Sanjay Kulkarni

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

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Publications (30)178.78 Total impact

  • Gastroenterology 04/2015; 148(4):S-1094-S-1095. DOI:10.1016/S0016-5085(15)33733-1 · 16.72 Impact Factor
  • Carrie Thiessen · Yunsoo A Kim · Richard Formica · Margaret Bia · Sanjay Kulkarni ·
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    ABSTRACT: Ethicists and guidelines have suggested that potential living kidney donors who withdraw from evaluation be offered an 'alibi.' We sought to determine what potential living kidney donors are told about their ability to opt out, alibi availability and postwithdrawal confidentiality. We reviewed 148 consent forms for living kidney donor evaluation from US transplant centres that performed >5 living kidney transplants in 2010-2011 (response rate 87%). We found that while 98% of centres used evaluation consent forms that indicated that the donor could withdraw, only 21% of these documents offered an alibi. Another 23% of centres' consent forms indicated that the transplant team would be willing to inform the intended recipient that an individual was not a potential donor. Relatively few consent documents explicitly addressed the confidentiality of the donor's health information (31%), candidacy status (18%), decision (24%) or reasons (23%) following withdrawal. To preserve potential donors' autonomy and relationships, we advocate that all transplant centres offer general alibis in their evaluation consent forms. We conclude by offering recommendations for evaluation consent discussions of opting out, alibis and postwithdrawal confidentiality.
    Journal of Medical Ethics 11/2014; 41(7). DOI:10.1136/medethics-2014-102184 · 1.51 Impact Factor

  • Annual Meeting of the American-College-of-Clinical-Pharmacy (ACCP); 10/2014
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    ABSTRACT: Background & aims: In children with liver failure, as many as half remain of indeterminate aetiology. This hinders timely consideration of optimal treatment options. We posit that a significant subset of these children harbour known inherited metabolic liver diseases with atypical presentation or novel inborn errors of metabolism. We investigated the utility of whole-exome sequencing in three children with advanced liver disease of indeterminate aetiology. Methods: Patient 1 was a 10 year-old female diagnosed with Wilson disease but no detectable ATP7B mutations, and decompensated liver cirrhosis who underwent liver transplant and subsequently developed onset of neurodegenerative disease. Patient 2 was a full-term 2 day-old male with fatal acute liver failure of indeterminate aetiology. Patient 3 was an 8 year-old female with progressive syndromic cholestasis of unknown aetiology since age 3 months. Results: Unbiased whole-exome sequencing of germline DNA revealed homozygous mutations in MPV17 and SERAC1 as the disease causing genes in patient 1 and 2, respectively. This is the first demonstration of SERAC1 loss-of-function associated fatal acute liver failure. Patient 1 expands the phenotypic spectrum of the MPV17-related hepatocerebral mitochondrial DNA depletion syndrome. Patient 3 was found to have syndromic cholestasis due to bi-allelic NOTCH2 mutations. Conclusions: Our findings validate the application of whole-exome sequencing in the diagnosis and management of children with advanced liver disease of indeterminate aetiology, with the potential to enhance optimal selection of treatment options and adequate counselling of families. Moreover, whole-exome sequencing revealed a hitherto unrecognized phenotypic spectrum of inherited metabolic liver diseases.
    Journal of Hepatology 07/2014; 61(5). DOI:10.1016/j.jhep.2014.06.038 · 11.34 Impact Factor
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    ABSTRACT: We examined written informed consent forms for living liver donor evaluations to determine whether they incorporated 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 1 living donor liver transplant in 2011; 37 centers reported active living donor evaluation programs. 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 used consent forms that addressed at least two‐thirds of the elements recommended by OPTN. Only 17% of the centers provided written offers of an alibi to donors who withdrew from the evaluation. On the basis of our findings, we offer suggestions that may be relevant to ongoing revisions to the OPTN living liver donor consent policy and may help centers to improve the clarity of their written consent forms. Liver Transpl 20:416–424, 2014. © 2014 AASLD.
    Liver Transplantation 04/2014; 20(4). DOI:10.1002/lt.23822 · 4.24 Impact Factor

  • Hepatology 12/2013; 58(6):1390A-1390A. · 11.06 Impact Factor
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    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; 149(1). DOI:10.1001/jamasurg.2013.3384 · 3.94 Impact Factor
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    ABSTRACT: Objective: The purpose of this article is to retrospectively investigate the diagnostic accuracy, image quality, and radiation dose of renal artery CT angiography (CTA), at 80 kVp compared with 120 kVp, in adult kidney donors. Materials and methods: CTA examinations of 258 consecutive potential kidney donors were retrospectively evaluated; 189 patients were scanned using 64-MDCT scanners (higher maximal tube current), and 69 patients were scanned using 16-MDCT scanners (lower maximal tube current). On the basis of the tube potential and scanners, the study population was divided into four groups. Qualitative and quantitative analysis include vascular attenuation measurements, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR). Volume CT dose index (CTDIvol) was recorded, and size-specific dose estimate was also estimated. Results: Using 80 kVp for the 16-MDCT scanner, there was a 64.9% reduction in size-specific dose estimate (66.1% reduction in CTDIvol), increased noise, and tube current saturation in all cases. Axial image quality was significantly lower compared with that obtained at 120 kVp (p = 0.02), but image quality and visibility of renal artery branch order were comparable. Using 80 kVp for the 64-MDCT scanner, there was a 40.5% reduction in size-specific dose estimate (43.6% reduction in CTDIvol) and increased SNR and CNR (p < 0.001). No significant differences in 3D image quality and branch order visibility were observed. Tube current saturation was reached in 31% of cases. One hundred fifty-one patients (86 imaged at 80 kVp and 65 imaged at 120 kVp) underwent donor nephrectomy; CTA diagnostic accuracy was 100%. Conclusion: Renal artery CTA using 80 kVp combined with limiting the tube current results in a significant reduction in radiation dose and improved SNR and CNR, without deterioration of image quality.
    American Journal of Roentgenology 11/2013; 201(5):W753-60. DOI:10.2214/AJR.12.10439 · 2.73 Impact Factor
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    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; 128(23). DOI:10.1161/CIRCULATIONAHA.113.002972 · 14.43 Impact Factor
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    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. DOI:10.2146/ajhp120783 · 1.88 Impact Factor
  • Jason A Gandelman · Peter S Yoo · Sanjay Kulkarni ·
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    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; 217(3). DOI:10.1016/j.jamcollsurg.2013.03.026 · 5.12 Impact Factor
  • Peter S Yoo · C.K. Kristian Enestvedt · Sanjay Kulkarni ·
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    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; 47. DOI:10.1097/MCG.0b013e318280ce5f · 3.50 Impact Factor
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    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; 123(4). DOI:10.1172/JCI66204 · 13.22 Impact Factor
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    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. DOI:10.1111/j.1349-7006.2012.02341.x · 3.52 Impact Factor
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    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. DOI:10.1053/j.ajkd.2012.04.008 · 5.90 Impact Factor
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    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. DOI:10.4049/jimmunol.1003774 · 4.92 Impact Factor
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    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. DOI:10.1161/ATVBAHA.111.239285 · 6.00 Impact Factor
  • Mansher Singh · Gayatri Singh · Ambarish Pandey · Charles H Cha · Sanjay Kulkarni ·
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    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. DOI:10.1111/j.1872-034X.2011.00865.x · 2.74 Impact Factor
  • Xiaojia Guo · John Schmitz · Edward Uchio · Barton Kenney · Sanjay Kulkarni · Charles Cha ·

    Cancer Research 07/2011; 71(8 Supplement):5149-5149. DOI:10.1158/1538-7445.AM2011-5149 · 9.33 Impact Factor
  • Sanjay Kulkarni · Tamar H Taddei ·

    Seminars in Dialysis 07/2011; 24(4):438-9. DOI:10.1111/j.1525-139X.2011.00898.x · 1.75 Impact Factor

Publication Stats

222 Citations
178.78 Total Impact Points


  • 2010-2014
    • Yale-New Haven Hospital
      • Department of Pathology
      New Haven, Connecticut, United States
    • University of Toronto
      Toronto, Ontario, Canada
  • 2008-2014
    • Yale University
      • • Department of Surgery
      • • School of Medicine
      New Haven, Connecticut, United States