Atherosclerotic vascular disease is more prevalent among black ESKD patients on long-term CAPD in South Africa.

BACKGROUND: Occurrence of cardiovascular disease (CVD) in the setting of chronic kidney disease (CKD) can be described as a "cruel alliance", with CVD responsible for about half of all deaths among CKD patients. Chronic kidney disease patients are more likely to die from CVD than progress to end stage kidney disease (ESKD). Dyslipidaemia, a known traditional risk factor for CVD, is highly prevalent among CKD patients and with an even higher frequency among ESKD patients on dialytic therapies. Prolonged exposure of continuous ambulatory peritoneal dialysis (CAPD) patients to high glucose concentrations in CAPD fluid have been associated with increased risk of cardiovascular events. In this study, we investigated the relationship of atherosclerotic vascular disease (AsVD) to clinical and echocardiographic parameters among black South Africans with CKD (stage 3) and ESKD on CAPD and haemodialysis (HD). METHODS: This was a cross-sectional study of 40 adult (18-65 years) non-diabetic CKD patients (kidney disease outcome quality initiative [KDOQI] stage 3), 40 ESKD patients on CAPD, 40 ESKD patients on HD and 41 age and sex-matched healthy controls. An interviewer-administered questionnaire was used to obtain information on participants' sociodemographic and cardiovascular risk factors. Anthropometric parameters were measured. Serum blood samples were analysed for creatinine, albumin and lipid profile; lipoprotein ratios, Framingham's risk score and the 10-year risk of developing coronary heart disease (CHD) were calculated. Echocardiography was performed on all patients and carotid intima media thickness (CIMT) was measured in both right and left carotid arteries at 1 cm proximal to the carotid bulb. Spearman's rank correlation and binary logistic regression were conducted to determine the relationship of AsVD to clinical and echocardiographic parameters. RESULTS: Atherosclerotic vascular disease was most prevalent among ESKD patients on CAPD (70%, n = 28/40). Chronic kidney disease and HD patients exhibited a similar prevalence (47.5%, n = 19/40), while the prevalence in controls was 17.1% (n = 7/41). Presence of AsVD was associated with significantly older age, higher waist hip ratio (WHR), left ventricular mass index (LVMI) and Framingham's 10-year risk of developing CHD. Significant differences in clinical and echocardiographic parameters were observed when the study groups were compared. Age and LVH independently predicted AsVD. CONCLUSION: Atherosclerotic vascular disease was more prevalent among CAPD patients compared to pre-dialysis CKD and HD patients. Among all lipoprotein ratios assessed, non-HDL-C showed the most consistent significant difference between the groups. Age (> 40 years) and presence of LVH were independent predictors of AsVD.

Environmental isotopic and hydrochemical characteristics of groundwater from the Sandspruit Catchment, Berg River Basin, South Africa.

The Sandspruit catchment (a tributary of the Berg River) represents a drainage system, whereby saline groundwater with total dissolved solids (TDS) up to 10,870 mg/l, and electrical conductivity (EC) up to 2,140 mS/m has been documented. The catchment belongs to the winter rainfall region with precipitation seldom exceeding 400 mm/yr, as such, groundwater recharge occurs predominantly from May to August. Recharge estimation using the catchment water-balance method, chloride mass balance method, and qualified guesses produced recharge rates between 8 and 70 mm/yr. To understand the origin, occurrence and dynamics of the saline groundwater, a coupled analysis of major ion hydrochemistry and environmental isotopes (δ(18)O, δ(2)H and (3)H) data supported by conventional hydrogeological information has been undertaken. These spatial and multi-temporal hydrochemical and environmental isotope data provided insight into the origin, mechanisms and spatial evolution of the groundwater salinity. These data also illustrate that the saline groundwater within the catchment can be attributed to the combined effects of evaporation, salt dissolution, and groundwater mixing. The salinity of the groundwater tends to vary seasonally and evolves in the direction of groundwater flow. The stable isotope signatures further indicate two possible mechanisms of recharge; namely, (1) a slow diffuse type modern recharge through a relatively low permeability material as explained by heavy isotope signal and (2) a relatively quick recharge prior to evaporation from a distant high altitude source as explained by the relatively depleted isotopic signal and sub-modern to old tritium values.

Impact of socio-economic factors on quality of life in patients on continuous ambulatory peritoneal dialysis in an African setting.

BACKGROUND: Quality of life (QOL) is an important outcome following the treatment of disease. It is influenced by physical, psychological, social and economic factors. We proposed to determine the effect of some socioeconomic factors on QOL of patients on CAPD. STUDY DESIGN: A cross sectional study in which all patients on CAPD attending three clinics attached to the University of the Witwatersrand, Johannesburg were recruited excluding those with intercurrent illness. The WHO quality of life instrument, WHOQOL-Bref, was used to measure QOL. The patients were grouped according to marital status, highest level of education attained, income, employment, and QOL domain scores were compared using ANOVA and Student t test. RESULTS: A total of 140 patients comprising 80 males and 40 females were assessed. The mean age of patients was 41.9 ± 11.5 years, 95%of patients were black, 44.3% married, 69.3% had secondary education, 22% were employed and 51.4% had a monthly income of less than five thousand Rand (500 US dollars). Single patients scored better in the social relationships domain compared to separated patients (p=0.02, CI: 5.6-32.9). The group with secondary education scored low in the psychological domain compared with those with primary education (p=0.02, CI: 1.35-15.8) and those with tertiary education (p=0.02, CI: 1.72-18.07).The highest income group had best scores in all domains except the physical domain. Those in employment had better scores in the physical domain (p=0.04, CI: 0.356-12.549). CONCLUSION: Income had the most impact on QOL in study participants.

Developing an intervention package to optimise the management of vancomycin therapy using theory informed co-design.

BACKGROUND: Optimising the management of vancomycin by achieving target therapeutic concentrations early during therapy has been associated with reduced mortality and morbidity. Despite the availability of guidelines and training, the management of vancomycin remains suboptimal. OBJECTIVES: The primary outcome was the development of interventions and associated implementation strategies to optimise the management of vancomycin therapy. This paper describes how co-design process was used to build a theory informed intervention package, which was implemented across a wide range of in-patient hospital settings in Queensland, Australia. METHODS: This multiple methods study was conducted in four phases: 1) a baseline audit to identify the nature of the problem and associated determinants informed by stakeholder interviews 2) mapping these findings to the Theoretical Domains Framework (TDF) to identify behavioural correlates and modifiers 3) prioritising the behavioural modifiers and associated implementation strategies to inform a protype of the intervention in a series of co-design sessions and 4) implementing and evaluating the intervention package. The study was conducted across the four teaching hospitals in a large Queensland Hospital and Health Service across multiple healthcare disciplines namely nurses, doctors, and pharmacists. This intervention package was subsequently implemented across Queensland Health with the support of the local champions under the guidance of the steering group. RESULTS: Clinicians identified that a multifaceted intervention package and training which can be tailored to the health-care professional disciplines, would be best suited to shift clinician behaviour to align with guidelines. The findings from the co-design process aligned with theory-informed intervention package. Each of the intervention strategies varied in their frequency and popularity of use. CONCLUSIONS: The use of theory-informed and participatory approach assisted with the intervention development process and aligned the intervention content with the priorities of stakeholders. The TDF provided a structured process for developing intervention content which is both acceptable and useful to stakeholders and may improve the management of vancomycin.

CyBorD-DARA in Newly Diagnosed Transplant-Eligible Multiple Myeloma: Results from the 16-BCNI-001/CTRIAL-IE 16-02 Study Show High Rates of MRD Negativity at End of Treatment.

The phase 1b 16-BCNI-001/CTRIAL-IE 16-02 CyBorD-DARA trial investigated the combination of Daratumumab with cyclophosphamide, bortezomib and dexamethasone in patients with newly diagnosed multiple myeloma (NDMM), followed by autologous stem cell transplantation and Daratumumab maintenance. CR/sCR rates were 50% after transplant and 62.5% at end of treatment. The overall percentage of patients achieving complete response or better was 77.8%. Progression-free survival rate at end of maintenance was 81.3% and estimated 2-year overall survival was 88.9%. 37.5% of patients demonstrated sustained MRD negativity to a level of 10-5 from transplant to analysis at EOT. In this phase 1b study, we have shown CyBorD-DARA to be an effective and well-tolerated immunomodulatory agent-free regiment in transplant-eligible NDMM.

Wastewater-based epidemiology in hazard forecasting and early-warning systems for global health risks.

With the advent of the SARS-CoV-2 pandemic, Wastewater-Based Epidemiology (WBE) has been applied to track community infection in cities worldwide and has proven succesful as an early warning system for identification of hotspots and changingprevalence of infections (both symptomatic and asymptomatic) at a city or sub-city level. Wastewater is only one of environmental compartments that requires consideration. In this manuscript, we have critically evaluated the knowledge-base and preparedness for building early warning systems in a rapidly urbanising world, with particular attention to Africa, which experiences rapid population growth and urbanisation. We have proposed a Digital Urban Environment Fingerprinting Platform (DUEF) - a new approach in hazard forecasting and early-warning systems for global health risks and an extension to the existing concept of smart cities. The urban environment (especially wastewater) contains a complex mixture of substances including toxic chemicals, infectious biological agents and human excretion products. DUEF assumes that these specific endo- and exogenous residues, anonymously pooled by communities' wastewater, are indicative of community-wide exposure and the resulting effects. DUEF postulates that the measurement of the substances continuously and anonymously pooled by the receiving environment (sewage, surface water, soils and air), can provide near real-time dynamic information about the quantity and type of physical, biological or chemical stressors to which the surveyed systems are exposed, and can create a risk profile on the potential effects of these exposures. Successful development and utilisation of a DUEF globally requires a tiered approach including: Stage I: network building, capacity building, stakeholder engagement as well as a conceptual model, followed by Stage II: DUEF development, Stage III: implementation, and Stage IV: management and utilization. We have identified four key pillars required for the establishment of a DUEF framework: (1) Environmental fingerprints, (2) Socioeconomic fingerprints, (3) Statistics and modelling and (4) Information systems. This manuscript critically evaluates the current knowledge base within each pillar and provides recommendations for further developments with an aim of laying grounds for successful development of global DUEF platforms.

Qualitative and quantitative detection of SARS-CoV-2 RNA in untreated wastewater in Western Cape Province, South Africa.

Recent studies have shown that the detection of SARS-CoV-2 genetic material in wastewater may provide the basis for a surveillance system to track the environmental dissemination of this virus in communities. An effective wastewater-based epidemiology (WBE) system may prove critical in South Africa (SA), where health systems infrastructure, testing capacity, personal protective equipment and human resource capacity are constrained. In this proof-of-concept study, we investigated the potential of SARS-CoV-2 RNA surveillance in untreated wastewater as the basis for a system to monitor COVID-19 prevalence in the population, an early warning system for increased transmission, and a monitoring system to assess the effectiveness of interventions. The laboratory confirmed the presence (qualitative analysis) and determined the RNA copy number of SARS-CoV-2 viral RNA by reverse transcription polymerase chain reaction (quantitative) analysis from 24-hour composite samples collected on 18 June 2020 from five wastewater treatment plants in Western Cape Province, SA. The study has shown that a WBE system for monitoring the status and trends of COVID-19 mass infection in SA is viable, and its development and implementation may facilitate the rapid identification of hotspots for evidence-informed interventions.

Burden of end-stage renal disease in sub-Saharan Africa.

AIMS: To review prevalence, causes and management of end-stage renal disease (ESRD) in sub-Saharan Africa (SSA). MATERIALS AND METHODS: Review of literature and data. RESULTS: Approximately 70% of the least developed countries of the world are in SSA. Rapid urbanization is occurring in many parts of the continent, contributing to overcrowding and poverty. While infections and parasitic diseases are still the leading cause of death in Africa, non-communicable diseases are coming to the forefront. There is a continuing "brain drain" of healthcare workers (physicians and nurses) from Africa to more affluent regions. There are large rural areas of Africa that have no health professionals to serve these populations. There are no nephrologists in many parts of SSA; the numbers vary from 0.5 per million population (pmp) in Kenya to 0.6 pmp in Nigeria, 0.7 pmp in Sudan and 1.1 pmp in South Africa. Chronic kidney disease affects mainly young adults aged 20 - 50 years in SSA and is primarily due to hypertension and glomerular diseases. HIV- related glomerular disease often presents late, with patients requiring dialysis. Diabetes mellitus affects 9.4 million people in Africa. The prevalence of diabetic nephropathy is estimated to be 6 - 16% in SSA. The current dialysis treatment rate is < 20 pmp (and nil in many countries of SSA), with in-center hemodialysis the modality of RRT for the majority. Transplantation is carried out in a few SSA countries: South Africa, Nigeria, Mauritius and Ghana, with most of the transplants being living donor transplants, except in South Africa where the majority are from deceased donors. CONCLUSION: Chronic kidney disease care is especially challenging in SSA, with large numbers of ESRD patients, inadequate facilities, funding and support.

Risk factors for the development of chronic kidney disease with HIV/AIDS.

AIMS: A review of the prevalence and risk factors for chronic kidney disease (CKD) in HIV infection. MATERIALS AND METHODS: A review of published literature. RESULTS: High risk for development of chronic kidney disease with HIV infection are black race, CD4 count < 200 cells/mm3, HIV RNA levels > 4,000 copies/ml, family history of CKD and presence of diabetes mellitus, hypertension or hepatitis C co-infection. In 2004, the risk of developing ESRD was reported as 50 times higher in HIV-infected African-Americans than in HIV-infected whites and in 2007, African Americans accounted for nearly 90% of ESRD attributed to HIVAN. Once CKD was established, African-Americans were 18 times more likely to progress to ESRD than whites and their decline in GFR was six times more rapid than white subjects. The prevalence of CKD with HIV infection was 3.5 - 4.7% in 31 European countries, Israel and Argentina, and 1.1 - 5.6% Brazil; 18% Switzerland; 27% India and 12.3% Iran. Reported prevalence of CKD in HIV-infected patients in sub-Saharan Africa ranges from 6 - 48.5%. Few renal biopsy studies have been performed. In South Africa, HIVAN was present in variable numbers in three studies, ranging from 5 - 83% and immune complex disease in 21 - 40%. A variation in the MYH9 locus of chromosome 22 has been associated with increased risk for idiopathic FSGS, hypertensive nephrosclerosis and HIVAN and may explain much of the increased risks of ESRD and FSGS among African-Americans. A strong correlation with serum creatinine levels and progression to ESRD in HIV patients has been linked to an index of chronic damage on renal histology. CONCLUSION: The role of genetics and variations in MYH9 gene loci in renal disease has to be established in other HIV-infected populations. The histological classification for HIV-associated chronic kidney disease requires review, as well as the utility of chronicity scores to evaluate prognosis and response to therapy of HIV-associated kidney disease.

Is there a need for early detection programs for chronic kidney disease?

The aims of this paper are to examine whether early detection programs are needed to assist in detecting and managing chronic kidney disease (CKD). It draws on existing material which indicates that CKD and its precursor risk factors or illnesses such as hypertension, diabetes mellitus and HIV infection are very clearly major challenges faced by health systems worldwide. This paper evaluates whether CKD meets the epidemiological criteria to justify early screening. More compelling evidence is becoming available which indicates that the prevalence of CKD is significant in both developing and developed countries and that CKD can be easily detected and treated with only small changes to existing practice and this may be improved through screening programs. A brief evaluation of the challenges of establishing early detection programs is provided, as well as an examination of the capacity which exists for establishing such programs. It concludes that, despite the lack of randomized studies, these programs appear to provide an opportunity to integrate CKD management with common chronic illnesses and, through this approach, provide clinical and cost-effective management of both CKD and cardiovascular disease.

Shortage of healthcare workers in sub-Saharan Africa: a nephrological perspective.

AIMS: The paper assesses the lack of healthcare workers, the consequences, and possible solutions. MATERIALS AND METHODS: Review of existing literature and global health reports. RESULTS: The 47 countries of sub-Saharan Africa have a critical shortage of healthcare workers, the deficit amounting to 2.4 million doctors and nurses. There are 2 doctors and 11 nursing/midwifery personnel per 10,000 population, compared with 19 doctors and 49 nursing/midwifery personnel per 10,000 for the Americas, and 32 doctors and 78 nursing/midwifery personnel per 10,000 for Europe. And, whereas there are 28 doctors and 87 nurses/midwifery personnel per 10,000 in high income regions of the world, there are only 5 doctors and 11 nurses/ midwifery personnel per 10,000 in low income regions. The shortage of nephrologists in Africa, and especially sub-Saharan Africa, remains a critical issue, with many countries having < 1 nephrologist per million population; some have no nephrologists at all. The USA, UK, Canada and Australia have benefitted considerably from the migration of nurses and doctors over the past half century. Opportunities for training as well as employment have attracted doctors from many countries to these developed countries. Since 2006, new legislation in the UK has limited the inflow of health workers. Developing countries are also beginning to take steps to mitigate the problem of health worker loss and are developing strategies to both train increasing numbers of different cadres of healthcare worker and also to retain those already working in these countries. CONCLUSIONS: The forces of globalization are tending to increase the worldwide movement of all types of professionals, including those working in health care. It is this lack of health workers in developing countries that has been such a major constraint in limiting progress on initiatives such as the HIV "3 by 5" and Millennium Development Goals. More specifically, lack of resources, both human and financial, in developing countries has hampered nephrology programs both in the detection and prevention of chronic kidney disease and in the ability of doctors, nurses and other nephrological personnel to provide acute/chronic dialysis and transplantation.

Non-polymyxin-based combinations as potential alternatives in treatment against carbapenem-resistant Acinetobacter baumannii infections.

Due to limited therapeutic options, combination therapy has been used empirically to treat carbapenem-resistant Acinetobacter baumannii (CRAB). Polymyxin-based combinations have been widely studied and used in the clinical setting. However, the use of polymyxins is often limited due to nephrotoxicity and neurotoxicity. This study aimed to evaluate the activity of non-polymyxin-based combinations relative to polymyxin-based combinations and to identify potential synergistic and bactericidal two-drug non-polymyxin-based combinations against CRAB. In vitro activity of 14 two-drug combinations against 50 A. baumannii isolates was evaluated using the checkerboard method. Subsequently, the two best-performing non-polymyxin-based combinations from the checkerboard assay were explored in static time-kill experiments. Concentrations of antibiotics corresponding to the fractional inhibitory concentrations (FIC) and the highest serum concentration achievable clinically were tested. The most synergistic combinations were fosfomycin/sulbactam (synergistic against 37/50 isolates; 74%), followed by meropenem/sulbactam (synergistic against 28/50 isolates; 56%). No antagonism was observed for any combination. Both fosfomycin/sulbactam and meropenem/sulbactam combinations exhibited bactericidal and synergistic activity against both isolates at the highest clinically achievable concentrations in the time-kill experiments. The meropenem/sulbactam combination displayed synergistic and bactericidal activity against one of two strains at concentrations equal to the FIC. Non-polymyxin-based combinations such as fosfomycin/sulbactam and meropenem/sulbactam may have a role in the treatment of CRAB. Further in vivo and clinical studies are required to scrutinise these activities further.

Patterns of renal disease: A 30-year renal biopsy study at Chris Hani Baragwanath Academic Hospital, Soweto, Johannesburg, South Africa.

BACKGROUND: Data on renal pathology from sub-Saharan Africa are limited. OBJECTIVES: To report on biopsy-confirmed renal pathology over 30 years in Soweto, South Africa (SA). METHODS: Retrospective analysis was conducted of 1 848 adult native renal biopsies performed at Chris Hani Baragwanath Academic Hospital between 1 January 1982 and 31 December 2011. RESULTS: There was an even gender distribution, and 96.4% of patients were of black ethnicity. The mean (standard deviation) age of patients was 33.5 (12.6) years. The main clinical indications for renal biopsy were nephrotic syndrome (47.7%), acute kidney injury (19.8%) and asymptomatic urine abnormalities (8.1%). Secondary glomerular diseases (SGNs) (49.3%) occurred more frequently than primary glomerular diseases (PGNs) (39.7%). SGNs increased during the study period, while PGNs decreased (p<0.001). The most frequent PGNs were focal segmental glomerulosclerosis (FSGS) (29.6%), membranous glomerulonephritis (25.7%) and membranoproliferative glomerulonephritis (18.1%). Lupus nephritis (LN) (31.0%) was the most frequent SGN, followed by HIV-associated nephropathy (HIVAN) (13.3%) and malignant hypertension (12.5%). HIV-positive biopsies constituted 19.7% of all biopsies, and the proportion increased over time. In HIV-positive patients, the most common diagnoses were HIVAN (32.7%), HIV immune complex disease (11.8%) and FSGS (11.3%). CONCLUSIONS: This study contributes to our knowledge of renal pathology in SA and shows some data that differ from studies in other regions. The increase in SGNs probably reflects the influence of HIV and LN in the study population.

CyBorD-DARA is potent initial induction for MM and enhances ADCP: initial results of the 16-BCNI-001/CTRIAL-IE 16-02 study.

Daratumumab (DARA) has shown impressive activity in combination with other agents for the treatment of multiple myeloma (MM). We conducted a phase 1b study to assess the safety and preliminary efficacy, as well as potential mechanisms of action, of DARA (16 mg/kg) in combination with a weekly schedule of subcutaneous bortezomib (1.3-1.5 mg/m2), cyclophosphamide (150-300 mg/m2), and dexamethasone (40 mg) (CyBorD DARA) as initial induction before autologous stem cell transplantation (ASCT). Eligible patients were ≤70 years of age with untreated MM requiring treatment and who lacked significant comorbidities. A total of 18 patients were enrolled. Their median age was 56 years (range, 32-66 years), and all patients had Eastern Cooperative Oncology Group performance status ≤1. The International Staging System stages were I, II, and III in 78%, 17%, and 6% of patients, respectively; 28% of patients had high-risk genetic features. There was no dose-limiting toxicity, and the incidence of grade 3 or 4 infection or neutropenia was <10%. On an intention-to-treat basis, 94% achieved ≥very good partial response with ≥complete response in 44% of patients. Among 14 of 15 patients who underwent ASCT and were evaluable for response, all 14 achieved at least very good partial response, with 8 (57%) of 14 achieving complete response. After ASCT, 10 (83%) of 12 patients in whom minimal residual disease analysis was possible were negative at a sensitivity of 10-5 (56% on intention-to-treat/whole study population) according to next-generation sequencing. Flow cytometry analysis of patient samples indicated CyBorD DARA induced activation of macrophage-mediated antibody-dependent cellular phagocytosis. This trial was registered at www.clinicaltrials.gov as #NCT02955810.

Chronic kidney disease in human immunodeficiency virus infection.

The number of people living with human immunodeficiency virus (HIV) worldwide was estimated to be 39.5 million in 2006, 2.6 million more than in 2004. The manifestations of HIV infection in the kidney are multiple and varied, highlighting the complexity of the disease process. There is a wide spectrum of renal disease that occurs in the course of HIV infection. Biopsy studies reveal varying frequencies of histological patterns. HIV-associated nephropathy (HIVAN) is most common. A biopsy study at Chris Baragwanath Hospital in Soweto, South Africa showed that HIVAN was present in 27% and immune complex disease in 21%. Han et al. studied HIV-positive patients in Durban, South Africa and screened for proteinuria, including microalbuminuria. They found persistent proteinuria in 6%; HIVAN in 21/30 (72.4%) and the prevalence of HIVAN in patients with persistent microalbuminuria was 85.7%. Studies in black patients have shown a higher prevalence of both severe glomerular lesions (focal glomerulosclerosis) and nephrotic range proteinuria with renal dysfunction in the presence of normo-hypotension. There have been no prospective randomised controlled studies with any form of therapy for HIVAN to date. Therapy of HIVAN has included corticosteroids, cyclosporine and antiretroviral therapy (ART). ART appears to be a logical choice in the management of HIV-associated renal disease. Regimens containing protease inhibitors have been shown to be associated with significant slowing of the decline in creatinine clearance. Both peritoneal dialysis and haemodialysis are appropriate treatment modalities for HIV-infected patients with end stage renal disease. The choice of dialysis modality between haemodialysis and peritoneal dialysis is not a factor in predicting survival, if patients are stable on ART. Preliminary short-term data in case reports and small cohorts of liver, kidney, and heart transplant recipients suggest that patient survival rates may be similar to those in HIV-uninfected transplant recipients. However, high rates of acute and chronic rejection have been observed among HIV-infected kidney transplant recipients. The Infectious Diseases Society of America (IDSA) published guidelines in 2005, recommending that all individuals be assessed for kidney disease at the time of diagnosis of HIV infection with a screening urinalysis for proteinuria and a calculated estimate of renal function. Therefore any patient with persistent proteinuria, persistent haematuria or glomerular filtration rate < 60 mL/min per 1.73 m(2) should be referred to an institution where a specialist can evaluate this patient for further investigations. An integrated plan to reduce the progression to kidney failure together with lifestyle measures, focusing also on high risk groups with effective management at all levels of chronic kidney disease remains essential.

Loss of health professionals from sub-Saharan Africa: the pivotal role of the UK.

The already inadequate health systems of sub-Saharan Africa have been badly damaged by the emigration of their health professionals, a process in which the UK has played a prominent part. In 2005, there are special opportunities for the UK to take the lead in addressing that damage, and in focusing the attention of the G8 on the wider problems of health-professional migration from poor to rich countries. We suggest some practical measures to these ends. These include action the UK could take on its own, with the African countries most affected, and with other developed countries and WHO.

Proteinuria, graft outcomes, and cardiovascular risk among kidney transplant recipients in a South African Public Hospital.

Proteinuria is a marker of poor long-term graft survival and an independent risk factor for total and cardiovascular mortality in the transplant population. We investigated the prevalence of proteinuria and its relationship with graft function and cardiovascular risk factors in kidney transplant recipients (KTRs). Adult KTRs at the Charlotte Maxeke Johannesburg Academic Hospital were recruited. Patients' records were reviewed for information on their posttransplant follow-up. Echocardiography and carotid Doppler were performed for the assessment of cardiac status and carotid intima-media thickness (CIMT), respectively. Proteinuria was analyzed both as a categorical and continuous variable. Graft dysfunction was defined as estimated glomerular filtration rate of <60 mL/min/1.73 m 2 based on the modification of diet in renal disease formula. Framingham's risk score was used to categorize patients' cardiovascular risk. Inferential and modeling statistics were applied as appropriate using Statistical Package for Social Sciences, and P ≤0.05 was considered statistically significant. One hundred KTRs including 63% males were recruited. Proteinuria was present in 51%, the mean ± standard deviation 24 h urinary protein excretion per day was 1.67 ± 2.0 g/day with a range of 0.4-9.4 g/day. Graft dysfunction was found in 52% of patients and 36% had high cardiovascular disease (CVD) risk. Proteinuric KTRs had high CVD risk, P = 0.002. Proteinuria was associated with graft dysfunction, increased left ventricular mass index, increased CIMT, and anemia. Proteinuria is prevalent; it is a marker of graft dysfunction and is associated with markers of atherosclerosis.

Endothelins: vasoactive modulators of renal function in health and disease.

Vasoactive autocoids with directly opposing actions on the renal vasculature, glomerular function, and in salt and water homeostasis have been demonstrated in the kidney. In the renal cortex, endothelin (ET)-1 and angiotensin-II cause vasoconstriction, decreasing renal blood flow, and glomerular filtration rate, whereas bradykinin and atrial natriuretic peptide cause vasodilation and increase glomerular capillary permeability. ET-1 causes vasoconstriction of the afferent and efferent arteries and outer medullary descending vasa recta, thereby decreasing vasa recta and papillary blood flow, while bradykinin has the opposite effect. ET-1 stimulates cell proliferation, increasing the expression of several genes, including collagenase, prostaglandin endoperoxidase synthase, and platelet-derived growth factor. ET-1 promotes natriuresis via the ET-B receptor, causing down-regulation of the epithelial Na(+) channel in the renal tubule. Thus, ETs affect three major aspects of renal physiology: vascular and mesangial tone, Na(+) and water excretion, and cell proliferation and matrix formation.

Obesity and graft dysfunction among kidney transplant recipients: Increased risk for atherosclerosis.

Weight gain after kidney transplant is common, and may be related to graft dysfunction and high cardiovascular risk. We investigated the prevalence of obesity and evaluated the relationship between obesity and graft dysfunction in kidney transplant recipients (KTRs). All patients who received kidney transplant at the Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) between January 2005 and December 2009 were recruited. Information on demographics, clinical characteristics and post-transplant care were documented. All patients underwent transthoracic echocardiography and carotid Doppler ultrasound for the assessment of cardiac status and carotid intima-media thickness (cIMT), respectively. Inferential and modelling statistics were applied. One hundred KTRs were recruited, of which 63 were males. The mean age was 42.2 ± 12.42 years with a range of 19-70 years. The mean body mass index and waist circumference of the recipients were 26.4 ± 4.81 kg/m(2) and 90.73 ± 14.76 cm, respectively. Twenty-nine patients (29%) were obese; of these, 24 (82.8%) had moderate obesity, 4 (13.8%) had severe obesity, and 1 (3.4%) had morbid obesity. Graft dysfunction was present in 52%. Obese patients were older (P < 0.0001), had graft dysfunction (P = 0.03), higher mean arterial blood pressure (P = 0.022), total cholesterol (P = 0.019), triglycerides (P < 0.0001), left ventricular mass index (P = 0.035) and cIMT (P = 0.036). Logistic regression showed obesity to be independently associated with graft dysfunction (P = 0.033). Obesity after kidney transplantation is common and is associated with graft dysfunction and markers of atherosclerosis.

Important causes of chronic kidney disease in South Africa.

In hypertensive patients without chronic kidney disease (CKD) the goal is to keep blood pressure (BP) at ≤140/90 mmHg. When CKD ispresent, especially where there is proteinuria of ≥0.5 g/day, the goal is a BP of ≤130/80 mmHg. Lifestyle measures are mandatory, especiallylimitation of salt intake, ingestion of adequate quantities of potassium, and weight control. Patients with stages 4 - 5 CKD must be carefullymonitored for hyperkalaemia and deteriorating kidney function if angiotensin-converting enzyme (ACE) inhibitors or angiotensin IIreceptor blockers (ARBs) are used, especially in patients >60 years of age with diabetes or atherosclerosis. BP should be regularly monitoredand, where possible, home BP-measuring devices are recommended for optimal control.Guidelines on the use of antidiabetic agents in CKD are presented, with the warning that metformin is contraindicated in patients withstages 4 - 5 CKD.There is a wide clinical spectrum of renal disease in the course of HIV infection, including acute kidney injury, electrolyte and acid-basedisturbances, HIV-associated glomerular disease, acute-on-chronic renal disease and side-effects related to the treatment of HIV.