Severe hyponatremia in a patient with schizophrenia associated with prolonged consciousness disturbance.

Hyponatremia presents with various central nervous system symptoms during its course and treatment. We treated a patient who presented with a prolonged consciousness disorder and was suspected of having complications of neuroleptic malignant syndrome and osmotic demyelination syndrome (ODS) during the treatment for his hyponatremia, which was caused by syndrome of inappropriate secretion of antidiuretic hormone (SIADH). The patient was a 30-year-old Japanese man who had been under treatment for schizophrenia. He presented with profound hyponatremia (96 mEq/L) and a consciousness disorder. Because he was taking a number of antipsychotic drugs and since psychogenic polydipsia was present along with laboratory findings, the patient was diagnosed with SIADH. However, the consciousness disorder reappeared after his serum sodium concentrations were normalized, and it persisted over a long period. Although ODS was suspected from the clinical course and imaging findings, there were several inconsistencies, such as the lack of quadriplegia. The patient also showed muscular rigidity and fever, and we, therefore, diagnosed complications of malignant hyperthermia syndrome caused by the discontinuation of all antipsychotic drugs at the time of onset. There have been no reports of complications of these two conditions, and we report this case for its clinically valuable information.

How to monitor vascular access in our hospital.

BACKGROUND: The number of dialysis patients in Japan has amounted to approximately 310,000. Most of the patients undergo hemodialysis. The reason why they can undergo hemodialysis is because maintaining and managing vascular access (VA) has improved. Recently, thanks to the progress of medical equipment, a variety of monitoring systems have been developed. It is important to make good use of these monitoring systems. RESULTS: In our hospital, we have been monitoring with an ultrasonic device and HD02. We measure blood flow of brachial artery with an ultrasonic device during nondialysis treatment. We examine real blood flow and blood recirculation with HD02 and evaluate the function of VA during dialysis. CONCLUSIONS: In order to provide good dialysis care, good use of monitoring devices of VA is significant.

The Impact of Buttonhole Cannulation on Patients and Staff in Hemodialysis Facilities.

The two reasons that patients desire buttonhole cannulation are avoidance of puncture pain and extension of arteriovenous fistula life. Despite the desire to receive buttonhole cannulation by many patients, medical staff at most local hemodialysis facilities tend to hesitate to implement the cannulation method. This method is used on patients in the dialysis unit at Saitama Medical Center, but tends to be discontinued for those patients upon their transfer to local hemodialysis facilities. Medical staff members of one local hemodialysis facility report the percentage of patients on the buttonhole method was 53% in 2007, but that it sharply decreased to 17% in 2013. Hesitation by local hemodialysis facilities to adopt the buttonhole method is due to, but not limited to, several factors. These factors include the frequently occurring trampoline effect, the difficulty of removing scabs, formation of a false buttonhole track, and the pain from insertion of a dull needle. Perceived differences in the value of buttonhole cannulation may potentially affect communication between patients and staff in local hemodialysis facilities.

Clinical significance of fractional magnesium excretion (FEMg) as a predictor of interstitial nephropathy and its correlation with conventional parameters.

BACKGROUND: Elevated urine Mg excretion and its correlation with histological damage in tubulo-interstitial nephropathy (TIN) were reported. Here we investigated the clinical significance of the fractional excretion of Mg (FEMg) for the prediction of TIN. METHODS: We enrolled and assessed 94 adult patients with various renal diseases diagnosed principally by renal biopsy. RESULTS: Our stratified analysis based on the value of the conventional TIN parameter N-acetylglucosaminidase (NAG) excretion showed that the high-NAG index group (more than median value of NAG-to-Cr ratio, n = 47) demonstrated significantly high FEMg values (p = 0.017). A univariate analysis revealed a significant correlation between the FEMg and the NAG index (R = 0.60) but not for other parameters. A multivariate regression analysis confirmed the significance of the FEMg as an effective predictor of the NAG index. The FEMg showed a significant correlation with the estimated glomerular filtration rate (eGFR) in the patients with eGFR ≤ 30 mL/min. The correlation of FEMg with the NAG index was not observed in the primary glomerulonephritis patients but was apparent in the patients with hypertensive nephrosclerosis or interstitial nephritis. CONCLUSION: 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.

Downregulation of transient receptor potential M6 channels as a cause of hypermagnesiuric hypomagnesemia in obese type 2 diabetic rats.

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.

Release from glomerular overload by the addition of low-dose thiazide in patients with angiotensin receptor blocker-resistant hypertension.

BACKGROUND/AIMS: This multicenter, prospective, observational study assessed the renoprotective effects of losartan/thiazide combination therapy in terms of lowering the estimated glomerular filtration rate (eGFR). METHODS: Adult patients with angiotensin receptor blocker (ARB)-resistant essential hypertension (n = 104) were enrolled and switched to combination therapy with losartan (50 mg/day) and hydrochlorothiazide (12.5 mg/day). RESULTS: eGFR values declined significantly during the first 3 months, and changes in eGFR were assessed according to tertiles of the eGFR decrease ratio at 3 months. Only the high eGFR decrease (1st tertile) group showed significantly greater decreases in baseline eGFR and albumin-to-creatinine ratio (ACR) during the first 3 months. Additionally, the assessment according to tertiles of the baseline eGFR showed a signifcant decrease in eGFR and ACR during the first 3 months in the high baseline eGFR (1st tertile) group, but not in the moderate (2nd tertile) and low baseline eGFR (3rd tertile) groups. CONCLUSION: The present results revealed that losartan/thiazide combination therapy attenuated glomerular overload, indicating that this therapy may provide glomerular protection in patients with an elevated GFR without causing prolonged damage to renal function.

Prevention of lipopolysaccharide-induced peritoneal damage by eplerenone in rats undergoing peritoneal dialysis.

BACKGROUND: Bacterial peritonitis in patients undergoing peritoneal dialysis (PD) is a major cause of therapy interruption due to peritoneal insufficiency. Here we studied the effect of a selective mineralocorticoid receptor (MR) blocker, eplerenone, on the prevention of peritoneal damage.
 METHODS: Male Sprague-Dawley rats were treated with a daily infusion of human use PD solution (100 mL/kg i.p., PD group, n = 5), or with PD solution and intermittent intraperitoneal injections of lipopolysaccharide (LPS group, n = 5) or with LPS and eplerenone (100 mg/kg/d, po, Ep group, n = 5) for 4 weeks. Peritoneal samples were subjected to assessment following the peritoneal equilibration test (PET). RESULTS: Histological observations revealed that LPS treatment resulted in significant peritoneal thickening associated with increased ED-1-positive cell infiltration and the number of transforming growth factor (TGF)-ß1-positive cells, and that eplerenone reduced these changes. LPS administration also evoked significant upregulation of monocyte chemotactic protein-1 and TGF-ß1, which were inhibited by eplerenone. PET revealed that ultrafiltration and transperitoneal osmotic diffusion were significantly impaired by LPS and restored by eplerenone. Increased value of the mass transfer area coefficients for creatinine values was also recovered by Ep (0.10 ± 0.01 in the PD, 0.14 ± 0.02 in the LPS and 0.08 ± 0.0 in the Ep groups). Immunostaining for von Willebrand factor showed a significant increase by LPS and its restoration by Ep.
 CONCLUSIONS: Ep effectively diminished LPS-induced peritoneal insufficiency. A selective blockade of MR might prevent peritoneal insufficiency associated with bacterial peritonitis.

Renoprotective effect of pioglitazone by the prevention of glomerular hyperfiltration through the possible restoration of altered macula densa signaling in rats with type 2 diabetic nephropathy.

BACKGROUND/AIMS: Pioglitazone (PGZ), one of the thiazolidinediones, has been known to show renoprotective effects. In this study, we focused on the effect of PGZ on glomerular hyperfiltration (GHF), resultant glomerular injury and altered macula densa signaling as a cause of sustained GHF through modified tubuloglomerular feedback in rats with diabetic nephropathy. METHODS: Kidneys from 24-week-old male OLETF rats and LET rats, nondiabetic controls, were used for the experiment. PGZ was administered (10 mg/kg/day, p.o.) for 2 weeks from 22 to 24 weeks of age in some of the OLETF rats (OLETF+PGZ). RESULTS: Parameters relating GHF, kidney weight, creatinine clearance, urine albumin/creatinine ratio and glomerular surface were all increased in OLETF rats and partially restored in OLETF+PGZ rats. Expressions of desmin and TGF-ß were also increased in OLETF rats and restored in OLETF+PGZ rats. The changes in TGF-ß expression were confirmed to be independent of podocyte number. Finally, the immunoreactivity of neuronal nitric oxide synthase (nNOS) and cyclooxygenase 2 (COX-2) in the macula densa was assessed for the evaluation of macula densa signaling. Altered intensities of nNOS and COX-2 in OLETF rats were restored in OLETF+PGZ rats, which agreed with the gene expression analysis (nNOS: 100.2 ± 2.9% in LET, 64.2 ± 2.7% in OLETF, 87.4 ± 12.1% in OLETF+PGZ; COX-2: 100.8 ± 7.4% in LET, 249.2 ± 19.4% in OLETF, 179.9 ± 13.5% in OLETF+PGZ; n = 5) and the semiquantitative analysis of nNOS/COX-2-positive cells. CONCLUSION: PGZ effectively attenuated the GHF and hyperfiltration-associated glomerular injury in diabetic nephropathy. The restoration of altered macula densa signaling might be involved in the renoprotective effect of PGZ.