Research & Innovations

Overview

The Glickman Urological & Kidney Institute conducts a robust research program that fosters a culture of innovation and collaboration. Physicians and scientists within the institute work closely with colleagues in the Lerner Research Institute, the basic science research arm of Cleveland Clinic, pursuing laboratory-based and clinical research as well as translational research that applies laboratory findings to improve patient care.

Cleveland Clinic patients benefit from the latest treatment modalities in kidney medicine and urology, where scientists and clinicians working together continue to advance innovations and accelerate the process of bringing novel therapeutic agents from the laboratory to the bedside.

Research & News

Publications & ConsultQD

Glickman Urological & Kidney Institute publications provide information about the latest developments and treatment options in kidney medicine and urology.
Consult QD - Urology & Nephrology. Get the latest insights and perspectives from Cleveland Clinic clinicians and researchers on innovations, research, technology, patient care and treatment.
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Research

Glickman Urological & Kidney Institute works in close collaboration with Cleveland Clinic Lerner Research Institute to offer clinical trials and the latest research outcomes.

Learn more about our research and outcomes:

Research Labs

Urology and Kidney Medicine Research Labs

Center for Genitourinary (GU) Malignancies Research
Novick Center for Clinical and Translational Research
Department of Cellular and Molecular Medicine
Genomic Medicine Laboratory
Center for Pelvic Medicine and Surgery Laboratories
Kidney Precision Medicine Center
Minimally Invasive and Robotic Research Laboratory
Center for Pelvic Medicine and Surgery Laboratories
Center of Excellence in Prostate Cancer Research
Renal Carcinoma Immunology Laboratory
Center for Reproductive Medicine
Translational Stones Laboratory
Transplant Immunology Laboratory

Center for Genitourinary (GU) Malignancies Research

The Center for Genitourinary (GU) Malignancies Research focuses on advancing discoveries to better understand, diagnose and treat cancer of the prostate, bladder and kidney. The center is a cross-institute partnership with members from the Lerner Research Institute, Taussig Cancer Institute and Glickman Urological & Kidney Institute to leverage clinical strengths and patients from all backgrounds for translational and clinical studies.

The center is led by Nima Sharifi, MD, who holds appointments in all three institutes. Dr. Sharifi is an expert in cancer endocrinology and metabolism, specifically prostate cancer. He has published landmark studies linking a specific genetic variant to a deadly form of advanced prostate cancer. The work has won him numerous awards, including the national Top 10 Clinical Achievement Award from the Clinical Research Forum. He is a member of the Association of American Physicians and was elected a fellow of the American Association for the Advancement of Science. He also holds the Kendrick Family Endowed Chair for Prostate Cancer Research.

The overarching goal of the center is to make practice-changing discoveries in GU cancer. Combining the expertise of our medical oncologists, urologists, pathologists and radiation oncologists with disease-focused basic scientists will help us to rapidly bring transformative changes to clinical practice at Cleveland Clinic and around the world.

The Novick Center for Clinical and Translational Research

The center supports the research efforts of all members of the Glickman Urological & Kidney Institute. The center is headed by John Sedor, MD. Basic research studies are predominantly focused in the areas of transplantation biology, renal epithelial cell biology, urologic oncology, andrology and bladder physiology. Renal cell carcinoma and prostate cancer are the two urologic malignancies being extensively studied. The emphasis within the Center is on translational research studies that can enhance our understanding of the pathogenesis, presentation, and management of urologic diseases. All urology residents spend a full year training in one of these research laboratories; the period of research training for postgraduate urology fellows is two or three years. Members of the Center meet monthly for research presentations. In addition, research residents meet weekly to present data and for didactic lectures on research topics such as statistics, study design, scientific writing and grantsmanship. The Novick Center for Clinical and Translational Research manages a number of clinical trials and disease-specific databases that serve as a source for clinical projects and outcomes reporting. Biostatistical support is provided through the Department of Quantitative Health Sciences Center and personnel frequently collaborate with scientists in Cleveland Clinic’s Lerner Research Institute.

Department of Cellular and Molecular Medicine

This lab, headed by Byron Lee, MD, PhD, focuses on understanding the effects of chromatin modifier gene mutations in bladder cancer initiation, progression, and response to therapy.

Genomic Medicine Laboratory

Angela Ting, PhD, and her team focus on the study of epigenetic mechanisms in human diseases, focusing on prostate and colon cancer. Epigenetic gene regulation is important for both normal development and disease states. In cancers, aberrant promoter CpG island hypermethylation correlates highly with gene inactivation and can account for lack of gene expression where mutations do not exist. The lab is interested in dissecting the mechanisms of epigenetic gene silencing and understanding the functional relevance of DNA methylation in diseases.

Kidney Precision Medicine Center

The center’s mission is to conduct research that improves the lives of patients with kidney diseases. By collecting and integrating detailed demographic, clinical, radiographic, histologic and molecular phenotypes, it is possible to generate better patient outcomes and quality of life and drive discovery of mechanisms, new therapeutic targets and predictive tools for CKD risk. The center is run by John Sedor, MD.

Minimally Invasive and Robotic Research Laboratory

Headed by Jihad Kaouk, MD, this lab was created in partnership with the Department of Biomedical Engineering centers on novel approaches to automating robotic surgery. The lab includes experts in the development of innovative surgical techniques and is a leader in kidney ablative therapies research.

Center for Pelvic Medicine and Surgery Laboratories

Led by Margot Damaser, PhD, this laboratory researches the causes and potential therapies for urinary incontinence and voiding dysfunction, as well as other pelvic floor disorders, with a particular focus on solutions from regenerative medicine and device development.

Center of Excellence in Prostate Cancer Research

The laboratory's research focus is on understanding the biology of abnormal prostate growth and to identify how intratumoral androgen synthesis governs androgen receptor gain-of-function in castration-resistant prostate cancer.

Renal Carcinoma Immunology Laboratory

Led by Claudia Marcela Diaz-Montero, PhD, the overall goal of this laboratory research effort is to understand how renal tumors can inhibit the development of an effective anti-tumor immune response. Findings suggest that tumors secrete inflammatory factors that affect the normal production of myeloid cells by the bone marrow, resulting in the accumulation of an aberrant cell type known as MDSCs which can promote tumor growth by suppressing immune responses and promoting angiogenesis. One major, ongoing project involves defining how inflammation within tumors affects the recruitment and function of MDSCs, and includes elucidating how the products of specific cellular components of the tumor microenvironment, such as fibroblasts and endothelial cells, contribute to those processes. Additional studies focus on determining the impact of inflammation-driven accumulation of MDSCs on the response to immunotherapy against kidney cancer.

Translational Stones Laboratory

Aaron Miller, PhD, is the head of this lab which employs multi-omics and bioinformatic approaches to understand how the microbiome facilitates or inhibits urinary stone disease, using in vitro models, animal models, and clinical studies. The goal of this research program is to develop a suite of bacteriotherapies designed to inhibit recurrent episodes of urinary stone disease.

Transplant Immunology Laboratory

Headed by Robert Fairchild, PhD, this lab focuses on mechanisms of immune-mediated injury to solid organ allografts. The focus of the first laboratory is inflammatory factors directing T cells and other leukocytes into renal allografts. Current projects are investigating: 1) the expression of inflammatory genes during ischemia and reperfusion of kidneys during urology transplantation and in mouse models; 2) the expression of inflammatory genes and proteins in urine as markers indicating the presence of rejection in renal allografts; and 3) the role of adhesion molecules and chemokines in directing leukocyte infiltration into organ allografts. The second laboratory continues to focus attention on transplantation immunobiology in mouse models and translational studies of human immunology in transplant recipients. The animal studies provided new and important information on the role of memory T cells as barriers to transplant tolerance. The team additionally identified a new effector pathway for alloreactive T cells.

Kidney Medicine Research

The following are active NIH-funded studies.

COPE-AKI: Caring for OutPatiEnts after Acute Kidney Injury (COPE-AKI), Drs. A. Huml, S. Demirjian, E. Poggio, B. Hu, E. Pfoh, B. Udeh
Summary: Acute kidney injury (AKI) is associated with high morbidity, risk of chronic kidney disease (CKD), end-stage kidney disease (ESKD), cardiovascular disease, and mortality. There is limited evidence to inform recommendations for processes of care or therapeutic interventions targeting progression of kidney disease and the associated morbidity and mortality in AKI survivors. Cleveland Clinic is 1 of 3 Clinical Centers that will develop and test interventions that aim to reduce morbidity compared with usual care in Stage 2 and 3 AKI survivors.
CRIC/Chronic Renal Insufficiency Cohort Study, Drs. J. Taliercio, H. Rincon, G. Thomas
Summary: The Chronic Renal Insufficiency Cohort (CRIC) Study is a longitudinal observational study of 5,500 CKD patients originally aimed to study novel predictors of CKD progression and to elucidate the risk and manifestations of cardiovascular disease. The study has become a national resource for investigation of a broad spectrum of CKD-related topics, promoting many young investigators, and fostered international collaborations focused on understanding the global burden of CKD.
Kidney Precision Medicine Project (KPMP), Drs. J. O'Toole, E. Poggio, J. Taliercio, J. Sedor, C. O’Malley, C. Gadegbeku, J. Schold, L. Herlitz
Summary: The Kidney Precision Medicine Project (KPMP) is a prospective cohort study, whose goal is to use deep molecular phenotypes of kidney biopsies, along with longitudinally collected clinical phenotypic data, in order to develop new disease ontologies, classification systems, and treatments for acute kidney injury (AKI) and chronic kidney disease (CKD).
APOL 1 Studies in Kidney Transplant (ASK-CCC) and APOL1 Long-term Kidney Transplantation Outcomes Network, Drs. E. Poggio, N. Agrawal
Summary: This study is being done in an attempt to improve outcomes after kidney transplantation and to improve the safety of living kidney donation based upon variation in the apolipoprotein L1 gene (APOL1).

The following are active Cleveland Clinic Philanthropy Institute-funded studies.

Acceleration of Referral for Kidney Transplant Through an Automated Process, A. Huml, J. Schold
Summary: Developing a care process to identify patients early, in CKD clinics, and automate referrals for kidney transplant evaluation for patients who are eligible prior to starting dialysis. By expediting their care, patients will have higher chances of placement on the kidney transplant waiting list and receiving a transplant. Within this care process, we will track patient progress through a multi-step evaluation to understand barriers to completing the steps for a transplant. Lastly, we will understand how barriers differ between patients with different demographic characteristics. By doing this, we can develop services to support patients through the process and become successful candidates for wait listing.

The following clinical trials are currently enrolling in Kidney Transplant

ASSESSMENT OF BIOMARKER-GUIDED CNI SUBSTITUTION IN KIDNEY TRANSPLANTATION (ABCs Trial) Dr. E. Poggio Summary: multi-center, observational study of 800 kidney transplant recipients at clinically low risk for alloimmune memory (DSAnegative pre-kidney transplant) who are initiated on SOC therapy will be used to satisfy the FDA requirement to prospectively evaluate the HLA mMM score as a prognostic biomarker for post-kidney transplant outcomes in a real world cohort.42 Donor-recipient HLA-DR/DQ mMM score will be determined at enrollment and recipients will be followed over 24 months post-kidney transplant for primary alloimmune events(i.e. TCMR, DSA, and ABMR).
A multi-center, prospective, adaptive subject enrollment, and specimen collection protocol in support of the clinical utility of the One Lambda Exosomes Assay DR. E. Poggio Summary: this study is to provide urine specimen(s) from subjects who have received a kidney or kidney plus another organ transplant from a related or unrelated, living or deceased donor and who would either normally be referred for a tissue biopsy by a healthcare provider for “for cause” biopsy due to clinical indications of allograft rejection, for surveillance protocol biopsy that are performed at pre-defined intervals post-transplant, regardless of graft dysfunction, or at timepoints defined by the Sponsor without biopsy for the clinical utility evaluations of the One Lambda Exosomes Assay .
A Double-Blind, Placebo-Controlled, Multicenter, Randomized Phase 3 Trial Evaluating the Efficacy and Safety of Felzartamab in Kidney Transplant Recipients with Late Antibody-Mediated Rejection (AMR) (TRANSCEND) Dr. E.Poggio Summary: Participants with active AMR or chronic active AMR at least 6 months after kidney transplant. The Intent-to-Treat (ITT) Analysis Set will be the primary population for efficacy evaluation.
Pilot study to evaluate the correlation between urinary gene expression profile testing, tissue-based gene expression profiling, donor-derived cell-free DNA, and histopathology among high-risk kidney transplant recipients Dr. Z. Zaky Summary: to evaluate the performance of urinary Gene expression profile (GEP), Donor-derived cell-free DNA (ddcfDNA), Molecular Microscope Diagnostic System (MMDx), and histopathology with respect to their ability to accurately diagnose various types of injury, inclusive of early cellular and humoral rejection, against ddcfDNA when confirmed by histopathology andMMDx
Combination use of dd-cfDNA and gene expression profile OmniGraf™ in Multi-Organ Transplant Rejection Detection Dr. Z. ZakySummary: The purpose of this study is to determine the appropriate cut off values for OmniGraf™ when used in a dual transplant situation, and to evaluate the diagnostic capability of OmniGraf™ to detect rejection in these patients.
Immune monitoring and prediction of allograft injury using biomarkers in kidney transplant recipients with malignancy receiving immune checkpoint inhibitors. DR. I. Owoyemi Summary: patients with kidney transplantation who develop incurable locally advanced or metastatic cancer that has progressed despite first line standard therapy will be enrolled into this pilot study. The patients will receive immune checkpoint inhibitors as per the approved label. They will be monitored closely for signs of early rejection and for evidence of safety/toxicity and anti-tumor effect. The immune checkpoint inhibitors will continue with ongoing evidence of stable kidney function and tumor response.

The following clinical trials are currently enrolling General Kidney Medicine

A Phase 2/3 Adaptive, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of VX-147 in Subjects Aged 18 Years & Older with APOL1-mediated Proteinuric Kidney Disease (VX21-147-301), Dr. J. Sedor and Dr. J. O’Toole
Summary: This study is an adaptive Phase 2/3 study of VX-147 in subjects with APOL1-mediated proteinuric kidney disease that is designed to select a dose of VX-147 and establish the efficacy & safety of the selected dose. Subjects, investigators, and the sponsor will be blinded to treatment assignments in Phase 2 and Phase 3. In Phase 2, approximately 66 subjects will be randomized 1:1:1 to receive VX-147 15mg daily, VX-147 45mg daily or placebo on a background of standard of care. Phase 2 completes the Week 12 visit. Approximately 400 subjects are planned to be enrolled in Phase 3. Study will last for about 4 years overall.
Efficacy of Belimumab and Rituximab Compared to Rituximab Alone for the Treatment of primary Membranous Nephropathy (REBOOT), Dr. J. Sedor and Dr. J. O’Toole
Summary: This trial is a two-part study (Part A and Part B) of adults with primary membranous nephropathy, ages 18-75 inclusive. Part A is an open-label, PK phase to compare belimumab exposure between participants who have low proteinuria (> or = 4 to < 8 g/day) and high proteinuria (< or = 8 g/day). Part B is a prospective, randomized, phase II, double-blind, placebo-controlled trial in adults with primary MN. The total duration of study participation for Part A & B is 156 weeks. Study participation is divided into two phases: study treatment phase from weeks 0-52, and post-treatment observation period from after week 52 to week 156.
A phase 3, randomized, double-blind, placebo-controlled study of BION-1301 in adults with IgA Nephropathy (The Beyond Study) Dr. J. Sedor Summary: Adults with primary immunoglobulin A nephropathy (IgAN) at risk of progressive kidney function loss. Randomization is stratified by region (Asia vs. all other regions), Baseline proteinuria (≥ 2 g/day vs. < 2 g/day), and eGFR (≤ 45 mL/min/1.73m2 vs. > 45 mL/min/1.73m2). A target of approximately 272 subjects with eGFR ≥ 30 mL/min/1.73m2 at Screening will be randomized 1:1 to receive BION-1301 600 mg Q2W or a matched placebo for 104 weeks.
Studies of Heart & Kidney Protection with BI 690517 in combination with empagliflozin: A multicenter, international, randomized, double-blind, placebo-controlled clinical trial of the aldosterone synthase inhibitor BI 690517 in combination with empagliflozin in patients with chronic kidney disease (EASi-KIDNEY) Dr. G. Thomas Summary:trial will compare BI 690517 10mg once daily versus matching placebo, given in addition to empagliflozin 10mg once daily, in about 11,000 participants with established CKD.
An Open-Label Phase 2 Study to Evaluate the Safety, Tolerability, and Effect on Albuminuria of MZE829 in Adults with Proteinuric Chronic Kidney Disease and the APOL1 High Risk Genotype (MAZE) Dr. CGadegbekuSummary: Adults aged 18 to 65 years with proteinuric chronic kidney disease (CKD) and the APOL1 high risk genotype, or APOL1 Kidney Disease (AKD). The study with MZE829 in will consist of 2 cohorts comprised of approximately 28-34 participants. Cohort 1 will be comprised of participants with the APOL1 high risk genotype, proteinuric kidney disease and concurrent diabetes. Cohort 2 will be comprised of participants with the APOL1 high risk genotype, proteinuric kidney disease and without concurrent diabetes.
Establishment of ProNephro AKITM (NGAL) Cut off Value for Risk Assessment of Moderate to Severe Acute Kidney Injury in Adults (EPACRA- AKI) Dr. S. DemirjianSummary: observational, non-interventional study, to determine actionable cut-off(s) for ProNephro AKITM (NGAL) assay to predict patients at risk for AKI in the general adult ICU population and subgroups of particular interest, such as sepsis or cardiac surgery patients.
An adaptive, randomized, double-blind, dose exploration, parallel group, placebo-controlled, multicenter phase 2 trial to evaluate the efficacy, safety and tolerability of LNP023 in combination with standard-of-care with and without oral corticosteroids in adult patients with active lupus nephritis Class III-IV, +/- V Dr. L. Ferreira-Provenzano Summary: two-part study is to evaluate the efficacy, safety and tolerability of iptacopan (LNP023) in addition to mycophenolate mofetil/mycophenolate sodium (MMF/MPS) immunosuppressive treatment both in combination with and as an alternative to a tapering corticosteroid regimen in patients with active lupus nephritis (LN) Class III or IV, with or without co-existing class V features.