PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of agdisAging and DiseaseAboutEditorial BoardSubmissionAchieves
 
Aging Dis. 2012 October; 3(5): 360–372.
Published online 2012 August 6.
PMCID: PMC3501392

Diagnosis and Management of Chronic Kidney Disease in the Elderly: a Field of Ongoing Debate

Abstract

Chronic kidney disease (CKD) is rather common in elderly adults who comprise the fastest growing subset of patients with end-stage renal disease (ESRD). At present, there are no specific guidelines and recommendations regarding early identification and management of elderly with CKD and the current CKD classification system may overestimate its exact prevalence. Screening strategies based either in a more accurate formula of estimation of GFR alone, or preferably in combination with proteinuria are urgently needed in order to raise awareness and to promote early diagnosis of CKD in the elderly. The number of elderly dialysis patients is also increasing and may lead to severe socio-economic problems worldwide. Both hemodialysis and peritoneal dialysis can sustain life, but present various disadvantages. There is a trend for home based dialysis therapies but the results are based on a small number of patients. Recent reports indicate that dialysis may not provide a clear benefit over non-dialysis regarding survival and quality of life issues, especially in the presence of extensive comorbidities. Current practices around the world regarding access to dialysis in the elderly are rather controversial, reflecting each country’s health policies and ethical patterns. Although advanced age should not be considered as an absolute contraindication for kidney transplantation, it is not frequently offered in elderly ESRD patients due to the shortage of renal grafts. Global judgment of all physical and mental/psychological issues and full informed consent regarding possible complications are mandatory before listing elderly ESRD patients for kidney transplantation. As scientific evidence is rather scarce, there is an urgent need for prospective studies and an individualized approach for the diagnosis and treatment of the elderly CKD patients, in order to optimize care and improve quality of life in this special population.

Keywords: Chronic kidney disease, elderly, hemodialysis, peritoneal dialysis, renal transplantation

The population in developed countries ages, due to the decline of mortality and the increased numbers of ‘baby boomers’. In USA, the elderly are the fastest growing subpopulation, with the number of individual aged ≥ 65 years approaching above 20% of the general population by 2030 [1]. As a result, the number of older adults with Chronic Kidney Disease (CKD) is increasing. According to the United States Renal Data System, elderly adults over 65 years comprise the most rapidly increasing subset of the end-stage renal disease (ESRD) population in US [2,3]. In Europe, incident ESRD patients aged >65 years were also increased up to 55% in 2005 [4]. Patients over 65 years undergoing dialysis have a much lower life expectancy and quality of life in comparison with persons of the same age without ERSD [5,6].

In-center hemodialysis (HD) is the most frequently used kidney replacement therapy in elderly patients over 75 years [6]. Peritoneal dialysis (PD) compared to HD may improve the quality of life of elderly patients on dialysis [7]. Assisted [8] and Intermittent PD (IPD) may be alternative options for elderly patients who are unable to undergo HD or PD at home for various reasons [9] whereas renal transplantation is limited in the elderly [10,11].

Palliative care does not preclude dialysis and must be incorporated in the care of elderly patients with CKD and multiple geriatric syndromes in an effort to improve their quality of life [12].

Diagnosing kidney disease in the elderly

CKD is silent and asymptomatic at earlier stages and quite often undiagnosed, but can be detected by estimated Glomerular Filtration rate (eGFR) or/and albumin-to-creatinine ratio, as a marker of kidney damage.

An important question that must be addressed is whether all elderly patients classified as having CKD based on a single reduced eGFR value and without other evidence of kidney damage, should be considered as having a disease? [13]. It is important to avoid false-positive diagnoses of CKD in elderly, because this may lead to financial, social and psychological consequences [14]. Early recognition and identification of elderly patients with CKD may prevent this growing social-economic problem, as early referral to nephrologists has been associated with arrest or reversal of CKD and decreased mortality [1517].

The Kidney Disease Outcomes Quality Initiative (KDOQI) has described a definition and a staging system of CKD relied on eGFR. At present, eGFR is considered the best indicator of kidney function and CKD is defined by a reduction of GFR < 60 mL//min and/or evidence of kidney damage, if there is proteinuria (albuminuria > 30 mg/g of creatinine), renal hematuria, or abnormal renal imaging and renal pathology for 3 months or longer [18].

Thus, CKD has been classified in 5 stages, and the same criteria are used for the diagnosis of CKD in older and in younger patients. This classification uses an estimated value of GFR rather than the measured (mGFR). mGFR can be assessed by measuring the urinary clearance of inulin,125 I-iotholamate, iohexol, or other exogenous filtration markers. However, all these techniques are expensive, complicated and difficult to be performed, and their use is confined to the research setting. Thus, for all of these reasons formulas based on serum creatinine have been used for the calculation of eGFR in clinical practice (Table 1).

Table 1.
Equations for eGFR calculation, based on serum creatinine (Scr)

Creatinine Clearance (Ccr), which is often used in clinical practice, overestimates GFR due to the secretion of creatinine by the renal tubules. Moreover, Ccr is susceptible to urine collection errors especially in elderly patients [19] and is a poor screening test for CKD as it underestimates renal failure in this subpopulation [20]. Swedko et al [20] reported that a serum creatinine level greater than 1.7 mg/dL (>150 μmol/L) had an overall sensitivity of only12.6% for the detection of CKD (GFR ≤ 50 mL/min). Physicians using only serum creatinine, fail to diagnose CKD in older patients [20,21]. Branten et al have also reported that hypoalbuminemia influences the tubular secretion of creatinine leading to errors in estimation of GFR. Thus, serum creatinine is a poor marker of GFR in disease states with heavy proteinuria as in nephrotic syndrome [22].

Cockcroft-Gault formula is an equation used to estimate the endogenous creatinine clearance as follows:

equation mm1

[23]

Ccr is expressed in milliliters per minute, age in years, body weight in kilograms and serum creatinine (Scr) in milligrams per deciliter. This equation provides an estimate of Ccr but it is not equivalent to GFR due to the effect of tubular secretion of creatinine [24]. Moreover, in the Cockcroft-Gault equation body weight is considered as a surrogate for muscle mass, so it overestimates Ccr in edematous states and in obese patients [25]. Verhave et al [26] have reported that the Cockcroft-Gault equation underestimates GFR in patients over 65 years old. In addition, Cirrilo et al [27] have found that the Cockcroft-Gault equation systematically under-estimated GFR in the elderly.

The Modification of Diet in Renal Disease (MDRD) study equation was developed using data from 1628 patients with a GFR below 60 ml/min, for the estimation of GFR adjusted for 1.73m2 [28]. The MDRD equation was re-expressed with a standardized serum creatinine assay [29] as follows:

equation mm2

The MDRD equation does not require a body weight variable and it has been recommended by the KDOQI study group for the diagnosis and classification of CKD [18]. Nevertheless, it is important to note that the use of MDRD equation leads to errors in the classification of CKD due to variable degrees of bias, imprecision and inaccuracy [24]. Therefore it is important to investigate how gold the used gold standards actually are [30]. It is worth noting the existence of differences between various laboratories regarding the calibration of the creatinine assay that leads to differences in GFR estimation [31]. Lamb et al [32] reported a similar effect of the creatinine assay calibration on eGFR estimates in older patients. They found that the effect of the calibration of creatinine assay led the Cockroft-Gault formula to underestimate the eGFR, whereas the MDRD Study equation overestimated it [32].

However, the MDRD equation has been considered as more accurate for the elderly in comparison with the Cockroft-Gault formula [33] and for this reason it has been recommended by National Kidney Foundation [18]. The MDRD equation was evolved in 1999 and was recommended by NKF in 2002, for the diagnosis and the classification of CKD but has received a lot of criticism recently. In addition, both equations overestimate mGFR in pathological states, as in nephrotic syndrome, hypoalbuminemia and in CKD at stage 5 [34].

Recently, Levey et al [35] using data from 16 studies developed a new equation to estimate GFR, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. The CKD-EPI equation was developed in an attempt to create a more accurate equation than this proposed by the MDRD Study. The equation was expressed as follow:

equation mm3

Scr is serum creatinine expressed as mg/dL, k is 0.7 for females and 0.9 for males, α is −0.329 for females and – 0.411 for males, min indicates the minimum of Scr/k or 1, and max indicates the maximum of Scr/k or 1.

The prevalence estimate of CKD in US by using the CKD-EPI equation was 1.6% lower than that obtained by the MDRD equation (11.5% compared to 13.1%) [36]. Moreover, the CKD-EPI equation had lower bias, especially at eGFR ≥ 60 ml/ min/ 1.73m2 [35]. Juutilainen et al [37] from Finland have also reported that the MDRD equation augmented the trend of increasing the prevalence of CKD in the general population compared with the CKD-EPI formula. Murata et al [38] have shown that the CKD-EPI equation improves performance in the healthier populations at the expense of slightly reduced performance in more diseased populations, whereas the CKD-MDRD formula provides more reliable results regarding renal function. Earley et al [39] have recently reviewed the performance of the CKD-EPI and MDRD equations and reported that both were suboptimal for all populations and GFR ranges. The MDRD Study equation was developed in a study population with CKD and a mean GFR of 40 mL/min per 1.73 m2, whereas the CKD-EPI equation was developed in a more diverse study population, including participants with and without CKD, with a mean GFR of 68 mL/min per 1.73 m2.

It is important to note that even by the CKD-EPI formula, the prevalence of CKD in elderly remained high. The authors reported a limited number of participants older than 70 years and they also reported incomplete data on measures of muscle mass and other conditions or medications that may influence the serum creatinine [35]. Matsushita et al [40] in a meta-analysis of data from 1.1 million adults have reported that the CKD-EPI equation classified fewer individuals as having CKD and more accurately categorized the risk for mortality and ESRD than did the MDRD equation across a broad range of populations, lowering the prevalence of CKD in all cohorts except for the elderly. Stengel et al [41] in a prospective population-based cohort study from France reported that the CKD-EPI and the MDRD equations provided very similar prevalence and long-term risk estimates in the elderly (>65 years) and an eGFR<45 ml/min/1.73m2 was associated with worse outcomes.

Rule et al [42] developed the Mayo Clinic Quadratic (MCQ) equation in an effort to create a better formula for estimating GFR especially in patients with preserved kidney function. The equation was expressed as follow:

equation mm4

In a recent study, Carnevale et al [43] suggested that it is possible that the MCQ equation systematically overestimated GFR in patients aged over 85 years, by including age.

Cystatin C

Cystatin C is an alternative agent for estimation of GFR. It is filtered by the glomeruli and is totally reabsorbed and degraded by tubules, so it could be used as a novel agent for GFR estimation [44]. Cystatin C concentration is less dependent upon muscle mass, weight or status disease and it is dependent on kidney function, age, sex, smoking and inflammation [45,46]. New estimating equations based on cystatin C have been studied in patients with CKD, diabetes, anorexia nervosa and cystic fibrosis [4749] (Table 2). Moreover, Stevens et al [50] reported that an equation incorporating both cystatin C and serum creatinine provides a better estimation of GFR (Table 2):

equation mm5
Table 2.
Equations for eGFR based on serum cystatin C (CysC) and creatinine (Scr) in various clinical presentations.

Peralta et al [51] have also examined the potential benefits of adding information from a cystatin-based measure of estimated GFR and albuminuria to the current standard of CKD-EPI eGFR estimation. This triple-marker approach for predicting all-cause death and kidney failure was found to be superior compared with eGFR alone [51]. However, this approach has several limitations and can not be adopted so easily due to its additional costs and complexity for the laboratories [52]. Nevertheless, the idea of cystatin C based equations to estimate GFR seems very promising.

Limitations of the present classification system for the elderly

There are various limitations of the present classification system because it leads to over- and misdiagnosis of CKD especially in elderly. It is well known that a decline in GFR occurs with aging, so in the case of the absence of any evidence of a complication of aging, a decline in eGFR below 60 mL/min/1.73m2 should not be considered as CKD in the elderly [5355].

Wetzels et al [56] reported that there is a systematic decline in eGFR and mGFR at a level of 7–10 mL/min/1.73m2 per decade after the age of 30–40 years. In addition, this age dependent decline in eGFR is not associated with the underlying renal morphology [57]. However, findings from a longitudinal study showed that the rate of the decline in GFR with ageing was greater in individuals with hypertension than without [58]. The authors reported a decline in creatinine clearance of 0.75 ml/min/year. However, one-third of subjects enrolled the study had no decline in kidney function and a small number of subjects had even an increase in creatinine clearance [58].

In addition, a moderate decline in GFR with aging may occur as part of “normal aging” [5658] and for many nephrologists this phenomenon reflects just normal physiology. Although, not all the elderly display a decline in GFR, aged patients with a decline in renal function have probably a genetic predisposition to biological vascular aging and/or increased exposure to cardiovascular risk factors [59]. On the other hand, Gansevoort and Jong [30] suggested that “normal physiology” indicates a kind of benefit and the loss of glomeruli among elderly is not beneficial at all. Moreover, these authors have suggested that there is no strong reason to introduce age-specific cut-off values indicating CKD [30].

Regarding the prevalence of CKD stage 3, around 5–8% of the general population can be defined having CKD stage III (overall higher among elderly), whereas individuals with an eGFR around 45 mL/min/1.73m2 are at increased risk for all cause mortality in comparison with these with higher eGFR [60,61]. Thus, for many nephrologists it should be better to subdivide CKD stage III into two stages: one not necessary pathological being 45–60 mL/min/1.73m2 and another separate always pathologic stage being 30–45 mL/min/1.73m2 [30]. Given all these considerations, various revisions of the current system of defining and classifying CKD have been suggested. Some revisions include lowering the threshold of eGFR below 45 mL/min/1.73m2 for the definition of stage III [53], introducing an additional evidence of renal damage in individuals with e GFR ≥ 30 mL/ min/1.73m2 in order to consider them as having CKD [54], adding two subcategories to stage III [62], introducing age- and sex-dependent thresholds after 50 years of age [60] and setting age- and sex-specific GFR reference values [6064].

Albuminuria and CKD

The current system for the definition and classification of CKD does not include the presence of albuminuria in stages III–V. Reduced eGFR and/or proteinuria (albuminuria > 30 mg/g of creatinine) indicates a higher risk of kidney failure, cardiovascular disease, cognitive impairment and all-cause mortality in the elderly [6569]. Moreover, Hemmelgarn et al [70] have investigated the importance of macro-abuminuria on the patients prognosis reporting that proteinuria is a worse prognostic factor in comparison with the reduction of eGFR alone and that there is a synergy between them.

According to the NHANES study, the majority (over 90%) of patients with CKD stages I and II, had only microalbuminuria (30–300 mg per day or 17–250 mg albumin/g creatinine, if men, or 25–350 mg albumin/g creatinine, if female) as a diagnostic criterion [71]. It is well known that microalbuminuria is an independent indicator of cardiovascular disease and morbidity reflecting the systemic endothelial dysfunction [72]. However, microalbuminuria can also be present, or may be influenced by other conditions not necessary “pathological” such as obesity, fever, exercise, aging and inflammation. Recent studies, have shown that patients with microalbuminuria, have an increased risk for ESRD independent of eGFR levels [73,74].

The risk of an elderly person with CKD stage 3 to develop ESRD is around 0.2–0.4% per year and the presence of concomitant proteinuria increases this risk [74]. However, patients with CKD stage 3 without micro- or macro-albuminuria have no increased risk for cardiovascular or renal events [75]. It is important to note that this group of patients constitutes 4–6% of the general population and most of them are elderly. Normoalbuminuric patients with CKD stage 3 have a better prognosis than patients with CKD stage 1 with microalbuminuria [75]. In addition, Tonelli et al [76] in a large cohort study with > 900.000 participants in Canada has reported that heavier levels of proteinuria, regardless of baseline eGFR (low, intermediate, or high), were strongly and independently associated with worse clinical outcomes.

In conclusion, microalbuminuria should be considered as a risk factor for a systemic vascular disease including kidney disease rather than a sign of CKD [76,77]. Thus, it should be re-evaluated whether microalbuminuria alone without other evidence of kidney damage is a diagnostic criterion for CKD, because its presence leads to an overestimation of CKD especially in elderly. Additional information regarding the presence of albuminuria should be incorporated in all stages of the current classification because of its prognostic value [7678]

Our opinion is that since a new more accurate and precise equation has not been yet evolved, elderly patients with a decreased e GFR (≤ 45ml/min) and concomitant proteinuria should be labeled as having definitely CKD.

Management of CKD in the elderly

At present, there are no specific guidelines and recommendations regarding early identification, and management of elderly with CKD. The major goal of a screening program should be to identify elderly with CKD at an early stage in order to prevent cardiovascular events and/or progression to ESRD.

Moreover, primary care clinicians may fail to diagnose CKD in this subset of patients and frequently these patients are not under appropriate treatment. It is well known that early referral to nephrologists has been associated with decreased mortality, better outcome and cost saving [16,17]. Pharmaceutical and life style interventions of elderly patients with CKD may have a favorable effect on patients’ outcomes.

Regarding the diagnosis of CKD in elderly, many nephrologists hesitate to perform a kidney biopsy due to the possible complications. However, in elderly there is no increased risk for complications [79]. Thus, advanced age should not be considered a contraindication for kidney biopsy if indicated.

The management of elderly patients with CKD may differ to that of younger patients and there are ongoing questions regarding this issue. One concern is that at present, there is no clear consensus regarding the optimal target of blood pressure or/and the benefit of the treatment of blood pressure on the clinical outcomes among elderly patients with CKD [80]. The prevalence of isolated systolic hypertension is higher in elderly patients. In the elderly, there is a strong relation of systolic hypertension and cardiovascular complications and more focusing is needed on its treatment [81]. It is worth noting, that there is a J-shaped relationship between blood pressure and survival of elderly patients. Thus, in elderly the optimal blood pressure should be higher than in younger patients. Intensive treatment of isolated systolic pressure may lower diastolic pressure to suboptimal levels with concomitant impaired perfusion during diastole. Moreover, elderly patients may also have orthostatic hypotension which may be aggravated by anti-hypertensive treatment.

A second special issue that needs to be clarified is the management of bone disease in elderly patients with CKD at advanced stages. Bone disease and concomitant fractures has been associated with significant morbidity and mortality in the elderly. Epidemiological studies reported an increase fractures risk among patients with advanced CKD in comparison with the general population [82]. Elderly patients with CKD have two prevalent causes for bone disease: a) the osteoporosis with bone loss due to aging and b) the renal osteodystrophy due to metabolic and endocrine alterations. Thus, a new term the CKD-mineral and bone disorder (CKD-MBD) has emerged in order to understand the underlying disease process. In patients with CKD stages 1 and 2, the CKD-MBD can be managed as in the general population, whereas there are no specific recommendations regarding the pharmacological treatment of CKD-MBD in elderly patients with more advanced CKD or undergoing dialysis [83].

Dialysis vs conservative treatment

Regarding the elderly with ESRD (eGFR < 10 ml/min), there are conflicting data about survival among patients undergoing dialysis versus those receiving nondialytic management. In the US, the 1-year survival rate of patients over 80 years of age after dialysis initiation is above 54%, whereas mortality rate is high (above 20%) during the first 3 months, probably due to underlying illness and to the significant comorbidities [84].

Older age, dementia, hypoalbuminemia, diagnosis of peripheral vascular occlusive disease, and negative response to the “surprise” question “Would I be surprised if this patient died in the next 12 months?,” has been recognized [85] and validated [86] as a simple and reliable method of identifying sicker incident dialysis patients with high risk for early death.

On the other hand, regarding especially the very olds there is a dilemma whether it is proper to use an expensive treatment such as HD which charges all the national health systems, or to prefer a nondialytic management in a growing subpopulation with a limited life expectancy [8]. For many nephrologists nondialytic management or delayed dialysis initiation in association with protein restriction could be an alternative strategy [87], but the benefit of this approach is needed to be proven by further studies. Kurella Tamura et al [88] studied the trajectory of functional status before and after the initiation of dialysis among elderly nursing home residents with ESRD, reporting not only high mortality rates but also a dramatic decline of functional status, with only one of eight patients maintaining their predialysis functional level. Two-thirds of patients with CKD in the study of Davison et al [89] reported that they chose HD over supportive care because it was their physician’s, or family’s wish, and 61% of these dialysis patients regretted having started HD, underscoring the importance of advance care planning (ACP) and suggesting the need to evaluate processes by which these patients are informed and ultimately, consent to dialysis [90]. Nephrologists are frequently balancing on a tight rope between providing their patients and their families with rather unrealistic expectations of the benefits of dialysis or explaining clearly its associated risks and its impact on survival and quality of life [91,92].

Conservative management consists of control of fluid, electrolyte balance, correction of anemia with erythropoietin if needed, pharmaceutical treatment and dietary recommendations, in order to improve the symptoms and the quality of life. Joly et al [93] from France reported that the median survival of elderly patients on dialysis was 20 months longer than that of the patients choosing nondialytic management and Murtagh et al [94] reported that the survival rates of elderly patients on HD at 1 and 2 years were higher in comparison with those obtained by conservative treatment. However, it should also be noted that the survival benefit among elderly patients with high comorbidity and ischemic heart disease was the same, either choosing dialytic or nondialytic management [94]. Recently, Chandna et al [95] reported that in patients aged over 75 years with severe comorbidities, the survival advantage obtained by dialysis is small (median survival above 5 months longer) compared with this obtained by conservative management. Large prospective studies are urgently needed to clarify the potential benefit of these two different treatments in elderly patients with ESRD.

Regarding the cost, Scalone et al [96] reported that the economic benefit of the conservative treatment with a low protein diet in elderly patients with CKD stage 5 is about 21000 euro/patient in comparison with dialysis.

Hemmelgarn et al [97] in a retrospective Canadian cohort study reported that the rates of untreated kidney failure are significantly higher in older compared with younger individuals, questioning not only the current concept [98] that elderly patients are less likely to develop ESRD compared with younger patients and are more likely to die than to progress to dialysis even at the lowest levels of eGFR, but also implicating the impact of national health systems policies.

However, except survival, that is usually small in the elderly with ESRD, quality of life issues should not be neglected. Dialysis in the elderly has been associated with impaired quality of life and loss of independence and these issues raise major ethical concerns [99,100].

Hemodialysis vs Peritoneal Dialysis

Quality of life and survival rates are two parameters which should be carefully considered in elderly patients which are candidates for starting renal replacement therapy. Some studies reported an increased risk for mortality for elderly patients on PD compared to those patients on HD [101103].

The success of HD in elderly depends on the good function of the vascular access. Diabetes, accelerated atherosclerosis and heart failure are very common in elderly. All these parameters may contribute to a limited rate of success of a good functioning vascular access and elderly patients had an increased risk of maturation failure of arterio-venous fistulas (AVF) [104]. In addition, AVF is not benign (innocent) especially in elderly patients with high cardiovascular co-morbidity. It is well known that the creation of an AVF may aggravate persistent congestive heart failure and/or coronary artery disease [92].

HD catheters are another option and are used with a growing frequency in patients with late referral or in those patients with AVF failure [105]. Of note, catheters have obvious complications including dysfunction, central venous stenosis and infections and their use has been associated with higher rate of hospitalizations [106].

On the other hand, PD especially in elderly patients with cardiovascular disease and dysfunction of sympathetic system offers a greater sense of well-being and fewer dialysis-related symptoms including intradialytic hypotension [107]. Under certain circumstances such as congestive heart failure with moderate CKD, the use of PD with a unique exchange with icodextrin may improve the quality of life of these patients and should be considered as an alternative approach [108,109]. It should be noted that elderly patients have no increased risk for peritonitis in comparison with younger patients, but peritonitis is more lethal [110]. Paradoxically, elderly patients have lower frequency of exit-site and tunnel infection probably due to a decreased activity [111]. In addition, Nessim et al [112] reported that catheter infection was less frequent in elderly PD patients in comparison with younger patients. More recently, Lim et al [113] using data from the Australian and New Zealand Dialysis Registry reported that elderly PD patients aged over 65 years had superior technique survival and similar peritonitis-free survival compared with the younger. However, the authors confirmed that the elderly present an increased peritonitis- related mortality risk [110, 113].

PD may contribute to persistent malnutrition of elderly patients by lose of protein and free amino acids through the PD solutions. This problem can be resolved by using amino acid PD solutions and/or increased intake of dietary protein [114].

A high proportion of elderly patients present impaired cognitive function and disability. The need of assistance by family members or nurses creates further socio-economic problems especially in the health system of countries with financial problems. Assisted PD (aPD) by nurses at home and in hospital IPD [9,115] are two alternative approaches for these patients with the disadvantage of the increased cost of treatment. In France, aPD programs based on community nurses are available for a long time. Thus, PD might be the first choice of management of elderly patients over 70 years with ESRD [116].

Regarding cost-effectiveness, PD and particularly continuous ambulatory peritoneal dialysis (CAPD) have lower cost in comparison with in center HD. A recent retrospective cohort study reported that PD patients had significantly lower total healthcare costs over a 12- month follow up period. [117]. In contrast, Grun et al [118] did not find any significant difference regarding the total costs between elderly patients (≥70 years) on PD or HD. Pre-dialysis modality education may actuate the elderly patients and their family members to choose the proper treatment.

Both HD and PD have advantages and disadvantages and the final choice should be based on patients’ wishes, functional status, comorbidities, financial health system policies and family/social support [92].

Kidney Transplantation in the elderly

Kidney transplantation is not frequently offered in elderly patients with ESRD due to the scarce of organs. Thus, the advanced recipient’s age has been considered as a relative contraindication for kidney transplantation. However, the survival rate of elderly patients which received a kidney transplant is favorable [103]. Additionally, kidney transplantation in the elderly increases both life expectancy and quality of life [119]. According to the Scientific Registry of Transplant Recipients, elderly recipients (> 70 years) have a lower risk of mortality in comparison with elderly patients on HD which remain in the wait-list for kidney transplantation [120]. Recently, Heldal et al [121] reported that renal transplantation offers a long-term survival benefit in patients over 70 years aged. Moreover, Rebollo et al [122] reported that transplanted elderly patients had a better quality of life compared with elderly patients on HD, but the access to kidney transplantation is limited in this particular growing population [11, 120, 123], although Schaeffner et al [124] reported that in the U.S the access of elderly to transplantation doubled in the last decade.

Donor age is the major risk factor for graft loss, whereas the recipient’s age does not seem to affect graft survival [125]. Thus recipient’s age alone should not be considered as criterion to exclude elderly patients from renal transplantation and the elderly are doing quite well with lower doses of immunosuppressive medications [126]. However, patient selection is not an easy job for a transplant team facing a transplant candidate aged > 70 years. A global judgment of all physical and mental/psychological issues should be undertaken before the final decision to list an elderly for renal transplantation [127].

Conclusions & Perspectives

Elderly patients with CKD are a growing social and economic problem. Early identification and appropriate treatment of CKD in this population may prevent its future expansion. However, current classifications based on various eGFR formulas in the elderly, are like a fishing trawler that captures a lot of “healthy” elderly patients without overt CKD [48]. Overdiagnosis of CKD contributes to overtreatment in the form of unnecessary referrals to nephrologists and unnecessary surgeries for dialysis vascular access among patients unlikely to progress to ESRD. The consequences of underdiagnosis may range from underuse of preventive therapies to poor preparation for eventual treatment of ESRD, including late referrals for HD vascular access placement, peritoneal dialysis, or kidney transplantation. Finding the right balance between overtreatment and undertreatment is challenging but necessary. [128,129].

The association between CKD and cardiovascular disease seen in many epidemiological studies in the elderly might not be causal but just a consequence of the shared risk factors for both conditions [130,131]. The CKD-EPI equation should probably replace the MDRD equation, but the search for better filtration markers and eGFR equations should not stop. Meanwhile, a wiser cut-off level, may be an eGFR lower than 45 mL/min/1.73m2 measured by the CKD-EPI equation [129]. Incorporation of proteinuria will definitely increase the sensitivity of the screening for CKD [76,132].

Regarding the elderly patient with ESRD, the choice to offer dialysis or not, is not so simple and should be based on patients’ wishes, life expectancy, quality of life, and socio-economic status. Current practices around the world are rather controversial, reflecting each country’s health policies and ethical patterns [5]. Both HD and PD can sustain life in the elderly with ESRD, but have many disadvantages. There is a trend for home based therapies (PD or home HD) but the results are based on a small number of patients and are mainly focusing on the reduced financial cost and the better quality of life at home. Palliative care should not be neglected and should be incorporated in the care of elderly patients with advanced CKD and multiple comorbidities.

There is an urgent need for large prospective studies and an individualized approach for the diagnosis and treatment of CKD in the elderly, in order to optimize care and improve quality of life in this special population. A new sub-subspeciality, the “geriatric nephrology” is coming of age [133].

Acknowledgments

The authors are dedicating the present manuscript to the memory of Prof. Dimitrios G. Oreopoulos (1936- 2012), a pioneer of “geriatric nephrology”.

References

[1] Centers for Disease Control and Prevention (CDC) Trends in aging-United States and world-wide. MMWR Morb Mortal Wkly Rep. 2003;52:101–4. [PubMed]
[2] Collins AJ, Foley R, Herzog C, Chavers BM, Gilbertson D, Ishani A, Kasiske BL, Liu J, Mau LW, McBean M, Murray A, St Peter W, Guo H, Li Q, Li S, Li S, Peng Y, Qiu Y, Roberts T, Skeans M, Snyder J, Solid C, Wang C, Weinhandl E, Zaun D, Arko C, Chen SC, Dalleska F, Daniels F, Dunning S, Ebben J, Frazier E, Hanzlik C, Johnson R, Sheets D, Wang X, Forrest B, Constantini E, Everson S, Eggers PW, Agodoa L. Experts from the United States Renal Data System-2009 Annual Data Report. Am J Kidney Dis. 2010;55(Suppl 1):S1–420. [PMC free article] [PubMed]
[3] Collins AJ, Foley R, Herzog C, Chavers BM, Gilbertson D, Ishani A, Kasiske BL, Liu J, Mau LW, McBean M, Murray A, St Peter W, Guo H, Li Q, Li S, Li S, Peng Y, Qiu Y, Roberts T, Skeans M, Snyder J, Solid C, Wang C, Weinhandl E, Zaun D, Arko C, Chen SC, Dalleska F, Daniels F, Dunning S, Ebben J, Frazier E, Hanzlik C, Johnson R, Sheets D, Wang X, Forrest B, Constantini E, Everson S, Eggers PW, Agodoa L. Experts from the United States Renal Data System 2007 Annual Data Report. Am J Kidney Dis. 2008;51(Suppl 1):S1–320. [PubMed]
[4] Jager KJ, van Dijk PC, Dekker FW, Stengel B, Simpson K, Briggs JD, ERA-EDTA Registry Committee The epidemic of aging in renal replacement therapy: An update on elderly patients and their outcomes. Clin Nephrol. 2003;60:352–60. [PubMed]
[5] Canaud B, Tong F, Tentori F, Akiba T, Karaboyas A, Gillespie B, Akizawa T, Pisoni RL, Bommer J, Port FK. Clinical practice and outcomes in elderly hemodialysis patients: results from the dialysis outcomes and practice patterns study (DOPPS) Clin J Am Soc Nephrol. 2011;6:1651–62. [PubMed]
[6] Collins AJ, Kasiske B, Herzog C, Chavers B, Foley R, Gilbertson D, Grimm R, Liu J, Louis T, Manning W, McBean M, Murray A, St Peter W, Xue J, Fan Q, Guo H, Li Q, Li S, Qiu Y, Li S, Roberts T, Skeans M, Snyder J, Solid C, Wang C, Weinhandl E, Zhang R, Arko C, Chen SC, Dalleska F, Daniels F, Dunning S, Ebben J, Frazier E, Hanzlik C, Johnson R, Sheets D, Wang X, Forrest B, Berrini D, Constantini E, Everson S, Eggers P, Agodoa L. Experts from the United States Renal Data System 2006 Annual Data Report. Am J Kidney Dis. 2007;49(Suppl 1):S1–296. [PubMed]
[7] Dimkovic N, Oreopoulos DG. Assisted peritoneal dialysis as a method of choice for elderly with end–stage renal disease. Int Urol Nephrol. 2008;40:1143–50. [PubMed]
[8] Dimkovic N, Oreopoulos DG. Management of elderly patients with end-stage kidney disease. Semin Nephrol. 2009;29:643–9. [PubMed]
[9] Fourtounas C, Hardalias A, Dousdampanis P, Savidaki E, Vlachojannis JG. Intermittent peritoneal dialysis (IPD): an old but still effective modality for severely disabled ESRD patients. Nephrol Dial Transplant. 2009;24:3215–8. [PubMed]
[10] Vamos EP, Novak M, Mucsi I. Non-medicals factors influencing access to renal transplantation. Int Urol Nephrol. 2009;41:607–16. [PubMed]
[11] Saxena R, Yu X, Giraldo M, Arenas J, Vazquez M, Lu CY, Vaziri ND, Silva FG, Zhou XJ. Renal transplantation in the elderly. Int Urol Nephrol. 2009;41:195–210. [PubMed]
[12] Swidler M. Geriatric renal palliative care is coming of age. Int Urol Nephrol. 2010;42:851–5. [PubMed]
[13] Eckardt KU, Berns JS, Rocco MV, Kasiske BL. Definition and classification of CKD: The debate should be about patient prognosis - a position statement from KDOQI and KDIGO. Am J Kidney Dis. 2009;53:915–20. [PubMed]
[14] Hallan SI, Stevens P. Screening for chronic kidney disease: which strategy? J Nephrol. 2010;23:147–55. [PubMed]
[15] Chen SC, Chang JM, Chou MC, Lin MY, Chen JH, Sun JH, Guh JY, Hwang SJ, Chen HC. Slowing renal function decline in chronic kidney disease patients after nephrology referral. Nephrology (Carlton) 2008;13:730–6. [PubMed]
[16] 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;21:2133–43. [PubMed]
[17] Winklmayer WC, Owen WF, Jr, Levin R, Avorn J. A propensity analysis of late versus early nephrologist referral and mortality on dialysis. J Am Soc Nephrol. 2003;14:486–92. [PubMed]
[18] National Kidney Foundation K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39(Suppl 1):S1–266. [PubMed]
[19] Stevens LA, Coresh J, Green T, Levey AS. Assessing kidney function: measured and estimated glomerular filtration rate. N Engl J Med. 2006;354:2473–83. [PubMed]
[20] Swedko PJ, Clark HD, Paramsothy K, Akbari A. Serum creatinine is an inadequate screening test for renal failure in elderly patients. Arch Intern Med. 2003;163:356–60. [PubMed]
[21] Wyatt C, Konduri V, Eng J, Rohatgi R. Reporting of estimated GFR in the primary care clinic. Am J Kidney Dis. 2007;49:634–41. [PubMed]
[22] Branten AJ, Vervoort G, Wetzels JF. Serum creatinine is a poor marker of GFR in nephrotic syndrome. Nephrol Dial Transplant. 2005;20:707–11. [PubMed]
[23] Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16:31–41. [PubMed]
[24] Glassock RJ, Winearls CG. eGFR: Readjusting its rating. Clin J Am Soc Nephrol. 2009;4:867–9. [PubMed]
[25] Coresh J, Stevens LA. Kidney function estimating equations: where do we stand? Curr Opin Nephrol Hypertens. 2006;15:276–84. [PubMed]
[26] Verhave JC, Fesler P, Ribstein J, du Cailar G, Mimran A. Estimation of renal function in subjects with normal serum creatinine levels: influence of age and body mass index. Am J Kidney Dis. 2005;46:233–41. [PubMed]
[27] Cirillo A, Anastasio P, De Santo NG. Relationship of gender, age, and body mass index to errors in predicted kidney function. Nephrol Dial Transpl. 2005;20:1791–8. [PubMed]
[28] Levey AS, Bosch JP, Lewis JB, 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;130:461–70. [PubMed]
[29] Levey AS, Coresh J, Green T, Marsh J, Stevens LA, Kusek JW, Van Lente F, Chronic Kidney Disease Epidemiology Collaboration Expressing the Modification of Diet in Renal Disease Study equation for estimating glomerular filtration rate with standardized serum creatinine values. Clin Chem. 2007;53:766–72. [PubMed]
[30] Gansevoort RT, de Jong PE. Challenges for the present classification system. Curr Opin Nephrol Hypertens. 2010;19:308–14. [PubMed]
[31] Myers GL, Miller WG, Coresh J, Fleming J, Greenberg N, Greene T, Hostetter T, Levey AS, Panteghini M, Welch M, Eckfeldt JH, National Kidney Disease Education Program Laboratory Working Group Recommendations for improving serum creatinine measurement: a report from the Laboratory Working Group of the National Kidney Disease Education Program. Clin Chem. 2006;52:5–18. [PubMed]
[32] Lamb EJ, Wood J, Stowe HJ, O'Riordan SE, Webb MC, Dalton RN. Susceptibility of glomerular filtration rate estimations to variations in creatinine methodology: a study in older patients. Ann Clin Biochem. 2005;42:11–8. [PubMed]
[33] Garg AX, Papaioanou A, Ferko N, Campbell G, Clarke JA, Ray JG. Estimating the prevalence of renal insufficiency in seniors requiring long-term care. Kidney Int. 2004;65:649–53. [PubMed]
[34] Botev R, Mallie JP, Couchoud C, Schück O, Fauvel JP, Wetzels JF, Lee N, De Santo NG, Cirillo M. Estimating glomerular filtration rate: Cockcroft-Gault and Modification of Diet in Renal Disease formulas compared to renal inulin clearance. Clin J Am Soc Nephrol. 2009;4:899–906. [PubMed]
[35] Levey SA, Stevens LA, Schmid CH, Zhang YL, Castro AF, 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J, CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) A new equation to estimate Glomerular Filtration Rate. Ann Intern Med. 2009;150:604–12. [PMC free article] [PubMed]
[36] Matsushita K, Selvin E, Bash LD, Astor BC, Coresh J. Risk implications of the new CKD Epidemiology Collaboration (CKD-EPI) equation compared with the MDRD Study equation for estimated GFR: the Atherosclerosis Risk in Communities (ARIC) Study. Am J Kidney Dis. 2010;55:648–59. [PMC free article] [PubMed]
[37] Juutilainen A, Kastarinen H, Antikainen R, Peltonen M, Salomaa V, Tuomilehto J, Jousilahti P, Sundvall J, Laatikainen T, Kastarinen M. Comparison of the MDRD Study and the CKD-EPI Study equations in evaluating trends of estimated kidney function at population level: findings from the National FINRISK Study. Nephrol Dial Transplant. 2012;27:3210–7. [PubMed]
[38] Murata K, Baumann NA, Saenger AK, Larson TS, Rule AD, Lieske JC. Relative performance of the MDRD and CKD-EPI equations for estimating glomerular filtration rate among patients with varied clinical presentations. Clin J Am Soc Nephrol. 2011;6:1963–72. [PubMed]
[39] Earley A, Miskulin D, Lamb EJ, Levey AS, Uhlig K. Estimating equations for glomerular filtration rate in the era of creatinine standardization: a systematic review. Ann Intern Med. 2012;156:785–95. [PubMed]
[40] Matsushita K, Mahmoodi BK, Woodward M, Emberson JR, Jafar TH, Jee SH, Polkinghorne KR, Shankar A, Smith DH, Tonelli M, Warnock DG, Wen CP, Coresh J, Gansevoort RT, Hemmelgarn BR, Levey AS, Chronic Kidney Disease Prognosis Consortium Comparison of risk prediction using the CKD-EPI equation and the MDRD study equation for estimated glomerular filtration rate. JAMA. 2012;307:1941–51. [PubMed]
[41] Stengel B, Metzger M, Froissart M, Rainfray M, Berr C, Tzourio C, Helmer C. Epidemiology and prognostic significance of chronic kidney disease in the elderly--the Three-City prospective cohort study. Nephrol Dial Transplant. 2011;26:3286–95. [PubMed]
[42] Rule AD, Larson TS, Bergstralh EJ, Slezak JM, Jacobsen SJ, Cosio FG. Using serum creatinine to estimate glomerular filtration rate: accuracy in good health and in chronic kidney disease. Ann Intern Med. 2004;141:929–37. [PubMed]
[43] Carnevale V, Pastore L, Camaioni M, Mellozzi M, Sabatini M, Arietti E, Fusilli S, Scillitani A, Pontecorvi M. Estimate of renal function in oldest old patients by MDRD study equation, Mayo Clinic equation and creatinine clearance. J Nephrol. 2010;23:306–13. [PubMed]
[44] Chew JS, Saleem M, Florkowski CM, George PM. Cystatin C - a paradigm of evidence based laboratory medicine. Clin Biochem Rev. 2008;29:47–62. [PMC free article] [PubMed]
[45] Knight EL, Verhave JC, Spiegelman D, Hillege HL, de Zeeuw D, Curhan GC, de Jong PE. Factors influencing serum cystatin C levels other than renal function and the impact on renal function measurement. Kidney Int. 2004;65:1416–21. [PubMed]
[46] Stevens LA, Schmid CH, Green T, Li L, Beck GJ, Joffe MM, Froissart M, Kusek JW, Zhang YL, Coresh J, Levey AS. Factors other than glomerular filtration rate affect serum cystatin C levels. Kidney Int. 2009;75:652–60. [PubMed]
[47] Rigalleau V, Beauvieux MC, Le Moigne F, Lasseur C, Chauveau P, Raffaitin C, Perlemoine C, Barthe N, Combe C, Gin H. Cystatin C improves the diagnosis and stratification of chronic kidney disease, and the estimation of glomerular filtration rate in diabetes. Diabetes Metab. 2008;34:482–9. [PubMed]
[48] Beringer PM, Hidayat L, Heed A, Zheng L, Owens H, Benitez D, Rao AP. GFR estimates using cystatin C are superior to serum creatinine in adult patients with cystic fibrosis. J Cyst Fibros. 2009;8:19–25. [PubMed]
[49] Delanaye P, Cavalier R, Radermecker RP, Paquot N, Depas G, Chapelle JP, Scheen AJ, Krzesinski JM. Estimation of GFR by different creatinine and cystatin C based equations in anorexia nervosa. Clin Nephrol. 2009;71:482–91. [PubMed]
[50] Stevens LA, Coresh J, Schmid CH, Feldman HI, Froissart M, Kusek J, Rossert J, Van Lente F, Bruce RD, 3rd, Zhang YL, Greene T, Levey AS. Estimating GFR using serum cystatin C alone and in combination with serum creatinine: a pooled analysis of 3,418 individuals with CKD. Am J Kidney Dis. 2008;51:395–406. [PMC free article] [PubMed]
[51] Peralta CA, Shlipak MG, Judd S, Cushman M, McClellan W, Zakai NA, Safford MM, Zhang X, Muntner P, Warnock D. Detection of chronic kidney disease with creatinine, cystatin C, and urine albumin-to-creatinine ratio and association with progression to end-stage renal disease and mortality. JAMA. 2011;305:1545–52. [PubMed]
[52] Tonelli M, Manns B. Supplementing creatinine-based estimates of risk in chronic kidney disease: is it time? JAMA. 2011;305:1593–5. [PubMed]
[53] Glassock RJ, Winearls C. An epidemic of chronic kidney disease: Fact or fiction? Nephrol Dial Transplant. 2008;23:1117–21. [PubMed]
[54] Glassock RJ, Winearls CG. Screening for CKD with e GFR: Doubts and dangers. Clin J Am Soc Nephrol. 2008;3:1563–8. [PubMed]
[55] Winearls CG, Glassock RJ. Classification of chronic kidney disease in the elderly: pitfalls and errors. Nephron Clin Pract. 2011;119(Suppl 1):c2–4. [PubMed]
[56] Wetzels JF, Kiemeney LA, Swinkels DW, Willems HL, den Heijer M. Age-and gender-specific reference values of estimated GFR in Caucasians: the Nijmegen Biomedical Study. Kidney Int. 2007;72:632–7. [PubMed]
[57] Rule AD, Amer H, Cornell LD, Taler SJ, Cosio FG, Kremers WK, Textor SC, Stegall MD. The association between age and nephrosclerosis on renal biopsy among healthy adults. Ann Intern Med. 2010;152:561–7. [PMC free article] [PubMed]
[58] Lindeman RD, Tobin J, Shock NW. Longitudinal studies on the rate of decline in renal function with age. J Am Geriatr Soc. 1985;33:278–85. [PubMed]
[59] Abdelhafiz AH, Brown SH, Bello A, El Nahas M. Chronic kidney disease in older people: Physiology, pathology or both? Nephron Clin Pract. 2010;116:c19–24. [PubMed]
[60] Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351:1296–1305. [PubMed]
[61] Wen CP, Cheng TY, Tsai MK, Chang YC, Chan HT, Tsai SP, Chiang PH, Hsu CC, Sung PK, Hsu YH, Wen SF. All-cause mortality attributable to chronic kidney disease: a prospective cohort study based on 462293 adults in Taiwan. Lancet. 2008;371:2173–82. [PubMed]
[62] Crowe E, Halpin D, Stevens P, Guideline Development Group Early identification and management of chronic kidney disease: Summary of NICE guidance. BMJ. 2008;337:a1530. [PubMed]
[63] Bauer C, Melamed ML, Hostetter TH. Staging of chronic kidney disease: Time for a course of correction. J Am Soc Nephrol. 2008;19:844–6. [PubMed]
[64] Glassock RJ, Winearls CG. The global burden of chronic kidney disease: How valid are the estimates? Nephron Clin Pract. 2008;110:c39–47. [PubMed]
[65] Kurella Tamura M, Wadley V, Yaffe K, McClure LA, Howard G, Go R, Allman RM, Warnock DG, McClellan W. Kidney function and cognitive impairment in US adults: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. Am J Kidney Dis. 2008;52:227–34. [PMC free article] [PubMed]
[66] Manjunath G, Tighiourat H, Coresh J, Macleod B, Salem DN, Griffith JL, Levey AS, Sarnak MJ. Level of kidney function as a risk factor for cardiovascular outcomes in elderly. Kidney Int. 2003;63:1121–9. [PubMed]
[67] Hallan SI, Astor B, Romunstad S, Aasarød K, Kvenild K, Coresh J. Association of kidney function and albuminuria with cardiovascular mortality in older vs younger individuals: The HUNT II study. Arch Intern Med. 2007;167:2490–6. [PubMed]
[68] Van der Velde M, Bakker SJL, de Jong PE, Gansevoort RT. Influence of age and measure of eGFR on the association between renal function and cardiovascular events. Clin J Am Soc Nephrol. 2010;5:2053–9. [PubMed]
[69] Van der Velde M, Matsushita K, Coresh J, Astor BC, Woodward M, Levey A, de Jong P, Gansevoort RT, Chronic Kidney Disease Prognosis Consortium. van der Velde M, Matsushita K, Coresh J, Astor BC, Woodward M, Levey AS, de Jong PE, Gansevoort RT, Levey A, El-Nahas M, Eckardt KU, Kasiske BL, Ninomiya T, Chalmers J, Macmahon S, Tonelli M, Hemmelgarn B, Sacks F, Curhan G, Collins AJ, Li S, Chen SC, Hawaii Cohort KP, Lee BJ, Ishani A, Neaton J, Svendsen K, Mann JF, Yusuf S, Teo KK, Gao P, Nelson RG, Knowler WC, Bilo HJ, Joosten H, Kleefstra N, Groenier KH, Auguste P, Veldhuis K, Wang Y, Camarata L, Thomas B, Manley T. Lower estimated glomerular filtration rate and higher albuminuria are associated with all-cause and cardiovascular mortality. A collaborative meta-analysis of high-risk population cohorts. Kidney Int. 2011;79:1341–52. [PubMed]
[70] Hemmelgarn BR, Manns BJ, Lloyd A, James MT, Klarenbach S, Quinn RR, Wiebe N, Tonelli M, Alberta Kidney Disease Network Relation between kidney function, proteinuria, and adverse outcomes. JAMA. 2010;303:423–9. [PubMed]
[71] Coresh J, Selvin E, Stevens LA, Manzi J, Kusek JW, Eggers P, Van Lente F, Levey AS. Prevalence of chronic kidney disease in the United States. JAMA. 2007;298:2038–47. [PubMed]
[72] Hillege HL, Janssen WM, Bak AA, Diercks GF, Grobbee DE, Crijns HJ, Van Gilst WH, De Zeeuw D, De Jong PE, Prevend Study Group Microalbuminuria is common, also in a non diabetic, nonhypertensive population, and an independent indicator of cardiovascular risk factors and cardiovascular morbidity. J Intern Med. 2001;249:519–26. [PubMed]
[73] Van der Velde M, Halbesma N, de Charro FT, Bakker SJ, de Zeeuw D, de Jong PE, Gansevoort RT. Can screening for albuminuria identify subjects at increased renal risk? J Am Soc Nephrol. 2009;20:852–62. [PubMed]
[74] Hallan SI, Ritz E, Lydersen S, Romundstad S, Kvenild K, Orth SR. Combining GFR and albuminuria to classify CKD improves prediction of ERSD. J Am Soc Nephrol. 2009;20:1069–77. [PubMed]
[75] Brantsma AH, Bakker SJ, Hillege HL, de Zeeuw D, de Jong PE, Gansevoort RT, PREVEND Study Group Cardiovascular and renal outcome in subjects with K/DOQI stage 1–3 chronic kidney disease: the importance of urinary albumin excretion. PREVEND Study Group. Nephrol Dial Transplant. 2008;23:3851–8. [PubMed]
[76] Tonelli M, Klarenbach SW, Lloyd AM, James MT, Bello AK, Manns BJ, Hemmelgarn BR. Higher estimated glomerular filtration rates may be associated with increased risk of adverse outcomes, especially with concomitant proteinuria. Kidney Int. 2011;80:1306–14. [PubMed]
[77] Glassock RJ, Winearls CG. Diagnosing chronic kidney disease. Curr Opin Nephrol Hypertens. 2010;19:123–8. [PubMed]
[78] Cirillo M, Lombardi C, Mele AA, Marcarelli F, Bilancio G. A population-based approach for the definition of chronic kidney disease: the CKD Prognosis Consortium. J Nephrol. 2012;25:7–12. [PubMed]
[79] Nair R, Bell JM, Walker PD. Renal biopsy in patients aged 80 years and older. Am J Kid Dis. 2004;44:618–26. [PubMed]
[80] Fischer MJ, O’ Hare AM. Epidemiology of hypertension in the elderly with chronic kidney disease. Adv Chronic Kidney Dis. 2010;17:329–40. [PubMed]
[81] Del Giudice A, Pompa G, Aucella F. Hypertension in the elderly. J Nephrol. 2010;23(Suppl15):S61–7. [PubMed]
[82] Alem AM, Sherrard DJ, Gillen DL, Weiss NS, Beresford SA, Heckbert SR, Wong C, Stehman-Breen C. Increased risk of hip fracture among patients with end-stage renal disease. Kidney Int. 2000;58:396–9. [PubMed]
[83] Kansal S, Fried L. Bone disease in elderly individuals with CKD. Adv Chronic Kidney Dis. 2010;17:e41–51. [PubMed]
[84] KurellaTamura M. Incidence, management, and outcomes of end-stage renal disease in the elderly. Curr Opin Nephrol Hypertens. 2009;18:252–7. [PMC free article] [PubMed]
[85] Moss AH, Ganjoo J, Sharma S, Gansor J, Senft S, Weaner B, Dalton C, MacKay K, Pellegrino B, Anantharaman P, Schmidt R. Utility of the “surprise” question to identify dialysis patients with high mortality. Clin J Am Soc Nephrol. 2008;3:1379–84. [PubMed]
[86] Cohen LM, Ruthhazer R, Moss AH, Germain MJ. Predicting six month mortality for patients who are on maintenance hemodialysis. Clin J Am Soc Nephrol. 2010;5:72–9. [PubMed]
[87] Brunori G, Viola BF, Parrinello G, De Biase V, Como G, Franco V, Garibotto G, Zubani R, Cancarini GC. Efficacy and safety of a very-low-protein diet when postponing dialysis in the elderly: a prospective randomized multicenter controlled study. Am J Kidney Dis. 2007;49:569–80. [PubMed]
[88] Kurella Tamura M, Covinsky KE, Chertow GM, Yaffe K, Landefeld CS, McCulloch CE. Functional status of elderly adults before and after initiation of dialysis. N Engl J Med. 2009;361:1539–47. [PMC free article] [PubMed]
[89] Davison SN. End-of-life care preferences and needs: perceptions of patients with chronic kidney disease. Clin J Am Soc Nephrol. 2010;5:195–204. [PubMed]
[90] Schmidt RJ. Informing our elders about dialysis: is an age-attuned approach warranted? Clin J Am Soc Nephrol. 2012;7:185–91. [PubMed]
[91] Thorsteinsdottir B, Swetz KM, Feely MA, Mueller PS, Williams AW. Are there alternatives to hemodialysis for the elderly patient with end-stage renal failure? Mayo Clin Proc. 2012;87:514–6. [PMC free article] [PubMed]
[92] Berger JR, Hedayati SS. Renal replacement therapy in the elderly population. Clin J Am Soc Nephrol. 2012;7:1039–46. [PubMed]
[93] Joly D, Anglicheau D, Alberti C, Nguyen AT, Touam M, Grünfeld JP, Jungers P. Octogenarians reaching end-stage renal disease: cohort study decision-making and clinical outcomes. J Am Soc Nephrol. 2003;14:1012–21. [PubMed]
[94] Murtagh FE, Marsh JE, Donohoe P, Ekbal NJ, Sheerin NS, Harris FE. Dialysis or not? A comparative survival study of patients over 75 years with chronic kidney disease stage 5. Nephrol Dial Transplant. 2007;22:1955–62. [PubMed]
[95] Chandna SM, Da Silva-Gane M, Marshall C, Warwicker P, Greenwood RN, Farrington K. Survival of elderly patients with 5 CKD: comparison of conservative management and renal replacement therapy. Nephrol Dial Transplant. 2011;26:1608–14. [PMC free article] [PubMed]
[96] Scalone L, Borghetti F, Brunori G, Viola BF, Brancati B, Sottini L, Mantovani LG, Cancarini G. Cost-benefit analysis of supplemented very low-protein diet versus dialysis in elderly CKD 5 patients. Nephrol Dial Transplant. 2011;25:907–13. [PubMed]
[97] Hemmelgarn BR, James MT, Manns BJ, O’Hare AM, Muntner P, Ravani P, Quinn RR, Turin TC, Tan Z, Tonelli M, for the Alberta Kidney Disease Network Rates of treated and untreated kidney failure in older vs younger adults. JAMA. 2012;307:2507–15. [PubMed]
[98] O'Hare AM, Choi AI, Bertenthal D, Bacchetti P, Garg AX, Kaufman JS, Walter LC, Mehta KM, Steinman MA, Allon M, McClellan WM, Landefeld CS. Age affects outcomes in chronic kidney disease. J Am Soc Nephrol. 2007;18:2758–65. [PubMed]
[99] Jassal SV, Watson D. Dialysis in late life: benefit or burden. Clin J Am Soc Nephrol. 2009;4:2008–12. [PubMed]
[100] Jassal SV, Chiu E, Hladunewich MA. Loss of independence in patients starting dialysis at 80 years of age or older. N Engl J Med. 2009;361:1612–3. [PubMed]
[101] Collins AJ, Weinhandl E, Snyder JJ, Chen SC, Gilbertson D. Comparison and survival of hemodialysis and peritoneal dialysis in the elderly. Semin Dial. 2002;15:98–102. [PubMed]
[102] Winkelmayer WC, Glynn RJ, Mittleman MA, Levin R, Pliskin JS, Avorn J. Comparing mortality of elderly patients on hemodialysis versus peritoneal dialysis: a propensity score approach. J Am Soc Nephrol. 2002;13:2353–62. [PubMed]
[103] Couchoud C, Moranne O, Frimat L, Labeeuw M, Allot V, Stengel B. Associations between comorbidities, treatment choice and outcome in the elderly with end-stage renal disease. Nephrol Dial Transplant. 2007;22:3246–54. [PubMed]
[104] Lazarides MK, Georgiades GS, Antoniou GA, Staramos DN. A meta-analysis of dialysis access outcome in elderly patients. J Vasc Surg. 2007;45:420–6. [PubMed]
[105] 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;6:1663–7. [PubMed]
[106] Basic-Jukic N, Kes P, Juric I, Brunetta-Gavranic B. Octogenarians on hemodialysis: a prospective study. Arch Gerontol Geriatr. 2008;47:19–24. [PubMed]
[107] Nissenson AR. Quality of life in elderly and diabetic patients on peritoneal dialysis. Perit Dial Int. 1996;16(Suppl1):S406–9. [PubMed]
[108] Jeloka AT. ‘Icodextrin alone’ for initiation of peritoneal dialysis. Perit Dial Int. 2008;28:563–4. [PubMed]
[109] Bertoli SV, Ciurlino D, Maccario M, Martino S, Bigatti G, Traversi L, Procaccio M, Buzzi L. Home peritoneal ultrafiltration in patients with severe congestive heart failure without end-stage renal disease. Adv Perit Dial. 2005;21:123–7. [PubMed]
[110] Piccoli G, Quarello F, Salomone M, Pacciti A, Beltrame G, Piccoli GB, Vercellone A. Dialysis in the elderly: comparison of different dialysis modalities. Adv Perit Dial. 1990;6:72–81. [PubMed]
[111] Dimkovic N, Oreopoulos DG. Chronic peritoneal dialysis in the elderly. Semin Dial. 2002;15:94–7. [PubMed]
[112] Nessim SJ, Bargman JM, Austin PC, Story K, Jassal SV. Impact of age on peritonitis risk in peritoneal dialysis patients: an era effect. Clin J Am Soc Nephrol. 2009;4:135–41. [PubMed]
[113] Lim W, Dogra G, McDonald SP, Brown FG, Johnson DW. Compared with younger peritoneal dialysis patients, elderly patients have similar peritonitis-free survival and lower risk of technique failure, but higher risk of peritonitis- related mortality. Perit Dial Int. 2011;31:663–71. [PubMed]
[114] Tjiong HL, Swart R, van der Berg JW, Fieren MW. Amino Acid-based peritoneal dialysis solutions for malnutrition: new perspectives. Perit Dial Int. 2009;29:384–93. [PubMed]
[115] Fourtounas C. The present and the future of Peritoneal Dialysis. Hippokratia. 2011;15(Suppl 2):15–20.
[116] Verger C, Ryckelynck JP, Duman M, Veniez G, Lobbedez T, Boulanger E, Moranne O. French Peritoneal Dialysis Registry (RDPLF): outline and main results. Kidney Int. 2006;(Suppl 103):S12–20. [PubMed]
[117] Berger A, Edelsberg J, Inglese GW, Bhattacharyya SK, Oster G. Cost comparison of peritoneal dialysis versus hemodialysis in end-stage renal disease. Am J Manag Care. 2009;15:509–18. [PubMed]
[118] Grun RP, Constantinovici N, Normand C, Lamping DL, North Thames Dialysis Study Group Costs of dialysis for elderly people in the UK. Nephrol Dial Transplant. 2003;18:2122–7. [PubMed]
[119] Jassal SV, Krahn MD, Naglie G, Zaltzman JS, Roscoe JM, Cole EH, Redelmeier DA. Kidney transplantation in the elderly: a decision analysis. J Am Soc Nephrol. 2003;14:187–96. [PubMed]
[120] Rao PS, Merion RM, Ashby VB, Port FK, Wolfe RA, Kayler LK. Renal transplantation in elderly patients older than 70 years of age: results from the Scientific Registry of Transplant Recipients. Transplantation. 2007;83:1069–74. [PubMed]
[121] Heldal K, Hartmann A, Grootendorst DC, de Jager DJ, Leivestad T, Foss A, Midtvedt K. Benefit of kidney transplantation beyond 70 years of age. Nephrol Dial Transplant. 2010;25:1680–7. [PMC free article] [PubMed]
[122] Rebollo P, Ortega F, Baltar JM, Díaz-Corte C, Navascués RA, Naves M, Naves M, Ureña A, Badía X, Alvarez-Ude F, Alvarez-Grande J. Health-related quality of life (HRQOL) in end-stage renal disease (ESRD) patients over 65 years. Geriatr Nephrol. 1998;8:85–94. [PubMed]
[123] Friedman AL. Cautious renal transplantation for the elderly is realistic. Nephron Clin Pract. 2011;119(Suppl 1):c14–8. [PubMed]
[124] Schaeffner ES, Rose C, Gill JS. Access to kidney transplantation among the elderly in the United States: a glass half full, not half empty. Clin J Am Soc Nephrol. 2010;5:2109–14. [PubMed]
[125] Otero-Ravina F, Rodriguez-Martinez M, Gude F, González-Juanatey JR, Valdés F, Sánchez-Guisande D. Renal transplantation in the elderly: does patient age determine the results? Age Ageing. 2005;34:583–7. [PubMed]
[126] Badowski M, Gurk-Turner C, Cangro C, Weir M, Philosophe B, Klassen D, Haririan A. The impact of reduced immunosuppression on graft outcomes in elderly renal transplant recipients. Clin Transplant. 2009;23:930–7. [PubMed]
[127] Hubbard WJ, Dashti N. Aging and transplantation - a topic for biomedicine or bioethics? Aging Dis. 2011;2:181–5. [PMC free article] [PubMed]
[128] Kurella Tamura M, Winkelmayer WC. Treated and untreated kidney failure in older adults. What’s the right balance? JAMA. 2012;307:2545–6. [PubMed]
[129] Kalantar-Zadeh K, Amin AN. Toward more accurate detection and risk stratification of chronic kidney disease. JAMA. 2012;307:1976–7. [PubMed]
[130] White S, Leichtman A. Does reduced glomerular filtration rate equate to chronic kidney disease? BMJ. 2012;344:e1167. [PubMed]
[131] El Nahas M. Cardio-Kidney-Damage: a unifying concept. Kidney Int. 2010;78:14–8. [PubMed]
[132] Tonelli M, Muntner P, Lloyd A, Manns BJ, James MT, Klarenbach S, Quinn RR, Wiebe N, Hemmelgarn BR, Alberta Kidney Disease Network Using proteinuria and estimated glomerular filtration rate to classify risk in patients with chronic kidney disease. Ann Intern Med. 2011;154:12–21. [PubMed]
[133] Oreopoulos DG, Dimkovic N. Geriatric nephrology is coming of age. J Am Soc Nephrol. 2003;14:1099–101. [PubMed]

Articles from Aging and Disease are provided here courtesy of JKL International LLC