Response to Heyman et al. and Bredewold et al.
Authors: Charles M. van Slambrouck, Anthony Chang
Journal: Kidney International (2014)

We thank Dr Heyman et al.1.Heyman S. Darmon D. Ackerman Z. et al.Bile cast nephropathy.Kidney Int. 2014; 85: 479Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar for their interest in our study on bile cast nephropathy. Without further details, we cannot directly respond to their unpublished observations in a rat model of bile duct ligation. However, we would note that chronic liver disease in humans often spans months to years, which is difficult to replicate in animal models. The clinical studies that have observed beneficial effects of serum bilirubin were based on values between 0.5 and 1.4mg/dl and specifically excluded patients with chronic liver disease.2.Fukui M. Tanaka M. Shiraishi E. et al.Relationship between serum bilirubin and albuminuria in patients with type 2 diabetes.Kidney Int. 2008; 74: 1197-1201Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar, 3.Huang S.S. Huang P.H. Wu T.C. et al.Association of serum bilirubin with contrast-induced nephropathy and future cardiovascular events in patients undergoing coronary intervention.PLoS One. 2012; 7: e42594Crossref PubMed Scopus (26) Google Scholar, 4.Shin H.S. Jung Y.S. Rim H. Relationship of serum bilirubin concentration to kidney function and 24-hour urine protein in korean adults.BMC Nephrol. 2011; 12: 29Crossref PubMed Scopus (30) Google Scholar, 5.Deetman P.E. Zelle D.M. Homan van der Heide J.J. et al.Plasma bilirubin and late graft failure in renal transplant recipients.Transpl Int. 2012; 25: 876-881Crossref PubMed Scopus (17) Google Scholar In contrast, serum bilirubin levels in our patients with bile casts typically exceeded 20mg/dl with substantially greater concentrations likely present in the distal nephron segments, where most bile casts were located. Furthermore, both bilirubin and bile acids have the potential to disrupt cellular and mitochondrial integrity,6.Bomzon A. Holt S. Moore K. Bile acids, oxidative stress, and renal function in biliary obstruction.Semin Nephrol. 1997; 17: 549-562PubMed Google Scholar and these harmful effects would easily negate any minor beneficial effects from modest elevations of serum bilirubin on endothelial cells. In addition, the prolonged presence of these tubular casts over months to years is detrimental to kidneys. Fong et al.7.Fong T.L. Khemichian S. Shah T. et al.Combined liver-kidney transplantation is preferable to liver transplant alone for cirrhotic patients with renal failure.Transplantation. 2012; 94: 411-416Crossref PubMed Scopus (83) Google Scholar recently analyzed the outcomes of patients undergoing combined liver–kidney (CLK) transplantation versus liver transplant alone (LTA) using the United Network for Organ Sharing database containing over 4000 patients. Post-transplantation renal failure rates were higher for the LTA group at both 6 months and 3 years post-transplant (P<0.001). Given that there was previously no awareness of bile cast nephropathy, the specific parameter of bile casts was not studied. However, we postulate that bile casts may have contributed to the irreversible kidney injury in these liver transplant patients. Therefore, we appreciate the interest of Dr Bredewold et al.8.Bredewold O.W. de Fijter J. Rabelink T. Response to: Bile cast nephropathy is a common pathologic finding for kidney injury associated with severe liver dysfunction.Kidney Int. 2013Google Scholar in our study and concur with their supposition that the identification of bile casts in pre-transplant kidney biopsy might be useful for stratifying transplant patients to either CLK or LTA. However, we also acknowledge that more studies are needed before clinical decision making can be based on the presence or absence of bile cast nephropathy.