Pathophysiology of proteinuria and its value as an outcome measure in chronic kidney disease

British Journal of Clinical Pharmacology

Volumn 76, Issue 4, 2013, Pages 516-523

  Cravedi, Paolo ^a   Remuzzi, Giuseppe ^a,b  

^a MARIO NEGRI INSTITUTE FOR PHARMACOLOGICAL RESEARCH   (Italy)

^b OSPEDALI RIUNITI   (Italy)

Author keywords

Biomarker; Cardiovascular; Chronic kidney disease; Proteinuria

Indexed keywords

ALBUMIN; BARDOXOLONE METHYL; CREATININE; ENALAPRIL; ENDOTHELIN 1; FRACTALKINE; IRBESARTAN; LOSARTAN; PLACEBO; RAMIPRIL; RANTES;

ALBUMINURIA; ANTIHYPERTENSIVE THERAPY; ARTICLE; CAPILLARY PRESSURE; CARDIOVASCULAR MORTALITY; CARDIOVASCULAR RISK; CELL INFILTRATION; CHRONIC KIDNEY DISEASE; CLINICAL TRIAL (TOPIC); COMPLEMENT ACTIVATION; DIABETES MELLITUS; DIABETIC NEPHROPATHY; DIABETIC PATIENT; DIASTOLIC BLOOD PRESSURE; DISEASE COURSE; DISEASE SEVERITY; FIBROGENESIS; FOLLOW UP; GLOMERULOSCLEROSIS; GLOMERULUS FILTRATION RATE; HEART PROTECTION; HUMAN; INFLAMMATORY CELL; INSULIN DEPENDENT DIABETES MELLITUS; KIDNEY DISEASE; KIDNEY FUNCTION; KIDNEY INTERSTITIUM; MESANGIUM CELL; MICROALBUMINURIA; MYOFIBROBLAST; NEPHRECTOMY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OUTCOME ASSESSMENT; PATHOPHYSIOLOGY; PERFUSION PRESSURE; PLASMA CLEARANCE; PODOCYTE; PREDICTIVE VALUE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN URINE LEVEL; PROTEINURIA; RISK FACTOR; URINARY EXCRETION;

BIOMARKER; CARDIOVASCULAR; CHRONIC KIDNEY DISEASE; PROTEINURIA;

CARDIOVASCULAR DISEASES; CHEMOKINES; COMPLEMENT ACTIVATION; GLOMERULAR FILTRATION RATE; HUMANS; KIDNEY TUBULES; PROTEINURIA; RENAL INSUFFICIENCY, CHRONIC; RISK FACTORS;

EID: 84884696986     PISSN: 03065251     EISSN: 13652125     Source Type: Journal    
DOI: 10.1111/bcp.12104     Document Type: Article

References (52)

1. Tonelli M, Muntner P, Lloyd A, Manns BJ, Klarenbach S, Pannu N, James MT, Hemmelgarn BR. Risk of coronary events in people with chronic kidney disease compared with those with diabetes: a population-level cohort study. Lancet 2012; 380: 807-814.
2. Donadelli R, Zanchi C, Morigi M, Buelli S, Batani C, Tomasoni S, Corna D, Rottoli D, Benigni A, Abbate M, Remuzzi G, Zoja C. Protein overload induces fractalkine upregulation in proximal tubular cells through nuclear factor kappaB- and p38 mitogen-activated protein kinase-dependent pathways. J Am Soc Nephrol 2003; 14: 2436-2446.
3. Cravedi P, Ruggenenti P, Remuzzi G. Kidney failure stabilizes after an increase over 2 decades. J Ren Care 2007; 33: 100-104.
4. Poggio ED, Nef PC, Wang X, Greene T, Van Lente F, Dennis VW, Hall PM. Performance of the Cockcroft-Gault and modification of diet in renal disease equations in estimating GFR in ill hospitalized patients. Am J Kidney Dis 2005; 46: 242-252.
5. Ruggenenti P, Gaspari F, Cannata A, Carrara F, Cella C, Ferrari S, Stucchi N, Prandini S, Ene-Iordache B, Diadei O, Perico N, Ondei P, Pisani A, Buongiorno E, Messa P, Dugo M, Remuzzi G. Measuring and estimating GFR and treatment effect in ADPKD patients: results and implications of a longitudinal cohort study. PLoS ONE 2012; 7: e32533.
6. Cravedi P, Ruggenenti P, Remuzzi G. Proteinuria should be used as a surrogate in CKD. Nat Rev Nephrol 2012; 8: 301-306.
7. Iseki K, Iseki C, Ikemiya Y, Fukiyama K. Risk of developing end-stage renal disease in a cohort of mass screening. Kidney Int 1996; 49: 800-805.
8. Ruggenenti P, Perna A, Mosconi L, Matalone M, Pisoni R, Gaspari F, Remuzzi G. Proteinuria predicts end-stage renal failure in non-diabetic chronic nephropathies. The 'Gruppo Italiano di Studi Epidemiologici in Nefrologia' (GISEN). Kidney Int Suppl 1997; 63: S54-57.
9. Peterson JC, Adler S, Burkart JM, Greene T, Hebert LA, Hunsicker LG, King AJ, Klahr S, Massry SG, Seifter JL, Group ftMoDiRDMS. Blood pressure control, proteinuria, and the progression of renal disease. The modification of diet in renal disease study. Ann Intern Med 1995; 123: 754-762.
10. Wright JT Jr, Bakris G, Greene T, Agodoa LY, Appel LJ, Charleston J, Cheek D, Douglas-Baltimore JG, Gassman J, Glassock R, Hebert L, Jamerson K, Lewis J, Phillips RA, Toto RD, Middleton JP, Rostand SG. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. JAMA 2002; 288: 2421-2431.
11. Retnakaran R, Cull CA, Thorne KI, Adler AI, Holman RR. Risk factors for renal dysfunction in type 2 diabetes: U.K. Prospective Diabetes Study 74. Diabetes 2006; 55: 1832-1839.
12. Keane WF, Zhang Z, Lyle PA, Cooper ME, de Zeeuw D, Grunfeld JP, Lash JP, McGill JB, Mitch WE, Remuzzi G, Shahinfar S, Snapinn SM, Toto R, Brenner BM. Risk scores for predicting outcomes in patients with type 2 diabetes and nephropathy: the RENAAL study. Clin J Am Soc Nephrol 2006; 1: 761-767.
13. Atkins RC, Briganti EM, Lewis JB, Hunsicker LG, Braden G, Champion de Crespigny PJ, DeFerrari G, Drury P, Locatelli F, Wiegmann TB, Lewis EJ. Proteinuria reduction and progression to renal failure in patients with type 2 diabetes mellitus and overt nephropathy. Am J Kidney Dis 2005; 45: 281-287.
14. de Zeeuw D, Ramjit D, Zhang Z, Ribeiro AB, Kurokawa K, Lash JP, Chan J, Remuzzi G, Brenner BM, Shahinfar S. Renal risk and renoprotection among ethnic groups with type 2 diabetic nephropathy: a post hoc analysis of RENAAL. Kidney Int 2006; 69: 1675-1682.
15. Remuzzi G, Benigni A, Remuzzi A. Mechanisms of progression and regression of renal lesions of chronic nephropathies and diabetes. J Clin Invest 2006; 116: 288-296.
16. Weil EJ, Lemley KV, Mason CC, Yee B, Jones LI, Blouch K, Lovato T, Richardson M, Myers BD, Nelson RG. Podocyte detachment and reduced glomerular capillary endothelial fenestration promote kidney disease in type 2 diabetic nephropathy. Kidney Int 2012; 82: 1010-1017.
17. Toyoda M, Najafian B, Kim Y, Caramori ML, Mauer M. Podocyte detachment and reduced glomerular capillary endothelial fenestration in human type 1 diabetic nephropathy. Diabetes 2007; 56: 2155-2160.
18. Barnes JL, Gorin Y. Myofibroblast differentiation during fibrosis: role of NAD(P)H oxidases. Kidney Int 2011; 79: 944-956.
19. Zoja C, Morigi M, Figliuzzi M, Bruzzi I, Oldroyd S, Benigni A, Ronco P, Remuzzi G. Proximal tubular cell synthesis and secretion of endothelin-1 on challenge with albumin and other proteins. Am J Kidney Dis 1995; 26: 934-941.
20. Drumm K, Bauer B, Freudinger R, Gekle M. Albumin induces NF-kappaB expression in human proximal tubule-derived cells (IHKE-1). Cell Physiol Biochem 2002; 12: 187-196.
21. Tang S, Leung JC, Abe K, Chan KW, Chan LY, Chan TM, Lai KN. Albumin stimulates interleukin-8 expression in proximal tubular epithelial cells in vitro and in vivo. J Clin Invest 2003; 111: 515-527.
22. Abbate M, Zoja C, Remuzzi G. How does proteinuria cause progressive renal damage? J Am Soc Nephrol 2006; 17: 2974-2984.
23. Rudnicki M, Eder S, Perco P, Enrich J, Scheiber K, Koppelstatter C, Schratzberger G, Mayer B, Oberbauer R, Meyer TW, Mayer G. Gene expression profiles of human proximal tubular epithelial cells in proteinuric nephropathies. Kidney Int 2007; 71: 325-335.
24. Johnson DW, Saunders HJ, Baxter RC, Field MJ, Pollock CA. Paracrine stimulation of human renal fibroblasts by proximal tubule cells. Kidney Int 1998; 54: 747-757.
25. Biancone L, David S, Della Pietra V, Montrucchio G, Cambi V, Camussi G. Alternative pathway activation of complement by cultured human proximal tubular epithelial cells. Kidney Int 1994; 45: 451-460.
26. Nangaku M, Pippin J, Couser WG. Complement membrane attack complex (C5b-9) mediates interstitial disease in experimental nephrotic syndrome. J Am Soc Nephrol 1999; 10: 2323-2331.
27. Rangan GK, Pippin JW, Coombes JD, Couser WG. C5b-9 does not mediate chronic tubulointerstitial disease in the absence of proteinuria. Kidney Int 2005; 67: 492-503.
28. Macconi D, Chiabrando C, Schiarea S, Aiello S, Cassis L, Gagliardini E, Noris M, Buelli S, Zoja C, Corna D, Mele C, Fanelli R, Remuzzi G, Benigni A. Proteasomal processing of albumin by renal dendritic cells generates antigenic peptides. J Am Soc Nephrol 2009; 20: 123-130.
29. Remuzzi G, Bertani T. Pathophysiology of progressive nephropathies. N Engl J Med 1998; 339: 1448-1456.
30. Bazzi C, Petrini C, Rizza V, Arrigo G, Beltrame A, Pisano L, D'Amico G. Urinary excretion of IgG and alpha(1)-microglobulin predicts clinical course better than extent of proteinuria in membranous nephropathy. Am J Kidney Dis 2001; 38: 240-248.
31. McQuarrie EP, Shakerdi L, Jardine AG, Fox JG, Mackinnon B. Fractional excretions of albumin and IgG are the best predictors of progression in primary glomerulonephritis. Nephrol Dial Transplant 2011; 26: 1563-1569.
32. Group TG. Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. Lancet 1997; 349: 1857-1863.
33. Ruggenenti P, Perna A, Remuzzi G. Retarding progression of chronic renal disease: the neglected issue of residual proteinuria. Kidney Int 2003; 63: 2254-2261.
34. Bjorck S, Mulec H, Johnsen SA, Norden G, Aurell M. Renal protective effect of enalapril in diabetic nephropathy. BMJ 1992; 304: 339-343.
35. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med 1993; 329: 1456-1462.
36. Jafar TH, Schmid CH, Landa M, Giatras I, Toto R, Remuzzi G, Maschio G, Brenner BM, Kamper A, Zucchelli P, Becker G, Himmelmann A, Bannister K, Landais P, Shahinfar S, de Jong PE, de Zeeuw D, Lau J, Levey AS. Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease. A meta-analysis of patient-level data. Ann Intern Med 2001; 135: 73-87.
37. Ruggenenti P, Schieppati A, Remuzzi G. Progression, remission, regression of chronic renal diseases. Lancet 2001; 357: 1601-1608.
38. Pergola PE, Raskin P, Toto RD, Meyer CJ, Huff JW, Grossman EB, Krauth M, Ruiz S, Audhya P, Christ-Schmidt H, Wittes J, Warnock DG. Bardoxolone methyl and kidney function in CKD with type 2 diabetes. N Engl J Med 2011; 365: 327-336.
39. Zoja C, Corna D, Nava V, Locatelli M, Abbate M, Gaspari F, Carrara F, Sangalli F, Remuzzi G, Benigni A. Analogues of bardoxolone methyl worsen diabetic nephropathy in rats with additional adverse effects. Am J Physiol Renal Physiol 2013; 304: f808-819.
40. Agrawal V, Marinescu V, Agarwal M, McCullough PA. Cardiovascular implications of proteinuria: an indicator of chronic kidney disease. Nat Rev Cardiol 2009; 6: 301-311.
41. de Zeeuw D, Remuzzi G, Parving HH, Keane WF, Zhang Z, Shahinfar S, Snapinn S, Cooper ME, Mitch WE, Brenner BM. Albuminuria, a therapeutic target for cardiovascular protection in type 2 diabetic patients with nephropathy. Circulation 2004; 110: 921-927.
42. Ibsen H, Olsen MH, Wachtell K, Borch-Johnsen K, Lindholm LH, Mogensen CE, Dahlof B, Devereux RB, de Faire U, Fyhrquist F, Julius S, Kjeldse n SE, Lederballe-Pedersen O, Nieminen MS, Omvik P, Oparil S, Wan Y. Reduction in albuminuria translates to reduction in cardiovascular events in hypertensive patients: losartan intervention for endpoint reduction in hypertension study. Hypertension 2005; 45: 198-202.
43. Holtkamp FA, de Zeeuw D, de Graeff PA, Laverman GD, Berl T, Remuzzi G, Packham D, Lewis JB, Parving HH, Lambers Heerspink HJ. Albuminuria and blood pressure, independent targets for cardioprotective therapy in patients with diabetes and nephropathy: a post hoc analysis of the combined RENAAL and IDNT trials. Eur Heart J 2011; 32: 1493-1499.
44. Hunsicker LG, Atkins RC, Lewis JB, Braden G, de Crespigny PJ, DeFerrari G, Drury P, Locatelli F, Wiegmann TB, Lewis EJ. Impact of irbesartan, blood pressure control, and proteinuria on renal outcomes in the Irbesartan Diabetic Nephropathy Trial. Kidney Int Suppl 2004; 66: S99-101.
45. Dinneen SF, Gerstein HC. The association of microalbuminuria and mortality in non-insulin-dependent diabetes mellitus. A systematic overview of the literature. Arch Intern Med 1997; 157: 1413-1418.
46. Sasso FC, Chiodini P, Carbonara O, De Nicola L, Conte G, Salvatore T, Nasti R, Marfella R, Gallo C, Signoriello S, Torella R, Minutolo R. High cardiovascular risk in patients with type 2 diabetic nephropathy: the predictive role of albuminuria and glomerular filtration rate. The NID-2 Prospective Cohort Study. Nephrol Dial Transplant 2012; 27: 2269-2274.
47. Klausen K, Borch-Johnsen K, Feldt-Rasmussen B, Jensen G, Clausen P, Scharling H, Appleyard M, Jensen JS. Very low levels of microalbuminuria are associated with increased risk of coronary heart disease and death independently of renal function, hypertension, and diabetes. Circulation 2004; 110: 32-35.
48. Arnlov J, Evans JC, Meigs JB, Wang TJ, Fox CS, Levy D, Benjamin EJ, D'Agostino RB, Vasan RS. Low-grade albuminuria and incidence of cardiovascular disease events in nonhypertensive and nondiabetic individuals: the Framingham Heart Study. Circulation 2005; 112: 969-975.
49. Ruggenenti P, Porrini E, Motterlini N, Perna A, Ilieva AP, Iliev IP, Dodesini AR, Trevisan R, Bossi A, Sampietro G, Capitoni E, Gaspari F, Rubis N, Ene-Iordache B, Remuzzi G. Measurable urinary albumin predicts cardiovascular risk among normoalbuminuric patients with type 2 diabetes. J Am Soc Nephrol 2012; 23: 1717-1724.
50. Levey AS, Cattran D, Friedman A, Miller WG, Sedor J, Tuttle K, Kasiske B, Hostetter T. Proteinuria as a surrogate outcome in CKD: report of a scientific workshop sponsored by the National Kidney Foundation and the US Food and Drug Administration. Am J Kidney Dis 2009; 54: 205-226.
51. Nitsch D, Grams M, Sang Y, Black C, Cirillo M, Djurdjev O, Iseki K, Jassal SK, Kimm H, Kronenberg F, Oien CM, Levey AS, Levin A, Woodward M, Hemmelgarn BR. Associations of estimated glomerular filtration rate and albuminuria with mortality and renal failure by sex: a meta-analysis. BMJ 2013; 346: f324.
52. Ruggenenti P, Cravedi P, Remuzzi G. Mechanisms and treatment of CKD. J Am Soc Nephrol 2012; 23: 1917-1928.