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eGFR from serum creatinine–based equations informs diagnosis and staging of CKD. The guideline-recommended Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-based equation includes age, sex, and race (Black versus non-Black) variables and increases the eGFR estimate by

Considerable excitement has been building in nephrology. A new paradigm for the treatment of the anemia associated with advanced CKD has arisen from Nobel Prize-winning science on the hypoxia-inducible factor (HIF) pathway, an ancient biologic system designed to protect the organism from damage in

Background: Heart failure (HF) after kidney transplantation is a significant but understudied problem. Pretransplant dialysis modality could influence incident HF risk through differing cardiac stressors. However, whether pretransplant dialysis modality is associated with the development of posttransplant HF is unknown. Methods: We used the US Renal Data System to assemble a cohort of 27,701 patients who underwent their first kidney transplant in the USA between the years 2005 and 2012 and who had Medicare fee-for-service coverage for >6 months preceding their transplant date. Patients with any HF diagnosis prior to transplant were excluded. Detailed baseline patient characteristics and comorbidities were abstracted. The outcome of interest was de novo posttransplant HF. Pretransplant dialysis modality was defined as the dialysis modality used at the time of transplant. We conducted time-to-event analyses using Cox regression. Death was treated as a competing risk in the study’s primary analysis. Graft failure was included as a time-varying covariate. Results: Among eligible patients, 81% were treated with hemodialysis prior to transplant, and hemodialysis patients were more likely to be male, had a shorter dialysis vintage, and had more diabetes and vascular disease diagnoses. When adjusted for all available demographic and clinical data, pretransplant treatment with hemodialysis (vs. peritoneal dialysis) was associated with a 19% increased risk in de novo posttransplant HF, with sub-distribution HR 1.19 (95% CI: 1.09–1.29). Conclusions: Our results suggest that choice of pretransplant dialysis modality may impact the development of posttransplant HF.

Background Treatment with renin–angiotensin system inhibitors (RASIs), angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) is the standard of care for those with chronic kidney disease (CKD) and albuminuria. However, ACEI/ARB treatment is often discontinued for various reasons. We investigated the association of ACEI/ARB discontinuation with outcomes among US veterans with non-dialysis-dependent CKD. Methods We performed a retrospective cohort study of patients in the Veterans Affairs healthcare system with non-dialysis-dependent CKD who subsequently were started on ACEI/ARB therapy (new user design). Discontinuation events were defined as a gap in ACEI/ARB therapy of ≥14 days and were classified further based on duration (14–30, 31–60, 61–90, 91–180 and >180 days). This was treated as a time-varying risk factor in adjusted Cox proportional hazards models for the outcomes of death and incident end-stage kidney disease (ESKD), which also adjusted for relevant confounders. Results We identified 141 252 people with CKD and incident ACEI/ARB use who met the inclusion criteria; these were followed for a mean 4.87 years. There were 135 356 discontinuation events, 68 699 deaths and 6152 incident ESKD events. Discontinuation of ACEI/ARB was associated with a higher risk of death [hazard ratio (HR) 2.3, 2.0, 1.99, 1.92 and 1.74 for those discontinued for 14–30, 31–60, 61–90, 91–180 and >180 days, respectively]. Similar associations were noted between ACEI and ARB discontinuation and ESKD (HR 1.64, 1.47, 1.54, 1.65 and 1.59 for those discontinued for 14–30, 31–60, 61–90, 91–180 and >180 days, respectively). Conclusions In a cohort of predominantly male veterans with CKD Stages 3 and 4, ACEI/ARB discontinuation was independently associated with an increased risk of subsequent death and ESKD. This may be due to the severity of illness factors that drive the decision to discontinue therapy. Further investigations to determine the causes of discontinuations and to provide an evidence base for discontinuation decisions are needed.

Purpose of review Iron deficiency is common and associated with adverse outcomes in heart failure, regardless of anemia. Iron deficiency, absolute and functional, with and without anemia, is associated with adverse outcomes in chronic kidney disease (CKD). Heart failure and CKD frequently occur together. Intravenous iron therapy has been shown to reduce heart failure symptoms and improve physical function in heart failure with reduced ejection fraction with iron deficiency. In CKD, intravenous or oral iron therapy are often used for management of anemia, along with erythropoiesis stimulating agents, yet the risks and benefits of intravenous iron use is controversial. In this review, we survey available evidence and ongoing studies of iron deficiency and iron supplementation in heart failure, and integrate with recent evidence on effectiveness and safety of intravenous iron therapy in CKD. Recent findings Intravenous iron therapy improves heart failure symptoms and physical function in heart failure with reduced ejection fraction and iron deficiency, regardless of anemia, and may reduce heart failure hospitalizations and cardiovascular mortality. Sustained intravenous iron therapy regardless of hemoglobin level in selected patients with end-stage kidney disease receiving hemodialysis improves outcomes, and does not appear to cause infectious complications. Summary Iron therapy has important effects in heart failure and CKD, and appears safe in the short term. Ongoing trials will provide additional important information.

Pulmonary hypertension (PH) is a highly prevalent and important condition in adults with chronic kidney disease (CKD). In this review, we summarize the definition of PH, discuss its pathophysiology and classifications, and describe diagnostic and management strategies in patients with CKD, including those with kidney failure treated by kidney replacement therapy. In the general population, PH is classified into 5 groups based on clinical presentation, pathology, hemodynamics, and management strategies. In this classification system, PH in CKD is placed in a diverse group with unclear or multifactorial mechanisms, although underlying cardiovascular disease may account for most cases. CKD may itself directly incite pulmonary circulatory dysfunction and remodeling through uremic toxins, inflammation, endothelial dysfunction, and altered vasoregulation. Despite several studies describing the higher prevalence of PH in CKD and kidney failure, along with an association with poor outcomes, high-quality evidence is not available for its diagnostic and management strategies in those with CKD. In CKD not requiring kidney replacement therapy, volume management along with treatment of underlying risk factors for PH are critical. In those receiving hemodialysis, options are limited and transition to peritoneal dialysis may be considered if recurrent hypotension precludes optimal volume control.

Background: Patients with chronic kidney disease (CKD) who are hospitalized with a critical illness are at increased risk for adverse outcomes. We studied the predictors of hospitalization with critical illness among patients with non-dialysis-dependent CKD stages 3 and 4 in a safety-net healthcare setting. Methods: A retrospective cohort study was conducted among patients ≥18 years of age with CKD stages 3 and 4 using a CKD registry from a safety-net healthcare system. Hospitalizations with critical illness were identified among patients requiring nonelective admission or transfer to the intermediate or intensive care unit during a 3-year period after the diagnosis of CKD. Poisson regression was used to determine associations between baseline characteristics and hospitalization requiring intermediate or intensive care among all CKD patients and in those with different stages of CKD. Outcomes of these hospitalizations were also tabulated. Results: Among 8,302 patients with CKD stages 3 and 4, 1,298 were hospitalized and 495 required intermediate or intensive care during a 3-year follow-up period. In the adjusted analysis, advanced CKD, Hispanics (incident rate ratio [IRR]: 1.88), non-Hispanic Blacks (IRR: 1.48), presence of congestive heart failure (IRR: 2.09), cardiovascular disease (IRR: 1.57), chronic pulmonary disease (IRR: 1.60), liver disease, malignancy, and anemia were associated with higher risk of hospitalization requiring intermediate or intensive care. The association of age, gender, race/ethnicity, congestive heart failure, anemia, and body mass index with hospitalization requiring intermediate or intensive care differed significantly by CKD stage (p value for interaction term Conclusions: The burden of hospitalization with critical illness among patients with non-dialysis-dependent CKD stages 3 and 4 remains high and was associated with demographic factors and comorbid medical conditions, especially among those with congestive heart failure and cardiovascular disease. Targeted, effective interventions to reduce the burden of hospitalization and critical illness in CKD patients within safety-net healthcare systems are needed.

Summary: Many US states published crisis standards of care (CSC) guidelines for allocating scarce critical care resources during the COVID-19 pandemic. However, the performance of these guidelines in maximizing their population benefit has not been well tested. In 2,272 adults with COVID-19 requiring mechanical ventilation drawn from the Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19 (STOP-COVID) multicenter cohort, we test the following three approaches to CSC algorithms: Sequential Organ Failure Assessment (SOFA) scores grouped into ranges, SOFA score ranges plus comorbidities, and a hypothetical approach using raw SOFA scores not grouped into ranges. We find that area under receiver operating characteristic (AUROC) curves for all three algorithms demonstrate only modest discrimination for 28-day mortality. Adding comorbidity scoring modestly improves algorithm performance over SOFA scores alone. The algorithm incorporating comorbidities has modestly worse predictive performance for Black compared to white patients. CSC algorithms should be empirically examined to refine approaches to the allocation of scarce resources during pandemics and to avoid potential exacerbation of racial inequities.

Background: The relationship of opioid use with the incidence of acute ischemic stroke (AIS) and subsequent complications remains poorly understood. However, both opioid use and AIS have been independently associated with increased risk of subsequent acute kidney injury (AKI). In patients with AIS patients, AKI is associated with increased in-hospital and 10-year mortality. We evaluate whether opioid use in patients with AIS is associated with increased risk of AKI, near-term complications, mortality, and increased healthcare utilization. Methods: All records of patients within the Nationwide Inpatient Sample carrying a primary discharge diagnosis of AIS and secondary diagnosis of AKI between 2012-2014 were stratified by opioid status. The effect of opioid use on outcomes following AIS was analyzed after adjusting for confounders using logistic regression analysis. Results: Of 3,396,664 patients with AIS, 17,575 were diagnosed with an opioid-use disorder. There were 4,786 (27.2%) patients with AIS with opioid use that experienced in-hospital AKI compared to 426,823 (12.6%, p Conclusions: We demonstrate that opioid use in patients with acute ischemic stroke is independently associated with twofold increased risk of AKI (27% vs. 12%, p

Rationale & Objective Underlying kidney disease is an emerging risk factor for more severe COVID-19 illness. We examined the clinical courses of critically ill COVID-19 patients with and without pre-existing kidney disease and investigated the association between degree of underlying kidney disease and in-hospital outcomes. Study Design Retrospective cohort study Settings & Participants 4,264 critically ill COVID-19 patients (143 dialysis patients, 521 chronic kidney disease [CKD] patients, and 3,600 patients without CKD) admitted to ICUs at 68 hospitals in the United States. Predictor(s) Presence (versus absence) of pre-existing kidney disease Outcome(s) In-hospital mortality (primary); respiratory failure, shock, ventricular arrhythmia/ cardiac arrest, thromboembolic event, major bleed, and acute liver injury (secondary) Analytical Approach We used standardized differences to compare patient characteristics (values >0.10 indicate a meaningful difference between groups) and multivariable adjusted Fine and Gray survival models to examine outcome associations. Results Dialysis patients had a shorter time from symptom onset to ICU admission compared to other groups (median [quartile 1-quartile 3] days: 4 [2-9] for dialysis patients; 7 [3-10] for CKD patients; 7 [4-10] for patients without pre-existing kidney disease). More dialysis patients (25%) reported altered mental status than those with CKD (20%, standardized difference = 0.12) and no kidney disease (12%, standardized difference = 0.36). Half of dialysis and CKD patients died within 28-days of ICU admission versus 35% of patients without pre-existing kidney disease. Compared to patients without pre-existing kidney disease, dialysis patients had a higher risk of 28-day in-hospital death (adjusted HR 1.41; 95% CI 1.09, 1.81), while patients with CKD had an intermediate risk (adjusted HR 1.25; 95% CI 1.08, 1.44). Limitations Potential residual confounding Conclusions Findings highlight the high mortality of individuals with underlying kidney disease and severe COVID-19, underscoring the importance of identifying safe and effective COVID-19 therapies for this vulnerable population., Individuals with underlying kidney disease may be particularly vulnerable to severe COVID-19 illness, marked by multi-system organ failure, thrombosis, and a heightened inflammatory response. Among 4,264 critically ill adults with COVID-19 admitted to 68 intensive care units across the U.S., we found that both chronic kidney disease and dialysis patients had a ∼50% 28-day in-hospital mortality rate. Patients with underlying kidney disease had higher in-hospital mortality than patients without kidney disease, with patients on maintenance dialysis having the highest risk. As evidenced by differences in symptoms and clinical trajectories, patients with pre-existing kidney disease may have unique susceptibility to COVID-19-related complications which warrants additional study and special consideration in the pursuit and development of targeted therapies.

Rationale & Objective Pulmonary hypertension (PH) is highly prevalent among patients with chronic kidney disease (CKD) not requiring kidney replacement therapy. We studied the associations of PH with mortality, kidney failure, as well as cardiovascular (CV) and non-CV hospitalization among Medicare beneficiaries with a CKD diagnosis. Study Design Retrospective, observational study using a matched cohort design. Setting & Participants Patients with PH (based on 2 claims within 2 years) and patients without PH matched on CKD stage from the Medicare 5% CKD sample (1996-2016). Predictor Presence of pulmonary hypertension. Outcome Mortality, kidney failure, and all-cause, CV, and non-CV hospitalization. Analytical Approach Cox proportional hazards models to assess the association between PH and mortality, adjusting for age, sex, race, and comorbidities. Death was considered as a competing event in Fine-Gray models to assess the association between PH and kidney failure. Negative binomial model was used to evaluate the relationship between PH and all-cause, CV, and non-CV hospitalizations. Results 30,052 patients with PH and CKD and 150,260 CKD stage-matched patients without diagnosed PH were studied. The median age of the study population was 80.7 years, 57.8% were women, and 10.3% were African Americans. The presence of PH was associated with an increased risk of mortality after 1 (HR, 2.87 [95% CI, 2.79-2.95]), 2-3 (HR, 1.56 [95% CI, 1.51-1.61]), and 4-5 (HR, 1.47 [95% CI, 1.40-1.53]) years of follow-up, and a higher risk of all-cause, CV, and non-CV hospitalization during the same period. PH was also associated with kidney failure in after 1 and 2-3 years but not after 4-5 years of follow-up evaluation. Patients with PH also experienced higher rates of acute kidney injury (AKI), and AKI requiring dialysis support within 30 and 90 days of AKI. Limitations Reliance on billing codes and lack of echocardiogram or right heart catheterization data Conclusions Among older Medicare beneficiaries with a CKD diagnosis not requiring kidney replacement therapy, the presence of PH was associated with an increased risk of mortality, kidney failure, and hospitalization. Understanding of the mechanism of these associations, especially the increased risk of kidney failure, requires further study.

Introduction Left ventricular assist devices (LVAD) are used as a bridge to heart transplant or destination therapy for patients with the New York Heart Association (NYHA) class 3 or 4 heart failure. Acute kidney injury (AKI) or need for renal replacement therapy (RRT) post-LVAD implant can lead to poor outcomes. Identifying risk factors of AKI post-LVAD implant can help stratify potential LVAD candidates. Methods This is a retrospective study of all patients who received continuous-flow LVAD at our institution from January 2015 until August 2017. We calculated the incidence of AKI and the need for RRT post-LVAD implant, as well as the rate of renal recovery and survival rates at 30 days and 1-year post-LVAD implant. The presence of chronic kidney disease (CKD) and proteinuria was assessed, and kidney ultrasound results were reviewed on all patients, if available. CKD was present if estimated glomerular filtration rate (eGFR) was

Purpose of review Observational and interventional studies provide conflicting evidence regarding optimal blood pressure (BP) control in persons with chronic kidney disease (CKD). Recent publications provide additional information to inform therapeutic decision-making. Recent findings Targeting SBP to less than 120 mmHg, versus less than 140 mmHg, decreased cardiovascular events and all-cause mortality in persons with nondiabetic CKD. A meta-analysis of trials testing blood pressure management among nondialysis-dependent CKD patients (15 924 total patients) found more intensive therapies generally reduced mortality in all subgroups. Observational studies demonstrate that low SBP is associated with higher mortality in CKD. A recent report suggests that this is because of death from cardiovascular and noncardiovascular and nonmalignant causes, whereas higher BP is associated with death from cardiovascular causes. The shape of association between BP and cardiovascular and noncardiovascular events also appears to vary depending on baseline risk factors. Furthermore, BP measurement methodology may differ importantly between observational and interventional studies. Summary We review and summarize observational and interventional literature relating BP parameters to key clinical outcomes in persons with CKD. Apart from the inherent differences between these study designs, the disparate findings from trials and observational studies may be because of differences in patient characteristics and BP measurement techniques.

Background: Acute kidney injury (AKI) frequently complicates hospitalizations for left ventricular assist device (LVAD) implantation. Little is known about the relationship of AKI with subsequent readmissions, and we investigated the relationship of AKI during LVAD implantation hospitalization with all-cause and cause-specific 30-day readmissions. Methods: We used a United States (US) nationwide all-payer administrative database, identifying patients who underwent implantable LVAD placement 2010–2015. Patients were classified into 3 mutually exclusive groups based on presence and severity of AKI during the LVAD placement hospitalization: no AKI, AKI, and AKI requiring dialysis (AKI-D). Outcomes were all-cause and cause-specific 30-day readmissions. Results: Within 30 days after discharge 25.4% of patients were readmitted. Of those without AKI, 23.9% were readmitted, compared to 25.5% of those with AKI and 42.2% of those with AKI-D. Compared to no AKI (adjusted for demographics, index hospitalization and chronic comorbidity factors, and year), odds of 30-day readmission were 2.18 (95% CI 1.37–3.49) times higher for those with AKI-D, whereas those with AKI not requiring dialysis had similar 30-day readmission risk (OR 1.03 [95% CI 0.89–1.20]). Those with AKI-D had higher risk of 30-day readmission for infection (OR 2.02 [95% CI 1.13–3.61]), gastrointestinal (GI) bleed (2.32 [95% CI 1.24–4.34]), and kidney disease (13.9 [95% CI 4.0–48]). There was no increased risk for stroke readmission with AKI or AKI-D. Conclusion: AKI-D was associated with highest ­30-day readmission risk, possibly related to negatively synergistic effects of LVAD, kidney dysfunction, and dialysis related factors on infection and GI bleeding risks. AKI alone was not associated with increased readmission risk.

BackgroundAnemia is associated with adverse outcomes in those with chronic kidney disease (CKD). We examined the association of absolute and functional iron deficiency anemia (IDA) with adverse outcomes (cardiovascular hospitalization, dialysis and mortality) in those with nondialysis-dependent CKD.MethodsNondialysis-dependent CKD patients followed in the US Veterans Administration with hemoglobin level measured within 90 days of the date of the second estimated glomerular filtration rate 100–500 ng/mL) IDA and the associations of absolute and functional IDA with mortality, dialysis and cardiovascular hospitalization.ResultsOf 933 463 patients with CKD, 20.6% had anemia. Among those with anemia, 23.6% of patients had both TSAT and ferritin level measured, of whom 30% had absolute IDA and 19% had functional IDA. Absolute IDA in CKD was not associated with an increased risk of mortality or dialysis but was associated with a higher risk of 1-year {risk ratio [RR] 1.20 [95% confidence interval (CI) 1.12–1.28]} and 2-year cardiovascular hospitalization [RR 1.11 (95% CI 1.05–1.17)]. CKD patients with functional IDA had a higher risk of mortality [hazard ratio (HR) 1.11 (95% CI 1.07–1.14)] along with a higher risk of 1-year [RR 1.21 (95% CI 1.1–1.30)] and 2-year cardiovascular hospitalization [RR 1.13 (95% CI 1.07–1.21)]. Ferritin >500 ng/mL (treated as a separate category) was only associated with an increased risk of mortality [HR 1.38 (95% CI 1.26–1.51)].ConclusionsIn a large population of CKD patients with anemia, absolute and functional IDA were associated with various clinical covariates. Functional IDA was associated with an increased risk of mortality and cardiovascular hospitalization, but absolute IDA was associated only with a higher risk of hospitalization.

Statin-based treatments reduce cardiovascular disease (CVD) risk in patients with non-dialysis chronic kidney disease (CKD), but it is unclear which regimen is the most cost-effective. We used the Study of Heart and Renal Protection (SHARP) CKD-CVD policy model to evaluate the effect of statins and ezetimibe on quality-adjusted life years (QALYs) and health care costs in the United States (US) and the United Kingdom (UK). Net costs below $100,000/QALY (US) or £20,000/QALY (UK) were considered cost-effective. We investigated statin regimens with or without ezetimibe 10 mg. Treatment effects on cardiovascular risk were estimated per 1-mmol/L reduction in low-density lipoprotein (LDL) cholesterol as reported in the Cholesterol Treatment Trialists’ Collaboration meta-analysis, and reductions in LDL cholesterol were estimated for each statin/ezetimibe regimen. In the US, atorvastatin 40 mg ($0.103/day as of January 2019) increased life expectancy by 0.23 to 0.31 QALYs in non-dialysis patients with stages 3B to 5 CKD, at a net cost of $20,300 to $78,200/QALY. Adding ezetimibe 10 mg ($0.203/day) increased life expectancy by an additional 0.05 to 0.07 QALYs, at a net cost of $43,600 to $91,500/QALY. The cost-effectiveness findings and policy implications in the UK were similar. In summary, in patients with non-dialysis-dependent CKD, the evidence suggests that statin/ezetimibe combination therapy is a cost-effective treatment to reduce the risk of CVD., Graphical abstract

Rationale & Objective Ventricular assist devices (VADs) are used for end-stage heart failure not amenable to medical therapy. Acute kidney injury (AKI) in this setting is common due to heart failure decompensation, surgical stress, and other factors. Little is known about national trends in AKI diagnosis and AKI requiring dialysis (AKI-D) and associated outcomes with VAD implantation. We investigated national estimates and trends for diagnosed AKI, AKI-D, and associated patient and resource utilization outcomes in hospitalizations in which implantable VADs were placed. Study Design Cohort study of 20% stratified sample of US hospitalizations. Setting & Participants Patients who underwent implantable VAD placement in 2006 to 2015. Exposure No AKI diagnosis, AKI without dialysis, AKI-D. Outcomes In-hospital mortality, length of stay, estimated hospitalization costs. Analytical Approach Multivariate logistic and linear regression using survey design methods to account for stratification, clustering, and weighting. Results An estimated 24,140 implantable VADs were placed, increasing from 853 in 2006 to 3,945 in 2015. AKI was diagnosed in 56.1% of hospitalizations and AKI-D occurred in 6.5%. AKI diagnosis increased from 44.0% in 2006 to 2007 to 61.7% in 2014 to 2015; AKI-D declined from 9.3% in 2006 to 2007 to 5.2% in 2014 to 2015. Mortality declined in all AKI categories but this varied by category: those with AKI-D had the smallest decline. Adjusted hospitalization costs were 19.1% higher in those with diagnosed AKI and 39.6% higher in those with AKI-D, compared to no AKI. Limitations Administrative data; timing of AKI with respect to VAD implantation cannot be determined; limited pre-existing chronic kidney disease ascertainment; discharge weights not derived for subpopulation of interest. Conclusions A decreasing proportion of patients undergoing VAD implantation experience AKI-D, but mortality among these patients remains high. AKI diagnosis with VAD implantation is increasing, possibly reflecting changes in AKI surveillance, awareness, and coding.

Background People with end‐stage renal disease ( ESRD ) are at risk for advanced heart failure, but little is known about use and outcomes of durable mechanical circulatory support in this setting. We examined use and outcomes of implantable ventricular assist devices ( VAD s) in a national ESRD cohort. Methods and Results We performed a retrospective cohort study of Medicare beneficiaries with ESRD who underwent implantable VAD placement from 2006 to 2014. We examined in‐hospital and 1‐year mortality, all‐cause and cause‐specific hospitalizations, and heart/kidney transplantation outcomes. We investigated as predictors demographic factors, time‐period of VAD implantation, primary or post‐cardiotomy implantation, and duration of ESRD before VAD implantation. We identified 96 people with ESRD who underwent implantable VAD placement. At time of VAD implantation, 74 (77.1%) were receiving hemodialysis, 10 (10.4%) were receiving peritoneal dialysis and 12 (12.5%) had renal transplant. Time from incident ESRD to VAD implantation was median 4.0 (interquartile range 1.1, 8.2) years. Mortality during the implantation hospitalization was 40.6%. Within 1 year of implantation 61.5% of people had died. On multivariable analysis, males had half the mortality risk of females. Lower mortality risk was also seen with VAD implantation in a primary setting, and with more recent year of implantation, but these results did not reach statistical significance. Conclusions Medicare beneficiaries with ESRD are undergoing durable VAD implantation, often several years after incident ESRD , although in low numbers. Mortality is high among these patients, highlighting the need for investigations to improve treatment selection and management.

BACKGROUND The 2013 American College of Cardiology/American Heart Association lipid guideline recommends statin dosing based on intensity, rather than targeting specific low-density lipoprotein cholesterol (LDL-C) concentrations, among general populations. The 2013 Kidney Disease: Improving Global Outcomes (KDIGO) lipid guideline recommends statins for most adults with chronic kidney disease (CKD), but dose-dependent statin effects in CKD are unclear. METHODS We performed a retrospective cohort study of US veterans with CKD Stages G3a, G3b or G4, and new, persistent statin use, from 2005 to 2015. We tested the association of intensity of statin therapy [categorized as low (expected LDL-C reduction

Vascular endothelial dysfunction and increased arterial stiffness contribute to increased cardiovascular risk in patients with CKD who exhibit chronic systemic inflammation. Because chronic inflammation contributes to vascular dysfunction, blocking inflammation may reduce cardiovascular risk in patients with CKD. In a two-site, double-blind trial, we randomized 42 adult patients with stage 3-4 CKD who were already receiving optimal background therapy to receive either IL-1 trap rilonacept or placebo for 12 weeks. Coprimary end points included change in brachial artery flow-mediated dilation (FMD

Background Recent data suggest a U-shaped association between high-density lipoprotein cholesterol (HDL-c) and death in chronic kidney disease (CKD). However, whether the increased mortality in patients with extreme levels is explained by specific causes of death remains unclear. Objectives We studied the associations between HDL-c and cause-specific deaths in CKD. Methods We included 38,377 patients with estimated glomerular filtration rate 15–59 mL/min/1.73 m 2 . We classified deaths into 3 major categories: (1) cardiovascular; (2) malignant; and (3) noncardiovascular/nonmalignant causes. We fitted Cox regression models for overall mortality and separate competing risk models for each major cause of death category to evaluate their respective associations with categories of HDL-c (≤30, 31–40, 41–50 [referent], 51–60, >60 mg/dL). Separate analyses were conducted for men and women. Results During a median follow-up of 4.5 years, 9665 patients died. After adjusting for relevant covariates, in both sexes, HDL-c 31 to 40 mg/dL and ≤30 mg/dL were associated with higher risk of all-cause mortality, cardiovascular mortality, malignancy-related deaths, and noncardiovascular/nonmalignancy–related deaths. HDL-c >60 mg/dL was associated with lower all-cause (hazard ratio: 0.75, 95% confidence interval: 0.69, 0.81), cardiovascular, malignancy-related, and noncardiovascular/nonmalignancy–related deaths among women but not in men. Similar results were noted when HDL-c was examined as a continuous measure. Conclusions In a non–dialysis-dependent CKD population, HDL-c ≤40 mg/dL was associated with risk of higher all-cause, cardiovascular, malignant, and noncardiovascular/nonmalignant mortality in men and women. HDL >60 mg/dL was associated with lower risk of all-cause, cardiovascular, malignant, and noncardiovascular/nonmalignant mortality in women but not in men.

Background Serum albumin concentration is a commonly available biomarker with prognostic value in many disease states. It is uncertain whether serum albumin concentrations are associated with incident end-stage renal disease (ESRD) independently of urine albumin-to-creatinine ratio (ACR). Methods A longitudinal evaluation was performed of a population-based community-living cohort from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study. Participants were ≥45 years of age at study entry and had serum albumin, creatinine, cystatin C and spot urine ACR measured at the baseline visit (n = 19 633). Estimated glomerular filtration rate (eGFR) was from the Chronic Kidney Disease Epidemiology Collaboration combined creatinine-cystatin C equation. Baseline serum albumin concentration was the predictor variable, and hazard ratios (HRs) for incident ESRD (from US Renal Data System linkage) were calculated in sequentially adjusted models. Results Age at study entry was 63.9 ± 9.7 years, 62% of the participants were female and 40% were black. Mean eGFR at baseline was 83.3 ± 20.8 mL/min/1.73 m2. Over a median 8-year follow-up, 1.2% (n = 236) developed ESRD. In models adjusted for baseline eGFR, ACR and other ESRD risk factors, the HR for incident ESRD was 1.16 [95% confidence interval (CI) 1.01–1.33] for each standard deviation (0.33 g/dL) lower serum albumin concentration. The HR comparing the lowest ( Conclusions In community-dwelling US adults, lower serum albumin concentration is associated with higher risk of incident ESRD independently of baseline urine ACR, eGFR and other ESRD risk factors.

Protein-energy wasting is common in patients on maintenance hemodialysis and is strongly associated with poor quality of life and mortality. However, clinical assessment of protein-energy wasting remains difficult. Predialysis creatinine levels are associated with mortality risk but may be influenced by both muscle mass and dialysis dose. This might be overcome by examining the rate of rise in creatinine between dialysis sessions.We conducted an observational cohort study among 81 patients on maintenance hemodialysis at our Veterans Affairs unit. Predialysis serum creatinine and change in serum creatinine between midweek dialysis sessions served as the predictor variables of interest and clinically available proxies of nutritional status and time to mortality served as the outcome variables. Linear regression and Cox proportional hazards models evaluated relationships, respectively.The mean age of the study participants was 63 ± 10 years, 77 (95%) were male, mean body mass index was 27 ± 6 kg/m(2) and 69% had diabetes. Median follow-up time was 13 months, during which 12 patients (15%) died. Interdialytic change in serum creatinine showed a strong direct correlation with predialysis serum creatinine (R = 0.96). Higher levels of both markers were associated with younger age, less residual urine volume and higher serum albumin, serum phosphorus and normalized protein catabolic rate (P0.05 for all). Both markers were approximately equally strongly associated with mortality. For example, compared to the highest predialysis creatinine tertile, participants in the lowest tertile (6 mg/dL) had 5.5-fold [95% confidence interval (CI) 1.1, 26.6] higher risk of death. Similarly, participants in the lowest tertile of interdialytic change in creatinine (change3.7 mg/dL/48 h), had 5.0-fold (95% CI 1.0, 24.4) higher death risk.Predialysis creatinine and interdialytic change in creatinine are both strongly associated with proxies of nutritional status and mortality in hemodialysis patients and are highly correlated. Interdialytic change in creatinine provided little additional information about nutritional status or mortality risk above and beyond predialysis creatinine levels alone.

Background: KDIGO (Kidney Disease: Improving Global Outcomes) guidelines recommend lateral abdominal radiographs to assess vascular calcification in incident dialysis patients. However, nearly all dialysis patients in the United States receive chest radiographs at dialysis therapy inception, which may provide readily available information on coronary artery (CAC) and aortic arch calcification (AAC). We determined the prevalence of CAC and AAC visible on plain chest radiographs and their associations with mortality in our dialysis population. Study Design: Retrospective analysis. Setting & Participants: 93 participants who received maintenance hemodialysis at the San Diego Veterans Affairs Medical Center in 2009-2010. Predictor: Presence of CAC and AAC as evaluated by a radiologist. Outcome: All-cause mortality. Results: Average age was 64 years, 22% were African American, and 97% were men. CAC and AAC prevalences were 25% and 58%, respectively. During 20 months’ follow-up, 28% died. CAC was associated with mortality in models including cardiovascular (HR, 2.41; 95% CI, 1.04-5.59) and dialysis-related (HR, 2.86; 95% CI, 1.24-6.60) risk factors. AAC was associated with HRs of 5.25 (95% CI, 1.46-17.72) in cardiovascular risk factor‐adjusted models and 7.31 (95% CI, 2.03-26.34) in dialysis models. When CAC and AAC were both included in models, both CAC (HR, 3.40; 95% CI, 1.24-9.36) and AAC (HR, 6.23; 95% CI, 1.64-23.66) remained significantly associated with mortality. Limitations: The study sample is relatively small and mostly male. Conclusions: CAC and AAC are highly prevalent on chest radiographs in dialysis patients and strongly associated with mortality independent of one another. Because these images are nearly ubiquitous, inexpensive, and often obtained for other indications, they should be considered for risk assessment in hemodialysis patients. Future studies are required to determine whether CAC or AAC on chest radiography is additive or duplicative of the risk of aorto-iliac calcification on lateral abdominal radiographs currently suggested by KDIGO.