Kidney disease in the setting of HIV infection: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Writing Group Duncan Churchill, Chair, Royal Sussex County Hospital, Brighton, UK Laura Waters, Vice Chair, Mortimer Market Centre, London, UK Nadia Ahmed, Mortimer Market Centre, London, UK Brian Angus, University of Oxford, UK Marta Boffito, Chelsea and Westminster Hospital, London, UK Mark Bower, Chelsea and Westminster Hospital, London, UK David Dunn, University College London, UK Simon Edwards, Central and North West London NHS Foundation Trust, UK Carol Emerson, Royal Victoria Hospital, Belfast, UK Sarah Fidler, Imperial College School of Medicine at St Mary’s, London, UK †Martin Fisher, Royal Sussex County Hospital, Brighton, UK Rob Horne, University College London, UK Saye Khoo, University of Liverpool, UK Clifford Leen, Western General Hospital, Edinburgh, UK Nicola Mackie, Imperial College Healthcare NHS Trust, London, UK Neal Marshall, Royal Free Hospital NHS Trust, London, UK Fernando Monteiro, UK-CAB Mark Nelson, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK

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British HIV Association guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy 2015

Kidney transplantation is a viable treatment for select patients with HIV and ESRD, but data are lacking regarding long-term outcomes and comparisons with appropriately matched HIV-negative patients. We analyzed data from the Scientific Registry of Transplant Recipients (SRTR; 2002–2011): 510 adult kidney transplant recipients with HIV (median follow-up, 3.8 years) matched 1:10 to HIV-negative controls. Compared with HIV-negative controls, HIV-infected recipients had significantly lower 5-year (75.3% versus 69.2%) and 10-year (54.4% versus 49.8%) post-transplant graft survival (GS) (hazard ratio [HR], 1.37; 95% confidence interval [95% CI], 1.15 to 1.64; P P =0.005). However, compared with HIV-negative/hepatitis C virus (HCV)–negative controls, HIV monoinfected recipients had similar 5-year and 10-year GS, whereas HIV/HCV coinfected recipients had worse GS (5-year: 64.0% versus 52.0%, P =0.02; 10-year: 36.2% versus 27.0%, P =0.004 [HR, 1.38; 95% CI, 1.08 to 1.77; P =0.01]). Patient survival (PS) among HIV-infected recipients was 83.5% at 5 years and 51.6% at 10 years and was significantly lower than PS among HIV-negative controls (HR, 1.34; 95% CI, 1.08 to 1.68; P P =0.007; 10-year: 29.3% versus 56.23%, P =0.002 [HR, 1.57; 95% CI, 1.11 to 2.22; P =0.01]). In conclusion, HIV-negative and HIV monoinfected kidney transplant recipients had similar GS and PS, whereas HIV/HCV coinfected recipients had worse outcomes. Although encouraging, these results suggest caution in transplanting coinfected patients.

A National Study of Outcomes among HIV-Infected Kidney Transplant Recipients

1. Gathogo E, Jose S, Jones R, Levy JB, Mackie NE, Booth J, et al. End-stage kidney disease and kidney transplantation in HIVpositive patients: an observational cohort study. J Acquir Immune Defic Syndr 2014; 67:177–180. 2. Stock PG, Barin B, Murphy B, Hanto D, Diego JM, Light J, et al. Outcomes of kidney transplantation in HIV-infected recipients. N Engl J Med 2010; 363:2004–2014. 3. Mazuecos A, Fernandez A, Zarraga S, Andres A, RodriguezBenot A, Jimenez C, et al. High incidence of delayed graft function in HIV-infected kidney transplant recipients. Transpl Int 2013; 26:893–902. 4. Gathogo EN, Hamzah L, Hilton R, Marshall N, Ashley C, Harber M, et al., UK HIV/Kidney Transplantation Study Group. Kidney transplantation in HIV-positive adults: the UK experience. Int J STD AIDS 2014; 25:57–66. 5. Locke JE, James NT, Mannon RB, Mehta SG, Pappas PG, Baddley JW, et al. Immunosuppression regimen and the risk of acute rejection in HIV-infected kidney transplant recipients. Transplantation 2014; 97:446–450. 6. Canaud G, Dejucq-Rainsford N, Avettand-Fenoel V, Viard JP, Anglicheau D, Bienaime F, et al. The kidney as a reservoir for HIV-1 after renal transplantation. J Am Soc Nephrol 2014; 25:407–419. 7. Gathogo E, Harber M, Bhagani S, Levy J, Jones R, Hilton R, et al. Impact of tacrolimus compared with cyclosporin on the incidence of acute allograft rejection in human immunodeficiency virus-positive kidney transplant recipients. Transplantation 2016; 100:871–878. 8. Marfo K, Greenstein S. Antiretroviral and immunosuppressive drug-drug interactions in human immunodeficiency virus-infected liver and kidney transplant recipients. Transplant Proc 2009; 41:3796–3799. 9. Lorio MA, Rosa R, Suarez JF, Ruiz P, Ciancio G, Burke GW, et al. Influence of immune activation on the risk of allograft rejection in human immunodeficiency virus-infected kidney transplant recipients. Transpl Immunol 2016; 38:40–43. 10. Locke JE, Mehta S, Reed RD, MacLennan P, Massie A, Nellore A, et al. A national study of outcomes among HIV-infected kidney transplant recipients. J Am Soc Nephrol 2015; 26:2222–2229. 11. Hutchings A, Purcell WM, Benfield MR. Increased costimulatory responses in African-American kidney allograft recipients. Transplantation 2001; 71:692–695. 12. MacPhee IA, Fredericks S, Tai T, Syrris P, Carter ND, Johnston A, et al. The influence of pharmacogenetics on the time to achieve target tacrolimus concentrations after kidney transplantation. Am J Transplant 2004; 4:914–919. 13. McLean F, Gathogo E, Goodall D, Kinloch S, Jones R, Post FA. Alemtuzumab induction therapy in HIV positive renal transplant recipients. AIDS 2017(in press).

Neuropsychiatric adverse effects on dolutegravir: an emerging concern in Europe

https://onlinelibrary.wiley.com/doi/pdf/10.1111/ajt.14419

Impact of Protease Inhibitor–Based Anti‐Retroviral Therapy on Outcomes for HIV+ Kidney Transplant Recipients

HIV-positive patients are at increased risk of end-stage kidney disease. Kidney transplantation is an established treatment modality for end-stage kidney disease in the general population. Recent data have confirmed the feasibility of kidney transplantation in HIV-positive patients, and kidney transplantation is increasingly offered to end-stage kidney disease patients with well-controlled HIV infection. We report clinical outcomes in a national cohort study of kidney trans- plantation in HIV-positive patients. In all, 35 HIV-positive KT recipients who had undergone KT up to December 2010 (66% male, 74% black ethnicity) were identified; the median CD4 cell count was 366, all had undetectable HIV RNA levels at kidney transplantation, and 44% received a kidney from a live donor. Patient survival at 1 and 3 years was 91.3%, and graft survival 91.3% and 84.7%, respectively. At one-year post-kidney transplantation, the cumulative incidence of acute rejection was 48%, and the median (IQR) eGFR 64 (46, 78) mL/min/1.73m 2 . Although HIV viraemia and HIV disease progression were uncommon, renal complications were relatively frequent. Our study corroborates the feasibility of kidney transplantation in HIV-positive patients. The high rates of acute rejection suggest that the optimal immune suppression strategy in this population remains to be refined.

Kidney transplantation in HIV-positive adults: the UK experience

https://www.medicinejournal.co.uk/article/S1357-3039(11)00072-7/pdf

Drugs and renal insufficiency

The kidney plays an important role in the handling of drugs in the body; therefore patients with renal impairment will invariably require different dosage regimes to those with normal renal function. Unfortunately, there are no absolute guidelines on how to adjust doses in renal impairment, and pharmaceutical company literature often excludes patients with renal impairment in the dosage guidelines. Where information can be found, the advice may not be specific and different texts may give different advice [2]. Therefore, it is important to have an understanding of the potential effects of renal impairment on the pharmacodynamic and pharmacokinetic properties of a drug so that appropriate dosing decisions can be made. Although a reduced GFR is the primary reason for reduced excretion of drugs in renal failure, absorption, distribution, protein binding, metabolism and pharmacodynamics are all relevant.

Pharmacology and the Kidney

https://www.medicinejournal.co.uk/article/S1357-3039(15)00099-7/pdf

Caroline Ashley

Papers

Kidney transplantation in HIV-positive adults: the UK experience

Drugs and renal insufficiency

Pharmacology and the Kidney

Nephrotoxins and drugs in renal insufficiency