Publications by authors named "Kazuhiko Tsuruya"

340 Publications

Renal histological continuum of TAFRO syndrome: A case report and literature review.

Clin Nephrol 2021 Dec 2. Epub 2021 Dec 2.

TAFRO syndrome is a rare systemic inflammatory disorder that is characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly. Progressive renal involvement is frequently observed in patients with TAFRO syndrome, and the renal histological findings remain limited. A 52-year-old man with thymoma that was detected by chest computed tomography was admitted to our hospital because of dyspnea and abdominal distension. He had a rapid reappearance of pleural and abdominal effusion following repeated puncture with inflammation and kidney involvement on admission. Renal histology showed glomerular lesions denoting diffuse endocapillary proliferative glomerulonephritis, without any crescentic glomeruli, which was diagnosed as thrombotic microangiopathy (TMA)-like glomerulopathy. Together with histological findings of thymoma and progressively emergent thrombocytopenia, the patient was diagnosed with TAFRO syndrome. Corticosteroid and tocilizumab administration ameliorated the renal insufficiency and his clinical condition relevant to TAFRO syndrome, but there was a rapid concomitant appearance of massive proteinuria. A second renal biopsy revealed membranoproliferative glomerulonephritis (MPGN)-like glomerulopathy with de novo sclerosing and crescentic glomeruli development. Patients with TAFRO syndrome show glomerular lesions that are consistent with TMA- or MPGN-like lesions, but their clinical data are similar between the two glomerulopathies. It remains controversial whether the two are a histopathological continuum or distinct diseases. This case shows that glomerular lesions had TMA-like glomerulopathy in the acute stage of TAFRO syndrome, while the histopathology pattern favors MPGN in the chronic stage, as confirmed by repeated renal biopsies. TAFRO syndrome disease activity may not always correspond to that of glomerulopathy that is associated with TAFRO syndrome.
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http://dx.doi.org/10.5414/CN110290DOI Listing
December 2021

Blood Pressure, Hypertension and The Risk of Aortic Dissection Incidence and Mortality: results from the Japan-Specific Health Checkups Study, the UK Biobank Study and a Meta-analysis of Cohort Studies.

Circulation 2021 Nov 8. Epub 2021 Nov 8.

Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St. Mary's Campus, Norfolk Place, London, UK; Department of Nutrition, Bjørknes University College, Oslo, Norway; Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway; Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

Hypertension or elevated blood pressure (BP) is an important risk factor for aortic dissection (AD); however, few prospective studies concerning this topic have been published. We investigated the association between hypertension/elevated BP and AD in two cohorts and conducted a meta-analysis of published prospective studies, including these two studies. We analyzed data from the Japan Specific Health Checkups (J-SHC) Study and UK Biobank, which prospectively followed 534,378 and 502,424 participants, respectively. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association of hypertension/elevated BP with AD incidence in the UK Biobank and AD mortality in the J-SHC Study. In the meta-analysis, summary relative risks (RRs) were calculated using random effects models. A potential nonlinear dose-response relationship between BP and AD was tested using fractional polynomial models, and the best-fitting second-order fractional polynomial regression model was determined. In the J-SHC Study and UK Biobank, there were 84 and 182 ADs during 4- and 9-year follow-up, and the adjusted HRs of AD were 3.57 (95% CI, 2.17-6.11) and 2.68 (95% CI: 1.78-4.04) in hypertensive individuals, 1.33 (95% CI: 1.05-1.68) and 1.27 (95% CI: 1.11-1.48) per 20-mmHg increase in systolic BP (SBP), and 1.67 (95% CI: 1.40-2.00) and 1.66 (95% CI: 1.46-1.89) per 10-mmHg increase in diastolic BP (DBP), respectively. In the meta-analysis, the summary RRs were 3.07 (95% CI 2.15-4.38, I2=76.7%, n=7 studies, 2,818 ADs, 4,563,501 participants) for hypertension and 1.39 (95% CI: 1.16-1.66, I2=47.7%, n=3) and 1.79 (95% CI: 1.51-2.12, I2=57.0%, n=3) per 20-mmHg increase in SBP and per 10-mmHg in DBP, respectively. The AD risk showed a strong, positive dose-response relationship with SBP and even more so with DBP. The risk of AD in the nonlinear dose-response analysis was significant at SBP >132 mmHg and DBP >75 mmHg. Hypertension and elevated SBP and DBP are associated with a high risk of AD. The risk of AD was positively dose-dependent, even within the normal BP range. These findings provide further evidence for the optimization of BP to prevent AD.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.121.056546DOI Listing
November 2021

External Validation of a Prediction Model for Acute Kidney Injury Following Noncardiac Surgery.

JAMA Netw Open 2021 Oct 1;4(10):e2127362. Epub 2021 Oct 1.

Department of Nephrology, Nara Medical University, Kashihara, Nara, Japan.

Importance: The Simple Postoperative AKI Risk (SPARK) index is a prediction model for postoperative acute kidney injury (PO-AKI) in patients undergoing noncardiac surgery. External validation has not been performed.

Objective: To externally validate the SPARK index.

Design, Setting, And Participants: This single-center retrospective cohort study included adults who underwent noncardiac surgery under general anesthesia from 2007 to 2011. Those with obstetric or urological surgery, estimated glomerular filtration rate (eGFR) of less than 15 mL/min/1.73 m2, preoperative dialysis, or an expected surgical duration of less than 1 hour were excluded. The study was conducted at Nara Medical University Hospital. Data analysis was conducted from January to July 2021.

Exposures: Risk factors for AKI included in SPARK index.

Main Outcomes And Measures: PO-AKI, defined as an increase in serum creatinine of at least 0.3 mg/dL within 48 hours or 150% compared with preoperative baseline value or urine output of less than 0.5 mL/kg/h for at least 6 hours within 1 week after surgery, and critical AKI, defined as either AKI stage 2 or greater and/or any AKI connected to postoperative death or requiring kidney replacement therapy before discharge. The discrimination and calibration of the SPARK index were examined with area under the receiver operating characteristic curves (AUC) and calibration plots, respectively.

Results: Among 5135 participants (2410 [46.9%] men), 303 (5.9%) developed PO-AKI, and 137 (2.7%) developed critical AKI. Compared with the SPARK cohort, participants in our cohort were older (median [IQR] age, 56 [44-66] years vs 63 [50-73] years), had lower baseline eGFR (median [IQR], 82.1 [71.4-95.1] mL/min/1.73 m2 vs 78.2 [65.6-92.2] mL/min/1.73 m2), and had a higher prevalence of comorbidities (eg, diabetes: 3956 of 51 041 [7.8%] vs 802 [15.6%]). The incidence of PO-AKI and critical AKI increased as the scores on the SPARK index increased. For example, 10 of 593 participants (1.7%) in SPARK class A, indicating lowest risk, experienced PO-AKI, while 53 of 332 (16.0%) in SPARK class D, indicating highest risk, experienced PO-AKI. However, AUCs for PO-AKI and critical AKI were 0.67 (95% CI, 0.63-0.70) and 0.62 (95% CI, 0.57-0.67), respectively, and the calibration was poor (PO-AKI: y = 0.24x + 3.28; R2 = 0.86; critical AKI: y = 0.20x + 2.08; R2 = 0.51). Older age, diabetes, expected surgical duration, emergency surgery, renin-angiotensin-aldosterone system blockade use, and hyponatremia were not associated with PO-AKI in our cohort, resulting in overestimation of the predicted probability of AKI in our cohort.

Conclusions And Relevance: In this study, the incidence of PO-AKI increased as the scores on the SPARK index increased. However, the predicted probability might not be accurate in cohorts with older patients with more comorbidities.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.27362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8524308PMC
October 2021

Association between Multimorbidity and Kidney Function among Patients with Non-Dialysis-Dependent CKD.

J Atheroscler Thromb 2021 Oct 2. Epub 2021 Oct 2.

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University.

Aim: Individuals with chronic kidney disease (CKD) have a high prevalence of comorbidities, including cardiovascular disease (CVD) and its risk factors. However, epidemiological results to assess the association between multimorbidity and kidney function among the CKD population remains limited.

Methods: We performed a cross-sectional analysis of the association between 23 comorbid conditions and reduced kidney function in 4,476 patients with non-dialysis-dependent CKD enrolled in a multicenter cohort in Japan. Reduced kidney function was defined as an estimated glomerular filtration rate of ≤ 60 mL/min/1.73 m.

Results: The mean age of patients was 67 years (male, 56.0%). The prevalence of hypertension, diabetes mellitus, dyslipidemia, prior CVD, cancer, and bone fracture, which are the major comorbidities, was 83.3%, 28.7%, 45.9%, 23.3%, 12.7%, and 6.3%, respectively. Multivariable-adjusted analyses revealed that age, male sex, hypertension, dyslipidemia, prior CVD, body mass index, urinary protein excretion, and underlying kidney disease were independent factors associated with reduced kidney function. Importantly, the odds ratios (ORs) for reduced kidney function increased linearly as the number of major comorbid conditions increased (OR for 1-2 conditions: 2.22, 95% confidence interval [CI]: 1.65-2.97; OR for 3-4 conditions: 3.04, 95% CI: 2.12-4.37; OR for ≥ 5 conditions: 4.37, 95% CI: 1.75-10.9). The upward trend in OR was more pronounced with cardiovascular comorbidities but not significant with non-cardiovascular comorbidities.

Conclusions: In conclusion, we observed an independent association between cardiovascular comorbidity and its risk factors and reduced kidney function. The results of this study highlight the importance of managing multimorbidity among patients with CKD.
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http://dx.doi.org/10.5551/jat.62900DOI Listing
October 2021

Kidney Outcomes Associated With SGLT2 Inhibitors Versus Other Glucose-Lowering Drugs in Real-world Clinical Practice: The Japan Chronic Kidney Disease Database.

Diabetes Care 2021 Nov 30;44(11):2542-2551. Epub 2021 Sep 30.

Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan.

Objective: Randomized controlled trials have shown kidney-protective effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors, and clinical practice databases have suggested that these effects translate to clinical practice. However, long-term efficacy, as well as whether the presence or absence of proteinuria and the rate of estimated glomerular filtration rates (eGFR) decline prior to SGLT2 inhibitor initiation modify treatment efficacy among type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) patients, is unknown.

Research Design And Methods: Using the Japan Chronic Kidney Disease Database (J-CKD-DB), a nationwide multicenter CKD registry, we developed propensity scores for SGLT2 inhibitor initiation, with 1:1 matching with patients who were initiated on other glucose-lowering drugs. The primary outcome included rate of eGFR decline, and the secondary outcomes included a composite outcome of 50% eGFR decline or end-stage kidney disease.

Results: At baseline, mean age at initiation of the SGLT2 inhibitor ( = 1,033) or other glucose-lowering drug ( = 1,033) was 64.4 years, mean eGFR was 68.1 mL/min per 1.73 m, and proteinuria was apparent in 578 (28.0%) of included patients. During follow-up, SGLT2 inhibitor initiation was associated with reduced eGFR decline (difference in slope for SGLT2 inhibitors vs. other drugs 0.75 mL/min/1.73 m per year [0.51 to 1.00]). During a mean follow-up of 24 months, 103 composite kidney outcomes occurred: 30 (14 events per 1,000 patient-years) among the SGLT2 inhibitors group and 73 (36 events per 1,000 patient-years) among the other drugs group (hazard ratio 0.40, 95% CI 0.26-0.61). The benefit provided by SGLT2 inhibitors was consistent irrespective of proteinuria and rate of eGFR decline before initiation of SGLT2 inhibitors ( ≥ 0.35).

Conclusions: The benefits of SGLT2 inhibitors on kidney function as observed in clinical trials translate to patients treated in clinical practice with no evidence that the effects are modified by the underlying rate of kidney function decline or the presence of proteinuria.
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http://dx.doi.org/10.2337/dc21-1081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8546274PMC
November 2021

Autophagy gene regulates albumin transcytosis in renal tubule epithelial cells.

Am J Physiol Renal Physiol 2021 11 20;321(5):F572-F586. Epub 2021 Sep 20.

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Receptor-mediated albumin transport in proximal tubule epithelial cells (PTECs) is important to control proteinuria. Autophagy is an evolutionarily conserved degradation pathway, and its role in intracellular trafficking through interactions with the endocytic pathway has recently been highlighted. Here, we determined whether autophagy regulates albumin transcytosis in PTECs and suppresses albumin-induced cytotoxicity using human proximal tubule (HK-2) cells. The neonatal Fc receptor (FcRn), a receptor for albumin transcytosis, is partially colocalized with autophagosomes. Recycling of FcRn was attenuated, and FcRn accumulated in autophagy-related 7 () knockdown HK-2 cells. Colocalization of FcRn with RAB7-positive late endosomes and RAB11-positive recycling endosomes was reduced in knockdown cells, which decreased recycling of FcRn to the plasma membrane. In or autophagy-related 5 () knockdown cells and or knockout mouse embryonic fibroblasts, albumin transcytosis was significantly reduced and intracellular albumin accumulation was increased. Finally, the release of kidney injury molecule-1, a marker of tubule injury, from or knockdown cells was increased in response to excess albumin. In conclusion, suppression of autophagy in tubules impairs FcRn transport, thereby inhibiting albumin transcytosis. The resulting accumulation of albumin induces cytotoxicity in tubules. Albumin transport in proximal tubule epithelial cells (PTECs) is important to control proteinuria. The neonatal Fc receptor (FcRn), a receptor for albumin transcytosis, is partially colocalized with autophagosomes. Recycling of FcRn to the plasma membrane was decreased in autophagy-related 7 () knockdown cells. In addition, albumin transcytosis was decreased in or autophagy-related 5 () knockdown PTECs. Finally, release of kidney injury molecule-1 from or knockdown cells was increased in response to excess albumin.
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http://dx.doi.org/10.1152/ajprenal.00172.2021DOI Listing
November 2021

A case of peritoneal dialysis-related peritonitis caused by dialysate leakage with successful treatment by intravenous and intraperitoneal antibiotic therapy.

CEN Case Rep 2021 Sep 12. Epub 2021 Sep 12.

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.

Dialysate leakage is one of the causes of peritoneal dialysis (PD)-related peritonitis. The rate of catheter removal in PD-related peritonitis caused by dialysate leakage (PDPDL) is high, and the correct treatment is unclear. We experienced a case of PDPDL that was treated with intravenous and intraperitoneal antibiotic therapy. A 44-year-old Japanese man had high glucose discharge from the exit site after 14 days of initiating PD, and he had a fever and cloudy effluent with a high white cell count. We diagnosed him with PDPDL and began to administer vancomycin and ceftazidime intraperitoneally. However, the peritonitis could not be ameliorated. A culture examination showed Staphylococcus aureus from the effluent of peritoneal cavity and exit site cultures. We began intraperitoneal cefazolin administration according to a drug susceptibility test, but the effluent cell count remained high. As we added intravenous cefazolin administration, his symptoms and cloudy effluent improved, and the effluent cell count normalized. He has not developed any recurrence of dialysate leakage or peritonitis. Our findings suggest that PD-related peritonitis accompanied by other infectious sites, such as PDPDL, should be treated with additional intravenous antibiotic therapy to taking effect on the infectious sites except for peritoneum and to keep plasma concentration of antibiotics sufficient especially in cases with preserved residual kidney function.
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http://dx.doi.org/10.1007/s13730-021-00644-4DOI Listing
September 2021

One-Year Change in Diastolic Blood Pressure and Aortic Disease-Related Mortality in a Japanese General Population Aged 50-75 Years.

Circ J 2021 Nov 3;85(12):2222-2231. Epub 2021 Sep 3.

The Japan Specific Health Checkups study (J-SHC study) Group.

Background: Aortic diseases (ADs), including aortic dissection, aortic aneurysm, and aortic rupture, are fatal diseases with extremely high mortality rates. Hypertension has been reported to be associated with AD development; however, it remains unclear whether a 1-year change in diastolic blood pressure (DBP) is a risk factor for AD-related mortality in the general population.Methods and Results:This study used a nationwide database of 235,076 individuals (aged 50-75 years) who participated in the annual "Specific Health Check and Guidance in Japan" for 2 consecutive years between 2008 and 2010. There were 55 AD-related deaths during the follow-up period of 1,770 days. All subjects were divided into 4 groups based on the baseline DBP and change in DBP at 1 year: persistent high DBP, increasing DBP, decreasing DBP, and normal DBP. Kaplan-Meier analysis demonstrated that the persistent high DBP group had the greatest risk among the 4 groups. Multivariate Cox proportional hazard regression analysis demonstrated that both DBP and 1-year change in DBP were significantly associated with AD-related deaths. The prediction capacity was significantly improved by the addition of 1-year change in DBP to confounding risk factors.

Conclusions: This study demonstrated for the first time that a 1-year change in DBP was associated with AD-related deaths in the general population. Monitoring changes in DBP are of critical importance in the primary prevention of AD-related deaths in apparently healthy subjects aged 50-75 years.
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http://dx.doi.org/10.1253/circj.CJ-21-0514DOI Listing
November 2021

Association between the urinary sodium-to-potassium ratio and renal outcomes in patients with chronic kidney disease: a prospective cohort study.

Hypertens Res 2021 Nov 3;44(11):1492-1504. Epub 2021 Sep 3.

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

A higher urinary sodium-to-potassium (UNa/K) ratio has been reported to be associated with high blood pressure and subsequent cardiovascular events. However, the association between the UNa/K ratio and renal outcomes remains uncertain. We prospectively investigated the association between the UNa/K ratio and renal outcomes in patients with chronic kidney disease (CKD). We enrolled 716 patients with CKD, and 24-h urinary sodium and potassium excretion were measured. Patients were divided into UNa/K ratio tertiles (T1-T3). Endpoints were defined as a composite of doubling of serum creatinine (SCr), end-stage kidney disease (ESKD), or death and a composite of doubling of SCr or ESKD (added as an alternative outcome). We investigated the association between the UNa/K ratio and renal outcomes using a Cox proportional hazards model. During a median follow-up of 2.3 years, doubling of SCr, ESKD, or death and doubling of SCr or ESKD occurred in 332 and 293 patients, respectively. After adjustment for covariates including potentially confounding variables such as plasma renin activity, plasma aldosterone concentration, and B-type natriuretic peptide, the hazard ratios (HRs) (95% confidence intervals [CIs]) for the composite of doubling of SCr, ESKD, or death for T2 and T3 were 1.44 (1.06-1.96) and 1.59 (1.14-2.21), respectively, compared with T1. Additionally, compared with T1, the highest tertile (T3) of the UNa/K ratio was associated with a composite of doubling of SCr or ESKD (HR 1.55, 95% CI 1.09-2.20). A higher UNa/K ratio was independently associated with poor renal outcomes in patients with CKD.
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http://dx.doi.org/10.1038/s41440-021-00741-yDOI Listing
November 2021

Association of dialysis-related amyloidosis with lower quality of life in patients undergoing hemodialysis for more than 10 years: The Kyushu Dialysis-Related Amyloidosis Study.

PLoS One 2021 24;16(8):e0256421. Epub 2021 Aug 24.

Fukuoka Renal Clinic, Fukuoka, Japan.

Background: Dialysis-related amyloidosis (DRA) commonly develops in patients undergoing long-term dialysis and can lead to a decline in activities of daily living and quality of life (QOL), mainly owing to orthopedic complications.

Methods: First, we determined utility scores of the EuroQol 5-Dimensions 3-Levels (EQ-5D-3L) questionnaire in 1,323 patients with DRA who had undergone dialysis for more than 10 years and compared the score between those with and without DRA. Second, a 2-year follow-up was also performed, in which patients were divided into three groups: those complicated by DRA from the beginning, those with newly developed DRA within the 2-year period, and those not complicated by DRA throughout the survey period; changes in the EQ-5D-3L utility score were compared. In the group already complicated by DRA at the survey baseline, changes in the EQ-5D-3L utility score were compared according to the dialysis treatment method.

Results: A total of 1,314 and 931 patients were included in the first and second studies, respectively. EQ-5D-3L utility scores among patients diagnosed with DRA were significantly lower than scores in those not diagnosed with DRA. The reduction in the EQ-5D-3L utility score over the 2-year follow-up was significantly greater in patients newly complicated by DRA during the follow-up period after enrollment but not in those complicated by DRA from the beginning, as compared with patients not complicated by DRA throughout the survey period. The reduction in utility score tended to be lower in patients routinely treated with a β2-microglobulin adsorption column than in untreated patients with DRA.

Conclusion: Complication by DRA in patients undergoing long-term hemodialysis was significantly associated with a decline in QOL.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0256421PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384206PMC
August 2021

Trace proteinuria as a risk factor for cancer death in a general population.

Sci Rep 2021 08 19;11(1):16890. Epub 2021 Aug 19.

Steering Committee of Research on Design of the Comprehensive Health Care System for Chronic Kidney Disease (CKD), Based on the Individual Risk Assessment by Specific Health Checkup, The Ministry of Health, Labour and Welfare of Japan, Fukushima, Japan.

Growing evidence has demonstrated an association between nondialysis chronic kidney disease and cancer incidence, although the association between trace proteinuria and cancer death remains unclear. The aim of this study was to investigate the association between trace proteinuria and cancer death in a community-based population in Japan. This was a prospective cohort study of 377,202 adults who participated in the Japanese Specific Health Check and Guidance System from 2008 to 2011. Exposure was dipstick proteinuria categorized as - (negative), ± (trace), 1 + (mild), or ≥ 2 + (moderate to heavy). Outcome was cancer death based on information from the national database of death certificates. Adjusted Cox hazard regression model was used to evaluate the associations between trace proteinuria and cancer death. During median follow-up of 3.7 years, 3056 cancer deaths occurred, corresponding to overall cancer death rate of 21.7/10,000 person-years. In the fully adjusted model, risk of cancer death increased significantly in each successive category of proteinuria: hazard ratio (HR) (95% confidence interval [95% CI]) for risk of cancer death was 1.16 (1.03-1.31), 1.47 (1.27-1.70), and 1.61 (1.33-1.96) for trace, mild, and moderate to heavy proteinuria, respectively. Sensitivity analyses revealed a similar association between trace proteinuria and cancer death, and participants with trace proteinuria had greater risk of mortality from hematological cancers (HR: 1.59 [95% CI: 1.09-2.31]). Both mild to heavy and trace proteinuria were significantly associated with risk of mortality from cancer in a general population.
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http://dx.doi.org/10.1038/s41598-021-96388-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8376860PMC
August 2021

Association of the nutritional risk index for Japanese hemodialysis patients with long-term mortality: The Q-Cohort Study.

Clin Exp Nephrol 2021 Aug 17. Epub 2021 Aug 17.

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 8128582, Japan.

Background: Protein-energy wasting (PEW) is a risk factor for mortality in patients undergoing hemodialysis. Recently, a nutritional risk index for Japanese hemodialysis patients (NRI-JH) has been proposed as a surrogate index of PEW. However, no study has determined the association of the NRI-JH with long-term mortality in patients undergoing hemodialysis. Furthermore, the validity of the NRI-JH has not been confirmed.

Methods: In total, 3046 patients undergoing hemodialysis and registered in the Q-Cohort Study were followed up for 10 years. The NRI-JH was calculated on the basis of body mass index and serum levels of albumin, total cholesterol, and creatinine. The patients were divided into four groups according to the NRI-JH scores: 0-3 (G1, n = 1343), 4-7 (G2, n = 1136), 8-10 (G3, n = 321), and 11-13 (G4, n = 246). We examined the association between the NRI-JH and the 4-year and 10-year risks of all-cause, cardiovascular, and infection-related deaths using the Cox proportional hazards model.

Results: During the follow-up period, 647 patients died during the first 4 years, and 1503 patients died within 10 years. The 4-year prognosis was analyzed and compared with the lowest NRI-JH score group. Multivariable-adjusted hazard ratios (95% confidence intervals) for all-cause death were 1.93 (1.57-2.38), 2.68 (2.05-3.50), and 3.16 (2.40-4.16) in the G2, G3, and G4 groups, respectively. Similarly, a higher NRI-JH score was associated with an increased risk of cardiovascular and infection-related deaths.

Conclusion: A higher NRI-JH score was associated with an increased risk of long-term mortality in patients undergoing maintenance hemodialysis.

Trial Registration: The study protocol was registered in the University Hospital Medical Information Network (UMIN) clinical trial registry (UMIN ID: 000000556).
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http://dx.doi.org/10.1007/s10157-021-02124-6DOI Listing
August 2021

Association between chronic kidney disease and new-onset dyslipidemia: The Japan Specific Health Checkups (J-SHC) study.

Atherosclerosis 2021 09 4;332:24-32. Epub 2021 Aug 4.

Department of Nephrology, Nara Medical University, Kashihara, Nara, Japan; Steering Committee of The Japan Specific Health Checkups (J-SHC) Study Group, Fukushima, Japan.

Background And Aims: Dyslipidemias are common among patients with chronic kidney disease (CKD) and are a major risk factor for cardiovascular disease. This study aimed to investigate the association between early-stage CKD and new-onset dyslipidemia for each lipid profile.

Methods: This nationwide longitudinal study included data from the Japan Specific Health Checkups (J-SHC) Study. New-onset dyslipidemia was indicated by hypertriglyceridemia (High-TG; ≥150 mg/dL), hyper-LDL cholesterolemia (High-LDL-C; ≥140 mg/dL), or hypo-HDL chelesterolemia (Low-HDL-C; <40 mg/dL) levels according to the guideline of Japan Atherosclerosis Society, or High-TG/HDL-C ratio (≥3.5) which was a good predictor of atherosclerosis. The incidence of new-onset dyslipidemia was compared between participants with and without CKD. Survival curves were used to analyze the incidence of each dyslipidemia.

Results: Of 289,462 participants with a median follow-up period of 3 years, the incidence of High-TG, High-LDL-C, Low-HDL-C, and High-TG/HDL-C ratios were 64.4/1000 person-years, 83.1/1000 person-years, 14.5/1000 person-years, and 39.6/1000 person-years, respectively. The adjusted hazard ratios (95% confidence intervals) for High-TG, High-LDL-C, Low-HDL-C, and High-TG/HDL-C ratio were 1.09 (1.05-1.13), 0.99 (0.95-1.04), 1.12 (1.05-1.18), and 1.14 (1.09-1.18), respectively, in CKD participants as compared to non-CKD participants. Decreased eGFR and presence of proteinuria were independently associated with higher risks for new-onset of High-TG, Low-HDL-C, and High-TG/HDL-C ratios.

Conclusions: CKD was associated with a higher risk of new-onset High-TG, Low-HDL-C, and High-TG/HDL-C ratios, but not High-LDL-C, in the general population. These CKD-specific lipid abnormalities may explain the residual risk for CKD-related cardiovascular disease.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.08.004DOI Listing
September 2021

Clinical epidemiological analysis of cohort studies investigating the pathogenesis of kidney disease.

Clin Exp Nephrol 2021 Aug 10. Epub 2021 Aug 10.

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

In recent years, large cohort studies of patients with chronic kidney disease (CKD) have been established all over the world. These studies have attempted to analyze the pathogenesis of CKD using a large body of published evidence. The design of cohort studies is characterized by the measurement of the exposure prior to the occurrence of the outcome, which has the advantage of clarifying the temporal relationship between predictors and outcomes and estimating the strength of the causal relationship between predictors and multiple outcomes. Recent advances in biostatistical analysis methods, such as propensity scores and risk prediction models, are facilitating causal inference using higher quality evidence with greater precision in observational studies. In this review, we will discuss clinical epidemiological research of kidney disease based on the analysis of observational cohort data sets, with a focus on our previous studies.
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http://dx.doi.org/10.1007/s10157-021-02121-9DOI Listing
August 2021

Association of initial prednisolone dose with remission, relapse, and infectious complications in adult-onset minimal change disease.

Clin Exp Nephrol 2021 Aug 7. Epub 2021 Aug 7.

Department of Nephrology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan.

Background: A dose of 0.5-1 mg/kg/day of prednisolone (PSL) is administered for the initial treatment of minimal change disease (MCD). However, little is known about the optimal PSL dose for the initial treatment of MCD.

Methods: We conducted a retrospective multicenter cohort study of treatment-naive adult patients with MCD diagnosed by renal biopsy from 1981 to 2015 in whom PSL monotherapy was performed as the initial treatment. The exposure of interest was an initial median PSL dose of < 0.63 mg/kg/day (Group L) compared to ≥ 0.63 mg/kg/day (Group H). Cumulative remission and relapse after remission were compared between these groups using Cox regression adjusted for baseline characteristics.

Results: Ninety-one patients met the inclusion criteria. During a median follow-up of 2.98 years, 87 (95.6%) patients achieved complete remission, and 47.1% relapsed after remission. There was no significant difference in the remission rate between the groups at 4 weeks of follow-up (66.7 vs. 82.6%). The median time to remission in Group L was comparable to that in Group H (17.0 vs. 14.0 days). A multivariable Cox hazard model revealed that the initial PSL dose was not a significant predictor of remission. The cumulative steroid doses at 6 months, 1 year, and 2 years after treatment initiation were significantly lower in Group L than in Group H.

Conclusion: The initial PSL dose was not associated with time to remission, remission rate, time to relapse, or relapse rate. Therefore, a low initial steroid dose may be sufficient to achieve remission.
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http://dx.doi.org/10.1007/s10157-021-02119-3DOI Listing
August 2021

Weight loss reduces the incidence of dipstick proteinuria: a cohort study from the Japanese general population.

Clin Exp Nephrol 2021 Dec 17;25(12):1329-1335. Epub 2021 Jul 17.

The Steering Committee for "Japan Specific Health Checkups Study (J-SHC Study) Group", Fukushima, Japan.

Background: Though elimination of obesity is one of main therapeutic goal for lifestyle-related diseases, the impact of appropriate weight loss on reduction of the incidence of proteinuria in the general population is still unclear.

Methods: The study cohort was based on a general population of 9,33,490 from 40 to 74 years of age who had undergone annual specific health checkups. The subjects who were finally included were the 2,74,598 people for whom all the data necessary for this study were available. The incidence of proteinuria in this study was defined as negative proteinuria at the primary and secondary survey years, and newly developed proteinuria during subsequent follow-up years.

Results: Whereas people with rapidly decreased weight tended to have a high incidence of proteinuria in the underweight (BMI < 18.5 kg/m) and normal weight (18.5-24.9 kg/m) groups, the obese group (≥ 25.0 kg/m) with rapidly decreased weight had a lower incidence compared to those with stable weight. In the obese population, a rapid decline of BMI (- 1 to - 5 kg/m per year) was associated with a reduced risk (hazard ratio [95% confidence interval]; 0.89 [0.80-0.98], P = 0.02) of proteinuria.

Conclusions: Weight reduction can lead to a risk reduction of 11% in the incidence of proteinuria in obese Japanese adults. This is the first study to report the effects of weight reduction on the early phase of chronic kidney disease in obesity relevant to the characteristics of the Japanese general population. The present findings might have a role in renal health promotion in Japan.
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http://dx.doi.org/10.1007/s10157-021-02114-8DOI Listing
December 2021

One-year change in plasma volume and mortality in the Japanese general population: An observational cohort study.

PLoS One 2021 13;16(7):e0254665. Epub 2021 Jul 13.

Steering Committee of Research on Design of the Comprehensive Health Care System for Chronic Kidney Disease (CKD) Based on the Individual Risk Assessment by Specific Health Check, Fukushima, Japan.

Background: Changes in plasma volume, a marker of plasma volume expansion and contraction, are gaining attention in the field of cardiovascular disease because of its role in the prevention and management of heart failure. However, it remains unknown whether a 1-year change in plasma volume is a risk factor for all-cause, cardiovascular, and non-cardiovascular mortality in the general population.

Methods And Results: We used a nationwide database of 134,291 subjects (age 40-75 years) who participated in the annual "Specific Health Check and Guidance in Japan" check-up for 2 consecutive years between 2008 and 2011. A 1-year change in plasm volume was calculated using the Strauss-Davis-Rosenbaum formula. There were 220 cardiovascular deaths, 1,001 non-cardiovascular deaths including 718 cancer deaths, and 1,221 all-cause deaths during the follow-up period of 3.9 years. All subjects were divided into quintiles based on the 1-year change in plasma volume. Kaplan-Meier analysis demonstrated that the highest 5th quintile had the greatest risk among the five groups. Multivariate Cox proportional hazard regression analysis demonstrated that a 1-year change in plasma volume was an independent risk factor for all-cause, cardiovascular, non-cardiovascular, and cancer deaths. The addition of a 1-year change in plasma volume to cardiovascular risk factors significantly improved the C-statistic, net reclassification, and integrated discrimination indexes.

Conclusions: Here, we have demonstrated for the first time that a 1-year change in plasma volume could be an additional risk factor for all-cause, cardiovascular, and non-cardiovascular (mainly cancer) mortality in the general population.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254665PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277070PMC
November 2021

Association of blood pressure after peritoneal dialysis initiation with the decline rate of residual kidney function in newly-initiated peritoneal dialysis patients.

PLoS One 2021 8;16(7):e0254169. Epub 2021 Jul 8.

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Background: Lower blood pressure (BP) levels are linked to a slower decline of kidney function in patients with chronic kidney disease (CKD) without kidney replacement therapy. However, there are limited data on this relation in peritoneal dialysis (PD) patients. Here we evaluated the association of BP levels with the decline of residual kidney function (RKF) in a retrospective cohort study.

Methods: We enrolled 228 patients whose PD was initiated between 1998 and 2014. RKF was measured as the average of creatinine and urea clearance in 24-hr urine collections. We calculated the annual decline rate of RKF by determining the regression line for individual patients. RKF is thought to decline exponentially, and thus we also calculated the annual decline rate of logarithmic scale of RKF (log RKF). We categorized the patients' BP levels at 3 months after PD initiation (BP3M) into four groups (Optimal, Normal & High normal, Grade 1 hypertension, Grade 2 & 3 hypertension) according to the 2018 European Society of Cardiology and European Society of Hypertension Guidelines for the management of arterial hypertension.

Results: The unadjusted, age- and sex-adjusted, and multivariable-adjusted decline rate of RKF and log RKF decreased significantly with higher BP3M levels (P for trend <0.01). Compared to those of the Optimal group, the multivariable-adjusted odds ratios (95% confidence interval) for the faster side of the median decline rate of RKF and log RKF were 4.04 (1.24-13.2) and 5.50 (1.58-19.2) in the Grade 2 and 3 hypertension group, respectively (p<0.05).

Conclusions: Higher BP levels after PD initiation are associated with a faster decline in RKF among PD patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254169PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266121PMC
November 2021

The distribution of eGFR by age in a community-based healthy population: the Japan specific health checkups study (J-SHC study).

Clin Exp Nephrol 2021 Dec 3;25(12):1303-1310. Epub 2021 Jul 3.

The Japan Specific Health Checkups Study (J-SHC Study) Group, Fukushima, Japan.

Background: Renal function gradually declines with age. However, the association between changes in renal function and healthy aging has not been determined. This study examined the distribution of estimated glomerular filtration rate (eGFR) values in healthy subjects by age using large-scale cross-sectional data of health check-up participants in Japan.

Methods: Among the 394,180 health check-up participants, 75,217 (19.1%) subjects without hypertension, diabetes, hyperlipidemia, obesity, proteinuria, smoking, past history of cardiovascular diseases, and renal failure/not undergoing dialysis were included in the healthy group. The distribution of eGFR values was determined at each age between 39 and 74 years.

Results: in healthy subjects, the mean (± 2 SD range) values of eGFR (mL/min/1.73 m) at ages 40, 50, 60, and 70 were 88.0 (55.4-121.7), 82.3 (51.2-113.3), 77.8 (48.1-107.6), and 72.9 (44.7-101.1), respectively. The difference in the mean eGFR by age was almost constant across all ages. In the linear regression analysis adjusted for sex, the regression coefficient of mean eGFR for a one-year increase in age was -0.46 mL/min/1.73 m in healthy subjects (P < 0.001). By sex, the distribution of eGFR and the 1-year change in eGFR showed similar results in both men and women.

Conclusions: Renal function slowly declined with age in a healthy population; however, it was relatively preserved until the mid 70 s. This result suggests that a decline in renal function often observed in the elderly does not attribute to aging alone, and further examination might be required to clarify the cause of renal impairment.
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http://dx.doi.org/10.1007/s10157-021-02107-7DOI Listing
December 2021

Serum Alkaline Phosphatase Levels and Increased Risk of Brain Hemorrhage in Hemodialysis Patients: The Q-Cohort Study.

J Atheroscler Thromb 2021 Jun 10. Epub 2021 Jun 10.

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University.

Aim: Elevated serum alkaline phosphatase (ALP) levels have been associated with increased risks of all-cause and cardiovascular mortality in patients receiving hemodialysis. However, little is known about the impact of serum ALP levels on the development of stroke, such as brain hemorrhage and infarction.

Methods: A total of 3,497 patients receiving maintenance hemodialysis registered in the multicenter observational Q-Cohort Study were analyzed. The primary outcomes were the incidences of brain hemorrhage and infarction. The covariate of interest was serum ALP levels. Patients were divided into tertiles based on their serum ALP levels (U/L) at baseline (T1, <69.3; T2, 69.3-98.4; T3, >98.4). The risks of brain hemorrhage, brain infarction, and composite stroke were estimated using Cox proportional hazards models and competing risk models with all-cause death as a competing risk.

Results: A total of 89 patients developed brain hemorrhage and 195 patients developed brain infarction during the 4-year follow-up period. The risk of brain hemorrhage in the highest tertile (T3) was significantly higher than that in the lowest tertile (T1) (multivariable-adjusted hazard ratio [95% confidence interval], 1.93 [1.12-3.35], subdistribution hazard ratio, 1.91 [1.10-3.30]). However, there was no significant association between serum ALP levels and the risk of brain infarction or composite stroke.

Conclusions: Higher serum ALP levels are associated with an increased risk of brain hemorrhage, but not brain infarction, in patients receiving maintenance hemodialysis. High serum ALP level is thus an important risk factor for brain hemorrhage in hemodialysis patients.
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http://dx.doi.org/10.5551/jat.62885DOI Listing
June 2021

Causes of death in patients undergoing maintenance hemodialysis in Japan: 10-year outcomes of the Q-Cohort Study.

Clin Exp Nephrol 2021 Oct 7;25(10):1121-1130. Epub 2021 Jun 7.

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 8128582, Japan.

Background: Although the mortality rate in patients on hemodialysis remains extremely high, detailed information on causes of death over long-term periods is limited. The aim of this study was to clarify the underlying causes of death in patients undergoing maintenance hemodialysis in Japan.

Methods: This was a 10-year, multicenter, observational study of 3528 outpatients undergoing maintenance hemodialysis in Japan. Clinical outcomes were analyzed and causes of death were classified into six broad categories including cardiovascular diseases, infectious diseases, malignant neoplasms, cachexia, trauma/accidents, and other diseases, and more detailed subcategories.

Results: During the 10-year follow-up period, 1748 (49.5%) patients died. The most frequent causes of death were cardiovascular diseases (36.1%), followed by infectious diseases (25.8%) and malignant neoplasms (13.5%). In a detailed classification, sudden death, pulmonary infection, and lung cancer were the most common causes of death in cardiovascular diseases, infectious diseases, and malignant neoplasms, respectively.

Conclusion: Our study determined details on causes of death in Japanese hemodialysis patients during the 10-year follow-up period. Cardiovascular disease, especially sudden death is noticeable cause of death among patients on hemodialysis.
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http://dx.doi.org/10.1007/s10157-021-02089-6DOI Listing
October 2021

Favorable therapeutic efficacy of low-density lipoprotein apheresis for nephrotic syndrome with impaired renal function.

Ther Apher Dial 2021 May 31. Epub 2021 May 31.

Department of Medicine, Diabetes Center, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan.

Many reports have shown the therapeutic efficacy of LDL apheresis (LDL-A) in drug-resistant nephrotic syndrome (NS) for improvement of heavy proteinuria and severely impaired renal function. To obtain comprehensive results in a large number of cases, a post hoc analysis of the Prospective Observational survey on the Long-Term Effects of the LDL-Apheresis on the Drug Resistant Nephrotic Syndrome (POLARIS) study was performed by stratifying enrolled cases according to the pretreatment estimated glomerular filtration rate (eGFR) levels indicating normal (N) (≥60 ml/min/1.73 m ), moderately impaired (M) (≥30 to <60 ml/min/1.73 m ), and severely impaired (S) (<30 ml/min/1.73 m ) renal function. Significant improvements of proteinuria and renal function were found in Group N and, most interestingly, in Group M. A tendency for improvement in proteinuria was found in Group S. Most cases in all groups had not entered end-stage renal disease at 2 years after LDL-A treatment. These results suggest that LDL-A has therapeutic efficacy even in cases in which renal function has declined to 30 ml/min/1.73 m .
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http://dx.doi.org/10.1111/1744-9987.13694DOI Listing
May 2021

Worldwide Early Impact of COVID-19 on Dialysis Patients and Staff and Lessons Learned: A DOPPS Roundtable Discussion.

Kidney Med 2021 Jul-Aug;3(4):619-634. Epub 2021 May 14.

Arbor Research Collaborative for Health, Ann Arbor, MI.

As the worst global pandemic of the past century, coronavirus disease 2019 (COVID-19) has had a disproportionate effect on maintenance dialysis patients and their health care providers. At a virtual roundtable on June 12, 2020, Dialysis Outcomes and Practice Patterns Study (DOPPS) investigators from 15 countries in Asia, Europe, and the Americas described and compared the effects of COVID-19 on dialysis care, with recent updates added. Most striking is the huge difference in risk to dialysis patients and staff across the world. Per-population cases and deaths among dialysis patients vary more than 100-fold across participating countries, mirroring burden in the general population. International data indicate that the case-fatality ratio remains at 10% to 30% among dialysis patients, confirming the gravity of infection, and that cases are much more common among in-center than home dialysis patients. This latter finding merits urgent study because in-center patients often have greater community exposure, and in-center transmission may be uncommon under optimal protocols. Greater telemedicine use is a welcome change here to stay, and our community needs to improve emergency planning and protect dialysis staff from the next pandemic. Finally, the pandemic's challenges have prompted widespread partnering and innovation in kidney care and research that must be sustained after this global health crisis.
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http://dx.doi.org/10.1016/j.xkme.2021.03.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120787PMC
May 2021

Impact of self-reported walking habit on slower decline in renal function among the general population in a longitudinal study: the Japan Specific Health Checkups (J-SHC) Study.

J Nephrol 2021 Dec 30;34(6):1845-1853. Epub 2021 Apr 30.

Department of Nephrology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan.

Background: Association between physical activity and decline in renal function among the general population is not fully understood.

Methods: This is a longitudinal study on subjects who participated in the Japanese nationwide Specific Health Checkup program between 2008 and 2014. The exposure of interest was baseline self-reported walking habit. The outcomes were annual change and incidence of 30% decline in estimated glomerular filtration rate (eGFR). Changes in eGFR were compared using a linear mixed-effects model. Cox proportional hazard models were used to examine the association between self-reported walking habit and 30% decline in eGFR.

Results: Among 332,166 subjects, 168,574 reported walking habit at baseline. The annual changes in eGFR [95% confidence interval (CI)] among subjects with and without baseline self-reported walking habit were - 0.17 (- 0.19 to - 0.16) and - 0.26 (- 0.27 to - 0.24) mL/min/1.73 m/year, respectively (P for interaction between time and baseline self-reported walking habit, < 0.001). During a median follow-up of 3.3 years, 9166 of 314,489 subjects exhibited 30% decline in eGFR. The incidence of 30% decline in eGFR was significantly lower among subjects with self-reported walking habit after adjustment for potential confounders including time-varying blood pressure, body mass index, lipid profile, and hemoglobin A1c, with hazard ratio (95% CI) of 0.93 (0.89-0.97). Sensitivity analysis restricted to subjects with unchanged self-reported walking habit from baseline or analysis with time-varying self-reported walking habit yielded similar results.

Conclusions: Self-reported walking habit was associated with significantly slower decline in eGFR. This association appeared to be independent of its effects on metabolic improvement.
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http://dx.doi.org/10.1007/s40620-021-01041-xDOI Listing
December 2021

Factors predicting decline in renal function and kidney volume growth in autosomal dominant polycystic kidney disease: a prospective cohort study (Japanese Polycystic Kidney Disease registry: J-PKD).

Clin Exp Nephrol 2021 Sep 29;25(9):970-980. Epub 2021 Apr 29.

Department of Advanced Informatics for Genetic Disease, Juntendo University, Tokyo, Japan.

Background: Factors affecting decline in renal function and cyst growth in patients with autosomal polycystic kidney disease (ADPKD) are not fully described, particularly in Japan.

Methods: This was the first multi-facility, prospective, observational cohort study conducted in ADPKD patients at 14 centers in Japan. Patients in the J-PKD registry were assessed from December 2009 to June 2012 (follow-up until June 2017). Patients' data including estimated glomerular filtration rate (eGFR) and total kidney volume (TKV) were assessed initially and a maximum of five times annually. Contributing factors to eGFR decline and TKV growth were identified using multiple linear regression analysis.

Results: Of the 340 patients in the J-PKD registry, data analysis was performed for 192 patients in whom serial changes for both eGFR and TKV were obtained. eGFR slope, eGFR change, and TKV change values were as follows: - 2.7 (- 4.2 to - 1.5) (ml/min/1.73 m/year), - 5.0 (- 9.6 to - 2.3) (%/year), and 4.78 (0.86-8.22) (%/year), respectively. Lower high-density lipoprotein (HDL) cholesterol was an independent predictor of eGFR decline, using both eGFR slope and change (P = 0.04, P = 0.02, respectively), whereas lower hemoglobin and higher uric acid were significantly associated with greater eGFR change only (P = 0.02, P = 0.002, respectively). Younger age and higher fasting blood sugar were independent predictors of greater TKV change (P = 0.01, P = 0.02, respectively).

Conclusions: This real-world study in Japan identified risk factors for renal function decline in ADPKD patients. These included lower HDL cholesterol, lower hemoglobin and higher uric acid for eGFR decline, and youth and higher blood sugar levels for TKV growth.
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http://dx.doi.org/10.1007/s10157-021-02068-xDOI Listing
September 2021

Associations Between Surrogates of Skeletal Muscle Mass and History of Bone Fracture in Patients with Chronic Kidney Disease: The Fukuoka Kidney disease Registry (FKR) Study.

Calcif Tissue Int 2021 10 27;109(4):393-404. Epub 2021 Apr 27.

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Patients with chronic kidney disease (CKD) are at increased risks of both sarcopenia and fragility fractures. However, information on the association between skeletal muscle mass (SMM) and the risk of bone fractures in patients with CKD is lacking. We performed a cross-sectional analysis of 4146 patients with CKD using the baseline dataset of the Fukuoka Kidney disease Registry Study, as a multicenter, prospective cohort study of pre-dialysis CKD patients. The main measure was estimated SMM (eSMM) calculated using an equation validated by bioelectrical impedance analysis with two independent datasets of 100 and 81 CKD patients. The main outcome was historical bone fractures. The associations between sex-specific quartiles (Q1-Q4) of eSMM and fracture history were assessed by logistic regression analyses. The prevalence of a history of fractures increased and eSMM decreased with progressive CKD stages. Among the 4146 patients, 249 had prior bone fractures, including 111 patients in Q1 (lowest quartile), 65 in Q2, 46 in Q3, and 27 in Q4 (highest quartile). A multivariable-adjusted model revealed that patients in Q1 had a significantly higher odds ratio (95% confidence interval) for bone fracture history than those in Q4 (reference): Q1, 2.77 (1.32-5.80); Q2, 1.95 (1.05-3.65); and Q3, 1.57 (0.90-2.75) (P-value for trend < 0.001). Similar associations were obtained when other skeletal muscle surrogates were applied: serum creatinine to serum cystatin C and daily urinary creatinine excretion. These results suggest that a lower eSMM is associated with an increased prevalence of historical bone fractures in pre-dialysis CKD patients.
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http://dx.doi.org/10.1007/s00223-021-00851-2DOI Listing
October 2021

Possible burden of hyperuricaemia on mortality in a community-based population: a large-scale cohort study.

Sci Rep 2021 04 26;11(1):8999. Epub 2021 Apr 26.

Steering Committee of Research on "Design of the Comprehensive Health Care System for Chronic Kidney Disease (CKD) Based On the Individual Risk Assessment By Specific Health Checkup", Fukushima Medical University, Fukushima, Japan.

Hyperuricaemia is a risk for premature death. This study evaluated the burden of hyperuricaemia (serum urate > 7 mg/dL) for all-cause and cardiovascular mortality in 515,979 health checkup participants using an index of population attributable fraction (PAF). Prevalence of hyperuricaemia at baseline was 10.8% in total subjects (21.8% for men and 2.5% for women). During 9-year follow-up, 5952 deaths were noted, including 1164 cardiovascular deaths. In the Cox proportional hazard analysis adjusted for confounding factors, hyperuricaemia was independently associated with all-cause and cardiovascular mortality (adjusted hazard ratios [95% confidence interval]; 1.36 [1.25-1.49] and 1.69 [1.41-2.01], respectively). Adjusted PAFs of hyperuricaemia for all-cause and cardiovascular deaths were 2.9% and 4.4% (approximately 1 in 34 all-cause deaths and 1 in 23 cardiovascular deaths), respectively. In the subgroup analysis, the association between hyperuricaemia and death was stronger in men, smokers, and subjects with renal insufficiency. Adjusted PAFs for all-cause and cardiovascular deaths were 5.3% and 8.1% in men; 5.8% and 7.5% in smokers; and 5.5% and 7.3% in subjects with renal insufficiency. These results disclosed that a substantial number of all-cause and cardiovascular deaths were statistically relevant to hyperuricaemia in the community-based population, especially men, smokers, and subjects with renal insufficiency.
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http://dx.doi.org/10.1038/s41598-021-88631-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076257PMC
April 2021

Non-invasive fibrosis assessments of non-alcoholic fatty liver disease associated with low estimated glomerular filtration rate among CKD patients: the Fukuoka Kidney disease Registry Study.

Clin Exp Nephrol 2021 Aug 15;25(8):822-834. Epub 2021 Apr 15.

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Background: A growing body of evidence has shown that non-alcoholic fatty liver disease (NAFLD) is associated with chronic kidney disease (CKD). Non-invasive fibrosis assessments of NAFLD such as Fibrosis-4 (FIB-4) index and NAFLD fibrosis score (NFS) have been developed to substitute liver biopsy. Little is known about the association between FIB-4 index or NFS and the components of CKD.

Methods: In the present cross-sectional study, we assessed of 3640 Japanese CKD patients. We examined the association between FIB-4index or NFS and the odds of having low estimated glomerular filtration rate (eGFR) defined as eGFR < 60 mL/min/1.73 m or albuminuria defined as urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g. Patients were divided into quartiles according to their baseline FIB-4 index and NFS levels. Linear and logistic regression analysis were conducted, with adjustment for potential confounding factors.

Results: FIB-4 index and NFS were negatively associated with eGFR, but not UACR, after adjustment for potential confounding factors. Both FIB-4 index and NFS were significantly associated with low eGFR after adjustment for potential confounding factors. Meanwhile, in the multivariable-adjusted model, no associations were found between FIB-4 index or NFS and albuminuria. The addition of FIB-4 index or NFS to the established clinical CKD risk factors improved diagnostic accuracy of prevalence of low eGFR. We also found that there was a significant trend of higher FIB-4 index and NFS with more advanced renal fibrosis using the kidney biopsy data.

Conclusions: Higher non-invasive fibrosis assessments of NAFLD were associated with higher odds of decreased eGFR.
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http://dx.doi.org/10.1007/s10157-020-02018-zDOI Listing
August 2021

Association between geriatric nutritional risk index and stroke risk in hemodialysis patients: 10-Years outcome of the Q-Cohort study.

Atherosclerosis 2021 04 12;323:30-36. Epub 2021 Mar 12.

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Backgrounds And Aims: The geriatric nutritional risk index (GNRI), which is calculated using the serum albumin level and body mass index, is a nutritional marker associated with an increased risk of cardiovascular events in patients who are receiving hemodialysis. However, no studies have examined the association between the GNRI level and the incidence of stroke in this population.

Methods: Three thousand forty-five patients were registered in the Q-Cohort Study, which is a multicenter, observational cohort of hemodialysis patients. The main outcomes were brain infarction and brain hemorrhage. The main exposure was GNRI levels at baseline. Patients were divided into quartiles on the basis of baseline GNRI levels: Q1, <90.7; Q2, 90.7-95.5; Q3, 95.6-99.8; Q4, >99.8. The risk of brain infarction or hemorrhage was estimated using the multivariable-adjusted Cox proportional hazard risk models and restricted cubic spline analyses.

Results: During the 10-year follow-up period, 326 patients developed brain infarction and 149 patients developed brain hemorrhage. Cox proportional hazard risk models showed that the risk of brain infarction and hemorrhage in Q1 was significantly higher than that in Q4 group. The hazard ratios [95% confidence intervals] were 1.49 [1.05-2.12] and 1.89 [1.11-3.20], respectively. Restricted cubic spline curves showed that a lower GNRI was incrementally associated with an increased risk for both brain infarction and brain hemorrhage.

Conclusions: Our results suggest that a lower GNRI is an independent risk factor for both brain infarction and hemorrhage in patients who are receiving maintenance hemodialysis.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.03.006DOI Listing
April 2021
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