About

Paige Cunningham is associated with the Bronfenbrenner Center for Translational Research at Cornell University. The center assists faculty in developing translational research projects by providing support such as proposal preparation assistance, training, technical support, and facilitating collaborative relationships. The center offers various events including workshops on translational research, an intensive summer institute, and talks on current research topics. Its mission is to support research that bridges scientific findings with practical applications, fostering innovative approaches in the field of human ecology.

Research topics

• Immunology
• Biology
• Cell biology
• Internal medicine
• Medicine
• Urology
• Gastroenterology
• Surgery

Selected publications

• Outcomes of Simultaneous Kidney and Pancreas Transplantation in Patients with Type 2 Diabetes Mellitus: A Single-Center Experience

  American Journal of Transplantation · 2025-08-01 · 1 citations

  articleOpen access
  PublisherOA PDFDOI

• Histopathology of Delayed Graft Function in Early Posttransplant Kidney Biopsies

  American Journal of Transplantation · 2025-08-01

  articleOpen access
  PublisherOA PDFDOI

• Efficacy and Safety of Bleselumab in Preventing the Recurrence of Primary Focal Segmental Glomerulosclerosis in Kidney Transplant Recipients: A Phase 2a, Randomized, Multicenter Study

  Transplantation · 2024 · 12 citations

  • Medicine
  • Internal medicine
  • Urology

  BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage kidney disease and frequently recurs after kidney transplantation. Recurrent FSGS (rFSGS) is associated with poor allograft and patient outcomes. Bleselumab, a fully human immunoglobulin G4 anti-CD40 antagonistic monoclonal antibody, disrupts CD40-related processes in FSGS, potentially preventing rFSGS. METHODS: A phase 2a, randomized, multicenter, open-label study of adult recipients (aged ≥18 y) of a living or deceased donor kidney transplant with a history of biopsy-proven primary FSGS. The study assessed the efficacy of bleselumab combined with tacrolimus and corticosteroids as maintenance immunosuppression in the prevention of rFSGS >12 mo posttransplantation, versus standard of care (SOC) comprising tacrolimus, mycophenolate mofetil, and corticosteroids. All patients received basiliximab induction. The primary endpoint was rFSGS, defined as proteinuria (protein-creatinine ratio ≥3.0 g/g) with death, graft loss, or loss to follow-up imputed as rFSGS, through 3 mo posttransplant. RESULTS: Sixty-three patients were followed for 12 mo posttransplantation. Relative decrease in rFSGS occurrence through 3 mo with bleselumab versus SOC was 40.7% (95% confidence interval, -89.8 to 26.8; P = 0.37; absolute decrease 12.7% [95% confidence interval, -34.5 to 9.0]). Central-blinded biopsy review found relative (absolute) decreases in rFSGS of 10.9% (3.9%), 17.0% (6.2%), and 20.5% (7.5%) at 3, 6, and 12 mo posttransplant, respectively; these differences were not statistically significant. Adverse events were similar for both treatments. No deaths occurred during the study. CONCLUSIONS: In at-risk kidney transplant recipients, bleselumab numerically reduced proteinuria occurrence versus SOC, but no notable difference in occurrence of biopsy-proven rFSGS was observed.

  PublisherDOI

• Systemic Thrombotic Microangiopathy Induced by Antibody-Mediated Rejection in a Highly Sensitized Kidney Transplant Recipient

  Journal of the American Society of Nephrology · 2024-10-01

  article

  Introduction: Atypical HUS (aHUS) is a form of thrombotic microangiopathy (TMA), which is defined by thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury. aHUS is caused by uncontrolled activation of the alternative pathway of the complement cascade, and can be due to a variety of causes, such as genetic defects in complement related factors or acquired autoantibodies to complement regulators. Here we present a unique case of aHUS post kidney transplant in a highly sensitized recipient. Case Description: A 38 year old female with history of ESRD secondary to bilateral ureteral reflux disease, presented for deceased donor kidney transplantation. The patient was highly sensitized with panel reactive antibody of 100% due to history of blood transfusions and pregnancy. She underwent desensitization while on the waiting list with eight sessions of plasmapheresis and replacement IVIG. This resulted in a flow negative T and B cell crossmatch kidney transplant offer with pre-existing class I and II donor specific HLA antibodies (DSAs). On post-operative day 1, she developed acute kidney injury, acute anemia, thrombocytopenia, and schistocytes were found on the blood smear. Additional labs showed low C3, elevated LDH, and undetectable haptoglobin level. ADAMTS13 functional assay was 54%. aHUS was suspected, and patient was immediately started on eculizumab. Subsequent kidney biopsy showed evidence of microangiopathy with focal C4d positivity. Hematologic markers improved within 24-48 hours after initiation of eculizumab, as did renal function. Follow up genetic testing revealed homozygous CFHR1 deletion. Discussion: This case illustrates an early development of acute antibody mediated rejection manifested as systemic TMA post kidney transplantation. This process was likely triggered by the presence of DSAs in the setting of homozygous CFHR1 deletion, and promptly responded to eculizumab. This case supports the use of pre-transplant genetic testing to stratify patients who are at high risk for developing post-transplant TMA, and such can help guide the decision-making process of peri-operative use of eculizumab.

  PublisherDOI

• P.482: Advantages of simultaneous kidney and pancreas transplantation in selected patients with type 2 Diabetes Mellitus: A single-center study.

  Transplantation · 2024-09-01

  article

  Objective: While simultaneous pancreas and kidney transplantation (SPK) is well-established for patients with end-stage renal disease (ESRD) and type 1 diabetes mellitus (T1DM), its efficacy in patients with type 2 diabetes mellitus (T2DM) remains less clear as the selection criteria allowing for favorable outcomes are not well established. This study aims to evaluate the outcomes of SPK in patients with T2DM at our institution. Methods: Nineteen patients with T2DM and chronic kidney disease (CKD) were included in this study. Demographic and clinical data were collected, and SPK procedures were performed according to standard protocols with systemic venous and enteric duodenal drainage. Postoperative outcomes, including graft function and complications, were assessed. Patients were followed up to 4 years post-transplantation. Results: They were 14 men and 5 females in median age of 47 (32-60). Most of the patients required hemodialysis -74%, or peritoneal dialysis- 21%. The median BMI was 26 (19-33), weight 81kg (51-102), fasting c- peptide 1.93pmol/ml (0.21-6.46), and HbA1c 7.2 (5.4-14.6). Median insulin requirements were 33 units per day (4-80). The median length of hospital stay was 11 days (8-25). Pancreas graft thrombosis requiring surgical excision occurred in 10% of patients. Additional complications, such as bleeding or abscess, necessitated re-laparotomy in 16% of patients. More than half of the patients experienced complications requiring hospital readmission. However, all patients who maintained pancreas graft function showed improvement in blood glucose control, with none requiring chronic insulin therapy post-surgery. HbA1c dropped after transplanttion in 81% of patients to median 5.5 (4.7-7.1) and increased up to 6.1- 6.5 in remaining 19% of patients. Fasting c-peptide increased in 70%, and decreased in 30% of patients. Kidney graft function remained stable in all patients, with no instances of delayed graft function or graft loss. Moreover, the waiting time for SPK was significantly shorter than that for kidney transplantation alone in our region: 80% of patients waited less than 3 years, 63% less than 2 years and 26% less than one 1 year. Conclusion: Simultaneous pancreas and kidney transplantation in patients with T2DM offers several benefits, including expedited access to high-quality kidney grafts, improved long-term blood glucose control without the need for insulin therapy, and preservation of kidney graft function. However, this approach is associated with an increased risk of complications than a kidney transplant alone, necessitating more frequent hospital readmission and reoperation.

  PublisherDOI

• Acute Kidney Injury in Coronavirus Disease and Association with Thrombosis

  American Journal of Nephrology · 2023-01-01 · 2 citations

  article

  Introduction: Coronavirus disease (COVID-19) is a global pandemic which continues to cause systemic inflammation, leading to multi-system organ damage including acute kidney injury (AKI) and thrombotic complications. We hypothesize that D-dimer level predicts an increased risk of AKI and thrombotic complications in COVID-19. Methods: This was a retrospective cohort study performed at a single-center academic center. Patients hospitalized with COVID-19 between January 1, 2020, and January 1, 2021, were included in the analysis. Demographics and associated medical records were reviewed from the electronic medical record. Statistical analysis was done to determine the incidence of AKI and thrombosis and if D-dimer was predictive of an adverse event. Results: The study included 389 patients with the diagnosis of COVID-19 who were hospitalized. AKI was evident in 143 patients with 59 experiencing a thrombotic event. Factors associated with AKI included age, chronic kidney disease, proteinuria, use of outpatient angiotensin-blocking medications, and D-dimer greater than 1.75 (p < 0.05). Factors associated with thrombosis included use of outpatient anticoagulants, elevated WBC, interleukin-6 (IL-6), and D-dimer greater than 1.75 (p < 0.05). When D-dimer was dichotomized at the median value for the entire dataset (value greater than 1.75), there was good discrimination for AKI and very good discrimination for thrombosis. Conclusions: Complications of acute renal failure and thrombosis are common in patients presenting with COVID-19. D-dimer was found to be predictive of both. Future studies to validate the association of these two events in patients presenting with COVID-19 are warranted as early treatment with antithrombotic agents may have a role in preventing adverse sequelae and outcomes.

  PublisherDOI

• Collapsing Focal Segmental Glomerulosclerosis Complicating BK Allograft Nephropathy in a Heart-Kidney Transplant Recipient

  Journal of the American Society of Nephrology · 2022-11-01

  articleSenior author
  PublisherDOI

• Innate-like self-reactive B cells infiltrate human renal allografts during transplant rejection

  Nature Communications · 2021 · 55 citations

  • Immunology
  • Biology
  • Cell biology

  Intrarenal B cells in human renal allografts indicate transplant recipients with a poor prognosis, but how these cells contribute to rejection is unclear. Here we show using single-cell RNA sequencing that intrarenal class-switched B cells have an innate cell transcriptional state resembling mouse peritoneal B1 or B-innate (Bin) cells. Antibodies generated by Bin cells do not bind donor-specific antigens nor are they enriched for reactivity to ubiquitously expressed self-antigens. Rather, Bin cells frequently express antibodies reactive with either renal-specific or inflammation-associated antigens. Furthermore, local antigens can drive Bin cell proliferation and differentiation into plasma cells expressing self-reactive antibodies. These data show a mechanism of human inflammation in which a breach in organ-restricted tolerance by infiltrating innate-like B cells drives local tissue destruction.

  PublisherOA PDFDOI

• Intrarenal B cells integrate <i>in situ</i> innate and adaptive immunity in human renal allograft rejection

  bioRxiv (Cold Spring Harbor Laboratory) · 2020 · 1 citations

  • Biology
  • Immunology
  • Cell biology

  Abstract In human allograft rejection, intrarenal B cell infiltrates identify those with a poor prognosis. However, how intrarenal B cells contribute to rejection is not known. Single cell RNA-sequencing of intrarenal class-switched B cells revealed a unique innate cell transcriptional state resembling murine peritoneal B1 cells (Bin cells). Comparison to the transcriptome of whole renal allograft rejecting tissue revealed that Bin cells existed within a complex autocrine and paracrine network of signaling axes. The immunoglobulins expressed by Bin cells did not bind donor specific antigens nor were they enriched for reactivity to ubiquitously expressed self-antigens. Rather, Bin cells frequently expressed antibodies reactive with renal expressed antigens. Furthermore, local antigens could drive Bin cell proliferation and differentiation into plasma cells expressing self-reactive antibodies. By contributing to local innate immune networks, and expressing antibodies reactive with renal expressed antigens, Bin cells are predicted to amplify local inflammation and tissue destruction.

  PublisherOA PDFDOI

• The Future of Pharmacogenetics in the Treatment of Hypertension

  Pharmacogenomics · 2019-02-01 · 18 citations

  editorialOpen access1st authorCorresponding

  a streamlined pharmacogenomic approach to get hypertensive patients on the most effective, efficient and well-tolerated drug regimen would be enormously worthwhile.

  PublisherOA PDFDOI

Recent grants

• NIH Grant K08DK061375

  NIH · $628k · 2007

• Endothelial Injury in Endotoxin-Induced Acute Renal Failure

  NIH · $1.7M · 2010–2015

Frequent coauthors

• Richard J. Quigg

  University at Buffalo, State University of New York

  30 shared

• Gerard J. Hickey

  19 shared

• Jessy J. Alexander

  University at Buffalo, State University of New York

  19 shared

• R G Smith

  Scripps Research Institute

  19 shared

• Ching-Hsin Chang

  National Yang Ming Chiao Tung University

  17 shared

• Susan Nicolich

  Merck & Co., Inc., Rahway, NJ, USA (United States)

  17 shared

• Eric L. Rickes

  Département Santé Animale

  17 shared

• Lesley A. McNamara

  National Cancer Institute

  16 shared

Education

• B.S., Psychology

  Yale University

• Ph.D., Nutritional Sciences

  The Pennsylvania State University

Awards & honors

• The Obesity Society
• Society for the Study of Ingestive Behavior