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Kidney Transplantation: Posttransplant Preventive Care

For many years, the medical community speculated about the possibility of organ transplantation. The first successful transplant of any kind involving humans was a corneal transplant in 1905.1

It wasn’t until 1954 that the first successful organ transplant, a kidney transplant between identical twins, occurred.2 Several new concepts emerged: organ rejection plays a major role in the failure or success of a transplant; and donors and recipients must be matched based on blood group.

Today, about 169,000 people in the US live with a donated kidney. Each year, some 10,500 cadaveric organs are transplanted, and 6,400 donors are living donors.3 The National Kidney Foundation’s recent 10-year initiative, End the Wait!,4 seeks to close the gap between the more than 50,000 people on the transplant waiting list3 and the number of available donor organs.

Since many patients live for years with their transplanted organs, the primary care clinician is likely to see transplant recipients in a family practice or internal medicine setting. While each patient has unique needs, there are commonalities among them.

Renal Consult welcomes any additional comments or questions regarding care of the renal patient. Please address them to [email protected].
Jane S. Davis, CRNP, DNP

Q: I am in primary care and have a kidney transplant patient that I see annually for her Pap test and pelvic exam. Is there anything in particular that I am supposed to look for? I feel out of my comfort zone.

As with most people, preventive care is vital and posttransplant patients are no different. However, there are a few “special circumstances” to keep in mind.

Besides ascertaining that posttransplant patients are taking their medications every day, determine whether they have recently had a generic substituted for their regular anti-rejection meds. Many transplant medications have generic equivalents now; while we want changes made only with the approval of a transplant center, it is legal for a pharmacy to substitute a generic without notifying the transplant nephrologist. We have seen rejection, toxicities, or changes in creatinine levels due to substitution of generics—or even substitution from one generic equivalent to another. These medications have a small effective window and have to be closely monitored whenever different manufacturers are used.

In addition, some patients will stop taking their immunosuppressive drug, either because they “feel better” and don’t believe they need it anymore, or because they can no longer afford it. Medicare will only pay for 36 months of these medications, and patients often halve the dose or stop taking the medication altogether when the cost becomes too high.5

There is a very useful Web site on transplant medications from the United States Renal Data System.6 The site, which also offers a wealth of information on chronic kidney disease (CKD), is www.usrds.org/presentations.htm

Dosing for any medication is based on the patient’s glomerular filtration rate (GFR). Your transplant patients have been taught their baseline creatinine level, but some do forget. Even after transplant (whether of a kidney, a pancreas, a liver, lungs, or a heart), the immunosuppressive medications will affect the GFR, and the patient is a CKD patient.

If a patient’s creatinine level is 1.9 mg/dL (normal range, 0.6 to 1.2), but it has varied between 1.8 and 2.0 ever since the transplant and they are not having any other issues, this is “normal” for them and no cause for alarm. On the other hand, if the creatinine level is 1.9 mg/dL and the patient reports that it is always 1.2, they need immediate referral. If the patient is new to the area, you can find a local transplant center on the Organ Procurement and Transplantation Network directory7:  optn.transplant.hrsa.gov/mem bers/search.asp

Screening for infections and malignancies is another important aspect of posttransplant care. I advise all patients to see a dermatologist at least once annually, as the risk for skin cancer is increased sevenfold in a transplant patient, compared with the general population.8 Annual Pap test, pelvic exam, and mammogram are important for female posttransplant patients, as is annual prostate-specific antigen testing for male posttransplant patients older than 45 with a life expectancy of at least 10 years.9

During the physical exam, the clinician should always check for lymphadenopathy or any other “lumps and bumps,” as posttransplant lymphoproliferative disorder is also a risk associated with long-term immunosuppression.10 A wonderful online resource for patients and providers, “Transplant Living,”11 has an excellent section on posttransplant care: www.transplantliving.org/af terthetransplant/default.aspx. This Web site is managed by the United Network of Organ Sharing12 (UNOS; www.unos.org), the organization that manages organ transplantation and donation under contract with the federal government.

 

 

Routine vaccinations are recommended—especially pneumococcal vaccine and an annual flu shot. Diphtheria-pertussis-tetanus, hepatitis A, hepatitis B, inactivated polio, and typhoid are also acceptable vaccines for a transplant patient. Vaccines that are contraindicated after transplantation include varicella, bacillus Calmette-Guérin, smallpox, intranasal influenza, live oral typhoid, measles, mumps, rubella, oral polio, live Japanese B encephalitis, and yellow fever.13,14

References
1. Armitage WJ, Tullo AB, Larkin DFP. The first successful full-thickness corneal transplant: a commentary on Eduard Zirm’s landmark paper of 1906. Br J Ophthalmol. 2006;90(10):1222-1223.

2. Kidney transplantation: past, present, and future. www.stanford.edu/dept/HPS/transplant/html/history.html. Accessed September 16, 2011.

3. United States Renal Data System. Atlas. www .usrds.org/atlas.htm. Accessed September 16, 2011.

4. National Kidney Foundation. End the wait! www.kidney.org/news/end_the_wait/index.cfm. Accessed September 16, 2011.

5. National Kidney Foundation. Kidney transplant (2011). www.kidney.org/atoz/content/kidneytransnewlease.cfm. Accessed September 16, 2011.

6. United States Renal Data Systems. Presentations and posters (2000-2011). www.usrds.org/presentations.htm. Accessed September 16, 2011.

7. Organ Procurement and Transplantation Network. Members: member directory. optn.transplant.hrsa.gov/members/search.asp. Accessed September 16, 2011.

8. Jensen P, Møller B, Hansen S. Skin cancer in kidney and heart transplant recipients and different long-term immunosuppressive therapy regimens. J Am Acad Dermatol. 2000;42(2 pt 1):307.

9. Wong G, Chapman JR, Craig JC. Cancer screening in renal transplant recipients: what is the evidence? Clin J Am Soc Nephrol. 2008;3 suppl 2:S87-S100.

10. Parker A, Bowles K, Bradley JA, et al; Haemato-oncology subgroup of the British Committee for Standards in Haematology and the British Transplantation Society. Diagnosis of post-transplant lymphoproliferative disorder in solid organ transplant patients. Br J Haematol. 2010;149(5):675-692.

11. Transplant Living. After the transplant (2011). www.transplantliving.org/afterthetransplant/default.aspx. Accessed September 16, 2011.

12. United Network for Organ Sharing. www.unos.org. Accessed September 16, 2011.

13. Kidney Disease Improving Global Outcomes. Managing your adult patients who have a kidney transplant (2010). www.kidney.org/professionals/tools/pdf/02-50-4079_ABB_ManagingTransRecip Bk_PC.pdf. Accessed September 16, 2011.

14. Abbud-Filho M, Adams P, Alberu J, et al. A report of the Lisbon Conference on the care of the kidney transplant recipient. Transplantation. 2007; (Suppl 8):83:1-22.

15. Heldal K, Hartmann A, Leivestad T, et al. Risk variables associated with the outcome of kidney recipients >70 years of age in the new millennium. Nephrol Dial Transplant. 2011;26(8):2706-2711.

16. Chava SP, Singh B, Stangou A, et al. Simultaneous combined liver and kidney transplantation: a single center experience. Clin Transplant. 2010; 24(3):E62-E68.

17. Ruiz R, Kunitake H, Wilkinson AH, et al. Long-term analysis of combined liver and kidney transplantation at a single center. Arch Surg. 2006;141 (8):735-741.

18. Veroux P, Veroux M, Puliatti C, et al. Kidney transplantation from hepatitis C virus-positive donors into hepatitis C virus-positive recipients: a safe way to expand the donor pool? Transplant Proc. 2005;37(6):2571-2573.

19. United States Renal Data Systems, Annual Data Reports. National Kidney and Urologic Disease Information Clearinghouse. Figure 6ii. Transplant (kidney only) wait list and wait times. www.usrds.org/2010/pdf/v2_07.pdf. Accessed September 16, 2011.

20. Arbor Research Collaborative for Health. Kidney waiting time calculator. www.ustransplant.org/Calculators/KidneyWaitTime.aspx. Accessed September 16, 2011.

21. Karakayali FY, Ozdemir H, Kivrakdal S, et al. Recurrent glomerular diseases after renal transplantation. Transplant Proc. 2006;38(2):470-472.

22. Nojima M, Ichikawa Y, Ihara H, et al. Significant effect of HLA-DRB1 matching on acute rejection of kidney transplants within 3 months. Transplant Proc. 2001;33(1-2):1182-1184.

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For many years, the medical community speculated about the possibility of organ transplantation. The first successful transplant of any kind involving humans was a corneal transplant in 1905.1

It wasn’t until 1954 that the first successful organ transplant, a kidney transplant between identical twins, occurred.2 Several new concepts emerged: organ rejection plays a major role in the failure or success of a transplant; and donors and recipients must be matched based on blood group.

Today, about 169,000 people in the US live with a donated kidney. Each year, some 10,500 cadaveric organs are transplanted, and 6,400 donors are living donors.3 The National Kidney Foundation’s recent 10-year initiative, End the Wait!,4 seeks to close the gap between the more than 50,000 people on the transplant waiting list3 and the number of available donor organs.

Since many patients live for years with their transplanted organs, the primary care clinician is likely to see transplant recipients in a family practice or internal medicine setting. While each patient has unique needs, there are commonalities among them.

Renal Consult welcomes any additional comments or questions regarding care of the renal patient. Please address them to [email protected].
Jane S. Davis, CRNP, DNP

Q: I am in primary care and have a kidney transplant patient that I see annually for her Pap test and pelvic exam. Is there anything in particular that I am supposed to look for? I feel out of my comfort zone.

As with most people, preventive care is vital and posttransplant patients are no different. However, there are a few “special circumstances” to keep in mind.

Besides ascertaining that posttransplant patients are taking their medications every day, determine whether they have recently had a generic substituted for their regular anti-rejection meds. Many transplant medications have generic equivalents now; while we want changes made only with the approval of a transplant center, it is legal for a pharmacy to substitute a generic without notifying the transplant nephrologist. We have seen rejection, toxicities, or changes in creatinine levels due to substitution of generics—or even substitution from one generic equivalent to another. These medications have a small effective window and have to be closely monitored whenever different manufacturers are used.

In addition, some patients will stop taking their immunosuppressive drug, either because they “feel better” and don’t believe they need it anymore, or because they can no longer afford it. Medicare will only pay for 36 months of these medications, and patients often halve the dose or stop taking the medication altogether when the cost becomes too high.5

There is a very useful Web site on transplant medications from the United States Renal Data System.6 The site, which also offers a wealth of information on chronic kidney disease (CKD), is www.usrds.org/presentations.htm

Dosing for any medication is based on the patient’s glomerular filtration rate (GFR). Your transplant patients have been taught their baseline creatinine level, but some do forget. Even after transplant (whether of a kidney, a pancreas, a liver, lungs, or a heart), the immunosuppressive medications will affect the GFR, and the patient is a CKD patient.

If a patient’s creatinine level is 1.9 mg/dL (normal range, 0.6 to 1.2), but it has varied between 1.8 and 2.0 ever since the transplant and they are not having any other issues, this is “normal” for them and no cause for alarm. On the other hand, if the creatinine level is 1.9 mg/dL and the patient reports that it is always 1.2, they need immediate referral. If the patient is new to the area, you can find a local transplant center on the Organ Procurement and Transplantation Network directory7:  optn.transplant.hrsa.gov/mem bers/search.asp

Screening for infections and malignancies is another important aspect of posttransplant care. I advise all patients to see a dermatologist at least once annually, as the risk for skin cancer is increased sevenfold in a transplant patient, compared with the general population.8 Annual Pap test, pelvic exam, and mammogram are important for female posttransplant patients, as is annual prostate-specific antigen testing for male posttransplant patients older than 45 with a life expectancy of at least 10 years.9

During the physical exam, the clinician should always check for lymphadenopathy or any other “lumps and bumps,” as posttransplant lymphoproliferative disorder is also a risk associated with long-term immunosuppression.10 A wonderful online resource for patients and providers, “Transplant Living,”11 has an excellent section on posttransplant care: www.transplantliving.org/af terthetransplant/default.aspx. This Web site is managed by the United Network of Organ Sharing12 (UNOS; www.unos.org), the organization that manages organ transplantation and donation under contract with the federal government.

 

 

Routine vaccinations are recommended—especially pneumococcal vaccine and an annual flu shot. Diphtheria-pertussis-tetanus, hepatitis A, hepatitis B, inactivated polio, and typhoid are also acceptable vaccines for a transplant patient. Vaccines that are contraindicated after transplantation include varicella, bacillus Calmette-Guérin, smallpox, intranasal influenza, live oral typhoid, measles, mumps, rubella, oral polio, live Japanese B encephalitis, and yellow fever.13,14

References
1. Armitage WJ, Tullo AB, Larkin DFP. The first successful full-thickness corneal transplant: a commentary on Eduard Zirm’s landmark paper of 1906. Br J Ophthalmol. 2006;90(10):1222-1223.

2. Kidney transplantation: past, present, and future. www.stanford.edu/dept/HPS/transplant/html/history.html. Accessed September 16, 2011.

3. United States Renal Data System. Atlas. www .usrds.org/atlas.htm. Accessed September 16, 2011.

4. National Kidney Foundation. End the wait! www.kidney.org/news/end_the_wait/index.cfm. Accessed September 16, 2011.

5. National Kidney Foundation. Kidney transplant (2011). www.kidney.org/atoz/content/kidneytransnewlease.cfm. Accessed September 16, 2011.

6. United States Renal Data Systems. Presentations and posters (2000-2011). www.usrds.org/presentations.htm. Accessed September 16, 2011.

7. Organ Procurement and Transplantation Network. Members: member directory. optn.transplant.hrsa.gov/members/search.asp. Accessed September 16, 2011.

8. Jensen P, Møller B, Hansen S. Skin cancer in kidney and heart transplant recipients and different long-term immunosuppressive therapy regimens. J Am Acad Dermatol. 2000;42(2 pt 1):307.

9. Wong G, Chapman JR, Craig JC. Cancer screening in renal transplant recipients: what is the evidence? Clin J Am Soc Nephrol. 2008;3 suppl 2:S87-S100.

10. Parker A, Bowles K, Bradley JA, et al; Haemato-oncology subgroup of the British Committee for Standards in Haematology and the British Transplantation Society. Diagnosis of post-transplant lymphoproliferative disorder in solid organ transplant patients. Br J Haematol. 2010;149(5):675-692.

11. Transplant Living. After the transplant (2011). www.transplantliving.org/afterthetransplant/default.aspx. Accessed September 16, 2011.

12. United Network for Organ Sharing. www.unos.org. Accessed September 16, 2011.

13. Kidney Disease Improving Global Outcomes. Managing your adult patients who have a kidney transplant (2010). www.kidney.org/professionals/tools/pdf/02-50-4079_ABB_ManagingTransRecip Bk_PC.pdf. Accessed September 16, 2011.

14. Abbud-Filho M, Adams P, Alberu J, et al. A report of the Lisbon Conference on the care of the kidney transplant recipient. Transplantation. 2007; (Suppl 8):83:1-22.

15. Heldal K, Hartmann A, Leivestad T, et al. Risk variables associated with the outcome of kidney recipients >70 years of age in the new millennium. Nephrol Dial Transplant. 2011;26(8):2706-2711.

16. Chava SP, Singh B, Stangou A, et al. Simultaneous combined liver and kidney transplantation: a single center experience. Clin Transplant. 2010; 24(3):E62-E68.

17. Ruiz R, Kunitake H, Wilkinson AH, et al. Long-term analysis of combined liver and kidney transplantation at a single center. Arch Surg. 2006;141 (8):735-741.

18. Veroux P, Veroux M, Puliatti C, et al. Kidney transplantation from hepatitis C virus-positive donors into hepatitis C virus-positive recipients: a safe way to expand the donor pool? Transplant Proc. 2005;37(6):2571-2573.

19. United States Renal Data Systems, Annual Data Reports. National Kidney and Urologic Disease Information Clearinghouse. Figure 6ii. Transplant (kidney only) wait list and wait times. www.usrds.org/2010/pdf/v2_07.pdf. Accessed September 16, 2011.

20. Arbor Research Collaborative for Health. Kidney waiting time calculator. www.ustransplant.org/Calculators/KidneyWaitTime.aspx. Accessed September 16, 2011.

21. Karakayali FY, Ozdemir H, Kivrakdal S, et al. Recurrent glomerular diseases after renal transplantation. Transplant Proc. 2006;38(2):470-472.

22. Nojima M, Ichikawa Y, Ihara H, et al. Significant effect of HLA-DRB1 matching on acute rejection of kidney transplants within 3 months. Transplant Proc. 2001;33(1-2):1182-1184.

For many years, the medical community speculated about the possibility of organ transplantation. The first successful transplant of any kind involving humans was a corneal transplant in 1905.1

It wasn’t until 1954 that the first successful organ transplant, a kidney transplant between identical twins, occurred.2 Several new concepts emerged: organ rejection plays a major role in the failure or success of a transplant; and donors and recipients must be matched based on blood group.

Today, about 169,000 people in the US live with a donated kidney. Each year, some 10,500 cadaveric organs are transplanted, and 6,400 donors are living donors.3 The National Kidney Foundation’s recent 10-year initiative, End the Wait!,4 seeks to close the gap between the more than 50,000 people on the transplant waiting list3 and the number of available donor organs.

Since many patients live for years with their transplanted organs, the primary care clinician is likely to see transplant recipients in a family practice or internal medicine setting. While each patient has unique needs, there are commonalities among them.

Renal Consult welcomes any additional comments or questions regarding care of the renal patient. Please address them to [email protected].
Jane S. Davis, CRNP, DNP

Q: I am in primary care and have a kidney transplant patient that I see annually for her Pap test and pelvic exam. Is there anything in particular that I am supposed to look for? I feel out of my comfort zone.

As with most people, preventive care is vital and posttransplant patients are no different. However, there are a few “special circumstances” to keep in mind.

Besides ascertaining that posttransplant patients are taking their medications every day, determine whether they have recently had a generic substituted for their regular anti-rejection meds. Many transplant medications have generic equivalents now; while we want changes made only with the approval of a transplant center, it is legal for a pharmacy to substitute a generic without notifying the transplant nephrologist. We have seen rejection, toxicities, or changes in creatinine levels due to substitution of generics—or even substitution from one generic equivalent to another. These medications have a small effective window and have to be closely monitored whenever different manufacturers are used.

In addition, some patients will stop taking their immunosuppressive drug, either because they “feel better” and don’t believe they need it anymore, or because they can no longer afford it. Medicare will only pay for 36 months of these medications, and patients often halve the dose or stop taking the medication altogether when the cost becomes too high.5

There is a very useful Web site on transplant medications from the United States Renal Data System.6 The site, which also offers a wealth of information on chronic kidney disease (CKD), is www.usrds.org/presentations.htm

Dosing for any medication is based on the patient’s glomerular filtration rate (GFR). Your transplant patients have been taught their baseline creatinine level, but some do forget. Even after transplant (whether of a kidney, a pancreas, a liver, lungs, or a heart), the immunosuppressive medications will affect the GFR, and the patient is a CKD patient.

If a patient’s creatinine level is 1.9 mg/dL (normal range, 0.6 to 1.2), but it has varied between 1.8 and 2.0 ever since the transplant and they are not having any other issues, this is “normal” for them and no cause for alarm. On the other hand, if the creatinine level is 1.9 mg/dL and the patient reports that it is always 1.2, they need immediate referral. If the patient is new to the area, you can find a local transplant center on the Organ Procurement and Transplantation Network directory7:  optn.transplant.hrsa.gov/mem bers/search.asp

Screening for infections and malignancies is another important aspect of posttransplant care. I advise all patients to see a dermatologist at least once annually, as the risk for skin cancer is increased sevenfold in a transplant patient, compared with the general population.8 Annual Pap test, pelvic exam, and mammogram are important for female posttransplant patients, as is annual prostate-specific antigen testing for male posttransplant patients older than 45 with a life expectancy of at least 10 years.9

During the physical exam, the clinician should always check for lymphadenopathy or any other “lumps and bumps,” as posttransplant lymphoproliferative disorder is also a risk associated with long-term immunosuppression.10 A wonderful online resource for patients and providers, “Transplant Living,”11 has an excellent section on posttransplant care: www.transplantliving.org/af terthetransplant/default.aspx. This Web site is managed by the United Network of Organ Sharing12 (UNOS; www.unos.org), the organization that manages organ transplantation and donation under contract with the federal government.

 

 

Routine vaccinations are recommended—especially pneumococcal vaccine and an annual flu shot. Diphtheria-pertussis-tetanus, hepatitis A, hepatitis B, inactivated polio, and typhoid are also acceptable vaccines for a transplant patient. Vaccines that are contraindicated after transplantation include varicella, bacillus Calmette-Guérin, smallpox, intranasal influenza, live oral typhoid, measles, mumps, rubella, oral polio, live Japanese B encephalitis, and yellow fever.13,14

References
1. Armitage WJ, Tullo AB, Larkin DFP. The first successful full-thickness corneal transplant: a commentary on Eduard Zirm’s landmark paper of 1906. Br J Ophthalmol. 2006;90(10):1222-1223.

2. Kidney transplantation: past, present, and future. www.stanford.edu/dept/HPS/transplant/html/history.html. Accessed September 16, 2011.

3. United States Renal Data System. Atlas. www .usrds.org/atlas.htm. Accessed September 16, 2011.

4. National Kidney Foundation. End the wait! www.kidney.org/news/end_the_wait/index.cfm. Accessed September 16, 2011.

5. National Kidney Foundation. Kidney transplant (2011). www.kidney.org/atoz/content/kidneytransnewlease.cfm. Accessed September 16, 2011.

6. United States Renal Data Systems. Presentations and posters (2000-2011). www.usrds.org/presentations.htm. Accessed September 16, 2011.

7. Organ Procurement and Transplantation Network. Members: member directory. optn.transplant.hrsa.gov/members/search.asp. Accessed September 16, 2011.

8. Jensen P, Møller B, Hansen S. Skin cancer in kidney and heart transplant recipients and different long-term immunosuppressive therapy regimens. J Am Acad Dermatol. 2000;42(2 pt 1):307.

9. Wong G, Chapman JR, Craig JC. Cancer screening in renal transplant recipients: what is the evidence? Clin J Am Soc Nephrol. 2008;3 suppl 2:S87-S100.

10. Parker A, Bowles K, Bradley JA, et al; Haemato-oncology subgroup of the British Committee for Standards in Haematology and the British Transplantation Society. Diagnosis of post-transplant lymphoproliferative disorder in solid organ transplant patients. Br J Haematol. 2010;149(5):675-692.

11. Transplant Living. After the transplant (2011). www.transplantliving.org/afterthetransplant/default.aspx. Accessed September 16, 2011.

12. United Network for Organ Sharing. www.unos.org. Accessed September 16, 2011.

13. Kidney Disease Improving Global Outcomes. Managing your adult patients who have a kidney transplant (2010). www.kidney.org/professionals/tools/pdf/02-50-4079_ABB_ManagingTransRecip Bk_PC.pdf. Accessed September 16, 2011.

14. Abbud-Filho M, Adams P, Alberu J, et al. A report of the Lisbon Conference on the care of the kidney transplant recipient. Transplantation. 2007; (Suppl 8):83:1-22.

15. Heldal K, Hartmann A, Leivestad T, et al. Risk variables associated with the outcome of kidney recipients >70 years of age in the new millennium. Nephrol Dial Transplant. 2011;26(8):2706-2711.

16. Chava SP, Singh B, Stangou A, et al. Simultaneous combined liver and kidney transplantation: a single center experience. Clin Transplant. 2010; 24(3):E62-E68.

17. Ruiz R, Kunitake H, Wilkinson AH, et al. Long-term analysis of combined liver and kidney transplantation at a single center. Arch Surg. 2006;141 (8):735-741.

18. Veroux P, Veroux M, Puliatti C, et al. Kidney transplantation from hepatitis C virus-positive donors into hepatitis C virus-positive recipients: a safe way to expand the donor pool? Transplant Proc. 2005;37(6):2571-2573.

19. United States Renal Data Systems, Annual Data Reports. National Kidney and Urologic Disease Information Clearinghouse. Figure 6ii. Transplant (kidney only) wait list and wait times. www.usrds.org/2010/pdf/v2_07.pdf. Accessed September 16, 2011.

20. Arbor Research Collaborative for Health. Kidney waiting time calculator. www.ustransplant.org/Calculators/KidneyWaitTime.aspx. Accessed September 16, 2011.

21. Karakayali FY, Ozdemir H, Kivrakdal S, et al. Recurrent glomerular diseases after renal transplantation. Transplant Proc. 2006;38(2):470-472.

22. Nojima M, Ichikawa Y, Ihara H, et al. Significant effect of HLA-DRB1 matching on acute rejection of kidney transplants within 3 months. Transplant Proc. 2001;33(1-2):1182-1184.

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