Haruhisa Miyazawa

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.

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.

Aggravation of Cerebral Oxygenation due to Intradialytic Hypotension Induced by Blood Volume Reduction During Hemodialysis: A Case Report.

1. Schubert C, Moosa MR. Infective endocarditis in a hemodialysis patient: a dreaded complication. Hemodial Int 2007;11:379–84. 2. Cook RJ, Ashton RW, Aughenbaugh GL, Ryu JH. Septic pulmonary embolism : presenting features and clinical course of 14 patients. Chest 2005;128:162–6. Aggravation of Cerebral Oxygenation due to Intradialytic Hypotension Induced by Blood Volume Reduction During Hemodialysis: A Case Report

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.

Changes in urinary potassium excretion in patients with chronic kidney disease.

Background Hyperkalemia is one of the more serious complications of chronic kidney disease (CKD), and the cause of potassium retention is a reduction in urinary potassium excretion. However, few studies have examined the extent of the decrease of urinary potassium excretion in detail with respect to decreased renal function. Methods Nine hundred eighty-nine patients with CKD (CKD stages G1 and G2 combined: 135; G3a: 107; G3b: 170; G4: 289; and G5: 288) were evaluated retrospectively. Values for urinary potassium excretion were compared between CKD stages, and the associations between urinary potassium excretion and clinical parameters, including diabetes mellitus status and use of renin–angiotensin–aldosterone system inhibitors, were analyzed using a multivariable linear regression analysis. Results Urinary potassium excretion gradually decreased with worsening of CKD (G5: 24.8 ± 0.8 mEq/d, P < 0.001 vs. earlier CKD stages). In contrast, the value of fractional excretion of potassium at CKD G5 was significantly higher than that at the other stages (30.63 ± 0.93%, P < 0.001). Multivariable linear regression analysis revealed that urinary potassium excretion was independently associated with urinary sodium excretion (standardized coefficient, 0.499), the estimated glomerular filtration rate (0.281), and serum chloride concentration (–0.086). Conclusion This study demonstrated that urinary potassium excretion decreased with reductions in renal function. Furthermore, urinary potassium excretion was mainly affected by urinary sodium excretion and estimated glomerular filtration rate in patients with CKD, whereas the presence of diabetes mellitus and use of renin–angiotensin–aldosterone system inhibitors were not associated with urinary potassium excretion in this study.

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.

Factors associating with oxygenation of lower-limb muscle tissue in hemodialysis patients

AIM To evaluate the lower-limb muscle oxygenation in hemodialysis (HD) patients and identify the factors associating with muscle oxygenation. METHODS Sixty-seven HD patients (53 men and 14 women; mean age, 67.1 ± 1.2 years; mean HD duration, 5.6 ± 0.9 years) were recruited. In addition, 15 healthy individuals (nine men and six women; mean age, 38.2 ± 4.6 years) were recruited as the control group. Lower-limb muscle regional saturation of oxygen (rSO2) was monitored on the lateral side of the gastrocnemius muscle before HD using an INVOS 5100C (Covidien Japan, Tokyo, Japan), which utilizes near-infrared spectroscopy. Here, we evaluated the association between lower-limb muscle rSO2 and clinical parameters. RESULTS The rSO2 values were significantly lower in patients undergoing HD than in healthy individuals (50.0% ± 1.7% vs 76.8% ± 2.5%, P < 0.001). Lower-limb muscle rSO2 showed significant positive correlations with diastolic blood pressure, blood urea nitrogen concentration, serum creatinine concentration, serum potassium concentration, serum inorganic phosphate concentration, and serum albumin concentration as well as negative correlation with HD duration. We conducted a multiple linear regression analysis using parameters that were significantly correlated with the lower-limb muscle rSO2 in a simple linear regression analysis. Multiple regression analysis demonstrated that lower-limb muscle rSO2 was independently associated with serum inorganic phosphate (standardized coefficient: 0.27) and serum albumin concentrations (standardized coefficient: 0.24). In addition, there were no differences in lower-limb muscle rSO2 between diabetic and non-diabetic HD patients. This study has several limitations. Firstly, its sample size was relatively small. Secondly, we could not evaluate the association between lower-limb muscle rSO2 and calculated nutritional markers, including normalized protein catabolic rate and body mass index, anthropometric measurements representing nutritional status, and the severity of protein-energy wasting. Finally, we did not routinely examine the arterial vascular status of HD patients without symptoms of peripheral artery disease. As such, it is possible that some HD patients with subclinical peripheral artery disease may have been included in this study. CONCLUSION In HD patients, the oxygenation of lower-limb muscle tissue was associated with serum inorganic phosphate and albumin concentrations, both of which represent nutritional status.

Changes in Cerebral Oxygenation Associated with Intradialytic Blood Transfusion in Patients with Severe Anemia Undergoing Hemodialysis

Background: Hemodialysis (HD) patients frequently suffer from severe anemia caused by various hemorrhagic disorders in addition to renal anemia. Intradialytic blood transfusion is sometimes performed; however, the cerebral oxygenation changes associated with this procedure remain unclear. Methods: Sixteen HD patients with severe anemia who required intradialytic blood transfusion were included (12 men and 4 women; mean age, 64.8 ± 9.8 years). Cerebral regional oxygen saturation (rSO2) was monitored using near-infrared spectroscopy, and cerebral fractional oxygen extraction (FOE) was calculated before and after HD. Twenty-five HD patients with well-maintained hemoglobin (Hb) levels were included as a control group. Results: Cerebral rSO2 values were significantly lower in HD patients with severe anemia than in the control group (42.4 ± 9.9 vs. 52.5 ± 8.5%, p = 0.001). Following intradialytic blood transfusion (385 ± 140 mL of concentrated red blood cells), Hb levels significantly increased (from 7.2 ± 0.9 to 9.1 ± 1.1 g/dL, p < 0.001), and cerebral rSO2 values significantly improved after HD (from 42.4 ± 9.9 to 46.3 ± 9.0%, p < 0.001). Cerebral FOE values before HD in patients with severe anemia were significantly higher than those in the control group (severe anemia, 0.56 ± 0.10; controls, 0.45 ± 0.08; p < 0.001). After HD with intradialytic blood transfusion, these values significantly decreased (0.52 ± 0.09 after HD versus 0.56 ± 0.10 before HD, p = 0.002). Conclusion: HD patients with severe anemia represented cerebral oxygen metabolism deterioration, which could be significantly improved by intradialytic blood transfusion.

Nano-sized carriers in gene therapy for renal fibrosis in vivo

ABSTRACT Renal fibrosis is the final common pathway leading to end-stage renal failure regardless of underlying initial nephropathies. No specific therapy has been established for renal fibrosis. Gene therapy is a promising strategy for the treatment of renal fibrosis. Nano-sized carriers including viral vectors and non-viral vectors have been shown to enhance the delivery and treatment effects of gene therapy for renal fibrosis in vivo. This review focuses on the mechanisms of renal fibrosis and the in vivo technologies and methodologies of nano-sized carriers in gene therapy for renal fibrosis. RESPONSIBLE EDITOR Alexander Seifalian Director of Nanotechnology & Regenerative Medicine Ltd., The London BioScience Innovation Centre, London, UNITED KINGDOM

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.