Other risk factors
Although CNI exposure is the most important risk factor for developing CKD after NRSOT, multiple other factors contribute to the risk. These factors include hypertension (HTN), diabetes mellitus (DM), and acute kidney injury (AKI) prior to transplant.
Therefore, it is important for clinicians to strive for optimal control of HTN and DM after NRSOT. This is particularly relevant because almost 25% of recipients will develop DM after transplant22 and nearly 80% of patients will depend on medications to control their HTN. Targeting BP of 130/80 mm Hg or lower will hinder the progression of CKD.23
Encouraging patients to exercise after transplant may be beneficial in controlling their DM and HTN and will encourage them to take ownership of their post-transplant care. Another simple but important modifiable, but less appreciated factor is that optimal control of lipids with statins might decrease the risk of CKD progression by decreasing inflammation.24,25
AKI before and early after transplantation has tremendous implications for recipient survival and the risk of developing CKD.26-29 However, clinicians should focus more on preventing AKI prior to transplantation. It seems clear that severe AKI requiring renal replacement may be required in up to 25% of NRSOT recipients and translates into a major risk for developing CKD in all NRSOT.6,30
Yet clinicians often fail to consider the impact of infection/sepsis, vasopressive medications, and antimicrobials on the development of AKI. AKI prevention should be considered one of the most important measures to lower CKD risk after NRSOT. This has become particularly important in liver transplants as the MELD scoring system for liver allocation favors potential recipients with renal dysfunction.
CKD after NRSOT is a growing problem with tremendous implication for our health care system. The success in preventing episodes of rejection has led to more recipients being able to enjoy long-term survival after transplant while unfortunately putting them at increased risk of CKD.
Until newer medications can be developed that prevent rejection without associated renal toxicity, clinicians need to rely on conservative measures to slow CKD progression. Further research into AKI biomarkers may be able to identify AKI at an earlier stage and ameliorate its negative effects on long-term renal function. Until then, nephrologists need to raise their awareness of AKI prevention prior to NRSOT. As the old adage goes, “an ounce of prevention is worth a pound of cure.”
Dr. Hofmann is Associate Professor of Nephrology at the University of Wisconsin in Madison.
- SRTR 2008 Annual Report. 2008.
- Cattaneo D, Perico N. Gaspari F, Remuzzi G. Nephrotoxic aspects of cyclosporine. Transplant Proc. 2004;36(2 Suppl):234S-239S.
- Myers BD, Sibley R, Newton L, et al. The long-term course of cyclosporine-associated chronic nephropathy. Kidney Int. 1988;33:590-600.
- Barraclough K, Menahem SA, Bailey M, Thomson NM. Predictors of decline in renal function after lung transplantation. J Heart Lung Transplant. 2006;25:1431-1435.
- Taylor, DO, Edwards LB, Aurora P, et al. Registry of the International Society for Heart and Lung Transplantation: twenty-fifth official adult heart transplant report–2008. J Heart Lung Transplant. 2008;27:943-956.
- Hamour IM, Omar F, Myster HS, et al. Chronic kidney disease after heart transplantation. Nephrol Dial Transplant. 2009;24:1655-1662.
- Gonwa TA, Mai ML, Melton LB, et al. End-stage renal disease (ESRD) after orthotopic liver transplantation (OLTX) using calcineurin-based immunotherapy: risk of development and treatment. Transplantation. 2001;72;1934-1939.
- Broekroelofs J, Navis GJ, Stegeman CA, et al. Long-term renal outcome after lung transplantation is predicted by the 1-month postoperative renal function loss. Transplantation. 2000;69:1624-1628.
- Ojo, AO, Held PJ, Port FK, et al. Chronic renal failure after transplantation of a nonrenal organ. N Engl J Med. 2003;349:931-940.
- Alam A, Badovinac K, Ivis F, et al. The outcome of heart transplant recipients following the development of end-stage renal disease: analysis of the Canadian Organ Replacement Register (CORR). Am J Transplant. 2007;7:461-465.
- Villar E, Redondo M, Rodrigo I, et al. Poor prognosis of heart transplant patients with end-stage renal failure. Nephrol Dial Transplant. 2007;22:1383-1389.
- Khan SS, Kazmi WH, Abichandani R, et al. Health care utilization among patients with chronic kidney disease. Kidney Int. 2002;62:229-236.
- Angermann CE, Störk S, Costard-Jäckle A, et al. Reduction of cyclosporine after introduction of mycophenolate mofetil improves chronic renal dysfunction in heart transplant recipients–the IMPROVED multi-centre study. Eur Heart J. 2004;25:1626-1634.
- Castroagudin JF, Molina E, Romero R, et al. Improvement of renal function after the switch from a calcineurin inhibitor to everolimus in liver transplant recipients with chronic renal dysfunction. Liver Transpl. 2009;15:1792-1797.
- DuBay D, Smith RJ, Qiu KG, et al. Sirolimus in liver transplant recipients with renal dysfunction offers no advantage over low-dose calcineurin inhibitor regimens. Liver Transpl. 2008;14:651-659.
- Groetzner J, Kaczmarek I, Schulz U, et al. Mycophenolate and sirolimus as calcineurin inhibitor-free immunosuppression improves renal function better than calcineurin inhibitor-reduction in late cardiac transplant recipients with chronic renal failure. Transplantation. 2009;87:726-733.
- Lyster H, Leaver N, Hamour I, et al. Transfer from ciclosporin to mycophenolate-sirolimus immunosuppression for chronic renal disease after heart transplantation: safety and efficacy of two regimens. Nephrol Dial Transplant. 2009;24:3872-3875.
- Stallone G, Infante B, Grandaliano G, Gesualdo L. Management of side effects of sirolimus therapy. Transplantation. 2009;87(8 Suppl):S23-S26.
- van den Akker, JM, Wetzels JF, Hoitsma AJ. Proteinuria following conversion from azathioprine to sirolimus in renal transplant recipients. Kidney Int. 2006; 70:1355-1357.
- Gustafsson F, Ross HJ, Delgado MS, et al. Sirolimus-based immunosuppression after cardiac transplantation: predictors of recovery from calcineurin inhibitor-induced renal dysfunction. J Heart Lung Transplant. 2007;26:998-1003.
- Stephany BR, Boumitri M, Budev M, et al. Absence of proteinuria predicts improvement in renal function after conversion to sirolimus-based immunosuppressive regimens in lung transplant survivors with chronic kidney disease. J Heart Lung Transplant. 2009;28:564-571.
- Pageaux GP, Faure S, Bouyabrine H, et al. Long-term outcomes of liver transplantation: diabetes mellitus. Liver Transpl. 2009;Suppl 2:S79-S82.
- Jafar TH, Stark PC, Schmid CH, et al. Progression of chronic kidney disease: the role of blood pressure control, proteinuria, and angiotensin-converting enzyme inhibition: a patient-level meta-analysis. Ann Intern Med. 2003;139:244-252.
- Stephany BR, Alao B, Budev M, et al. Hyperlipidemia is associated with accelerated chronic kidney disease progression after lung transplantation. Am J Transplant. 2007;7:2553-2560.
- Lubitz SA, Pinney S, Wisnivesky JP, et al. Statin therapy associated with a reduced risk of chronic renal failure after cardiac transplantation. J Heart Lung Transplant. 2007;26:264-272.
- Barri YM, Sanchez EQ, Jennings LW, et al. Acute kidney injury following liver transplantation: definition and outcome. Liver Transpl. 2009;15:475-483.
- Bahirwani R, Campbell MS, Siropaides T, et al. Transplantation: impact of pretransplant renal insufficiency. Liver Transpl. 2008;14:665-671.
- Zuckermann A, Ploner M, Czerny M, et al. Even slightly impaired kideny function (creatinine>1.79 MMOL/L) one year after cardiac transplantation has a negative impact on long term survival. J Heart Lung Transplant. 2001;20:206.
- Odim J, Wheat J, Laks H, et al. Peri-operative renal function and outcome after orthotopic heart transplantation. J Heart Lung Transplant. 2006;25:162-166.
- Pham PT, Slavov C, Pham PC. Acute kidney injury after liver, heart, and lung transplants: dialysis modality, predictors of renal function recovery, and impact on survival. Adv Chronic Kidney Dis. 2009;16:256-267.