423
and growth factors, epithelial and interstitial cell changes would ultimately lead to the tubulointerstitial lesions that are part of the end-stage kidney.
was supported by USPHS NIDDK grants: #DK37097, and I wish to thank Ms Judy Hurst for her assistance in the preparation of this manuscript and my collaborators in the Vanderbilt Kidney and Urologic Disease Center for their support.
This work
#DK39261.
Hirschenberg R, Kopple JD. Response of insulin-like growth factor I and renal hemodynamics to a high- and low-protein diet in the rat. J Am Soc Nephrol 1991; 1: 1034-40. 12. Daniel TO, Gibbs VC, Milfay DF, Garovoy MR, Williams LT. Thrombin stimulates c-sis gene expression in microvascular endothelial cells. J Biol Chem 1986; 261: 9579-82. 13. Rubin K, Hansson GK, Claussen-Welch L, et al. Induction of &bgr;-type receptors for platelet-derived growth factor in vascular inflammation: possible implications for development of vascular proliferative lesions. Lancet 1988; ii: 1353-56. 14. Fogo A, Ichikawa I. Evidence for the central role of glomerular growth promoters in the development of sclerosis. Semin Nephrol 1989; 9:
11.
329-42.
REFERENCES
et al. Glomerular hypertrophy in change disease predicts subsequent progression to focal glomerular sclerosis. Kidney Int 1990; 38: 115-23. 16. Elfenbein IB, Baluarte HJ, Gruskin AB. Renal hypoplasia with oligomeganephronia. Arch Pathol 1974; 97: 143-49. 17. Baldwin DS, Neugarten J. Hypertension and renal diseases. Am J Kid
15.
Fogo A, Hawkins EP, Berry PL, minimal
Nephron adaptation to renal injury or ablation. Am J Physiol 1985; 249: F324-37. 2. Abrahamson DR. Structure and development of the glomerular capillary wall and basement membrane. Am J Physiol 1987; 253: F783-94. 3. Striker LJ, Peten EP, Elliot SJ, Doi T, Striker GE. Biology of disease: mesangial cell turnover: effect of heparin and peptide growth factors. 1. Brenner BM.
Lab Invest 1991; 64: 446-56. G, Neilson EG. Molecular mechanisms of tubulointerstitial hypertrophy and hyperplasia. Kidney Int 1991; 39: 401-20. 5. Bohle A, Bader R, Grund KE, Mackensen S, Tolon M. Correlations between renal interstitium and level of serum creatinine: morphometric investigations of biopsies in perimembranous glomerulonephritis. Virchows Arch (A) 1977; 373: 14-22. 6. Bohle A, Bader R, Grund KE, Mackensen S, Neunhoffer J. Serum creatinine concentration and renal interstitial volume: analysis of correlations in endocapillary (acute) glomerulonephritis. Virchows Arch (A) 1977; 375: 87-96. 7. Segal R, Fine FG. Polypeptide growth factors and the kidney. Kidney Int 1989; 36: S2-10. 8. Okuda S, Languino LR, Ruoslahti E, Border WA. Elevated expression of transforming growth factor-&bgr; and proteoglycan production in experimental glomerulonephritis: possible role in expansion of the mesangial extracellular matrix. J Clin Invest 1990; 86: 453-62. 9. Border WA, Okuda S, Landuino LR, Sporn MB, Ruoslahti E. Suppression of experimental glomerulonephritis by antiserum against transforming growth factor &bgr;-1. Nature 1990; 346: 371-74. 10. Fagin JA, Melmed S. Relative increase in insulin-like growth factor I messenger ribonucleic acid levels in compensatory renal hypertrophy. Endocrinology 1987; 120: 718-24. 4. Wolf
Dis 1987; 10: 186-91. 18. Watson PA. Function follows form: generation of intracellular signals by cell deformation. FASEB J 1991; 5: 2013-19. 19. Dworkin LD. Effects of calcium channel blockers on experimental glomerular injury. J Am Soc Nephrol 1990; 1: S21-27. 20. Remuzzi G, Bertani T. Editorial review: is glomerulosclerosis a consequence of altered glomerular permeability to macromolecules? Kidney Int 1990; 38: 384-94. 21. Keane WF, Mulcahy WS, Kasiske BL, Kim Y, O’Donnell MP. Hyperlipidemia and progressive renal disease. Kidney Int 1991; 39: S41-48. 22. Klahr S, Harris K. Role of dietary lipids and renal eicosanoids on the progression of renal disease. Kidney Int 1989; 36: S27-31. 23. Diamond JR. Brief review: effects of dietary interventions on glomerular pathophysiology. Am J Physiol 1990; 27: F1-8. 24. Lau K. Nephrology forum: phosphate excess and progressive renal failure: the precipitation-calcification hypothesis. Kidney Int 1989; 36: 918-37. 25. Brown SA, Crowell WA, Barsanti JA, White JV, Finco DR. Beneficial effects of dietary mineral restriction in dogs with marked reduction of functional renal mass. J Am Soc Nephrol 1991; 1: 1169-79. 26. Klahr S, Schreiner G, Ichikawa I. The progression of renal disease. N Engl J Med 1988; 318: 1657-66. 27. Yee J, Kuncio GS, Neilson EG. Tubulointerstitial injury following glomerulonephritis. Semin Nephrol 1991; 11: 361-66.
Chronic renal failure: management
An increased serum urea or creatinine concentration indicates impaired renal function. Identification of the cause of the renal insufficiency, as well as secondary factors contributing to it, will help classify the condition as acute or chronic. Although acute and chronic renal disease states do not have mutually exclusive causes, the diagnosis of chronic renal disease can be established, firstly, by assessment of the extent and severity of the disease-eg, diabetes or glomerulonephritis-that underlies renal damage and, secondly, by showing the constant presence and progressive nature of the renal impairment. In kidney diseases characterised by irreversible injury, once a critical amount of functional renal loss has taken place, progression to end-stage disease seems common, even if the initiating event or condition is resolved or eradicated. Moreover, of the cause of chronic renal failure, several irrespective intercurrent events (table i) may accelerate the rate of loss of renal function. These events may lead to either a transient or a permanent loss of renal function. The importance of such intercurrent events cannot be overemphasised because their detection and correction may slow the progression of renal insufficiency and delay the need for renal replacement
therapy.
Clinical assessment
progression of chronic renal failure is best assessed by sequential measurements of glomerular filtration rate (GFR) with exogenous markers such as inulin, 1251iothalamate, 9
and growth factors, epithelial and interstitial cell changes would ultimately lead to the tubulointerstitial lesions that are part of the end-stage kidney.
was supported by USPHS NIDDK grants: #DK37097, and I wish to thank Ms Judy Hurst for her assistance in the preparation of this manuscript and my collaborators in the Vanderbilt Kidney and Urologic Disease Center for their support.
This work
#DK39261.
Hirschenberg R, Kopple JD. Response of insulin-like growth factor I and renal hemodynamics to a high- and low-protein diet in the rat. J Am Soc Nephrol 1991; 1: 1034-40. 12. Daniel TO, Gibbs VC, Milfay DF, Garovoy MR, Williams LT. Thrombin stimulates c-sis gene expression in microvascular endothelial cells. J Biol Chem 1986; 261: 9579-82. 13. Rubin K, Hansson GK, Claussen-Welch L, et al. Induction of &bgr;-type receptors for platelet-derived growth factor in vascular inflammation: possible implications for development of vascular proliferative lesions. Lancet 1988; ii: 1353-56. 14. Fogo A, Ichikawa I. Evidence for the central role of glomerular growth promoters in the development of sclerosis. Semin Nephrol 1989; 9:
11.
329-42.
REFERENCES
et al. Glomerular hypertrophy in change disease predicts subsequent progression to focal glomerular sclerosis. Kidney Int 1990; 38: 115-23. 16. Elfenbein IB, Baluarte HJ, Gruskin AB. Renal hypoplasia with oligomeganephronia. Arch Pathol 1974; 97: 143-49. 17. Baldwin DS, Neugarten J. Hypertension and renal diseases. Am J Kid
15.
Fogo A, Hawkins EP, Berry PL, minimal
Nephron adaptation to renal injury or ablation. Am J Physiol 1985; 249: F324-37. 2. Abrahamson DR. Structure and development of the glomerular capillary wall and basement membrane. Am J Physiol 1987; 253: F783-94. 3. Striker LJ, Peten EP, Elliot SJ, Doi T, Striker GE. Biology of disease: mesangial cell turnover: effect of heparin and peptide growth factors. 1. Brenner BM.
Lab Invest 1991; 64: 446-56. G, Neilson EG. Molecular mechanisms of tubulointerstitial hypertrophy and hyperplasia. Kidney Int 1991; 39: 401-20. 5. Bohle A, Bader R, Grund KE, Mackensen S, Tolon M. Correlations between renal interstitium and level of serum creatinine: morphometric investigations of biopsies in perimembranous glomerulonephritis. Virchows Arch (A) 1977; 373: 14-22. 6. Bohle A, Bader R, Grund KE, Mackensen S, Neunhoffer J. Serum creatinine concentration and renal interstitial volume: analysis of correlations in endocapillary (acute) glomerulonephritis. Virchows Arch (A) 1977; 375: 87-96. 7. Segal R, Fine FG. Polypeptide growth factors and the kidney. Kidney Int 1989; 36: S2-10. 8. Okuda S, Languino LR, Ruoslahti E, Border WA. Elevated expression of transforming growth factor-&bgr; and proteoglycan production in experimental glomerulonephritis: possible role in expansion of the mesangial extracellular matrix. J Clin Invest 1990; 86: 453-62. 9. Border WA, Okuda S, Landuino LR, Sporn MB, Ruoslahti E. Suppression of experimental glomerulonephritis by antiserum against transforming growth factor &bgr;-1. Nature 1990; 346: 371-74. 10. Fagin JA, Melmed S. Relative increase in insulin-like growth factor I messenger ribonucleic acid levels in compensatory renal hypertrophy. Endocrinology 1987; 120: 718-24. 4. Wolf
Dis 1987; 10: 186-91. 18. Watson PA. Function follows form: generation of intracellular signals by cell deformation. FASEB J 1991; 5: 2013-19. 19. Dworkin LD. Effects of calcium channel blockers on experimental glomerular injury. J Am Soc Nephrol 1990; 1: S21-27. 20. Remuzzi G, Bertani T. Editorial review: is glomerulosclerosis a consequence of altered glomerular permeability to macromolecules? Kidney Int 1990; 38: 384-94. 21. Keane WF, Mulcahy WS, Kasiske BL, Kim Y, O’Donnell MP. Hyperlipidemia and progressive renal disease. Kidney Int 1991; 39: S41-48. 22. Klahr S, Harris K. Role of dietary lipids and renal eicosanoids on the progression of renal disease. Kidney Int 1989; 36: S27-31. 23. Diamond JR. Brief review: effects of dietary interventions on glomerular pathophysiology. Am J Physiol 1990; 27: F1-8. 24. Lau K. Nephrology forum: phosphate excess and progressive renal failure: the precipitation-calcification hypothesis. Kidney Int 1989; 36: 918-37. 25. Brown SA, Crowell WA, Barsanti JA, White JV, Finco DR. Beneficial effects of dietary mineral restriction in dogs with marked reduction of functional renal mass. J Am Soc Nephrol 1991; 1: 1169-79. 26. Klahr S, Schreiner G, Ichikawa I. The progression of renal disease. N Engl J Med 1988; 318: 1657-66. 27. Yee J, Kuncio GS, Neilson EG. Tubulointerstitial injury following glomerulonephritis. Semin Nephrol 1991; 11: 361-66.
Chronic renal failure: management
An increased serum urea or creatinine concentration indicates impaired renal function. Identification of the cause of the renal insufficiency, as well as secondary factors contributing to it, will help classify the condition as acute or chronic. Although acute and chronic renal disease states do not have mutually exclusive causes, the diagnosis of chronic renal disease can be established, firstly, by assessment of the extent and severity of the disease-eg, diabetes or glomerulonephritis-that underlies renal damage and, secondly, by showing the constant presence and progressive nature of the renal impairment. In kidney diseases characterised by irreversible injury, once a critical amount of functional renal loss has taken place, progression to end-stage disease seems common, even if the initiating event or condition is resolved or eradicated. Moreover, of the cause of chronic renal failure, several irrespective intercurrent events (table i) may accelerate the rate of loss of renal function. These events may lead to either a transient or a permanent loss of renal function. The importance of such intercurrent events cannot be overemphasised because their detection and correction may slow the progression of renal insufficiency and delay the need for renal replacement
therapy.
Clinical assessment
progression of chronic renal failure is best assessed by sequential measurements of glomerular filtration rate (GFR) with exogenous markers such as inulin, 1251iothalamate, 9
