Search

Objective: In Africa, the treatment outcomes of lupus nephritis (LN) are not well known. This is especially true in the current era where contemporary treatment options are more widely available. This retrospective study aimed to measure the outcomes of biopsy-proven LN treated at the Livingstone Tertiary Hospital (LTH) Renal Unit in Gqeberha (formerly Port Elizabeth), South Africa and to identify predictors of a poor outcome., Methods: A retrospective cohort study of 131 patients with biopsy-proven LN who had a kidney biopsy between 01 January 2012 to 31 December 2021 as identified from the biopsy register. A sub-analysis of 107 patients with proliferative and/or membranous LN was performed., Results: Mean age was 31.4 ± 12.7 years with a female predominance of 86.3%. At 6-month follow-up, 69.6% of patients had complete or partial response to treatment. This increased to 70.3% and 72.6% at 18 and 30 months, respectively. Twenty-seven patients were lost to follow-up, while 7 (5.3%) patients progressed to kidney failure (KF). There were 3 (2.3%) deaths. Predictors of poor response were an elevated baseline serum creatinine (OR = 2.53, 95% CI 0.99 - 6.52, p = .054), a decreased eGFR (OR = 2.92, 95% CI 0.94 - 9.09, p = .065) and an elevated blood pressure (OR = 6.06, 95% CI 1.11 - 33.33, p = .038) at the time of biopsy. Infections were the most common adverse event with 50 infections seen in 39 (29.8%) patients. Herpes viral infections were frequently noted ( n = 12) accounting for 24.0% of all documented infections., Conclusion: Response rates were similar in this cohort when compared to other contemporary studies. Predictors of poor response were an elevated baseline serum creatinine, a decreased eGFR and an elevated blood pressure at time of the biopsy. Infections were the most common occurring adverse event, although the mortality rate remained low at 2.3%., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Angiotensin-converting enzyme inhibitor-induced angioedema (AE-ACEI) is a life-threatening adverse event and, globally, the commonest cause of emergency presentations with angioedema. Several large genome-wide association studies (GWAS) have found genomic associations with AE-ACEI. However, despite African Americans having a 5-fold increased risk of AE-ACEI, there are no published GWAS from Africa. The aim of this study was to conduct a case-control GWAS of AE-ACEI in a South African population and perform a meta-analysis with an African American and European American population., Methods: The GWAS included 202 South African adults with a history of AE-ACEI and 513 controls without angioedema following angiotensin-converting enzyme inhibitor (ACEI) treatment for at least 2 years. A meta-analysis was conducted with GWAS summary statistics from an African American and European American cohort (from Vanderbilt/Marshfield with 174 cases and 489 controls)., Results: No SNPs attained genome-wide significance. However, 26 SNPs in the post-imputation standard GWAS of the South African cohort and 37 SNPs in the meta-analysis were associated to AE-ACEI with suggestive threshold(p-value<5.0×10 -06 ). Some of these SNPs were found to be located close to the genes PRKCQ and RIMS1, previously linked with drug-induced angioedema, and also close to the CSMD1 gene linked to ACEI cough, providing replication at the gene level, but with novel lead SNPs., Conclusions: Our results highlight the importance of African populations to detect novel variants in replication studies. Further increased sampling across the continent and matched functional work are needed to confirm the importance of genetic variation in understanding the biology of AE-ACEI.

Background: Hospital-acquired infections (HAI) are a leading cause of morbidity and mortality globally. These infections are diverse, but the majority are lower respiratory tract infection (LRTI), surgical site infection (SSI), bloodstream infection (BSI), and urinary tract infection (UTI). For most sub-Saharan African countries, studies revealing the burden and impact of HAI are scarce, and few systematic reviews and meta-analysis have been attempted. We sought to fill this gap by reporting recent trends in HAI in sub-Saharan Africa (SSA) with attention to key patient populations, geographic variation, and associated mortality., Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a literature search of six electronic databases (Web of Science, Pubmed, APA PsycInfo, CINAHL, Embase, and the Cochrane Library) to identify studies assessing the prevalence of HAI in SSA countries. Studies published between 01 January 2014 and 31 December 2023 were included. We applied no language or publication restrictions. Record screening and data extractions were independently conducted by teams of two or more reviewers. Using the R software (version 4.3.1) meta and metafor packages, we calculated the pooled prevalence estimates from random-effect meta-analysis, and further explored sources of heterogeneity through subgroup analyses and meta-regression. This study is registered with PROSPERO, CRD42023433271., Findings: Forty-one relevant studies were identified for analysis, consisting of 15 from West Africa (n = 2107), 12 from Southern Africa (n = 2963), 11 from East Africa (n = 2142), and 3 from Central Africa (n = 124). A total of 59.4% of the patient population were associated with paediatric admissions. The pooled prevalence of HAI was estimated at 12.9% (95% CI: 8.9-17.4; n = 7336; number of included estimates [k] = 41, p < 0.001). By subregions, the pooled current prevalence of HAI in the West Africa, Southern Africa, East Africa and Central Africa were estimated at 15.5% (95% CI: 8.3-24.4; n = 2107; k = 15), 6.5% (95% CI: 3.3-10.7; n = 2963; k = 12), 19.7% (95% CI: 10.8-30.5; n = 2142; k = 11) and 10.3% (95% CI: 1.1-27.0; n = 124; k = 3) of the patient populations respectively. We estimated mortality resulting from HAI in SSA at 22.2% (95% CI: 14.2-31.4; n = 1118; k = 9)., Interpretation: Our estimates reveal a high burden of HAI in SSA with significant heterogeneity between regions. Variations in HAI distribution highlight the need for infection prevention and surveillance strategies specifically tailored to enhance prevention and management with special focus on West and East Africa, as part of the broader global control effort., Funding: No funding was received for this study., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Introduction: The management of complex interactions between antiretroviral therapy (ART) and calcineurin inhibitor (CNI) immunosuppression regimens in HIV-positive to HIV-positive renal transplant recipients can be challenging. Literature describing ART regimens and indications for regimen switching in these patients is limited., Methods: This retrospective review included 53 HIV-positive to HIV-positive renal transplant recipients. Data on ART regimens, reasons for ART switching, and timing of switches were described from day of transplant to study endpoint (end of study date, death, or graft failure). The association between rejection and ART regimen (protease inhibitor [PI] -based vs. non-PI-based regimen) was analyzed using negative binomial regression., Results: There were a total of 46 switches in 31 of 53 patients (58%). Protocol switches ( n  = 17 of 46, 37%) accounted for most switches, of which the majority were from non-nucleoside reverse transcriptase inhibitors (NNRTIs) to PIs. Other common reasons for switching include cytochrome P450 enzyme induction from efavirenz (EFV) (9 of 46, 20%), tenofovir disoproxil fumarate (TDF) nephrotoxicity (8 of 46, 17%) or side effects (6 of 46, 13%). Of the 46 switches, nearly half ( n  = 21, 46%) occurred during the transplant admission period, and approximately two-thirds ( n  = 28, 62%) were during the first year post-transplantation. There was an association between rejection and being maintained on a PI-based regimen (incidence rate ratio 2.77 (95% confidence interval 1.03-7.48), P  = 0.044)., Conclusion: Despite frequent switching of ART regimens, HIV viral loads remained supressed and graft function remained stable in most HIV-positive kidney transplant recipients in our cohort. There was however a concerning signal for increased rejection rates in those on a PI-based regimen., (© 2022 International Society of Nephrology. Published by Elsevier Inc.)

Kawasaki-like multisystem inflammatory syndrome related to SARS-CoV-2 infection is a well-described condition in children and adolescents (MIS-C) and now also in adults (MIS-A). We report a case of MIS-A in a previously well woman in her mid-30s who presented with vasopressor-dependent shock 2 weeks after initial recovery from suspected SARS-CoV-2 infection, accompanied by fever, vomiting, diarrhoea, weakness, arthralgia, rash, cough and headache. Examination was notable for fever, tachycardia, hypotension, cervical lymphadenopathy, mucocutaneous involvement, neck stiffness, pansystolic murmur and bilateral crepitations. Inflammatory markers were elevated. Echocardiogram showed mitral regurgitation with preserved ejection fraction. She was treated with vasopressors, admitted to the intensive care unit and subsequently required invasive mechanical ventilation. Both PCR and antibodies for SARS-CoV-2 were positive. Treatment with intravenous methylprednisolone and intravenous immunoglobulin was initiated with rapid improvement in clinical condition and inflammatory markers. She has since made a full recovery with normal echocardiogram 8 months later., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

We report a case of severe hypokalaemia and moderate hypophosphataemia from clay ingestion. A 60-year-old woman presented with flaccid paralysis. Investigations revealed a serum potassium level of 1.8 mmol/L, phosphate level of 0.56 mmol/L and creatine kinase level of 30 747 IU/L. She had marked proximal and distal muscle weakness due to severe hypokalaemia and concurrent hypophosphataemia, which likely contributed to the onset of rhabdomyolysis. The patient subsequently admitted to significant pica, most likely secondary to an associated iron deficiency. We conclude that the ingested clay acted as a potassium and phosphate binder. Although we did not investigate the content of the clay in this case, it has been reported that clay can bind potassium in vitro and is rich in minerals such as aluminium that could play a role in the binding of phosphate, although the exact mechanism remains unclear. The patient recovered fully and outpatient follow-up at 6 months and again at 40 months confirmed no electrolyte abnormality, myopathy nor any further geophagia., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

Background: No African countries were included in the development of the Simplified Acute Physiology Score 3 (SAPS 3). This study aimed to assess the performance of the SAPS 3 as a predictor of hospital mortality in patients admitted to a multi-disciplinary tertiary intensive care unit (ICU) in South Africa., Methods: A prospective cohort study was undertaken in a tertiary single-centre closed multidisciplinary ICU with 16 beds over 12 months in 2017. First time admissions 12 years and over were included. Exclusions were patients who died within six hours of admission, incomplete data sets and unknown outcome after ICU discharge. Demographic data, clinical admission data and co-morbidities were recorded. The SAPS 3 score was calculated within the first hour of ICU admission. The highest Sequential Organ Failure Assessment score, vasopressor use, mechanical ventilation requirements and details of acute kidney injury, if present, were recorded. Discrimination of the model was evaluated using an area under the receiver operating characteristic curve (AUROC) and calibration by the Hosmer-Lemeshow (HL) Goodness of Fit Test (Ĉ and Ĥ statistic). The observed versus the SAPS 3 model predicted mortality ratios were compared and the standardized mortality ratio (SMR) was calculated., Results: A total of 829 admissions with a mean SAPS 3 (SD) of 48.1 (16) were included. Of patients with a known human immunodeficiency virus (HIV) status, 32,4% were positive. The ICU and hospital mortality rates were 13.3% and 21.4% respectively. The SAPS 3 model had a AUROC of 0.796 and HL Ĉ and Ĥ statistics were 12.1 and 11.8 (p-values 0.15 and 0.16). The SMR for the model was 1.002 (95%CI: 0.91-1.10). The mortality of 41% for the subgroup with sepsis/septic shock was higher than predicted with a SMR of 1.24 (95% CI 1.11-1.37)., Conclusions: The SAPS 3 model showed good calibration and fair discrimination when applied to the cohort. The SAPS 3 model can be used to describe the case mix in this African ICU with a high incidence of HIV. Ongoing efforts should be made to improve outcomes of septic patients., Competing Interests: Roche South Africa provided an unrestricted research grant that was used to fund data capturing, analysis, presentation and publication of the study. Roche SA was not involved in the design or writing of this research. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

We report here a case that highlights tuberculosis (TB) as a possible cause for pauci-immune crescentic glomerulonephritis (c-GN), an important and often treatable cause of kidney injury. A 47-year-old HIV-negative man of mixed ethnicity presented with a 2-week history of cough, haemoptysis and unintentional weight loss. Chest examination revealed crepitations over the right upper zone and urinalysis demonstrated an active urinary sediment with red cell casts. Chest radiograph confirmed right upper lobe cavitation. Serum laboratory investigations revealed a serum creatinine of 632 µmol/L and were negative for antineutrophil cytoplasmic antibodies. A diagnosis of pauci-immune c-GN was made on renal biopsy. In addition, sputum PCR confirmed infection with drug-sensitive Mycobacterium tuberculosis Standard TB treatment and immunosuppression with prednisone and cyclophosphamide was commenced, and over the course of 6 months, renal function improved to an estimated glomerular filtration rate >60 mL/min., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Resistant hypertension is a common clinical problem in South Africa and is frequently associated with low renin and aldosterone levels, especially in black Africans. In South Africa, novel variants in the epithelial sodium channel (ENaC) have been described to be associated with varying degrees of hypokalaemia and hypertension due to primary sodium retention. We report here a case of Liddle's syndrome due to a novel c.1709del11 (p.Ser570Tyrfs*20) deletion in the beta-subunit of the ENaC in a young black African male. We discuss the likely pathogenesis of hypertension in this setting as well as the treatment options available in South Africa aimed at the ENaC. This case highlights the need for vigilance in detecting and appropriately treating low-renin and low-aldosterone hypertension in view of the frequency of the described variants of the ENaC channel in our country. Specific therapy such as amiloride should be made more widely available.

Aim: Studies from the US have shown little effect of ethnicity on vascular calcification in dialysis patients. This has not been examined in the multi-ethnic population of South Africa where genetic and environmental differences may exist. We assessed the extent and severity of vascular calcification in South African dialysis patients according to race and known risk factors. We further evaluated the association of abdominal aorta calcification with coronary artery calcification., Method: Seventy-five CKD-5D patients and 20 healthy controls were enrolled consecutively. All subjects underwent chest computed tomography for coronary calcium score and abdominal X-ray for abdominal aorta calcium score. Ambulatory blood pressure monitoring was generated via radial artery applanation tonometry., Results: Coronary calcification was present in 38.6% of patients and was associated with age and prior cardiovascular disease on multivariate analyses. The median coronary calcium score in black patients was 0 (IQR 0) and 66 in non-Blacks (IQR 383, P < 0.001); controls had a coronary calcium score of 0 (IQR 0). Black race remained a significant negative predictor for coronary calcification after adjustment, prevalence ratio = 0.14 and 95% confidence interval (CI): 0.0-0.53. Vascular calcification was not associated with any ambulatory blood pressure parameter. Using receiver operator characteristic curves, an abdominal aorta calcification score of ≥1 showed an area under the curve of 0.83 to predict a coronary calcium score ≥ 10., Conclusion: Black race appears to protect from vascular calcification in South African CKD-5D patients and this warrants further study regarding the underlying mechanism. The abdominal X-ray is a useful screening tool for coronary calcification., (© 2012 The Authors. Nephrology © 2012 Asian Pacific Society of Nephrology.)

Background: Non-diabetic patients presenting with an acute stroke often have hyperglycaemia. In most populations it is unknown whether the hyperglycaemia is transient and due to the acute stress response or whether it represents undiagnosed abnormal glucose metabolism., Aim: To evaluate the prevalence and predictors of persistent hyperglycaemia in non-diabetic patients with an acute stroke., Design: Prospective observational study., Methods: Non-diabetic patients over 40 years old with an acute stroke were enrolled over a 2-year period. On admission patients were evaluated with an HbA(1c) and a 75 g oral glucose tolerance test (OGTT). The OGTT was repeated 3 months later. A meta-analysis was performed to interpret our results in the context of published data., Results: One hundred and seven patients were analysed. On admission 26 (24%) patients had diabetes, 39 (37%) had impaired glucose tolerance and 42 (39%) had normal glucose tolerance. Forty-four (68%) patients with hyperglycaemia on admission were re-investigated at least 3 months after discharge. Of these, 6 (14%) had diabetes, 12 (27%) had impaired glucose tolerance and 26 (59%) had normal glucose tolerance. A 2-h post-load glucose value >or=10 mmol/l predicted persistent hyperglycaemia with 72.2% sensitivity, 65.4% specificity and a positive predictive value and negative predictive value of 59.1 and 77.3%, respectively. A meta-analysis of prevalence data of impaired glucose metabolism in non-diabetic individuals 3 months after having had an acute stroke revealed a combined prevalence of 58% (95% confidence interval 25.4-90.5%)., Conclusion: In this study hyperglycaemia in the setting of an acute stroke was transient in the majority of patients.