Exploring the Cognitive Profiles of Haemodialysis Patients using Objective and Subjective Indicators: A Cross-sectional Observational Study.

BACKGROUND: Cognitive impairment is common in haemodialysis patients and associated with adverse health outcomes. Previous work focused primarily on neuropsychological tests, the gold standard measure of cognition. However, these tests reflect performance under optimal conditions rather than performance in everyday life. This study aims to assess both objective and subjective cognition in haemodialysis patients. METHODS: Adult haemodialysis patients completed measures of objective cognitive impairment (Montreal Cognitive Assessment), subjective cognitive complaints, mood and fatigue symptoms, and provided sociodemographic information. Clinical data such as comorbidity were extracted from patients' medical record. RESULTS: A total of 268 haemodialysis patients (mean age = 59.87 years; 42.5% female) participated. Only 25.0% of the sample had normal cognition, while the rest had either objective cognitive impairments or clinically significant cognitive complaints, or both (both objective impairments and subjective complaints: 26.1%; objective impairments without complaint: 38.4%; significant complaints without objective impairments: 10.4%). Lower education was associated with the presence of objective cognitive impairments, whereas depression was associated with the presence of clinically significant cognitive complaints. Patients who exhibited both objective cognitive impairments and significant cognitive complaints were more likely to have diabetes and higher dialysis dose (Kt/V). Patients with objective cognitive impairments but no significant complaints were significantly older. CONCLUSIONS: The cognitive burden of haemodialysis patients can be manifested as objective impairments and/or subjective complaints. When combined the two indicators may better represent the overall cognitive well-being in this population. There is a need to screen for cognitive difficulties and develop cognitive rehabilitative strategies in dialysis settings.

Human SLC26A1 gene variants: a pilot study.

Kidney stones are a global health problem, incurring massive health costs annually. Why stones recur in many patients remains unknown but likely involves environmental, physiological, and genetic factors. The solute linked carrier (SLC) 26A1 gene has previously been linked to kidney stones in mice. SLC26A1 encodes the sulfate anion transporter 1 (SAT1) protein, and its loss in mice leads to hyperoxaluria and calcium oxalate renal stones. To investigate the possible involvement of SAT1 in human urolithiasis, we screened the SLC26A1 gene in a cohort of 13 individuals with recurrent calcium oxalate urolithiasis, which is the commonest type. DNA sequence analyses showed missense mutations in seven patients: one individual was heterozygous R372H; 4 individuals were heterozygous Q556R; one patient was homozygous Q556R; and one patient with severe nephrocalcinosis (requiring nephrectomy) was homozygous Q556R and heterozygous M132T. The M132 amino acid in human SAT1 is conserved with 15 other species and is located within the third transmembrane domain of the predicted SAT1 protein structure, suggesting that this amino acid may be important for SAT1 function. These initial findings demonstrate genetic variants in SLC26A1 of recurrent stone formers and warrant wider independent studies of SLC26A1 in humans with recurrent calcium oxalate stones.

Fetal loss and hyposulfataemia in pregnant NaS1 transporter null mice.

Sulfate is important for growth and development, and is supplied from mother to fetus throughout pregnancy. We used NaS1 sulfate transporter null (Nas1(-/-)) mice to investigate the role of NaS1 in maintaining sulfate homeostasis during pregnancy and to determine the physiological consequences of maternal hyposulfataemia on fetal, placental and postnatal growth. We show that maternal serum (≤0.5 mM), fetal serum (<0.1 mM) and amniotic fluid (≤0.5 mM) sulfate levels were significantly lower in pregnant Nas1(-/-) mice when compared with maternal serum (≍2.0 mM), fetal serum (≍1.5 mM) and amniotic fluid (≍1.7 mM) sulfate levels in pregnant Nas1(+/+) mice. After 12 days of pregnancy, fetal reabsorptions led to markedly reduced (by ≥50%) fetal numbers in Nas1(-/-) mice. Placental labyrinth and spongiotrophoblast layers were increased (by ≍140%) in pregnant Nas1(-/-) mice when compared to pregnant Nas1(+/+) mice. Birth weights of progeny from female Nas1(-/-) mice were increased (by ≍7%) when compared to progeny of Nas1(+/+) mice. These findings show that NaS1 is essential to maintain high maternal and fetal sulfate levels, which is important for maintaining pregnancy, placental development and normal birth weight.