Non-indicated initiation of proton pump inhibitor and risk of adverse outcomes in patients with underlying chronic kidney disease: a nationwide, retrospective, cohort study.

OBJECTIVE: Evidence related to the risk of kidney damage by proton pump inhibitor (PPI) initiation in patients with 'underlying' chronic kidney disease (CKD) remains scarce, although PPI use is generally associated with acute interstitial nephritis or incident CKD. We aimed to investigate the association between PPI initiation and the risk of adverse outcomes in patients with CKD in the absence of any deterministic indications for PPI usage. DESIGN: Retrospective observational study. SETTING: Korea National Health Insurance Service database from 2009 to 2017. PARTICIPANTS: A retrospective cohort of new PPI and histamine H2-receptor antagonists (H2RA) users among people with CKD. Patients with a history of gastrointestinal bleeding or those who had an endoscopic or image-based upper gastrointestinal tract evaluation were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: The study subjects were followed to ascertain clinical outcomes including mortality, end-stage kidney disease (ESKD), myocardial infarction and stroke. The HRs of outcomes were measured using a Cox regression model after adjusting for multiple variables. We applied an inverse probability of treatment weighting (IPTW) model to control for residual confounders. RESULTS: We included a total of 1038 PPI and 3090 H2RA users without deterministic indications for treatment. IPTW-weighted Cox regression analysis showed that PPI initiation was more significantly associated with a higher ESKD risk compared with that of H2RA initiation (adjusted HR 1.72 (95% CI 1.19 to 2.48)), whereas the risks of mortality or cardiovascular outcomes were similar between the two groups. In the subgroup analysis, multivariable Cox regression analysis showed that the association between PPI use and the progression to ESKD remained significant in non-diabetic and low estimated glomerular filtration rate (<60 mL/min/1.73 m2) groups (adjusted HR 1.72 (95% CI 1.19 to 2.48) and 1.63 (95% CI 1.09 to 2.43), respectively). CONCLUSIONS: Initiation of PPI administration may not be recommended in patients with CKD without deterministic indication, as their usage was associated with a higher risk of ESKD.

Causal Effect of Chondroitin, Glucosamine, Vitamin, and Mineral Intake on Kidney Function: A Mendelian Randomization Study.

The causal effects of chondroitin, glucosamine, and vitamin/mineral supplement intake on kidney function remain unknown, despite being commonly used. We conducted a two-sample summary-level Mendelian randomization (MR) analysis to test for causal associations between regular dietary supplement intake and kidney function. Genetic instruments for chondroitin, glucosamine, and vitamin/mineral supplement intake were obtained from a genome-wide association study of European ancestry. Summary statistics for the log-transformed estimated glomerular filtration rate (log-eGFR) were provided by the CKDGen consortium. The multiplicative random-effects inverse-variance weighted method showed that genetically predicted chondroitin and glucosamine intake was causally associated with a lower eGFR (chondroitin, eGFR change beta = -0.113%, standard error (SE) = 0.03%, p-value = 2 × 10-4; glucosamine, eGFR change beta = -0.240%, SE = 0.035%, p-value = 6 × 10-12). However, a genetically predicted vitamin/mineral supplement intake was associated with a higher eGFR (eGFR change beta = 1.426%, SE = 0.136%, p-value = 1 × 10-25). Validation analyses and pleiotropy-robust MR results for chondroitin and vitamin/mineral supplement intake supported the main results. Our MR study suggests a potential causal effect of chondroitin and glucosamine intake on kidney function. Therefore, clinicians should carefully monitor their long-term effects.

Chemokine (C-C Motif) Ligand 8 and Tubulo-Interstitial Injury in Chronic Kidney Disease.

Kidney fibrosis has been accepted to be a common pathological outcome of chronic kidney disease (CKD). We aimed to examine serum levels and tissue expression of chemokine (C-C motif) ligand 8 (CCL8) in patients with CKD and to investigate their association with kidney fibrosis in CKD model. Serum levels and tissue expression of CCL8 significantly increased with advancing CKD stage, proteinuria level, and pathologic deterioration. In Western blot analysis of primary cultured human tubular epithelial cells after induction of fibrosis with rTGF-ß, CCL8 was upregulated by rTGF-ß treatment and the simultaneous treatment with anti-CCL8 mAb mitigated the rTGF-ß-induced an increase in fibronectin and a decrease E-cadherin and BCL-2 protein levels. The antiapoptotic effect of the anti-CCL8 mAb was also demonstrated by Annexin V/propidium iodide staining assay. In qRT-PCR analysis, mRNA expression levels of the markers for fibrosis and apoptosis showed similar expression patterns to those observed by western blotting. The immunohistochemical analysis revealed CCL8 and fibrosis- and apoptosis-related markers significantly increased in the unilateral ureteral obstruction model, which agrees with our in vitro findings. In conclusion, CCL8 pathway is associated with increased risk of kidney fibrosis and that CCL8 blockade can ameliorate kidney fibrosis and apoptosis.

Optimal target blood pressure for major adverse cardiovascular and cerebrovascular events in hypertensive patients: a nationwide population-based study.

BACKGROUND: Generalizing an 'optimal' blood pressure (BP) level for individuals with hypertension remains controversial due to the implementation of different medical guidelines. This study investigated the association of BP with major adverse cardiovascular and cerebrovascular events (MACCE) and determined the optimal BP for patients with hypertension. METHOD: A total of 934 179 individuals who received antihypertensive medications were selected from the National Health Insurance Service Examination Database between 2003 and 2011 in Korea. Their BP was measured at the index date, which was the first health examination. The study outcomes were MACCE, including acute myocardial infarction, heart failure, stroke, and all-cause mortality. The participants were monitored until in December, 2017. The hazard ratios were calculated using Cox proportional hazard models. The cumulative incidence of MACCE for each BP group was estimated using the Kaplan-Meier method. RESULTS: A lower risk of MACCE was observed at a SBP of 120-129 mmHg and a DBP of 80-89 mmHg. The endpoint-specific incidence rates and hazard ratios for acute myocardial infarction, heart failure, stroke, and all-cause mortality were the lowest at a SBP of 120-129 mmHg and a DBP of 80-89 mmHg. CONCLUSION: Even though this observational study did not support inference of a causal relationship, a SBP of 120-129 mmHg and a DBP of 80-89 mmHg may be safely recommended considering the possibility of MACCE in Korean patients with hypertension. In addition, the target BP should be tailored individually according to age, sex, and comorbidities.

Evolving outcomes of peritoneal dialysis: secular trends at a single large center over three decades.

BACKGROUND: Peritoneal dialysis (PD) is improving as a renal replacement therapy for end-stage renal disease (ESRD) patients. We analyzed the main outcomes of PD over the last three decades at a single large-scale PD center with an established high-quality care system. METHODS: As a retrospective cohort study, we included participants (n = 1,203) who began PD between 1990 and 2019. Major PD-related outcomes were compared among the three 10-year cohorts. RESULTS: The 1,203 participants were 58.3% male with a mean age of 47.9 ± 13.8 years. The median PD treatment duration was 45 months (interquartile range, 19-77 months); 362 patients (30.1%) transferred to hemodialysis, 289 (24.0%) received kidney transplants, and 224 (18.6%) died. Overall, the 5- and 8-year adjust patient survival rates were 64% and 49%, respectively. Common causes of death included infection (n = 55), cardiac (n = 38), and cerebrovascular (n = 17) events. The 5- and 8-year technique survival rates were 77% and 62%, respectively, with common causes of technique failure being infection (42.3%) and solute/water clearance problems (22.7%). The 5-year patient survival significantly improved over time (64% for the 1990-1999 cohort vs. 93% for the 2010-2019 cohort). The peritonitis rate also substantially decreased over time, from 0.278 episodes/patient-year (2000-2004) to 0.162 episodes/patient-year (2015-2019). CONCLUSION: PD is an effective treatment option for ESRD patients. There was a substantial improvement in the patient survival and peritonitis rates over time. Establishing adequate infrastructure and an effective system for high-quality PD therapy may be warranted to improve PD outcomes.

Effectiveness of Clinical Pharmacist Service on Drug-Related Problems and Patient Outcomes for Hospitalized Patients with Chronic Kidney Disease: A Randomized Controlled Trial.

(1) Background: The study aimed to analyze the effectiveness of clinical pharmacist services on drug-related problems (DRPs) and patient outcomes in inpatients with chronic kidney disease (CKD). (2) Methods: In a randomized controlled trial, the participants in the intervention group received pharmacist services, including medication reconciliation, medication evaluation and management, and discharge pharmaceutical care transition services. Participants in the control group received usual care. The primary outcome was the number of DRPs per patient at discharge. (3) Results: The baseline characteristics of 100 participants included the following: mean age, 52.5 years; median eGFR, 9.2 mL/min/1.73 m2. The number of DRPs in the intervention group during hospitalization increased significantly with decreasing eGFR (PR, 0.970; 95% CI, 0.951-0.989) and an increasing number of unintentional medication discrepancies at admission (PR, 1.294; 95% CI, 1.034-1.620). At discharge, the number of DRPs per patient was 0.94 ± 1.03 and 1.96 ± 1.25 in the intervention and control groups, respectively (p < 0.001). The service had a significant effect on the reduction of the unintentional discrepancies at discharge (p < 0.001). (4) Conclusion: Hospital pharmacists play an important role in the prevention of DRPs at discharge and unintentional medication discrepancies in inpatients with CKD.

Causal Effects of Serum Levels of n-3 or n-6 Polyunsaturated Fatty Acids on Coronary Artery Disease: Mendelian Randomization Study.

We aimed to investigate the causal effects of n-3 and n-6 polyunsaturated fatty acids (PUFAs) on the risk of coronary artery disease (CAD) through Mendelian randomization (MR) analysis. This MR study utilized a genetic instrument developed from previous genome-wide association studies for various serum n-3 and n-6 PUFA levels. First, we calculated the allele scores for genetic predisposition of PUFAs in individuals of European ancestry in the UK Biobank data (N = 337,129). The allele score-based MR was obtained by regressing the allele scores to CAD risks. Second, summary-level MR was performed with the CARDIoGRAMplusC4D data for CAD (N = 184,305). Higher genetically predicted eicosapentaenoic acid and dihomo-gamma-linolenic acid levels were significantly associated with a lower risk of CAD both in the allele-score-based and summary-level MR analyses. Higher allele scores for linoleic acid level were significantly associated with lower CAD risks, and in the summary-level MR, the causal estimates by the pleiotropy-robust MR methods also indicated that higher linoleic acid levels cause a lower risk of CAD. Arachidonic acid showed significant causal estimates for a higher risk of CAD. This study supports the causal effects of certain n-3 and n-6 PUFA types on the risk of CAD.

Predictive value of cardio-ankle vascular index for the risk of end-stage renal disease.

BACKGROUND: Arterial stiffness is associated with increased cardiovascular morbidity and mortality. However, the predictive value of the cardio-ankle vascular index (CAVI), one of the indicators for arterial stiffness, for the risk of end-stage renal disease (ESRD) remains unknown. METHODS: A total of 8701 patients with documented CAVI measurements by pulse wave velocity (PWV) were included in the study. Patients were divided according to the quartiles of CAVI. The hazard ratio (HR) of ESRD was calculated using the Cox model, after adjustment for multiple variables or death. RESULTS: During the median follow-up period of 7 years (maximum 12 years), ESRD and mortality occurred in 203 and 1071 patients, respectively. The median value of CAVI was 8.5 (interquartile range 7.7-9.3). The risk of ESRD was higher in the fourth-quartile group than the first-quartile group [adjusted HR 2.46 (IQR 1.62-3.71), P < 0.001]. When a death-adjusted risk analysis was performed, the fourth quartile of CAVI had a higher risk of ESRD than the first quartile [adjusted HR 2.35 (IQR 1.58-3.49), P < 0.001]. CONCLUSIONS: The measurement of CAVI by PWV may be needed to predict the risk of ESRD.

Low serum total CO2 and its association with mortality in patients being followed up in the nephrology outpatients clinic.

Large-scale studies have not been conducted to assess whether serum hypobicarbonatemia increases the risk for kidney function deterioration and mortality among East-Asians. We aimed to determine the association between serum total CO2 (TCO2) concentrations measured at the first outpatient visit and clinical outcomes. In this multicenter cohort study, a total of 42,231 adult nephrology outpatients from 2001 to 2016 were included. End-stage renal disease (ESRD) patients on dialysis within 3 months of the first visit were excluded. Instrumental variable (IV) was used to define regions based on the proportion of patients with serum TCO2 < 22 mEq/L. The crude mortality rate was 12.2% during a median 77.0-month follow-up period. The Cox-proportional hazard regression model adjusted for initial kidney function, alkali supplementation, and the use of diuretics demonstrated that low TCO2 concentration was not associated with progression to ESRD, but significantly increased the risk of death. The IV analysis also confirmed a significant association between initial TCO2 concentration and mortality (HR 0.56; 95% CI 0.49-0.64). This result was consistently significant regardless of the underlying renal function. In conclusion, low TCO2 levels are significantly associated with mortality but not with progression to ESRD in patients with ambulatory care.

Ratio of triglyceride to high-density lipoprotein cholesterol and risk of major cardiovascular events in kidney transplant recipients.

BACKGROUND: Dyslipidemia is common in kidney transplant (KT) recipients. We analyzed the ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) in KT recipients to identify risk factors for major cardiovascular events (MACE). METHODS: We retrospectively included KT recipients with a lipid profile performed 1 year after transplantation. We classified patients according to the TG/HDL-C divided into quintiles. Subsequently, we analyzed the association between TG/HDL-C and MACE, defined as heart failure, coronary artery disease, and cerebrovascular disease confirmed by imaging studies. RESULTS: A total of 1301 KT recipients were enrolled. The median follow-up duration was 7.4 years (interquartile range 4.4-11.1 years). During the follow-up period, 80 (6.2%) patients developed MACE, which included 38 of unstable anginas, 9 of MIs, 19 of heart failures, 18 of cerebral infarcts, and 4 of cerebral hemorrhages. The fourth and fifth quintiles of TG/HDL-C showed a significantly increased risk of MACE [fourth quintile: adjusted hazard ratio (aHR), 3.38; 95% confidence interval (CI) 1.44-7.95; p = 0.005, fifth quintile: aHR, 2.67; 95% CI 1.13-6.30; p = 0.02]) compared to the second quintile of TG/HDL-C. This association is particularly evident in subgroups of non-DM, HTN, no history of CVD, and statin users. CONCLUSIONS: Higher TG/HDL-C levels may be associated with MACE risk in KT recipients.

Timing of referral for vascular access for hemodialysis: Analysis of the current status and the barriers to timely referral.

INTRODUCTION: Current guidelines recommend the placement of vascular access 6 months before the anticipated start of hemodialysis therapy; however, many patients start hemodialysis using a central venous catheter. We investigated the timing of referral for vascular access, the vascular access type at hemodialysis initiation, and the barriers to a timely referral. METHODS: The study involved a retrospective review of 237 patients for whom the first vascular access for hemodialysis was created between January and November 2017. RESULTS: Among the 237 patients, 58.2% were referred before hemodialysis initiation, while 41.8% were referred after hemodialysis initiation. Among the 138 patients, 55, 59, and 24 patients were referred more than 6 months, between 2 and 6 months, and within 2 months before hemodialysis initiation, respectively. Within these subgroups, 3.6%, 10.2%, and 75.0% patients underwent hemodialysis initiation with a central venous catheter, respectively. Among the 99 patients referred after hemodialysis initiation, the reasons for late referral were as follows: unexpected rapid progression of kidney disease (n = 23), noncompliance (n = 21), late visit to the nephrologist (initial visit within 2 months of hemodialysis initiation; n = 14), change of treatment strategy from peritoneal dialysis or transplants (n = 9), and unknown reasons (n = 32). CONCLUSION: Only 23% of patients were referred for vascular access 6 months before the anticipated hemodialysis therapy. In addition, 53% of patients initiated hemodialysis with a central venous catheter. Avoidance of catheter insertion was mostly successful in patients referred 2 months before hemodialysis initiation. The most common modifiable barrier to the timely referral was noncompliance.

Hyperuricemia is associated with acute kidney injury and all-cause mortality in hospitalized patients.

AIM: Hyperuricemia is a risk factor for high morbidity and mortality in several diseases. However, the relationship between uric acid (UA) and the risk of acute kidney injury (AKI) and mortality remain unresolved in hospitalized patients. METHODS: Data from 18 444 hospitalized patients were retrospectively reviewed. The odds ratio (OR) for AKI and the hazard ratio (HR) for all-cause mortality were calculated based on the UA quartiles after adjustment for multiple variables. All analyses were performed after stratification by sex. RESULTS: The fourth quartile group (male, UA > 6.7 mg/dL; female, UA > 5.4 mg/dL) showed a higher risk of AKI compared with the first quartile group (male, UA < 4.5 mg/dL; female, UA < 3.6 mg/dL), with the following OR: 3.2 (2.55-4.10) in males (P < 0.001); and 3.1 (2.40-4.19) in females (P < 0.001). There were more patients who did not recover from AKI in the fourth quartile compared with the first quartile, with the following OR: 2.0 (1.32-3.04) in males (P = 0.001) and 2.4 (1.43-3.96) in females (P = 0.001). The fourth quartile group had a higher risk of all-cause mortality compared with the first quartile group, with the following HR: 1.4 (1.20-1.58) in males (P < 0.001) and 1.2 (1.03-1.46) in females (P = 0.019). The in-hospital mortality risk was also higher in the fourth quartile compared with the first quartile, which was significant only in males (OR, 2.1 (1.33-3.31) (P = 0.002)). CONCLUSION: Hyperuricemia increases the risks of AKI and all-cause mortality in hospitalized patients.

Does Routine Bioimpedance-Guided Fluid Management Provide Additional Benefit to Non-Anuric Peritoneal Dialysis Patients? Results from COMPASS Clinical Trial.

INTRODUCTION: In peritoneal dialysis (PD) patients, volume overload is related to cardiac dysfunction and mortality, while intravascular volume depletion is associated with a rapid decline in the residual renal function (RRF). This study sought to determine the clinical usefulness of bioimpedance spectroscopy (BIS)-guided fluid management for preserving RRF and cardiac function in PD patients. SUBJECTS AND METHODS: This is a multicenter, prospective, open-label study that was conducted over a 1-year period (NCT01887262). Non-anuric (urine volume > 500 mL/day) subjects on PD were enrolled. Subjects in the control group received fluid management based on the clinical information alone. Those in the BIS group received BIS-guided fluid management along with clinical information. RESULTS: The subjects (N = 137, mean age 51.3 ± 12.8 years, 54% male) were randomly assigned to the BIS group (n = 67) or to the control group (n = 70). There were no significant differences between the 2 groups with regard to age, sex ratio, cause of kidney failure, duration of PD, baseline comorbidity, RRF, PD method, or peritoneal transport type. At baseline, the 2 groups were not different in terms of RRF (glomerular filtration rate [GFR], 5.1 ± 2.9 vs 5.5 ± 3.7 mL/min/1.73 m2). After follow-up, changes in the GFR between the 2 groups were not different (-1.5 ± 2.4 vs -1.3 ± 2.6 mL/min/1.73 m2, p = 0.593). Over the 1-year study period, both groups maintained stability of various fluid status parameters. Between the 2 groups, there were no differences in the net change of various fluid status parameters such as overhydration (OH) and extracellular water/total body water (ECW/TBW). A net change in ECW over 1 year was slightly but significantly higher in the control group (net increase, 0.57 ± 1.27 vs 0.05 ± 1.63 L, p = 0.047). However, this difference was not translated into an improvement in RRF in the BIS group. There were no differences in echocardiographic parameters or arterial stiffness at the end of follow-up. CONCLUSION: Routine BIS-guided fluid management in non-anuric PD patients did not provide additional benefit in volume control, RRF preservation, or cardiovascular (CV) parameters. However, our study cannot be generalized to the whole PD population. Further research is warranted in order to investigate the subpopulation of PD patients who may benefit from routine BIS-guided fluid management.

Changes in bioimpedance analysis components before and after hemodialysis.

BACKGROUND: This study compared nutritional parameters in hemodialysis (HD) subjects and controls using bioimpedance analysis (BIA) and investigated how BIA components changed before and after HD. METHODS: This cross-sectional study included 147 subjects on maintenance HD from two hospitals and 298 propensity score-matched controls from one healthcare center. BIA was performed pre- and post-HD at mid-week dialysis sessions. RESULTS: Extracellular water/total body water (ECW/TBW) and waist-hip ratio were higher in the HD patients; the other variables were higher in the control group. The cardiothoracic ratio correlated best with overhydration (r = 0.425, P < 0.01) in HD subjects. Blood pressure, hemoglobin, creatinine, and uric acid positively correlated with the lean tissue index in controls; however, most of these nutritional markers did not show significant correlations in HD subjects. Normal hydrated weight was predicted to be higher in the pre-HD than post-HD measurements. Predicted ultrafiltration (UF) volume difference based on pre- and post-HD ECW/TBW and measured UF volume difference showed a close correlation (r 2 = 0.924, P < 0.01). Remarkably, the leg phase angle increased in the post-HD period. CONCLUSION: The estimated normal hydrated weight using ECW/TBW can be a good marker for determining dry weight. HD subjects had higher ECW/TBW but most nutritional indices were inferior to those of controls. It was possible to predict UF volume differences using BIA, but the post-HD increase in leg phase angle, a nutritional marker, must be interpreted with caution.

An effective strategy to prevent allopurinol-induced hypersensitivity by HLA typing.

PURPOSE: This study was conducted to evaluate the usefulness of human leukocyte antigen (HLA) typing in preventing allopurinol-induced severe cutaneous adverse reactions (SCARs) through the application of an allopurinol tolerance induction protocol or prescription of other alternative medications in high-risk patients. METHODS: HLA typing was performed in patients with chronic renal insufficiency who needed allopurinol. HLA-B*58:01-negative patients were prescribed the usual dose of allopurinol. For HLA-B*58:01-positive patients, administration of either allopurinol based on a 28-day tolerance induction protocol or alternative medications was initiated. Hypersensitivity reactions were surveyed for 90 days and compared with the result of a previous retrospective cohort study. RESULTS: Among a total of 401 study subjects, no SCARs were noted in HLA-B*58:01-positive patients with application of the tolerance induction protocol (n = 30) or alternative medications (n = 16), nor were any SCARs observed in HLA-B*58:01-negative patients who started allopurinol at the usual dose (n = 355). Compared with the previous retrospective cohort study, a significant reduction in SCARs was observed in HLA-B*58:01-positive patients (0 vs. 18%; P = 0.002). CONCLUSION: This study shows the usefulness of HLA-B*58:01 screening in identifying patients at high risk for the development of allopurinol-induced SCARs and suggests that application of a tolerance induction protocol or alternative medications could be an effective strategy to prevent allopurinol-induced SCARs in HLA-B*58:01-positive patients.

Control of fluid balance guided by body composition monitoring in patients on peritoneal dialysis (COMPASS): study protocol for a randomized controlled trial.

BACKGROUND: The clinical benefits of bioimpedance spectroscopy (BIS)-guided fluid management in patients on hemodialysis have been widely demonstrated. However, no previous reports have evaluated the effect of regular and serial BIS-guided fluid management on the residual renal function (RRF) in patients on peritoneal dialysis (PD). Therefore, we will evaluate the clinical efficacy of BIS-guided fluid management for preserving RRF and protecting cardiovascular events in patients on PD. METHODS/DESIGN: This is a multicenter, prospective, randomized controlled trial. A total of 138 participants on PD will be enrolled and randomly assigned to receive either BIS-guided fluid management or fluid management based only on the clinical information for 1 year. The primary outcome is the change in the glomerular filtration rate (GFR) between months 0 and 12 after starting treatment. The secondary outcomes will include GFR at month 12, time to the anuric state (urine volume <100 ml/day), and fatal and nonfatal cardiovascular events during treatment. DISCUSSION: This is the first clinical trial to investigate the effect of BIS-guided fluid management on RRF and for protecting against cardiovascular events in patients on PD. TRIAL REGISTRATION: Clinical Trials.gov number NCT01887262, June 24, 2013.

Renal adverse effects of sunitinib and its clinical significance: a single-center experience in Korea.

BACKGROUND/AIMS: Sunitinib is an oral multitargeted tyrosine kinase inhibitor used mainly for the treatment of metastatic renal cell carcinoma. The renal adverse effects (RAEs) of sunitinib have not been investigated. The aim of this study was to determine the incidence and risk factors of RAEs (proteinuria [PU] and renal insufficiency [RI]) and to investigate the relationship between PU and antitumor efficacy. METHODS: We performed a retrospective review of medical records of patients who had received sunitinib for more than 3 months. RESULTS: One hundred and fifty-five patients (mean age, 58.7 ± 12.6 years) were enrolled, and the mean baseline creatinine level was 1.24 mg/dL. PU developed in 15 of 111 patients, and preexisting PU was aggravated in six of 111 patients. Only one patient developed typical nephrotic syndrome. Following discontinuation of sunitinib, PU was improved in 12 of 17 patients but persisted in five of 17 patients. RI occurred in 12 of 155 patients, and the maximum creatinine level was 3.31 mg/dL. RI improved in two of 12 patients but persisted in 10 of 12 patients. Risk factors for PU were hypertension, dyslipidemia, and chronic kidney disease. Older age was a risk factor for RI. The median progression-free survival was significantly better for patients who showed PU. CONCLUSIONS: The incidence of RAEs associated with sunitinib was lower than those of previous reports. The severity of RAEs was mild to moderate, and partially reversible after cessation of sunitinib. We suggest that blood pressure, urinalysis, and renal function in patients receiving sunitinib should be monitored closely.

Correction of anemia with continuous erythropoietin receptor activator in Korean patients on long-term hemodialysis.

Continuous erythropoietin receptor activator (CERA) is an erythropoietin with a long-half life. This study investigated the efficacy of CERA for correcting anemia in Korean patients on dialysis. Patients (≥ 18 yr) who were not receiving any ESAs for more than 8 weeks were randomly assigned to either intravenous CERA once every 2 weeks (n=39) or epoetin beta thrice-weekly (n=41) during a 24-week correction phase. Hemoglobin (Hb) response was defined as increase of Hb by at least 1 g/dL and Hb ≥ 11 g/dL without red blood cell (RBC) transfusion. Median dialysis duration was 1.7 (0.3-20.8) and 1.6 (0.4-13.8) yr in CERA and epoetin beta group, respectively. Hemoglobin response rate of CERA was 79.5% (95% confidence interval [CI], 63.5-90.7). As the lower limit of 95% CI was higher than pre-specified 60% response rate, it can be concluded that CERA corrected anemia (P<0.05). Hb response rate of epoetin beta was 87.8% (95% CI, 73.8-95.9) (P=0.37). Median time to response was 12 weeks in CERA and 10.3 weeks in epoetin beta (P=0.03). It is suggested that once every 2 weeks administration of CERA is effective for correcting anemia in Korean patients on long-term hemodialysis with longer time-to-response than thrice weekly epoetin beta. (ClinicalTrials.gov registry No. NCT00546481).

Serum resistin as a novel marker of erythropoietin resistance in nondiabetic patients on hemodialysis.

The use of higher erythropoietin (EPO) doses is associated with an increased risk of an adverse outcome and increased mortality in patients with renal failure. Resistin is related to heart disease, and may contribute to an increased atherosclerotic risk. We hypothesized that a link between resistin and EPO responsiveness may exist. We therefore investigated the relationship between resistin and the EPO resistance index (ERI) in nondiabetic hemodialysis (HD) patients. Fifty-seven patients enrolled in the study underwent HD for ≥ 3 months and intravenous EPO therapy to maintain a target hemoglobin (Hb) level of 11.0 g/dl. The ERI was defined as the weekly EPO dose per unit Hb per body weight. The mean patient age was 52.6 ± 11.9 years and the mean time on dialysis was 4.9 ± 4.4 years. Serum Hb and ERI were 10.4 ± 0.7 g/dl, and 13.3 ± 7.0 (IU/kg/week/g/dl), respectively. Serum resistin levels were 23.6 ± 9.3 µg/L. EPO resistance is associated with low body mass index (BMI) (coefficient ß =-0.393, p = 0.002) and with high serum resistin levels (coefficient ß = 0.332, p = 0.018). According to a multiple regression analysis, the serum resistin level was a significant independent factor related to EPO resistance (p = 0.017). The results suggest that serum resistin levels reflect EPO responsiveness in nondiabetic HD patients. Resistin may therefore be considered as a new marker of EPO responsiveness in HD patients.