Biomedical subjects

Connie L Davis

Publications and source records attributed to Connie L Davis.

23 records · Page 2Linked to original sources

PubMed2003

Association between ABCB1 (multidrug resistance transporter) genotype and post-liver transplantation renal dysfunction in patients receiving calcineurin inhibitors.

OBJECTIVE: Renal dysfunction is a common and costly adverse outcome of long-term treatment with calcineurin inhibitors (CNIs). We conducted a retrospective, case-control study to test whether the risk of renal dysfunction in liver transplantation patients receiving CNIs is associated with the 2677G>T transversion in exon-21 of the gene (ABCB1) encoding P-glycoprotein. A total of 120 non-Hispanic white patients were evaluated. RESULTS: The overall incidence of renal dysfunction by year 3 post-transplantation was 40%. The frequency of renal dysfunction was reduced among patients with an ABCB1 2677TT genotype, as compared to those with a 2677GG genotype. Subjects with a heterozygote genotype behaved phenotypically like the 2677GG group. Comparing those subjects with a 2677TT genotype to the combined group of subjects with a 2677GG, TG, AT, or AG genotype resulted in an odds ratio of 0.26 (0.09-0.77). When subjects were stratified by gender, the frequency of renal dysfunction was reduced among men with an ABCB1 2677TT genotype, relative to men with different genotypes. A similar odds ratio was obtained for women, but it did not achieve significance. When 18 subjects with an elevated SCr concentration just prior to surgery were excluded from the year 3 analysis, the association between the 2677TT genotype and chronic renal dysfunction in the remaining cohort was strengthened comparing genotype groups. CONCLUSIONS: Based on these results, we conclude that homozygosity for the ABCB1 2677T (S893) allele is associated with reduced risk of chronic renal dysfunction among liver transplantation patients receiving an immunosuppressive regimen containing CNIs.

Calcineurin Inhibitors↗

PubMed2003

Delayed graft function and cast nephropathy associated with tacrolimus plus rapamycin use.

Delayed graft function (DGF) occurs in 15 to 25% (range, 10 to 62%) of cadaveric kidney transplant recipients and up to 9% of living donor recipients. In addition to donor, recipient, and procedural factors, the choice of immunosuppression may influence the development of DGF. The impact of immunosuppression on DGF was studied. The frequency of DGF was evaluated in first cadaveric or living donor kidney allograft recipients (n = 144) transplanted at the University of Washington from November 1999 through September 1, 2001. Donor, recipient, and procedural factors, as well as biopsy results, were compared between patients who developed DGF and those who did not. DGF was more common in patients treated with rapamycin than without (25% versus 8.9%, P = 0.02) and positively correlated with rapamycin dose (P = 0.008). In those developing DGF, the duration of posttransplant dialysis increased with donor age (P = 0.003) but decreased with mycophenolate mofetil use (P = 0.01). All biopsies during episodes of DGF demonstrated changes of acute tubular injury. Of the patients with tubular injury, 12 treated with rapamycin and tacrolimus developed intratubular cast formation indistinguishable from myeloma cast nephropathy. Histologic, immunohistochemical, and ultrastructural studies indicated that these casts were composed at least in part of degenerating renal tubular epithelial cells. These findings suggest that rapamycin therapy exerts increased toxicity on tubular epithelial cells and/or retards healing, leading to an increased incidence of DGF. Additionally, rapamycin treatment combined with a calcineurin inhibitor may lead to extensive tubular cell injury and death and a unique form of cast nephropathy.

Adult↗

PubMed2002

Pathophysiology of renal disease associated with liver disorders: implications for liver transplantation. Part I.

Renal and hepatic function are often intertwined through both the existence of associated primary organ diseases and hemodynamic interrelationships. This connection occasionally results in the chronic failure of both organs, necessitating combined liver-kidney transplantation (LKT). Since 1988, more than 850 patients in the United States have received such transplants, with patient survival somewhat less than that for patients receiving either organ alone. Patients with renal failure caused by acute injury or hepatorenal syndrome have classically not been included as candidates for combined transplantation because of the reversibility of renal dysfunction after liver transplantation. However, the rate and duration of renal failure before liver transplantation is increasing in association with prolonged waiting list times. Thus, the issue of acquired permanent renal damage in the setting of hepatic failure continues to confront the transplant community. The following article and its sequel (Part II, to be published in vol 8, no 3 of this journal) attempt to review the problem of primary and secondary renal disease in patients with end-stage liver disease, elements involved in renal disease progression and recovery, the impact of renal disease on liver transplant outcome, and results of combined LKT; outline the steps in the pretransplantation renal evaluation; and provide the beginnings of an algorithm for making the decision for combined LKT.

Humans↗

PubMed2002

Identification of patients best suited for combined liver-kidney transplantation: part II.

Liver-kidney transplantation (LKT) should be reserved for those recipients with primary disease affecting both organs. However, increasing transplant list waiting times have increased the development and duration of acute renal failure before liver transplantation. Furthermore, the need for posttransplant calcineurin inhibitors can render healing from acute renal failure difficult. Because of the increasing requests for and controversy over the topic of a kidney with a liver transplant (OLT) when complete failure of the kidney is not known, the following article will review the impact of renal failure on liver transplant outcome, treatment of peri-OLT renal failure, rejection rates after LKT, survival after LKT, and information on renal histology and progression of disease into the beginnings of an algorithm for making a decision about combined LKT.

Acute Kidney Injury↗

PubMedDate not supplied

Managing the failing allograft.

Managing the failing allograft juxtaposes immunosuppressive management and routine chronic kidney disease care. The complications of immunosuppression can be more pronounced in those with renal failure (infection, anemia, bone disease). The withdrawal of immunosuppression may be associated with acute allograft rejection, arthralgias, and the development of antidonor antibodies. Likewise depression is prevalent. Improving well-being and overall survival necessitates proper titration of immunosuppressive medications and control of blood pressure, anemia, lipids, and glucose along with attention to treatment of depression.

Graft Rejection↗