Urinary creatinine excretion is used as a marker of completeness of timed urine collections, which are a keystone of several metabolic evaluations in clinical investigations and epidemiological surveys. The current reference values for 24-hour urinary creatinine excretion rely on observations performed in the 1960s and 1970s in relatively small and mostly selected groups, and may thus poorly fit to the present-day general European population. The aim of this study was to establish and validate anthropometry-based age- and sex-specific reference values of the 24-hour urinary creatinine excretion on adult populations with preserved renal function. We used data from two independent Swiss cross-sectional population-based studies with standardised 24-hour urinary collection and measured anthropometric variables. Only data from adults of European descent, with estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m2 and reported completeness of the urinary collection were retained. A linear regression model was developed to predict centiles of the 24-hour urinary creatinine excretion in 1,137 participants from the Swiss Survey on Salt and validated in 994 participants from the Swiss Kidney Project on Genes in Hypertension. The mean urinary creatinine excretion was 193 ± 41 μmol/kg/24 hours in men and 151 ± 38 μmol/kg/24 hours in women in the Swiss Survey on Salt. The values were inversely correlated with age and body mass index (BMI). Based on current reference values (177 to 221 μmol/kg/24 hours in men and 133 to 177 μmol/kg/24 hours in women), 56% of the urinary collections in the whole population and 67% in people >60 years old would have been considered as inaccurate. A linear regression model with sex, BMI and age as predictor variables was found to provide the best prediction of the observed values and showed a good fit when applied to the validation population. We propose a validated prediction equation for 24-hour urinary creatinine excretion in the general European population, based on readily available variables such as age, sex and BMI, and a few derived normograms to ease its clinical application. This should help healthcare providers to interpret the completeness of a 24-hour urine collection in daily clinical practice and in epidemiological population studies.
Background and objectives Fluid removal via ultrafiltration is a primary function of hemodialysis, and inadequate volume control is associated with significant morbidity and mortality among chronic dialysis patients. Treatment-to-treatment fluid removal goals are typically calculated on the basis of interdialytic weight gain and prescribed target weight. The clinical effect of frequent missed target weights is unclear. This study was designed to evaluate the associations of postdialysis weights above and below the prescribed target weight (separately) and outcomes. Design, setting, participants, & measurements Data were taken from a national cohort of 10,785 prevalent, thrice-weekly, in-center hemodialysis patients dialyzing from 2005 to 2008 (median time at risk, 2.1 [25th percentile, 75th percentile] years) at a single dialysis organization. Patients were characterized as having an above target weight miss if their postdialysis weight was >2 kg above target weight in at least 30% of baseline treatments (14.6% of cohort), or they were characterized as control otherwise. Below target weight miss characterization was analogous for patients with postdialysis weight >2 kg below target weight (6.6% of cohort). Coprimary endpoints were all-cause and cardiovascular mortality. Results Above target weight miss in at least 30% of treatments (versus not) was associated with greater all-cause mortality (adjusted hazard ratio, 1.28; 95% confidence interval, 1.15 to 1.43); and below target weight miss in at least 30% of treatments (versus not) was associated with greater all-cause mortality (adjusted hazard ratio, 1.22; 95% confidence interval, 1.05 to 1.40). Both above and below target weight misses were also significantly associated with greater cardiovascular mortality. Secondary analyses demonstrated dose-response relationships between target weight misses and mortality. Results from sensitivity analyses considering the difference in postdialysis and target weights as a proportion of body weight were analogous to the primary results. Conclusions Postdialysis weights >2 kg above and below target weight are associated with higher all-cause and cardiovascular mortality. Consistent target weight achievement is a viable target for improving fluid management.
We read with interest the article by Weatherald et al . on the long-term outcomes of pulmonary arterial hypertension (PAH) induced by dasatinib [1]. The authors reported 21 incident cases of PAH confirmed by right heart catheterisation (RHC) and associated with dasatinib. Although a majority of patients improved after dasatinib discontinuation, PAH persisted in over one-third of cases during long-term follow-up and two additional patients had persistent exercise pulmonary hypertension despite normalisation of resting haemodynamic measures. Similarly, Shah et al . reported 41 cases of dasatinib-induced PAH confirmed by RHC with complete resolution of PAH in only 58% of patients, provided that follow-up RHC or echocardiography was most often not documented [2]. As mentioned by Weatherald and colleagues, these data suggest that dasatinib is likely to cause irreversible pulmonary vascular dysfunction and remodelling. An experimental model in rats and human pulmonary endothelial cells supports this hypothesis as it showed that dasatinib causes dose-dependent pulmonary endothelial dysfunction and apoptosis through the production of mitochondrial reactive oxygen species, a phenomenon that was not observed with imatinib [3]. To date, there is no published evidence of such pathological abnormalities on human lung. We report the case of a patient who developed dasatinib-induced severe PAH that progressed in spite of drug cessation and aggressive PAH-specific therapy and ultimately underwent lung transplantation. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.