Page 752 - Small Animal Clinical Nutrition 5th Edition

780 Small Animal Clinical Nutrition

tein restriction inhibits secretion of TGF-β and glomerular
Table 37-8. Potential etiopathogenic mechanisms in chronic
VetBooks.ir kidney disease and therapeutic approaches for each. scarring in rats with glomerulonephritis (Fukui et al, 1993).
Furthermore, the renin-angiotensin-aldosterone system is
Factors
Maintain hydration (increased water
Chronic renal hypoxia Therapeutic approaches linked to activation of the TGF-β pathway, which in turn pro-
motes interstitial fibrosis (Figure 37-7) (Wolf, 2006).
intake)
Avoid excessive sodium intake Tubulointerstitial injury can impair renal function by a num-
ACE inhibitors ber of mechanisms: 1) vascular effects, 2) glomerular injury, 3)
Control anemia (erythropoietin) interstitial and tubuloepithelial processes, 4) nephron obstruc-
Glomerular hypertension Avoid excessive dietary protein
and hyperfiltration and sodium tion and 5) deposition of crystals (Nath, 1992). Postglomerular
Increased dietary omega-3 fatty acids blood flow is decreased when the cortical interstitium expands
ACE inhibitors due to fibrosis and mononuclear infiltration. Decreased blood
Hyperphosphatemia Limit dietary phosphorus
and secondary renal Intestinal phosphate binders supply also results from release of vasoactive cytokines, growth
hyperparathyroidism Calcitriol (after normophosphatemia is factors and ROS produced by the interstitial infiltrate and
achieved) damaged tubules. Decreased postglomerular blood flow de-
Hypokalemia Potassium supplementation
Metabolic acidosis Avoid excessive dietary protein creases tubular blood flow and changes glomerular size and
Alkalinizing foods (therapeutic renal pressure. Decreased tubular blood flow may impair tubular
foods) function and glomerular size and pressure changes may lead to
Alkalinizing agents (bicarbonate,
potassium citrate) glomerular injury (Nath, 1992).
Proteinuria Avoid excessive dietary protein As discussed above, abnormal glomerular function can incite
Increased dietary omega-3 fatty acids tubulointerstitial injury (Diamond and Anderson, 1990). Loss
ACE inhibitors
Renal oxidative stress Avoid excessive dietary protein, of glomerular permselectivity and resultant proteinuria are
phosphorus and sodium accompanied by tubulointerstitial damage.Increased trafficking
Increased dietary antioxidants of protein in the proximal tubules may cause cellular damage.
Omega-3 fatty acid supplementation
Systemic hypertension Avoid excessive dietary sodium Filtered protein is endocytosed in the proximal tubules and
ACE inhibitors subsequently degraded by lysosomal action. Excessive release of
Calcium-channel antagonists lysosomal enzymes may be one of the pathways for tubular
(amlodipine)
Tubulointerstitial Increased dietary omega-3 fatty acids damage. Tubular damage may also be induced by plasma pro-
inflammation/fibrosis Avoid excessive dietary phosphorus teins that have escaped into the urine. Incriminated plasma
and protein proteins include albumin, lipoproteins, complement compo-
Key: ACE = angiotensin-converting enzyme.
nents and transferrin. Studies in cats with spontaneously occur-
ring CKD demonstrated that progression of CKD is most
closely linked to severity of proteinuria, which may be ex-
plained by tubular damage during tubular resorption of leaked
involved (Eddy, 1994). The extent of tubulointerstitial injury proteins (Syme et al, 2006; Jepson et al, 2007). Progression of
correlates with the decline in renal function, whereas the sever- spontaneously occurring CKD in dogs is also related to severi-
ity of glomerular injury does not correlate well with progression ty of proteinuria (Jacob et al, 2005).
of CKD models. It appears that GFR is influenced to a greater
degree by interstitial fibrosis than by glomerulosclerosis (Nath, Effects of Renal Aging
1992). The kidney is one of the most vulnerable organs to age-associ-
Although chronic, progressive tubulointerstitial disease plays ated changes. Renal changes associated with aging are mani-
a critical role in progression of renal lesions, the basic mecha- fested by significant structural and functional alterations.
nisms that generate the tubulointerstitial damage remain un- Functional changes include decreased GFR, decreased renal
clear. There appears to be a clinically silent acute phase that is blood flow, decreased urine concentrating ability and decreased
characterized by inflammation and tubular cell injury. Possible ability to maintain sodium, water, endocrine and acid-base
mediators of tubular injury include antibodies, ROS, obstruc- homeostasis. Structural changes include alterations in renal
tion, complement and lysosomal enzymes (Eddy, 1994). weight, volume and histologic appearance. Fibroconnective tis-
Damaged tubular cells can regenerate or die. Factors responsi- sue replaces functionally active parenchyma in aging kidneys. In
ble for recruitment of mononuclear cells to the interstitium are a study of dogs with spontaneous glomerulonephritis, the inci-
important because of evidence that monocytes and macro- dence of interstitial nephritis increased with increasing age.
phages play a key role in interstitial fibrosis (Eddy et al, 1991). Interstitial nephritis was present in 10% of dogs less than one
Recruitment is probably mediated by the release of fibrosis- year of age, in 60% of dogs between one and five years of age
promoting cytokines, such as TGF-β (Wolf, 2006). TGF-β and in 85% of dogs more than five years of age (Muller-
directly stimulates transcription of many extracellular matrix Peddinghaus and Trautwein, 1977). In another study, 59% of
genes in renal cells including mesangial, endothelial and tubu- the dogs older than four years had evidence of interstitial
lar cells. TGF-β also appears to trigger increased matrix pro- nephritis (Shirota et al, 1979). Glomerular lesions were noted
duction by perivascular and interstitial fibroblasts. Dietary pro- in 43 to 78% of these dogs. Based on these reports, interstitial