IRIS CKD treatment recommendations - Katt

Question 1

Generellt

Answer 1

In general, at the early stages of CKD (stages 1 and 2), there are few clinical extra-renal signs of the disease and the therapeutic emphasis is on slowing progression. From stage 3 onwards, extra-renal signs become more common and more severe. The importance of administering treatments which address the clinical signs of CKD and improve the cat’s quality of life assume greater importance and exceeds the importance of treatments designed to slow progression by stage 4.

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 to minimize the risk of extra-renal target organ damage (CNS, retinal, cardiac problems/damage). If there is no evidence of such damage but systolic blood pressure persistently exceeds 160 mm Hg, increasing the risk of this occurring, treatment should be instituted.

If evidence of target organ damage exists, cats should be treated without the need to demonstrate persistently increased systolic blood pressure. Reducing blood pressure is a long term aim in managing the patient with CKD and a gradual and sustained reduction should be the goal, avoiding any sudden or severe decreases leading to hypotension.

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. Calcium channel blocker (CCB), such as amlodipine (0.125 to 0.25 mg/kg once daily) or angiotensin receptor blocker (ARB), telmisartan (2 mg/kg once daily).
3. Double the dose of amlodipine (0.25 to 0.5 mg/kg once daily) if this is treatment selected. Note telmisartan label does not advise a dose increase from 2 mg/kg once daily.
4. Combine amlodipine and telmisartan if either drug alone does not lead to adequate control of blood pressure.

Note: Take care not to introduce CCB/RAAS inhibitor treatment to unstable dehydrated cats as glomerular filtration rate may drop precipitously if these drugs are introduced before the patient is adequately hydrated.

Hypertensive cats normally require lifelong therapy and may require treatment adjustments. Serial monitoring is essential. 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 or 0.5 mg/dl increase) or SDMA concentration (<2.0 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

Cats in Stage 1 with UP/C >0.4 should be investigated for disease processes leading to proteinuria (see 1 and 2 below) and treated with anti-proteinuric measures (see 3
and 4 below).

Those with borderline proteinuria (UP/C 0.2 to 0.4) require close monitoring (see 1 and 4 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 RAAS inhibitor (ACEI or ARB ) and feed a clinical renal diet.
4. Monitor response to treatment / progression of disease:
   – stable blood creatinine concentration and decreasing UP/C = good response.
   – serially increasing blood creatinine concentrations and/or increasing UP/C = disease is progressing.

Note:
a. The use of an RAAS inhibitor is contraindicated in any cat that is clinically dehydrated or is showing signs of hypovolemia. Correct dehydration before using these drugs otherwise glomerular filtration rate may drop precipitously.

b. Cats with proteinuria and hypoalbuminemia likely share the same thromboembolic risk as dogs (although evidence is lacking in the published literature), but aspirin is difficult to use in cats to achieve a selective antiplatelet effect. A suggested dose rate if plasma albumin is below 20 g/l (2 g/dl) is 1 mg/kg every 72 hours and an alternative to aspirin is clopidogrel (10 to 18.75 mg/day).

c. Cats with serum phosphate within the IRIS target (4.5 mg/dl or 1.5 mmol/l) may be at increased risk of developing hypercalcemia when renal diets are introduced.
Monitor serum calcium and if total calcium exceeds 12 mg/dl (3 mmol/l) switch the cat to a senior diet or mix renal diet (50:50 by volume) with standard grocery food.

d. If borderline proteinuria persists, antiproteinuric treatment could be offered, because the association between progression of CKD and proteinuria includes the borderline category. However, there is at present no evidence that intervention with anti-proteinuric drugs slows progression.

Question 4

Fostat - Stage 2-4

Answer 4

Many cats in Stage 2 will have normal plasma phosphate concentrations but will have increased plasma PTH concentration. Evidence suggests that chronic reduction of phosphate intake to maintain a 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 kidney disease. 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 and neurological signs suggest aluminum toxicity if using an aluminum containing binder – switch
to another form of phosphate binder should this occur. It should be noted, however, unlike the dog, aluminum toxicity has not been reported in the cat and it is possible to measure blood aluminum levels to confirm suspected cases.

Hypercalcemia should be avoided – combinations of aluminum and calcium containing phosphate binders may
be necessary in some cases.

Question 5

Ytterligare behandling - Stage 2-4

Answer 5

Additional recommendations for Stage 2, 3 and 4 patients:
1. If the patient is hypokalemic, then potassium gluconate or potassium citrate should be supplemented to effect (typically 1-2 mmol/kg/day).

Additional recommendations for Stage 3 and 4 patients:

2. If metabolic acidosis exists (blood bicarbonate or total CO2 <16 mmol/l) once the patient is stabilized on the 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 16-24 mmol/l.
3. 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.
4. Treat vomiting / decreased appetite / nausea / weight loss with an antiemetic/ /appetite stimulant / antinausea agent (such as maropitant, ondansetron or mirtazapine). Evidence suggests mirtazapine (1.88 mg/cat every 48 h for 3 weeks) reduces vomiting, improves appetite and leads to weight gain in cats showing signs of inappetence and vomiting in this stage. Maropitant (1 mg/kg daily for2 weeks) reduced vomiting but did not lead to weight gain/ improved appetite. Further investigations are needed on the use of these and other drugs to determine whether they are useful for managing gastrointestinal disturbances in cats with CKD and uremia when administered longer
   term.
5. Give appropriate maintenance fluids parenterally as necessary to maintain hydration (see Footnote).

Additional recommendations for Stage 4 patients:

6. Intensify efforts to prevent protein / calorie malnutrition. Consider feeding tube intervention (e.g., 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.
   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.

Question 6

Njurbiopsi

Answer 6

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