{"doi":"10.2215/cjn.08410621","title":"Cerebrovascular Response during Acute Exercise in Kidney Transplant Recipients","abstract":"Despite well-known benefits of kidney transplantation, the risk of stroke and cognitive impairment (1) remain higher in transplant recipients than the general population. Underlying mechanisms may not be solely related to eGFR (2), and altered cerebral blood flow (3) and possibly cerebrovascular response may contribute. Middle cerebral artery blood velocity (MCAV) response to exercise quantifies the physiologic increase in cerebral blood flow with exercise and determines the ability to maintain cerebral blood flow through physiologic stresses; it is measured by the increase in MCAV from rest to steady-state exercise (4,5). We hypothesized that kidney transplant recipients have a blunted MCAV response and impaired MCAV kinetics response profile with exercise. In this cross-sectional, observational study, we compared MCAv response and MCAV kinetics response profile with exercise in 50 kidney transplant recipients to 50 age- and sex-matched healthy controls without CKD using transcranial Doppler ultrasound during an acute bout of moderate-intensity exercise. We enrolled transplant recipients from our transplant clinic, and healthy controls from the community by word-of-mouth and flyers. All experimental procedures were approved by the Human Subjects Committee, and all participants gave informed consent. Inclusion criteria were: age 20–85 years, ≥3 months since transplantation, stable kidney function, a serum creatinine <3 mg/dl, and ability to perform moderate-intensity exercise. Patients were excluded if they had a dual organ transplant, acute stroke, concussion, traumatic brain injury, Parkinson’s disease, dementia, multiple sclerosis, severe pulmonary disease or dependency on supplemental oxygen, or if they were using antipsychotics or antiepileptics. Participants were excluded from the analysis if study staff were not able to acquire MCA signal using transcranial Doppler ultrasound. All transplant recipients were on calcineurin inhibitors per institutional protocol. The experimental protocol used was identical to our prior work (4,5). Briefly, beat to beat heart rate (HR), mean arterial pressure, MCAV, and end-tidal carbon dioxide (PETCO2) were measured at rest and at steady state moderate-intensity exercise defined as 45%–55% of HR reserve calculated using the Karvonen formula. Participants completed two exercise bouts and data points were averaged to optimize signal-to-noise ratio. Our primary outcome, MCAv response to exercise, was calculated as the change in mean beat to beat MCAV from rest to steady-state moderate-intensity exercise. Our secondary outcome, MCAV kinetics response profile, was measured using 3-second time-binned means over the entire rest and exercise bout with a mono-exponential model: MCAV(t)=BL+Amp(1−e−(t−TD)/τ)) where MCAV(t) is the MCAV at any point in time, BL is the baseline resting MCAV prior to starting exercise, TD is the time delay preceding the exponential increase in MCAV, Amp is the peak amplitude of the response, and tau (τ) is the time constant. Demographic characteristics, MCAv response to exercise, and MCAV kinetics response profile are presented in Table 1. Baseline mean arterial pressure and HR were higher in the transplant recipients. There was no difference in resting MCAV between transplant recipients and controls (P=0.31), likely because the two groups were age-matched (4). PETCO2 monitoring did not reveal hyperventilation. Both groups reached moderate-intensity exercise. However, transplant recipients reached a similar HR at a lower work rate, likely indicating that they were more “deconditioned” than the controls. Transplant recipients had a blunted MCAv response to exercise (P=0.003). There was no association between MCAv response to exercise and duration of dialysis or time since transplantation. Because of poor model fit (i.e., nonexponential response), three transplant recipients were excluded from the MCAV kinetics response profile analysis. Transplant recipients achieved tar","journal":"Clinical Journal of the American Society of Nephrology","year":2021,"id":202865,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.963,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":784122,"name":"Madhuri Ramakrishnan","orcid":null,"position":1,"is_corresponding":false},{"id":784123,"name":"Andrew Jurgensen","orcid":null,"position":2,"is_corresponding":false},{"id":784124,"name":"Sandra Billinger","orcid":null,"position":3,"is_corresponding":false},{"id":424353,"name":"Aditi Gupta","orcid":"0000-0002-6286-802X","position":4,"is_corresponding":false},{"id":386217,"name":"Jaimie L. Ward","orcid":null,"position":0,"is_corresponding":true}],"reference_count":5,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:51:14.206397Z","pmid":"34615658","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}