Symposium 8.3 – Hypertension treatment in special populations

Symposium Summary

Written by Jasna Trbojevic-Stankovic
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Hypertension management in transition from CKD to ESRD

Aldo Peixoto, United States of America

The Kidney Disease: Improving Global Outcomes (KDIGO) 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease (CKD) for non-dialyzed patients has recently presented an update to the KDIGO 2012 guideline on this topic. New recommendations are based on systematic reviews of relevant studies and appraisal of the quality of the evidence. The scope includes proper blood pressure (BP) measurement, optimal BP targets, lifestyle interventions, and choice of medications for specific patient groups. The proposed target systolic BP for most non-dialyzed CKD patients is less than 120 mmHg using standardized office reading. Renin-angiotensin system (RAS) blockers represent the recommended cornerstone of therapeutic intervention regardless of the level of eGFR, presence of diabetes, or albuminuria.

Figure 1. Summary of recommendations from the 2021 KDIGO Clinical Practice Guidelines for the Management of Blood Pressure in CKD

Earlier guidelines on this subject, such as those from the American College of Cardiology / American Heart Association (ACC/AHA) from 2017 and European Society of Cardiology / European Society of Hypertension (ESC/ESH) from 2018, suggested somewhat higher target BP levels. The targets defined in the KDIGO 2021 are primarily based on the results from the Systolic Blood Pressure Intervention Trial (SPRINT) published in 2017. This trial reported that targeting systolic BP <120mmHg compared with <140mmHg reduced rates of major cardiovascular events and overall mortality in non-diabetic CKD patients without deleterious effect on main kidney outcome. Nevertheless, there is still a lack of relevant data on the optimum BP targets in patients with advanced CKD and those on renal replacement therapies, mainly because of an altered benefit-risk balance associated with BP reduction in these patients.

ACC/AHA 2017 and ESC/ESH 2018 Previous suggested the use of calcium channel blockers and thiazide diuretics along with RAS blockers as first-line therapy. Recommendations for the treatment approach to hypertension in CKD patients in the KDIGO 2021 guidelines rely on the latest studies reporting that RAS blockers reduce the risk of kidney failure, cardiovascular events, and all-cause mortality in CKD patients. In practice, however, a notable decline of RAS blocker use is observed in advanced CKD, and data on the benefits from RAS blockage in this population of patients is still limited. The latest studies have also highlighted the promising results of the novel nonsteroidal, selective mineralocorticoid receptor antagonist (MAR) finerenone in reducing cardiovascular and renal events among patients with diabetic kidney disease. Nevertheless, both RAS blockers and MAR use may be associated with decreased eGFR and hyperkalaemia thus requiring close follow-up of volume status, adequate dietary adjustments, and adding non-potassium sparing diuretic or potassium binder.

Hypertension in patients with renal transplantation: current concepts and future directions

Jean-Michel Halimi, France

The prevalence of hypertension remains high in transplant recipients, ranging from 60% five years after liver transplant, to as high as 95% five years after heart and kidney transplant. Hypertension is associated with significant adverse kidney and cardiovascular outcomes and reduced one-year graft survival in kidney transplant recipients (KTR).

There are three groups of factors contributing to hypertension in KTR: the pre-existing, the issues related to the transplant procedure, and the circumstances appearing after the procedure. Increased sympathetic afferent renal nerve signalling from native kidneys causes increased contractility and heart rate, RAS activation, and expansion of effective circulating volume. Procedure-related factors encompass fluid overload during dialysis, increased body weight, high donor age and familial history of hypertension, parenteral fluid administration, and delayed graft function. A multitude of hypertension-contributing factors may also appear following the procedure, such as acute and chronic rejection, calcineurin inhibitors associated with nephrotoxicity, graft artery stenosis or chronic neuropathy, sodium retention due to high dose glucocorticoids, and thrombotic microangiopathy.

The current transplant guidelines recommend only office BP assessments for risk stratification in KTR, even though it has been reported that nearly half of these patients require a change in treatment after ambulatory blood pressure monitoring. The latest consensus statement of the ‘hypertension and the kidney’ working group of the European Society of Hypertension calls for a reconsideration of such practice, given the prevalence of white-coat hypertension and masked hypertension, the hypertension misclassification, and the better prediction of adverse outcomes by 24-h ambulatory BP monitoring as indicated in recent systematic reviews.

Available guidelines are insufficient and inconsistent concerning recommendations for BP goals in KTR. While anticipating the results of randomized controlled trials which shall define optimal BP targets in this population, it seems reasonable to suggest relying on those employed in the wider CKD population, i.e. <130/80 mmHg.

Figure 2. Blood pressure goals in current guidelines in CKD and KTR

Conflicting results are also present related to the choice of optimal antihypertensive therapeutics in KTR, as no clear benefit is documented for RAS blockers use over conventional treatment in the current literature. Current evidence suggests calcium channel blockers could be the preferred first-step antihypertensive agents in this group of patients, as they improve graft function and reduce graft loss. The new consensus statement from the „hypertension and the kidney“ working group of the European Society of Hypertension which is currently in press shall address all the major issue regarding hypertension in KTR.

Hypertension in children and adolescents in CKD

Stella Stabouli, Greece

Hypertension is largely present in the paediatric population with renal disease. Over half of the children with non-dialysis CKD and over two-thirds of those on renal replacement therapy are hypertensive. Even though neither of the currently published guidelines for the management of high BP in the paediatric population differentiates BP diagnostic thresholds for children with CKD from those in the general paediatric population, they do propose different BP targets for hypertension treatment in this specific population. This is based on the data suggesting that elevated BP is associated with significantly faster renal function deterioration in children and adolescents with both glomerular and non glomerular kidney disease.

Previous studies have shown that intensified BP control targeting 24-hour BP levels in the low range of normal, confers a substantial benefit for renal function among children with CKD. The findings from the European Effect of Strict Blood Pressure Control and ACE Inhibition on Progression of Chronic Renal Failure in Paediatric Patients (ESCAPE) trial that the aggressive BP treatment to 24h MAP <50th percentile, provide a greater renal survival benefit in children with CKD remains the gold standard in clinical practice. This BP treatment target has also been adopted in the latest KDIGO Clinical Practice Guideline for the management of BP in children with CKD, despite raised concerns about the potential risks for adverse events from intense BP lowering, which may vary depending on the underlying cause of CKD, risk of dehydration, hypotension, and acute kidney injury.

Ambulatory BP monitoring remains the gold-standard method for diagnosing hypertension in children with CKD. Nevertheless, in children, it may represent a challenge, due to the limited availability of resources and lack of normative values in children younger than 5 years old or with a height <120 cm. Thus, it has been suggested that in clinical settings with limited availability of ambulatory BP monitoring in children with mild to moderate CKD decisions could be made based on BP obtained during a clinic visit.

There are currently no head-to-head randomized controlled trials comparing antihypertensive drug classes in children with and without CKD. Furthermore, there is no evidence of a consistent dose-response relationship for escalating doses of RAS blockers or calcium channel blockers. RAS inhibitors remain the cornerstone of antihypertensive treatment in children, but dose reduction or drug cessation could be considered in case of uncontrolled hyperkalaemia or hypotension, or if GFR decline >30%. The most used second-line medications are calcium channel blockers, but have been associated with higher levels of proteinuria and less efficient BP control in the pediatric population with CKD without concurrent RAS inhibitor treatment. Mineralocorticoid receptor antagonists exhibited promising results in controlling hypertension in adults and could be used to treat resistant hypertension in the pediatric CKD population, with caution on possible side effects. Pharmacological measures should always be supported by lifestyle changes, limited salt intake, adequate diet, and increased physical activity, especially in children with CKD and presence of obesity or metabolic syndrome.

Figure 3. Assessment and management of obesity and metabolic syndrome in children with CKD stages II-V and on renal replacement therapy (clinical practice recommendations from the Paediatric Renal Nutrition Taskforce, Paediatric Nephrology 2021, in press)

Despite the publication of guidelines for BP control in patients with CKD, it appears that hypertension remains undertreated and under-recognized in children with CKD and is associated with left ventricular hypertrophy in this population. Large multicentre normative data are still needed on this topic.

Further reading

Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease. Kidney Int. 2021;99(3S):S1-S87. doi: 10.1016/j.kint.2020.11.003.

Cheung AK, Rahman M, Reboussin DM; SPRINT Research Group. Effects of Intensive BP Control in CKD. J Am Soc Nephrol. 2017;28(9):2812-2823. doi: 10.1681/ASN.2017020148.

Turner JM, Peixoto AJ. Blood pressure targets for hemodialysis patients. Kidney Int. 2017;92(4):816-823. doi: 10.1016/j.kint.2017.01.038.

Xie X, Liu Y, Perkovic V, et al. Renin-Angiotensin System Inhibitors and Kidney and Cardiovascular Outcomes in Patients With CKD: A Bayesian Network Meta-analysis of Randomized Clinical Trials. Am J Kidney Dis. 2016;67(5):728-41. doi: 10.1053/j.ajkd.2015.10.011.

Bakris GL, Agarwal R, Anker SD; FIDELIO-DKD Investigators. Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes. N Engl J Med. 2020;383(23):2219-2229. doi: 10.1056/NEJMoa2025845.

Halimi JM, Persu A, Sarafidis PA, Burnier M, Abramowicz D, Sautenet B, Oberbauer R, Mallamaci F, London G, Rossignol P, Wuerzner G, Watschinger B, Zoccali C. Optimizing hypertension management in renal transplantation: a call to action. Nephrol Dial Transplant. 2017;32(12):1959-1962. doi: 10.1093/ndt/gfx283.

Halimi JM, Ortiz A, Sarafidis PA, Mallamaci F, Wuerzner G, Pisano A, London G, Persu A, Rossignol P, Sautenet B, Ferro C, Boletis J, Kanaan N, Vogt L, Bolignano D, Burnier M, Zoccali C. Hypertension in kidney transplantation: a consensus statement of the ‘hypertension and the kidney’ working group of the European Society of Hypertension. J Hypertens. (in press) doi: 10.1097/HJH.0000000000002879.

Pisano A, Mallamaci F, D’Arrigo G, et al. Blood pressure monitoring in kidney transplantation: a systematic review on hypertension and target organ damage. Nephrol Dial Transplant. 2021 Mar 25:gfab076. (online ahead of print) doi: 10.1093/ndt/gfab076.

Reynolds BC, Roem JL, Ng DKS, et al. Association of Time-Varying Blood Pressure With Chronic Kidney Disease Progression in Children. JAMA Netw Open. 2020;3(2):e1921213. doi: 10.1001/jamanetworkopen.2019.21213.

Barletta GM, Pierce C, Mitsnefes M, et al. Is Blood Pressure Improving in Children With Chronic Kidney Disease? A Period Analysis. Hypertension. 2018;71(3):444-450. doi: 10.1161/HYPERTENSIONAHA.117.09649.

Chaturvedi S, Lipszyc DH, Licht C, Craig JC, Parekh R. Pharmacological interventions for hypertension in children. Cochrane Database Syst Rev. 2014;(2):CD008117. doi: 10.1002/14651858.CD008117.pub2.

Chan EY, Ma AL, Tullus K. When should we start and stop ACEi/ARB in paediatric chronic kidney disease? Pediatr Nephrol. 2021;36(7):1751-1764. doi: 10.1007/s00467-020-04788-w.