ABSTRACT
BACKGROUND: Little is known concerning the risk of hospitalization and the risk of death before receiving dialysis by the stage of chronic kidney disease (CKD) in Japan. METHODS: The subjects comprised a total of 13,911 Japanese men (mean age 49.2 ± 9.9 years). Based on the results of a health checkup performed in 2006, they were divided into 5 groups according to their estimated glomerular filtration rate (GFR) levels and dialysis status: GFR ≥60, 45-59, 30-44, <30 mL/min/1.73 m2, and undergoing dialysis. From 2006 through to 2013, we investigated their hospitalization, dialysis initiation, and cause-specific death. The adjusted hazard ratios (HRs) for each end point were calculated compared with the GFR ≥60 mL/min/1.73 m2 group using a Cox proportional hazard model. RESULTS: A lower GFR was independently associated with higher risks of overall hospitalization, dialysis initiation, and all-cause death. In particular, the HRs for long-term hospitalization (≥1 month a year), dialysis, and cardiovascular disease (CVD) death markedly increased along with a decreased GFR. The rate ratios of dialysis to all-cause death (calculated based on the incidences of dialysis and death per 1000 person-years) were 0.03 (0.11 vs. 3.19), 0.08 (0.29 vs. 3.62), 0.51 (12.5 vs. 24.7), and 4.50 (179.8 vs. 40.0) for GFR ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2, respectively. CONCLUSION: In Japanese men, although the risk of CVD death before dialysis initiation can never be ignored, CKD patients aged <60 years with a GFR of <30 mL/min/1.73 m2 are more likely to undergo dialysis prior to death.
Subject(s)
Glomerular Filtration Rate , Hospitalization , Kidney/physiopathology , Renal Dialysis/mortality , Renal Insufficiency, Chronic/mortality , Renal Insufficiency, Chronic/therapy , Adult , Cardiovascular Diseases/mortality , Cause of Death , Humans , Japan/epidemiology , Longitudinal Studies , Male , Middle Aged , Multivariate Analysis , Proportional Hazards Models , Renal Dialysis/adverse effects , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/physiopathology , Risk Assessment , Risk Factors , Sex Factors , Time Factors , Treatment OutcomeABSTRACT
Glutamine synthetase (GS) is a key enzyme in the regulation of glutamate neurotransmission in the central nervous system. It is responsible for converting glutamate to glutamine, consuming one ATP and NH3 in the process. Glutamate is neurotoxic when it accumulates in extracellular fluids. We investigated the effects of GS in both a spinal cord injury (SCI) model and normal rats. 0.1-ml of low (2-microM) and high (55-microM) concentrations of GS were applied, intrathecally, to the spinal cord of rats under pentobarbital anesthesia. Immediately after an intrathecal injection into the L1-L3 space, the rats developed convulsive movements. These movements initially consisted of myoclonic twitches of the paravertebral muscles close to the injection site, repeated tonic and clonic contractions and extensions of the hind limbs (hind limb seizures) that spread to the fore limbs, and finally rotational axial movements of the body. An EMG of the paravertebral muscles, fore and hind limbs, showed the extent of the muscle activities. GS (2-microM) caused spinal seizures in the rats after the SCI, and GS (6-microM) produced seizures in the uninjured anesthetized rats. Denatured GS (70 degrees C, 1 hour) also produced spinal seizures, although higher concentrations were required. We suggest that GS may be directly blocking the release of GABA, or the receptors, in the spinal cord.
