Background and aims: There is an ongoing need to recognize early kidney injury and its progression in structural chronic pathologies. The proteins NGAL, IGFBP7, TIMP2, KIM-1, CXCL9, TGF-beta 1,... Show moreBackground and aims: There is an ongoing need to recognize early kidney injury and its progression in structural chronic pathologies. The proteins NGAL, IGFBP7, TIMP2, KIM-1, CXCL9, TGF-beta 1, SLC22A2, nephrin, cubilin and uromodulin have been proposed as early kidney injury biomarkers. To guide clinical interpretation, their urinary concentrations should be accompanied by reference intervals, which we here establish in a representative Dutch middle-aged population. Materials and Methods: The 24-h urine samples from 1443 Caucasian middle-aged men and women, were analyzed for the biomarkers by quantitative LC-MS/MS. Biomarker excretion per 24-h were calculated, and urine creatinine and osmolality were measured for dilution normalization. This population was characterized by demographic and anthropometric parameters, comorbid conditions, and conventional kidney function measures. Results: NGAL, IGFBP7, TIMP2, KIM-1 and uromodulin could be quantified in this population, whereas nephrin, SLC22A2 and CXCL9 were below their detection limits. Urine creatinine and osmolality ( r= -were correlated to urine volume (r = -0.71; -0.74) and to IGFBP7 (r = 0.73; 0.71) and TIMP2 (r = 0.71; 0.69). Crude and normalized biomarker concentrations were affected by sex, but not by age, BMI, smoking, kidney function or common comorbid conditions. The reference intervals (men; women) were 18-108; 21-131 pmol IGFBP7/mmol creatinine, 1- 63; 4-224 pmol NGAL/mmol creatinine, 7-48; 7- 59 pmol TIMP2/mmol creatinine, <1-9; <1-12 pmol KIM-1/mmol creatinine and 0.1-1.2; 0.1-1.7 mg uromodulin/mmol creatinine. Conclusion: We present dilution-normalized and sex-stratified urinary reference intervals of kidney injury biomarkers in a middle-aged Caucasian population. Show less
Terpstra, S.E.; Stadt, L. van de; Boonen, A.; Damman, W.; Rosendaal, F.; Kloppenburg, M. 2022
Objectives: Data on work participation impairment and related societal costs for patients with hand osteoarthritis (OA) are scarce. Therefore, we aimed to investigate the association of hand OA... Show moreObjectives: Data on work participation impairment and related societal costs for patients with hand osteoarthritis (OA) are scarce. Therefore, we aimed to investigate the association of hand OA with work limitations and costs of productivity loss in paid and unpaid work. Methods: We used data from the Hand Osteoarthritis in Secondary Care cohort, including patients with hand OA diagnosed by their treating rheumatologist. Using the validated Health and Labour Questionnaire, we assessed experienced unpaid and paid work restrictions, unpaid work replacement by others and inefficiency and absence during paid work related to hand OA over the last 2 weeks. Societal costs (euro) per hour of paid and unpaid work were estimated using Dutch salary data in 2019. Results: 381 patients were included (mean age 61 years, 84% women, 26% high education level, 55% having any comorbidity). Replacement of unpaid work by others due to hand OA was necessary for 171 out of 381 patients (45%). Paid work was reported by 181/381 patients (47%), of whom 13/181 (7%) reported absenteeism, 28/181 (15%) unproductive hours at work and 120/181 (66%) paid work restrictions due to hand OA. Total estimated work-related societal costs per patient with hand OA (381 patients) were euro94 (95% CI 59 to 130) per 2 weeks (euro2452, 95% CI 1528 to 3377 per year). Conclusions: Hand OA is associated with impairment in paid and unpaid work participation, which translates into substantial societal costs of lost productivity. These results highlight the importance of adequate hand OA treatment. Show less
Dijk, W.J. van; Saadah, N.H.; Numans, M.E.; Aardoom, J.J.; Bonten, T.N.; Brandjes, M.; ... ; Kiefte-de Jong, J. 2021
ObjectiveWe aimed to evaluate all-cause and cause-specific mortality in patients with systemic lupus erythematosus (SLE) and neuropsychiatric (NP) symptoms in the Netherlands between 2007-2018... Show moreObjectiveWe aimed to evaluate all-cause and cause-specific mortality in patients with systemic lupus erythematosus (SLE) and neuropsychiatric (NP) symptoms in the Netherlands between 2007-2018.MethodsPatients visiting the tertiary referral NPSLE clinic of the Leiden University Medical Center were included. NP symptoms were attributed to SLE requiring treatment (major NPSLE) or to other and mild causes (minor/non-NPSLE). Municipal registries were checked for current status (alive/deceased). Standardized mortality ratios (SMRs) and 95% confidence intervals (CI) were calculated using data from the Dutch population. Rate ratio (RR) and 95% CI were calculated using direct standardization to compare mortality between major NPSLE and minor/non-NPSLE.Results351 patients were included and 149 patients were classified as major NPSLE (42.5%). Compared with the general population, mortality was increased in major NPSLE (SMR 5.0 (95% CI: 2.6-8.5)) and minor/non-NPSLE patients (SMR 3.7 (95% CI: 2.2-6.0)). Compared with minor/non-NPSLE, mortality was similar in major NPSLE patients (RR: 1.0 (95% CI: 0.5-2.0)). Cause-specific mortality rates demonstrated an increased risk of death due to infections in both groups, whereas death due to cardiovascular disease was only increased in minor/non-NPSLE patients.ConclusionMortality was increased in both major NPSLE and minor/non-NPSLE patients in comparison with the general population. There was no difference in mortality between major NPSLE and minor/non-NPSLE patients. Show less
The risk of venous thrombosis (VT) varies according to the type of progestogen that is found in combined oral contraceptives (COCs). When combined with the estrogen component ethinylestradiol (EE),... Show moreThe risk of venous thrombosis (VT) varies according to the type of progestogen that is found in combined oral contraceptives (COCs). When combined with the estrogen component ethinylestradiol (EE), the androgenic progestogens are better able to counteract the EE-induced stimulation of liver proteins and hence are associated with a twofold decreased risk of VT compared with non- or antiandrogenic progestogens, which exert limited counteraction of EE. Because EE is responsible for the increased risk, novel estrogens such as estradiol were developed and seem to have a lower risk of VT than EE. Besides COCs, there are other methods of hormonal contraceptives, such as progestogen-only contraceptives, which do not increase VT risk, except for injectables. Other nonoral contraceptives are combined vaginal rings and patches. There is insufficient evidence regarding the risk of VT associated with these two methods compared with COCs. The increased risk associated with COCs is more pronounced in women with inherited thrombophilia. In these women, the progestogen levonorgestrel seems to be associated with the lowest risk of VT. Currently, there are no studies that have investigated the risk of VT in women who switch COCs. We hypothesize that switching COCs, even when switching from a high- to a low-risk COC, increases the risk of VT. Finally, risk prediction models in women who use COCs are lacking. Since there is a large number of VT cases associated with COC use, it is important to identify women at risk of VT and advise them on alternative contraception methods. Show less
Alshehri, T.; Boone, S.; Mutsert, R. de; Penninx, B.; Rosendaal, F.; Cessie, S. le; ... ; Mook-Kanamori, D. 2019
