Diet and Renal Failure
SCOTT A. BROWN*5 DELMAR /?. FINCO* AND L. GABRIEL NAVAR*
WAYNE A. CROWELLJ
Departments of "Physiology and Pharmacology and ^Pathology, College of Veterinary Medicine, The University of Georgia, Athens, GA 30602 and the ^Department of Physiology, Tulane University School of Medicine, New Orleans, LA 70112 After partial nephrectomy (Nx) in rats, progressive glomerulosclerosis and declining renal function are often observed (1, 2). This process, which occurs in remnant glomeruli that are initially normal, has been attributed to the adaptive changes in renal structure and function that occur in remnant nephrons after partial Nx (1-3). Important functional adaptations of remnant nephrons include preglomerular vasodilation and the consequent development of glomerular cap illary hypertension, which serves to increase single nephron glomerular filtration rate (SNGFR) (1-3). Structural changes that occur in response to partial Nx include the enlargement of remnant nephrons, a process referred to as compensatory renal growth. During this compensatory process, glomerular volume increases subsequent to glomerular hypertrophy (46). Adaptive changes in renal structure and function, including glomerular hypertension, hyperfiltration (increased SNGFR) and hypertrophy, appear to be re sponsible for the progressive nephropathy observed in rodent models of renal failure (2-6). A variety of ex perimental maneuvers, including dietary protein re striction, limit the extent of these adaptations and have
ABSTRACT After partial nephrectomy (Nx) in rats, a temporal pattern of progressively declining renal function often develops. This pattern has been attributed to the development of glomerular hyperflltration, hypertension and hypertrophy in remnant nephrons. In rats, dietary protein restriction prevents these adaptive changes in remnant nephrons, thereby preserving renal structure and function. However, long-term studies of the temporal pat tern of renal function have failed to identify a consistently progressive deterioration of renal function in partially NX dogs, and a protective effect of protein restriction has not been apparent in this species. To address these issues in dogs, we evaluated the single nephron adaptations to par tial NXin dogs and the effect of dietary protein restriction on these adaptations. Results of our micropuncture stud ies in partially NXdogs indicate that remnant nephrons of dogs exhibit glomerular hyperflltration (single nephron glomerular filtration rate of 144 ±8 vs. 71 ±4 nL/min in controls, P < 0.05), hypertension (glomerular capillary pressure of 75.1 ±1.6vs. 63.2 ±1.9mmHg in controls) and hypertrophy (glomerularvolume of 354 ±0.24 X 10e vs. 2.04 ±0.05 X IO6firn3 in controls, P < 0.05). Our studies of the effect of protein restriction on the adaptive changes of nephron structure and function after renal mass reduction in dogs indicate that moderate protein restriction did not prevent the development of glomerular hyperflltration (single nephron glomerular filtration rate of 187 ±15 vs. 62 ±9 nL/min in controls, P < 0.05), hypertension (glomerular capillary pressure of 79.2 ±3.2 vs. 59.3 ±5.1mmHg in controls) and hypertrophy (glo merular volume of 4.84 ±0.54 X IO6 vs. 1.86 ±0.25 X IO6 urn3 in controls, P < 0.05). These results dem onstrate that glomerular hyperfiltration, hypertension and hypertrophy occur after partial NXin dogs. However, ef fects of dietary intervention, specificallyprotein restriction, on these adaptations remain to be established. J. Nutr. 121: S125-S127, 1991.
1 Presented as part of the Waltham International Symposium on Nutrition of Small Companion Animals, at University of California, Davis, CA 95616, on September 4-8, 1990. Guest editors for the symposium were James G. Morris, D'Ann C. Finley and Quinton R. Rogers. 1 Portions of this work were supported by National Heart, Lung, and Blood Institute Grant HL-1846, National Institutes of Diabetes and Digestive and Kidney Diseases Grant DK-39258, and by the Morris Animal Foundation, Englewood, CO. 3 S. A. Brown was the recipient of a postdoctoral fellowship from the American Veterinary Medical Association Research Foundation. 4 Portions of this work have been published in manuscript form (Am J Physiol. 258 (Renal Fluid Electrolyte Physiol. 27): F495-F503, 1990). 5 To whom correspondence should be addressed: Department of Physiology, University of GA College of Veterinary Medicine, Ath ens, GA 30602.
INDEXINGKEYWORDS: •symposium •dogs •dietary protein •nephrectomy
S125
Downloaded from https://academic.oup.com/jn/article-abstract/121/suppl_11/S125/4744104 by Tulane University Library, Serials Acquisitions Dept. user on 10 January 2019
Dietary Protein Intake and the Glomerular Adaptations to Partial Nephrectomy in Dogs1-4
S126
BROWN
6 On a dry matter basis (in g/100 g), this diet consisted of 32.6 protein, 11.9 fat, 1.8 fiber and 8.1 ash. Principal ingredients were corn meal, casein, poultry meal, soybean meal, choice white grease, sodium chloride, potassium chloride, calcium carbonate and dicalcium phosphate.
TABLE 1
Systemic and renal measurements in sham-operated control and partially nephrectomized ¡l\l\ldogs fed a 32%protein diet1 Sham-operated
Partially NX
dogsDegree Number of NXDuration of 7/845. to wkProtein of NX, 0.33121.± O.I3124.1 2 ± wtDirect intake, g/kg body mmHgSNGFR,4 MAP,4 ±5.271 7 ±4.9144 nL/minGCPe,4 8*75.1± ±463.2 mmHgGlomerular 1.6'3.54 ± 1.92.04 ± ton3Mesangialvolume, X106 0.24'1.1 ± 0.050.8 ± score (0.0-3.0)60NA25.2 ±0.1163/4 ±0.2 1 Data have been published previously (reference 16). 2 NA = not applicable. 3 Values are means ±SEM. 4 MAP = mean systemic arterial pressure; SNGFR = single neph ron glomerular filtration rate; GCPe = estimated glomerular capillary pressure. * P < 0.05 vs. sham-operated control, Student's t test.
(1). Early in the adaptive process, glomerular capillary hypertension and hypertrophy do not apparently ex acerbate the histologie score in dogs with |- j NX, and long-term studies do not support the existence of a rapidly progressive glomerulopathy in partially NX dogs. Dogs are apparently resistant to the progressive glomerulosclerosis and loss of renal function asso ciated with glomerular capillary hypertension, hyper filtration and hypertrophy in rats after partial NX.The absence of overt systemic hypertension in dogs with |-g NX may be one factor contributing to protection of renal structure and function. Issue 2. Does protein restriction prevent the de velopment of these adaptive changes in nephrons of dogs with renal disease? To determine if protein restriction could prevent the development of glomerular capillary hypertension, glomerular hypertrophy and glomerular hyperfiltra tion, dogs with jf NX were fed a reduced protein diet (16% on a dry matter basis)7 for 8 wk after partial NX before micropuncture and morphometric studies. Al though protein intake was reduced by 50%, these studies revealed that these partially NX dogs had sig nificant elevations of GCPe, SNGFR, and glomerular size (Table 2). In addition, a mild increase in the glo merular score was associated with moderate systemic hypertension in these severely NX dogs. This degree of protein restriction did not prevent the development of glomerular hyperfiltration, hy pertension and hypertrophy. Further studies will be required to determine whether or not more severe 7 On a dry weight basis (in g/100 g), this diet consisted of 16.7 protein, 11.9 fat, 1.8 fiber and 3.2 ash. Principal ingredients the same as in the 32% protein diet.
were
Downloaded from https://academic.oup.com/jn/article-abstract/121/suppl_11/S125/4744104 by Tulane University Library, Serials Acquisitions Dept. user on 10 January 2019
been shown to preserve renal structure and prevent the progressive decline in renal function (2). Considerable information is available on renal hemodynamics and compensatory growth after partial renal ablation in dogs (7-15). However, long-term studies in partially NX dogs (7, 8, 13-15) have not identified the consistently progressive decline of renal function observed under the same circumstances in rats nor has a renal sparing effect of protein restriction been demonstrated in this species (8, 11, 13-15). To reconcile these unique differences between the rodent and canine remnant kidney models, we sum marize here the results of our recent efforts to address two of the critical issues pertaining to remnant nephron adaptations to renal injury in dogs: Issue 1. Do the adaptive changes in single nephron structure and function observed in rats after partial renal ablation also occur in dogs? Specifically, do glomerular hyperfiltration, hypertension and hypertrophy result when renal function is reduced in dogs? We have recently studied dogs fed a 32% protein diet6 for 4 wk after partial NX (|-g NX) to determine the adaptive changes in renal structure and function that occur in remnant nephrons in this species (16). We employed renal micropuncture techniques to de termine SNGFR and glomerular capillary pressure as estimated by the stop-flow technique (GCPe), and morphometric measurements to estimate changes in glomerular volume. Although there were no differences between groups in mean arterial pressure, partial NX promoted glo merular capillary hypertension (Table 1). Morpho metric studies revealed that the volume of glomeruli increased significantly with renal ablation. As a con sequence of glomerular capillary hypertension and glomerular hypertrophy, remnant canine nephrons exhibited significant glomerular hyperfiltration; the mean value for SNGFR of superficial nephrons in par tially NX dogs increased to >200% of the value in con trol glomeruli. Despite the presence of these adaptive changes, mesangial proliferation and matrix expansion were minimal, and significant changes were observed only in juxtamedullary nephrons of | NX dogs (16). These studies clearly demonstrated that glomerular hyperfiltration, hypertension and hypertrophy oc curred in dogs fed a 32% protein diet after partial NX. Glomerular capillary pressure was increased by ~12 mmHg and glomerular volume by nearly 75% in these partially NX dogs. This degree of glomerular capillary hypertension and glomerular enlargement is similar to that observed in studies of rats with partial NX (2, 5, 17, 18), where it is causally linked to glomerular capillary thrombosis and marked mesangial expansion
ET AL.
GLOMERULAR
ADAPTATIONS
TABLE 2
Control dogsDegree Number of NXDuration of wkProtein of NX, wtDirect intake, g/kg body mmHgSNGFR,3 MAP,3 nL/minGCPe,3 mmHgGlomerular urn3Mesangialvolume, XlO6 score (0.0-3.0)40NA12.6
0.31118±862 ±
Partially NX
0.22135 ±
±8187 15*79.2 ± ±4959.3 3.2*4.84 ± ±5.11.86 0.54*1.3 ± 0.250.8 + ±0.2415/1682.7 + 0.2*
1 NA = not applicable. 2 Values are means ±SEM. 3 MAP = mean systemic arterial pressure; SNGFR = single nephron glomerular filtration rate; GCPe = estimated glomerular capillary pressure. * P < 0.05 vs sham-operated control, Student's t test.
protein restriction will prevent these adaptations in remnant nephrons of partially NX dogs. LITERATURE
CITED
1. PURKERSON, M. L., HOFFSTEIN, P. E., K.LAHR, S. (1976) Pathogenesis of the glomerulopathy associated with renal in farction in rats. Kidney Int. 9: 407-417. 2. HOSTETTER, T. H.,
S127
5. YOSHIDA,T., FOGO, A. & ICHIKAWA,I. (1989) Glomerular hemodynamic changes vs. hypertrophy in experimental glomerular sclerosis. Kidney Int. 35: 654-660. £.FRIES,J. W. U., SANDSTROM,D. J., MEYER,T. W. & RENNKE, H. G. (1989) Glomerular hypertrophy and epithelial cell injury modulate progressive glomerulosclerosis in the rat. Lab. Invest. 60: 205-218. 7. BOURGOIGNIE,J. J., GAVELLAS,G., MARTINEZ, E. &. PARDO, V. (1987) Glomerular function and morphology after renal mass reduction in dogs. Lab. Clin. Med. 109: 380-388. 8. BOVEE,K. C., KRONFELD,D. S., RAMBERG,C. & GOLDSCHMIDT, M. (1979) Long-term measurement of renal function in par tially nephrectomized dogs fed 56, 27, or 19% protein. Invest. Urol 16: 378-384. 9. BRICKER, N. S., KLAHR, S. &. RIEDELBACH,R. E. (1964) The functional adaptation of the diseased kidney. I. Glomerular fil tration rate. /. Clin. Invest. 43: 1915-1921. 10. CARRIERE, S. &.GAGNAN-BRUNETTE, M. (1977) Compensatory renal hypertrophy in dogs: single nephron glomerular filtration rate. Can. J. Physiol. Pharmacol. 55: 105-110. 11. FINCO,D. R.,CROWELL,W.A. &BARSANTI,J.A. (1985) Effects of three diets on dogs with induced chronic renal failure. Am. ]. Vet. Res. 46: 646-653. 12. McNAY, J. L. &.MIYASAKI, M. (1973) Regional increases in mass and flow during compensatory renal hypertrophy. Am. /. Physio]. 224: 219-222. 13. POLZIN, D. J., OSBORNE, C. A., HAYDEN, D. W. & STEVENS, J. B.
14.
15.
OLSON, J. L., RENNKE, H. G., VENKATA-
CHALAM,M. A. & BRENNER,B. M. (1982) Hyperfiltration in remnant nephrons: a potentially adverse response to renal abla tion. Am. ]. Physiol. 241 [Renal Fluid Electrolyte Physiol. 30) F85-F92. 3. BRENNER,B. M., MEYER,T. W. & HOSTETTER,T. H. (1982) Dietary protein intake and the progressive nature of renal dis ease: the role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis in aging, renal ablation, and intrinsic renal disease. N. Eng]. /. Med. 307: 652-659. 4. SHEA,S. M., RASKOVA,J. &. MORRISON,A. B. (1978) A stereologic study of glomerular hypertrophy in the subtotally ne phrectomized rat. Am. ]. Pathol. 90: 201-210.
IN DOGS
16.
17.
18.
(1983) Influence of reduced protein diets on morbidity, mor tality, and renal function in dogs with induced chronic renal failure. Am. ]. Vet. Res. 45: 506-517. POLZIN, D. J., LEININGER,J. R., OSBORNE,C. A. & JERAJ, K. (1988) Development of renal lesions in dogs after 11/12 re duction of renal mass. Lab. Invest. 58: 172-183. ROBERTSON,J. L., GOLDSCHMIDT,M., KRONFELD,D. S., ToMASZEWSKi, J. E., HILL, G. S. & BovEE, K. C. (1986) Long-term responses to high dietary protein intake in dogs with 75% nephrectomy. Kidney Int. 29: 511-519. BROWN,S. A., FINCO,D. R., CROWELL, W. A., CHOAT,D. C. & NAVAR,L. G. (1990) Single nephron adaptations to partial renal ablation in the dog. Am. /. Physio]. 258 (Renal Fluid Electrolyte Physiol. 27): F495-F503. DWORKIN,L. D., HOSTETTER,T. H., RENNKE,H. G. &.BRENNER, B. M. (1984) Hemodynamic basis for glomerular injury in rats with desoxycorticosterone-salt hypertension. /. Clin. Invest. 73: 1448-1461. OLIVETTI,G. P., ANVERSA,P., RIGAMONTI,W., VITALI-MAZZI, L. &. LOUD, A. V. (1977) Morphometry of the renal corpuscle during normal postnatal growth and compensatory hypertrophy. /. Cell Biol. 75: 573-585.
Downloaded from https://academic.oup.com/jn/article-abstract/121/suppl_11/S125/4744104 by Tulane University Library, Serials Acquisitions Dept. user on 10 January 2019
Systemic and renal measaremen ta in con trol and partially nephrectomized ¡IMx.) dogs fed a 16%protein diet
TO RENAL INJURY
SCOTT A. BROWN*5 DELMAR /?. FINCO* AND L. GABRIEL NAVAR*
WAYNE A. CROWELLJ
Departments of "Physiology and Pharmacology and ^Pathology, College of Veterinary Medicine, The University of Georgia, Athens, GA 30602 and the ^Department of Physiology, Tulane University School of Medicine, New Orleans, LA 70112 After partial nephrectomy (Nx) in rats, progressive glomerulosclerosis and declining renal function are often observed (1, 2). This process, which occurs in remnant glomeruli that are initially normal, has been attributed to the adaptive changes in renal structure and function that occur in remnant nephrons after partial Nx (1-3). Important functional adaptations of remnant nephrons include preglomerular vasodilation and the consequent development of glomerular cap illary hypertension, which serves to increase single nephron glomerular filtration rate (SNGFR) (1-3). Structural changes that occur in response to partial Nx include the enlargement of remnant nephrons, a process referred to as compensatory renal growth. During this compensatory process, glomerular volume increases subsequent to glomerular hypertrophy (46). Adaptive changes in renal structure and function, including glomerular hypertension, hyperfiltration (increased SNGFR) and hypertrophy, appear to be re sponsible for the progressive nephropathy observed in rodent models of renal failure (2-6). A variety of ex perimental maneuvers, including dietary protein re striction, limit the extent of these adaptations and have
ABSTRACT After partial nephrectomy (Nx) in rats, a temporal pattern of progressively declining renal function often develops. This pattern has been attributed to the development of glomerular hyperflltration, hypertension and hypertrophy in remnant nephrons. In rats, dietary protein restriction prevents these adaptive changes in remnant nephrons, thereby preserving renal structure and function. However, long-term studies of the temporal pat tern of renal function have failed to identify a consistently progressive deterioration of renal function in partially NX dogs, and a protective effect of protein restriction has not been apparent in this species. To address these issues in dogs, we evaluated the single nephron adaptations to par tial NXin dogs and the effect of dietary protein restriction on these adaptations. Results of our micropuncture stud ies in partially NXdogs indicate that remnant nephrons of dogs exhibit glomerular hyperflltration (single nephron glomerular filtration rate of 144 ±8 vs. 71 ±4 nL/min in controls, P < 0.05), hypertension (glomerular capillary pressure of 75.1 ±1.6vs. 63.2 ±1.9mmHg in controls) and hypertrophy (glomerularvolume of 354 ±0.24 X 10e vs. 2.04 ±0.05 X IO6firn3 in controls, P < 0.05). Our studies of the effect of protein restriction on the adaptive changes of nephron structure and function after renal mass reduction in dogs indicate that moderate protein restriction did not prevent the development of glomerular hyperflltration (single nephron glomerular filtration rate of 187 ±15 vs. 62 ±9 nL/min in controls, P < 0.05), hypertension (glomerular capillary pressure of 79.2 ±3.2 vs. 59.3 ±5.1mmHg in controls) and hypertrophy (glo merular volume of 4.84 ±0.54 X IO6 vs. 1.86 ±0.25 X IO6 urn3 in controls, P < 0.05). These results dem onstrate that glomerular hyperfiltration, hypertension and hypertrophy occur after partial NXin dogs. However, ef fects of dietary intervention, specificallyprotein restriction, on these adaptations remain to be established. J. Nutr. 121: S125-S127, 1991.
1 Presented as part of the Waltham International Symposium on Nutrition of Small Companion Animals, at University of California, Davis, CA 95616, on September 4-8, 1990. Guest editors for the symposium were James G. Morris, D'Ann C. Finley and Quinton R. Rogers. 1 Portions of this work were supported by National Heart, Lung, and Blood Institute Grant HL-1846, National Institutes of Diabetes and Digestive and Kidney Diseases Grant DK-39258, and by the Morris Animal Foundation, Englewood, CO. 3 S. A. Brown was the recipient of a postdoctoral fellowship from the American Veterinary Medical Association Research Foundation. 4 Portions of this work have been published in manuscript form (Am J Physiol. 258 (Renal Fluid Electrolyte Physiol. 27): F495-F503, 1990). 5 To whom correspondence should be addressed: Department of Physiology, University of GA College of Veterinary Medicine, Ath ens, GA 30602.
INDEXINGKEYWORDS: •symposium •dogs •dietary protein •nephrectomy
S125
Downloaded from https://academic.oup.com/jn/article-abstract/121/suppl_11/S125/4744104 by Tulane University Library, Serials Acquisitions Dept. user on 10 January 2019
Dietary Protein Intake and the Glomerular Adaptations to Partial Nephrectomy in Dogs1-4
S126
BROWN
6 On a dry matter basis (in g/100 g), this diet consisted of 32.6 protein, 11.9 fat, 1.8 fiber and 8.1 ash. Principal ingredients were corn meal, casein, poultry meal, soybean meal, choice white grease, sodium chloride, potassium chloride, calcium carbonate and dicalcium phosphate.
TABLE 1
Systemic and renal measurements in sham-operated control and partially nephrectomized ¡l\l\ldogs fed a 32%protein diet1 Sham-operated
Partially NX
dogsDegree Number of NXDuration of 7/845. to wkProtein of NX, 0.33121.± O.I3124.1 2 ± wtDirect intake, g/kg body mmHgSNGFR,4 MAP,4 ±5.271 7 ±4.9144 nL/minGCPe,4 8*75.1± ±463.2 mmHgGlomerular 1.6'3.54 ± 1.92.04 ± ton3Mesangialvolume, X106 0.24'1.1 ± 0.050.8 ± score (0.0-3.0)60NA25.2 ±0.1163/4 ±0.2 1 Data have been published previously (reference 16). 2 NA = not applicable. 3 Values are means ±SEM. 4 MAP = mean systemic arterial pressure; SNGFR = single neph ron glomerular filtration rate; GCPe = estimated glomerular capillary pressure. * P < 0.05 vs. sham-operated control, Student's t test.
(1). Early in the adaptive process, glomerular capillary hypertension and hypertrophy do not apparently ex acerbate the histologie score in dogs with |- j NX, and long-term studies do not support the existence of a rapidly progressive glomerulopathy in partially NX dogs. Dogs are apparently resistant to the progressive glomerulosclerosis and loss of renal function asso ciated with glomerular capillary hypertension, hyper filtration and hypertrophy in rats after partial NX.The absence of overt systemic hypertension in dogs with |-g NX may be one factor contributing to protection of renal structure and function. Issue 2. Does protein restriction prevent the de velopment of these adaptive changes in nephrons of dogs with renal disease? To determine if protein restriction could prevent the development of glomerular capillary hypertension, glomerular hypertrophy and glomerular hyperfiltra tion, dogs with jf NX were fed a reduced protein diet (16% on a dry matter basis)7 for 8 wk after partial NX before micropuncture and morphometric studies. Al though protein intake was reduced by 50%, these studies revealed that these partially NX dogs had sig nificant elevations of GCPe, SNGFR, and glomerular size (Table 2). In addition, a mild increase in the glo merular score was associated with moderate systemic hypertension in these severely NX dogs. This degree of protein restriction did not prevent the development of glomerular hyperfiltration, hy pertension and hypertrophy. Further studies will be required to determine whether or not more severe 7 On a dry weight basis (in g/100 g), this diet consisted of 16.7 protein, 11.9 fat, 1.8 fiber and 3.2 ash. Principal ingredients the same as in the 32% protein diet.
were
Downloaded from https://academic.oup.com/jn/article-abstract/121/suppl_11/S125/4744104 by Tulane University Library, Serials Acquisitions Dept. user on 10 January 2019
been shown to preserve renal structure and prevent the progressive decline in renal function (2). Considerable information is available on renal hemodynamics and compensatory growth after partial renal ablation in dogs (7-15). However, long-term studies in partially NX dogs (7, 8, 13-15) have not identified the consistently progressive decline of renal function observed under the same circumstances in rats nor has a renal sparing effect of protein restriction been demonstrated in this species (8, 11, 13-15). To reconcile these unique differences between the rodent and canine remnant kidney models, we sum marize here the results of our recent efforts to address two of the critical issues pertaining to remnant nephron adaptations to renal injury in dogs: Issue 1. Do the adaptive changes in single nephron structure and function observed in rats after partial renal ablation also occur in dogs? Specifically, do glomerular hyperfiltration, hypertension and hypertrophy result when renal function is reduced in dogs? We have recently studied dogs fed a 32% protein diet6 for 4 wk after partial NX (|-g NX) to determine the adaptive changes in renal structure and function that occur in remnant nephrons in this species (16). We employed renal micropuncture techniques to de termine SNGFR and glomerular capillary pressure as estimated by the stop-flow technique (GCPe), and morphometric measurements to estimate changes in glomerular volume. Although there were no differences between groups in mean arterial pressure, partial NX promoted glo merular capillary hypertension (Table 1). Morpho metric studies revealed that the volume of glomeruli increased significantly with renal ablation. As a con sequence of glomerular capillary hypertension and glomerular hypertrophy, remnant canine nephrons exhibited significant glomerular hyperfiltration; the mean value for SNGFR of superficial nephrons in par tially NX dogs increased to >200% of the value in con trol glomeruli. Despite the presence of these adaptive changes, mesangial proliferation and matrix expansion were minimal, and significant changes were observed only in juxtamedullary nephrons of | NX dogs (16). These studies clearly demonstrated that glomerular hyperfiltration, hypertension and hypertrophy oc curred in dogs fed a 32% protein diet after partial NX. Glomerular capillary pressure was increased by ~12 mmHg and glomerular volume by nearly 75% in these partially NX dogs. This degree of glomerular capillary hypertension and glomerular enlargement is similar to that observed in studies of rats with partial NX (2, 5, 17, 18), where it is causally linked to glomerular capillary thrombosis and marked mesangial expansion
ET AL.
GLOMERULAR
ADAPTATIONS
TABLE 2
Control dogsDegree Number of NXDuration of wkProtein of NX, wtDirect intake, g/kg body mmHgSNGFR,3 MAP,3 nL/minGCPe,3 mmHgGlomerular urn3Mesangialvolume, XlO6 score (0.0-3.0)40NA12.6
0.31118±862 ±
Partially NX
0.22135 ±
±8187 15*79.2 ± ±4959.3 3.2*4.84 ± ±5.11.86 0.54*1.3 ± 0.250.8 + ±0.2415/1682.7 + 0.2*
1 NA = not applicable. 2 Values are means ±SEM. 3 MAP = mean systemic arterial pressure; SNGFR = single nephron glomerular filtration rate; GCPe = estimated glomerular capillary pressure. * P < 0.05 vs sham-operated control, Student's t test.
protein restriction will prevent these adaptations in remnant nephrons of partially NX dogs. LITERATURE
CITED
1. PURKERSON, M. L., HOFFSTEIN, P. E., K.LAHR, S. (1976) Pathogenesis of the glomerulopathy associated with renal in farction in rats. Kidney Int. 9: 407-417. 2. HOSTETTER, T. H.,
S127
5. YOSHIDA,T., FOGO, A. & ICHIKAWA,I. (1989) Glomerular hemodynamic changes vs. hypertrophy in experimental glomerular sclerosis. Kidney Int. 35: 654-660. £.FRIES,J. W. U., SANDSTROM,D. J., MEYER,T. W. & RENNKE, H. G. (1989) Glomerular hypertrophy and epithelial cell injury modulate progressive glomerulosclerosis in the rat. Lab. Invest. 60: 205-218. 7. BOURGOIGNIE,J. J., GAVELLAS,G., MARTINEZ, E. &. PARDO, V. (1987) Glomerular function and morphology after renal mass reduction in dogs. Lab. Clin. Med. 109: 380-388. 8. BOVEE,K. C., KRONFELD,D. S., RAMBERG,C. & GOLDSCHMIDT, M. (1979) Long-term measurement of renal function in par tially nephrectomized dogs fed 56, 27, or 19% protein. Invest. Urol 16: 378-384. 9. BRICKER, N. S., KLAHR, S. &. RIEDELBACH,R. E. (1964) The functional adaptation of the diseased kidney. I. Glomerular fil tration rate. /. Clin. Invest. 43: 1915-1921. 10. CARRIERE, S. &.GAGNAN-BRUNETTE, M. (1977) Compensatory renal hypertrophy in dogs: single nephron glomerular filtration rate. Can. J. Physiol. Pharmacol. 55: 105-110. 11. FINCO,D. R.,CROWELL,W.A. &BARSANTI,J.A. (1985) Effects of three diets on dogs with induced chronic renal failure. Am. ]. Vet. Res. 46: 646-653. 12. McNAY, J. L. &.MIYASAKI, M. (1973) Regional increases in mass and flow during compensatory renal hypertrophy. Am. /. Physio]. 224: 219-222. 13. POLZIN, D. J., OSBORNE, C. A., HAYDEN, D. W. & STEVENS, J. B.
14.
15.
OLSON, J. L., RENNKE, H. G., VENKATA-
CHALAM,M. A. & BRENNER,B. M. (1982) Hyperfiltration in remnant nephrons: a potentially adverse response to renal abla tion. Am. ]. Physiol. 241 [Renal Fluid Electrolyte Physiol. 30) F85-F92. 3. BRENNER,B. M., MEYER,T. W. & HOSTETTER,T. H. (1982) Dietary protein intake and the progressive nature of renal dis ease: the role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis in aging, renal ablation, and intrinsic renal disease. N. Eng]. /. Med. 307: 652-659. 4. SHEA,S. M., RASKOVA,J. &. MORRISON,A. B. (1978) A stereologic study of glomerular hypertrophy in the subtotally ne phrectomized rat. Am. ]. Pathol. 90: 201-210.
IN DOGS
16.
17.
18.
(1983) Influence of reduced protein diets on morbidity, mor tality, and renal function in dogs with induced chronic renal failure. Am. ]. Vet. Res. 45: 506-517. POLZIN, D. J., LEININGER,J. R., OSBORNE,C. A. & JERAJ, K. (1988) Development of renal lesions in dogs after 11/12 re duction of renal mass. Lab. Invest. 58: 172-183. ROBERTSON,J. L., GOLDSCHMIDT,M., KRONFELD,D. S., ToMASZEWSKi, J. E., HILL, G. S. & BovEE, K. C. (1986) Long-term responses to high dietary protein intake in dogs with 75% nephrectomy. Kidney Int. 29: 511-519. BROWN,S. A., FINCO,D. R., CROWELL, W. A., CHOAT,D. C. & NAVAR,L. G. (1990) Single nephron adaptations to partial renal ablation in the dog. Am. /. Physio]. 258 (Renal Fluid Electrolyte Physiol. 27): F495-F503. DWORKIN,L. D., HOSTETTER,T. H., RENNKE,H. G. &.BRENNER, B. M. (1984) Hemodynamic basis for glomerular injury in rats with desoxycorticosterone-salt hypertension. /. Clin. Invest. 73: 1448-1461. OLIVETTI,G. P., ANVERSA,P., RIGAMONTI,W., VITALI-MAZZI, L. &. LOUD, A. V. (1977) Morphometry of the renal corpuscle during normal postnatal growth and compensatory hypertrophy. /. Cell Biol. 75: 573-585.
Downloaded from https://academic.oup.com/jn/article-abstract/121/suppl_11/S125/4744104 by Tulane University Library, Serials Acquisitions Dept. user on 10 January 2019
Systemic and renal measaremen ta in con trol and partially nephrectomized ¡IMx.) dogs fed a 16%protein diet
TO RENAL INJURY
