Consistency of alerts generated by, and implementation of, the NHS England acute kidney injury detection algorithm in English laboratories.

BACKGROUND: National Health Services (NHS) England mandates that an acute kidney injury (AKI) detection algorithm be embedded in laboratories. We evaluated the implementation of the algorithm and the consistency of alerts submitted to the United Kingdom Renal Registry (UKRR). METHODS: Code was developed to simulate the syntax of the AKI detection algorithm, executed on data from local laboratories submitted to the UKRR, including alerts and serum creatinine (SCr) results spanning 15 months before and after the alert submission. Acute kidney injury alerts were categorized into stages 0/1/2/3. Inter-rater agreement (Gwet's AC1) was used to compare local and centrally derived alerts at individual laboratory and commercial laboratory information management system (LIMS) levels, penalizing extreme disagreements. RESULTS: The analysis included 9,096,667 SCr results from 29 labs (475,634 patients; median age 72 years, 47% female) between algorithm activation and data extraction (September 30, 2020). Laboratories and the central simulation generated 1,579,633 and 1,646,850 non-zero AKI alerts, respectively. Agreement was high within known laboratory information management system providers (0.97-0.98) but varied across individual laboratories (overall range 0.17-0.98, 0.17-0.23 in three). Agreement tended to be lower (Gwet's AC1 0.88) with the highest baseline SCr quartile (median 164 µmol/L). CONCLUSIONS: Overall, alerts submitted to the UKRR are a valid source of AKI surveillance but there are concerns about inconsistent laboratory practices, incomplete adoption of the NHSE algorithm code, alert suppression, and variable interpretation of guidelines. Future efforts should audit and support laboratories with low agreement rates, and explore reasons for lower agreement in individuals with pre-existing CKD.

Genetic Variation in ABCB1, ADRB1, CYP3A4, CYP3A5, NEDD4L and NR3C2 Confers Differential Susceptibility to Resistant Hypertension among South Africans.

Resistant hypertension (RHTN) prevalence ranges from 4 to 19% in Africa. There is a paucity of data on the role of genetic variation on RHTN among Africans. We set out to investigate the role of polymorphisms in ABCB1, ADRB1, CYP3A4, CYP3A5, NEDD4L, and NR3C2, on RHTN susceptibility among South Africans. Using a retrospective matched case-control study, 190 RHTN patients (cases: blood pressure (BP) ≥ 140/90 mmHg on ≥3 anti-hypertensives or BP < 140/90 mmHg on >3 anti-hypertensives) and 189 non-RHTN patients (controls: <3 anti-hypertensives, BP < 140/90 or ≥140/90 mmHg), 12 single nucleotide polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), quantitative PCR and Sanger sequencing. Genetic association analyses were conducted using the additive model and multivariable logistic regression. Homozygosity for CYP3A5 rs776746C/C genotype (p = 0.02; OR: 0.44; CI: 0.22-0.89) was associated with reduced risk for RHTN. Homozygous ADRB1 rs1801252G/G (p = 0.02; OR: 3.30; CI: 1.17-10.03) and NEDD4L rs4149601A/A genotypes (p = 0.001; OR: 3.82; CI: 1.67-9.07) were associated with increased risk for RHTN. Carriers of the of ADRB1 rs1801252-rs1801253 G-C haplotype had 2.83-fold odds of presenting with RHTN (p = 0.04; OR: 2.83; CI: 1.05-8.20). These variants that are associated with RHTN may have clinical utility in the selection of antihypertensive drugs in our population.

Genetic Factors Contributing to the Pathogenesis of Essential Hypertension in Two African Populations.

The African continent has the highest prevalence of hypertension globally, with South Africa reporting the highest prevalence in Southern Africa. While the influence of genetic variability in the pathogenesis of hypertension is well described internationally, limited reports are available for African populations. This study aimed to assess the association of genetic variants and essential hypertension in a cohort of two ethnic South African population groups. Two hundred and seventy-seven hypertensive and one hundred and seventy-six normotensive individuals were genotyped for 78 variants. Genotyping was performed using the Illumina GoldenGate Assay and allele-specific polymerase chain reaction. The association of variants was assessed using the Fisher Exact test under the additive and allelic genetic models, while multivariate logistic regression was used to predict the development of hypertension. Five variants (CYP11B2 rs179998, AGT rs5051 and rs699, AGTR1 rs5186, and ACE rs4646994) were significantly associated with essential hypertension in the cohort under study. Furthermore, AGTR1 rs5186 and AGT rs699 were identified as risk factors for the development of hypertension in both ethnic groups. In two ethnic South African populations, an association was observed between renin-angiotensin-aldosterone system (RAAS)-related genes and the development of hypertension.

Major Genetic Drivers of Statin Treatment Response in African Populations and Pharmacogenetics of Dyslipidemia Through a One Health Lens.

A One Health lens is increasingly significant to address the intertwined challenges in planetary health concerned with the health of humans, nonhuman animals, plants, and ecosystems. A One Health approach can benefit the public health systems in Africa that are overburdened by noncommunicable, infectious, and environmental diseases. Notably, the COVID-19 pandemic revealed the previously overlooked two-fold importance of pharmacogenetics (PGx), for individually tailored treatment of noncommunicable diseases and environmental pathogens. For example, dyslipidemia, a common cardiometabolic risk factor, has been identified as an independent COVID-19 severity risk factor. Observational data suggest that patients with COVID-19 infection receiving lipid-lowering therapy may have better outcomes. However, among African patients, the response to these drugs varies from patient to patient, pointing to the possible contribution of genetic variation in important pharmacogenes. The PGx of lipid-lowering therapies may underlie differences in treatment responses observed among dyslipidemia patients as well as patients comorbid with COVID-19 and dyslipidemia. Genetic variations in APOE, ABCB1, CETP, CYP2C9, CYP3A4, CYP3A5, HMGCR, LDLR, NPC1L1, and SLCO1B1 genes affect the pharmacogenomics of statins, and they have individually been linked to differential responses to dyslipidemia and COVID-19 treatment. African populations are underrepresented in PGx research. This leads to poor accounting of additional diverse genetic variants that could be important in understanding interindividual and between-population variations in therapeutic responses to dyslipidemia and COVID-19. This expert review examines and synthesizes the salient and priority PGx variations, as seen through a One Health lens in Africa, to improve and inform personalized medicine in both dyslipidemia and COVID-19.

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.

Changes in blood pressure after catheter-based renal denervation in South Africa.

BACKGROUND: Renal denervation (RDN) is an interventional treatment for patients with uncontrolled hypertension. The Global SYMPLICITY Registry (GSR) is a prospective, all-comer, world-wide registry designed to assess the safety and efficacy of RDN. We evaluated the outcomes in South African patients in the GSR over 12 months. METHODS: Eligible patients with hypertension had a daytime mean blood pressure (BP) > 135/85 mmHg or night-time mean BP > 120/70 mmHg. Office and 24-hour ambulatory systolic BP reduction and adverse events over 12 months were evaluated. RESULTS: South African patients (n = 36) in the GSR had a mean age of 54.4 ± 9.9 years with a median of four prescribed antihypertensive medication classes. At 12 months, mean changes in office and 24-hour ambulatory systolic BP were -16.9 ± 24.2 and -15.3 ± 18.5 mmHg, respectively, with only one adverse event recorded. CONCLUSIONS: RDN safety and efficacy in South African patients were consistent with world-wide GSR results.

The Evolving Spectrum of Kidney Histology in HIV-Positive Patients in South Africa.

Introduction: Sub-Saharan Africa remains challenged by the highest burden of human immunodeficiency virus (HIV), an epidemic of tuberculosis (TB), and increasing number of people with HIV (PWH) on antiretroviral therapy (ART), all of which may result in kidney injury. Methods: This observational cohort study describes the spectrum of kidney disease in PWH in South Africa, between 2005 and 2020. Kidney biopsies were analyzed in 4 time periods as follows: early ART rollout (2005-2009), tenofovir disoproxil (TDF) introduction (2010-2012), TDF-based fixed dose combination (2013-2015), and ART at HIV diagnosis (2016-2020). Logistic regression was used to identify factors associated with HIV-associated nephropathy or focal segmental glomerulosclerosis (HIVAN/FSGS) and tubulointerstitial disease (TID). Results: We included 671 participants (median age 36, interquartile range, 21-44 years; 49% female; median CD4 cell count 162 [interquartile range, 63-345] cells/mm3). Over time, ART (31%-65%, P < 0.001), rate of HIV suppression (20%-43%, P < 0.001), nonelective biopsies (53%-72%, P < 0.001), and creatinine at biopsy (242-449 µmol/l, P < 0.001) increased. A decrease in HIVAN (45%-29% P < 0.001) was accompanied by an increase in TID (13%-33%, P < 0.001). Granulomatous interstitial nephritis accounted for 48% of TID, mostly because of TB. Exposure to TDF was strongly associated with TID (adjusted odds ratio 2.99, 95% confidence interval 1.89-4.73 P < 0.001). Conclusion: As ART programs intensified and increasingly used TDF, the spectrum of kidney histology in PWH evolved from a predominance of HIVAN in the early ART era to TID in recent times. The increase in TID is likely due to multiple exposures that include TB, sepsis, and TDF as well as other insults.

Primary Sjögren's syndrome with renal tubular acidosis and central pontine myelinolysis: An unusual triad.

Primary Sjögren's syndrome (pSS) is a complex, multisystem autoimmune disorder. It is characterized by lymphocytic infiltration of the exocrine glands. In the setting of pSS, the presence of systemic disease is an important prognostic determinant, but involvement of the kidney is uncommon. The triad of pSS, distal renal tubular acidosis (dRTA), and central pontine myelinolysis (CPM) is rare and potentially fatal. A 42-year-old woman presented with dRTA, profound hypokalemia, and CPM characterized by progressive global quadriparesis, ophthalmoplegia, and encephalopathy. Sjögren's syndrome was diagnosed based on sicca symptoms, clinical features, and strongly positive anti-SSA/Ro and anti-SSB/La autoantibodies. The patient responded well to electrolyte replacement, acid-base correction, corticosteroids, and subsequent cyclophosphamide therapy. Early recognition and appropriate treatment resulted in good kidney and neurological outcomes in this case. This report highlights the need to consider the diagnosis of pSS in unexplained dRTA and CPM, as it has a favorable prognosis if recognized and managed timeously.

Pharmacogenomics of Hypertension in Africa: Paving the Way for a Pharmacogenetic-Based Approach for the Treatment of Hypertension in Africans.

In Africa, the burden of hypertension has been rising at an alarming rate for the last two decades and is a major cause for cardiovascular disease (CVD) mortality and morbidity. Hypertension is characterised by elevated blood pressure (BP) ≥ 140/90 mmHg. Current hypertension guidelines recommend the use of antihypertensives belonging to the following classes: calcium channel blockers (CCB), angiotensin converting inhibitors (ACEI), angiotensin receptor blockers (ARB), diuretics, ß-blockers, and mineralocorticoid receptor antagonists (MRAs), to manage hypertension. Still, a considerable number of hypertensives in Africa have their BP uncontrolled due to poor drug response and remain at the risk of CVD events. Genetic factors are a major contributing factor, accounting for 20% to 80% of individual variability in therapy and poor response. Poor response to antihypertensive drug therapy is characterised by elevated BPs and occurrence of adverse drug reactions (ADRs). As a result, there have been numerous studies which have examined the role of genetic variation and its influence on antihypertensive drug response. These studies are predominantly carried out in non-African populations, including Europeans and Asians, with few or no Africans participating. It is important to note that the greatest genetic diversity is observed in African populations as well as the highest prevalence of hypertension. As a result, this warrants a need to focus on how genetic variation affects response to therapeutic interventions used to manage hypertension in African populations. In this paper, we discuss the implications of genetic diversity in CYP11B2, GRK4, NEDD4L, NPPA, SCNN1B, UMOD, CYP411, WNK, CYP3A4/5, ACE, ADBR1/2, GNB3, NOS3, B2, BEST3, SLC25A31, LRRC15 genes, and chromosome 12q loci on hypertension susceptibility and response to antihypertensive therapy. We show that African populations are poorly explored genetically, and for the few characterised genes, they exhibit qualitative and quantitative differences in the profile of pharmacogene variants when compared to other ethnic groups. We conclude by proposing prioritization of pharmacogenetics research in Africa and possible adoption of pharmacogenetic-guided therapies for hypertension in African patients. Finally, we outline the implications, challenges, and opportunities these studies present for populations of non-European descent.

Disseminated Mycobacterium Tuberculosis and IgA Nephropathy.

Mycobacterium tuberculosis (MTB) is an under-recognised cause of genitourinary disease. IgA nephropathy (IgAN), a leading cause of glomerulonephritis worldwide, has been described as a rare consequence of disseminated MTB infection. In this case report, we present the first case of MTB associated IgAN in Africa. Finding IgAN on kidney biopsy in an MTB endemic area should prompt a thorough investigation for MTB to increase the chance of remission of IgAN and prevent inappropriate use of immunosuppression.

Effect of 3, 2-Drug Combinations of Antihypertensive Therapies on Blood Pressure Variability in Black African Patients: Secondary Analyses of the CREOLE Trial.

BACKGROUND: The effect of 3 commonly recommended combinations of anti-hypertensive agents-amlodipine plus hydrochlorothiazide (calcium channel blocker [CCB]+thiazide), amlodipine plus perindopril (CCB+ACE [angiotensin-converting enzyme]-inhibitor), and perindopril plus hydrochlorothiazide (ACE-inhibitor+thiazide) on blood pressure variability (V) are unknown. METHODS: We calculated the blood pressure variability (BPV) in 405 patients (130, 146, and 129 randomized to ACE-inhibitor+thiazide, CCB+thiazide, and CCB+ACE-inhibitor, respectively) who underwent ambulatory blood pressure monitoring after 6 months of treatment in the Comparisons of Three Combinations Therapies in Lowering Blood Pressure in Black Africans trial (CREOLE) of Black African patients. BPV was calculated using the SD of 30-minute interval values for 24-hour ambulatory BPs and for confirmation using the coefficient of variation. Linear mixed model regression was used to calculate mean differences in BPV between treatment arms. Within-clinic BPV was also calculated from the mean SD and coefficient of variation of 3 readings at clinic visits. RESULTS: Baseline distributions of age, sex, and blood pressure parameters were similar across treatment groups. Participants were predominately male (62.2%) with mean age 50.4 years. Those taking CCB+thiazide had significantly reduced ambulatory systolic and diastolic BPV compared with those taking ACE-inhibitor+thiazide. The CCB+thiazide and CCB+ACE-inhibitor groups showed similar BPV. Similar patterns of BPV were apparent among groups using within-clinic blood pressures and when assessed by coefficient of variation. CONCLUSIONS: Compared with CCB-containing combinations, ACE-inhibitor plus thiazide was associated with higher levels, generally significant, of ambulatory and within-clinic systolic and diastolic BPV. These results supplement the differential ambulatory blood pressure-lowering effects of these therapies in the CREOLE trial.

Challenges of Conducting Clinical Trials during the SARS-CoV-2 Pandemic: The ASCEND Global Program Experience.

The coronavirus disease 2019 pandemic has had an unprecedented effect on health and health care and posed challenges to the conduct of clinical trials.Targeted mitigating strategies, on the basis of early and continued data collection from site surveys, limited disruption to the ASCEND trials.Flexibly allowing hemoglobin assessment at local laboratories to inform randomized treatment dosing was key to limiting the discontinuation of treatment.

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.

Hypertension Pharmacological Treatment in Adults: A World Health Organization Guideline Executive Summary.

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, <14% of adults with hypertension have BP controlled to a systolic/diastolic BP <140/90 mm Hg. We report new hypertension treatment guidelines, developed in accordance with the World Health Organization Handbook for Guideline Development. Overviews of reviews of the evidence were conducted and summary tables were developed according to the Grading of Recommendations, Assessment, Development, and Evaluations approach. In these guidelines, the World Health Organization provides the most current and relevant evidence-based guidance for the pharmacological treatment of nonpregnant adults with hypertension. The recommendations pertain to adults with an accurate diagnosis of hypertension who have already received lifestyle modification counseling. The guidelines recommend BP threshold to initiate pharmacological therapy, BP treatment targets, intervals for follow-up visits, and best use of health care workers in the management of hypertension. The guidelines provide guidance for choice of monotherapy or dual therapy, treatment with single pill combination medications, and use of treatment algorithms for hypertension management. Strength of the recommendations was guided by the quality of the underlying evidence; the tradeoffs between desirable and undesirable effects; patient's values, resource considerations and cost-effectiveness; health equity; acceptability, and feasibility consideration of different treatment options. The goal of the guideline is to facilitate standard approaches to pharmacological treatment and management of hypertension which, if widely implemented, will increase the hypertension control rate world-wide.

High prevalence of non-dipping patterns among Black Africans with uncontrolled hypertension: a secondary analysis of the CREOLE trial.

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).

The relevance of performing 24-hour ambulatory blood pressure and pulse wave analysis in kidney transplant recipients.

Hypertension guidelines recommend out-of-office blood pressure (BP) measurement especially 24-hour ambulatory measurement (ABPM), to diagnose and manage hypertension but this is not routinely performed in kidney transplant units. This study was to determine if 24-hour ABPM, compared with office BP in kidney transplant recipients, would be more informative regarding BP management, and if pulse wave analysis (PWA) would assist in risk stratification. This study included patients older than 18 years, with working graft kidney for > 12 months, and without problems affecting BP measurement and interpretation. After performing office BP measurements, a 24-hour ABPM with additional capability of calculating pulse wave velocity (PWV), augmentation index and central BP was undertaken. Patients were assessed for controlled hypertension, uncontrolled hypertension, masked hypertension, nocturnal hypertension, white coat hypertension, and dipping BP status. Data were analyzed using standard statistical tests. Of 30 patients, 15 were Black Africans and 15 were of Mixed Ancestry with a mean age of 48.9 years. 17 patients were males and 36.7% had controlled hypertension, 30% uncontrolled hypertension, 6.7% white coat hypertension, and 33.3% masked hypertension, of whom 70% had isolated nocturnal hypertension. 70% had a non-dipping, 26.7% a reverse dipping and only 3.3% had a normal dipping BP pattern. The mean difference between brachial systolic BP and central systolic BP was 10.4 mmHg, whereas PWV and augmentation index were similar to healthy populations. Conclusion: In kidney transplant recipients, 24-hour ABPM was superior to office BP in defining hypertensive status that qualified for modification of therapy, but PWA did not contribute to risk assessment.

Clinical Outcomes by Albuminuria Status with Dulaglutide versus Insulin Glargine in Participants with Diabetes and CKD: AWARD-7 Exploratory Analysis.

Background: In the AWARD-7 trial of participants with type 2 diabetes (T2DM) and moderate-to-severe CKD, dulaglutide (DU) treatment slowed decline in eGFR compared with insulin glargine (IG). Treatment with doses of either DU or IG resulted in similar levels of glycemic control and BP. The aim of this analysis was to determine the risk of clinical event outcomes between treatment groups. Methods: Participants with T2DM and CKD categories 3-4 were randomized (1:1:1) to 0.75 or 1.5 mg DU weekly or IG daily as basal therapy, with titrated insulin lispro, for 1 year. The time to occurrence of the composite outcome of ≥40% eGFR decline, ESKD, or death due to kidney disease was compared using a Cox proportional-hazards model. Results: Patients treated with 1.5 mg DU weekly versus IG daily for 1 year had a lower risk of ≥40% eGFR decline or ESKD events in the overall study population (5% versus 11%; hazard ratio, 0.45; 95% CI, 0.20 to 0.97; P=0.04). Most events occurred in the subset of patients with macroalbuminuria, where risk of the composite outcome was substantially lower for 1.5 mg DU versus IG (7% versus 22%; hazard ratio, 0.25; 95% CI, 0.10 to 0.68; P=0.006). No deaths due to kidney disease occurred. Conclusions: Treatment with 1.5 mg DU weekly was associated with a clinically relevant risk reduction of ≥40% eGFR decline or ESKD compared with IG daily, particularly in the macroalbuminuria subgroup of participants with T2DM and moderate-to-severe CKD.

The importance of the epithelial sodium channel in determining salt sensitivity in people of African origin.

Hypertension is highly prevalent in Black Africans and has been found to be associated with worse blood pressure (BP) control and more cardiovascular disease. Black Africans are more salt sensitive with low renin and aldosterone levels. This can be explained in part by variants in the epithelial sodium channel (ENaC) causing an increase in channel activity resulting in sodium and water retention. These variants in the ENaC are increased in the Black African populations presumably due to selective pressure for sodium retention in traditionally low-salt diets. Furthermore, increased endothelial sodium channel activity contributes to the risk of vascular stiffness, which may also result in more difficult to control hypertension. Patients with increased activity of the ENaC are more likely to respond to amiloride (a selective sodium channel antagonist), which has implications for the management of severe and resistant hypertension in Black Africans. A large-scale controlled trial on the use of amiloride compared to usual care is warranted in Blacks with severe or resistant hypertension.

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.