Circulating Extracellular Vesicle-Propagated microRNA Signature as a Vascular Calcification Factor in Chronic Kidney Disease.

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.

A case of unexpected diagnosis of fibronectin glomerulopathy with histological features of membranoproliferative glomerulonephritis.

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.

Associations Between Dietary Potassium Intake From Different Food Sources and Hyperkalemia in Patients With Chronic Kidney Disease.

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.

Rapidly progressive IgA nephropathy with membranoproliferative glomerulonephritis-like lesions in an elderly man following the third dose of an mRNA COVID-19 vaccine: a case report.

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.

Association among kidney function, frailty, and oral function in patients with chronic kidney disease: a cross-sectional study.

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.

Postoperative renal impairment and longitudinal change in renal function after adrenalectomy in patients with Cushing's syndrome.

OBJECTIVES: To evaluate the renal function after adrenalectomy in patients with Cushing's syndrome in comparison with that in patients with primary aldosteronism. METHODS: This retrospective study included 35 patients with Cushing's syndrome and 51 patients with primary aldosteronism who underwent unilateral adrenalectomy and were followed up for >6 months. The renal function was analyzed before and after adrenalectomy using the estimated glomerular filtration rate. Postoperative renal impairment was defined as a >25% reduction in the estimated glomerular filtration rate from baseline at 1 month after adrenalectomy. Multivariate logistic regression analyses were carried out to examine whether the differences between Cushing's syndrome and primary aldosteronism increased the risk of postoperative renal impairment. Longitudinal changes were calculated starting 1 month after adrenalectomy using the linear mixed model. RESULTS: The mean estimated glomerular filtration rate in both groups significantly decreased at 1 month after adrenalectomy from baseline. Postoperative renal impairment was observed in four (11%) and 12 (24%) patients in the Cushing's syndrome and primary aldosteronism groups, respectively. Multivariate analysis showed that preoperative systolic blood pressure was independently associated with postoperative renal impairment, but not with the type of the disease. There was no significant increase or decrease in postoperative estimated glomerular filtration rate observed after the initial decrease after adrenalectomy in either group. CONCLUSIONS: Patients with Cushing's syndrome show the same persistent renal impairment after adrenalectomy as that reported in patients with primary aldosteronism. Attention should be given to possible masked renal damage in clinical practice for the management of Cushing's syndrome.

Low white blood cell count is independently associated with chronic kidney disease progression in the elderly: the CKD-ROUTE study.

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.

Association of serum chloride level with mortality and cardiovascular events in chronic kidney disease: the CKD-ROUTE study.

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.

The use of vitamin D analogs is independently associated with the favorable renal prognosis in chronic kidney disease stages 4-5: the CKD-ROUTE study.

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 m2, 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.

Combination of low body mass index and serum albumin level is associated with chronic kidney disease progression: the chronic kidney disease-research of outcomes in treatment and epidemiology (CKD-ROUTE) study.

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/m2); group 2, high serum albumin level (≥4 g/dL) and low BMI; group 3, low serum albumin level and high BMI (≥23.5 kg/m2); 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 m2/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 ß (standard error) -2.62 (0.75), p = 0.001]. CONCLUSION: This study suggests that combined effects of low BMI (<23.5 kg/m2) and serum albumin level (<4 g/dL) are associated with CKD progression.

Anaemia management and mortality risk in newly visiting patients with chronic kidney disease in Japan: The CKD-ROUTE study.

AIM: To investigate the association between iron deficiency anaemia and mortality risk and assess the changes in anaemia and iron status after primary management by a nephrologist. METHODS: In this prospective cohort study, we stratified 951 non-dialysis chronic kidney disease (CKD) G2-G5 patients newly visiting 16 nephrology centres into four groups according to the presence of anaemia with or without iron deficiency. All-cause mortality, cardiovascular (CV)-related mortality, and a change in anaemia and iron status after specialized primary care were the endpoints evaluated. RESULTS: During a median follow-up time of 19 months, the number of all-cause deaths and CV-related deaths were 56 and 26, respectively. Compared with the control group, the groups with isolated anaemia and iron deficiency anaemia had significantly higher all-cause mortalities (isolated anaemia: hazard ratio (HR), 3.37; 95% confidence intervals (CI), 1.76-6.44; iron deficiency anaemia: HR, 3.11; 95% CI, 1.21-8.01) and CV-related mortalities (isolated anaemia: HR, 3.64; 95% CI, 1.36-9.73; iron deficiency anaemia: HR, 3.86; 95% CI, 1.11-13.41). In the isolated anaemia group, erythropoietin-stimulating agent (ESA) prescriptions significantly increased to approximately 70%. However, in patients with both anaemia and iron deficiency, iron prescriptions only increased to 48.1%. CONCLUSIONS: Iron deficiency anaemia and isolated anaemia were associated with all-cause and CV-related mortality. The absence of relative increase in iron prescriptions suggests that iron deficiency should be accurately assessed and iron supplementation should be appropriately used to manage anaemia in non-dialysis patients with CKD.

Investigation of treatment volume versus circulating blood volume during Rheocarna treatment.

INTRODUCTION: Rheocarna's therapeutic effect is associated with fibrinogen (Fib) and low-density lipoprotein cholesterol (LDL-C) adsorptive removal. This study aimed to retrospectively investigate the association between treatment volume (TV) and circulating blood volume (CBV) and the Fib removal rate (Fib-RR) and LDL-C-RR. METHODS: CBV and TV/CBV, cut-off value (CO value), and area under the receiver operating characteristic (ROC) curve (AUC) were calculated. The Fib-RR and LDL-C-RR at the midterm and end of treatment were compared. The groups were further categorized into three groups with TV/CBV lower than or higher than the CO value at the midterm and end (midterm/end; Group L: lower than/lower than CO; Group L/H: lower than/higher than CO; Group H: higher than/higher than CO), and the Fib-RR and LDL-RR of each group at the midterm and end were compared. RESULTS: ROC analysis revealed a TV of 1.480 times the BV as CO value, which showed a maximum Youden index predicting a Fib-RR of 20% (AUC: 0.828). Among the three groups, Group L and Group L/H demonstrated significantly higher Fib-RR and LDL-C-RR at the end of the study than in the midterm, while Group H exhibited no difference. CONCLUSION: The results reveal that a treatment volume of 1.5 times the circulating blood volume is a sufficient solute removal capacity in the Rheocarna-enabled cases.

Effect of osteosarcopenia on longitudinal mortality risk and chronic kidney disease progression in older adults.

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 m2, 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.

Impact of COVID-19 versus other pneumonia on in-hospital mortality and functional decline among Japanese dialysis patients: a retrospective cohort study.

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.

Baseline characteristics and prevalence of cardiovascular disease in newly visiting or referred chronic kidney disease patients to nephrology centers in Japan: a prospective cohort study.

BACKGROUND: About 39,000 patients were newly prescribed renal replacement therapy in Japan in 2011, resulting in a total of more than 300,000 patients being treated with dialysis. This high prevalence of treated end stage kidney disease (ESKD) patients is an emergent problem that requires immediate attention. We launched a prospective cohort study to evaluate population specific characteristics of the progression of chronic kidney disease (CKD). In this report, we describe the baseline characteristics and risk factors for cardiovascular disease (CVD) prevalence among this cohort. METHODS: New patients from 16 nephrology centers who were older than 20 years of age and who visited or were referred for the treatment of CKD stage 2-5, but were not on dialysis therapy, were recruited in this study. At enrollment, medical history, lifestyle behaviors, functional status and current medications were recorded, and blood and urine samples were collected. Estimated glomerular filtration rate (eGFR) was calculated by a modified three-variable equation. RESULTS: We enrolled 1138 patients, 69.6% of whom were male, with a mean age of 68 years. Compared with Western cohorts, patients in this study had a lower body mass index (BMI) and higher proteinuria. The prevalence of CVD was 26.8%, which was lower than that in Western cohorts but higher than that in the general Japanese population. Multivariate analysis demonstrated the following association with CVD prevalence: hypertension (adjusted odds ratio (aOR) 3.57; 95% confidence interval (CI) 1.82-7.02); diabetes (aOR 2.45; 95% CI 1.86-3.23); hemoglobin level less than 11 g/dl (aOR 1.61; 95% CI 1.21-2.15); receiving anti-hypertensive agents (aOR 3.54; 95% CI 2.27-5.53); and statin therapy (aOR 2.73; 95% CI 2.04-3.66). The combination of decreased eGFR and increased proteinuria was also associated with a higher prevalence of CVD. CONCLUSIONS: The participants in this cohort had a lower BMI, higher proteinuria and lower prevalence of CVD compared with Western cohorts. Lower eGFR and high proteinuria were associated with CVD prevalence. Prospective follow up of these study patients will contribute to establishment of individual population-based treatment of CKD.

Low-Density Lipoprotein Adsorption by Centrifugal Plasma Separation Can Shorten Treatment Time.

Low-density lipoprotein (LDL) apheresis is effective for nephrotic syndrome in drug-resistant focal segmental glomerulosclerosis (FSGS). Dextran sulfate adsorption of LDL (DSAL) is widely used for this purpose. The Liposorber LA-15 system performs DSAL by membrane plasma separation (mDSAL) using an MA-03 plasma purification device. However, sufficient blood flow (Qb) frequently cannot be obtained from a peripheral vein with mDSAL. The recommended plasma filtration flow rate (Qf) when using the OP-05W membrane plasma separator is no more than 1/3 of Qb, giving plasma removal efficiency (PRE) of about 30%. In contrast, the centrifugal blood component separator Spectra Optia has PRE of 87-92.5% because centrifugal separation enables effective separation of plasma components even at low Qb. Here, we present the case of a man in his 40s with FSGS, for whom we began treatment with mDSAL with the intention of completing a 12-session cycle, but extended treatment times were required due to low Qb. Therefore, we switched to DSAL by centrifugation (cDSAL) using the Liposorber LA-40 system from the 6th session onward. Treatment time decreased from 190 min for the fifth session using mDSAL to 140 min for the sixth session using cDSAL. Mean treatment time also decreased from 155 ± 9 min for mDSAL (5 sessions) to 119 ± 20 min for cDSAL (7 sessions). Moreover, the LDL removal rate at a processed plasma volume was similar for both modalities. In conclusion, cDSAL can enable efficient plasma separation even with low Qb, with a comparable LDL removal rate and shorter treatment time relative to mDSAL.

Systemic Capillary Leak Syndrome as a Rare, Potentially Fatal Complication of COVID-19: A Case Report and Literature Review.

Systemic capillary leak syndrome (SCLS), also known as Clarkson's disease, is a rare and potentially lethal condition characterized by hypotension, hemoconcentration, and hypoalbuminemia; however, the cause of SCLS is still uncertain. We present the case of a 62-year-old male with flu-like symptoms who presented to the emergency department with shock. Initial evaluation revealed hemoconcentration, hypoalbuminemia, acute kidney failure, and positive polymerase chain reaction (PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite aggressive fluid resuscitation, the shock persisted, and the patient's condition deteriorated. After ruling out ischemia and septic shock, the patient was diagnosed with coronavirus disease 2019 (COVID-19)-associated SCLS. Treatment with remdesivir and intravenous immunoglobulin (IVIG), along with the restoration of intravascular volume, led to the gradual improvement of the patient's condition. The patient experienced pulmonary edema, which was managed by correcting the fluid balance through continuous hemodiafiltration. Eventually, the patient recovered without any residual organ complications. SCLS is often misdiagnosed because of its rarity and non-specific symptoms. Accurate diagnosis and understanding of the disease's pathophysiology are crucial for effective management. This report contributes to the existing literature by presenting a case of COVID-19-associated SCLS and emphasizes the need for further research on its occurrence and outcomes.

Thrombocytopenia during avacopan administration: A case report.

Avacopan is a novel C5a receptor antagonist recently approved for the treatment of microscopic polyangiitis and granulomatosis with polyangiitis. To our knowledge, thrombocytopenia induced by avacopan has not been reported. We report a case of a 78-year-old man with microscopic polyangiitis who developed rapidly progressive glomerulonephritis (RPGN) and vasculitis neuropathy. After developing RPGN, he was treated with prednisolone, which was ineffective. As the dosage of corticosteroids was decreased, he developed impaired dorsiflexion of the left ankle, tingling and numbness in his feet, consistent with vasculitis neuropathy. After a 3-day administration of methylprednisolone, we started avacopan and prednisolone 20 mg/d to reduce the corticosteroid dosage. One week after starting avacopan, platelet counts began to decrease, eventually leading to the cessation of the drug. The possibility of thrombotic microangiopathy and heparin-induced thrombocytopenia was considered unlikely given the clinical course and laboratory studies. After 3 weeks of avacopan cessation, platelet counts began to increase, suggesting avacopan as the most probable cause of thrombocytopenia. Our case highlights the importance of postmarketing surveillance of avacopan to identify its adverse events that were not reported in clinical trials to ensure its safe use. Clinicians should carefully monitor platelet counts when using avacopan.

Evaluation of the treatment volume and removal rate of Rheocarna: A novel adsorption-type blood purification device for patients with chronic limb-threatening ischemia.

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.

Association of Admission Functional Status and Body Mass Index with Mortality in Patients Receiving Chronic Dialysis: A Nationwide Observational Cohort Study.

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.