The major strength of the OPAIR study is its prospective and observational design with measurements of QoL and cognitive function. We focused on CKD management in Octogenarians and Nonagenarians before dialysis decision-making in addition to previous studies devoted to elderly including patients starting dialysis [9, 10], and those conducted in general population [4, 33, 34]. We provided useful information on a very elderly pre-ESRD French population newly referred to nephrologists, and dialysis decision-making in usual clinical practice in this population. Death and dialysis initiation were found to be independent clinical outcomes, except for acute congestive heart failure patients. Finally, we highlighted that the patient’s age had no impact on dialysis decision as nephrologists seem to use similar acceptance criteria for dialysis in very elderly as those in younger subjects.
The OPAIR study prospectively profiled the clinical characteristics of very elderly French patients with an advanced CKD newly referred to nephrologists. Regarding kidney disease, most of them had a severely impaired renal function, and should potentially progress to ESRD requiring a renal therapy replacement or die. Nephrologists considered going into aetiology of renal disease in patients (2% biopsies) of no importance, suggesting a probabilistic aetiology. However, CKD-related complications were meticulously controlled; most of them had a haemoglobin level over 11 g/dL, and normal calcium and phosphate levels. Among OPAIR participants, the 3-year probabilities of death and dialysis initiation amounted to 27% and 11%, respectively. Such findings suggest that participants were 2.5-fold more likely to die than to progress to ESRD requiring dialysis. Our results were relatively consistent with those found in previous studies with disparate settings showing death, largely cardiovascular, as the most common outcome in CKD patients rather than progression to advanced stages of CKD, even among patients with stage 4 CKD, and especially true in elderly [4, 8–10, 13, 15, 33, 35].
This specific geriatric population was relatively healthy. Included patients had moderate co-morbidities, a preserved cognitive function and no deterioration of QoL. Their physical and mental health summary scores illustrated indeed a good health status despite their age and were close to those of younger elderly (≥75 years) in general population . They were also well-fed. With regard to management of very elderly (≥80 years) with renal disease, there was therefore an indication bias in the selection process on behalf of GPs towards referring patients for nephrology consultation in the OPAIR study. GPs, consciously or unconsciously, had restricted access to patients who could potentially require a dialysis, based on renal criteria and good health. Indeed most patients referred to nephrologists were neither elderly institution residents, nor malnourished frail elderly with geriatric syndrome. Such results outlined that the clinical profile of these very elderly pre-ESRD patients did not fit to the profile of geriatric patients.
Congestive heart failure or a history of cancer had a significant impact on access to dialysis. No included patients with acute congestive heart failure underwent dialysis. This condition, by contrast, was found as a strong predictor of death. Additionally, no patients with a history of cancer underwent dialysis, whereas no increased risk of death from cancer was found. Thus 26% of patients with one of these two antecedents, easily recognized by clinicians, were not offered dialysis. The observational nature of data cannot explain the process that has led to a lack of dialysis for these patients. Several hypotheses can be advanced. First, patients with congestive heart failure had a higher risk of death, and therefore died maybe before requiring dialysis. Second, nephrologists decided not to offer dialysis for fear of worsening the quality of life without improving survival in such patients. Indeed a recent study has suggested that there is no benefit in terms of survival for patients with cardiovascular co-morbidities . Third, patients with heart failure or a history of cancer were more able to decline to undergo dialysis. As none of these patients underwent dialysis, it is likely that these three hypotheses were combined. Such a result suggests that nephrologists have introduced a dialysis indication bias in patients with congestive heart failure or a history of cancer.
Finally, competing risk-analyses in the OPAIR study focused on a geriatric population newly referred to nephrologists with a good health status, despite their old age. As both competing-risk analyses (Cox, Fine and Gray) enable us to conclude that probabilities of death and dialysis initiation were independent in this specific geriatric population, they reinforce the identification of both indication bias in the selection process on behalf of GPs and nephrologists. The nephrologists’ dialysis decision-making was based exclusively on renal criteria as we found that eGFR <23 mL/min/1.73 m2 was the main predictive factor of dialysis initiation. In the opposite, eGFR <23 ml/min/1.73 m2 was not a predictor of death in competing-risk frameworks of the OPAIR study. Our findings suggest that predictors of death, such as age, walking impairment and anaemia (Hb <10 g/dL) in very elderly pre-ESRD patients newly referred to nephrologists seem to be features of physiological ageing process.
It is well-known that patients with severe co-morbidities may not always benefit from dialysis [15, 37, 38]. Of note, the prevalence of diabetes and cardiovascular diseases in French 2009 incident dialysis patients, 41% and 57% respectively, was significantly higher than in the largely older OPAIR patients . Otherwise, in a vignette study, a consensus seemed to exist across GPs, non nephrology specialists and nephrologists about recognizing that dialysis was not appropriate for elderly patients under some circumstances such as terminal cancer, but still on debate about other co-morbidities, such as mild shortness of breath, diabetes and mild cognitive impairments . At the opposite, younger CKD patients are usually referred to nephrologists on the basis of the level of renal function whatever their co-morbid conditions, QoL and cognitive function are. Finally, our study reinforce recommendations, emphasizing the importance of referral to specialist nephrology services largely for CKD patients on the basis of glomerular filtration rate (stage 4-5) or high levels of proteinuria .
In clinical practice, it is usual to start dialysis aimed to potentially improve among CKD patients less than 80 years of age and stop it if no improvement of patient’s condition is observed. At the opposite, decision to initiate dialysis among patients aged 80 years and over is based on medical considerations with strong arguments that dialysis will offer sufficient survival benefit taking into account the treatment burden of dialysis, in the best interest of the patients. In clinical practice, the appropriate decision-making in CKD elderly is based on a subtle balance between overtreatment by initiating dialysis earlier than may be necessary or maintaining dialysis with no increase in life expectancy or no improvement of QoL, and undertreatment involving late referrals to nephrologists and unplanned dialysis that leads to severely impaired QoL [11, 41]. Among more than 1.8 million adults in a community-based cohort, untreated CKD among adults aged 75 years or older with baseline eGFR of 15 to 29 mL/min/1.73 m2 was approximately 2- to 10-fold more common than CKD treated by dialysis . After dialysis decision-making, primary concerns of nephrologists are focused on the right moment to adequately prepare patients for dialysis and initiate dialysis in elderly. Other challenge for nephrologists treating very elderly population is posed by the choice of access and the timing of its creation. Recently, Hiremath et al. have suggested that the optimal strategy in elderly with stage 4 CKD, excluding those with a proteinuric diabetic nephropathy, should be to wait and start with a central venous catheter when required followed by an arteriovenous fistula creation, whereas most guidelines have recommended assessment of patients for access creation at stage 4 CKD [43–45].
The latest updated guidelines suggested that the timing of dialysis therapy initiation in older patients with advanced CKD should remain focused on individualized decision-making guided by clinical judgment, symptom burden and patient preference [46, 47]. This approach consisted in identifying motivated patients with a good prognosis (no risk of renal progression) or those with many co-morbid conditions giving more importance to CKD compared to risk of death. This could probably explain that MMSE and QoL scores were not linked to renal prognosis in the OPAIR study. We can suppose that patients with the lowest QoL scores had no regular follow-up care and were withdrawn from dialysis. Previous data showed that an individualized model may be more appropriate than a disease-oriented model of care for many older adults with CKD [37, 46–49]. Such individualized approach calls for listening to the patient, and providing prognosis and treatment information to patients and/or families. In particular, they should be informed that QoL is better improved in autonomous CKD patients on self-care dialysis than in those non-autonomous . The patient will have anyway the final decision to be admitted or not into a dialysis program.
Our study has several limitations. First, the number of included patients was lower than expected. This highlighted the difficulty to establish a regular nephrology care in very elderly. As nephrology consultations are overloaded, elderly CKD patients are often followed-up by GPs. As a result, the analysis of risk factors for initiation of dialysis was underpowered. Indeed, only 17 dialysis initiations were observed during the study. For a multivariate analysis in survival analysis, it is recommended to have at least 10 events observed for each covariate . Additionally, the risk of death was 2.5-fold greater than the risk of initiation of dialysis in our study. According to the incidence of dialysis initiation and death events in our study, it would be necessary to include at least 1,000 patients to study 10 covariates. Increasing the number of included patients and consequently the number of patients who initiated dialysis would require the extension of the enrolment period beyond 12 months. However, such decision would require a complex organization given the age of our patients. Second, the choice of both prevalent and incident CKD cases to be included into the study may have introduced a selection bias with an overrepresentation of prevalent cases with low risk of death as they had survived until study initiation. However, the study initiation started with the inclusion of patient to avoid the immortality bias. Third, we used the MDRD’s formula whereas it has not been yet validated in elderly. Additionally, as a function of both residual GFR and changes in lean body muscle mass (sarcopaenia) perhaps related to inflammation and chronic acidosis in stage 5 CKD, eGFR (MDRS’ formula) overestimates true GFR (inulin clearance) by about 3.3 mL/min/1.73 m2 or by about 42% . Given the dependence of serum creatinine on muscle mass, there is a particular concern that eGFR slope in the elderly may be affected by changes in muscle over time. However, although potentially inaccurate as indicator of true GFR, eGFR is widely used in clinical practice and does seem to have prognostic value for death and ESRD . Fourth, despite collecting extensive information about cognitive function and QoL, no positive association was drawn about their role as predictors of dialysis likelihood, on condition of no bias related to the small size of population.