Honami Mori

Monocyte chemoattractant protein-1 A-2518G gene polymorphism and renal survival of Japanese patients with immunoglobulin A nephropathy.

BackgroundMonocyte chemoattractant protein (MCP)-1 is closely related to the pathogenesis of the progression of various chronic renal diseases, including IgA nephropathy (IgAN), through its chemoattractant effect on macrophages. However, the correlation of MCP-1 gene polymorphism with the long-term prognosis of Japanese patients with IgAN has not been clearly determined yet.MethodsWe investigated 277 Japanese patients diagnosed with IgAN based on renal biopsy to clarify the association between the progression of IgAN and MCP-1 gene polymorphism at position A-2518G, which regulates the transcription of the MCP-1 gene.ResultsThe incidence of endstage renal disease was significantly higher in patients with the AA genotype (47.1%) compared to those with the AG (24.1%) or GG (27.4%) genotype (P = 0.024). Moreover, Kaplan-Meier analysis revealed that the AA genotype significantly facilitated the progression of renal disease (log rank; P = 0.0029), and Cox proportional hazards regression model analysis showed that the AA genotype represented a 2.058-fold risk for the progression of renal disease (P = 0.026) compared to the AG/GG genotype. However, when the patients were treated with angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker, or corticosteroid, homozygosity for the -2518A allele was not associated with a higher rate of incidence of endstage renal disease. Serum MCP-1 levels were higher although not significantly so, in the patients with IgAN possessing the AA genotype.ConclusionsThe AA genotype at MCP-1 -2518 was an independent risk factor for the progression of renal disease in Japanese patients with IgAN, and was closely associated with renal survival.

A New Device to Monitor Blood Volume in Hemodialysis Patients

We developed a new optical device (Nikkiso) to assess changes through blood volume monitoring (BVM) during hemodialysis and were able to determine the ideal levels in which changes in blood volume percentage (BV%) occur among hemodialysis patients in one hemodialysis center. We evaluated both the reliability of BVM and these ideal levels in a multicenter group. The purpose of this manuscript is to develop a navigating system to set dry weight in a variety of situations as the final goal. First, based on the obtained BVM (BV%BVM) measurements, the relationships between BV% and hematocrit (BV%HT) and between BV% and CRIT‐LINE (BV%CLM; Hema Metrics, Kaysville, UT, USA) were then evaluated. In 30 hemodialysis patients, there was a close correlation between both BV%BVM vs. BV%HT and BV%BVM vs. BV%CLM (n = 30, r = 0.967, P < 0.001, and n = 36, r = 0.7867, P < 0.001, respectively). Second, BV% data were obtained from 464 treatment cases performed on 26 subjects in one satellite hemodialysis center on patients whose body weight was deemed clinically suitable. The formulas for the levels of BV% (standardized by the percent change in body weight at the end of hemodialysis treatment: BW%end) were determined.

A clinicopathological study on the long-term efficacy of tonsillectomy in patients with IgA nephropathy.

Our study evaluated the clinical efficacy of tonsillectomy on the long-term renal survival in patients with primary IgA nephropathy (IgAN). Forty-six patients underwent tonsillectomy, and 74 patients did not. The mean of follow-up duration of all patients was 197.0±29.3 months (61–339 months). The baseline clinical and histological data at renal biopsy were not statistically different between the two groups with and without tonsillectomy. Five (10.9%) of the tonsillectomy group reached end stage renal failure (ESRF), whereas 19 (25.8%) of the non-tonsillectomy group did. The chi-square test between the two groups showed a significant difference (p<0.05). The renal survival of the tonsillectomy group was significantly higher than that of the non-tonsillectomy group by the Kaplan-Meier method with log-rank test (p<0.05). The Cox regression model also revealed that tonsillectomy had a significant favorable impact on the renal survival in long-term follow-up duration (p<0.05). Although our study was done by retrospective analyses, all the results proved that tonsillectomy had significant favorable effects on the long-term renal survival in patients with IgAN.

Evaluation of Cerebral Oxygenation in Patients Undergoing Long-Term Hemodialysis

Background/Aims: Patients undergoing hemodialysis (HD) have higher occurrence rates of cerebral diseases, including uremic encephalopathy, cognitive impairment, dementia, and cerebrovascular disease, than the general population. During HD, ultrafiltration is performed to maintain an adequate fluid condition and is associated with subsequent blood volume (BV) reduction. We aimed to (1) monitor changes in cerebral oxygenation and BV reduction during HD, and (2) clarify the mechanism that influences cerebral oxygenation in HD patients. Methods: Eighteen HD patients and 12 healthy controls were recruited. Regional saturation of oxygen (rSO2) was continuously monitored in the frontal cortex using INVOS 5100C before, during, and after HD, and in healthy controls. Relative change in BV (%ΔBV) was simultaneously monitored during HD using a BV monitor. Results: Before HD, patients had significantly lower rSO2 values than controls (56.1 ± 1.4 vs. 70.4 ± 2.5%, p < 0.001). Although %ΔBV significantly decreased from 20 min to the end of HD (20 min: -3.3 ± 0.3%, p < 0.05; end of HD: -12.0 ± 1.0%, p < 0.01), changes in rSO2 values during HD were not significant. No relationship existed between rSO2 values and blood pressure levels, hemoglobin levels, oxygen pressure, HCO3- , oxygen saturation, and arterial O2 content before and after HD. Furthermore, changes in rSO2 were not correlated with changes in these parameters. Conclusion: rSO2 values before HD were significantly lower in HD patients than in healthy controls. rSO2 values were maintained during HD and were not influenced by BV reduction.

Pathological study on the relationship between C4d, CD59 and C5b-9 in acute renal allograft rejection

Abstract:  In order to evaluate the activation or inhibition of the later phases of classical complement cascade in renal allograft presenting with acute rejection, particularly with C4d deposition on the peritubular capillary (PTC), we observed the expression of CD59 and C5b‐9 on the PTC. Subjective cases were divided into two groups, an acute rejection group, of 4 males and 6 females, and a normal donor group, of 5 males and 5 females. Renal biopsies were performed at the onset of acute rejection and at the transplant operation, before reperfusion. C4d deposition on PTC was found in three of 10 cases (30%) with biopsy proven acute rejection, whereas CD59 on PTC was positively expressed in all of the rejection cases. Although C5b‐9 was not observed on PTC in the acute rejection group, it was intensively deposited on the tubular basement membrane (TBM) in five cases, including the three with positive C4d on PTC. In the normal donor group, CD59 on PTC was intensively observed, whereas C5b‐9 was weakly expressed on TBM. CD59, a complement regulatory factor, works as an inhibitory factor against the formation of C5b‐9, a membrane attack complex. From our data, we noted the dissociation between the depositions of C4d and C5b‐9 on PTC. The substantially expressed CD59 on PTC may affect this dissociation between C4d and C5b‐9 on PTC. The intensive deposition of C5b‐9 on TBM in acute rejection cases may suggest an independent immunological injury attacking tubular cells.

Factors affecting cerebral oxygenation in hemodialysis patients: cerebral oxygenation associates with pH, hemodialysis duration, serum albumin concentration, and diabetes mellitus.

Background Patients undergoing hemodialysis (HD) often develop cerebral disease complications. Furthermore, cerebral regional saturation of oxygen (rSO2) was previously reported to be significantly lower in HD patients than in healthy subjects. We aimed to identify the factors affecting the cerebral rSO2 in HD patients. Methods Fifty-four HD patients (38 men and 16 women; mean age, 67.7 ± 1.2 years, HD duration, 6.5 ± 1.9 years) were recruited. Cerebral rSO2 was monitored at the forehead before HD using an INVOS 5100C (Covidien Japan, Tokyo, Japan). Results The rSO2 levels were significantly lower in HD patients compared with healthy controls (49.5 ± 1.7% vs. 68.9 ± 1.6%, p <0.001). Multiple regression analysis showed that cerebral rSO2 independently associated with pH (standardized coefficient: -0.35), HD duration (standardized coefficient: -0.33), and serum albumin concentration (standardized coefficient: 0.28). Furthermore, the rSO2 was significantly lower in HD patients with diabetes mellitus (DM), compared with patients without DM (46.8 ± 1.7% vs. 52.1 ± 1.8%, p <0.05). Conclusions In HD patients, cerebral rSO2 was affected by multiple factors, including pH, HD duration, and serum albumin concentration. Furthermore, this is the first report describing significantly lower levels of rSO2 in HD patients with DM than in those without DM.

Stimulation of NHE3 in OKP Cells by an Autocrine Mechanism

Background/Aims: Chronic hypokalemia increases NHE3 activity in OKP cells. The aim of the present study was to determine whether an autocrine mechanism is involved in this activation. Methods: After incubation of OKP cells in normal-K⁺ and low-K⁺ media for 24 h, the potassium concentration in the low-K⁺ media was adjusted to a normal level. These conditioned media were then used as the normal-K⁺ and low-K⁺ supernatants. Other OKP cells were incubated in these normal-K⁺ and low-K⁺ supernatants and the mechanism of Na⁺/H⁺ antiporter activation was examined. Results: The EIPA-resistant Na⁺/H⁺ antiporter activity of OKP cells increased after 4 h incubation in the low-K⁺ supernatant, and the amount of NHE3 protein increased at 24 h. Since both BQ788 and saralasin blocked this antiporter activation, the supernatant concentration of endothelin I (ET-I) and angiotensin II (Ang-II) were measured. The ET-I concentration was reduced, but the Ang-II concentration remained unchanged. There was a significant association between a reduction in the ET-I concentration and an increase in Na⁺/H⁺ antiporter activity, but only when Ang-II was present in the supernatant. Conclusion: An autocrine mechanism is involved in the activation of NHE3 in OKP cells. Both ET-I and Ang-II play a role in this activation.

New Method for the Approximation of Corrected Calcium Concentrations in Chronic Kidney Disease Patients

The following conventional calcium correction formula (Payne) is broadly applied for serum calcium estimation: corrected total calcium (TCa) (mg/dL) = TCa (mg/dL) + (4 – albumin (g/dL)); however, it is inapplicable to chronic kidney disease (CKD) patients. A total of 2503 venous samples were collected from 942 all‐stage CKD patients, and levels of TCa (mg/dL), ionized calcium ([iCa2+] mmol/L), phosphate (mg/dL), albumin (g/dL), and pH, and other clinical parameters were measured. We assumed corrected TCa (the gold standard) to be equal to eight times the iCa2+ value (measured corrected TCa). Then, we performed stepwise multiple linear regression analysis by using the clinical parameters and derived a simple formula for corrected TCa approximation. The following formula was devised from multiple linear regression analysis: Approximated corrected TCa (mg/dL) = TCa + 0.25 × (4 − albumin) + 4 × (7.4 − p H) + 0.1 × (6 − phosphate) + 0.3. Receiver operating characteristic curves analysis illustrated that area under the curve of approximated corrected TCa for detection of measured corrected TCa ≥ 8.4 mg/dL and ≤ 10.4 mg/dL were 0.994 and 0.919, respectively. The intraclass correlation coefficient demonstrated superior agreement using this new formula compared to other formulas (new formula: 0.826, Payne: 0.537, Jain: 0.312, Portale: 0.582, Ferrari: 0.362). In CKD patients, TCa correction should include not only albumin but also pH and phosphate. The approximated corrected TCa from this formula demonstrates superior agreement with the measured corrected TCa in comparison to other formulas.

Blood Volume Changes Induced By Low-Intensity Intradialytic Exercise in Long-Term Hemodialysis Patients.

Intradialytic exercise-induced blood volume (BV) reduction may cause intradialytic hypotension in hemodialysis (HD) patients. However, BV recovery time after intradialytic exercise remains unknown. Hemodialysis patients were recruited, and their relative BV change (%&Dgr;BV) were measured with intradialytic exercise (n = 12). After confirming the linearity of %&Dgr;BV for 30 min, patients exercised using a stationary cycle in the supine position. The target exercise intensity was a 10% increase in heart rate (HR), corresponding to relatively low-intensity exercise. Baseline %&Dgr;BV (assumed baseline) were calculated for the 30 min before exercise using linear regression analysis. The mean intradialytic exercise start and end times after HD initiation were 93.0 ± 8.4 and 116.4 ± 8.3 min, respectively, a mean exercise duration of 23.5 ± 2.6 min. Percentage change in blood volume declined rapidly upon exercise initiation and gradually increased above the assumed baseline throughout HD. At the end of HD, %&Dgr;BV in the exercise group was significantly higher than the assumed baseline (measured – assumed baseline %&Dgr;BV: 2.17 ± 0.62%; p = 0.02). Intradialytic exercise with low intensity in the supine position attenuated ultrafiltration-induced BV reduction at the end of HD. Therefore, intradialytic exercise may prevent intradialytic hypotension during later HD, although its intensity was relatively low level.

Approximation of Corrected Calcium Concentrations in Advanced Chronic Kidney Disease Patients with or without Dialysis Therapy.

Background: The following calcium (Ca) correction formula (Payne) is conventionally used for serum Ca estimation: corrected total Ca (TCa) (mg/dl) = TCa (mg/dl) + [4 - albumin (g/dl)]; however, it is inapplicable to advanced chronic kidney disease (CKD) patients. Methods: 1,922 samples in CKD G4 + G5 patients and 341 samples in CKD G5D patients were collected. Levels of TCa (mg/day), ionized Ca2+ (iCa2+) (mmol/l) and other clinical parameters were measured. We assumed the corrected TCa to be equal to eight times the iCa2+ value (measured corrected TCa). We subsequently performed stepwise multiple linear regression analysis using the clinical parameters. Results: The following formula was devised from multiple linear regression analysis. For CKD G4 + G5 patients: approximated corrected TCa (mg/dl) = TCa + 0.25 × (4 - albumin) + 4 × (7.4 - pH) + 0.1 × (6 - P) + 0.22. For CKD G5D patients: approximated corrected TCa (mg/dl) = TCa + 0.25 × (4 - albumin) + 0.1 × (6 - P) + 0.05 × (24 - HCO3-) + 0.35. Receiver operating characteristic analysis showed the high values of the area under the curve of approximated corrected TCa for the detection of measured corrected TCa ≥8.4 mg/dl and ≤10.4 mg/dl for each CKD sample. Both intraclass correlation coefficients for each CKD sample demonstrated superior agreement using the new formula compared to the previously reported formulas. Conclusion: Compared to other formulas, the approximated corrected TCa values calculated from the new formula for patients with CKD G4 + G5 and CKD G5D demonstrates superior agreement with the measured corrected TCa.