Background. There are limited data on kidney replacement therapy (KRT) allocation and outcomes in patients in kidney failure (KF) who access public healthcare in South Africa. Methods. This retrospective cohort study included patients referred for KRT at the time of KF diagnosis. Incident KF cases were identified between 2012 and 2020, followed from referral until death, kidney transplantation, or continued waitlisting at study end (December 31, 2023). Descriptive analyses and comparisons were performed between KRT allocation and outcomes. Time-to-event analyses employed competing risk models to estimate cumulative incidence functions, whereas Kaplan-Meier methods were applied to calculate survival probabilities. Results. Overall, 761 patients were referred with KF, of which 598 (79%) were untreated and presumed to have died. Untreated patients were either not considered at referral (n = 432), or not accepted at KRT committee meeting (n = 175) because of policy-driven factors. Of those presented to the KRT committee (n = 338), 48% (n = 163) were accepted onto the dialysis program and waitlisted for transplantation. Accepted patients were younger and had greater medical stability and socioeconomic circumstances compared with non-accepted patients. Only 21% (n = 34) of patients initiated on dialysis were transplanted. At 5 y post-KRT initiation, there was a greater probability of dying on the waitlist compared with receiving a transplant (cumulative incidence function 35% [95% CI, 27-42] versus 18% [95% CI, 13-25]), and post-transplantation survival was significantly greater than pre-transplant survival (100% versus 61% [95% CI, 53-69]). Conclusions. Our study findings align with the challenges of providing dialysis and transplantation in a lower- to middle-income setting where patients were most often precluded from KRT because of poorly controlled comorbidities or a lack of unit capacity. There was a clear survival advantage in patients who were transplanted over those who remained on dialysis; however, transplant services remain limited.

Background: Kidney failure is a major health issue in South Africa. The public health sector has adopted a ‘peritoneal dialysis (PD) first’ policy for kidney replacement therapy. PD may be characterized by high failure rates, commonly due to PD-associated peritonitis (PDP), although no data exist for the Eastern Cape (EC) province. Here we describe PDP episodes and their outcomes at a tertiary hospital in Gqeberha, EC.Methods: A retrospective study was conducted on all adult patients receiving chronic PD at Livingstone Tertiary Hospital from 2022–2024, evaluating microbiological profiles and outcomes of all PDP episodes.Results: Of 91 patients (mean age 38.8 years; 52% male), 61 (67%) experienced PDP. Overall, 117 episodes of PDP occurred over 126.9 patient-years (0.85 episodes/patient-year). Twelve patients (20%) had ≥3 episodes. The culture negative rate was low (11%); Gram-positive organisms predominated (71%). The medical cure rate was 65%. Relapse (OR 0.21; 95% CI 0.06–0.76) and fungal episodes (OR 0.09; CI 0.02–0.39) were associated with lower odds of cure, whereas Gram-positive cases had higher odds than Gram-negatives (OR 3.19; 1.18–8.64). HIV was not associated with episode profile or outcomes. Catheter removal occurred in 21 (18%) episodes; 16 (14%) episodes required modality switch to haemodialysis. Only four patients successfully resumed PD after interval haemodialysis.Conclusions: PDP rates in EC exceed international targets and contribute to technique failure. Culture-negative and medical cure rates were acceptable. Gram-positive organisms predominated, suggesting a need for improved patient training. Resource restrictions and socio-economic factors may contribute to the high rate.

Introduction: Hepatitis B virus (HBV) infection remains a concern in dialysis populations where vaccination has been less successful than in the general population. Possible reasons for poor response to vaccination in this population include malnutrition, age, uraemia, dialysis vintage, human immunodeficiency virus (HIV) infection and the generalized immunosuppressive state of patients with chronic kidney disease (CKD). Methods: This retrospective point prevalent cohort study evaluated the prevalence of HBV infection in a dialysis population at a tertiary centre in South Africa where there is a high prevalence of HIV. In addition, antibody responses following natural HBV infection versus vaccination were examined in the same population as well as factors that may affect the HBV vaccination antibody response. Results: There were 107 study participants. The prevalence rate of chronic HBV was high at 6.5% (n = 7), whereas 48 (45%) patients demonstrated evidence of HBV exposure. Patients with naturally acquired immunity demonstrated a more robust and sustained antibody response over the study period, whereas booster dose(s) were required to achieve similar levels of protection in the vaccinated group. Only one (2.1%) of those requiring vaccination never achieved an adequate seroprotection response to vaccination at any time point during the study period. Older age was the only factor shown to reduce seroconversion after primary vaccination. Despite high HIV prevalence (23%), HIV status did not affect antibody response to vaccination. Conclusion: We therefore conclude that in a cohort of dialysis patients with high HBV prevalence, natural immunity provides sustained and adequate protection. HBV vaccination in this dialysis cohort was successful, but additional booster doses were frequently required to achieve adequate seroprotection, regardless of HIV status.

Background. The characteristics and mortality outcomes of patients admitted to South African intensive care units (ICUs) owing to medical conditions are unknown. Available literature is derived from studies based on data from high-income countries.Objectives. To determine ICU utilisation by medical patients and evaluate the scope of admissions and clinical associations with hospital mortality in ICU patients 12 years and older admitted to an Eastern Cape tertiary ICU, particularly in the subset with HIV disease. Methods. A retrospective descriptive one-year cohort study. Data were obtained from the LivAKI study database and demographic data, comorbidities, diagnosis, and mortality outcomes and associations were determined.Results. There were 261 (29.8%) medical ICU admissions. The mean age of the cohort was 40.2 years; 51.7% were female. When compared with the surgical emergencies, the medical subgroup had higher sequential organ failure assessment (SOFA) scores (median score 5 v. 4, respectively) and simplified acute physiology score III (SAPS 3) scores (median 52.7 v. 48.5), a higher incidence of acute respiratory distress syndrome (ARDS) (7.7% v. 2.9%) and required more frequent dialysis (20.3% v. 5.5%). Of the medical admissions, sepsis accounted for 32.4% of admission diagnoses. The HIV seroprevalence rate was 34.0%, of whom 57.4% were on antiretroviral therapy. ICU and hospital mortality rates were 11.1% and 21.5% respectively, while only acute kidney injury (AKI) and sepsis were independently associated with mortality. The HIV-positive subgroup had a higher burden of tuberculosis (TB), higher admission SOFA and SAPS 3 scores and required more organ support. Conclusion. Among medical patients admitted to ICU, there was a high HIV seroprevalence with low uptake of antiretroviral therapy. Sepsis was the most frequently identified ICU admission diagnosis. Sepsis and AKI (not HIV) were independent predictors of mortality. Co-infection with HIV and TB was associated with increased mortality.

Background. Tacrolimus forms the cornerstone for immunosuppression in solid-organ transplantation. It has a narrow therapeutic window with wide inter- and intra-patient variability (IPV). Cytochrome P-450 3A5 (CYP3A5) is the main enzyme involved in tacrolimus metabolism, and rs776746A>G is the most frequently studied polymorphism in the CYP3A5 gene. The rs776746A>G (i.e. CYP3A5(star)3) single-nucleotide polymorphism in CYP3A5 alters tacrolimus predose trough concentration (C-0) and may also affect IPV, which may lead to immune- and/or drug-mediated allograft injury. CYP3A5(star)3 may result in absent ((star)3/(star)3), partial ((star)1/(star)3) or normal ((star)1/(star)1) CYP3A5 expression. The effect of CYP3A5(star)3 on tacrolimus exposure and variability has not been examined in South African (SA) transplant recipients. Objectives. To determine the frequencies and effect of CYP3A5 and adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) polymorphisms on tacrolimus C-0/dose ratios in different ethnic groups attending a tertiary renal transplant clinic in SA, and other factors that may explain inter- and IPV in tacrolimus C-0. Methods. All consenting stable renal transplant recipients on tacrolimus at the Livingstone Hospital Renal Unit in Port Elizabeth, SA, were included. Tacrolimus concentrations were obtained using a microparticle enzyme immunoassay method (ARCHITECT analyser, Abbott Laboratories). Polymerase chain reaction/restriction fragment length polymorphism was used to genotype for CYP3A5(star)3 and (star)6 allelic variants. Results. There were 43 participants (35% black African, 44% mixed ancestry and 21% white), with a mean age of 44.5 years, median duration post-transplant of 47 months and median (interquartile range) creatinine and estimated glomerular filtration rate levels of 118 (92 - 140) mu mol/L and 62 (49 - 76) mL/min at study inclusion. The mean tacrolimus C-0 in the study was 6.7 ng/mL, with no difference across the different ethnic groups. However, the mean total daily dose of tacrolimus required was 9.1 mg (0.12 mg/kg), 7.2 mg (0.09 mg/kg) and 4.3 mg (0.06 mg/kg) in black, mixed-ancestry and white patients, respectively (p=0.017). The frequencies for CYP3A5 expressors (i.e. CYP3A5(star)1/(star)1 + CYP3A5(star)1/(star)3 genotypes) were 72%, 100%, 76% and 12% for all patients combined and black, mixed-ancestry and white patients, respectively. The frequencies for CYP3A5 non-expressors (i.e. CYP3A5(star)3/(star)3 genotypes) were 0%, 24% and 88% among the black, mixed-ancestry and white patients, respectively. None of the patients carried the CYP3A5(star)6 allele. CYP3A5(star)1/(star)1 and CYP3A5(star)1/(star)3 genotype carriers required a two-fold increase in dose compared with the non-expressor genotype carriers, CYP3A5(star)3/(star)3 (p<0.05). CYP3A5(star)3/(star)3 carriers also demonstrated higher IPV than CYP3A5(star)1/(star)1 and (star)1/(star)3 carriers (18.1% v. 14.2%; p=0.125). Conclusions. Compared with global transplant populations, SA renal transplant recipients demonstrated a very high rate of CYP3A5 expression, with a significant impact on tacrolimus pharmacokinetics. Genetic variation in CYP3A5 expression affects tacrolimus dosing requirements, and knowing the CYP3A5 genotype of transplant patients may allow better dose prediction compared with current standard dosing recommendations in a multi-ethnic population. Overall, black African patients required higher doses of tacrolimus than their white counterparts. While further prospective studies are needed to better evaluate dosing algorithms, it would appear that the starting dose of tacrolimus should be higher in black and mixed-race patients.

Background: There is a marked paucity of data concerning AKI in Sub-Saharan Africa, where there is a substantial burden of trauma and HIV. Methods: Prospective data was collected on all patients admitted to a multi-disciplinary ICU in South Africa during 2017. Development of AKI (before or during ICU admission) was recorded and renal recovery 90 days after ICU discharge was determined. Results: Of 849 admissions, the mean age was 42.5 years and mean SAPS 3 score was 48.1. Comorbidities included hypertension (30.5%), HIV (32.6%), diabetes (13.3%), CKD (7.8%) and active tuberculosis (6.2%). The most common reason for admission was trauma (26%). AKI developed in 497 (58.5%). Male gender, illness severity, length of stay, vasopressor drugs and sepsis were independently associated with AKI. AKI was associated with a higher in-hospital mortality rate of 31.8% vs 7.23% in those without AKI. Age, active tuberculosis, higher SAPS 3 score, mechanical ventilation, vasopressor support and sepsis were associated with an increased adjusted odds ratio for death. HIV was not independently associated with AKI or hospital mortality. CKD developed in 14 of 110 (12.7%) patients with stage 3 AKI; none were dialysis-dependent. Conclusions: In this large prospective multidisciplinary ICU cohort of younger patients, AKI was common, often associated with trauma in addition to traditional risk factors and was associated with good functional renal recovery at 90 days in most survivors. Although the HIV prevalence was high and associated with higher mortality, this was related to the severity of illness and not to HIV status per se.

Acute Kidney Injury (AKI) is associated with substantial morbidity and mortality in the Intensive Care Unit (ICU). There are wide variations in the reported incidence of AKI in high-income country ICU's. However, there is a paucity of data concerning AKI and its incidence, aetiology and effect on mortality as well as functional renal recovery in Sub-Saharan Africa, where there is a substantial burden of HIV.

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.

Nephrotoxicity due to chronic use of tenofovir disoproxil fumarate (TDF) is well described, but very little is known or published about the effects of acute toxicity or the clinical management of this condition. We present here a case of acute and irreversible renal failure that followed an intentional overdose of fixed dose combination antiretroviral therapy containing efavirenz, TDF and emtricitabine. The renal histology findings are discussed and a rationale for the use of emergency haemodialysis in the management of TDF overdose is presented.

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.