Kidney Precision Medicine Project

NCT04334707 | Recruiting DMC

• 20 other identifiers: STUDY-24-01176U2CDK114886UH3DK114861UH3DK114866UH3DK114870UH3DK114908UH3DK114915UH3DK114926UH3DK114907UH3DK114920UH3DK114923UH3DK114933UH3DK114937U01DK144994U01DK144965U01DK133095U01DK133081U01DK133097U01DK133093SITE00000750
• Study Type: observational
• Target: 1,000
• Locations: 1 country
• Sites: 13

Brief Summary

Acute kidney injury (AKI) and chronic kidney disease (CKD) impose a significant global health burden. Yet, no effective therapies currently exist for AKI, and only a few are available for CKD. Despite significant effort from industry and academia, development of pharmacologic therapies for AKI and CKD has been hampered by: Non-predictive animal models The inability to identify and prioritize human targets The limited availability of human kidney biopsy tissue A poor understanding of AKI and CKD heterogeneity Historically, AKI and CKD have been described as single, uniform diseases. However, growing consensus suggests that different disease pathways lead to different subgroups of AKI and CKD (AKIs and CKDs). Access to human kidney biopsy tissue is a critical first step to define disease heterogeneity and determine the precise molecular pathways that will facilitate identification of specific drug targets and ultimately enable individualized care for people with AKI and CKD. A number of research centers across the United States are collaborating to bring state-of-the-art technologies together to:

• Ethically obtain and evaluate kidney biopsies from participants with AKI or CKD
• Define disease subgroups
• Create a kidney tissue atlas
• Identify critical cells, pathways, and targets for novel therapies The KPMP is made up of three distinct, but highly interactive, activity groups:
• Recruitment Sites: The recruitment sites (RS) are responsible for recruiting participants with AKI or CKD into the longitudinal study and performing the kidney biopsy.
• Tissue Interrogation Sites: The tissue interrogation sites (TIS) are responsible for developing and using innovative technologies to analyze the biopsy tissue.
• Central Hub: The central hub is responsible for aggregating, analyzing, and visualizing the generated data and providing scientific, infrastructure, and administrative support for the KPMP consortium.

Conditions

Acute Kidney Failure; Acute Kidney Insufficiency; Acute Renal Failure; Acute Renal Injury; Acute Renal Insufficiency; Kidney Failure, Acute; Kidney Insufficiency, Acute; Renal Failure, Acute; Renal Insufficiency, Acute; Chronic Kidney Diseases; Chronic Kidney Insufficiency; Chronic Renal Diseases; Chronic Renal Insufficiency; Kidney Insufficiency, Chronic; Type 1 Diabetes (T1D)

Outcome Measures

Primary Outcomes (4)

• Biopsy-related outcomes

  Biopsy-related complications will be collected by KPMP study staff using standardized case report forms. Clinical utility of the biopsy results will be assessed using standardized surveys of clinical providers, and participant-reported outcomes will be assessed using standardized questionnaires. Biopsy-related outcomes data will be collected around the time of the biopsy and within the six months following procurement of the kidney biopsy.

  Immediately after the procedure for up to 6 months

• Kidney disease progression outcomes

  Longitudinal change in estimated glomerular filtration rate (eGFR): * Primary composite longitudinal outcome, defined by any of the following: * ESRD, defined as initiation of maintenance dialysis or kidney transplantation * Sustained decline in eGFR by 40% or more from baseline * Individual components of the primary composite outcome * Slope of eGFR change (from baseline to the latest value)

  Through study completion (up to 10 years, depending on enrollment date of participant)

• Kidney disease progression outcomes

  Longitudinal change in urine albumin excretion defined by the following: -Slope of change in urine albumin-creatinine ratio

  Through study completion (up to 10 years, depending on enrollment date of participant)

• Kidney disease progression outcomes

  Longitudinal change in urine albumin excretion defined by the following: -Change of Kidney Disease Improving Global Outcomes (KDIGO) albuminuria stage

  Through study completion (up to 10 years, depending on enrollment date of participant)

Other Outcomes (2)

• Number of Participants with Additional Outcome Measures

  Through study completion (up to 10 years, depending on enrollment date of participant)

• Number of Participants with Outcomes Specific to AKI

  Through study completion (up to 10 years, depending on enrollment date of participant)

Study Arms (4)

Acute Kidney Injury Cohort

The focus will be on acute intrinsic non-glomerular disease, primarily on acute tubular necrosis (ATN).

Procedure: Kidney Biopsy

Chronic Kidney Diseases Cohort

High priority populations include CKD in the setting of diabetes (diabetic kidney disease, DKD) and hypertension-associated CKD (H-CKD).

Procedure: Kidney Biopsy; Other: MRI; Other: Retina Scan

Type 1 Diabetes (T1D)

Clinical diagnosis of Type 1 diabetes without evidence of other diabetes types (monogenic, secondary to pancreas disease, etc.) and has or is at risk of CKD.

Procedure: Kidney Biopsy; Other: MRI; Other: Retina Scan

Diabetes Mellitus-Resistant (DM-R)

Diabetes Mellitus-Resistant: A special population of people with long-standing type 1 diabetes (more than 25 years) who remain free of clinically-evident DKD will also be included.

Procedure: Kidney Biopsy; Other: Retina Scan

Interventions

MRI OTHER

Images will be acquired using 3.0T whole body scanner. The participant will undergo a series of sequences (e.g., BOLD, diffusion-weighted, ASL MRI, native T1, and fat fraction sequences). The participant will receive 20 mg of IV furosemide as a bolus. BOLD MRI sequences will be repeated 15 minutes after furosemide administration. ASL sequences are acquired using investigational protocols that are not FDA-approved. Siemens machines will use Body ASL PCASL Perfusion WIP 1023, Phillips will use Body ASL 2D PCASL Perfusion software, and GE machines will use Body ASL PCASL Perfusion software.

Chronic Kidney Diseases Cohort; Type 1 Diabetes (T1D)

Retina Scan OTHER

Fundus photography, fluorescein angiography, optical coherence tomography, optical coherence tomography angiography, and ophthalmologic exam and history will take place during one retina study visit. The retina visit will take place up to 6 weeks prior to the KPMP kidney biopsy OR up to 8 weeks post-biopsy.

Chronic Kidney Diseases Cohort; Diabetes Mellitus-Resistant (DM-R); Type 1 Diabetes (T1D)

Kidney Biopsy PROCEDURE

A kidney biopsy is a procedure that involves taking a small piece of kidney tissue for examination with a microscope. A licensed health care provider will perform a kidney biopsy.

Acute Kidney Injury Cohort; Chronic Kidney Diseases Cohort; Diabetes Mellitus-Resistant (DM-R); Type 1 Diabetes (T1D)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The KPMP will focus on participant populations that account for large proportions of the public health burden of acute and chronic kidney diseases as evidenced by research and federal data. For CKD, high priority populations include CKD in the setting of diabetes (diabetic kidney disease, DKD) and hypertension-associated CKD (H-CKD). A special population of people with long-standing type 1 diabetes (more than 25 years) who remain free of clinically-evident DKD will also be included. For AKI, the focus will be on acute intrinsic non-glomerular disease, primarily on acute tubular necrosis (ATN). KPMP will also include a special population of patients at risk for AKI or with early AKI captured by an open (surgical) kidney biopsy performed at the time of clinically indicated laparotomy. The rationale for including this special AKI population is that AKI often occurs early in the clinical course of conditions like sepsis, major surgery and trauma.

You may qualify if:

• Diagnosis of diabetes mellitus (type 1 or 2) established by at least one of the following criteria:
• o Hemoglobin A1C greater than or equal to 6.5%, confirmed with a repeat test within the past year
• o Fasting blood sugar greater than or equal to 126 mg/dL, confirmed with a repeat test within the past year
• Use of glucose-lowering therapy (insulin or oral or other subcutaneous agents)
• International Classification of Diseases (ICD) 9/10 diagnostic code for diabetes
• Evidence of persistent kidney damage, manifest as any of the following present on at least two clinic assessments prior to enrollment and at least 3 months apart and excluding people with acute medical illnesses and changing kidney function:
• Estimated glomerular filtration rate 30-59 mL/min/1.73m2 or
• Estimated glomerular filtration rate greater than or equal to 30 mL/min/1.73m2 with urine albumin excretion greater than or equal to 30 mg/g creatinine (or mg/day) or
• Estimated glomerular filtration rate greater than or equal to 30 mL/min/1.73m2 with urine protein excretion greater than or equal to 150 mg/g creatinine (or mg/day)
• Most recent eGFR must be within the past year and be ≥30 mL/min/1.73m\^2.
• Hypertension-associated Chronic Kidney Disease (H-CKD)
• Diagnosis of hypertension (HTN) established by at least one of the following criteria:
• BP greater than 140/90 mmHg measured on three occasions over at least 1 month
• Taking antihypertensive medication for blood pressure (BP) control
• International Classification of Diseases (ICD) 9/10 diagnostic code for hypertension

You may not qualify if:

• Under 18 years of age
• Severe allergy to iodinated contrast
• Pregnancy
• Transplant recipient (includes solid transplant and bone marrow)
• Additional vulnerable individuals (incarcerated, institutionalized, or otherwise unable to participate in the study)
• Inability to provide informed consent
• Clinical diagnosis of kidney disease from an autoimmune disease, dysproteinemia, viral disease or glomerular disease other than DKD or H-CKD
• Unwilling to receive blood transfusion (if needed)
• Potential participants will be excluded if the risk of kidney biopsy is considered too high by either the clinicians caring for the potential participant or the investigators at the RS.
• Kidney size less than 8 cm (percutaneous biopsies only)
• Solitary or single functioning kidney
• Evidence of urinary tract obstruction or hydronephrosis
• Multiple bilateral kidney cysts that will interfere with the safe performance of the biopsy
• Kidney infection, peri-renal infection, or cutaneous infection that overlies the kidney (percutaneous biopsies only)
• Any other imaging abnormality, which in the judgement of the operator, prevents biopsy being performed safely.

Sponsors & Collaborators

• Mayo Clinic: collaborator
• University of North Carolina, Chapel Hill: collaborator
• University of Illinois at Chicago: collaborator
• Vanderbilt University: collaborator
• Providence Health & Services: collaborator
• Harvard University: collaborator
• University of Arizona: collaborator
• University of Washington: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• University of Michigan: collaborator
• Brigham and Women's Hospital: collaborator
• Broad Institute of MIT and Harvard: collaborator
• The Cleveland Clinic: collaborator
• Columbia University: collaborator
• Indiana University: collaborator
• Johns Hopkins University: collaborator
• Joslin Diabetes Center: collaborator
• Pacific Northwest National Laboratory: collaborator
• Princeton University: collaborator
• Ohio State University: collaborator
• University of Pittsburgh: collaborator
• The University of Texas Health Science Center at San Antonio: collaborator
• University of Texas: collaborator
• Washington University School of Medicine: collaborator
• Yale University: collaborator
• Icahn School of Medicine at Mount Sinai: lead

Study Sites (13)

University of Arizona

Tucson, Arizona, 85721, United States

RECRUITING

Yale University

New Haven, Connecticut, 06520, United States

RECRUITING

University of Illinois Chicago

Chicago, Illinois, 60607, United States

RECRUITING

Johns Hopkins University

Baltimore, Maryland, 21287, United States

RECRUITING

Boston Medical Center

Boston, Massachusetts, 02115, United States

RECRUITING

Joslin Diabetes Center

Boston, Massachusetts, 48374, United States

RECRUITING

University of Minnesota

Minneapolis, Minnesota, 55455, United States

RECRUITING

Mayo Clinic, Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Mount Sinai

New York, New York, 10029, United States

RECRUITING

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

University of Texas at Southwestern

Dallas, Texas, 75390, United States

RECRUITING

University of Washington

Seattle, Washington, 98195, United States

RECRUITING

Related Publications (27)

• de Boer IH, Alpers CE, Azeloglu EU, Balis UGJ, Barasch JM, Barisoni L, Blank KN, Bomback AS, Brown K, Dagher PC, Dighe AL, Eadon MT, El-Achkar TM, Gaut JP, Hacohen N, He Y, Hodgin JB, Jain S, Kellum JA, Kiryluk K, Knight R, Laszik ZG, Lienczewski C, Mariani LH, McClelland RL, Menez S, Moledina DG, Mooney SD, O'Toole JF, Palevsky PM, Parikh CR, Poggio ED, Rosas SE, Rosengart MR, Sarwal MM, Schaub JA, Sedor JR, Sharma K, Steck B, Toto RD, Troyanskaya OG, Tuttle KR, Vazquez MA, Waikar SS, Williams K, Wilson FP, Zhang K, Iyengar R, Kretzler M, Himmelfarb J; Kidney Precision Medicine Project. Rationale and design of the Kidney Precision Medicine Project. Kidney Int. 2021 Mar;99(3):498-510. doi: 10.1016/j.kint.2020.08.039.

  PMID: 33637194 BACKGROUND

• USGAO, Kidney disease research funding and priority setting. 2017: [online] https://www.gao.gov/assets/690/681714.pdf.

  BACKGROUND

• RM, B., Social security amendments of 1972: summary and legislative history. 1973

  BACKGROUND

• Rettig RA. Special treatment--the story of Medicare's ESRD entitlement. N Engl J Med. 2011 Feb 17;364(7):596-8. doi: 10.1056/NEJMp1014193. No abstract available.

  PMID: 21323539 BACKGROUND

• CfMaM., S., Chronic Conditions among medicare beneficiaries. Chartbook, 2012 Edition. Baltimore 2012.

  BACKGROUND

• Norris KC, Williams SF, Rhee CM, Nicholas SB, Kovesdy CP, Kalantar-Zadeh K, Ebony Boulware L. Hemodialysis Disparities in African Americans: The Deeply Integrated Concept of Race in the Social Fabric of Our Society. Semin Dial. 2017 May;30(3):213-223. doi: 10.1111/sdi.12589. Epub 2017 Mar 9.

  PMID: 28281281 BACKGROUND

• Prevention, C.f.D.C.a., National Chronic Kidney Disease Fact Sheet, 2017, U.D.o.H.a.H. Services, Editor. 2017: Atlanta, GA.

  BACKGROUND

• Mendu ML, Erickson KF, Hostetter TH, Winkelmayer WC, Olan G, Meyer RN, Hakim R, Sedor JR. Federal Funding for Kidney Disease Research: A Missed Opportunity. Am J Public Health. 2016 Mar;106(3):406-7. doi: 10.2105/AJPH.2015.303009. No abstract available.

  PMID: 26885959 BACKGROUND

• Linde PG, Archdeacon P, Breyer MD, Ibrahim T, Inrig JK, Kewalramani R, Lee CC, Neuland CY, Roy-Chaudhury P, Sloand JA, Meyer R, Smith KA, Snook J, West M, Falk RJ. Overcoming Barriers in Kidney Health-Forging a Platform for Innovation. J Am Soc Nephrol. 2016 Jul;27(7):1902-10. doi: 10.1681/ASN.2015090976. Epub 2016 Apr 28.

  PMID: 27127187 BACKGROUND

• Inrig JK, Califf RM, Tasneem A, Vegunta RK, Molina C, Stanifer JW, Chiswell K, Patel UD. The landscape of clinical trials in nephrology: a systematic review of Clinicaltrials.gov. Am J Kidney Dis. 2014 May;63(5):771-80. doi: 10.1053/j.ajkd.2013.10.043. Epub 2013 Dec 6.

  PMID: 24315119 BACKGROUND

• Hsu RK, McCulloch CE, Dudley RA, Lo LJ, Hsu CY. Temporal changes in incidence of dialysis-requiring AKI. J Am Soc Nephrol. 2013 Jan;24(1):37-42. doi: 10.1681/ASN.2012080800. Epub 2012 Dec 6.

  PMID: 23222124 BACKGROUND

• Lameire NH, Bagga A, Cruz D, De Maeseneer J, Endre Z, Kellum JA, Liu KD, Mehta RL, Pannu N, Van Biesen W, Vanholder R. Acute kidney injury: an increasing global concern. Lancet. 2013 Jul 13;382(9887):170-9. doi: 10.1016/S0140-6736(13)60647-9. Epub 2013 May 31.

  PMID: 23727171 BACKGROUND

• Collister D, Pannu N, Ye F, James M, Hemmelgarn B, Chui B, Manns B, Klarenbach S; Alberta Kidney Disease Network. Health Care Costs Associated with AKI. Clin J Am Soc Nephrol. 2017 Nov 7;12(11):1733-1743. doi: 10.2215/CJN.00950117. Epub 2017 Oct 19.

  PMID: 29051143 BACKGROUND

• Kellum JA, Bellomo R, Ronco C. Kidney attack. JAMA. 2012 Jun 6;307(21):2265-6. doi: 10.1001/jama.2012.4315. No abstract available.

  PMID: 22572776 BACKGROUND

• USRDS, United States Renal Data Systems 2013 Annual Data Report. United States Renal Data Systems. 2013: [online] http://http://www.usrds.org/2013/pdf/v1_ch6_13.pdf.

  BACKGROUND

• Waikar SS, Liu KD, Chertow GM. Diagnosis, epidemiology and outcomes of acute kidney injury. Clin J Am Soc Nephrol. 2008 May;3(3):844-61. doi: 10.2215/CJN.05191107. Epub 2008 Mar 12.

  PMID: 18337550 BACKGROUND

• Sileanu FE, Murugan R, Lucko N, Clermont G, Kane-Gill SL, Handler SM, Kellum JA. AKI in low-risk versus high-risk patients in intensive care. Clin J Am Soc Nephrol. 2015 Feb 6;10(2):187-96. doi: 10.2215/CJN.03200314. Epub 2014 Nov 25.

  PMID: 25424992 BACKGROUND

• Murugan R, Karajala-Subramanyam V, Lee M, Yende S, Kong L, Carter M, Angus DC, Kellum JA; Genetic and Inflammatory Markers of Sepsis (GenIMS) Investigators. Acute kidney injury in non-severe pneumonia is associated with an increased immune response and lower survival. Kidney Int. 2010 Mar;77(6):527-35. doi: 10.1038/ki.2009.502. Epub 2009 Dec 23.

  PMID: 20032961 BACKGROUND

• Coca SG, Yusuf B, Shlipak MG, Garg AX, Parikh CR. Long-term risk of mortality and other adverse outcomes after acute kidney injury: a systematic review and meta-analysis. Am J Kidney Dis. 2009 Jun;53(6):961-73. doi: 10.1053/j.ajkd.2008.11.034. Epub 2009 Apr 5.

  PMID: 19346042 BACKGROUND

• Waikar SS, Winkelmayer WC. Chronic on acute renal failure: long-term implications of severe acute kidney injury. JAMA. 2009 Sep 16;302(11):1227-9. doi: 10.1001/jama.2009.1364. No abstract available.

  PMID: 19755705 BACKGROUND

• Coca SG, Singanamala S, Parikh CR. Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis. Kidney Int. 2012 Mar;81(5):442-8. doi: 10.1038/ki.2011.379. Epub 2011 Nov 23.

  PMID: 22113526 BACKGROUND

• Kellum JA, Sileanu FE, Murugan R, Lucko N, Shaw AD, Clermont G. Classifying AKI by Urine Output versus Serum Creatinine Level. J Am Soc Nephrol. 2015 Sep;26(9):2231-8. doi: 10.1681/ASN.2014070724. Epub 2015 Jan 7.

  PMID: 25568178 BACKGROUND

• AKIWG, K., Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Acute Kidney Injury. Kidney inter., Suppl., 2012. 2: p. 1-138.

  BACKGROUND

• Chu R, Li C, Wang S, Zou W, Liu G, Yang L. Assessment of KDIGO definitions in patients with histopathologic evidence of acute renal disease. Clin J Am Soc Nephrol. 2014 Jul;9(7):1175-82. doi: 10.2215/CJN.06150613. Epub 2014 May 1.

  PMID: 24789552 BACKGROUND

• Perazella MA, Coca SG, Hall IE, Iyanam U, Koraishy M, Parikh CR. Urine microscopy is associated with severity and worsening of acute kidney injury in hospitalized patients. Clin J Am Soc Nephrol. 2010 Mar;5(3):402-8. doi: 10.2215/CJN.06960909. Epub 2010 Jan 14.

  PMID: 20089493 BACKGROUND

• Corapi KM, Chen JL, Balk EM, Gordon CE. Bleeding complications of native kidney biopsy: a systematic review and meta-analysis. Am J Kidney Dis. 2012 Jul;60(1):62-73. doi: 10.1053/j.ajkd.2012.02.330. Epub 2012 Apr 24.

  PMID: 22537423 BACKGROUND

• Rodriguez LL, Brooks LD, Greenberg JH, Green ED. Research ethics. The complexities of genomic identifiability. Science. 2013 Jan 18;339(6117):275-6. doi: 10.1126/science.1234593. No abstract available.

  PMID: 23329035 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Kidney (renal) tissue will be obtained from all study participants at study entry Blood and urine will be collected longitudinally, including DNA One-time stool sample

MeSH Terms

Conditions

Acute Kidney Injury; Renal Insufficiency, Chronic; Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Jonathan Himmelfarb, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ashveena Dighe, MS, MPH

CONTACT

800-555-5555; ashveena.dighe@mssm.edu

Kristina Blank, MPH

CONTACT

206-897-1957; blankk@uw.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 23, 2020
• First Posted: April 6, 2020
• Study Start: September 1, 2019
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: April 14, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: September 2019
• Access Criteria: De-identified IPD is public via atlas.kpmp.org. A minimal amount of clinical data is public. Non-public data can be accessed via a data use agreement.

Locations

US (13)