Estimation of glomerular filtration rate in patients with cirrhosis: evaluation of equations currently used in clinical practice and validation of Royal Free Hospital cirrhosis glomerular filtration rate

OBJECTIVE: Conventional creatinine-based glomerular filtration rate (GFR) equations have been reported to overestimate renal function in patients with cirrhosis. The Royal Free Hospital (RFH) cirrhosis GFR equation was developed to accurately estimate GFR in this population. The aim of this study was to evaluate the ability of widely available equations [Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI), Modification of Diet in Renal Disease equations (MDRD-4, MDRD-6)] and the RFH equation to correctly estimate the GFR of patients with cirrhosis. METHODS: We retrospectively analyzed data from patients with cirrhosis who underwent measurement of GFR with the use of 51Cr-EDTA (GFR-M). The CKD-EPI, MDRD-4, MDRD-6 and RFH equations were calculated, while bias, precision and accuracy were estimated for each one of them and then compared with paired t-tests. Bias was defined as the mean difference between the GFR-M and the result of each equation; precision was defined as the SD of the differences and accuracy was defined as the square root of the mean squared error (mean of the squared differences). Higher values are associated with worse bias and better precision/accuracy. RESULTS: One-hundred and thirty-four cirrhotic patients were included. Bias was estimated for CKD-EPI, MDRD-4, MDRD-6 and RFH at -5.91, -3.13, 0.92 and 18.24, respectively. Significant differences were observed between all equations (P < 0.001). Regarding precision, only the comparison between MDRD-4 (20.81) and RFH (16.6) yielded a statistically significant result (P = 0.037). Finally, CKD-EPI (19.32) and MDRD-6 (18.81) exhibited better accuracy than GFR-RFH (24.61) (P = 0.006 and 0.001). CONCLUSION: RFH demonstrates inferior accuracy in predicting renal function in patients with cirrhosis, in comparison to conventional equations. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved

The Effects of Long-Term Administration of Sodium Nedocromil on Bronchial Hypereactivity

The effect of long-term treatment with sodium nedocromil on airway hypereactivity was investigated in two groups of 20 patients each. Group I patients presented with allergic asthma while Group II patients presented with intrinsic asthma. For each subject of the two groups, the base FEV1 was measured and nebulized methacholine was administrated in consecutively higher concentrations until a decrease in FEV1 of >20 % was observed. Following measurement, all patients included in the study were treated with 12 mg of sodium nedocromil per day for 12 months. At the end of the treatment, bronchial hyperreactivity was evaluated for a second time by administering the same dosage of methacholine that originally produced a decline in FEV1 of >20 %. In Group I patients (allergic asthma) mean FEV1 was 3126 ml, before challenge, while after methacholine challenge FEV1 was 2400ml. Following 1-year of sodium nedocromil administration the FEV1 was 2601ml (P<0.05). Before treatment, the mean fall in FEV1, following methacholine challenge, was 23.67% while following a 1-year-long sodium nedocromil administration this value reduced to 15.70% (P<0.05). Correspondingly, PC 20 was 5.59 while after sodium nedocromil administration it increased to 11.66 (P<0.05). In Group II patients (intrinsic asthma) mean FEV1 was 2750 ml, before challenge, while after methacholine challenge FEV1 was 2066ml. Following 1-year of sodium nedocromil administration the FEV1 was 2223ml (P<0.05). Before treatment, the mean fall in FEV1, following methacholine challenge, was 27.65 % while following a 1-year-long sodium nedocromil administration this value reduced to 21.92 % (P<0.05). Correspondingly, PC 20 was 5.91 while after sodium nedocromil administration it increased to 6.19 (P<0.05). The results suggest a positive effect of long-term sodium nedocromil administration in bronchial hyperreactivity for both groups of patients

Common ABCB1 polymorphisms in Greek patients with chronic hepatitis C infection: A comparison with hyperlipidemic patients and the general population

Background Hepatitis C virus infectivity and replication efficiency appears to be dependent on the lipid content and organization of the plasma membrane of the host cell, as well as of the intracellular membranous web. As there is increasing awareness of a role played by the efflux pump ABCB1 (p-glycoprotein, P-gp) in lipid homeostasis, its function could be a determinant of chronic HCV infection. The aim of the present study was to examine and compare the distribution of common ABCB1 genotypes in patients with chronic HCV infection (n = 168), hyperlipidemic patients (n = 168) and a control group (n = 173), all from Greece. Methods Participants were genotyped for the ABCB12677G&amp;gt;T/A and 3435C&amp;gt;T polymorphisms with previously reported PCR-RFLP methods. Genotype and allele frequency distributions were compared between the three groups with the χ2 test of independence. Results The ABCB1 2677GG (ancestral) genotypes were significantly over-represented in patients with chronic hepatitis C compared to controls (39.3% vs. 26.6%, p = 0.015 according to the dominant model). A similar result was obtained when hyperlipidemic patients were compared to controls (45.2% vs. 26.6%, p &amp;lt; 0.001 according to the dominant model). Comparison of ABCB1 3435C&amp;gt;T genotype and allele distributions provided similar but not as significant differences. Genotype and allele distributions for both ABCB12677G&amp;gt;T/A and 3435C&amp;gt;T were very similar between HCV patients and hyperlipidemic patients. Conclusion Our findings imply an influence of ABCB1 polymorphisms on HCV infectivity, possibly through an effect on lipid homeostasis. © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o.o. All rights reserved