Sug Kyun Shin

Influence of ketoanalogs supplementation on the progression in chronic kidney disease patients who had training on low-protein diet.

Aim:  A low‐protein diet (LPD) is a conservative treatment in patients with chronic kidney disease (CKD) to improve uremic symptoms and slow the progression of renal dysfunction. However, the deleterious effects of protein restriction on nutritional status have raised concern. We investigated whether ketoanalogs supplementation in CKD patients who had training on LPD retards the progression of CKD and maintains nutritional status.

Prognostic value of elevated cardiac troponin I in ESRD patients with sepsis

BACKGROUND Elevated cardiac troponin (cTn) levels have been reported to predict adverse cardiovascular outcomes in asymptomatic ESRD patients. However, the prognostic value of elevated cTn levels associated with sepsis in ESRD patients is unknown. Therefore, this study aimed to elucidate the clinical implications of elevated cTnI levels in ESRD patients with sepsis. METHODS Of the 305 ESRD patients in whom cTnI was measured between January 2003 and December 2005, sepsis developed in 121 patients during follow-up. Based on cTnI levels at the onset of sepsis, patients were classified as elevated cTnI group (ET, n = 50, >0.2 ng/ml) and lower cTnI group (LT, n = 71, < or =0.2 ng/ml). Study endpoints were short- and long-term mortality. Short-term mortality was defined as death occurring within 90 days after sepsis, and patients who survived during this period were followed till death after 90 days. RESULTS Before sepsis, the median concentration of cTnI was 0.05 (0.01-3.59) ng/ml and it was significantly increased to 0.11 (0.01-22.0) ng/ml when sepsis supervened (P < 0.01). Compared to the LT group, the short-term mortality rate was significantly higher in the ET group (P < 0.05). After adjustment for age, diabetes, serum albumin and CRP levels, presence of shock and previous cardiovascular disease history, the ET group had a greater odds ratio of short-term mortality (OR 5.13, P < 0.01). In addition, the Kaplan-Meier plot for long-term survival revealed a significantly higher mortality rate in the ET group. In a multivariate Cox regression analysis, the elevation of cTnI levels was an independent determinant for long-term mortality (HR 5.90, P < 0.01). CONCLUSION This study showed that elevated cTnI levels were significantly associated with short- and long-term mortality in ESRD patients with sepsis. Therefore, elevated cTnI levels in these patients should not be overlooked and be followed for adverse outcomes.

Hyponatremia as a Predictor of Mortality in Peritoneal Dialysis Patients

Background and Aim Hyponatremia is common in patients with chronic kidney disease and is associated with increased mortality in hemodialysis patients. However, few studies have addressed this issue in peritoneal dialysis (PD) patients. Methods This prospective observational study included a total of 441 incident patients who started PD between January 2000 and December 2005. Using time-averaged serum sodium (TA-Na) levels, we aimed to investigate whether hyponatremia can predict mortality in these patients. Results Among the baseline parameters, serum sodium level was positively associated with serum albumin (β = 0.145; p = 0.003) and residual renal function (RRF) (β = 0.130; p = 0.018) and inversely associated with PD ultrafiltration (β = −0.114; p = 0.024) in a multivariable linear regression analysis. During a median follow-up of 34.8 months, 149 deaths were recorded. All-cause death occurred in 81 (55.9%) patients in the lowest tertile compared to 37 (25.0%) and 31 (20.9%) patients in the middle and highest tertiles, respectively. After adjusting for multiple potentially confounding covariates, increased TA-Na level was associated with a significantly decreased risk of all-cause (HR per 1 mEq/L increase, 0.79; 95% CI, 0.73–0.86; p<0.001) and infection-related (HR per 1 mEq/L increase, 0.77; 95% CI, 0.70–0.85; p<0.001) deaths. Conclusions This study showed that hyponatremia is an independent predictor of mortality in PD patients. Nevertheless, whether correcting hyponatremia improves patient survival is unknown. Future interventional studies should address this question more appropriately.

The impact of dialysis modality on arterial stiffness in patients with end-stage renal disease.

Background: Arterial stiffness determined by brachial–ankle pulse wave velocity (baPWV) has been established as a powerful predictor of cardiovascular mortality in hemodialysis (HD) patients. There are, however, few studies regarding the comparative impact of different renal replacement therapies (RRTs) on PWV. Therefore, we conducted a cross-sectional study to compare arterial wall properties and cardiac function between patients treated with continuous ambulatory peritoneal dialysis (CAPD) and those with HD who were matched for age, dialysis duration, and blood pressure. Methods: baPWV and transthoracic echocardiography (TTE) were performed in HD patients (n = 23) after 1 h of midweek dialysis session and CAPD patients (n = 26) with empty abdomen after drainage of dialysate. The baseline data were retrospectively reviewed. Results: baPWV was significantly higher in HD patients than in CAPD patients (18.1 ± 2.8 vs. 16.1 ± 2.7 m/s, p = 0.015). TTE revealed significantly increased E/E′, left atrial volume index (LAVI), and inferior vena cava (IVC) diameter index in HD patients compared with CAPD patients (p < 0.05). In a multivariate regression analysis adjusted for dialysis modality, age, systolic BP, residual glomerular filtration rate, diabetes, and echocardiographic parameters, HD was independently associated with increased baPWV. Conclusion: This study showed that HD patients had significantly increased arterial stiffness and severe diastolic dysfunction compared with CAPD patients.

Effect of lanthanum carbonate on phosphate control in continuous ambulatory peritoneal dialysis patients in Korea: a randomized prospective study.

BACKGROUND Hyperphosphatemia is a common complication in end-stage renal disease (ESRD) patients. Reducing the serum phosphate level is crucial in management of ESRD. METHODS This study was a randomized prospective study, designed to compare patients with hyperphosphatemia undergoing peritoneal dialysis while taking lanthanum carbonate or calcium carbonate. We divided 72 continuous ambulatory peritoneal dialysis (CAPD) patients whose serum phosphate levels were over 5.6 mg/dl into two groups to receive either lanthanum carbonate or calcium carbonate. Serum calcium, phosphate and PTH levels were examined serially for 24 weeks. RESULTS Both lanthanum carbonate and calcium carbonate reduced serum phosphate levels, from 6.79 ± 1.05 to 5.44 ± 1.44 and from 6.31 ± 1.13 to 4.74 ± 0.78 mg/dl, respectively. The calcium × phosphate product level was reduced in the lanthanum carbonate and calcium carbonate groups from 60.23 ± 10.23 to 46.97 ± 16.42 and from 57.92 ± 11.05 to 44.50 ± 7.74 mg2/dl2, respectively. The serum parathyroid hormone (PTH) level in the lanthanum carbonate group did not change significantly compared to baseline during the study, but in the calcium carbonate group, the serum PTH level decreased significantly. Gastrointestinal complications were the main adverse effects of lanthanum carbonate and 11 out of 35 patients dropped out of the study due to this complication. CONCLUSIONS Lanthanum carbonate was as effective as calcium carbonate in reducing serum phosphate level, and serum PTH level tended to be steadier in the lanthanum carbonate group compared to the calcium carbonate group. Though the ifference was not significant, lanthanum carbonate tended not to elevate serum calcium level in CAPD patients compared to calcium carbonate. The high incidence of gastrointestinal adverse effect in the lanthanum carbonate group will need further evaluation.

Serum calcium and phosphorus levels in patients undergoing maintenance hemodialysis: A multicentre study in Korea.

Background In many countries, nephrologists follow clinical practice guidelines for mineral bone disorders to control secondary hyperparathyroidism (SHPT) associated with abnormal serum calcium (Ca) and phosphorus (P) levels in patients undergoing maintenance hemodialysis (MHD). The Kidney Disease Outcomes Quality Initiative (KDOQI) Guidelines have long been used in Korea, and this study was undertaken to investigate the current status of serum Ca and P control in MHD patients. Methods Data were collected from a total of 1,018 patients undergoing MHD without intercurrent illness, in 17 hemodialysis centers throughout the country. Serum levels of Ca, P, and intact parathyroid hormone (iPTH) were measured over 1 year, and the average values were retrospectively analyzed. Results Serum levels of Ca, P, and the Ca×P product were 9.1±0.7 mg/dL, 5.3±1.4 mg/dL, and 48.0±13.6 mg2/dL2, respectively. However, the percentages of patients with Ca, P, and Ca × P product levels within the KDOQI guideline ranges were 58.7%, 51.0%, and 70.7%, respectively. Of the 1,018 patients, 270 (26.5%) had iPTH >300 pg/mL (uncontrolled SHPT), whereas 435 patients (42.7%) showed iPTH <150 pg/mL. Patients with uncontrolled SHPT had significantly higher values of serum Ca, P, and Ca×P product than those with iPTH ≤300 pg/mL. Conclusion Despite the current clinical practice guidelines, SHPT seems to be inadequately controlled in many MHD patients. Uncontrolled SHPT was associated with higher levels of serum Ca, P, and Ca × P product, suggestive of the importance of SHPT management.

Effect of Conversion from ESA with Shorter Half-Life to CERA Once Monthly for Maintaining Hb Concentration in Pre-Dialysis CKD Patients

Background: The purpose of this study is to identify whether hemoglobin (Hb) concentrations can be maintained, and to investigate changes in biomarkers, when switching from erythropoietin stimulating agents (ESA) with shorter half-life to once-monthly subcutaneous methoxy polyethylene glycol-epoetin β (CERA) in pre-dialysis chronic kidney disease (CKD) patients. Methods: Pre-dialysis CKD patients (n=191) aged ≥18 years who maintained their Hb level 10-12 g/dL through use of epoetin-α, epoetin-β, or darbepoetin-α were enrolled. Hb levels and CERA dose was assessed prospectively for 24 weeks. Serum biomarkers related to coagulation, endothelial function, and iron metabolism were measured at weeks 0 and 24. Results: Baseline Hb concentration was 10.8±0.6 g/dL Twelve and 24 weeks after conversion, mean Hb levels were 11.9±0.9 and 11.2±0.9 g/dL, respectively. The mean monthly CERA dose required to maintain Hb levels was gradually reduced. Of total 387 dose adjustments, dose increases and decreases occurred in 35 (9.0%) and 352 (91.0%) episodes, respectively. Hb overshoot occurred in 14 (9.7%) patients. P-selectin was significantly decreased, whereas VCAM was significantly increased 24 weeks after conversion (P < 0.05). Serum soluble transferrin receptor E-selectin and prohepcidin levels were similar before and after switching to CERA (P=N-S). Conclusion: Conversion from ESA with shorter half-life to subcutaneous once-monthly CERA in pre-dialysis CKD patients can efficaciously maintain Hb. The CERA dose requirement decreased significantly. The conversion ratio may need to be reduced when switching from ESA with shorter half-life to CERA. CERA may change biomarkers associated with platelet reactivity and endothelial microenvironment.

Low Triiodothyronine Syndrome and Long-Term Cardiovascular Outcome in Incident Peritoneal Dialysis Patients

BACKGROUND AND OBJECTIVES A direct association between low triiodothyronine (T3) syndrome and cardiovascular (CV) mortality has been reported in hemodialysis patients. However, the implications of this syndrome in peritoneal dialysis (PD) patients have not been properly investigated. This study examined the association between low T3 syndrome and CV mortality including sudden death in a large cohort of incident PD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This prospective observational study included 447 euthyroid patients who started PD between January 2000 and December 2009. Measurement of thyroid hormones was performed at baseline. All-cause and cause-specific deaths were registered during the median 46 months of follow-up. The survival rate was compared among three groups based on tertile of T3 levels. RESULTS In Kaplan-Meyer analysis, patients with the lowest tertile were significantly associated with higher risk of all-cause and CV mortality including sudden death (P<0.001 for trend). In Cox analyses, T3 level was a significant predictor of all-cause mortality (per 10-unit increase, adjusted hazard ratio [HR], 0.86; 95% confidence interval [95% CI], 0.78 to 0.94; P=0.002), CV death (per 10-unit increase, adjusted HR, 0.84; 95% CI, 0.75 to 0.98; P=0.01), and sudden death (per 10-unit increase, adjusted HR, 0.69; 95% CI, 0.56 to 0.86; P=0.001) after adjusting for well known risk factors including inflammation and malnutrition. The higher T3 level was also independently associated with lower risk for sudden death (per 10-unit increase, adjusted HR, 0.71; 95% CI, 0.56 to 0.90; P=0.01) even when accounting for competing risks of death from other causes. CONCLUSIONS T3 level at the initiation of PD was a strong independent predictor of long-term CV mortality, particularly sudden death, even after adjusting well known risk factors. Low T3 syndrome might represent a factor directly implicated in cardiac complications in PD patients.

Higher Peritoneal Protein Clearance as a Risk Factor for Cardiovascular Disease in Peritoneal Dialysis Patient

Background and Aims Although a number of studies have been published on peritoneal protein clearance (PrCl) and its association with patient outcomes, the results have been inconsistent. Therefore, the intent of this study was to evaluate the impact of PrCl on cardiovascular disease (CVD) and mortality in peritoneal dialysis (PD) patients. Methods This prospective observational study included a total of 540 incident patients who started PD at NHIC Ilsan Hospital, Korea from January 2000 to December 2009. Two different types of analyses such as intention-to-treat and as-treated were used. Results Correlation analyses revealed that PrCl was positively correlated with diabetes, pulse pressure, C–reactive protein (CRP) level, dialysate/plasma creatinine ratio (D/P cr) at 4 h, and peritoneal Kt/V urea. PrCl was inversely correlated with serum albumin and triglyceride levels. On multivariate analysis, serum albumin, pulse pressure, D/P cr at 4 h, and peritoneal Kt/V urea were found to be independent determinants of PrCl. A total of 129 (23.9%) patients in intention-to-treat analysis and 117 (21.7%) patients in as-treated analysis developed new cardiovascular events. Time to occurrence of cardiovascular event was significantly longer in patients with a value of PrCl below the median (89.4 ml/day). In multivariate analysis, older age, presence of diabetes or previous CVD, and higher PrCl were independent predictors of cardiovascular events. Patients above the median value of PrCl had a significantly lower rate of survival than those below the median. However, a higher PrCl was not associated with increased mortality in multivariate Cox analysis. Conclusions A higher PrCl is a risk for occurrence of cardiovascular event, but not mortality in PD patients. Large randomized clinical trials are warranted to confirm this finding.

A Low Serum Bicarbonate Concentration as a Risk Factor for Mortality in Peritoneal Dialysis Patients

Background and Aim Metabolic acidosis is common in patients with chronic kidney disease and is associated with increased mortality in hemodialysis patients. However, this relationship has not yet been determined in peritoneal dialysis (PD) patients. Methods This prospective observational study included a total of 441 incident patients who started PD between January 2000 and December 2005. Using time-averaged serum bicarbonate (TA-Bic) levels, we aimed to investigate whether a low serum bicarbonate concentration can predict mortality in these patients. Results Among the baseline parameters, serum bicarbonate level was positively associated with hemoglobin level and residual glomerular filtration rate (GFR), while it was negatively associated with albumin, C-reactive protein (CRP) levels, peritoneal Kt/V urea, and normalized protein catabolic rate (nPCR) in a multivariable linear regression analysis. During a median follow-up of 34.8 months, 149 deaths were recorded. After adjustment for age, diabetes, coronary artery disease, serum albumin, ferritin, CRP, residual GFR, peritoneal Kt/V urea, nPCR, and percentage of lean body mass, TA-Bic level was associated with a significantly decreased risk of mortality (HR per 1 mEq/L increase, 0.83; 95% CI, 0.76-0.91; p < 0.001). In addition, compared to patients with a TA-Bic level of 24-26 mEq/L, those with a TA-Bic level < 22 and between 22-24 mEq/L conferred a 13.10- and 2.13-fold increased risk of death, respectively. Conclusions This study showed that a low serum bicarbonate concentration is an independent risk factor for mortality in PD patients. This relationship between low bicarbonate levels and adverse outcome could be related to enhanced inflammation and a more rapid loss of RRF associated with metabolic acidosis. Large randomized clinical trials to correct acidosis are warranted to confirm our findings.