ 5.5 mEq/L on two consecutive occasions. Hyperkalemia in two patients was transient and resolved during the treatment period. One patient discontinued following two consecutive serum K+ values ≥ 5.5 mEq/L. The maximum change from baseline in eGFR was − 8.3 mL/min/1.73 m2 at week 24. Conclusions Esaxerenone reduced UACR in Japanese patients with T2D and UACR ≥ 300 mg/g creatinine; more than half experienced a transition from UACR ≥ 300 mg/g creatinine to UACR Clinical trial registration JapicCTI-173696

The relationship between cellular senescence and fibrosis in the kidney is being elucidated and we have identified it as therapeutic target in recent studies. Chronic kidney disease has also become a lifestyle disease, often developing on the background of hypertension and dyslipidemia. In this study, we clarify the effect of interaction between these two conditions on kidney fibrosis and senescence. Wild type mice (WT), apolipoprotein E-/- mice (ApoEKO), and endothelial nitric oxide synthase (eNOS)-/- ApoE-/- mice (DKO) were obtained by breeding. Unilateral ureteral obstruction (UUO) was performed on 8-10 week old male mice and the degree of renal tubular injury, fibrosis and kidney senescence were evaluated. DKO manifested elevated blood pressure, higher total cholesterol and lower HDL than WT. DKO showed sustained kidney injury molecule-1 protein expression. Kidney fibrosis was significantly higher in ApoEKO and DKO. mRNA expression of genes related to kidney fibrosis was the highest in DKO. The mRNA expression of Zinc-α2-Glycoprotein and heme oxygenase-1 were significantly decreased in DKO. Furthermore, mRNA expression of p53, p21 and p16 were increased both in ApoEKO and DKO, with DKO being the highest. Senescence associated β-gal positive tubule area was significantly increased in DKO. Increased DNA damage and target of rapamycin-autophagy spatial coupling compartments (TASCCs) formation was found in DKO. Mice with endothelial dysfunction and dyslipidemia developed kidney fibrosis and accelerated senescence even in young mice after injury. These data highlight the fact managing lifestyle-related diseases from a young age is important for CKD prevention.

Background There are no reports of a large-scale survey on the infection prevention measures against coronavirus disease 2019 (COVID-19) in nephrology facilities. This study investigated the facility-level nephrology practices adopted during the COVID-19 pandemic and their associated challenges. Additionally, the treatment patterns and outcomes of chronic kidney disease (CKD) patients with COVID-19 were reviewed. Methods We conducted a nationwide questionnaire survey of 704 educational facilities that were certified by the Japanese Society of Nephrology (JSN) from October 20, 2020 to November 16, 2020. The questionnaire reviewed the facility characteristics, infection prevention measures taken during routine nephrology practice, impact of COVID-19 on nephrology practice, experiences in managing CKD patients with COVID-19, and nosocomial transmission in the nephrology unit. Results Of the 347 facilities that responded, 95.1% checked outpatients’ body temperatures and COVID-19 symptoms at their visits. To reduce face-to-face contact, 80% and 70% of the facilities lengthened the intervals between outpatient visits and introduced online/telephonic consultations, respectively. As a result, more than half of the hospitals experienced a decrease in the numbers of outpatients and inpatients (64% and 50%, respectively). During the study period, 347 facilities managed 479 CKD patients with COVID-19. Oxygen administration and mechanical ventilation were performed for 47.8% and 16.5% of the patients, respectively, with a 9.2% total mortality rate. Conclusion This survey demonstrated that JSN-certified educational nephrology facilities adopted multiple measures to manage the COVID-19 pandemic; however, they faced several challenges. Sharing these experiences could standardize these approaches and prepare us better for the future. Supplementary Information The online version contains supplementary material available at 10.1007/s10157-021-02082-z.

Background Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic affecting a variety of medical treatments, including hemodialysis. This study aims to investigate the implementation of infection control measures, to examine the shortage of personal protective equipment (PPE) and disinfectants, and to quantify the number of nosocomial COVID-19 transmissions in hemodialysis facilities in Japan during the pandemic. Methods We conducted a nationwide questionnaire survey between 20 October and 16 November 2020 (i.e., between the “second wave” and “third wave” in Japan) in the 4198 dialysis facilities of the Japanese Association of Dialysis Physicians and the Japanese Society for Dialysis Therapy. A total of 2227 facilities (53.0%) responded. The questionnaire consisted of (i) characteristics of facilities, (ii) infection prevention measures in routine dialysis practices, (iii) shortage of PPE, (iv) feasibility of various isolation measures, and (v) nosocomial transmission. Results Half of the responding facilities were hospitals with multiple departments, and the other half were clinics specialized in dialysis. Several infection prevention measures such as health checks of staff and patients, donning of masks before and after hemodialysis, and disinfection of frequently contacted areas were implemented during the COVID-19 pandemic. There was a significant improvement in the implementation rate of these measures during the pandemic, compared to before it, which reached over 90%. More than half of the facilities reported a shortage of disposable masks (67.2%) and hand sanitizer alcohol (56.7%). Isolation of COVID-19 patients in private rooms was possible only in 52.7% of the facilities. The majority of facilities (73.3%) could not accept COVID-19 dialysis patients due to lack of space and manpower. Nosocomial transmission of COVID-19 occurred in 4.0% of the facilities. Of those infected, 51.9% were staff. Conclusions This survey revealed that most hemodialysis facilities in Japan had improved implementation of infection control measures and had shortage of PPEs and disinfectants, though some facilities did not implement infection prevention measures adequately, mainly due to the limited space of the facility. It may be recommended that each facility immediately establishes isolation measures to prepare for the pandemic of COVID-19.

Angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) are recommended as first-line drugs for hypertension with diabetic nephropathy owing to their renoprotective effect; however, their effect beyond lowering blood pressure (BP) has not been confirmed. Recent studies have shown that aldosterone plays a key role in causing renal injury; therefore, it is likely that mineralocorticoid receptor (MR) blockers inhibit aldosterone-induced renal damage in different ways from ACE inhibitors and ARBs. Therefore, we investigated the mechanism of the effect of an MR blocker on reducing the urinary albumin-to-creatinine ratio (UACR) using data from a randomized, double-blind, placebo-controlled phase 3 study (ESAX-DN) of a new nonsteroidal MR blocker, esaxerenone. This post hoc analysis used a novel statistical method to quantitatively estimate the effect of esaxerenone on UACR reduction mediated, or not mediated, by changes in systolic BP (SBP) and/or estimated glomerular filtration rate (eGFR). The proportion of the mediated effect by SBP changes to the total effect on UACR reduction was 9.8–10.7%; the UACR was reduced to 0.903–0.911 times the baseline at the end of treatment through the SBP-related pathway and to 0.422–0.426 times the baseline through the non-SBP-related pathway. Even considering both SBP and eGFR simultaneously, the proportion of the mediated effect was 21.9–28.1%. These results confirm that esaxerenone has a direct UACR-lowering effect independent of BP lowering and that its magnitude is much larger than that of the BP-dependent effect. Thus, esaxerenone could be a UACR-reducing treatment option for patients with diabetic nephropathy.

We evaluated the effect of co-administration of esaxerenone and a sodium-glucose cotransporter 2 (SGLT2) inhibitor on the magnitude of serum potassium elevation in Japanese patients with diabetic kidney disease.We carried out a prespecified subanalysis of data from two phase III studies: a multicenter, randomized, double-blind, placebo-controlled trial in patients with type 2 diabetes and microalbuminuria (J308); and a multicenter, single-arm, open-label trial in patients with type 2 diabetes and macroalbuminuria (J309). Changes in serum potassium levels during the studies and other measures were evaluated according to SGLT2 inhibitor use.In both studies, time-course changes in serum potassium levels, and incidence rates of serum potassium elevation were lower in patients with co-administration of SGLT2 inhibitor in both the placebo and esaxerenone groups than those without the inhibitor. In contrast, time-course changes and mean percentage changes from baseline in urinary albumin-to-creatinine ratio, the proportion of patients with albuminuria remission and time-course changes in blood pressure did not change with or without SGLT2 inhibitor, whereas the albumin-to-creatinine ratio and blood pressure were reduced with esaxerenone. The blood glucose-lowering effect of SGLT2 inhibitor was not affected by esaxerenone.In Japanese patients with type 2 diabetes and albuminuria treated with esaxerenone, concomitant use of SGLT2 inhibitor reduced the magnitude of serum potassium elevation without any change of its antihypertensive and albuminuria-suppressing effects. Co-administration of esaxerenone and SGLT2 inhibitor might be a beneficial treatment option for patients with diabetic kidney disease.

Background Hyperkalemia is associated with many chronic diseases and renin-angiotensin-aldosterone system inhibitor therapy. Sodium zirconium cyclosilicate (SZC), an oral, highly selective cation-exchanger, is approved for the treatment of hyperkalemia. Methods This phase 3, multicenter, open-label, single-arm, flexible-dose study assessed the safety and efficacy of SZC in Japanese patients with hyperkalemia during a correction phase of up to 3 days and long-term (1 year) maintenance phase (NCT03172702). Results Overall, 150 patients received treatment during both study phases; the study population was generally representative of hyperkalemic Japanese patients in clinical practice. Most patients (78.7%) had three doses of SZC during the correction phase. All but one patient received SZC for ≤ 48 h before transitioning to the maintenance phase. In the maintenance phase, mean (standard deviation; SD) exposure to the study drug was 319.4 (98.1) days and mean (SD) dose was 7.38 (2.85) g/day. Adverse events (AEs) were reported in 131 patients (87.3%); most were mild. The most common treatment-related AEs as evaluated by investigators were constipation (6.7%), peripheral edema (4.0%), and hypertension (2.7%). In the correction phase, 78.7% of patients were normokalemic at 24 h and 98.7% within 48 h; ≥ 65.5% maintained normokalemia throughout the maintenance phase. Conclusion After a year of exposure, SZC treatment was well tolerated by Japanese patients and potassium levels were well controlled.

Background Sodium zirconium cyclosilicate (SZC) is an oral potassium binder approved to treat hyperkalemia in adults in a number of countries, including Japan. Methods This phase 2/3, randomized, double-blind, placebo-controlled, dose–response study (ClinicalTrials.gov: NCT03127644) was designed to determine the efficacy and safety of SZC in Japanese adults with hyperkalemia. Patients with serum potassium (sK+) concentrations ≥ 5.1– ≤ 6.5 mmol/L were randomized 1:1:1 to SZC 5 g, SZC 10 g, or placebo three times daily for 48 h (six doses total). The primary efficacy endpoint was the exponential rate of change in sK+ over 48 h. The proportion of patients with normokalemia (sK+ 3.5–5.0 mmol/L) at 48 h and adverse events (AEs) were also evaluated. Results Overall, 103 patients (mean age, 73.2 years; range 50–89 years) received SZC 5 g (n = 34), SZC 10 g (n = 36), or placebo (n = 33). The exponential rate of sK+ change from 0 to 48 h versus placebo was − 0.00261 (SZC 5 g) and – 0.00496 (SZC 10 g; both P + Conclusion SZC is effective and well tolerated in Japanese patients with hyperkalemia.

BACKGROUND Our aims were to assess whether arterial stiffness is associated with a higher risk for kidney dysfunction among persons without chronic kidney disease (CKD). METHODS We analyzed data from the national health checkup system in Japan; for our analyses, we selected records of individuals who completed assessments of cardio-ankle vascular index (CAVI) and kidney function from 2005 to 2016. We excluded participants who had CKD at baseline, defined as the presence of proteinuria or estimated glomerular filtration rate (eGFR) RESULTS The mean age of the 24,297 included participants was 46.2 years, and 60% were female. Over a mean follow-up of 3.1 years, 1,435 CKD events occurred. In a multivariable analysis, the hazard ratios with 95% confidence intervals (CIs) for the highest vs. combined lower quartiles of CAVI measurements were 1.3 (1.1, 1.5) for CKD events, 1.3 (0.96, 1.62) for proteinuria, 1.4 (1.1, 1.7) for eGFR CONCLUSIONS Persons with CAVI measurements ≧8.1 had a higher risk for CKD events compared with their counterparts with CAVI measurements

Background Despite recent advances in immunosuppressive therapy for patients with primary nephrotic syndrome, its effectiveness and safety have not been fully studied in recent nationwide real-world clinical data in Japan. Methods A 5-year cohort study, the Japan Nephrotic Syndrome Cohort Study, enrolled 374 patients with primary nephrotic syndrome in 55 hospitals in Japan, including 155, 148, 38, and 33 patients with minimal change disease (MCD), membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), and other glomerulonephritides, respectively. The incidence rates of remission and relapse of proteinuria, 50% and 100% increases in serum creatinine, end-stage kidney disease (ESKD), all-cause mortality, and other major adverse outcomes were compared among glomerulonephritides using the Log-rank test. Incidence of hospitalization for infection, the most common cause of mortality, was compared using a multivariable-adjusted Cox proportional hazard model. Results Immunosuppressive therapy was administered in 339 (90.6%) patients. The cumulative probabilities of complete remission within 3 years of the baseline visit was ≥ 0.75 in patients with MCD, MN, and FSGS (0.95, 0.77, and 0.79, respectively). Diabetes was the most common adverse events associated with immunosuppressive therapy (incidence rate, 71.0 per 1000 person-years). All-cause mortality (15.6 per 1000 person-years), mainly infection-related mortality (47.8%), was more common than ESKD (8.9 per 1000 person-years), especially in patients with MCD and MN. MCD was significantly associated with hospitalization for infection than MN. Conclusions Patients with MCD and MN had a higher mortality, especially infection-related mortality, than ESKD. Nephrologists should pay more attention to infections in patients with primary nephrotic syndrome.

Background Recent cardiovascular outcome trials have shown that sodium–glucose co-transporter 2 (SGLT2) inhibitors slow the progression of chronic kidney disease (CKD) in patients with type 2 diabetes at high cardiovascular risk. Whether these benefits extend to CKD patients without type 2 diabetes or cardiovascular disease is unknown. The Dapagliflozin and Prevention of Adverse Outcomes in CKD (DAPA-CKD) trial (NCT03036150) will assess the effect of the SGLT2 inhibitor dapagliflozin on renal and cardiovascular events in a broad range of patients with CKD with and without diabetes. Methods DAPA-CKD is a randomized, double-blind, placebo-controlled, trial in which ∼4300 patients with CKD Stages 2–4 and elevated urinary albumin excretion will be enrolled. The vast majority will be receiving a maximum tolerated dose of a renin–angiotensin system inhibitor at enrolment. Results After a screening assessment, eligible patients with a urinary albumin:creatinine ratio ≥200 mg/g and estimated glomerular filtration rate (eGFR) between 25 and 75 mL/min/1.73 m2 are randomly assigned to placebo or dapagliflozin 10 mg/day. Enrolment is monitored to ensure that at least 30% of patients do not have diabetes and that no more than 10% have an eGFR >60 mL/min/1.73 m2. The primary endpoint is a composite of a sustained decline in eGFR of ≥50%, end-stage renal disease, renal death or cardiovascular death. The trial will conclude when 681 primary renal events have occurred, providing 90% power to detect a 22% relative risk reduction (α level of 0.05). Conclusion DAPA-CKD will determine whether the SGLT2 inhibitor dapagliflozin, added to guideline-recommended therapies, safely reduces the rate of renal and cardiovascular events in patients across multiple CKD stages with and without diabetes., Graphical Abstract Graphical Abstract

Emerging data have demonstrated that sodium-glucose cotransporter-2 (SGLT2) inhibitors prevent cardiovascular events, especially heart failure-associated endpoints. Cardiovascular outcome trials have also suggested their renoprotective effects. One large clinical trial investigated renal primary endpoints and demonstrated that SGLT2 inhibitors slowed the progression of diabetic kidney disease (DKD). This review summarizes clinical trial data on renal outcomes and discusses potential underlying mechanisms.The EMPA-REG, CANVAS, and DECLARE-TIMI 58 studies revealed that SGLT2 inhibitors reduce the risk of cardiovascular events and concomitantly suggested that these drugs slow the progression of kidney disease in type 2 diabetes. The CREDENCE trial on patients with high-risk type 2 diabetes and chronic kidney disease demonstrated that canagliflozin treatment reduced the relative risk of a composite outcome, including end-stage kidney disease, serum creatinine doubling, and renal/cardiovascular death, by 30% in these patients. Animal experiments revealed that oxidative stress, inflammation, fibrosis, and tubuloglomerular feedback are underlying renoprotective mechanisms behind SGLT2 inhibitors.Recent clinical trials have established the renoprotective effects of SGLT2 inhibitors. Further investigations on mechanisms of these renoprotective effects will provide deeper insights and understanding of pathogenetic properties of DKD.

Funder: Government Department of Business, Funder: Energy and Industrial Strategy (BEIS), Funder: Vice-Chancellor Fellowship from the University of Bristol, Funder: Shanghai Thousand Talents Program, Funder: Academy of Medical Sciences (AMS) Springboard Award, Funder: BBSRC Innovation fellowship, Funder: NIHR Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and the University of Bristol, BACKGROUND: This study was to systematically test whether previously reported risk factors for chronic kidney disease (CKD) are causally related to CKD in European and East Asian ancestries using Mendelian randomization. METHODS: A total of 45 risk factors with genetic data in European ancestry and 17 risk factors in East Asian participants were identified as exposures from PubMed. We defined the CKD by clinical diagnosis or by estimated glomerular filtration rate of 25 kg/m2. CONCLUSIONS: Eight cardiometabolic risk factors showed causal effects on CKD in Europeans and three of them showed causality in East Asians, providing insights into the design of future interventions to reduce the burden of CKD.

Disease-specific trajectories of renal function in advanced chronic kidney disease (CKD) are not well defined. Here, we compared these trajectories in the estimated glomerular filtration rate (eGFR) by CKD stages. Patients with multiple eGFR measurements during the 5-year preregistration period of the REACH-J study were enrolled. Mean annual eGFR declines were calculated from linear mixed effect models with the adjustment variables of baseline CKD stage, age, sex and the current CKD stage and the level of proteinuria (CKDA1-3). Among 1,969 eligible patients with CKDG3b-5, the adjusted eGFR decline (ml/min/1.73 m2/year) was significantly faster in diabetic kidney disease (DKD) patients and polycystic kidney disease (PKD) patients than in patients with other kidney diseases (DKD, − 2.96 ± 0.13; PKD, − 2.82 ± 0.17; and others, − 1.95 ± 0.05, p

BACKGROUNDS: Data on how lifestyle changes due to the coronavirus disease 2019 (COVID-19) pandemic have influenced the clinical features of kidney disease patients remain scarce. METHODS: This study retrospectively analyzed clinical variables in patients with stage G1-G4 chronic kidney disease (CKD) with complete or incomplete remission of proteinuria, who were managed in a nephrology outpatient clinic of a university hospital in Tokyo. The clinical variables during the COVID-19 pandemic (term 1, June-July 2020) were compared to those one year before the pandemic (term 0, June-July 2019). The urinary protein excretion (UPE) was used as the primary outcome measure. RESULTS: This study included 325 patients with stage G1-G4 CKD (mean age 58.5 years old, 37.5% female, 80.6% on renin-angiotensin aldosterone system inhibitors [RAASis], 12.0% on maintenance dose immunosuppression therapy) evaluated at term 0. The UPE at terms 0 and 1 was 247 (92-624) and 203 (84-508) mg/day [median (25th-75th percentile)], respectively; the value in term 1 was 18% lower than that in term 0 (p

Chronic kidney disease is a common problem in the elderly and is associated with increased mortality. We have reported on the role of nitric oxide, which is generated from endothelial nitric oxide synthase (eNOS), in the progression of aged kidneys. To elucidate the role of endothelial dysfunction and the lack of an eNOS-NO pathway in ageing kidneys, we conducted experiments using eNOS and ASC-deficient mice. C57B/6 J mice (wild type (WT)), eNOS knockout (eNOS KO), and ASC knockout (ASC KO) mice were used in the present study. Then, eNOS/ASC double-knockout (eNOS/ASC DKO) mice were generated by crossing eNOS KO and ASC KO mice. These mice were sacrificed at 17−19 months old. The Masson positive area and the KIM-1 positive area tended to increase in eNOS KO mice, compared with WT mice, but not eNOS/ASC DKO mice. The COX-positive area was significantly reduced in eNOS KO mice, compared with WT and eNOS/ASC DKO mice. To determine whether inflammasomes were activated in infiltrating macrophages, the double staining of IL-18 and F4/80 was performed. IL-18 and F4/80 were found to be co-localised in the tubulointerstitial areas. Inflammasomes play a pivotal role in inflammaging in ageing kidneys. Furthermore, inflammasome activation may accelerate cellular senescence via mitochondrial dysfunction. The importance of endothelial function as a regulatory mechanism suggests that protection of endothelial function may be a potential therapeutic target.

Hypoxia-inducible factor prolyl-hydroxylase inhibitors belong to a new class of orally administered drugs for treating anemia in patients with chronic kidney disease (CKD). The prevalence of hypothyroidism is disproportionately high in patients with CKD on hemodialysis. We report a rapid suppression of thyroid-stimulating hormone (TSH) and decrease in free triiodothyronine (T3) and free tetraiodothyronine levels after switching from darbepoetin alfa to roxadustat in a hemodialysis patient with hypothyroidism on levothyroxine therapy. This was reversed after stopping roxadustat. Roxadustat has structural similarity with T3 and is a selective activating ligand for thyroid hormone receptor-β possibly suppressing TSH release.

AIM Chronic kidney disease (CKD) is an important public health problem. Recently, CKD has been found to be associated with poor physical functioning in community-dwelling elderly individuals. However, the physical functioning of non-dialysis (ND) patients with advanced CKD treated by nephrologists is unknown. METHODS Patients with ND-CKD stage G3b-5 who participated in a nationwide Reach-J CKD cohort study were included in this study. Physical functioning and physical activity were assessed by the Katz Index, Lawton-Body instrumental activities of daily living (IADL) scale, and Rapid Assessment of Physical Activity questionnaire of the international CKD Outcomes and Practice Patterns Study (CKDopps) questionnaires. Dichotomies between good and poor physical functioning and physical activity scores were explored. RESULTS Among 1628 patients, 84.3% had good physical functioning. Poor physical functioning was more common with older age (p

OBJECTIVE Randomized controlled trials have shown kidney-protective effects of sodium–glucose cotransporter 2 (SGLT2) inhibitors, and clinical practice databases have suggested that these effects translate to clinical practice. However, long-term efficacy, as well as whether the presence or absence of proteinuria and the rate of estimated glomerular filtration rates (eGFR) decline prior to SGLT2 inhibitor initiation modify treatment efficacy among type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) patients, is unknown. RESEARCH DESIGN AND METHODS Using the Japan Chronic Kidney Disease Database (J-CKD-DB), a nationwide multicenter CKD registry, we developed propensity scores for SGLT2 inhibitor initiation, with 1:1 matching with patients who were initiated on other glucose-lowering drugs. The primary outcome included rate of eGFR decline, and the secondary outcomes included a composite outcome of 50% eGFR decline or end-stage kidney disease. RESULTS At baseline, mean age at initiation of the SGLT2 inhibitor (n = 1,033) or other glucose-lowering drug (n = 1,033) was 64.4 years, mean eGFR was 68.1 mL/min per 1.73 m2, and proteinuria was apparent in 578 (28.0%) of included patients. During follow-up, SGLT2 inhibitor initiation was associated with reduced eGFR decline (difference in slope for SGLT2 inhibitors vs. other drugs 0.75 mL/min/1.73 m2 per year [0.51 to 1.00]). During a mean follow-up of 24 months, 103 composite kidney outcomes occurred: 30 (14 events per 1,000 patient-years) among the SGLT2 inhibitors group and 73 (36 events per 1,000 patient-years) among the other drugs group (hazard ratio 0.40, 95% CI 0.26–0.61). The benefit provided by SGLT2 inhibitors was consistent irrespective of proteinuria and rate of eGFR decline before initiation of SGLT2 inhibitors (Pheterogeneity ≥ 0.35). CONCLUSIONS The benefits of SGLT2 inhibitors on kidney function as observed in clinical trials translate to patients treated in clinical practice with no evidence that the effects are modified by the underlying rate of kidney function decline or the presence of proteinuria.

Objective To examine the association between hyperkalemia and long-term cardiovascular and renal outcomes in patients with chronic kidney disease. Patients and Methods An observational retrospective cohort study was performed using a Japanese hospital claims registry, Medical Data Vision (April 1, 2008, to September 30, 2018). Of 1,208,894 patients with at least 1 potassium measurement, 167,465 patients with chronic kidney disease were selected based on International Classification of Diseases, Tenth Revision codes or estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2. Hyperkalemia was defined as at least 2 potassium measurements of 5.1 mmol/L or greater within 12 months. Normokalemic controls were patients without a record of potassium levels of 5.1 mmol/L or greater and 3.5 mmol/L or less. Changes in eGFRs and hazard ratios of death, hospitalization for cardiac events, heart failure, and renal replacement therapy introduction were assessed between propensity score–matched hyperkalemic patients and normokalemic controls. Results Of 16,133 hyperkalemic patients and 11,898 normokalemic controls eligible for analyses, 5859 (36.3%) patients and 5859 (49.2%) controls were selected after propensity score matching. The mean follow-up period was 3.5 years. The 3-year eGFR change in patients and controls was −5.75 and −1.79 mL/min/1.73 m2, respectively. Overall, hyperkalemic patients had higher risks for death, hospitalization for cardiac events, heart failure, and renal replacement therapy introduction than controls, with hazard ratios of 4.40 (95% CI, 3.74 to 5.18), 1.95 (95% CI, 1.59 to 2.39), 5.09 (95% CI, 4.17 to 6.21), and 7.54 (95% CI, 5.73 to 9.91), respectively. Conclusion Hyperkalemia was associated with significant risks for mortality and adverse clinical outcomes, with more rapid decline of renal function. These findings underscore the significance of hyperkalemia as a predisposition to future adverse events in patients with chronic kidney disease.

Background and Aims IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. It is an autoimmune disease characterized by deposits of IgA1-containing immune complexes in the glomerular mesangium leading to local inflammation and subsequent decline in kidney function. Currently, there are no targeted therapies for IgAN. The KDIGO guidelines (2012) recommend optimized long-term supportive care including inhibition of the RAS (ACEi or ARB) as well as lifestyle modification for blood pressure control and proteinuria reduction. Patients who remain at high risk of progressive CKD despite maximal supportive care might be considered for high-dose corticosteroids or immunosuppressants. In recent years, mounting evidence has supported an important role for complement activation in disease onset and progression of IgAN. The alternative complement pathway (AP) and lectin complement pathway (LP) are found to be activated in 75-90% and 17-25% of IgAN patients, respectively (Floege et al 2014, Maillard et al 2015). Factor B (FB) is an essential component of C3- and C5-convertases. Iptacopan (LNP023) is an oral, first-in-class, highly potent selective inhibitor of FB and thereby blocks the activity of AP C3 and C5 convertases, inhibiting the AP as well as the amplification of the classic and lectin complement pathways. Currently, iptacopan is being evaluated in an ongoing adaptive seamless double-blind and placebo-controlled dose-ranging Phase 2 study (CLNP023X2203, Part 1 and Part 2) in patients with biopsy-confirmed IgAN and elevated proteinuria [urine protein to creatinine ratio (UPCR) ≥ 0.75 g/g]. An interim analysis (IA) at 90 days of treatment in the Part 1 study showed that iptacopan administered up to 200 mg b.i.d for 90 days was safe, well tolerated and may be effective in reducing proteinuria. A further IA combining participants in Part 1 and Part 2 will be completed in early 2021 and the pivotal phase 3 trial is to start in early 2021. Aim APPLAUSE-IgAN (NCT04578834; CLNP023A2301) is a multicenter, randomized, double-blind, placebo-controlled parallel-group Phase 3 study which aims to evaluate the efficacy and safety of iptacopan (LNP023) compared with placebo in addition to supportive therapy on proteinuria reduction and slowing kidney disease progression in primary IgAN patients. Method Adult patients diagnosed with primary IgAN (based on kidney biopsy and elevated proteinuria [UPCR ≥ 1 g/day]) will be recruited. A run-in period will ensure that patients have received ACEi/ARB at a maximally tolerated dose for at least 90 days and receive required vaccinations at least 2 weeks prior to first dosing. Patients will be randomized in a 1:1 ratio to either iptacopan 200 mg b.i.d or matching placebo for a 24-month treatment period. The trial will enroll approximately 450 participants, aiming for 430 with eGFR ≥30 mL /min/1.73m2 (main study population). About 20 participants with eGFR 20 to Primary objectives 1) At IA (when approximately 250 patients have completed the 9 months visit): To demonstrate superiority of iptacopan vs. placebo in the reduction of proteinuria. The IA results may be submitted to support accelerated/conditional approval. 2) At final analysis (when approximately 430 patients have completed 24 months of active treatment): to demonstrate superiority of iptacopan vs. placebo in slowing kidney disease progression measured by the annualized total slope of eGFR decline over 24 months. Results Recruitment will start in Q1 2021. Conclusion This trial will evaluate the efficacy of iptacopan, a promising new therapy for IgAN, in reducing proteinuria and slowing loss of kidney function over 2 years.

Since 2008, the Japanese government has started measures against chronic kidney disease (CKD), and steady changes have been achieved, including a decrease in the age-adjusted rate of new dialysis introduction. However, the total number of dialysis patients has not declined because of the progression of aging. Therefore, the Japanese government has started more concrete measures since 2018. It aims to prevent CKD exacerbation mainly by early referrals to nephrologists using “criteria for referral from a primary care physician to a kidney specialist/specialized medical institution”. In addition, key performance indicators are set to reduce the number of new dialysis patients from 39,000 in 2016 to ≤ 35,000 by 2028. We hope that you can refer to this measure all over the world and proceed with CKD measures. This report has been originally notified from the Ministry of Health, Labor and Welfare in Japanese. This is the English version of it.

Introduction An abnormal serum potassium (S-K) level is an important electrolyte disturbance. However, its relation to clinical outcomes in real-world patients, particularly hyperkalemia burden, is not extensively studied. Methods An observational retrospective cohort study using a Japanese hospital claims database was done (April 2008–September 2017; N = 1,022,087). Associations between index S-K level and 3-year survival were modeled using cubic spline regression. Cox regression model was applied to estimate the time to death according to different S-K levels. Prevalence, patient characteristics, treatment patterns, and management of patients with hyperkalemia from first episode were assessed. Results Hyperkalemia prevalence was 67.9 (95% confidence interval [CI]: 67.1–68.8) per 1000 and increased in patients with chronic kidney disease (CKD) (227.9; 95% CI: 224.3–231.5), heart failure (134.0; 95% CI: 131.2–136.8), and renin-angiotensin-aldosterone system inhibitor (RAASi) use (142.2; 95% CI: 139.6–144.7). U-shaped associations between S-K level and 3-year survival were observed with nadir 4.0 mEq/l. The risk of death was increased at S-K 5.1–5.4 mEq with hazard ratio of 7.6 (95% CI: 7.2–8.0). The 3-year mortality rate in patients with CKD stages 3a, 3b, 4, and 5 with normokalemia were 1.51%, 3.93%, 10.86%, and 12.09%, whereas that in patients with CKD stage 3a at S-K 5.1–5.4, 5.5–5.9, and ≥6.0 mEq/l increased to 10.31%, 11.43%, and 22.64%, respectively. Despite treatment with loop diuretics (18.5%) and potassium binders (5.8%), >30% of patients had persistently high S-K (≥5.1 mEq/l). Conclusion This study provides real-world insight on hyperkalemia based on a large number of patients with various medical backgrounds., Graphical abstract

Diabetic kidney disease is the leading cause of end-stage kidney disease. Patients with diabetic kidney disease are at extremely high risk for cardiovascular disease. Tight blood pressure control is a key component for prevention of progression of kidney disease and cardiovascular events as well. If strict blood pressure control and blood sugar level control can be accomplished at least until microalbuminuria levels are achieved, in addition to inhibition of the onset and progression of nephropathy, remission induction can also be expected.

Background The Dapagliflozin and Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD; NCT03036150) trial was designed to assess the effect of the sodium–glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin on kidney and cardiovascular events in participants with CKD with and without type 2 diabetes (T2D). This analysis reports the baseline characteristics of those recruited, comparing them with those enrolled in other trials. Methods In DAPA-CKD, 4304 participants with a urinary albumin:creatinine ratio (UACR) ≥200 mg/g and estimated glomerular filtration rate (eGFR) between 25 and 75 mL/min/1.73 m2 were randomized to dapagliflozin 10 mg once daily or placebo. Mean eGFR was 43.1 mL/min/1.73 m2 and median UACR was 949 mg/g (108 mg/mmol). Results Overall, 2906 participants (68%) had a diagnosis of T2D and of these, 396 had CKD ascribed to a cause other than diabetes. The most common causes of CKD after diabetes (n = 2510) were ischaemic/hypertensive nephropathy (n = 687) and chronic glomerulonephritis (n = 695), of which immunoglobulin A nephropathy (n = 270) was the most common. A total of 4174 participants (97%) were receiving an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, 1882 (43.7%) diuretics, 229 (5.3%) mineralocorticoid receptor antagonists and 122 (2.8%) glucagon-like peptide 1 receptor agonists. In contrast to the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE), the DAPA-CKD trial enrolled participants with CKD due to diabetes and to causes other than diabetes. The mean eGFR of participants in the DAPA-CKD trial was 13.1 mL/min/1.73 m2 lower than in CREDENCE, similar to that in the Finerenone in Reducing Kidney Failure and Disease Progression in DKD (FIDELIO-DKD) trial and the Study Of diabetic Nephropathy with AtRasentan (SONAR). Conclusions Participants with a wide range of underlying kidney diseases receiving renin–angiotensin system blocking therapy have been enrolled in the DAPA-CKD trial. The trial will examine the efficacy and safety of dapagliflozin in participants with CKD Stages 2–4 and increased albuminuria, with and without T2D.

Endothelial dysfunction represents a predominant early feature of diabetes, rendering patients with diabetes prone to renal complications, e.g., proteinuria. Recent studies have indicated a possible role for xanthine oxidase (XO) in the pathogenesis of vascular dysfunctions associated with diabetes. In the present study, we investigated the contribution of XO activation on the progression of diabetic nephropathy in a mouse model using selective XO inhibitors. Male Ins2Akita heterozygous mice were used with wild-type mice as controls. Akita mice were treated with topiroxostat (Topi) or vehicle for 4 wk. Serum uric acid levels were significantly reduced in Akita + Topi mice compared with Akita + vehicle mice. The Akita + Topi group had a significant reduction in urinary albumin excretion compared with the Akita + vehicle group. Mesangial expansion, glomerular collagen type IV deposition, and glomerular endothelial injury (assessed by lectin staining and transmission electron microscopy) were considerably reduced in the Akita + topi group compared with the Akita + vehicle group. Furthermore, glomerular permeability was significantly higher in the Akita + vehicle group compared with the wild-type group. These changes were reduced with the administration of Topi. We conclude that XO inhibitors preserve glomerular endothelial functions and rescue compromised glomerular permeability, suggesting that XO activation plays a vital role in the pathogenesis of diabetic nephropathy.

BACKGROUNDThe chronic kidney disease (CKD) public health burden is substantial and has not declined as expected with current interventions on disease treatments. A large number of clinical, biological, and behavioural risk factors have been associated with CKD. However, it is unclear which of them are causal.OBJECTIVETo systematically test whether previously reported risk factors for CKD are causally related to the disease in European and East Asian ancestries.DESIGNTwo-sample Mendelian randomization (MR) and non-linear MR analyses.PARTICIPANTS53,703 CKD cases and 960,624 controls of European ancestry from CKDGen, UK Biobank and HUNT, and 13,480 CKD cases and 238,118 controls of East Asian ancestry from Biobank Japan, China Kadoorie Biobank and Japan-Kidney-Biobank/ToMMo.MEASURESSystematic literature mining of PubMed studies identified 45 clinical risk factors and biomarkers with robustly associated genetic variants, including phenotypes related to blood pressure, diabetes, glucose, insulin, lipids, obesity, smoking, sleep disorders, nephrolithiasis, uric acid, coronary artery disease, bone mineral density, homocysteine, C-reactive protein, micro-nutrients and thyroid function, which were selected as exposures. The outcome was CKD (defined by clinical diagnosis or by estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2).RESULTSEight risk factors showed evidence of causal effects on CKD in European ancestry, including body mass index (BMI), hypertension, systolic blood pressure, high density lipoprotein cholesterol, apolipoprotein A-I, lipoprotein A, type 2 diabetes (T2D) and nephrolithiasis. In East Asian ancestry, BMI, T2D and nephrolithiasis showed evidence of causal effects on CKD. Hypertension showed reliable evidence of a strong causal effect on CKD in Europeans but in contrast appeared to show a null effect in East Asians, suggesting the possibility of different causal risk factors in Europeans and East Asians. Although liability to T2D showed consistent effects on CKD, the effect of glycemic traits on CKD was weak, suggesting T2D may have glucose-independent mechanisms to influence CKD. Nonlinear MR indicated a threshold relationship between genetically predicted BMI and CKD, with increased risk at BMI above 25 kg/m2.LIMITATIONDue to the unbalanced distribution of data between ancestries, we could only test 17 of the 45 risk factors in East Asian participants.CONCLUSIONSEight CKD-associated risk factors showed evidence of causal effects on the disease in over 1.2 million European and East Asian ancestries. These risk factors were predominantly related to cardio-metabolic health, which supports the shared causal link between cardio-metabolic health and kidney function. This study provides evidence of potential intervention targets for primary prevention of CKD, which could help reduce the global burden of CKD and its cardio-metabolic co-morbidities.Research in contextEvidence before this studyChronic kidney disease (CKD) has a major effect on global health, both as a direct cause of morbidity and mortality, and as an important complication for cardio-metabolic diseases. However, even with the existing interventions, the burden of CKD has not declined as expected over the last 30 years. Existing epidemiological studies of CKD have mainly focused on disease treatment in patients from specific populations and estimated association rather than causality. A systematic assessment of the causal determinants of CKD in different populations is urgently needed, to help promote a shift from treatment of CKD patients to prevention of the disease in high-risk groups. The use of genetic data and the latest Mendelian randomization (MR) methodologies offers a cost-effective way to evaluate the potential intervention targets for prevention of CKD in high-risk groups.Added value of this studyIn this study, we systematically constructed a causal atlas of 45 risk factors on CKD in European and East Asian ancestries using MR. To maximise power of these analyses and accuracy of the findings, we collected and harmonised CKD genetic association data from six large-scale biobanks (in over 1.1 million Europeans and 250,000 East Asians). By applying a comprehensive MR framework, including linear two-sample MR, bidirectional MR, multivariable MR and non-linear MR approaches, we identified eight risk factors with reliable evidence of causal effects on CKD in European ancestry studies, including body mass index (BMI), hypertension, systolic blood pressure, high density lipoprotein cholesterol, apolipoprotein A-I, lipoprotein A, type 2 diabetes (T2D) and nephrolithiasis. In East Asian studies, BMI, T2D and nephrolithiasis also showed causal effects on CKD. Among other factors, hypertension showed reliable evidence of a strong causal effect on CKD in Europeans but in contrast appeared to show a null effect in East Asians. This MR finding together with previous literature evidence opens up the possibility that hypertension could play different causal roles on CKD across ancestries. For diabetes and glycemic phenotypes, our MR and sensitivity analyses suggested the causal role of liability of T2D on CKD but suggested weak effects of glycemic phenotypes on CKD. This aligns with the recent trial of SGLT2 inhibitors on kidney disease, which implies T2D may have glucose-independent mechanisms to influence CKD. For lipids phenotypes, we found good evidence to support the role of high-density lipoprotein cholesterol on CKD and further suggested the effects of two lipids targets: circulating CETP level and lipoprotein A concentration. For body weight, our study quantified a threshold relationship between BMI and CKD, with increased risk at BMI above 25 kg/m2. The causal relationship between nephrolithiasis and CKD were reported in previous studies, but our study confirmed the causal links between the two for the first time.Implication of all the available evidenceThis study makes a significant advance in comprehensively prioritising intervention targets for CKD in over 1.2 million participants. Our study presents causal evidence from both European and East Asian population samples, widening the generalisability of the causal atlas. Importantly, the prioritised risk factors are predominantly related to cardio-metabolic health, which supports the shared causal link between cardio-metabolic health and kidney function. Clinically, the high-quality evidence from this study highlights the value of exploring these causal factors in the general population and prioritizes drug targets and life-style interventions for CKD primary prevention, which could help reduce the global burden of CKD and its cardio-metabolic co-morbidities.

Background and Aims In most developed countries, diabetic kidney disease (DKD) is the most common cause of chronic kidney disease, which can lead to end-stage renal disease. In recent clinical trials, sodium–glucose cotransporter 2 inhibitors (SGLT2is) slowed the progression of kidney disease as compared with a placebo in patients with type 2 diabetes. One of the main mechanisms of the renoprotective effects of SCLT2is in DKD is considered the ability of these inhibitors to improve glomerular hyperfiltration. We previously demonstrated that the adenosine/adenosine A1 receptor pathway played a pivotal role in the tubuloglomerular feedback(TGF) system in a type 1 diabetic model, Akita mice (Circulation, 2019). We also reported that increased oxidative stress was involved in the pathogenesis of diabetic vascular complications. Uncoupling of endothelial nitric oxide (NO) synthase (eNOS) via oxidation of tetrahydrobiopterin (BH4), a cofactor required for NO production, played a major role in generation of oxidative stress (AJPRP, 2005; JASN, 2013). In the present study, we explored the renal protective effects of SGLT2 inhibition, with a focus on glomerular hemodynamics and glomerular oxidative stress. Method This study used type 2 diabetic db/db mice and db/m+ mice as a control (male, 8wk old). We developed a novel method to measure the glomerular filtration rate of single nephrons (SNGFRs) in mice using multiphoton laser microscopy. In the first experiment, we measured the SNGFRs in 12 wk-old db/db and db/m+ mice to confirm glomerular hyperfiltration. Next, we evaluated the SNGFRs change before and after the administration of a single dose of canagliflozin (CANA) (10 mg/kg). The SNGFRs, glomerular permeability of macromolecules, glomerular reactive oxygen species (ROS) and NO production, and tetrahydrobiopterin (BH4) level in serum and kidney were evaluated after the CANA treatment for 8 wk. Finally, human glomerular endothelial cells (hGECs) were exposed to normal glucose (5 mmol/L), high glucose (30 mmol/L of D-glucose), or a hyperosmotic control (5 mmol/L of D-glucose plus 25 mmol/L of L-glucose) in the presence or absence of CANA (10 μmol/L). Results The CANA treatment ameliorated glomerular hyperfiltration in the db/db mice. In the db/db mice, glomerulus ROS production increased, and NO production decreased as compared with the levels in the control mice. CANA improved the imbalance between ROS and NO production. The serum and kidney concentrations of BH4 declined in the non-treated db/db mice, whereas the CANA treatment preserved the BH4 level. Leakage of 70-kD FITC-labeled albumin into the urinary space was observed in the db/db mice. The CANA treatment reduced the amount of FITC-labeled albumin in the urinary space of the db/db mice. The CANA treatment also alleviated vascular endothelial damage in glomeruli. BH4 levels decreased in the hGECs exposed to high glucose. CANA did not improved BH4 level in the hGECs exposed to high glucose. Conclusion SGLT2i ameliorated glomerular hyperfiltration, preserving BH4 levels and improving the glomerular ROS/NO imbalance in type 2 diabetic mice.

Background and Aims CKD progression in Japanese patients with advanced chronic kidney disease (CKD)—an estimated glomerular filtration rate (eGFR) Method We conducted a nationwide cohort study of Japanese patients with advanced CKD. We recruited 2,249 advanced CKD patients (eGFR Results The reported causes of CKD were 552(25%) had diabetic kidney diseases (DKD), 131(6%) had PKD, 591(26%) had nephrosclerosis, 299(13%) had glomerulonephritis, and 676(30%) had other renal diseases. Of 1939 eligible patients with eGFR data more than two years, median (IQR) annual eGFR declines (ml/min/1.73m2/year) in PKD and DKD patients were 2.30 (1.16, 3.38) and 1.18 (0.23, 3.69) in G3b, 2.60 (1.81, 3.40) and 1.97 (0.20, 4.75) in G4, and 4.00 (2.00, 5.60) and 3.94 (2.05, 7.05) in G5, respectively. These eGFR declines were significantly faster than those of other kidney diseases. On the other hand, the variability of the decline in PKD patients was significantly smaller than that of DKD patients (0.43 vs 0.71, p Conclusion Our study clarified that, similar to DKD patients, annual eGFR decline of PKD patients was significantly faster than those of other kidney diseases throughout all stages. Furthermore, the variability of the decline in PKD patients was smaller than those of others. These data suggest that comprehensive nephrology care should be needed especially for these patients.

Background and Aims In 2012, the Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommended categorising and prognosticating chronic kidney disease (CKD) based on estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR). Contemporary studies describing the prevalence and characteristics of patients with CKD categorised according KDIGO 2012 and how studies of new pharmacotherapies relate to these categories are scarce. One such new therapy class of key interest are the sodium glucose co-transporter 2 inhibitors (SGLT-2i), shown to delay the progression to renal failure and prevent cardiovascular/renal death in patients with CKD. We aimed to describe patient characteristics and the prevalence of CKD according to the 2012 KDIGO categories in a large real-world US cohort of patients with CKD (part A). We also describe a subset of the population according to the DAPA-CKD trial inclusion criteria (eGFR [25-75ml/min/1.73m2] and UACR [200-5000mg/g]) (part B). Method DISCOVER-CKD is an international observational study in patients with CKD. The DISCOVER-CKD retrospective US cohort of patients was extracted using real-world data from the integrated Limited Claims and Electronic Health Record data (IBM Health, Armonk, NY) and HealthVerity. Patients were aged ≥18 years, with ≥1 UACR measure. For part A, required first diagnostic code of CKD (Stages 3A, 3B, 4, 5, or ESRD) or two eGFR of Results Of the overall study cohort (N=4330, 49.1% women, mean age 65.3±10.64 years), by KDIGO categories (part A): 85.7% (n=3601) had normal to mildly increased albuminuria, 11.0% (n=463) had moderately increased albuminuria and 3.3% (n=137) had severely increased albuminuria (Figure 1). 4.6% (n=193) fulfilled DAPA-CKD trial inclusion criteria (part B). In both populations, the most common comorbidities were hypertension (HTN, 73.0% for both) and type 2 diabetes (T2D, 57.6% and 56.2%, respectively). Anti-hypertensive drugs were frequently used (76.4% and 76.9%, respectively). Conclusion This study, utilising real-world data, adds to the scarcity of knowledge reporting the characteristics of patients with CKD in different eGFR and UACR strata according to the KDIGO 2012 definitions. We observed a trend in higher UACR in the group of patients with lower eGFR and report a high prevalence of T2D and HTN in the study population, demonstrating the high co-morbidity burden in patients, for whom new therapies may be beneficial.

The aim of the present study was to clarify the prevalence of immunosuppressive drug use and outcomes in elderly and non-elderly patients with primary membranous nephropathy (MN) in nationwide real-world practice in Japan. Between 2009 and 2010, 374 patients with primary nephrotic syndrome were enrolled in the cohort study (The Japan Nephrotic Syndrome Cohort Study, JNSCS), including 126 adult patients with MN. Their clinical characteristics were compared with those of nephrotic patients with primary MN registered in a large nationwide registry (The Japan Renal Biopsy Registry, J-RBR). Outcomes and predictors in the elderly (≥ 65 years) and non-elderly groups were identified. Similar clinical characteristics were observed in JNSCS patients and J-RBR patients (n = 1808). At the early stage of 1 month, 84.1% of patients were treated with immunosuppressive therapies. No significant differences were observed in therapies between age groups. However, elderly patients achieved complete remission (CR) more frequently than non-elderly patients, particularly those treated with therapies that included corticosteroids. No significant differences were noted in serum creatinine (sCr) elevations at 50 or 100%, end-stage kidney disease, or all-cause mortality between age groups. Corticosteroids were identified as an independent predictor of CR (HR 2.749, 95%CI 1.593–4.745, p = 0.000) in the multivariate Cox’s model. sCr levels, hemoglobin levels, immunosuppressants, clinical remission, and relapse after CR were independent predictors of sCr × 1.5 or × 2.0. Early immunosuppressive therapy including corticosteroids for primary MN showed better remission rates in elderly patients in a nationwide cohort study.

BackgroundThe Japan Chronic Kidney Disease Database (J-CKD-DB) is a nationwide clinical database of patients with chronic kidney disease (CKD) based on electronic health records. The objective of this study was to assess the prevalences of hyperuricemia and electrolyte abnormalities in Japanese patients with CKD.MethodsIn total, 35,508 adult outpatients with estimated glomerular filtration rates of 5-60 ml/min/1.73 m2 in seven university hospitals were included this analysis. The proportions of patients with CKD stages G3b, G4, and G5 were 23.5%, 7.6%, and 3.1%, respectively.ResultsLogistic regression analysis showed that prevalence of hyperuricemia was associated with CKD stages G3b (adjusted odds ratio [95% confidence interval]: 2.12 [1.90-2.37]), G4 (4.57 [3.92-5.32]), and G5 (2.25 [1.80-2.80]). The respective prevalences of hyponatremia, hypercalcemia, hyperphosphatemia, and narrower difference between serum sodium and chloride concentrations were elevated in patients with CKD stages G3b, G4, and G5, compared with those prevalences in patients with CKD stage G3a. The prevalences of hyperkalemia were 8.3% and 11.6% in patients with CKD stages G4 and G5, respectively. In patients with CKD stage G5, the proportions of patients with optimal ranges of serum uric acid, potassium, corrected calcium, and phosphate were 49.6%, 73.5%, 81.9%, and 56.1%, respectively.ConclusionsWe determined the prevalences of hyperuricemia and electrolyte abnormalities in Japanese patients with CKD using data from a nationwide cohort study.