(2023)

All treatments for chronic kidney disease (CKD) need to be tailored to the
individual patient. The following recommendations are useful
starting points for the majority of dogs at each stage. Serial monitoring of
these patients is ideal and treatment should be modified according to the
response to treatment. Note that staging of disease is undertaken following
diagnosis of CKD – an increased blood creatinine or symmetric
dimethylarginine (SDMA) concentration alone is not diagnostic of CKD.
Treatment recommendations fall into two broad categories, namely:
1. Those that slow progression of CKD and thereby preserve remaining
kidney function for longer
2. Those that seek to improve the quality of life of the dog, reducing signs
of CKD
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. Some of the treatment
recommendations are not authorized for use in all geographical regions and
some may not be authorized for use in dogs. Such recommended dose rates
are therefore empirical. It is the treating veterinarian’s duty to make a
risk:benefit assessment for each dog prior to administering any treatment.

1
© 2023
2019 International Renal Interest Society (IRIS) Ltd. IRIS Ltd. is an independent non-profit organization limited by guarantee in the UK (Registered Number 10213173).
 (2023)

1
Treatment recommendations for Dogs with CKD

Stage 1 Canine patients:

1. Discontinue all potentially nephrotoxic drugs if possible.
2. Identify and treat any pre-renal or post-renal abnormalities.
3. Rule out any treatable conditions like pyelonephritis and ureteral obstruction
renal urolithiasis with
with
radiographs and/or ultrasonography.
4. Measure blood pressure and urine protein to creatinine ratio (UP/C).

Management of dehydration:
In these patients, urine concentrating ability may be somewhat impaired and therefore
ensure:
• They have fresh water available at all times for drinking
• If become ill for any reason that leads to fluid losses, correct clinical dehydration with
isotonic polyioinic replacement fluid solutions (e.g. lactated Ringer’s) IV or SQ, promptly
as needed

Systemic hypertension:
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). If there is no
evidence of such damage but systolic blood pressure persistently exceeds 160 mm
Hg, treatment should be instituted.
‘Persistence’ of increase in systolic blood pressure should be judged on multiple
measurements made over the following time-scales in these blood pressure
substages:
• Hypertensive (moderate risk of future target organ damage) – systolic blood
pressure 160 to 179 mm Hg, persistence demonstrated over 1 to 2 week s
• Severely hypertensive (high risk of future target organ damage) – systolic blood
pressure 180 mm Hg persistence demonstrated over 1 to 2 weeks
If evidence of target organ damage exists, dogs should be treated without the need
to demonstrate persistently increased systolic blood pressure. Reducing blood
pressure is a long term aim when managing the patient with CKD and a gradual and
sustained reduction should be the goal, avoiding any sudden or severe decreases
leading to hypotension.
It is recognized that some breeds (such as sight hounds) tend to have higher blood
pressure (see Appendix 1) and that this may influence interpretation.
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.

© 2019
2023 International Renal Interest Society (IRIS) Ltd. IRIS Ltd. is an independent non-profit organization limited by guarantee in the UK (Registered Number 10213173)..
 (2023)

1 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) and/or hydralazine if additional treatment is required.
Note: Take care not to introduce ACEI/CCB with or without ARB to unstable
dehydrated dogs as glomerular filtration rate may drop precipitously if these
drugs are introduced before the patient is adequately hydrated. The risk
benefit analysis of combining ACEI with ARBs needs to be made on an
individual dog basis and careful monitoring is required to ensure any
deterioration in kidney function is detected.

Monitoring response to antihypertensive treatment:

Hypertensive dogs normally require lifelong therapy and frequently require
adjustments in treatment. 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)
and/or SDMA (< 2 µg/dl), but a marked increase suggests an adverse drug effect.
Progressively increasing concentrations indicate progressive kidney
damage/disease.

Proteinuria:
Dogs in Stage 1 with UP/C >0.5 should be investigated for disease processes leading
to proteinuria (see 1 and 2 below) andThose with confirmed
treated and persistent
with antiproteinuric renal proteinuria
measures (see 3,
should
4, 5 andbe6 treated
below).with antiproteinuric measures (see 3, 4, 5 and 6 below).
Those with
Those with borderline
borderlineproteinuria
proteinuria(UP/C
(UP/C0.2 to to
0.2 0.5) require
0.5) close
require monitoring
close (see(see
monitoring 1 and1 6
below).
and The goal of treatment is nuanced. Treatment should be aimed to have the
6 below).
reduction in proteinuria to the lowest UPC possible without doing harm (see point 6).
1. Look for any concurrent associated disease process that may be treated/corrected.
2. Consider kidney biopsy as a means of identifying underlying disease (see
1.Appendix
Look for any concurrent
2 and/or associated
consult experts disease process
if unsure that mayfor
of indications bekidney
treated/corrected.
biopsy).
3. Administer an ACEI and feed a clinical renal diet.
2. Consider kidney biopsy (for dogs in stages 1 to 3, not stage 4) as a means of
4.identifying
Combine underlying
ACEI and diet with(see
disease an angiotensin receptor
Appendix 2 and/or blocker
consult (ARB)
experts if proteinuria
if unsure of is
not controlled.
indications for kidney biopsy).
5. Administer low-dose acetylsalicylic acid (1 to 5 mg/kg once daily) or
3.clopidogrel
Administer (1.1-3
an angiotensin receptor
mg/kg orally everyblocker (ARB)ifand
24 hours) feed albumin
serum a clinical is
renal
<20diet.
g/l (2.0 g/dl).
6.4.Monitor
Combination
responseof antoACEI and diet/ progression
treatment with an angiotensin receptor blocker (ARB) if
of disease:
proteinuria is notcreatinine
– stable blood controlledconcentration
should be done judiciously
and decreasingandUP/C
cautiously,
= good ideally under
response.
consultation with a veterinary nephrologist (see note 1 below).
– serially increasing blood creatinine concentration and/or increasing UP/C =
disease is progressing.
5. Administer
Ordinarily therapy clopidogrel (1.1-3 mg/kg
will be maintained orally every
lifelong unless24the
hours) if serumdisease
underlying albuminhasis <20 g/l
been
(2.0 g/dl). If clopidogrel is not available, low-dose acetylsalicylic acid
resolved in which case dose reduction whilst monitoring UP/C might be considered. (2 to 5 mg/kg once
daily) is an acceptable alternative (see note 2 below).

2023 International Renal Interest Society (IRIS) Ltd. IRIS Ltd. is an independent non-profit organization limited by guarantee in the UK (Registered Number 10213173)..
© 2019
 (2023)

1 Note
6. Monitor 1: ACEItoortreatment
Note:
response ARB use /isprogression
contraindicated in any dog that is clinically dehydrated
of disease:
and/or is showing signs of hypovolemia. Correct dehydration before using these
– stable blood creatinine concentration, decreasing UP/C and/or increasing serum
drugs otherwise glomerular filtration rate may drop precipitously. The risk benefit
albumin (if previously low) = good response.
analysis of combining ACEI with ARBs needs to be made on an individual dog basis
– a UPCandof <careful
0.5 is not achievable
monitoring for many to
is required dogs with primary
ensure glomerularindisease.
any deterioration kidney For
function is
these dogs the goal
detected. shoulddetailed
Further be a 50% reduction in UPC from
recommendations baseline and management of
for diagnosis
– serially increasingdisease
glomerular blood creatinine
in dogs canconcentration
be found inand/or increasing
the IRIS UP/CStatements
Consensus = disease
is progressing.
published in Journal of Veterinary Internal Medicine in 2013 (supplement to volume
27).
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.

Note 1:
ACEI or ARB use is contraindicated in any dog that is clinically dehydrated and/or is
showing signs of hypovolemia. Correct dehydration before using these drugs otherwise
glomerular filtration rate may drop precipitously. The risk benefit analysis of combining
ACEI with ARBs needs to be made on an individual dog basis and careful monitoring is
required to ensure any deterioration in kidney function is detected. Further detailed
recommendations for diagnosis and management of glomerular disease in dogs can be
found in the IRIS Consensus Statements published in Journal of Veterinary Internal
Medicine in 2013 (supplement to volume 27).

Note 2:
Dogs with PLN are at risk of thrombosis however it is not possible to predict the risk for
thrombosis in the individual patient as serum albumin, antithrombin and degree of
proteinuria are poorly associated with thrombotic risk. Tests such as
thromboelastography, thrombin generation and markers of activated clotting can be used
to document hypercoagulability, however, identification of a hypercoagulable state has
not been shown to correlate to risk of developing thrombosis. Prothrombin and partiel
thrombloplastin times (PT, PTT) also cannot be used to predict thrombotic risk.
Antithrombotic therapy is indicated in dogs with PLN (CURATIVE Guidelines DOI:
10.1111/vec.12801). Clopidogrel (1-4mg/kg orally once daily) administration may be
more effective than low dose acetylsalicylic acid (1-5mg/kg orally once daily) for
thromboprophylaxis

2023 International Renal Interest Society (IRIS) Ltd. IRIS Ltd. is an independent non-profit organization limited by guarantee in the UK (Registered Number 10213173)..
© 2019
 (2023)

2 Stage 2 Canine patients:

All of the above listed for Stage 1 (listed here again for convenience), plus any additional
steps indicated below.
1. Discontinue all potentially nephrotoxic drugs if possible.
2. Identify and treat any pre-renal or post-renal abnormalities.
3. Rule out any treatable conditions like pyelonephritis and ureteral obstruction
renal urolithiasis with
with
radiographs and/or ultrasonography.
4. Measure blood pressure and urine protein to creatinine ratio (UP/C).
5. Consider feeding a clinical renal diet: this may be accomplished more easily
early in the course of CKD, before inappetence develops.

Management of dehydration:
These canine patients have decreased urine concentrating ability and therefore ensure:
• They have fresh water available at all times for drinking.
• If they become ill for any reason leading to fluid losses, correct clinical
dehydration/hypovolemia with isotonic, polyionic replacement fluid solutions (e.g.,
lactated Ringer’s) IV or SQ promptly as needed

Systemic hypertension:
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). If there is
no evidence of this but systolic blood pressure persistently exceeds 160 mm Hg,
increasing the risk of such damage, treatment should be instituted.
‘Persistence’ of increase in systolic blood pressure should be judged on multiple
measurements made over the following time-scales in these blood pressure
substages:
• Hypertensive (moderate risk of future target organ damage) – systolic blood
pressure 160 to 179 mm Hg – persistence demonstrated over 1 to 2 weeks
• Severely hypertensive (high risk of future target organ damage) – systolic blood
pressure 180 mm Hg persistence demonstrated over 1 to 2 weeks
If evidence of target organ damage exists, dogs should be treated without the need
to demonstrate persistently increased systolic blood pressure. Reducing blood
pressure is a long term aim in a patient with CKD and a gradual and sustained
reduction should be the goal, avoiding any sudden decreases or hypotension.

2023 International Renal Interest Society (IRIS) Ltd. IRIS Ltd. is an independent non-profit organization limited by guarantee in the UK (Registered Number 10213173)..
© 2019
 (2023)

2
It is recognized that some breeds (such as sight hounds) tend to have higher blood
pressure (see Appendix 1) and that this may influence interpretation.
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 patients, 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 blocker (ARB, such as telmisartan)
and/or hydralazine if additional treatment is required.
Note: Take care not to introduce ACEI/CCB with or without ARB treatment to
unstable dehydrated dogs as glomerular filtration rate may drop precipitously
if these drugs are introduced before the patient is adequately hydrated. The
risk benefit analysis of combining ACEI with ARBs needs to be made on an
individual dog basis and careful monitoring is required to ensure any
deterioration in kidney function is detected.

Monitoring response to antihypertensive treatment:

Hypertensive dogs normally require lifelong therapy and frequently require
adjustments in treatment dosages. 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 (<45 µmol/l or 0.5 mg/dl increase) and/or SDMA (<
2 µg/dl), but a marked increase suggests an adverse drug effect. Progressively
increasing concentrations indicate progressive kidney damage/disease.

Proteinuria:
Dogsin
Dogs inStage
Stage 22 with
with UP/C
UP/C>0.5
>0.5should
should bebeinvestigated
investigatedforfor
thethe
disease processes
disease leading
processes
to proteinuria (see 1 and 2 below). Those with confirmed and persistent renal proteinuria
leading to proteinuria (see 1 and 2 below) and treated with anti-proteinuric measures
should be treated with anti-proteinuric measures (see 3, 4, 5 and 6 below). The goal of
(see 3, 4, 5 and 6 below).
treatment is nuanced. Treatment should be aimed to have the reduction in proteinuria to
the lowest
Those with UPC possible
borderline without doing
proteinuria harm
(0.2 to 0.5)(see pointclose
require 6). monitoring
(see 1 and 6 below).
Those with borderline proteinuria (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.
1. Look for any concurrent associated disease process that may be treated/corrected.
2. 2.Consider
Considerkidney
kidneybiopsy
biopsy as
(foradogs
means of identifying
in stages underlying
1 to 3, not disease
stage 4) as (see
a means of
Appendix 2 and/or consult experts if unsure of indications for kidney biopsy).
identifying underlying disease (see Appendix 2 and/or consult experts if unsure of
3. indications
Administerfor
ankidney biopsy).
ACEI and feed a clinical renal diet.
3. Administer an angiotensin receptor blocker (ARB) and feed a clinical renal diet.

© 2023
2019 International Renal Interest Society (IRIS) Ltd. IRIS Ltd. is an independent non-profit organization limited by guarantee in the UK (Registered Number 10213173)..
 (2023)

4.4. Combination
Combine ACEI of an
andACEI
dietand diet
with anwith an ARB ifreceptor
angiotensin proteinuria is not(ARB)
blocker controlled should be
if proteinuria
2 done judiciously and cautiously, ideally under consultation with a veterinary
is not controlled.
nephrologist (see note 1 below).
5. Low-dose acetylsalicylic acid (1 to 5 mg/kg once daily) or clopidogrel
5. Administer clopidogrel (1.1-3 mg/kg orally every 24 hours) if serum albumin is <20 g/l
(1.1-3 mg/kg orally every 24 hours) if serum albumin is <20 g/l (2.0
(2.0 g/dl). If clopidogrel is not available, low-dose acetylsalicylic acid (2 to 5 mg/kg once
g/dl).
daily) is an acceptable alternative (see note 2 below).
6.6. Monitor
Monitor response
responseto totreatment
treatment/ /progression
progressionofof disease:
disease:
–– stable
stableblood
bloodcreatinine
creatinineconcentration,
concentrationdecreasing
and decreasing UP/C increasing
UP/C and/or = good response.
serum
– serially(ifincreasing
albumin previouslybloodlow) =creatinine concentrations and/or increasing UP/C
good response.
– a=UPC of < 0.5
disease is not achievable for many dogs with primary glomerular disease. For
is progressing.
these dogs the goal should be a 50% reduction in UPC from baseline.
Ordinarily therapy will be maintained lifelong unless the underlying disease has been
– serially increasing blood creatinine concentrations and/or increasing UP/C and/or
resolved in which
increasing serum case dose(ifreduction
albumin previously whilst
low) monitoring
= disease is UP/C might be considered.
progressing.
Note: ACEI or ARB use is contraindicated in any animal that is clinically dehydrated
Ordinarily
and/or showingtherapysignswill be
of maintained
hypovolemia. lifelong unless
Correct the underlying
dehydration beforedisease
using has
thesebeendrugs
resolved in which case dose reduction whilst monitoring UP/C might
otherwise glomerular filtration rate may drop precipitously. The risk benefit analysisbe considered.
of combining ACEI with ARBs needs to be made on an individual dog basis and
Note 1: ACEI or ARB use is contraindicated in any animal that is clinicallydehydrated
careful monitoring is required to ensure any deterioration in kidney function is
and/or showing signs of hypovolemia. Correct dehydration before using these drugs
detected.glomerular
otherwise Further detailed recommendations
filtration for diagnosis
rate may drop precipitously. Theand
riskmanagement
benefit analysis of of
glomerular disease in dogs can be found in the IRIS Consensus
combining ACEI with ARBs needs to be made on an individual dog basis and careful Statements
published in
monitoring Journal of
is required toVeterinary
ensure any Internal Medicine
deterioration in 2013
in kidney (supplement
function to volume
is detected. Further
27).
detailed recommendations for diagnosis and management of glomerular disease in dogs
can be found in the IRIS Consensus Statements published in Journal of Veterinary Internal
Reduction
Medicine of phosphate
in 2013 (supplement intake:
to volume 27).
Evidence suggests that chronic reduction of phosphate intake to maintain plasma
Note 2: Dogs with PLN are at risk of thrombosis however it is not possible to predict the
phosphate concentration below 1.5 mmol/l (but not less than 0.9 mmol/l; <4.6 mg/
risk for thrombosis in the individual patient as serum albumin, antithrombin and degree
dlproteinuria
of but >2.7 mg/dl) is beneficial
are poorly to patients
associated with CKD.
with thrombotic risk.The following
Tests such as measures can be
introduced sequentially
thromboelastography, in an attempt
thrombin generationto achieve this: of activated clotting can be used
and markers
to
1.document hypercoagulability,
Dietary phosphate restrictionhowever, identification
(i.e., clinical renal dietoftherapy).
a hypercoagulable state has
not been shown to correlate to risk of developing thrombosis. Prothrombin and partiel
2. If plasma phosphate
thrombloplastin times (PT,concentration
PTT) also cannot remains
be usedabove 1.5 mmol/l
to predict (4.6 mg/dl)
thrombotic risk.
after dietarytherapy
Antithrombotic restriction, give enteric
is indicated in dogsphosphate
with PLN binders
(CURATIVE (such as aluminum
Guidelines DOI:
hydroxide, aluminum
10.1111/vec.12801). carbonate,
Clopidogrel calcium
(1-4mg/kg carbonate,
orally once daily)calcium acetate, lanthanum
administration may be
more effective than
carbonate) low dose
to effect, acetylsalicylic
starting acid (1-5mg/kg
at 30-60 mg/kg/day orally once
in divided dosesdaily)
to beformixed
thromboprophylaxis.
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.

Where there is a discrepancy between creatinine and SDMA:

If serum or plasma SDMA is >35 µg/dl in a patient whose creatinine is between
1.4 and 2.8 mg/dl (IRIS CKD stage 2 based on blood creatinine), this patient,
should be staged and treated as an IRIS CKD Stage 3 patient.

2023 International Renal Interest Society (IRIS) Ltd. IRIS Ltd. is an independent non-profit organization limited by guarantee in the UK (Registered Number 10213173)
© 2019
 (2023)

4.4. Combination
Combine ACEI of an
andACEI
dietand
withdiet
anwith an ARB ifreceptor
angiotensin proteinuria is not(ARB)
blocker controlled should be
if proteinuria
2 done judiciously and cautiously, ideally under consultation with a veterinary
is not controlled.
nephrologist (see note 1 below).
5. Low-dose acetylsalicylic acid (1 to 5 mg/kg once daily) or clopidogrel
5. Administer clopidogrel (1.1-3 mg/kg orally every 24 hours) if serum albumin is <20 g/l
(1.1-3 mg/kg orally every 24 hours) if serum albumin is <20 g/l (2.0
(2.0 g/dl). If clopidogrel is not available, low-dose acetylsalicylic acid (2 to 5 mg/kg once
g/dl).
daily) is an acceptable alternative (see note 2 below).
6.6. Monitor
Monitor response
responseto totreatment
treatment/ /progression
progressionofof disease:
disease:
–– stable
stableblood
bloodcreatinine
creatinineconcentration,
concentrationdecreasing
and decreasing UP/C increasing
UP/C and/or = good response.
serum
– serially(ifincreasing
albumin previouslyblood
low) =creatinine concentrations and/or increasing UP/C
good response.
– serially increasing
= disease blood creatinine concentrations and/or increasing UP/C and/or
is progressing.
increasing serum albumin (if previously low) = disease is progressing.
Ordinarily therapy will be maintained lifelong unless the underlying disease has been
resolved in
Ordinarily whichwill
therapy casebedose reduction
maintained whilst
lifelong monitoring
unless UP/C might
the underlying be considered.
disease has been
resolved in which
Note: ACEI caseuse
or ARB dose reduction whilst monitoring
is contraindicated in any animal UP/C might
that be considered.
is clinically dehydrated
and/or showing signs of hypovolemia. Correct dehydration before using these drugs
Note 1: ACEIglomerular
otherwise or ARB usefiltration
is contraindicated in anyprecipitously.
rate may drop animal that is clinicallydehydrated
The risk benefit analysis
and/or showing signs of hypovolemia. Correct dehydration before using these drugs
of combining ACEI with ARBs needs to be made on an individual dog basis and
otherwise glomerular filtration rate may drop precipitously. The risk benefit analysis of
careful monitoring is required to ensure any deterioration in kidney function is
combining ACEI with ARBs needs to be made on an individual dog basis and careful
detected. Further
monitoring detailed
is required recommendations
to ensure forindiagnosis
any deterioration and management
kidney function of
is detected. Further
glomerular disease in dogs can be found in the IRIS Consensus Statements
detailed recommendations for diagnosis and management of glomerular disease in dogs
published
can be foundin in
Journal
the IRISofConsensus
VeterinaryStatements
Internal Medicine
published in in
2013 (supplement
Journal to volume
of Veterinary Internal
27).
Medicine in 2013 (supplement to volume 27).

Reduction of phosphate intake:

Additional treatments for stage 2 patients aimed at improving their quality of life:
Evidence suggests that chronic reduction of phosphate intake to maintain plasma
Treat phosphate
suspected nausea with anti-emetics
concentration below 1.5such as maropitant
mmol/l or ondansetron.
(but not less Treat<4.6 mg/
than 0.9 mmol/l;
decreased
dl butappetite/weight and/or muscle
>2.7 mg/dl) is beneficial loss with
to patients appetite
with stimulants
CKD. The suchmeasures
following as can be
capromorelin
introducedor mirtazapine.
sequentiallyIfinmuscle loss isto
an attempt marked,
achieve consider
this: staging based on serum
SDMA concentration rather than creatinine and following treatment recommendations for
SDMA1.stage
Dietary
(see phosphate
below). restriction (i.e., clinical renal diet therapy).
2. If plasma phosphate concentration remains above 1.5 mmol/l (4.6 mg/dl)
Considerafter
omeprazole
dietary in dogs withgive
restriction, suspected
entericgastric bleeding
phosphate (eg melena,
binders (such asiron deficiency)
aluminum
or vomiting-induced esophagitis.
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.

Where there is a discrepancy between creatinine and SDMA:

If serum or plasma SDMA is >35 µg/dl in a patient whose creatinine is between
1.4 and 2.8 mg/dl (IRIS CKD stage 2 based on blood creatinine), this patient,
should be staged and treated as an IRIS CKD Stage 3 patient.

2023 International Renal Interest Society (IRIS) Ltd. IRIS Ltd. is an independent non-profit organization limited by guarantee in the UK (Registered Number 10213173)
© 2019
 (2023)

3
Stage 3 Canine patients:
The range of presentations for dogs in Stage 3 is wide, from no clinical signs to
quite marked extra-renal signs. The treatments mentioned so far for Stages 1 and
2 aimed at slowing progression of CKD also apply in Stage 3 and may be all that
i s required for dogs with no or mild clinical signs. But treatments designed to
improve the quality of life are more important as extra-renal signs become
increasingly evident. These include treatments to address dehydration, nausea
and vomiting, anemia and acidosis.
Treatment recommendations include all of the above listed for Stage 1 and 2 (listed again
here for convenience) plus any additional steps indicated below.
1. Discontinue all potentially nephrotoxic drugs if possible.
2. Identify and treat any pre-renal or post-renal abnormalities.
3. Rule out any treatable conditions like pyelonephritis and ureteral obstruction
renal urolithiasis with
with
radiographs and/or ultrasonography.
4. Measure blood pressure and urine protein to creatinine ratio (UP/C).
5. Feed a clinical renal diet.

Management of dehydration:
These patients have decreased urine concentrating ability and therefore
• correct clinical dehydration/hypovolemia with isotonic, polyionic replacement
fluid solutions (e.g., lactated Ringer’s) IV or SQ promptly as needed.
• have fresh water available at all times for drinking
• In addition, some of these dogs may require maintenance fluids administered routinely to
maintain hydration (see below)

Systemic hypertension:
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). If there is
no evidence of this but systolic blood pressure persistently exceeds 160 mm Hg,
increasing the risk of such damage, treatment should be instituted.
‘Persistence’ of increased systolic blood pressure should be judged on multiple
measurements made over the following time-scales in these blood pressure
substages:
• Hypertensive (moderate risk of future target organ damage) – systolic blood
pressure 160 to 179 mm Hg, persistence demonstrated over 1 to 2 weeks
• Severely hypertensive (high risk of future target organ damage – systolic blood
pressure 180 mm Hg measured, persistence demonstrated over 1 to 2 weeks
If evidence of target organ damage exists, dogs should be treated without the need
to demonstrate persistently increased systolic blood pressure. Reducing blood
pressure is a long term aim when managing the patient with CKD and a gradual and
sustained reduction should be the goal, avoiding any sudden or severe decreases
leading to hypotension.
Some breeds (such as sight hounds) tend to have higher blood pressure (see
Appendix) and that this may influence interpretation.
© 2023
2019 International Renal Interest Society (IRIS) Ltd. IRIS Ltd. is an independent non-profit organization limited by guarantee in the UK (Registered Number 10213173)
 (2023)
A logical stepwise approach to managing hypertension is as follows:

3 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 patients, 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) and/or hydralazine if additional treatment is required.
Note: Take care not to introduce ACEI/CCB with or without ARB treatment to
unstable dehydrated dogs as glomerular filtration rate may drop precipitously if
these drugs are introduced before the patient is adequately hydrated. The risk
benefit analysis of combining ACEI with ARBs needs to be made on an individual
dog basis and careful monitoring is required to ensure any deterioration in kidney
function is detected. The risk is higher in CKD stages 3 and 4.

Monitoring response to antihypertensive treatment:

Hypertensive dogs 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 blood creatinine (<45 µmol/l or 0.5 mg/dl increase) and/or
SDMA (< 2 µg/dl),, but a marked increase suggests an adverse drug effect.
Progressively increasing creatinine concentrations indicate progressive kidney
damage/disease.

Proteinuria:
Dogs in Stage 3 with urine protein to creatinine ratio (UP/C) >0.5 should be investigated
Dogs in Stage 3 with urine protein to creatinine ratio (UP/C) >0.5 should be
for disease processes leading to proteinuria (see 1 and 2 below). Those with confirmed
investigated
and persistent forrenal
disease processes
proteinuria leading
should to proteinuria
be treated (see 1 and measures
with anti-proteinuric 2 below) (see 3, 4,
and treated with anti-proteinuric measures (see 3, 4, 5 and 6 below).
5 and 6 below). The goal of treatment is nuanced. Treatment should be aimed to have the
reduction
Those withinborderline
proteinuriaproteinuria
to the lowest UPC
(0.2 possible
to 0.5) without
require closedoing harm (see point 6).
monitoring
(see 1 and 6 below).
Those with borderline proteinuria (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.
1. Look for any concurrent associated disease process that may be treated/corrected.
2. Consider kidney biopsy as a means of identifying underlying disease (see
2.Appendix
Consider kidney
2 and/orbiopsy (forexperts
consult dogs in stages 1 toof3,indications
if unsure not stage 4)for
askidney
a meansbiopsy).
of
identifying underlying disease (see Appendix 2 and/or consult experts if unsure of
3. Administer an ACEI and feed a clinical renal diet.
indications for kidney biopsy).
4.3.Combine
AdministerACEI and diet with
an angiotensin an angiotensin
receptor receptor
blocker (ARB) blocker
and feed (ARB)
a clinical if proteinuria
renal diet.
is not controlled.
4. Combination of an ACEI and diet with an ARB if proteinuria is not controlled, should be
5.done
Low-dose acetylsalicylic
judiciously acid ideally
and cautiously, (1 to 5 under
mg/kgconsultation
once daily) with
or clopidogrel
a veterinary(1.1-
3 mg/kg orally every 24 hours)
nephrologist (see note 1 below). if serum albumin is <20 g/l (2.0 g/dl).

© 2023
2019 International Renal Interest Society (IRIS) Ltd. IRIS Ltd. is an independent non-profit organization limited by guarantee in the UK (Registered Number 10213173).
 (2023)

5. Administer clopidogrel (1.1- 3 mg/kg orally every 24 hours) if serum albumin is <20 g/l
(2.0 g/dl). If clopidogrel is not available, low-dose acetylsalicylic acid (2 to 5 mg/kg once
3 daily) is an acceptable alternative (see note 2 below).
6. Monitor response to treatment / progression of disease:
– stable response
6. Monitor blood creatinine concentration
to treatment / progressionandofdecreasing
disease: UP/C = good response.
– serially increasing blood creatinine concentration
– stable blood creatinine concentration, decreasing UP/C and/or
and/orincreasing
increasingUP/C
serum
= disease
albumin is progressing.
(if previously low) = good response.
– a UPC of < 0.5 is not achievable for many dogs with primary glomerular disease. For
Ordinarily
these dogs therapy willshould
the goal be maintained
be a 50%lifelong
reductionunless
in UPCthefrom
underlying
baselinedisease has been
– serially
resolved in increasing
which case blood
dosecreatinine
reductionconcentration and/or
whilst monitoring increasing
UP/C might UP/C = disease is
be considered.
progressing.
Note: ACEI or ARB use is contraindicated in any animal that is clinically dehydrated
and/or
Ordinarilyis therapy
showingwill signs of hypovolemia.
be maintained lifelong Correct
unlessdehydration
the underlying before using
disease hasthese
been
drugs otherwise
resolved in which caseglomerular filtrationwhilst
dose reduction rate may drop precipitously.
monitoring UP/C might be The risk benefit
considered.
analysis of combining ACEI with ARBs needs to be made on an individual dog basis
and 1:
Note careful
ACEI ormonitoring
ARB use isiscontraindicated
required to ensure in anyany deterioration
animal in kidney
that is clinically function is
dehydrated
detected.
and/or The risk
is showing is higher
signs in CKD stages
of hypovolemia. Correct 3 and 4. Further
dehydration detailed
before using these drugs
otherwise glomerularforfiltration
recommendations diagnosisrateand
maymanagement
drop precipitously. The risk benefit
of glomerular diseaseanalysis
in dogsofcan
combining
be found inACEI thewith
IRISARBs needs toStatements
Consensus be made onpublished
an individual dog basis
in Journal of and careful
Veterinary
monitoring is required
Internal Medicine to ensure
in 2013 any deterioration
(supplement to volume in 27).
kidney function is detected. The risk
is higher in CKD stages 3 and 4. Further detailed recommendations for diagnosis and
management of glomerular disease in dogs can be found in the IRIS Consensus
Statements published in Journal of Veterinary Internal Medicine in 2013 (supplement to
Reduction
volume 27). of phosphate intake:
Evidence suggests that chronic reduction of phosphate intake to maintain a plasma
Note 2: Dogs with PLN are at risk of thrombosis however it is not possible to predict the
phosphate concentration below 1.5 mmol/l (but not less than 0.9 mmol/l; <4.6 mg/dl
risk for thrombosis in the individual patient as serum albumin, antithrombin and degree
but >2.7 mg/dl) is beneficial to patients with CKD.
of proteinuria are poorly associated with thrombotic risk. Tests such as
thromboelastography, thrombin generation
A more realistic post-treatment and markers
target for dogs of activated
at Stage 3 is <1.6 clotting can be
mmol/l (5.0 used
mg/dl).
to document hypercoagulability, however, identification of a hypercoagulable state has
Thebeen
not following
shownmeasures
to correlatecan
to be
riskintroduced sequentially
of developing in an
thrombosis. attempt to and
Prothrombin achieve
partielthis:
thrombloplastin times (PT, PTT) also cannot be used to predict
1. Dietary phosphate restriction (i.e., clinical renal diet therapy). thrombotic risk.
Antithrombotic therapy is indicated in dogs with PLN (CURATIVE Guidelines DOI:
2. If plasma phosphate
10.1111/vec.12801). concentration
Clopidogrel remains
(1-4mg/kg orally above 1.6 mmol/l
once daily) (5.0 mg/dl)
administration mayafter
be
more dietary restriction,
effective than lowgivedoseenteric phosphate
acetylsalicylic acid binders
(1-5mg/kg(such asonce
orally aluminum hydroxide,
daily) for
aluminum carbonate, calcium carbonate, calcium acetate; lanthanum carbonate)
thromboprophylaxis
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 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.

© 2023
2019 International Renal Interest Society (IRIS) Ltd. IRIS Ltd. is an independent non-profit organization limited by guarantee in the UK (Registered Number 10213173).
 (2023)

3 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.
Note: ACEI or ARB use is contraindicated in any animal that is clinically dehydrated
and/or is showing signs of hypovolemia. Correct dehydration before using these
drugs otherwise glomerular filtration rate may drop precipitously. The risk benefit
analysis of combining ACEI with ARBs needs to be made on an individual dog basis
and careful monitoring is required to ensure any deterioration in kidney function is
detected. The risk is higher in CKD stages 3 and 4. Further detailed
recommendations for diagnosis and management of glomerular disease in dogs can
be found in the IRIS Consensus Statements published in Journal of Veterinary
Internal Medicine in 2013 (supplement to volume 27).

Reduction of phosphate intake:

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.
A more realistic post-treatment target for dogs at Stage 3 is <1.6 mmol/l (5.0 mg/dl).
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 1.6 mmol/l (5.0 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 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.

© 2019 International Renal Interest Society (IRIS) Ltd. IRIS Ltd. is an independent non-profit organization limited by guarantee in the UK (Registered Number 10213173).
 (2023)

Additional recommendations for Stage 3 patients aimed at improving

3 quality of life:

If metabolic acidosis exists (blood bicarbonate or total CO 2 <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 2 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
Treat andand
vomiting suspected nausea
suspected with anti-emetics
nausea such assuch
with anti-emetics maropitant
as or
ondansetron.
maropitant Treat decreased
or ondansetron. appetite/weight
Consider intermittentand/or muscleinloss
omeprazole withwith
dogs appetite
stimulants
suspected suchbleeding
gastric as capromorelin or mirtazapine.
(eg melena, Consider
iron deficiency) intermittent omeprazole in
or vomiting-induced
dogs with suspected gastric bleeding (eg melena, iron deficiency) or
esophagitis.
vomiting-induced esophagitis. If pharmacological management of appetite is
4. ineffective
Give appropriate maintenance
and/or supplemental fluids parenterally
hydration as
is required long-term, enteral feeding
necessary to maintain hydration
tube should be considered. (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 3 CKD. It may be necessary to adjust the dose of these drugs
(depending on their therapeutic indices) to avoid accumulation.

Where there is a discrepancy between creatinine and SDMA:

If serum or plasma SDMA is >54 µg/dl in a dog with a blood creatinine

concentration of between 2.8 and 5 mg/dl (IRIS CKD Stage 3 based on
creatinine), the patient should be staged an IRIS CKD Stage 4 patient and
receive the recommended treatments for Stage 4 patients.

1
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2019 International Renal Interest Society (IRIS) Ltd. IRIS Ltd. is an independent non-profit organization limited by guarantee in the UK (Registered Number 10213173).
 (2023)

4 Stage 4 Canine patients:

Most dogs with Stage 4 CKD exhibit many extra-renal signs. Although it is still
advisable to try to slow progression of CKD, treatments to improve quality of life
become more important, especially management of dehydration, acidosis,
vomiting, nausea and inappetance, weight loss and anemia. Treatment
recommendations therefore include all of the above listed for Stages 1, 2 and 3,
(listed again here for convenience) plus any additional steps indicated below.

1. Discontinue all potentially nephrotoxic drugs if possible.

2. Identify and treat any pre-renal or post-renal abnormalities.
3. Rule out any treatable conditions like pyelonephritis (any urinary tract infection
should be regarded as a potential pyelonephritis and treated appropriately) and
ureteral
renal obstruction
urolithiasis with
with radiographs
radiographs and/or
and/or ultrasonography.
ultrasonography.
4. Measure blood pressure and urine protein to creatinine ratio (UP/C).
5. Clinical renal diet therapy.

Management of dehydration:
These patients have decreased urine concentrating ability and therefore
• correct clinical dehydration/hypovolemia with isotonic, polyionic replacement
fluid solutions (e.g., lactated Ringer’s) IV or SQ, promptly as needed.
• have fresh water available at all times for drinking.
• In addition, some of these dogs may require maintenance fluids administered routinely to
maintain hydration (see below)

Systemic hypertension:
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). If there is
no evidence of this but systolic blood pressure persistently exceeds 160 mm Hg,
increasing the risk of such damage, treatment should be instituted.
‘Persistence’ of increased systolic blood pressure should be judged on multiple
measurements made over the following time-scales in these blood pressure substages:
• Hypertensive (moderate risk of future target organ damage) – systolic blood
pressure 160 to 179 mm Hg, persistence demonstrated over 1 to 2 weeks
• Severely hypertensive (high risk of future target organ damage) – systolic blood
pressure 180 mm Hg, persistence demonstrated over 1 to 2 weeks
If evidence of target organ damage exists, dogs should be treated without the need
to demonstrate persistently increased systolic blood pressure. Reducing blood
pressure is a long term aim when managing the patient with CKD and a gradual and
sustained reduction should be the goal, avoiding any sudden or severe decreases
leading to hypotension.
It is recognized that some breeds (such as sight hounds) tend to have higher blood
pressure (see Appendix 1) and that this may influence interpretation.

11
© 2023
2019 International Renal Interest Society (IRIS) Ltd. IRIS Ltd. is an independent non-profit organization limited by guarantee in the UK (Registered Number 10213173).
 (2023)

A logical stepwise approach to managing hypertension is as follows:

4 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 patients, 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 an angiotensin receptor blocker (ARB, such as
telmisartan) and/or hydralazine if additional treatment is required.
Note: Take care not to introduce ACEI/CCB with or without ARB treatment to
unstable dehydrated dogs as glomerular filtration rate may drop precipitously if
these drugs are introduced before the patient is adequately hydrated. The risk
benefit analysis of combining ACEI with ARBs needs to be made on an individual dog
basis and careful monitoring is required to ensure any deterioration in kidney function
is detected. The risk is higher for CKD stages 3 and 4 patients.

Monitoring response to antihypertensive treatment:

Hypertensive dogs 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 (<45 µmol/l or 0.5 mg/dl increase) and/or SDMA
(< 2 µg/dl), but a marked increase suggests an adverse drug effect.
Progressively increasing creatinine concentrations indicate progressive kidney
damage/disease.

Proteinuria:
Dogs in Stage 4 with urine protein to creatinine ratio (UP/C) >0.5 should be
investigated for the disease processes leading to proteinuria (see 1 and 2 below)
and treated with anti-proteinuric measures (see 3, 4, 5 and 6 below).
Those with borderline proteinuria (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 (see
Appendix 2 and/or consult experts if unsure of indications for kidney biopsy).
3. Administer an ACEI and feed a clinical renal diet.
4. Combine ACEI and diet with angiotensin receptor blocker (ARB) if proteinuria
is not controlled.

1
© 2023
2019 International Renal Interest Society (IRIS) Ltd. IRIS Ltd. is an independent non-profit organization limited by guarantee in the UK (Registered Number 10213173).
 (2023)

A logical stepwise approach to managing hypertension is as follows:

Proteinuria:
4 1. Dietary sodium (Na) reduction – there is no evidence that lowering dietary Na
Dogs inwillStage 4 with
reduce urine
blood protein to
pressure. creatinine
If dietary Naratio (UP/C)is>0.5
reduction should beit investigated
attempted, should be
for theaccomplished
disease processes leading
gradually to in
and proteinuria
combination(see with
1 andpharmacological
2 below). Those with confirmed
therapy.
and persistent renal proteinuria should be treated with anti-proteinuric measures (see 3, 4,
5 and 6 below). Theconverting
2. Angiotensin goal of treatment
enzyme is inhibitor
nuanced.(ACEI,
Treatment
suchshould be aimed therapy
as benazepril) to have the
reduction in proteinuria
at standard to the lowest UPC possible without doing harm (see point 6).
dose rate.
3. Double
Those the doseproteinuria
with borderline of ACEI (in some
(0.2 patients,
to 0.5) requireincreasing the dose
close monitoring (seemay improve
1 and 6 below).
the antihypertensive effect).
1.4.Look for anyACEI
Combine concurrent associated
and calcium disease
channel process
blocker that such
(CCB, may be
astreated/corrected.
amlodipine) treatment,
2. Consider kidney
especially biopsy (for
if severely dogs in stages 1 to 3, not stage 4) as a means of
hypertensive.
identifying underlying disease (see Appendix 2 and/or consult experts if unsure of
5. Combine
indications for ACEI
kidneyand CCB with an angiotensin receptor blocker (ARB, such as
biopsy).
telmisartan) and/or hydralazine if additional treatment is required.
3. Administer an angiotensin receptor blocker (ARB) and feed a clinical renal diet.
4.Note: Take care
Combination notACEI
of an to introduce ACEI/CCB
and diet with with or without
ARB if proteinuria is not ARB treatment
controlled, to be
should
unstable dehydrated dogs as glomerular filtration rate may drop
done judiciously and cautiously, ideally under consultation with a veterinary precipitously if
these drugs(see
nephrologist are note
introduced before the patient is adequately hydrated. The risk
1 below).
benefit analysis of combining ACEI with ARBs needs to be made on an individual dog
5. Administer an angiotensin receptor blocker (ARB) and feed a clinical renal diet. If
basis and is
clopidogrel careful monitoring
not available, is required
low-dose to ensure
acetylsalicylic any
acid (2 deterioration in kidney
to 5 mg/kg once daily) isfunction
an
is detected.
acceptable The risk(see
alternative is higher
note 2for CKD stages 3 and 4 patients.
below).

6.Monitoring response
Monitor response to antihypertensive
to treatment treatment:
/ progression of disease:
– stable blooddogs
Hypertensive creatinine concentration,
normally decreasing
require lifelong UP/C
therapy andand/or increasing
may require serum
treatment
albumin (if previously
adjustments. low) = good
Serial monitoring response. After stabilization, monitoring should
is essential.
occur atof
– a UPC least every
< 0.5 is not3achievable
months. for many dogs with primary glomerular disease. For
these dogs
Systolic thepressure
blood goal should be amm
<120 50%Hgreduction in UPC signs
and/or clinical from baseline
such as weakness or
tachycardia indicate hypotension, which is to be avoided.
– serially increasing blood creatinine concentrations and/or increasing UP/C = disease
is progressing.
Blood creatinine concentration – reducing blood pressure may lead to small and
persistent increases in creatinine (<45 µmol/l or 0.5 mg/dl increase) and/or SDMA
Ordinarily therapy will be maintained lifelong unless the underlying disease has been
(< 2 µg/dl), but a marked increase suggests an adverse drug effect.
resolved in which case dose reduction whilst monitoring UP/C might be considered.
Progressively increasing creatinine concentrations indicate progressive kidney
damage/disease.
Note 1: ACEI or ARB use is contraindicated in any animal that is clinically dehydrated
and/or is showing signs of hypovolemia. Correct dehydration before using these drugs
Proteinuria:
otherwise glomerular filtration rate may drop precipitously. The risk benefit analysis of
combining
Dogs in ACEI
Stage with ARBs
4 with needs
urine to be to
protein made on an individual
creatinine dog>0.5
ratio (UP/C) basisshould
and careful
be
monitoring is required to ensure any deterioration in kidney function is detected.
investigated for the disease processes leading to proteinuria (see 1 and 2 below) The risk
is higher in CKD stages 3 and 4. Further detailed recommendations
and treated with anti-proteinuric measures (see 3, 4, 5 and 6 below). for diagnosis and
management of glomerular disease in dogs can be found in the IRIS Consensus
Those with
Statements borderline
published proteinuria
in Journal (0.2 to 0.5)
of Veterinary require
Internal close inmonitoring
Medicine 2013 (supplement to
volume 27).
(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 (see
Appendix 2 and/or consult experts if unsure of indications for kidney biopsy).
3. Administer an ACEI and feed a clinical renal diet.
4. Combine ACEI and diet with angiotensin receptor blocker (ARB) if proteinuria
is not controlled.

1
© 2019 International Renal Interest Society (IRIS) Ltd. IRIS Ltd. is an independent non-profit organization limited by guarantee in the UK (Registered Number 10213173).
 (2023)

5. Low-dose acetylsalicylic acid (1 to 5 mg/kg once daily) clopidogrel (1.1-3 mg/kg orally
4 Note 2: Dogs
every with PLN
24 hours) are at risk
if serum of thrombosis
albumin is <20 g/lhowever it is not possible to predict the
(2.0 g/dl).
risk for thrombosis in the individual patient as serum albumin, antithrombin and degree
of proteinuria are poorly associated with thrombotic risk. Tests such as
6. Monitor response to treatment / progression of disease:
thromboelastography, thrombin generation and markers of activated clotting can be used
– stable blood creatinine concentration and decreasing UP/C – good response.
to document hypercoagulability, however, identification of a hypercoagulable state has
not–been
serially
shownincreasing blood
to correlate to creatinine concentrations
risk of developing and/or
thrombosis. Prothrombin and partiel
increasing UP/C – disease is progressing.
thrombloplastin times (PT, PTT) also cannot be used to predict thrombotic risk.
Antithrombotic therapy is indicated in dogs with PLN (CURATIVE Guidelines DOI:
Ordinarily therapy will
10.1111/vec.12801). be maintained
Clopidogrel lifelong
(1-4mg/kg unless
orally oncethe underlying
daily) disease
administration has
may bebeen
resolved in which case dose reduction whilst monitoring UP/C might
more effective than low dose acetylsalicylic acid (1-5mg/kg orally once daily) for be considered.
thromboprophylaxis
Note: ACEI or ARB use is contraindicated in any animal that is clinically dehydrated
and/or is showing signs of hypovolemia. Correct dehydration before using these drugs
otherwise glomerular filtration rate may drop precipitously. The risk benefit analysis of
combining ACEI with ARBs needs to be made on an individual dog basis and careful
monitoring is required to ensure any deterioration in kidney function is detected. The
risk is higher in CKD stages 3 and 4. Further detailed recommendations for diagnosis
and management of glomerular disease in dogs can be found in the IRIS Consensus
Statements published in Journal of Veterinary Internal Medicine in 2013 (supplement to
volume 27).

Reduction of phosphate intake:

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.
A more realistic post-treatment target for dogs at Stage 4 is <1.9 mmol/l (6.0 mg/dl).
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 1.9 mmol/l (6.0 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. Aluminum toxicity has been reported in a small number of dogs with
stage 4 CKD. Clinical signs included muscle weakness, encephalopathy and
microcytosis. If aluminium toxicity is suspected, serum aluminium levels can be
measured and, if required, alternative phosphate binders recommended.
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 at Stage 4 where phosphate is controlled and ionized calcium
and PTH are monitored.

1
2023 International Renal Interest Society (IRIS) Ltd. IRIS Ltd. is an independent non-profit organization limited by guarantee in the UK (Registered Number 10213173).
© 2019
 (2023)

Further treatments aimed at improving quality of life (applicable to Stages 3 &4)

4
If metabolic acidosis exists (blood bicarbonate or total 2
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 bicarbonate2
/ 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
Treatvomiting
vomitingand
andsuspected
suspected nausea
nausea with
with anti-emetics
anti-emetics suchsuch as maropitant,
as maropitant, or
or ondansetron.
ondansetron. Consider appetite/weight
Treat decreased intermittent omeprazole in dogs
and/or muscle losswith
withsuspected
appetite
gastric bleeding
stimulants (e.g. melena,
such as capromorelin oriron deficiency)
mirtazapine. or vomiting-induced
Consider intermittent omeprazole in
dogs with suspected gastric bleeding (e.g. melena, iron deficiency) or
esophagitis.
vomiting-induced esophagitis. If pharmacological management of appetite is
4. Give fluids parenterally as necessary to maintain hydration (see Footnote).
ineffective and/or supplemental hydration is required long-term, enteral feeding
tube should
5. Drugs bepredominantly
that rely considered. 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.

1
2023 International Renal Interest Society (IRIS) Ltd. IRIS Ltd. is an independent non-profit organization limited by guarantee in the UK (Registered Number 10213173).
© 2019
 (2023)

Appendix 1

Adapted Blood Pressure Substaging

For most dogs, the IRIS blood pressure substages are as follows:
• Severely hypertensive (high risk of future target organ damage) – systolic blood
pressure 180 mm Hg
• Hypertensive (moderate risk of future target organ damage) – systolic blood
pressure 160 to 179 mm Hg
• Prehypertensive (low risk of future target organ damage) – systolic blood
pressure 140 to 159 mm Hg
• Normotensive (minimal risk of future target organ damage) – systolic blood
pressure ‹140 mm Hg

It is recognized that some breeds, particularly sight hounds, tend to have higher
blood pressure than many other breeds.
When dealing with these “high-pressure” breeds the classification of risk for future
target organ damage might be adjusted as follows:
• High risk >40 mm Hg above breed-specific reference range
• Moderate risk 20-40 mm Hg above breed-specific reference range
• Low risk 10-20 mm Hg above breed-specific reference range

Appendix 2

Reasons for Undertaking Renal Biopsy

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

1
2023 International Renal Interest Society (IRIS) Ltd. IRIS Ltd. is an independent non-profit organization limited by guarantee in the UK (Registered Number 10213173).
© 2019
 (2023)

Footnote

Maintenance fluids to maintain hydration status are low in sodium (30-40mmol/l) and
ideally have added potassium (about 13 mmol/l) to ensure daily requirements for fluid
and electrolytes are met (e.g. Normosol-M® or 5% Dextrose plus 0.18% NaCl with
added KCl).

Disclaimer

Although every effort has been made to ensure the completeness and accuracy of the
information provided herein, the IRIS Board assumes no responsibility for the
completeness or accuracy of the information. All information is provided “as is” without
any warranties, either expressed or implied.

1
2023 International Renal Interest Society (IRIS) Ltd. IRIS Ltd. is an independent non-profit organization limited by guarantee in the UK (Registered Number 10213173).
© 2019