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Recent data in the veterinary and human literature concur regarding the beneficial effects of Angiotensinogen Converting Enzyme (ACE) inhibitors in the management of various stages of renal disease and renal failure. ACE inhibitors, such as enalapril, benazepril, linisopril...and others...are readily employed adjuncts in the management of some cardiomyopathies and congestive heart failure. These indications are independent of that which is to be discussed here for slowing the progression of renal disease and putting off the onset of renal failure. References for portions of this discussion can be found in the Veterinary Forum 12/20/97; Compendium for Continuing Education , 18: pp279, March, 1996; Clinics of North America, (Small Animal), November, 1996; and Hospital Medicine 33: pp11, 1997. A partially altered text version of the latter, which discusses this subject in humans, is available here. The ensuing discussion represents the opinion of the author only. Diagnostic and treatment options for veterinary patients remain solely the responsibility of the attending veterinarian.

Before proceding with the topic at hand, it is important to state the obvious: Early recognition of occult renal disease will, most likely, result in the most favorable long-term clinical outcome via pre-emptive life-style/medical/pharmocological intervention. It is important to realize that in most instances, this is NOT achievable via the routine laboratory screenings...blood work and urinalysis. Dilute urine and/or azotemia resulting from reduced renal functionality are not apparent until 2/3 to 3/4 of kidney function is affected, respectively. By the time such laboratory abberations are noted, much damage has already transpired. The key is to rethink our approach. Raise the index of suspicion based upon signalment (e.g. middle age or geriatric kitty), history...especially of chronic inflammation/infection (e.g. dental-periodontal disease, recurrent urinary tract inflammation-infection, skin or other sources of chronic inflammation), the physical exam..and the "intuitive-gut feeling" based upon the experiences of you, the veterinarian.

This publication will not focus upon the special laboratory methodolgy required to form a diagnosis of occult renal disease...though that may come in the future. However the following guidelines and suggested screening tests may provide the framework for the veterinarian-detective to begin the investigation:

• Urinalysis: Finding proteinuria (even mild proteinuria) NOT referable to the lower urinary tract or to transient physiological/non-renal etiologies; elevated urine protein:urine creatinine ratio; finding sediment clearly referrable to kidney and possibly representing pathological process(es)
• Glomerular Filtration Rate Measure urinary creatinine excretion over 24 hour..or calculate fractional creatinine excretion (creatinine clearance)
• Urinary Clearance Tests Examples are Creatinine Clearance, Fractional Excretion tests (phosphorus is a good one, electrolytes e.g. potassium)
• Serum Parathyroid Hormone Level of intact Parathyroid Hormone (iPTH) may rise early in occult renal disease..this is bad as persistent renal secondary hyperparathyroidism furthur damages many tissues, including the kidney.
• Obvious Chronic Inflammatory Disease (e.g. dermatitis, dental/periodontal disease, arthritides, inflammatory bowel disease, recurent pancreatitis and urinary tract infections or FLUTD)..these are but examples of problems that are likely to contribute to occult kidney deterioration via accumulation/deposition of antigen-antibody complexes in renal (glomerular basement membrane) tissue. . Their presence should warrant exploratory testing for kidney involvement.
• Signs of Cardiovascular Disease: the RAAS system may already be active and contributing to renal damage. Treating for underlying problem, possibly including ACE inhibitors, may quell the tide to deterioration However, the use of ACE inhibitors in slowing renal deterioration is NOT believed to be due in greatest measure to its obvious beneficial effects limiting aldosterone secretion, and fluid accumulation
• Signs of Hypertension Signs of systemic hypertension, discussed elsewhere on the web, may indicate the presence of occult renal disease
• Signs of Hypercoagulability With proteinuria, there is the possibility for loss of specific anticoagulants in the urine (e.g. antithrombin III). Evidence for hypercoagulability...e.g. thromboembolic events, should prompt consideration of underlying renal disease (which may have preceeded or followed the "events")
• Others Other methodolgies, e.g. plain and contrast radiography, ultrasound, renal biopsy...and possibly more...may also be useful

• Identify Underlying Diseases that Predispose to Renal Deterioration: DO AN ANTIGEN SEARCH if signs of Occult Renal Disease is apparent based upon laboratory tests recommended above (certainly, only a short list is given here...). Rule out concurrent cardiovascular disease and hypertension as well. Consider also that there is,already occult renal disease if a predisposing condition is identified

• Dietary Modification It is clear that phosphorus restriction is beneficial in the treatment of canine renal disease via decreasing stimulus for PTH (which is, in itself harmful to kidney and to non-kidney tissue!) and decreasing the probabilties of inappropriate soft-tissue mineralization.. Thus, if during your testing for occult renal disease you find elevation of iPTH (and you have ruled out primary hyperparathyroidism), and/or serum phosphorus is already elevated (and no other etiology for this is evident)...then you have occult renal disease and PHOSPHORUS RESTRICTION IS APPROPRIATE. In the presence of occult renal deterioration...even if there is not frank failure, there are those who still recommend phosphorus restriction to about 0.9% to 1.5% on a dry weight basis

• Treat Renal Secondary Hyperparathyroidism: If Renal Secondary Hyperparathyroidism ( demonstrated via increased iPTH that is NOT associated with primary hyperparathyroidism and increased urinary phosphorus clearance), then consider treatment to prevent damage to kidney and non-kidney tissues that occurs with prolongued elevations in blood parathyroid hormone (A nice discussion of Calcitriol in the treatmentof renal secondary hyperparathyroidism is found in Clinics of North America, Small Animals, November, 1996; and Current Veterinary Therapy, volume X).

  Angiotensin-Converting Enzyme-Inhibitors (ACE-Inhibitors): There is now considerable evidence in human and veterinary literature that ACE-inhibitor therapy instituted during the occult phase of renal disease will slow progression and complications of renal damage. The exact mechanismis unclear but is apparently not be related to its local and systemic anti-hypertensive properties. The postulated mechanism(s) are vaguely related to dilatory effects on glomerular efferent arterioles, the concommitant reduction of intraglomerular pressure and decreased damage from hyperfiltration. These drug, by mechanisms not yet appreciated, restore glomerular permiselectivity and significantly reduce renal protein losses. Heretofore in veterinary medicine, this class of medication has been largely employed in the medical management of cardiomyopathies and/or congestive heart failure. Some have used these drugs to manage hypertension, (though, other vaso-active medications e.g. the vaso-specific calcium channel blockers such as amlodipine, are gaining more favor. This issue is addressed elsewhere on this web).
  
  When using ACE inhibitors, remember that it is possible to negatively effect glomerular filtration (...azotemia...) via reduction in glomerular hydrostatic pressure which results from efferent arteriolar vasodilation. Thus, to this author a steady tendency towards elevation of BUN or creatinine after instituting treatment (even if BUN and Creatinine are in still in the normal range) should alert the clinician to consider a dose adjustment (lower). Ironically, overzealous therapy for occult renal disease could hasten development of overt renal failure!

  This author plans to update and expand upon particular aspects of the above discussion. Previous publication schedules have been disappointing and in the interest of providing at least some information, this unfinished work is presented along with an adulterated version of a published discussion of this subject, but with reference to human beings.

Copyright© 1997-2012 Newman Veterinary Medical Services®, Seattle, WA

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