Hypertension in sub-Saharan Africa: the current profile, recent advances, gaps, and priorities.

Recent global and regional reports consistently confirm the high and increasing prevalence of hypertension in sub-Saharan Africa (SSA), with poor detection, treatment, and control rates. This narrative review summarises the burden of hypertension in SSA and recent findings from community-based hypertension management strategies. We further outline prominent risk factors according to recent data and associated underlying mechanisms for hypertension development. An extensive review of literature showed that most countries have reported on the prevalence of hypertension during 2017-2023, despite limitations linked to the lack of nationally representative studies, heterogeneity of sampling and data collection methods. Task-shifting approaches that assign roles to model patients and community health workers reported improved linkage to healthcare services and adherence to medication, with inconsistent findings on blood pressure (BP)-lowering effects over time. The regularly reported risk factors include unhealthy diet, sedentary lifestyle, increased adiposity and underweight, ageing, level of education, and/or income as well as psychosocial factors. Newer data on the pathophysiological mechanisms leading to hypertension and potential areas of intervention are reported from children and adults and include, among others, salt-handling and volume overload, endothelial function, BP dipping patterns and the role of human immunodeficiency virus . To conclude, significant strides have been made in data reporting from SSA on the burden of hypertension in the region as well as biomarker research to improve understanding and identification of areas of intervention. However, gaps remain on linkage between knowledge generation, translation, and implementation research. Coordinated studies addressing both discovery science and public health are crucial to curb hypertension development and improve management in SSA.

Kidney adolescent and young adult clinic: A transition model in Africa.

Adolescents and Young Adults (AYAs) with chronic kidney disease (CKD) have challenges unique to this developmental period, with increased rates of high-risk behavior and non-adherence to therapy which may impact the progression of kidney disease and their requirement for kidney replacement therapy (KRT). Successful transition of AYA patients are particularly important in low- and middle-income countries (LMICs) where KRT is limited, rationed or not available. Kidney AYA transition clinics have the potential to improve clinical outcomes but there is a paucity of data on the clinical translational impact of these clinics in Africa. This review is a reflection of the 20-year growth and development of the first South African kidney AYA transition clinic. We describe a model of care for patients with CKD, irrespective of etiology, aged 10-25 years, transitioning from pediatric to adult nephrology services. This unique service was established in 2002 and re-designed in 2015. This multidisciplinary integrated transition model has improved patient outcomes, created peer support groups and formed a training platform for future pediatric and adult nephrologists. In addition, an Adolescent Centre of Excellence has been created to compliment the kidney AYA transition model of care. The development of this transition pathway challenges and solutions are explored in this article. This is the first kidney AYA transition clinic in Africa. The scope of this service has expanded over the last two decades. With limited resources in LMICs, such as KRT, the structured transition of AYAs with kidney disease is not only possible but essential. It is imperative to preserve residual kidney function, maximize the kidney allograft lifespan and improve adherence, to enable young individuals an opportunity to lead productive lives.

High prevalence but lack of awareness of hypertension in South Africa, particularly among men and young adults.

Cardiovascular disease (CVD) is a leading cause of death in South Africa (SA) and high blood pressure (BP) is the primary risk factor. However, hypertension prevalence is high, BP control is poor and CV events occur at a younger age than in Europe or America. Increasing screening, raising awareness and improving management of hypertension are critical to prevent CVD in SA. May Measurement Month (MMM) is a global initiative of the International Society of Hypertension aimed at raising awareness of high BP. As part of the MMM campaign, in SA (2017, 2018, 2019 and 2021), BP measurements and a cross-sectional survey of volunteers aged ≥ 18years were performed. Of 11,320 individuals (age 36.6 ± 16.8years) screened, 29.7% had hypertension (systolic BP/diastolic BP ≥ 140/90 mmHg or antihypertensive medication use) and the prevalence was higher (p < 0.0001) in men (35.6%) than in women (26.3%). Of those with hypertension, only 54.3% were aware and 46.8% were receiving antihypertensive medication, and 53.7% of these had controlled BP. In men with hypertension, awareness (45.2%, treatment (38.2%) and controlled BP on antihypertensive medication (45.2%) were lower (p < 0.0001) than in women (awareness: 60.8%; treatment: 53.5%; controlled BP: 58.3%). In young participants (age < 40years), 15.6% had hypertension, 18.6% of these were on treatment but 76.0% were not aware, and only 57.7% had controlled BP. The high prevalence of hypertension, but low levels of awareness, treatment, and BP control in SA, especially in young adults and men, highlight the need for systematic BP screening programmes and improvements in education and management of hypertension.

Comparing Cardiovascular Outcomes and Costs of Perindopril-, Enalapril- or Losartan-Based Antihypertensive Regimens in South Africa: Real-World Medical Claims Database Analysis.

INTRODUCTION: Differences in class or molecule-specific effects between renin-angiotensin-aldosterone system (RAAS) inhibitors have not been conclusively demonstrated. This study used South African data to assess clinical and cost outcomes of antihypertensive therapy with the three most common RAAS inhibitors: perindopril, losartan and enalapril. METHODS: Using a large, South African private health insurance claims database, we identified patients with a hypertension diagnosis in January 2015 receiving standard doses of perindopril, enalapril or losartan, alone or in combination with other agents. From claims over the subsequent 5 years, we calculated the risk-adjusted rate of the composite primary outcome of myocardial infarction, ischaemic heart disease, heart failure or stroke; rate of all-cause mortality; and costs per life per month (PLPM), with adjustments based on demographic characteristics, healthcare plan and comorbidity. RESULTS: Overall, 32,857 individuals received perindopril, 16,693 losartan and 13,939 enalapril. Perindopril-based regimens were associated with a significantly lower primary outcome rate (205 per 1000 patients over 5 years) versus losartan (221; P < 0.0001) or enalapril (223; P < 0.0001). The risk-adjusted all-cause mortality rate was lower with perindopril than enalapril (100 vs. 139 deaths per 1000 patients over 5 years; P = 0.007), but not losartan (100 vs. 94; P = 0.650). Mean (95% confidence interval) overall risk-adjusted cost PLPM was Rands (ZAR) 1342 (87-8973) for perindopril, ZAR 1466 (104-9365) for losartan (P = 0.0044) and ZAR 1540 (77-10,546) for enalapril (P = 0.0003). CONCLUSION: In South African individuals with private health insurance, a perindopril-based antihypertensive regimen provided better clinical and cost outcomes compared with other regimens.

Towards Evidence-Based Implementation of Pharmacogenomics in Southern Africa: Comorbidities and Polypharmacy Profiles across Diseases.

Pharmacogenomics may improve patient care by guiding drug selection and dosing; however, this requires prior knowledge of the pharmacogenomics of drugs commonly used in a specific setting. The aim of this study was to identify a preliminary set of pharmacogenetic variants important in Southern Africa. We describe comorbidities in 3997 patients from Malawi, South Africa, and Zimbabwe. These patient cohorts were included in pharmacogenomic studies of anticoagulation, dyslipidemia, hypertension, HIV and breast cancer. The 20 topmost prescribed drugs in this population were identified. Using the literature, a list of pharmacogenes vital in the response to the top 20 drugs was constructed leading to drug-gene pairs potentially informative in translation of pharmacogenomics. The most reported morbidity was hypertension (58.4%), making antihypertensives the most prescribed drugs, particularly amlodipine. Dyslipidemia occurred in 31.5% of the participants, and statins were the most frequently prescribed as cholesterol-lowering drugs. HIV was reported in 20.3% of the study participants, with lamivudine/stavudine/efavirenz being the most prescribed antiretroviral combination. Based on these data, pharmacogenes of immediate interest in Southern African populations include ABCB1, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, SLC22A1, SLCO1B1 and UGT1A1. Variants in these genes are a good starting point for pharmacogenomic translation programs in Southern Africa.

Task shifting roles, interventions and outcomes for kidney and cardiovascular health service delivery among African populations: a scoping review.

BACKGROUND: Human resources for health (HRH) shortages are a major limitation to equitable access to healthcare. African countries have the most severe shortage of HRH in the world despite rising communicable and non-communicable disease (NCD) burden. Task shifting provides an opportunity to fill the gaps in HRH shortage in Africa. The aim of this scoping review is to evaluate task shifting roles, interventions and outcomes for addressing kidney and cardiovascular (CV) health problems in African populations. METHODS: We conducted this scoping review to answer the question: "what are the roles, interventions and outcomes of task shifting strategies for CV and kidney health in Africa?" Eligible studies were selected after searching MEDLINE (Ovid), Embase (Ovid), CINAHL, ISI Web of Science, and Africa journal online (AJOL). We analyzed the data descriptively. RESULTS: Thirty-three studies, conducted in 10 African countries (South Africa, Nigeria, Ghana, Kenya, Cameroon, Democratic Republic of Congo, Ethiopia, Malawi, Rwanda, and Uganda) were eligible for inclusion. There were few randomized controlled trials (n = 6; 18.2%), and tasks were mostly shifted for hypertension (n = 27; 81.8%) than for diabetes (n = 16; 48.5%). More tasks were shifted to nurses (n = 19; 57.6%) than pharmacists (n = 6; 18.2%) or community health workers (n = 5; 15.2%). Across all studies, the most common role played by HRH in task shifting was for treatment and adherence (n = 28; 84.9%) followed by screening and detection (n = 24; 72.7%), education and counselling (n = 24; 72.7%), and triage (n = 13; 39.4%). Improved blood pressure levels were reported in 78.6%, 66.7%, and 80.0% for hypertension-related task shifting roles to nurses, pharmacists, and CHWs, respectively. Improved glycaemic indices were reported as 66.7%, 50.0%, and 66.7% for diabetes-related task shifting roles to nurses, pharmacists, and CHWs, respectively. CONCLUSION: Despite the numerus HRH challenges that are present in Africa for CV and kidney health, this study suggests that task shifting initiatives can improve process of care measures (access and efficiency) as well as identification, awareness and treatment of CV and kidney disease in the region. The impact of task shifting on long-term outcomes of kidney and CV diseases and the sustainability of NCD programs based on task shifting remains to be determined.

It is strongly recommended to not conduct, fund, or publish research studies that use spot urine samples with estimating equations to assess individuals' sodium (salt) intake in association with health outcomes: a policy statement of the World Hypertension League, International Society of Hypertension and Resolve to Save Lives.

Spot urine samples with estimating equations have been used to assess individuals' sodium (salt) intake in association with health outcomes. There is large random and systematic error in estimating sodium intake using this method and spurious health outcome associations. Substantial controversy has resulted from false claims the method is valid. Hence, the World Hypertension League, International Society of Hypertension and Resolve to Save Lives, supported by 21 other health organizations, have issued this policy statement that strongly recommends that research using spot urine samples with estimating equations to assess individuals' sodium (salt) intake in association with health outcomes should not be conducted, funded or published. Literature reviews on the health impacts of reducing dietary sodium that include studies that have used spot and short duration timed urine samples with estimating equations need to explicitly acknowledge that the method is not recommended to be used and is associated with spurious health outcome associations.

Addressing global disparities in blood pressure control: perspectives of the International Society of Hypertension.

ABSTRACT: Raised blood pressure (BP) is the leading cause of preventable death in the world. Yet, its global prevalence is increasing, and it remains poorly detected, treated, and controlled in both high- and low-resource settings. From the perspective of members of the International Society of Hypertension based in all regions, we reflect on the past, present, and future of hypertension care, highlighting key challenges and opportunities, which are often region-specific. We report that most countries failed to show sufficient improvements in BP control rates over the past three decades, with greater improvements mainly seen in some high-income countries, also reflected in substantial reductions in the burden of cardiovascular disease and deaths. Globally, there are significant inequities and disparities based on resources, sociodemographic environment, and race with subsequent disproportionate hypertension-related outcomes. Additional unique challenges in specific regions include conflict, wars, migration, unemployment, rapid urbanization, extremely limited funding, pollution, COVID-19-related restrictions and inequalities, obesity, and excessive salt and alcohol intake. Immediate action is needed to address suboptimal hypertension care and related disparities on a global scale. We propose a Global Hypertension Care Taskforce including multiple stakeholders and societies to identify and implement actions in reducing inequities, addressing social, commercial, and environmental determinants, and strengthening health systems implement a well-designed customized quality-of-care improvement framework.

A Differential Response to Antihypertensive Therapy in African Men and Women: Insights From the CREOLE Trial.

BACKGROUND: We sought to address the paucity of data to support the evidence-based management of hypertension to achieve optimal blood pressure (BP) control on a sex-specific basis in Africa. METHODS: We undertook a post hoc analysis of the multicenter, randomized CREOLE (Comparison of Three Combination Therapies in Lowering Blood Pressure in Black Africans) Trial to test the hypothesis that there would be clinically important differences in office BP control between African men and women. We compared the BP levels of 397 and 238 hypertensive women (63%, 50.9 ± 10.5 years) and men (51.2 ± 11.3 years) from 10 sites across sub-Saharan Africa who completed baseline and 6-month profiling according to their randomly allocated antihypertensive treatment. RESULTS: Overall, 442/635 (69.6%) participants achieved an office BP target of <140/90 mm Hg at 6 months; comprising more women (286/72.0%) than men (156/65.5%) (adjusted odds ratio [OR] 1.59, 95% confidence interval [CI] 1.07-2.39; P = 0.023). Women randomized to amlodipine-hydrochlorothiazide (HCTZ) (adjusted OR 3.03, 95% CI 1.71-5.35; P < 0.001) or amlodipine-perindopril (adjusted OR 2.62, 95% CI 1.49-4.58; P = 0.01) were more likely to achieve this target compared with perindopril-HCTZ. Among men, there were no equivalent treatment differences-amlodipine-HCTZ (OR 1.54, 95% CI 0.76-3.12; P = 0.23) or amlodipine-perindopril (OR 1.32, 95% CI 0.65-2.67; P = 0.44) vs. perindopril-HCTZ. Among the 613 participants (97%) with 24-hour ambulatory BP monitoring, women had significantly lower systolic (124.1 ± 18.1 vs. 127.3 ± 16.9; P = 0.028) and diastolic (72.7 ± 10.4 vs. 75.1 ± 10.5; P = 0.007) BP levels at 6 months compared with men. CONCLUSIONS: These data suggest clinically important differences in the therapeutic response to antihypertensive combination therapy among African women compared with African men.

Preventing the Next Pandemic: The Case for Investing in Circulatory Health - A Global Coalition for Circulatory Health Position Paper.

The Coronavirus Disease 2019 (COVID-19) has had a continuous and robust impact on world health. The resulting COVID-19 pandemic has had a devastating physical, mental and fiscal impact on the millions of people living with noncommunicable diseases (NCDs). In addition to older age, people living with CVD, stroke, obesity, diabetes, kidney disease, and hypertension are at a particularly greater risk for severe forms of COVID-19 and its consequences. Meta-analysis indicates that hypertension, diabetes, chronic kidney disease, and thrombotic complications have been observed as both the most prevalent and most dangerous co-morbidities in COVID-19 patients. And despite the nearly incalculable physical, mental, emotional, and economic toll of this pandemic, forthcoming public health figures continue to place cardiovascular disease as the number one cause of death across the globe in the year 2020. The world simply cannot wait for the next pandemic to invest in NCDs. Social determinants of health cannot be addressed only through the healthcare system, but a more holistic multisectoral approach with at its basis the Sustainable Development Goals (SDGs) is needed to truly address social and economic inequalities and build more resilient systems. Yet there is reason for hope: the 2019 UN Political Declaration on UHC provides a strong framework for building more resilient health systems, with explicit calls for investment in NCDs and references to fiscal policies that put such investment firmly within reach. By further cementing the importance of addressing circulatory health in a future Framework Convention on Emergency Preparedness, WHO Member States can take concrete steps towards a pandemic-free future. As the chief representatives of the global circulatory health community and patients, the Global Coalition for Circulatory Health calls for increased support for the healthcare workforce, global vaccine equity, embracing new models of care and digital health solutions, as well as fiscal policies on unhealthy commodities to support these investments.

COVID-19 and the kidney: A South African state healthcare experience.

The first documented case of SARS-CoV-2 infection was confirmed in South Africa (SA) in March 2020. The Western Cape (WC) province was the initial epicenter. The pandemic peaked in July 2020 when 76,851 cases were documented and 2,323 deaths reported. COVID-19 can have multisystem involvement. Acute kidney injury (AKI) is well-documented and associated with increased mortality. We report our experience as the pandemic evolved in the WC province, focusing on those patients with a SARS-CoV-2 positive test presenting with AKI. We also reviewed our chronic dialysis cohort and renal transplant recipients who tested positive to assess incidence and outcomes. All patients presenting to nephrology services at the four main public hospitals were included. Information regarding demographics, co-morbidities, medical care, laboratory data, and outcomes were recorded. There were 86 patients referred with AKI, 48 required dialysis, and 47 died. There were 52 patients admitted to the intensive care unit with AKI (37 received dialysis, 1 of whom survived). In those presenting with AKI, diabetes, obesity, hypertension, and HIV were the most common comorbidities. Of the 295 patients receiving chronic dialysis within our services, 31 tested positive for SARS-CoV-2, and 6 died. Of the 45 kidney transplant recipients who tested positive, 9 died. Only 3 required dialysis. In conclusion, we report a high rate of AKI and poor prognosis in those requiring kidney replacement therapy, a better prognosis than anticipated was found in our chronic dialysis cohort, and high numbers of admissions were required for renal transplant recipients.

Hypertension in adolescents and young adults referred to a tertiary hypertension clinic in Cape Town, South Africa.

To audit the young patients referred to the Hypertension Clinic at Groote Schuur Hospital that predominately serves the underprivileged communities of Cape Town.Folders of patients between the ages of 15 and 30 years over a 2 year period were reviewed. The data collected included demographic, clinical and laboratory data, investigations, causes of hypertension, and presence of hypertensive organ damage.Of the 110 patients reviewed, 61 (55.5%) were females, 22 (20%) Black African, and 88 (80%) of Mixed Ancestry. Eight (7.3%) were found to be normotensive, 16 (14.5%) had a secondary cause and 86 (78.2%) had essential hypertension. Thirty five (31.8%) were current or previous smokers, and 11 (10%) admitted to current or prior use of metamphetamines. A family history of hypertension in a first degree relative was present in 80 (72.7%) patients. Comorbidities present were diabetes in 7 (6.4%) patients, metabolic syndrome in 13 (11.8%), and obesity in 26 (23.6%), but 42.6% had a body mass index (BMI) <25 kg/m. Chronic kidney disease (CKD) was present in 29 (26.4%) patients and ECG left ventricular hypertrophy in 56 (50.9%). Overall organ damage was present in 72 (65.5%) patients.In this cohort of young hypertensives most patients had essential hypertension with a strong family history. Significant organ damage was identified. High risk behavior, including smoking and illicit drug use, and obesity were identified as contributing factors. Secondary causes were identified in 14.2%. These results suggest a targeted approach to the investigation of young hypertensives for secondary causes, and significant opportunities for lifestyle intervention.

Granulomatous interstitial nephritis on renal biopsy in human immunodeficiency virus positive patients: Prevalence and causes in Cape Town, South Africa.

South Africa continues to be burdened by human immunodeficiency virus (HIV) and tuberculosis (TB). In Cape Town, the epidemic of HIV-TB co-infection is as high as 70%. Granulomatous interstitial nephritis (GIN) has increased in frequency on renal biopsy. This study aimed to determine GIN prevalence and causes in HIV-positive patients as well as renal outcomes, patient survival and associated factors. This observational cohort study reviewed HIV-positive renal biopsies for GIN from 2005 to 2012. Causes of GIN (medications, TB, fungal and other), and baseline characteristics were analysed. A comparison of baseline data, renal function and survival was made between GIN and non-GIN cohorts. There were 45/316 biopsies demonstrating GIN. TB was the likely cause of GIN in 27 (60%) and 9 (20%) were due to a drug. Low estimated glomerular filtration rate was a statistically significant factor associated with mortality in both GIN (P = 0.045) and non-GIN cohorts (P < 0.000). In the GIN group, there were 12 (26.7%) deaths. Mortality for all patients was greatest in the first 6 months (P = 0.057). TB co-infection in both cohorts was associated with a higher mortality. The multivariate logistic regression demonstrated that a higher urine protein/creatinine ratio (uPCR) and lower estimated glomerular filtration rate were statistically associated with death. GIN is common in HIV-positive renal biopsies in Cape Town. TB-GIN was the commonest cause and associated with a high early mortality. GIN should be considered in HIV-positive patients with acute kidney injury, its presence conveys a survival benefit. There is a need for improved diagnostic accuracy and treatment strategies of TB-GIN.

Outcomes and challenges of a kidney transplant programme at Groote Schuur Hospital, Cape Town: A South African perspective.

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.

Physiological Phenotyping for Personalized Therapy of Uncontrolled Hypertension in Africa.

OBJECTIVES: African and African American hypertensives tend to retain salt and water, with lower levels of plasma renin and more resistant hypertension. We tested the hypothesis that physiological phenotyping with plasma renin and aldosterone would improve blood pressure control in uncontrolled hypertensives in Africa. METHODS: Patients at hypertension clinics in Nigeria, Kenya, and South Africa with a systolic blood pressure >140 mm Hg or diastolic pressure > 90 mm Hg despite treatment were allocated to usual care (UC) vs. physiologically individualized care (PhysRx). Plasma renin activity and aldosterone were measured using ELISA kits. Patients were followed for 1 year; the primary outcome was the percentage of patients achieving blood pressure <140 mm Hg and diastolic <90 mm Hg. RESULTS: Results are presented for the 94/105 participants who completed the study (42 UC, 52 PhysRx). Control of both systolic and diastolic pressures was obtained in 11.1% of UC vs. 50.0% of PhysRx (P = 0.0001). Systolic control was achieved in 13.9% of UC vs. 60.3% of PhysRx (P = 0.0001); diastolic control in 36.1% of UC vs. 67.2% of PhysRx, vs. (P = 0.003). Number of visits and total number of medications were not significantly different between treatment groups, but there were differences across the sites. There were important differences in prescription of amiloride as specified in the PhysRx algorithm. CONCLUSIONS: Physiologically individualized therapy based on renin/aldosterone phenotyping significantly improved blood pressure control in a sample of African patients with uncontrolled hypertension. This approach should be tested in African American and other patients with resistant hypertension. Registered as ISRCTN69440037.

Disparities in dialysis allocation: An audit from the new South Africa.

End Stage Kidney Disease (ESKD) is a public health problem with an enormous economic burden. In resource limited settings management of ESKD is often rationed. Racial and socio-economic inequalities in selecting candidates have been previously documented in South Africa. New guidelines for dialysis developed in the Western Cape have focused on prioritizing treatment. With this in mind we aimed at exploring whether the new guidelines would improve inequalities previously documented. A retrospective study of patients presented to the selection committee was conducted at Groote Schuur Hospital. A total of 564 ESKD patients presented between 1 January 2008 and 31 December 2012 were assessed. Half of the patients came from low socioeconomic areas, and presentation was late with either overt uremia (n = 181, 44·4%) or fluid overload (n = 179, 43·9%). More than half (53·9%) of the patients were not selected for the program. Predictors of non-acceptance onto the program included age above 50 years (OR 0·3, p = 0·001), unemployment (OR 0·3, p<0·001), substance abuse (OR 0·2, p<0·001), diabetes (OR 0·4, p = 0·016) and a poor psychosocial assessment (OR 0·13, p<0·001). Race, gender and marital status were not predictors. The use of new guidelines has not led to an increase in inequalities. In view of the advanced nature of presentation greater efforts need to be made to prevent early kidney disease, to allocate more resources to renal replacement therapy in view of the loss of young and potentially productive life.

The association of the R563Q genotype of the ENaC with phenotypic variation in Southern Africa.

BACKGROUND: The epithelial sodium channel (ENaC) may be a common underlying pathway for the development of primary hypertension. In South Africa, the R563Q variant of the ENaC is associated with low-renin-low-aldosterone hypertension and preeclampsia in black Africans and mixed-ancestry peoples. The purpose of this study was to investigate the prevalence of the R563Q variant in the multiethnic populations of South Africa, its association with hypertension and response to amiloride in patients with resistant hypertension. METHODS: Samples were obtained from hypertensives and normotensive controls in Cape Town and Johannesburg, and unselected San living in the rural areas of the Northern Cape and Namibia. Resistant hypertensives with the R563Q variant were treated with amiloride. RESULTS: One thousand nine hundred and thirty nine (1,468 hypertensives, 471 controls) subjects were recruited. Eighty-seven (5.9%) of the hypertensives were R563Q heterozygote vs. 8 (1.7%) of the normotensives (P < 0.0005). In the Namibian and Northern Cape San 19.5% and 18.8% of subjects were R563Q positive. There was no association with hypertension. Spot sodium excretion was lower in the San compared to urban subjects (7.3 vs. 12.2 mmol/mmol, P = 0.016). Twenty-two R563Q heterozygote patients with resistant hypertension received amiloride with a mean reduction in blood pressure (BP) of 36/17 mm Hg (P < 0.0001). CONCLUSIONS: The R563Q variant is strongly associated with hypertension in urban areas in South Africa. The San are the likely origin of the variant, but it is not associated with hypertension, presumably due to their lower sodium intake. Screening patients with resistant hypertension in South Africa for the R563Q variant provides a feasible pharmacogenetic approach to treatment.