CPD ACCREDITED ARTICLE
The kidney tries to maintain GFR by increasing SNGFR
(single nephron GFR) but this causes glomerular
hypertrophy, hypertension and hyperfiltration, and is
ultimately detrimental as it causes self-perpetuating
nephron loss.
RAAS activation
Systemic and tissue specific RAAS exist. The kidney
has all components for RAAS. Renal Angiotensin II
concentrations are higher than plasma concentrations,
thus what happens in the kidney is not represented in
the plasma.
Angiotension II
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is a potent vasoconstrictor of the EFFERENT
arteriole - thus causing glomerular hypertension
and hyperfiltration and damage.
Reduces renal oxygenation due to
vasconcostriction of the efferent arteriole,
which still needs to perfuse the remainder of the
nephron.
Modulates permeability of glomerulus
(podocytes) promoting proteinuria
Has a direct fibroproliferative and inflammatory
effect causing glomerulosclerosis
Stimulates aldosterone production by adrenals
and aldosterone is pro-fibrotic
Chronic RAAS-activation has several harmful effects in
the kidneys such as glomerular hypertension, fibrosis
and cell infiltration, higher glomerular permeability
and oxidative stress, all of which cause progression
of CKD.
Tubulointerstitial infiltration of lymphocytes and
macrophages is an early feature of CKD and may
be induced by proteinuria, reactive oxygen species
generation and up regulation of angiotensin II.
Regardless of the initial cause, chronic renal
inflammation is believed to play a critical role in the
pathophysiology of CKD and the perpetuation of
renal fibrosis.
Renal hypoxia
Blood flow follows the afferent arteriole, into the
glomerular capillaries and then into the efferent
arteriole and on to the peritubular capillary complex
for tubular cells. Glomerulosclerosis may decrease
down–the-line blood supply and cause tubular
hypoxia. RAAS activated vasoconstriction of efferent
arteriole will also cause tubular hypoxia. Oxygen
delivery by diffusion will also be interrupted by fibrosis
and inflammation.
vet360
Issue 05 | NOVEMBER 2018 | 8
Proteinuria
Marked proteinuria is uncommon in the cat with CKD.
Almost all CKD cats (90%) have a UPC of <1, half have
a UPC of <0.2 and only 20% are overtly proteinuric
(UPC >0.4). Proteinuria is a negative prognostic marker
and increases the relative risk for death: three-fold
increase with UPC 0.2-0.4, four-fold increase with
UPC > 0.4. Another way of looking at it is to correlate
the median UPC with the IRIS staging of the CKD; IRIS
stage 2 has a median UPC of 0,15; IRIS Stage 3 of 0,22
and IRIS stage 4 of 0,65.
A paper by Syme et al (JVIM 2006) showed that
hypertension at initial presentation was not associated
with the development of azotaemia or survival in cats
with CKD. All the cats in the trial were on treatment
with amlodipine , which is very effective at controlling
hypertension and follow up SBP measurements
were in the acceptable range.
The take home
message should be that cats with CKD and controlled
hypertension do not have poorer survival than those
without hypertension. This study also showed that
increased urinary protein excretion is a very good
predictor of reduced survival in cats with CKD.
Proteinuria is a significant predictor of future azotaemia
and is also significantly associated with the severity of
inflammation, fibrosis and tubular damage on renal
histopathology.
Hyperphosphataemia
Hyperphosphataemia is present in 60% of cats with
CKD and is a trigger for secondary renal hyper-
parathyroidism and nephrocalcinosis. Hyperphospha-
taemia contributes to clinical signs of disease, pro-
gression of disease and restriction is recommended in
ALL IRIS stages. Phosphate restriction is a key reason
why renal diets are effective.
Factors found to be associated with decreased
survival time in Feline CKD patients:
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High plasma creatinine
High plasma phosphate
High plasma urea
High blood leukocyte counts
Low blood haemoglobin and haematocrit
Uraemic patients - IRIS stage 4
High UPC and BP at any IRIS stage