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.

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.

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.

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.

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.

The 'other' big complication: how chronic kidney disease impacts on cancer risks and outcomes.

Cancer is the second leading cause of death in people with chronic kidney disease (CKD) after cardiovascular disease. The incidence of CKD in patients with cancer is higher than in the non-cancer population. Across various populations, CKD is associated with an elevated risk of cancer incidence and cancer death compared with people without CKD, although the risks are cancer site-specific. Higher risk of cancer is detectable in mild CKD [estimated glomerular filtration rate (eGFR) 60-89 mL/min/1.73 m2], although this risk is more obvious if sensitive markers of kidney disease are used, such as cystatin C. Independent of eGFR, albuminuria is associated with increased risk of site-specific cancer incidence and death. Here, we explore the potential mechanisms for the increased risk of cancer observed in CKD, including patient factors (shared risks such as cardiometabolic disease, obesity, smoking, diet, lifestyle and environment), disease (genetic, inflammatory and infective) and treatment factors. In particular, we discuss the ways in which renal adverse events associated with conventional chemotherapies and newer systemic anti-cancer therapies (including targeted and immunotherapies) may contribute to worse cancer outcomes in people with CKD. Finally, we review the potential benefits of acknowledging increased risk of cancer in risk prediction tools used for the management of CKD.

A systematic review and meta-analysis of the effect of intravitreal VEGF inhibitors on cardiorenal outcomes.

BACKGROUND: Vascular endothelial growth factor inhibitors (VEGFis) have transformed the treatment of many retinal diseases, including diabetic maculopathy. Increasing evidence supports systemic absorption of intravitreal VEGFi and development of significant cardiorenal side effects. METHODS: We conducted a systematic review and meta-analysis (PROSPERO: CRD42020189037) of randomised controlled trials of intravitreal VEGFi treatments (bevacizumab, ranibizumab and aflibercept) for any eye disease. Outcomes of interest were cardiorenal side effects (hypertension, proteinuria, kidney function decline and heart failure). Fixed effects meta-analyses were conducted where possible. RESULTS: There were 78 trials (81 comparisons; 13 175 participants) that met the criteria for inclusion: 47% were trials in diabetic eye disease. Hypertension (29 trials; 8570 participants) was equally common in VEGFi and control groups {7.3 versus 5.4%; relative risk [RR] 1.08 [95% confidence interval (CI) 0.91-1.28]}. New or worsening heart failure (10 trials; 3384 participants) had a similar incidence in VEGFi and control groups [RR 1.03 (95% CI 0.70-1.51)]. Proteinuria (5 trials; 1902 participants) was detectable in some VEGFi-treated participants (0.2%) but not controls [0.0%; RR 4.43 (95% CI 0.49-40.0)]. Kidney function decline (9 trials; 3471 participants) was similar in VEGFi and control groups. In participants with diabetic eye disease, the risk of all-cause mortality was higher in VEGFi-treated participants [RR 1.62 (95% CI 1.04-2.46)]. CONCLUSION: In trials of intravitreal VEGFi, we did not identify an increased risk of cardiorenal outcomes, although these outcomes were reported in only a minority of cases. There was an increased risk of death in VEGFi-treated participants with diabetic eye disease. Additional scrutiny of post-licensing observational data may improve the recognition of safety concerns in VEGFi-treated patients.

Insights into vitamin K metabolism in chronic kidney disease: more complicated than kale deficiency.

Vascular calcification is a major manifestation of cardiovascular disease in advanced chronic kidney disease and is inhibited by vitamin K-dependent proteins. Clinical trials of vitamin K supplementation in chronic kidney disease have failed to demonstrate benefits on vascular calcification. Recent laboratory, human, and animal studies have shown that vitamin K handling and metabolism in chronic kidney disease is complex and suggest vitamin K2 subtype supplementation in isolation is unlikely to have significant clinical impact.

Bioimpedance Indices of Fluid Overload and Cardiorenal Outcomes in Heart Failure and Chronic Kidney Disease: a Systematic Review.

BACKGROUND: Bioimpedance-based estimates of fluid overload have been widely studied and systematically reviewed in populations of those undergoing dialysis, but data from populations with heart failure or nondialysis chronic kidney disease (CKD) have not. METHODS AND RESULTS: We conducted a systematic review of studies using whole-body bioimpedance from populations with heart failure and nondialysis CKD that reported associations with mortality, cardiovascular outcomes and/or CKD progression. We searched MEDLINE, Embase databases and the Cochrane CENTRAL registry from inception to March 14, 2022. We identified 31 eligible studies: 20 heart failure and 11 CKD cohorts, with 2 studies including over 1000 participants. A wide range of various bioimpedance methods were used across the studies (heart failure: 8 parameters; CKD: 6). Studies generally reported positive associations, but between-study differences in bioimpedance methods, fluid overload exposure definitions and modeling approaches precluded meta-analysis. The largest identified study was in nondialysis CKD (Chronic Renal Insufficiency Cohort, 3751 participants), which reported adjusted hazard ratios (95% confidence intervals) for phase angle < 5.59 vs ≥ 6.4 of 2.02 (1.67-2.43) for all-cause mortality; 1.80 (1.46-2.23) for heart failure events; and 1.78 (1.56-2.04) for CKD progression. CONCLUSIONS: Bioimpedance indices of fluid overload are associated with risk of important cardiorenal outcomes in heart failure and CKD. Facilitation of more widespread use of bioimpedance requires consensus on the optimum device, standardized analytical methods and larger studies, including more detailed characterization of cardiac and renal phenotypes.

Acute kidney injury in patients hospitalized with COVID-19 from the ISARIC WHO CCP-UK Study: a prospective, multicentre cohort study.

BACKGROUND: Acute kidney injury (AKI) is common in coronavirus disease 2019 (COVID-19). This study investigated adults hospitalized with COVID-19 and hypothesized that risk factors for AKI would include comorbidities and non-White race. METHODS: A prospective multicentre cohort study was performed using patients admitted to 254 UK hospitals with COVID-19 between 17 January 2020 and 5 December 2020. RESULTS: Of 85 687 patients, 2198 (2.6%) received acute kidney replacement therapy (KRT). Of 41 294 patients with biochemistry data, 13 000 (31.5%) had biochemical AKI: 8562 stage 1 (65.9%), 2609 stage 2 (20.1%) and 1829 stage 3 (14.1%). The main risk factors for KRT were chronic kidney disease (CKD) [adjusted odds ratio (aOR) 3.41: 95% confidence interval 3.06-3.81], male sex (aOR 2.43: 2.18-2.71) and Black race (aOR 2.17: 1.79-2.63). The main risk factors for biochemical AKI were admission respiratory rate >30 breaths per minute (aOR 1.68: 1.56-1.81), CKD (aOR 1.66: 1.57-1.76) and Black race (aOR 1.44: 1.28-1.61). There was a gradated rise in the risk of 28-day mortality by increasing severity of AKI: stage 1 aOR 1.58 (1.49-1.67), stage 2 aOR 2.41 (2.20-2.64), stage 3 aOR 3.50 (3.14-3.91) and KRT aOR 3.06 (2.75-3.39). AKI rates peaked in April 2020 and the subsequent fall in rates could not be explained by the use of dexamethasone or remdesivir. CONCLUSIONS: AKI is common in adults hospitalized with COVID-19 and it is associated with a heightened risk of mortality. Although the rates of AKI have fallen from the early months of the pandemic, high-risk patients should have their kidney function and fluid status monitored closely.

The ViKTORIES trial: A randomized, double-blind, placebo-controlled trial of vitamin K supplementation to improve vascular health in kidney transplant recipients.

Premature cardiovascular disease and death with a functioning graft are leading causes of death and graft loss, respectively, in kidney transplant recipients (KTRs). Vascular stiffness and calcification are markers of cardiovascular disease that are prevalent in KTR and associated with subclinical vitamin K deficiency. We performed a single-center, phase II, parallel-group, randomized, double-blind, placebo-controlled trial (ISRCTN22012044) to test whether vitamin K supplementation reduced vascular stiffness (MRI-based aortic distensibility) or calcification (coronary artery calcium score on computed tomography) in KTR over 1 year of treatment. The primary outcome was between-group difference in vascular stiffness (ascending aortic distensibility). KTRs were recruited between September 2017 and June 2018, and randomized 1:1 to vitamin K (menadiol diphosphate 5 mg; n = 45) or placebo (n = 45) thrice weekly. Baseline demographics, clinical history, and immunosuppression regimens were similar between groups. There was no impact of vitamin K on vascular stiffness (treatment effect -0.23 [95% CI -0.75 to 0.29] × 10-3  mmHg-1 ; p = .377), vascular calcification (treatment effect -141 [95% CI - 320 to 38] units; p = .124), nor any other outcome measure. In this heterogeneous cohort of prevalent KTR, vitamin K supplementation did not reduce vascular stiffness or calcification over 1 year. Improving vascular health in KTR is likely to require a multifaceted approach.

Vitamin K and vascular calcification.

PURPOSE OF REVIEW: Vascular calcification is a common and important cardiovascular risk factor in patients with chronic kidney disease (CKD). Recent advances in the understanding of the biology of vascular calcification implicate vitamin K-dependent proteins as important regulators in this process. This review highlights recent key advances in vascular biology, epidemiology, and clinical trials in this rapidly evolving field. RECENT FINDINGS: Vitamin K deficiency is associated with increasing severity of vascular calcification among patients with CKD, but the relationship with cardiovascular disease and mortality is inconsistent. Vitamin K may reduce calcification propensity by improving the activity of vitamin K-dependent calcification inhibitors or by down-regulating components of the innate immune system to reduce inflammation. However, recent randomized controlled trials in patients with diabetes, CKD, renal transplant, and on hemodialysis have failed to demonstrate improvement in vascular calcification or stiffness after vitamin K treatment. SUMMARY: Current evidence does not support a clinically useful role for vitamin K supplementation to prevent or reverse vascular calcification in patients with CKD. Knowledge gaps remain, particularly whether higher doses of vitamin K, longer duration of supplementations, or use a vitamin K as a part of a package of measures to counteract vascular calcification might be effective.

Cardiovascular magnetic resonance for the detection of descending thoracic aorta calcification in patients with end-stage renal disease.

BACKGROUND: Vascular calcification is an independent predictor of cardiovascular disease in patients with chronic kidney disease. Computed tomography (CT) is the gold-standard for detecting vascular calcification. Radial volumetric-interpolated breath-hold examination (radial-VIBE), a free-breathing gradient-echo cardiovascular magnetic resonance (CMR) sequence, has advantages over CT as it is ionising radiation-free. However, its capability in detecting thoracic aortic calcification (TAC) has not been investigated. This study aims to compare radial-VIBE to CT for the detection of TAC in the descending aorta of patients with end-stage renal disease (ESRD) using semi-automated methods, and to investigate the association between TAC and coronary artery calcification (CAC). METHODS: Paired cardiac CT and radial-VIBE CMR scans from ESRD patients participating in 2 prospective studies were obtained. Calcification volume was quantified using semi-automated methods in a 9 cm segment of the thoracic aorta. Correlation and agreement between TAC volume measured on CMR and CT were assessed with Spearman's correlation coefficient (ρ), linear regression, Bland-Altman plots and intraclass correlation coefficient (ICC). Association between CAC Agatston score and TAC volume determined by CT and CMR was measured with Spearman's correlation coefficient. RESULTS: Scans from 96 participants were analysed. Positive correlation was found between CMR and CT calcification volume [ρ = 0.61, 95% confidence interval (CI) 0.45-0.73]. ICC for consistency was 0.537 (95% CI 0.378-0.665). Bland-Altman plot revealed that compared to CT, CMR volumes were systematically higher at low calcification volume, and lower at high calcification volume. CT did not detect calcification in 41.7% of participants, while radial-VIBE CMR detected signal which the semi-quantitative algorithm reported as calcification in all of those individuals. Instances of suboptimal radial-VIBE CMR image quality were deemed to be the major contributors to the discrepancy. Correlations between CAC Agatston score and TAC volume measured by CT and CMR were ρ = 0.404 (95% CI 0.214-0.565) and ρ = 0.211 (95% CI 0.008-0.396), respectively. CONCLUSION: Radial-VIBE CMR can detect TAC with strong positive association to CT, albeit with the presence of proportional bias. Quantification of vascular calcification by radial-VIBE remains a promising area for future research, but improvements in image quality are necessary.

Myocardial changes on 3T cardiovascular magnetic resonance imaging in response to haemodialysis with fluid removal.

BACKGROUND: Mapping of left ventricular (LV) native T1 is a promising non-invasive, non-contrast imaging biomarker. Native myocardial T1 times are prolonged in patients requiring dialysis, but there are concerns that the dialysis process and fluctuating fluid status may confound results in this population. We aimed to assess the changes in cardiac parameters on 3T cardiovascular magnetic resonance (CMR) before and after haemodialysis, with a specific focus on native T1 mapping. METHODS: This is a single centre, prospective observational study in which maintenance haemodialysis patients underwent CMR before and after dialysis (both scans within 24 h). Weight measurement, bio-impedance body composition monitoring, haemodialysis details and fluid intake were recorded. CMR protocol included cine imaging and mapping native T1 and T2. RESULTS: Twenty-six participants (16 male, 65 ± 9 years) were included in the analysis. The median net ultrafiltration volume on dialysis was 2.3 L (IQR 1.8, 2.5), resulting in a median weight reduction at post-dialysis scan of 1.35 kg (IQR 1.0, 1.9), with a median reduction in over-hydration (as measured by bioimpedance) of 0.75 L (IQR 0.5, 1.4). Significant reductions were observed in LV end-diastolic volume (- 25 ml, p = 0.002), LV stroke volume (- 13 ml, p = 0.007), global T1 (21 ms, p = 0.02), global T2 (- 1.2 ms, p = 0.02) following dialysis. There was no change in LV mass (p = 0.35), LV ejection fraction (p = 0.13) or global longitudinal strain (p = 0.22). On linear regression there was no association between baseline over-hydration (as defined by bioimpedance) and global native T1 or global T2, nor was there an association between the change in over-hydration and the change in these parameters. CONCLUSIONS: Acute changes in cardiac volumes and myocardial native T1 are detectable on 3T CMR following haemodialysis with fluid removal. The reduction in global T1 suggests that the abnormal native T1 observed in patients on haemodialysis is not entirely due to myocardial fibrosis.

Prolonged SARS-CoV-2 viral shedding in patients with chronic kidney disease.

Recent World Health Organization guidance has aimed to provide pragmatic guidance acknowledging the role of sequential nasopharyngeal swabs taken >24 hours apart for SARS-CoV-2 in high-risk populations. Patients with chronic kidney disease (CKD) are known to have an altered immune milieu which may be associated with a delay in viral clearance. Here, a cross-sectional observational study of 138 patients admitted with SARS-CoV-2 infection at two large regional hospitals in Scotland, UK examined the median time to two consecutive negative nasopharyngeal swabs for SARS-CoV-2 in an inpatient population. The median time from admission to the first of two consecutive negative nasopharyngeal swabs was 18 days (range = 1-44) in patients with CKD, compared with 11 days (range: 1-71) in patients without CKD (P = .0007). Multivariable linear regression analysis using explanatory variables of age, sex, SARS-CoV-2 disease severity, key comorbidities and renal function showed that declining estimated glomerular filtration rate was independently associated with prolonged time to viral clearance. Our data suggest that patients with CKD who are admitted to hospital with SARS-CoV-2 take longer to achieve sequential negative nasopharyngeal swab reverse transcription-polymerase chain reaction results than those without CKD. This has implications for renal service provision, discharge planning and hospital capacity as well as a direct impact on patients due to extended hospital stay, anxiety and stigmatisation.

Vitamin K Supplementation to Improve Vascular Stiffness in CKD: The K4Kidneys Randomized Controlled Trial.

BACKGROUND: Vascular calcification, a risk factor for cardiovascular disease, is common among patients with CKD and is an independent contributor to increased vascular stiffness and vascular risk in this patient group. Vitamin K is a cofactor for proteins involved in prevention of vascular calcification. Whether or not vitamin K supplementation could improve arterial stiffness in patients with CKD is unknown. METHODS: To determine if vitamin K supplementation might improve arterial stiffness in patients in CKD, we conducted a parallel-group, double-blind, randomized trial in participants aged 18 or older with CKD stage 3b or 4 (eGFR 15-45 ml/min per 1.73 m2). We randomly assigned participants to receive 400 µg oral vitamin K2 or matching placebo once daily for a year. The primary outcome was the adjusted between-group difference in carotid-femoral pulse wave velocity at 12 months. Secondary outcomes included augmentation index, abdominal aortic calcification, BP, physical function, and blood markers of mineral metabolism and vascular health. We also updated a recently published meta-analysis of trials to include the findings of this study. RESULTS: We included 159 randomized participants in the modified intention-to-treat analysis, with 80 allocated to receive vitamin K and 79 to receive placebo. Mean age was 66 years, 62 (39%) were female, and 87 (55%) had CKD stage 4. We found no differences in pulse wave velocity at 12 months, augmentation index at 12 months, BP, B-type natriuretic peptide, or physical function. The updated meta-analysis showed no effect of vitamin K supplementation on vascular stiffness or vascular calcification measures. CONCLUSIONS: Vitamin K2 supplementation did not improve vascular stiffness or other measures of vascular health in this trial involving individuals with CKD. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Vitamin K therapy to improve vascular health in patients with chronic kidney disease, ISRCTN21444964 (www.isrctn.com).

Interaction between socioeconomic deprivation and likelihood of pre-emptive transplantation: influence of competing risks and referral characteristics - a retrospective study.

Socioeconomic deprivation (SED) influences likelihood of pre-emptive kidney transplantation (PET), but the mechanisms behind this are unclear. We explored the relationships between SED and patient characteristics at referral, which might explain this discrepancy. A retrospective cohort study was performed. SED was measured by Scottish Index of Multiple Deprivation (SIMD). Logistic regression evaluated predictors of PET. A competing risks survival analysis evaluated the interaction between SED and progression to end-stage kidney disease (ESKD) and death. Of 7765 patients with follow-up of 5.69 ± 6.52 years, 1298 developed ESKD requiring RRT; 113 received PET, 64 of which were from live donors. Patients receiving PET were "less deprived" with higher SIMD (5 ± 7 vs. 4 ± 5; P = 0.003). This appeared independent of overall comorbidity burden. SED was associated with a higher risk of death but not ESKD. Higher SIMD decile was associated with a higher likelihood of PET (OR 1.14, 95% CI 1.06, 1.23); the presence of diabetes and malignancy also reduced PET. SED was associated with reduced likelihood of PET after adjustment for baseline comorbidity, and this was not explained by risk of death or faster progression to ESKD. Education and outreach into transplantation should be augmented in areas with higher deprivation.

Obesity is not associated with progression to end stage renal disease in patients with biopsy-proven glomerular diseases.

BACKGROUND: Body mass index (BMI) is associated with renal disease progression in unspecified CKD. The relationship between BMI and primary glomerular disease (GN) may be more complex. We aimed to evaluate the association between BMI and renal disease progression in patients with primary glomerular disease (GN). METHODS: This was a single-centre retrospective cohort study performed in adult patients with biopsy-proven primary GN (excluding minimal change disease) from January 2000 to December 2015, with follow-up data until June 2017. BMI at time of biopsy was categorised as ≤25 kg/m2, > 25 to ≤30 kg/m2 and > 30 kg/m2. We used univariate and multivariate survival analyses to evaluate factors associated with progression to a composite endpoint of stage 5 CKD or renal replacement therapy (Major Adverse Renal Event - MARE) censoring for competing risk of death using Fine and Gray subdistribution hazards model. RESULTS: We included 560 patients with biopsy-proven primary GN and available BMI data: 66.1% were male with median age 54.8 (IQR 41.1-66.2) years and BMI 28.2 (IQR 24.9-32.1) kg/m2. Those with BMI 25-30 kg/m2 (n = 210) and with BMI > 30 kg/m2 (n = 207) were older (p = 0.007) with higher systolic and diastolic blood pressures (p = 0.02 and 0.004 respectively) than those with BMI < 25 kg/m2 (n = 132). There was a greater proportion of focal segmental glomerulosclerosis in those with higher BMI (3.9% in BMI < 25 kg/m2, 7.9% in BMI 25-30 kg/m2 and 10.7% in BMI > 30 kg/m2 of biopsies (p = 0.01)), but similar proportions of other GN diagnoses across BMI groups. Baseline eGFR (p = 0.40) and uPCR (p = 0.17) were similar across BMI groups. There was no interaction between BMI and time to MARE (log-rank p = 0.98) or death (log-rank p = 0.42). Censoring for competing risk of death, factors associated with progression to MARE were: younger age, lower baseline eGFR and higher uPCR, but not BMI (SHR 0.99, 95%CI 0.97-1.01, p = 0.31) nor blood pressure or GN diagnosis. CONCLUSION: BMI was not associated with progression to MARE in this patient cohort with primary GN. Efforts should be directed to managing other known risk factors for CKD progression.