Individuals with ESKD requiring maintenance hemodialysis face a unique hemodynamic challenge, typically on a thrice-weekly basis. In an effort to achieve some degree of euvolemia, ultrafiltration ...goals often involve removal of the equivalent of an entire plasma volume. Maintenance of adequate end-organ perfusion in this setting is dependent on the institution of a variety of complex compensatory mechanisms. Unfortunately, secondary to a myriad of patient- and dialysis-related factors, this compensation often falls short and results in intradialytic hypotension. Physicians and patients have developed a greater appreciation for the breadth of adverse outcomes associated with intradialytic hypotension, including higher cardiovascular and all-cause mortality. In this review, we summarize the evidence for adverse outcomes associated with intradialytic hypotension, explore the underlying pathophysiology, and use this as a basis to introduce potential strategies for its prevention and treatment.
Background
Solid‐organ transplant (SOT) recipients with coronavirus disease 2019 (COVID‐19) have higher risk of adverse outcomes compared to the general population. Whether hospitalized SOT ...recipients with COVID‐19 are at higher risk of mortality than SOT recipients hospitalized for other causes, including non‐COVID‐19 pneumonia, remains unclear.
Methods
We used logistic regression to compare outcomes of SOT recipients hospitalized with COVID‐19 to non‐COVID‐19 related admissions and with non‐COVID‐19 pneumonia.
Results
Of 17,012 hospitalized SOT recipients, 1682 had COVID‐19. Those with COVID‐19 had higher odds of ICU admission (adjusted odds ratio aOR 2.12 95%CI: 1.88–2.39) and mechanical ventilation (aOR 3.75 95%CI: 3.24–4.33). COVID‐19 was associated with higher odds of in‐hospital death, which was more pronounced earlier in the pandemic (aOR 9.74 95%CI: 7.08–13.39 for April/May vs. aOR 7.08 95%CI: 5.62–8.93 for June through November 2020; P‐interaction = .03). Compared to SOT recipients hospitalized with non‐COVID‐19 pneumonia, odds of in‐hospital death were higher in SOT recipients with COVID‐19 (aOR 2.44 95% CI: 1.90–3.13), regardless of time of hospitalization (P‐interaction > .40).
Conclusions
In this large cohort of SOT recipients, hospitalization with COVID‐19 was associated with higher odds of complications and in‐hospital mortality than non‐COVID‐19 related admissions, and 2.5‐fold higher odds of in‐hospital mortality, compared to SOT recipients with non‐COVID‐19 pneumonia.
Iron, Hepcidin, and Death in Human AKI Leaf, David E; Rajapurkar, Mohan; Lele, Suhas S ...
Journal of the American Society of Nephrology,
03/2019, Letnik:
30, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Iron is a key mediator of AKI in animal models, but data on circulating iron parameters in human AKI are limited.
We examined results from the ARF Trial Network study to assess the association of ...plasma catalytic iron, total iron, transferrin, ferritin, free hemoglobin, and hepcidin with 60-day mortality. Participants included critically ill patients with AKI requiring RRT who were enrolled in the study.
Of the 807 study participants, 409 (51%) died by day 60. In both unadjusted and multivariable adjusted models, higher plasma concentrations of catalytic iron were associated with a significantly greater risk of death, as were lower concentrations of hepcidin. After adjusting for other factors, patients with catalytic iron levels in the highest quintile versus the lowest quintile had a 4.06-fold increased risk of death, and patients with hepcidin levels in the lowest quintile versus the highest quintile of hepcidin had a 3.87-fold increased risk of death. These findings were consistent across multiple subgroups. Other iron markers were also associated with death, but the magnitude of the association was greatest for catalytic iron and hepcidin. Higher plasma concentrations of catalytic iron and lower concentrations of hepcidin are each independently associated with mortality in critically ill patients with AKI requiring RRT.
These findings suggest that plasma concentrations of catalytic iron and hepcidin may be useful prognostic markers in patients with AKI. Studies are needed to determine whether strategies to reduce catalytic iron or increase hepcidin might be beneficial in this patient population.
Background and Purpose- Albuminuria is associated with stroke risk among individuals with diabetes. However, the association of albuminuria with incident stroke among nondiabetic patients is less ...clear. Methods- We performed a post hoc analysis of the SPRINT (Systolic Blood Pressure Intervention Trial), which examined the effect of higher versus lower intensity blood pressure management on mortality in 8913 participants without diabetes. We fit unadjusted and adjusted Cox proportional hazards models to estimate the association of baseline albuminuria (urinary albumin-to-creatinine ratio ≥30 mg/g versus<30 mg/g) with stroke risk. We also assessed effect modification according to treatment arms. Results- Mean age was 68±9 years, 35% were female, and 30% were black. Median follow-up was 3.2 years, and 19% patients had baseline albuminuria. Incident stroke occurred in 129 individuals during follow-up. Albuminuria was associated with increased stroke risk (unadjusted hazard ratio, 2.24; 95% CI, 1.55-3.23; adjusted hazard ratio 1.73; 95% CI, 1.17-2.56). The association of albuminuria with incident stroke differed according to the randomized treatment arm (
interaction=0.03). In the intensive treatment arm, the association of albuminuria and stroke was nonsignificant (unadjusted hazard ratio, 1.25; 95% CI, 0.69-2.28), whereas, in the standard treatment arm, it was significant (unadjusted hazard ratio, 3.44; 95% CI, 2.11-5.61). Conclusions- In a post hoc analysis of SPRINT, baseline albuminuria (versus not) was associated with a higher risk of incident stroke, but this relationship appeared to be restricted to those in the standard treatment arm. Further studies are required to conclusively determine if reduction of albuminuria in itself is beneficial in reducing stroke risk. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT01206062.
Hypertension is common in hemodialysis patients. A subset of patients experience systolic blood pressure increases from prehemodialysis to posthemodialysis (intradialytic hypertension), which are ...associated with adverse outcomes. However, little consensus exists on an evidence-based definition.
In 3198 hemodialysis patients, Cox models were fit to examine the association of various definitions of intradialytic hypertension (≥30% of baseline sessions with an increase in prehemodialysis to posthemodialysis systolic blood pressure of (1) ≥0 mm Hg Hyper0; (2) ≥10 mm Hg Hyper10, or (3) ≥20 mm Hg increase Hyper20) with all-cause mortality. Effect modification was assessed using interaction terms according to prespecified variables.
At baseline, mean age was 62±15 years, 57% were male, and 14% of patients were Black. During the baseline period, 47% of individuals met the Hyper0 definition and experienced 32% (hazard ratio, 1.32 95% CI, 1.05-1.66) higher adjusted risk of death, compared with no systolic blood pressure increase. Hyper10 was present in 21.2% and associated with 18% higher adjusted risk of death (hazard ratio, 1.18 95% CI, 0.94-1.48). Hyper20 was present in 6.8% and associated with 3% higher adjusted risk of death (hazard ratio 1.03 95% CI, 0.74-1.44). Effect modification by age and peripheral vascular disease was observed (
interaction=0.04 for age and 0.02 for peripheral vascular disease), with higher associated risk of death for those aged 45 to 70 years and those without peripheral vascular disease.
Individuals with any systolic blood pressure increase from prehemodialysis to posthemodialysis had the highest adjusted risk of mortality, compared with other threshold-based definitions.
Most patients receiving maintenance hemodialysis (HD) experience adverse symptoms, which are associated with decreased quality of life. Despite decades of experience, our understanding of causes of ...HD symptoms remains limited. We aimed to identify modifiable patient- and HD-related predictors of intradialytic symptoms.
Prospective cohort.
We leveraged patient-level (n=1,838) and HD session–level (n=64,797) data from the Hemodialysis Trial.
Pre-HD serum urea nitrogen (SUN) level, pre-HD systolic blood pressure (SBP), intradialytic SBP decline, and ultrafiltration rate (UFR).
Intra-HD symptoms, including cramps, nausea, chest pain, headache, and lightheadedness.
Random-effects logistic regression models.
Overall, symptoms occurred in 10.7% of HD sessions. Higher pre-HD SUN level (per 10 mg/dL) was associated with higher adjusted odds of muscle cramping and lightheadedness (adjusted ORs aORs of 1.20 95% CI, 1.17-1.22 and 1.13 95% CI, 1.08-1.18, respectively). SBP decline (from the predialysis value to the dialysis session nadir, per each 10–mm Hg decrease) was associated with greater risk for muscle cramping, headache, chest pain, vomiting, and lightheadedness (the largest aORs were for the 2 latter symptoms: 1.24 95% CI, 1.20-1.28 and 1.37 95% CI, 1.33-1.42, respectively). Higher UFR (per 1 mL/kg/h) was associated with greater odds of cramping (aOR, 1.03; 95% CI, 1.02-1.03). Conversely, higher pre-HD SBP (per 10 mm Hg) was associated with reduced risk for vomiting (aOR, 0.88; 95% CI, 0.85-0.92) and lightheadedness (aOR, 0.82; 95% CI, 0.80-0.85).
Measured osmolality, dialysate prescription data, and time stamps for symptom occurrence were not available. Clinical trial data may not be broadly generalizable.
Higher pre-HD SUN level, UFR, pre-HD SBP, and SBP decline are independently associated with different patterns of adverse intradialytic symptoms. Recognition that different symptoms may have variable causes may allow tailoring of personalized treatments in future interventional studies.
Abstract
Purpose
Despite our understanding of diabetes as an established risk factor for progressive kidney disease and cardiac complications, the prognostic significance of prediabetes in patients ...with chronic kidney disease (CKD) remains largely unknown.
Methods
Participants of the Chronic Renal Insufficiency Cohort (CRIC) were categorized as having normoglycemia, prediabetes, or diabetes according to fasting plasma glucose, glycated hemoglobin A1c (HbA1c), and treatment with antidiabetic drugs at baseline. Unadjusted and adjusted proportional hazards models were fit to estimate the association of prediabetes and diabetes (versus normoglycemia) with: (1) composite renal outcome (end-stage renal disease, 50% decline in estimated glomerular filtration rate to ≤ 15 mL/min/1.73 m2, or doubling of urine protein-to-creatinine ratio to ≥ 0.22 g/g creatinine); (2) composite cardiovascular (CV) outcome (congestive heart failure, myocardial infarction or stroke); and (3) all-cause mortality.
Results
Of the 3701 individuals analyzed, 945 were normoglycemic, 847 had prediabetes and 1909 had diabetes. The median follow-up was 7.5 years. Prediabetes was not associated with the composite renal outcome (adjusted hazard ratio aHR 1.13; 95% confidence interval CI, 0.96–1.32; P = 0.14), but was associated with proteinuria progression (aHR 1.23; 95% CI, 1.03–1.47; P = 0.02). Prediabetes was associated with a higher risk of the composite CV outcome (aHR 1.38; 95% CI, 1.05–1.82; P = 0.02) and a trend towards all-cause mortality (aHR 1.28; 95% CI, 0.99–1.66; P = 0.07). Participants with diabetes had an increased risk of the composite renal outcome, the composite CV outcome, and all-cause mortality.
Conclusions
In individuals with CKD, prediabetes was not associated with composite renal outcome, but was associated with an increased risk of proteinuria progression and adverse CV outcomes.
Mitochondrial DNA (mtDNA) is a critical activator of inflammation and the innate immune system. However, mtDNA level has not been tested for its role as a biomarker in the intensive care unit (ICU). ...We hypothesized that circulating cell-free mtDNA levels would be associated with mortality and improve risk prediction in ICU patients.
Analyses of mtDNA levels were performed on blood samples obtained from two prospective observational cohort studies of ICU patients (the Brigham and Women's Hospital Registry of Critical Illness BWH RoCI, n = 200 and Molecular Epidemiology of Acute Respiratory Distress Syndrome ME ARDS, n = 243). mtDNA levels in plasma were assessed by measuring the copy number of the NADH dehydrogenase 1 gene using quantitative real-time PCR. Medical ICU patients with an elevated mtDNA level (≥3,200 copies/µl plasma) had increased odds of dying within 28 d of ICU admission in both the BWH RoCI (odds ratio OR 7.5, 95% CI 3.6-15.8, p = 1×10(-7)) and ME ARDS (OR 8.4, 95% CI 2.9-24.2, p = 9×10(-5)) cohorts, while no evidence for association was noted in non-medical ICU patients. The addition of an elevated mtDNA level improved the net reclassification index (NRI) of 28-d mortality among medical ICU patients when added to clinical models in both the BWH RoCI (NRI 79%, standard error 14%, p<1×10(-4)) and ME ARDS (NRI 55%, standard error 20%, p = 0.007) cohorts. In the BWH RoCI cohort, those with an elevated mtDNA level had an increased risk of death, even in analyses limited to patients with sepsis or acute respiratory distress syndrome. Study limitations include the lack of data elucidating the concise pathological roles of mtDNA in the patients, and the limited numbers of measurements for some of biomarkers.
Increased mtDNA levels are associated with ICU mortality, and inclusion of mtDNA level improves risk prediction in medical ICU patients. Our data suggest that mtDNA could serve as a viable plasma biomarker in medical ICU patients.
Background The rapid reduction in plasma osmolality during hemodialysis (HD) may induce temporary gradients that promote the movement of water from the extracellular to the intracellular compartment, ...predisposing to the development of intradialytic hypotension (IDH). Study Design Observational cohort study. Setting & Participants 3,142 prevalent patients receiving thrice-weekly HD from a single dialysis provider organization. Predictor Predialysis calculated plasma osmolarity (calculated after the 2-day interval as 2 × serum sodium + serum urea nitrogen/2.8 + serum glucose/18). Outcome Magnitude of systolic blood pressure (SBP) decline (predialysis SBP − nadir intradialytic SBP) and risk of IDH (SBP decline > 35 or nadir SBP < 90 mm Hg). Measurements Unadjusted and multivariable-adjusted generalized linear models were fit to estimate the association of calculated osmolarity with intradialytic SBP decline and the odds of developing IDH. Results Mean age of participants was 62.6 ± 15.2 (SD) years, 57.1% were men, and 61.0% had diabetes. Mean predialysis calculated osmolarity during follow-up was 306.4 ± 9.5 mOsm/L. After case-mix adjustment, each 10-mOsm/L increase in predialysis calculated osmolarity was associated with 1.48 (95% CI, 0.86-2.09) mm Hg ( P < 0.001) greater decline in intradialytic SBP and 10% greater odds of IDH (OR, 1.10; 95% CI, 1.05-1.15). In adjusted models, lower predialysis sodium and higher serum urea nitrogen and serum glucose levels were associated with greater decline in intradialytic SBP. Limitations Measured serum osmolality, timing of changes in intradialytic osmolality, dialysate osmolality, and dialysate temperature were not available. Conclusions Higher predialysis calculated osmolarity is associated with greater decline in intradialytic SBP and greater risk of IDH in maintenance HD patients. Strategies to minimize rapid shifts in osmolality should be tested prospectively to minimize excess SBP decline in susceptible patients.
PDF
