Contents

Search

renal transplantation

The 1st renal transplant was performed in 1954. Indications: 1) end-stage renal disease* 2) the patient must not have cancer 3) infections must be erradicated 4) cholecystectomy must be done for gallstones * treatment of choice for eligible patients * eligible patients should be referred to nephrology when eGFR is < 20 mL/min/1.73 m2 [2] * renal transplantation associated with superior quality of life, improved survival, less expensive than long-term renal dialysis [1] * preemptive renal transplantation associated with better outcomes than transplantation after renal dialysis [[2] Contraindications: 1) active infection, excluding HIV1 infection [5] - HIV-positive-to-HIV-positive kidney transplantation in selected donors & recipients appears to be feasible & safe [16,23] 2) active malignancy 3) dementia, other neuropsychiatric disorders [2] 4) significant heart, lung or liver disease 5) a chronically debilitated state 6) substance abuse 7) non-compliant patients Procedure: Benefits: (with good allograft function, GFR > 50 mL/min) 1) resolution of anemia 2) return to full-time employment 3) return of normal endocrine, sexual & reproductive function 4) enhanced energy levels 5) return to strenuous exercise 6) having children is feasible (see management) 7) resolution of autonomic neuropathy in diabetics Donors: 1) living* a) > 18 years of age b) without systemic or renal disease c) contraindications - uncontrolled hypertension - diabetes mellitus - long-term NSAID use - family history of kidney disease [15] d) 6000 live doners/year 2) cadaveric a) > 6 months old b) without infection or malignancy (except non-metastasizing brain tumor) c) inferior renal allograft survival time relative to live donor kidney [2] * transplant from HLA-incompatible donor associated with extended survival vs waiting for a cadaveric kidney [17] * prophylaxis/treatment with antivirals (elbasvir-grazoprevir) may enable safe kidney transplantation from hepatitis C-infected deceased donors to uninfected patients [20,21] Evaluation: 1) evaluation for coronary artery disease (CAD) 2) viral serologies a) hepatitis B serology & hepatitis C serology b) HIV testing c) cytomegalovirus serology (CMV) 3) dental exam for dental abscesses Laboratory: - pretransplant - type & screen - Quantiferon TB - hepatitis B surface antigen & hepatitis B surface antibody - hepatitis C antibody - HIV1 serology - CMV IgG, CMV IgM - BK polyomavirus DNA in serum/plasma/urine & urine cytology during the 1st year after renal transplantation & when there has been a decline in renal function [2] Radiology: post-transplant DPTA/hippuran renal scan Complications: 1) surgical complications a) renal artery stenosis (late complication) b) ureteral obstruction or leak c) lymphocele 2) wound & urinary tract infections most common complications in 1st month following transplantation 3) after 1st month, opportunistic infections* become prevalent a) BK virus associated nephropathy with immunosuppression - decrease immunosuppression [2] b) cytomegalovirus 1] high risk with seropositive donor & seronegative recipient 2] fever, leukopenia diarrhea 3] retinitis, encephalitis, pneumonia, hepatitis, gastrointestinal ulceration [2] c) Pneumocystis jirovecii d) Nocardia 4) graft rejection a) graft failure commonly due to chronic rejection b) acute tubular necrosis occurs in 20-50% of patients after transplantation c) stages of rejection 1] hyperacute (hours) 2] acute (days to years) 3] chronic (months to years) d) treat only acute stages of rejection e) graft rejection may occur after 7-10 years f) graft rejection more common when 1] kidney is from older donor 2] kidney is transplanted into younger recipient [7,8] 5) recurrent allograft renal disease a) membranoproliferative glomerulonephritis b) membranous nephropathy c) focal segmental glomerulosclerosis 1] clinically, most problematic 2] treat with aggressive plasmapheresis (pheresible protein) d) diabetes mellitus e) primary hyperoxaluria f) hemolytic uremic syndrome g) IgA nephropathy (generally not clinically significant) 6) cardiovascular complications* - statin dose should be reduced in renal transplant patients taking cyclosporin [2] 7) hyperlipidemia 8) cancer (1%) a) skin cancer, especially squamous cell carcinoma of the skin [2] b) sarcomas - Kaposi's sarcoma - reduce immunosuppression & switch to sirolimus [2] c) lymphoma (Epstein-Barr virus (EBV) associated) - reduce immunosuppression, add rituximab if CD20+ [2] d) solid tumors, lung cancer [6] 9) erythrocytosis a) no leukocytosis or thrombocytosis b) phlebotomize if hematocrit > 52 c) ACE inhibitors 10) renal tubular acidosis (RTA) a) both proximal (type 2) & distal (types 1,4) b) type 4 RTA most common 11) urolithiasis (uncommon) 12) complications due to pharmaceutical agents - corticosteroid-related complications - aseptic necrosis of hip or knee - increased risk of fractures 13) gout 14) underlying kidney disease that may recur after renal transplantation a) focal segmental glomerulosclerosis b) IgA nephropathy c) diabetic nephropathy d) lupus nephritis e) membranous nephropathy f) hemolytic uremic syndrome * 2 most common causes of death Management: 1) immunosuppression unless donor is identical twin a) induction therapy - thymoglobulin depletes lymphocytes - IL2 receptor antibodies - daclizumab - basiliximab, depletes lymphocytes - targets IL2 receptor - causes lymphocyte arrest - alemtuzumab targets CD52, - muromonab-CD3 targets CD3, depletes lymphocytes b) maintenance therapy - lifetime immunosuppression is required - agents - tacrolimus - cyclosporine - sirolimus (rapamycin), everolimus - azathioprine - myocophenoloate - prednisone 2) immunizations: see organ transplantation 3) prognosis: a) 96-99% 1 year & 84-91% 5 year patient survival - survival is better with graft from living donor [2] b) 93% 1 year & 72% 5 year cadaveric graft survival c) graft survival is better in recipients of living kidneys - 93% 1 year & 81% 5 year living graft survival - 5-10% less in black Americans, recipients of a 2nd kidney & highly sensitized individuals d) old organs transplanted into young recipients have by far the highest rejection rates [8] e) old organs may be successfully transplanted into older patients [8] f) preemptive renal transplantation before dialysis & transplantation shortly after initiation of dialysis associated with patient & allograft survival advantage g) HIV patients likely to do as well as other patients, albeit with higher transplant rejection rates [5] 4) renal transplant patients with gout: - mycophenolate rather than azathioprine may permit use of allopurinol 5) conception/pregnancy a) women should wait at least 1-2 years after transplantation prior toconception [2] b) considered high-risk pregnancy c) pregnancy not recommended if serum creatinine > 2 mg/dL [2] d) mycophenolate & sirolimus are teratogenic & must be discontinued prior to conception [2] Notes: - current system of allocating kidneys is flawed, with organs being discarded that might otherwise have benefited people [9] - Medicare covers the cost of immunosuppressive drugs for only 3 years after transplantation; European countries generally do not restrict length of coverage

Interactions

disease interactions

Related

end-stage renal disease (ESRD) renal graft rejection

General

organ transplantation

References

  1. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 618
  2. Medical Knowledge Self Assessment Program (MKSAP) 11, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2009, 2012, 2015, 2018, 2021. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  3. Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 1282
  4. FDA Medwatch http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm171828.htm
  5. Stock PG et al. Outcomes of kidney transplantation in HIV-infected recipients. N Engl J Med 2010 Nov 18; 363:2004. PMID: 21083386 - Szczech LA. Tackling the unknowns in HIV-related kidney diseases. N Engl J Med 2010 Nov 18; 363:2058. PMID: 21083392
  6. Engels EA et al. Spectrum of cancer risk among US solid organ transplant recipients. JAMA 2011 Nov 2; 306:1891. PMID: 22045767
  7. de Fijter JW The impact of age on rejection in kidney transplantation. Drugs Aging. 2005;22(5):433-49. Review PMID: 15903355
  8. Tullius SG, Milford E. Kidney allocation and the aging immune response. N Engl J Med 2011; 364:1369-1370 PMID: 21410395
  9. Physician's First Watch, Sept 21, 2012 Massachusetts Medical Society http://www.jwatch.org (subscription required) - New York Times, Sept 19, 2012 In Discarding of Kidneys, System Reveals Its Flaw http://www.nytimes.com/2012/09/20/health/transplant-experts-blame-allocation-system-for-discarding-kidneys.html?_r=0
  10. Gondos A et al Kidney Graft Survival in Europe and the United States: Strikingly Different Long-term Outcomes Transplantation, 10 October 2012 PMID: 23060279 http://journals.lww.com/transplantjournal/Abstract/publishahead/Kidney_Graft_Survival_in_Europe_and_the_United.98853.aspx
  11. Avery RK. Infectious disease following kidney transplant: core curriculum 2010. Am J Kidney Dis. 2010 Apr;55(4):755-71 PMID: 20338466
  12. Helantera I, Lautenschlager I, Koskinen P. The risk of cytomegalovirus recurrence after kidney transplantation. Transpl Int. 2011 Dec;24(12):1170-8. PMID: 21902725
  13. Barraclough KA, Isbel NM, Staatz CE, Johnson DW. BK Virus in Kidney Transplant Recipients: The Influence of Immunosuppression. J Transplant. 2011;2011:750836 PMID: 21766009
  14. Axelrod DA, McCullough KP, Brewer ED et al Kidney and pancreas transplantation in the United States, 1999-2008: the changing face of living donation. Am J Transplant. 2010 Apr;10(4 Pt 2):987-1002 PMID: 20420648
  15. Pavlakis M. Live kidney donation: a 36-year-old woman hoping to donate a kidney to her mother. JAMA. 2011;305(6):592-599. PMID: 21245171
  16. Muller E et al. HIV-positive-to-HIV-positive kidney transplantation - results at 3 to 5 years. N Engl J Med 2015 Feb 12; 372:610 PMID: 25671253 http://www.nejm.org/doi/full/10.1056/NEJMoa1408896
  17. Orandi BJ et al Survival Benefit with Kidney Transplants from HLA-Incompatible Live Donors. N Engl J Med 2016; 374:940-95. March 10, 2016 PMID: 26962729 http://www.nejm.org/doi/full/10.1056/NEJMoa1508380 - Rostaing LPE and Malvezzi P.HLA-incompatible kidney transplantation - worth the risk? N Engl J Med 2016 Mar 10; 374:982 PMID: 26962734
  18. Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant. 2009 Nov;9 Suppl 3:S1-155 PMID: 19845597 Free full text
  19. Tonelli M, Wiebe N, Knoll G et al Systematic review: kidney transplantation compared with dialysis in clinically relevant outcomes. Am J Transplant. 2011 Oct;11(10):2093-109. PMID: 21883901 Free Article
  20. Durand CM, Bowring MG, Brown DM et al Direct-Acting Antiviral Prophylaxis in Kidney Transplantation From Hepatitis C Virus-Infected Donors to Noninfected Recipients: An Open-Label Nonrandomized Trial. Ann Intern Med. 2018. March 6. PMID: 29507971 http://annals.org/aim/article-abstract/2674335/direct-acting-antiviral-prophylaxis-kidney-transplantation-from-hepatitis-c-virus
  21. Reese PP, Abt PL, Blumberg EA Twelve-Month Outcomes After Transplant of Hepatitis C-Infected Kidneys Into Uninfected Recipients: A Single-Group Trial. Ann Intern Med. 2018. Aug 7 PMID: 30083748 http://annals.org/aim/article-abstract/2696495/twelve-month-outcomes-after-transplant-hepatitis-c-infected-kidneys-uninfected - Sharif A Transplanting Kidneys From Hepatitis C-Infected Donors Into Uninfected Recipients: Ready for the Mainstream. Ann Intern Med. 2018. Aug 7 PMID: 30083764 http://annals.org/aim/article-abstract/2696496/transplanting-kidneys-from-hepatitis-c-infected-donors-uninfected-recipients-ready
  22. Hou S. Pregnancy in renal transplant recipients. Adv Chronic Kidney Dis. 2013 May;20(3):253-9. Review. PMID: 23928390
  23. Monaco K People With HIV Can Safely Receive Kidneys From Donors With HIV. U.S. study findings should help squash "remaining doubts" about safety, researcher says. MedPage Today October 16, 2024 https://www.medpagetoday.com/nephrology/kidneytransplantation/112428 - Durand CM, Massie A, Florman S et al for the HOPE in Action Investigators. Safety of Kidney Transplantation from Donors with HIV. N Engl J Med. 2024 Oct 17;391(15):1390-1401. PMID: 39413376 https://www.nejm.org/doi/full/10.1056/NEJMoa2403733
  24. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Kidney Transplant https://www.niddk.nih.gov/health-information/kidney-disease/kidney-failure/kidney-transplant/