Abstract Background The Kidney Disease Improving Global Outcomes guidelines recommend nephrology referral for patients with chronic kidney disease (CKD) stages 4 to 5, significant proteinuria and persistent microscopic haematuria. However, the recommendations are opinion‐based and which patients with CKD benefit more from nephrology referral has not been elucidated. Methods In this retrospective cohort study, patients referred to our nephrology outpatient clinic from April 2017 to March 2019 were included. We excluded patients considered to have an acute decline in kidney function (annual decline in estimated glomerular filtration rate [eGFR] >10 mL/min/1.73 m²). The slopes of eGFR before and after nephrology referral were estimated and compared by linear mixed effects models. Interaction between time and referral status (before or after referral) was assessed and effect modifications by the presence of diabetes, proteinuria (defined by urine dipstick protein 2+ or more), urine occult blood, hypoalbuminemia (defined by albumin levels less than 3.5 g/dL) and anaemia (defined by haemoglobin levels less than 11.0 g/dL) were evaluated. Results The eGFR slope significantly improved from −2.05 (−2.39 to −1.72) to −0.96 (−1.36 to −0.56) mL/min/1.73 m²/year after nephrology referral (p < .001). The improvement in eGFR slope was more prominent among those with diabetes mellitus, anaemia, and hypoalbuminemia (all p‐values for three‐way interaction <.001 after adjustment for covariates). Further adjustments for time‐dependent haemoglobin levels, the use of erythropoiesis‐stimulating agents, iron supplementation, anti‐hypertensives and anti‐diabetic medications did not change the significance of the interactions. Conclusions Nephrology referral slows CKD progression, especially among those with hypoalbuminemia, diabetes or anaemia. Patients with hypoalbuminemia, diabetes or anaemia might benefit more from specialized care and lifestyle modifications by nephrologists. The inclusion of anaemia and hypoalbuminemia in nephrology referral criteria should be considered. image

Abstract Introduction This study aimed to examine the associations of vitamin D receptor activators (VDRA) and calcimimetics use with falls. Methods This is a prospective cohort study on hemodialysis patients in the Japan Dialysis Outcomes and Practice Patterns Study. We excluded those who were unable to walk. The associations of VDRA or calcimimetics use with falls and effect modifications by physical activity were analyzed using marginal structural models. Results In total, 1875 patients were included. VDRA and calcimimetics use was not associated with falls (risk ratio [95% CI]: 1.13 [0.84–1.51] and 1.02 [0.72–1.44]). The risk ratio for falls associated with VDRA use was lower among those with poor physical activity (p for interaction <0.1). Conclusions Although vitamin D receptor activators and calcimimetics use was not associated with falls, the lower risk ratio for falls with vitamin D receptor activators use among those with poor physical activity suggests that vitamin D receptor activators use might be beneficial among these patients.

BACKGROUND: Associations of calcium, phosphate and intact parathyroid hormone (iPTH) levels with outcomes may be different between patients on peritoneal dialysis (PD) and hemodialysis (HD). The aim of the study is to evaluate these associations among PD patients. METHODS: In this prospective cohort study on the Japan Renal Data Registry, adults on PD at the end of 2009 were included. The observation period was until the end of 2018 and the data were censored at the time of transplantation or transition to HD. Exposures were time-averaged or time-dependent albumin-corrected calcium (cCa), phosphate and iPTH levels. Outcomes were all-cause and cardiovascular mortality, transition to HD and urine output. Data were analyzed using Cox regression models or linear mixed-effects models and the results were shown as cubic spline curves. RESULTS: Among 7393 patients, 590 deaths and 211 cardiovascular deaths were observed during a median follow-up of 3.0 years. Higher cCa and phosphate levels were associated with higher mortality. Lower cCa levels were associated with a faster decline, whereas lower phosphate was associated with a slower decline in urine output. Lower phosphate and iPTH levels were associated with a lower incidence of transition to HD. CONCLUSIONS: Among PD patients, the observed associations of cCa, phosphate and iPTH with mortality, residual kidney function and technical failure suggest that avoiding high cCa, phosphate and iPTH levels might improve outcomes.

Association of preoperative regular use of anti-adrenergic agents with postoperative acute kidney injury (AKI) and with trajectory of kidney function after AKI is still unknown. In a retrospective cohort study, adults undergoing non-cardiac surgery under general anesthesia were included. Obstetric or urological surgery, missing data, or preoperative dialysis was excluded. The exposure of interest was preoperative regular use of anti-adrenergic agents. The outcomes were AKI within 1 week postoperatively and trajectories of kidney function within 2 weeks postoperatively among patients with AKI. Multivariable logistic regression models were used to examine the association of anti-adrenergic agents with AKI. Linear mixed-effects models were used to compare the trajectories of postoperative kidney function after AKI between patients with and without anti-adrenergic agents. Among 5168 patients, 245 had used anti-adrenergic agents. A total of 309 (6.0%) developed AKI, and the use of anti-adrenergic agents was independently associated with postoperative AKI even after adjustment for preoperative and intraoperative potential confounders [odds ratio (95% confidence interval): 1.76 (1.14-2.71)]. The association was similar across preexisting hypertension or cardiovascular disease. Analyses restricted to patients with AKI suggested that the timing and stage of AKI were similar among those with and without anti-adrenergic agents; however, the recovery of kidney function was delayed among those with anti-adrenergic agents (P for interaction = 0.004). The use of anti-adrenergic agents was associated with postoperative AKI and delayed recovery of kidney function after AKI. Temporary withdrawal of anti-adrenergic agents during perioperative periods may contribute to prevent AKI and shorten the duration of AKI.

BACKGROUND: Cisplatin-induced acute kidney injury (AKI) is common during preoperative chemotherapy for esophageal cancer. The purpose of this study was to investigate the association between AKI after preoperative chemotherapy and postoperative complications in patients with esophageal cancer. METHODS: In this retrospective cohort study, we included patients who had received preoperative chemotherapy with cisplatin and underwent surgical resection for esophageal cancer under general anesthesia from January 2017 to February 2022 at an education hospital. A predictor was stage 2 or higher cisplatin-induced AKI (c-AKI) defined by the KDIGO criteria within 10 days after chemotherapy. Outcomes were postoperative complications and length of hospital stays. Associations between c-AKI and outcomes including postoperative complications and length of hospital stays were examined with logistic regression models. RESULTS: Among 101 subjects, 22 developed c-AKI with full recovery of the estimated glomerular filtration (eGFR) before surgery. Demographics were not significantly different between patients with and without c-AKI. Patients with c-AKI had significantly longer hospital stays than those without c-AKI [mean (95% confidence interval (95%CI)) 27.6 days (23.3-31.9) and 43.8 days (26.5-61.2), respectively, mean difference (95%CI) 16.2 days (4.4-28.1)]. Those with c-AKI had higher C-reactive protein (CRP) levels and prolonged weight gain after surgery and before the events of interest despite having comparable eGFR trajectories after surgery. c-AKI was significantly associated with anastomotic leakage and postoperative pneumonia [odds ratios (95%CI) 4.14 (1.30-13.18) and 3.87 (1.35-11.0), respectively]. Propensity score adjustment and inverse probability weighing yielded similar results. Mediation analysis showed that a higher incidence of anastomotic leakage in patients with c-AKI was primarily mediated by CRP levels (mediation percentage 48%). CONCLUSION: c-AKI after preoperative chemotherapy in esophageal cancer patients was significantly associated with the development of postoperative complications and led to a resultant longer hospital stay. Increased vascular permeability and tissue edema due to prolonged inflammation might explain the mechanisms for the higher incidence of postoperative complications.

BACKGROUND: The relationship between kidney function at 3 months after acute kidney injury (AKI) and kidney function prognosis has not been characterized. METHODS: This retrospective cohort study included adults who underwent noncardiac surgery under general anesthesia. Exclusion criteria included obstetric or urological surgery, missing data and preoperative dialysis. Linear mixed-effects models were used to compare estimated glomerular filtration rate (eGFR) slopes in patients with and without AKI. Multivariable Cox proportional hazard models were used to examine the associations of AKI with incident chronic kidney disease (CKD) and decline in eGFR ≥30%. RESULTS: Among 5272 patients, 316 (6.0%) developed AKI. Among 1194 patients with follow-up creatinine values, eGFR was stable or increased in patients with and without AKI at 3 months postoperatively and declined thereafter. eGFR decline after 3 months postoperatively was faster among patients with AKI than among patients without AKI (P = .09). Among 938 patients without CKD-both at baseline and at 3 months postoperatively-226 and 161 developed incident CKD and a decline in eGFR ≥30%, respectively. Despite adjustment for eGFR at 3 months, AKI was associated with incident CKD {hazard ratio [HR] 1.73 [95% confidence interval (CI) 1.06-2.84]} and a decline in eGFR ≥30% [HR 2.41 (95% CI 1.51-3.84)]. CONCLUSIONS: AKI was associated with worse kidney outcomes, regardless of eGFR at 3 months after surgery. Creatinine-based eGFR values at 3 months after AKI might be affected by acute illness-induced loss of muscle mass. Kidney function might be more accurately evaluated much later after surgery or using cystatin C values.

BACKGROUND: Outcomes of a combination of peritoneal dialysis (PD) and once-weekly hemodialysis (PD+HD) have not been extensively studied. METHODS: This prospective cohort study on Japanese Society for Dialysis Therapy Renal Data Registry included those who transited from PD to PD+HD therapy or thrice-weekly HD from 2011 to 2018. Exposure was PD+HD therapy compared with thrice-weekly HD. The outcome was time to all-cause or cause-specific death. Associations between PD+HD therapy and outcomes were examined by Cox regression. Sensitivity analyses were performed by propensity score (PS) matching, PS matching with shared frailty model in which dialysis facilities were treated as a random effect, inverse probability weighting (IPW), PS adjustment, PS stratification, competing risk regression, and on-treatment analyses in which data were censored at the transition to thrice-weekly HD for those on PD+HD therapy. RESULTS: During a study period, 1001 subjects transited to PD+HD therapy and 2031 to thrice-weekly HD, respectively. During a median follow-up of 3.5 years, 575 subjects died. All-cause, cardiovascular, congestive heart failure-related, or infection-related mortality were not significantly different between those on PD+HD and those on thrice-weekly HD (HR: 0.95 [0.78-1.16], 1.26 [0.92-1.72], 1.24 [0.77-1.99], and 0.89 [0.57-1.39], respectively). Sensitivity analyses yielded similar results except that PD+HD therapy was associated with significantly lower all-cause mortality by PS adjustment and PS matching with the shared frailty model and lower infection-related mortality by PS adjustment and IPW. CONCLUSIONS: PD+HD therapy was associated with similar or potentially lower mortality compared with thrice-weekly HD. Considering a flexible lifestyle, PD+HD therapy could be a great option.

Immobilization osteoporosis is characterized by excess bone resorption. Vitamin D receptor activators (VDRA) might have adverse effects in immobilized patients. The objective of this study was to elucidate the impact of performance status (PS) on the associations between VDRA use and outcomes among hemodialysis patients. This is a prospective cohort study. Adults on hemodialysis in the Japanese Society for Dialysis Therapy (JSDT) Renal Data Registry were included. Exposure of interest was the use of VDRA. Outcomes were all-cause mortality and hip fracture. Associations between VDRA use and mortality or hip fractures were examined by Cox and Poisson regression analyses, respectively. Among 208,512 subjects, 128,535 were on VDRA. Poor PS was associated with higher calcium (Ca), lower parathyroid hormone, and higher alkaline phosphatase levels. The association between higher Ca levels and VDRA use was stronger among those with poor PS (p interaction 0.007). Adjusted hazard ratio (HR) (95% confidence interval [CI]) for mortality and incidence rate ratio (IRR) for hip fracture was 1.02 (95% CI, 0.99-1.05) and 0.93 (0.86-1.00) among users of VDRA, respectively. The VDRA use was associated with lower mortality and incidence of hip fractures among subjects with good PS but not among subjects with poor PS (p interaction 0.03 and 0.05). Effect modification by PS was observed for cardiovascular (CV) mortality but not for non-CV mortality. In conclusion, VDRA use was associated with better outcomes only among those with good PS. These results suggest that bone and mineral disorders among hemodialysis patients should be treated differently, depending on their performance status. © 2022 American Society for Bone and Mineral Research (ASBMR).

AIMS/INTRODUCTION: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) were reported to increase hemoglobin levels in short-term clinical trials. Whether it is also true in real clinical practice is unknown. MATERIALS AND METHODS: This is a retrospective cohort study. Inclusion criterion was diabetes patients who visited our outpatient clinic from January 2019 to August 2020. Exposure of interest was the use of SGLT2i. Outcomes were hemoglobin levels. For the cross-sectional analyses, non-linear regression models were fitted with restricted cubic splines to investigate the association between hemoglobin levels and estimated glomerular filtration rate (eGFR) for users and non-users of SGLT2i. For the case-control study, cases (anemia defined as hemoglobin <120 g/L for men, <110 g/L for women or the use of erythropoiesis stimulating agents) and controls were matched by age, sex and eGFR. RESULTS: Among 2,063 diabetes patients, 723 were taking SGLT2i. In the cross-sectional analyses, hemoglobin levels were higher among SGLT2i users compared with non-users at eGFR >15 mL/min/1.73 m2 . For the case-control study, 197 cases and controls were matched. Conditional logistic regression showed that the use of SGLT2i was associated with significantly lower prevalence of anemia (odd ratio 0.35, 95% confidence interval 0.21-0.58). Adjusted mean differences in hemoglobin levels between users and propensity score-matched non-users of SGLT2i were 7.0 g/L (95% confidence interval 3.0-10.0 g/L) at 6 months. Among SGLT2i users, the odds of an increase in 6-month hemoglobin were similar across eGFR categories, except for eGFR <15 mL/min/1.73 m2 . CONCLUSIONS: The use of SGLT2i was associated with higher hemoglobin levels and lower prevalence of anemia in real clinical practice.

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.

Background: Approximately 20% of patients on peritoneal dialysis (PD) in Japan are on combination with once-weekly haemodialysis (HD). This study aimed to compare outcomes of combination therapy and PD alone. Methods: This longitudinal study on the Japanese Renal Data Registry included patients on PD from 2010 to 2014. Subjects were followed until the end of 2015. Exposure of interest was combination therapy compared with PD alone. Outcomes were complete transition to HD, all-cause mortality, cardiovascular (CV) mortality and congestive heart failure (CHF)-related mortality. Patients who initiated combination therapy were matched with those on PD alone by propensity scores. Data were analysed using Cox regression models. Results: Among the matched cohort, 608 patients were on combination therapy and 869 were on PD alone. Decline in body weight and residual renal function was more prominent in the combination therapy group. During a median follow-up of 2.5 years, 224 deaths occurred. All-cause mortality {hazard ratio (HR) [95% confidence interval (CI)] 0.56 (0.42-0.75)}, CV mortality [HR 0.48 (0.32-0.72)] and CHF-related mortality [HR 0.19 (0.07-0.55)] were significantly lower, but complete transition to HD was significantly earlier [HR 1.72 (1.45-2.03)] in the combination therapy group. Sensitivity analyses considering the effects of dialysis facilities yielded similar results. Assuming causality, numbers needed to treat to prevent one death per year were 34 patients. Conclusions: Combination therapy was associated with lower all-cause mortality, CV mortality and CHF-related mortality, but earlier transition to HD compared with PD alone, which might be due to better fluid removal by HD.

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 m2/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.

BACKGROUND: This study was conducted to investigate whether acute kidney injury (AKI) is an independent predictor of anemia and whether anemia following AKI is a mediator of mortality after AKI. METHODS: This is a retrospective cohort study. Adults with noncardiac surgery from 2007 to 2011 were included. Obstetric or urological surgery, missing data or preoperative dialysis were excluded. Subjects were followed until the end of 2015 or lost to follow-up. Exposures of interest were postoperative AKI. Outcome variables were hematocrit values at 3, 6 and 12 months postoperatively and mortality. Associations between AKI and hematocrit or association between AKI and mortality were examined by multivariable linear regression or Cox regression, respectively. RESULTS: Among 6692 subjects, 445 (6.6%) developed AKI. Among those with postoperative data, AKI was independently associated with lower hematocrit at 3, 6 and 12 months postoperatively, with coefficients of -0.79 [95% confidence interval (CI) -1.47 to -0.11; n = 1750], -1.35 (-2.11 to -0.60; n = 1558) and -0.91 (-1.59 to -0.22; n = 2463), respectively. Higher stages or longer duration of AKI were associated with more severe anemia. AKI was associated with higher mortality after 3 months postoperatively with a hazard ratio of 1.54 (95% CI 1.12-2.12). Further adjustment with hematocrit at 3 months attenuated the association. The mediation effect was significant (P = 0.02) by mediation analysis. CONCLUSIONS: AKI was an independent predictor of anemia following AKI. Higher mortality associated with AKI was at least partially mediated by anemia following AKI. Whether correction of anemia following AKI improves mortality requires further research.

INTRODUCTION: Previous studies showed that the combination of peritoneal dialysis (PD) and once-weekly hemodialysis is associated with lower all-cause and cardiovascular mortality. This study aimed to compare the incidence of encapsulating peritoneal sclerosis (EPS) and infection-related mortality among those on combination therapy and those on PD alone. METHODS: This prospective study on the Japanese Renal Data Registry included patients on PD from 2010 to 2014. Subjects were followed up until the end of 2015. Exposure of interest was combination therapy compared with PD alone. Patients who transitioned to combination therapy were matched with those on PD alone by propensity scores. Outcomes were EPS and infection-related mortality. Data were analyzed using Cox regression models. RESULTS: Among the matched cohort, 608 and 869 patients were on combination therapy and on PD alone, respectively. Dialysate-to-plasma creatinine (D/P Cr) ratio decreased over time among those on combination therapy, while the ratio increased among those on PD alone (p = 0.01 by the mixed-effects model). During a median follow-up of 2.5 years, 33 experienced EPS and 55 died of infection. Combination therapy was associated with lower infection-related mortality (HR [95% CI]: 0.52 [0.28-0.95]) but not with EPS (HR: 1.21 [0.61-2.40]). Lower mortality was not limited to intra-abdominal infection but also observed for pulmonary infection. Sensitivity analyses considering the effects of dialysis facilities yielded similar results. CONCLUSIONS: Combination therapy was associated with lower infection-related mortality. It was also associated with a decline in the D/P Cr ratio over time but not with lower incidence of EPS during the short observation period.

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.

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.

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.

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.

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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This is a longitudinal study on 53,560 hemodialysis patients from the Japan Renal Data Registry. Predictor was D[Ca] ≥3.0 vs 2.5 mEq/L. Outcomes were the first CV events during 1-year observation period. Association of D[Ca] with CV events and effect modifications were tested using multivariate logistic regression analyses. Diabetes mellitus (DM) was a significant effect modifier for association of higher D[Ca] and myocardial infarction (MI) (OR: 1.26 (1.03-1.55) among DM and 0.86 (0.72-1.03) among non-DM, p for interaction <0.01). The effect size was not affected by further adjustment for serum albumin-corrected Ca or intact parathyroid hormone (iPTH) levels, but was attenuated by adjustment for intradialytic change in serum Ca concentration (ΔCa) (1.16 [0.89-1.51]). Among DM, D[Ca] ≥3.0 mEq/L was significantly associated with MI in the first tertile of corrected Ca or iPTH ≤60 pg/ml (p for interaction 0.03 and 0.03, respectively). In conclusion, higher D[Ca] was associated with incident MI in DM, especially with low serum Ca or iPTH levels. Attenuation of the effect size by adjustment for ΔCa and stratified analyses suggest that larger Ca influx during dialysis with higher D[Ca] in patients suggestive of low bone turnover leads to vascular calcification and subsequent MI in DM.

Paroxysmal nocturnal hemoglobinuria is a rare clonal hematopoietic stem cell disorder characterized by intravascular hemolysis, hemoglobinuria, and inflammatory thrombotic state. Intravascular hemolysis in paroxysmal nocturnal hemoglobinuria (PNH) can lead to acute and chronic renal injury through hemoglobin-mediated toxicity. A 32-year-old pregnant woman with myelodysplastic syndrome was admitted to our hospital with severe preeclampsia. Shortly after an urgent caesarean section, she became obtunded and showed signs of acute kidney injury (AKI) with anuria, severe intravascular hemolysis, and hypermagnesemia. She was diagnosed with PNH with a positive Ham test and flow cytometry analysis. Renal magnetic resonance imaging revealed decreased signal intensity in the renal cortex due to hemosiderin deposition. Hemodialysis, plasma exchange, and administration of corticosteroids ameliorated her clinical condition and renal function. This case illustrates that careful management is required to prevent postpartum AKI in pregnant women with PNH.

Technique failure remains a frequent cause of peritoneal dialysis (PD) withdrawal. Many post-commencement predictors of PD technique failure have been identified, while predialysis predictors have remained unclear. The aim of this study was to identify predialysis indices for technique failure in PD patients. We recruited 206 consecutive PD patients who were treated at Nara Medical University Hospital between 1 April 1997 and 31 December 2012. Forty-eight patients were excluded because of transition from hemodialysis (HD) or withdrawal from PD within 3 months, leaving 158 patients for analysis. Clinical characteristics and laboratory data from within 3 months preceding PD commencement were analyzed. The primary outcome was the composite of time to combined use of HD, transition to HD, and all-cause mortality within 2 years after PD commencement. During the study period, the primary outcome was observed in 50 patients. Using multivariate analysis, greater age (odds ratios (ORs) [95%CI], 3.08 [1.72-5.61]), anemia (ORs [95%CI], 2.12 [1.08-4.43]), overweight/obesity (ORs [95%CI], 2.09 [1.16-3.72]), and hypocalcemia (ORs [95%CI], 1.86 [1.04-3.35]) were independently associated with technique failure. Adding corrected calcium to the model incorporating age, body mass index, and hemoglobin significantly increased the c-statistic from 0.678 to 0.755 (P = 0.048) relative to the model incorporating age alone. The integrated discrimination improvement was 0.085 (95% CI 0.036-0.134, P < 0.001) and the continuous net reclassification improvement was 0.395 (95% CI 0.066-0.724, P = 0.02). In conclusion, the combination of predialysis indices comprising age, overweight/obesity, anemia, and corrected calcium could provide a significant predictive value for technique failure of PD.

Autosomal-dominant polycystic kidney disease (ADPKD) is the most prevalent cystic kidney disease, with approximately half of the patients reaching end-stage renal disease by the age of 60. Tolvaptan prevents renal cyst growth by inhibiting intracellular cyclic AMP and is recommended for patients with ADPKD. Reports of thrombotic complications with tolvaptan have been limited. We report a case of a 60-year-old man who developed thromboembolisms during tolvaptan treatment for ADPKD. The patient started tolvaptan in July 2014. He was brought to our hospital in February 2015 with a sudden onset of dyspnea and chest pain after 6 days of persistent watery diarrhea. Blood tests revealed enhanced coagulation and fibrinolysis, and contrast-enhanced computed tomography confirmed the presence of multiple thromboembolisms. Venous thromboembolism (VTE) with acute pulmonary and lower extremity thrombi was diagnosed, and the patient was immediately admitted. Tolvaptan was discontinued on admission, and intravenous fluid loading and monteplase were started. Subsequently, chest pain and dyspnea resolved, with thrombi resolution occurring by day 14; the patient was discharged on day 18 in stable condition. VTE was attributed to continued tolvaptan during diarrhea and dehydration; tolvaptan itself was not associated with enhanced coagulability. Dehydrated patients with ADPKD, such as the patient in this case, are at an increased risk for thrombus formation. Proper education should be provided to maintain appropriate fluid status and discontinue tolvaptan upon volume depletion.

BACKGROUND: Placental growth factor (PlGF) is a member of the vascular endothelial growth factor family that acts as a pleiotropic cytokine capable of stimulating angiogenesis and accelerating atherogenesis. Soluble fms-like tyrosine kinase-1 (sFlt-1) antagonizes PlGF action. Higher levels of PlGF and sFlt-1 have been associated with cardiovascular events in patients with chronic kidney disease, yet little is known about their relationship with adverse outcomes in patients on peritoneal dialysis (PD). The aim of this study was to investigate the association of PlGF and sFlt-1 with technique survival and cardiovascular events. METHODS: We measured serum levels of PlGF and plasma levels of sFlt-1 in 40 PD patients at Nara Medical University. RESULTS: PlGF and sFlt-1 levels were significantly correlated with the dialysate-to-plasma ratio of creatinine (r = 0.342, p = 0.04 and r = 0.554, p < 0.001) although PlGF and sFlt-1 levels were not correlated with total creatinine clearance and total Kt/V. Additionally, both PlGF and sFlt-1 levels were significantly higher in patients with high transport membranes compared to those without (p = 0.039 and p < 0.001, respectively). Patients with PlGF levels above the median had lower technique survival and higher incidence of cardiovascular events than patients with levels below the median, with hazard ratios of 11.9 and 7.7, respectively, in univariate Cox regression analysis. However, sFlt-1 levels were not associated with technique survival or cardiovascular events (p = 0.11 and p = 0.10, respectively). CONCLUSION: Elevated PlGF and sFlt-1 are significantly associated with high transport membrane status. PlGF may be a useful predictor of technique survival and cardiovascular events in PD patients.

BACKGROUND AND OBJECTIVES: Pre- and/or intra-operative use of diuretics, angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin II receptor blockers (ARB) constitutes a potentially modifiable risk factor for postoperative acute kidney injury (AKI). It has been studied whether use of these drugs predicts AKI after cardiac surgery. The objective of this study was to examine whether administration of these agents was independently associated with AKI after non-cardiac surgery. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: This was a retrospective observational study. Inclusion criteria were adult patients (age ≥ 18) who underwent non-cardiac surgery under general anesthesia from 2007 to 2009 at Kyoto Katsura Hospital. Exclusion criteria were urological surgery, missing creatinine values, and preoperative dialysis. The exposures of interest were pre- and/or intra-operative use of diuretics or ACE-I/ARB. Outcome variables were postoperative AKI as defined by the AKI Network (increase in creatinine ≥ 0.3 mg/dL or 150% within 48 hours, or urine output < 0.5 ml/kg/hour for > 6 hours). Multivariable logistic regression analyses were conducted and adjusted for potential confounders. Propensity scores (PS) for receiving diuretics or ACE-I/ARB therapy were estimated and PS adjustment, PS matching, and inverse probability weighting were performed. RESULTS: There were 137 AKI cases (5.0%) among 2,725 subjects. After statistical adjustment for patient and surgical characteristics, odds (95% CI) of postoperative AKI were 2.07 (1.10-3.89) (p = 0.02) and 0.89 (0.56-1.42) (p = 0.63) in users of diuretics and ACE-I/ARB, respectively, compared with non-users. PS adjustment, PS matching, and inverse probability weighting yielded similar results. The effect size of diuretics was significantly greater in the patients with lower propensity for diuretic use (p for interaction < 0.1). CONCLUSIONS: Prescription of diuretics, but not ACE-I/ARB, was independently associated with postoperative AKI after non-cardiac surgery, especially in patients with low propensity for diuretic use. It might be reasonable to withhold preoperative diuretics in these patients.

BACKGROUND: Placental growth factor (PlGF), a member of the vascular endothelial growth factor (VEGF) family, has recently emerged as a predictor of survival and cardiovascular risk. Along with others, we have shown an independent association between PlGF and cardiovascular events in CKD patients, but not much is known about patients receiving dialysis. METHODS: We studied 205 dialysis patients undergoing cardiac catheterization at the Nara Medical University between April 1, 2004, and December 31, 2012. Serum levels of PlGF and VEGF were measured with ELISA in all the patients. RESULTS: During a median follow-up of 20 months, 121 participants died from any cause or experienced a cardiovascular event. In the fully adjusted analysis, having an above-median PlGF or VEGF level was associated with a hazards ratio for adverse outcomes of 2.55 (1.72-3.83) and 1.39 (0.95-2.04), respectively. Using a multimarker strategy in a model with age, serum albumin, history of coronary artery disease, brain natriuretic peptide and PlGF, patients with 2, 3 and 4 positive markers had a 3.82-, 5.77- and 6.59-fold higher risk of mortality or a cardiovascular event, respectively, compared to those with no positive markers. The model with PlGF had a significantly higher c-statistic, integrated discrimination improvement index and category-free net reclassification improvement index than the model without PlGF. CONCLUSION: PlGF is independently associated with mortality and cardiovascular events, but the association between VEGF and adverse events was attenuated with covariate adjustment. The addition of PlGF to models with established clinical predictors provides additional useful prognostic information in patients receiving dialysis.

Reactivation of the hepatitis B virus (HBV) has been reported in patients receiving immunosuppressive therapy or chemotherapy. We report a case of HBV reactivation in a patient negative for hepatitis B surface antigen (HBsAg), positive for hepatitis B core antibody (anti-HBc), and positive for hepatitis B surface antibody (anti-HBs), who was undergoing chronic maintenance hemodialysis without immunosuppressive therapy or chemotherapy. The patient was an 85-year-old woman with end-stage renal disease due to nephrosclerosis who had undergone maintenance hemodialysis for a year. She had been HBsAg-negative, anti-HBc- and anti-HBs-positive previously, but biannual routine surveillance for HBV showed positivity for HBsAg, negativity for anti-HBs, and positivity for HBV DNA (5.9 log copies/mL). She was asymptomatic, and transaminases were within normal limits. She was dialyzed in an isolated room with a dedicated staff member for the control of infection. HBV is a blood-borne pathogen, which is highly infectious. Hemodialysis is a procedure associated with high risk for blood-borne infection. We should recognize the risk of reactivation of HBV in HBsAg-negative, anti-HBc-positive patients, and consider how to incorporate anti-HBc screening and infection control in isolated anti-HBc-positive hemodialysis patients in clinical practice.

We report a case of membranous nephropathy associated with type 1 autoimmune pancreatitis. A 58-year-old man presented with anorexia. Work-up revealed a mass in the pancreatic head, which was subsequently resected. Pathological examination showed diffuse infiltration of immunoglobulin (Ig) G4-positive plasma cells, which was compatible with the diagnosis of type 1 autoimmune pancreatitis. Serum IgG4 was elevated. He developed nephrotic syndrome around the time of the surgery. Kidney biopsy confirmed the diagnosis of membranous nephropathy. Immunofluorescent staining showed predominant glomerular IgG4 deposit among IgG subclasses. Tubulointerstitial nephritis, which is usually a dominant feature of renal involvement in IgG4-related disease, was not observed. The patient was treated with prednisolone and several immunosuppressants. During the course, the degree of proteinuria was associated with the serum IgG4 level. Serum antibody against phospholipase A2 receptor was negative. These findings together with IgG4-dominant glomerular deposit suggest that IgG4 may play a unique role in the pathogenesis of secondary membranous nephropathy caused by IgG4-related diseases.

BACKGROUND/AIMS: The associations between phosphate, calcium, and intact parathyroid hormone (PTH) levels and composite cardiovascular end points have been studied. This study examined the associations of these markers with myocardial infarction (MI) and stroke separately. METHODS: This is a longitudinal study on 65,849 hemodialysis patients from the Japan Renal Data Registry. Patients with prior events at baseline were excluded. Predictors were phosphate, albumin-corrected calcium, intact PTH, and calcium times phosphate product levels. Outcome was the first episode of MI or stroke during a 1-year observation period. Data were analyzed using multiple logistic regression analyses, adjusted for potential confounders. RESULTS: There were 1,048, 651, and 2,089 events of incident MI, hemorrhagic, and ischemic stroke, respectively. Incident MI was associated with phosphate levels ≥6.5 mg/dL (odds ratio 1.49; confidence interval 1.23-1.80) compared with phosphate levels of 4.7-5.4 mg/dL and intact PTH levels>500 pg/mL (1.35; 1.03-1.79) compared with intact PTH levels of 151-300 pg/mL. Higher albumin-corrected calcium level was positively associated with MI (p = 0.04 by trend analysis). Hemorrhagic stroke was associated only with intact PTH levels>500 pg/mL (1.54; 1.10-2.17). Incident ischemic stroke had no association with phosphate, calcium, or intact PTH levels. The association of calcium times phosphate product with outcomes was essentially the same pattern as that of phosphate and outcomes. CONCLUSIONS: MI was associated with phosphate, calcium, and intact PTH levels, whereas hemorrhagic stroke was associated only with intact PTH. Ischemic stroke was not associated with any of them. The potential distinct beneficial effect on MI and stroke by managing bone and mineral disease should be investigated in future studies.

Endothelial progenitor cells (EPCs) are thought to be important for maintaining normal vascular function. We conducted a prospective study evaluating the effect of the erythropoiesis-stimulating agent darbepoetin alfa on EPCs and vascular function in patients with chronic kidney disease (CKD), with or without diabetes. Thirty subjects with CKD (20 subjects with type II diabetes mellitus and 10 without diabetes mellitus) received weekly subcutaneous administration of darbepoetin alfa for 4 weeks. EPCs were measured at baseline and 2 and 4 weeks after drug administration. Vascular function was measured with brachial ultrasound and cell activity was measured with a cell proliferation assay. Cells expressing CD133, CD34, CD146 and CD146/31 were significantly elevated (all p < 0.05), flow-mediated vasodilatation increased 2.1%, 95% CI: (0.4%, 3.8%) and colony-forming units increased twofold, 95% CI: (1.7, 2.3) after 4 weeks of treatment with darbepoetin alfa. Subjects with diabetes exhibited an increase in a subset of EPCs (CD133( +) and 34(+), p < 0.01 and p = 0.06, respectively), vasodilatation and proliferation. In conclusion, the administration of darbepoetin alfa for 4 weeks increased a subset of EPCs, improved endothelial function and increased cell proliferation, including those with diabetes, which is consistent with a favorable improvement in vascular health.

We report a case of a patient with chronic kidney disease likely due to lead nephropathy. He was a manufacturer of Buddhist altar fittings and had chronic lead exposure. The blood lead level was 41 microg/dL and urinary lead excretion at 24 hours after the administration of ethylenediaminetetraacetic acid (EDTA)was 600 microg (first time)and 687 microg (second time), respectively. Urinary lead excretion at 72 hours was 834 microg (first time) and 1,071 microg (second time), respectively. Renal biopsy showed interstitial fibrosis and focal monocyte infiltration. Lead content in the renal biopsy specimen was 130 ng/g of wet weight. We preformed weekly EDTA chelation therapy twelve times. During the therapy, serum creatinine was 1.1 mg/dL. The chelation therapy was interrupted by an episode of acute renal failure due to hypotension and heart failure. Urinary lead excretion exceeding 600 microg at 72 hours after chelation therapy indicated a lead body burden capable of causing lead nephropathy. In this case, urinary lead excretion exceeded 600 microg at 72 hours. Based on the report that repeated lead chelation therapy can slow the progression of non-diabetic chronic kidney disease with 72-hour-urinary lead excretion of 60-600 microg, we performed chelation therapy. This case suggests that lead nephropathy currently can occur in Japan. It is possible that renal dysfunction from lead nephropathy is reversed by minimizing lead exposure and chelation therapy. Lead nephropathy should be included in the differenitial diagnosis of causes of chronic kidney disease and occupational and environmental lead exposure should be investigated carefully during the medical history.

Intradialytic blood pressure (BP) variability may be associated with increased mortality. We examined the effect of short daily hemodialysis (SDHD) on intradialytic BP variability relative to conventional thrice-weekly HD (CHD). This is a retrospective cohort study. Subjects were those converted from CHD to SDHD (n=12). All intradialytic BPs were collected on the last month of CHD, and on month 6 of SDHD. Absolute predialysis BP level and intradialytic BP variability were defined as the intercept and average residual terms, respectively, from a mixed-effects linear regression model of time on BP. Dialysis modality was a predictor variable (CHD vs. SDHD). Outcome variables were intradialytic BP variability and hypotension (BP<90/55 mmHg at any time during HD). In addition to a predictor and outcomes, the demographics, estimated dry weight, and ultrafiltration ratio were examined. The median (range) age of the patients was 48 (34-77); all had hypertension, and 4 (33%) had diabetes. By a mixed effects linear regression model, the intradialytic systolic BP variability was 13.2 (quartile range 9.5-14.0) mmHg and 10.0 (8.3-10.9) mmHg for CHD and SDHD, respectively (P<0.006). Intradialytic diastolic BP variability was also significantly reduced (7.7 [6.4-9.2] vs. 6.1 [5.5-6.6] mmHg, P=0.005). Relative to CHD, less hypotension was observed during treatment on SDHD: the odds ratio (95% confidence interval) was 0.36 (0.16-0.81; P=0.008). In this retrospective study, SDHD was associated with less intradialytic BP variability and with fewer episodes of hypotension during treatments. Further studies are necessary to generalize these findings.

Adrenal venous sampling (AVS) remains controversial in the management of primary aldosteronism. Retrospective chart review was conducted at the Hospital of the University of Pennsylvania from July 2001 to September 2007. A total of 113 patients underwent AVS, 16 patients were excluded as records were unavailable. Among 97 remaining patients, 61 had unilateral disease and 57 underwent unilateral adrenalectomy. Blood pressure (BP) improved significantly with less antihypertensive medication requirement. Among those with different BP responses to adrenalectomy (cure, improvement, or no change), a higher number of preoperative antihypertensive medications was associated with persistent hypertension (P = .03). There were no significant differences in age (P = .14), duration of hypertension (P = .60), family history of hypertension (P = .68), or serum creatinine (P = .34). When AVS shows lateralization, age, duration of hypertension, family history, or renal dysfunction did not predict BP response to adrenalectomy. Results suggest that these factors should not preclude AVS and subsequent adrenalectomy. Further studies are indicated to confirm these findings.

We report a case of a patient on maintenance peritoneal dialysis therapy treated with a high-dose methotrexate regimen for central nervous system lymphoma. For the initial methotrexate cycles, he had received temporary daily high-flux hemodialysis starting 24 hours after the infusion of methotrexate to avoid toxicity. However, on account of issues with vascular access, he was treated with continuous multiple-exchange peritoneal dialysis for the last 2 cycles of chemotherapy. Time-averaged clearances (dose divided by area under the curve, combination of endogenous and dialysis clearance) during treatment with high-flux hemodialysis and continuous multiple-exchange peritoneal dialysis were 0.77 mL/min/kg (0.013 mL/s/kg) and 0.65 mL/min/kg (0.011 mL/s/kg), respectively. Peritoneal clearance of methotrexate was estimated to be 0.124 +/- 0.037 mL/min/kg (0.00207 +/- 0.00062 mL/s/kg). Despite lower clearance by means of peritoneal dialysis compared with hemodialysis, the patient did not develop clinical evidence of methotrexate toxicity.

We report a case of chronic tubulointerstitial nephritis associated with multiple nodular lesions of the kidneys in a patient with autoimmune pancreatitis. Serum immunoglobulin G4 (IgG4) level was increased, and immunohistochemical staining for IgG4 on the renal biopsy specimen showed positive staining of plasma cells and tubular basement membrane within areas of chronic tubulointerstitial nephritis. There are a few reports of nodular lesions of kidneys or interstitial nephritis associated with autoimmune pancreatitis. Our case is unique in that all 3 conditions presented together and suggests that interstitial nephritis can present as nodular lesions.

当院で2018年から2020年までの間に抗癌剤治療を受けた2644名の後方視的観察研究を行った。eGFRが前回のeGFRに比して30％以上低下するものをAKIと定義して、AKIに関連する抗がん剤をまずは見だした。平均年齢は65歳で平均eGFR は71 (59-84) mL/min/1.73m2であった。Pembrolizumab, trastuzumabと oxaliplatinがAKIと関連し、そのオッズ比(95%信頼区間)はそれぞれ 1.52 [1.03-2.23], 2.78 [1.26-6.12],1.72 [1.20-2.46]であった。 抗癌剤以外のリスク因子は高いCRPとループ利尿薬やトルバプタン、抗血小板薬の使用であった。PembrolizumabやtrastuzumabとAKIの関連はNSAIDs使用患者で特に強かった。 抗腫瘍薬による電解質異常を早期に捕捉できるようにするため、2021年5月から当院で電子カルテ上で自動的に各科主治医に腎臓内科受診を促す「電解質バスターズ」なるシステムを構築した。実際に依頼を行うかどうかは担当医師の判断にゆだねた。紹介基準はNa<125, Na>160, K<2.5, K>6.0, 補正Ca<7.5, 補正Ca>11.5, Mg<1.0, Mg>4.0 mEq/Lとした。電解質バスターズ導入前後6か月の依頼箋数を比較したところ、K異常は導入前後で紹介数は変わらなかったが、Na, Ca, Mg異常は各々2倍に増え、３つの電解質異常をまとめると依頼のincident rate ratioは2.01（95% CI: 1.00-4.24）となった。依頼の最も多い低Na血症16例のうち、5例がSIADH、5例が薬剤性（抗癌剤や利尿剤）を含む腎性Na喪失、3例が水中毒と診断され、SIADHの２例にトルバプタンを導入しNa濃度が改善した。

本研究では、急性腎障害を起こした患者を前向きに長期経過観察を行い、一般的な心血管系イベントや末期腎不全のリスク因子（血圧、蛋白尿、脂質、血糖、喫煙など）だけではなく、炎症、貧血、骨代謝などについても、予後との関連を検討し、今後の介入研究につなげていくことを目的とする。対象患者は慢性腎臓病(推定糸球体ろ過量(eGFR)が60ml/min/1.73m2未満が3か月以上持続)、尿蛋白陽性：尿定性検査における尿蛋白が(2+)あるいはそれ以上の患者で、心臓血管外科で心臓手術あるいは大血管手術を受ける患者、または消化器外科で、全身麻酔下に腹腔内手術を受ける患者、または悪性腫瘍に対する化学療法を受ける患者である。主要評価項目は全死亡、心血管系イベント（侵襲的処置を必要とする狭心症、閉塞性動脈硬化症、心筋梗塞、脳梗塞、脳出血、入院を要する心不全） 、入院を要する感染症、悪性腫瘍の再発及び新規診断、骨折、functional status、腎機能、透析導入の有無、QOL(SF-36の点数)である。関係各科（心臓血管外科、消化器外科、臨床腫瘍部）の了承を得て、当該年度において、Institutional Review Boardの承認を得て、患者の登録を開始した。現在、２５例を登録している。上記の評価項目に加えて、CTで計測される腎容積と急性腎障害の関連、急性腎障害の予後と腎容積の関連も今後、解析していく予定としている。