Comparison of creatinine and cystatin formulae with 51 Chromium-ethylenediaminetetraacetic acid glomerular filtration rate in patients with decompensated cirrhosis.

BACKGROUND AND AIM: Evaluation of renal function, that is, glomerular filtration rate (GFR), has become very important, but conventional mathematical formulae for GFR assessment are inaccurate in patients with cirrhosis. The aim of the present study was to compare serum creatinine (sCr)-based and serum cystatin C (cysC)-based estimated GFR (eGFR) formulae with 51 Chromium-ethylenediaminetetraacetic acid GFR (51 Chr-GFR) in patients with stable decompensated cirrhosis. METHODS: In 129 Caucasian patients with decompensated cirrhosis, we assessed sCr-based GFRs [Modification of Diet in Renal Disease and chronic kidney disease-epidemiology (CKD-EPI)-sCr formulae], cysC-based GFRs [Hoek, Larsson, and CKD-EPI-cysC equations], and the mathematical formulae, which combined both sCr and cysC [i.e. CKD-EPI-sCr-cysC and the specific for cirrhotics formula recently proposed by Mindikoglu et al. (Mindikoglu-eGFR)]. Multivariate linear regression analysis was used for GFR predictors in our cohort. RESULTS: The correlations between 51 Chr-GFR and all mathematical formulae were good (Spearman r2 > 0.68, P < 0.001). Modification of Diet in Renal Disease and CKD-EPI-sCr had lower bias (6.6 and -4.8, respectively), compared with the other eGFRs, while Mindikoglu-eGFR and CKD-EPI-sCr-cysC formulae had greater precision (17.1 and 17.3, respectively), compared with the other eGFRs. CKD-EPI-sCr and Mindikoglu-eGFR had higher accuracy (39% and 41%, respectively), compared with the other eGFRs. The factors independently associated with the 51 Chr-GFR were age, cysC, and sCr, and the new derived formula had lower bias (0.89) and similar precision (17.2) and accuracy (41%) with Mindikoglu-eGFR formula. CONCLUSION: The specific mathematical formulae derived from patients with cirrhosis seem to provide superior assessment of renal function, compared with the conventional used sCr-based and cysC-based formulae.

Diastolic dysfunction is associated with low urinary sodium excretion in patients with decompensated cirrhosis.

BACKGROUND/AIM: The pathogenesis and the clinical impact of diastolic dysfunction (DD) in cirrhosis remain unclear. Our aim was to investigate the factors significantly associated with the presence of DD in patients with decompensated cirrhosis on the waiting list for liver transplantation. MATERIAL AND METHODS: consecutive patients with decompensated cirrhosis, who admitted for transplant assessment, were prospectively evaluated. We assessed the independent factors associated with the presence of DD, while their discriminative ability was evaluated by AUC curve. The diagnosis of DD was based on Doppler echocardiography and classified into three categories according to the current guidelines. RESULTS: we evaluated 115 consecutive patients. Sixty six patients (57.3%-group 1) had DD and 49 (42.7%-group 2) had not DD. The 2 groups had similar Child-Pugh/MELD scores and survival. In multivariable logistic regression analysis, pulse rate (OR: 1.082, 95% CI: 1.03-1.15, p = 0.004), and UNa24h (OR: 0.98, 95% CI: 0.97- 0.99, p = 0.004) were the only variables independently associated with the presence of DD. In the subgroup of consecutive patients (n = 31) with evaluation of cytokines, those (n = 22) with DD, compared to those (n = 9) without DD, had significantly higher levels of inteleukin-6 [145 (45-2000) vs. 56 (10-149)pg/mL, p = 0.043]. CONCLUSIONS: We found that DD was independently associated with lower 24-hour urine sodium. Although no correlation was found between DD and severity of liver disease or survival, further studies are needed for final conclusions.

Glomerular filtration rate is an independent factor of mortality in patients with decompensated cirrhosis.

AIM: Although serum creatinine is included in the Model for End-Stage Liver Disease (MELD) score, it is an inaccurate marker of renal function, namely, of glomerular filtration rate ("true" GFR) in patients with decompensated cirrhosis. Our aim was to investigate the impact of MELD score and "true" GFR as determinants of survival in patients with decompensated cirrhosis. METHODS: We included all consecutive patients with decompensated cirrhosis who were admitted to our department. Renal function was assessed by creatinine- and cystatin-based estimated GFR and "true" GFR using (51) Cr-ethylenediaminetetraacetic acid. The independent factors associated with survival were evaluated. The discriminative ability of the prognostic scores (MELD and modifications of MELD score) were evaluated by using the area under the receiver-operator curve (AUC). RESULTS: One hundred and ten consecutive patients (77 men, aged 56 ± 12 years); at the end of follow up (8 months; range, 6-18), 92 patients (84%) were alive and 18 (16%) had died. In multivariate analysis, serum bilirubin (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.05-1.26; P = 0.020) and "true" GFR (HR, 0.96; 95% CI, 0.93-0.98; P = 0.003) were the only independent factors significantly associated with the outcome. The derived new prognostic model had high discriminative ability (AUC, 0.90), which was confirmed in the validation sample of 77 patients. CONCLUSION: In our cohort of patients with decompensated cirrhosis, "true" GFR and bilirubin were the independent factors of the outcome.

Association between ratio of sodium to potassium in random urine samples and renal dysfunction and mortality in patients with decompensated cirrhosis.

BACKGROUND & AIMS: Estimates of glomerular filtration rate (GFR) are used to assess renal function and are an independent prognostic factor for patients with decompensated cirrhosis, but are impractical for routine use. We investigated whether the ratio of sodium to potassium in randomly collected urine samples (UNa/K) is associated with mortality and renal dysfunction in patients with decompensated cirrhosis and ascites. METHODS: We assessed data from 126 consecutive patients with decompensated cirrhosis and ascites (93 men; age, 56 ± 12 y; 55% with viral-related disease) admitted to the Hippokration General Hospital of Thessaloniki, Greece, from September 2010 through January 2012. At admission, clinical and laboratory variables were recorded, including GFR, measured with (51)Cr-EDTA. Urine samples were collected, and UNa/K was determined. We evaluated the association between UNa/K and patient mortality using the area under the receiver operating characteristic curve analysis. RESULTS: Forty-one patients (32%; group 1) had a GFR less than 60 mL/min, and 85 patients (68%; group 2) had a GFR of 60 mL/min or greater. In the multivariable analysis, 3 variables were associated independently with the presence of severe renal dysfunction (GFR, <60 mL/min): age (odds ratio [OR], 0.93; P = .008), systolic blood pressure (OR, 1.05; P = .022), and UNa/K (OR, 1.5; P = .025). A UNa/K less than 1.0 had high sensitivity and a negative predictive value for the presence of GFR less than 60 mL/min (79% and 87%, respectively) and mortality (68% and 91%, respectively). CONCLUSIONS: In patients with decompensated cirrhosis and ascites, a ratio of sodium to potassium of less than 1 in randomly collected urine samples was associated with renal dysfunction and short-term mortality. These findings require confirmation in additional studies.

Hepatitis B virus reactivation in HBsAg-negative, anti-HBc-positive patients receiving immunosuppressive therapy: a systematic review.

BACKGROUND: The optimal management of HBsAg-negative, anti-HBc-positive patients who receive immunosuppression remains unclarified. We systematically reviewed the available data on potential predictors of the risk of hepatitis B virus (HBV) reactivation in such patients. METHODS: A literature search identified 55 studies with 3640 HBsAg-negative, anti-HBc-positive patients who received immunosuppressive regimens. RESULTS: HBV reactivation was reported in 236 (6.5%) patients. The pooled HBV reactivation rates did not differ between patients with detectable or undetectable HBV DNA in studies with hematological diseases or regimens containing rituximab, but it was higher in patients with detectable than in those with undetectable HBV DNA who were taking rituximab-free regimens (14% vs. 2.6%; risk ratio [RR] 12.67, 95% CI: 95%CI 2.39-67.04, P=0.003) or had non-hematological diseases, although the latter was not confirmed by sensitivity analysis (RR 8.80, 95%CI 0.71-109.00, P=0.09). The pooled HBV reactivation rates were lower in patients with positive than in those with negative anti-HBs in studies with hematological (7.1% vs. 21.8%; RR 0.29, 95%CI 0.19-0.46, P<0.001) or non-hematological (2.5% vs. 10.7%; RR 0.28, 95%CI 0.11-0.76, P=0.012) diseases, and rituximab-containing (6.6% vs. 19.8%; RR 0.32, 95%CI 0.15-0.69, P=0.003) or rituximab-free (3.3% vs. 9.2%; RR 0.36, 95%CI 0.14-0.96, P=0.042) regimens. CONCLUSIONS: The risk of HBV reactivation is high; therefore, anti-HBV prophylaxis should be recommended in HBsAg-negative, anti-HBc-positive patients with hematological diseases and/or rituximab-containing regimens, regardless of HBV DNA and anti-HBs status. In contrast, patients with non-hematological diseases or rituximab-free regimens have a low risk of HBV reactivation and may not require anti-HBV prophylaxis if they have undetectable HBV DNA and positive anti-HBs.

Urine albumin-to-creatinine ratio is associated with the severity of liver disease, renal function and survival in patients with decompensated cirrhosis.

BACKGROUND AND AIMS: To investigate if urine albumin-to-creatinine ratio (UACR) is associated with the presence of glomerular filtration rate (GFR) <60 mL/min, severity of liver disease and survival in patients with stable decompensated cirrhosis. METHODS: We evaluated prospectively 220 patients (73 % male, age 52.8 ± 12 years). In each patient, assessment of GFR was based on 51chromium-EDTA. Random urine samples were obtained for measurement of UACR. RESULTS: Thirty-eight patients (17 %, group 1) had UACR ≥30 mg/g and 182 (83 %, group 2) had UACR <30 mg/g. Group 1, compared to group 2 patients, had significantly lower levels of "true" GFR (61 vs. 71 ml/min, p = 0.035). Patients with "true" GFR <60 mL/min (n = 93), compared to those with "true" GFR ≥60 mL/min (n = 127), had higher levels of UACR (16 vs. 11.3 mg/g, p = 0.023). In multivariate analysis, serum creatinine and UACR (ΟR 0.98, 95 % CI 0.95-0.99, p = 0.04) were independently associated with the presence of GFR <60 mL/min. Based on the area under the ROC curves, the best cut-off point for UACR was >16.51 mg/g giving a sensitivity 70 %, specificity 49 %, PPV 68 % and NPV 51 %. During the follow-up period [17 (6-52) months], the patients who died or underwent LT (n = 158), compared to those who remained alive (n = 62), had higher levels of UACR (41 vs. 13 mg/g, p = 0.025). Patients with UACR ≥30 mg/g had worse outcome, compared to those with UACR <30 mg/g (log rank p = 0.053). CONCLUSIONS: We showed for the first time that UACR ≥30 mg/g was associated with more severe liver disease, lower GFR and worse LT-free survival in patients with decompensated cirrhosis. However, further studies are needed to confirm these findings.