Cardiovascular benefit of blood-pressure lowering in chronic kidney disease.

# Cardiovascular benefit of blood-pressure lowering in chronic kidney disease *The Lancet 2026* Comment Cardiovascular benefit of blood-pressure lowering in chronic kidney disease Chronic kidney disease (CKD) has long remained at the stage 3b or more advanced disease (estimated margins of the evidence base for the cardiovascular glomerular filtration rate <45 mL/min per 1·73 m²). benefits of blood-pressure lowering. The absolute risk The mean age in the CKD subgroup was 69·8 years, of cardiovascular events in people with CKD is among 30 541 (51·6%) were women, and 29 309 (64·0%) the highest across major clinical populations.1 However, of 45 792 were categorised as White, Caucasian, research into the cardiovascular benefits of blood- or European. Over a median follow-up of 4·4 years pressure lowering in this population has, for decades, (IQR 3·2–5·1), a 5 mm Hg lower systolic blood pressure relied largely on extrapolation, subgroup analyses, and saw a reduction in the primary outcome of major secondary meta-analyses,2,3 rather than trials spanning cardiovascular events—defined as stroke, ischaemic multiple CKD stages with cardiovascular outcomes as heart disease, or hospitalisation for or death from primary endpoints. In clinical practice, cardiovascular heart failure—among participants with CKD (hazard protection is often taken for granted. However, a long- ratio 0·91, 95% CI 0·87–0·94), with a similar treatment standing structural misalignment has persisted in the effect in those without CKD (0·90, 0·88–0·93; evidence: people with CKD who stand to benefit the p >0·99). This relative benefit was preserved interaction most have, paradoxically, relied on relatively indirect across CKD stages 1–5, including stages 4–5, although evidence. This persistent imbalance between risk and patients with end-stage kidney disease or receiving evidence highlights a substantial yet unresolved gap in dialysis were not specifically characterised. the field. In contrast to the consistency observed in the In this context, in The Lancet, Guyu Zeng and present analysis, the evidence base for blood-pressure colleagues4 provide a systematic reappraisal with the lowering in people with CKD has long been structurally latest individual participant data (IPD) analysis. Using fragmented. Early CKD-focused trials prioritised a one-stage IPD approach, the investigators pooled renal outcomes, with cardiovascular events largely as 46 large clinical trials including 285 124 participants, secondary outcomes.5 Subsequent large-scale trials of whom 59 185 (20·7%) had CKD at baseline, forming on blood pressure or intensive treatment included the largest trial-derived dataset of cardiovascular participants with CKD, but inference was mainly drawn outcomes in people with CKD to date. Notably, from subgroup analyses with little representation 23·9% of the CKD cohort (n=14 148) had of advanced stages.2 Later meta-analyses sought to reconcile these data, yet differences in study inclusion, CKD definitions, treatment intensity, and outcome ascertainment produced inconsistent conclusions and restricted cross-stage reproducibility.3,6 Contemporary guidelines therefore differ in emphasis, with some highlighting potential cardiovascular or all-cause mortality benefit and others prioritising renal endpoints or overall risk management.7–11 These differences do not stem from a fundamental disagreement about whether blood pressure should be lowered in people with CKD. Rather, they arise from the need to interpret an incomplete and heterogeneous evidence structure. Ultimately, the question remains: how certain are we that blood-pressure lowering in people with CKD confers a reproducible cardiovascular benefit? 1578 segamI ytteG aiv toksaM See Articles page 1626 Comment The present study by Zeng and colleagues4 offers a more balanced benefit–risk framework rather than an important contribution to this core question. relying solely on cardiovascular or mortality outcomes. Unlike aggregate-data meta-analyses, IPD meta- Equally important will be the need to define the analyses preserve individual-level information and lower boundary of treatment intensity and to better estimate effects across CKD stages and key clinical understand how low blood pressure can be safely subgroups within a single model, improving internal reduced before net benefit starts to diminish. Second, comparability and reducing the reliance on indirect attention could move from mean treatment effects to inference. By pooling 46 large randomised trials more individualised decision making. The heterogeneity from the latest phase of the Blood Pressure Lowering observed in Zeng and colleagues’ study,4 particularly Treatment Trialists’ Collaboration, the investigators among participants with coexisting diabetes, suggests tested this question at an unprecedented scale. that an overall benefit does not necessarily imply Within this unified framework, the study supports uniform benefit across all patients. Models that estimate a cardiovascular benefit of blood-pressure lowering individual treatment effects, potentially supported in people with CKD and, importantly, shows the by advanced predictive methods including artificial consistency of that benefit. The relative reduction intelligence and large language models, could help in major cardiovascular events extended across CKD refine precision strategies for blood-pressure control in stages 1–5, including stages 4–5; a population in people with CKD. Third, the focus should extend from whom randomised evidence has historically been evidentiary certainty to real-world implementation. poor. Except for the landmark advanced-CKD trial by Sustaining blood-pressure control in people with CKD Hou and colleagues,12 subsequent randomised studies remains challenging in routine practice, particularly in in later-stage disease have emerged but have largely advanced stages and in the presence of multimorbidity. focused on renal endpoints and mortality. In Zeng Whether the benefits observed in trials translate and colleagues’ analysis,4 no directional reversal or into population-level health gains will ultimately material attenuation was observed in stages 4–5 for depend on the feasibility of durable, context-sensitive cardiovascular outcomes. Similar stability was evident implementation strategies. across strata defined by proteinuria and lower baseline We declare no competing interests. blood pressures. Furthermore, cardiovascular effects *Yingxian Sun, Xiaofan Guo did not differ systematically across antihypertensive yxsun@cmu.edu.cn drug classes, which is a finding that informs treatment Department of Cardiology, The First Hospital of China Medical University, selection in practice; however, renal endpoints were Shenyang 110001, China (YS, XG); Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical not assessed. University, Shenyang, China (YS) Important limitations remain. Safety outcomes, 1 Jankowski J, Floege J, Fliser D, Böhm M, Marx N. Cardiovascular disease in chronic kidney disease: pathophysiological insights and therapeutic including acute kidney injury, hyperkalaemia, and options. Circulation 2021; 143: 1157–72. symptomatic hypotension, were not systematically 2 Cheung AK, Rahman M, Reboussin DM, et al. Effects of intensive BP control in CKD. J Am Soc Nephrol 2017; 28: 2812–23. integrated. In CKD, in which renal reserve is poor 3 Malhotra R, Nguyen HA, Benavente O, et al. Association between more and electrolyte homoeostasis is fragile, showing a intensive vs less intensive blood pressure lowering and risk of mortality in chronic kidney disease stages 3 to 5: a systematic review and meta- cardiovascular benefit is not the same as defining how analysis. JAMA Intern Med 2017; 177: 1498–505. intensively blood pressure should be lowered and how 4 Zeng G, Bidel Z, Yang Q, et al. Pharmacological blood-pressure lowering for the prevention of cardiovascular disease and death across the full patients should be monitored to reach net benefit spectrum of chronic kidney disease severity: an individual-participant data meta-analysis. Lancet 2026; 407: 1626–38. safely; answering the latter will require further data. 5 Wright JT Jr, Bakris G, Greene T, et al. Effect of blood pressure If Zeng and colleagues’ study4 strengthens our lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. JAMA 2002; confidence that blood-pressure lowering in people with 288: 2421–31. CKD confers cardiovascular benefit, the next phase of 6 Tsai WC, Wu HY, Peng YS, et al. Association of intensive blood pressure control and kidney disease progression in nondiabetic patients with inquiry should focus on three practical priorities. First, chronic kidney disease: a systematic review and meta-analysis. JAMA Intern Med 2017; 177: 792–99. the emphasis should shift from single endpoints to the 7 Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. integration of net clinical benefit. Future analyses could KDIGO 2021 clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Int 2021; 99: S1–87. systematically integrate adverse events to construct Comment 8 Stevens PE, Ahmed SB, Carrero JJ, et al. KDIGO 2024 clinical practice 11 Jones DW, Ferdinand KC, Taler SJ, et al. 2025 AHA/ACC/AANP/AAPA/ABC/ guideline for the evaluation and management of chronic kidney disease. ACCP/ACPM/AGS/AMA/ASPC/NMA/PCNA/SGIM guideline for the Kidney Int 2024; 105: S117–314. prevention, detection, evaluation and management of high blood pressure 9 McEvoy JW, McCarthy CP, Bruno RM, et al. 2024 ESC guidelines for the in adults: a report of the American College of Cardiology/American Heart management of elevated blood pressure and hypertension. Eur Heart J Association Joint Committee on Clinical Practice Guidelines. Circulation 2024; 45: 3912–4018. 2025; 152: e114–218. 10 Schwartz AR, Sosnov J, Brown J, et al. 2025 US Department of Veterans 12 Hou FF, Zhang X, Zhang GH, et al. Efficacy and safety of benazepril for Affairs and US Department of Defense clinical practice guideline for the advanced chronic renal insufficiency. N Engl J Med 2006; 354: 131–40. primary care management of chronic kidney disease. Ann Intern Med 2025; 179: 411–24. Transforming WHO: incremental reform is no longer sufficient WHO was founded in 1948 as the UN agency that goods related to disease control and health promotion: connects nations, partners, and people to ensure normative guidance, surveillance, data governance, that everyone, everywhere can attain the highest emergency coordination, and convening power. WHO level of health. As it has taken on more activities should maintain the technical and advisory committees and programmes, WHO has grown enormously. mandated to develop guidance in these areas and Between 2017 to 2024, its workforce increased re-establish its science division, which brought the by 70% and the number of top-ranked directors nearly organisation much needed scientific rigour. doubled.1 Successive global health crises, including Second, we suggest that WHO reforms its structural most recently the COVID-19 pandemic, have exposed organisation and governance to make it more effective. long-standing structural weaknesses in WHO’s At present, it functions as a loosely constructed Published Online April 9, 2026 governance, financing, and operational model. Despite confederation, composed of its Geneva headquarters, https://doi.org/10.1016/ repeated calls for reform over more than 30 years, six regional offices, and 153 country offices. The regional S0140-6736(26)00609-4 changes in these areas have been largely incremental directors are elected by regional governments, which and insufficient.1–3 limits their accountability to the WHO Director-General.6 Today, WHO stands at a crossroads. The US Government Regional offices have substantial authority over their has withdrawn its membership of WHO and, along with budgets, staffing, and priorities, which stems from a most European countries, has reduced funding for global 1976 World Health Assembly resolution that shifted health.4 Country health sovereignty is finally on the rise much of WHO’s budget from its Geneva headquarters to and requires a strong WHO enabler that reinforces this its regional offices.7 sovereignty. WHO is entering its first period of enforced Although this arrangement respects political diversity contraction in decades. This creates a rare opportunity for and decentralisation, this fragmented authority the organisation to improve its efficiency and effectiveness complicates decision making, delays responses, through far more extensive institutional reform rather dilutes responsibility for performance, and produces than incremental change. We offer recommendations for inconsistent guidance.8 The delays in responding to such reform and identify potential barriers and challenges the 2014–16 outbreak of Ebola virus disease in west that must be overcome for their implementation. Africa and the COVID-19 pandemic are examples.9,10 First, we believe that WHO should prioritise essential In an era when global health threats are increasingly functions that are based on its mandate and strengths transnational, such institutional fragmentation carries and that no other institution can credibly perform on risk. A more integrated WHO would enhance strategic a global scale. Programmes with little comparative clarity and operational efficiency. In such a model, most value should be eliminated, even if they are supported core technical functions, emergency preparedness, and by donors. This could result in further staff reductions normative work would be centrally governed. Only for and the elimination of programmes that are costly and diseases with a uniquely strong regional focus—such often have only a limited impact.5 At its core, we believe as some of the neglected tropical diseases which are WHO’s comparative advantage lies not in programme almost entirely endemic to the African region11—should implementation but in provision of global public operational control be managed by a regional office. 1580 segamI ytteG aiv PFA/inirffoC ecirbaF --- [PDF原文](https://sci-net.xyz/storage/7932541/0406b1aa5babec71fefebe0ec132e7343320ac310d64d5329b19176c0ebef88e/Cardiovascular-benefit-of-blood-pressure-lowering-in-chronic-kidney-disease.pdf) DOI: 10.1016/S0140-6736(26)00553-2