Community acquired bacteraemia : a prospective survey of 239 cases

The incidence and epidemiology of bacteraemia has been widely reported in the United States and Europe but little data is available from Southern Africa. In addition, most studies have concentrated on the overall incidence of bacteraemia, on individual organisms, or clinical situations, and it is difficult to interpret the data from these studies with regard to community acquired bacteraemia. From a retrospective survey of summaries from a single medical ward at Groote Schuur Hospital it was estimated that bacteraemia accounted for about 4% of the total admissions. It was therefore thought useful to provide clinicians particularly at Groote Schuur Hospital with information about community acquired bacteraemia to improve overall patient management. With this in mind it was decided to undertake a comprehensive prospective study of community acquired bacteraemia at Groote Schuur Hospital

Investigation of the ethnic differences and genetics of salt sensivity and salt-sensitive hypertension in South Africa

Includes abstract. Includes bibliographical references

Update on the role of candesartan in the optimal management of hypertension and cardiovascular risk reduction

Hypertension is the most prevalent cardiovascular disease of adults and is a major risk factor for cardiovascular (CV) and cerebrovascular morbidity and mortality worldwide. Treatment of hypertension leads to reduction of CV morbidity and mortality through blood pressure reduction. The role of renin–angiotensin–aldosterone system (RAAS) in the pathophysiology of hypertension is mainly through generation of potent vasoconstrictor angiotensin II, stimulation of aldosterone secretion, and increase in sympathetic activation. Angiotensin II receptor blockers such as candesartan, a long-acting agent, alter this system by blocking the activation of angiotensin I receptors. Several important clinical trials have tested the efficacy of candesartan with placebo, antihypertensive agents, or other agents that block the RAAS for the control of hypertension and reduction of key CV risk factors such as microalbuminuria, heart failure, retinopathy, and carotid intima medial thickness. Candesartan has been shown to be a well-tolerated and effective antihypertensive agent with positive metabolic characteristics and additional benefits on CV and cerebrovascular outcomes. The aim of this review is to discuss the pharmacology, efficacy, and safety of candesartan, with an overview of key hypertension and CV studies involving candesartan

Renal function, sodium and water homeostasis in patients with idiopathic extrahepatic portal vein thrombosis compared with normal healthy controls

Objectives. To determine whether portal hypertension in the absence of liver disease contributes to changes in renal function and renal sodium and water handling.Methods. Nine patients with extrahepatic portal vein thrombosis (PVT) with normal liver function and histology were compared with 9 matched healthy control subjects. All underwent standard measurements of glomerular filtration rate and effective renal blood flow using inulin and paraaminohippuric acid (PAH) clearances, respectively. Sodium excretion and renin and aldosterone levels were studied before, during and after an intravenous saline infusion,Results. At baseline there were no differences in inulin clearance, PAH clearance, fractional excretion of sodium and free water excretion. During and after the saline infusion both groups showed a significant increase in sodium excretion with a reduction in water excretion, while the PAH and inulin clearances remained unchanged. Although aldosterone and renin levels both fell after the infusion, aldosterone levels were significantly lower in the PVT group. There were no other significant differences between the PVT and control groups.Conclusion. Renal function and sodium and water handling were comparable in healthy controls and patients with PVT. It is unlikely that portal hypertension alone plays a significant role in the impaired ability to excrete sodium and water in patients with liver cirrhosi

Screening for primary aldosteronism- normal ranges for aldosterone and renin in three South African population groups

Objective. To establish normal ranges for plasma aldosterone, renin and aldosterone / renin (A/ R) ratio in South African normotensives under typical ou tpatient conditions, and to estimate the prevalence of primary aldosteronism (PA) among hypertensives in primary care settings.Design and methods. One hundred and thirty-six normotensive subjects and 154 sex- and age-matched hypertensives at three primary care clinics had measurements of blood pressure, plasma creatinine, K+, aldosterone, plasma renin activity, and spot urine for urinary Na+/ creatinine ratio. Medication was not withdrawn before testing.Results. Mean plasma renin activity in black normotensive subjects (0.95 ± 1.25 ng/ ml/ h, mean± standard deviation (SD)) was significantly lower than in white (2.09 ± 1.12 ng/ ml/ h; P < 0.0001) and coloured (1.81 ± 1.86 ng/ ml/ h, P = 0.013) normotensives. Mean plasma aldosterone in black normotensives (306 ± 147 pmol/ 1) was also significantly lower than in white (506 ± 324 pmol/1, P = 0.0002) and coloured (418 ± 304 pmol/1, P = 0.0148) normotensives. In hypertensives, there were no significant differences in renin or aldosterone levels between the three population groups. Urinary Na+ /creatinine ratios, an index of Na+ intake, were not significantly different in the three population groups. None of the normotensives had an A/R ratio ≥ 1 000 plus aldosterone ≥ 750, while 7.1% of hypertensives exceeded these levels, suggesting that they are appropriate criteria for screening for PA.Conclusions. A large fraction of black normotensive subjects had low renin and aldosterone levels compared with whites, suggesting a salt-retaining tendency in black subjects. These results have important implications for the interpretation of plasma renin and aldosterone levels in hypertensive patients. In primary care settings, 7.1% of hypertensives had biochemical results indicating the need for investigation of PA

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 \u3e140 mm Hg or diastolic pressure \u3e 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 \u3c140 mm Hg and diastolic \u3c90 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 ISRCTN6944003

High frequency of variants of candidate genes in black Africans with low renin-resistant hypertension

OBJECTIVES Black subjects tend to retain salt and water, be more sensitive to aldosterone, and have suppression of plasma renin activity. Variants of the renal sodium channel (ENaC, SCNN1B) account for approximately 6% of resistant hypertension (RHT) in Blacks; other candidate genes may be important. METHODS Six candidate genes associated with low renin-resistant hypertension were sequenced in Black Africans from clinics in Kenya and South Africa. CYP11B2 was sequenced if the aldosterone level was high (primary aldosteronism phenotype); SCNN1B, NEDD4L, GRK4, UMOD, and NPPA genes were sequenced if the aldosterone level was low (Liddle phenotype). RESULTS There were 14 nonsynonymous variants (NSVs) of CYP11B2: 3 previously described and associated with alterations in aldosterone synthase production (R87G, V386A, and G435S). Out of 14, 9 variants were found in all 9 patients sequenced. There were 4 NSV of GRK4 (R65L, A116T, A142V, V486A): At least one was found in all 9 patients; 3 were previously described and associated with hypertension. There were 3 NSV of SCNN1B (R206Q, G442V, and R563Q); 2 previously described and 1 associated with hypertension. NPPA was found to have 1 NSV (V32M), not previously described and NEDD4L did not have any variants. UMOD had 3 NSV: D25G, L180V, and T585I. CONCLUSIONS A phenotypic approach to investigating the genetic architecture of RHT uncovered a surprisingly high yield of variants in candidate genes. These preliminary findings suggest that this novel approach may assist in understanding the genetic architecture of RHT in Blacks and explain their two fold risk of stroke

Genetic Variation at Selected SNPs in the Leptin Gene and Association of Alleles with Markers of Kidney Disease in a Xhosa Population of South Africa

BACKGROUND: Chronic 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 FINDINGS: Black 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/SIGNIFICANCE: These results suggest that genetic variations of the LEP may be associated with phenotypes that are markers of CKD in black Africans