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Global trends in chronic kidney disease-related mortality: a systematic review protocol
  1. Somkanya Tungsanga1,2,3,
  2. Anukul Ghimire1,4,
  3. Vinash K Hariramani1,
  4. Abdullah Abdulrahman1,
  5. Ana S Khan5,
  6. Feng Ye1,
  7. Janice Y Kung6,
  8. Scott Klarenbach1,
  9. Stephanie Thompson1,
  10. David Collister1,
  11. Nattachai Srisawat3,7,8,9,
  12. Ikechi G Okpechi1,
  13. Aminu K Bello1
  1. 1Division of Nephrology and Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
  2. 2Division of General Internal Medicine, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
  3. 3Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
  4. 4Division of Nephrology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
  5. 5School of Medicine, Royal College of Surgeons in Ireland, Adliya, Bahrain
  6. 6John W. Scott Health Sciences Library, University of Alberta, Edmonton, Alberta, Canada
  7. 7Center of Excellence in Critical Care Nephrology and Critical Care Nephrology Research Unit, Chulalongkorn University, Bangkok, Thailand
  8. 8Excellence Center for Critical Care Nephrology, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
  9. 9Academy of Science, Royal Society of Thailand, Bangkok, Thailand
  1. Correspondence to Dr Somkanya Tungsanga; s.tungsanga{at}


Introduction In recent decades, all-cause mortality has increased among individuals with chronic kidney disease (CKD), influenced by factors such as aetiology, standards of care and access to kidney replacement therapies (dialysis and transplantation). The recent COVID-19 pandemic also affected mortality over the past few years. Here, we outline the protocol for a systematic review to investigate global temporal trends in all-cause mortality among patients with CKD at any stage from 1990 to current. We also aim to assess temporal trends in the mortality rate associated with the COVID-19 pandemic.

Methods and analysis We will conduct a systematic review of studies reporting mortality for patients with CKD following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We will search electronic databases, national and multiregional kidney registries and grey literature to identify observational studies that reported on mortality associated with any cause for patients with CKD of all ages with any stage of the disease. We will collect data between April and August 2023 to include all studies published from 1990 to August 2023. There will be no language restriction, and clinical trials will be excluded. Primary outcome will be temporal trends in CKD-related mortality. Secondary outcomes include assessing mortality differences before and during the COVID-19 pandemic, exploring causes of death and examining trends across CKD stages, country classifications, income levels and demographics.

Ethics and dissemination A systematic review will analyse existing data from previously published studies and have no direct involvement with patient data. Thus, ethical approval is not required. Our findings will be published in an open-access peer-reviewed journal and presented at scientific conferences.

PROSPERO registration number CRD42023416084.

  • Chronic renal failure
  • Dialysis
  • Renal transplantation
  • Systematic Review
  • Mortality

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Strengths and limitations of this study

  • We aim to investigate temporal trends in mortality among patients with any stage of chronic kidney disease (CKD) over the past 30 years.

  • In addition to electronic databases of published studies, we will use national and regional databases (registries and related surveillance systems) from around the world to provide a more comprehensive understanding of mortality among patients with CKD.

  • We will examine not only the mortality rate among patients with CKD but also changes in overall mortality and CKD-related mortality during the COVID-19 pandemic.

  • Our analysis will offer valuable insights into the effectiveness of current treatments and healthcare policies, as well as guide the development of future research and healthcare strategies.

  • Our findings may be limited by the quality of the observational studies and data registries included in the review. Patients on dialysis may have more comprehensive and organised data registries at the national or regional level compared with patients with non-dialysis CKD. This discrepancy could affect the availability and quality of data for patients with non-dialysis CKD.


The incidence of mortality in patients with chronic kidney disease (CKD) has increased in recent decades. The 2013 Global Burden of Disease (GBD) study revealed that although the overall age-standardised mortality rate decreased by 80% between 1990 and 2013, the age-standardised deaths attributable to CKD increased by 36.9%. Consequently, CKD rose from the 36th to the 19th leading cause of death and disability globally in 2013, especially in regions such as Latin America, Southeast and East Asia, Oceania, North Africa and the Middle East, where there is a high prevalence of CKD.1

Subsequent GBD reports indicated that CKD became the 13th most common cause of death in 20162 and the 12th most common cause of death in 2017.3 The prevalence of all-age mortality associated with CKD increased by 41.5% between 1990 and 2017.3 CKD also emerged as one of the top 10 causes of disability-adjusted life years for people aged 50 years or more, with high costs related to the treatment of kidney failure.2 With this escalating trend, CKD is predicted to become the fifth leading cause of years of life lost by 2040.4

Several factors contribute to mortality among patients with CKD. Cardiovascular disease is the leading cause of mortality among patients whose estimated glomerular filtration rate has decreased to less than 60 mL/min/1.73 m2.5 6 In the USA, the age-adjusted mortality rate associated with CKD rose by 50% between 1999 and 2020; notably, 39% of all deaths were attributed to cardiovascular disease,5 but GBD reports did not indicate what percentage of those deaths were indirectly related to CKD. Furthermore, deaths from acute kidney injury (AKI), which co-occur with CKD, were not reported. Thus, the true burden of CKD-related mortality could be underestimated.

Patients with CKD who require dialysis are at increased risk of complications from dialysis treatment. Moreover, patients who are older and/or have more comorbidities have higher mortality rates than those who progress to kidney failure, even if they do not receive dialysis.7 8 Mortality rates vary among different modalities of kidney replacement therapy (KRT). Those who receive kidney transplants have a lower mortality rate than those who remain on dialysis,9 10 with haemodialysis and peritoneal dialysis increasing risk of cardiovascular mortality.11 Patients who receive haemodialysis at home or frequent in-centre haemodialysis may have lower mortality rates than those receiving conventional in-centre haemodialysis.12 Early referral to a nephrologist and timely initiation of dialysis can also improve survival rates among kidney failure patients.13 14 These factors contribute to variations in mortality among countries based on differences in availability and access to various modalities of KRT.15

Patients with CKD and kidney failure are susceptible to immune dysregulation and infection, particularly those receiving KRT. Pre-existing CKD increases the risk of COVID-19 infection and AKI, worsening outcomes, including in-hospital mortality and exacerbating kidney injuries.16 Since 2019, the coronavirus pandemic has contributed to morbidity and mortality among patients with CKD. A recent systematic review and meta-analysis of 348 studies worldwide demonstrated that patients with both CKD and COVID-19 infection had higher mortality rates than those without infection.17 The risk of hospitalisation and all-cause mortality increased by 63% and 48%, respectively, among patients with patients and had COVID-19 infection.18 Thus, the COVID-19 pandemic may have impacted the rate of change in CKD-related mortality over the past 5 years and may continue to do so in the future.

The primary aim is to conduct a systematic review of the trends (rates per million population) in mortality across the full spectrum of CKD (non-dialytic CKD, dialysis and kidney transplant populations) from January 1990 to date. The study also aims to assess changes in the overall mortality rate during the COVID-19 pandemic period. The specific objectives are:

  1. Determine the burden and changes over time in mortality risk in patients with CKD across the entire spectrum.

  2. Conduct a stratified analysis on the impact of population demographics, geographic and clinical factors on the trend in mortality risk in the studied population.

  3. Outline the mortality rate, cause of deaths and trends across the substrata of patients by CKD status (non-dialytic CKD, haemodialysis, peritoneal dialysis, kidney transplant).


Study design

We will conduct a systematic review of studies reporting mortality for patients with CKD following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Protocols 2015 (PRISMA-P-2015)19 and the PRISMA 2020 methodological guidelines (PRISMA 2020).20 The review will include all original peer-reviewed observational studies published from 1990 to date involving patients with CKD, regardless of age, geographic area or stage of disease, that reported on their rate of mortality from any cause. All stages of CKD (stages G1–5) as defined by KDIGO (Kidney Disease-Improving Global Outcomes) criteria,21 patients undergoing dialysis (haemodialysis and peritoneal dialysis) and kidney transplant recipients. Operational definitions are specified in table 1. Studies that do not provide an operational definition of CKD will not be included. Clinical trials will also be excluded from this systematic review because they may not reflect the true mortality rates in the general population due to influences of the interventions or treatments being studied. Non-English language articles will be considered with translation.

Table 1

Operational definitions used in the systematic review

Inclusion criteria

  1. Studies conducted in patients with CKD (stages 1–5, dialysis and transplant) across all ages.

  2. Studies reporting mortality from any cause in patients with CKD.

  3. National- or regional-based cross-sectional or cohort studies.

  4. Publication date from 1 January 1990.

  5. No restriction on language.

Exclusion criteria

  1. Studies conducted in patients with acute care settings, including critical illness and hospitalisation.

  2. Studies that included patients with CKD as a subpopulation.

  3. Studies conducted exclusively on patients with a specific cause of CKD.

  4. Studies that do not provide an operational definition of CKD.

  5. Clinical trials, review articles, case studies, case reports, case series, images, editorials, letters to editors and commentaries.

  6. Studies where we cannot obtain relevant data.

  7. Studies reporting only mortality rate before 1990.

  8. Duplicate of articles with multiple publications.

Study process

This study will comprise four sections regarding CKD/dialysis status as follows:

  1. Patients undergoing long-term haemodialysis, including in-centre and home haemodialysis.

  2. Patients undergoing long-term peritoneal dialysis.

  3. Kidney transplant recipients.

  4. Patients with non-dialysis CKD defined by KDIGO criteria21

The data of each CKD/dialysis/transplant status population will be extracted, analysed and displayed separately.

Search strategy

The research librarian (JYK) collaborated in the development of the search strategy, which will involve an exhaustive exploration of electronic databases, as well as national and multiregional databases (online supplemental table S1), to identify eligible studies. The list of controlled vocabulary search terms (see online supplemental table S2) developed for the Ovid MEDLINE search strategy will be adapted for other databases. Any additional eligible publications will also be identified through manual searches. To ensure the inclusiveness of our research, we will also search for grey literature, including proceedings, organisational reports, policy papers and working papers, with the assistance of the research librarian (JYK).

Study outcomes

  1. Primary outcome

    1. Temporal trend in mortality rates stratified by era of the study by decade (1990–2000, 2001–2010, 2011–current).

  2. Secondary outcomes

    1. Differences in the mortality rate before and during the COVID-19 pandemic (after 2019).

    2. A distribution of attributable causes (pattern) of death.

    3. Temporal trends in mortality, including all-cause mortality versus CKD-related mortality, as well as across CKD stages, World Bank country classifications, income levels and demographic characteristics.

Data sources

Sources of data will include published studies in electronic databases (including Ovid MEDLINE, Ovid Embase, Cochrane Library (via Wiley), CINAHL, ProQuest Dissertations & Theses Global, Web of Science Core Collection and WHO ICTRP). The first 200 results from Google Scholar will also be evaluated for inclusion. Grey literature will include national and multiregional renal registries of CKD and KRT (online supplemental table S1), including the United States Renal Data System, European Renal Association-European Dialysis and Transplant Association Registry, United Kingdom Renal Registry, Australian and New Zealand Renal Registry, Latin American Dialysis and Transplant Registry, French Chronic Kidney Disease-Le Reseau Epidemiologie et Information en Nephrologie and Dialysis Outcomes and Practice Patterns Study. Kidney transplantation registries (Global Observatory on Donation and Transplantation, Scientific Registry of Transplant Recipients, Canadian Transplant Registry) and WHO reports will also be included.

Data collection and analysis

The study selection process is summarised in the PRISMA flow diagram (figure 1). We will use a two-stage collaborative review process. First, four reviewers (ST, AG, VKH and AA) will independently review titles and abstracts to screen the retrieved studies. In order for a study to be included or excluded in the full-text review, it must receive a favourable vote from at least two of the four reviewers. Then, full texts of selected studies will be examined by two reviewers (ST and AG) to determine their eligibility for inclusion. Studies will be included at each stage when there is consensus between the two reviewers (ST and AG). If there is a conflict between the two reviewers, an adjudicator (IO) will make the final decision. Reasons for exclusion will be reported.

Figure 1

Study selection process. *Other sources will include online publications, scientific abstracts, proceedings, organisational reports and policy papers.

Data extraction and management

Two reviewers will independently extract and enter the data into the standardised forms. Extracted data will include the type and scope of the study, publication year, first author, study site and country, study population, demographic information, comorbidities, stage of CKD, dialysis type, dialysis vintage, withdrawal from dialysis, kidney transplant status, kidney transplant vintage, COVID-19 infection, other infection, malignancy, death from any cause, disease-specific mortality and uncategorised mortality. In case of conflicts, an adjudicator will be responsible for resolving any discrepancies.

Assessment of risk of bias in included studies

The risk of bias in the included studies will be determined using the Cochrane Risk Of Bias In Non-randomized Studies-of Exposure (ROBINS-E) tool.22 23 The quality of evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation methodology.24 We will present the risk of bias for each study in a risk of bias summary table. Publication bias will be assessed using the regression-based test and inspecting funnel plots if more than 10 studies reported the data for each outcome.

Data synthesis and analysis

We will calculate relative risk values with 95% CIs to determine the rate of change in mortality over time and report secular trends by CKD status and regional groups. Missing data will be noted in the data extraction form and reported in the risk of bias section. Heterogeneity will be quantified using I2 statistics in each analysis. If there is high statistical heterogeneity between studies, defined as I2>50%, we will describe the results and perform a narrative synthesis in accordance with the Synthesis Without Meta-analysis reporting guideline.25 If an adequate number of studies with reasonable methodological heterogeneity can be retrieved, we will perform meta-analyses using a random effects model in Stata/MP V.17.0 (StataCorp) and present the pooled proportions of included studies in a forest plot. Sensitivity analysis will be conducted to evaluate the influence of individual study.

Subgroup analyses will be conducted by age, gender, pre-COVID-19 and post-COVID-19 pandemic, cause of death, CKD/dialysis status (eg, non-dialysis, haemodialysis, peritoneal dialysis and kidney transplantation), country, region and income based on World Bank country classifications (eg, low, lower-middle, upper-middle and high income). We will perform meta-regression to identify potential explanations for the observed between-study heterogeneity.

Patient and public involvement

This is a study protocol for a systematic review, which does not require patient involvement. No additional patient data will be collected during the study.


We plan to collect and organise our data between April and August 2023 and plan to analyse our data and compile the results from September to December 2023. From January to June 2024, we will engage in knowledge translation activities to disseminate our findings to the public (figure 2).

Ethics and dissemination

A systematic review involves analysing existing data from previously published studies. Thus, ethical approval is not required. Our findings will be published in an open-access peer-reviewed journal and presented at scientific conferences.


Global data on the risk and trend in mortality in patients with CKD across the spectrum is limited particularly for patients on KRT. Events in recent years including the COVID-19 pandemic have led to an alarming rate in mortality risk among patients living with CKD, dialysis or transplant. The overarching goal of this review is to provide a comprehensive global overview of mortality burden and trends over time among patients living with various forms of kidney diseases using data available in electronic databases as well as national and regional databases around the world. This can provide a broader view of mortality, particularly for dialysis patients, who tend to have more organised data registries. In addition to examining the temporal trend in all-cause mortality, our analysis will explore changes in mortality rates during the COVID-19 pandemic, CKD-related mortality and other factors associated with mortality among patients with CKD. By understanding the mortality rate and causes of death in patients with CKD, healthcare providers and policymakers can identify areas for improvement in the management and prevention of CKD and its complications. This knowledge can also aid in the development of targeted interventions to reduce mortality and improve the quality of life of this patient population. Moreover, studying mortality trends from 1990 can provide insights into the effectiveness of current treatments and healthcare policies and guide the development of future research and healthcare strategies.

Ethics statements

Patient consent for publication



  • Twitter @janicekung, @StephanieTh11

  • Contributors ST, AG, FY, JYK, IO and AKB developed the concept and drafted the manuscript. ST produced figures for the manuscript. ST and JYK drafted the search strategy. ST registered the study with PROSPERO. ST, AG, VKH, AA, ASK, FY, JYK, SK, ST, DC, NS, IO and AKB were involved in developing the protocol methods and revising the manuscript. All authors approved the final version of the protocol to be published.

  • Funding This research received no specific grants from any funding agency in the public, commercial or not-for-profit sectors. ST receives supports from the International Society of Nephrology (ISN)-Salmasi funded Fellowship and the Kidney Foundation of Thailand.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.