Contrast Medium Administration in the Elderly Patient: Is Advancing Age an Independent Risk Factor for Contrast Nephropathy after Angiographic Procedures?
2007; Elsevier BV; Volume: 18; Issue: 2 Linguagem: Inglês
10.1016/j.jvir.2006.12.009
ISSN1535-7732
AutoresSimona Detrenis, Michele Meschi, Laura Bertolini, G Savazzi,
Tópico(s)Trauma, Hemostasis, Coagulopathy, Resuscitation
ResumoContrast medium–induced nephropathy (CMIN) is the third leading cause of hospital-acquired acute renal dysfunction. Even if the number of patients over 75 years of age undergoing diagnostic and/or interventional procedures and requiring administration of contrast medium (CM) is growing constantly, at present there is no definitive consensus regarding the role of advancing age and related morphologic or functional renal changes as an independent risk factor for CMIN. The authors review the evidence from recent medical literature on the definition, pathophysiology, and clinical presentation of CMIN as well as therapeutic approaches to its prophylaxis. Attention is focused on advancing age as a preexisting physiologic condition that is, per se, able to predispose the patient to CM-induced renal impairment, assuming that every elderly patient is potentially at risk for CMIN. Contrast medium–induced nephropathy (CMIN) is the third leading cause of hospital-acquired acute renal dysfunction. Even if the number of patients over 75 years of age undergoing diagnostic and/or interventional procedures and requiring administration of contrast medium (CM) is growing constantly, at present there is no definitive consensus regarding the role of advancing age and related morphologic or functional renal changes as an independent risk factor for CMIN. The authors review the evidence from recent medical literature on the definition, pathophysiology, and clinical presentation of CMIN as well as therapeutic approaches to its prophylaxis. Attention is focused on advancing age as a preexisting physiologic condition that is, per se, able to predispose the patient to CM-induced renal impairment, assuming that every elderly patient is potentially at risk for CMIN. THE increasing use of new low-osmolar and isoosmolar iodinated contrast media in interventional radiology has permitted a significant although not total reduction in the incidence of contrast medium–induced nephropathy (CMIN).Contrast medium–induced nephropathy is currently defined either as an acute decrease in renal function after intravascular administration of an iodinated contrast medium (CM) without evidence of other causes or as an absolute increase in serum creatinine values ≥0.5 mg/dL (or 44 μmol/L) or a ≥25% relative increase from baseline values within 48–72 hours after injection of a CM. Contrast medium–induced damage is the third highest cause of hospital-acquired acute renal failure, and in half the cases it occurs after invasive cardiac procedures (1McCullough P. Outcomes of contrast-induced nephropathy: experience in patients undergoing cardiovascular intervention.Catheter Cardiovasc Interv. 2006; 67: 335-343Crossref PubMed Scopus (85) Google Scholar).Various factors may be involved in determining an increased risk of CMIN, in particular the impairment of renal function preceding CM administration, especially when associated with diabetes mellitus (2Morcos S.K. Prevention of contrast media-induced nephrotoxicity after angiographic procedures.J Vasc Interv Radiol. 2005; 16: 13-23Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar). In any case, there is general consensus that hypovolemia and/or dehydration of patients undergoing procedures with use of CM is one of the most significant risk factors for the onset of CM-induced renal damage (3Meschi M. Detrenis S. Musini S. Strada E. Savazzi G. Facts and fallacies concerning the prevention of contrast medium-induced nephropathy.Crit Care Med. 2006; 34: 2060-2068Crossref PubMed Scopus (45) Google Scholar). The injection of CM could be followed by prolonged intrarenal vasoconstriction, which would lead to a reduction in the glomerular filtration rate (GFR). In addition, an overlap of ischemic damage, in part mediated by reactive oxygen species and toxic injury to the renal tubules and endothelial cells, could contribute to radiocontrast-related impairment in renal function (4Detrenis S. Meschi M. Musini S. Savazzi G. Lights and shadows on the pathogenesis of contrast-induced nephropathy: state of the art.Nephrol Dial Transplant. 2005; 20: 1542-1550Crossref PubMed Scopus (125) Google Scholar).Contrast medium–induced nephropathy in elderly patientsRecent improvements in radiodiagnostic procedures and in cardiovascular percutaneous interventions, together with increased life expectancy, have resulted in the subjection of an increasing number of aged patients to CM-enhanced examinations or cardiac and angiographic procedures requiring iodinated CM injection (5Huber W. Eckel F. Hennig M. et al.Prophylaxis of contrast material-induced nephropathy in patients in intensive care: acetylcysteine, theophylline, or both? A randomized study.Radiology. 2006; 239: 793-804Crossref PubMed Scopus (68) Google Scholar).Chronic alteration of renal function requiring hemodialysis can occur in up to 10%–12% of all subjects with preexisting renal impairment who develop a further decrease in renal function after percutaneous coronary procedures but in less than 1% of the total population who undergo these interventions (4Detrenis S. Meschi M. Musini S. Savazzi G. Lights and shadows on the pathogenesis of contrast-induced nephropathy: state of the art.Nephrol Dial Transplant. 2005; 20: 1542-1550Crossref PubMed Scopus (125) Google Scholar). In-hospital mortality requiring hemodialysis after acute renal damage in these subjects could reach 35%–36%, even if this rate might be partially due to the influence of possible coexisting comorbidities (4Detrenis S. Meschi M. Musini S. Savazzi G. Lights and shadows on the pathogenesis of contrast-induced nephropathy: state of the art.Nephrol Dial Transplant. 2005; 20: 1542-1550Crossref PubMed Scopus (125) Google Scholar).Retrospective and/or prospective large-scale studies to determine the prevalence and incidence of CMIN in elderly subjects and to circumscribe the dimensions of the problem within this subpopulation have not been yet performed. The age of >75 years has recently been included in some recapitulatory predictive risk scores evaluating the overall single probability of CMIN in subjects undergoing percutaneous coronary interventions (6Mehran R. Aymong E.D. Nikolsky E. et al.A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: development and initial validation.J Am Coll Cardiol. 2004; 44: 1393-1399PubMed Scopus (0) Google Scholar, 7Bartholomew B.A. Harjai K.J. Dukkipati S. et al.Impact of nephropathy after percutaneous coronary intervention and a method for risk stratification.Am J Cardiol. 2004; 93: 1515-1519Abstract Full Text Full Text PDF PubMed Scopus (403) Google Scholar). Yet only some studies have provided indirect evidence that older age is an independent risk factor (8Parfrey P.S. Griffiths S.M. Barrett B.J. et al.Contrast material-induced renal failure in patients with diabetes mellitus, renal insufficiency, or both A prospective controlled study.New Engl J Med. 1989; 320: 143-149Crossref PubMed Scopus (886) Google Scholar, 9Gussenhoven M.J. Ravensbergen J. Van Bockel J.H. Feuth J.D. Aarts J.C. Renal dysfunction after angiography; a risk factor analysis in patients with peripheral vascular disease.J Cardiovasc Surg. 1991; 157: 49-58Google Scholar, 10Kini A.S. Mitre C.A. Kim M. Kamran M. Reich D. Sharma S.K. A protocol for prevention of radiographic contrast nephropathy during percutaneous coronary intervention: effect of selective dopamine receptor agonist fenoldopam.Catheter Cardiovasc Interv. 2002; 55: 169-173Crossref PubMed Scopus (78) Google Scholar). Also, there is no general consensus regarding this matter. At present, the incidences of CMIN in elderly patients reported in the medical literature have been attributed to senile panvasculopathy and nephroangiosclerosis (11Berg U.B. Differences in decline in GFR with age between males and females Reference data on clearances of inulin and PAH in potential kidney donors.Nephrol Dial Transplant. 2006; 21: 2577-2582Crossref PubMed Scopus (150) Google Scholar).Estimation of Renal Function in the Elderly Patient Before Contrast Medium ExposureIn the general population, the presence of preexisting renal impairment is considered as the highest risk factor for development of CMIN after iodinated CM administration in diagnostic and/or interventional procedures. This risk appears to increase even further when creatinine clearance values are less than 60 mL/min/1.73 m2 (stages 3, 4, and 5 of chronic kidney disease for the National Kidney Foundation) (3Meschi M. Detrenis S. Musini S. Strada E. Savazzi G. Facts and fallacies concerning the prevention of contrast medium-induced nephropathy.Crit Care Med. 2006; 34: 2060-2068Crossref PubMed Scopus (45) Google Scholar).Even if a preexisting increasing level of serum creatinine is related to the incidence of CMIN (from 1.8%–2% in subjects with serum creatinine 2.5 mg/dL), it should be remembered that GFR evaluation is the true measurement of renal function (12Cirillo M. Anastasio P. De Santo N.G. Relationship of gender, age, and body mass index to errors in predicted kidney function.Nephrol Dial Transplant. 2005; 20: 1791-1798Crossref PubMed Scopus (199) Google Scholar).The most frequently used test in daily clinical evaluation of glomerular function is the determination of serum creatinine (13Van Biesen W. Vanholder R. Veys N. et al.The importance of standardization of creatinine in the implementation of guidelines and recommendations for CKD: implications for CKD management programmes.Nephrol Dial Transplant. 2006; 21: 77-83Crossref PubMed Scopus (89) Google Scholar). It is recognized that GFR, as estimated by creatinine clearance, can decrease with age (14Konta T. Hao Z. Abiko H. et al.Prevalence and risk factor analysis of microalbuminuria in Japanese general population: the Takahata study.Kidney Int. 2006; 70: 751-756Crossref PubMed Scopus (118) Google Scholar). This decrease in creatinine clearance may not be appreciated by measurement of serum creatinine in elderly patients (3Meschi M. Detrenis S. Musini S. Strada E. Savazzi G. Facts and fallacies concerning the prevention of contrast medium-induced nephropathy.Crit Care Med. 2006; 34: 2060-2068Crossref PubMed Scopus (45) Google Scholar). There is a nonlinear inverse relationship between GFR and the serum concentration of creatinine, which reflects muscular mass, age, and sex of the subject under examination, as it is a muscular creatine catabolite. In fact, aged subjects generally experience a decrease in muscle mass, which, in turn, is associated with a decrease in muscle creatinine production. Because the decrease in creatinine production may parallel the physiologic decrease in GFR, serum creatinine may remain unchanged despite declining renal function. Thus elderly patients, with the reduced total muscular mass typical of old age, often have a truly significant decrease in GFR even when their serum creatinine values appear normal (3Meschi M. Detrenis S. Musini S. Strada E. Savazzi G. Facts and fallacies concerning the prevention of contrast medium-induced nephropathy.Crit Care Med. 2006; 34: 2060-2068Crossref PubMed Scopus (45) Google Scholar) (Fig 1).A more accurate evaluation of GFR would be better obtained by inulin clearance, but this method may have limited practical application (15Inet L. Dejours P. Leblanc M. Simultaneous measurement of inuline and p-aminohippuric acid clearance in rats.J Physiol. 1956; 48: 803-816Google Scholar). The 24-hour creatinine clearance measurement could be considered as a useful system despite problems related to correct daily urine collection, which is often inconvenient and time consuming (3Meschi M. Detrenis S. Musini S. Strada E. Savazzi G. Facts and fallacies concerning the prevention of contrast medium-induced nephropathy.Crit Care Med. 2006; 34: 2060-2068Crossref PubMed Scopus (45) Google Scholar):cl=[cr]u×Vu[cr]s where cl = creatinine clearance (mL/min), [cr]u = daily urinary creatinine concentration (mg/dL), Vu = daily urinary volume/minute, and [cr]s = serum creatinine concentration (mg/dL).Various mathematical formulations have been proposed to predict GFR more or less roughly by using some indirect indices of muscular mass, such as body weight, gender, and age, in association with serum creatinine evaluation. For example, creatinine clearance estimation using the Cockcroft-Gault formula (16Cockcroft D.W. Gault M.H. Prediction of creatinine clearance from serum creatinine.Nephron. 1976; 16: 31-41Crossref PubMed Scopus (12987) Google Scholar), which is able to predict the daily urine creatinine excretion given body weight, sex, and age of the patient, assumes that a 90-year-old woman who weighs 50 kg and has an apparently normal serum creatinine value of 0.9 mg/dL should have a creatinine clearance of 33 mL/min and not 120 mL/min as one might believe:cl=(140−a)×bw72×[cr]s where cl = creatinine clearance (mL/min), a = age (years), bw = body weight (kg), [cr]s = serum creatinine concentration (mg/dL) (×0.85 correction factor for female gender).Analogously, the more recent equation from the Modification of Diet in Renal Disease Study (MDRD equation) also considers serum urea, albumin, and race as correction factors and evaluates the GFR in mL/min × 1.73 m2 (an abbreviated version of this formula, which does not require urea or albumin, has been published) (17Levey A.S. Bosch J.P. Lewis J.B. Greene T. Rogers N. Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation Modification of Diet in Renal Disease Study Group.Ann Intern Med. 1999; 130: 461-470Crossref PubMed Scopus (12869) Google Scholar):eGFR=186×[cr]s−1.154×a−0.203 where eGFR = estimated glomerular filtration rate (mL/min/1.73 m2), [cr]s = serum creatinine concentration (mg/dL), and a = age (years) (×0.74 correction factor for female gender, ×1.21 if the patient is African American).Recent meta-analyses would confirm the superiority of the use of cystatin C to serum creatinine as a marker of GFR (18Dharnidharka V.R. Kwon C. Stevens C. Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis.Am J Kidney Dis. 2002; 40: 221-226Abstract Full Text Full Text PDF PubMed Scopus (1297) Google Scholar). Cystatin C is a 13-kd protein that is produced by all nucleated cells at a constant rate, and its extrarenal clearance appears to be minimal. Consequently, serum cystatin C concentrations would be mainly determined by the GFR, which begins to increase as GFR falls below 80 mL/min/1.73 m2 (18Dharnidharka V.R. Kwon C. Stevens C. Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis.Am J Kidney Dis. 2002; 40: 221-226Abstract Full Text Full Text PDF PubMed Scopus (1297) Google Scholar). However, for cystatin C, too, few studies in older people exist (18Dharnidharka V.R. Kwon C. Stevens C. Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis.Am J Kidney Dis. 2002; 40: 221-226Abstract Full Text Full Text PDF PubMed Scopus (1297) Google Scholar).The various methods of renal function evaluation have a few imperfections. In particular, the Cockcroft-Gault formula tends to underestimate slightly the corresponding GFR in the elderly, and the MDRD equation could underestimate the GFR in women (17Levey A.S. Bosch J.P. Lewis J.B. Greene T. Rogers N. Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation Modification of Diet in Renal Disease Study Group.Ann Intern Med. 1999; 130: 461-470Crossref PubMed Scopus (12869) Google Scholar). It is important to consider in clinical practice that an aged patient who also has normal serum creatinine could truly be at risk for CMIN after radiocontrast exposure and that possible preventive measures to avoid CM-induced renal damage must be employed above all in these patients.Age-related Decrease in Renal Function and Contrast Medium–induced DamageIn addition to variations in the estimation of renal function, the GFR really decreases gradually with aging over time. Renal function is said to decline after the age of 40 years at rates of up to 1 mL/min/yr of GFR, associated with a greater fall in total renal blood flow (TRBF) and total renal plasma flow (TRPF), at an approximate rate of 10% per decade (19Abreu P.F. Ramos L.R. Sesso R. Abnormalities of renal function in the elderly.Geriatr Nephrol Urol. 1999; 9: 141-145Crossref PubMed Scopus (7) Google Scholar). Actually, among the various hypotheses for "kidney aging," alteration in glomerular hemodynamics and imbalance between synthesis and degradation of matrix proteins causing glomerulosclerosis are favored (20Suzuki H. Tokuriki T. Kamita H. et al.Age-related patho-physiological changes in rat oligo-meganephronic hypoplastic kidney.Pediatr Nephrol. 2006; 21: 637-642Crossref PubMed Scopus (15) Google Scholar).Many authors have reported age-dependent morphologic and structural alterations in glomerular and tubular renal function during aging. The aging human kidney develops progressive glomerulosclerosis and interstitial fibrosis, and the number of nephron units becomes significantly decreased per unit tissue mass (21Lameire N. Nelde A. Hoeben H. Vanholder R. Acute renal failure in the elderly.Geriatr Nephrol Urol. 1999; 9: 153-165Crossref PubMed Scopus (6) Google Scholar). Both renal weight and size decrease steadily with increasing age. Microscopically, the number of renal glomeruli decreases in parallel to the total renal mass, particularly in the cortex. Glomerular alterations appear with thickening of the glomerular basement membrane (GBM) and hyaline degeneration of the glomerulus (22Chan R. Michelis M.F. Nephrologic complications of drug therapy in the elderly.Geriatr Nephrol Urol. 1998; 8: 29-44Crossref PubMed Scopus (3) Google Scholar). Glomerular basement membrane thickening may result in a loss of lobulation of the glomerular tuft and in a decreased effective filtering surface. Furthermore, there is a progressive increase in the number of mesangial cells, accompanied by an overall expansion of mesangial tissue, with an increase from 8%–10% of total glomerular volume at age 40 years to 10%–15% by age 80 years (23Savazzi G. Cusmano F. Allegri L. Garini G. Physiopathology, clinical aspects and prevention of renal insufficiency caused by contrast media.Recenti Prog Med. 1997; 88: 109-114PubMed Google Scholar).Other vascular changes are observed in the aging kidney. The arcuate arteries may become irregular and angulated, and the interlobular and intralobular vessels show an increased sclerosis, tapering, and tortuosity (24Tylicki L. Rutkowski B. Horl W.H. Multifactorial determination of hypertensive nephroangiosclerosis.Kidney Blood Press Res. 2002; 25: 341-353Crossref PubMed Scopus (22) Google Scholar). Interstitial sclerosis is common. In areas with glomerulosclerosis, afferent and efferent arterioles may have direct shunts, diverting blood from the cortex to the relatively preserved juxta-medullary glomeruli, this appearance being referred to as glomerular arterioles (24Tylicki L. Rutkowski B. Horl W.H. Multifactorial determination of hypertensive nephroangiosclerosis.Kidney Blood Press Res. 2002; 25: 341-353Crossref PubMed Scopus (22) Google Scholar).Finally, various changes in the number of tubules also may correlate with the alterations of total renal mass. In addition to a fall in the absolute number of proximal tubules, the length of each tubule may shorten with advancing age, and tubular structures appear sparsely scattered with interstitial fibrosis. Microscopically, the tubular basement membrane becomes thickened with focal loss of the brush border and the presence of heterophagic vacuoles and apical vesicles (22Chan R. Michelis M.F. Nephrologic complications of drug therapy in the elderly.Geriatr Nephrol Urol. 1998; 8: 29-44Crossref PubMed Scopus (3) Google Scholar).Accumulation of extracellular matrix appears to justify both glomerulosclerosis and tubular atrophy. An increased extracellular matrix protein deposition in the renal interstitium could be due to thrombospondin, laminin, and fibronectin accumulation with a relative absence of other morphostructural elements, such as collagen IV (23Savazzi G. Cusmano F. Allegri L. Garini G. Physiopathology, clinical aspects and prevention of renal insufficiency caused by contrast media.Recenti Prog Med. 1997; 88: 109-114PubMed Google Scholar).Intraglomerular capillary blood flow rate and hydraulic pressures are maintained at a stable level using a physiologic balance of vasodilatory and vasoconstrictor mediators (4Detrenis S. Meschi M. Musini S. Savazzi G. Lights and shadows on the pathogenesis of contrast-induced nephropathy: state of the art.Nephrol Dial Transplant. 2005; 20: 1542-1550Crossref PubMed Scopus (125) Google Scholar). The reduced number of glomeruli may cause increased capillary blood flow through each glomerular capillary and a correspondingly high intracapillary pressure (24Tylicki L. Rutkowski B. Horl W.H. Multifactorial determination of hypertensive nephroangiosclerosis.Kidney Blood Press Res. 2002; 25: 341-353Crossref PubMed Scopus (22) Google Scholar). In age-related glomerulosclerosis, the number of vessels progressively reduces, with an increase in the filtration rate across the GBM of each individual nephron. Consequent local high pressure results in endothelial cell damage, platelet aggregation, thrombin production, and finally glomerular injury (25Meyrier A. Simon P. Nephroangiosclerosis and hypertension: things are not as simple as you might think.Nephrol Dial Transplant. 1996; 11: 2116-2120Crossref PubMed Scopus (27) Google Scholar). Furthermore, this pattern leads to the release of various substances (fibroblast growth factor, platelet-derived growth factor, epidermal growth factor, tumor necrosis factor) associated with increased fibroblast collagen production and mesangial cell sclerosis. As a various number of glomeruli become sclerosed, the alterations in endothelial homeostasis and renal vascular hemodynamics can increase the amount of blood flow directed to each of the remaining nephrons, further potentiating the damage (23Savazzi G. Cusmano F. Allegri L. Garini G. Physiopathology, clinical aspects and prevention of renal insufficiency caused by contrast media.Recenti Prog Med. 1997; 88: 109-114PubMed Google Scholar).Under physiologic conditions, these variations in aging renal structures may have no clinical impact, because the renal functional reserve could be sufficient to meet the homeostatic necessities. However, the adaptive capacity commonly is restricted, and aging might adversely affect the course of a superimposed acute renal damage. Contrast medium administration during diagnostic and/or interventional angiographic procedures may impair the autoregulatory protective adaptations of TRBF and GFR (4Detrenis S. Meschi M. Musini S. Savazzi G. Lights and shadows on the pathogenesis of contrast-induced nephropathy: state of the art.Nephrol Dial Transplant. 2005; 20: 1542-1550Crossref PubMed Scopus (125) Google Scholar). In fact, the injection of CM is followed by a prolonged intrarenal vasoconstriction, in addition to direct toxic injury and ischemic damage mediated by reactive oxygen species (26Fiaccadori E. Maggiore U. Rotelli C. et al.Plasma and urinary free 3-nitrotyrosine following cardiac angiography procedures with nonionic radiocontrast media.Nephrol Dial Transplant. 2004; 19: 865-869Crossref PubMed Scopus (34) Google Scholar). Consequent reduction in renal perfusion pressure, in combination with eventually coexisting dehydration, may more rapidly provoke ischemic damage in aged kidneys (4Detrenis S. Meschi M. Musini S. Savazzi G. Lights and shadows on the pathogenesis of contrast-induced nephropathy: state of the art.Nephrol Dial Transplant. 2005; 20: 1542-1550Crossref PubMed Scopus (125) Google Scholar). Nitric oxide (NO) is another mediator that could play a role in the propensity for more frequent acute impairment in renal function of the elderly. Studies have shown that NO synthesis blockade decreases TRBF and GFR in aged than in young animals, suggesting that NO may play a progressively increasing role in controlling renal function in advancing age than in the young (26Fiaccadori E. Maggiore U. Rotelli C. et al.Plasma and urinary free 3-nitrotyrosine following cardiac angiography procedures with nonionic radiocontrast media.Nephrol Dial Transplant. 2004; 19: 865-869Crossref PubMed Scopus (34) Google Scholar). It has not been shown that CM-induced hemodynamic alterations of the renal vessels are directly related to the synthesis and release of active mediators such as NO and prostaglandins. It has been suggested that a number of factors are implicated in this decrease in NO concentration during CMIN (26Fiaccadori E. Maggiore U. Rotelli C. et al.Plasma and urinary free 3-nitrotyrosine following cardiac angiography procedures with nonionic radiocontrast media.Nephrol Dial Transplant. 2004; 19: 865-869Crossref PubMed Scopus (34) Google Scholar). According to some recent studies, CM could induce a depletion of cofactors involved in NO synthesis, such as tetrahydrobiopterin, or modify substrates, such as l-arginine, or interfere with its synthesis through the nuclear factor kappa B (NF-κB), which inhibits mRNA transcription of inducible NO synthase (4Detrenis S. Meschi M. Musini S. Savazzi G. Lights and shadows on the pathogenesis of contrast-induced nephropathy: state of the art.Nephrol Dial Transplant. 2005; 20: 1542-1550Crossref PubMed Scopus (125) Google Scholar).As aging is also associated with changes in renal tubular function (ie, decreased ability for renal sodium conservation during sodium depletion, limitation of urinary concentrating and diluting ability, and decreased distal tubular capacity for ion excretion) and hormonal alterations (such as decreased renin and aldosterone secretion and increased activity of atrial natriuretic peptide), renal sodium handling in elderly patients can be impaired (27Savazzi G. Castiglioni A. Cavatorta A. Garini G. Montanari M. Borghetti A. Effect of age on the pharmacokinetics of indobufen.Int J Clin Pharmacol Ther Toxicol. 1986; 24: 265-269PubMed Google Scholar). However, how much these findings can be influenced by a superimposed CM-mediated damage is unknown (4Detrenis S. Meschi M. Musini S. Savazzi G. Lights and shadows on the pathogenesis of contrast-induced nephropathy: state of the art.Nephrol Dial Transplant. 2005; 20: 1542-1550Crossref PubMed Scopus (125) Google Scholar).Finally, overlapping mutations in nucleic acids, increased oxidative damage, and advanced glycosylation end-products could be involved in kidney aging and predispose to chronic physiologic impairment in global renal function (4Detrenis S. Meschi M. Musini S. Savazzi G. Lights and shadows on the pathogenesis of contrast-induced nephropathy: state of the art.Nephrol Dial Transplant. 2005; 20: 1542-1550Crossref PubMed Scopus (125) Google Scholar).The age-related renal alterations are summarized in Figure 2.Figure 2Age-related decrease in renal function. Renal function is said to decline after the age of 40 years at rates of up to 1 mL/min/yr of GFR. Among the various hypotheses for renal aging, alteration in glomerular hemodynamics and imbalance between synthesis and degradation of matrix proteins causing glomerulosclerosis are favored (see text for discussion and citations).View Large Image Figure ViewerDownload Hi-res image Download (PPT)Coexisting Risk Factors for Contrast Medium–induced Nephropathy in Elderly PatientsBecause of the general and progressive decrease in renal function, the elderly population could be more susceptible to CM-induced acute renal damage compared with younger adults. However, whether the process of deterioration of renal function is genetically mediated and universally present as age increases is controversial, and the role of secondary external factors or coexisting subclinical injuries is unclear.A study conducted among U.S. adult subjects surveyed from 1999 to 2000 indicated that age is an important factor for progressive renal impairment even in the absence of coexisting arterial hypertension and/or diabetes mellitus (28Coresh J. Byrd-Holt D. Astor B.C. et al.Chronic kidney disease awareness, prevalence, and trends among U.S. adults, 1999 to 2000.J Am Soc Nephrol. 2005; 16: 180-188Crossref PubMed Scopus (686) Google Scholar). In this work, the prevalence of a decrease in renal function in adults >65 years was 12%, whereas in another study, up to 11% of individuals >65 years had stage 3 (GFR 30 to 59 mL/min/1.73 m2) or worse chronic kidney disease in the absence of diabetes and/or hypertension (28Coresh J. Byrd-Holt D. Astor B.C. et al.Chronic kidney disease awareness, prevalence, and trends among U.S. adults, 1999 to 2000.J Am Soc Nephrol. 2005; 16: 180-188Crossref PubMed Scopus (686) Google Scholar). A similar investigation in a Chinese adult population led to similar conclusions. Increasing age is related per se to a greater prevalence of renal failure in both males and in females, even if it has been verified that patients with hypertension and/or diabetes are at a greater risk of developing chronic renal failure than subjects of the same age without coexisting pathologies (29Chen J. Wildman R.P. Gu D. et al.Prevalence of decreased kidney function in Chinese adults aged 35 to 74 years.Kidney Int. 2005; 68: 2837-2845Crossref PubMed Scopus (117) Google Scholar). An epidemiologic study in a large French urban area has indicated an incidence of about 250 patients in a population of 1 million annually obs
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