Introduction. Understanding the mechanisms underlying the differences in renal decline between men and women may improve sex-specific clinical monitoring and management. To this end, we aimed to... Show moreIntroduction. Understanding the mechanisms underlying the differences in renal decline between men and women may improve sex-specific clinical monitoring and management. To this end, we aimed to compare the slope of renal function decline in older men and women in chronic kidney disease (CKD) Stages 4 and 5, taking into account informative censoring related to the sex-specific risks of mortality and dialysis initiation.Methods. The European QUALity Study on treatment in advanced CKD (EQUAL) study is an observational prospective cohort study in Stages 4 and 5 CKD patients >= 65years not on dialysis. Data on clinical and demographic patient characteristics were collected between April 2012 and December 2018. Estimated glomerular filtration rate (eGFR) was calculated using the CKD Epidemiology Collaboration equation. eGFR trajectory by sex was modelled using linear mixed models, and joint models were applied to deal with informative censoring.Results. We included 7801 eGFR measurements in 1682 patients over a total of 2911years of follow-up. Renal function declined by 14.0% [95% confidence interval (CI) 12.9-15.1%] on average each year. Renal function declined faster in men (16.2%/year, 95% CI 15.9-17.1%) compared with women (9.6%/year, 95% CI 6.3-12.1%), which remained largely unchanged after accounting for various mediators and for informative censoring due to mortality and dialysis initiation. Diabetes was identified as an important determinant of renal decline specifically in women.Conclusion. In conclusion, renal function declines faster in men compared with women, which remained similar after adjustment for mediators and despite a higher risk of informative censoring in men. We demonstrate a disproportional negative impact of diabetes specifically in women. Show less
Background and objectives Predictingdiseaseprogression in patientswith autosomaldominantpolycystic kidney disease (ADPKD) poses a challenge, especially in early- stage disease when kidney function... Show moreBackground and objectives Predictingdiseaseprogression in patientswith autosomaldominantpolycystic kidney disease (ADPKD) poses a challenge, especially in early- stage disease when kidney function is not yet affected. Ongoing growth of cysts causes maximal urine-concentrating capacity to decrease from early on. We therefore hypothesized that the urine-to-plasmaurea ratio, as a reflection of the urine-concentrating capacity, can be used as a marker to predict ADPKD progression. Design The urine- to-plasma urea ratio was calculated by dividing concentrations of early morning fasting spot urine urea by plasma urea. First, this ratio was validated as surrogate marker in 30 patients with ADPKD who underwent a prolongedwater deprivation test. Thereafter, associationwith kidney outcomewas evaluated in 583 patients with ADPKDwith a broad range of kidney function. Multivariable mixed-model regressionwas used to assess association with eGFR slope, and logarithmic regression to identify patients with rapidly progressive disease, using a cutoff of 23.0 ml/min per 1.73 m2 per year. The urine-to-plasma urea ratio was compared with established predictors, namely, sex, age, baseline eGFR, Mayo Clinic height-adjusted total kidney volume class, and PKD gene mutation. Results The maximal urine-concentrating capacity and urine-to-plasma urea ratio correlated strongly (R50.90; P,0.001). Next, the urine-to-plasma urea ratio was significantly associated with rate of eGFR decline during a median follow-up of 4.0 (interquartile range, 2.6-5.0) years, both crude and after correction for established predictors (b50.58; P50.02). The odds ratio of rapidly progressive diseasewas 1.35 (95% confidence interval, 1.19 to 1.52; P,0.001) for every 10 units decrease in urine-to-plasma urea ratio, with adjustment for predictors. A combined risk score of the urine-to-plasma urea ratio, MayoClinic height-adjusted total kidney volume class, and PKD mutation predicted rapidly progressive disease better than each of the predictors separately. Conclusions The urine-to-plasma urea ratio, which is calculated fromroutine laboratory measurements, predicts disease progression in ADPKD in addition to other risk markers. Show less
