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Update of dialysis initiation timing in end stage kidney disease patients: is it a resolved question? A systematic literature review

BMC Nephrology volume 24, Article number: 162 (2023) Cite this article

Abstract

Background

The exact optimal timing of dialysis for ESKD patients remains unknown. This study systematically reviewed the available evidence with regard to the optimal initiation of maintenance dialysis in ESKD patients.

Methods

An electronic search was performed in Embase, PubMed and the Cochrane Library in order to find studies investigating associations between variables reference to “start of dialysis” and outcomes. Quality assessment and bias assessment were performed by the Newcastle–Ottawa scale and the ROBINSI tool. Due to the heterogeneity of studies, a meta-analysis could not be performed.

Results

Thirteen studies were included; four studies included only haemodialysis patients, three peritoneal dialysis, six both; study outcomes included mortality, cardiovascular events, technique failure, quality of life and others. Nine studies mainly focused on the optimal GFR of maintenance dialysis initiation; five studies showed none association between GFR and mortality or other adverse outcomes, two studies showed dialysis initiation at higher GFR levels were with poor prognosis, and 2 studies showed higher GFR levels with better prognosis. Three studies paid attention to comprehensive assessment of uremic signs and/or symptoms for optimal dialysis initiation; uremic burden based on 7 uremic indicators (hemoglobin, serum albumin, blood urea nitrogen, serum creatinine, potassium, phosphorus, and bicarbonate) were not associated with mortality; another equation (combination of sex, age, serum creatinine, blood urea nitrogen, serum albumin, haemoglobin, serum phosphorus, diabetes mellitus, and heart failure) based on fuzzy mathematics to assess the timing of haemodialysis initiation was accuracy to prognose 3-year survival; the third study found that volume overload or hypertension was associated with the highest risk for subsequent mortality. Two studies compared urgent or optimal start in dialysis, a study reported increased survival in optimal start patients, another reported no differences between Urgent-Start-PD and Early-Start-PD regarding 6-month outcomes. Limitations: Heterogeneity among the studies was quite high, with differences in sample size, variable and group characteristics; no RCT studies were included, which weakened the strength of evidences.

Conclusions

The criteria for dialysis initiation were varied. Most studies proved that GFR at dialysis initiation was not associated with mortality, timing of dialysis initiation should not be based on GFR, assessments of volume load and patient’s tolerance to volume overload are prospective approaches.

Peer Review reports

Introduction

Chronic kidney disease (CKD) is a major global public health problem [1], and there is an increasing number of end stage kidney disease (ESKD) patients start dialysis annually. The decision on optimal initiation of maintenance dialysis is a common problem faced by nephrologists. During 1980s-2000s, extensive observational studies have been attempted to investigate the optimal estimated glomerular filtration rate (eGFR) at the start of dialysis. In 2010 a randomized controlled trial named “trial Initiating Dialysis Early and Late (IDEAL)” showed that a strategy of early dialysis initiation (target eGFR: 10-14 mL/min/1.73m2) was not superior to late initiation (waiting until symptoms develop or eGFR is 5-7 mL/min/1.73m2) [2]. Since then, clinical practice guidelines suggest that the decision of initiate maintenance dialysis should be guided primarily by clinical constellation of signs and symptoms attributable to uremic syndrome [3,4,5,6]. However, symptoms or signs of uremia are varied and complex, mainly depends on clinical judgment; what’s more, typical uremic symptoms such as pericarditis and encephalopathy in patients without volume overload often occur at a very low GFR, these conditions are often combined with severe metabolic disorders and/or organ damages; the exact optimal timing of dialysis for ESKD patients remains unknown.

Therefore, the aim of our study is to systematically review the available evidence with regard to the optimal initiation of maintenance dialysis in ESKD patients.

Methods

The systematic review adopted PRISMA protocol. The quality of studies was assessed through the Newcastle–Ottawa scale.

Data source and search strategy

The PUBMED, EMBASE and COCHRANE databases were searched for English-language articles between Jan 2017 and Jan 2022, and with search terms as described in Supplementary data, Table S1.

Study selection

Articles should meet any of the following criteria to be included: every study with reference to “start of dialysis” decision criteria that also (i) provided outcome data in patients; (ii) reported outcome data of an interaction analysis; (iii) there are predefined specific levels of kidney function at which RRT was initiated that were deemed early or late start of dialysis; (iv) RRT encompassed all forms of haemodialysis (HD) and peritoneal dialysis (PD); (v)editorials, case reports, reviews, letters and studies performed in children (age < 18 years) or animals should be excluded after screening for relevant references; (vi)primary study-objective was not the effect of the situation at the beginning of dialysis on prognosis, cross-sectional study, or study without follow-up results should be excluded.

Quality and risk of bias assessment

Study quality was assessed by the Newcastle–Ottawa scale for observational studies, which provides a quality score per study based on three items: study participants (0–4 points), adjustment for confounding (0–2 points) and exposure/outcome of interest ascertainment (0–3 points). A study that meets all the criteria for these three dimensions would score a maximum of 9 points [7].Newcastle–Ottawa scale were assessed by two reviewers (Xiaoyan Jia and Xueqing tang), a third reviewer (Dongmei Xu) was consulted in case of doubt.

Data extraction and analysis

After the selected titles were reviewed, two reviewers independently read the abstracts to select the relevant articles for full-text review. After this full-text review, the data in the full-text articles that met the inclusion criteria were extracted, tabulated and analyzed. Discrepancies between the two reviewers were solved by asking a third author to review the problematic articles and reach consensus. Two additional authors made a general revision of the whole text.

Results

Search results

Six hundred and ninety potentially relevant articles were retrieved by the search, and 238 articles were excluded due to search overlap. Based on title and abstract, 383 articles were excluded because the population or the exposure of the study did not meet our inclusion/exclusion criteria. A flow diagram of the article selection process is depicted in Fig. 1. Of the 69 studies selected for full-text examination, 56 were excluded because after full-text review it became apparent that the primary objective of these studies was not the effect of the situation at the beginning of dialysis on prognosis or due to cross-sectional study/no follow-up results after dialysis. Finally, 13 studies were reviewed in detail and included in this review. The characteristics of these studies can be found in Table 1.

Fig. 1
figure 1

PRISMA flow chart for paper selection

Full size image
Table 1 Characteristics and risk of bias of the included studies
Full size table

Characteristics of selected studies

Thirteen studies were reviewed, among which four were prospective [9, 15, 16, 18] and nine were retrospective cohort studies [8, 10,11,12,13,14, 17, 19, 20]. Six studies were published in 2017 [9, 15,16,17, 19, 20], one study was published in 2018 [18] and one in 2019 [8], four studies were published in 2020 [11,12,13,14] and the most recent in 2021 [10]. The smallest study included 72 patients [12] and the largest included 10 692 patients [8]. Four studies included only haemodialysis patients [11, 14, 17, 18], three studies only peritoneal dialysis patients [9, 12, 13] and the rest included both. All but two studies used Cox proportional hazards regression to calculate hazard ratios (HRs) for mortality. The study about urgent vs. early-start peritoneal dialysis by Silva et al. [12] was the one study that did not use Cox regression and used first 30-day complications, 6-month hospitalization events and 6-month dropout as outcomes. The nationwide cohort study from Sweden was the one study which estimated the effect of each dialysis initiation strategy on 5-year all-cause mortality and major adverse cardiovascular events by using a weighted pooled logistic regression model [10].

Quality and risk of bias

For quality assessment, the Newcastle–Ottawa score of these 13 studies was 6 to 7. A detailed overview of the characteristics of the 13 studies is displayed in Table 1. In the absence of RCT studies, observational studies on timing of dialysis initiation face immortal time bias, selection/survivor bias, and lead time bias. Some studies provided strategies in the study design, data collection and statistical analysis phases to eliminate these biases; specifically, as follows: propensity score matching (PSM) [15], survival time counted from the time of dialysis initiation and/or from a common starting point (for example: GFR 20 mL/min/1.73m2) [16], target trial emulation using cloning, censoring and weighting [10]. By applying these methods, well conducted observational studies could provide strong evidences for clinical decisions. The possible causes of heterogeneity among study results were regional and ethnic discrepancy, and different types of dialysis, especially the disparate definitions of early dialysis. For example, some studies defined early dialysis in terms of GFR levels, while other studies are defined by a comprehensive determination of laboratory indicators (such as hemoglobin, serum albumin, blood urea nitrogen, serum creatinine, potassium, phosphorus, and so on) and/or clinical symptoms (including acute heart failure, pulmo-nary edema or hypertension that was difficult to control with medication).

Study outcomes

Mortality

Four studies showed that patients with an optimal start of renal replacement therapy or patients who started dialysis at higher eGFR levels have a better survival. Martínez et al. [8] observed that these patients with an optimal start of dialysis (haemodialysis or peritoneal dialysis) have a greater survival than those who had a non-optimal start. The optimal start was defined when all the following criteria were met: a planned dialysis start, a minimum of 6-month follow-up by a nephrologist, and a first dialysis method coinciding with the one registered at 90 days. This result remained present and did not change materially after adjustment for sex, age, primary renal disease and dialysis modality [HRCrude = 0.635 (95% CI 0.598–0.674), P < 0.001 versus HRAdj = 0.669 (95% CI 0.628–0.712), < 0.001]. Matthew et al. [19] also found patients initiating dialysis therapy due to volume overload may have increased risk for mortality compared with patients initiating routine dialysis due to laboratory evidence of kidney function decline. Adjusting for demographic variables, coexisting illnesses, and estimated glomerular filtration rate, initiation of dialysis therapy for volume overload or hypertension was associated with 1.69 (95% CI, 1.02–2.80) times higher risk for subsequent mortality compared to initiation for laboratory evidence of kidney function decline.

Fu et al. [10] compared 15 dialysis initiation strategies with eGFR values ranging between 4 and 19 mL/min/1.73m2 in increments of 1 mL/min/1.73 m2 and observed that dialysis initiation at eGFR15-16 was associated with a 5.1% (95% CI 2.5% to 6.9%) lower absolute 5-year mortality risk compared with initiation at eGFR6-7. The 5.1% absolute risk difference corresponded to a mean postponement of death of 1.6 months over 5 years of follow-up. Prasad et al. [9] included exclusively patients with peritoneal dialysis in a prospective study and found that patient survival were better in higher baseline GFR groups. The 1-, 2-, 3-, and 5-year patient survival in patients with GFR ≤ 5 ml/min/1.73 m2 were 78.2%, 41.9%, 24.8%, and 7.8%; GFR between > 5 and 10 ml/min/1.73 m2 were 87.2%, 64.8%, 43.1%, and 19.1%; and GFR > 10 ml/min/1.73 m2 were 91.6%, 74.1%, 51.1%, and 20.2%; respectively. Compared to patients with GFR > 10 ml/min/1.73 m2, both patients with GFR ≤ 5 ml/min/1.73 m2 (HR—3.42, 95% CI—1.85–6.30, P = 0.000) and patients with GFR between > 5 and 10 ml/min/1.73 m2 (HR—2.16, 95% CI—1.26–3.71, P = 0.005) had higher risk of mortality in the adjusted model.

Escoli et al. [17] and Liang et al. [20] were the only studies observing higher all-cause mortality in the early starters. Escoli et al. [17] included just patients with haemodialysis and revealed early dialysis initiation with an eGFR of ≥ 10 mL/min per 1.73 m2 was associated with an increased mortality risk compared with the patients with an eGFR of < 10 mL/min per 1.73 m2 (P = 0.027), arguing against aggressive early dialysis initiation based primarily on eGFR alone. Independent factors (P < 0.05) associated with mortality in the multivariable Cox model in early dialysis start were: hypertension (HR 9.32, CI: 1.34–17.87), diabetes (HR 1.8, CI: 0.4–13.2) and albumin < 3.5 g/dL (HR 1.5, CI: 0.8–6.2). Liang et al. [20] found both early (eGFR ≥ 10 ml/min/1.73 m2) and intermediate (5 ml/min/1.73 m2 ≤ eGFR < 10 ml/min/1.73 m2) dialysis initiation groups were at greater risk of death relative to late (eGFR < 5 ml/min/1.73 m2) dialysis (Early: HR = 1.91; Intermediate: HR = 1.23) in adjusted analysis. The findings were further stratified by age and observed that early versus later initiation of dialysis was associated with significantly higher risk of mortality in Singapore’s non-elderly population, but not in patients aged 65 years or older (p = 0.12).

The remaining six studies all showed that the early start of dialysis had no association with the prognosis of survival, of which three from Chinese HD patients. Liu et al. [11] demonstrated that after adjusting for effectors of age, gender, diabetes, type of vascular access at initiation, clinical signs, and/or symptoms at the initiation of dialysis, and serum albumin, there was no significant difference in survival rate between the 3 groups (< 4 mL/min/1.73 m2 was used as the reference, in comparison with 4–8 mL/min/1.73 m2 [p = 0.681] and > 8 mL/min/1.73 m2 [p = 0.403]). Chang et al. [14] also found the fully adjusted hazards ratios of mortality for the late (3–5indicators) and very late (6–7 indicators) groups were 0.97 (95% confidence interval 0.76–1.24) and 0.83 (0.61–1.15) compared with the standard (met 0–2 uremic indicators) group. The 7 uremic indicators that reached the predefined threshold in case period, namely hemoglobin, serum albumin, blood urea nitrogen, serum creatinine, potassium, phosphorus, and bicarbonate. So the study concluded that it is safe to defer dialysis initiation among patients with CKD having an eGFR of < 5 mL/min/1.73 m2 even when patients having multiple biochemical uremic burdens. Zhang et al. [18] in a prospective observational cohort study indicated that Charlson comorbidity index, cerebrovascular diseases and chronic obstructive pulmonary disease were significantly associated with mortality, but not eGFR at the dialysis initiation by multivariate Cox regression analysis. Furthermore, stratified analyses confirmed elevated eGFR that had no advantage on long‑term prognosis. Therefore, the long‑term prognosis of patients with high eGFRs prior to hemodialysis was not improved.

For PD patients, Nathaphop et al. [13] found that a slightly lower median survival time (35 months) in early-late (eGFR > 5 ml/min/1.73m2) group than that in very late (eGFR < 5 ml/min/1.73m2) group (40 months), but the difference of the two groups were not statistically significant (p = 0.56). Park et al. [15] conducted a multicenter prospective cohort study in HD/PD elderly patients and observed that the cumulative survival rates were lower in the early initiation group, but the difference was not significant after propensity score matching (PSM) or adjusting for age, sex, Charlson comorbidity index and hemoglobin, serum albumin, serum calcium and phosphorus levels. Janmaat et al. [16] also found taking account of lead-time bias, early dialysis initiation (eGFR > 7.9, measured GFR (mGFR) > 6.6 mL/min/1.73 m2) was not associated with an improvement in survival in HD/PD patients and suggested that in some patients, dialysis could be started even later than an eGFR < 5.7 and mGFR < 4.3 mL/min/1.73 m2.

Cardiovascular events

Cardiovascular events included cardiovascular death, non-fatal myocardial infarction, admission for ischemic heart disease, congestive heart failure, arrhythmia, or cerebrovascular disease. Fu et al. [10] showed that compared with dialysis initiation at eGFR6-7, initiation at eGFR15-16 was associated with a 2.9% (0.2% to 5.5%) lower risk of a major adverse cardiovascular event, corresponding to hazard ratios of 0.94 (0.91 to 0.98) and concluded that very early initiation of dialysis was associated with a modest reduction in cardiovascular events. However, Park et al. [15] indicated that differences in the cumulative cardiovascular event-free survival rates between early and late dialysis groups in elderly Korean patients were not observed before and after PSM.

Technique failure

Prasad et al. [9] and Nathaphop et al. [13] investigated technique failure on peritoneal dialysis. Prasad et al. [9] found initial mGFR of ≤ 5 ml/min/1.73 m2 was significant risk factor for discontinuation of PD as compared to others (vs. GFR > 10 ml/min/1.73 m2; HR—3.42, 95% CI—1.63–7.15, P = 0.001 and vs. GFR between > 5 and 10 ml/min/1.73 m2; HR—2.83, 95% CI—1.83–4.33, P = 0.004). Therefore, initiation of PD at a lower baseline mGFR is associated with poorer technique survival in Indian ESKD patients. On the contrary, Nathaphop et al. [13] observed that the median time to technique failure in early-late group and very late group were similar (25 months). The log rank test of the two curves were not statistically significant different.

Quality of life and other outcomes

Park et al. [15] also investigated the 1-year changes in the Kidney Disease Quality of Life-36 (KDQOL-36) survey, KPS values, Beck’s depression inventory (BDI) values, and SGA scores in elderly dialysis population. They showed that although the early initiation group showed a lower physical component summary score on the KDQOL-36 3 months after dialysis, the difference in scores was not significant 12 months after dialysis. Furthermore, the difference was not significant after PSM. The Karnofsky performance scale, Beck’s depression inventory, and subjective global assessments were not significantly different 3 and 12 months after dialysis initiation.

Silva et al. [12] just compared 30-day complications and 6-month hospitalization and dropout rate in patients that started PD therapy defined as urgent and early-start and found no differences between Urgent-Start-PD and Early-Start-PD regarding first 30-day complications, 6-month hospitalization, and dropout events were found.

Discussion

Currently, clinical practice guidelines [3,4,5,6] recommend that: decision to initiate maintenance dialysis primarily depends on clinical signs and symptoms which may be attributed to uremic syndrome. In this regard, the Improving Global Outcomes (KDIGO) CKD Work Group suggested that the decision is usually occurring within the GFR range between 5 and 10 ml/min/1.73 m2″ [3, 6]. The Additionally, the Canadian Society of Nephrology suggested that in the absence of these factors,the eGFR should only serve as a sole criterion for the initiation of dialysis if it is 6 mL/min/1.73m2 or less”; [4]. The Japanese Society for Dialysis Therapy proposes that patients endure under conservative treatment until the GFR < 8 mL/min/1.73m2, even if symptoms of renal failure are observed and hemodialysis is recommended to be initiated prior to a GFR of 2 mL/min/1.73 m2, [21]. Our present systematic review included 13 studies of the last 5 years which investigated optimal dialysis initiation in ESKD patients, 9 of the 13 studies mainly focused on the optimal GFR of maintenance dialysis initiation; 7 studies used eGFR [10, 11, 13, 15, 17, 18, 20], 1 study used mGFR [9], 1 study used both [16]. Compared to previous studies, wider range of GFR values and more detailed data stratification were applied in the study design and data processing stages; 7 studies [9,10,11, 13, 16, 20] taken GFR ≤ 5 mL/min/1.73 m2 or even lower into account, the lowest data range was mGFR < 4.3 mL/min/1.73m2 [16] and the highest range was eGFR 15–16 mL/min/1.73 m2 [10]. 5 studies [11, 13, 15, 16, 18] showed none association between GFR and mortality or other adverse outcomes, 2 studies [17, 20] showed dialysis initiation at higher GFR levels were with poor prognosis, and 2 studies [9, 10] showed higher GFR levels with better prognosis. However, it’s worth noting that Fu et al. [10] observed a parabolic relation between eGFR and mortality, with the lowest mortality risk at eGFR15-16 mL/min/1.73m2; compared with dialysis initiation at eGFR6-7 mL/min/1.73m2, initiation at eGFR15-16 mL/min/1.73m2 was associated with a 5.1% lower absolute 5 year mortality risk and 2.9% lower risk of a major adverse cardiovascular; this 5.1% absolute risk difference corresponded to a mean postponement of death of 1.6 months over 5 years of follow-up, and dialysis would need to be started 4 years earlier; so they concluded that “although very early dialysis initiation was associated with a modest reduction in mortality and cardiovascular events, this may not outweigh the burden of a substantially longer period spent on dialysis. In recent years there has been an increase in the prevalence of elderly population, which, along with advances in dialysis technology and increasing survival of maintenance dialysis patients, lead to an increasing proportion of elder dialysis patients [22,23,24]. Two studies researched timing of dialysis initiation in elderly ESKD patients, and they both concluded that eGFR at dialysis initiation was not associated with mortality [15, 20] and quality of life [15]. So to summarize, most studies proved that GFR at dialysis initiation was not associated with mortality, timing of dialysis initiation should not be based on GFR both in all maintenance dialysis population and in elderly, which is consistent with present clinical guidelines.

In patients with ESKD, because of artificial low plasma creatinine levels in patients with fluid overload or low muscle mass, eGFR is falsely overestimated compared to their true GFR, some guidelines recommend mGFR instead of creatinine-based eGFR equations as the measure of dialysis in ESKD patients [21, 25]. However, perhaps because mGFR is simpler and easier than eGFR in clinical practice, there were 2 studies involved mGFR and showed different results; Prasad et al. [9] concluded that “initiation of chronic ambulatory peritoneal dialysis at a lower baseline mGFR is associated with poorer patient and technique survival” in Indian ESKD patients; Janmaat et al. [16] summarized that early dialysis initiation (mGFR > 6.6 mL/min/1.73m2) was not associated with an improvement in survival in dialysis PD/HD patients. This finding is similar to statistic analysis based on eGFR. Based on only the above 2 studies, we can’t draw any conclusions on to what extent mGFR is essential to determine dialysis initiation in ESKD patients; however, this does not mean that the importance and reliability of mGFR in evaluating residual renal function of ESKD patients can be denied.

Hence, a number of other studies paid attention to comprehensive assessment of uremic signs and/or symptoms for optimal dialysis initiation. Chang et al. [14] quantified uremic burden based on 7 uremic indicators that reached the predefined threshold (hemoglobin, serum albumin, blood urea nitrogen, serum creatinine, potassium, phosphorus, and bicarbonate); dialysis timing was classified as standard (met 0–2 uremic indicators), late (3–5indicators), and very late (6–7 indicators); and no correlation was found between late or very late group and mortality. Ying et al. [26] developed an equation based on fuzzy mathematics to assess the timing of haemodialysis initiation, the results showed that the combination of sex, age, serum creatinine, blood urea nitrogen, serum albumin, haemoglobin, serum phosphorus, diabetes mellitus, and heart failure as equation variables resulted in the best accuracy to prognose 3-year survival. Matthew et al. [19] categorized clinically documented primary indication for dialysis initiation into 4 groups: laboratory evidence of kidney function decline (reference category), uremic symptoms, volume overload or hypertension, and other/unknown; and found that volume overload or hypertension was associated with the highest risk for subsequent mortality. These studies highlight future directions of comprehensive evaluation of dialysis timing, especially in patients with volume overload and complications sensitive to volume changes during dialysis, mainly varied causes of cardiovascular instabilities. It is well known that the main functions of PD or HD are to remove excess volumetric loads, filter solutes and balance electrolytes. As discussed above, previous studies about dialysis timing focused on GFR, which represent functions of solutes filter and electrolytes balance, showed no positive findings. Present novel finding is that: heart failure, volume overload or hypertension at dialysis initiation was associated with the highest risk for subsequent mortality; and suggests assessments of volume load and patient’s tolerance to volume overload as prospective approaches, especially in ESKD patients with cardiovascular disease. Meanwhile, gathering more symptoms and biological disturbances compared to a start only based on GFR in future study is probably of upmost importance.

Strengths of our study include: firstly, we performed a systematic search according to a strict methodology; secondly, we provided approaches and methods for investigation of optimal dialysis initiation. Limitations: firstly, heterogeneity among the studies was quite high, with differences in sample size, variable and group characteristics; secondly, no RCT studies were included, which weakened the strength of evidences; thirdly, the review was not registered and the protocol was not prepared.

Further studies dedicated to generate evidence on this topic, while assuming recent general proposals for healthcare research [27,28,29], should diversify and innovate namely through technological solutions, apps and platforms, becoming widely available to support trial designs. Electronic informed consent (eConsent) and web-based questionnaires are two new trial elements to influence methodologies. Adoption of decentralized and hybrid clinical research designs, electronic patient-reported outcome (ePRO) to generate real-world evidence (RWE) and real-world data (RWD) and the adoption of artificial intelligence (AI), Big Data, application programming interfaces (APIs) and digital platforms expected to improve patient selection, enhance data collection, integration and analysis, while at the same time reduce time, this level of digital transformation would improve both pre-clinical and clinical research, namely on improving the available evidence on optimal initiation of maintenance dialysis in end stage kidney disease patients.

Conclusions

In conclusion, most studies proved that GFR at dialysis initiation was not associated with mortality, timing of dialysis initiation should not be based on GFR, assessments of volume load and patient’s tolerance to volume overload are prospective approaches.

Availability of data and materials

All data generated or analysed during this study are included in this published article [and its supplementary information files].

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Acknowledgements

Not applicable.

Funding

Nephropathy Medical Development Research Project of China Primary Health Care Foundation (SO.20220217SD to Xiaoyan Jia) was responsible for analysis of data and manuscript writing.

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Author notes

  1. Xiaoyan Jia and Xueqing Tang are equivalent to first authors.

Authors and Affiliations

  1. Department of Nephrology, the First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, 250014, China

    Xiaoyan Jia, Xueqing Tang & Dongmei Xu

  2. Shandong Institute of Nephrology, No.16766 Jingshi Road, Jinan, 250014, China

    Xiaoyan Jia, Xueqing Tang & Dongmei Xu

  3. Department of Nursing, the First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, 250014, China

    Yunfeng Li

  4. International Healthcare Management Research & Development Centre, Shandong Provincial Qianfoshan Hospital AND Atlantica Instituto Universitario, Gestao em Saude, Oeiras, Portugal, Jinan, 250014, China

    Paulo Moreira

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  1. Xiaoyan Jia
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  2. Xueqing Tang
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Contributions

Xiaoyan Jia, Xueqing tang, Dongmei Xu and Paulo Moreira contributed to the Conceptualization and design of the study. Xiaoyan Jia, Xueqing tang and Paulo Moreira contributed to the validation of the systematic search of the literature and selection of studies. Xiaoyan Jia, Xueqing tang and Dongmei Xu conducted data analysis and interpretation. Xiaoyan Jia and Xueqing tang drafted the first version of the article with early revision by Paulo Moreira and Yunfeng Li. All authors critically revised the article and approved the final version for submission for publication. Dongmei Xu and Paulo Moreira had full access to all the data in the study and had final responsibility for the decision to submit for publication and required revisions. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Dongmei Xu or Paulo Moreira.

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Supplementary Information

Additional file 1: Table S1.

Search terms used in the PUBMED, EMBASE and COCHRANE databases.

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Jia, X., Tang, X., Li, Y. et al. Update of dialysis initiation timing in end stage kidney disease patients: is it a resolved question? A systematic literature review. BMC Nephrol 24, 162 (2023). https://doi.org/10.1186/s12882-023-03184-4

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Keywords

BMC Nephrology

ISSN: 1471-2369

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