Cognitive changes associated with switching to frequent nocturnal hemodialysis or renal transplantation.

BACKGROUND: It is uncertain whether switching to frequent nocturnal hemodialysis improves cognitive function in well-dialyzed patients and how this compares to patients who receive a kidney transplant. METHODS: We conducted a multicenter observational study with longitudinal follow-up of the effect on cognitive performance of switching dialysis treatment modality from conventional thrice-weekly hemodialysis to frequent nocturnal hemodialysis, a functioning renal transplant or remaining on thrice-weekly conventional hemodialysis. Neuropsychological tests of memory, attention, psychomotor processing speed, executive function and fluency as well as measures of solute clearance were performed at baseline and again after switching modality. The change in cognitive performance measured by neuropsychological tests assessing multiple cognitive domains at baseline, 4 and 12 months after switching dialysis modality were analyzed using a linear mixed model. RESULTS: Seventy-seven patients were enrolled; 21 of these 77 patients were recruited from the randomized Frequent Hemodialysis Network (FHN) Nocturnal Trial. Of these, 18 patients started frequent nocturnal hemodialysis, 28 patients received a kidney transplant and 31 patients remained on conventional thrice-weekly hemodialysis. Forty-eight patients (62 %) returned for the 12-month follow-up. Despite a significant improvement in solute clearance, 12 months treatment with frequent nocturnal hemodialysis was not associated with substantial improvement in cognitive performance. By contrast, renal transplantation, which led to near normalization of solute clearance was associated with clinically relevant and significant improvements in verbal learning and memory with a trend towards improvements in psychomotor processing speed. Cognitive performance in patients on conventional hemodialysis remained stable with the exception of an improvement in psychomotor processing speed and a decline in verbal fluency. CONCLUSIONS: In patients on conventional thrice-weekly hemodialysis, receiving a functioning renal transplant was associated with improvement in auditory-verbal memory and psychomotor processing speed, which was not observed after 12 months of frequent nocturnal hemodialysis.

Mice defective in Trpm6 show embryonic mortality and neural tube defects.

The syndrome of hypomagnesemia with secondary hypocalcemia is caused by defective TRPM6. This protein is an ion channel that also contains a kinase in its C-terminus. It is usually diagnosed in childhood and, without treatment with supplemental Mg, affected children suffer from mental retardation, seizures and retarded development. We developed a mouse lacking Trpm6 in order to understand in greater detail the function of this protein. In contrast to our expectations, Trpm6(-/-) mice almost never survived to weaning. Many mice died by embryonic day 12.5. Most that survived to term had neural tube defects consisting of both exencephaly and spina bifida occulta, an unusual combination. Feeding dams a high Mg diet marginally improved offspring survival to weaning. The few Trpm6(-/-) mice that survived were fertile but matings between Trpm6(-/-) mice produced no viable pregnancies. Trpm6(+/-) mice had normal electrolytes except for modestly low plasma [Mg]. In addition, some Trpm6(+/-) mice died prematurely. Absence of Trpm6 produces an apparently different phenotype in mice than in humans. The presence of neural tube defects identifies a previously unsuspected role of Trpm6 in effecting neural tube closure. This genetic defect produces one of very few mouse models of spina bifida occulta. These results point to a critical role of Trpm6 in development and suggest an important role in neural tube closure.