The impact of vascular calcification among dialysis-dependent South African patients: A 5-year follow-up study
.

BACKGROUND: Vascular calcification is a major risk factor for cardiovascular morbidity and mortality in patients with end-stage renal disease (ESRD). In Western countries, Blacks appear to have lesser degrees of vascular calcification compared to non-Blacks. However, there is no published data from sub-Saharan Africa. MATERIALS AND METHODS: This study assessed the 5-year change in vascular calcification and mortality in a previously published cohort of patients with ESRD. Vascular calcification was assessed by abdominal aortic calcification score and vascular stiffness by pulse wave velocity (PWV). RESULTS: 66 of the original 74 participants studied at baseline were identified. The median age was 46.6 years (37.6 - 59.2), and 57.6% were women. Abdominal aortic calcification showed no progression among Blacks (baseline range 0 - 5, follow-up range 0 - 8 (p = 1.00)), but a trend to progression among non-Blacks (baseline range 0 - 19, follow up range 0 - 22 (p = 0.066)). Black participants did not display a survival advantage (p = 0.870). Non-Blacks had higher parathyroidectomy rates than Blacks with 9/30 cases compared to 2/36 (p = 0.036). After adjustment for parathyroidectomy at follow-up, the odds ratio of having abdominal vascular calcification score of ≥ 1 amongst non-Blacks was 8.6-fold greater compared to Blacks (p = 0.03). A positive correlation (r = 0.5) was observed between PWV and abdominal aortic calcification (p = 0.047). Elevated baseline coronary artery calcification score and FGF-23 level at baseline were not associated with a difference in mortality. CONCLUSION: There was no significant progression in vascular calcification among Blacks. After adjusting for increased parathyroidectomy rates, there was a greater progression of vascular calcification amongst non-Blacks compared to Blacks.

The effects of add-on corticosteroids on renal outcomes in patients with biopsy proven HIV associated nephropathy: a single centre study from South Africa.

BACKGROUND: The aim of this study was to assess, the efficacy and safety of add-on corticosteroids to antiretroviral therapy [ART] in patients with biopsy proven HIV associated nephropathy. METHODS: All included patients had histological evidence of either collapsing or non-collapsing focal segmental glomerulosclerosis (FSGS) or podocyte and/or parietal cell hypertrophy or hyperplasia. All patients had evidence of tubulointerstitial inflammation with microcysts. Patients were randomized to ART with the addition of 1 mg/kg of corticosteroids [ART+C] or remained in the group [ART Alone] and followed for 2 years. A repeat biopsy was performed at 6 months. RESULTS: Twenty-one patients were randomized to [ART+C] and 17 to [ART Alone]. The baseline estimated glomerular filtration rate (eGFR) was significantly lower in the [ART+C] vs. [ART Alone] group [35mls/min/1.73m2 vs. 47 mls/min/1.73m2, p = 0.015]. The [ART+C] cohort had a statistically significant improvement in median (eGFR) from baseline to last follow up compared with [ART Alone] i.e. [Δ = 25mls/min (IQR: 15;51) vs 9 mls/min (IQR: 0-24), p = 0.008]. There were no statistically significant differences between the groups when proteinuria and histology were analyzed. There were 8 deaths during the trial period, 7 from [ART+C] (Log rank p = 0.071). CONCLUSIONS: In the [ART+C] cohort there was a significant improvement in eGFR over 2-years with increased mortality. Routine corticosteroid use cannot currently be recommended. Further investigation to define which subgroup of this cohort would safely benefit from the positive effects is required. TRIAL REGISTRATION: ISRCTN study ID ( 56112439 ] was retrospectively registered on the 5 September 2018.

Clinical profile and outcome of patients with biopsy-proven acute interstitial nephritis in Cape Town: a 10-year review
.

BACKGROUND: Acute interstitial nephritis (AIN) is a common cause of acute kidney injury that has not been adequately characterized in Sub-Saharan Africa (SSA) despite an increasing use of potentially inciting agents for the treatment of human immunodeficiency virus (HIV) and tuberculosis in the region. METHODS: A retrospective audit of records of patients with biopsy-proven AIN diagnosed at Groote Schuur Hospital, Cape Town from the 1st of January, 2006, to the 31st of December, 2015. RESULTS: 54 patients with biopsy-proven AIN were reviewed. The majority were of black African origin (59.2%), with HIV (42.8%) and HIV-tuberculosis coinfection (30.5%) as the most common comorbidities. Drug-related AIN was seen in 38 (67.9%) patients, with rifampicin as the most often implicated medication. Probable drug-related AIN was seen in 3 (5.4%) patients, infection-related AIN in 8 (14.3%), and unspecified causes in 4 (7.4%). AIN was suspected in 44.6% of patients before biopsy. 18 patients (34%) received hemodialysis, while 19 (35.2%) were treated with corticosteroids. Complete renal recovery at 30 and 90 days was seen in 23 (42.6%) patients and 24 (45.3%) patients, respectively, with the majority seen among those with drug-induced AIN. Six (11.1%) patients died; 4 (10.5%) of the patients were in the drug-related group. There was no correlation between degree of interstitial inflammation and severity of renal failure (p = 0.10). On multivariate logistic regression, drug-related causes of AIN were predictive of complete recovery at day 30 (OR 16.63; 95% CI: 1.71 - 161.6, p = 0.02), and presence of interstitial fibrosis reduced likelihood of recovery (OR 0.03; 95% CI 0.002 - 0.46, p = 0.012). Steroid use did not influence partial recovery (OR 0.59, 95% CI 0.17 - 1.77; p = 0.32) or complete recovery (OR 3.38, 95% CI 0.38 - 30.39, p = 0.28). CONCLUSIONS: AIN is common in patients with HIV or those on treatment for tuberculosis. Drug-related AIN is often associated with improved outcomes. This is particularly reassuring in the SSA region where the use of potentially-inciting medications is rife from a high burden of HIV and tuberculosis.
.

Kidney disease in elderly South Africans.

BACKGROUND: Life expectancy is low in many African countries due to several factors including the ongoing HIV epidemic. However, the global increase in life expectancy has translated to more elderly patients living with chronic kidney disease (CKD). The patterns of kidney disease in the elderly have never been described from sub-Saharan Africa. METHODS: This study was a retrospective study of 111 elderly patients (age ≥ 60 years) who had a renal biopsy performed at the Groote Schuur Hospital in Cape Town between 1st January 2000 and 31st December 2009. RESULTS: The mean age of patients at time of biopsy was 66.3 ± 5.7 years (males: 66.4 ± 5.6; females: 66.3 ± 5.9 years). Primary glomerular diseases were seen in 38.7%, secondary glomerular diseases in 36.0%, tubulointerstitial diseases in 17.1% and diseases classified as miscellaneous in 8.1% of all patients. Nephrotic syndrome was the most common indication for the performance of a renal biopsy (48.6%). Membranous lomerulonephritis (MGN) was the most common type of disease observed (14.4%) and was significantly more frequent in males than in females (p = 0.029). Other common histological diagnoses included diabetes nephropathy (12.6%), chronic glomerulonephritis (5.4%), and lupus nephritis (4.5%). HIV associated nephropathy (HIVAN) was only seen in 1 patient (0.9%). CONCLUSION: The patterns of renal disease currently seen in elderly South Africans closely resembles that reported from other countries but is at complete variance with the pattern reported in the general population of South Africa in which HIV plays a significant role.

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.

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.

Nephrotic syndrome in adult black South Africans: HIV-associated nephropathy as the main culprit.

BACKGROUND: Glomerular diseases, accompanied by nephrotic syndrome, contribute significantly to end-stage renal disease (ESRD) worldwide. We sought to show the distribution and frequency of biopsy-proven causes of nephrotic syndrome in native black Africans attending the Groote Schuur Hospital in Cape Town, South Africa. METHODS: We retrospectively reviewed the biopsy data of 294 black South Africans with biopsy-proven cause of nephrotic syndrome in Cape Town over a 10-year period. Nephrotic proteinuria was accepted as urine protein excretion of at least 3.5 g in 24 hours. Glomerular diseases were classified into primary and secondary types. Serum creatinine concentrations were stratified into 3 levels to reflect the degree of renal dysfunction at the time of presentation. The frequency and distribution of disease were recorded according to age and gender. RESULTS: Young adults (< or = 40 years of age) constituted 74.1% of the study population. Secondary glomerular diseases were more frequent (58.8%) and human immunodeficiency virus-associated nephropathy (HIVAN) was observed as the leading cause of nephrotic syndrome in both males and females (42.8%). Most patients with HIVAN (73.6%) presented for the first time with severe renal impairment and more than half of patients with non-HIVAN glomerular diseases presented with an abnormal serum creatinine. Of the primary glomerular diseases, mesangiocapillary glomerulonephritis was the commonest cause of the nephrotic syndrome (19.0%), while IgA nephropathy was the least common cause (1.7%). CONCLUSIONS: HIVAN is a major cause of nephrotic syndrome in black South Africans and may be responsible for the rising incidence of ESRD in Africa.

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.

Survey on available treatment for acute kidney injury in the Southern African Development Community and Nigeria: are we ready for zero deaths by 2025 in sub-Saharan Africa?

OBJECTIVES: The International Society of Nephrology (ISN) has called for zero deaths by 2025. This survey aimed to determine the preparedness of Southern African Development Community (SADC) countries and Nigeria to heed this call. SETTING: A questionnaire was emailed to facilities, where renal replacement therapy is available; to determine type of services available; quality of care and identify clinicians involved. PARTICIPANTS: Clinicians and administrators involved in the care of patients with acute kidney injury (AKI) completed the questionnaire. RESULTS: Completed questionnaires were received from 12 of the 15 SADC countries and Nigeria, covering 48 service providers. The government provided partial funding for dialysis in 41.7% of services. There was no funding for acute dialysis in two countries. Interdisciplinary teams in 72.9% of hospitals covered the intensive care units (ICUs), which included at least one nephrologist in 75%. Only 77% were able to provide dialysis in ICU. Intermittent haemodialysis was the most common modality available (91.7% of facilities), sustained low-efficiency dialysis in 50%, continuous therapies in 35% and peritoneal dialysis in 33.3%. Almost half (47.9%) of the sites were limited to one mode of dialysis and unable to care for severely ill patients. The clinical status was used to initiate and monitor dialysis, with very few sites having clear written standard operating procedures. CONCLUSION: In the 16 countries surveyed, the majority had limited ability to provide comprehensive dialysis programmes for patients with AKI due to lack of facilities and government funding. Additionally, nephrologists are scarce; modes of dialysis are limited; as is the care for severely ill patients and lack of standard operating procedures. Resources, training and funding need to be made available to create universal coverage of dialysis for AKI. The ISN goal of providing renal replacement therapy to all by 2025 is unlikely to be achieved in SADC and Nigeria.

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

INTRODUCTION: Access to dialysis and transplantation in the developing world remains limited. Therefore, optimising renal allograft survival is essential. This study aimed to evaluate clinical outcomes and identify poor prognostic factors in the renal transplant programme at Groote Schuur Hospital [GSH], Cape Town. . METHOD: Data were collected on all patients who underwent a kidney transplant at GSH from 1st July 2010 to the 30 June 2015. Analyses were performed to assess baseline characteristics, graft and patient survival, as well as predictors of poor outcome. . RESULTS: 198 patients were transplanted. The mean age was 38 +/- 10.5 years, 127 (64.1%) were male, and 86 (43.4%) were of African ethnicity. Deceased donor organs were used for 130 (66.7%) patients and living donors for 65 (33.3%). There were > 5 HLA mismatches in 58.9% of transplants. Sepsis was the commonest cause of death and delayed graft function [DGF] occurred in 41 (21.4%) recipients. Patient survival was 90.4% at 1 year and 83.1% at 5 years. Graft survival was 89.4% at 1 year and 80.0% at 5 years. DGF (HR 2.83 (1.12-7.19), p value = 0.028) and recipient age > 40 years (HR 3.12 (1.26-7.77), p value = 0.014) were predictors of death. CONCLUSION: Despite the high infectious burden, stratified immunosuppression and limited tissue typing this study reports encouraging results from a resource constrained transplant programme in South Africa. Renal transplantation is critical to improve access to treatment of end stage kidney disease where access to dialysis is limited.

Chronic kidney disease in the global adult HIV-infected population: A systematic review and meta-analysis.

INTRODUCTION: The widespread use of antiretroviral therapies (ART) has increased life expectancy in HIV patients, predisposing them to chronic non-communicable diseases including Chronic Kidney Disease (CKD). We performed a systematic review and meta-analysis (PROSPERO registration number CRD42016036246) to determine the global and regional prevalence of CKD in HIV patients. METHODS: We searched PubMed, Web of Science, EBSCO and AJOL for articles published between January 1982 and May 2016. CKD was defined as estimated glomerular filtration rate (eGFR) <60ml/min using the MDRD, Cockcroft-Gault or CKD-EPI equations. Random effects model was used to combine prevalence estimates from across studies after variance stabilization via Freeman-Tukey transformation. RESULT: Sixty-one eligible articles (n = 209,078 HIV patients) in 60 countries were selected. The overall CKD prevalence was 6.4% (95%CI 5.2-7.7%) with MDRD, 4.8% (95%CI 2.9-7.1%) with CKD-EPI and 12.3% (95%CI 8.4-16.7%) with Cockcroft-Gault; p = 0.003 for difference across estimators. Sub-group analysis identified differences in prevalence by WHO region with Africa having the highest MDRD-based prevalence at 7.9% (95%CI 5.2-11.1%). Within Africa, the pooled MDRD-based prevalence was highest in West Africa [14.6% (95%CI 9.9-20.0%)] and lowest in Southern Africa (3.2%, 95%CI 3.0-3.4%). The heterogeneity observed could be explained by WHO region, comorbid hypertension and diabetes mellitus, but not by gender, hepatitis B or C coinfection, CD4 count or antiretroviral status. CONCLUSION: CKD is common in HIV-infected people, particularly in Africa. HIV treatment programs need to intensify screening for CKD with added need to introduce global guidelines for CKD identification and treatment in HIV positive patients.

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 >or= 11.1 mmol/L after a glucose tolerance test, were excluded. Spot urine for albumin-to-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.

Hypertension in blacks: insights from Africa.

Although the consequences of hypertension are universal, blacks (African-Americans or indigenous Africans) have been the subject of a differential approach to causation, outcome, and treatment. Blacks have a greater propensity to salt sensitivity and suppressed plasma renin suggesting a predisposition to sodium retention. Target organ damage is more frequent and blood pressure is more difficult to control. We explore potential underlying causes, both genetic and environmental, particularly in the South African population, and propose a more physiological approach to the treatment of resistant hypertension in blacks.

Physiological Phenotyping for Personalized Therapy of Uncontrolled Hypertension in Africa.

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

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.

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

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

Effect of losartan versus candesartan on uric acid, renal function, and fibrinogen in patients with hypertension and hyperuricemia associated with diuretics.

BACKGROUND: Hyperuricemia may counter benefits of blood pressure (BP) reduction, although this is controversial. METHODS: We examined the effects of candesartan and losartan on uric acid, creatinine, and fibrinogen. Patients with hypertension and serum uric acid > or = 0.42 mmol/L (7 mg/dL) associated with diuretics were randomized to receive losartan 50 to 100 mg or candesartan 8 to 16 mg for 24 weeks. At randomization and after 24 weeks, systolic and diastolic BP, serum uric acid, creatinine, and fibrinogen were measured. RESULTS: A total of 59 patients were entered into the study (30 in the losartan and 29 in the candesartan group). Mean systolic and diastolic BP were reduced in the candesartan group, from 156 mm Hg at baseline to 132 mm Hg at 24 weeks, and from 90.9 to 80.8 mm Hg respectively, P < .0001), and in the losartan group from 150.3 to 132 mm Hg and from 89.6 to 77.6 respectively, P < 0001). Overall mean values of fibrinogen levels were again reduced from 4.39 g/L at baseline to 4.01 g/L at 24 weeks (P < .02). Mean values of serum uric acid in the losartan and candesartan groups were similar at baseline (0.44 and 0.46 mmol/L, respectively), but they were lower in the losartan group after 24 weeks (0.39 and 0.48 mmol/L, P = .01). Twelve patients (44%) in the candesartan group had a 10% increase in serum creatinine compared with four patients (14.2%) in the losartan group (P < .02). CONCLUSIONS: Candesartan and losartan lowered BP, but only losartan reduced uric acid. The lowering of fibrinogen in both groups may explain the reduction in stroke with angiotensin receptor blockers. The effect of persistent hyperuricemia on renal function requires further study.

Regional and physician specialty-associated variations in the medical management of atherosclerotic renal-artery stenosis.

For people enrolled in Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL), we sought to examine whether variation exists in the baseline medical therapy of different geographic regions and if any variations in prescribing patterns were associated with physician specialty. Patients were grouped by location within the United States (US) and outside the US (OUS), which includes Canada, South America, Europe, South Africa, New Zealand, and Australia. When comparing US to OUS, participants in the US took fewer anti-hypertensive medications (1.9 ± 1.5 vs. 2.4 ± 1.4; P < .001) and were less likely to be treated with an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker (46% vs. 62%; P < .001), calcium channel antagonist (37% vs. 58%; P < .001), and statin (64% vs. 75%; P < .05). In CORAL, the identification of variations in baseline medical therapy suggests that substantial opportunities exist to improve the medical management of patients with atherosclerotic renal-artery stenosis.

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 Liddle's syndrome phenotype.