Canine Chronic Kidney Disease: Current Diagnoses and Goals for Long-Term Management (2023)

Chronic kidney disease (CKD) is an irreversible and progressive deterioration of kidney function, as a result of a decrease in the number of functional nephrons. Unfortunately, compensatory mechanisms that respond to nephron loss (glomerular hypertension, hyperfiltration) help facilitate CKD progression, potentially contributing more to it than the original lesion.tabla 1).

Patients of any age can develop CKD, but the highest incidence is in geriatric patients. However, congenital kidney diseases, including dysplasia and various glomerulopathies, can cause CKD at a very early age. Once diagnosed, CKD usually remains a lifelong condition.

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PRESENTATION

Medical history

A complete medical history plays 2 essential roles; he:

1. Helps determine a management plan by assessing the severity of polyuria and polydipsia, diet, appetite, change in body mass, and energy level.
2. It provides a baseline (the degree of CKD-related disease at the time of presentation) to use as a comparison after therapeutic interventions have been implemented.

Clinical signs

The first signs of CKD can be mild, even imperceptible to the pet owner. Because isosthenuria and azotemia do not develop until 66% and 75% loss of nephrons, respectively, most renal function has been lost by the onset of clinical signs.

Common clinical signs include:

• Polyuria y polydipsia compensatoria
• Decreased appetite, weight loss, and lethargy.
• Gastrointestinal (GI) signs, which may be present in early CKD, but are very common in moderate to advanced CKD.

Physical exam

During a physical examination in patients with suspected or confirmed CKD, pay particular attention to body condition score, cardiovascular status, evidence of dehydration, and renal palpation.

• Loss of muscle mass can indicate poor nutritional status.
• New heart murmurs may indicate a physiologic flow murmur due to anemia or hypertension (however, sick or febrile patients should also be evaluated for endocarditis).
• Dehydration is common in CKD, usually as a result of patients' inability to ingest enough water to compensate for increased urinary losses.
• An assessment of kidney size and shape, and the presence of pain should always be performed, but may be difficult in medium to large breed dogs.

System-specific exams include:

• Fundal examination to assess for vessel tortuosity and retinal detachment, which may suggest systemic hypertension
• Rectal examination to assess for evidence of melena or hematochezia, which may indicate uremic ulcers.

DIAGNOSIS

A comprehensive diagnostic evaluation (Tabla 2) can confirm the diagnosis of CKD. These tests can identify underlying causes, ongoing kidney injury, and consequences of CKD, providing information about prognosis and treatment goals.

Interpretation of Azotemia

• Persistent azotemia (despite normal hydration status) may confirm CKD. However, since 75% nephron loss occurs before azotemia, this criterion only identifies the most advanced cases.
• Isosthenuria can be seen earlier (66% loss of nephrons); however, without azotemia, all other causes of isosthenuria must be excluded before attributing it to CKD.
• Extrarenal factors may alter creatinine or blood urea nitrogen (BUN) when interpreting azotemia:
  • Creatinine: Decreased in patients with muscle wasting
  • BUN: increased in patients with gastrointestinal bleeding or in those consuming a high-protein diet; decreased with malnutrition, severe protein restriction, or synthetic liver failure
• Prerenal or postrenal factors may simultaneously contribute to azotemia:
  • Prerenal factors: Consider decreased renal perfusion, which is seen more often in dehydrated, hypovolemic, or hypotensive patients.
  • Postrenal factors: consider unilateral ureteral obstruction, which can be ruled out by abdominal radiographs and ultrasound; It can also manifest with renal pain and abnormal renal palpation.

glomerular filtration rate

The glomerular filtration rate (GFR) is the gold standard measure of kidney function; however, its measurement is rarely indicated in patients with CKD. Creatinine and, to a lesser extent, BUN correlate with GFR, but, as noted above, GFR must be reduced by 75% before azotemia is seen. However, measurement of glomerular filtration rate (typically through creatinine or iohexol clearance tests) can confirm reduced renal function in isosthenuric patients.

IRIS STAGING SYSTEM

The International Renal Interest Society (IRIS) has proposed a tiered stratification system to help provide guidelines for the clinical management of CKD. Staging is based on serum creatinine values, with substages identified for blood pressure and proteinuria (Tabla 3).

Importance of hydration

Treatment goals and recommendations are specific to stage IRIS CKD. Since prerenal contributions will often increase the degree of azotemia to the next stage, normal renal perfusion (adequate patient hydration and effective circulating volume) should be restored before the patient's CKD stage is determined.

stage determination

Including the IRIS CKD stage in the medical record conveys important information about the severity of CKD. For example, if a dog has a creatinine of 2.5 mg/dL, a urine protein:creatinine ratio (UPC) of 1, and a blood pressure of 155 mm Hg, its IRIS CKD stage would be considered IRIS 3 P AP 1 , either:

• Serum creatinine: IRIS 3 (Step 3)
• Proteinuria understatement: P (proteinuric)
• Blood pressure substage: AP I (Blood Pressure Stage 1).

OBJECTIVES OF THE TREATMENT

CKD treatment must be individually tailored to each patient. Although not all interventions have been evaluated by clinical trials, some evidence-based information supports their role in the management of CKD. IRIS CKD stage management guidelines are listed inTabla 4; Medications to help achieve treatment goals are listed inTabla 5.

Uremia

As stated above, IRIS CKD staging should be applied to patients only after exclusion of prerenal and postrenal contributions.

Uremic toxins, many of which are byproducts of protein metabolism, are solutes that accumulate due to decreased renal clearance, causing deleterious effects. Urea and creatinine are not significant uremic toxins; however, they serve as surrogate markers and provide some information about renal function and the degree of uraemic toxin retention.

Hydration

As CKD is irreversible, the decrease in GFR caused by intrinsic renal dysfunction cannot be ameliorated. Hypovolemic or dehydrated patients will have decreased renal perfusion, leading to reduced prerenal GFR, which is compounded if patients are unable to maintain hydration voluntarily.

Steps should be taken to prophylactically maintain hydration in patients who are unable to do so on their own (urine output exceeds fluid intake).

THERAPEUTIC OBJECTIVE: Maintain Hydration

• Feed canned food diets; many patients will tolerate extra water added to canned foods.
• Offer low sodium or no sodium chicken broth.
• Feeding tubes (esophagostomy, gastric) can provide access for water supply, medication, and nutrition.
• Subcutaneous fluids can be helpful, but they contain large amounts of sodium, which some CKD patients may not tolerate, contributing to hypertension.
• Consider feeding a prescription renal diet (see Nutrition Therapy).

gastrointestinal complications

Antacids and antiemetics are useful in controlling the gastrointestinal complications of uremia. Due to the reduced ability to produce erythropoietin, dogs with CKD take longer to normalize the anemia associated with gastrointestinal ulcers.

THERAPEUTIC OBJECTIVE: Manage gastrointestinal complications of uremia

• Proton pump inhibitors: more effective than histamine antagonists in neutralizing gastric acid secretion; no dose adjustment required in CKD patients
• H2-receptor antagonists: Dose adjustment required with renal insufficiency; they are less effective in neutralizing gastric pH.
• Sucralfate: helps facilitate healing of gastrointestinal ulcerations; it can alter the absorption of many drugs and must be administered alone and without food.
• Antiemetics: can be given as needed or as daily therapy.

hiperfosfatemia

Plasma phosphorus concentrations are inversely proportional to GFR; therefore, as renal function declines, phosphate retention occurs. Hyperphosphatemia increases parathyroid hormone (PTH) production by the parathyroid glands, one of the key steps in the development of secondary renal hyperparathyroidism.

THERAPEUTIC OBJECTIVE: Treat hyperphosphatemia

Phosphate binders are used in combination with a prescribed renal diet when diet alone is insufficient to control hyperphosphatemia and they form nonabsorbable complexes with dietary phosphate within the GI tract.

• Aluminum hydroxide: Often used as a first-line drug; however, toxicity in dogs has been reported when administered above recommended doses.
• Calcium salts: should be avoided in patients with hypercalcemia and used with caution in those with calcium-phosphorus products significantly greater than 70.
• Lanthanum Carbonate: Compounding may be required to obtain capsules of proper size; it can be used in combination with aluminum hydroxide (it may be necessary to reduce the dose of the latter due to synergistic effects).
• Sevalamer hydrochloride: expands when in contact with water; tablets or capsules must be administered intact.

The dose of phosphate binders can be increased to produce more pronounced effects. In general, the more severe the hyperphosphatemia, the higher the dose (maintained within the recommended dose range) of phosphate binder needed for successful correction. Treatment should be directed at achieving the recommendations based on the IRIS CKD stage.

These medications must be administered with food; feeding phosphate-rich foods or treats without using a phosphate binder decreases its effectiveness.

Acidemia

CKD patients have metabolic acidosis due to the accumulation of acid uremic toxins; patients with hypoperfusion may also have lactic acidosis. If venous blood gas evaluation is not available to assess the patient's acid-base status, a serum total carbon dioxide (TCO2) level can be used as an estimate of the serum bicarbonate concentration. Falsely decreased TCO2 levels occur when blood collection tubes are exposed to air or are not completely filled.

THERAPEUTIC OBJECTIVE: Treat Acidemia

Feed a diet that produces a neutral pH, which prescription renal diets are designed to achieve (but is not a feature of some urolithiasis diets). Use alkaline therapy (Tabla 5) for patients with persistent acidemia despite an adequate diet. The goal is to maintain a bicarbonate (TCO2) level between 18 and 25 mmol/L.

• Baking Soda: Administer as a whole tablet as some dogs find it unpleasant when mixed with food.
• Potassium Citrate: Each 540 mg tablet produces 5 mEq of potassium and 1.7 mEq of citrate, which is metabolized to 420 mg of bicarbonate.

Although potassium citrate provides some potassium supplementation, which is beneficial for patients with hypokalemia, it may exacerbate hyperkalemia in patients with normal or slightly increased serum potassium concentrations. In addition, angiotensin-converting enzyme (ACE) inhibitor therapy can also cause mild to moderate hyperkalemia. Use potassium supplements with caution in patients receiving such drugs and avoid their use in patients with hyperkalemia.

Hypokalemia and hyperkalemia

Hypokalemia is more common in cats than in dogs. Severe hyperkalemia can be life-threatening and is more often associated with oliguric or anuric acute kidney injury than with CKD.

Patients with end-stage CKD and markedly reduced GFR may also show hyperkalemia, regardless of the degree of diuresis. By inhibiting the production of angiotensin II, which causes urinary potassium excretion, ACE inhibitor drugs can also cause mild to moderate hyperkalemia as a side effect.

THERAPEUTIC OBJECTIVE: Treat Hypokalemia or Hyperkalemia

• For hypokalemia, oral supplementation is the preferred treatment.
• For mild hyperkalemia, a prescription renal diet with the lowest potassium content may be helpful. Oral potassium binders (sodium polystyrene) may prevent absorption of potassium from the diet. Rare gastrointestinal adverse effects have been reported in humans and are possible in dogs.
• Monitor hyperkalemic patients receiving ACE inhibitors; reduce dose if ACE inhibitors cause significant hyperkalemia.
• Discontinue potassium supplementation in all hyperkalemic patients.

Anemia

The lack of erythropoietin is the driving force behind the chronic, progressive, non-regenerative anemia of CKD. Always consider the possibility of GI ulceration resulting in blood loss if CKD patients have new or worsening anemia.

THERAPEUTIC OBJECTIVE: Treat Anemia

• • For moderate to advanced anemia (packed cell volume [PCV] <= 20%):
  • Consider hormonal supplementation with darbepoetin.
  • Monitor PCV weekly until target PCV is obtained; then decrease the frequency of administration.
  • Monitor blood pressure as some patients may develop hypertension after starting darbepoetin therapy.
• For severe anemia, proceed with a blood transfusion.

Darbepoetin, a synthetic form of erythropoietin, is thought to be less antigenic than human erythropoietin, which can cause the development of cross-reactive anti-erythropoietin antibodies and potentially destroy the patient's endogenous erythropoietin, causing the patient is dependent on transfusions. Lack of response to darbepoetin may indicate the formation of anti-darbepoetin/anti-erythropoietin antibodies; however, concurrent inflammatory disease may also result in a decreased response to darbepoetin.

Hypertension

Blood pressure is routinely assessed during CKD treatment. Normotensive patients may develop hypertension as kidney disease progresses. Ideally, assess blood pressure early in the visit before additional stress builds up, leading to nonpathologic increases in blood pressure ("white coat hypertension"). Perform a fundal examination to check for retinal damage.

THERAPEUTIC OBJECTIVE: Treat Hypertension

• ACE inhibitors are the first-line therapy for hypertension and are crucial in mitigating the renin-angiotensin-aldosterone system (RAAS); however, they are weak antihypertensives, lowering blood pressure by only about 10 mm Hg.
• The calcium channel blocker amlodipine is more effective, but must be used with an ACE inhibitor.

After starting or increasing the ACE inhibitor dose, mild increases in BUN and creatinine may be noted. Control slight increases that do not cause uremia; however, reduce or discontinue the dose if azotemia, accompanied by uremia, increases significantly, suggesting that the ACE inhibitor has caused a significant decrease in GFR.

proteinuria

Renal protein loss may be due to glomerular or tubular lesions, but glomerular lesions are more likely to result in a greater magnitude of proteinuria and hypoalbuminemia. Proteinuria is a risk factor for the progression of CKD; however, only weak evidence suggests that reducing proteinuria slows the progression of canine CKD.

THERAPEUTIC OBJECTIVE: Treat proteinuria

The first step in therapy is a protein-restricted renal diet. In addition, controlling hypertension also helps to minimize proteinuria. ACE inhibitors can cause hyperkalemia due to RAAS blockade, reduce GFR, and increase azotemia; therefore, use these drugs with caution in patients with stage 3 and 4 IRIS CKD.

For persistent proteinuria, therapeutic intervention is recommended:

• ACE inhibitor: Increase dose for hypertension to help minimize proteinuria; however, contraindicated in hypotensive or dehydrated patients.
• Omega 3 polyunsaturated fatty acids: Demonstrated to decrease proteinuria.
• Losartan: Consider this angiotensin receptor blocker for proteinuria refractory to ACE inhibitors; veterinary use has been limited, with conflicting opinions regarding efficacy.

Anticoagulants may be considered when there is proteinuria; however, serum albumin, UPC, or antithrombin levels do not adequately predict hypercoagulability.

Renal Secondary Hyperparathyroidism

The consequences of CKD, including phosphorus retention and decreased calcitriol synthesis, establish secondary renal hyperparathyroidism.

1. In response to hyperphosphatemia, the parathyroid glands increase the synthesis of PTH, a uremic toxin.
2. Calcitriol inhibits PTH release, but hyperphosphatemia inhibits calcitriol synthesis, creating a feedback loop that results in elevated phosphorus and PTH levels (Figure).
3. Due to decreased renal function, PTH activity is decreased, resulting in inadequate phosphorus excretion and suboptimal calcitriol production.