Zunaid Barday

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.).

HIV-positive-to-HIV-positive kidney transplantation.

To the Editor: Muller et al. (Feb. 12 issue)1 report that among 27 patients with human immunodeficiency virus (HIV) infection who received kidneys from HIV-positive deceased donors, recurrent HIV-associated nephropathy developed in the transplanted kidney in 3 patients, even though viremia was undetectable. This observation is consistent with our recent report showing that the allografted kidney is a reservoir for HIV type 1 (HIV-1).2 The glomerular lesions in the 3 patients might be the tip of the iceberg, since we observed that up to 68% of transplant recipients with HIV-1 infection have virus in kidney cells after transplantation, even with normal results on histologic analysis. In addition, we found that the presence of HIV-1 in a kidney correlates with the presence of HIV-1 in the patient’s urine. Indeed, the identification of virus in the urine is associated with the presence of HIV-1 in the kidney. The situation is highly relevant for HIV-1–positive donors, because lesions might be related to the virus in the recipient, the donor, or both. We suggest that looking at HIV-1 that is shed into the urine or detected on biopsy might help to monitor kidneygraft infection and also allow the determination of which virus (from donor or recipient) is involved by means of phylogenetic analysis.

Slow early graft function: a neglected entity after renal transplantation.

Background: After renal transplantation, early graft function (EGF) can be divided into delayed graft function (DGF), slow graft function (SGF) and immediate graft function (IGF). DGF is well documented. However, when evaluating the long-term significance of early function, the literature shows conflicting definitions and inconsistent results. In addition, SGF, a new entity separate to DGF and IGF, is a recent and poorly understood development. Aim: To investigate the risk factors for and the impact of poor EGF (PEGF) on long-term outcome. Methods: This retrospective study reviewed the records of local adult patients who underwent renal transplantation at the Groote Schuur Hospital (Cape Town, South Africa) between 2004 and 2008. EGF was divided according to day 5 serum creatinine into IGF (serum creatinine <150 µmol/l), SGF (serum creatinine >150 but <450 µmol/l) and DGF (serum creatinine >450 µmol/l or dialysis in the first week). DGF and SGF together comprised PEGF, with IGF alone representing good EGF (GEGF). Results: A total of 121 patients (77 men, 44 women; mean age 39 years, range 14–67) were included in the study. Eighteen were excluded due to nephrectomy (n = 8), death (n = 6) or loss to follow-up (n = 4) within the first year. Analysis of cadaveric donors showed no significant risk factors for PEGF with the exception of cold ischaemic time, which differed significantly between the GEGF and PEGF groups, with means of 12 and 16 h, respectively (p = 0.013). Considering both living and cadaveric grafts, the 1-year estimated glomerular filtration rate (eGFR) was significantly different between IGF and DGF (p = 0.038) as well as between IGF and SGF (p = 0.028), with no significant difference between SGF and DGF (p > 0.05). A comparison of the PEGF and GEGF groups yielded significantly different 1-year eGFR values (60 and 50 ml/min, respectively; p = 0.07), with PEGF also associated with a longer hospital stay (20 vs. 14 days; p = 0.00005). Acute rejection was independently associated with a lower 1-year eGFR (p = 0.028), but in the absence of rejection, GEGF and PEGF remained significantly different with regards to 1-year eGFR (p = 0.024). Conclusions: SGF is not related to IGF but rather to DGF and should thus be regarded as a form of PEGF as opposed to GEGF. PEGF has a worse long-term outcome, and this indicates the need for increased efforts in its prevention and greater attention to its management.

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.

Driving pressure as a key ventilation variable.

n engl j med 372;21 nejm.org may 21, 2015 2071 interference with the dose of calcineurin inhibitors, a factor that might improve graft outcomes by lowering rejection rates. Currently, in South Africa, we are using raltegravir in salvage regimens only, but once these drugs become more affordable and available in South Africa, it will be interesting to see whether they are a good option for HIV-positive patients who receive a transplant. In our study, all the patients had completely mismatched human leukocyte antibodies with the donors, and the levels of panel reactive antibody ranged from 0 to 90%. We agree that this factor might be important in the high kidney-rejection rates among our patients. Elmi Muller, M.B., Ch.B., M.Med. Zunaid Barday, M.B., Ch.B. Delawir Kahn, M.B., Ch.B., Ch.M.

Contents Vol. 120, 2012

Clinical Nephrology Guidelines J. Cunningham, London G. Eknoyan, Houston, Tex. A. Khwaja, Sheffield Clinical Appraisal/Evidence Based Nephrology A.K. El-Sherif, Ismailia R.J. Glassock, Laguna Niguel, Calif. A. Meyrier, Paris Global CKD G. Remuzzi, Bergamo N. Perico, Bergamo R. Atkins, Melbourne, Vic. Clinical Trials D. de Zeeuw, Groningen F. Locatelli, Lecco D. Wheeler, London Continuing Nephrology Education R. Barsoum, Cairo M. Field, Sydney, N.S.W. C. Zoccali, Reggio Calabria Clinico-Pathological Conferences T.H. Jafar, Karachi Editor-in-Chief