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Canine Chronic Kidney Disease Current Diagnostics & Goals for Long-Term
Management
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CANINE CHRONIC
KIDNEy DISEASE
Current Diagnostics & Goals for
Long-Term Management
JD Foster, VMD, Diplomate ACVIM
C
hronic kidney disease (CKD) is an irreversible and • New heart murmurs may indicate a physiologic flow
progressive deterioration of renal function, resulting murmur due to anemia or hypertension (however, sick
from a decreased number of functional nephrons. or febrile patients should also be evaluated for endocar-
Unfortunately, the compensatory mechanisms that respond ditis).
to nephron loss (glomerular hypertension, hyperfiltration) • Dehydration is common in CKD, typically resulting
help facilitate progression of CKD, potentially contributing from patients’ inability to ingest enough water to com-
to it more so than the original injury (Table 1). pensate for increased urinary losses.
Patients of any age may develop CKD, but the greatest • Assessment of renal size and shape, and for the pres-
incidence is in geriatric ence of pain, should always be performed, but may be
patients. However, con- difficult in medium or large breed dogs.
Table 1. Causes of CKd genital renal diseases,
• Calculi/obstruction including dysplasia and Specific system examinations include:
• Familial renal disease various glomerulopa- • Fundic examination to assess for vessel tortuosity and
• infection thies, may produce CKD retinal detachment, which may suggest systemic hyper-
• inflammation at very early ages. Once tension
• ischemia diagnosed, CKD typi- • Rectal examination to evaluate for evidence of melena
• Unknown cally remains a life-long or hematochezia, which may indicate uremic ulcers.
• Vascular injury condition.
DIAGNOSTICS
PRESENTATION A thorough diagnostic evaluation (Table 2) can confirm
Medical History the diagnosis of CKD. These tests may identify underlying
A thorough medical history plays 2 essential roles; it: causes, ongoing renal injury, and consequences of CKD,
1. Helps determine a management plan by assessing sever- providing information about prognosis and treatment goals.
ity of polyuria and polydipsia, diet, appetite, change in
body mass, and energy level. Azotemia Interpretation
2. Provides a baseline—the degree of illness related to • Persistent azotemia (despite normal hydration status)
CKD at presentation—to use for comparison after thera- can confirm CKD. However, since 75% nephron loss
peutic interventions have been implemented. occurs before azotemia, this criteria only identifies the
most advanced cases.
Clinical Signs • Isosthenuria may be seen earlier (66% nephron loss);
Early signs of CKD may be mild, even inapparent to the however, without azotemia, all other causes of isosthe-
pet owner. Because isosthenuria and azotemia do not nuria need to be excluded before attributing it to CKD.
develop until 66% and 75% nephron loss, respectively, • Extrarenal factors may alter creatinine or blood urea
most renal function has been lost by onset of clinical signs. nitrogen (BUN) when interpreting azotemia:
Common clinical signs include: » Creatinine: Decreased in patients with muscle wasting
• Polyuria and compensatory polydipsia » BUN: Increased in patients with GI bleeding or those
• Decreasing appetite, weight loss, and lethargy consuming a high-protein diet; decreased with malnutri-
• Gastrointestinal (GI) signs, which may be present tion, severe protein restriction, or synthetic liver failure
in early CKD, but are very common in moderate to • Prerenal or postrenal factors may concurrently con-
advanced CKD. tribute to azotemia:
» Prerenal factors: Consider decreased renal perfusion,
Physical Examination most commonly seen in dehydrated, hypovolemic, or
During a physical examination in patients with suspected hypotensive patients
or confirmed CKD, pay particular attention to body condi- » Postrenal factors: Consider unilateral ureteral obstruc-
tion scoring, cardiovascular status, evidence of dehydra- tion, which can be ruled out by abdominal radio-
tion, and renal palpation. graphs and ultrasound; may also manifest with renal
• Muscle wasting may indicate poor nutritional status. pain and abnormal renal palpation.
Uremia
As stated earlier, IRIS CKD Table 4. iris CKd stage Management Guidelines
staging should be applied Goal First-line Therapy Additional Therapy
to patients only after exclu- IRIS CKD STAGE 1
sion of pre- and postrenal
Phosphorus < 4.5 mg/dl renal diet Phosphate binders
contributions.
Uremic toxins, many of UPC <2 renal diet aCe inhibitor
which are byproducts of Blood Pressure < 160 mm hg aCe inhibitor amlodipine
protein metabolism, are sol- IRIS CKD STAGE 2
utes that accumulate due to Phosphorus < 4.5 mg/dl renal diet Phosphate binders
decreased renal clearance,
UPC < 0.5 renal diet aCe inhibitor
causing detrimental effects.
Urea and creatinine are not Blood Pressure < 160 mm hg aCe inhibitor amlodipine
significant uremic toxins; Bicarbonate 18–24 mmol/l Correct dehydra- sodium bicarbonate,
however, they serve as sur- tion potassium citrate
rogate markers, providing Notes: ARBs may be beneficial
some information on renal IRIS CKD STAGE 3
function and degree of ure-
Phosphorus < 5 mg/dl renal diet Phosphate binders
mic toxin retention.
UPC < 0.5 renal diet aCe inhibitor
Hydration Blood Pressure & same as iris stage 2
As CKD is irreversible, Bicarbonate
decreased GFR caused by Notes: Use ACE inhibitors and ARBs with caution
intrinsic renal dysfunction IRIS CKD STAGE 4
cannot be improved. Hypo-
volemic or dehydrated Phosphorus < 6 mg/dl renal diet Phosphate binders
patients will have decreased UPC, Blood Pressure, same as iris stage 2
renal perfusion, causing & Bicarbonate
prerenal reduction in GFR, ACe = angiotensin-converting enzyme; ArB = angiotensin receptor blocker; UPC = urine
which is complicated if protein:creatinine
patients cannot voluntarily
maintain hydration.
• H2-receptor antagonists: Require dose adjustment
Measures should be taken to prophylactically maintain
with renal impairment; are less effective in neutralizing
hydration in patients that cannot do so on their own (urine
gastric pH.
output exceeds fluid intake).
• Sucralfate: Helps facilitate GI ulceration healing; may
impair absorption of numerous drugs and should be
THERAPEUTIC GOAL: Maintain Hydration
• Feed canned food diets; many patients will tolerate addi- administered alone and without food.
tional water added to canned food. • Antiemetics: May be given as needed or as daily therapy.
• Offer low- or no-sodium chicken broth.
• Feeding tubes (esophagostomy, gastric) can provide Hyperphosphatemia
access for water, medication, and nutrition delivery. Plasma phosphorus concentrations are inversely propor-
• Subcutaneous fluids can be helpful, but contain large tional to GFR; therefore, as renal function declines, phos-
amounts of sodium, which some CKD patients may not phate retention occurs. Hyperphosphatemia increases the
tolerate, contributing to hypertension. production of parathyroid hormone (PTH) by the parathy-
• Consider feeding prescription renal diet (see Nutrition- roid glands, one of the key steps in development of renal
al Therapy). secondary hyperparathyroidism.
more often associated with oliguric or anuric acute kidney THERAPEUTIC GOAL: Treat Hypertension
injury, rather than CKD. • ACE inhibitors are first line therapy for hypertension, and
Patients with end-stage CKD and marked reduction in crucial to blunting the renin–angiotensin–aldosterone sys-
GFR may also demonstrate hyperkalemia, regardless of tem (RAAS); however, they are weak antihypertensives,
degree of urine output. By inhibiting the production of only reducing blood pressure approximately 10 mm Hg.
angiotensin II, which causes urinary potassium excretion, • The calcium channel blocker amlodipine is more
ACE inhibitor drugs may also produce mild to moderate effective, but should be used with an ACE inhibitor.
hyperkalemia as a side effect. Following initiation or increase of ACE inhibitor dosage,
mild increases in BUN and creatinine may be noted. Mon-
THERAPEUTIC GOAL: Treat Hypokalemia or itor mild increases that do not cause uremia; however,
Hyperkalemia reduce or discontinue the dosage if azotemia, accompa-
• For hypokalemia, oral supplementation is the pre- nied by uremia, significantly increases, which suggests the
ferred treatment. ACE inhibitor has caused a significant decrease in GFR.
• For mild hyperkalemia, a prescription renal diet with
the lowest potassium content can be useful. Oral potas- Proteinuria
sium binders (sodium polystyrene) can prevent absorp- Renal protein loss may be due to glomerular or tubular
tion of dietary potassium. Rare GI adverse effects are lesions, but glomerular lesions more likely result in great-
reported in humans and are possible in dogs. er magnitude of proteinuria and hypoalbuminemia. Pro-
• Monitor hyperkalemic patients receiving ACE inhibi- teinuria is a risk factor for progression of CKD; however,
tors; reduce dose if ACE inhibitors produce significant only weak evidence suggests that reducing proteinuria
hyperkalemia. slows progression of canine CKD.
• Discontinue potassium supplementation in all hyper-
kalemic patients. THERAPEUTIC GOAL: Treat Proteinuria
The first step in therapy is a protein-restricted renal diet.
Anemia In addition, managing hypertension also helps minimize
Lack of erythropoietin is the driving force behind the proteinuria. ACE inhibitors may cause hyperkalemia due
chronic, progressive, nonregenerative anemia of CKD. to RAAS blockade, reduce GFR, and increase azotemia;
Always consider GI ulceration resulting in blood loss if therefore, use these drugs cautiously in IRIS CKD stage 3
CKD patients have new or worsened anemia. and 4 patients.
For persistent proteinuria, therapeutic intervention is
THERAPEUTIC GOAL: Treat Anemia recommended:
• For moderate to advanced anemia anemia (packed • ACE inhibitor: Increase hypertension dosage to help
cell volume [PCV] ≤ 20%): minimize proteinuria; however, contraindicated in
» Consider hormone supplementation with darbepoi- hypotensive or dehydrated patients.
etin. • Omega 3-polyunsaturated fatty acids: Shown to less-
» Monitor PCV weekly until target PCV is obtained; then en proteinuria.
taper frequency of administration. • Losartan: Consider this angiotensin receptor block-
» Monitor blood pressure as some patients may develop er for proteinuria refractory to ACE inhibitors; veteri-
hypertension after initiation of darbepoietin therapy. nary use has been limited, with contradicting opinions
• For severe anemia, proceed with a blood transfusion. regarding efficacy.
Darbepoietin, a synthetic form of erythropoietin, is Anticoagulants can be considered when proteinuria is
thought to be less antigenic than human erythropoietin, present; however, serum albumin, UPC, or antithrombin
which can cause development of anti-erythropoietin anti- levels do not adequately predict hypercoagulability.
bodies that crossreact and potentially destroy the patient’s
endogenous erythropoietin, leaving the patient dependent Renal Secondary Hyperparathyroidism
on transfusions. Failure to respond to darbepoietin may Consequences of CKD, including phosphorus retention
indicate formation of antidarbepoietin/anti-erythropoietin and decreased synthesis of calcitriol, establish renal sec-
antibodies; however, concurrent inflammatory disease can ondary hyperparathyroidism.
also result in diminished response to darbepoietin. 1. In response to hyperphosphatemia, parathyroid glands
increase PTH—a uremic toxin—synthesis
Hypertension 2. Calcitriol inhibits PTH release, but hyperphosphatemia
Blood pressure is routinely evaluated throughout treat- inhibits synthesis of calcitriol, creating a feedback loop that
ment of CKD. Normotensive patients may develop hyper- results in elevated phosphorus and PTH levels (Figure).
tension as renal disease progresses. Ideally, assess blood 3. Due to decreased renal function, PTH activity is dimin-
pressure early in the visit before additional stress accrues, ished, resulting in inadequate excretion of phosphorus
leading to nonpathologic increases in blood pressure and suboptimal production of calcitriol.
(“white coat hypertension”). Perform fundic examination Serum calcium is regulated by PTH; however, normal cal-
to investigate for retinal damage. cium handling does not occur in renal secondary hyper-
PROGNOSIS
Prognosis is associated with severity of disease. Studies
have shown shorter median survival times in dogs with
higher IRIS stages. Median survival time for IRIS Stage 1
dogs was over 400 days, Stage 2 ranged from 200 to 400
days, Stage 3 ranged from 110 to 200 days, and Stage 4
ranged from 14 to 80 days.2,3 Successful treatment of CKD
delays disease progression, likely provides greater sur-
vival times, and increases patient quality of life. n