Advertisement

Journal of Nephrology

, Volume 32, Issue 1, pp 129–137 | Cite as

Key role of renal biopsy in management of progressive chronic kidney disease in liver graft recipients

  • Martin-Walter WelkerEmail author
  • Nina Weiler
  • Wolf Otto Bechstein
  • Eva Herrmann
  • Christoph Betz
  • Mark Schöffauer
  • Stefan Zeuzem
  • Christoph Sarrazin
  • Kerstin Amann
  • Oliver Jung
Original Article

Abstract

Aims

Chronic kidney disease (CKD) is a common complication after liver transplantation (LT). The etiology of CKD is broad and may only be assessed accurately by renal histology. The current study aimed to analyze the safety of renal biopsy in daily clinical practice as well as its usefulness regarding management of CKD after LT.

Methods

We performed a retrospective analysis of clinical data and renal biopsies obtained from patients with severe renal impairment (overt proteinuria, progressive deterioration of renal function) after LT with respect to safety, etiology of renal disease, and therapeutic consequences.

Results

Renal biopsies were obtained from 14 patients at median (minimum–maximum) 3 (0.2–12) years after LT. No major complications associated with renal biopsy were observed. Histomorphological alterations were varied (nephrosclerosis, n = 5; IgA-glomerulonephritis, n = 4; tenofovir-associated nephropathy, membranoproliferative glomerulonephritis type 1, membranous glomerulonephritis, amyloid A amyloidosis, and calcineurin inhibitor nephropathy, n = 1, respectively). The diagnosis of specific renal diseases other than calcineurin-inhibitor nephrotoxicity facilitated specific treaments and avoided unnecessary modification of immunosuppression in the majority of patients.

Conclusions

Renal biopsy in patients with CKD after LT seems safe and may offer specific therapeutic options. Furthermore, unnecessary changes of immunosuppression can be avoided in a considerable number of patients.

Keywords

Chronic kidney disease Liver transplantation Biopsy Etiology 

Abbreviations

ALT

Alanine transaminase

AST

Aspartate transaminase

CKD-EPI

Chronic Kidney Disease Epidemiology Collaboration

CKD

Chronic kidney disease

CMV

Cytomegalovirus

CNI

Calcineurin inhibitor(s)

CsA

Cyclosporine A

DN

Diabetic nephropathy

eGFR

Estimated glomerular filtration rate

HBV

Hepatitis B virus

HCC

Hepatocellular carcinoma

HCV

Hepatitis C virus

Maximum

Max.

MELD

Model of end stage liver disease

Minimum

Min.

MMF

Mycophenolate mofetil

mTOR

Mechanistic target of rapamycine

LT

Liver transplantation

SIR

Sirolimus

SD

Standard deviation

sec

Seconds

TAC

Tacrolimus

ULN

Upper limit of normal

Notes

Compliance with ethical standards

Conflict of interest

Martin-Walter Welker, Consultancies/speaker’s fees: AbbVie, Amgen, Bayer, BMS, Gilead, Novartis, Roche, Sequana Medical. Travel Support: AbbVie, Astellas, Bayer, BMS, Novartis, Janssen, Roche. Nina Weiler, Consultancies/speaker´s bureau for Astellas, Novartis. Wolf Otto Bechstein, Consultancies/speaker’s fees: Astellas, Celgene, Gilead, Integra, Medupdate, MerckSerono, Novartis, Teva. Eva Herrmann, nothing to report. Christoph Betz, noting to report. Mark Schöffauer, nothing to report. Stefan Zeuzem, Consultancies/speaker’s bureau for Abbvie, BMS, Gilead, Janssen, Merck. Christoph Sarrazin, Consultancies/Advisory boards: Abbott, BMS, Gilead, Janssen, Merck/MSD, Roche. Research support: Abbott, Gilead, Janssen, Siemens. Speaker: Abbott, BMS, Gilead, Janssen, Merck/MSD, Qiagen, Roche, Siemens. Kerstin Amann, Speaker/Advisory boards: Alexion, Böhringer Ingelheim. Oliver Jung, nothing to report. On behalf of the remaining authors, no financial, personal, or professional interests that could be construed to have influenced the paper have to be reported.

Ethical statement

Study approval was obtained by the local Ethics Committee for Medical Research in accordance with the 1975 Declaration of Helsinki.

Informed consent

For this type of study formal consent is not required.

References

  1. 1.
    Ojo AO, Held PJ, Port FK, Wolfe RA, Leichtman AB, Young EW et al (2003) Chronic renal failure after transplantation of a nonrenal organ. N Engl J Med 349(10):931–940CrossRefGoogle Scholar
  2. 2.
    Allen AM, Kim WR, Therneau TM, Larson JJ, Heimbach JK, Rule AD (2014) Chronic kidney disease and associated mortality after liver transplantation—a time-dependent analysis using measured glomerular filtration rate. J Hepatol 61(2):286–292CrossRefGoogle Scholar
  3. 3.
    Moreno JM, Cuervas-Mons V, Rubio E, Pons F, Herreros de TA, Turrión VS et al (2003) Chronic renal dysfunction after liver transplantation in adult patients: prevalence, risk factors, and impact on mortality. Transpl Proc 35(5):1907–1908CrossRefGoogle Scholar
  4. 4.
    Ziolkowski J, Paczek L, Senatorski G, Niewczas M, Oldakowska-Jedynak U, Wyzgal J et al (2003) Renal function after liver transplantation: calcineurin inhibitor nephrotoxicity. Transpl Proc 35(6):2307–2309CrossRefGoogle Scholar
  5. 5.
    Kim J-Y, Akalin E, Dikman S, Gagliardi R, Schiano T, Bromberg J et al (2010) The variable pathology of kidney disease after liver transplantation. Transplantation 89(2):215–221CrossRefGoogle Scholar
  6. 6.
    Giusto M, Berenguer M, Merkel C, Aguilera V, Rubin A, Ginanni Corradini S et al (2013) Chronic kidney disease after liver transplantation: pretransplantation risk factors and predictors during follow-up. Transplantation 95(9):1148–1153CrossRefGoogle Scholar
  7. 7.
    Boudjema K, Camus C, Saliba F, Calmus Y, Salamé E, Pageaux G et al (2011) Reduced-dose tacrolimus with mycophenolate mofetil vs. standard-dose tacrolimus in liver transplantation: a randomized study. Am J Transpl 11(5):965–976CrossRefGoogle Scholar
  8. 8.
    Neuberger JM, Mamelok RD, Neuhaus P, Pirenne J, Samuel D, Isoniemi H et al (2009) Delayed introduction of reduced-dose tacrolimus, and renal function in liver transplantation: the “ReSpECT” study. Am J Transpl 9(2):327–336CrossRefGoogle Scholar
  9. 9.
    TruneČka P, Klempnauer J, Bechstein WO, Pirenne J, Friman S, Zhao A et al (2015) Renal Function in de novo liver transplant recipients receiving different prolonged-release tacrolimus regimens—the DIAMOND study. Am J Transpl 15(7):1843–1845CrossRefGoogle Scholar
  10. 10.
    De Simone P, Nevens F, De Carlis L, Metselaar HJ, Beckebaum S, Saliba F et al (2012) Everolimus with reduced tacrolimus improves renal function in de novo liver transplant recipients: a randomized controlled trial. Am J Transpl 12(11):3008–3020CrossRefGoogle Scholar
  11. 11.
    Sterneck M, Kaiser GM, Heyne N, Richter N, Rauchfuss F, Pascher A et al (2014) Everolimus and early calcineurin inhibitor withdrawal: 3-year results from a randomized trial in liver transplantation. Am J Transpl 14(3):701–710CrossRefGoogle Scholar
  12. 12.
    Masetti M, Montalti R, Rompianesi G, Codeluppi M, Gerring R, Romano A et al (2010) Early withdrawal of calcineurin inhibitors and everolimus monotherapy in de novo liver transplant recipients preserves renal function. Am J Transpl 10(10):2252–2262CrossRefGoogle Scholar
  13. 13.
    Kornberg A, Küpper B, Thrum K, Krause B, Büchler P, Kornberg J et al (2011) Sustained renal response to mycophenolate mofetil and CNI taper promotes survival in liver transplant patients with CNI-related renal dysfunction. Dig Dis Sci 56(1):244–251CrossRefGoogle Scholar
  14. 14.
    Teperman L, Moonka D, Sebastian A, Sher L, Marotta P, Marsh C et al (2013) Calcineurin inhibitor-free mycophenolate mofetil/sirolimus maintenance in liver transplantation: the randomized spare-the-nephron trial. Liver Transpl 19(7):675–689CrossRefGoogle Scholar
  15. 15.
    Cicinnati VR, Yu Z, Klein CG, Sotiropoulos GC, Saner F, Malagó M et al (2007) Clinical trial: switch to combined mycophenolate mofetil and minimal dose calcineurin inhibitor in stable liver transplant patients—assessment of renal and allograft function, cardiovascular risk factors and immune monitoring. Aliment Pharmacol Ther 26(9):1195–1208CrossRefGoogle Scholar
  16. 16.
    Créput C, Blandin F, Deroure B, Roche B, Saliba F, Charpentier B et al (2007) Long-term effects of calcineurin inhibitor conversion to mycophenolate mofetil on renal function after liver transplantation. Liver Tanspl 13(7):1004–1010CrossRefGoogle Scholar
  17. 17.
    Ponton C, Vizcaíno L, Tomé S, Otero E, Molina E, Castroagudín JF et al (2010) Improvement of renal function after conversion to mycophenolate mofetil combined with low-level calcineurin inhibitor in liver transplant recipients with chronic renal dysfunction. Transpl Proc 42(2):656–659CrossRefGoogle Scholar
  18. 18.
    Kong Y, Wang D, Shang Y, Liang W, Ling X, Guo Z et al (2011) Calcineurin-inhibitor minimization in liver transplant patients with calcineurin-inhibitor-related renal dysfunction: a meta-analysis. PLoS One 6(9):e24387CrossRefGoogle Scholar
  19. 19.
    Reich DJ, Clavien PA, Hodge EE (2005) Mycophenolate mofetil for renal dysfunction in liver transplant recipients on cyclosporine or tacrolimus: randomized, prospective, multicenter pilot study results. Transplantation 80(1):18–25CrossRefGoogle Scholar
  20. 20.
    Pageaux G-P, Rostaing L, Calmus Y, Duvoux C, Vanlemmens C, Hardgwissen J et al (2006) Mycophenolate mofetil in combination with reduction of calcineurin inhibitors for chronic renal dysfunction after liver transplantation. Liver Tanspl 12(12):1755–1760CrossRefGoogle Scholar
  21. 21.
    Watson CJE, Gimson AES, Alexander GJ, Allison MED, Gibbs P, Smith JC et al (2007) A randomized controlled trial of late conversion from calcineurin inhibitor (CNI)-based to sirolimus-based immunosuppression in liver transplant recipients with impaired renal function. Liver Tanspl 13(12):1694–1702CrossRefGoogle Scholar
  22. 22.
    De Simone P, Carrai P, Precisi A, Petruccelli S, Baldoni L, Balzano E et al (2009) Conversion to everolimus monotherapy in maintenance liver transplantation: feasibility, safety, and impact on renal function. Transpl Int 22(3):279–286CrossRefGoogle Scholar
  23. 23.
    Gerhardt T, Terjung B, Knipper P, Palmedo H, Woitas RP, Kalff J et al (2009) Renal impairment after liver transplantation—a pilot trial of calcineurin inhibitor-free vs. calcineurin inhibitor sparing immunosuppression in patients with mildly impaired renal function after liver transplantation. Eur J Med Res 14(5):210–215CrossRefGoogle Scholar
  24. 24.
    Beckebaum S, Klein CG, Sotiropoulos GC, Saner FH, Gerken G, Paul A et al (2009) Combined mycophenolate mofetil and minimal dose calcineurin inhibitor therapy in liver transplant patients: clinical results of a prospective randomized study. Transpl Proc 41(6):2567–2569CrossRefGoogle Scholar
  25. 25.
    Herlenius G, Felldin M, Nordén G, Olausson M, Bäckman L, Gustafsson B et al (2010) Conversion from calcineurin inhibitor to either mycophenolate mofetil or sirolimus improves renal function in liver transplant recipients with chronic kidney disease: results of a prospective randomized trial. Transpl Proc 42(10):4441–4448CrossRefGoogle Scholar
  26. 26.
    Schnitzbauer AA, Sothmann J, Baier L, Bein T, Geissler EK, Scherer MN et al (2015) Calcineurin inhibitor free de novo immunosuppression in liver transplant recipients with pretransplant renal impairment: results of a pilot study (PATRON07). Transplantation 99(12):2565–2575CrossRefGoogle Scholar
  27. 27.
    Fujinaga K, Usui M, Yamamoto N, Ishikawa E, Nakatani A, Kishiwada M et al (2014) Hypertension and hepatitis C virus infection are strong risk factors for developing late renal dysfunction after living donor liver transplantation: significance of renal biopsy. Transpl Proc 46(3):804–810CrossRefGoogle Scholar
  28. 28.
    Lee JH, Cho YH, Ryu SJ, Kim SS, Lee YH, Jang I-A et al (2013) Clinical usefulness of kidney biopsy in liver transplant recipients with renal impairment. Kidney Res Clin Pr 32(4):153–157CrossRefGoogle Scholar
  29. 29.
    Pillebout E, Nochy D, Hill G, Conti F, Antoine C, Calmus Y et al (2005) Renal histopathological lesions after orthotopic liver transplantation (OLT). Am J Transpl 5(5):1120–1129CrossRefGoogle Scholar
  30. 30.
    Pichler RH, Huskey J, Kowalewska J, Moiz A, Perkins J, Davis CL et al (2016) Kidney biopsies may help predict renal function after liver transplantation. Transplantation 100(10):2122–2128CrossRefGoogle Scholar
  31. 31.
    Del Bello A, Congy-Jolivet N, Danjoux M, Muscari F, Lavayssière L, Esposito L et al (2015) De novo donor-specific anti-HLA antibodies mediated rejection in liver-transplant patients. Transpl Int 28(12):1371–1382CrossRefGoogle Scholar
  32. 32.
    Fuiano G, Mazza G, Comi N, Caglioti A, De Nicola L, Iodice C et al (2000) Current indications for renal biopsy: a questionnaire-based survey. Am J Kidney Dis 35(3):448–457CrossRefGoogle Scholar
  33. 33.
    Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, Feldman HI et al (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150(9):604–612CrossRefGoogle Scholar
  34. 34.
    Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group (2012) KDIGO clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Int S2(5):337–341Google Scholar
  35. 35.
    Kidney Disease: Improving Global Outcomes (KDIGO) Lipid Work Group (2013) KDIGO clinical practice guideline for lipid management in chronic kidney disease. Kidney Int S3(3):259–305Google Scholar
  36. 36.
    Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group (2013) KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int S3(1):1–150Google Scholar
  37. 37.
    Jung O, Haack HS, Buettner M, Betz C, Stephan C, Gruetzmacher P et al (2012) Renal AA-amyloidosis in intravenous drug users—a role for HIV-infection? BMC Nephrol 13:151CrossRefGoogle Scholar
  38. 38.
    Naesens M, Kuypers DRJ, Sarwal M (2009) Calcineurin inhibitor nephrotoxicity. Clin J Am Soc Nephrol 4(2):481–508Google Scholar
  39. 39.
    Esposito V, Mazzon G, Baiardi P, Torreggiani M, Semeraro L, Catucci D et al (2018) Safety and adequacy of percutaneous kidney biopsy performed by nephrology trainees. BMC Nephrol 19(1):14CrossRefGoogle Scholar
  40. 40.
    Collins BS, Davis CL, Marsh CL, McVicar JP, Perkins JD, Alpers CE (1992) Reversible cyclosporine arteriolopathy. Transplantation 54(4):732–734CrossRefGoogle Scholar
  41. 41.
    Morozumi K, Thiel G, Albert FW, Banfi G, Gudat F, Mihatsch MJ (1992) Studies on morphological outcome of cyclosporine-associated arteriolopathy after discontinuation of cyclosporine in renal allografts. Clin Nephrol 38(1):1–8Google Scholar

Copyright information

© Italian Society of Nephrology 2018

Authors and Affiliations

  • Martin-Walter Welker
    • 1
    Email author
  • Nina Weiler
    • 1
  • Wolf Otto Bechstein
    • 2
  • Eva Herrmann
    • 3
  • Christoph Betz
    • 4
  • Mark Schöffauer
    • 1
    • 4
  • Stefan Zeuzem
    • 1
  • Christoph Sarrazin
    • 1
    • 5
  • Kerstin Amann
    • 6
  • Oliver Jung
    • 4
    • 7
  1. 1.Medizinische Klinik IUniversitätsklinikum FrankfurtFrankfurt am MainGermany
  2. 2.Klinik für Allgemein- und ViszeralchirurgieUniversitätsklinikum FrankfurtFrankfurt am MainGermany
  3. 3.Institut für Biostatistik und mathematische ModellierungUniversitätsklinikum FrankfurtFrankfurt am MainGermany
  4. 4.Medizinische Klinik IIIUniversitätsklinikum FrankfurtFrankfurt am MainGermany
  5. 5.St. Josefs-HospitalWiesbadenGermany
  6. 6.Abteilung für NephropathologieUniversitätsklinikum ErlangenErlangenGermany
  7. 7.KfH Kuratorium für Dialyse und Nierentransplantation e.V., Standort Klinikum Frankfurt HöchstFrankfurt am MainGermany

Personalised recommendations