This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator. End-Stage Renal Disease (ESRD) is associated with brain damage, usually seen as cognitive deficits. Clinical research in this area is complicated by several factors. ESRD patients suffer from several comorbidities, which could cause brain damage and cognitive deficits by themselves; therefore, cross-sectional comparisons to the general population cannot directly address the ESRD itself. Second, ESRD is not a static condition but a progressive disease: any understanding of its causes and consequences must account for its longitudinal course. Third, the most common treatment, hemodialysis (HD), is itself a highly complex process with a significant possibility of iatrogenic effects. In previous studies, we have replicated the findings of cerebral atrophy and neuropsychological deficits in dialyzed ESRD patients. We have also found severe reductions of cerebral perfusion, and dramatic deficits in cortical oxygenation. The perfusion deficits, but not the hypoxia, returned to normal levels at the end of each dialysis sesssion, only to fall again in the inter-dialytic interval. In a small group of ESRD patients treated with the more benign peritoneal dialysis (PD), these abnormalities were less pronounced. These findings strongly indicate a severe cerebrovascular insufficiency that may underlie some features of uremic encephalopathy. These findings also suggest that the risks of HD may be nontrivial, and that the possibility exists of modifying the procedure or adding treatments to ameliorate the consequences. In the immediate future, if our preliminary findings are confirmed in a large prospective study, they suggest a rational basis for strongly preferring PD over HD. In preparation for an NIH grant application, we need to collect additional preliminary data with the new 3T MRI, as well as increase the size of our PD sample. This is the purpose of the current GCRC application. We propose to study up to 20 ESRD patients, including 10 PD patients, 5 HD patients and 5 untreated ESRD patients. They will undergo three procedures: quantitative carotid Doppler, Cerebral Oxymetry by Near-Infrared Spectroscopy, and MRI (anatomy, DTI, MRS and ASL). These procedures are all Minimal Risk. Based on these data, we will submit a larger study for NIH funding.Hypothesis: We posit that the brain is already compromised in undialyzed CKD patients, and the damage is progressive with duration and/or severity of disease. We further hypothesize that the damage is maintained or ameliorated with PD, but accelerated with HD.
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