Although the correlation between chronic kidney disease (CKD) and risk of cardiovascular morbidity and mortality has been thoroughly investigated, studies evaluating the impact of CKD on health-related quality of life (HRQOL) are somewhat scarce 1 2 3 . In particular, the relationship between quality of pre-dialysis care and HRQoL at dialysis onset has not been investigated to date. However, numerous studies have shown associations between quality of pre-dialysis care and dialysis mortality on one hand 4 and, HRQoL at dialysis onset and dialysis mortality on the other hand 5 6 7 .

The quality of pre-dialysis care is a multidimensional concept that includes several aspects, for example, clinical follow-up by nephrologists, the quality of therapeutic care, the quality of dialysis preparation, and counselling.

A positive association between early referral to a nephrologist and survival after starting renal replacement therapy (RRT) has been clearly demonstrated 8 but the impact of early referral on HRQoL at initiation of dialysis is still a matter for debate 2 9 . Moreover, the lack of a consensus over the definition of 'early' and 'late' nephrology referral has left primary care providers unsure about the optimum timing and pattern of nephrology care. Nephrological care was recently assessed from a quantitative rather than a qualitative perspective, focusing on the number of nephrology consultations before RRT 10 . Moreover, a favourable association between early referral or a high number of pre-ESRD nephrology consultations and quality of therapeutic care has been suggested 11 12 . Likewise, quality of pre-ESRD therapeutic practices has been found to be associated with survival after RRT 4 .

We used data from the pharmacoepidemiologic AVENIR (AVantagE de la Néphroprotection dans l'Insuffisance Rénale) study to explore the impact on HRQoL at dialysis onset of three pre-dialysis indicators of quality of care: quality of therapeutic practices, time since referral to a nephrologist and number of nephrology consultations during the year preceding dialysis. Our hypothesis is that the higher the quality of pre-dialysis care, the better the HRQoL. Our aim is to heighten nephrologists' awareness of the outstanding importance of the quality of pre-dialysis care.

To our knowledge, this observational study is the first to explore in depth the association between the quality of pre-ESRD nephrological care, evaluated across three indicators, and HRQoL at dialysis onset. In a field where randomized controlled studies cannot be ethically designed, our results suggest: first, a mild, but statistically significant, association between quality of therapeutic practices, evaluated across five therapeutic aspects, and mental, but not physical, quality of life; second, the earlier the referral to a nephrologist, the better the control of symptoms, problems and effects of CKD; third, a lack of association between the number of nephrology consultations and HRQoL.

HRQoL was measured with the validated French version of the KDQoL V36 20 . The two generic scores allowed ESRD patients to be compared with the general population, whereas the three specific scores explored the impact of the kidney disease on daily life. Both physical and mental summary scores were well below 50, which is the expected average from the US general population. These results are consistent with previous studies 1 7 . Moreover, HRQoL at dialysis onset was altered compared to the French general population, particularly the physical component 25 . Disease-specific scores observed in our ESRD sample were close to scores reported by Molsted et al 26 , but well below than those observed by Mujais et al 27 in their CKD stage V patients. Nevertheless, in this last study, HRQoL was measured when patients were not yet under dialysis treatment, which seems to have a marked impact on the specific dimensions of HRQoL, particularly the 'Burden of kidney disease'. In any case, this dimension was always the most impaired HRQoL dimension in CKD or ESRD patients. This emphasises the need for psychological support of ESRD patients at dialysis onset.

Previous studies using the SF36 suggest that scores in the range of 2 or 3 points on the physical and mental summary scores (equivalent to 0.2 to 0.3 SD) are likely to be clinically important 28 . We observed, in the MCS12 score, differences according to the level of quality of therapeutic practices that were around 2 to 4 points, suggesting that they are likely to be noticeable and meaningful to patients at dialysis initiation. As perceived mental health is an independent predictor of mortality and morbidity 7 , attaining the target of MCS12 score observed in patients with high quality of therapeutic practices is of interest. No other study to date has investigated the impact of the quality of pre-ESRD therapeutic practices on HRQoL at dialysis initiation.

Concerning the impact of time since referral to a nephrologist on HRQoL, results from previous studies are conflicting 1 9 . Sesso and Yoshihiro 9 have demonstrated that patients referred late to a nephrologist (≤ one month before starting dialysis) have significantly worse HRQoL than those referred early (≥ 6 months). We found similar tendencies in two of the three specific HRQoL dimensions (symptoms and effects) but no comparison can be made in HRQoL scores because Sesso and Yoshihiro used another quality of life questionnaire (Kidney Disease Questionnaire). These associations we found between time referral to a nephrologist and specific dimensions of HRQoL may reflect the benefit of the nephrologist's having had more time to evaluate and treat properly somatic symptoms and consequences of CKD on his patients. Conversely, Caskey et al found no significant difference between early and late referral patients in any of the SF36 summary scores or domain scores 1 . However, in this study, patients were considered 'early referred' if they had been followed by a nephrologist for >1 month before their first dialysis. As we considered early referred patients those who had been followed for more than 12 months before dialysis onset, the results are not comparable. The main difficulty in comparing results of studies investigating the time of referral to a nephrologist is the use of multiple definitions of 'early' and 'late'.

Another way of assessing pre-ESRD nephrological care is to consider the frequency of nephrology consultations before RRT rather than timing of referral 10 . In our study, we found no association between the number of nephrology consultations during the year preceding RRT and HRQoL at initiation of dialysis. Studies published to date have investigated the relationship between the frequency of patient-nephrologist visits during maintenance dialysis and HRQoL 10 29 but none has looked at the impact on HRQoL of frequency of visits before RRT. Moreover, neither Plantinga et al 10 nor Mentari et al 29 found any association between the frequency of patient-nephrologist contact and HRQoL of dialyzed patients.

Some possible limitations should be considered when interpreting our findings. First, as this study was observational, it allows us to measure associations between pre-dialysis indicators and HRQoL, but cannot demonstrate strictly causal relationships. However, given that a controlled trial in which patients would be randomized on quality of pre-dialysis care is clearly impractical for ethical reasons, our study is of value. Second, almost one third of included patients did not complete the HRQoL questionnaire. Nevertheless, given the relatively minor differences (only age) between respondents and non-respondents, we can assume that these non-responses probably did not introduce a systematic bias that would distort our conclusions. Third, HRQoL was measured up to three months after the start of dialysis. This may reflect care received on dialysis as much as pre-dialysis care, but sensitivity analyses including only patients who completed the HRQoL within the first 10 days after the dialysis onset did not change the results. Fourth, despite adjustment for the main patient characteristics known to be associated with HRQoL in CKD, residual confounding due to the lack of data on variables - such as socioeconomics parameters - for which we could not account may still exist. Fifth, several aspects of quality of pre-dialysis care were taken into account in our study, but not all. For example, the quality of dialysis preparation and counseling was not considered here.

Concerning management of CKD, clinicians have always recognized the importance of diagnosing functional impairments. Our study provides finally an accurate measure of patient-perceived health status at dialysis onset, and highlights the impact of quality of therapeutic practices and early nephrology referral on HRQoL, independently of the number of consultations.

To our knowledge, this observational study is the first to explore the association between the quality of pre-ESRD nephrological care and HRQoL at dialysis onset. The mental component, but not the physical, is significantly influenced by the quality of pre-dialysis nephrological care, evaluated across five therapeutic aspects. Late referral to a nephrologist is associated with poor HRQoL (symptoms/problems and effects of disease dimensions). Therefore, CKD disease management incorporating psychological support should be emphasized.

The authors declare that they have no competing interests.

SBo & NT participated in the design of this ancillary work, reviewed the literature, performed the statistical analysis, and drafted the manuscript. LF participated in the design of this work and provided feedback on it. MK and SBr participated in the design and provided feedback. All authors collaborated interactively, and read and approved the final version.