Fibrotic Burden in Patients With Hepatitis B Virus-Related Cirrhosis Is Independently Associated With Poorer Kidney Outcomes.

BACKGROUND: We investigated whether higher fibrotic burden was independently associated with poorer kidney outcomes in patients with hepatitis B virus (HBV)-related cirrhosis. METHODS: A total of 1691 patients with radiologically diagnosed HBV-related cirrhosis but without baseline chronic kidney disease (CKD) who underwent transient elastography (TE) between March 2012 and August 2018 were selected. The study outcome was the composite of development of incident CKD, defined as the occurrence of estimated glomerular filtration rate (eGFR) <60 mL/minute/1.73 m2 or proteinuria (≥1+ on dipstick test) on 2 consecutive measurements during follow-up, 50% decline in eGFR or onset of end-stage kidney disease (initiation of chronic dialysis), or all-cause mortality. RESULTS: The mean age was 53.4 years and 1030 (60.9%) patients were male. During 8379 person-years of follow-up (median 5.2 years), 60 (3.5%) patients experienced study outcomes. When stratified according to TE-defined fibrotic burden, multivariable Cox models revealed that risk of poorer kidney outcomes was 2.77-fold (95% confidence interval, 1.16-6.63; P < .001) higher in patients with liver stiffness range indicating cirrhosis (≥11.7 kPa), compared to those without significant liver fibrosis (<7.9 kPa). These associations remained significant even after adjusting for vigorous confounders. CONCLUSIONS: Higher fibrotic burden assessed using TE was independently associated with poorer kidney outcomes in patients with HBV-related cirrhosis.

Advanced liver fibrosis measured by transient elastography predicts chronic kidney disease development in individuals with non-alcoholic fatty liver disease.

AIMS/HYPOTHESIS: Non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) are progressive chronic conditions that share important cardiometabolic risk factors and pathogenic mechanisms. We investigated the association between liver fibrosis measured by transient elastography (TE) and the risk of incident CKD in individuals with NAFLD. METHODS: A total of 5983 participants with NAFLD (defined as controlled attenuation parameter >222 dB/m) but without CKD who underwent TE between March 2012 and August 2018 were selected. The primary outcome was incident CKD, defined as the occurrence of eGFR <60 ml min-1 [1.73 m]-2 or proteinuria (≥1+ on dipstick test) on two consecutive measurements during follow-up. The secondary outcome was a 25% decline in eGFR measured on two consecutive visits. RESULTS: The mean age was 51.8 years and 3756 (62.8%) participants were male. During 17,801 person-years of follow-up (mean follow-up of 3.0 years), 62 participants (1.0%) developed incident CKD. When stratified into TE-defined fibrosis stages (F0-F4), multivariable Cox models revealed that risk of incident CKD was 5.40-fold (95% CI 2.46, 11.84; p < 0.001) higher in the F3/F4 group (≥9.5 kPa) than in the F0 group (<5.5 kPa). During 17,577 person-years of follow-up (mean follow-up of 3.0 years), 201 participants (3.4%) experienced the secondary outcome, for which the F3/F4 group had a 3.22-fold higher risk (95% CI 1.96, 5.28; p < 0.001) than the F0 group. CONCLUSIONS/INTERPRETATION: In this large cohort of individuals with NAFLD but without baseline CKD, advanced liver fibrosis measured by TE was significantly associated with a higher risk of incident CKD.

Incidence of Acute Kidney Injury after Adrenalectomy in Patients with Primary Aldosteronism.

BACKGROUND: Aldosterone-induced glomerular hyperfiltration can lead to masked preoperative renal dysfunction in primary aldosteronism(PA) patients. We evaluated whether PA patients had a higher prevalence of acute kidney injury (AKI) after unilateral adrenalectomy. In addition, we identified risk factors for AKI in these subjects. METHODS: This retrospective study included 107 PA patients, and 186 pheochromocytoma patients as a control group, all of whom underwent adrenalectomy between January 2006 and November 2017 at Yonsei University Severance Hospital. The primary outcome was AKI within 48 hours after adrenalectomy. Univariate and multivariate logistic regression analyses were performed to identify predictors of AKI after adrenalectomy. RESULTS: Overall incidence of AKI was 49/293 (16.7%). In PA patients, the incidence of AKI was 29/107 (27.1%). In contrast, incidence of AKI was 20/186 (10.7%) in pheochromocytoma patients. Univariate and multivariate logistic regression analysis both showed a higher risk of postoperative AKI in PA patients compared to pheochromocytoma patients. In addition, old age, diabetes, longer duration of hypertension, lower preoperative estimated glomerular filtration rate, high aldosterone-cortisol ratio (ACR) and lateralization index (LI) were identified as independent risk factors for postoperative AKI in PA patients after unilateral adrenalectomy. CONCLUSION: Incidence and risk of postoperative AKI were significantly higher in PA patients after surgical treatment. High ACR on the tumor side and high LI were associated with higher risk of AKI in PA patients compared to pheochromocytoma patients.

Low serum intact parathyroid hormone level is an independent risk factor for overall mortality and major adverse cardiac and cerebrovascular events in incident dialysis patients.

UNLABELLED: Abnormal bone dynamics is a major risk factor for cardiovascular disease in patients with chronic kidney disease. The level of serum intact parathyroid hormone (iPTH) is widely used as a bone dynamic marker. We investigated the effect of the mean level of serum iPTH on overall mortality and cardiovascular outcomes in incident dialysis patients. PURPOSE: Chronic kidney disease-mineral bone disorder (CKD-MBD) is a major risk factor for cardiovascular disease (CVD) in patients with end-stage renal disease (ESRD). CKD-MBD is classified as low- or high-turnover bone disease according to the bone dynamics; both are related to vascular calcification in ESRD. To evaluate the prognostic value of abnormal serum parathyroid hormone (PTH) levels on ESRD patients, we investigated the effects of time-averaged serum intact PTH (TA-iPTH) levels on overall mortality and major adverse cardiac and cerebrovascular events (MACCEs) in incident dialysis patients. METHODS: Four hundred thirteen patients who started dialysis between January 2009 and September 2013 at Yonsei University Health System were enrolled. The patients were divided into three groups according to TA-iPTH levels during the 12 months after the initiation of dialysis: group 1, <65 pg/ml; group 2, 65-300 pg/ml; and group 3, >300 pg/ml. Cox regression analyses were performed to determine the prognostic value of TA-iPTH for overall mortality and MACCEs. RESULTS: The mean age of the patients was 57 ± 15 years, and 222 patients (54 %) were men. During the median follow-up of 40.8 ± 29.3 months, 49 patients (12 %) died, and MACCEs occurred in 55 patients (13 %). The multivariate Cox regression analyses demonstrated that a low TA-iPTH level was an independent risk factor for both overall mortality (group 2 as reference; group 1: hazard ratio (HR) = 2.06, 95 % confidence interval (CI) = 1.11-3.83, P = 0.023) and MACCEs (HR = 1.82, 95 % CI = 1.04-3.20, P = 0.036) in incident dialysis patients after adjustment for confounding factors. CONCLUSION: Low serum TA-iPTH is a useful clinical marker of both overall mortality and MACCEs in patients undergoing incident dialysis, mediated by vascular calcification.

Preoperative Low Serum Bicarbonate Levels Predict Acute Kidney Injury After Cardiac Surgery.

Acute kidney injury (AKI) after cardiac surgery is a common and serious complication. Although lower than normal serum bicarbonate levels are known to be associated with consecutive renal function deterioration in patients with chronic kidney injury, it is not well-known whether preoperative low serum bicarbonate levels are associated with the development of AKI in patients who undergo cardiac surgery. Therefore, the clinical implication of preoperative serum bicarbonate levels on AKI occurrence after cardiac surgery was investigated. Patients who underwent coronary artery bypass or valve surgery at Yonsei University Health System from January 2013 to December 2014 were enrolled. The patients were divided into 3 groups based on preoperative serum bicarbonate levels, which represented group 1 (below normal levels) <23 mEq/L; group 2 (normal levels) 23 to 24 mEq/L; and group 3 (elevated levels) >24 mEq/L. The primary outcome was the predicated incidence of AKI 48 hours after cardiac surgery. AKI was defined according to Acute Kidney Injury Network criteria. Among 875 patients, 228 (26.1%) developed AKI within 48 hours after cardiac surgery. The incidence of AKI was higher in group 1 (40.9%) than in group 2 (26.5%) and group 3 (19.5%) (P < 0.001). In addition, the duration of postoperative stay in a hospital intensive care unit (ICU) was longer for AKI patients and for those in the low-preoperative-serum-bicarbonate-level groups. A multivariate logistic regression analysis showed that low preoperative serum bicarbonate levels were significantly associated with AKI even after adjustment for age, sex, hypertension, diabetes mellitus, operation type, preoperative hemoglobin, and estimated glomerular filtration rate. In conclusion, low serum bicarbonate levels were associated with higher incidence of AKI and prolonged ICU stay. Further studies are needed to clarify whether strict correction of bicarbonate levels close to normal limits may have a protective role in preventing further AKI development.

Serum Ferritin Predicts Mortality Regardless of Inflammatory and Nutritional Status in Patients Starting Dialysis: A Prospective Cohort Study.

BACKGROUND: The impact of serum ferritin on prognosis in patients starting hemodialysis (HD) is not fully elucidated. METHODS: A prospective cohort of 946 incident HD patients from 26 dialysis centers in Korea was selected for this study. Patients were divided into tertiles according to natural logarithm (Ln) ferritin concentrations. RESULTS: During a median follow-up of 39 months, 88 (9.3%) patients died. Multivariate Cox proportional hazard analysis demonstrated that Ln ferritin was independently associated with an increase in cardiovascular mortality risk (hazard ratio (HR) 1.604, 95% CI 1.040-2.474, p = 0.033), infection-related mortality risk (HR 1.916, 95% CI 1.056-3.476, p = 0.032), and all-cause mortality risk (HR 1.547, 95% CI 1.156-2.069, p = 0.003). CONCLUSION: Serum ferritin levels at the time of HD commencement were a significant independent risk factor for mortality regardless of systemic inflammation and nutritional status. Therefore, elevated serum ferritin levels could be an effective indicator for prognosis.

Low Serum Bicarbonate Predicts Residual Renal Function Loss in Peritoneal Dialysis Patients.

Low residual renal function (RRF) and serum bicarbonate are associated with adverse outcomes in peritoneal dialysis (PD) patients. However, a relationship between the 2 has not yet been determined in these patients. Therefore, this study aimed to investigate whether low serum bicarbonate has a deteriorating effect on RRF in PD patients.This prospective observational study included a total of 405 incident patients who started PD between January 2000 and December 2005. We determined risk factors for complete loss of RRF using competing risk methods and evaluated the effects of time-averaged serum bicarbonate (TA-Bic) on the decline of RRF over the first 3 years of dialysis treatment using generalized linear mixed models.During the first 3 years of dialysis, 95 (23.5%) patients became anuric. The mean time until patients became anuric was 20.8 ±â€Š9.0 months. After adjusting for multiple potentially confounding covariates, an increase in TA-Bic level was associated with a significantly decreased risk of loss of RRF (hazard ratio per 1 mEq/L increase, 0.84; 0.75-0.93; P = 0.002), and in comparison to TA-Bic ≥ 24 mEq/L, TA-Bic < 24 mEq/L conferred a 2.62-fold higher risk of becoming anuric. Furthermore, the rate of RRF decline estimated by generalized linear mixed models was significantly greater in patients with TA-Bic < 24 mEq/L compared with those with TA-Bic ≥ 24 mEq/L (-0.16 vs -0.11 mL/min/mo/1.73 m, P < 0.001).In this study, a clear association was found between low serum bicarbonate and loss of RRF in PD patients. Nevertheless, whether correction of metabolic acidosis for this indication provides additional protection for preserving RRF in these patients is unknown. Future interventional studies should more appropriately address this question.

Hyponatremia Predicts New-Onset Cardiovascular Events in Peritoneal Dialysis Patients.

BACKGROUND AND AIM: Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients on peritoneal dialysis (PD). Hyponatremia was recently shown to be a modifiable factor that is strongly associated with increased mortality in PD patients. However, the clinical impact of hyponatremia on CV outcomes in these patients is unclear. METHODS: To determine whether a low serum sodium level predicts the development of CV disease, we carried out a prospective observational study of 441 incident patients who started PD between January 2000 and December 2005. Time-averaged serum sodium (TA-Na) levels were determined to investigate the ability of hyponatremia to predict newly developed CV events in these patients. RESULTS: During a mean follow-up of 43.2 months, 106 (24.0%) patients developed new CV events. The cumulative incidence of new-onset CV events after the initiation of PD was significantly higher in patients with TA-Na levels ≤ 138 mEq/L than in those with a TA-Na > 138 mEq/L. After adjustment for multiple potentially confounding covariates, an increase in TA-Na level was found to be associated with a significantly lower risk of CV events (subdistribution hazard ratio per 1 mEq/L increase, 0.90; 95% confidence interval, 0.83-0.96; p = 0.003). Patients with a TA-Na ≤ 138 mEq/L had a 2.31-fold higher risk of suffering a CV event. CONCLUSIONS: These results provide evidence of a clear association between low serum sodium and new-onset CV events after dialysis initiation in PD patients. Whether the correction of hyponatremia for this indication provides additional protection for the development of CV disease in these patients remains to be addressed in interventional studies.

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 (ß = 0.145; p = 0.003) and residual renal function (RRF) (ß = 0.130; p = 0.018) and inversely associated with PD ultrafiltration (ß = -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.