Interdialytic Weight Gain and Cardiovascular Outcome in Incident Hemodialysis Patients

BACKGROUND: Interdialytic weight gain (IDWG) has been regarded as a surrogate of volume overload, but also as a marker of a better nutritional status in end-stage renal disease (ESRD) patients on hemodialysis (HD). This paradoxical meaning of IDWG requires further investigation, particularly in adverse cardiovascular outcomes. METHODS: A prospective cohort of 1,013 incident HD patients from 36 HD centers of the Clinical Research Center for ESRD in Korea was included. Patients were categorized into five groups according to the IDWG%, a ratio of absolute IDWG to dry weight: <1.0, ≥4.0, and every 1.0 increment in between. Primary outcome was major adverse cardiac and cerebrovascular events (MACCE). RESULTS: During a mean follow-up of 18.7 months, primary outcome was observed in 104 patients (10.3%). In multivariate analysis, compared to patients with IDWG% of 1.0-1.9 (reference group), the hazard ratios (HRs) for primary outcome in the IDWG% <1.0, 2.0-2.9, 3.0-3.9, and ≥4.0 groups were 1.10 [95% confidence interval (CI) 0.55-2.20, p = 0.80], 1.15 (95% CI 0.59-2.27, p = 0.68), 1.80 (95% CI 0.95-3.41, p = 0.07), and 1.93 (95% CI 1.02-3.64, p = 0.04), respectively. Furthermore, even when residual renal function and 24-hour urine volume were adjusted, IDWG% ≥4.0 remained as a significant predictor of primary outcome (HR 2.03, 95% CI 1.02-4.02, p = 0.04). CONCLUSION: Increased IDWG% is a significant independent predictor of MACCE in incident HD patients. It could be helpful to prevent excessive IDWG for improving clinical outcomes in incident HD patients.ope

Diastolic dysfunction is associated with an increased risk of contrast-induced nephropathy: a retrospective cohort study

BACKGROUND: Contrast-induced nephropathy (CIN) is the third leading cause of hospital-acquired acute kidney injury, and it is associated with poor long-term clinical outcomes. Although systolic heart failure is a well-known risk factor for CIN, no studies have yet evaluated the association between diastolic dysfunction and CIN. METHODS: We conducted a retrospective study of 735 patients who underwent percutaneous transluminal coronary angioplasty (PTCA) and had an echocardiography performed within one month of the procedure at our institute, between January 2009 and December 2010. CIN was defined as an increase of ≥ 0.5 mg/dL or ≥ 25% in serum creatinine level during the 72 hours following PTCA. RESULTS: CIN occurred in 64 patients (8.7%). Patients with CIN were older, had more comorbidities, and had an intra-aortic balloon pump (IABP) placed more frequently during PTCA than patients without CIN. They showed greater high-sensitivity C-reactive protein (hs-CRP) levels and lower estimated glomerular filtration rates (eGFR). Echocardiographic findings revealed lower ejection fraction and higher left atrial volume index and E/E' in the CIN group compared with non-CIN group. When patients were classified into 3 groups according to the E/E' values of 8 and 15, CIN occurred in 42 (21.6%) patients in the highest tertile compared with 20 (4.0%) in the middle and 2 (4.3%) in the lowest tertile (p 15 was identified as an independent risk factor for the development of CIN after adjustment for age, diabetes, dose of contrast media, IABP use, eGFR, hs-CRP, and echocardiographic parameters [odds ratio (OR) 2.579, 95% confidence interval (CI) 1.082-5.964, p = 0.035]. In addition, the area under the receiver operating characteristic curve of E/E' was 0.751 (95% CI 0.684-0.819, p < 0.001), which was comparable to that of ejection fraction and left atrial volume index (0.739 and 0.656, respectively, p < 0.001). CONCLUSIONS: This study demonstrated that, among echocardiographic variables, E/E' was an independent predictor of CIN. This in turn suggests that diastolic dysfunction may be a useful parameter in CIN risk stratification.ope

Stepwise Treatment Using Corticosteroids Alone and in Combination with Cyclosporine in Korean Patients with Idiopathic Membranous Nephropathy

PURPOSE: We undertook an observational study to investigate the effects of immunosuppressive treatment on proteinuria and renal function in 179 Korean idiopathic membranous nephropathy patients with nephrotic syndrome. MATERIALS AND METHODS: The primary outcome was regarded as the first appearance of remission and the secondary outcomes as a decline in estimated glomerular filtration rate (eGFR) >50% or initiation of dialysis, and all-cause mortality. Seventy-two (40.2%) and 50 (27.9%) patients were treated with corticosteroids alone (C) and corticosteroids plus cyclosporine (C+C), respectively, whereas 57 (31.8%) did not receive immunosuppressants (NTx). Cyclosporine was added if there was no reduction in proteinuria of >50% from baseline by corticosteroids alone within 3 months. RESULTS: There were no differences in baseline renal function and the amount of proteinuria among the three groups. Overall, complete remission (CR) was achieved in 88 (72.1%) patients by immunosuppressants. In a multivariate analysis adjusted for covariates associated with adverse renal outcome, the probability of reaching CR was significantly higher in the C [hazard ratio (HR), 4.09; p<0.001] and C+C groups (HR, 2.57; p=0.003) than in the NTx group. Kaplan-Meier analysis revealed that 5-year CR rates of C, C+C, and NTx groups were 88.5%, 86.2%, and 56.7% (p<0.001). Ten-year event-free rates for the secondary endpoints in these three groups were 91.7%, 79.9%, and 57.2% (p=0.01). CONCLUSION: Immunosuppressive treatment was effective in inducing remission and preserving renal function in these patients. Therefore, stepwise treatment using corticosteroids alone and in combination with cyclosporine is warranted in these patients.ope

Preservation of renal function by thyroid hormone replacement therapy in chronic kidney disease patients with subclinical hypothyroidism

CONTEXT: Subclinical hypothyroidism is not a rare condition, but the use of thyroid hormone to treat subclinical hypothyroidism is an issue of debate. OBJECTIVE: This study was undertaken to investigate the impact of thyroid hormone therapy on the changes in estimated glomerular filtration rate (eGFR) in subclinical hypothyroidism patients with stage 2-4 chronic kidney disease. PATIENTS: A total of 309 patients were included in the final analysis. MAIN OUTCOME MEASURE: The changes in eGFR over time were compared between patients with and without thyroid hormone replacement therapy using a linear mixed model. Kaplan-Meier curves were constructed to determine the effect of thyroid hormone on renal outcome, a reduction of eGFR by 50%, or end-stage renal disease. The independent prognostic value of subclinical hypothyroidism treatment for renal outcome was ascertained by multivariate Cox regression analysis. RESULTS: Among the 309 patients, 180 (58.3%) took thyroid hormone (treatment group), whereas 129 (41.7%) did not (nontreatment group). During the mean follow-up duration of 34.8 ± 24.3 months, the overall rate of decline in eGFR was significantly greater in the nontreatment group compared to the treatment group (-5.93 ± 1.65 vs. -2.11 ± 1.12 ml/min/yr/1.73 m(2); P = 0.04). Moreover, a linear mixed model revealed that there was a significant difference in the rates of eGFR decline over time between the two groups (P < 0.01). Kaplan-Meier analysis also showed that renal event-free survival was significantly lower in the nontreatment group (P < 0.01). In multivariate Cox regression analysis, thyroid hormone replacement therapy was found to be an independent predictor of renal outcome (hazard ratio, 0.28; 95% CI, 0.12-0.68; P = 0.01). CONCLUSION: Thyroid hormone therapy not only preserved renal function better, but was also an independent predictor of renal outcome in chronic kidney disease patients with subclinical hypothyroidism.ope

Decreased circulating C3 levels and mesangial C3 deposition predict renal outcome in patients with IgA nephropathy

BACKGROUND AND AIMS: Mesangial C3 deposition is frequently observed in patients with IgA nephropathy (IgAN). However, the role of complement in the pathogenesis or progression of IgAN is uncertain. In this observational cohort study, we aimed to identify the clinical implications of circulating C3 levels and mesangial C3 deposition and to investigate their utility as predictors of renal outcomes in patients with IgAN. METHODS: A total of 343 patients with biopsy-proven IgAN were enrolled between January 2000 and December 2008. Decreased serum C3 level (hypoC3) was defined as C3 <90 mg/dl. The study endpoint was end-stage renal disease (ESRD) and a doubling of the baseline serum creatinine (D-SCr). RESULTS: Of the patients, there were 66 patients (19.2%) with hypoC3. During a mean follow-up of 53.7 months, ESRD occurred in 5 patients (7.6%) with hypoC3 compared with 9 patients (3.2%) with normal C3 levels (P = 0.11). However, 12 patients (18.2%) with hypoC3 reached D-SCr compared with 17 patients (6.1%) with normal C3 levels [Hazard ratio (HR), 3.59; 95% confidence interval (CI), 1.33-10.36; P = 0.018]. In a multivariable model in which serum C3 levels were treated as a continuous variable, hypoC3 significantly predicted renal outcome of D-SCr (per 1 mg/dl increase of C3; HR, 0.95; 95% CI, 0.92-0.99; P = 0.011). The risk of reaching renal outcome was significantly higher in patients with mesangial C3 deposition 2+ to 3+ than in patients without deposition (HR 9.37; 95% CI, 1.10-80.26; P = 0.04). CONCLUSIONS: This study showed that hypoC3 and mesangial C3 deposition were independent risk factors for progression, suggesting that complement activation may play a pathogenic role in patients with IgAN.ope

The Relationship of Initial Transferrin Saturation to Cardiovascular Parameters and Outcomes in Patients Initiating Dialysis

BACKGROUND: The prognostic importance of anemia for cardiovascular (CV) events and mortality has been extensively investigated. However, little is known about the impact of transferrin saturation (TSAT), a marker reflecting the availability of iron for erythropoiesis, on clinical outcome in dialysis patients. METHODS: A total of 879 anemic incident dialysis patients were recruited from the Clinical Research Center for End-Stage Renal Disease in Korea and were divided into 3 groups according to baseline TSAT of ≤20%, 20-40%, and >40%. RESULTS: There were no differences in hemoglobin levels and the proportion of patients on erythropoiesis-stimulating agents or iron supplements among the 3 groups. During a mean follow-up duration of 19.3 months, 51 (5.8%) patients died. CV composite (11.71 vs. 5.55 events/100 patient-years, P = 0.001) and all-cause mortality rates (5.38 vs. 2.31 events/100 patient-years, P = 0.016) were significantly higher in patients with TSAT ≤20% compared to those with TSAT 20-40% (reference group). Cox regression analysis revealed that patients with TSAT ≤20% had 1.62- and 2.19-fold higher risks for CV composite outcome (P = 0.046) and all-cause mortality (P = 0.030). Moreover, TSAT ≤20% was significantly associated with left ventricular hypertrophy [odds ratio (OR)  = 1.46], high-sensitivity C-reactive protein ≥3 mg/dL (OR = 2.09), N-terminal pro B-type natriuretic peptide ≥10000 pg/mL (OR  = 2.04), and troponin-T≥0.1 ng/mL (OR  = 2.02), on logistic regression analysis. CONCLUSIONS: Low TSAT was a significant independent risk factor for adverse clinical outcome in incident dialysis patients with anemia, which may be partly attributed to cardiac dysfunction and inflammation.ope

Diastolic dysfunction is an independent predictor of cardiovascular events in incident dialysis patients with preserved systolic function

BACKGROUND: Diastolic heart failure (HF), the prevalence of which is gradually increasing, is associated with cardiovascular (CV) morbidity and mortality in the general population and, more specifically, in patients with end-stage renal disease (ESRD). However, the impact of diastolic dysfunction on CV outcomes has not been studied in incident dialysis patients with preserved systolic function. METHODS: This prospective observational cohort study investigates the clinical consequence of diastolic dysfunction and the predictive power of diastolic echocardiographic parameters for CV events in 194 incident ESRD patients with normal or near normal systolic function, who started dialysis between July 2008 and August 2012. RESULTS: During a mean follow-up duration of 27.2 months, 57 patients (29.4%) experienced CV events. Compared to the CV event-free group, patients with CV events had a significantly higher left ventricular (LV) mass index, ratio of early mitral flow velocity (E) to early mitral annulus velocity (E') (E/E'), LA volume index (LAVI), deceleration time, and right ventricular systolic pressure, and a significantly lower LV ejection fraction and E'. In multivariate Cox proportional hazard analysis, E/E'>15 and LAVI>32 mL/m2 significantly predicted CV events (E/E'>15: hazard ratio [HR] = 5.40, 95% confidence interval [CI] = 2.73-10.70, P32 mL/m2: HR = 5.56, 95% CI = 2.28-13.59, P15 and LAVI>32 mL/m2 had the worst CV outcomes. CONCLUSION: An increase in E/E' or LAVI is a significant risk factor for CV events in incident dialysis patients with preserved LV systolic function.ope

Changes in echocardiographic parameters according to the rate of residual renal function decline in incident peritoneal dialysis patients

Residual renal function (RRF) is associated with left ventricular (LV) hypertrophy as well as all-cause and cardiovascular (CV) mortality in patients with end-stage renal disease. However, no studies have yet examined the serial changes in echocardiographic findings according to the rate of RRF decline in incident dialysis patients. A total of 81 patients who started peritoneal dialysis (PD) between 2005 and 2012 at Yonsei University Health System, Seoul, South Korea, and who underwent baseline and follow-up echocardiography within the first year of PD were recruited. Patients were dichotomized into "faster" and "slower" RRF decline groups according to the median values of RRF decline slope (-1.60 mL/min/y/1.73 m(2)). Baseline RRF and echocardiographic parameters were comparable between the 2 groups. During the first year of PD, there were no significant changes in LV end-diastolic volume index (LVEDVI), left atrial volume index (LAVI), or LV mass index (LVMI) in the "faster" RRT decline group, while these indices decreased in the "slower" RRT decline group. The rate of RRF decline was a significant determinant of 1-year changes in LVEDVI, LAVI, and LVMI. The linear mixed model further confirmed that there were significant differences in the changes in LVEDVI, LAVI, and LVMI between the 2 groups (P = 0.047, 0.048, and 0.001, respectively). During a mean follow-up duration of 31.9 months, 4 (4.9%) patients died. Compared with the "slower" RRF decline group, CV composite (20.29/100 vs 7.18/100 patient-years [PY], P = 0.098), technique failure (18.80/100 vs 4.19/100 PY, P = 0.006), and PD peritonitis (15.73/100 vs 4.95/100 PY, P = 0.064) developed more frequently in patients with "faster" RRF decline rate. On multivariate Cox regression analysis, patients with "faster" RRF decline rate showed 4.82-, 4.44-, and 7.37-fold higher risks, respectively, for each clinical outcome. Preservation of RRF is important for conserving cardiac performance, resulting in an improvement in clinical outcomes of incident PD patients.ope

Progression of aortic arch calcification over 1 year is an independent predictor of mortality in incident peritoneal dialysis patients

BACKGROUNDS AND AIMS: The presence and progression of vascular calcification have been demonstrated as important risk factors for mortality in dialysis patients. However, since the majority of subjects included in most previous studies were hemodialysis patients, limited information was available in peritoneal dialysis (PD) patients. Therefore, the aim of this study was to investigate the prevalence of aortic arch calcification (AoAC) and prognostic value of AoAC progression in PD patients. METHODS: We prospectively determined AoAC by chest X-ray at PD start and after 12 months, and evaluated the impact of AoAC progression on mortality in 415 incident PD patients. RESULTS: Of 415 patients, 169 patients (40.7%) had AoAC at baseline with a mean of 18.1±11.2%. The presence of baseline AoAC was an independent predictor of all-cause [Hazard ratio (HR): 2.181, 95% confidence interval (CI): 1.336-3.561, P = 0.002] and cardiovascular mortality (HR: 3.582, 95% CI: 1.577-8.132, P = 0.002). Among 363 patients with follow-up chest X-rays at 12 months after PD start, the proportion of patients with AoAC progression was significantly higher in patients with baseline AoAC (64.2 vs. 5.3%, P<0.001). Moreover, all-cause and cardiovascular death rates were significantly higher in the progression groups than in the non-progression group (P<0.001). Multivariate Cox analysis revealed that AoAC progression was an independent predictor for all-cause (HR: 2.625, 95% CI: 1.150-5.991, P = 0.022) and cardiovascular mortality (HR: 4.008, 95% CI: 1.079-14.890, P = 0.038) in patients with AoAC at baseline. CONCLUSIONS: The presence and progression of AoAC assessed by chest X-ray were independently associated with unfavorable outcomes in incident PD patients. Regular follow-up by chest X-ray could be a simple and useful method to stratify mortality risk in these patients.ope

Sagittal Abdominal Diameter Is an Independent Predictor of All-Cause and Cardiovascular Mortality in Incident Peritoneal Dialysis Patients

BACKGROUNDS AND AIMS: Visceral fat has a crucial role in the development and progression of cardiovascular disease, the major cause of death in end-stage renal disease (ESRD). Although sagittal abdominal diameter (SAD), as an index of visceral fat, significantly correlated with mortality in the general population, the impact of SAD on clinical outcomes has never been explored in ESRD patients. Therefore, we sought to elucidate the prognostic value of SAD in incident peritoneal dialysis (PD) patients. METHODS: We prospectively determined SAD by lateral abdominal X-ray at PD initiation, and evaluated the association of SAD with all-cause and cardiovascular mortality in 418 incident PD patients. RESULTS: The mean SAD was 24.5 ± 4.3 cm, and during a mean follow-up of 39.4 months, 97 patients (23.2%) died, and 49.4% of them died due to cardiovascular disease. SAD was a significant independent predictor of all-cause [3rd versus 1st tertile, HR (hazard ratio): 3.333, 95% CI (confidence interval): 1.514-7.388, P = 0.01; per 1 cm increase, HR: 1.071, 95% CI: 1.005-1.141, P = 0.03] and cardiovascular mortality (3rd versus 1st tertile, HR: 8.021, 95% CI: 1.994-32.273, P = 0.01; per 1 cm increase, HR: 1.106, 95% CI: 1.007-1.214, P = 0.03). Multivariate fractional polynomial analysis also showed that all-cause and cardiovascular mortality risk increased steadily with higher SAD values. In addition, SAD provided higher predictive value for all-cause (AUC: 0.691 vs. 0.547, P<0.001) and cardiovascular mortality (AUC: 0.644 vs. 0.483, P<0.001) than body mass index (BMI). Subgroup analysis revealed higher SAD (≥ 24.2 cm) was significantly associated with all-cause mortality in men, women, younger patients (<65 years), and patients with lower BMI (<22.3 kg/m(2)). CONCLUSIONS: SAD determined by lateral abdominal X-ray at PD initiation was a significant independent predictor of all-cause and cardiovascular mortality in incident PD patients. Estimating visceral fat by SAD could be useful to stratify mortality risk in these patients.ope