Page 725 - Small Animal Internal Medicine, 6th Edition

CHAPTER 41 Acute Kidney Injury and Chronic Kidney Disease 697

stimulation of PTH secretion. Calcitriol normally feeds back consequence of the large reservoir of buffer (e.g., calcium
to receptors on the parathyroid gland cells and decreases the carbonate) in bone. Buffering of metabolic acidosis by the
VetBooks.ir synthesis and secretion of PTH. This negative feedback loop release of calcium carbonate from bone contributes to bone
demineralization, and accumulation of ammonia in the
is impaired in CKD because of decreased renal production
of calcitriol and further contributes to increased PTH
example of the trade-off hypothesis. Alkali therapy to correct
secretion. kidney may elicit tubulointerstitial inflammation, another
FGF-23 is a phosphatonin produced in bone that inhibits metabolic acidosis may slow the progression of CKD.
proximal renal tubular reabsorption of phosphate and also
inhibits 1α-hydroxylase activity in the kidney, thus decreas- ANEMIA
ing calcitriol production. It increases in CKD to facilitate Erythropoietin is a glycoprotein hormone that regulates red
phosphate excretion, and may contribute to renal secondary cell production by the bone marrow, and the kidney is the
hyperparathyroidism by decreasing the negative feedback of major source of erythropoietin in the adult animal. A non-
calcitriol to the parathyroid glands. FGF-23 increases with regenerative (i.e., normochormic normocytic) anemia is
increasing stage of CKD in dogs and cats and has been common in CKD but variable in severity. Its main cause is
shown to be predictive of disease progression in cats with inadequate production of erythropoietin by the diseased
CKD. Baseline FGF-23 concentrations were higher in non- kidneys to meet the demand for new red cells because of loss
azotemic geriatric cats that went on to develop azotemia over from hemolysis and hemorrhage. The life span of red cells in
12 months of follow-up as compared with those that did not. uremic patients is approximately 50% of that of healthy indi-
Renal secondary hyperparathyroidism can be prevented viduals, which is thought to be caused by a uremic toxin in
or reversed in dogs with experimentally induced CKD by plasma. Platelet dysfunction in CKD promotes insidious,
decreasing the dietary intake of phosphorus in proportion to ongoing blood loss (e.g., GI hemorrhage). Recombinant
the decrease in GFR (see Fig. 41.7, B). Feeding a renal diet human erythropoietin has been used successfully to correct
decreased FGF-23 concentrations in both normophospha- the anemia of CKD in human patients. This product also is
temic and hyperphosphatemic cats with stable azotemic effective in correcting the anemia of CKD in dogs and cats,
CKD, indicating that dietary phosphorus restriction allows but the potential for antibody formation limits its usefulness
maintenance of normal serum phosphate concentrations in these species.
with lower FGF-23 concentrations.
Early in the course of CKD, decreased phosphorus intake HEMOSTATIC DEFECTS
stimulates renal 1α-hydroxylase, which results in increased Uremia is characterized by abnormal hemostasis and a pre-
calcitriol production. This increase in calcitriol results in disposition to hemorrhage. GI blood loss is observed more
enhanced intestinal absorption of calcium, increased serum commonly in dogs than cats. A qualitative platelet function
ionized calcium concentration, and decreased PTH secre- defect (platelet numbers are normal) is most important. Risk
tion. Later in the course of CKD, the kidneys are unable to of hemorrhage is best correlated with the buccal mucosal
produce sufficient calcitriol to promote normal intestinal bleeding time (normally <2-3 minutes). Other coagulation
absorption of calcium. Phosphorus restriction slows the pro- test results (e.g., prothrombin time, partial thromboplastin
gression of CKD by blunting renal secondary hyperparathy- time, activated coagulation time) usually are normal. Abnor-
roidism and limiting renal interstitial mineralization, malities of platelet function include abnormal platelet adhe-
inflammation, and fibrosis. These observations form the siveness and aggregation, decreased clot retraction, and
basis for the use of phosphorus restriction in the medical decreased thromboxane production by platelets. Platelet dys-
management of dogs and cats with CKD. function also is thought to be the consequence of uremic
toxins (e.g., guanidines, PTH).
ACID-BASE BALANCE
The main cause of metabolic acidosis in CKD is limitation GASTROINTESTINAL DISTURBANCES
of renal ammonium excretion. The chronically diseased Erosions and ulcers of the buccal mucosa and tongue may
kidney maintains hydrogen ion balance by increased renal be observed in uremic dogs but much less commonly in cats.
ammoniagenesis from glutamine. Absolute ammonium Ulcers may be caused by the excretion of urea into saliva and
excretion falls during progressive CKD, but ammonium breakdown to ammonia by oral bacteria. Tongue tip necrosis
excretion is markedly increased when expressed per remnant may occur in uremic dogs; it results from fibrinoid necrosis
nephron. On a per nephron basis, the diseased kidney can and arteritis with focal ischemia, necrosis, and ulceration.
increase its ammonium excretion by threefold to fivefold. Gastroenteritis with GI hemorrhage is relatively common in
This adaptive mechanism reaches its limit when the GFR dogs with CKD. It arises as a consequence of bleeding caused
falls to 10% to 20% of normal. At this point, the diseased by platelet dysfunction, ammonia production from urea by
kidneys can no longer cope with the daily fixed acid load bacteria in the GI tract, ischemia caused by vascular lesions,
effectively, and a new steady state is established at a lower and increased concentrations of gastrin because of impaired
than normal plasma bicarbonate concentration. The meta- renal excretion. In one study, gastric ulceration, edema, and
bolic acidosis of CKD usually is not severe, and the relatively vascular fibrinoid change were not observed in the stomachs
mild decrease in plasma bicarbonate concentration is a of cats with CKD. Serum gastrin concentrations were high