Functional sympatholysis is impaired in end-stage renal disease.

Patients with end-stage renal disease (ESRD) have decreased exercise capacity and exercise intolerance that contribute to cardiovascular risk. One potential mechanism underlying exercise intolerance in ESRD is impaired ability to oppose sympathetically mediated vasoconstriction within exercising skeletal muscle (i.e., functional sympatholysis, FS). We hypothesized that ESRD patients have impaired FS compared with healthy (CON) and hypertensive (HTN) controls and that impaired FS is related to circulating levels of the uremic toxin asymmetric dimethyl arginine (ADMA), an endogenous nitric oxide synthase inhibitor. Near-infrared spectroscopy-derived oxygen tissue saturation index (TSI) of the forearm muscle was measured continuously in 33 participants (9 CON, 14 HTN, 10 ESRD) at rest and during low-dose (-20 mmHg) lower body negative pressure (LBNP), moderate rhythmic handgrip exercise, and LBNP with concomitant handgrip exercise (LBNP+handgrip). Resting muscle TSI was lower in ESRD than in CON and HTN groups (CON = 67.8 ± 1.9%, HTN = 67.2 ± 1.1%, ESRD = 62.7 ± 1.5%, P = 0.03). Whereas CON and HTN groups had an attenuation in sympathetically mediated reduction in TSI during LBNP + handgrip compared with LBNP alone (P ≤ 0.05), this response was not present in ESRD (P = 0.71), suggesting impaired FS. There was no difference in plasma [ADMA] between groups (CON = 0.47 ± 0.05 µmol/l, HTN = 0.42 ± 0.06 µmol/l, ESRD = 0.63 ± 0.14 µmol/l, P = 0.106) and no correlation between plasma [ADMA] and resting muscle TSI (P = 0.84) or FS (P = 0.75). Collectively, these findings suggest that ESRD patients have lower muscle perfusion at rest and impaired FS but that these derangements are not related to circulating [ADMA].

Metabolic acidosis augments exercise pressor responses in chronic kidney disease.

Chronic kidney disease (CKD) patients experience augmented blood pressure (BP) reactivity during exercise that is associated with an increased risk of cardiovascular mortality. Exaggerated exercise pressor responses in CKD are in part mediated by augmented sympathetic nerve activation due to heightened muscle mechanoreflex. One mechanism that may lead to sensitization of the muscle mechanoreflex in CKD is metabolic acidosis. We hypothesized that CKD patients with low serum [bicarbonate] would exhibit exaggerated increases in arterial BP, greater reductions in muscle interstitial pH, and fatigue earlier during exercise compared with CKD patients with normal serum bicarbonate concentration ([bicarbonate]). Eighteen CKD participants with normal serum [bicarbonate] (≥24 mmol/l, normal-bicarb) and 9 CKD participants with mild metabolic acidosis ([bicarbonate] range 20-22 mmol/l, low-bicarb) performed rhythmic handgrip (RHG) exercise to volitional fatigue at 40% of maximal voluntary contraction. BP, heart rate, and muscle interstitial pH using near infrared spectroscopy were measured continuously. While mean arterial pressure (MAP) increased with exercise in both groups (P ≤ 0.002), CKD with low-bicarb had an exaggerated MAP response compared with CKD with normal-bicarb (+5.9 ± 1.3 mmHg/30 s vs. +2.6 ± 0.5 mmHg/30 s, P = 0.01). The low-bicarb group reached exhaustion earlier than the normal-bicarb group (179 ± 21 vs. 279 ± 19 s, P = 0.003). There were no differences in the change in muscle interstitial pH during exercise between groups (P = 0.31). CKD patients with metabolic acidosis have augmented exercise-induced increases in BP and poorer exercise tolerance. There was no difference in change in muscle interstitial pH between groups, however, suggesting that augmented exercise BP responses in metabolic acidosis are not due to impaired muscle-buffering capacity.

Association Between Nephrologist Ownership of Dialysis Facilities and Clinical Outcomes.

Importance: Ownership of US dialysis facilities presents a financial conflict of interest for nephrologists, who may change their clinical practice to improve facility profitability. Objective: To investigate the association between nephrologist ownership of freestanding dialysis facilities and clinical outcomes. Design, Setting, and Participants: This cross-sectional study was conducted using US Renal Data System data linked to a data set of freestanding nonpediatric dialysis facility owners. Participants were a sample of all adults with fee-for-service Medicare receiving dialysis for end-stage kidney disease from January 2017 to November 2017 at included facilities. Data were analyzed from April 2020 through August 2022. Exposures: Outcomes associated with nephrologist ownership were assessed using a difference-in-differences analysis comparing the difference in outcomes between patients treated by nephrologist owners and patients treated by nonowners within facilities owned by nephrologists after accounting for differences in patient outcomes between nephrologist owners and nonowners in other facilities. Main Outcomes and Measures: Outcomes plausibly associated with nephrologist ownership were evaluated: (1) treatment volumes (missed treatments and transplant waitlist status); (2) erythropoietin-stimulating agent (ESA) use and related outcomes (anemia, defined as hemoglobin level <10 g/dL, and blood transfusions), (3) quality metrics (mortality, hospitalizations, 30-day readmissions, hemodialysis adequacy, arteriovenous fistula use, and hemodialysis catheter use for ≥3 months), and (4) home dialysis use. Results: A cohort of 251 651 patients (median [IQR] age, 66 [46-85] years; 112 054 [44.5%] women; 9765 Asian [3.9%], 86 837 Black [34.5%], and 148 617 White [59.1%]; 38 938 Hispanic [15.5%]) receiving dialysis for end-stage kidney disease were included. Patient treatment by nephrologist owners at their owned facilities was associated with a 2.4 percentage point (95% CI, 1.1-3.8 percentage points) higher probability of home dialysis, a 2.2 percentage point (95% CI, 3.6-0.7 percentage points) lower probability of receiving an ESA, and no significant difference in anemia or blood transfusions. Patient treatment by nephrologist owners at their owned facilities was not associated with differences in missed treatments, transplant waitlisting, mortality, hospitalizations, 30-day readmissions, hemodialysis adequacy, or fistula or long-term dialysis catheter use. Conclusions and Relevance: This cross-sectional cohort study found that nephrologist ownership was associated with increased home dialysis use, decreased ESA use, and no change in anemia or blood transfusions.