Various prediction models have been developed to predict the risk of kidney failure in patients with CKD. However, guideline-recommended models have yet to be compared head to head, their validation ...in patients with advanced CKD is lacking, and most do not account for competing risks.
To externally validate 11 existing models of kidney failure, taking the competing risk of death into account, we included patients with advanced CKD from two large cohorts: the European Quality Study (EQUAL), an ongoing European prospective, multicenter cohort study of older patients with advanced CKD, and the Swedish Renal Registry (SRR), an ongoing registry of nephrology-referred patients with CKD in Sweden. The outcome of the models was kidney failure (defined as RRT-treated ESKD). We assessed model performance with discrimination and calibration.
The study included 1580 patients from EQUAL and 13,489 patients from SRR. The average
statistic over the 11 validated models was 0.74 in EQUAL and 0.80 in SRR, compared with 0.89 in previous validations. Most models with longer prediction horizons overestimated the risk of kidney failure considerably. The 5-year Kidney Failure Risk Equation (KFRE) overpredicted risk by 10%-18%. The four- and eight-variable 2-year KFRE and the 4-year Grams model showed excellent calibration and good discrimination in both cohorts.
Some existing models can accurately predict kidney failure in patients with advanced CKD. KFRE performed well for a shorter time frame (2 years), despite not accounting for competing events. Models predicting over a longer time frame (5 years) overestimated risk because of the competing risk of death. The Grams model, which accounts for the latter, is suitable for longer-term predictions (4 years).
ABSTRACT
Background
Patients with chronic kidney disease (CKD) are at a higher risk of major adverse cardiovascular events (MACE) compared with the general population, but gender differences in this ...risk, especially in older adults, are not fully known. We aim to identify gender differences in the risk of MACE in older European CKD patients, and explore factors that may explain these differences.
Methods
The European Quality study (EQUAL) is a prospective study on stage 4–5 CKD patients, ≥65 years old, not on dialysis, from Germany, Italy, the Netherlands, Poland, Sweden and the UK. Cox regression and cumulative incidence competing risk curves were used to identify gender differences in MACE risks. Mediation analysis was used to identify variables which may explain risk differences between men and women.
Results
A total of 417 men out of 1134 (37%) and 185 women out of 602 women (31%) experienced at least one MACE, over a follow-up period of 5 years. Women had an 18% lower risk of first MACE compared with men (hazard ratio 0.82; 95% confidence interval 0.69–0.97; P = .02), which was attenuated after adjusting for pre-existing cardiometabolic comorbidities and cardiovascular risk factors. There were no significant gender differences in the risk of recurrent MACE or fatal MACE. The risk difference in MACE by gender was larger in patients aged 65–75 years, compared with patients over 75 years.
Conclusions
In a cohort of older adults with advanced CKD, women had lower risks of MACE. These risk differences were partially explained by pre-existing cardiometabolic comorbidities and cardiovascular risk factors.
Graphical Abstract
Graphical Abstract
Patients with stage 4/5 chronic kidney disease (CKD) suffer from various symptoms. The retention of uremic solutes is thought to be associated with those symptoms. However, there are relatively few ...rigorous studies on the potential links between uremic toxins and symptoms in patients with CKD.
The EQUAL study is an ongoing observational cohort study of non-dialyzed patients with stage 4/5 CKD. EQUAL patients from Germany, Poland, Sweden and the UK were included in the present study (
= 795). Data and symptom self-report questionnaires were collected between April 2012 and September 2020. Baseline uric acid and parathyroid hormone and 10 uremic toxins were quantified. We tested the association between uremic toxins and symptoms and adjusted P-values for multiple testing.
Symptoms were more frequent in women than in men with stage 4/5 CKD, while levels of various uremic toxins were higher in men. Only trimethylamine
-oxide (TMAO; positive association with fatigue),
-cresyl sulfate (PCS) with constipation and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (negative association with shortness of breath) demonstrated moderately strong associations with symptoms in adjusted analyses. The association of phenylacetylglutamine with shortness of breath was consistent in both sexes, although it only reached statistical significance in the full population. In contrast, TMAO (fatigue) and PCS and phenylacetylglutamine (constipation) were only associated with symptoms in men, who presented higher serum levels than women.
Only a limited number of toxins were associated with symptoms in persons with stage 4/5 CKD. Other uremic toxins, uremia-related factors or psychosocial factors not yet explored might contribute to symptom burden.
Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases ...of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex.
CKD patients (≥65 years; estimated glomerular filtration rate ≤20 mL/min/1.73 m
) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off ≤70; 0-100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders.
Overall kidney function decline in 1326 patients was -0.12 mL/min/1.73 m
/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms adjusted hazard ratio 1.41 (95% confidence interval 1.03-1.93). Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality).
There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men.
Efavirenz is currently suggested as an alternative to recommended antiretroviral (ARV) regimens by the Department of Health and Human Services for the treatment of HIV-1 in ARV-naive patients. A ...mid-dosing interval therapeutic range between 1000 and 4000 ng/mL for efavirenz has been proposed in the literature, with patients more likely to experience virologic failure below this range and adverse effects above. The current study reports an analysis of virologic outcome between those above, below, or within the reported efavirenz therapeutic range (1000-4000 ng/mL) and within subgroups.
This analysis examined efavirenz plasma concentrations obtained from participants enrolled in AIDS Clinical Trials Group Study A5202. This investigation divided subjects into those who experienced virologic failure and those who did not. These subjects were further separated to investigate those who had "high," "within," or "low" plasma concentrations, based on the therapeutic range. The association between virologic failure and plasma concentration was statistically examined in addition to the variables: race/ethnicity, sex, assigned nucleos(t)ide reverse transcriptase inhibitor backbone, age at study entry, history of intravenous drug use, weight, and screening HIV-1 RNA stratification level.
In univariate analyses, a statistically significant difference was found when comparing the efavirenz concentration groups, (22 failures among the "low" concentration group 19%, 65 failures among the "within" concentration group 12%, and 11 failures among the "high" concentration group 9%) when evaluating virologic failure as an outcome (P = 0.04). In addition, the proportion of participants with virologic failure differed across race/ethnicity groups (P = 0.03) with black non-Hispanic participants observed to have the highest rate (17%). Efavirenz concentration group, race/ethnicity, age, weight, and the interaction between efavirenz concentration group and weight were found to be significantly associated with virologic failure in multivariable logistic regression analysis.
The proposed efavirenz therapeutic range, combined with the impact of a patient's weight, is associated with virologic failure in HIV-infected ARV-naive individuals in the United States. Additional analysis is recommended to determine the most appropriate concentration value that defines the lower limit of the efavirenz therapeutic range.
Predicting the timing and occurrence of kidney replacement therapy (KRT), cardiovascular events, and death among patients with advanced chronic kidney disease (CKD) is clinically useful and relevant. ...We aimed to externally validate a recently developed CKD G4+ risk calculator for these outcomes and to assess its potential clinical impact in guiding vascular access placement.
We included 1517 patients from the European Quality (EQUAL) study, a European multicentre prospective cohort study of nephrology-referred advanced CKD patients aged ≥65 years. Model performance was assessed based on discrimination and calibration. Potential clinical utility for timing of referral for vascular access placement was studied with diagnostic measures and decision curve analysis (DCA).
The model showed a good discrimination for KRT and “death after KRT,” with 2-year concordance (C) statistics of 0.74 and 0.76, respectively. Discrimination for cardiovascular events (2-year C-statistic: 0.70) and overall death (2-year C-statistic: 0.61) was poorer. Calibration was fairly accurate. Decision curves illustrated that using the model to guide vascular access referral would generally lead to less unused arteriovenous fistulas (AVFs) than following estimated glomerular filtration rate (eGFR) thresholds.
This study shows moderate to good predictive performance of the model in an older cohort of nephrology-referred patients with advanced CKD. Using the model to guide referral for vascular access placement has potential in combating unnecessary vascular surgeries.
La cetoacidosis diabética (CAD) es una de las complicaciones agudas severas de la diabetes mellitus. La mayoría de los pacientes con CAD tienen diabetes autoinmune tipo 1, sin embargo, los pacientes ...con diabetes tipo 2 (DM2) también están en riesgo de padecerla durante el estrés catabólico de una enfermedad aguda como traumatismo, cirugía o infección. Se presenta una serie de 20 casos donde se diagnosticó CAD en sujetos con DM2, la edad media fue 62 años, todas eran mujeres, cuya principal causa precipitante fue la infección. La forma clínica moderada (85%) fue la predominante.
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