Detecting and managing the patient with chronic kidney disease in primary care: A review of the latest guidelines.

Chronic kidney disease (CKD) is a major global health problem, affecting about 9.5% of the population and 850 million people worldwide. In primary care, most CKD is caused by diabetes and/or hypertension, but a substantial proportion of cases may have alternative causes. During the early stages, CKD is asymptomatic, and many people are unaware that they are living with the disease. Despite the lack of symptoms, CKD is associated with elevated risks of cardiovascular disease, progressive kidney disease, kidney failure and premature mortality. Risk reduction strategies are effective and cost-effective but require early diagnosis through testing of the estimated glomerular filtration rate and albuminuria in high-risk populations. Once diagnosed, the treatment of CKD centres around lifestyle interventions, blood pressure and glycaemic control, and preventative treatments for cardiovascular disease and kidney disease progression. Most patients with CKD should be managed with statins, renin-angiotensin-aldosterone system inhibitors and sodium-glucose cotransporter-2 inhibitors. Additional treatment options to reduce cardiorenal risk are available in patients with diabetes, including glucagon-like peptide-1 receptor agonists and non-steroidal mineralocorticoid receptor antagonists. The Kidney Failure Risk Equation is a new tool that can support the identification of patients at high risk of progressive kidney disease and kidney failure and can be used to guide referrals to nephrology. This review summarizes the latest guidance relevant to managing adults with, or at risk of, CKD and provides practical advice for managing patients with CKD in primary care.

Participant characteristics and exclusion from phase 3/4 industry funded trials of chronic medical conditions: meta-analysis of individual participant level data.

Objectives: To assess whether age, sex, comorbidity count, and race and ethnic group are associated with the likelihood of trial participants not being enrolled in a trial for any reason (ie, screen failure). Design: Bayesian meta-analysis of individual participant level data. Setting: Industry funded phase 3/4 trials of chronic medical conditions. Participants: Participants were identified using individual participant level data to be in either the enrolled group or screen failure group. Data were available for 52 trials involving 72 178 screened individuals of whom 24 733 (34%) were excluded from the trial at the screening stage. Main outcome measures: For each trial, logistic regression models were constructed to assess likelihood of screen failure in people who had been invited to screening, and were regressed on age (per 10 year increment), sex (male v female), comorbidity count (per one additional comorbidity), and race or ethnic group. Trial level analyses were combined in Bayesian hierarchical models with pooling across condition. Results: In age and sex adjusted models across all trials, neither age nor sex was associated with increased odds of screen failure, although weak associations were detected after additionally adjusting for comorbidity (odds ratio of age, per 10 year increment was 1.02 (95% credibility interval 1.01 to 1.04) and male sex (0.95 (0.91 to 1.00)). Comorbidity count was weakly associated with screen failure, but in an unexpected direction (0.97 per additional comorbidity (0.94 to 1.00), adjusted for age and sex). People who self-reported as black seemed to be slightly more likely to fail screening than people reporting as white (1.04 (0.99 to 1.09)); a weak effect that seemed to persist after adjustment for age, sex, and comorbidity count (1.05 (0.98 to 1.12)). The between-trial heterogeneity was generally low, evidence of heterogeneity by sex was noted across conditions (variation in odds ratios on log scale of 0.01-0.13). Conclusions: Although the conclusions are limited by uncertainty about the completeness or accuracy of data collection among participants who were not randomised, we identified mostly weak associations with an increased likelihood of screen failure for age, sex, comorbidity count, and black race or ethnic group. Proportionate increases in screening these underserved populations may improve representation in trials. Trial registration number: PROSPERO CRD42018048202.

Cardiovascular Eligibility Criteria and Adverse Event Reporting in Combined Immune Checkpoint and VEGF Inhibitor Trials.

Background: Combination therapy with immune checkpoint inhibitors (ICIs) and vascular endothelial growth factor inhibitors (VEGFIs) has improved cancer outcomes and is increasingly used. These drug classes are associated with cardiovascular toxicities when used alone, but heterogeneity in trial design and reporting may limit knowledge of toxicities in patients receiving these in combination. Objectives: The aim of this study was to assess consistency and clarity in definitions and reporting of cardiovascular eligibility criteria, baseline characteristics, and cardiovascular adverse events in ICI and VEGFI combination trials. Methods: A scoping review was conducted of phase 2 to 4 randomized controlled trials of ICI and VEGFI combination therapy for solid tumors. Trial cardiovascular eligibility criteria and baseline cardiovascular characteristic reporting in trial publications was assessed, and cardiovascular adverse event definitions and reporting criteria were also examined. Results: Seventeen trials (N = 10,313; published 2018-2022) were included. There were multiple cardiovascular exclusion criteria in 15 trials. No primary trial publication reported baseline cardiovascular characteristics. Thirteen trials excluded patients with prior heart failure, myocardial infarction, hypertension, or stroke. There was heterogeneity in defining cardiovascular conditions. "Grade 1 to 4" cardiovascular adverse events were reported when incidence was ≥5% to 25% in 15 trials. Incident hypertension was recorded in all trials, but other cardiovascular events were not consistently reported. No trial specifically noted the absence of cardiovascular events. Conclusions: In ICI and VEGFI combination trials, there is heterogeneity in cardiovascular exclusion criteria, reporting of baseline characteristics, and reporting of cardiovascular adverse events. This limits an optimal understanding of the incidence and severity of events relating to these combinations. Better standardization of these elements should be pursued. (Exclusions and Representation of Patients With Kidney Disease and Cardiovascular Disease in Drug Trials of the Novel Systemic Anti-Cancer Therapies VEGF-Signalling Pathway Inhibitors Alone or in Combination With Immune Checkpoint Inhibitors; CRD42022337942).

Cystatin C- and Creatinine-based Estimated GFR Differences: Prevalence and Predictors in the UK Biobank.

Rationale & Objective: Large differences between estimated glomerular filtration rate (eGFR) based on cystatin C (eGFRcys) and creatinine (eGFRcr) occur commonly. A comprehensive evaluation of factors that contribute to these differences is needed to guide the interpretation of discrepant eGFR values. Study Design: Cohort study. Setting & Participants: 468,969 participants in the UK Biobank. Exposures: Candidate sociodemographic, lifestyle factors, comorbidities, medication usage, and physical and laboratory predictors. Outcomes: eGFRdiff, defined as eGFRcys minus eGFRcr, categorized into 3 levels: lower eGFRcys (eGFRdiff, less than -15 mL/min/1.73 m2), concordant eGFRcys and eGFRcr (eGFRdiff, -15 to < 15 mL/min/1.73 m2), and lower eGFRcr (eGFRdiff, ≥15 mL/min/1.73 m2). Analytical Approach: Multinomial logistic regression models were constructed to identify predictors of lower eGFRcys or lower eGFRcr. We developed 2 prediction models comprising 375,175 participants: (1) a clinical model using clinically available variables and (2) an enriched model additionally including lifestyle variables. The models were internally validated in an additional 93,794 participants. Results: Mean ± standard deviation of eGFRcys was 88 ± 16 mL/min/1.73 m2, and eGFRcr was 95 ± 13 mL/min/1.73 m2; 25% and 5% of participants were in the lower eGFRcys and lower eGFRcr groups, respectively. In the multivariable enriched model, strong predictors of lower eGFRcys were older age, male sex, South Asian ethnicity, current smoker (vs never smoker), history of thyroid dysfunction, chronic inflammatory disease, steroid use, higher waist circumference and body fat, and urinary albumin-creatinine ratio >300 mg/g. Odds ratio estimates for these predictors were largely inverse of those in the lower eGFRcr group. The model's area under the curve was 0.75 in the validation set, with good calibration (1.00). Limitations: Limited generalizability. Conclusions: This study highlights the multitude of demographic, lifestyle, and health characteristics that are associated with large eGFRdiff. The clinical model may identify individuals who are likely to have discrepant eGFR values and thus should be prioritized for cystatin C testing.

Estimated glomerular filtration rate (eGFR) based on cystatin C and creatinine may differ substantially within an individual. Although most clinicians are aware that creatinine is influenced by muscle mass, there are additional numerous lifestyle and health characteristics that may affect serum concentrations of either biomarker. Our analyses of 468,969 individuals in the UK Biobank identified independent predictors of large differences between eGFR based on cystatin C and eGFR based on creatinine, which may inform the interpretation of discrepant eGFR values within an individual. We developed models that may be implemented at a population level to help health systems identify individuals who are likely to have large differences between eGFR based on cystatin C and eGFR based on creatinine and thus should be prioritized for cystatin C testing.

Sex differences in cancer outcomes across the range of eGFR.

BACKGROUND AND HYPOTHESIS: People with chronic kidney disease (CKD) have increased incidence and mortality from most cancer types. We hypothesised that odds of presenting with advanced cancer may vary according to differences in eGFR, that this could contribute to increased all-cause mortality and that sex differences may exist. METHODS: Data were from Secure Anonymised Information Linkage Databank, including people with de-novo cancer diagnosis (2011-2017) and two kidney function tests within two years prior to diagnosis to determine baseline eGFR (mL/min/1.73m2). Logistic regression models determined odds of presenting with advanced cancer by baseline eGFR. Cox proportional hazards models tested associations between baseline eGFRcr and all-cause mortality. RESULTS: eGFR < 30 was associated with higher odds of presenting with advanced cancer of prostate, breast and female genital organs, but not other cancer sites. Compared to eGFR > 75-90, eGFR < 30 was associated with greater hazards of all-cause mortality in both sexes, but the association was stronger in females (female: HR 1.71, 95%CI 1.56-1.88; male versus female comparison HR 0.88, 95%CI 0.78-0.90). CONCLUSIONS: Lower or higher eGFR was not associated with substantially higher odds of presenting with advanced cancer across most cancer sites, but was associated with reduced survival. A stronger assocation with all-cause mortality in females compared to males with eGFR < 30 is concerning and warrants further scrutiny.

Cystatin C should be routinely available for estimating kidney function.

PURPOSE OF REVIEW: In this report, we summarize why the availability of cystatin C is important across a variety of clinical scenarios, the recent literature on when, why and in whom cystatin C testing should be considered, and how nephrologists can take practical steps to incorporate cystatin C testing into their practice. RECENT FINDINGS: Large intra-individual discrepancies between estimated glomerular filtration rate by creatinine (eGFRcr) and estimated glomerular filtration rate by creatinine eGFRcys (known as eGFRdiff) are observed in at least 1 in 4 people. These differences are seen more commonly among more vulnerable individuals: older adults, females, non-White individuals and those living with multiple medical conditions. A large eGFRdiff, where eGFRcys is lower than eGFRcr, is associated with a plethora of adverse outcomes, including medication-associated adverse events, acute kidney injury, cardiovascular disease, kidney failure and all-cause mortality. Among studies that have measured GFR, eGFRcr-cys usually provides the most accurate estimation of kidney function compared to mGFR, including among participants with large discrepancies between eGFRcr and eGFRcys. SUMMARY: Cystatin C improves sensitivity and specificity of chronic kidney disease diagnosis, improves detection of harmful acute and chronic changes in kidney function, improves precision of treatment eligibility and safety, and may reduce healthcare inequalities. Better education, curiosity, and motivation among nephrologists could substantially improve the availability and utilization of cystatin C.

Effects of Empagliflozin on Fluid Overload, Weight, and Blood Pressure in CKD.

SIGNIFICANCE STATEMENT: SGLT2 inhibitors reduce risk of kidney progression, AKI, and cardiovascular disease, but the mechanisms of benefit are incompletely understood. Bioimpedance spectroscopy can estimate body water and fat mass. One quarter of the EMPA-KIDNEY bioimpedance substudy CKD population had clinically significant levels of bioimpedance-derived "Fluid Overload" at recruitment. Empagliflozin induced a prompt and sustained reduction in "Fluid Overload," irrespective of sex, diabetes, and baseline N-terminal pro B-type natriuretic peptide or eGFR. No significant effect on bioimpedance-derived fat mass was observed. The effects of SGLT2 inhibitors on body water may be one of the contributing mechanisms by which they mediate effects on cardiovascular risk. BACKGROUND: CKD is associated with fluid excess that can be estimated by bioimpedance spectroscopy. We aimed to assess effects of sodium glucose co-transporter 2 inhibition on bioimpedance-derived "Fluid Overload" and adiposity in a CKD population. METHODS: EMPA-KIDNEY was a double-blind placebo-controlled trial of empagliflozin 10 mg once daily in patients with CKD at risk of progression. In a substudy, bioimpedance measurements were added to the main trial procedures at randomization and at 2- and 18-month follow-up visits. The substudy's primary outcome was the study-average difference in absolute "Fluid Overload" (an estimate of excess extracellular water) analyzed using a mixed model repeated measures approach. RESULTS: The 660 substudy participants were broadly representative of the 6609-participant trial population. Substudy mean baseline absolute "Fluid Overload" was 0.4±1.7 L. Compared with placebo, the overall mean absolute "Fluid Overload" difference among those allocated empagliflozin was -0.24 L (95% confidence interval [CI], -0.38 to -0.11), with similar sized differences at 2 and 18 months, and in prespecified subgroups. Total body water differences comprised between-group differences in extracellular water of -0.49 L (95% CI, -0.69 to -0.30, including the -0.24 L "Fluid Overload" difference) and a -0.30 L (95% CI, -0.57 to -0.03) difference in intracellular water. There was no significant effect of empagliflozin on bioimpedance-derived adipose tissue mass (-0.28 kg [95% CI, -1.41 to 0.85]). The between-group difference in weight was -0.7 kg (95% CI, -1.3 to -0.1). CONCLUSIONS: In a broad range of patients with CKD, empagliflozin resulted in a sustained reduction in a bioimpedance-derived estimate of fluid overload, with no statistically significant effect on fat mass. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03594110 ; EuDRACT: 2017-002971-24 ( https://eudract.ema.europa.eu/ ).

The Improved Kidney Risk Score in ANCA-Associated Vasculitis for Clinical Practice and Trials.

SIGNIFICANCE STATEMENT: Reliable prediction tools are needed to personalize treatment in ANCA-associated GN. More than 1500 patients were collated in an international longitudinal study to revise the ANCA kidney risk score. The score showed satisfactory performance, mimicking the original study (Harrell's C=0.779). In the development cohort of 959 patients, no additional parameters aiding the tool were detected, but replacing the GFR with creatinine identified an additional cutoff. The parameter interstitial fibrosis and tubular atrophy was modified to allow wider access, risk points were reweighted, and a fourth risk group was created, improving predictive ability (C=0.831). In the validation, the new model performed similarly well with excellent calibration and discrimination ( n =480, C=0.821). The revised score optimizes prognostication for clinical practice and trials. BACKGROUND: Reliable prediction tools are needed to personalize treatment in ANCA-associated GN. A retrospective international longitudinal cohort was collated to revise the ANCA renal risk score. METHODS: The primary end point was ESKD with patients censored at last follow-up. Cox proportional hazards were used to reweight risk factors. Kaplan-Meier curves, Harrell's C statistic, receiver operating characteristics, and calibration plots were used to assess model performance. RESULTS: Of 1591 patients, 1439 were included in the final analyses, 2:1 randomly allocated per center to development and validation cohorts (52% male, median age 64 years). In the development cohort ( n =959), the ANCA renal risk score was validated and calibrated, and parameters were reinvestigated modifying interstitial fibrosis and tubular atrophy allowing semiquantitative reporting. An additional cutoff for kidney function (K) was identified, and serum creatinine replaced GFR (K0: <250 µ mol/L=0, K1: 250-450 µ mol/L=4, K2: >450 µ mol/L=11 points). The risk points for the percentage of normal glomeruli (N) and interstitial fibrosis and tubular atrophy (T) were reweighted (N0: >25%=0, N1: 10%-25%=4, N2: <10%=7, T0: none/mild or <25%=0, T1: ≥ mild-moderate or ≥25%=3 points), and four risk groups created: low (0-4 points), moderate (5-11), high (12-18), and very high (21). Discrimination was C=0.831, and the 3-year kidney survival was 96%, 79%, 54%, and 19%, respectively. The revised score performed similarly well in the validation cohort with excellent calibration and discrimination ( n =480, C=0.821). CONCLUSIONS: The updated score optimizes clinicopathologic prognostication for clinical practice and trials.

Estimated Glomerular Filtration Rate, Albuminuria, and Adverse Outcomes: An Individual-Participant Data Meta-Analysis.

Importance: Chronic kidney disease (low estimated glomerular filtration rate [eGFR] or albuminuria) affects approximately 14% of adults in the US. Objective: To evaluate associations of lower eGFR based on creatinine alone, lower eGFR based on creatinine combined with cystatin C, and more severe albuminuria with adverse kidney outcomes, cardiovascular outcomes, and other health outcomes. Design, Setting, and Participants: Individual-participant data meta-analysis of 27 503 140 individuals from 114 global cohorts (eGFR based on creatinine alone) and 720 736 individuals from 20 cohorts (eGFR based on creatinine and cystatin C) and 9 067 753 individuals from 114 cohorts (albuminuria) from 1980 to 2021. Exposures: The Chronic Kidney Disease Epidemiology Collaboration 2021 equations for eGFR based on creatinine alone and eGFR based on creatinine and cystatin C; and albuminuria estimated as urine albumin to creatinine ratio (UACR). Main Outcomes and Measures: The risk of kidney failure requiring replacement therapy, all-cause mortality, cardiovascular mortality, acute kidney injury, any hospitalization, coronary heart disease, stroke, heart failure, atrial fibrillation, and peripheral artery disease. The analyses were performed within each cohort and summarized with random-effects meta-analyses. Results: Within the population using eGFR based on creatinine alone (mean age, 54 years [SD, 17 years]; 51% were women; mean follow-up time, 4.8 years [SD, 3.3 years]), the mean eGFR was 90 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 11 mg/g (IQR, 8-16 mg/g). Within the population using eGFR based on creatinine and cystatin C (mean age, 59 years [SD, 12 years]; 53% were women; mean follow-up time, 10.8 years [SD, 4.1 years]), the mean eGFR was 88 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 9 mg/g (IQR, 6-18 mg/g). Lower eGFR (whether based on creatinine alone or based on creatinine and cystatin C) and higher UACR were each significantly associated with higher risk for each of the 10 adverse outcomes, including those in the mildest categories of chronic kidney disease. For example, among people with a UACR less than 10 mg/g, an eGFR of 45 to 59 mL/min/1.73 m2 based on creatinine alone was associated with significantly higher hospitalization rates compared with an eGFR of 90 to 104 mL/min/1.73 m2 (adjusted hazard ratio, 1.3 [95% CI, 1.2-1.3]; 161 vs 79 events per 1000 person-years; excess absolute risk, 22 events per 1000 person-years [95% CI, 19-25 events per 1000 person-years]). Conclusions and Relevance: In this retrospective analysis of 114 cohorts, lower eGFR based on creatinine alone, lower eGFR based on creatinine and cystatin C, and more severe UACR were each associated with increased rates of 10 adverse outcomes, including adverse kidney outcomes, cardiovascular diseases, and hospitalizations.

Personalised lung cancer risk stratification and lung cancer screening: do general practice electronic medical records have a role?

BACKGROUND: In the United Kingdom (UK), cancer screening invitations are based on general practice (GP) registrations. We hypothesize that GP electronic medical records (EMR) can be utilised to calculate a lung cancer risk score with good accuracy/clinical utility. METHODS: The development cohort was Secure Anonymised Information Linkage-SAIL (2.3 million GP EMR) and the validation cohort was UK Biobank-UKB (N = 211,597 with GP-EMR availability). Fast backward method was applied for variable selection and area under the curve (AUC) evaluated discrimination. RESULTS: Age 55-75 were included (SAIL: N = 574,196; UKB: N = 137,918). Six-year lung cancer incidence was 1.1% (6430) in SAIL and 0.48% (656) in UKB. The final model included 17/56 variables in SAIL for the EMR-derived score: age, sex, socioeconomic status, smoking status, family history, body mass index (BMI), BMI:smoking interaction, alcohol misuse, chronic obstructive pulmonary disease, coronary heart disease, dementia, hypertension, painful condition, stroke, peripheral vascular disease and history of previous cancer and previous pneumonia. The GP-EMR-derived score had AUC of 80.4% in SAIL and 74.4% in UKB and outperformed ever-smoked criteria (currently the first step in UK lung cancer screening pilots). DISCUSSION: A GP-EMR-derived score may have a role in UK lung cancer screening by accurately targeting high-risk individuals without requiring patient contact.

Outcomes in ANCA-Associated Vasculitis in Scotland: Validation of the Renal Risk Score in a Complete National Cohort.

Introduction: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) causes autoimmune-mediated inflammation of small blood vessels in multiple organs, including the kidneys. The ability to accurately predict kidney outcomes would enable a more personalized therapeutic approach. Methods: We used our national renal biopsy registry to validate the ability of ANCA Renal Risk Score (ARRS) to predict end-stage kidney disease (ESKD) for individual patients. This score uses histopathological and biochemical data to stratify patients as high, medium, or low risk for developing ESKD. Results: A total of 288 patients were eligible for inclusion in the study (low risk n = 144, medium risk n = 122, high risk n = 12). Using adjusted Cox proportional hazard models with the low-risk group as reference, we show that outcome differs between the categories: high-risk hazard ratio (HR) 16.69 (2.91-95.81, P = 0.002); medium risk HR 4.14 (1.07-16.01, P = 0.039). Incremental multivariable-adjusted Cox proportional hazards models demonstrated that adding ARRS to a model adjusted for multiple clinical parameters enhanced predictive discrimination (basic model C-statistic 0.864 [95% CI 0.813-0.914], basic model plus ARRS C-statistic 0.877 [95% CI 0.823-0.931]; P <0.01). Conclusion: The ARRS better discriminates risk of ESKD in AAV and offers clinicians more prognostic information than the use of standard biochemical and clinical measures alone. This is the first time the ARRS has been validated in a national cohort. The proportion of patients with high-risk scores is lower in our cohort compared to others and should be noted as a limitation of this study.

Sex differences in associations between creatinine and cystatin C-based kidney function measures with stroke and major bleeding.

PURPOSE: We sought to explore whether adding kidney function biomarkers based on creatinine (eGFRCr), cystatin C (eGFRCys) or a combination of the two (eGFRCr-Cys) could improve risk stratification for stroke and major bleeding, and whether there were sex differences in any additive value of kidney function biomarkers. METHOD: We included participants from the UK Biobank who had not had a previous ischaemic or haemorrhagic stroke or major bleeding episode, and who had kidney function measures available at baseline. Cause-specific Cox proportional hazards models tested associations between eGFRCr, eGFRCys and eGFRCr-Cys (mL/min/1.73 m2) with ischaemic and haemorrhagic stroke, major bleeding (gastrointestinal or intracranial, including haemorrhagic stroke) and all-cause mortality. FINDINGS: Among 452,879 eligible participants, 246,244 (54.4%) were women. Over 11.5 (IQR 10.8-12.2) years, there were 3706 ischaemic strokes, 795 haemorrhagic strokes, 26,025 major bleeding events and 28,851 deaths. eGFRCys was more strongly associated with ischaemic stroke than eGFRCr: an effect that was more pronounced in women (men - HR: 1.16, 95% CI: 1.12-1.19; female to male comparison - HR: 1.11, 95% CI: 1.05-1.16, per 10 mL/min/1.73 m2 decline in eGFRCys). This interaction effect was also demonstrated for eGFRCr-Cys, but not eGFRCr. eGFRCys and eGFRCr-Cys were more strongly associated with major bleeding and all-cause mortality than eGFRCr in both men and women. Event numbers were small for haemorrhagic stroke. DISCUSSION: To a greater degree than is seen in men, eGFRCr underestimates risk of ischaemic stroke and major bleeding in women compared to eGFRCys. The difference between measures is likely explained by non-GFR biology of creatinine and cystatin C. CONCLUSION: Enhanced measurement of cystatin C may improve risk stratification for ischaemic stroke and major bleeding and clinical treatment decisions in a general population setting, particularly for women.

Deprivation and chronic kidney disease-a review of the evidence.

The relationship between socioeconomic deprivation and health is inequitable. Chronic kidney disease (CKD) is an archetypal disease of inequality, being more common amongst those living in deprivation. The prevalence of CKD is rising driven by an increase in lifestyle-related conditions. This narrative review describes deprivation and its association with adverse outcomes in adults with non-dialysis-dependent CKD including disease progression, end-stage kidney disease, cardiovascular disease and all-cause mortality. We explore the social determinants of health and individual lifestyle factors to address whether patients with CKD who are socioeconomically deprived have poorer outcomes than those of higher socioeconomic status. We describe whether observed differences in outcomes are associated with income, employment, educational attainment, health literacy, access to healthcare, housing, air pollution, cigarette smoking, alcohol use or aerobic exercise. The impact of socioeconomic deprivation in adults with non-dialysis-dependent CKD is complex, multi-faceted and frequently under-explored within the literature. There is evidence that patients with CKD who are socioeconomically deprived have faster disease progression, higher risk of cardiovascular disease and premature mortality. This appears to be the result of both socioeconomic and individual lifestyle factors. However, there is a paucity of studies and methodological limitations. Extrapolation of findings to different societies and healthcare systems is challenging, however, the disproportionate effect of deprivation in patients with CKD necessitates a call to action. Further empirical study is warranted to establish the true cost of deprivation in CKD to patients and societies.

Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios: associations with mortality in a haemodialysis cohort.

Background: Lymphocyte ratios reflect inflammation and have been associated with adverse outcomes in a range of diseases. We sought to determine any association between neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) and mortality in a haemodialysis cohort, including a coronavirus disease 2019 (COVID-19) infection subpopulation. Methods: A retrospective analysis was performed of adults commencing hospital haemodialysis in the West of Scotland during 2010-21. NLR and PLR were calculated from routine samples around haemodialysis initiation. Kaplan-Meier and Cox proportional hazards analyses were used to assess mortality associations. Results: In 1720 haemodialysis patients over a median of 21.9 (interquartile range 9.1-42.9) months, there were 840 all-cause deaths. NLR but not PLR was associated with all-cause mortality after multivariable adjustment [adjusted hazard ratio (aHR) for in participants with baseline NLR in quartile 4 (NLR ≥8.23) versus quartile 1 (NLR <3.12) 1.63, 95% confidence interval (CI) 1.32-2.00]. The association was stronger for cardiovascular death (NLR quartile 4 versus 1 aHR 3.06, 95% CI 1.53-6.09) than for non-cardiovascular death (NLR quartile 4 versus 1 aHR 1.85, 95% CI 1.34-2.56). In the COVID-19 subpopulation, both NLR and PLR at haemodialysis initiation were associated with risk of COVID-19-related death after adjustment for age and sex (NLR: aHR 4.69, 95% CI 1.48-14.92 and PLR: aHR 3.40, 95% CI 1.02-11.36; for highest vs lowest quartiles). Conclusions: NLR is strongly associated with mortality in haemodialysis patients while the association between PLR and adverse outcomes is weaker. NLR is an inexpensive, readily available biomarker with potential utility in risk stratification of haemodialysis patients.