As the aging of the population progresses in Japan, the nutritional problems in dialysis patients are being highlighted. Frailty is a clinical concept including body weight loss, muscle weakness, fatigability, decreased walking speed, and decreased physical activity, which means an intermediate concept between healthy subjects and disability subjects, indicating that their activities of daily living are not decreased but they cannot smoothly perform housework or exercise. Morbidity of dialysis patients is known to be high, and mortality of dialysis patients with frailty is 3 times higher. Sarcopenia is one of the principal reasons for or triggers of frailty. It is a disease setting showing decreased muscle volume and quality associated with decreased physical function or quality of life. Recent mean age at dialysis therapy induction is getting near to 70 years old in Japan. Japanese dialysis patients who are elderly and present organ failure would have a double risk for sarcopenia. Patients with advanced stages of CKD are generally given protein diet, and it has been reported that a low protein intake in dialysis patients would be a significant risk for developing sarcopenia and increasing mortality. Recently, the focus has been on protein energy wasting (PEW) - an underlying disease condition in sarcopenia or frailty. PEW is an energy wasting condition occurring in dialysis patients, and the cause of PEW is principally decreased food intake and increased catabolism. It has recently been revealed that decreased protein intake would be a risk factor for increased mortality in dialysis patients. The incidence of PEW in dialysis patients is reported to be 14%. To avoid sarcopenia and PEW leading to frailty, we should pay much more attention to an appropriate protein and calorie intake rather than restriction in dialysis patients.

We assessed the expression profile of Mg(2+)-transporting molecules in obese diabetic rats as a cause of hypermagnesiuric hypomagnesemia, which is involved in the development of insulin resistance, hypertension, and coronary diseases. Kidneys were obtained from male Otsuka Long-Evans Tokushima fatty (OLETF) and Long-Evans Tokushima Otsuka (LETO) obese diabetic rats at the ages of 16, 24, and 34 wk. Expression profiles were studied by real-time PCR and immunohistochemistry together with measurements of urine Mg(2+) excretion. Urine Mg(2+) excretion was increased in 24-wk-old OLETF rats and hypomagnesemia was apparent in 34-wk-old OLETF rats but not in LETO rats (urine Mg(2+) excretion: 0.16 ± 0.01 μg·min(-1)·g body wt(-1) in 24-wk-old LETO rats and 0.28 ± 0.01 μg·min(-1)·g body wt(-1) in 24-wk-old OLETF rats). Gene expression of transient receptor potential (TRP)M6 was downregulated (85.5 ± 5.6% in 34-wk-old LETO rats and 63.0 ± 3.5% in 34-wk-old OLETF rats) concomitant with Na(+)-Cl(-) cotransporter downregulation, whereas the expression of claudin-16 in tight junctions of the thick ascending limb of Henle was not different. The results of the semiquantitative analysis of immunohistochemistry were consistent with these findings (TRPM6: 0.49 ± 0.04% in 16-wk-old LETO rats, 0.10 ± 0.01% in 16-wk-old OLETF rats, 0.52 ± 0.03% in 24-wk-old LETO rats, 0.10 ± 0.01% in 24-wk-old OLETF rats, 0.48 ± 0.02% in 34-wk-old LETO rats, and 0.12 ± 0.02% in 34-wk-old OLETF rats). Gene expression of fibrosis-related proinflammatory cytokines as well as histological changes showed that the hypermagnesiuria-related molecular changes and tubulointerstitial nephropathy developed independently. TRPM6, located principally in distal convoluted tubules, appears to be a susceptible molecule that causes hypermagnesiuric hypomagnesemia as a tubulointerstitial nephropathy-independent altered tubular function in diabetic nephropathy.

Our findings may indicate that the combination of the FEMg and the NAG index can provide a specific, sensitive assessment for TIN in patients without renal insufficiency.