Patients with ESRD treated with hemodialysis (HD) have previously been described to have progressive brain atrophy. Whether this is due to kidney disease or unique features of HD (intradialytic hypotension, exposure of blood to an artificial membrane, etc.) is unknown. In an article recently published in AJKD, Tsuruya et al report their study of Japanese peritoneal dialysis (PD) patients undergoing T1-weighted MRI brain scanning. Patients with CKD not on dialysis (eGFR <60 mL/min /1.73 m2) were used as comparators, and both a cross-sectional and 2-year longitudinal approach was employed. Measurements were taken for total grey matter volume (GMV), total white matter volume (WMV), and cerebrospinal fluid space volume, all normalized for total intracranial volume. Patients in the 2 groups were well matched for age, sex, prior cardiovascular disease, and diabetes. However, PD patients had higher systolic blood pressure, lower hemoglobin, and, unsurprisingly, much higher rates of EPO use. The comparator group was mostly CKD stage 3, and mean eGFR was almost 40mL/min/1.73m2.
In the cross-sectional study of 62 PD and 69 CKD patients, normalized GMV was significantly lower in PD patients at baseline, with no difference in WMV. Of these 131 patients, 34 PD and 61 CKD patients entered into the longitudinal study with MRI data available at 2 years. The dropouts from the longitudinal study were not significantly different from those who were included. Normalized GMV after 2 years was also significantly lower in the PD patients, and had a more rapid decrease in GMV than the comparators, irrespective of baseline GMV and adjusting for confounding variables. The changes were especially evident in the parietal and temporal lobes.
This is the first study to investigate brain atrophy in an exclusive PD cohort. The observational nature of the study precludes determination of causality, but the authors speculate that uremia-induced oxidative injury may be the reason, with increased BP possibly a contributing factor. Hypertension is a known risk factor for brain atrophy, and is often present in PD patients, perhaps more so that in HD patients. Moreover, the PD cohort had higher mean systolic BP than CKD patients; however, BP difference was adjusted for in the multi-factorial model, as pointed out by the authors.
It would be interesting to compare the degree of atrophy in HD patients, PD patients, and individuals with normal kidney function. It would also be informative if the structural changes were correlated with objective cognitive function testing. Also, the large dropout of PD patients from the cross-sectional to the longitudinal arm leaves a potential for bias, despite the dropouts having similar clinical features as included patients.
This study demonstrates a rapid decline in brain grey matter volume in PD patients over a 2-year period. Declining cognitive function is common in our ESRD patients. This study illustrates the likely structural correlate of this clinical observation, and highlights the need for additional study into the precise mechanism and prevention.
Dr. Paul Phelan
AJKD Blog Contributor