Abstract
Prognostic models that aim to improve the prediction of clinical events, individualized treatment and decision-making are increasingly being developed and published. However, relatively few ...models are externally validated and validation by independent researchers is rare. External validation is necessary to determine a prediction model’s reproducibility and generalizability to new and different patients. Various methodological considerations are important when assessing or designing an external validation study. In this article, an overview is provided of these considerations, starting with what external validation is, what types of external validation can be distinguished and why such studies are a crucial step towards the clinical implementation of accurate prediction models. Statistical analyses and interpretation of external validation results are reviewed in an intuitive manner and considerations for selecting an appropriate existing prediction model and external validation population are discussed. This study enables clinicians and researchers to gain a deeper understanding of how to interpret model validation results and how to translate these results to their own patient population.
CKD: A Call for an Age-Adapted Definition Delanaye, Pierre; Jager, Kitty J; Bökenkamp, Arend ...
Journal of the American Society of Nephrology,
10/2019, Letnik:
30, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Current criteria for the diagnosis of CKD in adults include persistent signs of kidney damage, such as increased urine albumin-to-creatinine ratio or a GFR below the threshold of 60 ml/min per 1.73 m
...This threshold has important caveats because it does not separate kidney disease from kidney aging, and therefore does not hold for all ages. In an extensive review of the literature, we found that GFR declines with healthy aging without any overt signs of compensation (such as elevated single-nephron GFR) or kidney damage. Older living kidney donors, who are carefully selected based on good health, have a lower predonation GFR compared with younger donors. Furthermore, the results from the large meta-analyses conducted by the CKD Prognosis Consortium and from numerous other studies indicate that the GFR threshold above which the risk of mortality is increased is not consistent across all ages. Among younger persons, mortality is increased at GFR <75 ml/min per 1.73 m
, whereas in elderly people it is increased at levels <45 ml/min per 1.73 m
Therefore, we suggest that amending the CKD definition to include age-specific thresholds for GFR. The implications of an updated definition are far reaching. Having fewer healthy elderly individuals diagnosed with CKD could help reduce inappropriate care and its associated adverse effects. Global prevalence estimates for CKD would be substantially reduced. Also, using an age-specific threshold for younger persons might lead to earlier identification of CKD onset for such individuals, at a point when progressive kidney damage may still be preventable.
General population-based studies, the chronic kidney disease (CKD) prognosis consortium and renal registries worldwide have contributed to the description of the scale of CKD as a public health ...problem. Since 1990, CKD has been included in the list of non-communicable diseases investigated by the Global Burden of Disease (GBD) study. The GBD represents a systematic, high-quality, scientific effort to quantify the comparative magnitude of health loss from all major diseases, injuries and risk factors. This article provides an outline of the place of CKD in the ranking of these diseases and the change over time. Whereas age-standardized death and disability-adjusted life years (DALYs) rates due to non-communicable diseases in general have been declining, such favourable trends do not exist for CKD. Altogether the GBD reports indicate increasing rates for death and DALYs due to CKD with huge variation across the globe. A substantial component of the observed increase in mortality attributable to CKD relates to that caused by diabetes mellitus and hypertension. For the increase in DALYs, CKD due to diabetes mellitus appears to be the main contributor. It is possible that these trends are in part due to new data becoming available or different coding behaviour over time, including greater specificity of coding. Although some feel there is evidence of overdiagnosis, it seems clear that in many regions CKD and its risk factors are a growing public health problem and in some of them rank very high as cause of years of life lost and DALYs. Therefore, public health policies to address this problem as well as secondary prevention in high-risk groups remain greatly needed.
The aim of this study was to investigate 28-day mortality after COVID-19 diagnosis in the European kidney replacement therapy population. In addition, we determined the role of patient ...characteristics, treatment factors, and country on mortality risk with the use of ERA-EDTA Registry data on patients receiving kidney replacement therapy in Europe from February 1, 2020, to April 30, 2020. Additional data on all patients with a diagnosis of COVID-19 were collected from 7 European countries encompassing 4298 patients. COVID-19–attributable mortality was calculated using propensity score–matched historic control data and after 28 days of follow-up was 20.0% (95% confidence interval 18.7%–21.4%) in 3285 patients receiving dialysis and 19.9% (17.5%–22.5%) in 1013 recipients of a transplant. We identified differences in COVID-19 mortality across countries, and an increased mortality risk in older patients receiving kidney replacement therapy and male patients receiving dialysis. In recipients of kidney transplants ≥75 years of age, 44.3% (35.7%–53.9%) did not survive COVID-19. Mortality risk was 1.28 (1.02–1.60) times higher in transplant recipients compared with matched dialysis patients. Thus, the pandemic has had a substantial effect on mortality in patients receiving kidney replacement therapy, a highly vulnerable population due to underlying chronic kidney disease and a high prevalence of multimorbidity.
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Summary More than 2 million people worldwide are being treated for end-stage kidney disease (ESKD). This Series paper provides an overview of incidence, modality use (in-centre haemodialysis, home ...dialysis, or transplantation), and mortality for patients with ESKD based on national registry data. We also present data from an international cohort study to highlight differences in haemodialysis practices that affect survival and the experience of patients who rely on this therapy, which is both life-sustaining and profoundly disruptive to their quality of life. Data illustrate disparities in access to renal replacement therapy of any kind and in the use of transplantation or home dialysis, both of which are widely considered preferable to in-centre haemodialysis for many patients with ESKD in settings where infrastructure permits. For most patients with ESKD worldwide who are treated with in-centre haemodialysis, overall survival is poor, but longer in some Asian countries than elsewhere in the world, and longer in Europe than in the USA, although this gap has reduced. Commendable haemodialysis practice includes exceptionally high use of surgical vascular access in Japan and in some European countries, and the use of longer or more frequent dialysis sessions in some countries, allowing for more effective volume management. Mortality is especially high soon after ESKD onset, and improved preparation for ESKD is needed including alignment of decision making with the wishes of patients and families.
ABSTRACT
In this article we introduce the concept of inverse probability of treatment weighting (IPTW) and describe how this method can be applied to adjust for measured confounding in observational ...research, illustrated by a clinical example from nephrology. IPTW involves two main steps. First, the probability—or propensity—of being exposed to the risk factor or intervention of interest is calculated, given an individual’s characteristics (i.e. propensity score). Second, weights are calculated as the inverse of the propensity score. The application of these weights to the study population creates a pseudopopulation in which confounders are equally distributed across exposed and unexposed groups. We also elaborate on how weighting can be applied in longitudinal studies to deal with informative censoring and time-dependent confounding in the setting of treatment-confounder feedback.
In clinical epidemiology, experimental studies usually take the form of randomized controlled clinical trials (RCTs). The data analysis of an RCT can be performed by using two complementary ...strategies, that is according to the intention to treat (ITT) principle and the per protocol (PP) analysis. By using the ITT approach, investigators aim to assess the effect of assigning a drug whereas by adopting the PP analysis, researchers investigate the effect of receiving the assigned treatment, as specified in the protocol. Both ITT and PP analyses are essentially valid but they have different scopes and interpretations dependent on the context.
SUMMARY AT A GLANCE
RCTs are analyzed according to the intention to treat (ITT) principle and the per protocol (PP) approach. The authors explained how ITT aims to assess the effect of assigning a drug and how the PP analysis investigates the effect of receiving an assigned treatment. Both analyses are valid but have different scopes and interpretations depending on the context.
Abstract
Diabetes, hypertension and cardiovascular disease have been listed as risk factors for severe coronavirus disease 2019 (COVID-19) since the first report of the disease in January 2020. ...However, this report did not mention chronic kidney disease (CKD) nor did it provide information on the relevance of estimated glomerular filtration rate (eGFR) or albuminuria. As the disease spread across the globe, information on larger populations with greater granularity on risk factors emerged. The recently published OpenSAFELY project analysed factors associated with COVID-19 death in 17 million patients. The picture that arose differs significantly from initial reports. For example, hypertension is not an independent risk factor for COVID-19 death adjusted hazard ratio (aHR) 0.89, but renal disease very much is. Dialysis (aHR 3.69), organ transplantation (aHR 3.53) and CKD (aHR 2.52 for patients with eGFR <30 mL/min/1.73 m2) represent three of the four comorbidities associated with the highest mortality risk from COVID-19. The risk associated with CKD Stages 4 and 5 is higher than the risk associated with diabetes mellitus (aHR range 1.31–1.95, depending upon glycaemic control) or chronic heart disease (aHR 1.17). In another recent publication, the Global Burden of Disease collaboration identified that worldwide, CKD is the most prevalent risk factor for severe COVID-19. Moreover, the distribution of risk factors for COVID-19 mortality appears to be different in patients with CKD when compared with the general population. The high prevalence of CKD in combination with the elevated risk of mortality from COVID-19 in CKD necessitates urgent action for this group of patients. This article defines essential action points (summarized in Box 1), among which is advocating the inclusion of CKD patients in clinical trials testing the efficacy of drugs and vaccines to prevent severe COVID-19.
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