Persistent Infectious Diarrhea as a Risk Factor for Deterioration of Renal Function in Kidney Transplant Recipients
Main Article Content
Abstract
Background: Gastrointestinal complications are common in kidney transplant recipients. Severe diarrhea might result in graft dysfunction or rejection if being ignored. The study aim was to describe the relationship between kidney allograft function and diarrhea, and to determine how diarrhea is influenced by various immunosuppressive regimens at a single center in Taiwan.
Methods: This was a retrospective and comparative study. We included kidney transplant recipients who suffered from persistent diarrhea between January 2009 and August 2015. Survival and regression analyses and sub-analyses of creatinine levels over different diarrhea periods were performed.
Results: We eventually collected 62 patients for analyses, including 16 with infectious diarrhea and 46 with non-infectious diarrhea. At 3rd year post transplantation, patients with infectious diarrhea demonstrated a significantly lower cumulative renal function rate (56.3% vs. 84.7%, p<0.05). No significant differences were found between recipients receiving different immunosuppressive regimens in terms of renal function. However, recipients receiving mammalian target of rapamycin (mTOR) inhibitor and mycophenolate mofetil (MMF) tended to show a slower rate for deterioration of renal function.
Conclusion: In this study, infectious diarrhea, especially when persisting for more than 10.5 days, does significant damages to renal function and predicts for deterioration of renal function. Besides, regimen of mTOR inhibitor and MMF showed a trend toward reducing incidence of deterioration of renal function. Better understanding of the diarrhea etiologies to provide timely treatment for this illness and appropriate choice of immunosuppressive regimen might help maintain renal function for kidney transplant recipients.Article Details
How to Cite
WANG, Hue Yu et al.
Persistent Infectious Diarrhea as a Risk Factor for Deterioration of Renal Function in Kidney Transplant Recipients.
Medical Research Archives, [S.l.], v. 4, n. 6, oct. 2016.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/757>. Date accessed: 18 apr. 2024.
Keywords
Diarrhea, kidney transplantation, immunosuppressive, infection, mycophenolate
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
[1] F. Gonzalez, Valjalo R., Combining cytochrome P-450 3A4 modulators and cyclosporine or everolimus in transplantation is successful., World J Transplant. 5 (2015) 338-347. doi:10.5500/wjt.v5.i4.338.
[2] L. Fu, Huang Z., Song T., He S., Zeng D., Rao Z., et al., Short-term therapeutic drug monitoring of mycophenolic acid reduces infection: a prospective, single-center cohort study in Chinese living-related kidney transplantation., Transpl Infect Dis. 16 (2014) 760-766. doi:10.1111/tid.12275.
[3] M. J. Felix, Felipe C. R., Tedesco-Silva H., Osmar Medina-Pestana J., Time-Dependent and Immunosuppressive Drug-Associated Adverse Event Profiles in De Novo Kidney Transplant Recipients Converted from Tacrolimus to Sirolimus Regimens., Pharmacotherapy. 36 (2016) 152-165. doi:10.1002/phar.1692.
[4] Y. J. Zhao, Wen J. Q., Cheng K., Ming Y. Z., She X. G., Liu H., et al., Late, severe, noninfectious diarrhea after renal transplantation: high-risk factors, therapy, and prognosis., Transplant Proc. 45 (2013) 2226-2232. doi:10.1016/j.transproceed.2013.02.131.
[5] E. Savvidaki, Papachristou E., Kazakopoulos P., Papasotiriou M., Vardoulaki M., Goumenos D. S., Gastrointestinal disorders after renal transplantation., Transplant Proc. 46 (2014) 3183-3186. doi:10.1016/j.transproceed.2014.09.155.
[6] B. Maes, Hadaya K., de Moor B., Cambier P., Peeters P., de Meester J., et al., Severe diarrhea in renal transplant patients: results of the DIDACT study., Am J Transplant. 6 (2006) 1466-1472. doi:10.1111/j.1600-6143.2006.01320.x.
[7] S. Brakemeier, Taxeidi S. I., Durr M., Hofmann J., Schmidt D., Bachmann F., et al., Clinical outcome of norovirus infection in renal transplant patients., Clin Transplant. (2016) doi:10.1111/ctr.12820.
[8] K. Raja, Abbas Z., Hassan S. M., Luck N. H., Aziz T., Mubarak M., Prevalence of cryptosporidiosis in renal transplant recipients presenting with acute diarrhea at a single center in Pakistan., J Nephropathol. 3 (2014) 127-131. doi:10.12860/jnp.2014.25.
[9] T. S. Altıparmak MR, Pamuk O¨ N, Apaydın S, Sarıyar M, O¨ ztu¨ rk R,, Ataman R S. t. K., Erek E, Diarrhoea following renal transplantation., Clin Transplant. 16 (2002) 212-216.
[10] H. Y. Wang, Yeh M. K., Tian Y. F., Huang Y. B., Effect of Prolonged Diarrhea in Renal Transplant Recipients at a Single Center in Taiwan., Transplant Proc. 48 (2016) 870-873. doi:10.1016/j.transproceed.2015.12.075 S0041-1345(16)00173-1 [pii].
[11] G. Guerra, Ciancio G., Gaynor J. J., Zarak A., Brown R., Hanson L., et al., Randomized trial of immunosuppressive regimens in renal transplantation., J Am Soc Nephrol. 22 (2011) 1758-1768. doi:10.1681/ASN.2011010006 ASN.2011010006 [pii].
[12] M. Angarone, Ison M. G., Diarrhea in solid organ transplant recipients. Curr Opin Infect Dis. 28 (2015) 308-316. 10.1097/QCO.0000000000000172.
[13] H. Arslan, Inci E. K., Azap O. K., Karakayali H., Torgay A., Haberal M., Etiologic agents of diarrhea in solid organ recipients., Transpl Infect Dis. 9 (2007) 270-275. doi:10.1111/j.1399-3062.2007.00237.x.
[14] G. Bamias, Boletis J., Argyropoulos T., Skalioti C., Siakavellas S. I., Delladetsima I., et al., Early ileocolonoscopy with biopsy for the evaluation of persistent post-transplantation diarrhea., World J Gastroenterol. 16 (2010) 3834-3840. http://www.ncbi.nlm.nih.gov/pubmed/20698047.
[15] H. Ekberg, Kyllonen L., Madsen S., Grave G., Solbu D., Holdaas H., Increased prevalence of gastrointestinal symptoms associated with impaired quality of life in renal transplant recipients., Transplantation. 83 (2007) 282-289. doi:10.1097/01.tp.0000251923.14697.f5 00007890-200702150-00010 [pii].
[16] S. Bunnapradist, Neri L., Wong W., Lentine K. L., Burroughs T. E., Pinsky B. W., et al., Incidence and risk factors for diarrhea following kidney transplantation and association with graft loss and mortality., Am J Kidney Dis. 51 (2008) 478-486. doi:10.1053/j.ajkd.2007.11.013 S0272-6386(07)01587-9 [pii].
[17] R. S. Gaston, Kaplan B., Shah T., Cibrik D., Shaw L. M., Angelis M., et al., Fixed- or controlled-dose mycophenolate mofetil with standard- or reduced-dose calcineurin inhibitors: the Opticept trial., Am J Transplant. 9 (2009) 1607-1619.
doi:10.1111/j.1600-6143.2009.02668.x AJT2668 [pii].
[18] S. Gil-Vernet, Amado A., Ortega F., Alarcon A., Bernal G., Capdevila L., et al., Gastrointestinal complications in renal transplant recipients: MITOS study., Transplant Proc. 39 (2007) 2190-2193.
doi:S0041-1345(07)00804-4 [pii] 10.1016/j.transproceed.2007.07.015.
[19] K. Boudjema, Camus C., Saliba F., Calmus Y., Salame E., Pageaux G., et al., Reduced-dose tacrolimus with mycophenolate mofetil vs. standard-dose tacrolimus in liver transplantation: a randomized study., Am J Transplant. 11 (2011) 965-976. doi:10.1111/j.1600-6143.2011.03486.x.
[20] C. Pant, Deshpande A., Larson A., O'Connor J., Rolston D. D., Sferra T. J., Diarrhea in solid-organ transplant recipients: a review of the evidence., Curr Med Res Opin. 29 (2013) 1315-1328. doi:10.1185/03007995.2013.816278.
[21] N. M. Davies, Grinyo J., Heading R., Maes B., Meier-Kriesche H. U., Oellerich M., Gastrointestinal side effects of mycophenolic acid in renal transplant patients: a reappraisal., Nephrol Dial Transplant. 22 (2007) 2440-2448. doi:10.1093/ndt/gfm308.
[22] M. Behrend, Adverse gastrointestinal effects of mycophenolate mofetil: aetiology, incidence and management., Drug Saf. 24 (2001) 645-663.
[23] A. Aiyangar, Rajput P., Shah B. V., Mycophenolate induced diarrhoea., J Assoc Physicians India. 58 (2010) 192-194.
[24] A. Husing, Schmidt M., Beckebaum S., Cicinnati V. R., Koch R., Tholking G., et al., Long-Term Renal Function in Liver Transplant Recipients After Conversion From Calcineurin Inhibitors to mTOR Inhibitors., Ann Transplant. 20 (2015) 707-713. doi:895320 [pii].
[2] L. Fu, Huang Z., Song T., He S., Zeng D., Rao Z., et al., Short-term therapeutic drug monitoring of mycophenolic acid reduces infection: a prospective, single-center cohort study in Chinese living-related kidney transplantation., Transpl Infect Dis. 16 (2014) 760-766. doi:10.1111/tid.12275.
[3] M. J. Felix, Felipe C. R., Tedesco-Silva H., Osmar Medina-Pestana J., Time-Dependent and Immunosuppressive Drug-Associated Adverse Event Profiles in De Novo Kidney Transplant Recipients Converted from Tacrolimus to Sirolimus Regimens., Pharmacotherapy. 36 (2016) 152-165. doi:10.1002/phar.1692.
[4] Y. J. Zhao, Wen J. Q., Cheng K., Ming Y. Z., She X. G., Liu H., et al., Late, severe, noninfectious diarrhea after renal transplantation: high-risk factors, therapy, and prognosis., Transplant Proc. 45 (2013) 2226-2232. doi:10.1016/j.transproceed.2013.02.131.
[5] E. Savvidaki, Papachristou E., Kazakopoulos P., Papasotiriou M., Vardoulaki M., Goumenos D. S., Gastrointestinal disorders after renal transplantation., Transplant Proc. 46 (2014) 3183-3186. doi:10.1016/j.transproceed.2014.09.155.
[6] B. Maes, Hadaya K., de Moor B., Cambier P., Peeters P., de Meester J., et al., Severe diarrhea in renal transplant patients: results of the DIDACT study., Am J Transplant. 6 (2006) 1466-1472. doi:10.1111/j.1600-6143.2006.01320.x.
[7] S. Brakemeier, Taxeidi S. I., Durr M., Hofmann J., Schmidt D., Bachmann F., et al., Clinical outcome of norovirus infection in renal transplant patients., Clin Transplant. (2016) doi:10.1111/ctr.12820.
[8] K. Raja, Abbas Z., Hassan S. M., Luck N. H., Aziz T., Mubarak M., Prevalence of cryptosporidiosis in renal transplant recipients presenting with acute diarrhea at a single center in Pakistan., J Nephropathol. 3 (2014) 127-131. doi:10.12860/jnp.2014.25.
[9] T. S. Altıparmak MR, Pamuk O¨ N, Apaydın S, Sarıyar M, O¨ ztu¨ rk R,, Ataman R S. t. K., Erek E, Diarrhoea following renal transplantation., Clin Transplant. 16 (2002) 212-216.
[10] H. Y. Wang, Yeh M. K., Tian Y. F., Huang Y. B., Effect of Prolonged Diarrhea in Renal Transplant Recipients at a Single Center in Taiwan., Transplant Proc. 48 (2016) 870-873. doi:10.1016/j.transproceed.2015.12.075 S0041-1345(16)00173-1 [pii].
[11] G. Guerra, Ciancio G., Gaynor J. J., Zarak A., Brown R., Hanson L., et al., Randomized trial of immunosuppressive regimens in renal transplantation., J Am Soc Nephrol. 22 (2011) 1758-1768. doi:10.1681/ASN.2011010006 ASN.2011010006 [pii].
[12] M. Angarone, Ison M. G., Diarrhea in solid organ transplant recipients. Curr Opin Infect Dis. 28 (2015) 308-316. 10.1097/QCO.0000000000000172.
[13] H. Arslan, Inci E. K., Azap O. K., Karakayali H., Torgay A., Haberal M., Etiologic agents of diarrhea in solid organ recipients., Transpl Infect Dis. 9 (2007) 270-275. doi:10.1111/j.1399-3062.2007.00237.x.
[14] G. Bamias, Boletis J., Argyropoulos T., Skalioti C., Siakavellas S. I., Delladetsima I., et al., Early ileocolonoscopy with biopsy for the evaluation of persistent post-transplantation diarrhea., World J Gastroenterol. 16 (2010) 3834-3840. http://www.ncbi.nlm.nih.gov/pubmed/20698047.
[15] H. Ekberg, Kyllonen L., Madsen S., Grave G., Solbu D., Holdaas H., Increased prevalence of gastrointestinal symptoms associated with impaired quality of life in renal transplant recipients., Transplantation. 83 (2007) 282-289. doi:10.1097/01.tp.0000251923.14697.f5 00007890-200702150-00010 [pii].
[16] S. Bunnapradist, Neri L., Wong W., Lentine K. L., Burroughs T. E., Pinsky B. W., et al., Incidence and risk factors for diarrhea following kidney transplantation and association with graft loss and mortality., Am J Kidney Dis. 51 (2008) 478-486. doi:10.1053/j.ajkd.2007.11.013 S0272-6386(07)01587-9 [pii].
[17] R. S. Gaston, Kaplan B., Shah T., Cibrik D., Shaw L. M., Angelis M., et al., Fixed- or controlled-dose mycophenolate mofetil with standard- or reduced-dose calcineurin inhibitors: the Opticept trial., Am J Transplant. 9 (2009) 1607-1619.
doi:10.1111/j.1600-6143.2009.02668.x AJT2668 [pii].
[18] S. Gil-Vernet, Amado A., Ortega F., Alarcon A., Bernal G., Capdevila L., et al., Gastrointestinal complications in renal transplant recipients: MITOS study., Transplant Proc. 39 (2007) 2190-2193.
doi:S0041-1345(07)00804-4 [pii] 10.1016/j.transproceed.2007.07.015.
[19] K. Boudjema, Camus C., Saliba F., Calmus Y., Salame E., Pageaux G., et al., Reduced-dose tacrolimus with mycophenolate mofetil vs. standard-dose tacrolimus in liver transplantation: a randomized study., Am J Transplant. 11 (2011) 965-976. doi:10.1111/j.1600-6143.2011.03486.x.
[20] C. Pant, Deshpande A., Larson A., O'Connor J., Rolston D. D., Sferra T. J., Diarrhea in solid-organ transplant recipients: a review of the evidence., Curr Med Res Opin. 29 (2013) 1315-1328. doi:10.1185/03007995.2013.816278.
[21] N. M. Davies, Grinyo J., Heading R., Maes B., Meier-Kriesche H. U., Oellerich M., Gastrointestinal side effects of mycophenolic acid in renal transplant patients: a reappraisal., Nephrol Dial Transplant. 22 (2007) 2440-2448. doi:10.1093/ndt/gfm308.
[22] M. Behrend, Adverse gastrointestinal effects of mycophenolate mofetil: aetiology, incidence and management., Drug Saf. 24 (2001) 645-663.
[23] A. Aiyangar, Rajput P., Shah B. V., Mycophenolate induced diarrhoea., J Assoc Physicians India. 58 (2010) 192-194.
[24] A. Husing, Schmidt M., Beckebaum S., Cicinnati V. R., Koch R., Tholking G., et al., Long-Term Renal Function in Liver Transplant Recipients After Conversion From Calcineurin Inhibitors to mTOR Inhibitors., Ann Transplant. 20 (2015) 707-713. doi:895320 [pii].