Global health inequalities of chronic kidney disease: a meta-analysis.

BACKGROUND AND HYPOTHESIS: Chronic kidney disease (CKD) is a significant contributor to global morbidity and mortality. This study investigated disparities in age, sex and socio-economic status in CKD and updated global prevalence estimates through systematic review and meta-analysis. METHODS: Five databases were searched from 2014 to 2022, with 14 871 articles screened, 119 papers included and data analysed on 29 159 948 participants. Random effects meta-analyses were conducted to determine overall prevalence, prevalence of stages 3-5 and prevalence in males/females. Influences of age, sex and socio-economic status were assessed in subgroup analyses, and risk of bias assessment and meta-regressions were conducted to explore heterogeneity. RESULTS: Overall prevalence of CKD was 13.0% (11.3-14.8%) and 6.6% (5.6-7.8%) for stages 3-5. Prevalence was higher in studies of older populations (19.3% for stages 1-5, 15.0% for stages 3-5) and meta-regression demonstrated association of age, body mass index, diabetes and hypertension with prevalence of stages 3-5. The prevalence of CKD stages 1-5 was similar in males and females (13.1% versus 13.2%) but prevalence of stages 3-5 was higher in females (6.4% versus 7.5%). Overall prevalence was 11.4%, 15.0% and 10.8% in low, middle and high-income countries respectively; for stages 3-5 prevalence was 4.0%, 6.7% and 6.8%, respectively. Included studies were at moderate-high risk of bias in the majority of cases (92%), and heterogeneity was high. CONCLUSION: This study provides a comprehensive assessment of CKD prevalence, highlighting important disparities related to age, sex and socio-economic status. Future research should focus on targeted screening and treatment approaches, improving access to care and more effective data monitoring, particularly in low or middle income countries.

Recovery of kidney function after acute kidney disease-a multi-cohort analysis.

BACKGROUND: There are no consensus definitions for evaluating kidney function recovery after acute kidney injury (AKI) and acute kidney disease (AKD), nor is it clear how recovery varies across populations and clinical subsets. We present a federated analysis of four population-based cohorts from Canada, Denmark and Scotland, 2011-18. METHODS: We identified incident AKD defined by serum creatinine changes within 48 h, 7 days and 90 days based on KDIGO AKI and AKD criteria. Separately, we applied changes up to 365 days to address widely used e-alert implementations that extend beyond the KDIGO AKI and AKD timeframes. Kidney recovery was based on resolution of AKD and a subsequent creatinine measurement below 1.2× baseline. We evaluated transitions between non-recovery, recovery and death up to 1 year; within age, sex and comorbidity subgroups; between subset AKD definitions; and across cohorts. RESULTS: There were 464 868 incident cases, median age 67-75 years. At 1 year, results were consistent across cohorts, with pooled mortalities for creatinine changes within 48 h, 7 days, 90 days and 365 days (and 95% confidence interval) of 40% (34%-45%), 40% (34%-46%), 37% (31%-42%) and 22% (16%-29%) respectively, and non-recovery of kidney function of 19% (15%-23%), 30% (24%-35%), 25% (21%-29%) and 37% (30%-43%), respectively. Recovery by 14 and 90 days was frequently not sustained at 1 year. Older males and those with heart failure or cancer were more likely to die than to experience sustained non-recovery, whereas the converse was true for younger females and those with diabetes. CONCLUSION: Consistently across multiple cohorts, based on 1-year mortality and non-recovery, KDIGO AKD (up to 90 days) is at least prognostically similar to KDIGO AKI (7 days), and covers more people. Outcomes associated with AKD vary by age, sex and comorbidities such that older males are more likely to die, and younger females are less likely to recover.

The effect of adverse childhood experiences on chronic pain and major depression in adulthood: a systematic review and meta-analysis.

BACKGROUND: Adverse childhood experiences have been linked to increased multimorbidity, with physical and mental health consequences throughout life. Chronic pain is often associated with mood disorders, such as major depressive disorder (MDD); both have been linked to adverse childhood experiences. It is unclear how the effect of adverse childhood experiences on neural processing impacts on vulnerability to chronic pain, MDD, or both, and whether there are shared mechanisms. We aimed to assess evidence for central neural changes associated with adverse childhood experiences in subjects with chronic pain, MDD, or both using systematic review and meta-analysis. METHODS: Electronic databases were systematically searched for neuroimaging studies of adverse childhood experiences, with chronic pain, MDD, or both. Two independent reviewers screened title, abstracts, and full text, and assessed quality. After extraction of neuroimaging data, activation likelihood estimate meta-analysis was performed to identify significant brain regions associated with these comorbidities. RESULTS: Forty-nine of 2414 studies were eligible, of which 43 investigated adverse childhood experiences and MDD and six investigated adverse childhood experiences and chronic pain. None investigated adverse childhood experiences, chronic pain, and MDD together. Functional and structural brain abnormalities were identified in the superior frontal, lingual gyrus, hippocampus, insula, putamen, superior temporal, inferior temporal gyrus, and anterior cerebellum in patients with MDD exposed to adverse childhood experiences. In addition, brain function abnormalities were identified for patients with MDD or chronic pain and exposure to adverse childhood experiences in the cingulate gyrus, inferior parietal lobule, and precuneus in task-based functional MRI studies. CONCLUSIONS: We found that adverse childhood experiences exposure can result in different functional and structural brain alterations in adults with MDD or chronic pain compared with those without adverse childhood experiences. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42021233989.

Incidence and Outcomes of Patients Receiving Chronic Kidney Replacement Therapy Admitted to Scottish ICUs Between 2009 and 2019-A National Observational Cohort Study.

OBJECTIVES: To determine the incidence and characteristics of ICU admissions in the Scottish population of patients treated with chronic kidney replacement therapy (KRT) over an 11-year period and determine factors associated with post-ICU admission mortality. DESIGN: Retrospective observational cohort study. SETTING: We analyzed admissions to Scottish intensive care environments between January 1, 2009, and December 31, 2019. PATIENTS: All patients receiving chronic KRT-including maintenance dialysis and kidney transplant-in Scotland. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Descriptive statistics and factors associated with mortality using logistic regression and Cox proportional hazard models. From 10,657 unique individuals registered in the Scottish Renal Registry over the 11-year study period and alive as of January 1, 2009, 1,402 adult patients were identified as being admitted to a Scottish critical care setting. Between 2009 and 2019, admissions to ICU increased in a nonlinear manner driven by increases in admissions for renal causes and elective cardiac surgery. The ICU admission rate was higher among patients on chronic dialysis than in kidney transplant recipients (59.1 vs 19.9 per 1,000 person-years), but post-ICU mortality was similar (about 24% at 30 d and 40% at 1 year). Admissions for renal reasons were most common (20.9%) in patients undergoing chronic dialysis, whereas kidney transplant recipients were most frequently admitted for pneumonia (19.3%) or sepsis (12.8%). Adjusted Cox PH models showed that receiving invasive ventilation and vasoactive drugs was associated with an increased risk of death at 30 days post-ICU admission (HR, 1.75; 95% CI, 1.28-2.39 and 1.72; 95% CI, 1.28-2.31, respectively). CONCLUSIONS: With a growing population of kidney transplant recipients and the improved survival of patients on chronic dialysis, the number of ICU admissions is rising in the chronic KRT population. Mortality post-ICU admission is high for these patients.

Patient outcomes following AKI and AKD: a population-based cohort study.

BACKGROUND: Acute kidney injury (AKI) is common and associated with adverse outcomes as well as important healthcare costs. However, evidence examining the epidemiology of acute kidney disease (AKD)-recently defined as AKI persisting between 7 and 90 days-remains limited. The aims of this study were to establish the rates of early AKI recovery, progression to AKD and non-recovery; examine risk factors associated with non-recovery and investigate the association between recovery timing and adverse outcomes, in a population-based cohort. METHODS: All adult residents of Tayside & Fife, Scotland, UK, with at least one episode of community or hospital-managed AKI using KDIGO creatinine-based definition during the period 1 January 2010 to 31 December 2018 were identified. Logistic regression was used to examine factors associated with non-recovery, and Cox modelling was used to establish associations between AKI recovery timing and risks of mortality and development of de novo CKD. RESULTS: Over 9 years, 56,906 patients with at least one AKI episode were identified with 18,773 (33%) of these progressing to AKD. Of those progressing to AKD, 5059 (27%) had still not recovered at day 90 post AKI diagnosis. Risk factors for AKD included: increasing AKI severity, pre-existing cancer or chronic heart failure and recent use of loop diuretics. Compared with early AKI recovery, progression to AKD was associated with increased hazard of 1-year mortality and de novo CKD (HR = 1.20, 95% CI 1.13 to 1.26 and HR = 2.21, 95% CI 1.91 to 2.57 respectively). CONCLUSIONS: These findings highlight the importance of early AKI recognition and management to avoid progression to AKD and long-term adverse outcomes.

Systematic review and meta-analysis of prophylaxis use with intravenous contrast exposure to prevent contrast-induced nephropathy.

PURPOSE: Iodinated radiographic contrast media has been associated with an acute deterioration in renal function, termed contrast induced nephropathy (CIN). This review aims to establish the efficacy of prophylaxis interventions used in adult patients prior to intravenous exposure to iodinated contrast to reduce the risk of CIN. METHODS: An electronic search for published peer-reviewed articles was performed, supplemented with manual review of references from previous systematic reviews and the National Institute for Health and Care Excellence guidelines. Risk of bias was assessed using the Cochrane Collaboration's tool for assessing risk of bias. Random-effect meta-analyses were used to assess CIN incidence, need for kidney replacement therapy (KRT), mortality, fluid overload and persistent kidney dysfunction. RESULTS: 22 studies assessing a range of interventions were included in the qualitative analysis. The incidence of CIN was reduced by the use of N-acetylcysteine compared to a control group of saline (risk difference = -0.07, 95% CI -0.13 to -0.01) but not by sodium bicarbonate compared to control group of saline (risk difference = -0.02, 95% CI -0.04 to 0.01). Published studies give no indication that prophylactic interventions have significant impact on the need for KRT, mortality or persistent renal impairment. CONCLUSION: Evidence for prophylaxis against CIN in patients receiving intravenous iodinated contrast is limited. There was an association with the use of NAC with reduced incidence of CIN following intravenous contrast but there was no impact on other clinical outcomes assessed. The clinical significance of these findings remains unclear and further research focusing on these clinical outcomes is required.

Cardiovascular outcomes in patients with chronic kidney disease and COVID-19: a multi-regional data-linkage study.

BACKGROUND: Data describing cardiovascular outcomes in patients with coronavirus disease 2019 (COVID-19) and chronic kidney disease (CKD) are lacking. We compared cardiovascular outcomes of patients with and without COVID-19, stratified by CKD status. METHODS: This retrospective, multi-regional data-linkage study utilised individual patient-level data from two Scottish cohorts. All patients tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Cohort 1 between 1 February 2020 and 31 March 2021 and in Cohort 2 between 28 February 2020 and 8 February 2021 were included. RESULTS: Overall, 86 964 patients were tested for SARS-CoV-2. There were 36 904 patients (mean±sd age 61±21 years; 58.1% women; 15.9% CKD; 10.1% COVID-19 positive) in Cohort 1 and 50 060 patients (mean±sd age 63±20 years; 62.0% women; 16.4% CKD; 9.1% COVID-19 positive) in Cohort 2. In CKD patients, COVID-19 increased the risk of cardiovascular death by more than two-fold within 30 days (cause-specific hazard ratio (csHR) meta-estimate 2.34, 95% CI 1.83-2.99) and by 57% at the end of study follow-up (csHR meta-estimate 1.57, 95% CI 1.31-1.89). Similarly, the risk of all-cause death in COVID-19 positive versus negative CKD patients was greatest within 30 days (HR 4.53, 95% CI 3.97-5.16). Compared with patients without CKD, those with CKD had a higher risk of testing positive (11.5% versus 9.3%). Following a positive test, CKD patients had higher rates of cardiovascular death (11.1% versus 2.7%), cardiovascular complications and cardiovascular hospitalisations (7.1% versus 3.3%) than those without CKD. CONCLUSIONS: COVID-19 increases the risk of cardiovascular and all-cause death in CKD patients, especially in the short-term. CKD patients with COVID-19 are also at a disproportionate risk of cardiovascular complications than those without CKD.

The Impact of Vaccination on Incidence and Outcomes of SARS-CoV-2 Infection in Patients with Kidney Failure in Scotland.

BACKGROUND: Patients with kidney failure requiring KRT are at high risk of complications and death following SARS-CoV-2 infection, with variable antibody responses to vaccination reported. We investigated the effects of COVID-19 vaccination on the incidence of infection, hospitalization, and death from COVID-19 infection. METHODS: The study design was an observational data linkage cohort study. Multiple health care datasets were linked to ascertain all SARS-CoV-2 testing, vaccination, hospitalization, and mortality data for all patients treated with KRT in Scotland from the start of the pandemic over a period of 20 months. Descriptive statistics, survival analyses, and vaccine effectiveness were calculated. RESULTS: As of September 19, 2021, 93% (n=5281) of the established KRT population in Scotland had received two doses of an approved SARS-CoV-2 vaccine. Over the study period, there were 814 cases of SARS-CoV-2 infection (15.1% of the KRT population). Vaccine effectiveness rates against infection and hospitalization were 33% (95% CI, 0 to 52) and 38% (95% CI, 0 to 57), respectively. Within 28 days of a SARS-CoV-2-positive PCR test, 9.2% of fully vaccinated individuals died (7% patients on dialysis and 10% kidney transplant recipients). This compares to <0.1% of the vaccinated general Scottish population admitted to the hospital or dying due to COVID-19 during that period. CONCLUSIONS: These data demonstrate that a primary vaccine course of two doses has limited effect on COVID-19 infection and its complications in patients with KRT. Adjunctive strategies to reduce risk of both COVID-19 infection and its complications in this population are urgently required.

Analgesic use and associated adverse events in patients with chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: Treating pain in the context of chronic kidney disease (CKD) is challenging because of altered pharmacokinetics and pharmacodynamics, with an increased risk of toxicity and drug adverse events in this population. The aims of this systematic review and meta-analysis were to assess the prevalence of analgesic use and establish the risk of analgesics-related adverse events, in patients with CKD. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Medline, Embase, CINAHL, and CENTRAL were searched until January 2021. Random-effects meta-analyses and meta-regression were conducted to pool and summarise prevalence data and measures of association between analgesic use and adverse events. RESULTS: Sixty-two studies relevant to the prevalence of analgesic use and 33 to analgesic-related adverse events were included, combining data on 2.3 and 3 million individuals, respectively. Pooled analyses found that 41% (95% confidence interval [CI], 35-48) of the CKD population regularly use analgesia. The annual period prevalence was estimated at 50% for opioids and 21% for nonsteroidal anti-inflammatory drugs (NSAID). Overall, 20% and 7% of patients with CKD are on chronic opioid or NSAID therapy, respectively. Opioid use was associated with an increased risk of death (1.61; 95% CI, 1.12-2.31; n= 7, I2= 91%), hospitalisation (1.38; 95% CI, 1.32-1.45; n=2, I2=0%), and fractures (1.51; 95% CI, 1.16-1.96; n=3, I2=54%). CONCLUSION: High levels of analgesic consumption and related serious adverse outcomes were found in patients with CKD. Consideration needs to be given to how these patients are assessed and managed in order to minimise harms and improve outcomes. CLINICAL TRIAL REGISTRATION: CRD42019156491 (PROSPERO).

The prevalence of pain among patients with chronic kidney disease using systematic review and meta-analysis.

Pain is a common but often undertreated symptom in patients with chronic kidney disease (CKD) with a much higher prevalence than in the general population. The aim of this systematic review was to synthesize all available quantitative evidence, in order to gain a better understanding of pain prevalence and pain types in patients with CKD. Four databases and the grey literature were searched until 15th January 2021. Random-effect meta-analyses were conducted with multiple subgroup analyses and meta-regressions to further explore the between-study heterogeneity. The quality of studies included was assessed using the Newcastle-Ottawa scale and the level of evidence was determined using the GRADE approach. One hundred sixteen studies reported data on 40,678 individuals. Results from meta-analyses yielded an overall prevalence of 60% (95% confidence interval 56-64) for pain, 48% (42-55) for chronic pain and 10% (6-15) for neuropathic pain. The prevalence of pain was lower among kidney transplant recipients 46% (37-56) compared with patients undergoing dialysis 63% (57-68) and those with non-dialysis CKD 63% (55-70). Musculoskeletal pain appeared to be the most common pain symptom among patients with CKD managed conservatively 42% (28-56) or receiving dialysis 45% (36-55) whilst abdominal pain was most prevalent in kidney transplant recipients 41% (7-86). Thus, all subgroups of patients with CKD suffer from a high burden of pain. Hence, greater awareness and recognition of this issue is vital to inform policy and service provision in this area.

Case Report: First Molecular Diagnosis of Liver Abscesses Due to Fasciola hepatica Acute Infection Imported from Vietnam.

We report a case of Fasciola hepatica liver abscesses in a 67-year-old female returning from a trip to Vietnam. She has been suffering from a fever, right abdominal pain for 4 days, and major eosinophilia. Radiologic investigations showed multiple hypodense confluent abscesses in the right lobe of the liver, complicated by occlusive thrombosis of the right branch of the portal vein. The serological investigation of helminth-elicited eosinophilia showed only a positive serology for F. hepatica. Despite repeated negative stool examinations for any intestinal pathogen, the diagnosis was established by the detection of F. hepatica DNA in stool and pus aspirate samples.