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<\/a><\/p>\nJD Foster, VMD, Diplomate ACVIM<\/em><\/p>\n Chronic kidney disease (CKD) is an irreversible and progressive deterioration of renal function, resulting from a decreased number of functional nephrons. Unfortunately, the compensatory mechanisms that respond to nephron loss (glomerular hypertension, hyperfiltration) help facilitate progression of CKD, potentially contributing to it more so than the original injury (Table 1).<\/p>\n Patients of any age may develop CKD, but the greatest incidence is in geriatric patients. However, congenital renal diseases, including dysplasia and various glomerulopathies, may produce CKD at very early ages. Once diagnosed, CKD typically remains a life-long condition.<\/p>\n Medical History<\/strong> Clinical Signs<\/strong> Physical Examination<\/strong> Dehydration is common in CKD, typically resulting from patients’ inability to ingest enough water to compensate for increased urinary losses. A thorough diagnostic evaluation (Table 2) can confirm the diagnosis of CKD. These tests may identify underlying causes, ongoing renal injury, and consequences of CKD, providing information about prognosis and treatment goals.<\/p>\n Azotemia Interpretation<\/strong> Glomerular Filtration Rate<\/strong> A tiered stratification system has been proposed by the International Renal Interest Society (IRIS) to help provide guidelines for clinical management of CKD. Staging is based on serum creatinine values, with substages identified for blood pressure and proteinuria (Table 3).<\/p>\n Importance of Hydration<\/strong> Stage Determination<\/strong> Serum creatinine: IRIS 3 (Stage 3) Treatment of CKD should be individually tailored to each patient. Although not all interventions have been evaluated by clinical trials, some evidence-based information supports their role in management of CKD. IRIS CKD stage management guidelines are listed in Table 4; medications to help achieve treatment goals are listed in Table 5. Hydration<\/strong> Maintain Hydration<\/strong> Lower protein diets, such as senior diets, often do not have the appropriate alterations in phosphorus and electrolyte concentrations recommended for management of CKD; therefore, these diets should NOT be considered acceptable alternatives.<\/p>\n A future article in the Nutrition Notes column (see page 60) will address dietary therapy for renal disease in dogs and cats. Manage GI Complications of Uremia<\/strong> Hyperphosphatemia<\/strong> Treat Hyperphosphatemia<\/strong> Acidemia<\/strong>PRESENTATION<\/h2>\n
\nA thorough medical history plays 2 essential roles; it:
\n1. Helps determine a management plan by assessing severity of polyuria and polydipsia, diet, appetite, change in body mass, and energy level.
\n2. Provides a baseline\u2014the degree of illness related to CKD at presentation\u2014to use for comparison after therapeutic interventions have been implemented.<\/p>\n
\nEarly signs of CKD may be mild, even inapparent to the pet owner. Because isosthenuria and azotemia do not develop until 66% and 75% nephron loss, respectively, most renal function has been lost by onset of clinical signs.
\nCommon clinical signs include:
\n\u2022 Polyuria and compensatory polydipsia
\n\u2022 Decreasing appetite, weight loss, and lethargy
\n\u2022 Gastrointestinal (GI) signs, which may be present in early CKD, but are very common in moderate to advanced CKD.<\/p>\n
\nDuring a physical examination in patients with suspected or confirmed CKD, pay particular attention to body condition scoring, cardiovascular status, evidence of dehydration, and renal palpation.
\nMuscle wasting may indicate poor nutritional status.
\nNew heart murmurs may indicate a physiologic flow murmur due to anemia or hypertension (however, sick or febrile patients should also be evaluated for endocarditis).<\/p>\n
\nAssessment of renal size and shape, and for the presence of pain, should always be performed, but may be difficult in medium or large breed dogs.
\nSpecific system examinations include:
\nFundic examination to assess for vessel tortuosity and retinal detachment, which may suggest systemic hypertension
\nRectal examination to evaluate for evidence of melena or hematochezia, which may indicate uremic ulcers.<\/p>\nDIAGNOSTICS<\/h2>\n
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\nPersistent azotemia (despite normal hydration status) can confirm CKD. However, since 75% nephron loss occurs before azotemia, this criteria only identifies the most advanced cases.
\nIsosthenuria may be seen earlier (66% nephron loss); however, without azotemia, all other causes of isosthenuria need to be excluded before attributing it to CKD.
\nExtrarenal factors may alter creatinine or blood urea nitrogen (BUN) when interpreting azotemia:
\nCreatinine: Decreased in patients with muscle wasting
\nBUN: Increased in patients with GI bleeding or those consuming a high-protein diet; decreased with malnutrition, severe protein restriction, or synthetic liver failure
\nPrerenal or postrenal factors may concurrently contribute to azotemia:
\nPrerenal factors: Consider decreased renal perfusion, most commonly seen in dehydrated, hypovolemic, or hypotensive patients
\nPostrenal factors: Consider unilateral ureteral obstruction, which can be ruled out by abdominal radiographs and ultrasound; may also manifest with renal pain and abnormal renal palpation.<\/p>\n<\/a><\/p>\n
\nGlomerular filtration rate (GFR) is the gold standard measurement of renal function; however, its measurement is rarely indicated in patients with CKD. Creatinine and, to a lesser extent, BUN are correlated with GFR, but, as noted earlier, GFR must be reduced by 75% before azotemia is seen. However, measurement of GFR (typically through iohexol or creatinine clearance testing) may confirm reduced renal function in isosthenuric patients.<\/p>\nIRIS STAGING SYSTEM<\/h2>\n
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\nTreatment goals and recommendations are specific to IRIS CKD stage. 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 determining the patient’s stage of CKD.<\/p>\n
\nIncluding the IRIS CKD stage in the medical record relays important information about the severity of CKD. For example, if a dog has a creatinine of 2.5 mg\/dL, urine protein:creatinine (UPC) ratio of 1, and arterial blood pressure of 155 mm Hg, its IRIS CKD stage would be considered IRIS 3 P AP 1, or:<\/p>\n
\nProteinuria substaging: P (Proteinuric)
\nBlood pressure substaging: AP I (Arterial Pressure Stage 1).<\/p>\nTREATMENT GOALS<\/h2>\n
\nUremia
\nAs stated earlier, IRIS CKD staging should be applied to patients only after exclusion of pre- and postrenal contributions.
\nUremic toxins, many of which are byproducts of protein metabolism, are solutes that accumulate due to decreased renal clearance, causing detrimental effects. Urea and creatinine are not significant uremic toxins; however, they serve as surrogate markers, providing some information on renal function and degree of uremic toxin retention.<\/p>\n<\/a><\/p>\n
\nAs CKD is irreversible, decreased GFR caused by intrinsic renal dysfunction cannot be improved. Hypovolemic or dehydrated patients will have decreased renal perfusion, causing prerenal reduction in GFR, which is complicated if patients cannot voluntarily maintain hydration.
\nMeasures should be taken to prophylactically maintain hydration in patients that cannot do so on their own (urine output exceeds fluid intake).<\/p>\nTHERAPEUTIC GOAL:<\/h2>\n
\nFeed canned food diets; many patients will tolerate additional water added to canned food.
\nOffer low- or no-sodium chicken broth.
\nFeeding tubes (esophagostomy, gastric) can provide access for water, medication, and nutrition delivery.
\nSubcutaneous fluids can be helpful, but contain large amounts of sodium, which some CKD patients may not tolerate, contributing to hypertension.
\nConsider feeding prescription renal diet (see Nutritional Therapy).
\nNutritional therapy is a cornerstone of CKD management.
\nPrescription renal diets typically have:
\nReduced protein, phosphorus, and sodium concentrations
\nIncreased B-vitamins, fiber, and omega-3 fatty acids.
\nPrescription renal diet reduced the risk of uremic crisis by 72% in study dogs when compared to those fed a maintenance diet.1 Other benefits demonstrated by this study included prolonged median survival time, slower progression of CKD, and improved quality of life.<\/p>\n
\nGI Complications
\nAntacids and antiemetics are useful for managing GI complications of uremia. Due to diminished ability to produce erythropoietin, dogs with CKD take longer to normalize anemia related to GI ulcers.<\/p>\nTHERAPEUTIC GOAL:<\/h2>\n
\nProton pump inhibitors: More effective than histamine antagonists for neutralizing gastric acid secretion; no dose adjustment is required in patients with CKD
\nH2-receptor antagonists: Require dose adjustment with renal impairment; are less effective in neutralizing gastric pH.
\nSucralfate: Helps facilitate GI ulceration healing; may impair absorption of numerous drugs and should be administered alone and without food.
\nAntiemetics: May be given as needed or as daily therapy.<\/p>\n
\nPlasma phosphorus concentrations are inversely proportional to GFR; therefore, as renal function declines, phosphate retention occurs. Hyperphosphatemia increases the production of parathyroid hormone (PTH) by the parathyroid glands, one of the key steps in development of renal secondary hyperparathyroidism.<\/p>\nTHERAPEUTIC GOAL:<\/h2>\n
\nPhosphate binders are used in combination with a prescription renal diet when diet alone is insufficient to control hyperphosphatemia, and form nonabsorbable complexes with dietary phosphate within the GI tract.
\nAluminum hydroxide: Often used as first-line drug; however, toxicity has been reported in dogs when administrated above recommended doses.
\nCalcium salts: Must be avoided in patients with hypercalcemia and used cautiously in those with calcium-phosphorus products significantly exceeding 70.
\nLanthanum carbonate: Compounding may be required to obtain appropriately sized capsules; can be used in combination with aluminum hydroxide (dose of latter may need to be decreased due to synergistic effects).
\nSevalamer hydrochloride: Expands when it contacts water; tablets or capsules should be administered intact.
\nDose of phosphate binders can be titrated up to produce more pronounced effects. Generally, the more severe the hyperphosphatemia, the higher the dose (kept within the recommended dosage range) of phosphate binder required for successful correction. Treatment should be targeted to achieve recommendations according to IRIS CKD stage.
\nThese drugs must be administered with food; feeding meals or phosphate-rich treats without using a phosphate binder lessens their efficacy.<\/p>\n
\nPatients with CKD have metabolic acidosis due to accumulation of acidic uremic toxins; patients with hypoperfusion may additionally have lactic acidosis. If venous blood gas assessment is unavailable to evaluate patient acid\u2013base status, a serum total carbon dioxide level (TCO2) can be used as an estimate of serum bicarbonate concentration. Falsely decreased TCO2 levels occur when blood collection tubes are exposed to air or are not fully filled.<\/p>\nTHERAPEUTIC GOAL:<\/h2>\n