Management of patients with chronic kidney disease (CKD) emphasizes a current level of function as calculated from the modification of diet in renal disease glomerulofiltration rate equations (eGFR) and proteinuria for staging of CKD. Change in a patient’s eGFR over time (renal function trajectory) is an additional and potentially more important consideration in deciding which patients will progress to the point where they will require renal replacement therapy (RRT). Many patients with CKD 3–5 have stable renal function for years. Proteinuria/albuminuria is a primary determinant of renal trajectory which may be slowed by medications that decrease proteinuria and/or aggressively lower blood pressure. A renal trajectory of >3 ml/min/1.73 m2/year may relate to a need for closer renal follow-up and increased morbidity and mortality. Additional CKD population-based studies need to examine the relationship of renal trajectory to: baseline renal function; acute kidney injury episodes; age, race, sex and primary etiologies of renal disease; blood pressure control and therapies; dietary protein intake; blood glucose control in diabetics and the competitive risk of death versus the requirement for renal replacement therapy. In the elderly CKD 4 population with significant comorbidities and slow decline in renal function, the likelihood of death prior to the need for RRT should be considered before placing AV access for dialysis. Prediction models of renal progression must account for the competitive risk of death as well as stable or improved renal function to be clinically useful.

1.
Hallan SI, Ritz E, Lydersen S, Romundstad S, Kvenlid K, Orth SR: Combining GFR and albuminuria to classify CKD improves prediction of ESRD. J Am Soc Nephrol 2009;20:1069–1077.
2.
Froissart M, Rossert R, Jacquot, C, Paillard M, Houillier P: Predictive performance of the modification of diet in renal disease and Cockcroft-Gault equations for estimating renal function. J Am Soc Nephrol 2005;16:763–773.
3.
Hois R, Bevc S, Ekart R, et al: Serum cystatin C as an endogenous marker of renal function in patients with mild to moderate impairment of kidney function. Nephrol Dial Transplant 2006;21:1855–1862.
4.
Mitch WE, Walser M, Buffington GA, Lemann J Jr: A simple method of estimating progression of chronic renal failure. Lancet 1976;ii:1326–1328.
5.
Foley RN, Murray AM, Li S, et al: Chronic kidney disease and the risk for cardiovascular disease, renal replacement, and death in the United States Medicare population, 1998 to 1999. J Am Soc Nephrol 2005;16:489–495.
6.
Al-Aly Z, Zeringue A, Fu J, et al: Rate of kidney function decline associates with mortality. J Am Soc Nephrol 2010;21:1961–1969.
7.
Rifkin DE, Shlipak MG, Katz R: Rapid kidney function decline and mortality risk in older adults. Arch Intern Med 2008;168:2212–2218.
8.
Ishani A, Nelson D, Clothier B, et al: The magnitude of acute serum creatinine increase after cardiac surgery and the risk of chronic kidney disease, progression of kidney disease, and death. Arch Intern Med 2011;171:226–233.
9.
Murthy K, Stevens LA, Stark PC Levey AS: Variation in the serum creatinine assay calibration: a practical application to glomerular filtration rate estimation. Kidney Int 2005;68:1884–1887.
10.
Coresh J Astor B: Kidney function in the elderly. Ann Intern Med 2006;145:299–301.
11.
Grootendorst DC, Michels WM, Richardson JD, et al; for the NECOSAD Study Group: The MDRD formula does not reflect GFR in ESRD patients. Nephrol Dial Transplant 2011;26:1932–1937.
12.
Beddhu S, Samore MH, Roberts MS, et al: Creatinine production, nutrition, and glomerular filtration rate estimation. J Am Soc Nephrol 2003;14:1000–1005.
13.
Stevens LA, Schmid CH, Greene T, et al: Comparative performance of the CKD epidemiology collaboration (CKD-EPI) and the modification of diet in renal disease (MDRD) study equations for estimating GFR levels above 60 ml/min/1.73 m2. Am J Kidney Dis 2010;56:486–495.
14.
Fontseré N, Bonal J, Navarro M, et al: A comparison of prediction equations for estimating glomerular filtration rate in adult patients with chronic kidney disease stages 4–5, effect of nutritional status and age. Nephron Clin Pract 2006;104:c160–c168.
15.
Garcia-Naveiro R, Rodriguez-Carmona A, Pérez-Fontán M: Agreement between two routine methods of estimation of glomerular filtration rate in patients with advanced and terminal chronic renal failure. Clin Nephrol 2005;64:271–280.
16.
Levey AS, Gassman JJ, Hall PM, Walker WG; for the MDRD Study Group: Assessing the progression of renal disease in clinical studies: effects of duration of follow-up and regression to the mean. J Am Soc Nephrol 1991;1:1087–1094.
17.
Eriksen BO, Ingebretsen OC: In chronic kidney disease staging the use of the chronicity criterion affects prognosis and the rate of progression. Kidney Int 2007;72:1242–1248.
18.
Anderson AH: Screening for proteinuria: a tool for predicting rapid declines in kidney function? J Am Soc Nephrol 2011;22:1580–1583.
19.
Fontseré N, Salinas I, Bonal J, et al: Are prediction equations for glomerular filtration rate useful for the long-term monitoring of type 2 diabetic patients? Nephrol Dial Transplant 2006;21:2152–2158.
20.
Xie D, Joffe MM, Brunelli SM, et al: A comparison of change in measured and estimated glomerular filtration rate in patients with nondiabetic kidney disease. Clin J Am Soc Nephrol 2008;3:1332–1338.
21.
Wang X, Lewis J, Appel L, et al: Validation of creatinine-based estimates of GFR when evaluating risk factors in longitudinal studies of kidney disease. J Am Soc Nephrol 2003;14:1000–1005.
22.
Lewis J, Greene T, Appel L, et al; for the AASK Study Group; A comparison of iothalamate-GFR and serum creatinine-based outcomes: acceleration in the rate of GFR decline in the African-American study of kidney disease and hypertension. J Am Soc Nephrol 2004;15, 3175–3183.
23.
Clark WF, Macnab JJ, Sontrop JM, et al: Dipstick proteinuria as a screening strategy to identify rapid renal decline. J Am Soc Nephrol 2011;22:1729–1736.
24.
Levin A, Djurdjie O, Beaulieu M, Er L: Variability and risk factors for kidney disease progression and death following attainment of stage 4 CKD in a referred cohort. Am J Kidney Dis 2008;52:661–671.
25.
Eriksen BO Ingebretsen OC: The progression of chronic kidney disease: a 10-year population-based study of the effects of gender and age. Kidney Int 2006;69:375–382.
26.
Rottey S, Vanholder R, De Schoenmakere G, Lameire N: Progression of renal failure in patients with compromised renal function is not always present: evaluation of underlying disease. Clin Nephrol 2000;54:1–10.
27.
Hunsickler LG, Adler S, Caggiula A, et al: Predictors of the progression of renal disease in the modification of diet in renal disease study. Kidney Int 1997;51:1908–1919.
28.
Perkins RM, Bucalord JD, Kirchner HL, Ashouian N, Hartle JE, Yahya T: GFR decline and mortality risk among patients with chronic kidney disease. Clin J Am Soc Nephrol 2011;6:1879–1886.
29.
Lindeman RD, Tobin J, Shock NW: Longitudinal studies on the rate of decline in renal function with age. J Am Geriatr Soc 1985;33:278.
30.
Conway B, Webster A, Ramsay G, et al: Predicting mortality and uptake of renal replacement therapy in patients with stage 4 chronic kidney disease. Nephrol Dial Transplant 2009;24:1930–1937.
31.
O’Hare AM, Choi AI, Bertenthal D, et al: Age affects outcomes in chronic kidney disease. J Am Soc Nephrol 2007;18:2758–2765.
32.
Evan M, Fryzek JP, Elinder C-G, et al: The natural history of chronic renal failure: results from and unselected, population-based, inception cohort in Sweden. Am J Kidney Dis 2005;46:863–870.
33.
John R, Webb M, Young A, Stevens PE: Unreferred chronic kidney disease: a longitudinal study. Am J Kidney Dis 2004;43:825–835.
34.
Imai E, Horio M, Yamagata K, et al: Slower decline of glomerular filtration rate in the Japanese general population: a longitudinal 10-year follow-up study. Hypertens Res 2008;31:433–441.
35.
Neugarten J, Acharya A, Silbiger SR: Effect of gender on the progression of nondiabetic renal disease: a meta-analysis. J Am Soc Nephrol 2000;11:319–329.
36.
Jafar TH, Schmid CH, Stark PC, et al: The rate of progression of renal disease may not be slower in women compared with men: a patient-level meta-analysis. Nephrol Dial Transplant 2003;18:2047–2053.
37.
Levey AS, de Jong PE, Coresh J, et al: The definition, classification, and prognosis of chronic kidney disease: a KDIGO controversies conference report. Kidney Int 2011;80:17–28.
38.
Gansevoort RT, Matsushita K, van der Velde M, et al: Lower estimated GFR and higher albuminuria are associated with adverse kidney outcomes. A collaborative meta-analysis of general and high-risk population cohorts. Kidney Int 2011;80:93–104.
39.
Hemmelgarn BR, Manns BJ, Lloyd A, et al: Relation between kidney function, proteinuria, and adverse outcomes. JAMA 2010;303:423–429.
40.
Lea J, Greene T, Herbert L, et al: The relationship between magnitude of proteinuria reductiona and risk of end-stage renal disease. Arch Intern Med 2005;165:947–953.
41.
Keane WF, Brenner BM, de Zeeuw D, et al: The risk of developing end-stage renal disease in patients with type 2 diabetes and nephropathy: the RENAAL study. Kidney Int 2003;63:1499–1507.
42.
Peralta CA, Katz R, Deboer I, et al: Racial and ethnic differences in kidney function decline among persons without chronic kidney disease. J Am Soc Nephrol 2011;22:1327–1334.
43.
Barbour SJ, Schachter M, Er L, Djurdjev O, Levin A: A systematic review of ethnic differences in the rate of renal progression in CKD patients. Nephrol Dial Transplant 2010;25:2422–2430.
44.
Klag MJ, Whelton PK, Randall BL, Neaton JD, Brancati FL, Stamler J: End-stage renal disease in African-American and white men. JAMA 1997;277:1293–1298.
45.
McClellan WM, Warnock DG, Judd S, et al: Albuminuria and racial disparities in the risk for ESRD. J Am Soc Nephrol 2011;22:1721–1728.
46.
Menon V, Kopple JD, Wang X, et al: Effect of a very low-protein diet on outcomes: long-term follow-up of the modification of diet in renal disease (MDRD) study. Am J Kidney Dis 2009;53:208–217.
47.
Halbesma N, Bakker SJ, Jansen DF, et al: High protein intake associates with cardiovascular events but not with loss of renal function. J Am Soc Nephrol 2009;20:1797–1804.
48.
Hallan SI Orth SR: Smoking is a risk factor in the progression to kidney failure. Kidney Int 2011;80:516–523.
49.
Rosansky SJ, Hoover D, King L Gibson J: The association of blood pressure levels and change in renal function in hypertensive and non-hypertensive subjects. Arch Int Med 1990;150:2073–2076.
50.
Wright Jr JT, Bakris G, Greene T, et al: Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease. JAMA 2002;288:2421–2431.
51.
Appel LJ, Wright JT, Greene T, et al: Intensive blood-pressure control in hypertensive chronic kidney disease. N Engl J Med 2010;363:918–929.
52.
Jafar TH, Stark PC, Schmid CH, et al: Progression of chronic kidney disease: the role of blood pressure control, proteinuria, and angiotensin-converting enzyme inhibition, a patient-level meta-analysis. Ann Intern Med 2003;139:244–252.
53.
ACCORD Study Group: Effects of intensive blood-pressure control in type 2 diabetes. N Engl J Med 2008;358:2545–2559.
54.
Kent DM, Jafar TH, Hayward RA, et al: Progression risk, urinary protein excretion, and treatment effects of angiotensin-converting enzyme inhibitors in nondiabetic kidney disease. J Am Soc Nephrol 2007;18:1959–1965.
55.
Lewis EJ, Hunsicker LG, Clarke WR, et al: Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001;345:851–860.
56.
Brenner BM, Cooper ME, de Zeeuw D, et al: Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001;345:861–869.
57.
Bakris GL: Slowing nephropathy progression: focus on proteinuria reduction. Clin J Am Soc Nephrol 2008;3:S3–S10.
58.
Thomas MC, Jerums G, Salamandris C, MacIssac R, Panagiotopoulos S, Cooper ME, MDNSG Study Group: Increased tubular organic ion clearance following chronic ACE inhibition in patients with type 1 diabetes. Kidney Int 2005;67:2494–2499.
59.
Kunz R, Friedrich C, Wolbers M, Mann JFE: Meta-analysis: effects of monotherapy and combination therapy with inhibitors of the renin-angiotensin system on proteinuria in renal disease. Ann Intern Med 2008;148:30–48.
60.
Mann JFE, Schmieder RE, McQueen M, et al: Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet 2008;372:547–553.
61.
Ruggenenti P, Perna A, Remuzzi G; on behalf of the investigators of the GISEN group: Retarding progression of chronic renal disease: the neglected issue of residual proteinuria. Kidney Int 2003;63:2254–2261.
62.
Hou FF, Xie D, Zhang X, et al: Renoprotection of optimal antiproteinuric doses (ROAD) study: a randomized controlled study of benazepril and losartan in chronic renal insufficiency. J Am Soc Nephrol 2007;18:1889–1898.
63.
Holtkamp FA, de Zeeuw D, Thomas MC, et al: An acute fall in estimated glomerular filtration rate during treatment with losartan predicts a slower decrease in long-term renal function. Kidney Int 2011;80:282–287.
64.
De Boer IH, Sun W, Cleary PA, et al: Intensive diabetes therapy and glomerular filtration rate in type 1 diabetes. N Engl J Med 2011;365:2366–2376.
65.
Forsblom C, Harjutsalo V, Thorn LM: Compteting-risk analysis of ESRD and death among patients with type 1 diabetes and macroalbuminuria. J Am Soc Nephrol 2011;22:537–544.
66.
Hovind P, Rossing P, Tarnow L, Smidt UM, Parving HH: Progression of diabetic nephropathy. Kidney Int 2001;59:702–709.
67.
The ADVANCE Collaborative Group: Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008;358:2560–2572.
68.
Ismail-Beigi F, Craven T, Banerji MA, et al: Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial. Lancet 2010;376:419–430.
69.
Sahni V, Rosa RM, Batlle D: Potential benefits of alkali therapy to prevent GFR loss: time for a palatable ‘solution’ for the management of CKD. Kidney Int 2010;78:1065–1067.
70.
De Brito-Ashurst I, Varagunam M, Raftery MJ, Yagoob MM: Bicarbonate supplementation slows progression of CDK and improves nutritional status. J Am Soc Nephrol 2009;20:2075–2084.
71.
Bayliss EA, Bhardwaja B, Ross C, Beck A, Lanese DM: Multidisciplinary team care may slow the rate of decline in renal function. Clin J Am Soc Nephrol 2011;6:704–710.
72.
Barrett BJ, Garg AX, Goeree R, et al: A nurse-coordinated model of care versus usual care for stage 3/4 chronic kidney disease in the community: a randomized controlled trail. Clin J Am Soc Nephrol 2011;6:1241–1247.
73.
Wu V, Huang T-M, Lai C-F, et al: Acute-on-chronic kidney injury at hospital discharge is associated with long-term dialysis and mortality. Kidney Int 2011;80:1222–1230.
74.
Hsu CY, Ordoñez JD, Chertow GM, Fan D, McCulloch CE, Go AS: The risk of acute renal failure in patients with chronic kidney disease. Kidney Int 2008;74:101–107.
75.
Ishani A, Xue JL, Himmelfarb J, et al: Acute kidney injury increases risk of ESRD among elderly. J Am Soc Nephrol 2009;20:223–228.
76.
Onuigbo MAC: Syndrome of rapid-onset end-stage renal disease: a new unrecognized pattern of CKD progression to ESRD. Renal Failure 2010;32:964–958.
77.
Seabra VF, Balk EM, Liangos O, Sosa MA, Cendoroglo M, Jaber BL: Timing of renal replacement therapy initiation in acute renal failure: a meta-analysis. Am J Kidney Dis 2008;52:272–284.
78.
Rosansky SJ, Glassock RJ, Clark WF: Early start of dialysis: a critical review. Clin J Am Soc Nephrol 2011;6:1222–1228.
79.
Rosansky SJ, Hardin JW, Richards F, et al: Relationship between outpatient ‘AKI’, proteinuria, diagnosis diabetes, race and rate of decline in renal function, nine years prior to dialysis initiation. 2011;http://www.asn-online.org.
80.
Rosansky SJ, Hardin JW, Richards F, et al: The relationship of urine proteinuria to outpatient ‘AKI’ and renal progression. 2011;http://www.asn-online.org.
81.
Jones C, Roderick P, Harris S, Rogerson M: Decline in kidney function before and after nephrology referral and the effect on survival in moderate to advanced chronic kidney disease. Nephrol Dial Transplant 2006;21:2133–2143.
82.
Ambrogi V, Thilly N, Boini S, Virion J-M: Patterns and predictors of kidney function decline in the last year prior to dialsys. Nephron Clin Pract 2009;111:c95–c101.
83.
Tattersall J, Dekker F, Heimbürger O: When to start dialysis: updated guidance following publication of the initiating dialysis early and late (IDEAL) study. Nephrol Dial Transplant 2011;26:2082–2086.
84.
Tangri NA, Stevens LA, Griffith J: A predictive model for progression of chronic kidney disease to kidney failure. JAMA 2011;305:1553–1559.
85.
Shlipak MG, Katz R, Kestenbaum B, et al: Rapid decline of kidney function increases cardiovascular risk in the elderly. J Am Soc Nephrol 2009;20:2625–2630.
86.
Matsushita K, Selvin E, Bash LD, Franceschini N, Astor BC, Coresh J: Change in estimated GFR associates with coronary heart disease and mortality. Clin J Am Soc Nephrol 2009;20:2617–2624.
87.
Hsu CY, Chertow GM, McCulloch CE, Fan D, Ordoñez Go AS: Nonrecovery of kidney function and death after acute on chronic renal failure. Clin J Am Soc Nephrol 2009;4:891–898.
88.
Jaar BG, Khatib R, Plantinga L, Boulware, LE, Powe NR: Principles of screening for chronic kidney disease. Clin J Am Soc Nephrol 2008;3:601–609.
89.
Demoulin N, Beguin C, Labriola L, Jadoul M: Preparing renal replacement therapy in stage 4 CKD patients referred to nephrologists: a difficult balance between futility and insufficiency. A cohort study of 386 patients followed in Brussels. Nephrol Dial Transplant 2011;26:220–226.
90.
Alves TP, Wang X, Wright JT Jr, et al: Rate of ESRD exceeds mortality among African Americans with hypertensive nephrosclerosis. J Am Soc Nephrol 2010;21:1361–1369.
91.
Obi Y, Kimura R, Nagasawa Y, et al: Impact of age and overt proteinuria on outcomes of stage 3 to 5 chronic kidney disease in a referred cohort. Clin J Am Nephrol 2010;5:1558–1565.
92.
O’Hare AM, Bertenthal D, Walter LC, et al: When to refer patients with chronic kidney disease for vascular access surgery: should age be a consideration? Kidney Int 2007;71:555–561.
93.
Vachharajani TJ, Moossavi S, Jordan JR, Vachharajani V, Freedman BI, Burkart JM: Re-evaluating the fistula first initiative in octogenarians on hemodialysis. Clin J Am Soc Nephrol 2011;6:1663–1667.
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