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.
• Email GUKI@ccf.org to be added to our eNewsletter for Urology or Kidney Medicine. 

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:

• Gadolinium-Induced Nephrogenic Systemic Fibrosis: Classification, Risk and Guidelines
• Contrast-Induced Acute Kidney Injury: The Data and the Debate
• Long-Term Successes in Kidney Transplantation

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 a diverse patient population 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.

Nephrology & Hypertension Research

Active NIH Funded Studies (Open)

Sprint EHR/SPRINT Electronic Health Record

George Thomas, MD

Ancillary Study Merging SPRINT data with EHR data to assess the effect of standard versus intense BP targets on hospital AKI using the gold standard – change in creatinine. We will utilize SPRINT and EHR creatinine values to assess the effect of standard versus intense BP targets on the incidence of outpatient AKI and the impact of outpatient AKI on adverse cardiovascular and renal outcomes. The concordance between EHR and SPRINT data regarding renal outcomes will also be assessed. Finally, we will evaluate the effect of standard versus intense BP targets on long term, post-trial renal outcomes by extracting EHR data during the fourth year of the proposed study (approximately 2020).

SPRINT ASK (Alzheimer’s, Seniors and Kidneys)/Systolic Blood Pressure Intervention Trial

George Thomas, MD

The SPRINT-ASK protocol is a follow up study to IRB 10-915: Systolic Blood Pressure Intervention Trial (SPRINT). The SPRINT-ASK trial will conduct one additional in-person follow-up visit approximately 12-18 months after the date of the participant’s SPRINT closeout visit. SPRINT-ASK will test for differences, after 4-6 years of follow-up, in (1) the incidence of adjudicated all-cause dementia and (2) adjudicated mild cognitive impairment (MCI) between participants randomized to standard versus intensive treatment arms of the SPRINT trial. SPRINT-ASK will also compare the long term trajectories of eGFR and urinary albumin-creatinine ratio in the two arms of the SPRINT trial. The clinic visit will focus on cognitive assessments, collection of blood and urine samples, and measurement of BP. 36 patients were enrolled in the SPRINT-ASK trial. The trial is closed to further enrollment. The only ongoing research activity is data analysis, being performed at the Central Coordinating hub (Wake Forest).

CTOT 19/Randomized Controlled Trial of Infliximab (Remicade®) Induction Therapy For Deceased Donor Kidney Transplant Recipients

Emilio Poggio, MD

This is a phase II, multicenter, randomized, double blind, and placebo-controlled, two-arm study of 300 deceased donor kidney transplant recipients randomized 1:1 to the experimental and control arms (150 patients per arm). The objective of the study is to determine the efficacy of intravenous infliximab administered at the time of transplantation, prior to reperfusion, on 2-year kidney transplant survival and function. Subjects in the control arm will be treated with rATG plus placebo (sterile normal saline) induction followed by tacrolimus, mycophenolate mofetil (MMF) or mycophenolic acid (MPA), and corticosteroids. Subjects in the experimental arm will receive infliximab plus rATG induction followed by tacrolimus, mycophenolate mofetil (MMF) or mycophenolic acid (MPA), and corticosteroids.

CRIC/Chronic Renal Insufficiency Cohort Study

Jonathan Taliercio, DO

The Chronic Renal Insufficiency Cohort (CRIC) Study is a United States multicenter, prospective study of racially and ethnically diverse patients with CKD.  The study enrolled adults aged 21 to 74 years with a broad spectrum of kidney disease stages, half of whom were diagnosed with diabetes mellitus. Subjects underwent extensive clinical evaluation at baseline, annual clinic visits, and via telephone at 6 month intervals. Data on quality of life, dietary assessment, physical activity, health behaviors, depression, cognitive function, health care resource utilization, as well as blood and urine specimens were collected for future genetic analysis. Measures of kidney function and occurrence of new and worsening CVD are the primary outcomes, among others. Although the original aims of the study were to identify novel predictors of CKD progression and to elucidate the risk and manifestations of cardiovascular disease among the > 5,500 participants with CKD, the CRIC Study has evolved into a national resource for investigation of a broad spectrum of CKD-related topics. The study has produced >120 published scientific articles, promoted many young investigative careers in nephrology, and fostered international collaborations focused on understanding the global burden of CKD. 

Cleveland CRIC-KPMP/Chronic Renal Insufficiency Cohort Study- Kidney Precision Medicine Project

Jonathan Taliercio, DO

The Chronic Renal Insufficiency Cohort (CRIC) Study is a longitudinal observational study of CKD patients who have extensive clinical phenotypes and associated cardiovascular and metabolic co-morbidities with longitudinal biosamples. The Kidney Precision Medicine Project (KPMP) is a NIDDK initiative charged with developing detailed molecular phenotypes of research kidney biopsies of participants with diabetic and hypertension attributed chronic kidney disease. The Cleveland CRIC –KPMP is recruiting CRIC participants from Cleveland Clinic, University Hospital and MetroHealth Medical Center to undergo research kidney biopsies using KPMP protocols; thereby, combining the strengths of each of these two landmark trials. Integrating clinical and molecular phenotyping, datasharing, and collaboration between these two trials will help lead to new discoveries in disease subgroups, molecular pathways, and novel therapies in patients with CKD.

CTOT 21/Treg Adoptive Therapy in Subclinical Inflammation in Kidney Transplantation

Emilio Poggio, MD

This is a randomized open-label trial to determine the safety and efficacy of a single dose of autologous polyTregs or darTregs in renal transplant recipients with SCI in the 3-7 months post-transplant allograft biopsy compared to control patients treated with CNI-based immunosuppression. The efficacy of the Treg therapy will be assessed by the reduction of graft inflammation on biopsies performed at seven months after study group allocation compared to the eligibility biopsy. The study will also describe the safety of mTOR therapy after polyTregs or darTregs. The secondary efficacy endpoint, as well as safety and mechanistic endpoints relative to both Tregs and mTOR therapy.

Studies That Are in the Start-up Phase (Not Currently Open)

Kidney Precision Medicine Project (KPMP)

Emilio Poggio, MD and John Sedor, MD

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). The KPMP has publicly and operationally committed itself to always put patients and their best interests first and this foundational principle informs and undergirds every facet of the study. Both AKI and CKD are conditions that impose a significant global health burden. Yet, no effective therapies currently exist for AKI, and only a few are available for CKD. To address this need, KPMP will obtain kidney biopsy tissue from study participants with AKI or CKD. The network will utilize state-of-the-art methods to perform molecular interrogation of the tissue and to link the molecular data to kidney structure and clinical information in the form of a human kidney atlas. Molecular and imaging data derived from kidney tissue will be integrated with clinico-pathologic and genetic information, as well as other data derived from analyses of fluid biospecimens, including peripheral blood, urine, and stool. Using advanced analytics to integrate the data, KPMP will aim to define kidney disease subgroups in molecular terms by identifying critical cells, pathways, and targets for novel therapies.

APOL 1 Pre-Eclampsia

John O-Toole, MD

Role of APOL1 genotype and expression in preeclampsia.

APOL 1 Studies in Kidney Transplant (ASK-CCC)
APOL1 Long-term Kidney Transplantation Outcomes Network

Emilio Poggio, MD

APOLLO will prospectively conduct a census of kidney transplants involving deceased and living African American donors in the United States including Puerto Rico during a specified recruitment period. Prospective data on kidney transplants, donors and recipients will be collected and APOL1 genotyping performed; graft failures and other clinical outcomes will be collected during follow-up. This design is ideally suited to address the APOLLO Consortium’s aims of assessing the impact of donor APOL1 genotype as a predictor of premature kidney transplant failure and renal functional outcomes in recipients, and on post-donation kidney function, proteinuria and vital status in living kidney donors. The APOL1 genotyping results of APOLLO could prompt a revision of the current formula to calculate the KDRI by replacing the ethnicity/race component with APOL1 genotype, lessen the discard of good-quality deceased donor kidneys and lead to more successful kidney transplantations, improved quality of life and reduced healthcare costs.34 Despite strong retrospective data, implementation of APOL1 RRV screening in deceased kidney donors requires data from a well-powered national prospective study such as APOLLO. The results of this study may also inform guidelines and policies for the evaluation and selection of living kidney donors.