Children Are Not Small Adults: Similarities and Differences in Renal Transplantation Between Adults and Pediatrics.

Kidney transplantation is the treatment of choice for all patients with end-stage kidney disease, including pediatric patients. Graft survival in pediatrics was lagging behind adults, but now is comparable with the adult cohort. Although many of the protocols have been adopted from adults, there are issues unique to pediatrics that one should be aware of to take care of this population. These issues include recipient size consideration, increased incidence of viral infections, problems related to growth, common occurrence of underlying urological issues, and psychosocial issues. This article addresses the similarities and differences in renal transplantation, from preparing a patient for transplant, the transplant process, to post-transplant complications.

Task shifting roles, interventions and outcomes for kidney and cardiovascular health service delivery among African populations: a scoping review.

BACKGROUND: Human resources for health (HRH) shortages are a major limitation to equitable access to healthcare. African countries have the most severe shortage of HRH in the world despite rising communicable and non-communicable disease (NCD) burden. Task shifting provides an opportunity to fill the gaps in HRH shortage in Africa. The aim of this scoping review is to evaluate task shifting roles, interventions and outcomes for addressing kidney and cardiovascular (CV) health problems in African populations. METHODS: We conducted this scoping review to answer the question: "what are the roles, interventions and outcomes of task shifting strategies for CV and kidney health in Africa?" Eligible studies were selected after searching MEDLINE (Ovid), Embase (Ovid), CINAHL, ISI Web of Science, and Africa journal online (AJOL). We analyzed the data descriptively. RESULTS: Thirty-three studies, conducted in 10 African countries (South Africa, Nigeria, Ghana, Kenya, Cameroon, Democratic Republic of Congo, Ethiopia, Malawi, Rwanda, and Uganda) were eligible for inclusion. There were few randomized controlled trials (n = 6; 18.2%), and tasks were mostly shifted for hypertension (n = 27; 81.8%) than for diabetes (n = 16; 48.5%). More tasks were shifted to nurses (n = 19; 57.6%) than pharmacists (n = 6; 18.2%) or community health workers (n = 5; 15.2%). Across all studies, the most common role played by HRH in task shifting was for treatment and adherence (n = 28; 84.9%) followed by screening and detection (n = 24; 72.7%), education and counselling (n = 24; 72.7%), and triage (n = 13; 39.4%). Improved blood pressure levels were reported in 78.6%, 66.7%, and 80.0% for hypertension-related task shifting roles to nurses, pharmacists, and CHWs, respectively. Improved glycaemic indices were reported as 66.7%, 50.0%, and 66.7% for diabetes-related task shifting roles to nurses, pharmacists, and CHWs, respectively. CONCLUSION: Despite the numerus HRH challenges that are present in Africa for CV and kidney health, this study suggests that task shifting initiatives can improve process of care measures (access and efficiency) as well as identification, awareness and treatment of CV and kidney disease in the region. The impact of task shifting on long-term outcomes of kidney and CV diseases and the sustainability of NCD programs based on task shifting remains to be determined.

Retrospective Review of ART Regimens in HIV-Positive to HIV-Positive Kidney Transplant Recipients.

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.

The relevance of performing 24-hour ambulatory blood pressure and pulse wave analysis in kidney transplant recipients.

Hypertension guidelines recommend out-of-office blood pressure (BP) measurement especially 24-hour ambulatory measurement (ABPM), to diagnose and manage hypertension but this is not routinely performed in kidney transplant units. This study was to determine if 24-hour ABPM, compared with office BP in kidney transplant recipients, would be more informative regarding BP management, and if pulse wave analysis (PWA) would assist in risk stratification. This study included patients older than 18 years, with working graft kidney for > 12 months, and without problems affecting BP measurement and interpretation. After performing office BP measurements, a 24-hour ABPM with additional capability of calculating pulse wave velocity (PWV), augmentation index and central BP was undertaken. Patients were assessed for controlled hypertension, uncontrolled hypertension, masked hypertension, nocturnal hypertension, white coat hypertension, and dipping BP status. Data were analyzed using standard statistical tests. Of 30 patients, 15 were Black Africans and 15 were of Mixed Ancestry with a mean age of 48.9 years. 17 patients were males and 36.7% had controlled hypertension, 30% uncontrolled hypertension, 6.7% white coat hypertension, and 33.3% masked hypertension, of whom 70% had isolated nocturnal hypertension. 70% had a non-dipping, 26.7% a reverse dipping and only 3.3% had a normal dipping BP pattern. The mean difference between brachial systolic BP and central systolic BP was 10.4 mmHg, whereas PWV and augmentation index were similar to healthy populations. Conclusion: In kidney transplant recipients, 24-hour ABPM was superior to office BP in defining hypertensive status that qualified for modification of therapy, but PWA did not contribute to risk assessment.

COVID-19 and the kidney: A South African state healthcare experience.

The first documented case of SARS-CoV-2 infection was confirmed in South Africa (SA) in March 2020. The Western Cape (WC) province was the initial epicenter. The pandemic peaked in July 2020 when 76,851 cases were documented and 2,323 deaths reported. COVID-19 can have multisystem involvement. Acute kidney injury (AKI) is well-documented and associated with increased mortality. We report our experience as the pandemic evolved in the WC province, focusing on those patients with a SARS-CoV-2 positive test presenting with AKI. We also reviewed our chronic dialysis cohort and renal transplant recipients who tested positive to assess incidence and outcomes. All patients presenting to nephrology services at the four main public hospitals were included. Information regarding demographics, co-morbidities, medical care, laboratory data, and outcomes were recorded. There were 86 patients referred with AKI, 48 required dialysis, and 47 died. There were 52 patients admitted to the intensive care unit with AKI (37 received dialysis, 1 of whom survived). In those presenting with AKI, diabetes, obesity, hypertension, and HIV were the most common comorbidities. Of the 295 patients receiving chronic dialysis within our services, 31 tested positive for SARS-CoV-2, and 6 died. Of the 45 kidney transplant recipients who tested positive, 9 died. Only 3 required dialysis. In conclusion, we report a high rate of AKI and poor prognosis in those requiring kidney replacement therapy, a better prognosis than anticipated was found in our chronic dialysis cohort, and high numbers of admissions were required for renal transplant recipients.

Kidney Transplantation in HIV-positive Patients: Current Practice and Management Strategies.

BACKGROUND: HIV-positive patients had been successfully transplanted for the last 15 y and the donor pool had successfully been expanded to also include HIV-positive donors. METHODS: We aimed to evaluate the effectiveness of transplantation in HIV-positive patients and highlight some of the important issues reported in the literature. We pooled clinical data from different cohorts to show some of the common issues encountered in HIV-positive transplantation. Furthermore, we searched MEDLINE via PubMed, EMBASE, Cochrane CENTRAL to create a comprehensive table for current evidence for different issues currently encountered when transplanting HIV-positive patients. RESULTS: We included data from 19 cohort studies and reported on outcomes of the current HIV-positive transplant programs. We made recommendations based on personal experience as well as the experience reported in the literature regarding rejection, opportunistic infection, and HIV-associated nephropathy. Opportunistic infections and malignancies are not a major problem for this population group. CONCLUSIONS: HIV-positive patients encounter very specific issues after transplantation, specifically related to drug interactions and higher rejection rates. When utilizing HIV-positive donors, the recurrence of HIV-associated nephropathy in the graft kidney is an issue which can be important. Despite some issues with high rejection rates, HIV-positive patients have similar results to HIV-negative patients posttransplantation.

Outcomes and challenges of a kidney transplant programme at Groote Schuur Hospital, Cape Town: A South African perspective.

INTRODUCTION: Access to dialysis and transplantation in the developing world remains limited. Therefore, optimising renal allograft survival is essential. This study aimed to evaluate clinical outcomes and identify poor prognostic factors in the renal transplant programme at Groote Schuur Hospital [GSH], Cape Town. . METHOD: Data were collected on all patients who underwent a kidney transplant at GSH from 1st July 2010 to the 30 June 2015. Analyses were performed to assess baseline characteristics, graft and patient survival, as well as predictors of poor outcome. . RESULTS: 198 patients were transplanted. The mean age was 38 +/- 10.5 years, 127 (64.1%) were male, and 86 (43.4%) were of African ethnicity. Deceased donor organs were used for 130 (66.7%) patients and living donors for 65 (33.3%). There were > 5 HLA mismatches in 58.9% of transplants. Sepsis was the commonest cause of death and delayed graft function [DGF] occurred in 41 (21.4%) recipients. Patient survival was 90.4% at 1 year and 83.1% at 5 years. Graft survival was 89.4% at 1 year and 80.0% at 5 years. DGF (HR 2.83 (1.12-7.19), p value = 0.028) and recipient age > 40 years (HR 3.12 (1.26-7.77), p value = 0.014) were predictors of death. CONCLUSION: Despite the high infectious burden, stratified immunosuppression and limited tissue typing this study reports encouraging results from a resource constrained transplant programme in South Africa. Renal transplantation is critical to improve access to treatment of end stage kidney disease where access to dialysis is limited.

HIV-Positive Kidney Donor Selection for HIV-Positive Transplant Recipients.

The risks associated with transplanting HIV-positive kidneys into HIV-positive recipients have not been well studied. Since 2008, 43 kidneys from 25 HIV-positive deceased donors have been transplanted into patients who are HIV positive in Cape Town, South Africa. Among the donors, 19 (76%) died secondary to trauma. The average age for donors was 34 (interquartile range, 19-52) years old. In some donors, only one kidney was used because of a limited number of suitable recipients on the waiting list. Only two donors had been previously exposed to antiretroviral triple therapy. In 23 of the deceased organ donors, the HIV status was not known before the time of death. Initial concerns about transplanting HIV-positive allografts into HIV-positive recipients in this clinic revolved around the possibility of HIV superinfection. However, all recipients remained virally suppressed several years after the transplant. Only one recipient experienced an increased viral load after the transplant, which was related to a period of noncompliance on her medication. After counseling and improved compliance, the viral load decreased and became suppressed again. Herein, we discuss the findings of this study and review the literature available on this crucial topic.

Disparities in dialysis allocation: An audit from the new South Africa.

End Stage Kidney Disease (ESKD) is a public health problem with an enormous economic burden. In resource limited settings management of ESKD is often rationed. Racial and socio-economic inequalities in selecting candidates have been previously documented in South Africa. New guidelines for dialysis developed in the Western Cape have focused on prioritizing treatment. With this in mind we aimed at exploring whether the new guidelines would improve inequalities previously documented. A retrospective study of patients presented to the selection committee was conducted at Groote Schuur Hospital. A total of 564 ESKD patients presented between 1 January 2008 and 31 December 2012 were assessed. Half of the patients came from low socioeconomic areas, and presentation was late with either overt uremia (n = 181, 44·4%) or fluid overload (n = 179, 43·9%). More than half (53·9%) of the patients were not selected for the program. Predictors of non-acceptance onto the program included age above 50 years (OR 0·3, p = 0·001), unemployment (OR 0·3, p<0·001), substance abuse (OR 0·2, p<0·001), diabetes (OR 0·4, p = 0·016) and a poor psychosocial assessment (OR 0·13, p<0·001). Race, gender and marital status were not predictors. The use of new guidelines has not led to an increase in inequalities. In view of the advanced nature of presentation greater efforts need to be made to prevent early kidney disease, to allocate more resources to renal replacement therapy in view of the loss of young and potentially productive life.

HIV-positive-to-HIV-positive kidney transplantation--results at 3 to 5 years.

BACKGROUND: The outcome of kidney transplantation in human immunodeficiency virus (HIV)-positive patients who receive organs from HIV-negative donors has been reported to be similar to the outcome in HIV-negative recipients. We report the outcomes at 3 to 5 years in HIV-positive patients who received kidneys from HIV-positive deceased donors. METHODS: We conducted a prospective, nonrandomized study of kidney transplantation in HIV-infected patients who had a CD4 T-cell count of 200 per cubic millimeter or higher and an undetectable plasma HIV RNA level. All the patients were receiving antiretroviral therapy (ART). The patients received kidneys from deceased donors who tested positive for HIV with the use of fourth-generation enzyme-linked immunosorbent assay at the time of referral. All the donors either had received no ART previously or had received only first-line ART. RESULTS: From September 2008 through February 2014, a total of 27 HIV-positive patients underwent kidney transplantation. Survivors were followed for a median of 2.4 years. The rate of survival among the patients was 84% at 1 year, 84% at 3 years, and 74% at 5 years. The corresponding rates of graft survival were 93%, 84%, and 84%. (If a patient died with a functioning graft, the calculation was performed as if the graft had survived.) Rejection rates were 8% at 1 year and 22% at 3 years. HIV infection remained well controlled, with undetectable virus in blood after the transplantation. CONCLUSIONS: Kidney transplantation from an HIV-positive donor appears to be an additional treatment option for HIV-infected patients requiring renal-replacement therapy. (Funded by Sanofi South Africa and the Roche Organ Transplantation Research Foundation.).

Renal transplantation between HIV-positive donors and recipients justified.

HIV infection was previously an absolute contraindication to renal transplantation. However, with the advent of highly active antiretroviral therapy (HAART), renal transplantation using HIV-negative donor kidneys has successfully been employed for HIV-infected patients with end-stage renal failure. In resource-limited countries, places on dialysis programmes are severely restricted; HIV-infected patients, like many others with co-morbidity, are often denied treatment. Kidneys (and other organs) from HIV-infected deceased donors are discarded. The transplantation of HIV-positive donor kidneys to HIV-infected recipients is now a viable alternative to chronic dialysis or transplantation of HIV-negative donor kidneys. This significantly increases the pool of donor kidneys to the advantage of HIV-positive and -negative patients. Arguments are presented that led to our initiation of renal transplantation from HIV-positive deceased donors to HIV-positive recipients at Groote Schuur Hospital, Cape Town.

Rapidly progressive post-transplant lymphoproliferative disease following withdrawal of sirolimus.

Sirolimus, a potent inhibitor of B- and T-cell activation. is a commonly used immunosuppressant after renal transplantation. Withdrawal of sirolimus from the immunosuppression regimen may reduce B-cell surveillance. We present a case of rapidly progressive central nervous system (CNS) polymorphic Epstein-Barr virus (EBV)-related post-transplant lymphoproliferative disorder following the withdrawal of sirolimus.

Patterns of renal disease in Cape Town South Africa: a 10-year review of a single-centre renal biopsy database.

BACKGROUND: The patterns of glomerular diseases have been widely reported from different regional and national biopsy registries worldwide. However, there are scant studies on the epidemiology of biopsy-proven renal disease, particularly glomerular diseases in sub-Saharan Africa. METHODS: We retrospectively analysed the reports of 1284 native renal biopsies, reviewed by the same pathologist and performed at the Groote Schuur Hospital in Cape Town from 1 January 2000 to 31 December 2009. RESULTS: The mean age of all the patients biopsied was 36.8 ± 14.0 years with 61.8% of the patients being under 40 years of age. There was a preponderance of females (54.8%). There were more coloured patients (53.7%) than blacks (42.2%) or whites (3.9%). The frequencies of clinical indications for a renal biopsy were nephrotic range proteinuria (52.5%), acute renal failure (21.3%), asymptomatic urinary abnormalities (13.6%), chronic renal failure (6.4%), acute nephritic syndrome (5.8%) and haematuria (0.3%). The frequencies of the primary glomerulonephritis (GN) include mesangiocapillary GN (20.4%), mesangial proliferative GN (19.2%), membranous GN (18.5%), crescentic and necrotizing GN (11.4%), focal and segmental glomerulosclerosis (10.5%), post-infectious GN (8.2%), minimal change disease (6.0%) and IgA nephropathy (5.8%). Lupus nephritis was the most frequent secondary glomerular disease (39.0%) and was also the most frequent cause of the nephrotic range proteinuria (17.2%). HIV-associated nephropathy increased from 6.6% in 2000 to 25.7% in 2009 (P < 0.0001). CONCLUSION: Our data are an important contribution to the epidemiology of renal disease in Africa. We hope that this will form the basis for developing a renal biopsy registry in South Africa and across the continent.