Sung Gyun Kim

Benefits of biocompatible PD fluid for preservation of residual renal function in incident CAPD patients: a 1-year study

BACKGROUND In vitro studies of peritoneal dialysis (PD) solutions demonstrated that a biocompatible fluid with neutral-pH and low glucose degradation products (LF) has better biocompatibility than a conventional acidic lactate-buffered fluid (CF). However, few clinical trials have investigated the effects of the biocompatible solution on residual renal function (RRF). We performed a prospective, randomized trial with patients starting continuous ambulatory peritoneal dialysis (CAPD). METHODS Ninety-one incident patients started CAPD for 12-month treatment with either LF (Balance, Fresenius, n = 48) or CF (CAPD/DPCA, Fresenius, n = 43). RRF, peritoneal solute transport rate and solute clearance were measured every 6 months. RESULTS LF had a significant effect on the change of glomerular filtration rate (GFR) (P = 0.048 by the mixed model). In per-protocol analysis, GFR in the LF group did not decrease over a 12-month period, while GFR in the control group significantly decreased (0.13 +/- 33.4 L/ week/1.73 m(2) for LF versus -13.6 +/- 19.4 L/week/1.73 m(2) for CF, P = 0.049). Subgroup analysis for patients with initial GFR of 2 mL/min/1.73 m(2) or above showed a significantly higher GFR for the LF group over the 12-month period. At Month 13, serum total CO(2) levels were higher and serum albumin levels were lower in the LF group. No differences between the two groups were observed for the C-reactive protein. Over the 12-month period, effluent cancer antigen-125 levels significantly increased in the LF group, compared with those of the CF group, while effluent interleukin-6 levels were not different between the two groups. CONCLUSION Our study suggests that LF may better preserve RRF over the 12-month treatment period in incident CAPD patients.

Prevalence of and factors associated with sarcopenia in elderly patients with end-stage renal disease.

BACKGROUND & AIMS We investigated the prevalence of sarcopenia in elderly patients with end-stage renal disease (ESRD) and its relationship with various markers of nutrition, cognitive function, depressive symptoms, inflammation and β2-microglobulin. METHODS A cross-sectional study was conducted with 95 patients having ESRD aged over 50 years. Sarcopenia was defined as a decline in both muscle mass and strength. RESULTS The mean age was 63.9 ± 10.0 years; 56.8% were men and 52.6% had diabetes. Sarcopenia was highly prevalent in elderly patients with ESRD (37.0% in men and 29.3% in women). Subjective Global Assessment (SGA), inflammatory markers and β2-microglobulin levels were significantly associated with sarcopenia, even after adjustment for age, gender, diabetes, and body mass index. Additionally, patients with depressive symptoms showed a higher risk of sarcopenia relative to those without depressive symptoms (odds ratio, OR = 6.87, 95% confidence interval, CI = 2.06-22.96) and sarcopenia was more likely to be present in patients with mild cognitive dysfunction (OR = 6.35, 95% CI = 1.62-34.96). CONCLUSIONS Sarcopenia is highly prevalent in elderly patients with ESRD and is closely associated with SGA, inflammatory markers, β2-microglobulin, depression and cognitive dysfunction.

Plasma levels of soluble receptor for advanced glycation end products (sRAGE) and proinflammatory ligand for RAGE (EN-RAGE) are associated with carotid atherosclerosis in patients with peritoneal dialysis.

OBJECTIVES The soluble receptor for advanced glycation end products (sRAGE) exerts a protective effect on the development of atherosclerotic vascular complications by inhibiting RAGE-mediated inflammatory response. In contrast, extracellular newly identified RAGE-binding protein (EN-RAGE) contributes to increased atherosclerosis as a pro-inflammatory ligand for RAGE. We determined the levels of sRAGE and EN-RAGE in peritoneal dialysis (PD) patients and evaluated their relationship with carotid atherosclerosis. METHODS A cross-sectional study was performed in 91 PD patients and 29 control subjects. Carotid IMT (cIMT) and abdominal aortic vascular calcification score (VCS) were evaluated using high-resolution B-mode ultrasonography and plain radiographic film of the lateral abdomen. RESULTS Plasma sRAGE and EN-RAGE levels were more than twice as higher in PD patients compared to controls. EN-RAGE showed a strong positive correlation with serum high-sensitivity CRP (p=0.007) and IL-6 (p=0.002), whereas sRAGE was negatively associated with those inflammatory markers (p=0.001, p=0.031). Even after adjustments for traditional cardiovascular risk factors, both sRAGE and EN-RAGE were independently associated with cIMT (β=-0.230, p=0.037, β=0.155, p=0.045) and VCS (β=-0.205, p=0.049, β=0.197, p=0.156). Multivariate logistic analysis revealed that old age (OR 1.14, 95% CI 1.03-1.25, p=0.009), presence of diabetes (OR 13.4, 95% CI: 1.20-150.18, p=0.035) and elevated plasma EN-RAGE (OR 2.26, 95% CI: 1.05-5.11, p=0.048) were significant predictors for the occurrence of carotid atherosclerosis (cIMT>1.0mm and/or plaque formation). CONCLUSIONS Our findings suggest that elevated plasma EN-RAGE and decreased sRAGE level could play a crucial role in systemic inflammation and carotid atherosclerosis in PD patients.

A Randomized, Controlled Trial of Oral Intestinal Sorbent AST-120 on Renal Function Deterioration in Patients with Advanced Renal Dysfunction

BACKGROUND AND OBJECTIVES The notion that oral intestinal sorbent AST-120 slows renal disease progression has not been evaluated thoroughly. In this study, we investigated the long-term effect of AST-120 on renal disease progression (doubling of serum creatinine, eGFR decrease >50%, or initiation of RRT) in patients with advanced CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We prospectively recruited 579 patients (CKD stage 3 or 4) from 11 medical centers in Korea from March 4, 2009 to August 31, 2010 and randomized them into an AST-120 arm and a control arm. Patients in the AST-120 arm were given 6 g AST-120 in three divided doses per day, and those in the control arm received only standard conventional treatment (open-label design) for 36 months or until the occurrence of primary outcomes. RESULTS Levels of serum and urine indoxyl sulfate and β2-microglobulin decreased throughout the study period in both treatment arms; however, there was not a significant difference in change in uremic toxins in the AST-120 and control arms. The two arms were not different in the occurrence of composite primary outcomes (100 events in 272 individuals in the AST-120 arm and 100 events in 266 individuals in the control arm; hazard ratio, 1.12; 95% confidence interval, 0.85 to 1.48; log-rank P=0.45). The decline in eGFR and change in proteinuria were similar in the two treatment arms over time (Prandomization-time=0.64 and Prandomization-time=0.16, respectively). There was no difference in mortality (nine deaths in the AST-120 arm and 11 deaths in the control arm; log-rank P=0.73) or unplanned hospitalizations (102 in the AST-120 arm and 109 in the control arm; log-rank P=0.76) in the two treatment arms. There was no significant difference of the health-related quality of life score between the two arms. CONCLUSIONS Long-term use of AST-120 added to standard treatment did not change renal disease progression, proteinuria, mortality, and health-related quality of life in patients with advanced renal dysfunction.

Association between cardiac valvular calcification and myocardial ischemia in asymptomatic high-risk patients with end-stage renal disease

OBJECTIVE Valvular calcification is associated with significant morbidity and mortality in patients with end stage renal disease (ESRD). This study examined the hypothesis that valvular calcification is a marker of myocardial ischemia in asymptomatic high-risk patients with ESRD. METHODS Echocardiography and myocardial perfusion single-photon emission computed tomography were performed in 285 asymptomatic high-risk patients with ESRD at initiation of dialysis. We evaluated the extent and severity of myocardial ischemia by the summed difference score (SDS) and defined the presence of myocardial ischemia as SDS ≥ 3 and moderate to severe ischemia as SDS ≥ 8. The presence of cardiac valvular calcification was assessed by echocardiography and defined as aortic valve calcification or mitral valve calcification. RESULTS Eighty-five (29.9%) patients had echocardiographic evidence of cardiac valvular calcification. The presence of myocardial ischemia was significantly associated with aortic valve calcification (odds ratio [OR] = 3.19; 95% confidence interval [CI] = 1.76-5.78; p < 0.001), mitral valve calcification (OR = 3.31; 95% CI = 1.74-6.28; p < 0.001), and cardiac valvular calcification (OR = 3.18; 95% CI = 1.79-5.65; p < 0.001). The presence of moderate to severe myocardial ischemia (SDS ≥ 8) was independently associated with cardiac valvular calcification (OR = 2.86; 95% CI = 1.12-7.27; p = 0.028). CONCLUSION Valvular calcification was significantly associated with the presence of inducible myocardial ischemia in asymptomatic patients with ESRD, and may be a potential marker of patients at high-risk for the presence of silent myocardial ischemia.

Sustained uremic toxin control improves renal and cardiovascular outcomes in patients with advanced renal dysfunction: post-hoc analysis of the Kremezin Study against renal disease progression in Korea

Background We investigated the long-term effect of AST-120, which has been proposed as a therapeutic option against renal disease progression, in patients with advanced chronic kidney disease (CKD). Methods We performed post-hoc analysis with a per-protocol group of the K-STAR study (Kremezin study against renal disease progression in Korea) that randomized participants into an AST-120 and a control arm. Patients in the AST-120 arm were given 6 g of AST-120 in three divided doses, and those in both arms received standard conventional treatment. Results The two arms did not differ significantly in the occurrence of composite primary outcomes (log-rank P = 0.41). For AST-120 patients with higher compliance, there were fewer composite primary outcomes: intermediate tertile hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.38 to 1.01, P = 0.05; highest tertile HR 0.436, 95% CI 0.25 to 0.76, P = 0.003. The estimated glomerular filtration rate level was more stable in the AST-120 arm, especially in diabetic patients. At one year, the AST-120-induced decrease in the serum indoxyl sulfate concentration inversely correlated with the occurrence of composite primary outcomes: second tertile HR 1.59, 95% CI 0.82 to 3.07, P = 0.17; third tertile HR 2.11, 95% CI 1.07 to 4.17, P = 0.031. Furthermore, AST-120 showed a protective effect against the major cardiovascular adverse events (HR 0.51, 95% CI 0.26 to 0.99, P = 0.046). Conclusion Long-term use of AST-120 has potential for renal protection, especially in diabetic patients, as well as cardiovascular benefits. Reduction of the serum indoxyl sulfate level may be used to identify patients who would benefit from AST-120 administration.

Changes of blood pressure patterns and target organ damage in patients with chronic kidney disease: results of the APrODiTe-2 study.

Objective: Blood pressure (BP) control is the most established practice for preventing the progression of chronic kidney disease (CKD). We examined the BP control and nocturnal dipping pattern change in hypertensive patients with CKD and its effects on target organ damages. Design and Method: We recruited 378 hypertensive CKD patients from 4 centers in Korea. They underwent office and ambulatory BP monitoring at the time of enrollment and 1 year after. High office and ambulatory BP was defined as > 140/90 mmHg and > 135/85 mmHg (daytime)/> 120/70 mmHg (nighttime), respectively. Results: The BP control state at 2 time points were as follows: true controlled (14.8, 17.5%), white-coat (2.6, 0.4%), masked (45.0, 53.3%), and sustained uncontrolled (27.5, 28.8%) hypertension. The dipping state at 2 time points were as follows: extreme -dipping (11.4, 10.8%), dipping (22.2, 20.5%), non-dipping (31.3, 34.7%), and reverse -dipping (35.0, 34.0%). Better change (to true controlled and white-coat) of BP control status was associated with lower initial level of serum uric acid, urea nitrogen, and proteinuria and higher estimated GFR (eGFR). When we divided patients according to the median of eGFR and proteinuria change, more stable change of eGFR and proteinuria was associated with better initial and follow-up BP control status. And better BP control and dipping status (to dipper) change was also associated with more stable eGFR and proteinuria change. Good initial and follow-up BP control status was associated with less LVH. And masked and sustained uncontrolled hypertension was associated with more congestive heart failure and stroke. Conclusions: The large majority of Korean hypertensive CKD patients had uncontrolled BP and abnormal dipping pattern. And better BP control and dipping status change was associated with better renal function and proteinuria as well as less cardio-cerebrovascular damages.

Serum S100B protein is associated with depressive symptoms in patients with end-stage renal disease.

OBJECTIVES Depression is associated with a poorer prognosis in patients with end-stage renal disease (ESRD). Increasing evidence indicates that glial pathology and blood-brain-barrier (BBB) dysfunction are involved in the pathophysiology of depression. S100B, a protein expressed in astro- and oligodendroglia in the human brain is considered a biomarker of depression. Our objective was to investigate the relationship between S100B and depressive symptoms in patients undergoing hemodialysis (HD). DESIGN AND METHODS Seventy-eight Korean patients undergoing chronic HD without significant neurological issues participated in a cross-sectional observation study. Depressive symptoms were assessed with the Beck Depression Inventory-II (BDI-II), and serum S100B levels were measured using blood samples obtained prior to a mid-week HD session. RESULTS The mean age of patients was 59.0 years, and the mean dialysis duration was 51.7 months. About 45% of patients undergoing HD met criteria for depression (BDI-II≥20). Serum S100B levels were significantly higher in patients with depression compared with patients without depression (115.1±45.4 vs. 66.1±35.3 pg/mL, p<0.001). S100B (r=0.556, p<0.001) and high-sensitivity C-reactive protein (hs-CRP; r=0.422, p<0.001) and β2-microglobulin (r=0.391, p<0.001) levels were positively correlated with BDI-II scores. A multivariate regression analysis showed that both S100B and hs-CRP were significantly associated with BDI-II scores. CONCLUSIONS The results showed a close association between S100B and depressive symptoms in patients undergoing HD. However, the mechanisms underlying this relationship are currently unknown and warrant further investigation.

LOSS OF RESIDUAL RENAL FUNCTION WAS NOT ASSOCIATED WITH GLYCEMIC CONTROL IN PATIENTS ON PERITONEAL DIALYSIS

♦ Background: Better glycemic control has been reported to slow the progression of nephropathy in predialysis diabetic patients. However, the relationship between glycemic control and residual renal function (RRF) in patients on peritoneal dialysis (PD) is uncertain. ♦ Methods: 89 incident diabetic patients on PD were recruited from 5 centers. We measured glomerular filtration rate (GFR) and hemoglobin A1c (HbA1c) within 2 months (baseline) after the start of PD and at 6 and 12 months. GFR was calculated as the average of renal creatinine and urea clearances. We analyzed whether mean HbA1c was associated with change in GFR (ΔGFR) over 1 year. ♦ Results: During the first year of PD, ΔGFR was –1.7 ± 3.4 mL/min/1.73 m2 and was not affected by mean HbA1c. Acute hemodialysis before starting PD and mean arterial diastolic pressure were related to the decline of GFR in a multivariate analysis. ♦ Conclusion: Glycemic control was not associated with change in RRF in diabetic patients during the first year after starting PD.

Increased body fat rather than body weight has harmful effects on 4-year changes of renal function in the general elderly population with a normal or mildly impaired renal function

Background With increasing age, body fat increases and muscle mass reduces. Even people with a normal weight may have a higher percentage of body fat. The aim of this study is to investigate the association between increased body fat and renal function decline (RFD) in the general elderly population with normal or mildly impaired renal function. Method We conducted a prospective study of 615 healthy individuals in the general Korean population aged ≥60 years who participated in two health screening check-ups separated by a 4-year period. Obesity was defined as the highest sex-specific tertiles of the percentage body fat (PBF). The main outcome was changes of estimated glomerular filtration rate (eGFR) during the 4 years. Significant RFD was defined as a decrease of eGFR over the upper quartile (≤−2.1% per year). Results The mean age was 67.2±6.6 years. The median value of the absolute decline in the eGFR and the percent change was −3.0 mL/minute/1.73 m2 and −0.87%/year in men and −3.1 mL/minute/1.73 m2 and −0.89%/year in women, respectively. When stratified by sex-specific PBF tertiles, pronounced differences were observed in both sexes; those at the highest tertile of PBF showed the greatest decline in eGFR. Even after adjustments for traditional risk factors of RFD, PBF was independently associated with eGFR changes (β=−0.181; P<0.001). In addition, the harmful effect of a high PBF was consistently found in subjects with a normal weight, too (β=−0.141; P=0.006). Cases of significant RFD occurred in 181 participants (29.4%), and the risk was higher in obese participants as compared with the nonobese participants. The odd ratios (95% confidence interval) for significant RFD were 2.76 (1.28–7.74) in men and 2.02 (1.06–4.43) in women in a whole population and 3.15 (1.03–18.52) in men and 1.44 (1.01–3.28) in women with a normal weight, respectively. Conclusion Among the elderly population without comorbidities, increased body fat has a harmful effect on RFD, irrespective of body weight.