Pathogenesis of Kidney Disease in Type 1 Diabetes: a Modern Kidney Biopsy Cohort (The PANDA Study) (PANDA)

May 20, 2026 updated by: University of Colorado, Denver
Diabetic kidney disease (DKD) occurs in up to 40% of people with type 1 diabetes (T1D), often leading to kidney failure and markedly magnifying risks of cardiovascular disease and premature death. Landmark T1D kidney biopsy studies identified the classic pathological lesions of DKD, which have been attributed largely to hyperglycemia. Recent advances in continuous glucose monitoring (CGM) and automated insulin delivery have facilitated improved glycemic control, but the residual risk of DKD continues to be high. In addition, obesity and insulin resistance (IR) have accompanied intensive glycemic therapy and may promote mitochondrial dysfunction and inflammation. Deciphering the molecular underpinnings of DKD in modern-day T1D and identifying modifiable risk factors could lead to more effective and targeted therapies to prevent DKD.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The overall goal of this project is to characterize the molecular, morphometric, and metabolic features of DKD over the modern clinical course of T1D. The investigators hypothesize that perturbed kidney energetics and hypoxia are central metabolic pathways in the development of DKD. Kidney hypoxia stems from a mismatch between increased renal energy demand (e.g., increased glomerular filtration rate [GFR] and tubular reabsorption of sodium) and impaired substrate metabolism (e.g., IR and mitochondrial dysfunction) and results in activation of the hypoxia-inducible factor (HIF) system. Although upregulation of HIF1α confers favorable short-term effects, sustained activation promotes cellular injury. Supporting these hypotheses, data from our group and others have shown that obesity, IR, and The investigators also found that youth with T1D exhibit kidney hypoxia by MRI that strongly associates with IR and mitochondrial dysfunction. Moreover, our preliminary single-cell RNA sequencing (scRNA-seq) data from kidney biopsies demonstrate upregulated tubular expression of HIF1α in adults with T1D vs. healthy controls. The investigators propose to build a unique new longitudinal kidney biopsy cohort (N=100) spanning the critical duration of T1D over which DKD initiates and progresses (5-30 years). Participants will be enrolled from our existing CROCODILE study (adding longitudinal follow-up to completed kidney biopsies and baseline data and biosample acquisition) and from new enrollment at the University of Colorado and University of Washington. Normative kidney biopsy data will be provided from our existing cohort of healthy controls (N=20) and the Kidney Precision Medicine Project (KPMP). The investigators will implement state-of-the-art molecular (scRNA-seq) and morphometric interrogation of kidney tissue and rigorous metabolic phenotyping to include kidney magnetic resonance imaging (MRI), direct measurements of glycemia (continuous glucose monitoring), intraabdominal fat (dual-energy X-ray absorptiometry), estimation of insulin sensitivity by a T1D-validated equation, and (in a subset) GFR (iohexol clearance) and renal plasma flow (p-aminohippurate clearance). Participants will be followed longitudinally for DKD outcomes. A subset of 20 participants will undergo repeat kidney biopsies and associated procedures 3 years after baseline kidney biopsy.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Children's Hospital Colorado

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

The investigators propose to address the specific aims of this study in a cross-sectional project with 70 newly enrolled adults with T1D and 30 former CROCODILE participants (COMIRB #19-1282).

Description

Inclusion Criteria:

  • Age ≥ 18 years at enrollment (rationale: this study focuses on determinants of early DKD over the course of T1D in adults)
  • T1D duration >5 years (rationale: DKD in T1D rarely manifests prior to 5 years of disease duration)
  • HbA1c <11% (rationale: HbA1c ≥ 11% exceeds the average HbA1c at most academic center and would limiting the generalizability of our study findings)

Exclusion Criteria:

  • T2D and monogenic diabetes (rationale: our study focuses on T1D)
  • Recent diabetic ketoacidosis, i.e., <1 month (rationale: safety and insulin resistance and tubular dysfunction of DKA can confound study findings)
  • eGFR < 30 ml/min/1.73m2 or dialysis treatment (rationale: to reduce the likelihood of identifying secondary pathways that are not specific to kidney injury from T1D)
  • Kidney transplant recipients (rationale: molecular confounding from immunosuppression)

  • Kidney biopsy contraindications (rationale: safety - kidney biopsy):

    • Evidence of bleeding disorder or complications from bleeding
    • Use of aspirin, Nonsteroidal anti-inflammatory drugs (NSAIDS) or other blood thinner that cannot be safely stopped for a sufficient time before and after the biopsy to avoid additional risk of bleeding.
    • INR > 1.4
    • Hemoglobin (Hgb) < 10 mg/dL (Colorado) [altitude]
    • Hemoglobin (Hgb) < 9 mg/dL (Washington)
    • Platelet count < 100,000 / µL
    • Uncontrolled or difficult to control hypertension (> 150/90 mmHg at the day of biopsy)
    • Single kidney (either by history, documented by prior imaging or ultrasound performed prior to the biopsy)
    • Kidney size: One or both kidneys < 8 cm
    • Hydronephrosis or other important renal ultrasound findings such as significant stone disease
    • Any evidence of a current urinary tract infection as indicated on day of biopsy
    • Clinical evidence of non-diabetic renal disease
    • Positive urine pregnancy test or pregnancy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
PANDA, T1D
New participants with T1D will be enrolled at the University of Colorado and University of Washington.
PANDA Sub Study, Former CROCODILE Participants
Participants will be enrolled from the existing CROCODILE study (COMIRB # 19-1282), adding longitudinal follow-up to completed kidney biopsies and baseline data and biosample acquisition.
Drug: Aminohippurate Sodium Inj 20% Diagnostic aid/agent used to measure effective renal plasma flow (ERPF)
PAH (Basic Pharma, Geleen, Netherlands) has been used to measure ERPF in human research for 7 decades, and is very well tolerated and generally recognized as safe with low toxicity.
Other Names:
  • Sodium 4-amino hippurate (PAH) inj 20% 2g/10mL
  • Para-aminohippurate
Drug: Iohexol Inj 300 MG/ML Diagnostic aid/agent used to measure glomerular filtration rate (GFR)
Iohexol (Omnipaque 300, GE Healthcare, Chicago, IL) is a nonionic, low osmolar contrast agent with a history of extensive use in Radiology practice (for contrast x-rays) that shares many qualities of an ideal GFR marker, like inulin, such as not being absorbed, metabolized, or secreted by the kidney.
Other Names:
  • omnipaque 300

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Insulin Sensitivity
Time Frame: 4.5 hours
Hyperinsulinemic-Euglycemic Clamp
4.5 hours
Renal Oxygenation
Time Frame: 30 min
Blood oxygen level dependent (BOLD) MRI
30 min
Renal Perfusion
Time Frame: 30 min
Arterial Spin Labeling (ASL) MRI
30 min

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Glomerular Filtration Rate (GFR)
Time Frame: 3 hours
Iohexol Clearance Study
3 hours
Effective Renal Plasma Flow (ERPF)
Time Frame: 2.5 hours
PAH Clearance Study
2.5 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Colorado, Denver

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 9, 2022

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 1, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 1, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 11, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 22, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 20, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 22-0250

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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