Mizoribine therapy combined with steroids and mizoribine blood concentration monitoring for idiopathic membranous nephropathy with steroid-resistant nephrotic syndrome.

BACKGROUND: We designed a prospective and randomized trial of mizoribine (MZR) therapy combined with prednisolone (PSL) for idiopathic membranous nephropathy (IMN) with steroid-resistant nephrotic syndrome (SRNS). METHODS: Patients with IMN were divided into 2 groups, and MZR combined with PSL was administered for 2 years. PSL was initially prescribed at 40 mg/day and tapered. MZR was given once-a-day at 150 mg and 3-times-a-day at 50 mg each to groups 1 and 2. Serum MZR concentrations from 0 to 4 h after administration were examined within one month of treatment. The concentration curve and peak serum level (C max) of MZR were estimated by the population pharmacokinetic (PPK) parameters of MZR. RESULTS: At 2 years, 10 of 19 patients (52.6 %) in group 1 and 7 of 18 patients (38.9 %) in group 2 achieved complete remission (CR). The time-to-remission curve using the Kaplan-Meier technique revealed an increase in the cumulative CR rate in group 1, but no significant difference between the groups. Meanwhile, there was a significant difference in C max between groups 1 and 2 (mean ± SD: 1.20 ± 0.52 vs. 0.76 ± 0.39 µg/mL, p = 0.04), and C max levels in CR cases were significantly higher than those in non-CR cases. Receiver operating characteristic analysis showed that C max more than 1.1 µg/mL was necessary for CR in once-a-day administration. CONCLUSION: Administration of MZR once a day is useful when combined with PSL for treatment of IMN with SRNS. In addition, it is important to assay the serum concentration of MZR and to determine C max, and more than 1.1 µg/mL of C max is necessary for CR.

Effect of Behavior Modification on Outcome in Early- to Moderate-Stage Chronic Kidney Disease: A Cluster-Randomized Trial.

OBJECTIVES: Owing to recent changes in our understanding of the underlying cause of chronic kidney disease (CKD), the importance of lifestyle modification for preventing the progression of kidney dysfunction and complications has become obvious. In addition, effective cooperation between general physicians (GPs) and nephrologists is essential to ensure a better care system for CKD treatment. In this cluster-randomized study, we studied the effect of behavior modification on the outcome of early- to moderate-stage CKD. DESIGN: Stratified open cluster-randomized trial. SETTING: A total of 489 GPs belonging to 49 local medical associations (clusters) in Japan. PARTICIPANTS: A total of 2,379 patients (1,195 in group A (standard intervention) and 1,184 in group B (advanced intervention)) aged between 40 and 74 years, who had CKD and were under consultation with GPs. INTERVENTION: All patients were managed in accordance with the current CKD guidelines. The group B clusters received three additional interventions: patients received both educational intervention for lifestyle modification and a CKD status letter, attempting to prevent their withdrawal from treatment, and the group B GPs received data sheets to facilitate reducing the gap between target and practice. MAIN OUTCOME MEASURE: The primary outcome measures were 1) the non-adherence rate of accepting continuous medical follow-up of the patients, 2) the collaboration rate between GPs and nephrologists, and 3) the progression of CKD. RESULTS: The rate of discontinuous clinical visits was significantly lower in group B (16.2% in group A vs. 11.5% in group B, p = 0.01). Significantly higher referral and co-treatment rates were observed in group B (p<0.01). The average eGFR deterioration rate tended to be lower in group B (group A: 2.6±5.8 ml/min/1.73 m2/year, group B: 2.4±5.1 ml/min/1.73 m2/year, p = 0.07). A significant difference in eGFR deterioration rate was observed in subjects with Stage 3 CKD (group A: 2.4±5.9 ml/min/1.73 m2/year, group B: 1.9±4.4 ml/min/1.73 m2/year, p = 0.03). CONCLUSION: Our care system achieved behavior modification of CKD patients, namely, significantly lower discontinuous clinical visits, and behavior modification of both GPs and nephrologists, namely significantly higher referral and co-treatment rates, resulting in the retardation of CKD progression, especially in patients with proteinuric Stage 3 CKD. TRIAL REGISTRATION: The University Hospital Medical Information Network clinical trials registry UMIN000001159.

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.

Adrenomedullin in peritoneal effluent expressed by peritoneal mesothelial cells.

BACKGROUND: Adrenomedullin (AM) possesses vasodilative and cell-protective properties. Glycine combines with the C-terminal of AM to form mature, physiologically active AM (mAM). AM is reportedly induced by high glucose condition in vascular endothelial or smooth muscle cells; however, little is known on how AM is activated by amidation. To investigate the behavior of AM in patients undergoing peritoneal dialysis (PD), the concentrations of AM, mAM and CA125 were measured. The mAM to AM ratio (mAM/AM ratio) was also evaluated as a marker of amidation activity. METHODS: Twenty patients were recruited for this study. The effluent at the time of the peritoneal equilibration test was collected and AM, mAM and CA125 concentrations were measured. The expression of AM in peritoneal mesothelial cells (PMCs) collected from effluent was also examined with an indirect immunofluorescent method. RESULTS: Mean values of AM and mAM in effluent were 18.1 ± 1.6 and 4.1 ± 0.3 fmol/mL, respectively. In plasma, they were 42.6 ± 3.3 and 5.6 ± 0.6 fmol/mL, respectively. AM concentrations in effluent did not correlate with plasma AM level but correlated well with the dialysate-to-plasma ratio of creatinine (D/P ratio of creatinine). Moreover, in 7 of 20 cases, concentrations of the mAM and mAM/AM ratio in effluent were higher than in plasma. In effluent, AM concentration but not the mAM/AM ratio correlated with CA125 concentration. Immunocytological study revealed diffuse, cytoplasmic expression of AM in PMCs which were collected from effluent during PD. CONCLUSION: AM is expressed by PMCs and actively amidated in the abdominal cavity of patients undergoing PD.

Significance of combined cyclosporine-prednisolone therapy and cyclosporine blood concentration monitoring for idiopathic membranous nephropathy with steroid-resistant nephrotic syndrome: a randomized controlled multicenter trial.

BACKGROUND: Combined treatment with cyclosporine microemulsion preconcentrate (CyA MEPC) and steroids has been widely used for idiopathic membranous nephropathy (IMN) associated with steroid-resistant nephrotic syndrome (SRNS). Recent studies have shown that once-a-day and preprandial administration of CyA MEPC is more advantageous than the conventional twice-a-day administration in achieving the target blood CyA concentration at 2 h post dose (C2). We designed a randomized trial to compare these administrations. METHODS: IMN patients with SRNS (age 16-75 years) were divided prospectively and randomly into 2 groups. In group 1 (n = 23), 2-3 mg/kg body weight (BW) CyA MEPC was given orally once a day before breakfast. In group 2 (n = 25), 1.5 mg/kg BW CyA MEPC was given twice a day before meals. CyA + prednisolone was continued for 48 weeks. RESULTS: Group 1 showed a significantly higher cumulative complete remission (CR) rate (p = 0.0282), but not when incomplete remission 1 (ICR1; urine protein 0.3-1.0 g/day) was added (p = 0.314). Because a C2 of 600 ng/mL was determined as the best cut-off point, groups 1 and 2 were further divided into subgroups A (C2 ≥600 ng/mL) and B (C2 <600 ng/mL). Groups 1A and 2A revealed significantly higher cumulative remission (CR + ICR1) (p = 0.0069) and CR-alone (p = 0.0028) rates. On the other hand, 3 patients with high CyA levels (C2 >900 ng/mL) in Group 1A were withdrawn from the study because of complications. CONCLUSION: CyA + prednisolone treatment is effective for IMN with associated SRNS at a C2 of ≥600 ng/mL. To achieve remission, preprandial once-a-day administration of CyA at 2-3 mg/kg BW may be the most appropriate option. However, we should adjust the dosage of CyA by therapeutic drug monitoring to avoid complications.

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.

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.

Significance of estimated salt excretion as a possible predictor of the efficacy of concomitant angiotensin receptor blocker (ARB) and low-dose thiazide in patients with ARB resistance.

The purpose of this study was to assess the factors affecting the efficacy of combination therapy with losartan and thiazide, with a focus on the significance of salt excretion, via a multicenter observational study. Adult patients with essential hypertension showing therapy resistance to angiotensin receptor blocker (ARB) as a monotherapy or in combination with Ca channel blockers (CCB) were enrolled, and their previously administered ARBs were replaced with the combination tablet containing losartan (50 mg per day) and hydrochlorothiazide (12.5 mg per day). Blood pressure and biochemical parameters were monitored for a year. The baseline blood pressure (153.4±14.8/86.4±11.3 mm Hg) was significantly lowered at the 3rd month (137.3±17.4/78.2±11.1 mm Hg, n=93) and was maintained at this lower level until the 12th month (135.3±14.0/76.4±11.1 mm Hg, n=74). The baseline value of estimated salt excretion (eSE), calculated using Tanaka's formula, differed significantly between the high and low treatment response groups, which were defined by the average change in mean blood pressure (MBP-C, -11.3 mm Hg; eSE=10.8±2.9 g per day in high responders vs. 9.2±2.3 g per day in low responders, P=0.004). Univariate and multivariate analyses showed a significant correlation between eSE and MBP-C (R=-0.288, P=0.007) and indicated the clinical effectiveness of eSE as a possible predictor for MBP-C (P=0.021). In addition, the urine Na-to-Cr ratio (NCR) demonstrated significant correlations with eSE (R=0.848, P<0.001) and MBP-C (R=-0.344, P<0.001). These results suggest that eSE or NCR could, to a certain extent, predict the efficacy of combination therapy with losartan and low-dose thiazide in patients demonstrating ARB resistance. Combination therapy with losartan and thiazide might thus be suitable for patients with a large amount of salt excretion.

A case of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with lupus erythematosus in the central nervous system.

We report on a case of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with lupus erythematosus in the central nervous system (CNS). A 73-year-old woman with essential hypertension suddenly demonstrated consciousness disturbance. Upon her admission, laboratory data showed significant hyponatremia (114 mEq/L) and a lack of body fluid loss. Diminished free water excretion (urine osmolality 684 mOsm/kg) and normal urine Na excretion (FENa 1.70 %) were consistent with the diagnosis of SIADH, which was confirmed by an inappropriately high concentration of plasma antidiuretic hormone (ADH) (15.3 pg/mL at 256 mOsm/kg of plasma osmolality). The hyponatremia was corrected by a combination of oral water intake restriction and saline infusion with furosemide administration until the 20th hospital day. Simultaneously, the presence of exudative pleural effusion in both chest cavities, suggesting the existence of pleuritis, and high titer of anti-nuclear antibody (ANA, 5120×) and anti-double-strand DNA antibody (6500 IU/mL), indicated the subclinical development of systemic lupus erythematosus (SLE), although the diagnostic criteria were not satisfied at that time. On the 34th hospital day, the sudden onset of unknown consciousness disturbance confirmed the diagnosis of SLE as CNS lupus. In previous case reports on SLE and/or SIADH, a few cases in which SLE and SIADH developed concomitantly regularly showed high immunological activities, as in our case. Some common pathophysiological bases might be involved in the concomitant appearance of those disorders.

A case of water intoxication with prolonged hyponatremia caused by excessive water drinking and secondary SIADH.

Water intoxication is a life-threatening disorder accompanied by brain function impairment due to severe dilutional hyponatremia. We treated a 22-year-old man without psychotic illness who had been put in a detention facility. He drank 6 liters of water over a 3-hour period at the facility as a game's penalty, and he showed progressive psychiatric and neurological signs including restlessness, peculiar behavior and convulsions. On his admission, 15 h after the discontinuation of the water drinking, he was in a coma, showing intermittent convulsions and remarkable hyponatremia (120 mmol/l). Because his laboratory tests showed hypertonic urine and normal sodium excretion, the diagnosis of secondary development of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) was strongly suggested and later confirmed by the suppression of the renin-aldosterone system and the inappropriately elevated secretion of ADH. Saline infusion and an initial administration of furosemide in addition to dexamethasone as treatments for the patient's brain edema successfully improved his laboratory data and clinical signs by the 3rd hospital day, and he was returned to the facility without physical or psychiatric abnormalities on the 6th day. The secondary SIADH might have been due to the prolonged emesis, recurrent convulsions and rapid elevation of intracranial pressure.

The efficacy of intensive granulocyte and monocyte adsorption apheresis in a patient with Crohn's disease complicated by extensive subcutaneous aseptic neutrophilic abscesses.

BACKGROUND AND AIMS: Subcutaneous aseptic abscess is one phenotype of neutrophilic dermatitis. We were interested to see if a case of steroid refractory Crohn's disease (CD) complicated by subcutaneous aseptic neutrophilic abscesses responds to intensive granulocyte/monocyte adsorptive apheresis (GMA). METHODS: The patient was a 21-year-old male with worsening severe CD while on oral prednisolone (30 mg/day). His symptoms included fever, bloody diarrhoea and multiple painful subcutaneous nodules throughout his body. Skin biopsy showed chronic panniculitis with neutrophilic infiltrates. Further, colonoscopy showed oedematous sigmoid colon, while colonic biopsy showed non-caseous granuloma. Because biologics were feared to increase the risk of bacteraemia as the result of germ culture on his pus was not known at the time, we decided to treat this case with GMA. Five GMA sessions with the Adacolumn over 5 consecutive days (daily GMA) were initiated. RESULTS: On admission, his CD activity index (CDAI) was 355, C-reactive protein (CRP) 11.2 mg/dL. After 5 GMA sessions, CDAI decreased to 170, and CRP fell to 5.0 mg/dL, with no fever. GMA was restarted at 2 sessions/week (total 10 sessions). The patient's CDAI fell to <150, and the skin lesions re-epithelialized. CONCLUSIONS: In this CD case complicated by subcutaneous aseptic neutrophilic abscesses, GMA appeared to be effective. Our impression is that when biopsy reveals neutrophil infiltrate is a major feature of the lesions, GMA should be considered. As GMA appears to have no safety concerns, a frequent GMA protocol, like daily followed by 2 to 3 times/week should be preferred over the routine weekly GMA.

Dialysate purification after introduction of automated hot water disinfection system to central dialysis fluid delivery system.

Most dialysis clinics in Japan have mainly adopted the central dialysis fluid delivery system (CDDS) to provide constant treatment to many patients. Chemical disinfection is the major maintenance method of the CDDS. Our clinic introduced an automated hot water disinfection system that used the heat conduction effect to disinfect a reverse osmosis (RO) device and dialysis fluid supply equipment. Endotoxin level and the amount of viable bacteria often showed abnormal values before introduction of this system. After its introduction, weekly disinfection resulted in endotoxin levels and the amount of viable bacteria lower than measurement sensitivity. In hot water disinfection, water heated to 90°C in the RO tank flows into the dialysis fluid supply equipment. The maximum temperature inside the tank of the supply equipment is 86.3°C. (We confirmed that the temperature was maintained at 80°C or more for 10 minutes or more during the monitoring.) Dialysate purification was maintained even after introduction of the automated hot water disinfection system and the dialysate could be supplied stably by the CDDS. Therefore, this disinfection system might be very useful in terms of both cost and safety, and can be used for dialysis treatment of multiple patients.

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.

Endogenous factors modified by hemodialysis may interfere with the accuracy of blood glucose-measuring device.

In Japan, self-monitoring of blood glucose (SMBG) devices are widely used both at home and in hospitals, but many analytical errors and safety concerns have been reported about the SMBG devices used in hospitals. Analytical performances of StatStrip (Nova Biomedical Corporation, MA, USA), a new point-of-care testing device and Glutest (Sanwa Chemical, Aichi, Japan), a routinely used SMBG device were compared in glucose measurement of pre- and postdialysis blood samples and we evaluated which factors in blood modified by hemodialysis affect accuracy of these devices. Subjects in this study were 44 hemodialysis patients. Blood samples were obtained from patients just before and just after the hemodialysis. Blood glucose concentrations of samples were measured by StatStrip and Glutest. Hematocrit and plasma concentrations of electrolytes, metabolites, etc. of the samples were measured in the central laboratory. StatStrip showed no difference between pre- and postdialysis blood samples and showed very little bias from reference method. On the other hand, Glutest showed difference between pre- and postdialysis samples. Although there is no problem in the data of predialysis blood samples by Glutest, however, these of the postdialysis blood samples by Glutest were >10% less than reference method. Factors in blood modified by hemodialysis such as hematocrit, uric acid, albumin, potassium, and calcium affected glucose readings by Glutest. Glucose readings by Glutest of samples from hemodialysis patients were affected by hematocrit and several factors, which were modified by hemodialysis. StatStrip is considered as a better device in dialysis hospitals.

Contribution of residual renal function on peritoneal solute transport in dialysis patients.

BACKGROUND: Increased peritoneal solute transport rate (PSTR) is primarily a consequence of continuous exposure to bioincompatible glucose-based peritoneal dialysis (PD) solutions. However, relationships between increasing PSTR and dialysate glucose load remain unclear. As some PD patients with preserved residual renal function do not show increased PSTR despite long-term PD, we examined whether loss of residual renal function is associated with increased PSTR on long-term PD. METHODS: We evaluated 35 patients who started PD between 1997 and 2002 and received continuous PD treatment for >6 years. Data included baseline clinical data, residual renal function, urea and creatinine clearance, dialysate glucose load, ultrafiltration, and the use of icodextrin and renin-angiotensin system inhibitors. Peritoneal equilibration test results and data were collected annually for 6 years. RESULTS: Both the glomerular filtration rate and urine volume at 6 years on PD showed significant negative correlations with the dialysate-to-plasma creatinine ratio (D/P Cr) at 6 years (r = -0.716 and r = -0.717, respectively). Multivariate analysis showed only urine volume at 6 years on PD as an independent covariate of the D/P Cr at 6 years on PD. CONCLUSIONS: Loss of residual renal function is directly associated with increased PSTR in patients on long-term PD.

[Predictive value of ultrasonographical assessments of carotid artery for cardiovascular events in patients under hemodialysis: add on comparison with stroke patients].

BACKGROUND: The prognosis of patients on hemodialysis (HD) was determined with respect to cardiovascular disease. We analyzed the relationships between several parameters of carotid artery echograms and cardiovascular events (CVE) in patients on HD. We also compared the characteristic findings of carotid artery echography in patients with stroke and patients on HD. METHOD: We enrolled 104 patients on HD (male : female, 72: 32; mean age, 63.0 +/- 11.2 years) and 48 with stroke (male : female, 36: 12; mean age, 66.0 +/- 7.7 years) who were admitted to our hospital between 1998 and 2004. We measured intima media thickness (IMT), plaque score (PS), resistive index (RI), common carotid artery (CCA) stenosis and plaque echogenicity using B-mode ultrasonography. The correlation between carotid artery echographic findings and CVE were analyzed over a period of 37.5 +/- 22.9 months of follow-up. The characteristic findings of carotid artery echography were compared among groups of patients on initial HD (iHD) and maintenance HD (mHD) and with stroke accompanied by eGFR > 60 mL/min/1.73 m2. RESULTS: Both PS and RI significantly correlated with CVE (p < 0.005 and p < 0.05, respectively), and CVE occurred at the early phase of follow up in patients with increased PS. Both PS and RI were also higher in mHD than in stroke (p < 0.005). Both PS and CCA stenosis were higher in mHD than in iHD (p < 0.01, p< 0.05). More hard plaques were identified in patients on mHD than in those with stroke (p < 0.005). Multivariate analysis showed that the numbers of soft and hard plaques were significantly associated with CCA stenosis(p < 0.05) and the duration of dialysis (p < 0.05), respectively. CONCLUSIONS: Increasing PS and RI were powerful predictors of CVE in patients on HD. Atherosclerotic changes were equal in patients on iHD and those with stroke. Plaque score, the numbers of hard plaques and CCA stenosis were increased in mHD, suggesting the development of atherosclerotic changes in patients on HD.

Design and methods of a strategic outcome study for chronic kidney disease: Frontier of Renal Outcome Modifications in Japan.

BACKGROUND: The continuous increase in the number of people requiring dialysis is a major clinical and socioeconomical issue in Japan and other countries. This study was designed to encourage chronic kidney disease (CKD) patients to consult a physician, enhance cooperation between nephrologists and general practices, and prevent the progression of kidney disease. METHODS: Subjects comprise CKD patients aged between 40 and 74 years consulting a general physician, and patients in CKD stage 3 with proteinuria and diabetes or hypertension. This trial is a stratified open cluster-randomized study with two intervention groups: group A (weak intervention) and group B (strong intervention). We have recruited 49 local medical associations (clusters) in 15 different prefectures, which were classified into four regions (strata) based on the level of increase rate of dialysis patients. The patients in group A clusters were instructed initially to undergo treatment in accordance with the current CKD treatment guide, whereas patients in group B clusters were not only instructed in the same fashion but also received support from an information technology (IT)-based system designed to help achieve the goals of CKD treatment, consultation support centers, and consultations by dietitians visiting the local general practice offices. We assessed the rates of continued consultation, collaboration between general practitioners and nephrologists, and progression of CKD (as expressed by CKD stage). CONCLUSION: Through this study, filling the evidence-practice gap by facilitating effective communication and supporting general physicians and nephrologists, we will establish a CKD care system and decrease the number of advanced-stage CKD patients.