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Distinguishing autosomal‐dominant polycystic kidney disease (ADPKD) from other inherited renal cystic diseases in patients with adult polycystic kidney disease and no family history is critical for correct treatment and appropriate genetic counseling. However, for patients with no family history, there are no definitive imaging findings that provide an unequivocal ADPKD diagnosis. We analyzed 53 adult polycystic kidney disease patients with no family history. Comprehensive genetic testing was performed using capture‐based next‐generation sequencing for 69 genes currently known to cause hereditary renal cystic diseases including ADPKD. Through our analysis, 32 patients had PKD1 or PKD2 mutations. Additionally, 3 patients with disease‐causing mutations in NPHP4, PKHD1, and OFD1 were diagnosed with an inherited renal cystic disease other than ADPKD. In patients with PKD1 or PKD2 mutations, the prevalence of polycystic liver disease, defined as more than 20 liver cysts, was significantly higher (71.9% vs 33.3%, P = .006), total kidney volume was significantly increased (median, 1580.7 mL vs 791.0 mL, P = .027) and mean arterial pressure was significantly higher (median, 98 mm Hg vs 91 mm Hg, P = .012). The genetic screening approach and clinical features described here are potentially beneficial for optimal management of adult sporadic polycystic kidney disease patients. [ABSTRACT FROM AUTHOR]

Background: The incidence of acute type B aortic dissection is higher than that of acute type A aortic dissection among patients on dialysis. However, the impact of being on chronic dialysis on outcomes after type B aortic dissection remains unknown. This study aimed to investigate the trends in in-hospital mortality after type B aortic dissection and the association between body mass index (BMI) and survival paradox on dialysis., Methods: This study included 48,889 type B aortic dissection hospitalizations in Japan from 2010 to 2020 based on data from a nationwide administrative database. Logistic regression was used to examine mortality risks and restricted cubic spline to investigate the non-linear association between mortality and BMI., Results: There were 2,116 in-hospital deaths, and the mortality rates were 8.0% in patients receiving chronic dialysis and 4.3% in patients not receiving dialysis. Patients not receiving dialysis had decreased trends of absolute mortality. Meanwhile, patients receiving chronic dialysis had a higher mortality rate from 2010 to 2020. The mortality risk was high in patients receiving chronic dialysis who were underweight and had normal BMI, but not in those who were overweight. Restricted cubic spline analysis showed that a higher BMI was associated with a lower mortality risk in dialysis patients. This finding contrasted the U-shape observed in patients not receiving dialysis., Conclusions: A lower BMI was associated with a higher risk of in-hospital mortality after type B aortic dissection among dialysis patients, thereby illustrating the obesity paradox. Our findings provide insights that can enhance the management strategies for dialysis patients facing type B aortic dissection., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no competing interests. Ethical approval and consent to participate: This study was approved by the ethics committee of Tokyo Medical and Dental University (approval number: M2000-788). Informed consent was not required due to data anonymity. Consent for publication: Not applicable., (© 2024. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Objective: Previous studies reported mixed results on associations between dietary potassium intake and hyperkalemia in patients with chronic kidney disease (CKD). This study investigated the association between potassium intake from different food sources and hyperkalemia in patients with non-dialysis-dependent CKD., Methods: A total of 285 patients were recruited at a university hospital and 2 city hospitals in Tokyo. Dietary potassium intake was estimated by a validated diet history questionnaire. Associations of potassium intake from all foods and individual food groups with serum potassium were examined by multivariable linear regression among potassium binder nonusers. An association between tertile groups of potassium intake and hyperkalemia, defined as serum potassium ≥5.0 mEq/L, was evaluated by multivariable logistic regression., Results: Among 245 potassium binder nonusers, total potassium intake was weakly associated with serum potassium (regression coefficient = 0.147, 95% confidence interval (CI): 0.018-0.277), while an association with hyperkalemia was not observed (first vs third tertile: adjusted odds ratio = 0.98, 95% CI: 0.29-3.26). As for food groups, potassium intakes from potatoes, pulses, and green/yellow vegetables were positively associated with serum potassium. Patients in the highest tertile of potassium intake from potatoes had higher odds of hyperkalemia as compared to those in the lowest tertile (adjusted odds ratio = 4.12, 95% CI: 1.19-14.34)., Conclusion: Total potassium intake was weakly associated with serum potassium, but not with hyperkalemia. Potassium intake from potatoes was associated with hyperkalemia. These findings highlight the importance of considering food sources of potassium in the management of hyperkalemia in CKD., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

The global outcome of acute aortic dissection (AD) remains poor, with a high risk of the need for urgent dialysis. This study aimed to clarify the association between sex and the requirement for urgent dialysis within 30 days after admission among patients with AD. This study included 79,998 cases who were hospitalized due to AD in Japan from 2010 to 2020 using an administrative claims database. The association between the risk of urgent dialysis and sex was investigated using the Fine and Gray model. Patients were classified into two groups based on the Stanford classification: type A AD (TAAD) and type B AD (TBAD). The lower subdistribution hazard ratio (SHR) in women was observed in both groups: TAAD (SHR: 0.58, 95% confidence interval [CI]: 0.54-0.62); TBAD (SHR: 0.49, 95% CI: 0.41-0.58). Our study revealed that women had a lower risk of requiring urgent dialysis than men in TAAD and TBAD., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Background: While numerous studies have reported associations between low dietary potassium intake and adverse clinical outcomes, methods to estimate potassium intake, mainly self-reported dietary measures and urinary potassium excretion, entail certain limitations. Self-reported measures are subject to underreporting and overreporting. Urinary potassium excretion is affected by multiple factors including renal function. Revealing the degree of bias inherent in these measures would help accurately assess potassium intake and its association with disease risk. We aim to summarize evidence on the strength of the associations between potassium intake estimated from 24-h urinary potassium excretion and potassium intake estimated from self-reported dietary measures or objective quantification methods in populations with different kidney function levels and age groups. We also aim to identify factors that affect the association strength., Methods: We will search for potentially eligible studies that examined associations between self-reported potassium intake, 24-h urinary potassium excretion, and objectively quantified potassium intake, using MEDLINE (PubMed), Embase, Web of Science, and Scopus. Studies on children, adolescents, adults, and the elderly are eligible. Studies of patients on dialysis will be excluded. Collective study results, including a meta-analysis, will be synthesized if an adequate number of studies examining similar dietary potassium intake estimation methods are found. Analyses will be performed separately according to age groups and renal function. For the meta-analysis, fixed-effects or random-effect models will be employed depending on the degree of study heterogeneity to combine across studies the correlation coefficient, ratio, or standardized mean difference for potassium intake, comparing dietary potassium intake based on self-reported or objectively quantified methods and intake based on 24-h urinary potassium excretion. The degree of heterogeneity among included studies will be examined by calculating I 2 statistics. To investigate sources of study heterogeneity, random-effects meta-regression analyses will be performed., Discussion: Revealing the strength of the association between dietary and urinary measures in populations with different levels of kidney function and age groups will enhance researchers' and clinicians' ability to interpret studies that utilize these measures and help establish a more solid evidence base for the role of potassium intake in changing chronic disease risk. Identifying factors that modify the associations between these measures may aid in developing predictive models to estimate actual potassium intake., Systematic Review Registration: PROSPERO CRD42022357847., (© 2024. The Author(s).)

Introduction: Recently, the monoallelic loss-of-function IFT140 variant was identified as a causative gene for autosomal dominant polycystic kidney disease (ADPKD). In patients with polycystic kidneys who have a positive family history, >90% have pathogenic variants in PKD1 or PKD2 , whereas only 1% have IFT140 . However, approximately 40% of patients with polycystic kidneys without a family history do not have any pathogenic variants in PKD1 and PKD2 ., Methods: We conducted a comprehensive genetic analysis of 157 adult patients with polycystic kidneys whose parents did not have evident polycystic kidneys. We sequenced up to 92 genes associated with inherited cystic kidney disease, including IFT140 ., Results: Of the 157 patients, 7 (4.5%) presented with monoallelic loss-of-function variants in the IFT140 gene, 51 (32.5%) with pathogenic variants in the PKD1 or PKD2 gene, and 7 (4.5%) with pathogenic variants in other genes related to inherited kidney cystic disease. The proportion of monoallelic loss-of-function IFT140 variants in this cohort was higher than that in previously reported cohorts with polycystic kidneys who had a positive family history. None of the patients with monoallelic loss-of-function IFT140 variants had polycystic liver disease (PLD). Furthermore, patients with IFT140 pathogenic variants had a significantly smaller kidney volume and a remarkably higher estimated glomerular filtration rate (eGFR) than those with PKD1 pathogenic variants ( P  = 0.01 and 0.03, respectively)., Conclusion: Because the phenotype of polycystic kidneys caused by the IFT140 gene is mild, parental kidney disease may be overlooked. Therefore, patients without a positive family history are more likely to carry pathogenic variants in IFT140 ., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Coronavirus disease 2019 (COVID-19) affects both life and health. However, the differentiation from other types of pneumonia and effect of kidney disease remains uncertain. This retrospective observational study investigated the risk of in-hospital death and functional decline in ≥ 20% of Barthel Index scores after COVID-19 compared to other forms of pneumonia among Japanese adults, both with and without end-stage kidney disease (ESKD). The study enrolled 123,378 patients aged 18 years and older from a national inpatient administrative claims database in Japan that covers the first three waves of the COVID-19 pandemic in 2020. After a 1:1:1:1 propensity score matching into non-COVID-19/non-dialysis, COVID-19/non-dialysis, non-COVID-19/dialysis, and COVID-19/dialysis groups, 2136 adults were included in the analyses. The multivariable logistic regression analyses revealed greater odds ratios (ORs) of death [5.92 (95% CI 3.62-9.96)] and functional decline [1.93 (95% CI 1.26-2.99)] only in the COVID-19/dialysis group versus the non-COVID-19/non-dialysis group. The COVID-19/dialysis group had a higher risk of death directly due to pneumonia (OR 6.02, 95% CI 3.50-10.8) or death due to other diseases (OR 3.00, 95% CI 1.11-8.48; versus the non-COVID-19/non-dialysis group). COVID-19 displayed a greater impact on physical function than other types of pneumonia particularly in ESKD., (© 2024. The Author(s).)

Introduction: Chronic kidney disease (CKD) causes a progressive loss of muscle and bone mass, which frequently overlap with and affect clinical outcomes. However, the impact of sarcopenia, low bone mineral density (BMD; osteopenia or osteoporosis), and osteosarcopenia (sarcopenia and low BMD) on CKD progression is yet to be determined. We aimed to address these issues in patients with CKD without kidney replacement therapy (KRT)., Methods: This prospective cohort study included 251 outpatients aged ≥65 years with CKD without KRT enrolled in our hospital between June 2016 and March 2017. Sarcopenia was defined according to the 2014 criteria of the Asian Working Group for Sarcopenia (AWGS), and low BMD was defined as a T-score of ≤-1.0. The patients were divided into four groups: normal (no sarcopenia/normal BMD), only low BMD (no sarcopenia/low BMD), only sarcopenia (sarcopenia/normal BMD), and osteosarcopenia (sarcopenia/low BMD). The primary outcome was a composite of all-cause deaths, initiating KRT, and admissions owing to major adverse cardiovascular and cerebrovascular events (MACEs). The secondary outcome was a kidney composite outcome that included a 30 % reduction in creatinine-based estimated glomerular filtration rate (eGFR) and initiating KRT. The outcome risk was determined using the Cox regression models adjusted for potential confounders., Results: Median age (25th-75th percentile) and eGFR of the outpatients (35 % women) were 76 (69-81) years and 32.1 (20.8-41.7) ml/min/1.73 m 2 , respectively. During a median follow-up period of 5.2 years, there were 22 deaths, 117 30 % eGFR reductions, 48 KRTs, and 18 admissions owing to MACEs. The osteosarcopenia group rather than the only low BMD or only sarcopenia groups exhibited a higher risk of the primary (hazard ratio [HR]: 3.28, 95 % confidence interval [CI]: 1.52-7.08) and kidney composite (HR: 2.07, 95 % CI: 1.10-3.89) outcomes. Among the osteosarcopenia-related body compositions and physical functions, low handgrip strength (HGS) was strongly associated with a high risk of primary and kidney composite outcomes (HR: 2.44, 95 % CI: 1.46-4.08; HR: 1.48, 95 % CI: 0.97-2.24, respectively). The increase in HGS but not the body mass index, skeletal muscle mass index, or BMD was associated with lower risks of primary and kidney composite outcomes (HR: 0.93, 95 % CI: 0.89-0.98; HR: 0.96, 95 % CI: 0.92-0.99 per 1 kg, respectively)., Conclusions: Osteosarcopenia was associated with poor survival and kidney outcomes in older patients with CKD. Low HGS, which is common in patients with osteosarcopenia and CKD, was associated with increased mortality risk and kidney function decline. These findings can help the risk prediction and pathogenesis of the kidney-bone-muscle axis and improving muscle strength can help mitigate CKD progression., Competing Interests: Declaration of competing interest We declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Fibronectin (FN) glomerulopathy (FNG), a rare autosomal hereditary renal disease, is characterized by proteinuria resulting from the massive accumulation of FN in the glomeruli. It typically affects individuals aged 10-50 years. In this report, we describe the case of a 57-year-old man who was diagnosed with FNG through genetic analysis and histological examination that revealed membranoproliferative glomerulonephritis. Despite treatment with prednisolone, the therapeutic response was unsatisfactory. Prednisolone was subsequently tapered and discontinued because the patient had pulmonary thromboembolism. Subsequent comprehensive genetic testing, which was initially not conducted because the patient's parents did not have a history of kidney disease, identified a known disease-causing variant in the FN1 gene, indicating a de novo variant. FNG was further confirmed by positive staining of glomeruli with FN using an IST-4 antibody. Although corticosteroid therapy is commonly employed as the initial treatment for MPGN, its appropriateness depends on the underlying etiology. Thus, clinicians must be aware of potential rare genetic causes underlying MPGN., (© 2024. The Author(s).)

Introduction: Chronic limb-threatening ischemia (CLTI) is a clinical syndrome defined by peripheral arterial disease (PAD) combined with rest pain, gangrene, or leg ulceration for longer than two weeks resulting in lower extremity amputation. In recent years, low-density lipoprotein apheresis (LDL-A) has been implemented for PAD treatment. However, it has not been possible to ensure insurance coverage for patients with lower LDL levels than 140 mg/dL under cholesterol-lowering drugs. Rheocarna is a novel adsorption-type blood purification device for the treatment of CLTI by adsorbing LDL and fibrinogen (Fib) that is not constrained by hypercholesterolemia and is not amenable to or nonresponsive to revascularization surgery. The only requirements for use are that the blood flow rate increases up to 200 mL/min gradually., Methods: To evaluate the applicability of this treatment procedure, we compared the removal rates of Fib and LDL following Rheocarna therapy using various blood treatment volumes (6, 10.5, and 19.5 L)., Results: Fib and LDL removal rates were about 20% and 15%-25% per treatment, with no significant differences between treatment volumes. Following treatment with Rheocarna, blood pressure tends to decrease at first, which later increases, and the higher the treatment volume, the longer the time of low blood pressure tended to be., Conclusion: Although no significant difference was found in the removal rate of Fib and LDL in response to increase volume to 6 L or beyond in this study, the 6 L volume is considered effective enough for the removal of Fib and LDL., (© 2023 International Society for Apheresis and Japanese Society for Apheresis.)

Background: Despite increasing incidences of hypertension, recent trends in mortality and urgent dialysis following acute hypertension (AHT) remain undetermined., Methods: This retrospective observational cohort study evaluated 50 316 hospitalized AHT patients from 2010 to 2019, using an administrative claims database in Japan. We examined trends in incidence, urgent dialysis, mortality, and its risk factors using Poisson regression models. Using International Classification of Disease and Related Health Problems, 10th Revision codes, AHT was categorized into 5 spectrums: malignant hypertension ( n =1792), hypertensive emergency ( n =17 907), hypertensive urgency ( n =1562), hypertensive encephalopathy ( n =6593), and hypertensive heart failure (HHF; n =22 462)., Results: The median age of the patients was 76 years, and 54.9% were women. The total AHT incidence was 70 cases per 100 000 admission year. The absolute death rate increased from 1.83% (95% CI, 1.40-2.40) to 2.88% ([95% CI, 2.42-3.41]; Cochran-Armitage trend test, P< 0.0001). Upward trends were observed in patients aged ≥80, with lean body mass index ≤18.4, and with HHF. Urgent dialysis rates increased from 1.52% (95% CI, 1.12-2.06) to 2.60% (2.17-3.1; Cochran-Armitage trend test; P =0.0071) in 48 235 patients, excluding maintenance dialysis patients. Older age, men, lean body mass, malignant hypertension, HHF, and underlying chronic kidney disease correlated with higher mortality risk; greater hospital volume correlated with lower mortality risk; and malignant hypertension, HHF, diabetes, chronic kidney disease, and scleroderma correlated with a higher risk of urgent dialysis., Conclusions: Mortality and urgent dialysis rates following AHT have increased. Aging, complex comorbidities, and HHF-type AHT contributed to the rising trend of mortality., Competing Interests: Disclosures None.

Chronic kidney disease (CKD) causes cognitive impairment and contributes to the overall global burden of dementia. However, mechanisms through which the kidneys and brain communicate are not fully understood. We established a CKD mouse model through adenine-induced tubulointerstitial fibrosis. Novel object recognition tests indicated that CKD decreased recognition memory. Sarkosyl-insoluble-proteomic analyses of the CKD mouse hippocampus revealed an accumulation of insoluble MAPT (microtubule-associated protein tau) and RNA-binding proteins such as small nuclear ribonucleoprotein U1 subunit 70 (SNRNP70). Additionally, there was an accumulation of Immunoglobulin G (IgG), indicating blood-brain barrier (BBB) breakdown. We identified that expressions of essential tight-junction protein claudin-5 and adherens-junction protein platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) were decreased in the brain endothelial cells of CKD mice. We determined urea as a major uremic solute that dose dependently decreased both claudin-5 and PECAM-1 expression in the mouse brain endothelial cell line bEnd.3 cells. Gelatin zymography indicated that the serum of CKD mice activated matrix metalloproteinase-2 (MMP2), while marimastat ameliorated the reduction of claudin-5 expression by urea in bEnd.3 cells. This study established a brain proteomic signature of CKD indicating BBB breakdown and insolubility of tau protein, which are pathologically linked to Alzheimer's disease. Urea-mediated activation of MMP2 was partly responsible for BBB breakdown in CKD.

Introduction: Chronic kidney disease (CKD) significantly affects activities of daily living (ADLs) before and after the initiation of dialysis, particularly in elderly individuals. However, the impact of admission functional status on dialysis patients' outcome is not fully understood. This study aimed to investigate the effect of the number of ADL disabilities usually measured for all patients hospitalized in Japan on in-hospital outcome for dialysis patients., Methods: Using an inpatient administrative claims database, we included 104,557 admissions of patients undergoing chronic dialysis aged 65 years and above from 2012 to 2014. The primary outcome was in-hospital all-cause mortality (evaluated using logistic regression models), and the secondary outcomes were length of stay and care cost., Results: The mean age of the participants was 74.0 ± 6.2 years, the mean body mass index (BMI) was 21.8 ± 3.9, 31% needed assistance for one or more of five basic ADLs (feeding, transferring, going to toilet, dressing, and bathing) at admission, and 3.5% (n = 3,701) died after hospitalization. After adjusting for confounding factors, the odds ratios (ORs) (95% confidence intervals) of death for 1, 2, 3, 4, and 5 ADL disabilities were 1.43 (1.19-1.70), 2.04 (1.71-2.45), 2.58 (2.19-3.04), 3.74 (3.35-4.17), and 6.83 (6.29-7.41) versus a complete independence, respectively. The increasing number of ADL disabilities was also associated with greater length of stay and costs. Risk stratification by age, admission functional status, and BMI showed an 18-mortality risk matrix with a maximal risk of a 15.5-higher OR for lean patients aged ≥75 years with severe ADL disability compared with that for patients aged <75 years with middle BMI and no ADL disability on admission., Conclusions: Admission functional status decline significantly increases in-hospital mortality, length of stay, and costs. Routine assessment of functional status can facilitate the risk prediction of dialysis patients., Competing Interests: None, (Copyright © Japan Medical Association.)

Background: As messenger RNA (mRNA)-based vaccines for coronavirus disease 2019 (COVID-19) have been administered to millions of individuals worldwide, cases of de novo and relapsing glomerulonephritis after mRNA COVID-19 vaccination are increasing in the literature. While most previous publications reported glomerulonephritis after the first or second dose of an mRNA vaccine, few reports of glomerulonephritis occurring after the third dose of an mRNA vaccine currently exist., Case Presentation: We report a case of rapidly progressive glomerulonephritis in a patient following the third dose of an mRNA COVID-19 vaccine. A 77-year-old Japanese man with a history of hypertension and atrial fibrillation was referred to our hospital for evaluation of anorexia, pruritus, and lower extremity edema. One year before referral, he received two mRNA vaccines (BNT162b2) for COVID-19. Three months before the visit, he received a third mRNA vaccine (mRNA-1273) for COVID-19. On admission, the patient presented severe renal failure with a serum creatinine level of 16.29 mg/dL, which had increased from 1.67 mg/dL one month earlier, prompting us to initiate hemodialysis. Urinalysis showed nephrotic-range proteinuria and hematuria. Renal biopsy revealed mild mesangial proliferation and expansion, a lobular appearance, and double contours of the glomerular basement membrane. Renal tubules had severe atrophy. Immunofluorescence microscopy showed strong mesangial staining for IgA, IgM, and C3c. Electron microscopy exhibited mesangial and subendothelial electron-dense deposits, leading to a diagnosis of IgA nephropathy with membranoproliferative glomerulonephritis-like changes. The kidney function remained unchanged after steroid therapy., Conclusions: Although the link between renal lesions and mRNA vaccines remains unclear, a robust immune response induced by mRNA vaccines may play a role in the pathogenesis of glomerulonephritis. Further studies of the immunological effects of mRNA vaccines on the kidney are warranted., (© 2023. The Author(s).)

Background: Chronic kidney disease (CKD) accelerates vascular calcification via phenotypic switching of vascular smooth muscle cells (VSMCs). We investigated the roles of circulating small extracellular vesicles (sEVs) between the kidneys and VSMCs and uncovered relevant sEV-propagated microRNAs (miRNAs) and their biological signaling pathways., Methods and Results: We established CKD models in rats and mice by adenine-induced tubulointerstitial fibrosis. Cultures of A10 embryonic rat VSMCs showed increased calcification and transcription of osterix ( Sp7 ), osteocalcin ( Bglap ), and osteopontin ( Spp1 ) when treated with rat CKD serum. sEVs, but not sEV-depleted serum, accelerated calcification in VSMCs. Intraperitoneal administration of a neutral sphingomyelinase and biogenesis/release inhibitor of sEVs, GW4869 (2.5 mg/kg per 2 days), inhibited thoracic aortic calcification in CKD mice under a high-phosphorus diet. GW4869 induced a nearly full recovery of calcification and transcription of osteogenic marker genes. In CKD, the miRNA transcriptome of sEVs revealed a depletion of 4 miRNAs, miR-16-5p , miR-17~92 cluster-originated miR-17-5p / miR-20a-5p , and miR-106b-5p . Their expression decreased in sEVs from CKD patients as kidney function deteriorated. Transfection of VSMCs with each miRNA-mimic mitigated calcification. In silico analyses revealed VEGFA (vascular endothelial growth factor A) as a convergent target of these miRNAs. We found a 16-fold increase in VEGFA transcription in the thoracic aorta of CKD mice under a high-phosphorus diet, which GW4869 reversed. Inhibition of VEGFA-VEGFR2 signaling with sorafenib, fruquintinib, sunitinib, or VEGFR2 -targeted siRNA mitigated calcification in VSMCs. Orally administered fruquintinib (2.5 mg/kg per day) for 4 weeks suppressed the transcription of osteogenic marker genes in the mouse aorta. The area under the curve of miR-16-5p , miR-17-5p , 20a-5p , and miR-106b-5p for the prediction of abdominal aortic calcification was 0.7630, 0.7704, 0.7407, and 0.7704, respectively., Conclusions: The miRNA transcriptomic signature of circulating sEVs uncovered their pathologic role, devoid of the calcification-protective miRNAs that target VEGFA signaling in CKD-driven vascular calcification. These sEV-propagated miRNAs are potential biomarkers and therapeutic targets for vascular calcification.

Background: Chronic kidney disease is associated with perioperative mortality. However, outcomes of patients who perioperatively received acute dialysis have not been clarified. We aimed to determine risks for in-hospital death and functional decline following various surgeries with an acute dialysis requirement versus maintenance dialysis and non-dialysis., Materials and Methods: We analyzed 22,857 patients who underwent major surgeries during hospitalization in Japan from 2018 until 2019 using an inpatient administrative claims database. Risks of overall death and functional decline assessed by Barthel index scores were determined with logistic regression models., Results: Among the propensity score-matched groups, mortality rates were 8.54% [95% confidence interval (CI) 7.92-9.17], 5.97% (95% CI 5.44-6.50), and 1.12% (95% CI 0.88-1.35) with an acute dialysis requirement, maintenance dialysis, and non-dialysis, respectively. The survivor rates with ≥20%-decline in Barthel index scores were 7.67% (95% CI 7.07-8.26), 8.56% (95% CI 7.93-9.19), and 3.48% (95% CI 3.07-3.89), respectively. Lower preoperative Barthel index scores were strongly associated with mortality independent of surgeries. Cardiac surgery, colorectal resection, esophagectomy, and gastrectomy led to higher mortality, while cardiac surgery, and orthopedic surgery were associated with higher risk of functional decline. In addition, mortality rates after hepatic lobectomy/cholecystectomy/pancreatectomy [odds ratio (OR) 3.09, 95% CI 1.61-5.91] and esophagectomy/gastrectomy (OR 2.65, 95% CI 1.68-4.38) were markedly higher with an acute dialysis requirement when compared with maintenance dialysis., Conclusion: Perioperative acute dialysis requirements were associated with substantial risks for mortality and functional decline. Several types of surgeries led to even higher mortality rates for acute dialysis than maintenance dialysis., (Copyright © 2022 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Physicians have long noted a substantial discrepancy between the reasons for hospital admission and ultimate causes of death, particularly among older adults or patients with complex underlying diseases. However, objective data on this phenomenon are lacking. We aimed to examine the risk of in-hospital death caused by a reason other than the original reason for hospitalization and its association with underlying kidney disease in a nationwide inpatient database., Methods: In this retrospective cohort study, we studied 639,556 Japanese adults who died in the hospital from 2012 to 2015, using data from Japan's Diagnosis Procedure Combination database. We analyzed the discrepancy rate between reasons for hospital admission and death and associated factors using the International Classification of Diseases, 10th Revision (ICD-10) diagnostic codes and seven related categories., Results: Among non-chronic kidney disease (CKD) (590,551), CKD (24,708), and end-stage kidney disease (ESKD) (24,297) patients, the median age was 77 years (interquartile range [IQR]: 67-84 years), 83 years (IQR: 75-88), and 75 years (IQR: 67-81), and 25.7%, 30.3%, and 41.6% died from a reason other than the original reason for hospitalization, respectively. Multivariate logistic regression analyses determined CKD/ESKD as the predominant risk factor for this discrepancy, rather than older age, male sex, obesity, and other comorbidities. Sankey diagrams that presented diagnostic changes from hospital admission to death revealed multiple wider segments connecting to different disease classifications, particularly to congestive and septic death in CKD and ESKD patients, respectively. Death owing to another disease classification led to an increase in the median length of hospital stay by 5-7 days and to a 1.3--1.4-fold increase in medical costs across the populations., Conclusions: A substantial proportion of patients with CKD and ESKD died during hospitalization for a reason other than their original reason for admission, leading to increased length of hospital stay and cost., Competing Interests: The authors have declared that no competing interests exist.

Plasma volume (PV) variation during therapeutic apheresis (TA) (such as plasma exchange [PE] and selective PE using albumin solution as replacement solution or immunoadsorption plasmapheresis) has been considered to be unignorable. It changes the concentration of the target molecule and might impact its removal rate (RR.) This study aimed to evaluate the effects of PV variation on the calculation of the RR of fibrinogen and immunoglobulin by categorizing the hematocrit (Ht) change during TA into two patterns, that is, increased group and decreased group. In all modalities of TA, the Ht level frequently changed during apheresis sessions. In calculating RR, RR calculated with Ht adjustment was significantly higher than that calculated without adjustment in the increased group and significantly lower than it in the decreased group. Therefore, RR might have been underestimated in the increased group and overestimated in the decreased group when RR was calculated without Ht adjustment. Ht adjustment is suggested to be crucial in calculating RR in TA., (© 2021 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Introduction: Recently, nephronophthisis (NPH) has been considered a monogenic cause of end-stage renal disease (ESRD) in adults. However, adult-onset NPH is difficult to accurately diagnose and has not been reported in a cohort study. In this study, we assessed the genetic background and clinicopathologic features of adult NPH., Methods: We investigated 18 sporadic adult patients who were suspected as having NPH by renal biopsy. We analyzed 69 genes that cause hereditary cystic kidney disease and compared clinicopathologic findings between patients with and without pathogenic mutations in NPH-causing genes., Results: Seven of 18 patients had pathogenic NPH-causing mutations in NPHP1 , NPHP3 , NPHP4 , or CEP164 . Compared with patients without pathogenic mutations, those with pathogenic mutations were significantly younger but did not significantly differ in the classic NPH pathologic findings, such as tubular cysts. On the other hand, the number of tubules with thick tubular basement membrane (TBM) duplication, which was defined as >10-μm thickness, was significantly higher in patients with genetically proven adult NPH than in those without pathogenic mutations. α-Smooth muscle actin (α-SMA)-positive myofibroblasts were detected inside thick TBM duplication., Conclusions: In adult patients with NPH, thick TBM duplication was the specific finding. Our analysis also suggested that older patients tended to have no pathogenic mutations, even when they were suspected to have NPH by renal biopsy. These findings could be the novel clinical clue for the diagnosis of NPH in adult patients., (© 2021 International Society of Nephrology. Published by Elsevier Inc.)

Background: Chronic kidney disease (CKD) involves many factors that can cause frailty and oral hypofunction. We aimed to investigate the prevalence of frailty and oral hypofunction and to examine the associations among kidney function, frailty, and oral function in adults with CKD in Japan., Methods: This cross-sectional study was conducted at two institutions. The participants included 109 patients with CKD stages 3-5 who visited outpatient clinics or were admitted for inpatient treatment. Frailty was evaluated using the Japanese version of the Cardiovascular Health Study frailty criteria. Oral function was evaluated by assessing oral motor skills [oral diadochokinesis (ODK) rate], masticatory ability, and the repetitive saliva swallowing test. The estimated glomerular filtration rate (eGFR) was used to indicate kidney function. We examined the associations among kidney function, frailty, and oral function using binomial logistic regression analysis., Results: In total, 31 participants (28.4%) were classified as being frail. Univariate analysis showed that age, body mass index, eGFR, and haemoglobin level were significantly associated with frailty. ODK and swallowing function were significantly associated with frailty. Multivariate analysis revealed that frailty was significantly associated with eGFR [odds ratio (OR) 0.96, 95% confidence interval (CI) 0.92-1.00, p = 0.048] and ODK rate (OR 0.68, CI 0.47-0.98, p = 0.038). However, no significant association was found between CKD severity and masticatory or swallowing function., Conclusion: We found a high prevalence of frailty in patients with CKD and a significant association between frailty and oral motor skills, affecting the swallowing function of patients with nondialysis CKD. The high prevalence of frailty among patients with CKD suggests that routine assessment of frailty is necessary to prevent the development of severe complications. In addition, oral and kidney function should be carefully evaluated, and oral health education and interventions should be performed for patients with CKD.

Backgrounds: End-stage kidney disease (ESKD) is associated with increased risk of fracture and subsequent morbidity and mortality. However, fracture site-specific mortality in ESKD patients have yet to be elucidated in comparison with the general population., Methods: In this population-based cohort derived from the Diagnosis Procedure Combination database of Japan from 2012 to 2014, we included 9320 ESKD patients undergoing hemodialysis and 547,726 patients without ESKD who were hospitalized for five major fractures, including hip (proximal femur), spine, forearm, upper arm, and leg (distal femur and proximal tibia). Overall and site-specific risks of in-hospital death were determined by logistic regression models., Results: The age- and sex-adjusted mortality rates were 4.91% (95% confidence interval [CI], 4.46-5.37) and 1.02% (95% CI, 0.99-1.06) in the hemodialysis and general population groups, respectively. The multivariate odds ratio (OR) of death in hemodialysis patients versus the general population was 2.48 (95% CI, 2.25-2.74) for overall fractures, and was particularly high for a subgroup of upper arm fracture (OR 4.82, 95% CI, 3.19-7.28). The site-specific odds of death (95% CI) among hip, spine, forearm, upper arm, and leg (reference) fractures were 1.77 (0.98-3.18), 1.48 (0.79-2.75), 0.19 (0.04-0.86), and 2.01 (1.01-4.01) in hemodialysis patients, and 1.28 (1.13-1.45), 1.00 (0.88-1.14), 0.13 (0.10-0.17), and 0.83 (0.70-0.97) in the general population, respectively., Conclusion: Hemodialysis patients experienced a 4.8-fold higher mortality rate after fractures than the general population. Mortality after upper arm fracture was specifically high in patients on hemodialysis, likely due to the involvement of vascular access located on the fractured arm., (Copyright © 2019. Published by Elsevier Inc.)

Encephalopathy is a rare side effect of cephalosporin treatment. We herein present a case of encephalopathy induced by ceftriaxone, a third-generation cephalosporin, in a patient with renal failure. An 86-year-old woman on maintenance hemodialysis received ceftriaxone for Helicobacter cinaedi bacteremia. Her mental status deteriorated during antibiotic treatment, and an electroencephalogram revealed triphasic waves predominantly in the frontal area. Her consciousness improved after the discontinuation of the antibiotic due to the suspicion of ceftriaxone-induced encephalopathy. This is the first reported case of encephalopathy associated with high plasma and cerebrospinal fluid ceftriaxone concentrations, and provides significant evidence for a causal relationship between the administration of ceftriaxone and the onset of encephalopathy.

Autoimmune neurological diseases are often treated by immunoadsorption using a conventional plasma separator and tryptophan-immobilized column (IA). However, there is only one case report on treatment with immunoadsorption using a selective plasma separator and tryptophan-immobilized column (SeIA) in clinical practice. This study aimed to investigate the removal characteristics of antibodies against acetylcholine receptors (AChRAb), immunoglobulin G, fibrinogen, and factor XIII (FXIII) in IA and SeIA in four patients with myasthenia gravis. A total of 19 sessions of immunoadsorption were performed (five sessions of IA and 14 sessions of SeIA) when the processed plasma volume was 2 L. The corresponding reductions were 52.5% ± 6.2% for AChRAb, 58.8% ± 4.2% for fibrinogen, and 36.9% ± 5.5% for FXIII after one session of IA. The corresponding reductions were 45.2% ± 9.9% for AChRAb, 3.5% ± 6.9% for fibrinogen, and -4.6% ± 11.1% for FXIII after one session of SeIA. The removal rates for AChRAb, fibrinogen, and FXIII in IA were significantly higher than those in SeIA. IA could effectively remove AChRAb, and SeIA could retain fibrinogen and FXIII. IA can be combined with SeIA, resulting in both IgG autoantibodies removal by IA and retention of coagulation factors by SeIA., (© 2019 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Gallbladder metastasis from breast cancer, especially from ductal carcinoma, is rare. Herein, we report a rare case of gallbladder metastasis from ductal carcinoma of the breast that was diagnosed after laparoscopic cholecystectomy (LC) for acute cholecystitis. A 78-year-old woman presented with right upper abdominal tenderness and positive Murphy's sign during chemotherapy for advanced multiple metastases of the breast cancer. Abdominal ultrasonography and computed tomography showed a slightly thickened gallbladder wall and two calculi. After a diagnosis of acute calculous cholecystitis was established, LC was performed. Pathological examination revealed poorly differentiated adenocarcinoma infiltrating the submucosal and subserosal layer over the entire gallbladder, and a lymph node metastasis in the gallbladder neck. Immunohistochemical examination revealed that the tumor cells tested positive for estrogen receptor and negative for progesterone receptor, which was consistent with primary breast cancer. The patient was uneventfully discharged without abdominal pain 7 days later. Although she subsequently underwent several chemotherapies, she died 16 months later. In conclusion, gallbladder metastasis should be considered in patients with multiple metastatic breast cancer who present with signs or symptoms of cholecystitis. Moreover, LC should be considered to relieve the symptoms of cholecystitis for improved prognosis, even in a patient with multiple metastases.

In patients with chronic kidney disease (CKD), low body mass index (BMI) is associated with high mortality. This relationship in emergently hospitalized CKD patients is unknown. We investigated the association between obesity and short-term mortality in emergently admitted patients with dialysis-independent CKD (DI-CKD) with and without infection. This retrospective cohort study examined Diagnosis Procedure Combination data of 26103 emergently hospitalized DI-CKD patients. Patients were divided into 8 groups according to their BMI and the presence of infectious diseases. The primary outcome was in-hospital death within 100 days. Cox proportional hazards models adjusted for baseline characteristics showed that low BMI was associated with the outcome both in infected and in non-infected patients (reference group as non-infected and medium BMI [24-26 kg/m2] group): infected and the lowest BMI (≤20 kg/m2) group, hazard ratio (HR) 1.82 (95% confidence interval 1.51, 2.19); non-infected and the lowest BMI group, 1.39 (1.16, 1.67). When patients were stratified according to presence of diabetes mellitus (DM), patients with DM showed that low BMI was associated with the outcome both in infected and in non-infected patients, whereas in non-DM patients, this relationship was attenuated in the non-infected group. For emergently hospitalized CKD patients with infection, high BMI was associated with lower mortality irrespective of the DM status. For non-infected patients, the effects of obesity for in-hospital mortality were modified by the DM status., Competing Interests: The authors have declared that no competing interests exist.

Selective plasma exchange has been shown to be effective in various diseases, but no studies have assessed the benefits of daily treatment. We aimed to investigate the removal dynamics of immunoglobulins, fibrinogen, and factor XIII on three consecutive days in three patients. For mean processed plasma volumes of 1.06 × plasma volume, reductions of 79.6%, 49.3%, and 8.6% were seen for immunoglobulins G, A, and M, respectively. The reductions for fibrinogen and factor XIII were 18.4% and 13.0%, respectively. Removal dynamics were similar for immunoglobulin G-related autoantibodies and immunoglobulin G when using daily selective plasma exchange. Moreover, daily use effectively removed the immunoglobulin G while retaining the coagulation factors. When disease-specific autoantibodies are limited to immunoglobulin G, daily selective plasma exchange may be a useful and safe method of intensive induction treatment for plasmapheresis. However, further study is required in larger cohorts to confirm these findings., (© 2018 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Background: Elevated white blood cell (WBC) count is a well-known predictor of chronic kidney disease (CKD) progression. However, elderly patients commonly fail to develop a high WBC count in response to several diseased states and may instead present a low WBC count. Therefore, we hypothesized that low WBC count, in addition to high WBC count, is associated with CKD progression in the elderly., Methods: We conducted a prospective cohort study using 3-year follow-up data from the CKD Research of Outcomes in Treatment and Epidemiology study. In the present study, participants aged over 60 years with pre-dialysis CKD stages G2-G5 were eligible. Patients were stratified into three groups according to WBC count using tertiles (T). The primary outcome was a composite of end-stage renal disease and a 50% reduction in estimated glomerular filtration rate. Data were analyzed using Cox proportional hazard models with adjustments for covariates., Results: We enrolled 697 patients (males, 69%). The median WBC count was 6100 cells/µl (T1, <5400, n =  222; T2, 5400-6900, n =  235; T3, ≥6900, n = 240). During a median follow-up of 868 days, the primary outcome was observed in 170 patients, whereas 54 patients died. T1 and T3 had significantly higher hazard ratios (HR) than T2 (T1, HR 1.69, 95% confidence interval 1.14-2.51; T3, HR 1.63, 95% confidence interval 1.10-2.41). Moreover, T1 had a significantly higher adjusted HR (1.54, 95% confidence interval 1.00-2.37)., Conclusion: Low WBC count is independently associated with CKD progression in the elderly.

Introduction: Sarcopenia, the age-related loss of muscle mass and function, frequently accompanies chronic kidney disease. The aim of this study was to clarify the prevalence and the risk factors for sarcopenia among patients with non-dialysis-dependent chronic kidney disease (NDD-CKD), focusing on the use of drugs., Methods: We conducted a cross-sectional analysis on a cohort of 260 patients with NDD-CKD in a university hospital, recruited between June 2016 and March 2017. We extracted data on patient gender, age, cause of chronic kidney disease, use of drugs, and comorbidities that could potentially affect the prevalence of sarcopenia. Sarcopenia was diagnosed using the criteria of the Asian Working Group for Sarcopenia. Logistic regression analysis was performed to analyze the association of each factor on the prevalence of sarcopenia., Results: 25.0% of our study subjects had sarcopenia. Multivariable analysis revealed that an increased risk of sarcopenia was significantly associated with age, male gender, body mass index, diabetes mellitus, and loop diuretic use (odds ratio, 4.59: 95% confidence interval, 1.81-11.61: P-value 0.001)., Conclusions: In our cohort, the prevalence of sarcopenia in patients with NDD-CKD was high, and diuretics use, particularly loop diuretic use, was suggested to be a risk factor of sarcopenia. Although loop diuretics are commonly used in patients with CKD, careful consideration of the risk of sarcopenia may be necessary.

Background: Although lower estimated glomerular filtration rate (eGFR) and higher proteinuria are high risks for mortality and kidney outcomes, the prognosis of chronic kidney disease (CKD) in patients with normal-range proteinuria remains unclear., Methods: In this prospective cohort study, 1138 newly visiting stage G2-G5 CKD patients were stratified into normal-range and abnormal-range proteinuria groups. Study endpoints were CKD progression (>50% eGFR loss or initiation of dialysis), cardiovascular events, and all-cause death., Results: In total, 927 patients who were followed for >6 months were included in the analysis. The mean age was 67 years, and 70.2% were male. During a median follow-up of 35 months, CKD progression, cardiovascular events, and mortality were observed in 223, 110, and 55 patients, respectively. Patients with normal-range proteinuria had a significantly lower risk for CKD progression (hazard ratio, 0.20; 95% confidence interval, 0.10-0.38) than those with abnormal-proteinuria by multivariate Cox proportional hazard analysis. We also analyzed patients with normal-range proteinuria (n = 351). Nephrosclerosis was the most frequent cause of CKD among all patients with normal-range proteinuria (59.7%). During a median follow-up of 36 months, CKD progression, cardiovascular events, and mortality were observed in 10, 28, and 18 patients, respectively. The Kaplan-Meyer analysis demonstrated that the risks of CKD progression and cardiovascular events were not significantly different among CKD stages, whereas the risk of death was significantly higher in patients with advanced-stage CKD. Multivariate Cox proportional hazard analysis showed that the risk of three endpoints did not significantly differ among CKD stages., Conclusion: Newly visiting CKD patients with normal-range proteinuria, who tend to be overlooked during health checkups did not exhibit a decrease in kidney function even in advanced CKD stages under specialized nephrology care.

Introduction: Accumulating evidence suggests that a large hospital volume (HV) is associated with favorable outcomes in various diseases or surgical procedures. The aim of this study is to clarify the correlation of HV and dialysis case volume (DCV) with in-hospital death in patients on maintenance dialysis., Methods: The study cohort was derived from the Diagnosis Procedure Combination database, a national inpatient database in Japan, from 2012 to 2014. We included 382,689 admissions of maintenance dialysis patients over the age of 20 years in the analysis. HV was defined as the mean number of daily hospitalized patients, and DCV was defined as the mean number of annually hospitalized patients on maintenance dialysis. The primary outcome was in-hospital all-cause mortality, evaluated using multivariable logistic regression models across the respective quartiles of HV and DCV., Results: The mean age of participants was 69 ± 12 years; 94% were receiving hemodialysis, and 21,182 patients (5.5%) died after hospitalization. In unadjusted models, larger HV and DCV were both associated with lower in-hospital mortality. However, this association remained significant only for DCV after adjustment for potential confounders, with multivariable-adjusted odds ratios of 0.82 (95% confidence interval [CI], 0.79-0.85), 0.76 (95% CI, 0.73-0.80), and 0.68 (95% CI, 0.65-0.72) for DCV 249 to 432, 433 to 713, and ≥714 (vs. ≤ 248) admissions per year, respectively. Multivariable subgroup analyses determined that this association was independent of age, sex, dialysis modality, Charlson Comorbidity Index, and emergency admission., Conclusion: Selective admission to hospitals with a large DCV may improve outcomes of dialysis patients.

Fibrinogen is substantially reduced by most plasmapheresis modalities but retained in selective plasma exchange using Evacure EC-4A10 (EC-4A). Although EC-4A's fibrinogen sieving coefficient is 0, a session of selective plasma exchange reduced fibrinogen by approximately 19%. Here, we investigated sieving coefficient in five patients. When the mean processed plasma volume was 1.15 × plasma volume, the mean reduction of fibrinogen during selective plasma exchange was approximately 15%. Fibrinogen sieving coefficient was 0 when the processed plasma volume was 1.0 L, increasing to 0.07 when the processed plasma volume was 3.0 L, with a mean of 0.03 during selective plasma exchange. When fibrinogen sieving coefficient was 0, selective plasma exchange reduced fibrinogen by approximately 10%. Scanning electron microscopy images revealed internal fouling of EC-4A's hollow fiber membrane by substances such as fibrinogen fibrils. Thus, fibrinogen reduction by selective plasma exchange may be predominantly caused by membrane fouling rather than filtration., (© 2017 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Pemphigus vulgaris is a serious autoimmune skin disorder associated with desmoglein 1 and 3. Selective plasma exchange (SePE) for pemphigus vulgaris remains unknown. We investigated the removal characteristics of pemphigus autoantibodies, immunoglobulins, and fibrinogen in three cases. When the mean processed volume for SePE was 1.2 plasma volumes, the mean percent reduction was 50.7% for desmoglein 1, 48.9% for desmoglein 3, 50.3% for IgG, 29.8% for IgA, 1.9% for IgM, and 17.6% for fibrinogen. In one case, the percent reduction after four sessions of SePE within eight days was 87.0% for desmoglein 1, 85.1% for desmoglein 3, 76.6% for IgG, 53.5% for IgA, 7.9% for IgM, 41.6% for fibrinogen, and 31.4% for factor XIII. SePE can effectively remove pemphigus autoantibodies and retain coagulation factors, e.g. factor XIII and fibrinogen. In severe cases, SePE can be useful and safe for induction therapy., (© 2017 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Background: Vitamin D analogs have generally been recommended for treatment of mineral bone disease in chronic kidney disease (CKD). However, the association between this treatment and CKD progression has not yet been established., Methods: We designed a post hoc propensity score-matched cohort analysis derived from 3-year follow-up data of a prospective cohort. Adult participants with pre-dialysis CKD stages 4-5 who had newly been prescribed active vitamin D analogs during the observation period were eligible as matched cases. Then, matched controls were extracted from participants who had never been prescribed active vitamin D analogs. The primary outcome was a composite of end-stage renal disease or a 50 % reduction in estimated glomerular filtration rate (eGFR). A Cox proportional hazards model evaluated the association between the use of vitamin D analogs and the primary outcome., Results: We enrolled 240 patients (males, 65 %). The number of matched cases and controls was 30 and 210, respectively. The primary outcome was observed in 94 patients, whereas 25 patients died. The mean ± standard deviation age and eGFR were 69 ± 12 years and 17 ± 5.7 ml/min/1.73 m 2 , respectively. In a Cox proportional hazard model, the use of vitamin D analogs was independently associated with a lower risk of the primary outcome (crude hazard ratio 0.41; 95 % confidence interval 0.19, 0.89; adjusted hazard ratio 0.38; 95 % confidence interval 0.17, 0.88)., Conclusion: The use of vitamin D analogs is independently associated with the preservation of renal function in patients with pre-dialysis CKD stages 4-5.

Background: Electrolyte abnormalities, particularly dysnatremia, are independent predictors of adverse outcome in individuals with and without renal failure. However, the association of serum chloride level (Cl - ) with mortality or risk of cardiovascular (CV) events in chronic kidney disease (CKD) remains unclear., Methods: This prospective cohort study included 923 pre-dialysis CKD G2-G5 patients among the participants of the CKD Research of Outcomes in Treatment and Epidemiology (CKD-ROUTE) study, who newly visited 16 nephrology centers. The primary outcome was a composite of overall death and CV events, and the secondary outcome was overall death. Data were analyzed using the Cox hazards model with adjustment for potential confounders., Results: Median Cl - was 106.0 mEq/L at enrollment [quartile (Q) 1: ≤103.9, n =  207; Q2: 104.0-105.9, n =  207; Q3: 106.0-108.0, n =  289; Q4: ≥108.1, n = 220]. During a median follow-up of 33 months, there were 98 CV events, 66 deaths, and 154 composite outcomes. The hazard ratio (HR) for the composite outcome was higher for Q1 than Q3 [HR 1.72; 95 % confidence interval (CI) 1.08-2.72; P =  0.022]. As a continuous variable in a subset of patients whose Cl - was ≤106.0 mEq/L, higher Cl - was associated with lower risk of the composite outcome (HR 0.93; 95 % CI 0.87-0.99; P = 0.023). HR for all-cause mortality was also higher for Q1 than Q3 (HR 2.48; 95 % CI 1.22-5.03; P =  0.012)., Conclusion: Low Cl - was associated with increased mortality and risk of CV events in pre-dialysis CKD patients. Cl - may be an additional prognostic indicator in CKD.

Background: The relationship between protein-energy wasting and chronic kidney disease (CKD) progression is unknown. In the present prospective cohort study, we evaluated the hypothesis that a combination of low body mass index (BMI) and serum albumin level is associated with rapid CKD progression., Methods: The study cohort comprised 728 predialysis Japanese patients with CKD (stages 2-5) enrolled from 2010 to 2011. Patients were categorized into four groups according to their serum albumin levels and BMI: group 1, low serum albumin level (<4 g/dL) and low BMI (<23.5 kg/m 2 ); group 2, high serum albumin level (≥4 g/dL) and low BMI; group 3, low serum albumin level and high BMI (≥23.5 kg/m 2 ); and group 4, high serum albumin level and high BMI. The primary outcome was a 30 % decline in estimated glomerular filtration rate (eGFR) or start of dialysis within 2 years. The secondary outcome was an annual GFR decline (mL/min/1.73 m 2 /year)., Results: Logistic regression analysis adjusted for baseline characteristics (reference, group 4) showed that only group 1 was associated with a significant risk of CKD progression, with adjusted odds ratio of 3.51 [95 % confidence interval (CI) (1.63, 7.56)]. A multivariate linear regression analysis adjusted for baseline characteristics showed a significant difference in annual eGFR decline between groups 1 and 4 [coefficients β (standard error) -2.62 (0.75), p = 0.001]., Conclusion: This study suggests that combined effects of low BMI (<23.5 kg/m 2 ) and serum albumin level (<4 g/dL) are associated with CKD progression.