Patient outcomes in a PD First Program in Cape Town, South Africa

Background: South Africa [SA] currently performs the most peritoneal dialysis [PD] in Africa. Yet, outcome data is limited. With the collision of epidemics of communicable and non-communicable diseases in Africa the need for chronic dialysis is escalating. PD remains a life-saving modality especially as haemodialysis is limited in the state sector. Methods: We retrospectively analysed all patients undergoing PD at Groote Schuur Hospital from January 2008 until June 2014 and thereafter prospectively until June 2015. Variables included demographics, adequacy, modality, fluid, cardiovascular risk and diabetes. The influences of these variables on peritonitis rate, technique and patient survival were assessed. Results: 230 patients were initiated on PD, 31 were excluded as they were on PD for < 90 days. The mean age was 39.7 +/- 10.4 years [SD], 49.8% were male and 63.8% were mixed ancestry. 9.8 % were diabetic at dialysis initiation. The average length of time on PD was 17 months (IQR 8 - 32). The peritonitis rate was 0.87 events per patient years. One, 2 and 5 year patient and technique survival was 94.4%, 84.3% and 60.2% and 82.5%, 69.0% and 37.4% respectively. Fluid overload (p=0.019) and low haemoglobin (p=0.001) were independent risk factors for poor survival. African race (HR 1.97, 95% CI (1.16 - 3.37) and fluid overload (p= 0.002) were both predictors of technique failure. Conclusions: In our PD-First programme the results are encouraging, despite lack of home visits due to safety, resource limitations and a high disease burden. Technique failure in African race needs further evaluation. Peritoneal dialysis remains a viable, life-saving alternative in an African setting

Renal palliative and supportive care in South Africa – a consensus statement

In South Africa, there is a high burden of end-stage kidney disease (ESKD). This is due to the burgeoning epidemics of communicable diseases like HIV/AIDS and non-communicable diseases, particularly hypertension and diabetes mellitus. One of the most difficult situations encountered by healthcare professionals dealing with patients with ESKD in South Africa is the management of a conservative or palliative care pathway for the many patients who have no other option. Patients with advanced chronic kidney disease (CKD) have a high burden of physical and psychosocial symptoms, poor outcomes, and high costs of care. Many patients are managed in primary healthcare settings and either do not have access to palliative care or are not referred appropriately.Renal supportive and palliative care involves a multidisciplinary approach to managing patients with ESKD, to ensure that symptoms are managed optimally and to provide support during advanced disease. It aims to improve quality of life for patients and their families and must be provided alongside curative medical care. This support should include those unable to gain access to life-saving dialysis and it should also provide care for patients where dialysis is not the best option.The aim of this consensus statement is to assist healthcare providers to improve the management of symptoms and biosocial factors of patients with end-stage kidney disease in a South African context. The document was compiled through consensus building among healthcare professionals across South Africa. The professionals that are represented included nephrologists, palliative care physicians, social workers, nurses, paediatricians and hospital managers. We wish to acknowledge the contribution of Dr Frank Brennan, a leading expert in renal palliative and supportive care, who assisted greatly in the compilation of this document

Investigating toxic aluminium levels in haemodialysis patients after “Day Zero” drought in Cape Town, South Africa

Introduction: Aluminium is the most abundant metallic element in the earth’s crust and can be consumed through water, medications, and by using metallic cooking utensils. Aluminium levels become a concern when they are above biological exposure limits and can present with multiple clinical complications. When patients have chronic kidney disease and are on haemodialysis, impaired aluminium excretion can lead to its accumulation. Significantly elevated serum aluminium levels were noted in patients with chronic kidney disease (stage 5) on haemodialysis at Groote Schuur Hospital, Cape Town, South Africa. This coincided with one of the worst water crises ever experienced in this metropolitan area, with extreme water restrictions being imposed and alternative water sources being accessed.Method: A multidisciplinary task force performed a systematic evaluation of aluminium concentrations throughout the dialysis water system. Additionally, a thorough investigation was performed to assess the quality of the laboratory results.Results: Possible areas of contamination and potential sources of exposure were excluded. The laboratory results were verified, and potential sources of error were excluded. The investigation verified that aluminium was truly elevated in the serum of patients, and concluded that dialysis was not the cause. Subsequently, patients’ results have declined to baseline, making it possible that there was increased environmental exposure during the drought.Conclusion: This report serves as a reminder to clinicians of acceptable serum aluminium levels in people on dialysis, and in the water system. Furthermore, it highlights the importance of a multidisciplinary collaborative team approach for the investigation of unexpected results or changes in trends

Health-related quality of life in a PD-First programme in South Africa

Groote Schuur Hospital in Cape Town, South Africa, offers a PD-First policy as a result of haemodialysis (HD) restrictions and resource limitations. This study aimed to compare health-related quality of life (HRQOL) between HD and peritoneal dialysis (PD) patients, given the lack of autonomy in modality choice and the socio-economic challenges. This single-centre, cross-sectional study was performed between July 2015 and December 2016. Demographic, socio-economic variables and perceptions of safety were collected. HRQOL was assessed using the Kidney Disease Quality of Life-Short Form (KDQOL-SFTM) version 1.3. All data were compared between the two dialysis modalities; 77 HD and 33 PD patients were included in the study and there were no significant differences in demographics. Median age was 42.5 years (IQR: 32.4–48.6) and 57.3% were female. HD patients had less pain (P = 0.036), better emotional well-being (P = 0.020) and a better energy/fatigue score (P = 0.015). Both cohorts experienced role-limitations due to physical health with PD being more affected overall (P = 0.05). The only significant symptom in the kidney domain was that PD patients experienced more shortness of breath (P &lt; 0.001). Patients in both groups had very poor socio-economic circumstances, and safety within their communities was a major concern. The patients in our dialysis service have very challenging social circumstances. Those on PD scored worse in four HRQOL domains, possibly due to a lack of autonomy in dialysis modality choice and less frequent contact with dialysis staff. Additional psychological and social support needs to be instituted to help improve our patients’ well-being on PD

The repeatability and reproducibility of four techniques for measuring horizontal heterophoria: Implications for clinical practice

PURPOSE: Convergence insufficiency, the most common binocular vision anomaly, is characterised by a receded near point of convergence and an exophoria which is at least 4 prism dioptres (Δ) larger at near than at distance. However, the repeatability of standard heterophoria measures are poorly understood. This study assessed the ability of four common heterophoria tests to detect differences of 4Δ by evaluating the inter- and intra-examiner variability of the selected techniques. METHODS: Distance and near horizontal heterophorias of 20 visually-normal adults were measured with the alternating prism cover test, von Graefe prism dissociation, Howell Card and Maddox Rod by two examiners at two separate visits using standardised instructions and techniques. We investigated inter- and intra-examiner variability using repeatability and reproducibility indices, as well as Bland-Altman analysis with acceptable limits of agreement defined as ±2Δ. RESULTS: The Howell card test had the lowest intra-examiner variability at both distance and near, as well as the best 95% limits of agreement (±1.6Δ for distance and ±3.7Δ for near). Inter-examiner reproducibility results were similar, although at near the alternating prism cover test had better repeatability (1.1Δ, 95% confidence intervals −1.1Δ to 4.0Δ) than the Howell card (1.4Δ, 95% confidence intervals −1.9Δ to 5.9Δ). CONCLUSION: The low repeatability of many standard clinical heterophoria tests limits the ability to reliably detect a 4Δ difference. The Howell Card provided the most repeatable and reproducible results indicating that this technique should be used to detect small changes in heterophoria magnitude and direction

Capacity for the management of kidney failure in the International Society of Nephrology Africa region:Report from the 2023 ISN Global Kidney Atlas (ISN-GKHA)

The burden of chronic kidney disease (CKD) and associated risk of kidney failure are increasing in Africa. The management of people with CKD is fraught with numerous challenges because of limitations in health systems and infrastructures for care delivery. From the third iteration of the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA), we describe the status of kidney care in the ISN Africa region using the World Health Organization building blocks for health systems. We identified limited government health spending which in turn led to increased out-of-pocket costs for people with kidney disease at the point of service delivery. The healthcare workforce across Africa was sub-optimal and further challenged by the exodus of trained healthcare workers out of the continent. Medical products, technologies, and services for the management of people with non-dialysis CKD and for kidney replacement therapy (KRT) were scarce due to limitations in health infrastructure that was inequitably distributed. There were few kidney registries and advocacy groups championing kidney disease management in Africa compared to the rest of the world. Strategies for ensuring improved kidney care in Africa include focusing on CKD prevention and early detection, improving the effectiveness of the available healthcare workforce (e.g., multidisciplinary teams, task substitution, and telemedicine), augmenting kidney care financing, providing quality, up-to-date health information data, and improving the accessibility, affordability, and delivery of quality treatment (KRT or conservative kidney management) for all people living with kidney failure

Anti-CRISPR AcrIIA5 Potently Inhibits All Cas9 Homologs Used for Genome Editing

CRISPR-Cas9 systems provide powerful tools for genome editing. However, optimal employment of this technology will require control of Cas9 activity so that the timing, tissue specificity, and accuracy of editing may be precisely modulated. Anti-CRISPR proteins, which are small, naturally occurring inhibitors of CRISPR-Cas systems, are well suited for this purpose. A number of anti-CRISPR proteins have been shown to potently inhibit subgroups of CRISPR-Cas9 systems, but their maximal inhibitory activity is generally restricted to specific Cas9 homologs. Since Cas9 homologs vary in important properties, differing Cas9s may be optimal for particular genome-editing applications. To facilitate the practical exploitation of multiple Cas9 homologs, here we identify one anti-CRISPR, called AcrIIA5, that potently inhibits nine diverse type II-A and type II-C Cas9 homologs, including those currently used for genome editing. We show that the activity of AcrIIA5 results in partial in vivo cleavage of a single-guide RNA (sgRNA), suggesting that its mechanism involves RNA interaction

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

Long COVID and the cardiovascular system—elucidating causes and cellular mechanisms in order to develop targeted diagnostic and therapeutic strategies: a joint Scientific Statement of the ESC Working Groups on Cellular Biology of the Heart and Myocardial and Pericardial Diseases

Long COVID has become a world-wide, non-communicable epidemic, caused by long-lasting multiorgan symptoms that endure for weeks or months after SARS-CoV-2 infection has already subsided. This scientific document aims to provide insight into the possible causes and therapeutic options available for the cardiovascular manifestations of long COVID. In addition to chronic fatigue, which is a common symptom of long COVID, patients may present with chest pain, ECG abnormalities, postural orthostatic tachycardia, or newly developed supraventricular or ventricular arrhythmias. Imaging of the heart and vessels has provided evidence of chronic, post-infectious perimyocarditis with consequent left or right ventricular failure, arterial wall inflammation, or microthrombosis in certain patient populations. Better understanding of the underlying cellular and molecular mechanisms of long COVID will aid in the development of effective treatment strategies for its cardiovascular manifestations. A number of mechanisms have been proposed, including those involving direct effects on the myocardium, microthrombotic damage to vessels or endothelium, or persistent inflammation. Unfortunately, existing circulating biomarkers, coagulation, and inflammatory markers, are not highly predictive for either the presence or outcome of long COVID when measured 3 months after SARS-CoV-2 infection. Further studies are needed to understand underlying mechanisms, identify specific biomarkers, and guide future preventive strategies or treatments to address long COVID and its cardiovascular sequelae