Chronic kidney disease

Question 1

Why is it important to stage cats with CKD

Answer 1

Staging of CKD helps determine the appropriate monitoring and treatment strategies for the patient

It provides owners with an understanding of potential prognosis

It helps to standardize research

Question 2

What is the frequency of CKD in cats

Answer 2

CKD is a common and important cause of morbidity and mortality in cats

Question 3

What is the definition of CKD

Answer 3

The hallmark of CKD is a chronic (defined as > 3 months duration) decline in the population of functional nephrons to a point where the glomerular filtration rate and tubular function is no longer adequate to maintain normal excretory and re-absorptive capacity
- this leads to azotemia in the face of inadequate urine concentrating ability, and the retention of other plasma solutes and protein catabolic products normally eliminated via the kidneys (uremic toxins)

Question 4

Explain why the overall decline in GFR is not proportional to the number of functioning nephrons lost

Answer 4

In the early stages of CKD, the declining number of nephrons is compensated by increased individual nephron GFR

This increase is mediated through a number of adaptative changes including both glomerular hypertrophy (increasing the surface area of the glomerular capillaries) and glomerular hypertension (increasing the filtration pressure gradient)

This is one reason why early detection of renal disease is difficult

Question 5

What is the signalment for CKD

Answer 5

CKD can be seen in young cats (both congenital and hereditary causes are well recognizzed) but it is most commonly encountered as an acquired disease in middle to old-aged cats

The risk of cats developing CKD rises dramatically from around 7 years of age
- *2 between 7-10 years
- *5 between 10-15 years

Question 6

What is the cause of CKD in cats

Answer 6

The underlying etiology of feline CKD is often obscure
- in most cases the inciting cause is unknown and CKD represents a common pathway of a progressive disease

Question 7

What is the most common histological lesion identified in CKD

Answer 7

Histological evaluation of kidneys from affected cats most commonly reveals the presence of chronic interstitial nephritis characterized by:
- progressive fibrosis
- loss of nephrons
- presence of sterile inflammation

Unlike many cases of human renal failure, this is not predominantly a glomerular disease in cats, but rather a tubulointerstitial disease (with glomerular involvement) that results in nephron loss

Question 8

Can you give some important causes of CKD

Answer 8

Congenital/hereditary
- Renal aplasia
- Renal dysplasia
- Renal hypoplasia
- Inherited renal amyloidosis
- Polycystic kidney disease

Acquired
- Idiopathic tubulointerstitial nephritis (= the most common cause in cats)
- Glomerulonephritis
- Pyelonephritis
- Acquired amyloidosis
- Nephrotoxins
- Hypercalcemia
- Hydronephrosis
- Renal lymphoma
- Obstructive uropathy (ureteral or urethral)
- Progression of AKI
- FIP

Question 9

What is the typical history for cats suffering CKD

Answer 9

In general, signs are often non-specific, with dehydration, anorexia, lethargy and weight loss being most commonly reported

PU/PD is less frequently observed in cats than in dogs, until disease is quite advanced

Vomiting and/or diarrhea may be a feature, due to central effects of uremic toxins, hypergastrinemia and uremic gastric ulceration (even if this last point has been called into question)

Hypertensive cats may present with sudden onset blindness, other ocular abnormalities or behavioral changes

Question 10

What are the clinical signs encountered in cats suffering CKD

Answer 10

Reduced body and muscle condition scores

Unkempt hair coat

Halitosis may be noted

Pale mucous membranes secondary to anemia or dehydration

Cats with hypertension may present with:
- retinal detachment
- hyphema
- other evidence of hypertensive retinopathy
- cardiac murmur

Classically, feline CKD is associated with small and irregular kidneys on abdominal palpation but it is not always the case (e.g., PKD, renal lymphoma)

Dehydration and/or constipation

Question 11

List exemples of diseases that can be seen in cats suffering CKD and with renomegaly

Answer 11

Amyloidosis

Lymphoma

Polycystic kidney disease

Glomerulonephritis

Question 12

What are the ideal diagnostic tests for a cat suspected of CKD

Answer 12

Hematology

Serum biochemistries (including total thyroxine if older than 7 years)

Urinalysis with sediment examination

Question 13

How can you make a presumptive diagnosis of CKD

Answer 13

The diagnosis of CKD is usually based on the presence of appropriate clinical signs together with the demonstration of azotemia and/or inappropriately concentrated urine

Question 14

Explain why isosthenuria (USG < 1.015) is not necessarily observed in cats with CKD

Answer 14

Cats often retain some concentrating ability during CKD
- isosthenuria may only be seen in around 50% of cases of feline CKD

USG < 1.035 indicates reduced concentrating ability and should prompt further investigation, especially in cats on a predominantly dry-food diet

Question 15

Is azotemia alone sufficient to make a diagnosis of CKD

Answer 15

Azotemia alone is not sufficient because other factors (e.g., dehydration) can cause azotemia

The presence of azotemia should be interpreted together with a concomitant urine sample for measurement of USG
- the presence of azotemia with a USG < 1.035 is usually considered evidence of primary kidney disease

Question 16

What other important abnormalities should be evaluated in cats with suspected CKD

Answer 16

Hyperphosphatemia
- due to the decreased renal clearance

Acidosis
- due to an inability of the failing kidneys to excrete the normal acid load

Non-regenerative anemia
- due to reduced erythrocyte life-span, uremic suppression of erythropoiesis, a relative or absolute deficiency of erythropoietin, and gastrointestinal blood loss and subsequent iron deficiency

Hypokalemia
- due mainly to inappropriate kaliuresis

Question 17

What are the main tenants of IRIS renal stages

Answer 17

The three main tenants of IRIS renal stages are:
- firstly to establish that there is chronic kidney dysfunction, with a duration greater than 3 months
- to ensure that the cat is adequately hydrated at the time of definitive staging assessment
- the patient should be subsequently sub-staged with regards to systolic blood pressure and degree of proteinuria (ideally with a urine protein creatinine ratio)

Question 18

What is particularly important when staging according to SDMA and creatinine

Answer 18

The stage should only be allocated once pre-renal azotemia has been corrected as many cats will revert to a lower stage once they are rehydrated

The same is true in acute-on-chronic disease

Question 19

Can you give the IRIS renal stages according to creatinine and SDMA

Answer 19

stage 1:
- creat <140 µmol/l, 16 mg/l
- SDMA < 18 µg/dl and persistently above 14
- some other renal abnormalities present (e.g., unexplained USG < 1.035, abnormal renal morphology)

stage 2:
- creat 140-250 µmol/l, 16-28 mg/l
- SDMA 18-25 µg/dl
- usually no overt clinical signs

stage 3:
- creat 251-440 µmol/l, 29-50 mg/ml
- SDMA 26-38 µg/dl

stage4:
- creat > 440 µmol/l, > 50 mg/l
- SDMA > 38µg/dl

Question 20

Why is it important to sub-stage CKD patients according to proteinuria and how is it performed

Answer 20

Proteinuria is identified as a significant negative prognostic indicator in feline CKD

Staging is performed according to UPC measurement in patients with inactive sediments and normal plasma protein
- to exclude pre- and post-renal proteinuria
- note that in end-stage and severe renal disease, the UPC can actually fall as there simply are not enough glomeruli remaining to lose significant protein into the urine

Question 21

What are the different categories of sub-stages according to UPC

Answer 21

Non-proteinuric (NP)
- UPC < 0.2

Borderline proteinuric (BP)
- 0.2-0.4

Proteinuric (P)
- > 0.4

Question 22

What can you say about the link between hypertension and CKD

Answer 22

It is estimated that 20% of cats with CKD have hypertension

The presence and severity of hypertension is not closely correlated with the severity of the CKD

Question 23

How does hypertension affect the kidney and other organs

Answer 23

Systemic hypertension will result in glomerular hypertension and promote further glomerular damage and glomerulosclerosis, causing progression of renal disease as well as clinical signs and reduced quality of life in affected cats

Untreated hypertension causes end-organ damage including damage to the brain, heart and further renal damage

Ocular changes are also common including retinal detachment and hemorrhage, and total retinal detachment and blindness

Question 24

How IRIS substages are allocated according to blood pressure measurement

Answer 24

< 150 mm Hg
- minimal or no risk of end-organ damage (N)

150 - 159 mm Hg
- low risk of end-organ damage (L)

160 - 180 mm Hg
- moderate risk of end-organ damage (M)

> 180 mm Hg
- severe risk of end-organ damage (H)

If hypertension is noted then it is important to check for end-organ damage
- evidence of end-organ damage (c)
- no evidence (nc)

Question 25

Describe early changes observed in eyes with hypertension

Answer 25

The earliest observable change in systemic hypertension is bullous retinopathy
- Animals are likely to be visual
- small circular ‘doughnut” lesions are observable in varying numbers throughout the fundus, apearing as hypo-reflective grey circles
- increased vascular tortuosity may accompany this change

In the earliest cases, gross retinal hemorrhage may not be present
- when present, early retinal hemorrhage is seen as red to dark red blotches

Partial blindness may be detected by the most observant of owners

Question 26

Describe the more severe ocular changes associated with hypertension

Answer 26

Most cases are presented with hyphema or sudden-onset blindness
- hyphema is usuaally seen as a small hemorrhage in the anterior chamber
- an associated retinal detachment is often present

Severe cases will be blind

Question 27

How does hypertension affect the heart

Answer 27

Ventricular hypertrophy is a consequence of chronic hypertension
- equally hypertrophic cardiomyopathy can result in hypertension

Question 28

How does hypertension affect the brain

Answer 28

Neurological signs are rare with hypertension alone but can occur with severe and untreated hypertension