Sanjay Kulkarni

Yale-New Haven Hospital, New Haven, Connecticut, United States

Are you Sanjay Kulkarni?

Claim your profile

Publications (21)107.22 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: We examined the written informed consent forms for living liver donor evaluation to determine if they incorporated the elements required by the Centers for Medicare and Medicaid Services (CMS) and suggested by the Organ Procurement and Transplantation Network (OPTN). We contacted each of the 41 US centers that performed at least one living donor liver transplant in 2011. Twenty-six centers shared their consent form for living donor evaluation (response rate: 70%). Each document was double-coded for consent element content. We found that 57% of the centers included the 9 mandated CMS elements. Although the OPTN guidelines are non-binding, 78% of the centers utilized consent forms that addressed at least two-thirds of the elements recommended by OPTN. Only 17% of centers provided written offers of an alibi to donors who withdrew from evaluation. Based on our findings, we offer suggestions that may be relevant to ongoing revisions to OPTN living liver donor consent policy and may help centers improve the clarity of their written consent forms. Liver Transpl , 2014. © 2014 AASLD.
    Liver Transplantation 01/2014; · 3.94 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: IMPORTANCE The use of technically variant segmental grafts are key in offering transplantation to increase organ availability. OBJECTIVE To describe the use of segmental allograft in the current era of donor scarcity, minimizing vascular complications using innovative surgical techniques. DESIGN, SETTING, AND PARTICIPANTS Retrospective study from August 2007 to August 2012 at a university hospital. A total of 218 consecutive liver transplant patients were reviewed, and 69 patients (31.6%; 38 males and 31 females; mean age, 22.5 years) received segmental grafts from living donors or split/reduced-size grafts from deceased donors. MAIN OUTCOMES AND MEASURES Graft type, vascular and biliary complications, and patient and graft survival. RESULTS Of 69 segmental transplants, 47 were living donor liver transplants: 13 grafts (27.7%) were right lobes, 22 (46.8%) were left lobes, and 12 (25.5%) were left lateral segments. Twenty-two patients received deceased donor segmental grafts; of these, 11 (50.0%) were extended right lobes, 9 (40.9%) were left lateral segments, 1 (4.5%) was a right lobe, and 1 (4.5%) was a left lobe. Arterial anastomoses were done using 8-0 monofilament sutures in an interrupted fashion for living donor graft recipients and for pediatric patients. Most patients received a prophylactic dose of low-molecular-weight heparin for a week and aspirin indefinitely. There was no incidence of hepatic artery or portal vein thrombosis. Two patients developed hepatic artery stenosis and were treated with balloon angioplasty by radiology. Graft and patient survivals were 96% and 98%, respectively. CONCLUSIONS AND RELEVANCE Use of segmental allografts is essential to offer timely transplantation and decrease waiting list mortality. Living donor liver transplants and segmental grafts from deceased donors are complementary. It is possible to have excellent outcomes combining a multidisciplinary team approach, technical expertise, routine use of anticoagulation, and strict patient and donor selection.
    JAMA surgery. 11/2013;
  • [show abstract] [hide abstract]
    ABSTRACT: Cardiac allograft vasculopathy (CAV) is the major cause of late allograft loss following heart transplantation. CAV lesions contain alloreactive T cells that secrete IFN-γ, a vasculopathic cytokine, and occur more frequently in patients with donor specific antibody (DSA). Pathologic interactions between these immune effectors, representing cellular and humoral immunity, respectively, remain largely unexplored. We used human panel reactive antibody (PRA) to form membrane attack complexes (MAC) on allogeneic endothelial cells in vitro and in vivo. Rather than inducing cytolysis, MAC upregulated inflammatory genes, enhancing the capacity of EC to recruit and activate allogeneic IFN-γ-producing CD4(+) T cells in a manner dependent upon activation of non-canonical NF-κB signaling. Non-canonical NF-κB signaling was detected in situ within EC both in renal biopsies from transplant patients with chronic antibody-mediated rejection and in PRA-treated human coronary artery xenografts in immunodeficient mice. Upon re-transplantation into immunodeficient hosts engrafted with human T cells, PRA-treated grafts recruited more IFN-γ-producing T cells and enhanced CAV lesion formation. Alloantibody and complement deposition on graft EC activate non-canonical NF-κB signaling, initiating a pro-inflammatory gene program that enhances alloreactive T cell activation and development of CAV. Non-canonical NF-κB signaling in EC, observed in human allograft specimens and implicated in lesion pathogenesis, may represent a target for new pharmacotherapies to halt the progression of CAV.
    Circulation 09/2013; · 15.20 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: The safety of converting kidney transplant recipients on brand-name tacrolimus to generic tacrolimus during hospitalization was evaluated. A single-center observational study compared tacrolimus dosages and trough tacrolimus levels in kidney transplant recipients who had a kidney transplant more than 90 days before hospital admission. Patients in the "brand" group were maintained on brand-name tacrolimus throughout the entire study period. Patients in the generic group were maintained on brand-name tacrolimus before hospital admission, converted to the generic formulation during hospitalization, and returned to the brand-name product at discharge. Tacrolimus dosages were converted on a milligram-per-milligram basis and adjusted, if needed. Outcomes evaluated included the percentage of patients requiring a dosage change, absolute change in average tacrolimus trough level, and frequency of biopsy-proven acute rejection within six months of discharge. A total of 100 patients were evaluated for inclusion in the brand group, with 42 meeting study criteria; 98 patients were evaluated in the generic group, with 36 qualifying for the study. There were no significant differences between the brand and generic groups with respect to dosage adjustments required or trough tacrolimus levels at any point in the transition of care. Mean trough concentrations were similar between groups during all periods of care. The only occurrence of new-onset acute rejection within six months after admission occurred in the brand group. Substitution of a generic formulation of tacrolimus for the innovator product during hospitalization of kidney transplant recipients was safely implemented. Tacrolimus dosage adjustments were common throughout the transitions of care, regardless of the formulation used.
    American journal of health-system pharmacy: AJHP: official journal of the American Society of Health-System Pharmacists 09/2013; 70(17):1507-1512. · 2.10 Impact Factor
  • Jason A Gandelman, Peter S Yoo, Sanjay Kulkarni
    [show abstract] [hide abstract]
    ABSTRACT: Laparoscopic donor nephrectomy is preferentially performed on the left side vs the right, even in instances where more complex arterial vasculature is present on the left. This finding is significant given the observation that living donor kidneys with multiple arteries are associated with increased incidence of ureteral complications in the recipient. One common anatomic variant, retrocaval bifurcation of the right renal artery, has potential risks that prompt the decision to procure left-sided kidneys with more complex arterial anatomy. However, these risks may be mitigated by the surgical approaches that can successfully procure right kidneys with this type of arterial variant. Of 321 total nephrectomies performed, there were 44 right-sided laparoscopic donor nephrectomies. Nineteen of these 44 patients had retrocaval bifurcation and were compared with a cohort of 25 patients without this variant. Standardized parameters were collected including demographics, donor and recipient outcomes, graft function, and renal artery anastomotic velocity. The Mann-Whitney U test and Fisher's exact test were used to show statistical significance. Donor and recipient outcomes and complication rates were not significantly different between the retrocaval bifurcation group and the nonbifurcation group. Notably, graft anastomotic velocity and rates of delayed graft function (DGF) were the same between recipients in the 2 study groups. Comparisons between left-sided nephrectomies and kidneys from the retrocaval bifurcation group showed a slower reduction in immediate creatinine clearance in the retrocaval group; however, both groups had similar outcomes 30 days post-transplantation. This study provides a detailed, technical laparoscopic methodology for procurement of right-sided kidneys with retrocaval arterial bifurcation, which was associated with outcomes similar to right and left kidneys with single arteries.
    Journal of the American College of Surgeons 06/2013; · 4.50 Impact Factor
  • Peter S Yoo, C Kristian Enestvedt, Sanjay Kulkarni
    [show abstract] [hide abstract]
    ABSTRACT: Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is a common cause of cancer death worldwide. Treatment of HCC usually consists of combinations of locoregional therapy, surgical resection, orthotopic liver transplantation, and in advanced cases, systemic chemotherapy. The best rates of cure are achieved with surgical resection or orthotopic liver transplantation in well-selected patients. The success of surgical resection depends on the adequacy of the extent of resection, balanced with the need to preserve functional hepatic parenchyma. Nonanatomic resection for HCC has been proposed as a surgical technique to maximize residual liver mass, but has been shown by some to yield inferior oncologic outcomes compared with formal anatomic resection. This review discusses relevant surgical anatomy of the liver, classifications of hepatic resection, and the current literature regarding outcomes of anatomic and nonanatomic resection of the liver.
    Journal of clinical gastroenterology 04/2013; · 2.21 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Human graft endothelial cells (ECs) can act as antigen-presenting cells to initiate allograft rejection by host memory T cells. Rapamycin, an mTOR inhibitor used clinically to suppress T cell responses, also acts on DCs, rendering them tolerogenic. Here, we report the effects of rapamycin on EC alloimmunogenicity. Compared with mock-treated cells, rapamycin-pretreated human ECs (rapa-ECs) stimulated less proliferation and cytokine secretion from allogeneic CD4+ memory cells, an effect mimicked by shRNA knockdown of mTOR or raptor in ECs. The effects of rapamycin persisted for several days and were linked to upregulation of the inhibitory molecules PD-L1 and PD-L2 on rapa-ECs. Additionally, rapa-ECs produced lower levels of the inflammatory cytokine IL-6. CD4+ memory cells activated by allogeneic rapa-ECs became hyporesponsive to restimulation in an alloantigen-specific manner and contained higher percentages of suppressive CD4+CD25hiCD127loFoxP3+ cells that did not produce effector cytokines. In a human-mouse chimeric model of allograft rejection, rapamycin pretreatment of human arterial allografts increased graft EC expression of PD-L1 and PD-L2 and reduced subsequent infiltration of allogeneic effector T cells into the artery intima and intimal expansion. Preoperative conditioning of allograft ECs with rapamycin could potentially reduce immune-mediated rejection.
    The Journal of clinical investigation 03/2013; · 15.39 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Angiogenesis is one of the hallmarks of tumor growth and metastasis. Identification of tumor angiogenic factors has been a critical component in understanding cancer biology and treatment. Intermedin (IMD) has been reported to promote angiogenesis in a rat ischemic model and human umbilical vascular endothelial cells. Our study sought to determine the role of IMD in human hepatocellular carcinoma tumor progression. High IMD mRNA expression levels were observed in human hepatocellular carcinoma tumors, even in early stage disease, by real-time RT-PCR. Immunohistochemical analysis of hepatocellular carcinoma clinical samples demonstrated that the tumor regions were significantly more immunoreactive for IMD than adjacent benign liver. Inhibition of IMD expression using RNA interference reduced cell proliferation in SK-Hep-1 and SNU-398 cells. Blockage of IMD signaling using either an antagonist peptide or a neutralizing antibody inhibited growth in a dose-dependent manner with concomitant induction of apoptosis, causing cleavage of caspase-8 and downregulation of Gli1 and Bcl2. Conversely, addition of IMD active peptide increased the phosphorylation level of extracellular signal-regulated kinase. Thus, IMD might play an important role in cell proliferation and survival of hepatocellular carcinoma. Our data suggests that IMD is a potential biomarker and therapeutic target for hepatocellular carcinoma.
    Cancer Science 05/2012; 103(8):1474-80. · 3.48 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Waiting time for a kidney transplant is calculated from the date the patient is placed on the UNOS (United Network for Organ Sharing) waitlist to the date the patient undergoes transplant. Time from transplant evaluation to listing represents unaccounted waiting time, potentially resulting in longer dialysis exposure for some patients with prolonged evaluation times. There are established disparities demonstrating that groups of patients take longer to be placed on the waitlist and thus have less access to kidney transplant. Quality improvement report. 905 patients from a university-based hospital were evaluated for kidney transplant candidacy, and analysis was performed from July 1, 2004, to January 31, 2010. A 1-day centralized work-up was implemented on July 1, 2007, whereby the transplant center coordinated the necessary tests needed to fulfill minimal listing criteria. Time from evaluation to UNOS listing was compared between the 2 cohorts. Multivariable Cox proportional hazards models were created to assess the relative hazards of waitlist placement comparing 1-day versus conventional work-up and were adjusted for age, sex, race, and education. Of 905 patients analyzed, 378 underwent conventional evaluation and 527 underwent a 1-day center-coordinated evaluation. Median time to listing in the 1-day center-coordinated evaluation compared with conventional was significantly less (46 vs 226 days, P < 0.001). On multivariable analysis controlling for age, sex, and education level, the 1-day in-center group was 3 times more likely to place patients on the wait list (adjusted HR, 3.08; 95% CI, 2.64-3.59). Listing time was significantly decreased across race, sex, education, and ethnicity. Single center, retrospective. Variables that may influence transplant practitioners, such as comorbid conditions or functional status, were not assessed. A 1-day center-coordinated pretransplant work-up model significantly decreased time to listing for kidney transplant.
    American Journal of Kidney Diseases 05/2012; 60(2):288-94. · 5.29 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Perioperative injuries to an allograft exacerbate graft rejection, which in humans is primarily mediated by effector memory T cells. IL-6 transcripts in human coronary artery segments rapidly increase posttransplantation into immunodeficient mouse hosts compared with those of pretransplant specimens and fall dramatically by 30 d. Adoptive transfer of human PBMCs allogeneic to the artery 2 d postoperatively results in T cell infiltrates and intimal expansion 4 wk later. Ab neutralization of human IL-6 reduces the magnitude of intimal expansion and total T cell infiltration but increases the relative expression of CD161 while decreasing other Th17 markers. Coculture of MHC class II-expressing human endothelial cells (ECs) with allogeneic CD4(+) memory T cells results in T cell activation and EC secretion of IL-6. Neutralizing IL-6 in primary allogeneic T cell-EC cocultures results in enhanced T cell proliferation of CD161(+) CD4(+) T cells, reduces total T cell proliferation upon restimulation in secondary cultures (an effect dependent on CD161(+) T cells), increases expression of FOXP3 in CD161(+) T cells, and generates T cells that suppress proliferation of freshly isolated T cells. These data suggest that IL-6 released from injured allograft vessels enhances allogeneic T cell infiltration and intimal expansion in a model of human allograft rejection by inhibiting an increase in CD161(+) regulatory T cells.
    The Journal of Immunology 11/2011; 187(12):6268-80. · 5.52 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Perioperative nonimmune injuries to an allograft can decrease graft survival. We have developed a model for studying this process using human materials. Human artery segments were transplanted as infrarenal aortic interposition grafts into an immunodeficient mouse host, allowed to "heal in" for 30 days, and then retransplanted into a second mouse host. To induce a reperfusion injury, the healed-in artery segments were incubated for 3 hours under hypoxic conditions ex vivo before retransplantation. To induce immunologic rejection, the animals receiving the retransplanted artery segment were adoptively transferred with human peripheral blood mononuclear cells or purified T cells from a donor allogeneic to the artery 1 week before surgery. To compare rejection of injured versus healthy tissues, these manipulations were combined. Results were analyzed ex vivo by histology, morphometry, immunohistochemistry, and mRNA quantitation or in vivo by ultrasound. Our results showed that reperfusion injury, which otherwise heals with minimal sequelae, intensifies the degree of allogeneic T cell-mediated injury to human artery segments. We developed a new human-mouse chimeric model demonstrating interactions of reperfusion injury and alloimmunity using human cells and tissues that may be adapted to study other forms of nonimmune injury and other types of adaptive immune responses.
    Arteriosclerosis Thrombosis and Vascular Biology 11/2011; 32(2):353-60. · 6.34 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Radiofrequency ablation (RFA) is commonly used for treating unresectable hepatic malignancies. Some commonly associated complications of RFA include fever, symptomatic pleural effusion, abscess, hepatoma and hepatic insufficiency. Here, we report a case of diaphragmatic hernia in a patient following RFA for hepatic malignancy with cirrhosis.
    Hepatology Research 11/2011; 41(11):1132-6. · 2.07 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Ligands activating the transcription factor peroxisome proliferator-activated receptor-γ (PPARγ) have antiinflammatory effects. Vascular rejection induced by allogeneic T cells can be responsible for acute and chronic graft loss. Studies in rodents suggest that PPARγ agonists may inhibit graft vascular rejection, but human T-cell responses to allogeneic vascular cells differ from those in rodents, and the effects of PPARγ in human transplantation are unknown. We tested the effects of PPARγ agonists on human vascular graft rejection using a model in which human artery is interposed into the abdominal aorta of immunodeficient mice, followed by adoptive transfer of allogeneic (to the artery donor) human peripheral blood mononuclear cells. Interferon-γ-dependent rejection ensues within 4 weeks, characterized by intimal thickening, T-cell infiltrates, and vascular cell activation, a response resembling clinical intimal arteritis. The PPARγ agonists 15-deoxy-prostaglandin-J(2), ciglitazone, and pioglitazone reduced intimal expansion, intimal infiltration of CD45RO(+) memory T cells, and plasma levels of inflammatory cytokines. The PPARγ antagonist GW9662 reversed the protective effects of PPARγ agonists, confirming the involvement of PPARγ-mediated pathways. In vitro, pioglitazone inhibited both alloantigen-induced proliferation and superantigen-induced transendothelial migration of memory T cells, indicating the potential mechanisms of PPARγ effects. Our results suggest that PPARγ agonists inhibit allogeneic human memory T cell responses and may be useful for the treatment of vascular graft rejection.
    Circulation 06/2011; 124(2):196-205. · 15.20 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Nephrogenic systemic fibrosis (NSF) is a rare fibrosing disorder described among patients with renal disease. Currently, no standard therapy exists, although therapeutic modalities have included plasmapheresis, extracorporeal photopheresis, sodium thiosulphate, imatinib and renal transplantation. We describe a patient with NSF who was physically debilitated and underwent renal transplantation. After transplantation, the patient's lesions improved clinically, and the patient was ambulatory. Despite developing worsening renal function, her lesions remained unchanged. We conclude that renal transplantation improves symptoms of NSF, and believe that in patients with NSF, careful consideration should be made for early renal transplantation.
    Nephrology Dialysis Transplantation 11/2010; 26(3):1099-101. · 3.37 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Despite a trend toward patient autonomy in clinical practice, the decision whether or not to accept a kidney for transplantation is made predominantly by the transplant surgeon. The purpose of this study is to examine how patients and surgeons prioritize relevant factors when deciding to accept or decline an available kidney. We elicited patient and surgeon rankings for a list of factors involved in the decision using a validated computer survey. We computed the relative importance of each factor and examined associations between patient characteristics and priorities using Spearman's correlation coefficient and the Mann-Whitney U-test for continuous and categorical variables, respectively. Patients placed the greatest value on kidney quality and predictors of transplant outcome. Patients who were on the waiting list longer gave less importance to kidney quality and function. Surgeons placed the greatest value on kidney quality, difficulty for the patient to be matched to a kidney, and the age of the donor. The results of this study suggest that decision support tools can be used to improve the understanding of patient priorities in the decision to accept a donor kidney.
    Clinical Transplantation 10/2010; 25(5):786-93. · 1.63 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: In response to recently published KDIGO (Kidney Disease: Improving Global Outcomes) guidelines for the care of kidney transplant recipients (KTRs), the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) organized a working group of transplant nephrologists and surgeons to review these guidelines and comment on their relevance and applicability for US KTRs. The following commentaries on the KDIGO guidelines represent the consensus of our work group. The KDIGO transplant guidelines concentrated on aspects of transplant care most important to this population in the posttransplant period, such as immunosuppression, infection, malignancy, and cardiovascular care. Our KDOQI work group concurred with many of the KDIGO recommendations except in some important areas related to immunosuppression, in which decisions in the United States are largely made by transplant centers and are dependent in part on the specific patient population served. Most, but not all, KDIGO guidelines are relevant to US patients. However, implementation of many may remain a major challenge because of issues of limitation in resources needed to assist in the tasks of educating, counseling, and implementing and maintaining lifestyle changes. Although very few of the guidelines are based on evidence that is strong enough to justify their being used as the basis of policy or performance measures, they offer an excellent road map to navigate the complex care of KTRs.
    American Journal of Kidney Diseases 08/2010; 56(2):189-218. · 5.29 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Hepatic myelopathy (HM) is a rarely reported disorder characterized by progressive spastic paraparesis due to impaired corticospinal tract function in the setting of cirrhosis or portosystemic shunting. HM has not to date been recognized as a Model for End-Stage Liver Disease (MELD) exception for transplantation. Outcomes for a small number of patients from Europe and Asia who have undergone liver transplantation (LT) for HM suggest a potential neurological benefit, especially with earlier transplantation. We report the first use of MELD exception points for the condition of HM to enable early LT resulting in the reversal of marked spastic paraparesis. Our patient, whose myelopathy had markedly progressed without further hepatic decompensation, underwent LT 14 months after the diagnosis of HM with an adjusted MELD score of 30, which was granted as a United Network for Organ Sharing exception. After LT, there was significant neurological improvement as the patient progressed from wheelchair dependency to full ambulation. We reviewed the literature of other HM patients who had undergone LT. With our patient, there were in all 15 reported cases of LT in individuals with HM. LT can lead to a marked improvement in HM, particularly in the earlier clinical stages of the disorder. Early LT can be accomplished, as in our case, by the submission of an appeal for a MELD upgrade.
    Liver Transplantation 07/2010; 16(7):818-26. · 3.94 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: There exists an inherent conflict between a kidney donor's right to know key aspects of a recipient's medical history and specific disease, such as HIV, where federal and state statues protect this information. The authors of the live organ donor consensus group expressly stated the principal of a donor's right to recipient information. This information includes the risks and benefits of not only the donation procedure, but also the risks, benefits, and alternative treatment options of the recipient. In this paper, a case will be presented highlighting this conflict and the ethical and legal reasoning used to resolve it. A 22-year-old woman came forward as a directed kidney donor for an HIV-positive individual. The donor and recipient were medically appropriate for kidney donation and transplantation. During the donor advocacy panel review, there was disagreement regarding whether or not the potential donor had the right to know about the HIV status of the potential recipient. In living kidney transplantation to HIV-positive individuals, the recipient's right to privacy of information outweighs the donor's right to know. Although protecting the recipient's right to privacy is paramount, the donor is still entitled to consider factors a priori that could alter their decision to donate. This can be accomplished by informing the donor that they are not entitled to protected health information of the recipient and that their decision to donate should be based on knowing the recipient is medically appropriate for kidney transplantation.
    Clinical Journal of the American Society of Nephrology 03/2010; 5(5):924-8. · 5.07 Impact Factor
  • American Journal of Kidney Diseases - AMER J KIDNEY DIS. 01/2010; 55(4).
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: To report the potential clinically significant pharmacokinetic interaction between sirolimus and dronedarone. A 67-year-old man status post-kidney transplant in 2004 was maintained on an immunosuppressive regimen consisting of sirolimus, mycophenolate mofetil, and prednisone. He had been maintained for more than 1 year on a stable dose of sirolimus (5 mg/day), with concentrations ranging between 5 and 13.5 ng/mL. The patient was admitted to the hospital with a complaint of bloody diarrhea; shortly after admission, he developed atrial fibrillation for which dronedarone 400 mg twice daily was initiated. Sirolimus concentrations obtained 3 days after initiation of dronedarone revealed a trough concentration that was increased by more than 3-fold (38.6 ng/mL) from his baseline trough concentration. After sirolimus was held for 6 days, the trough concentration was 7.8 ng/mL. The dosage was reduced to 1 mg/day; there was no need for further adjustment. While the potential for an interaction between sirolimus and dronedarone is listed in the package insert of dronedarone, there are no documented reports of this interaction in the peer-reviewed literature. Since sirolimus is a narrow therapeutic index medication, information about the severity and magnitude of the interaction with dronedarone may help clinicians avoid therapeutic misadventures when this combination is employed. Our case clearly demonstrates a significant pharmacokinetic interaction between sirolimus and dronedarone. The Horn Drug Interaction Probability Scale indicates that the occurrence of an interaction between sirolimus and dronedarone in our case is probable. Due to the potential for sirolimus toxicity and excessive immunosuppression, the concurrent use of dronedarone and sirolimus should be avoided when possible. If concurrent administration cannot be avoided, we suggest close monitoring and a 50-75% dose reduction of sirolimus prior to dronedarone initiation.
    Annals of Pharmacotherapy 01/2010; 44(7-8):1338-41. · 2.57 Impact Factor

Publication Stats

68 Citations
107.22 Total Impact Points

Institutions

  • 2010–2014
    • Yale-New Haven Hospital
      New Haven, Connecticut, United States
  • 2013
    • Texas Transplant Institute
      San Antonio, Texas, United States
  • 2010–2012
    • Yale University
      • Section of Nephrology
      New Haven, CT, United States