Improving outcome in dogs with glomerular disease via pharmacodynamic-based dosing of enalapril

Purpose of the study

The purpose of this study is to determine if higher doses of enalapril than those currently recommended will further reduce urine protein excretion in dogs with glomerular disease, will survival time, slow rate of decline in kidney function, and delay onset of azotemia as compared to the standard enalapril dose.

Background information

One in five pet dogs will develop kidney disease. Proteinuric glomerular diseases may be the underlying cause of chronic renal failure in at least 50% of canine patients with chronic renal failure. Angiotensin converting enzyme (ACE)-inhibitors such as enalapril reduce urinary loss of proteins, and are the mainstay of glomerular disease treatment in both dogs and people. Lower urine protein concentrations are associated with slower declines in glomerular filtration rate and longer survival times, regardless of the histologic type of glomerular disease. The currently recommended enalapril dose was established using a target of 75% suppression of ACE activity; however, higher ACE-inhibitor doses in people may result in further reductions in urine protein excretion, and dramatically improve patient survival.

Inclusion criteria

  • Dogs must have primary glomerular disease (biopsy confirmation is not required)
  • Dogs must have a UPC ≥3.0
  • Dogs cannot have a serum creatinine concentration >1.5 mg/dl or nephrotic syndrome, be diagnosed with any concurrent disease that alters kidney function, or have any concurrent disease that will likely result in <12 month survival
  • Owners must commit to returning to OSU for regular recheck appointments

Study design/treatment schedule

Owners will be instructed to discontinue administration of all ACE-inhibitors and other anti-hypertensive medications 1 week prior to initial patient appointment.

  • Initial screening of dogs (week 0)
    • Eligibility for enrollment, disease staging, and confirmation that glomerular disease is likely primary (not due to a non-renal infectious or inflammatory disease)
    • Complete blood count (CBC), chemistry panel, urinalysis (UA), UPC, systolic blood pressure measurement, and abdominal ultrasonography.
    • All enrolled patients managed initially with an identical treatment regimen (0.5 mg/kg PO q12h) for 4 weeks; change to a ‘renal’ diet will be recommended , but not mandated
    • Blood also banked for later testing of angiotensin II and aldosterone concentrations
  • First recheck appointment (week 4)
    • Chemistry panel, UA, UPC, systolic blood pressure measurement, GFR assay, and banking of plasma for hormone assays
    • Dogs will be randomly assigned to either the standard enalapril dose group or the increased enalapril dose group; clinicians, veterinary staff, and owners will be aware of each dog’s treatment group.


  • Standard enalapril dose group
    • Dogs continue same enalapril dose prescribed at week 0
    • Recheck appointments at OSU at weeks 12, 24, and 36, with chemistry panel, UA, UPC, systolic blood pressure measurement, GFR assay, and banking of plasma for hormone assays performed at each visit
    • Follow-up with owners by phone at 52 and 78 weeks


  • Increased enalapril dose group
    • Enalapril dose increased by a predetermined amount
    • Recheck at OSU at week 7, with chemistry panel, UA, UPC, systolic blood pressure measurement, GFR assay, and banking of plasma for hormone assays
      • UPC results ≤75% of those at week 4 considered a positive response, and enalapril dose will be increased again
      • UPC results ≥75% of week 4 considered a negative response, and enalapril dose will be returned to the previous dose
      • Recheck of positive responders at week 10, with negative responders returned to the previous dose
      • Recheck appointments at OSU at weeks 12, 24, and 36

 Client compensation

  • The study will pay for study-associated costs associated for each study-associated follow-up visit.  Clients are responsible for charges associated with the initial screening visit, purchase of enalapril, and any other medications needed for standard treatment of their dog’s kidney disease.


  • If an unexpected event occurs which is associated with the initial or recheck appointments at OSU, or is presumptively due to an increase in enalapril dose, the study will cover up to $1000 of the treatment-associated costs.

Contact information

The Clinical Trials Office (Nicole Stingle or Tamra Mathie, clinicaltrials [at] cvm [dot] osu [dot] edu) for further information or to schedule an appointment.