IRIS CKD treatment recommendations - Hund

Question 1

Generellt

Answer 1

In general, there are few clinical extra-renal signs at the early stages of CKD (Stages 1 and 2) and the therapeutic emphasis is on slowing progression. From Stage 3 onwards, extra-renal signs become more common and more severe. By Stage 4, treatments that are symptomatic and improve quality of life assume greater importance, and become more relevant than those designed to slow progression of CKD.

Question 2

Hypertension - Stage 1-4

Answer 2

The blood pressure above which progressive renal injury may be induced is unknown. Our goal is to reduce systolic blood pressure to <160 mm Hg and minimize the risk of extra-renal target organ damage (CNS, retinal, cardiac problems/damage).

A logical stepwise approach to managing hypertension is as follows:

1. Dietary sodium (Na) reduction – there is no evidence that lowering dietary Na will reduce blood pressure. If dietary Na reduction is attempted, it should be accomplished gradually and in combination with pharmacological therapy.
2. Angiotensin converting enzyme inhibitor (ACEI, such as benazepril) therapy at standard dose rate.
3. Double the dose of ACEI (in some dogs, increasing the dose may improve the antihypertensive effect).
4. Combine ACEI and calcium channel blocker (CCB, such as amlodipine) treatment, especially if severely hypertensive.
5. Combine ACEI and CCB with angiotensin receptor blocker (ARB, such as telmisartan (Semintra)) and/or hydralazine if additional treatment is required.

After stabilization, monitoring should occur at least every 3 months.

Systolic blood pressure <120 mm Hg and/or clinical signs such as weakness or tachycardia indicate hypotension, which is to be avoided.

Blood creatinine concentration – reducing blood pressure may lead to small and persistent increases in creatinine concentration (<45 µmol/l increase) and/or SDMA (< 2 µg/dl), but a marked increase suggests an adverse drug effect.

Progressively increasing concentrations indicate progressive kidney damage/disease.

Question 3

Proteinuri - Stage 1-4

Answer 3

Dogs with UP/C >0.5 should be investigated for disease processes leading to proteinuria (see 1 and 2 below) and treated with antiproteinuric measures (see 3,
4, 5 and 6 below).

Those with borderline proteinuria (UP/C 0.2 to 0.5) require close monitoring (see 1 and 6 below).

1. Look for any concurrent associated disease process that may be treated/corrected.
2. Consider kidney biopsy as a means of identifying underlying disease
3. Administer an ACEI and feed a clinical renal diet.
4. Combine ACEI and diet with an angiotensin receptor blocker (ARB) if proteinuria is not controlled.
5. Administer low-dose acetylsalicylic acid (1 to 5 mg/kg once daily) or clopidogrel (1.1-3 mg/kg orally every 24 hours) if serum albumin is <20 g/l (2.0 g/dl).
6. Monitor response to treatment / progression of disease:
   – stable blood creatinine concentration and decreasing UP/C = good response.
   – serially increasing blood creatinine concentration and/or increasing UP/C = disease is progressing.

Ordinarily therapy will be maintained lifelong unless the underlying disease has been resolved in which case dose reduction whilst monitoring UP/C might be considered.

Question 4

Fosfat - CKD stage 2 och över

Answer 4

Evidence suggests that chronic reduction of phosphate intake to maintain plasma phosphate concentration below 1.5 mmol/l (but not less than 0.9 mmol/l; <4.6 mg/ dl but >2.7 mg/dl) is beneficial to patients with CKD.

The following measures can be introduced sequentially in an attempt to achieve this:

1. Dietary phosphate restriction (i.e., clinical renal diet therapy).
2. If plasma phosphate concentration remains above 1.5 mmol/l (4.6 mg/dl) after dietary restriction, give enteric phosphate binders (such as aluminum hydroxide, aluminum carbonate, calcium carbonate, calcium acetate, lanthanum carbonate) to effect, starting at 30-60 mg/kg/day in divided doses to be mixed with each meal (mixed with the food). The dose required will vary according to the amount of phosphate being fed and the stage of CKD. Treatment with phosphate binders should be to effect (as outlined above), with signs of toxicity limiting the upper dose rate possible in a given patient. Monitor serum calcium and phosphate concentrations every 4-6 weeks until stable and then every 12 weeks. Microcytosis and/or generalized muscle weakness suggests aluminum toxicity if using an aluminum containing binder – switch to another form of phosphate binder should this occur. Hypercalcemia should be avoided – combinations
   of aluminum and calcium containing phosphate binders may be necessary in some cases.
3. Evidence suggests that judicious use of calcitriol (1.5 to 3.5 ng/kg) prolongs
   survival in dogs in Stage 3 when phosphate is controlled and ionized calcium
   and PTH are monitored.

Question 5

Ytterligare behandling - Stage 3-4

Answer 5

1. Metabolic acidosis:
   If metabolic acidosis exists (blood bicarbonate or total CO <18 mmol/l) once
   the patient is stabilized on the clinical renal diet of choice, supplement with oral
   sodium bicarbonate (or potassium citrate if hypokalemic) to effect to maintain
   blood bicarbonate / total CO in the range of 18-24 mmol/l.
2. Consider treatment for anemia if it is affecting the patient’s quality of life: typically
   this occurs when the PCV is <0.20 l/l (20%) Human recombinant erythropoietin
   is the most effective treatment but is not approved for veterinary use:
   darbepoetin is preferable as it is less antigenic than epoetin alfa. Anabolic
   steroids are of no proven benefit and may be detrimental.
3. Treat vomiting and suspected nausea with anti-emetics such as maropitant,
   or ondansetron. Consider intermittent omeprazole in dogs with suspected
   gastric bleeding (e.g. melena, iron deficiency) or vomiting-induced
   esophagitis.
4. Give fluids parenterally as necessary to maintain hydration (see Footnote).
5. Drugs that rely predominantly on renal function for their clearance from the
   body should be used with caution in patients in Stage 4 CKD. It may be
   necessary to adjust the dose of these drugs (depending on their therapeutic
   indices) to avoid accumulation.

Further recommendations for Stage 4 patients:
6. Intensify efforts to prevent protein / calorie malnutrition. Consider
feeding tube intervention (such as percutaneous gastrostomy tube).
7. Intensify efforts to prevent dehydration. Feeding tubes can be used to
administer fluids as well as food.
8. Consider dialysis and/or renal transplantation.

Question 6

Njurbiopsi

Answer 6

1. Renomegaly
2. CKD in a young patient
3. Persistent and severe proteinuria (UP/C>2.0) in an IRIS CKD Stages 1 and 2 patient
4. Worsening proteinuria in a CKD patient
5. Acute kidney injury, where renal biopsy may provide a prognostic indicator