Pathogenesis of Kidney Disease in Type 1 Diabetes: a Modern Kidney Biopsy Cohort (The PANDA Study)
PANDA
1 other identifier
observational
100
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for all trials
Started Mar 2022
Longer than P75 for all trials
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 9, 2022
CompletedFirst Submitted
Initial submission to the registry
April 1, 2022
CompletedFirst Posted
Study publicly available on registry
April 11, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2027
April 10, 2024
April 1, 2024
5.3 years
April 1, 2022
April 9, 2024
Conditions
Outcome Measures
Primary Outcomes (3)
Renal Oxygenation
Blood oxygen level dependent (BOLD) MRI
30 min
Renal Perfusion
Arterial Spin Labeling (ASL) MRI
30 min
Insulin Sensitivity
Hyperinsulinemic-Euglycemic Clamp
4.5 hours
Secondary Outcomes (2)
Glomerular Filtration Rate (GFR)
3 hours
Effective Renal Plasma Flow (ERPF)
2.5 hours
Study Arms (2)
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.
Interventions
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.
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.
Eligibility Criteria
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).
You may qualify if:
- 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)
You may not qualify if:
- 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
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Biospecimen
During the study, the investigators will collect blood, urine, and tissue samples for assessment of kidney function and kidney injury markers.
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 1, 2022
First Posted
April 11, 2022
Study Start
March 9, 2022
Primary Completion (Estimated)
June 30, 2027
Study Completion (Estimated)
December 31, 2027
Last Updated
April 10, 2024
Record last verified: 2024-04