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The coronavirus disease 2019 (COVID-19) pandemic has had an unprecedented effect on health and health care. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has strained health care systems and caused disruption to non-COVID-19-related health care. Although the premature interruption or disruption of clinical trials is less well recognized, it has the potential to threaten the development of new non-COVID-19-related therapies (1⇓–3).\ud \ud Study disruptions need to be rapidly identified and addressed to preserve the integrity of ongoing studies and the design of new ones. Here, we describe the challenges that arose in three global phase 3 trials and the strategies undertaken to maintain and adapt the conduct of the studies safely during the COVID-19 pandemic.

Digital, Hypertension is a major cause of cardiovascular disease and deaths worldwide especially in low- and middle-income countries. Despite the availability of safe, well-tolerated, and cost-effective blood pressure (BP)-lowering therapies, Ciencias Médicas y de la Salud

Background Dipping of blood pressure (BP) at night is a normal physiological phenomenon. However, a non-dipping pattern is associated with hypertension mediated organ damage, secondary forms of hypertension and poorer long-term outcome. Identifying a non-dipping pattern may be useful in assessing risk, aiding the decision to investigate for secondary causes, initiating treatment, assisting decisions on choice and timing of antihypertensive therapy, and intensifying salt restriction. Objectives To estimate the prevalence and factors associated with non-dipping pattern and determine the effect of 6 months of three antihypertensive regimens on the dipping pattern among Black African hypertensive patients. Methods This was a secondary analysis of the CREOLE Study which was a randomized, single blind, three-group trial conducted in 10 sites in 6 Sub-Saharan African countries. The participants were 721 Black African patients, aged between 30 and 79 years, with uncontrolled hypertension and a baseline 24-h ambulatory blood pressure monitoring (ABPM). Dipping was calculated from the average day and average night systolic blood pressure measures. Results The prevalence of non-dipping pattern was 78% (564 of 721). Factors that were independently associated with non-dipping were: serum sodium > 140 mmol/l (OR = 1.72, 95% CI 1.17–2.51, p-value 0.005), a higher office systolic BP (OR = 1.03, 95% CI 1.01–1.05, p-value 0.003) and a lower office diastolic BP (OR = 0.97, 95% CI 0.95–0.99, p-value 0.03). Treatment allocation did not change dipping status at 6 months (McNemar’s Chi2 0.71, p-value 0.40). Conclusion There was a high prevalence of non-dipping among Black Africans with uncontrolled hypertension. ABPM should be considered more routinely in Black Africans with uncontrolled hypertension, if resources permit, to help personalise therapy. Further research is needed to understand the mechanisms and causes of non-dipping pattern and if targeting night-time BP improves clinical outcomes. Trial registration ClinicalTrials.gov (NCT02742467).

Background. The prevalence of hypertension in adults in South Africa (SA) is 35%. Hypertension is the most important modifiable risk factor for cardiovascular (CV) and chronic kidney disease (CKD) in sub-Saharan Africa. However, 49% of people are unaware of their blood pressure status. Screening for hypertension prior to surgery provides a unique opportunity to diagnose and treat affected individuals. Furthermore, assessing overall CV risk identifies patients at highest risk for complications, and improves the utilisation of scarce resources. Objectives. To evaluate the CV risk profile of hypertensive patients in the adult population of the Western Cape Province presenting for elective non-cardiac, non-obstetric surgery. Methods. This report documents the CV risk profile of patients recruited to the HASS-2 study (Hypertension and Surgery Study 2), which was undertaken in seven Western Cape hospitals. Patients were screened for hypertension and pharmacological treatment was initiated or adjusted in patients with stages 1 and 2 disease. Stage 3 patients were referred to a physician. In the present substudy, patients with stages 1 and 2 hypertension were assessed for associated CV risk factors, the presence of target organ damage, and documented CV or kidney disease; they received an overall risk stratification according to the 2018 European Society of Cardiology and the European Society of Hypertension Guidelines. Results. Sixty-one patients with stage 1 and 12 with stage 2 hypertension were analysed. Established CV disease was present in 13.7% of the study population, and CKD (eGFR

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m2 and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.

ObjectivesThe International Society of Nephrology (ISN) has called for zero deaths by 2025. This survey aimed to determine the preparedness of Southern African Development Community (SADC) countries and Nigeria to heed this call.SettingA questionnaire was emailed to facilities, where renal replacement therapy is available; to determine type of services available; quality of care and identify clinicians involved.ParticipantsClinicians and administrators involved in the care of patients with acute kidney injury (AKI) completed the questionnaire.ResultsCompleted questionnaires were received from 12 of the 15 SADC countries and Nigeria, covering 48 service providers. The government provided partial funding for dialysis in 41.7% of services. There was no funding for acute dialysis in two countries. Interdisciplinary teams in 72.9% of hospitals covered the intensive care units (ICUs), which included at least one nephrologist in 75%. Only 77% were able to provide dialysis in ICU. Intermittent haemodialysis was the most common modality available (91.7% of facilities), sustained low-efficiency dialysis in 50%, continuous therapies in 35% and peritoneal dialysis in 33.3%. Almost half (47.9%) of the sites were limited to one mode of dialysis and unable to care for severely ill patients. The clinical status was used to initiate and monitor dialysis, with very few sites having clear written standard operating procedures.ConclusionIn the 16 countries surveyed, the majority had limited ability to provide comprehensive dialysis programmes for patients with AKI due to lack of facilities and government funding. Additionally, nephrologists are scarce; modes of dialysis are limited; as is the care for severely ill patients and lack of standard operating procedures. Resources, training and funding need to be made available to create universal coverage of dialysis for AKI. The ISN goal of providing renal replacement therapy to all by 2025 is unlikely to be achieved in SADC and Nigeria.

Brian Rayner Kidney and Hypertension Research Unit, University of Cape Town, Groote Schuur Hospital, Observatory, Cape Town 7925, South Africa Purpose: To describe the efficacy of a stratified approach on automatic office blood pressure (BP), 24-hour ambulatory BP, and BP variability (BPV) in treatment-naïve patients with systolic hypertension using lercanidipine for stage 1 and lercanidipine/enalapril for stage 2. Patients and methods: This was an open-label, prospective interventional study conducted in 22 general practices in South Africa. Treatment-naïve patients with stage 1 hypertension received lercanidipine 10 mg and patients with stage 2 received lercanidipine 10 mg/enalapril 10 mg. After 6 weeks, patients not reaching target (

OBJECTIVE: To examine whether treatment with beta-blockers (BBs) in pregnant women with structural heart disease (SHD) resulted in a decrease in foetal birth weight (FBW) in a South African cohort. METHODS: This was a prospective cohort study conducted in a tertiary-level hospital in Cape Town from 2010 to 2016. Of the 178 pregnant women with SHD, 24.2% received BBs for a minimum of two weeks. Adverse foetal outcomes and mean FBW were compared between the BB groups and subgroups (congenital, valvular, cardiomyopathy and other). Adverse foetal outcome was defined as: low birth weight (LBW) < 2 500 g, Apgar score < 7, premature birth (< 37 weeks) and small for gestational age (SGA). RESULTS: BB exposure during pregnancy was found to be associated with a non-significant increased FBW (2 912 vs 2 807 g, p = 0.347). A significant decrease (p = 0.009) was noted in FBW for valvular SHD pregnancies using BBs, while a significant increase (p = 0.049) was observed for the same outcome in the cardiomyopathy subgroup using BBs. A significant increase was observed for SGA (p = 0.010) and LBW (p = 0.003) pregnancies within the valvular subgroup when exposed to BBs. CONCLUSION: BB use in pregnant women with SHD in a South African cohort showed no association with a decrease in FBW or an increase in adverse foetal outcomes when compared to non-BB usage.

Introduction Access to dialysis and transplantation in the developing world remains limited. Therefore, optimising renal allograft survival is essential. This study aimed to evaluate clinical outcomes and identify poor prognostic factors in the renal transplant programme at Groote Schuur Hospital [GSH], Cape Town. . Method Data were collected on all patients who underwent a kidney transplant at GSH from 1st July 2010 to the 30 June 2015. Analyses were performed to assess baseline characteristics, graft and patient survival, as well as predictors of poor outcome. . Results 198 patients were transplanted. The mean age was 38 +/- 10.5 years, 127 (64.1%) were male, and 86 (43.4%) were of African ethnicity. Deceased donor organs were used for 130 (66.7%) patients and living donors for 65 (33.3%). There were > 5 HLA mismatches in 58.9% of transplants. Sepsis was the commonest cause of death and delayed graft function [DGF] occurred in 41 (21.4%) recipients. Patient survival was 90.4% at 1 year and 83.1% at 5 years. Graft survival was 89.4% at 1 year and 80.0% at 5 years. DGF (HR 2.83 (1.12-7.19), p value = 0.028) and recipient age > 40 years (HR 3.12 (1.26-7.77), p value = 0.014) were predictors of death. Conclusion Despite the high infectious burden, stratified immunosuppression and limited tissue typing this study reports encouraging results from a resource constrained transplant programme in South Africa. Renal transplantation is critical to improve access to treatment of end stage kidney disease where access to dialysis is limited.

Summary Background and aim: The Pan-African Society of Cardiology (PASCAR) has identified hypertension as the highest area of priority for action to reduce heart disease and stroke on the continent. The aim of this PASCAR roadmap on hypertension was to develop practical guidance on how to implement strategies that translate existing knowledge into effective action and improve detection, treatment and control of hypertension and cardiovascular health in sub-Saharan Africa (SSA) by the year 2025. Methods: Development of this roadmap started with the creation of a consortium of experts with leadership skills in hypertension. In 2014, experts in different fields, including physicians and non-physicians, were invited to join. Via faceto- face meetings and teleconferences, the consortium made a situation analysis, set a goal, identified roadblocks and solutions to the management of hypertension and customised the World Heart Federation roadmap to Africa. Results: Hypertension is a major crisis on the continent but very few randomised, controlled trials have been conducted on its management. Also, only 25.8% of the countries have developed or adopted guidelines for the management of hypertension. Other major roadblocks are either government and health-system related or healthcare professional or patient related. The PASCAR hypertension task force identified a 10-point action plan to be implemented by African ministries of health to achieve 25% control of hypertension in Africa by 2025. Conclusions: Hypertension affects millions of people in SSA and if left untreated, is a major cause of heart disease and stroke. Very few SSA countries have a clear hypertension policy. This PASCAR roadmap identifies practical and effective solutions that would improve detection, treatment and control of hypertension on the continent and could be implemented as is or adapted to specific national settings.

Background. Non-adherence to antihypertensives is a cause of ‘pseudo-treatment-resistant’ hypertension. Objective. To determine whether monitoring plasma amlodipine concentrations and inhibition of angiotensin-converting enzyme (ACE) can be adjunct adherence tools. Methods. Patients with hypertension who were prescribed enalapril and amlodipine were enrolled. Blood pressures (BPs) were monitored and an adherence questionnaire was completed. Steady-state amlodipine was assayed using liquid chromatography-mass spectrometry and degree of ACE inhibition using the Z-FHL/HHL (z-phenylalanine-histidine-leucine/hippuryl-histidine-leucine) ratio. Results. One hundred patients (mean (standard deviation) age 50.5 (12) years, 46% male) were enrolled. Based on plasma assays, 26/97 patients (26.8%) were unsuppressed by enalapril and 20/100 (20%) were sub-therapeutic for amlodipine. There were significant BP differences based on plasma levels of the medication: 21/20 mmHg lower in the group with suppressed ACE and 26/20 mmHg in the group with steady-state amlodipine concentrations. Conclusions. Monitoring antihypertensive adherence by assaying plasma medication concentrations is a feasible option for evaluating true v. pseudo-resistant hypertension.S Afr Med J 2017;107(10):887-891

Hyperkalaemia is a potentially life-threatening condition frequently encountered in hospitalised patients. Among the many causes of hyperkalaemia, drugs have often been implicated. In the South African context, with the high burden of HIV, there is an increased incidence of opportunistic infections such as Pneumocystis jirovecii pneumonia (PJP), and consequently many patients receive high doses of trimethoprim-sulfamethoxazole. A lesser-known side-effect of the trimethoprim component of this combination antibiotic is hyperkalaemia. We report a case in which life-threatening hyperkalaemia developed after institution of high-dose co-trimoxazole for PJP.

Background HIV-infected individuals are at increased risk of tissue inflammation and accelerated vascular aging (‘inflamm-aging’). Abnormal diurnal blood pressure (BP) rhythms such as non-dipping may contribute to an increased risk of cardiovascular and cerebrovascular events in HIV infected individuals. However, little data exists on ambulatory blood pressure (ABP) and measures of vascular stiffness in the black African HIV infected population. Methods This is a cross-sectional analysis of otherwise well, HIV infected outpatients on ART for >5 years. Study assessments included: 24hr ABP monitoring, pulse wave velocity (PWV) and central aortic systolic pressure (CASP) using a AtCor Medical Sphygmocor device, fasting lipogram, oral glucose tolerance test, high-sensitivity C-reactive protein (hsCRP) and anthropometric data. Patients completed a questionnaire of autonomic symptoms. CD4+ counts and viral loads were obtained from the National Laboratory results system. Results Sixty seven black participants were included in the analysis of whom 91% (n = 61) were female with a mean age of 42.2 ± 8.6 years. The median duration on ART was 7.5 years (IQR = 6–10), 84% were virally supressed and the median CD4 count was 529.5cells/mm3 (IQR = 372.0–686.5). The majority (67%) were classified as overweight and 76% had an increased waist circumference, yet only 88% of participants were normotensive. A hsCRP level in the high cardiovascular risk category was found in 68% of participants. The prevalence of non-dipping BP was 65%. Interestingly, there was no association on multivariable analysis between dipping status and traditional risk factors for non-dipping BP, such as: obesity, autonomic dysfunction and older age. Conclusion This relatively young cross-sectional sample of predominantly normotensive, but overweight black women on effective ART >5 years showed: a high prevalence of non-dipping BP, inflammation and vascular stiffness. Causality cannot be inferred but cardiovascular risk reduction should be emphasized in these patients.

Background. Control of hypertension remains an elusive goal, but doctors' non-compliance with guidelines, patient attitudes and adherence to treatment, and poor delivery of care at clinics are important contributing factors.Objectives. To determine the overall quality of hypertensive care, and compliance with current hypertension guidelines at community health centres (CHCs) in the Western Cape.Methods. Consecutive patients attending hypertension clinics at two CHCs were selected to participate. A questionnaire was designed to determine patient demographics, doctors' compliance with hypertension guidelines, factors leading to treatment non-adherence, and delivery of care. Accuracy of blood pressure (BP) recording was evaluated by comparing the clinic BP with that measured using an approved manometer.Results. One hundred and sixty-one patients were evaluated, 100 from CHC 1 and 61 from CHC 2. There was no difference in both control systolic and diastolic BP measured by the hypertension nurse (147.9 v. 144.8 mmHg, p = 0.45, and 89.3 v. 85.6 mmHg, p = 0.14) respectively. All clinic BP readings were recorded to the nearest 10 mmHg mercury. The difference in both systolic and diastolic BP > 10 mmHg between the clinic and control BP was significantly greater at CHC 2 than CHC 1 (28% v. 56%, p = 0.005, and 43% v. 64%, p = 0.007) respectively. Overall, 39.8% of patients had a systolic and diastolic BP < 140 and< 90 mmHg. The mean number of antihypertensive drugs was 2.4 per patient. The use of non-steroidal antiinflammatory drugs (NSAIDs) and tricyclic antidepressants was high at both centres, and few patients underwent basic investigations, lifestyle interventions, risk stratification or global cardiovascular risk reduction.Conclusions. 39.8% of patients achieved a BP < 140/90 mmHg. There is significant scope for improvement in prescription of medication, application of uniform lifestyle changes, and avoidance of NSAIDs and tricyclic antidepressants. Major deficiencies were identified in BP measurement, assessment of target organ damage, risk stratification and the reduction of overall cardiovascular risk.

Background: Hypertension is a common cardiovascular disease, affecting adults worldwide and it accounts for up to 30% of all deaths. The need for better control of arterial hypertension justifies observational studies designed to better understand the real-life management of hypertensive patients. The ASTRAL study was primarily designed to evaluate the percentage of hypertensive patients achieving blood pressure goals after eight weeks of treatment with a fixeddose combination of ramipril/hydrochlorothiazide (HCTZ). Methods: The study was a multi-centre, non-comparative, open-label, observational study conducted in 36 centres in five sub-Saharan African countries, namely Cameroon, Congo Brazzaville, Democratic Republic of Congo (DRC), Madagascar and Nigeria. Four hundred and forty-nine men and women 18 years of age or older with hypertension not controlled by an ACE inhibitor, a diuretic or any other monotherapy or anti-hypertensive combination not containing a diuretic in a fixed dose were considered eligible for inclusion in this eight-week study. The study consisted of three visits, visit one (V1) at baseline, visit two (V2) after four weeks and visit three (V3) after eight weeks. Results: The mean age of the patients was 54.7 ± 11.7 years (20–90 years) and most were categorised by the WHO criteria as either overweight or obese (71.6%). After four and eight weeks of treatment with the study drug, systolic and diastolic blood pressures significantly changed from baseline: –24.7/–14.2 mmHg (p < 0.001) and –31.7/–17.9 mmHg (p < 0.001), respectively. There were 60.2% of the non-diabetics on prior monotherapy who, at eight weeks, fulfilled the primary blood pressure goal for SBP and DBP, versus 26.5% of the diabetic patients, also on monotherapy. Few adverse events were reported, with facial oedema and dry cough recurring twice in two patients. Conclusion: Fixed-dose combination of ramipril/HCTZ is therefore effective, tolerable and has a good safety profile for blood pressure control in black Africans.

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Summary Hypertension is more prevalent and severe in urban black populations compared to whites, and is associated with a greater degree of target-organ damage for any given blood pressure level. In general, compared to whites, blacks respond well to diuretics and calcium channel blockers and less well to β-blockers and ACE inhibitors. The exact mechanisms that contribute to differences in blood pressure between blacks and whites are still not fully understood, given the multi-factorial aetiology of essential hypertension. Various lines of evidence suggest black patients are more salt sensitive than whites, which is due to a tendency to retain sodium in the kidney. Inherent differences in ionic transport mechanisms, the renal epithelial sodium channel, the renin-angiotensin-aldosterone system and vasoactive substances may be a partial explanation, but analysis is compounded by disparate socio-economic conditions between blacks and whites. At present, there is no complete explanation for these differences and further research is required.

For people enrolled in Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL), we sought to examine whether variation exists in the baseline medical therapy of different geographic regions and if any variations in prescribing patterns were associated with physician specialty. Patients were grouped by location within the United States (US) and outside the US (OUS), which includes Canada, South America, Europe, South Africa, New Zealand, and Australia. When comparing US to OUS, participants in the US took fewer anti-hypertensive medications (1.9 ± 1.5 vs. 2.4 ± 1.4; P < .001) and were less likely to be treated with an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker (46% vs. 62%; P < .001), calcium channel antagonist (37% vs. 58%; P < .001), and statin (64% vs. 75%; P < .05). In CORAL, the identification of variations in baseline medical therapy suggests that substantial opportunities exist to improve the medical management of patients with atherosclerotic renal-artery stenosis.

Extensive data from randomised controlled trials have shown the benefit of treating hypertension. The target blood pressure (BP) for antihypertensive management is < 140/90 mmHg, and < 130/80 mmHg in patients with end-organ damage, coexisting risk factors, and co-morbidity. Benefits of management include reduced risk of death, stroke, cardiac failure, chronic kidney disease, and coronary heart disease. The correct BP measurement procedure is described, and evaluation of cardiovascular risk factors and recommendations for antihypertensive therapy, are stipulated. Lifestyle modification and patient education are cornerstones in the management of every patient. Major indications, precautions, and contraindications to each recommended antihypertensive drug are listed. Combination therapy should be considered ab initio if the BP is ≥ 20/10 mmHg above goal. First-line drug therapy for uncomplicated essential hypertension includes low-dose thiazide-like diuretics, calcium-channel blockers, angiotensin-converting enzyme inhibitors, or angiotensin-receptor blockers. The guideline was developed by the Southern African Hypertension Society.

BackgroundChronic kidney disease (CKD) is a significant public health problem that leads to end-stage renal disease (ESRD) with as many as 2 million people predicted to need therapy worldwide by 2010. Obesity is a risk factor for CKD and leptin, the obesity hormone, correlates with body fat mass and markers of renal function. A number of clinical and experimental studies have suggested a link between serum leptin and kidney disease. We hypothesised that variants in the leptin gene (LEP) may be associated with markers of CKD in indigenous black Africans.Methodology/principal findingsBlack South Africans of Xhosa (distinct cultural Bantu-speaking population) descent were recruited for the study and four common polymorphisms of the LEP (rs7799039, rs791620, rs2167270 and STS-U43653 [ENSSNP5824596]) were analysed for genotype and haplotype association with urine albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), Serum creatinine (Scr) and serum leptin level. In one of the four single nucleotide polymorphisms (SNPs) we examined, an association with the renal phenotypes was observed. Hypertensive subjects with the T allele (CT genotype) of the ENSSNP5824596 SNP had a significantly higher eGFR (p = 0.0141), and significantly lower Scr (p = 0.0137). This was confirmed by haplotype analysis. Also, the haplotype GAAC had a modest effect on urine albumin-to-creatinine ratio in normotensive subjects (p = 0.0482).Conclusions/significanceThese results suggest that genetic variations of the LEP may be associated with phenotypes that are markers of CKD in black Africans.

The Anglo-Scandanavian Cardiac Outcomes Trial - Blood Pressure Lowering Arm (ASCOT-BPLA) was a multi-centre, prospective, randomised, controlled trial in 19 257 patients with hypertension, aged 40-79 years, with at least three other cardiovascular (CVS) risk factors. Patients were assigned to either arnlodipine (5-10 mg), adding perindopril (4-8 mg) as required (arnlodipine-based regimen, n = 9 639), or atenolol (50-100 mg), adding bendroflumethiazide (1.25-2.5 mg) and potassium as required (atenolol-based regimen, n = 9 618). The primary end-point was non-fatal myocardial infarction (MI) and fatal coronary heart disease (CHD). Although there was a non-significant 10% reduction in the primary end-point in favour of the arnlodipine-based regimen, the study was prematurely stopped after a median follow up of 5.5 years by the Data and Safety Monitoring Committee, because of clinically important reductions in secondary end-points (Table I).

The importance of the renin-angiotensin-aldosterone system (RAAS) in the pathogenesis of hypertension and in renal disease, particularly in patients with diabetes, has become increasingly evident. Pharmacological blockade of the RAAS offers potential for the therapeutic management of these pathologies. Angiotensin converting enzyme (ACE) inhibitors and angiotensin II (AII) receptor blockers have been shown to exhibit effectiveness in the treatment of hypertension. AII receptor blockers have a renal protective effect owing to their ability to reduce systemic blood and intraglomerular pressures. Eprosartan is a chemically distinct AII blocker, which displays a dual mode of action whereby it blocks both pre- and postsynaptic AT1 receptors, potentially benefiting patients with hypertension and renal disease. In addition, evidence suggests that eprosartan is well tolerated by both healthy subjects and patients with varying degrees of renal impairment, such that the dose does not need to be - modified in patients with mild to moderate renal impairment. Results from preliminary studies demonstrate that eprosartan doses well below those required for blood pressure control have a pronounced effect on the kidney and do not compromise renal autoregulatory mechanisms. Therefore, eprosartan may have a benefit in the prevention or delay of renal damage in hypertensive patients with renal impairment, although this remains to be determined in a clinical setting.