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

Prior treatment

• Kidney transplant recipients (rationale: molecular confounding from immunosuppression)

Other illness

• T2D and monogenic diabetes (rationale: our study focuses on T1D)

Lab values

• 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 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

Other

• Recent diabetic ketoacidosis, i.e., \<1 month (rationale: safety and insulin resistance and tubular dysfunction of DKA can confound study findings)

• 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)