The state of kidney replacement therapy in Eastern Cape Province, South Africa: A call to action.

BACKGROUND: South Africa (SA) is one of the most financially unequal countries in the world. This situation is highlighted by disparate access to healthcare, particularly provision of kidney replacement therapy (KRT). Unlike the private sector, public sector access to KRT is highly rationed, and patient selection is based on suitability for transplantation and capacity. OBJECTIVES: To investigate the state of the KRT service in Eastern Cape Province, SA, by analysing access to and provision of KRT in the province for individuals with end-stage kidney disease, as well as disparities between the private and public healthcare systems. METHODS: This was a retrospective descriptive study to examine KRT provision and temporal trends in the Eastern Cape. Data were obtained from the South African Renal Registry and the National Transplant Waiting List. KRT provision was compared between the three main referral centres, in Gqeberha (formerly Port Elizabeth), East London and Mthatha, and between the private and public healthcare systems. RESULTS: There were 978 patients receiving KRT in the Eastern Cape, with an overall treatment rate of 146 per million population (pmp). The treatment rate for the private sector was 1 435 pmp, compared with 49 pmp in the public sector. Patients treated in the private sector were older at initiation of KRT (52 v. 34 years), and more likely to be male, to be HIV positive, and to receive haemodialysis as their KRT modality. Peritoneal dialysis was more commonly used in Gqeberha and East London as the first and subsequent KRT modality, compared with Mthatha. There were no patients from Mthatha on the transplant waiting list. There were no waitlisted HIV-positive patients in the public sector in East London, compared with 16% of the public sector patients in Gqeberha. The kidney transplant prevalence rate was 58 pmp in the private sector and 19 pmp in the public sector, with a combined prevalence of 22 pmp, constituting 14.9% of all patients on KRT. We estimated the shortfall of KRT provision in the public sector to be ~8 606 patients. CONCLUSION: Patients in the private sector were 29 times more likely to access KRT than their public sector counterparts, who were on average 18 years younger at initiation of KRT, probably reflecting selection bias in an overburdened public health system. Transplantation rates were low in both sectors, and lowest in Mthatha. A large public sector KRT provision gap exists in the Eastern Cape and needs to be addressed urgently.

The characteristics and costs of severe theophylline toxicity in a tertiary critical care unit in Eastern Cape Province, South Africa.

BACKGROUND: Severe theophylline toxicity requiring haemodialysis accounts for approximately one-third of drug toxicity cases admitted to the Livingstone Tertiary Hospital (LTH) intensive care unit (ICU) in Gqeberha, South Africa, imposing a significant resource burden. OBJECTIVES: To investigate the characteristics and burden of severe theophylline toxicity in an Eastern Cape Province tertiary hospital adult ICU. METHODS: A retrospective review of all severe theophylline toxicity admissions to the ICU from 1 January 2013 to 31 December 2018 was conducted. Demographic and clinical data were captured and analysed. The National Department of Health 2019 fees schedule was used to calculate costs based on duration of ICU stay and number of haemodialysis sessions received. RESULTS: Of the 57 patients included in the study, 84% were cases of deliberate self-harm. The majority were aged <40 years (77%) and female (79%). The mean (standard deviation (SD)) initial serum theophylline level was 612 (269) µmol/L. Complications included convulsions (n=12; 21%), arrhythmias (n=9; 16%), need for mechanical ventilation (n=7; 12%) and death (n=4; 7%). The main risk factors for these complications were age ≥30 years, an inappropriately normal or elevated initial serum potassium level, an elevated serum creatinine kinase level and an elevated initial serum theophylline level. Receiver operator characteristic curve analysis assessing the initial serum theophylline level as a discriminator for life-threatening complications produced an area under the curve of 0.71 for serum theophylline >400 µmol/L (sensitivity 88%, specificity 12%). All the 4 patients who died had an initial serum theophylline level >1 000 µmol/L. The mean (SD) cost per admission amounted to ZAR16 897 (10 718), with a mean of one 4-hour dialysis session per admission. CONCLUSION: Severe theophylline toxicity, usually in the context of  deliberate self-harm, is a preventable yet life-threatening toxicity encountered at  LTH.  Demographic  risk factors include young females from certain areas in and around Gqeberha.  Risk factors for complications include older age, paradoxically normal or elevated serum potassium levels, elevated serum creatinine kinase levels and an initial serum theophylline level >400 µmol/L. Patients with these clinical features should be closely monitored and treated timeously at an appropriate level of care. The need for ICU admission and dialysis, both limited resources, makes the treatment of severe theophylline toxicity costly. Further studies of the underlying psychosocial drivers, local prescribing practices and preventive interventions related to severe theophylline toxicity are required.

Scope and mortality of adult medical ICU patients in an Eastern Cape tertiary hospital.

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. Contributions of the study: The epidemiology and outcomes of adults who are critically ill from medical conditions in South African intensive care units was previously unknown but has been described in this study. The association of sepsis, TB, HIV and acute kidney injury with mortality is discussed.

THe characteristics and costs of severe theophylline toxicity in a tertiary critical care unit in Eastern Cape Province, South Africa

Severe theophylline toxicity requiring haemodialysis accounts for approximately one-third of drug toxicity cases admitted to the Livingstone Tertiary Hospital (LTH) intensive care unit (ICU) in Gqeberha, South Africa, imposing a significant resource burden.Objectives. To investigate the characteristics and burden of severe theophylline toxicity in an Eastern Cape Province tertiary hospital adult ICU.Methods. A retrospective review of all severe theophylline toxicity admissions to the ICU from 1 January 2013 to 31 December 2018 was conducted. Demographic and clinical data were captured and analysed. The National Department of Health 2019 fees schedule was used to calculate costs based on duration of ICU stay and number of haemodialysis sessions received.Results. Of the 57 patients included in the study, 84% were cases of deliberate self-harm. The majority were aged <40 years (77%) and female (79%). The mean (standard deviation (SD)) initial serum theophylline level was 612 (269) µmol/L. Complications included convulsions (n=12; 21%), arrhythmias (n=9; 16%), need for mechanical ventilation (n=7; 12%) and death (n=4; 7%). The main risk factors for these complications were age ≥30 years, an inappropriately normal or elevated initial serum potassium level, an elevated serum creatinine kinase level and an elevated initial serum theophylline level. Receiver operator characteristic curve analysis assessing the initial serum theophylline level as a discriminator for life-threatening complications produced an area under the curve of 0.71 for serum theophylline >400 µmol/L (sensitivity 88%, specificity 12%). All the 4 patients who died had an initial serum theophylline level >1 000 µmol/L. The mean (SD) cost per admission amounted to ZAR16 897 (10 718), with a mean of one 4-hour dialysis session per admission.Conclusion. Severe theophylline toxicity, usually in the context of deliberate self-harm, is a preventable yet life-threatening toxicity encountered at LTH. Demographic risk factors include young females from certain areas in and around Gqeberha. Risk factors for complications include older age, paradoxically normal or elevated serum potassium levels, elevated serum creatinine kinase levels and an initial serum theophylline level >400 µmol/L. Patients with these clinical features should be closely monitored and treated timeously at an appropriate level of care. The need for ICU admission and dialysis, both limited resources, makes the treatment of severe theophylline toxicity costly. Further studies of the underlying psychosocial drivers, local prescribing practices and preventive interventions related to severe theophylline toxicity are required.

Tuberculosis burden in stage 5 chronic kidney disease patients undergoing dialysis therapy at Livingstone Hospital, Port Elizabeth, South Africa.

BACKGROUND: Tuberculosis (TB) is currently the leading cause of death from a single infectious agent worldwide. Patients who receive dialysis are particularly vulnerable to TB infection owing to immune dysfunction. Nonetheless, there is a paucity of incidence data on dialysis patients infected with TB in high-burden countries, such as South Africa (SA). OBJECTIVES: To determine the incidence of TB in prevalent chronic kidney disease stage 5 (CKD-5D) patients on dialysis at a single centre in Eastern Cape Province, SA, and to identify the risk factors associated with TB infection. METHODS: We conducted a retrospective cohort study of all consenting CKD-5D patients between April 2010 and March 2014 at Livingstone Hospital Renal Unit, Port Elizabeth, the Eastern Cape. TB was defined as definite or probable according to World Health Organization (WHO) criteria, and the cohort was split into those who developed TB (TB+) and those who did not (TB-). RESULTS: One hundred and eleven patients were enrolled - predominantly black Africans (73%) and women (53%); the mean age (standard deviation (SD)) was 42 (9.8) years. The prevalence of HIV infection was 11%, all patients were receiving antiretroviral treatment and all had suppressed viral loads. Sixty-eight patients were on haemodialysis and 43 on peritoneal dialysis. Nineteen patients were diagnosed with 20 episodes of TB; 14 cases were pulmonary TB and 6 cases extrapulmonary TB. Of the patients with TB, 2 were HIV-infected, 7 (35%) were definite TB cases and 13 (65%) were probable cases. The calculated incidence rate was 4 505/100 000 patient years. Only informal housing (30% in TB+ v. 12% in TB-; p=0.042) and a history of hospitalisation (90% v. 76%, respectively; p=0.042) were significantly associated with a diagnosis of TB. CONCLUSIONS: Dialysis patients in the Eastern Cape region of SA are at extremely high risk of acquiring TB, with an incidence rate 4.1 times that of the local population and >5 times that of the general SA population. Only informal housing and a history of hospitalisation were identified as positive risk factors for TB in this young population with a low HIV prevalence. Isoniazid prophylaxis in this high-risk group might be of benefit, but further studies are required to inform such treatment.

CYP3A5 polymorphisms and their effects on tacrolimus exposure in an ethnically diverse South African renal transplant population.

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*3) single-nucleotide polymorphism in CYP3A5 alters tacrolimus predose trough concentration (C0) and may also affect IPV, which may lead to immune- and/or drug-mediated allograft injury. CYP3A5*3 may result in absent (*3/*3), partial (*1/*3) or normal (*1/*1) CYP3A5 expression. The effect of CYP3A5*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 C0/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 C0. 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*3 and *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) µmol/L and 62 (49 - 76) mL/min at study inclusion. The mean tacrolimus C0 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*1/*1 + CYP3A5*1/*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*3/*3 genotypes) were 0%, 24% and 88% among the black, mixed-ancestry and white patients, respectively. None of the patients carried the CYP3A5*6 allele. CYP3A5*1/*1 and CYP3A5*1/*3 genotype carriers required a two-fold increase in dose compared with the non-expressor genotype carriers, CYP3A5*3/*3 (p<0.05). CYP3A5*3/*3 carriers also demonstrated higher IPV than CYP3A5*1/*1 and *1/*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.

The utility of urine sulphosalicylic acid testing in the detection of non-albumin proteinuria.

We report two cases of immunoglobulin light chain proteinuria (Bence Jones proteinuria) detected by simple side-room invest-igations: urine dipstick negative/1+, but with strong positive pre-cipitation on addition of an equal volume of sulphosalicylic acid (SSA) 3%. We highlight a significant limitation of urine dipstick testing, namely specificity for albumin, and the utility of SSA testing for the detection of urinary free light chain immunoglobulins.

Abnormal glucose metabolism in non-diabetic patients presenting with an acute stroke: prospective study and systematic review.

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.