Comanagement With Nephrologist Care Is Associated With Fewer Cardiovascular Events Among Liver Transplant Recipients With Chronic Kidney Disease.

Chronic kidney disease (CKD) is associated with cardiovascular (CV) events, a leading complication in liver transplant recipients (LTRs). Timely subspecialty care is associated with improved clinical outcomes in patients with CKD. This study sought to assess associations between nephrology comanagement and CV events among LTRs at risk for or with CKD. METHODS: LTRs with CKD plus those at risk were identified in an inception cohort at a single tertiary care network between 2010 and 2016, using electronic health record data and manual chart review. CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m2 or International Classification of Diseases 9th or 10th revision code for CKD and at-risk CKD as estimated glomerular filtration rate 60-89 mL/min/1.73 m2. Cox proportional hazard models assessed the association between nephrology comanagement and CV events among LTRs with or at risk for CKD. RESULTS: Among 602 LTRs followed for up to 6 y posttransplant, prevalence of CKD plus those at risk increased yearly (71% in year 1, 86% in year 6) (P < 0.0001). Rates of nephrology comanagement decreased yearly posttransplant (35% in year 1, 28% in year 6). In multivariable models, nephrology comanagement was associated with lower CV events (adjusted hazard ratio, 0.57; 95% confidence interval, 0.33-0.99). CONCLUSIONS: Among LTRs with CKD, nephrology comanagement may be associated with lower CV events. A prospective study is needed to identify the reasons for improved outcomes and barriers to nephrology referral.

When evidence is lacking: a mixed-methods approach for the development of practice guidance in liver transplantation.

BACKGROUND: Most interventions for conditions with a small cohort size, such as transplantation, are unlikely to be part of a clinical trial. When condition-specific evidence is lacking, expert consensus can offer more precise guidance to improve care. Management of cardiovascular risk in liver-transplant recipients is one example for which clinicians have, to date, adapted evidence-based guidelines from studies in the general population. However, even when consensus is achieved, implementation of practice guidance is often inadequate and protracted. We report on a novel mixed-methods approach, the Northwestern Method©, for the development of clinical-practice guidance when condition-specific evidence is lacking. We illustrate the method through the development of practice guidance for managing cardiovascular risk in liver-transplant recipients. METHODS: The Northwestern Method© consists of (i) adaptation of relevant, existing, evidence-based clinical-practice guidelines for the target population; (ii) consensus by experts of the proposed practice guidance; (iii) identification of barriers to guidance adherence in current practice; and (iv) recommendation for implementation and dissemination of the practice guidance. The method is based on an iterative, user-centered approach in which the needs, wants, and limitations of all end users, including patients, are attended to at each stage of the design and development process. CONCLUSIONS: The Northwestern Method© for clinical-practice-guidance development uses a mixed-methods approach to bring together broad representation from multiple disciplines and practice settings to develop consensus considering the unique needs and preferences of patients, caregivers, and practitioners who are directly impacted by clinical-practice-guidance recommendations. We hypothesize that a priori involvement of end users in the guidance-development process will lead to sustainable implementation of guidance statements into clinical practice.

Nonalcoholic Fatty Liver Disease and Diabetes Mellitus Are Associated With Post-Transjugular Intrahepatic Portosystemic Shunt Renal Dysfunction: An Advancing Liver Therapeutic Approaches Group Study.

Transjugular intrahepatic portosystemic shunt (TIPS) is an effective intervention for portal hypertensive complications, but its effect on renal function is not well characterized. Here we describe renal function and characteristics associated with renal dysfunction at 30 days post-TIPS. Adults with cirrhosis who underwent TIPS at 9 hospitals in the United States from 2010 to 2015 were included. We defined "post-TIPS renal dysfunction" as a change in estimated glomerular filtration rate (ΔeGFR) ≤-15 and eGFR ≤ 60 mL/min/1.73 m2 or new renal replacement therapy (RRT) at day 30. We identified the characteristics associated with post-TIPS renal dysfunction by logistic regression and evaluated survival using adjusted competing risk regressions. Of the 673 patients, the median age was 57 years, 38% of the patients were female, 26% had diabetes mellitus, and the median MELD-Na was 17. After 30 days post-TIPS, 66 (10%) had renal dysfunction, of which 23 (35%) required new RRT. Patients with post-TIPS renal dysfunction, compared with those with stable renal function, were more likely to have nonalcoholic fatty liver disease (NAFLD; 33% versus 17%; P = 0.01) and comorbid diabetes mellitus (42% versus 24%; P = 0.001). Multivariate logistic regressions showed NAFLD (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.00-4.17; P = 0.05), serum sodium (Na; OR, 1.06 per mEq/L; 95% CI, 1.01-1.12; P = 0.03), and diabetes mellitus (OR, 2.04; 95% CI, 1.16-3.61; P = 0.01) were associated with post-TIPS renal dysfunction. Competing risk regressions showed that those with post-TIPS renal dysfunction were at a higher subhazard of death (subhazard ratio, 1.74; 95% CI, 1.18-2.56; P = 0.01). In this large, multicenter cohort, we found NAFLD, diabetes mellitus, and baseline Na associated with post-TIPS renal dysfunction. This study suggests that patients with NAFLD and diabetes mellitus undergoing TIPS evaluation may require additional attention to cardiac and renal comorbidities before proceeding with the procedure.

Blood pressure control according to clinical practice guidelines is associated with decreased mortality and cardiovascular events among liver transplant recipients.

Data for liver transplant recipients (LTRs) regarding the benefit of care concordant with clinical practice guidelines for management of blood pressure (BP) are sparse. This paper reports on clinician adherence with BP clinical practice guideline recommendations and whether BP control is associated with mortality and cardiovascular events (CVEs) among LTRs. We conducted a longitudinal cohort study of adult LTRs who survived to hospital discharge at a large tertiary care network between 2010 and 2016. The primary exposure was a BP of <140/<90 mm Hg within year 1 of LT. Among 602 LTRs (mean age 56.7 years, 64% men), 92% had hypertension and 38% had new onset hypertension. Less than 30% of LTRs achieved a BP of <140/<90 mm Hg over a mean of 43.2 months. In multivariable models, adjusted for key confounders, BP control post-LT compared with lack of control was associated with a significantly lower hazard of mortality (hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.39, 0.87) and of CVEs (HR 0.65, 95% CI 0.43, 0.97). The association between BP control of <140/<90 mm Hg with improved survival and decreased CVEs in LTRs suggests that efforts to improve clinician adherence to BP clinical practice recommendations should be intensified.

Receptor for Activated C-Kinase 1 (PfRACK1) is required for Plasmodium falciparum intra-erythrocytic proliferation.

Emerging resistance to current anti-malarials necessitates a more detailed understanding of the biological processes of Plasmodium falciparum proliferation, thus allowing identification of new drug targets. The well-conserved protein Receptor for Activated C-Kinase 1 (RACK1) was originally identified in mammalian cells as an anchoring protein for protein kinase C (PKC) and has since been shown to be important for cell migration, cytokinesis, transcription, epigenetics, and protein translation. The P. falciparum ortholog, PfRACK1, is expressed in blood stages of the parasite and is diffusely localized in the parasite cytoplasm. Using a destabilizing domain to allow inducible knockdown of the endogenous protein level, we evaluated the requirement for PfRACK1 during blood-stage replication. Following destabilization, the parasites demonstrate a nearly complete growth arrest at the trophozoite stage. The essential nature of PfRACK1 suggests that the protein itself or the pathways regulated by the protein are potential targets for novel anti-malarial therapeutics.