Pre-therapeutic evaluation and practical management of cardiovascular and renal toxicities in patients with metastatic radioiodine-refractory thyroid cancer treated with lenvatinib.

INTRODUCTION: Multi-receptor tyrosine kinase inhibitors with anti-angiogenic activity, particularly lenvatinib, have become the standard treatment for radioiodine-refractory metastatic differentiated thyroid cancer but are associated with a high incidence of toxicity. Although patients treated with lenvatinib have been shown to have a significant improvement in progression-free survival, lenvatinib-associated toxicity may result in dose reductions, dose interruptions or even complete lenvatinib withdrawal, compromising anti-tumor efficacy. AREAS COVERED: The article covers the main cardiological and renal toxicities of lenvatinib, including hypertension, prolonged QT interval, heart failure, arterial and venous thromboembolic events, proteinuria and renal failure, and proposes appropriate management of these events during lenvatinib therapy. We performed a literature review of cardiovascular and renal toxicities of Lenvatinib in radioiodine-refractory differentiated thyroid cancer. We discussed prophylactic and therapeutic management for each toxicity based on literature and clinical expertise. EXPERT OPINION: Specific pre-therapeutic evaluation and close monitoring of patients treated with lenvatinib is necessary to prevent and detect cardiovascular and/or renal toxicities early, and to propose appropriate management. Oncologists who treat patients with lenvatinib should know how to monitor and treat these adverse events, and when to ask for the advice of a specialist (cardiologist or nephrologist).

Contemporary issues and new challenges in chronic kidney disease amongst people living with HIV.

Chronic kidney disease (CKD) is a comorbidity of major clinical significance amongst people living with HIV (PLWHIV) and is associated with significant morbidity and mortality. The prevalence of CKD is rising, despite the widespread use of antiretroviral therapy (ART) and is increasingly related to prevalent non-infectious comorbidities (NICMs) and antiretroviral toxicity. There are great disparities evident, with the highest prevalence of CKD among PLWHIV seen in the African continent. The aetiology of kidney disease amongst PLWHIV includes HIV-related diseases, such as classic HIV-associated nephropathy or immune complex disease, CKD related to NICMs and CKD from antiretroviral toxicity. CKD, once established, is often relentlessly progressive and can lead to end-stage renal disease (ESRD). Identifying patients with risk factors for CKD, and appropriate screening for the early detection of CKD are vital to improve patient outcomes. Adherence to screening guidelines is variable, and often poor. The progression of CKD may be slowed with certain clinical interventions; however, data derived from studies involving PLWHIV with CKD are sparse and this represent an important area for future research. The control of blood pressure using angiotensin converting enzyme inhibitors and angiotensin receptor blockers, in particular, in the setting of proteinuria, likely slows the progression of CKD among PLWHIV. The cohort of PLWHIV is facing new challenges in regards to polypharmacy, drug-drug interactions and adverse drug reactions. The potential nephrotoxicity of ART is important, particularly as cumulative ART exposure increases as the cohort of PLWHIV ages. The number of PLWHIV with ESRD is increasing. PLWHIV should not be denied access to renal replacement therapy, either dialysis or kidney transplantation, based on their HIV status. Kidney transplantation amongst PLWHIV is successful and associated with an improved prognosis compared to remaining on dialysis. As the cohort of PLWHIV ages, comorbidity increases and CKD becomes more prevalent; models of care need to evolve to meet the new and changing chronic healthcare needs of these patients.

Prognostic value of viral eradication for major adverse cardiovascular events in hepatitis C cirrhotic patients.

BACKGROUND: The objective was to examine the role of a sustained virological response (SVR) on major adverse cardiovascular events (MACEs) in patients with compensated hepatitis C virus (HCV) cirrhosis. METHODS: Patients with the following criteria were enrolled in 35 French centers: (1) biopsy-proven HCV cirrhosis; (2) Child-Pugh A; (3) positive viremia; and (4) no prior liver complication, and then prospectively followed. All patients received HCV treatment after inclusion. MACEs included stroke, myocardial infarction, ischemic heart disease, heart failure, peripheral arterial disease, cardiac arrest, and cardiovascular death. SVR, defined as negative viremia 12 weeks posttreatment, was considered as a time-dependent covariate, and its effect on MACE occurrence was assessed. The median follow up was 57.5 months, ending in December 2015. RESULTS: Sixty-two of 878 (7.1%) patients presented a total of 79 MACEs. The main predictive baseline factors of MACEs were Asian ethnic origin, history of MACEs, arterial hypertension, diabetes mellitus, current smoking, low serum albumin level, high total bilirubin level, and low platelet count. In multivariate analysis, SVR was associated with a decreased risk of MACEs (hazard ratio=0.35, 95% CI 0.09-0.97, P=.044), whereas Asian ethnic origin, arterial hypertension, smoking, and low serum albumin level remained predictive of MACE occurrence. The 5-year survival rate was 60.1% versus 87.5% in patients who did versus those who did not present a MACE (P<.001). CONCLUSIONS: In patients with compensated HCV-related cirrhosis, Asian ethnic origin, arterial hypertension, smoking, and low serum albumin are independent predictive factors of cardiovascular events, whereas an SVR is associated with a decreased rate of cardiovascular events.

Is Tenofovir Alafenamide Safer than Tenofovir Disoproxil Fumarate for the Kidneys?

Tenofovir disoproxil fumarate is currently the cornerstone of HIV treatment. Although it shows an overall good safety profile, numerous cases of nephrotoxicity have been reported. Tenofovir alafenamide is a novel tenofovir prodrug that has been developed to improve renal safety. Pharmacokinetic studies suggest a better renal tolerance of tenofovir alafenamide than tenofovir disoproxil fumarate, probably because tenofovir plasma concentrations are lower after tenofovir alafenamide administration. Consistently in clinical trials, renal tolerance seems to be improved in patients treated with tenofovir alafenamide. However, some questions remain. First, whether tenofovir can accumulate and lead to nephrotoxicity under specific circumstances after tenofovir alafenamide administration is unknown. Second, only "real-world practice" will inform us on the long-term renal safety of tenofovir alafenamide. Last, tenofovir alafenamide renal safety in patients with chronic kidney disease has not been studied in any randomized clinical trial. In conclusion, tenofovir alafenamide appears as a very promising drug and long-term safety will be an important determinant of its expanded use.

Enhancing Clinicians' Well-Being and Patient-Centered Care Through Mindfulness.

INTRODUCTION: Mindful clinicians are resilient and more likely to provide patient-centered care. We aimed to enhance clinicians' well-being by offering a Mindfulness-Based Stress Reduction (MBSR) course that teaches mindfulness and stress management and then determine whether this impacted their subsequent medical encounters. METHODS: In a longitudinal cohort study with 27 clinicians, MBSR was taught by a certified instructor. Pre-MBSR and post-MBSR online questionnaires assessed burnout, depression, stress, meaningfulness, and mindfulness. Patients independently rated their clinicians using the Rochester Communication Rating Scale (RCRS) after a clinical encounter before and after their clinician took the MBSR course. Nine medical doctors audiorecorded the consultations before and after MBSR; the tapes were coded and analyzed by an independent team using the Roter interaction analyses system. RESULTS: Significant reductions in stress and burnout were found, and increases in mindfulness and meaningfulness. The decrease in stress was correlated with less judgmental attitudes and less reactivity-facets of mindfulness. The decrease in emotional exhaustion was correlated with more acting with awareness and less judgmental attitudes-facets of mindfulness. Patients' perceptions of the clinical encounter suggested that patient-centered care improved after MBSR. Decreased depersonalization was significantly associated with the RCRS subscale, "understanding of the patient's experience of illness." At both time points, doctors dominated the exchange and were patient-centered. DISCUSSION: Mindfulness has a direct and positive impact on clinicians' well-being. When clinicians' experienced less depersonalization, their patients reported being better understood.

Protease Inhibitors and Renal Function in Patients with HIV Infection: a Systematic Review.

INTRODUCTION: Despite antiretroviral (ARV) therapy reducing renal disease in human immunodeficiency virus overall, there is concern that certain ARVs, particularly tenofovir disoproxil fumarate (TDF) with or without a boosted protease inhibitor (PI), may reduce renal function over time. It is not known whether effects seen with PI-based regimens are independent, result from interactions with TDF coadministration, or are artefactual owing to inhibition of renal tubular creatinine transport by ritonavir or cobicistat pharmacoenhancement. The aim of this review was to conduct a systematic review of studies, weighted toward high-quality evidence, examining changes in renal function over time with PI-based regimens. METHODS: PubMed, Embase, and Medline databases and conference abstracts were searched using pre-defined terms for English language articles, published up to and including August 12, 2013, describing changes in renal function over time with PI-based regimens. All available randomized controlled trials (RCTs) were selected; however, to reduce bias, only observational studies recruiting from more than one center and analyzing data from more than 1,000 patients were included. Evidence was qualitatively evaluated according to levels established by the Oxford Centre for Evidence-Based Medicine (OCEBM). RESULTS: A total of 2,322 articles were retrieved by the initial search. Of these, 37 were selected for full review, comprising 24 RCTs (OCEBM Level 1 evidence: 4 reports of fully double-blinded or blinded with respect to the PI component). The remaining 20 RCTs and 13 observational studies qualified as OCEBM Level 2 evidence. Level 1 evidence showed initial but non-progressive increases in serum creatinine and corresponding decreases in estimated glomerular filtration rate (eGFR), suggesting an effect on renal tubular transport of creatinine. Level 2 evidence suggested that atazanavir and lopinavir especially in combination with TDF were associated with non-progressive reductions in eGFR over time, with a decreased risk for the development of chronic kidney disease (CKD) on cessation and without the development of advanced CKD or end-stage renal disease (ESRD); whether these reductions were independent or associated with interactions with coadministered TDF could not be established with certainty. Data on darunavir were insufficient to draw any conclusions. The principal limitation of the reviewed studies was the lack of standardization of creatinine measurements in virtually all studies and the lack of corroborative data on changes in proteinuria or other indices of renal function. DISCUSSION: In this review, there was little evidence for progressive changes in eGFR, or the development of advanced CKD, or ESRD with lopinavir or atazanavir. Further long-term studies, employing a wide range of validated renal function assessments, are required to fully evaluate potential association of PIs with CKD.

[Urinary tract infections in adults]. / Infections urinaires de l'adulte.

Urinary tract infections in adults are frequent and can induce several septic situations. Their economic cost (drugs, microbiologic samples, consultations and/or hospitalizations and stop working) and ecologic cost (second reasons of antibiotic prescription in winter and first in the rest of the year) are important. A better respect of recommendations can improve the outcome of this different infections and decrease their cost.

[Recurrent urinary tract infection]. / Infections urinaires récidivantes.

Recurrent urinary tract infection involves mainly women and exhibits an ecological as well as economical risk. 4% of all urinary tract infection are recurrent and usually secondary to general or local abnormalities. A multidisciplinary medical and surgical team (urology, nephrology, bacteriology, infectious disease) best performs diagnosis and treatment as well as rules out reversible etiology. Treatment relies on behavioral changes before offering cranberry products and/or antibioprophylaxis if necessary.

[Urinary tract infections in diabetic patients]. / Particularités des infections urinaires chez les sujets diabétiques.

Urinary tract infections occur more frequently in diabetic patients than in the general population, with a relative risk ranging from 1.5 to 4, depending on the type of infection. The reasons underlying this higher susceptibility have not been established with certainty; urine glucose excression (which could facilitate bacterial urinary proliferation), immunodeficiency, a modified urothelium (resulting in a higher bacterial adhesion), and chronic neurologic bladder dysfunction have been advocated. Clinical presentation, bacterial epidemiology, and treatment of urinary tract infections in diabetic patients are similar to that of the general population. Accordingly, diabetes mellitus has recently been withdrawn from the list of criteria which define an urinary tract infection as complicated. Asymptomatic bacteriuria is particularly frequent in diabetic patients and should be checked routinely as it constitutes an important risk for subsequent symptomatic infection.

KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron.

Familial hyperkalemic hypertension (FHHt) is a Mendelian form of arterial hypertension that is partially explained by mutations in WNK1 and WNK4 that lead to increased activity of the Na(+)-Cl(-) cotransporter (NCC) in the distal nephron. Using combined linkage analysis and whole-exome sequencing in two families, we identified KLHL3 as a third gene responsible for FHHt. Direct sequencing of 43 other affected individuals revealed 11 additional missense mutations that were associated with heterogeneous phenotypes and diverse modes of inheritance. Polymorphisms at KLHL3 were not associated with blood pressure. The KLHL3 protein belongs to the BTB-BACK-kelch family of actin-binding proteins that recruit substrates for Cullin3-based ubiquitin ligase complexes. KLHL3 is coexpressed with NCC and downregulates NCC expression at the cell surface. Our study establishes a role for KLHL3 as a new member of the complex signaling pathway regulating ion homeostasis in the distal nephron and indirectly blood pressure.

Risk factors of chronic kidney disease in HIV-infected patients.

BACKGROUND AND OBJECTIVES: The main aim of this study was determining the risk factors of chronic kidney disease (CKD) in HIV-1-infected patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients were followed from seven large HIV reference centers in France that maintain prospective databases on HIV-1-infected patients. The main outcome was the time to CKD defined as two consecutive measures of estimated GFR ≤60 ml/min per 1.73 m² over ≥3 months. A Cox's model with delayed entry was used to search predictive factors of time to CKD. RESULTS: From 1993 to 2006, 349 out of 7378 patients were found to have CKD. Of these, 166 had hypertension, 33 had diabetes, and 26 were antiretroviral therapy-naïve. Occurrence of acute kidney injury (hazard ratio [HR] = 2.40) and hypertension (HR = 2.39) were strongly associated with an increased risk of CKD. Patients with a durable level of CD4 count >200 cells/mm³ had a lower risk of CKD (HR = 0.63). Recent exposure to indinavir (HR = 2.03), totenofovir (HR = 1.55), and abacavir (HR = 1.37) were associated with an increased risk of CKD. Past exposure to tenofovir was also associated with an increased risk of CKD (HR = 2.23), and a trend toward significance was observed for past exposure to indinavir (HR = 1.28). CONCLUSIONS: CKD was not rare in HIV-infected patients and occurs preferentially in HIV-infected patients exposed to certain ARVs, specifically abacavir, indinavir and tenofovir. This requires closer monitoring of renal function in patients exposed to one of these drugs.

[The first haemodialysis session as experienced by patients and caregivers]. / La premiere séance d'hémodialyse, vécu des patients et des soignants.

An investigation into the way in which patients experience their first haemodialysis session, carried out at Pitié-Salpêtrière hospital in Paris, in 2009, provided an assessment of their degree of preparation and compliance with treatment. The caregivers also talked about the experience from their perspective. Information and support upstream would help patients to accept the treatment and reduce the difficulties encountered by caregivers.