Mo109characterization of resistant hypertension in ckd patients

Abstract Background and Aims Hypertension resistant to drug treatment is common among CKD patients. However, the phenotype of resistant hypertension in the CKD population is still loosely defined and scarcely characterized. Method In a cohort of 759 stage 2-5 CKD patients, we identified a subgroup of 647 patients with >4 longitudinal visits (range 4-7 visits) over a median follow-up time of 36 months. These patients did not differ from the original study population as for age (62±11 years vs 62±11), gender (59% vs 60%), diabetes (34% vs 35%) and eGFR (36±13 versus 36±13 ml/min/1.73m2). We adopted a conservative definition of resistant hypertension i.e. as a BP above the 2020 KDIGO guideline threshold (130/80 mmHg) in spite of concurrent use of 3 antihypertensive agents (at maximum tolerated doses) of different classes including a diuretic or BP controlled with four or more medications in at least 75% of visits. Adherence to drug treatment in this cohort was systematically checked by attending physicians across all visits. Data are given as mean ± SD or as median and interquartile range (IQR). Results Across the 36 months follow-up, 131 out of 647 patients (20%) had resistant hypertension in >75% of visits. Resistant hypertensive patients were older (64±8 years vs 61±11), more frequently diabetics (53% vs 29%) and with background cardiovascular comorbidities (38% vs 29%) , higher body mass index (BMI) (30±5 kg/m2 vs 28±4 kg/m2), serum phosphate (3.9±0.7 mg/dL vs 3.7±0.8 mg/dL), CRP (median: 3.2 mg/L, IQR: 1.6-6.5 vs 3.2 mg/L, IQR: 1.6-6.5 vs 2.1 mg/L, 0.9-5.1 mg/L), 24h urinary protein (median: 1.0 g/24h, IQR: 0.4-2.3 vs median: 0.5 g/24h, IQR: 0.2-1.0 g/24h) and lower serum albumin (4.1±0.5 g/dL vs 4.2±0.5 g/dL) and eGFR (34±13 ml/min/1.73m2 vs 37±14 ml/min/1.73m2 as compared to remaining patients (all P<0.03). In a multiple logistic regression model, 24h proteinuria [odds ratio (OR): 1.31, 95% CI: 1.13-1.53, P<0.001] and BMI [OR: 1.08, 95% CI: 1.03-1.13, P=0.001] resulted to be the first factors in rank explaining resistant hypertension followed by diabetes (OR: 1.83, 95% CI: 1.18-2.85, P=0.008). Age, background CV comorbidities, serum phosphate, serum CRP, albumin, and eGFR failed to be associated with resistant hypertension after multiple data adjustment (P ranging from: 0.14 to 0.61). Of note, the combination of 24h proteinuria, BMI and diabetes had a relevant discriminatory power for resistant hypertension because the area under the ROC curve area of these risk factors was 0.71 (95% CI: 0.66-0.76) (P<0.001). Conclusion A rigorously defined phenotype of resistant hypertension has a 20% prevalence in the CKD population. Proteinuria, high BMI and obesity are the main risk factors associated with this phenotype. Optimization of diabetes control, weight loss and pharmacotherapy targeting proteinuria may mitigate resistant hypertension in the CKD population.