Publications by authors named "Masahiro Eriguchi"

45 Publications

Routinely measured cardiac troponin I and N-terminal pro-B-type natriuretic peptide as predictors of mortality in haemodialysis patients.

ESC Heart Fail 2022 Jan 13. Epub 2022 Jan 13.

Fukuoka Renal Clinic, Fukuoka, Japan.

Aims: Cardiac troponin (cTn) and B-type natriuretic peptide (BNP) are elevated in haemodialysis (HD) patients, and this elevation is associated with HD-induced myocardial stunning/myocardial strain. However, studies using data from the international Dialysis Outcomes and Practice Patterns Study (DOPPS) have shown that these cardiac biomarkers are measured in <2% of HD patients in real-world practice. This study aimed to examine whether routinely measured N-terminal pro-BNP (NT-proBNP) and cTnI (contemporary assay) are more appropriate than clinical models for reclassifying the risk of HD patients who have the highest risk of death.

Methods And Results: Pre-dialysis levels of cTnI and NT-proBNP at study enrolment were measured in 1152 HD patients (Japan DOPPS Phase 5). The patients were prospectively followed for 3 years. Cox regression was used to test the associations of cardiac biomarkers with all-cause mortality, adjusting for potential confounders. Subgroup analyses were performed to assess potential effect modification of clinical characteristics, such as age, systolic blood pressure, HD vintage, diabetes mellitus, coronary artery disease, and a history of congestive heart failure. At baseline, 337 (29%) patients had elevated cTnI (99th percentile of a healthy population: >0.04 ng/mL) with a median (inter-quartile range) level of 0.020 (0.005-0.041) ng/mL, and 1140 (99%) patients had elevated NT-proBNP (cut-off for heart failure: >125 pg/mL) with a median level of 3658 (1689-9356) pg/mL. There were 167 deaths during a median follow-up of 2.8 (2.2-2.8) years. Higher levels of both cardiac biomarkers were incrementally associated with mortality after adjustment for potential confounders. Even after adjustment for alternative cardiac biomarkers, the overall P value for the association was <0.01 for both biomarkers. However, the prognostic significance of NT-proBNP was moderately diminished when cTnI was added to the model. The hazard ratios of mortality for cTnI > 0.04 ng/mL (vs. cTnI < 0.006 ng/mL) and NT-proBNP > 8000 pg/mL (vs. NT-proBNP < 2000 pg/mL) were 2.56 (95% confidence interval: 1.37-4.81) and 1.90 (95% confidence interval: 0.95-3.79), respectively. Subgroup analyses showed that the associations of both cardiac biomarkers with mortality were generally consistent between stratified groups.

Conclusions: Routinely measured NT-proBNP and cTnI levels are strongly associated with mortality among prevalent HD patients. These associations remain robust, even after adjustment for alternative biomarkers, suggesting that cTnI and NT-proBNP have identical prognostic significance and may reflect different pathological aspects of cardiac abnormalities.
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http://dx.doi.org/10.1002/ehf2.13784DOI Listing
January 2022

Tracing all patients who received insured dialysis treatment in Japan and the present situation of their number of deaths.

Clin Exp Nephrol 2022 Jan 1. Epub 2022 Jan 1.

Department of Public Health, Health Management and Policy, Nara Medical University, 840 Shijo-Cho, Kashihara, Nara, 634-8521, Japan.

Background: The survival rate of chronic dialysis patients in Japan remains the highest worldwide, so there is value in presenting Japan's situation internationally. We examined whether aggregate figures on dialysis patients in the National Database of Health Insurance Claims and Special Health Checkups of Japan (NDB), which contains data on insured procedures of approximately 100 million Japanese residents, complement corresponding figures in the Japanese Society for Dialysis Therapy Renal Data Registry (JRDR).

Methods: Subjects were patients with medical fee points for dialysis recorded in the NDB during 2014-2018. We analyzed annual numbers of dialysis cases, newly initiated dialysis cases- and deaths.

Results: Compared with the JRDR, the NDB had about 6-7% fewer dialysis cases but a similar number of newly initiated dialysis cases. In the NDB, the number of deaths was about 6-10% lower, and the number of hemodialysis cases was lower, while that of peritoneal dialysis cases was higher. The cumulative survival rate at dialysis initiation was approximately 6 percentage points lower in the NDB than in the JRDR, indicating that some patients die at dialysis initiation. Cumulative survival rate by age group was roughly the same between the NDB and JRDR in both sexes.

Conclusion: The use of the NDB enabled us to aggregate data of dialysis patients. With the definition of dialysis patients used in this study, analyses of concomitant medications, comorbidities, surgeries, and therapies will become possible, which will be useful in many future studies.
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http://dx.doi.org/10.1007/s10157-021-02163-zDOI Listing
January 2022

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

JAMA Netw Open 2021 10 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 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

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

Clin Exp Nephrol 2022 Jan 7;26(1):29-35. 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
January 2022

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

Stronger Effect of Azilsartan on Reduction of Proteinuria Compared to Candesartan in Patients with CKD: A Randomized Crossover Trial.

Kidney Blood Press Res 2021 5;46(2):173-184. Epub 2021 Mar 5.

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

Introduction: Angiotensin receptor blockers (ARBs) are preferably used in hypertensive patients with CKD. Azilsartan is a strong antihypertensive ARB, but its antiproteinuric effects are not well understood. We compared the antiproteinuric effect of azilsartan and candesartan in CKD patients in an open-label, randomized, crossover trial.

Methods: A total of 111 patients were treated with 20 mg of azilsartan daily for 2 months as a run-in period. After the run-in period, patients were randomized into 2 arms and received either 20 mg of azilsartan or 8 mg of candesartan daily for 3 months in a crossover trial. The primary outcome was the percent change in urinary protein-to-Cr ratio (UPCR).

Results: Ninety-five patients completed the trial. The mean age was 64.3 years. The estimated glomerular filtration rate (eGFR) and UPCR were 41.5 mL/min/1.73 m2 and 1.8 g/gCr, respectively. The baseline systolic and diastolic blood pressures were 131.4 and 71.0 mm Hg, respectively. The mean percent change in the UPCR was -3.8% in the azilsartan group and 30.8% in the candesartan group at the 1st endpoint (p = 0.0004), and 6.1% in the azilsartan group and 25.8% in the candesartan group at the 2nd (final) endpoint (p = 0.029). The incidence of adverse events, including eGFR levels and serum potassium levels, was not significantly different between the groups.

Conclusion: A 20 mg azilsartan dose had potent antiproteinuric effects compared with an 8 mg candesartan dose, without an increase in adverse events. Azilsartan may provide renal protection in addition to antihypertensive effects in CKD patients.
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http://dx.doi.org/10.1159/000512365DOI Listing
June 2021

27-Hydroxycholesterol regulates human SLC22A12 gene expression through estrogen receptor action.

FASEB J 2021 01;35(1):e21262

Department of Future Basic Medicine, Nara Medical University, Nara, Japan.

The excretion and reabsorption of uric acid both to and from urine are tightly regulated by uric acid transporters. Metabolic syndrome conditions, such as obesity, hypercholesterolemia, and insulin resistance, are believed to regulate the expression of uric acid transporters and decrease the excretion of uric acid. However, the mechanisms driving cholesterol impacts on uric acid transporters have been unknown. Here, we show that cholesterol metabolite 27-hydroxycholesterol (27HC) upregulates the uric acid reabsorption transporter URAT1 encoded by SLC22A12 via estrogen receptors (ER). Transcriptional motif analysis showed that the SLC22A12 gene promoter has more estrogen response elements (EREs) than other uric acid reabsorption transporters such as SLC22A11 and SLC22A13, and 27HC-activated SLC22A12 gene promoter via ER through EREs. Furthermore, 27HC increased SLC22A12 gene expression in human kidney organoids. Our results suggest that in hypercholesterolemic conditions, elevated levels of 27HC derived from cholesterol induce URAT1/SLC22A12 expression to increase uric acid reabsorption, and thereby, could increase serum uric acid levels.
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http://dx.doi.org/10.1096/fj.202002077RDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771643PMC
January 2021

Microscopic hematuria is a risk factor for end-stage kidney disease in patients with biopsy-proven diabetic nephropathy.

BMJ Open Diabetes Res Care 2020 11;8(2)

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

Introduction: There are fewer reports about whether the presence of hematuria affects the progression of chronic kidney disease in patients with diabetic nephropathy. We analyzed whether microscopic hematuria in diabetic nephropathy is a risk factor for end-stage kidney disease (ESKD).

Research Design And Methods: The present study was a retrospective cohort study of patients with biopsy-proven diabetic nephropathy. We recruited 397 patients with diabetic nephropathy, which was confirmed by renal biopsy between June 1981 and December 2014 and followed them until October 2018 or death. Patients with microscopic hematuria before renal biopsy were defined as the hematuria group (n=91), and the remainder as the no-hematuria group (n=306). The main outcome was the occurrence of ESKD, which was defined by the requirement of permanent renal replacement therapies.

Results: The systolic and diastolic blood pressure, serum creatinine and proteinuria were significantly higher, and the estimated glomerular filtration rate was significantly lower in the hematuria group compared with the no-hematuria group. Pathological evaluations revealed that glomerular, tubulointerstitial and vascular lesions in the hematuria group were significantly more severe. During a median of 10.1 years, 44 and 52 patients developed ESKD in the hematuria group and the no-hematuria group, respectively. Survival analyses showed that the incidence of ESKD was significantly higher in the hematuria group compared with the no-hematuria group (log-rank, p<0.0001). The multivariable Cox proportional hazards models revealed a significant association between hematuria and the incidence of ESKD after adjusting for clinically relevant factors, including proteinuria and renal pathology (adjusted HR 1.64, 95% CI 1.03 to 2.60). The subgroups of men, proteinuria ≥0.5 g/day, and systolic blood pressure ≥132 mm Hg showed a stronger association between hematuria and ESKD than their opposing subgroups.

Conclusions: Microscopic hematuria is a risk factor for ESKD in diabetic nephropathy, independent of proteinuria and renal pathology.
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http://dx.doi.org/10.1136/bmjdrc-2020-001863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643490PMC
November 2020

Relationship between initial peritoneal dialysis modality and risk of peritonitis.

Sci Rep 2020 10 30;10(1):18763. Epub 2020 Oct 30.

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

Peritonitis is a critical complication of peritoneal dialysis (PD). Investigators have reported the risk of peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD) versus automated peritoneal dialysis (APD), but the available evidence is predominantly based on observational studies which failed to report on the connection type. Our understanding of the relationship between peritonitis risk and PD modality thus remained insufficient. We studied 285 participants who began PD treatment between 1997 and 2014 at three hospitals in Nara Prefecture in Japan. We matched 106 APD patients with 106 CAPD patients based on their propensity scores. The primary outcome was time to first episode of peritonitis within 3 years after PD commencement. In total, PD peritonitis occurred in 64 patients during the study period. Patients initiated on APD had a lower risk of peritonitis than did those initiated on CAPD in both the unadjusted and adjusted models. The hazard ratio (HR) and 95% confidence interval (CI) for the primary endpoint were 0.30 (0.17-0.53) in the fully adjusted model including connection type. In the matched cohort, APD patients had a significantly lower risk of peritonitis than did CAPD patients (log-rank: p < 0.001, HR 0.32, 95% CI 0.16-0.59). The weighting-adjusted analysis of the inverse probability of treatment yielded a similar result (HR 0.35, 95% CI 0.18-0.67). In conclusion, patients initiated on APD at PD commencement had a reduced risk of peritonitis compared with those initiated on CAPD, suggesting APD may be preferable for prevention of peritonitis among PD patients.
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http://dx.doi.org/10.1038/s41598-020-75918-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599327PMC
October 2020

Advanced glycation end products are associated with immature angiogenesis and peritoneal dysfunction in patients on peritoneal dialysis.

Perit Dial Int 2020 01;40(1):67-75

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

Background: Deposition of advanced glycation end products (AGEs) is frequently found in the peritoneum of patients on peritoneal dialysis (PD). Angiogenesis is also observed in the peritoneum. However, the clinical significance of AGEs and angiogenesis in the peritoneum is not fully understood. We evaluated the maturation of capillary vessels and investigated whether AGEs are associated with angiogenesis and peritoneal function in the peritoneal membrane.

Methods: Peritoneum obtained when PD catheters were removed from 61 patients with PD was analyzed. The peritoneum was immunohistochemically stained with anti-CD34 (for endothelial cells), anti-alpha smooth muscle actin (αSMA) (for pericytes), and anti-AGE antibodies. We defined CD34-positive and αSMA-negative vessels as immature capillary vessels in peritoneal membranes using serial sections. We evaluated the associations between vessel density, peritoneal function (dialysate-to-plasma ratio for creatinine (D/P creatinine)), and the degree of AGE deposition.

Results: AGE accumulation in the interstitium was positively associated with the duration of PD ( < 0.01). AGE accumulation in the interstitium and vascular wall was positively correlated with the use of acidic solution ( < 0.05) and the maximum value of D/P creatinine ( < 0.05). AGE accumulation in the vascular wall was significantly associated with immature capillary density (CD34+/αSMA-) in the peritoneum ( < 0.01). Vessel density was not significantly correlated with the last measurement of D/P creatinine ( = 0.126, = 0.202), However, immature capillary density was positively correlated with the last measurement of D/P creatinine ( < 0.05, = 0.278).

Conclusions: AGE accumulation is significantly associated with immature angiogenesis and peritoneal dysfunction in patients undergoing PD.
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http://dx.doi.org/10.1177/0896860819878344DOI Listing
January 2020

Pre-operative proteinuria and post-operative acute kidney injury in noncardiac surgery: the NARA-Acute Kidney Injury cohort study.

Nephrol Dial Transplant 2020 12;35(12):2111-2116

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

Background: Little is known about the association between pre-operative proteinuria and post-operative acute kidney injury (AKI) in noncardiac surgery.

Methods: This is a retrospective cohort study. Adults who underwent noncardiac surgery under general anesthesia from 2007 to 2011 at Nara Medical University Hospital were included. Those with obstetric or urological surgery, missing data for analyses or pre-operative dialysis were excluded. Exposure of interest was pre-operative proteinuria, defined as (+) or more by dipstick test. The outcome variable was post-operative AKI, defined by Kidney Disease: Improving Global Outcomes criteria, within 1 week after surgery. Multivariable logistic regression analyses were performed.

Results: Among 5168 subjects, 309 (6.0%) developed AKI. Pre-operative proteinuria was independently associated with post-operative AKI, with an odds ratio (OR) [95% confidence interval (CI)] of 1.80 (1.30-2.51). A sensitivity analysis restricted to elective surgery yielded a similar result. As proteinuria increased, the association with AKI became stronger [OR (95% CI) 1.14 (0.75-1.73), 1.24 (0.79-1.95), 2.75 (1.74-4.35) and 3.95 (1.62-9.62) for urinary protein (+/-), (+), (2+) and (3+), respectively]. Subgroup analyses showed proteinuria was especially associated with post-operative AKI among subjects with renin-angiotensin system inhibitors, other anti-hypertensives, hypoalbuminemia or impaired renal function (P for interaction = 0.05, 0.003, 0.09 or 0.02, respectively).

Conclusions: In noncardiac surgery, pre-operative proteinuria was independently associated with post-operative AKI. Subjects with proteinuria should be managed with caution to avoid AKI peri-operatively.
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http://dx.doi.org/10.1093/ndt/gfz269DOI Listing
December 2020

Inflammation as a predictor of acute kidney injury and mediator of higher mortality after acute kidney injury in non-cardiac surgery.

Sci Rep 2019 12 30;9(1):20260. Epub 2019 Dec 30.

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

This retrospective cohort study examined the roles of inflammation in acute kidney injury (AKI). Serum albumin and C-reactive protein (CRP) were used as markers of inflammation. Adults who underwent non-cardiac surgery from 2007 to 2011 were included. Exclusion criteria were urological surgery, obstetric surgery, missing data, and pre-operative dialysis. Subjects were followed until the end of 2015 or loss to follow-up. Associations between pre-operative albumin or CRP and post-operative AKI or association between AKI and mortality were examined by logistic or Cox regression, respectively. Mediation analyses were performed using albumin and CRP as mediators. Among 4,538 subjects, 272 developed AKI. Pre-operative albumin was independently associated with AKI (odds ratio [95% confidence interval (CI)]: 0.63 [0.48-0.83]). During a median follow-up of 4.5 years, 649 died. AKI was significantly associated with mortality (hazard ratio [HR] [95% CI]: 1.58 [1.22-2.04]). Further adjustment for pre-operative albumin and CRP attenuated the association (HR [95% CI]: 1.28 [0.99-1.67]). The proportions explained by mediating effects of lnCRP and albumin were 29.3% and 39.2% and mediation effects were statistically significant. In conclusion, inflammation is a predictor of AKI and a mediator of mortality after AKI. Interventions targeting inflammation might improve outcomes of AKI.
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http://dx.doi.org/10.1038/s41598-019-56615-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937243PMC
December 2019

Positive association between intra-operative fluid balance and post-operative acute kidney injury in non-cardiac surgery: the NARA-AKI cohort study.

J Nephrol 2020 Jun 21;33(3):561-568. Epub 2019 Dec 21.

Department of Nephrology, Nara Medical University, 840 Shijo-cho, Kashihara-shi, Nara, 6348521, Japan.

Background: Little is known about the association between intra-operative fluid balance (IFB) and post-operative acute kidney injury (AKI) in non-cardiac surgery.

Methods: This is a retrospective cohort study. Adults who underwent non-cardiac surgery under general anesthesia from 2007 to 2011 at Nara Medical University Hospital were included. Those with obstetric or urological surgery, missing data, or pre-operative dialysis were excluded. Exposure of interest was IFB, defined as (amount of fluid administration - urine output - amount of bleeding)/body weight. Outcome variable was post-operative AKI within 1 week after surgery. Data were analyzed using logistic regression models and restricted cubic spline (RCS) analysis.

Results: Among 5168 subjects, AKI was observed in 309 (6.0%). Higher IFB (per 1 standard deviation) was independently associated with post-operative AKI after adjustment for potential confounders (odds ratio [95% confidence interval] of 1.18 [1.06-1.31]). The RCS curve showed an increase in expected probability of AKI associated with increase in IFB above 40 mL/kg. Subgroup analyses indicated higher IFB was especially associated with AKI among those with lower serum albumin, higher C-reactive protein, or positive proteinuria. The association was similar across intra-operative urine output or amount of bleeding (p for interaction 0.34 and 0.47, respectively), suggesting the association was not due to intra-operative oliguria or large amount of bleeding necessitating volume resuscitation.

Conclusions: Higher IFB was independently associated with increase in post-operative AKI. Excessive fluid administration might have caused renal congestion and subsequent AKI. Avoiding fluid overload might be important in prevention of AKI.
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http://dx.doi.org/10.1007/s40620-019-00688-xDOI Listing
June 2020

Acute kidney injury as an independent predictor of infection and malignancy: the NARA-AKI cohort study.

J Nephrol 2019 Dec 15;32(6):967-975. Epub 2019 Oct 15.

Department of Nephrology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 6348521, Japan.

Background: Acute kidney injury (AKI) is associated with higher mortality and cardiovascular events. However, association between AKI and non-cardiac events such as infection or malignancy is largely unknown.

Methods: This is a retrospective cohort study. Inclusion criteria were adults who underwent non-cardiac surgery from 2007 to 2011 at Nara Medical University Hospital. Exclusion criteria were urological surgery, obstetric surgery, missing creatinine values peri-operatively, and pre-operative dialysis. The end of observation period was at the end of 2015 or loss to follow-up. A predictor was AKI defined by KDIGO criteria within 1-week post-operatively. Outcomes were hospitalization for infection or diagnoses of malignancy. Associations between AKI and outcomes were examined by Cox regression models.

Results: Among 6692 subjects, 445 (6.6%) developed AKI. During median follow-up of 4.0 years, there were 485 hospitalizations for infection and 1138 diagnoses of malignancy (2.0 and 5.1 events/100 patient-years, respectively). After adjustment for potential confounders, AKI was independently associated with hospitalization for infection and diagnoses of malignancy (Hazard ratio [95% confidence interval]: 1.64 [1.23-2.20] and 1.31 [1.06-1.61], respectively). Excluding recurrence of malignancy from outcomes and analyses limited to those who recover renal function by the time of discharge yielded similar results. Absolute lymphocyte counts were significantly lower and neutrophil-to-lymphocyte ratios were significantly higher among those with AKI.

Conclusions: AKI was significantly associated with hospitalization for infection and development of malignancy during long-term follow-up. Those with AKI might be in persistent immunosuppressed state.
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http://dx.doi.org/10.1007/s40620-019-00662-7DOI Listing
December 2019

A Prediction Model with Lifestyle in Addition to Previously Known Risk Factors Improves Its Predictive Ability for Cardiovascular Death.

Sci Rep 2019 09 10;9(1):12953. Epub 2019 Sep 10.

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

This longitudinal cohort study aimed to create a novel prediction model for cardiovascular death with lifestyle factors. Subjects aged 40-74 years in the Japanese nationwide Specific Health Checkup Database in 2008 were included. Subjects were randomly assigned to the derivation and validation cohorts by a 2:1 ratio. Points for the prediction model were determined using regression coefficients that were derived from the Cox proportional hazards model in the derivation cohort. Models 1 and 2 were developed using known risk factors and known factors with lifestyle factors, respectively. The models were validated by comparing Kaplan-Meier curves between the derivation and validation cohorts, and by calibration plots in the validation cohort. Among 295,297 subjects, data for 120,823 were available. There were 310 cardiovascular deaths during a mean follow-up of 3.6 years. Model 1 included known risk factors. In model 2, weight gain, exercise habit, gait speed, and drinking alcohol were additionally included as protective factors. Kaplan-Meier curves matched better between the derivation and validation cohorts in model 2, and model 2 was better calibrated. In conclusion, our prediction model with lifestyle factors improved the predictive ability for cardiovascular death.
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http://dx.doi.org/10.1038/s41598-019-49003-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736867PMC
September 2019

ATP release drives heightened immune responses associated with hypertension.

Sci Immunol 2019 06;4(36)

Department of Physiology and Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

The cause of most hypertensive disease is unclear, but inflammation appears critical in disease progression. However, how elevated blood pressure initiates inflammation is unknown, as are the effects of high blood pressure on innate and adaptive immune responses. We now report that hypertensive mice have increased T cell responses to antigenic challenge and develop more severe T cell-mediated immunopathology. A root cause for this is hypertension-induced erythrocyte adenosine 5'-triphosphate (ATP) release, leading to an increase in plasma ATP levels, which begins soon after the onset of hypertension and stimulates P2X7 receptors on antigen-presenting cells (APCs), increasing APC expression of CD86. Hydrolyzing ATP or blocking the P2X7 receptor eliminated hypertension-induced T cell hyperactivation. In addition, pharmacologic or genetic blockade of P2X7 receptor activity suppressed the progression of hypertension. Consistent with the results in mice, we also found that untreated human hypertensive patients have significantly elevated plasma ATP levels compared with treated hypertensive patients or normotensive controls. Thus, a hypertension-induced increase in extracellular ATP triggers augmented APC and T cell function and contributes to the immune-mediated pathologic changes associated with hypertensive disease.
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http://dx.doi.org/10.1126/sciimmunol.aau6426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6699629PMC
June 2019

Peritonitis due to Moraxella osloensis: A case report and literature review.

J Infect Chemother 2019 Dec 10;25(12):1050-1052. Epub 2019 Jun 10.

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

A-26-year-old man was admitted to our hospital with diffuse abdominal pain, nausea, and vomiting. He had a history of malignant nephrosclerosis, for which he had been receiving peritoneal dialysis (PD) for the past 14 months. His PD effluent was cloudy and turbid (white blood cell count, 10,528/μL; neutrophils 95.2%). A Gram-negative coccobacillus was isolated from peritoneal fluid culture. However, the organism could not be identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) (Vitek MS, bioMérieux), but was identified as Moraxella osloensis by the 16S rRNA gene sequencing. He was successfully treated with intraperitoneal cefazolin therapy for 3 weeks without removing the intra-abdominal catheter. A literature review revealed three previous case reports all of which were diagnosed by MALDI Biotyper (Bruker Daltonics), suggesting that the identification of M. osloensis may vary depending on the type of MALDI-TOF MS system. In conclusion, we experienced a case of M. osloensis infection in a PD patient, which was successfully treated by antibiotic treatment, without removing the PD catheter.
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http://dx.doi.org/10.1016/j.jiac.2019.05.018DOI Listing
December 2019

Rapidly Progressive Glomerulonephritis with Delayed Appearance of Anti-Glomerular Basement Membrane Antibody Successfully Treated with Multiple Courses of Steroid Pulse Therapy.

Case Rep Nephrol Dial 2019 Jan-Apr;9(1):25-32. Epub 2019 Apr 16.

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

Patients with anti-glomerular basement membrane (GBM) antibody glomerulonephritis typically exhibit rapidly progressive glomerulonephritis (RPGN). The renal outcome as well as the prognosis of this disease is worse than other forms of RPGN such as those from microscopic polyangiitis. Therefore, early therapeutic intervention is essential to improve its prognosis. One month before referral to our hospital, a 54-year-old female attended another hospital because of macrohematuria. At that time, she had proteinuria and macrohematuria with normal renal function, was negative for anti-GBM antibodies, and was diagnosed with chronic glomerulonephritis. A month later when she was admitted to our hospital, she showed renal insufficiency and was positive for anti-GBM antibodies. Immediately after recognizing the anti-GBM antibody status, plasma exchange and the first course of steroid pulse therapy was started. After 5 days of therapy, renal biopsy confirmed severe crescentic glomerulonephritis in which all the observed glomeruli were involved with cellular crescents. Despite this, she survived without end-stage renal disease after three courses of steroid pulse therapy and seven sessions of plasma exchange. This favorable outcome reflects the repeated analysis of anti-GBM antibodies within a very short period and the rapid therapeutic intervention in addition to the intensive immunosuppressive therapies.
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http://dx.doi.org/10.1159/000499401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514513PMC
April 2019

The Absence of the ACE N-Domain Decreases Renal Inflammation and Facilitates Sodium Excretion during Diabetic Kidney Disease.

J Am Soc Nephrol 2018 10 5;29(10):2546-2561. Epub 2018 Sep 5.

Departments of Biomedical Sciences and

Background: Recent evidence emphasizes the critical role of inflammation in the development of diabetic nephropathy. Angiotensin-converting enzyme (ACE) plays an active role in regulating the renal inflammatory response associated with diabetes. Studies have also shown that ACE has roles in inflammation and the immune response that are independent of angiotensin II. ACE's two catalytically independent domains, the N- and C-domains, can process a variety of substrates other than angiotensin I.

Methods: To examine the relative contributions of each ACE domain to the sodium retentive state, renal inflammation, and renal injury associated with diabetic kidney disease, we used streptozotocin to induce diabetes in wild-type mice and in genetic mouse models lacking either a functional ACE N-domain (NKO mice) or C-domain (CKO mice).

Results: In response to a saline challenge, diabetic NKO mice excreted 32% more urinary sodium compared with diabetic wild-type or CKO mice. Diabetic NKO mice also exhibited 55% less renal epithelial sodium channel cleavage (a marker of channel activity), 55% less renal IL-1, 53% less renal TNF-, and 53% less albuminuria than diabetic wild-type mice. This protective phenotype was not associated with changes in renal angiotensin II levels. Further, we present evidence that the anti-inflammatory tetrapeptide N-acetyl-seryl-asparyl-lysyl-proline (AcSDKP), an ACE N-domain-specific substrate that accumulates in the urine of NKO mice, mediates the beneficial effects observed in the NKO.

Conclusions: These data indicate that increasing AcSDKP by blocking the ACE N-domain facilitates sodium excretion and ameliorates diabetic kidney disease independent of intrarenal angiotensin II regulation.
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http://dx.doi.org/10.1681/ASN.2018030323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6171283PMC
October 2018

Renal tubular ACE-mediated tubular injury is the major contributor to microalbuminuria in early diabetic nephropathy.

Am J Physiol Renal Physiol 2018 04 29;314(4):F531-F542. Epub 2017 Nov 29.

Department of Biomedical Sciences, Cedars-Sinai Medical Center , Los Angeles, California.

Diabetic nephropathy is a major cause of end-stage renal disease in developed countries. While angiotensin-converting enzyme (ACE) inhibitors are used to treat diabetic nephropathy, how intrarenal ACE contributes to diabetic renal injury is uncertain. Here, two mouse models with different patterns of renal ACE expression were studied to determine the specific contribution of tubular vs. glomerular ACE to early diabetic nephropathy: it-ACE mice, which make endothelial ACE but lack ACE expression by renal tubular epithelium, and ACE 3/9 mice, which lack endothelial ACE and only express renal ACE in tubular epithelial cells. The absence of endothelial ACE normalized the glomerular filtration rate and endothelial injury in diabetic ACE 3/9 mice. However, these mice developed tubular injury and albuminuria and displayed low renal levels of megalin that were similar to those observed in diabetic wild-type mice. In diabetic it-ACE mice, despite hyperfiltration, the absence of renal tubular ACE greatly reduced tubulointerstitial injury and albuminuria and increased renal megalin expression compared with diabetic wild-type and diabetic ACE 3/9 mice. These findings demonstrate that endothelial ACE is a central regulator of the glomerular filtration rate while tubular ACE is a key player in the development of tubular injury and albuminuria. These data suggest that tubular injury, rather than hyperfiltration, is the main cause of microalbuminuria in early diabetic nephropathy.
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http://dx.doi.org/10.1152/ajprenal.00523.2017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966765PMC
April 2018

Vascular endothelial growth factor-C ameliorates renal interstitial fibrosis through lymphangiogenesis in mouse unilateral ureteral obstruction.

Lab Invest 2017 12 30;97(12):1439-1452. Epub 2017 Oct 30.

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

Renal fibrosis is the final common pathway of chronic kidney diseases. Lymphatic vessel (LV) proliferation is found in human renal diseases and other fibrotic diseases, suggesting that lymphangiogenesis is associated with the progression or suppression of kidney diseases. However, the purpose of LV proliferation is not completely understood. We investigated the effect of vascular endothelial growth factor (VEGF)-C on lymphangiogenesis, inflammation, and fibrosis in the mouse kidney using the unilateral ureteral obstruction (UUO) model. In UUO mice, significant proliferation of LVs was accompanied by tubulointerstitial nephritis and fibrosis. We continuously administered recombinant human VEGF-C to UUO model mice using an osmotic pump (UUO+VEGF-C group). Lymphangiogenesis was significantly induced in the UUO+VEGF-C group compared with the vehicle group, despite similar numbers of capillaries in both groups. The number of infiltrating macrophages, and levels of inflammatory cytokines and transforming growth factor-β1 were reduced in the UUO+VEGF-C group compared with the vehicle group. Renal fibrosis was consequently attenuated in the UUO+VEGF-C group. In cultured lymphatic endothelial cells, administration of VEGF-C increased the activity and proliferation of lymphatic endothelial cells (LECs) and expression of adhesion molecules such as vascular cell adhesion molecule-1. These findings suggest that induction of lymphangiogenesis ameliorates inflammation and fibrosis in the renal interstitium. Enhancement of the VEGF-C signaling pathway in LECs may be a therapeutic strategy for renal fibrosis.
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http://dx.doi.org/10.1038/labinvest.2017.77DOI Listing
December 2017

Angiotensin-converting enzyme enhances the oxidative response and bactericidal activity of neutrophils.

Blood 2017 07 17;130(3):328-339. Epub 2017 May 17.

Department of Biomedical Sciences and.

Angiotensin-converting enzyme (ACE) inhibitors are widely used to reduce blood pressure. Here, we examined if an ACE is important for the antibacterial effectiveness of neutrophils. ACE knockout mice or mice treated with an ACE inhibitor were more susceptible to bacterial infection by methicillin-resistant (MRSA). In contrast, mice overexpressing ACE in neutrophils (Neu mice) have increased resistance to MRSA and better in vitro killing of MRSA, , and ACE overexpression increased neutrophil production of reactive oxygen species (ROS) following MRSA challenge, an effect independent of the angiotensin II AT1 receptor. Specifically, as compared with wild-type (WT) mice, there was a marked increase of superoxide generation (>twofold, < .0005) in Neu neutrophils following infection, whereas ACE knockout neutrophils decreased superoxide production. Analysis of membrane p47-phox and p67-phox indicates that ACE increases reduced NAD phosphate oxidase activity but does not increase expression of these subunits. Increased ROS generation mediates the enhanced bacterial resistance of Neu mice because the enhanced resistance is lost with DPI (an inhibitor of ROS production by flavoenzymes) inhibition. Neu granulocytes also have increased neutrophil extracellular trap formation and interleukin-1β release in response to MRSA. In a mouse model of chemotherapy-induced neutrophil depletion, transfusion of ACE-overexpressing neutrophils was superior to WT neutrophils in treating MRSA infection. These data indicate a previously unknown function of ACE in neutrophil antibacterial defenses and suggest caution in the treatment of certain individuals with ACE inhibitors. ACE overexpression in neutrophils may be useful in boosting the immune response to antibiotic-resistant bacterial infection.
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http://dx.doi.org/10.1182/blood-2016-11-752006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520468PMC
July 2017

Cardiothoracic Ratio and All-Cause Mortality and Cardiovascular Disease Events in Hemodialysis Patients: The Q-Cohort Study.

Am J Kidney Dis 2017 Jul 10;70(1):84-92. Epub 2017 Feb 10.

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Integrated Therapy for Chronic Kidney Disease, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address:

Background: Cardiothoracic ratio by chest radiography is commonly used to assess volume status. Little is known about the relationships between cardiothoracic ratio and the incidence of clinical outcomes in patients undergoing hemodialysis (HD).

Study Design: Prospective cohort study.

Setting & Participants: 3,436 participants in the Q-Cohort Study 18 years or older who underwent maintenance HD in Japan.

Predictor: Cardiothoracic ratio.

Outcomes & Measurements: All-cause mortality and cardiovascular disease (CVD) events.

Results: During a 4-year follow-up period, 564 (16.4%) patients died of any cause and 590 (17.2%) developed CVD events. From baseline cardiothoracic ratios, participants were categorized into sex-specific quartiles because cardiothoracic ratio distribution differed by sex. The 4-year event-free survival rate, in terms of all-cause mortality and CVD events, was significantly lower with higher cardiothoracic ratios. Compared to the lowest cardiothoracic ratio (quartile 1), multivariable-adjusted HRs for all-cause mortality were 0.89 (95% CI, 0.66-1.20), 1.41 (1.08-1.86), and 1.52 (1.17-2.00) in patients from quartiles 2, 3, and 4, respectively. Similarly, in comparison to quartile 1, multivariable-adjusted HRs for CVD events were 1.00 (95% CI, 0.77-1.31), 1.18 (0.92-1.53), and 1.37 (1.07-1.76) in patients from quartiles 2, 3, and 4, respectively. Furthermore, the combination of higher cardiothoracic ratio and normohypotension (systolic blood pressure < 140mmHg and diastolic blood pressure < 90mmHg) was associated with higher risk for CVD events.

Limitations: Single measurement of all variables, potentially less-heterogeneous patient population, and limited ascertainment of cardiac parameters and the outcomes.

Conclusions: Higher cardiothoracic ratio is associated with higher risk for both all-cause mortality and CVD events in patients undergoing HD.
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http://dx.doi.org/10.1053/j.ajkd.2016.11.026DOI Listing
July 2017

Renal tubular angiotensin converting enzyme is responsible for nitro-L-arginine methyl ester (L-NAME)-induced salt sensitivity.

Kidney Int 2017 04 15;91(4):856-867. Epub 2016 Dec 15.

Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA; CVMET Research Unit, Pfizer, Inc., Cambridge, Massachusetts, USA. Electronic address:

Renal parenchymal injury predisposes to salt-sensitive hypertension, but how this occurs is not known. Here we tested whether renal tubular angiotensin converting enzyme (ACE), the main site of kidney ACE expression, is central to the development of salt sensitivity in this setting. Two mouse models were used: it-ACE mice in which ACE expression is selectively eliminated from renal tubular epithelial cells; and ACE 3/9 mice, a compound heterozygous mouse model that makes ACE only in renal tubular epithelium from the ACE 9 allele, and in liver hepatocytes from the ACE 3 allele. Salt sensitivity was induced using a post L-NAME salt challenge. While both wild-type and ACE 3/9 mice developed arterial hypertension following three weeks of high salt administration, it-ACE mice remained normotensive with low levels of renal angiotensin II. These mice displayed increased sodium excretion, lower sodium accumulation, and an exaggerated reduction in distal sodium transporters. Thus, in mice with renal injury induced by L-NAME pretreatment, renal tubular epithelial ACE, and not ACE expression by renal endothelium, lung, brain, or plasma, is essential for renal angiotensin II accumulation and salt-sensitive hypertension.
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http://dx.doi.org/10.1016/j.kint.2016.10.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5657384PMC
April 2017

The potential role of perivascular lymphatic vessels in preservation of kidney allograft function.

Clin Exp Nephrol 2017 Aug 21;21(4):721-731. Epub 2016 Oct 21.

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

Background: Lymphangiogenesis occurs in diseased native kidneys and kidney allografts, and correlates with histological injury; however, the clinical significance of lymphatic vessels in kidney allografts is unclear.

Methods: This study retrospectively reviewed 63 kidney transplant patients who underwent protocol biopsies. Lymphatic vessels were identified by immunohistochemical staining for podoplanin, and were classified according to their location as perivascular or interstitial lymphatic vessels. The associations between perivascular lymphatic density and kidney allograft function and pathological findings were analyzed.

Results: There were no significant differences in perivascular lymphatic densities in kidney allograft biopsy specimens obtained at 0 h, 3 months and 12 months. The groups with higher perivascular lymphatic density showed a lower proportion of progression of interstitial fibrosis/tubular atrophy grade from 3 to 12 months (P for trend = 0.039). Perivascular lymphatic density was significantly associated with annual decline of estimated glomerular filtration rate after 12 months (r = -0.31, P = 0.017), even after adjusting for multiple confounders (standardized β = -0.30, P = 0.019).

Conclusions: High perivascular lymphatic density is associated with favourable kidney allograft function. The perivascular lymphatic network may be involved in inhibition of allograft fibrosis and stabilization of graft function.
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http://dx.doi.org/10.1007/s10157-016-1338-9DOI Listing
August 2017

Modified Simple Peritoneal Wall Anchor Technique (PWAT) in Peritoneal Dialysis.

Perit Dial Int 2017 1-2;37(1):103-108. Epub 2016 Oct 13.

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

♦ BACKGROUND: Outflow obstruction, a common complication in patients with peritoneal dialysis (PD), usually results in unnecessary catheter removal or replacement. This study describes a modified simple method of anchoring a PD catheter on the anterior peritoneal wall without using a laparoscopic system (peritoneal wall anchor technique, PWAT). ♦ METHODS: We performed a retrospective cohort study of consecutive PD catheter insertions, and compared the catheter survival rate between the traditional method and the modified simple PWAT. The traditional method was used in 54 cases and the modified simple PWAT was used in 17 cases. The primary endpoint was the occurrence of surgical catheter repair because of outflow obstruction by day 365. The secondary endpoint was the occurrence of catheter migration with obstruction requiring any interventions, including the alpha-replacement method by day 365. Catheter survival was analyzed by Kaplan-Meier survival curves. ♦ RESULTS: Migration-free catheter survival was significantly (p = 0.02) higher in the PWAT group (100%, 17/17) than in the traditional group (72.2%, 39/54). Catheter survival without surgical repair or cessation of PD was also significantly (p = 0.04) higher in the PWAT group (100%, 17/17) than in the traditional group (77.8%, 42/54). Similarly, migration-free and surgery-free catheter survival rates in cases with a straight-type catheter in the PWAT group were significantly higher than those in cases with a straight-type catheter in the traditional group. ♦ CONCLUSIONS: Our results suggest that the modified simple PWAT provides a better catheter survival rate than the traditional method by preventing catheter migration with obstruction in PD.
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http://dx.doi.org/10.3747/pdi.2016.00041DOI Listing
December 2017

Overexpression of angiotensin-converting enzyme in myelomonocytic cells enhances the immune response.

F1000Res 2016 23;5. Epub 2016 Mar 23.

Department of Biomedical Sciences and the Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Angiotensin-converting enzyme (ACE) converts angiotensin I to the vasoconstrictor angiotensin II and thereby plays an important role in blood pressure control. However, ACE is relatively non-specific in its substrate specificity and cleaves many other peptides. Recent analysis of mice overexpressing ACE in monocytes, macrophages, and other myelomonocytic cells shows that these animals have a marked increase in resistance to experimental melanoma and to infection by Listeria monocytogenes or methicillin-resistant Staphylococcus aureus (MRSA). Several other measures of immune responsiveness, including antibody production, are enhanced in these animals. These studies complement a variety of studies indicating an important role of ACE in the immune response.
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http://dx.doi.org/10.12688/f1000research.7508.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4806706PMC
March 2016

Extended Swan-Neck Catheter With Upper Abdominal Exit-Site Reduces Peritoneal Dialysis-Related Infections.

Ther Apher Dial 2016 Apr 14;20(2):158-64. Epub 2016 Jan 14.

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

Extended catheters with an upper abdominal exit-site (UAE) are reportedly associated with a lower incidence of peritoneal dialysis (PD)-related infections. However, little information about the optimal peritoneal catheter configuration for UAE is available. In this nonrandomized multicenter trial, 147 consecutive cases of a UAE involving either a conventional straight (CS; 80 cases) or extended swan-neck catheter (SN; 67 cases) were analyzed to compare exit-site and tunnel infections (ESTI), peritonitis, and catheter survival. The ESTI-free and catheter survival rates were significantly lower in the SN than in the CS group (P <0.01). However, the peritonitis-free survival rate was not different (P = 0.26). In terms of analyses for infection rates, fewer episodes of ESTI (1.284 vs 0.608 episodes/patient-year; P <0.01) and peritonitis (0.345 vs 0.152 episodes/patient-year; P = 0.06) were observed in the SN than CS group. Recurrence analyses showed that the mean number of cumulative episodes of ESTI and peritonitis between two groups were significantly different.
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http://dx.doi.org/10.1111/1744-9987.12358DOI Listing
April 2016
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