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Hypertension; Therapeutics; Weight management Hipertensió; Terapèutica; Gestió del pes Hipertensión; Terapéutica; Control de peso Hypertension is a common chronic medical condition. Treatment is not satisfactory in a significant proportion of patients with primary hypertension, despite the concurrent use of three or more medications with different mechanisms of action. Such treatment-resistant hypertension is a clinical challenge associated with poor prognosis and needs further investigation. The efficacy of lifestyle changes has not been established yet in patients with resistant hypertension, and educational efforts appear clinically irrelevant in patients who must achieve behavioral changes without supervision. A 6-month multidisciplinary pilot intervention enrolled 50 patients with established resistant hypertension. The aims were: (1) to examine whether intensive and supervised lifestyle changes contribute to decreasing blood pressure in this condition, and (2) to identify which components affect compliance and feasibility. The program provided intensive changes in nutrition, physical exercise, and control of sleep disturbances supervised by nutritionists, physiotherapists, and psychologists. Nurses and pharmacists followed up on adherence to the antihypertensive medication. The primary outcome was 24 h blood pressure control. Data in patients with full compliance (n = 30) indicate that lifestyle modifications in resistant hypertension significantly reduced 24 h both systolic and diastolic blood pressure (p < 0.01), body mass index (p < 0.01), medication burden (p = 0.04), improving physical fitness, and cardiovascular risk markers such as heart rate (p = 0.01) and augmentation index (p = 0.02). The adherence to the intervention was moderate, with an attrition rate of 12%. A modified version reducing visits and explorations will likely improve compliance and can be used to assess the long-term maintenance of these benefits in managing resistant hypertension by diverse healthcare providers. The program against Resistant Hypertension was supported, in part, by the Hospital Vall d’Hebron, the Menarini Foundation, and the Instituto de Salud Carlos III grant (PI21/00510) co-funded by the Fondo Europeo de Desarrollo Regional. H.C. is a recipient of a fellowship of the Department of Health of Catalonia (Government of Catalonia) “Pla Estratègic de Recerca i Innovació en Salut” (PERIS-SLT017/3501/2020).

The impact of corticosteroid withdrawal on medium-term graft histological changes in kidney transplant (KT) recipients under standard immunosuppression is uncertain. As part of an open-label, multicenter, prospective, phase IV, 24-month clinical trial (ClinicalTrials.gov, NCT02284464) in low-immunological-risk KT recipients, 105 patients were randomized, after a protocol-biopsy at 3 months, to corticosteroid continuation (CSC, n = 52) or corticosteroid withdrawal (CSW, n = 53). Both groups received tacrolimus and MMF and had another protocol-biopsy at 24 months. The acute rejection rate, including subclinical inflammation (SCI), was comparable between groups (21.2 vs. 24.5%). No patients developed dnDSA. Inflammatory and chronicity scores increased from 3 to 24 months in patients with, at baseline, no inflammation (NI) or SCI, regardless of treatment. CSW patients with SCI at 3 months had a significantly increased chronicity score at 24 months. HbA1c levels were lower in CSW patients (6.4 ± 1.2 vs. 5.7 ± 0.6%, p = 0.013) at 24 months, as was systolic blood pressure (134.2 ± 14.9 vs. 125.7 ± 15.3 mmHg, p = 0.016). Allograft function was comparable between groups and no patients died or lost their graft. An increase in chronicity scores at 2-years post-transplantation was observed in low-immunological-risk KT recipients with initial NI or SCI, but CSW may accelerate chronicity changes, especially in patients with early SCI. This strategy did, however, improve the cardiovascular profiles of patients.

The impact of human leukocyte antigen (HLA)-mismatching on the early appearance of subclinical inflammation (SCI) in low-immunological-risk kidney transplant (KT) recipients is undetermined. We aimed to assess whether HLA-mismatching (A-B-C-DR-DQ) is a risk factor for early SCI. As part of a clinical trial (Clinicaltrials.gov, number NCT02284464), a total of 105 low-immunological-risk KT patients underwent a protocol biopsy on the third month post-KT. As a result, 54 presented SCI, showing a greater number of total HLA-mismatches (p = 0.008) and worse allograft function compared with the no inflammation group (48.5 ± 13.6 vs. 60 ± 23.4 mL/min, p = 0.003). Multiple logistic regression showed that the only risk factor associated with SCI was the total HLA-mismatch score (OR 1.32, 95%CI 1.06–1.64, p = 0.013) or class II HLA mismatching (OR 1.51, 95%CI 1.04–2.19, p = 0.032) after adjusting for confounder variables (recipient age, delayed graft function, transfusion prior KT, and tacrolimus levels). The ROC curve illustrated that the HLA mismatching of six antigens was the optimal value in terms of sensitivity and specificity for predicting the SCI. Finally, a significantly higher proportion of SCI was seen in patients with &gt, 6 vs. ≤6 HLA-mismatches (62.3 vs. 37.7%, p = 0.008). HLA compatibility is an independent risk factor associated with early SCI. Thus, transplant physicians should perhaps be more aware of HLA mismatching to reduce these early harmful lesions.

Rejection-associated gene expression has been characterized in renal allograft biopsies for cause. The aim is to evaluate rejection gene expression in subclinical rejection and in biopsies with borderline changes or interstitial fibrosis and tubular atrophy (IFTA). We included 96 biopsies. Most differentially expressed genes between normal surveillance biopsies (n = 17) and clinical rejection (n = 12) were obtained. A rejection-associated gene (RAG) score was defined as its geometric mean. The following groups were considered: (a) subclinical rejection (REJ-S, n = 6), (b) borderline changes in biopsies for cause (BL-C, n = 13), (c) borderline changes in surveillance biopsies (BL-S, n = 12), (d) IFTA in biopsies for cause (IFTA-C, n = 20), and (e) IFTA in surveillance biopsies (IFTA-S, n = 16). The outcome variable was death-censored graft loss or glomerular filtration rate decline &ge, 30 % at 2 years. A RAG score containing 109 genes derived from normal and clinical rejection (area under the curve, AUC = 1) was employed to classify the study groups. A positive RAG score was observed in 83% REJ-S, 38% BL-C, 17% BL-S, 25% IFTA-C, and 5% IFTA-S. A positive RAG score was an independent predictor of graft outcome from histological diagnosis (hazard ratio: 3.5 and 95% confidence interval: 1.1&ndash, 10.9, p = 0.031). A positive RAG score predicts graft outcome in surveillance and for cause biopsies with a less severe phenotype than clinical rejection.