Background: The transition to dialysis period carries a substantial increased cardiovascular risk in patients with chronic kidney disease. Despite this, alterations in cardiovascular functional capacity during this transition are largely unknown. The present study therefore sought to assess ventilatory exercise response measures in patients within 1 year of initiating dialysis. Methods and Results: We conducted a cross‐sectional study of 241 patients with chronic kidney disease stage 5 from the CAPER (Cardiopulmonary Exercise Testing in Renal Failure) study and from the intradialytic low‐frequency electrical muscle stimulation pilot randomized controlled trial cohorts. Patients underwent cardiopulmonary exercise testing and echocardiography. Of the 241 patients (age, 48.9 [15.0] years; 154 [63.9%] men), 42 were predialytic (mean estimated glomerular filtration rate, 14 mL·min ⁻¹ ·1.73 m ⁻² ), 54 had a dialysis vintage ≤12 months, and 145 had a dialysis vintage >12 months. Dialysis vintage ≤12 months exhibited a significantly impaired cardiovascular functional capacity, as assessed by oxygen uptake at peak exercise (18.7 [5.8] mL·min ⁻¹ ·kg ⁻¹ ) compared with predialysis (22.7 [5.2] mL·min ⁻¹ ·kg ⁻¹ ; P <0.001). Dialysis vintage ≤12 months also exhibited reduced peak workload, impaired peak heart rate, reduced circulatory power, and increased left ventricular mass index ( P 12 months exhibited a lower oxygen uptake at peak exercise (17.0 [4.9] mL·min ⁻¹ ·kg ⁻¹ ) compared with dialysis vintage ≤12 months (18.9 [5.9] mL·min ⁻¹ ·kg ⁻¹ ; P =0.033). Conclusions: Initiating dialysis is associated with a significant impairment in oxygen uptake at peak exercise and overall decrements in ventilatory and hemodynamic exercise responses that predispose patients to functional dependence. The magnitude of these changes is comparable to the differences between low‐risk New York Heart Association class I and higher‐risk New York Heart Association class II to IV heart failure.

Mixed panel count data represent a common complex data structure in longitudinal survey studies. A major challenge in analyzing such data is variable selection and estimation while efficiently incorporating both the panel count and panel binary data components. Analyses in the medical literature have often ignored the panel binary component and treated it as missing with the unknown panel counts, while obviously such a simplification does not effectively utilize the original data information. In this research, we put forward a penalized likelihood variable selection and estimation procedure under the proportional mean model. A computationally efficient EM algorithm is developed that ensures sparse estimation for variable selection, and the resulting estimator is shown to have the desirable oracle property. Simulation studies assessed and confirmed the good finite-sample properties of the proposed method, and the method is applied to analyze a motivating dataset from the Health and Retirement Study.

Key Points: The highest fibroblast growth factor 23 (FGF23) quartile had impaired VO₂Max and ventilatory exercise response patterns compared with the lowest FGF23 quartile. FGF23 was associated with changes in VO₂Max in advanced CKD and after restitution of the failing kidney by transplantation. FGF23 was only associated with the progression of left ventricular mass index in patients with advanced CKD, however this association was lost after adjustment for dialysis status in the final model and was not associated after kidney transplantation in all models. Background: Fibroblast growth factor 23 (FGF23) is a bone-derived phosphatonin that is elevated in chronic kidney disease (CKD) and has been implicated in the development of cardiovascular disease. It is unknown whether elevated FGF23 in CKD is associated with impaired cardiovascular functional capacity, as assessed by maximum exercise oxygen consumption (VO₂Max). We sought to determine whether FGF23 is associated with cardiovascular functional capacity in patients with advanced CKD and after improvement of VO₂Max by kidney transplantation. Methods: We performed secondary analysis of 235 patients from the Cardiopulmonary Exercise Testing in Renal Failure and After Kidney Transplantation (CAPER) cohort, which recruited patients with stage 5 CKD who underwent kidney transplantation or were waitlisted and hypertensive controls. All patients underwent cardiopulmonary exercise testing (CPET) and echocardiography and were followed longitudinally for 1 year after study enrollment. Results: Patients across FGF23 quartiles differed in BMI (P=0.004) and mean arterial pressure (P<0.001) but did not significantly differ in sex (P=0.5) or age (P=0.08) compared with patients with lower levels of FGF23. Patients with higher FGF23 levels had impaired VO₂Max (Q1: 24.2±4.8 ml/min per kilogram; Q4: 18.6±5.2 ml/min per kilogram; P<0.001), greater left ventricular mass index (LVMI; P<0.001), reduced HR at peak exercise (P<0.001), and maximal workload (P<0.001). Kidney transplantation conferred a significant decline in FGF23 at 2 months (P<0.001) before improvement in VO₂Max at 1 year (P=0.008). Multivariable regression modeling revealed that changes in FGF23 was significantly associated with VO₂Max in advanced CKD (P<0.001) and after improvement after kidney transplantation (P=0.006). FGF23 was associated with LVMI before kidney transplantation (P=0.003), however this association was lost after adjustment for dialysis status (P=0.4). FGF23 was not associated with LVMI after kidney transplantation in all models. Conclusions: FGF23 levels are associated with alterations in cardiovascular functional capacity in advanced CKD and after kidney transplantation. FGF23 is only associated with structural cardiac adaptations in advanced CKD but this was modified by dialysis status, and was not associated after kidney transplantation.

Key Points: In individuals undergoing bariatric surgery, the magnitude of decline in GFR postbariatric surgery is directly associated with presurgery GFR. Reductions in GFR postsurgery were only weakly correlated with weight loss. In obese individuals, GFR-estimating equations performed best when deindexed and when applied in people with reduced kidney function. Background: Important questions remain about how bariatric ( i.e ., weight loss) surgery affects measured GFR (mGFR) and eGFR as well as what factors influence change in mGFR postsurgery. Methods: Data were pooled from all seven available studies (dates: 2004–2018) measuring GFR prebariatric and postbariatric surgery using gold standard methods. Change in postsurgery mGFR, factors that could influence change in mGFR, and effects on five GFR-estimating equations were analyzed using standard statistical methods. Results: The cohort included 105 individuals from the United States and Europe. Sixty-eight percent were female, 97% were White, the mean age was 50 years (range, 24–70), and the mean body mass index was 46±8 kg/m ² . The mean presurgery mGFR of 107 ml/min (range, 31–215) fell to 92 ml/min (−14%; 95% confidence interval, −21 to −10) postsurgery, with a strong linear relationship existing between presurgery mGFR and % change in GFR ( r =−0.51; −0.64 to −0.35). Individuals with presurgery mGFR ≥90, 60 to <90, and<60 ml/min had −25 (−32 to −19), 1 (−11 to 13), and 7 (0 to 14) ml/min mean postoperative changes in mGFR. Change in weight was significantly correlated with change in mGFR ( r =0.22; 0.03 to 0.40). After adjusting for sex, changes in mGFR postsurgery were associated with higher presurgical age (−0.6 ml/min per year; −1.1 to −0.2), mGFR (−0.5 ml/min per 1 ml/min; −0.6 to −0.4), and change in systolic BP (−0.3 ml/min per 1 mm Hg; −0.6 to 0.0). All GFR-estimating equations significantly underestimated postsurgical GFR reductions in people with preserved kidney function and had improved bias, precision, and accuracy when deindexed and applied to individuals with mGFR <90 ml/min. Conclusions: In individuals with obesity undergoing bariatric surgery, the magnitude of postsurgical decline in mGFR was directly associated with presurgery GFR and weakly correlated with weight loss. In addition, GFR-estimating equations' performance improved when deindexed and used in people with reduced kidney function, with the combined creatinine/cystatin C equations having the best overall performance.