Predicting Kidney Failure, Cardiovascular Disease and Death in Advanced CKD Patients

Introduction: Predicting the timing and occurrence of kidney replacement therapy (KRT), cardiovascular events, and death among patients with advanced chronic kidney disease (CKD) is clinically useful and relevant. We aimed to externally validate a recently developed CKD G4+ risk calculator for these outcomes and to assess its potential clinical impact in guiding vascular access placement. Methods: We included 1517 patients from the European Quality (EQUAL) study, a European multicentre prospective cohort study of nephrology-referred advanced CKD patients aged ≥65 years. Model performance was assessed based on discrimination and calibration. Potential clinical utility for timing of referral for vascular access placement was studied with diagnostic measures and decision curve analysis (DCA). Results: The model showed a good discrimination for KRT and “death after KRT,” with 2-year concordance (C) statistics of 0.74 and 0.76, respectively. Discrimination for cardiovascular events (2-year C-statistic: 0.70) and overall death (2-year C-statistic: 0.61) was poorer. Calibration was fairly accurate. Decision curves illustrated that using the model to guide vascular access referral would generally lead to less unused arteriovenous fistulas (AVFs) than following estimated glomerular filtration rate (eGFR) thresholds. Conclusion: This study shows moderate to good predictive performance of the model in an older cohort of nephrology-referred patients with advanced CKD. Using the model to guide referral for vascular access placement has potential in combating unnecessary vascular surgeries

Prognostic relevance of glomerular filtration rate estimation obtained through different equations in hospitalized elderly patients.

The estimated glomerular filtration rate (eGFR) is a predictor of important outcomes and its reduction has been associated with the risk of all-cause mortality in both general population and elderly patients. However while reduced renal function is common in older people, the best method for estimating GFR remains unclear, especially in an acute care setting. Most studies analyzing the accuracy of eGFR in the elderly were carried out in different heterogeneous settings. In this study, we compare the prognostic value of different formulas estimating GFR in predicting the risk of in-hospital morbidity and mortality within 3 months from discharge in elderly hospitalized patients. Data were extracted from "Registro Politerapia Società Italiana di Medicina Interna (REPOSI)". Patients with available creatinine values at hospital admission were selected and eGFR was calculated according to the different formulas: Cockcroft-Gault, Modification of Diet in Renal Disease equation, Chronic Kidney Disease Epidemiology Collaboration, Berlin Initiative Study and Full Age Spectrum. 4621 patients were included in the analysis. Among these, 4.2% and 14.2% died during hospitalization and within 3 months from discharge, respectively. eGFR > 60 ml/min/1.73 m2 at admission was associated with a very low risk of mortality during the hospital stay and within 90 days from discharge, while an eGFR < 60 ml/min/1.73 m2 was associated with unfavorable outcomes, although with a poor level of accuracy (AUC 0.60-0.66). No difference in predictive power between different equations was found. Physicians should be aware of the prognostic role of eGFR in a comprehensive assessment of elderly in-patients

Drug\u2013drug interactions involving CYP3A4 and p-glycoprotein in hospitalized elderly patients

Polypharmacy is very common in older patients and may be associated with drug-drug interactions. Hepatic cytochrome P450 (notably 3A4 subtype, CYP3A4) is a key enzyme which metabolizes most drugs; P-glycoprotein (P-gp) is a transporter which significantly influences distribution and bioavailability of many drugs. In this study, we assess the prevalence and patterns of potential interactions observed in an hospitalized older cohort (Registro Politerapia Societ\ue0 Italiana di Medicina Interna) exposed to at least two interacting drugs involving CYP3A4 and P-gp at admission, during hospitalization and at discharge. Individuals aged 65 and older (N-4039; mean age 79.2; male 48.1%), hospitalized between 2010 and 2016, were selected. The most common combinations of interacting drugs (relative frequency > 5%) and socio-demographic and clinical factors associated with the interactions were reported. The prevalence of interactions for CYP3A4 was 7.9% on admission, 10.3% during the stay and 10.7% at discharge; the corresponding figures for P-gp interactions were 2.2%, 3.8% and 3.8%. The most frequent interactions were amiodarone-statin for CYP3A4 and atorvastatin-verapamil-diltiazem for P-gp. The prevalence of some interactions, mainly those involving cardiovascular drugs, decreased at discharge, whereas that of others, e.g. those involving neuropsychiatric drugs, increased. The strongest factor associated with interactions was polypharmacy (OR 6.7, 95% CI 5.0\u20139.2). In conclusion, hospital admission is associated with an increased prevalence, but also a changing pattern of interactions concerning CYP3A4 and P-gp in elderly. Educational strategies and appropriate use of dedicated software seem desirable to limit drug interactions and the inherent risk of adverse events in older patients