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Article: Emerging role of cell-free DNA in kidney transplantation.

Chopra, Bhavna / Sureshkumar, Kalathil K

2021 Volume 11, Issue 5, Page(s) 55–65

Abstract: Monitoring kidney transplants for rejection conventionally includes serum creatinine, immunosuppressive drug levels, proteinuria, and donor-specific antibody (DSA). Serum creatinine is a late marker of allograft injury, and the predictive ability of DSA ... ...

Abstract	Monitoring kidney transplants for rejection conventionally includes serum creatinine, immunosuppressive drug levels, proteinuria, and donor-specific antibody (DSA). Serum creatinine is a late marker of allograft injury, and the predictive ability of DSA regarding risk of rejection is variable. Histological analysis of an allograft biopsy is the standard method for diagnosing rejection but is invasive, inconvenient, and carries risk of complications. There has been a long quest to find a perfect biomarker that noninvasively predicts tissue injury caused by rejection at an early stage, so that diagnosis and treatment could be pursued without delay in order to minimize irreversible damage to the allograft. In this review, we discuss relatively novel research on identifying biomarkers of tissue injury, specifically elaborating on donor-derived cell-free DNA, and its clinical utility.
Language	English
Publishing date	2021-11-20
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2764849-7
ISSN	2220-315X
ISSN	2220-315X
DOI	10.5493/wjem.v11.i5.55
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Article: Induction Therapy and Outcomes following Kidney Transplantation in Recipients of Previous Heart or Liver Transplants.

Sureshkumar, Kalathil K / Chopra, Bhavna / Sampaio, Marcelo S

Indian journal of nephrology

2022 Volume 32, Issue 2, Page(s) 116–126

Abstract: Introduction: Optimal induction for kidney transplantation in patients with previous nonrenal organ transplantation is unclear. We aimed to evaluate the impact of induction therapy on the outcomes following kidney transplantation in patients who ... ...

Abstract	Introduction: Optimal induction for kidney transplantation in patients with previous nonrenal organ transplantation is unclear. We aimed to evaluate the impact of induction therapy on the outcomes following kidney transplantation in patients who underwent prior heart or liver transplantation. Methods: Using the UNOS database, patients who underwent isolated heart or liver transplant from 2000 to 2016 followed by subsequent kidney transplant and maintained on calcineurin inhibitor (CNI)/mycophenolic acid (MPA) regimen were identified and stratified into three groups according to the induction used for kidney transplant: No induction, induction with interleukin-2 receptor antibody (IL-2RA), or T-cell depleting induction with Thymoglobulin. The outcomes were compared between no induction vs. IL-2RA and T-cell depleting induction, and IL-2RA vs. T-cell depleting induction. Results: Adjusted risk for delayed graft function was significantly higher for T-cell depleting vs. no induction (OR 4.56, 95% CI 1.14-18.3, Conclusions: The use of induction was not associated with graft or patient survival benefits for kidney transplantation in patients who had prior heart or liver transplants and maintained on CNI and MPA regimen.
Language	English
Publishing date	2022-03-09
Publishing country	India
Document type	Journal Article
ZDB-ID	2134388-3
ISSN	1998-3662 ; 0971-4065
ISSN (online)	1998-3662
ISSN	0971-4065
DOI	10.4103/ijn.IJN_183_20
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Article ; Online: Impact of kidney transplant type and previous transplant on baseline donor-derived cell free DNA.

Sureshkumar, Kalathil K / Lyons, Shelly / Chopra, Bhavna

Transplant international : official journal of the European Society for Organ Transplantation

2020 Volume 33, Issue 10, Page(s) 1324–1325

MeSH term(s)	Cell-Free Nucleic Acids ; Humans ; Kidney ; Kidney Transplantation ; Tissue Donors ; Transplant Recipients ; Transplants
Chemical Substances	Cell-Free Nucleic Acids
Language	English
Publishing date	2020-07-09
Publishing country	England
Document type	Letter
ZDB-ID	639435-8
ISSN	1432-2277 ; 0934-0874
ISSN (online)	1432-2277
ISSN	0934-0874
DOI	10.1111/tri.13673
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Article ; Online: Impact of body mass index and recipient age on baseline donor-derived cell free DNA (dd-cfDNA) in kidney transplant recipients.

Sureshkumar, Kalathil K / Aramada, Harsha R / Chopra, Bhavna

Clinical transplantation

2020 Volume 34, Issue 12, Page(s) e14101

MeSH term(s)	Body Mass Index ; Cell-Free Nucleic Acids ; Graft Rejection/etiology ; Humans ; Kidney Transplantation ; Tissue Donors ; Transplant Recipients
Chemical Substances	Cell-Free Nucleic Acids
Language	English
Publishing date	2020-10-22
Publishing country	Denmark
Document type	Letter
ZDB-ID	639001-8
ISSN	1399-0012 ; 0902-0063
ISSN (online)	1399-0012
ISSN	0902-0063
DOI	10.1111/ctr.14101
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Article ; Online: Impact of Donor Ethnicity on Long-Term Kidney Transplant Outcomes: Analysis by Kidney Donor Profile Index Categories.

Sureshkumar, Kalathil K / Chopra, Bhavna

Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation

2019 Volume 18, Issue 2, Page(s) 144–148

Abstract: Objectives: Risk of kidney disease is heightened in African American individuals. African American donor ethnicity is one of 10 risk factors in calculating the kidney donor profile index used in assessing organ quality. We aimed to evaluate outcomes of ... ...

Abstract	Objectives: Risk of kidney disease is heightened in African American individuals. African American donor ethnicity is one of 10 risk factors in calculating the kidney donor profile index used in assessing organ quality. We aimed to evaluate outcomes of deceased-donor kidney transplants from African American donors stratified by kidney donor profile index. Materials and methods: Using the Organ Procurement and Transplant Network/United Network for Organ Sharing database, we identified deceased-donor kidney transplant recipients from 2000 to 2015 who received induction and calcineurin inhibitor/mycophenolic acid maintenance. Patients were divided into 4 kidney donor profile index groups (0%-20%, 21%-50%, 51%-85%, and > 85%). Long-term outcomes of each group were compared between African American and non-African American kidney donations using Cox model. Results: Among 59 648 patients, 15 250 were in the 0% to 20% group (560 African American donors, 14 690 non-African American donors), 19 355 were in the 21% to 50% group (2807 African American donors, 16 548 non-African American donors), 19 412 were in the 51% to 85% group (2774 African American donors, 16 638 non-African American donors), and 5631 were in the > 85% group (1670 African American donors, 3961 non-African American donors). Adjusted overall and death-censored graft failure risks were higher for recipients of African American donor kidneys in the 51% to 85% (hazard ratio 1.12; 95% confidence interval, 1.01-1.25; P = .009 and hazard ratio 1.12; 95% confidence interval, 1.01-1.25; P = .03) and the > 85% kidney donor profile index (hazard ratio 1.12; 95% confidence interval, 1.04-1.24; P = .025 and hazard ratio 1.33; 95% confidence interval, 1.16-1.51; P < .001) groups. Conclusions: Inferior graft outcomes in recipients of African American kidneys in our study were limited to those with > 50% kidney donor profile index. Effects of risk factors such as APOL1 risk alleles and sickle cell trait on these observations need further study.
MeSH term(s)	African Americans ; Databases, Factual ; Donor Selection ; Graft Rejection/ethnology ; Graft Rejection/mortality ; Graft Survival ; Humans ; Kidney Transplantation/adverse effects ; Kidney Transplantation/mortality ; Race Factors ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Time Factors ; Tissue Donors ; Treatment Outcome ; United States/epidemiology
Language	English
Publishing date	2019-06-25
Publishing country	Turkey
Document type	Comparative Study ; Journal Article
ZDB-ID	2396778-X
ISSN	2146-8427 ; 1304-0855
ISSN (online)	2146-8427
ISSN	1304-0855
DOI	10.6002/ect.2018.0394
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Article ; Online: Induction Type and Outcomes in HLA-DR Mismatch Kidney Transplantation.

Sureshkumar, Kalathil K / Chopra, Bhavna

Transplantation proceedings

2019 Volume 51, Issue 6, Page(s) 1796–1800

Abstract: Background: In kidney transplantation, donor recipient human leukocyte antigen (HLA)-DR mismatch signals high immunologic risk and portends inferior outcomes. We compared the impacts of depleting vs non-depleting antibody induction on the outcomes in ... ...

Abstract	Background: In kidney transplantation, donor recipient human leukocyte antigen (HLA)-DR mismatch signals high immunologic risk and portends inferior outcomes. We compared the impacts of depleting vs non-depleting antibody induction on the outcomes in kidney transplant recipients (KTRs) at different levels of HLA-DR mismatches. Methods: Using the Organ Procurement and Transplantation Network/United Network for Organ Sharing database, we identified adult KTRs from 2001 to 2015 who received induction therapy with either depleting (thymoglobulin/alemtuzumab) or non-depleting (basiliximab/daclizumab) antibody and were discharged on calcineurin inhibitor/mycophenolic acid maintenance. Patients were then stratified by the number of donor-recipient HLA-DR mismatches (0, 1, 2) in both living donor (LD) and deceased donor (DD) KTRs. Under each HLA-DR mismatch category, long-term outcomes were compared for depleting vs non-depleting induction using a Cox model. Results: A total of 63,821 LD (HLA-DR mismatches: 0, n = 6945 [depleting = 4409, non-depleting = 2536]; 1, n = 19,557 [depleting = 13,558, non-depleting = 6019]; and 2, n = 10,727 [depleting = 7694, non-depleting = 3033]) and 64,922 DD (HLA-DR mismatches: 0, n = 13,915 [depleting = 10,124, non-depleting = 3791]; 1, n = 27,994 [depleting = 20,454, non-depleting = 7540]; and 2, n = 23,013 [depleting = 16,908, non-depleting = 6105]) KTRs were included in the analysis. Adjusted patient death risk was significantly lower in the depleting vs non-depleting antibody induction group among DD kidney recipients (hazard ratio 0.90, 95% CI 0.85-0.96, P = .001) and trended lower among LD kidney recipients (HR 0.88, 95% 0.79-1.01, P = .05) with 2 HLA-DR mismatches. Discussion: Our study found a patient survival benefit associated with the use of perioperative induction with depleting when compared to non-depleting antibody in KTRs with 2 HLA-DR mismatches and maintained on a calcineurin inhibitor/mycophenolic acid regimen.
MeSH term(s)	Adult ; Alemtuzumab/therapeutic use ; Antibodies/immunology ; Antilymphocyte Serum/immunology ; Antilymphocyte Serum/therapeutic use ; Basiliximab/immunology ; Basiliximab/therapeutic use ; Blood Group Incompatibility/immunology ; Calcineurin Inhibitors/immunology ; Calcineurin Inhibitors/therapeutic use ; Contraindications, Procedure ; Daclizumab/immunology ; Daclizumab/therapeutic use ; Databases, Factual ; Female ; Graft Survival/immunology ; HLA-DR Antigens/immunology ; Histocompatibility Testing ; Humans ; Immunosuppression/methods ; Immunosuppressive Agents/therapeutic use ; Kidney/immunology ; Kidney Transplantation/adverse effects ; Living Donors ; Male ; Middle Aged ; Mycophenolic Acid/immunology ; Mycophenolic Acid/therapeutic use ; Proportional Hazards Models ; Treatment Outcome
Chemical Substances	Antibodies ; Antilymphocyte Serum ; Calcineurin Inhibitors ; HLA-DR Antigens ; Immunosuppressive Agents ; Alemtuzumab (3A189DH42V) ; Basiliximab (9927MT646M) ; Daclizumab (CUJ2MVI71Y) ; thymoglobulin (D7RD81HE4W) ; Mycophenolic Acid (HU9DX48N0T)
Language	English
Publishing date	2019-08-09
Publishing country	United States
Document type	Comparative Study ; Journal Article
ZDB-ID	82046-5
ISSN	1873-2623 ; 0041-1345
ISSN (online)	1873-2623
ISSN	0041-1345
DOI	10.1016/j.transproceed.2019.04.059
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Article: Refining the Role of Simultaneous Liver Kidney Transplantation.

Hussain, Sabiha M / Sureshkumar, Kalathil K

Journal of clinical and translational hepatology

2018 Volume 6, Issue 3, Page(s) 289–295

Abstract: Adoption of the model for end-stage liver disease score by Organ Procurement and Transplant Network (OPTN) deceased donor liver allocation policy in 2002 has led to an increase in the number of simultaneous liver kidney (SLK) transplantation. Since ... ...

Abstract	Adoption of the model for end-stage liver disease score by Organ Procurement and Transplant Network (OPTN) deceased donor liver allocation policy in 2002 has led to an increase in the number of simultaneous liver kidney (SLK) transplantation. Since kidney function recovery following liver transplantation is difficult to predict, allocation of the kidney for SLK transplantation thus far has not been based on much rationale and evidence. Lack of OPTN policy towards SLK organ allocation has resulted in great variations among transplant centers regarding SLK transplantation. Increasing use of kidneys towards SLK transplantation diverts deceased donor kidneys away from candidates awaiting kidney-alone transplantation. Recently OPTN/United Network of Organ Sharing has implemented medical eligibility criteria for adult SLK transplantation which also includes a concept of safety net. Implementation of the new policy is a move in a positive direction, providing consistency in our practice and evidence-based guidelines in selecting candidates for SLK transplantation. This policy needs to be monitored prospectively and modified based on new data that will emerge over time. This review outlines the literature on SLK transplantation and efforts towards developing rational policy on SLK organ allocation.
Language	English
Publishing date	2018-06-08
Publishing country	China
Document type	Journal Article ; Review
ZDB-ID	3019822-7
ISSN	2310-8819 ; 2225-0719
ISSN (online)	2310-8819
ISSN	2225-0719
DOI	10.14218/JCTH.2017.00065
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Article: Kidney transplantation in older recipients: Preemptive high KDPI kidney

Chopra, Bhavna / Sureshkumar, Kalathil K

World journal of transplantation

2018 Volume 8, Issue 4, Page(s) 102–109

Abstract: Aim: To evaluate the outcomes of transplanting marginal kidneys preemptively compared to better-quality kidneys after varying dialysis vintage in older recipients.: Methods: Using OPTN/United Network for Organ Sharing database from 2001-2015, we ... ...

Abstract	Aim: To evaluate the outcomes of transplanting marginal kidneys preemptively compared to better-quality kidneys after varying dialysis vintage in older recipients. Methods: Using OPTN/United Network for Organ Sharing database from 2001-2015, we identified deceased donor kidney (DDK) transplant recipients > 60 years of age who either underwent preemptive transplantation of kidneys with kidney donor profile index (KDPI) ≥ 85% (marginal kidneys) or received kidneys with KDPI of 35%-84% (better quality kidneys that older wait-listed patients would likely receive if waited longer) after being on dialysis for either 1-4 or 4-8 years. Using a multivariate Cox model adjusting for donor, recipient and transplant related factors- overall and death-censored graft failure risks along with patient death risk of preemptive transplant recipients were compared to transplant recipients in the 1-4 and 4-8 year dialysis vintage groups.RESUTLSThe median follow up for the whole group was 37 mo (interquartile range of 57 mo). A total of 6110 DDK transplant recipients above the age of 60 years identified during the study period were found to be eligible to be included in the analysis. Among these patients 350 received preemptive transplantation of kidneys with KDPI ≥ 85. The remaining patients underwent transplantation of better quality kidneys with KDPI 35-84% after being on maintenance dialysis for either 1-4 years ( Conclusion: In summary, our study supports accepting a "marginal" quality high KDPI kidney preemptively in older wait-listed patients thus avoiding dialysis exposure.
Language	English
Publishing date	2018-08-18
Publishing country	United States
Document type	Journal Article
ISSN	2220-3230
ISSN	2220-3230
DOI	10.5500/wjt.v8.i4.102
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Article ; Online: Donor Ethnicity and Kidney Transplant Outcomes in African Americans.

Sureshkumar, Kalathil K / Nashar, Khaled / Chopra, Bhavna

Transplantation proceedings

2020 Volume 53, Issue 3, Page(s) 885–888

Abstract: Background: Transplantation of African American (AA) compared to non-AA donor kidneys is generally associated with inferior outcomes. It is unclear whether enhanced genetic risk associated with AA donor kidneys would be counterbalanced by favorable ... ...

Abstract	Background: Transplantation of African American (AA) compared to non-AA donor kidneys is generally associated with inferior outcomes. It is unclear whether enhanced genetic risk associated with AA donor kidneys would be counterbalanced by favorable immunologic matching when AA donor kidneys are transplanted into AA recipients. We aimed to compare the outcomes of AA vs non-AA deceased-donor kidneys (DDKs) stratified by kidney donor profile index (KDPI) that were transplanted into AA recipients. Methods: Using the Organ Procurement and Transplant Network/United Network for Organ Sharing database, we identified AA DDK recipients from 2000 to 2015 who received peri-operative induction followed by calcineurin inhibitor/mycophenolate mofetil maintenance. These patients were divided into 4 KDPI groups (0%-20%, 21%-50%, 51%-85%, and 86%-100%). Adjusted long-term graft and patient outcomes were compared between AA recipients of kidneys from AA vs non-AA donors in each KDPI category using a multivariable Cox model. Results: Among a total of 17,516 AA DDK transplant recipients, 3303 were in KDPI 0%-20% (AA donor = 239; non-AA donor = 3064), 5821 in KDPI 21%-50% (AA donor = 1414; non-AA donor = 4407), 6364 in KDPI 51%-85% (AA donor = 1619; non-AA donor = 4745), and 2028 in KDPI 86%-100% (AA donor = 932; non-AA donor = 1096) groups. Adjusted overall graft, death-censored graft, and patient survival were similar between AA recipients of AA vs non-AA donor kidneys across all KDPI groups. Discussion: Our study showed similar outcomes for transplanting AA vs non-AA deceased-donor kidneys into AA recipients despite the generally observed inferior outcomes associated with AA donor kidney transplantation.
MeSH term(s)	Adult ; African Americans/genetics ; Calcineurin Inhibitors/therapeutic use ; Databases, Factual ; Female ; Graft Survival/genetics ; Humans ; Kidney ; Kidney Failure, Chronic/ethnology ; Kidney Failure, Chronic/mortality ; Kidney Failure, Chronic/surgery ; Kidney Transplantation/methods ; Kidney Transplantation/mortality ; Male ; Middle Aged ; Mycophenolic Acid/therapeutic use ; Proportional Hazards Models ; Risk Factors ; Tissue Donors/statistics & numerical data ; Tissue and Organ Procurement/statistics & numerical data ; Treatment Outcome
Chemical Substances	Calcineurin Inhibitors ; Mycophenolic Acid (HU9DX48N0T)
Language	English
Publishing date	2020-09-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	82046-5
ISSN	1873-2623 ; 0041-1345
ISSN (online)	1873-2623
ISSN	0041-1345
DOI	10.1016/j.transproceed.2020.06.042
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Article ; Online: Does Induction Type Influence Outcomes in Kidney Transplant Recipients at Different Phases of Hepatitis B Infection?

Sureshkumar, Kalathil K / Chopra, Bhavna

Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation

2018 Volume 17, Issue 4, Page(s) 457–460

Abstract: Objectives: Immunosuppressive therapy in kidney transplant recipients with hepatitis B virus infection may increase the risk of disease progression. Here, we compared outcomes of depleting (antithymocyte globulin/alemtuzumab) versus nondepleting ( ... ...

Abstract	Objectives: Immunosuppressive therapy in kidney transplant recipients with hepatitis B virus infection may increase the risk of disease progression. Here, we compared outcomes of depleting (antithymocyte globulin/alemtuzumab) versus nondepleting (basiliximab/daclizumab) antibody induction in kidney transplant recipients at different serologic phases of hepatitis B virus infection. Materials and methods: We used the Organ Procurement and Transplantation Network/United Network for Organ Sharing database to identify adult kidney transplant recipients at different serologic phases of hepatitis B virus infection (transplants received from 2001-2011 after patients received perioperative induction with discharge on calcineurin inhibitors/mycophenolate mofetil with/without steroids). We used a Cox model to compare outcomes among patient groups. Results: Median follow-up was 50.7 months (range, 28.6 to 82.6 mo). Serologic phase for the 7681 study patients were as follows: 1098 at HBsAg+/anti-HBc- (depleting = 652, nondepleting = 446), 446 at HBsAg+/anti-HBc+ (depleting = 250, nondepleting = 216), and 6117 at HBsAg-/anti-HBc+ (depleting = 3562, nondepleting = 2555) (where anti-HBc denotes hepatitis B core antibody, HBsAg denotes hepatitis B surface antigen, and +/- denote positive/negative). When we compared those with depleting versus nondepleting agents, hazard ratios (95% confidence intervals) for adjusted overall graft, death-censored graft, and patient survival were 0.97 (0.78-1.26; P = .86), 1.20 (0.83-1.60; P = .44), and 0.92 (0.66-1.30; P = .51) in the HBsAg+/anti-HBc-; 0.81 (0.55-1.18; P = .27), 0.59 (0.32-1.12; P = .11), and 0.95 (0.60-1.49; P = .83) in the HBsAg+/anti-HBc+; and 0.96 (0.86-1.05; P = .37), 0.95 (0.60-1.49; P = .97), and 0.92 (0.80-1.05; P = 0.22) in the HBsAg-/anti-HBc+ groups. Conclusions: Our study did not show adverse graft and patient outcomes associated with depleting versus nondepleting antibody induction in kidney transplant recipients at different phases of hepatitis B virus infection. This supports the selection and use of induction agents based on immunologic risk in such patients.
MeSH term(s)	Adult ; Alemtuzumab/administration & dosage ; Alemtuzumab/adverse effects ; Antilymphocyte Serum/administration & dosage ; Antilymphocyte Serum/adverse effects ; Basiliximab/administration & dosage ; Basiliximab/adverse effects ; Clinical Decision-Making ; Daclizumab/administration & dosage ; Daclizumab/adverse effects ; Databases, Factual ; Disease Progression ; Drug Therapy, Combination ; Female ; Graft Rejection/immunology ; Graft Rejection/prevention & control ; Graft Survival/drug effects ; Hepatitis B/diagnosis ; Hepatitis B/immunology ; Hepatitis B/mortality ; Hepatitis B/virology ; Hepatitis B Antibodies/blood ; Hepatitis B Surface Antigens/blood ; Hepatitis B virus/drug effects ; Hepatitis B virus/immunology ; Humans ; Immunocompromised Host ; Immunosuppressive Agents/administration & dosage ; Immunosuppressive Agents/adverse effects ; Kidney Transplantation/adverse effects ; Kidney Transplantation/mortality ; Male ; Middle Aged ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Time Factors ; Treatment Outcome ; Young Adult
Chemical Substances	Antilymphocyte Serum ; Hepatitis B Antibodies ; Hepatitis B Surface Antigens ; Immunosuppressive Agents ; Alemtuzumab (3A189DH42V) ; Basiliximab (9927MT646M) ; Daclizumab (CUJ2MVI71Y)
Language	English
Publishing date	2018-07-31
Publishing country	Turkey
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2396778-X
ISSN	2146-8427 ; 1304-0855
ISSN (online)	2146-8427
ISSN	1304-0855
DOI	10.6002/ect.2017.0286
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