Chronic transplant nephropathy

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Classification according to ICD-10
T86.1 Kidney transplant failure and rejection
ICD-10 online (WHO version 2019)

The chronic allograft (CTN), English. Chronic allograft nephropathy , is a condition that can affect patients with a donor kidney. It is the leading cause of premature loss of function in a transplanted kidney.

Background and incidence

In the early days of kidney transplants, the main focus was on ensuring that the implanted organ was not rejected. The one-year rejection rate was around 50% in the 1970s. New, more effective immunosuppressants , namely ciclosporin , came into use over time to minimize the likelihood of an acute rejection reaction . These measures also showed a positive effect. The rejection rate at the end of the 1990s was only between 5% and 20% (within one year). The improved immunosuppression has indeed reduced the acute organ rejection, but has not shown any positive influence on the medium and long-term organ loss. The problems have therefore shifted to the long-term maintenance of the function of the transplant, especially since the data here are still quite unsatisfactory. In the same period (late 1990s), for example, the loss rate caused by a functional failure of the donor kidney was between 25% and 35% after five years and 50% after ten years.

Chronic graft nephropathy is detectable in around 40 to 60% of all biopsies that were routinely performed 24 months after transplantation. The nephropathies also developed with an optimal and stable acceptance of the foreign organ in the recipient's body.

Chronic transplant nephropathy is the leading cause of renal dialysis in patients with a donor kidney and is one of the most common causes of end-stage kidney failure in developed countries.

pathology

Chronic allograft is characterized by a deterioration of the renal function with a non-specific pathology of tubular atrophy , pathological proliferation of connective tissue ( fibrosis ), and intimal fibrosis (engl. Fibrous intimal thickening , FIT), as well as with a different damage to the renal ( glomerulopathy marked). The triad »tubular atrophy, fibrosis and intimal fibrosis« is the basis for the so-called Banff classification of CTN.

Various factors influencing the development of a CTN are known. Overall, much is still unclear about the etiology . Sometimes the causes overlap, sometimes it is not always possible to precisely differentiate between cause and effect . Chronic transplant nephropathy is therefore a clinical picture with a complex etiology. There is a triangle of interactions between:

Calcineurin inhibitors

The most common cause of CTN are immunosuppressants with kidney-toxic properties. As long as they have the donor organ, recipients of a donor kidney must take medication to prevent organ rejection (the only exception is if the donor and recipient are identical twins ). As most drugs are calcineurin - inhibitors , such as cyclosporine or tacrolimus , used. Calcineurin inhibitors, however, are toxic to the kidneys . One speaks of CNI nephrotoxicity .

Switching to another immunosuppressant that does not work by inhibiting calcineurin can sustainably increase the statistical probability of maintaining kidney function. The intake of sirolimus (rapamycin), which suppresses the proliferation of T lymphocytes by blocking interleukin-2 , is an option. Sirolimus is not toxic to the kidneys in monotherapy . A number of studies have shown that the duration of function of transplanted kidneys is significantly higher in patients treated with sirolimus than in patients treated with the "classic" immunosuppressants.

Another alternative is mycophenolate mofetil , which as an IMPDH inhibitor also uses a different mechanism to specifically reduce the function of the immune system.

Other possible causes

In addition to the calcineurin inhibitors, a number of other non-immunological factors play a role. Infections, proteinuria , the age and condition of the transplant kidney, ischemic kidney damage due to transplant shock, high blood pressure and smoking can all contribute significantly to the development of CTN. High blood pressure can be both a cause and an effect of the CTN.

Chronic transplant nephropathy is more common in cadaveric kidneys than in kidneys from living donors. The clinical course is largely the same for both types of donor kidneys. There is also a significant correlation between the frequency of CTN and the age of the donated kidney.

Symptoms and diagnosis

Chronic transplant nephropathy manifests itself as a slow deterioration of the filter function of the transplanted kidney over months or years, which can lead to terminal renal insufficiency (complete loss of function of the transplanted kidney and the recipient's two own kidneys).

By taking kidney tissue ( biopsy ), the chronic damage to the kidney can be determined. Typical of these are the pathological increase in connective tissue (fibrosis), damage to the kidney tubules ( tubular atrophy ) and the kidney corpuscles ( glomerulopathy ) as well as a thickening of the vessel walls caused by inflammatory processes , which leads to the narrowing of the lumen of the vessels.

The distinction between whether kidney function is impaired by chronic transplant nephropathy or by an immunologically induced rejection reaction is often not possible because of the histological similarity.

The Banff classification has been used since 1979. The last version is from 1997. With this classification, histopathological findings are divided into three classes: easy , moderate and difficult .

therapy

Switching to immunosuppressive drugs that do not act as calcineurin inhibitors may stop the progression of CTN. There is currently no special therapy for CTN. An adapted way of life without obesity and with the renunciation of tobacco consumption is advantageous for the preservation of the donor organ; likewise low to normal blood pressure. ACE inhibitors and AT1 antagonists can make positive contributions by reducing protein excretion. When ACE inhibitors are given, the dose of cyclosporine for immunosuppression can be significantly reduced.

An effective treatment or, better still, avoidance of chronic transplant nephropathy would not only have a positive effect for the affected patients, but also shorten the waiting time for donor organs in other patients.

further reading

  • JT Fletcher, BJ Nankivell, SI Alexander: Chronic allograft nephropathy. In: Pediatric nephrology. Volume 24, number 8, August 2009, pp. 1465-1471, doi : 10.1007 / s00467-008-0869-z , PMID 18584214 , PMC 2697362 (free full text) (review).
  • LM Birnbaum et al .: Management of chronic allograft nephropathy: a systematic review. In: Clin J Am Soc Nephrol 4, 2009, pp. 860-865. PMID 19339427 (Review)
  • HE Yoon and CW Yang: Established and newly proposed mechanisms of chronic cyclosporine nephropathy. In: Korean J Intern Med 24, 2009, pp. 81-92. PMID 19543484 (Review)
  • D. Serón: Chronic allograft nephropathy - clinical guidance for early detection and early intervention strategies. In: Nephrol Dial Transplant 23, 2008, pp. 2467-2473. PMID 18385386 (Review)
  • S. Tomasoni et al .: Allograft rejection: acute and chronic studies. In: Contrib Nephrol 159, 2008, pp. 122-134. PMID 18391589 (Review)
  • S. and A. Sar: Pathogenesis and management of chronic allograft nephropathy. In: Drugs 68, 2008, pp. 21-31. PMID 18442298 (Review)
  • B. Najafian and BL Kasiske: Chronic allograft nephropathy. In: Curr Opin Nephrol Hypertens 17, 2008, pp. 149–155. PMID 18277147 (Review)
  • P. Baluja et al .: Chronic allograft nephropathy. In: Adv Chronic Kidney Dis 13, 2006, pp. 56-61. PMID 16412971 (Review)

Individual evidence

  1. ↑ Pathogenetic significance of tissue transglutaminase in the development of chronic transplant nephropathy. (PDF; 196 kB) MHH Research Report 2004, pp. 518–522.
  2. ^ EM Briganti et al.: Risk of renal allograft loss from recurrent glomerulonephritis. In: NEJM 347, 2002, pp. 103-109. PMID 12110738
  3. ↑ a b c d S. Hariharan et al.: Improved graft survival after renal transplantation in the United States, 1988 to 1996. In: NEJM 342, 2000, pp. 605-612. PMID 10699159
  4. ^ A b W. M. Bennett et al.: Chronic cyclosporine nephropathy: the Achilles' heel if immunosuppressive therapy. In: Kidney Int 50, 1996, pp. 1089-1100. PMID 8887265 (Review)
  5. ↑ a b c d G. Stallone et al .: Rapamycin for treatment of chronic allograft nephropathy in renal transplant patients. In: J Am Soc Nephrol 16, 2005, pp. 3755-3762. PMID 16236802
  6. ↑ a b c d e f g P. F. Halloran et al .: Rethinking chronic allograft nephropathy: the concept of accelerated senescece. In: J Am Soc Nephrol 10, 1999, pp. 167-181. PMID 9890324 (Review)
  7. ↑ G. Remuzzi and N. Perico: Protecting single-kidney allografts from long-term functional deterioration. In: J Am Soc Nephrol 9, 1998, pp. 1321-1332. PMID 9644646 (Review)
  8. ↑ JM Campistol and JM Grinyo: Exploring treatment options in renal transplantation: the problems of chronic allograft dysfunction and drug-related nephrotoxicity. In: Transplantation 71, 2001, pp. 42-48. PMID 11583488 (Review)
  9. ↑ D. Seron et al .: Reliability of chronic allograft nephropathy diagnosis in sequential protocol biopsies. In: Kidney Int . 61, 2002, pp. 727-734. PMID 11849416
  10. ↑ LC Paul: Chronic renal transplant loss. In: Kidney Int 47, 1995, pp. 1491-1499. PMID 7643517 (Review)
  11. ↑ A. Räisänen-Sokolowski and P. Häyry: Chronic allograft arteriosclerosis: Contributing factors and molecular mechanisms in the light of experimental studies. In: Transplant Immunol 4, 1996, pp. 91-98. PMID 8843584 (Review)
  12. ↑ K. Solez et al .: International standardization of criteria for the histologic diagnosis of renal allograft rejection: The Banff working classification of kidney transplant pathology. In: Kidney Int 44, 1993, pp. 411-422. PMID 8377384
  13. ↑ K. Solez et al: Report of the third Banff conference on allograft pathology (July 20-24, 1995) on classification and lesion scoring in renal allograft pathology. In: Transplant Proc 28, 1996, pp. 441-444. PMID 8644308 (Review)
  14. ↑ AM Jevnikar and RB Mannon: Late kidney allograft loss: what we know about it, and what we can do about it. In: Clin J Am Soc Nephrol 3, 2008, pp. 56-67. PMID 18309004 (Review)
  15. ↑ A. Benigni et al.: Nature and mediators of renal lesions in kidney transplant patients given cyclosporine for more than one year. In: Kidney Int 55, 1999, pp. 674-685. PMID 9987092
  16. ^ WM Bennett: Insights into chronic cyclosporine nephrotoxicity. In: Int J Clin Pharmacol Ther 34, 1996, pp. 515-519. PMID 8937936 (Review)
  17. ^ VW Lee and JR Chapman: Sirolimus: its role in nephrology. In: Nephrology (Carlton) 10, 2005, pp. 606-614. PMID 16354246 (Review)
  18. ↑ JJ Augustine et al .: Use of sirolimus in solid organ transplantation. In: Drugs 67, 2007, pp. 369-391. PMID 17335296 (Review)
  19. ↑ W. Arns: Long-term protection for transplanted kidneys. (PDF; 1.1 MB) 2004, pp. 1–8.
  20. ↑ Conversion of rejection prophylaxis to sirolimus - chance of maintaining kidney transplant function for longer. In: Dialyse aktuell 12, 2008, pp. 526-528. doi : 10.1055 / s-0028-1104662
  21. ↑ C. Plank et al.: Reduction of calcineurin inhibitors in long-term immunosuppression after kidney transplantation in children and adolescents - less nephrotoxicity, better transplant function? ( Memento of the original from January 19, 2012 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. (PDF; 324 kB) In: Transplantationsmedizin 16, 2004, p. 81. @1@ 2Template: Webachiv / IABot / www.transplantation.de
  22. ↑ RK Wali and MR Weir: Chronic allograft dysfunction: can we use mammalian target of rapamycin inhibitors to replace calcineurin inhibitors to preserve graft function? In: Curr Opin Organ Transplant 13, 2008, pp. 614-621. PMID 19060552 (Review)
  23. ↑ C. Morath et al .: Sirolimus in renal transplantation. In: Nephrol Dial Transplant 22, 2007, pp. 61-65. PMID 17890266 (Review)
  24. ↑ G. Stallone et al .: There is a choice for immunosuppressive drug nephrotoxicity: Is it time to change? In: J Nephrol 22, 2009, pp. 326-332. PMID 19557709 (Review)
  25. ↑ : S. Chadban among others transplantation immunosuppression in renal: some aspects for the modern era. In: Transplant Rev (Orlando) 22, 2008, pp. 241-251. PMID 18657962 (Review)
  26. ↑ a b c d W. A. ​​Eisenhauer: Influence of therapy with ACE inhibitors on proteinuria in kidney transplant patients Dissertation, University of Münster, 2007
  27. ↑ G. Remuzzi et al.: Understanding the nature of renal disease progression. In: Kidney Int 51, 1997, pp. 2-15. PMID 8995712 (Review)
  28. ^ HM Kauffman et al: The expanded donor. In: Transplant Rev 11, 1997, pp. 165-190.
  29. ↑ G. Opelz include: The Collaborative Transplant Study: Association of chronic kidney graft failure with recipient blood pressure. In: Kidney Int 53, 1998, pp. 217-222. PMID 9453022
  30. ↑ N. Zitt et al: Cigarette smoking and chronic allograft nephropathy. In: Nephrol Dial Transplant 22, 2007, pp. 3034-3039. PMID 17517794
  31. ↑ PI Terasaki et al .: High survival rates of kidney transplants from spousal and living unrelated donors. In: NEJM 333, 1995, pp. 333-336. PMID 7609748
  32. ↑ P. Nickerson et al .: Identification of clinical and histopathologic risk factors for diminished renal function 2 years posttransplant. In: J Am Soc Nephrol 9, 1998, pp. 482-487. PMID 9513912
  33. ↑ Kidney Advisor: Chronic Transplant Nephropathy . ( Memento of the original from April 21, 2012 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. Retrieved January 9, 2010 @1@ 2Template: Webachiv / IABot / www.nierenratgeber.de
  34. ↑ AM Jevnikar and RB Mannon: Late kidney allograft loss: what we know about it, and what we can do about it. In: Clin J Am Soc Nephrol 3, 2008, pp. 56-67. PMID 18309004 (Review)

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