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Background: Although the association between Chronic Kidney Disease (CKD) and all-cause fractures was addressed in previous studies, the association between estimated glomerular filtration rate (eGFR) decline and fractures was poorly addressed. For the first time we examined the association between rapid kidney function decline (RKFD) and fracture incidence among Iranian general population., Methods: In a Tehranian community-based cohort, RKFD was defined as a 30 % decline in eGFR over 2-3 years. Cox proportional hazards models, adjusted for age, sex, current eGFR, diabetes mellitus, hypertension, dyslipidemia, current smoking, obesity status, waist circumference, prevalent cardiovascular diseases, aspirin, steroid use, education level, and marital status, were used to examine the association of RKFD with different fracture outcomes., Results: Among 5305 (3031 women) individuals aged ≥30 years, during the median follow-up of 9.62 years, 226 fracture events were observed. The multivariable hazard ratio of RKFD for any-fracture events, lower-extremity, and major osteoporotic fractures were 2.18 (95 % CI, 1.24-3.85), 2.32 (1.15-4.71), and 2.91 (1.29-6.58), respectively. These associations remained significant after accounting for the competing risk of death. The impact of RKFD on the development of incident all-cause fractures was not modified by gender [men: 2.64 (1.11-6.25) vs. women: 2.11 (1.00-4.47)] and according to current CKD status [without CKD: 2.34 (1.00-5.52) vs. with CKD: 2.59 (1.04-6.44)] (all P for interaction >0.5)., Conclusions: RKFD can increase the incidence of fractures among general population, the issue that was equally important among non-CKD individuals, emphasizing the need for early identification and management in those with rapidly declining eGFR., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier Inc.)

Background and Aims: We aimed to assess the potential socio-demographic, clinical, and lifestyle-related risk factors for kidney function decline (KFD), defined as ≥30% estimated glomerular filtration rate (eGFR) decline, in an Iranian cohort study., Methods: 7190 participants (4049 women) aged 20-90 years with 2-5 eGFR data from examinations (2001-2005 to 2015-2018) were included. Cox proportional hazard models were used to examine the association between potential risk factors and eGFR decline., Results: During 11.5 years of follow-up, 1471 (889 women) participants had incident KFD with a crude incidence rate of 192.1 (182.6-202.2) per 10,000 person-year. Among the total population, older age, female gender, prehypertension, hypertension, diabetes, widowed/divorced states, higher triglycerides (TG), prevalent cardiovascular diseases (CVD), and higher baseline eGFR were significantly associated with higher, while moderate physical activity and a positive family history of diabetes were associated with lower risk of KFD (all p values <.05). Prevalent CVD in women but not men, diabetes, and hypertension among postmenopausal than premenopausal women were significant risk factors of KFD. According to the presence of chronic kidney disease (CKD) at baseline, higher eGFR decreased the risk of KFD in patients with CKD and increased KFD risk in those without CKD (all p for interactions <.05)., Conclusion: KFD is associated with multiple modifiable risk factors among the Iranian urban population that is affected by gender, menopausal status, and initial kidney function. Interventions targeting these factors might potentially help reduce the burden of KFD.Key messages:Menopausal status may influence the relationship between cardiometabolic risk factors and KFD;The impact of higher baseline eGFR on the risk of KFD differed between subjects with preserved kidney function and CKD patients.The interaction between gender, menopausal status, and baseline kidney function with different risk factors on KFD may help to make renal risk prediction scores to identify those in the general population at risk who may benefit from early prevention.

Background: Glycemic variability (GV) is developing as a marker of glycemic control, which can be utilized as a promising predictor of complications. To determine whether long-term GV is associated with incident eGFR decline in two cohorts of Tehran Lipid and Glucose Study (TLGS) and Multi-Ethnic Study of Atherosclerosis (MESA) during a median follow-up of 12.2 years., Methods: Study participants included 4422 Iranian adults (including 528 patients with T2D) aged ≥ 20 years from TLGS and 4290 American adults (including 521 patients with T2D) aged ≥ 45 years from MESA. The Multivariate Cox proportional hazard models were used to assess the risk of incident eGFR decline for each of the fasting plasma glucose (FPG) variability measures including standard deviation (SD), coefficient of variation (CV), average real variability (ARV), and variability independent of the mean (VIM) both as continuous and categorical variables. The time of start for eGFR decline and FPG variability assessment was the same, but the event cases were excluded during the exposure period., Results: In TLGS participants without T2D, for each unit change in FPG variability measures, the hazards (HRs) and 95% confidence intervals (CI) for eGFR decline ≥ 40% of SD, CV, and VIM were 1.07(1.01-1.13), 1.06(1.01-1.11), and 1.07(1.01-1.13), respectively. Moreover, the third tertile of FPG-SD and FPG-VIM parameters was significantly associated with a 60 and 69% higher risk for eGFR decline ≥ 40%, respectively. In MESA participants with T2D, each unit change in FPG variability measures was significantly associated with a higher risk for eGFR decline ≥ 40%.Regarding eGFR decline ≥ 30% as the outcome, in the TLGS, regardless of diabetes status, no association was shown between FPG variability measures and risk of eGFR decline in any of the models; however, in the MESA the results were in line with those of GFR decline ≥ 40%.Using pooled data from the two cohorts we found that generally FPG variability were associated with higher risk of eGFR decline ≥ 40% only among non-T2D individuals., Conclusions: Higher FPG variability was associated with an increased risk of eGFR decline in the diabetic American population; however, this unfavorable impact was found only among the non-diabetic Iranian population., (© 2023. The Author(s).)