Evidence in chronic kidney disease-mineral and bone disorder guidelines: is it time to treat or time to wait?

Chronic kidney disease-mineral and bone disorder (CKD-MBD) is one of the many important complications associated with CKD and may at least partially explain the extremely high morbidity and mortality among CKD patients. The 2009 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline document was based on the best information available at that time and was designed not only to provide information but also to assist in decision-making. In addition to the international KDIGO Work Group, which included worldwide experts, an independent Evidence Review Team was assembled to ensure rigorous review and grading of the existing evidence. Based on the evidence from new clinical trials, an updated Clinical Practice Guideline was published in 2017. In this review, we focus on the conceptual and practical evolution of clinical guidelines (from eMinence-based medicine to eVidence-based medicine and 'living' guidelines), highlight some of the current important CKD-MBD-related changes, and underline the poor or extremely poor level of evidence present in those guidelines (as well as in other areas of nephrology). Finally, we emphasize the importance of individualization of treatments and shared decision-making (based on important ethical considerations and the 'best available evidence'), which may prove useful in the face of the uncertainty over the decision whether 'to treat' or 'to wait'.

Compassionate communities: design and preliminary results of the experience of Vic (Barcelona, Spain) caring city.

BACKGROUND: A program of Compassionate City or Community (CC) has been designed and developed in the City of Vic (43,964 habitants, Barcelona, Spain), based on The Compassionate City Charter and other public health literature and experiments, with the joint leadership of the City Council and the Chair of Palliative Care at the University of Vic, and as an expansion of a comprehensive and integrated system of palliative care. METHODS: The program started with an assessment of needs of the city as identified by 48 social organizations with a foundational workshop and a semi-structured survey. After this assessment, the mission, vision, values and aims were agreed. The main aims consisted in promoting changes in social and cultural attitudes toward the end of life (EoL) and providing integrated care for people with advanced chronic conditions and social needs such as loneliness, poverty, low access to services at home, or conflict. The selected slogan was "Living with meaning, dignity, and support the end of life". RESULTS: The program for the first year has included 19 activities (cultural, training, informative, and mixed) and followed by 1,260 attendants, and the training activities were followed by 147 people. Local and regional sponsors are funding the initiative. After a year, a quantitative and qualitative evaluation was performed, showing high participation and satisfaction of the attendants and organizations. In the second year, the care for particular vulnerable people defined as targets (EoL and social factors described before) will start with volunteers with more organizations to join the project. CONCLUSIONS: The key identified factors for the initial success are: the strong joint leadership between social department of the Council and the University; clear aims and targets; high participation rates; the limited size of the geographical context; which allowed high participation and recognition; and the commitment to evaluate results.

Cardiovascular disease risk factors in HIV patients--association with antiretroviral therapy. Results from the DAD study.

OBJECTIVE: To determine the prevalence of risk factors for cardiovascular disease (CVD) among HIV-infected persons, and to investigate any association between such risk factors, stage of HIV disease, and use of antiretroviral therapies. DESIGN: Baseline data from 17,852 subjects enrolled in DAD, a prospective multinational cohort study initiated in 1999. METHODS: Cross-sectional analyses of CVD risk factors at baseline. The data collected includes data on demographic variables, cigarette smoking, diabetes mellitus, hypertension, dyslipidaemia, body mass index, stage of HIV infection, antiretroviral therapy. RESULTS: Almost 25% of the study population were at an age where there is an appreciable risk of CVD, with those receiving a protease inhibitor (PI) and/or non-nucleoside reverse transcriptase inhibitor (NNRTI) tending to be older. 1.4% had a previous history of CVD and 51.5% were cigarette smokers. Increased prevalence of elevated total cholesterol (> or = 6.2 mmol/l) was observed among subjects receiving an NNRTI but no PI [odds ratio (OR), 1.79; 95% confidence interval (CI), 1.45-2.22], PI but no NNRTI (OR, 2.35; 95% CI, 1.92-2.87), or NNRTI + PI (OR, 5.48; 95% CI, 4.34-6.91) compared to the prevalence among antiretroviral therapy (ART)-naive subjects. Subjects who have discontinued ART as well as subjects receiving nucleoside reverse transcriptase inhibitors had similar cholesterol levels to treatment-naive subjects. Higher CD4 cell count, lower plasma HIV RNA levels, clinical signs of lipodystrophy, longer exposure times to NNRTI and PI, and older age were all also associated with elevated total cholesterol level. CONCLUSION: HIV-infected persons exhibit multiple known risk factors for CVD. Of specific concern is the fact that use of the NNRTI and PI drug classes (alone and especially in combination), particularly among older subjects with normalized CD4 cell counts and suppressed HIV replication, was associated with a lipid profile known to increase the risk of coronary heart disease.

Assessing the effectiveness of rapamycin on angiomyolipoma in tuberous sclerosis: a two years trial.

BACKGROUND: Tuberous sclerosis (TS) is a rare autosomal dominant systemic disease with an estimated prevalence of 1/6000. Renal angiomyolipoma (AML) is a benign tumour with high morbidity frequently present in TS. The aim of the study was to test the effect of rapamycin in reducing the volume of AML in TS. METHODS: Twenty four-month prospective open-label, single arm, unicentre Phases II andIII study. The primary endpoint was to evaluate the effect of treatment on the reduction of at least 50% AML volume from baseline at 24 months. The secondary endpoints were: average tumour reduction, surgical complications, skin lesions and drug safety.The study population comprised 17 patients, aged >10 years who were diagnosed with TS and had ≥1 renal AML >2 cm of diameter and had a serum creatinine < 2mg/dl and urine protein/creatinine ratio < 22.6 mg/mmol. The trial was conducted at Fundació Puigvert. Rapamycin was given to achieve stable plasma levels between 4 and 8 ng/ml. AML volume was estimated using orthogonal measurements by MRI at baseline, 6, 12 and 24 months. RESULTS: Ten out of 17 patients were success responders for the main outcome -58.8%, 95%CI: 32.9% to 81.6%-. After 6 months of therapy, the mean volume decrease was 55.18% (5.01 standard error (SE); p<0.001) and 66.38% (4.41 SE; p<0.001) at year 1. There was no significant decrease between year 1 and 2. According to RECIST criteria, all patients achieved a partial response at year 1 and all but two had already achieved this partial response after 6 months.The main analysis was performed according to the intention-to-treat principle analysis. Tumour volume was analyzed over time by means of mixed models for repeated measurement analysis. We used the baseline tumour volume as a covariate for the absolute change and percentage change from baseline data. The analysis was performed using SAS version 9.2 software, and the level of significance was established at 0.05 (two-sided). CONCLUSIONS: This study show that mTOR inhibitors are a relatively safe, efficacious and less aggressive alternative than currently available options in the management of AML in TS. TRIAL REGISTRATION: EudraCT number: 2007-005978-30, ClinicalTrials.gov number: NCT0121712.

Effects of rapamycin on angiomyolipomas in patients with tuberous sclerosis.

BACKGROUND: Tuberous sclerosis (TS) is a systemic disease, with an autosomal dominant pattern of inheritance caused by mutations in two genes (TSC1 and TSC2) that cause tumours (angiomyolipomas [AML], angiofibromas, astrocytomas). Constant and inadequate proliferation occurring in TS may be blocked by mTOR inhibitors (mammalian target of rapamycin), such as rapamycin. MATERIAL AND METHODS: At present, our study includes 17 patients with TS. All had at least one AML greater than 2cm in diameter diagnosed by MRI. They received rapamycin during 12 months. Plasma levels remained stable between 4-8ng/dl. The AML size was monitored every six months by abdominal MRI. RESULTS: At 12 months of inclusion, MRI indicated a decrease in the size of AML in all patients showing at least a 50% reduction in 82.4% (14/17, 95% CI [56.57%, 96.20%]). The mean percent reduction was 66.3% (95% CI [56.9%, 75.6%], P<.0001). The major side effects observed were: oral aphthous ulcers (5/17); hypertriglyceridemia (3/17); microcytosis and hypochromia (3/17); diarrhea (2/17); acne (1/17); acute pyelonephritis (1/17); and proteinuria (1/17). CONCLUSIONS: These preliminary clinical data suggest that rapamycin can play a beneficial role in the treatment of TS. Our experience in 17 patients treated for 12 months demonstrates safety and efficacy in reducing AML volume.