Abstract

Abstract Background and Aims Hypertension is the second leading cause of chronic kidney disease (CKD) following diabetes and occurs in most patients with CKD. Finding an optimal treatment regime for hypertension remains challenging due to the complex bidirectional cause-and-effect relationship between hypertension and CKD, and hypertensive CKD patients may require treatment with multiple antihypertensive drugs. Database studies and practice guidelines have continued to demonstrate international variability in antihypertensive treatment practices. We analysed data from the Salford Kidney Study (SKS) database in relation to antihypertensive prescribing patterns amongst study patients. Method The SKS is an ongoing prospective study recruiting patients with CKD since the year 2002. Data including patient demographics, comorbidities, physical parameters, concurrent medications, and biochemical results are collected at baseline (study enrolment). All patients are followed up annually until they reach their endpoints [reaching end-stage kidney disease (ESKD), death, or discharge from follow-up] individually, with updates in their medical records including a list of medications. We have used Cox regression analysis and Kaplan Meier charts to investigate the associations between Renin-Angiotensin-Aldosterone System inhibitor (RAASi) use and the number of antihypertensive agents (binary groups of ≤3 or >3), and clinical outcomes (ESKD and all-cause mortality). Results A total of 3230 patients recruited between October 2002 and December 2019 were included in this analysis. At baseline, the median age of the cohort was 67 years with a predominance of males (62%) and those of white ethnicity (96%). 90% had a history of hypertension and 32% were diabetic. The median blood pressure was 138/75 mmHg. Previous myocardial infarction was recorded in 15%, congestive cardiac failure in 17% and cerebrovascular disease in 7.7% of the patients. The median estimated glomerular filtration rate (eGFR) was 30 ml/min/1.73 m2 and the median urine protein creatinine ratio (uPCR) was 33 mg/mmol. RAASi agents (ACEi & ARB) (56%) were the most common antihypertensive medications to be prescribed, followed by diuretics (50%), calcium channel blockers (45%), and beta blockers (34%). The proportion of patients prescribed RAASi was associated with greater proteinuria (43 vs 33%, p<0.001). CKD patients with preexisting cardiovascular comorbidities were more likely to be prescribed beta blockers (44 vs 27%, p<0.001), diuretics (58 vs 39%, p<0.001) and mineralocorticoid antagonists (6.4 vs 1.85%, p<0.001). An increasing number of CKD patients were being prescribed ARBs over 24-month follow-up (34 vs 28%, p = 0.02). In a multivariable Cox-regression analysis, RAASi intake was not associated with reaching ESKD (HR 0.91; p = 0.49) but was associated with a significant survival benefit (HR 0.84; p = 0.001) (Figure 1). Use of a higher number of antihypertensive agents (i.e. >3) was associated with both greater mortality (HR 1.28; p = 0.02) and worse dialysis-free survival (HR 1.46; p = 0.007) (Figure 2). Conclusion Antihypertensive prescribing patterns in the SKS were consistent with current guidelines in the U.K. (e.g. NICE guidance 2022), with RAASi being predominantly prescribed as the first-line antihypertensive agent. An overall survival benefit was noted with RAASi use, although there was no signal for reducing progression towards ESRD. Outcomes were poor in patients with resistant hypertension needing multiple antihypertensive agents. Considering existing variations between the U.K. and other international guidelines regarding antihypertensive treatment in CKD, continued research is indicated to bridge the gaps between these recommendations and optimise patient outcomes.

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