Clinical course, management and outcomes of COVID-19 in HIV-infected renal transplant recipients: A case series.

BACKGROUND: HIV-infected kidney transplant recipients with COVID-19 are at increased risk of acute illness and death owing to their underlying comorbidities and chronic immunosuppression. OBJECTIVES: To describe the incidence, clinical presentation and course of COVID-19, vaccination status, and SARS-CoV-2 antibody positivity rate among HIV-infected-to-HIV-infected kidney transplant recipients in South Africa (SA). METHODS: This retrospective study reports on rates of SARS-CoV-2 infection, COVID-19 and mortality among SA HIV-infected kidney transplant recipients who received organs from HIV-infected donors (HIV positive to HIV positive), before and after vaccination. Patient demographics, clinical presentation, course, management and disease outcomes were analysed. Antibody serology tests were performed between May and September 2022. RESULTS: Among 39 HIV-positive-to-HIV-positive transplant recipients, 11 cases of COVID-19 were diagnosed from March 2020 to September 2022. Six patients (55%) required hospitalisation, of whom 3 were admitted to a high-care unit or intensive care unit. Two patients required mechanical ventilation, and 2 received acute dialysis. One patient was declined access to intensive care. Four patients (10%) died of COVID-19 pneumonia. All the COVID-19-positive patients had at least one comorbidity. Vaccination data were available for 24 patients, of whom 5 had refused SARS-CoV-2 vaccination. SARS-CoV-2 antibody data were available for 20 patients; 4 vaccinated patients had a negative nucleocapsid protein antibody test and a positive spike protein antibody test, suggesting vaccination-acquired immunity. The remaining 16 patients demonstrated immunity that was probably due to COVID infection, and of these, 14 were also vaccinated. Of the 11 COVID-19 cases, only 1 was observed after vaccination. CONCLUSION: In our case series, ~10% of the HIV-positive-to-HIV-positive transplant recipients died of COVID-19 pneumonia. This mortality rate appears higher than figures reported in other transplant cohorts. However, it is likely that the actual number of cases of SARS-CoV-2 infection was much higher, as the study only included polymerase chain reaction-confirmed cases. It remains unclear whether HIV infection, transplant or the combination of the two drives poorer outcomes, and larger studies adjusting for important demographic and biological factors may isolate these effects.

The state of paediatric deceased-organ donation at a South African tertiary public- sector hospital: A 14-year analysis.

BACKGROUND: Solid-organ transplantation (SOT) has been proven to be a highly effective and life-saving treatment modality for adults and children suffering from end-stage organ failure. However, high paediatric waiting-list mortality has been reported, and children may suffer irreversible physical and deleterious psychological effects if not transplanted timeously. OBJECTIVES: To identify in-hospital barriers to organ donation and gain a better understanding of the paediatric donor landscape. METHODS: A retrospective descriptive study of consecutive deceased-donor referrals at Red Cross War Memorial Children's Hospital over a 14-year period, from 1 January 2007 to 31 December 2020. RESULTS: During the study period, 156 in-hospital deaths were recorded in the trauma unit and 1 425 in the paediatric intensive care unit. Ninety-three of the 1 581 patients (5.9%) were referred to the on-call transplant co-ordinator as potential organ donors, of whom 69% had been involved in a traumatic accident, including 52% in road traffic collisions. The mean age of the potential donors was 7 years with 60.2% being boys. On initial assessment, 67 of the 93 potential donors (72%) were assessed as eligible for donation of at least one solid organ. The transplant co-ordinator attempted to approach all families for consent; however, five families/next of kin could not be located despite multiple attempts. Among the remaining 62 eligible donors, 44 families/next-of-kin declined consent for solid-organ donation, resulting in a consent rate of 29% (n=18). Several families refused consent for religious reasons. One of the consented donors did not proceed to procurement as there were no suitable recipients. Seventeen donors proceeded to theatre, the intention being solid-organ procurement, but in 2 donors the organs were assessed as being unsuitable for transplant. From the remaining 15 donors, a total of 46 organs were procured and successfully transplanted: 14 livers, 30 kidneys and 2 hearts. CONCLUSION: During the 14-year study period, only 15 deceased donors could be utilised for SOT, as a result of low in-hospital referral (5.9%) and consent rates (29%). The reasons for low referral and consent rates are complex and often multifactorial, which the current study was not designed to investigate in sufficient detail. Future studies should be designed to further interrogate our findings, while accommodating for nuances specific to the paediatric deceased-donor population and their families.

A tale of two kidneys, and the case for machine perfusion in South Africa.

Extended-criteria donors (ECDs) are seen as a means of addressing the shortfall in solid-organ availability for transplant. However, the use of ECD kidneys is associated with a greater risk of primary non-function compared with standard-criteria donor kidneys, and a higher discard rate has been described internationally. There seems to be a lack of consensus in the consideration of ECD kidneys for transplant, with reliance often placed on the subjective assessment of individual clinicians. The following case examines the difference in the institutional decision-making process applied to two kidneys from a single donor, and provides an argument for the use of hypothermic machine perfusion in low- to middle-income countries as an efficacious and objective means of assessing ECD kidney suitability.

Kidney transplant utilising donors after circulatory death: The first report from the African continent.

BACKGROUND: At Groote Schuur Hospital in Cape Town, South Africa, the number of deceased organ donors has declined over the past 2 decades, necessitating a more liberal approach to donor selection. In 2007, measures to expand the deceased kidney donor pool were implemented, including an HIV positive-to-positive transplant programme and the utilisation of extended-criteria donors as well as donors after circulatory death (DCDs). OBJECTIVES: To report on our institutional experience with DCD kidney transplants and to encourage this approach among other African centres to improve access to transplantation. METHODS: An observational cohort study of consecutive DCD kidney transplants at Groote Schuur Hospital over a 17-year period was performed. Primary endpoints were 1-, 2- and 5-year graft and patient survival. Secondary endpoints included the incidence of delayed graft function (DGF), 30-day morbidity, length of stay, and donor and recipient clinical characteristics. RESULTS: Fifteen DCD procurements were performed, with no kidneys discarded. Thirty kidney transplants were performed, with a median (interquartile range) cold ischaemic time of 11.5 (8 - 14) hours. The incidence of DGF was 60.0%, and 30-day morbidity (other than DGF) was 20.0%. Graft survival at 1, 2 and 5 years was 100%, 96.0% and 73.7%, respectively. Patient survival at 1, 2 and 5 years was 93.3%, 93.3% and 88.4%, respectively. CONCLUSION: Long-term graft and patient survival was comparable with the international literature. DCD may present a unique opportunity to expand deceased donation throughout Africa, particularly in areas affected by a lack of brain death legislation and religious or cultural objections to donation after brain death.

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.

Transplant Unit, Division of General Surgery, Department of Surgery, Faculty of Health Sciences, University of Cape Town, South Africa.

Organ and tissue donation depends on non-transplant clinicians to identify and timeously refer potential donors and to counsel families compassionately about the prognosis at end of life. Organ donation referral is often felt to be beyond the capacity of district-level hospital services. In this case series, we report on four referrals from a geographically remote, public sector district-level hospital, and review the identification, referral and consent process of potential donors after brain death, and also donors after circulatory death. For the one successfully consented donor we report on the donor work-up and management, and the outcome of the organ recovery and organ allocation process.

Organ transplantation during the COVID-19 pandemic - impact on deceased organ donor referrals and consent rates in the Western Cape, South Africa.

BACKGROUND: The impact of the COVID-19 pandemic on transplantation is multifactorial. This study reports on its influence on deceased donation for transplantation in the Western Cape. METHODS: The volume of referrals and those who were consented for organ donation in the province in the pre-pandemic period of May 2017 to February 2020 were compared to those of the initial pandemic period (March through December 2020). RESULTS: Prior to the pandemic, there were 201 deceased donor referrals in the Western Cape province - 152 (75.6%) and 49 (24.4%) in public and private sectors, respectively. The mean referral rates ranged between 59-69 referrals per year, translating into a monthly rate of 4.8 (range 2.8-5.8). During the first 10 months of the pandemic, there were 18 referrals - 12 (66.7%) and six (33.3%) in the public and private sectors; a decrease of 63%, with a mean monthly referral rate of 1.8. The overall consent rate prior to the pandemic in the public and private sectors was 36.6% (38% and 27%, respectively) with an increase to 44.4% (37.5% and 62.5%) during the pandemic. CONCLUSION: Despite a 10% increase in consent rate for deceased donation during the COVID-19 pandemic, there was a significant decrease in the number of potential donors referred. Strategies to improve organ donation and transplantation during and after the COVID-19 pandemic are required.

Investigating the threshold for early renal allograft biopsy: A South African single-centre perspective.

BACKGROUND: The most common clinical indication for renal biopsy in the early post-transplant period is early graft dysfunction (EGD), which may present either as delayed graft function (DGF) or acute graft dysfunction. Even though it is a valuable diagnostic tool, renal allograft biopsy is not without risk of major complications. Recent studies have suggested that, with modern immunosuppressive induction regimens and more accurate ways to determine high immunological risk transplants, early acute rejection (AR) is uncommon and routine biopsy for EGD does not result in a change in management. OBJECTIVES: To describe the histological findings and complications of renal allograft biopsies for EGD in our setting, and to determine whether our current threshold for biopsy is appropriate. METHODS: This study was a retrospective audit that included all patients who underwent renal allograft biopsy within the first 30 days of transplantation at Groote Schuur Hospital, Cape Town, South Africa, from 1 June 2010 to 30 June 2018. The indication for biopsy was any patient who showed significant EGD, characterised by acute graft dysfunction or DGF with dialysis dependence. RESULTS: During the study period, 330 patients underwent renal transplantation, of whom 105 (32%) had an early biopsy and were included in the study. The median age of recipients was 39 (range 17 - 62) years, with 65% males and 35% females. The majority of donors were deceased donations after brain death (70%), with an overall median cold ischaemic time of 9 hours (interquartile range (IQR) 4 - 16). The average number of human leukocyte antigen mismatches was 5 (IQR 4 - 7). A donor-specific antibody was recorded for 18% of recipients and a panel-reactive antibody score of >30% was recorded for 21%. The median duration after transplant for biopsy was 8 (IQR 6 - 10) days. During the first month of EGD, AR was diagnosed in 42% of patients who underwent biopsies. In 21% of these patients, there was acute cellular rejection, in 16% antibody-mediated rejection, and in 5% both of these. Acute tubular necrosis was the primary finding in 32%, with acute interstitial nephritis in 8%, and acute calcineurin toxicity in 4% of cases. A significant biopsy-related complication was recorded in 3 patients: 1 small-bowel perforation repaired via laparotomy, and 2 vascular injuries successfully embolised by interventional radiology. CONCLUSIONS: Considering the relative safety and high rate of detection of AR, a liberal approach to renal biopsy for EGD remains justifiable in our setting.

A 10-year analysis of organ donor referrals to a South African tertiary public sector hospital.

BACKGROUND: South Africa (SA) has one of the lowest deceased organ donor rates in the world (1.4 donors per million population), with thousands of patients awaiting solid-organ transplantation. In order to improve access to transplantation we have to clearly define the reasons for the low deceased donation rate, specific to the population we serve. OBJECTIVES: Review of actual donor statistics highlights our successes, yet is not able to contextualise the factors responsible for the unsuccessful conversion of referred organ donors to actual organ donors. In an attempt to identify key factors preventing referred donors from becoming actual donors, we analysed the donor referral patterns at our institution over a 10-year period. METHODS: This was a retrospective descriptive study of consecutive deceased donor referrals at Groote Schuur Hospital, Cape Town, SA (from January 2007 to December 2016), utilising a regional donor referral registry. Qualitative and quantitative data were collected and presented as descriptive statistics and temporal trends. RESULTS: Over the 10-year study period, 861 possible organ donors were referred, with a steady increase in the number of referrals over time. Of the referrals, 514 (59.7%) were eligible for donation of at least one solid organ. Of the 508 families that were approached for consent to donation, 342 declined consent for a variety of reasons, resulting in a consent rate of 32.7%. Ultimately, at least one solid organ was obtained from 159 of the 166 consented donors. Despite the increasing number of possible and eligible donors, a statistically significant decline in consent rate was observed over time (ptrend=0.023). Furthermore, increasing trends in medical (as opposed to trauma) (ptrend<0.001) and extended criteria (as opposed to standard criteria) donor referrals (ptrend<0.001) were observed over the 10-year study period. CONCLUSIONS: Donor referral patterns have changed over time, with a notable increase in medical and extended criteria donors. Despite the increase in possible and eligible donors, the consent rate has declined. Further qualitative and quantitative research studies are required to understand and address this trend.

Inguinal Herniation Containing Bladder, Causing Contralateral Allograft Hydroureteronephrosis-A Case Report and Literature Review.

We report the first documented case of an inguinal hernia containing bladder, resulting in contralateral allograft hydroureteronephrosis. A 39-year-old male patient presented with allograft dysfunction, a contralateral inguinoscrotal hernia, and marked hydroureteronephrosis on ultrasound (US). Percutaneous nephrostogram and a retrograde cystogram suggested bladder herniation with incorporation of the contralateral ureteroneocystostomy into the hernia. Paraperitoneal bladder herniation was confirmed at surgery and hernioplasty was performed. Six-week follow-up revealed normal renal function with no sign of hernia recurrence. Despite occurring rarely, transplant ureter or bladder herniation should be considered in the differential diagnosis of hydroureteronephrosis. This case illustrates that the contralateral position of hernia to allograft does not necessarily preclude the hernia as the source of ureteric obstruction.