Page 755 - Small Animal Clinical Nutrition 5th Edition

Chronic Kidney Disease 783

VetBooks.ir Box 37-1. Role of Dietary Protein in Progression of Chronic Kidney Disease.

There has been considerable debate about the effects of dietary
Another question that is not typically addressed in the debate on
protein on the progression of chronic kidney disease (CKD) in dogs the effect of dietary protein intake on progressive renal injury is
and cats. Studies that have attempted to evaluate the role of pro- whether studies had sufficient statistical power. Before declaring
tein intake alone (vs. other nutrients such as phosphorus) have been that there is no treatment effect, it is useful to consider whether the
conducted in dogs and cats with experimentally induced CKD (i.e., group size studied was sufficient to detect an effect if one truly
remnant kidney model or renal ablation); however, none have been existed. At the conclusion of one frequently cited study, there were
performed in patients with naturally occurring disease. Feeding a four dogs evaluated in the high-protein group, three dogs in the
veterinary therapeutic renal food, with decreased protein, signifi- moderate-protein group and four dogs in the low-protein group.
cantly prolongs survival time, decreases uremic episodes and However, this study did not address the question of whether group
delays disease progression in dogs and cats with naturally occur- sizes were adequate to support the conclusions made. Another
ring CKD. However, compared with typical maintenance pet foods, study that did not show an effect of dietary protein levels on
veterinary therapeutic renal foods have other features in addition to glomerular lesions in uninephrectomized dogs did mention low
less protein (i.e., decreased phosphorus, increased fat, increased power in their study (i.e., power calculations of 15 and 20%). The
omega-3 fatty acids), which likely contribute to their effectiveness. authors indicated that factors responsible for the low power includ-
When evaluating the evidence for or against limiting dietary protein ed small sample size and large inter-dog differences.
intake, factors to consider include mechanism(s) by which protein Finally, in evaluating the role of protein in CKD most veterinary
may exert its effect(s), experimental design of previously conducted investigators have used the remnant kidney model. Although this
studies and appropriateness of the remnant kidney model as a pre- model eliminates some of the variability associated with clinical tri-
dictor of what occurs in dogs and cats with naturally occurring CKD. als, it does not exactly mimic naturally occurring kidney disease and
Practically speaking, it’s also important to consider what foods are all conclusions drawn from this model may not be applicable to clin-
readily available for patients with CKD. ical patients. For example, in a study evaluating effects of different
When evaluating conclusions from reported studies, it is neces- dietary protein levels in dogs with 75% nephrectomy, mean plasma
sary to critically evaluate the research methods and results, which creatinine concentrations during the four-year study ranged from
could affect interpretation of data. For example, in a study widely 0.8 to 0.9 mg/dl in all diet groups; these values are much lower
cited to support the position that feeding less protein is ineffective than expected in clinical patients with progressive CKD. Although it
in slowing progression of kidney disease, some dogs in the high- may be appropriate to conclude that feeding high levels of protein
protein groups, but not the low-protein groups, were supplemented to dogs with 75% reduction in renal mass was not associated with
with potassium citrate to correct metabolic acidosis observed with a progressive decline in renal function, it would not be valid to state
high dietary protein intake. Metabolic acidosis may contribute to that similar dietary protein levels have the same effect in dogs with
renal injury by increasing renal ammoniagenesis and may increase naturally occurring CKD. Several studies evaluating the role of
renal oxygen consumption. Thus, conclusions regarding the effect dietary protein in limiting progression of CKD have been performed
of dietary protein on progression based on this study may be invalid in dogs and cats that maintained stable renal function throughout
because the study neutralized one mechanism by which protein the entire study period; the stable nature of renal dysfunction in
may exert its beneficial effect. In the same study, some dogs devel- such studies does not permit assessment of the role of dietary pro-
oped “diet-related uremia” when they were abruptly switched to the tein in limiting progression of CKD.
high-protein food following renal ablation. Those dogs were
removed from the study, which could have resulted in selecting for The Bibliography for Box 37-1 can be found at
study dogs that were “resistant” to the effects of protein. www.markmorris.org.

tein is from food or catabolism of a patient’s body tissue. GFR, which may increase filtration of plasma proteins through
Catabolism of a patient’s protein stores can occur if insufficient the glomerular membrane, resulting in proteinuria (Polzin et al,
energy (carbohydrates and fats) and/or protein are consumed. 1983a, 1984; Devaux et al, 1996; Bovee, 1991; Brown et al,
In the case of inadequate energy intake, the body’s amino acids 1992; Bovee et al, 1981). Proteinuria may result in direct mesan-
stores (tissue protein) are used for gluconeogenesis to meet glu- gial cell toxicity, glomerular fibrosis and eventual glomeruloscle-
cose needs. Avoiding dietary protein excess, without imposing rosis (Figure 37-3). Excessive albuminuria and abnormally fil-
dietary protein deficiency can help limit the acid load imposed tered transferrin may lead to increased oxidative stress, which
on patients with CKD (Burkholder, 2000). appears to be an important mechanism of progressive renal
Another potential benefit of limiting dietary protein is its injury (Figure 37-7). (See Renal Oxidative Stress.) The end
effects on proteinuria. Results of studies in rats with experimen- result of proteinuric-induced glomerulosclerosis and tubular
tally induced nephrotic syndrome suggest that the permselective damage is further loss of nephrons. This reduction of function-
properties of the filtration barrier are altered as a consequence of al renal mass and subsequent increase in single-nephron GFR
increasing dietary protein intake, permitting albumin to cross further increase proteinuria and progression of renal damage.
the capillary wall more readily (Kaysen et al, 1984; Hutchison et The impact of varying dietary protein intake on glomerular
al, 1987, 1990). In healthy dogs and in dogs with kidney disease, hemodynamics and structure in dogs and cats with CKD is less
increasing dietary protein intake increases renal blood flow and certain; however, studies in dogs have shown that feeding a vet-