renal transplantation
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Introduction
The 1st renal transplant was performed in 1954.
Indications
- end-stage renal disease*
- the patient must not have cancer
- infections must be erradicated
- 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
- active infection, excluding HIV1 infection[5]
- HIV-positive-to-HIV-positive kidney transplantation in selected donors & recipients appears to be feasible & safe[16]
- active malignancy
- dementia, other neuropsychiatric disorders[2]
- significant heart, lung or liver disease
- a chronically debilitated state
- substance abuse
- non-compliant patients
Laboratory
- pretransplant
- 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]
Procedure
Benefits: (with good allograft function, GFR > 50 mL/min)
- resolution of anemia
- return to full-time employment
- return of normal endocrine, sexual & reproductive function
- enhanced energy levels
- return to strenuous exercise
- having children is feasible (see management)
- resolution of autonomic neuropathy in diabetics
Donors:
- living*
- > 18 years of age
- without systemic or renal disease
- contraindications
- uncontrolled hypertension
- diabetes mellitus
- long-term NSAID use
- family history of kidney disease[15]
- 6000 live doners/year
- cadaveric
- > 6 months old
- without infection or malignancy (except non-metastasizing brain tumor)
- 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:
- evaluation for coronary artery disease (CAD)
- viral serologies
- dental exam for dental abscesses
Radiology
post-transplant DPTA/hippuran renal scan
Complications
- surgical complications
- renal artery stenosis (late complication)
- ureteral obstruction or leak
- lymphocele
- wound & urinary tract infections most common complications in 1st month following transplantation
- after 1st month, opportunistic infections* become prevalent
- BK virus associated nephropathy with immunosuppression
- decrease immunosuppression[2]
- cytomegalovirus
- high risk with seropositive donor & seronegative recipient
- fever, leukopenia diarrhea
- retinitis, encephalitis, pneumonia, hepatitis, gastrointestinal ulceration[2]
- Pneumocystis jirovecii
- Nocardia
- BK virus associated nephropathy with immunosuppression
- graft rejection
- graft failure commonly due to chronic rejection
- acute tubular necrosis occurs in 20-50% of patients after transplantation
- stages of rejection
- hyperacute (hours)
- acute (days to years)
- chronic (months to years)
- treat only acute stages of rejection
- graft rejection may occur after 7-10 years
- graft rejection more common when
- recurrent allograft renal disease
- membranoproliferative glomerulonephritis
- membranous nephropathy
- focal segmental glomerulosclerosis
- clinically, most problematic
- treat with aggressive plasmapheresis (pheresible protein)
- diabetes mellitus
- primary hyperoxaluria
- hemolytic uremic syndrome
- IgA nephropathy (generally not clinically significant)
- cardiovascular complications*
- statin dose should be reduced in renal transplant patients taking cyclosporin[2]
- hyperlipidemia
- cancer (1%)
- skin cancer, especially squamous cell carcinoma of the skin[2]
- sarcomas - Kaposi's sarcoma
- reduce immunosuppression & switch to sirolimus[2]
- lymphoma (Epstein-Barr virus (EBV) associated)
- reduce immunosuppression, add rituximab if CD20+[2]
- solid tumors, lung cancer[6]
- erythrocytosis
- no leukocytosis or thrombocytosis
- phlebotomize if hematocrit > 52
- ACE inhibitors
- renal tubular acidosis (RTA)
- both proximal (type 2) & distal (types 1,4)
- type 4 RTA most common
- urolithiasis (uncommon)
- complications due to pharmaceutical agents
- corticosteroid-related complications
- aseptic necrosis of hip or knee
- increased risk of fractures
- corticosteroid-related complications
- gout
- underlying kidney disease that may recur after renal transplantation
* 2 most common causes of death
Management
- immunosuppression unless donor is identical twin
- 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
- maintenance therapy
- lifetime immunosuppression is required
- agents
- tacrolimus
- cyclosporine
- sirolimus (rapamycin), everolimus
- azathioprine
- myocophenoloate
- prednisone
- induction therapy
- immunizations: see organ transplantation
- prognosis:
- 96-99% 1 year & 84-91% 5 year patient survival
- 93% 1 year & 72% 5 year cadaveric graft survival
- 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
- old organs transplanted into young recipients have by far the highest rejection rates[8]
- old organs may be successfully transplanted into older patients[8]
- preemptive renal transplantation before dialysis & transplantation shortly after initiation of dialysis associated with patient & allograft survival advantage
- HIV patients likely to do as well as other patients, albeit with higher transplant rejection rates[5]
- renal transplant patients with gout:
- mycophenolate rather than azathioprine may permit use of allopurinol
- conception/pregnancy
- women should wait at least 1-2 years after transplantation prior toconception[2]
- considered high-risk pregnancy
- pregnancy not recommended if serum creatinine > 2 mg/dL[2]
- 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
More general terms
Additional terms
References
- ↑ 1.0 1.1 Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 618
- ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 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 - ↑ Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 1282
- ↑ FDA Medwatch http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm171828.htm
- ↑ 5.0 5.1 5.2 Stock PG et al. Outcomes of kidney transplantation in HIV-infected recipients. N Engl J Med 2010 Nov 18; 363:2004. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21083386
Szczech LA. Tackling the unknowns in HIV-related kidney diseases. N Engl J Med 2010 Nov 18; 363:2058. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21083392 - ↑ 6.0 6.1 Engels EA et al. Spectrum of cancer risk among US solid organ transplant recipients. JAMA 2011 Nov 2; 306:1891. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22045767
- ↑ 7.0 7.1 de Fijter JW The impact of age on rejection in kidney transplantation. Drugs Aging. 2005;22(5):433-49. Review PMID: https://www.ncbi.nlm.nih.gov/pubmed/15903355
- ↑ 8.0 8.1 8.2 8.3 Tullius SG, Milford E. Kidney allocation and the aging immune response. N Engl J Med 2011; 364:1369-1370 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21410395
- ↑ 9.0 9.1 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 - ↑ Gondos A et al Kidney Graft Survival in Europe and the United States: Strikingly Different Long-term Outcomes Transplantation, 10 October 2012 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23060279 <Internet> http://journals.lww.com/transplantjournal/Abstract/publishahead/Kidney_Graft_Survival_in_Europe_and_the_United.98853.aspx
- ↑ Avery RK. Infectious disease following kidney transplant: core curriculum 2010. Am J Kidney Dis. 2010 Apr;55(4):755-71 PMID: https://www.ncbi.nlm.nih.gov/pubmed/20338466
- ↑ Helantera I, Lautenschlager I, Koskinen P. The risk of cytomegalovirus recurrence after kidney transplantation. Transpl Int. 2011 Dec;24(12):1170-8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21902725
- ↑ Barraclough KA, Isbel NM, Staatz CE, Johnson DW. BK Virus in Kidney Transplant Recipients: The Influence of Immunosuppression. J Transplant. 2011;2011:750836 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21766009
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/20420648
- ↑ 15.0 15.1 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: https://www.ncbi.nlm.nih.gov/pubmed/21245171
- ↑ 16.0 16.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25671253 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1408896
- ↑ 17.0 17.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26962729 <Internet> 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: https://www.ncbi.nlm.nih.gov/pubmed/26962734 - ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/19845597 Free full text
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/21883901 Free Article
- ↑ 20.0 20.1 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. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29507971 <Internet> http://annals.org/aim/article-abstract/2674335/direct-acting-antiviral-prophylaxis-kidney-transplantation-from-hepatitis-c-virus
- ↑ 21.0 21.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/30083748 <Internet> 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/30083764 <Internet> http://annals.org/aim/article-abstract/2696496/transplanting-kidneys-from-hepatitis-c-infected-donors-uninfected-recipients-ready - ↑ Hou S. Pregnancy in renal transplant recipients. Adv Chronic Kidney Dis. 2013 May;20(3):253-9. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23928390
- ↑ 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/