Delivery of Health Care; Kidney; Kidney Failure, Chronic; Liver; Nephrology; Risk; Transplantation; Living Donors
Public Health Interests
Health care delivery; Health Care Management; Health Disparities; Health risk behaviors; Kidney Disease; Psychosocial risk factors
Increasing living donation in a safe and effective manner is the only solution to the organ shortage. My research examines how kidney donors assess risk and how this information can be better used by transplant centers when they evaluate possible living donors. Carrie Thieseen MD PhD (Yale) and I are currently conducting a multicenter study and are in the analysis phase of this project, which is funded by the Greenwall Foundation.
I am also conducting a clinical study that tests an FDA approved system Airseal (Surgiquest, Inc.) to determine if we can reduce pain from the kidney donor surgery. There is a known association between intra-abdominal hypertension and kidney dysfunction, thus, successfully performing donor nephrectomies at low-pressure may benefit both donors and recipients, as well as, providing important mechanistic insights into the mechanisms of intra-abdominal hypertension induced kidney injury.
Unfortunately, kidneys don't last forever. There are new medications that may help some kidney transplant patients keep their kidney longer. We are conducting a clinical study using a complement inhibitor, eculizumab, to determine if we can stop antibodies from injuring kidneys. The study was recently completed and the results are available at the American Journal of Transplantation website under early view publications and at clinicaltrials.gov.
Specialized Terms: The role of complement inhibition in kidney and liver transplantation; Methods to decrease pain for living kidney donors; UNOS & CMS regulations and compliance; Living donor risks and perceptions.
Extensive Research Description
I am interested in the role of complement inhibition in both kidney and liver transplantation. We are conducting an industry-sponsored study to assess if complement inbhibition with eculizumab can reduce antibody-mediated injury seen in kidney patients with donor-specific antibodies. I work with Jordan Pober MD PhD (Yale Immunobiology) on this study to assess what affect complement inhibition will have on graft endothelial cells. Given that donor specific antibodies may increase markers of endothelial cell activation, we are testing if complement inhibition will reduce activation and thus preserve graft function.
Living donation is a principal interest of mine, both clincally and academically. Previous work on living donor consenting practices and the need for better structured alibi's for donor has lead to a greater question on how transplant centers evaluate and approve living donors. We examine if a greater participation of donor's wishes should translate into a rebalancing of donor autonomy and maleficence.
1. Inhibition of Complement in Chronic Allograft Injury & its affect on Circulating Endothelial Cells.
2. Randomized Controlled Trial of Reducing Operative & Post-Operative Morbidity in Living Kidney Donors Utilizing Low Pressure, Limited Variability Pneumoperitoneum.
3. Burden of Illness in Highly Sensitized ESRD Patients & Patients Who Experience Acute Antibody-Mediated Rejection.
4. Balancing non-maleficence and autonomy in living kidney donors.
Eculizumab Therapy for Chronic Antibody-Mediated Injury in Kidney Transplant Recipients: A Pilot Randomized Controlled Trial.
Kulkarni S, Kirkiles-Smith NC, Deng YH, Formica RN, Moeckel G, Broecker V, Bow L, Tomlin R, Pober JS. American Journal of Transplantation 2016. [epub ahead of print]
The Long-Term Follow-up and Support for Living Organ Donors: A Center-Based Initiative Founded on Developing a Community of Living Donors.
Kulkarni S, Thiessen C, Formica RN, Schilsky M, Mulligan D, D'Aquila R. American Journal of Transplantation 2016. [epub ahead of print]
Development of a Donor-Centered Approach to Risk Assessment: Rebalancing Nonmaleficence and Autonomy.
Thiessen C, Gordon EJ, Reese PP, Kulkarni S. American Journal of Transplantation 2015;15(9):2314-2323.
Opting out: confidentiality and availability of an 'alibi' for potential living kidney donors in the USA.
Thiessen C, Kim YA, Formica R, Bia M, Kulkarni S. Journal of Medical Ethics. 2015 Jul;41(7):506-10.
Written informed consent for living liver donor evaluation: compliance with Centers for Medicare and Medicaid Services and Organ Procurement and Transplantation Network Guidelines and alibi offers.
Thiessen C, Kim YA, Yoo PS, Rodriguez-Davalos M, Mulligan D, Kulkarni S. Liver Transpl. 2014 Apr;20(4):416-24
Written informed consent for living kidney donors: practices and compliance with CMS and OPTN requirements.
Thiessen C, Kim YA, Formica R, Bia M, Kulkarni S. American Journal of Transplantatation. 2013 Oct;13(10):2713-21.
Retrocaval renal artery bifurcation is not a contraindication to laparoscopic right donor nephrectomy.
Gandelman JA, Yoo PS, Kulkarni S. Journal of the American College of Surgeons 2013 Sep;217(3):406-11.
Full List of PubMed Publications
- Formica RN Jr, Kulkarni S: Being Thoughtful about Desensitization. Clin J Am Soc Nephrol. 2017 Oct 3; 2017 Oct 3. PMID: 28974523
- Choe J, Merola J, Kulkarni S, Mulligan DC: Allograft transmission of hepatitis C during the window period: Weighing the new risks and costs in the era of donor shortage. Clin Transplant. 2017 Aug; 2017 Jun 23. PMID: 28643333
- Thiessen C, Jaji Z, Joyce M, Zimbrean P, Reese P, Gordon EJ, Kulkarni S: Opting out: a single-centre pilot study assessing the reasons for and the psychosocial impact of withdrawing from living kidney donor evaluation. J Med Ethics. 2017 Mar 3; 2017 Mar 3. PMID: 28258071
- Callender GG, Malinowski J, Javid M, Zhang Y, Huang H, Quinn CE, Carling T, Tomlin R, Smith JD, Kulkarni S: Parathyroidectomy prior to kidney transplant decreases graft failure. Surgery. 2017 Jan; 2016 Nov 15. PMID: 27863776
- Thiessen C, Kulkarni S, Reese PP, Gordon EJ: A Call for Research on Individuals Who Opt Out of Living Kidney Donation: Challenges and Opportunities. Transplantation. 2016 Dec. PMID: 27495760
- Tooley JE, Bohl DD, Kulkarni S, Rodriguez-Davalos MI, Mangi A, Mulligan DC, Yoo PS: Perioperative outcomes of coronary artery bypass graft in renal transplant recipients in the United States: results from the Nationwide Inpatient Sample. Clin Transplant. 2016 Oct; 2016 Sep 25. PMID: 27440000
- Guerra CM, Formica RN, Kulkarni S, Asch WS, Tichy EM: Duration of prophylaxis against fungal infection in kidney transplant recipients. Prog Transplant. 2015 Dec. PMID: 26645924
- Thiessen C, Kim YA, Formica R, Bia M, Kulkarni S: Opting out: confidentiality and availability of an 'alibi' for potential living kidney donors in the USA. J Med Ethics. 2015 Jul; 2014 Nov 3. PMID: 25368413
- Vilarinho S, Choi M, Jain D, Malhotra A, Kulkarni S, Pashankar D, Phatak U, Patel M, Bale A, Mane S, Lifton RP, Mistry PK: Individual exome analysis in diagnosis and management of paediatric liver failure of indeterminate aetiology. J Hepatol. 2014 Nov; 2014 Jul 10. PMID: 25016221
- Thiessen C, Kim YA, Yoo PS, Rodriguez-Davalos M, Mulligan D, Kulkarni S: Written informed consent for living liver donor evaluation: compliance with Centers for Medicare and Medicaid Services and Organ Procurement and Transplantation Network Guidelines and alibi offers. Liver Transpl. 2014 Apr; 2014 Feb 25. PMID: 24415564
- Rodriguez-Davalos MI, Arvelakis A, Umman V, Tanjavur V, Yoo PS, Kulkarni S, Luczycki SM, Schilsky M, Emre S: Segmental grafts in adult and pediatric liver transplantation: improving outcomes by minimizing vascular complications. JAMA Surg. 2014 Jan. PMID: 24284803
- Jane-Wit D, Manes TD, Yi T, Qin L, Clark P, Kirkiles-Smith NC, Abrahimi P, Devalliere J, Moeckel G, Kulkarni S, Tellides G, Pober JS: Alloantibody and complement promote T cell-mediated cardiac allograft vasculopathy through noncanonical nuclear factor-κB signaling in endothelial cells. Circulation. 2013 Dec 3; 2013 Sep 17. PMID: 24045046
- Davarpanah AH, Pahade JK, Cornfeld D, Ghita M, Kulkarni S, Israel GM: CT angiography in potential living kidney donors: 80 kVp versus 120 kVp. AJR Am J Roentgenol. 2013 Nov. PMID: 24147505
- Heavner MS, Tichy EM, Yazdi M, Formica RN Jr, Kulkarni S, Emre S: Clinical outcomes associated with conversion from brand-name to generic tacrolimus in hospitalized kidney transplant recipients. Am J Health Syst Pharm. 2013 Sep 1. PMID: 23943182
- Gandelman JA, Yoo PS, Kulkarni S: Retrocaval renal artery bifurcation is not a contraindication to laparoscopic right donor nephrectomy. J Am Coll Surg. 2013 Sep; 2013 Jun 21. PMID: 23791562
- Yoo PS, Enestvedt CK, Kulkarni S: Anatomic considerations in the surgical resection of hepatocellular carcinoma. J Clin Gastroenterol. 2013 Jul. PMID: 23632343
- Wang C, Yi T, Qin L, Maldonado RA, von Andrian UH, Kulkarni S, Tellides G, Pober JS: Rapamycin-treated human endothelial cells preferentially activate allogeneic regulatory T cells. J Clin Invest. 2013 Apr; 2013 Mar 8. PMID: 23478407
- Formica RN Jr, Barrantes F, Asch WS, Bia MJ, Coca S, Kalyesubula R, McCloskey B, Leary T, Arvelakis A, Kulkarni S: A one-day centralized work-up for kidney transplant recipient candidates: a quality improvement report. Am J Kidney Dis. 2012 Aug; 2012 May 8. PMID: 22571868
- Guo X, Schmitz JC, Kenney BC, Uchio EM, Kulkarni S, Cha CH: Intermedin is overexpressed in hepatocellular carcinoma and regulates cell proliferation and survival. Cancer Sci. 2012 Aug; 2012 Jul 11. PMID: 22625651
- Yi T, Fogal B, Hao Z, Tobiasova Z, Wang C, Rao DA, Al-Lamki RS, Kirkiles-Smith NC, Kulkarni S, Bradley JR, Bothwell AL, Sessa WC, Tellides G, Pober JS: Reperfusion injury intensifies the adaptive human T cell alloresponse in a human-mouse chimeric artery model. Arterioscler Thromb Vasc Biol. 2012 Feb; 2011 Nov 3. PMID: 22053072
- Fogal B, Yi T, Wang C, Rao DA, Lebastchi A, Kulkarni S, Tellides G, Pober JS: Neutralizing IL-6 reduces human arterial allograft rejection by allowing emergence of CD161+ CD4+ regulatory T cells. J Immunol. 2011 Dec 15; 2011 Nov 14. PMID: 22084439
- Singh M, Singh G, Pandey A, Cha CH, Kulkarni S: Laparoscopic repair of iatrogenic diaphragmatic hernia following radiofrequency ablation for hepatocellular carcinoma. Hepatol Res. 2011 Nov. PMID: 22032681
- Solomon DA, Rabidou N, Kulkarni S, Formica R, Fraenkel L: Accepting a donor kidney: an evaluation of patients' and transplant surgeons' priorities. Clin Transplant. 2011 Sep-Oct; 2010 Oct 22. PMID: 20964716
- Tobiasova Z, Zhang L, Yi T, Qin L, Manes TD, Kulkarni S, Lorber MI, Rodriguez FC, Choi JM, Tellides G, Pober JS, Kawikova I, Bothwell AL: Peroxisome proliferator-activated receptor-γ agonists prevent in vivo remodeling of human artery induced by alloreactive T cells. Circulation. 2011 Jul 12; 2011 Jun 20. PMID: 21690493
- Kulkarni S, Taddei TH: When should a hepatitis C-positive ESRD patient receive a renal transplant? Semin Dial. 2011 Jul-Aug; 2011 Jul 29. PMID: 21801216
- Bia M, Adey DB, Bloom RD, Chan L, Kulkarni S, Tomlanovich S: KDOQI US commentary on the 2009 KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Kidney Dis. 2010 Aug; 2010 Jul 2. PMID: 20598411
- Tichy EM, Medwid AJ, Mills EA, Formica RN, Kulkarni S: Significant sirolimus and dronedarone interaction in a kidney transplant recipient. Ann Pharmacother. 2010 Jul-Aug; 2010 May 18. PMID: 20484171
- Caldwell C, Werdiger N, Jakab S, Schilsky M, Arvelakis A, Kulkarni S, Emre S: Use of model for end-stage liver disease exception points for early liver transplantation and successful reversal of hepatic myelopathy with a review of the literature. Liver Transpl. 2010 Jul. PMID: 20583082
- Formica RN Jr, Asch WS, Wagner KR, Kulkarni S: Kidney transplantation and HIV: does recipient privacy outweigh the donor's right to information? Clin J Am Soc Nephrol. 2010 May; 2010 Mar 4. PMID: 20203162
- Parekh AM, Gordon EJ, Garg AX, Waterman AD, Kulkarni S, Parikh CR: Living kidney donor informed consent practices vary between US and non-US centers. Nephrol Dial Transplant. 2008 Oct; 2008 Jul 3. PMID: 18599559
- Friedman AL, Geoghegan SR, Sowers NM, Kulkarni S, Formica RN Jr: Medication errors in the outpatient setting: classification and root cause analysis. Arch Surg. 2007 Mar. PMID: 17372053
- Kulkarni S, Cronin DC 2nd: Ethics in liver transplantation. Semin Liver Dis. 2006 Aug. PMID: 16850372
- Kulkarni S, Cronin DC 2nd: Ethical tensions in solid organ transplantation: the price of success. World J Gastroenterol. 2006 May 28. PMID: 16718849
- Kulkarni S, Malagò M, Cronin DC 2nd: Living donor liver transplantation for pediatric and adult recipients. Nat Clin Pract Gastroenterol Hepatol. 2006 Mar. PMID: 16511549