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1.
J Ren Nutr ; 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38621432

ABSTRACT

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.

2.
Sci Rep ; 14(1): 5177, 2024 03 02.
Article in English | MEDLINE | ID: mdl-38431709

ABSTRACT

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.


Subject(s)
COVID-19 , Kidney Failure, Chronic , Pneumonia , Adult , Humans , Renal Dialysis , COVID-19/epidemiology , Hospital Mortality , Japan/epidemiology , Retrospective Studies , Pandemics , Kidney Failure, Chronic/epidemiology , Kidney Failure, Chronic/therapy , Pneumonia/epidemiology
3.
Ther Apher Dial ; 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38453633

ABSTRACT

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.

4.
BMC Nephrol ; 25(1): 25, 2024 Jan 22.
Article in English | MEDLINE | ID: mdl-38254040

ABSTRACT

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.


Subject(s)
Glomerulonephritis, Membranoproliferative , Male , Humans , Middle Aged , Glomerulonephritis, Membranoproliferative/diagnosis , Glomerulonephritis, Membranoproliferative/drug therapy , Glomerulonephritis, Membranoproliferative/genetics , Kidney Glomerulus , Kidney , Prednisolone/therapeutic use
5.
Bone ; 179: 116975, 2024 02.
Article in English | MEDLINE | ID: mdl-37993037

ABSTRACT

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.


Subject(s)
Bone Diseases, Metabolic , Osteoporosis , Renal Insufficiency, Chronic , Sarcopenia , Humans , Female , Aged , Aged, 80 and over , Male , Sarcopenia/complications , Hand Strength , Prospective Studies , Osteoporosis/complications , Bone Diseases, Metabolic/complications , Bone Density/physiology , Renal Insufficiency, Chronic/complications
6.
JMA J ; 6(4): 404-413, 2023 Oct 16.
Article in English | MEDLINE | ID: mdl-37941718

ABSTRACT

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.

7.
Hypertension ; 80(12): 2591-2600, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37818643

ABSTRACT

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.


Subject(s)
Hypertension, Malignant , Hypertension , Renal Insufficiency, Chronic , Male , Humans , Female , Aged , Renal Dialysis/adverse effects , Retrospective Studies , Japan/epidemiology , Hypertension/epidemiology , Risk Factors
8.
Cureus ; 15(8): e42837, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37664276

ABSTRACT

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.

9.
Ther Apher Dial ; 27(6): 1017-1022, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37589198

ABSTRACT

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.


Subject(s)
Blood Component Removal , Hypercholesterolemia , Peripheral Arterial Disease , Humans , Chronic Limb-Threatening Ischemia , Adsorption , Hypercholesterolemia/therapy , Blood Component Removal/methods , Peripheral Arterial Disease/therapy , Treatment Outcome , Ischemia/therapy
10.
Perit Dial Int ; 43(6): 457-466, 2023 11.
Article in English | MEDLINE | ID: mdl-37632293

ABSTRACT

BACKGROUND: This multi-institutional, observational study examined whether the outcomes after peritoneal dialysis (PD) catheter placement in Japan meet the audit criteria of the International Society for Peritoneal Dialysis (ISPD) guideline and identified factors affecting technique survival and perioperative complications. METHODS: Adult patients who underwent first PD catheter placement for end-stage kidney disease between April 2019 and March 2021 were followed until PD withdrawal, kidney transplantation, transfer to other facilities, death, 1 year after PD start or March 2022, whichever came first. Primary outcomes were time to catheter patency failure and technique failure, and perioperative infectious complications within 30 days of catheter placement. Secondary outcomes were perioperative complications. Appropriate statistical analyses were performed to identify factors associated with the outcomes of interest. RESULTS: Of the total 409 patients, 8 who underwent the embedded catheter technique did not have externalised catheters. Of the 401 remaining patients, catheter patency failure occurred in 25 (6.2%). Technical failure at 12 months after PD catheter placement calculated from cumulative incidence function was 15.3%. On Cox proportional hazards model analysis, serum albumin (hazard ratio (HR) 0.44; 95% confidence interval (CI) 0.27-0.70) and straight type catheter (HR 2.14; 95% CI 1.24-3.69) were the independent risk factors for technique failure. On logistic regression analysis, diabetes mellitus was the only independent risk factor for perioperative infectious complications (odds ratio 2.70, 95% CI 1.30-5.58). The occurrence rate of perioperative complications generally met the audit criteria of the ISPD guidelines. CONCLUSION: PD catheter placement in Japan was proven to be safe and appropriate.


Subject(s)
Kidney Failure, Chronic , Peritoneal Dialysis , Adult , Humans , Peritoneal Dialysis/adverse effects , Peritoneal Dialysis/methods , Catheters, Indwelling/adverse effects , Japan , Catheterization/methods , Peritoneum , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/etiology
11.
Case Rep Nephrol Dial ; 13(1): 51-56, 2023.
Article in English | MEDLINE | ID: mdl-37484799

ABSTRACT

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.

12.
BMC Nephrol ; 24(1): 108, 2023 04 24.
Article in English | MEDLINE | ID: mdl-37095451

ABSTRACT

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.


Subject(s)
COVID-19 , Glomerulonephritis, IGA , Glomerulonephritis, Membranoproliferative , Glomerulonephritis , Male , Humans , Aged , Glomerulonephritis, IGA/diagnosis , Glomerulonephritis, Membranoproliferative/pathology , COVID-19 Vaccines , BNT162 Vaccine , COVID-19/complications , Glomerulonephritis/pathology
13.
Int J Rheum Dis ; 26(8): 1603-1607, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36880594

ABSTRACT

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.


Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Granulomatosis with Polyangiitis , Microscopic Polyangiitis , Thrombocytopenia , Male , Humans , Aged , Microscopic Polyangiitis/drug therapy , Thrombocytopenia/chemically induced , Thrombocytopenia/diagnosis , Thrombocytopenia/drug therapy , Aniline Compounds/adverse effects , Methylprednisolone/therapeutic use , Granulomatosis with Polyangiitis/drug therapy , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Antibodies, Antineutrophil Cytoplasmic
14.
Circ Res ; 132(4): 415-431, 2023 02 17.
Article in English | MEDLINE | ID: mdl-36700539

ABSTRACT

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.


Subject(s)
Extracellular Vesicles , MicroRNAs , Renal Insufficiency, Chronic , Vascular Calcification , Rats , Mice , Animals , MicroRNAs/genetics , MicroRNAs/metabolism , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism , Muscle, Smooth, Vascular/metabolism , Vascular Calcification/metabolism , Renal Insufficiency, Chronic/metabolism , Extracellular Vesicles/metabolism , Phosphorus/metabolism , Myocytes, Smooth Muscle/metabolism
15.
Int J Surg ; 104: 106816, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35944801

ABSTRACT

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.


Subject(s)
Renal Dialysis , Renal Insufficiency, Chronic , Hospital Mortality , Humans , Propensity Score , Retrospective Studies , Risk Factors
16.
PLoS One ; 16(11): e0258846, 2021.
Article in English | MEDLINE | ID: mdl-34731197

ABSTRACT

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.


Subject(s)
Hospital Mortality , Kidney Failure, Chronic/mortality , Renal Insufficiency, Chronic/mortality , Aged , Aged, 80 and over , Cohort Studies , Female , Hospitalization/statistics & numerical data , Humans , Inpatients , Japan/epidemiology , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/pathology , Length of Stay/statistics & numerical data , Male , Middle Aged , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/pathology , Retrospective Studies , Risk Factors
17.
Kidney Int Rep ; 6(5): 1346-1354, 2021 May.
Article in English | MEDLINE | ID: mdl-34013113

ABSTRACT

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.

18.
Ther Apher Dial ; 25(4): 425-431, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33887113

ABSTRACT

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.


Subject(s)
Blood Component Removal/methods , Fibrinogen , Hematocrit , Immunoglobulins/blood , Female , Humans , Male , Middle Aged , Plasma Volume , Retrospective Studies
19.
Intern Med ; 60(3): 457-461, 2021 Feb 01.
Article in English | MEDLINE | ID: mdl-33328409

ABSTRACT

We herein report a case of severe coronavirus disease 2019 (COVID-19) in which high-dose intravenous immunoglobulin (IVIg) treatment achieved significant clinical improvement of deterioration of pulmonary inflammation after temporary clinical improvement. In the present case, clinical and radiological deterioration occurred despite a decrease in viral load, suggesting that deterioration was caused by reactivation of proinflammatory factors, such as tumor necrosis factor-α and interleukin-6, rather than direct viral effects. IVIg treatment may provide not only immunosuppressive effects but also inhibition of proinflammatory cytokines, indicating that treatment including IVIg may be effective by inhibiting cytokine storm in severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection.


Subject(s)
COVID-19/therapy , Immunoglobulins, Intravenous/administration & dosage , Respiratory Insufficiency/therapy , SARS-CoV-2/isolation & purification , COVID-19/complications , Cytokine Release Syndrome/prevention & control , Cytokines/drug effects , Humans , Ivermectin/therapeutic use , Lung/diagnostic imaging , Lung/pathology , Male , Middle Aged , Radiography, Thoracic , SARS-CoV-2/immunology , Viral Load
20.
BMC Nephrol ; 21(1): 357, 2020 08 20.
Article in English | MEDLINE | ID: mdl-32819288

ABSTRACT

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.


Subject(s)
Deglutition/physiology , Frailty/epidemiology , Mastication/physiology , Motor Skills/physiology , Mouth/physiopathology , Renal Insufficiency, Chronic/epidemiology , Speech/physiology , Aged , Aged, 80 and over , Cross-Sectional Studies , Dentition , Female , Frailty/physiopathology , Glomerular Filtration Rate , Humans , Male , Middle Aged , Renal Insufficiency, Chronic/metabolism
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