Brian Rayner

Community-Acquired Bacteremia in the Elderly: A Prospective Study of 121 Cases

Objective: To describe community‐acquired bacteremia in the elderly and correlate clinical and laboratory findings with outcome.

A new mutation, R563Q, of the beta subunit of the epithelial sodium channel associated with low-renin, low-aldosterone hypertension.

Objective To determine the relationship between R563Q, a mutation of the renal epithelial sodium channel, and hypertension. Methods Hypertensive patients with low renin and aldosterone, hypokalemia or resistant hypertension were selected for DNA analysis. Genomic DNA encoding the C-terminal domain of the epithelial sodium channel beta subunit from hypertensives and controls was amplified by polymerase chain reaction and screened for the R563Q mutation by digestion with Sfc1 restriction enzyme, or sequenced. Results A previously undescribed mutation, R563Q, of the beta epithelial sodium channel was found in 10 of 139 black hypertensives, but was not present in any of 103 black normotensives, a significant (P = 0.0058) difference in frequency. The frequency of the mutation in the subgroup of black low-renin, low-aldosterone hypertensives (four of 14) was significantly (P = 0.0001) greater than in normotensives, and was also greater (P = 0.041) than in normal-high renin hypertensives, suggesting that R563Q is an activating mutation of the epithelial sodium channel. R563Q was also found in seven out of 250 mixed ancestry hypertensives, and was significantly (P = 0.017) associated with low-renin, low-aldosterone hypertension in this population group. The mutation was found in one of 100 mixed ancestry normotensives but not in any of 136 white hypertensives. Of the 18 R563Q patients, 11 had severe hypertension, leading to renal failure in two cases, while only two had hypokalaemia. Conclusions R563Q, a new variant of the beta epithelial sodium channel, is associated with low-renin, low-aldosterone hypertension, in South African black and mixed-ancestry patients. Only a minority of individuals with the R563Q allelle fully express the Liddles syndrome phenotype.

Recent advances in hypertension in sub-Saharan Africa

Background Hypertension was once considered rare in sub-Saharan Africa (SSA), but currently it has become a widespread problem with immense socioeconomic importance. The purpose of this review is to summarise new information on hypertension in SSA that has been published since the last major review in 2008. Methods and results A literature search was performed in Pubmed, Embase, WHO Global Cardiovascular Infobase, African Journal On-Line, and African Index Medicus using the following search criteria: hypertension, high blood pressure, and Africa/SSA. Epidemiological surveys that used the WHO STEPS approach or similar methods were also included. The overall prevalence of hypertension in SSA was estimated at 16.2% (95% CI 14.2% to 20.3%) with an estimated number of hypertensive individuals to be 74.7 million. The prevalence of hypertension varies widely from country to country. It is projected that the number of affected individuals will increase by 68% (125.5 million) by 2025. Mass migration of rural Africans to urban areas and rapid changes in lifestyle and risk factors account for the rising prevalence of hypertension. Conclusions Proactive public health interventions at a population level need to be introduced to control the growing hypertension epidemic, and there needs to be a major improvement in access to hypertensive care for the individual. There is an important need for better epidemiological data and hypertension related outcome trials in SSA.

The spectrum of renal histologies seen in HIV with outcomes, prognostic indicators and clinical correlations

BACKGROUND Two hundred and twenty-one HIV-positive renal biopsies were analysed from Groote Schuur Hospital to determine outcomes and prognostic indicators based on histology and clinical features. METHODS The histology findings were compared with patient demographics, clinical and renal parameters, mortality, CD4 count and date of commencing combined anti-retroviral therapy (cART). Follow-up was between 1 and 3.5 years. RESULTS We found a spectrum of renal histologies in HIV-positive patients of which HIV-associated nephropathy (HIVAN) was the most common histology. cART reduced the mortality in those with any feature of HIVAN by 57% [adjusted hazard ratio (AHR) 0.43, 95% confidence interval (CI) 0.22-0.85]. Of those patients with HIVAN who died, 79% died of renal failure as registered on their death certificate. Proteinuria and microcysts were shown to be poor prognostic indicators (AHR 1.36: 1.09-1.70 and 2.04: 1.24-3.37). In patients with HIVAN alone followed for up to 2 years on cART, estimated glomerular filtration rate remained stable and there was a trend towards decreased proteinuria. cART improved survival in patients with isolated immune complex disease. CONCLUSIONS As mortality is improved in patients with any feature of HIVAN or isolated immune complex disease, cART should be initiated once any of these histological features are established. We believe the spectrum of disease that constitutes HIVAN needs to be more specifically defined. The ultimate outcome may be determined by the histological subtype.

Mobile Phone Text Messages to Support Treatment Adherence in Adults With High Blood Pressure (SMS-Text Adherence Support [StAR]) A Single-Blind, Randomized Trial

Background— We assessed the effect of automated treatment adherence support delivered via mobile phone short message system (SMS) text messages on blood pressure. Methods and Results— In this pragmatic, single-blind, 3-arm, randomized trial (SMS-Text Adherence Support [StAR]) undertaken in South Africa, patients treated for high blood pressure were randomly allocated in a 1:1:1 ratio to information only, interactive SMS text messaging, or usual care. The primary outcome was change in systolic blood pressure at 12 months from baseline measured with a validated oscillometric device. All trial staff were masked to treatment allocation. Analyses were intention to treat. Between June 26, 2012, and November 23, 2012, 1372 participants were randomized to receive information-only SMS text messages (n=457), interactive SMS text messages (n=458), or usual care (n=457). Primary outcome data were available for 1256 participants (92%). At 12 months, the mean adjusted change in systolic blood pressure compared with usual care was −2.2 mm Hg (95% confidence interval, −4.4 to −0.04) with information-only SMS and −1.6 mm Hg (95% confidence interval, −3.7 to 0.6) with interactive SMS. Odds ratios for the proportion of participants with a blood pressure <140/90 mm Hg were 1.42 (95% confidence interval, 1.03–1.95) for information-only messaging and 1.41 (95% confidence interval, 1.02–1.95) for interactive messaging compared with usual care. Conclusions— In this randomized trial of an automated adherence support program delivered by SMS text message in a general outpatient population of adults with high blood pressure, we found a small reduction in systolic blood pressure control compared with usual care at 12 months. There was no evidence that an interactive intervention increased this effect. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT02019823. South African National Clinical Trials Register, number SANCTR DOH-27-1212-386; Pan Africa Trial Register, number PACTR201411000724141.

Dialysis Initiation: What's the Rush?

The recent trend to early initiation of dialysis (at eGFR >10 ml/min/1.73 m2) appears to have been based on conventional wisdoms that are not supported by evidence. Observational studies using administrative databases report worse comorbidity‐adjusted dialysis survival with early dialysis initiation. Although some have concluded that the IDEAL randomized controlled trial of dialysis start provided evidence that patients become symptomatic with late dialysis start, there is no definitive support for this view. The potential harms of early start of dialysis, including the loss of residual renal function (RRF), have been well documented. The rate of RRF loss (renal function trajectory) is an important consideration for the timing of the dialysis initiation decision. Patients with low glomerular filtration rate (GFR) may have sufficient RRF to be maintained off dialysis for years. Delay of dialysis start until a working arterio‐venous access is in place seems prudent in light of the lack of harm and possible benefit of late dialysis initiation. Prescribing frequent hemodialysis is not recommended when dialysis is initiated early. The benefits of early initiation of chronic dialysis after episodes of congestive heart failure or acute kidney injury require further study. There are no data to show that early start benefits diabetics or other patient groups. Preemptive start of dialysis in noncompliant patients may be necessary to avoid complications. The decision to initiate dialysis requires informed patient consent and a joint decision by the patient and dialysis provider. Possible talking points for obtaining informed consent are provided.

South African hypertension practice guideline 2014 : review article

Summary Outcomes Extensive data from many randomised, controlled trials have shown the benefit of treating hypertension (HTN). The target blood pressure (BP) for antihypertensive management is systolic < 140 mmHg and diastolic < 90 mmHg, with minimal or no drug side effects. Lower targets are no longer recommended. The reduction of BP in the elderly should be achieved gradually over one month. Co-existent cardiovascular (CV) risk factors should also be controlled. Benefits Reduction in risk of stroke, cardiac failure, chronic kidney disease and coronary artery disease. Recommendations Correct BP measurement procedure is described. Evaluation of cardiovascular risk factors and recommendations for antihypertensive therapy are stipulated. Lifestyle modification and patient education are cornerstones of management. The major indications, precautions and contra-indications are listed for each antihypertensive drug recommended. Drug therapy for the patient with uncomplicated HTN is either mono- or combination therapy with a low-dose diuretic, calcium channel blocker (CCB) and an ACE inhibitor (ACEI) or angiotensin receptor blocker (ARB). Combination therapy should be considered ab initio if the BP is ≥ 160/100 mmHg. In black patients, either a diuretic and/or a CCB is recommended initially because the response rate is better compared to an ACEI. In resistant hypertension, add an alpha-blocker, spironolactone, vasodilator or β-blocker. Validity The guideline was developed by the Southern African Hypertension Society 2014©.

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.

Microalbuminuria and the metabolic syndrome in non-diabetic black Africans

It is recognised that the metabolic syndrome promotes the development of cardiovascular disease. Although several studies have shown a relationship between the metabolic syndrome and kidney disease, few of these have used non-diabetic subjects, especially in the African population. This was a cross-sectional study of subjects of African origin, using the metabolic syndrome (MS) criteria of the National Cholesterol Education Program (NCEP) third Adult Treatment Panel (ATP III). Subjects with impaired fasting glucose, with two-hour glucose ≥ 11.1 mmol/L after a glucose tolerance test, were excluded. Spot urine for albuminto-creatinine ratio (ACR) was measured and the glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease (MDRD) equation. Microalbuminuria was defined as ACR between 3–30 mg/mmol. There was a significant decline in GFR and a significant increase in ACR with increasing number of MS traits. ACR increased four-fold between subjects with no MS traits and those with four or more traits. In subjects with the metabolic syndrome, there was a significant correlation between ACR and systolic blood pressure (SBP), diastolic blood pressure (DBP) and fasting glucose. Estimated GFR correlated significantly and inversely with body mass index (BMI) and serum leptin. These observations raise major clinical and public health concerns for developing countries, where both the metabolic syndrome and kidney disease are being reported more and more frequently. The potential economic impact is huge.

Short communication: Association of pre‐eclampsia with the R563Q mutation of the β‐subunit of the epithelial sodium channel

The R563Q mutation of the β‐subunit of the epithelial sodium channel (ENaC) is associated with hypertension in black and mixed ancestry (MA) men and women in South Africa. The frequency of the R563Q mutation in black and MA women with pre‐eclampsia (n= 230) and in controls (n= 198) was studied. The R563Q mutation was found in 7.8% of the women with pre‐eclampsia and in 2.6% of controls (P= 0.014). This remained significant if the black women were analysed separately (P= 0.031). We have demonstrated that a genetic variant of the ENaC is associated with pre‐eclampsia. This has implications for understanding the pathogenesis and treatment of pre‐eclampsia.