平井 啓之

Background: Proteinase 3-antineutrophil cytoplasmic antibody has been reported to be positive in 5-10% of cases of renal injury complicated by infective endocarditis however, histological findings have rarely been reported for these cases. Case presentation: A 71-year-old Japanese man with a history of aortic valve replacement developed rapidly progressive renal dysfunction with gross hematuria and proteinuria. Blood analysis showed a high proteinase 3-antineutrophil cytoplasmic antibody (163 IU/ml) titer. Streptococcus species was detected from two separate blood culture bottles. Transesophageal echocardiography detected mitral valve vegetation. Histological evaluation of renal biopsy specimens showed necrosis and cellular crescents in glomeruli without immune complex deposition. The patient met the modified Duke criteria for definitive infective endocarditis. On the basis of these findings, the patient was diagnosed with proteinase 3-antineutrophil cytoplasmic antibody-positive necrotizing crescentic glomerulonephritis complicated by Streptococcus infective endocarditis. His renal disease improved, and his proteinase 3-antineutrophil cytoplasmic antibody titer normalized with antibiotic monotherapy. Conclusion: Few case reports have described histological findings of proteinase 3-antineutrophil cytoplasmic antibody-positive renal injury complicated with infective endocarditis. We believe that an accumulation of histological findings and treatments is mandatory for establishment of optimal management for proteinase 3-antineutrophil cytoplasmic antibody-positive renal injury complicated with infective endocarditis.

Hemodialysis (HD) patients frequently experience severe anemia, requiring intradialytic blood transfusion. Severe anemia leads to deterioration of systemic tissue oxygenation. However, few reports have examined the effect of intradialytic blood transfusion on tissue oxygenation changes. This study aimed to (i) monitor the differences in tissue oxygenation in the brain and liver during intradialytic blood transfusion, and (ii) elucidate the clinical factors affecting cerebral and hepatic oxygenation. Thirty-eight HD patients with severe anemia requiring intradialytic blood transfusion were included (27 men, 11 women mean age, 70.2 ± 1.6 years). Cerebral and hepatic regional oxygen saturation (rSO2) values were monitored using near-infrared spectroscopy (INVOS 5100c oxygen saturation monitor). Cerebral and hepatic rSO2 were significantly higher after than before blood transfusion (p &lt 0.001, both). Furthermore, hepatic rSO2 was significantly higher than cerebral rSO2 after transfusion (p = 0.004). In multivariable linear regression analysis, cerebral rSO2 changes were independently associated with the natural logarithm of hemoglobin (Hb) ratio (Hb after/before transfusion) (standardized coefficient: 0.367, p = 0.023), whereas hepatic rSO2 changes were independently associated with the natural logarithm of [Hb ratio/colloid osmotic pressure ratio (colloid osmotic pressure after/before transfusion)] (standardized coefficient: 0.378, p = 0.019). In conclusion, throughout intradialytic blood transfusion, brain and liver tissue oxygenation improved. Hepatic rSO2 was significantly higher than cerebral rSO2 at the end of HD. Furthermore, cerebral oxygenation changes were associated with only transfusion-induced Hb increase, whereas hepatic oxygenation changes were associated with both transfusion-induced Hb increase (positive changes) and ultrafiltration-induced colloid osmotic pressure increase (negative changes).

Background Dietary management is highly important for the maintenance of renal function in patients with chronic kidney disease (CKD). Cerebral oxygen saturation (rSO2) was reportedly associated with the estimated glomerular filtration rate (eGFR) and cognitive function. However, data concerning the association between cerebral rSO2 and dietary intake of CKD patients is limited. Methods This was a single-center observational study. We recruited 67 CKD patients not undergoing dialysis. Cerebral rSO2 was monitored using the INVOS 5100c oxygen saturation monitor. Energy intake was evaluated by dietitians based on 3-day meal records. Daily protein and salt intakes were calculated from 24-h urine collection. Results Multivariable regression analysis showed that cerebral rSO2 was independently associated with energy intake (standardized coefficient: 0.370) and serum albumin concentration (standardized coefficient: 0.236) in Model 1 using parameters with p &lt 0.10 in simple linear regression analysis (body mass index, Hb level, serum albumin concentration, salt and energy intake) and confounding factors (eGFR, serum sodium concentration, protein intake), and the energy/salt index (standardized coefficient: 0.343) and Hb level (standardized coefficient: 0.284) in Model 2 using energy/protein index as indicated by energy intake/ protein intake and energy/salt index by energy intake/salt intake in place of salt, protein and energy intake. Conclusions Cerebral rSO2 is affected by energy intake, energy/salt index, serum albumin concentration and Hb level. Sufficient energy intake and adequate salt restriction is important to prevent deterioration of cerebral oxygenation, which might contribute to the maintenance of cognitive function in addition to the prevention of renal dysfunction in CKD patients.

High concentrations of lactate are considered to contribute to impairment of the peritoneal membrane. We investigated the longer-period effects of bicarbonate/lactate-buffered neutral peritoneal dialysis fluid (PDF) in patients undergoing PD for about 2 years. Patients undergoing PD were changed from a lactate-buffered neutral PDF to a bicarbonate/lactate-buffered neutral PDF. We then investigated the patients’ clinical outcomes and peritoneal membrane functions as well as the surrogate markers in the drained dialysate. Fourteen patients undergoing PD were enrolled. Peritonitis was observed in one patient. No other adverse events were observed. Peritoneal function did not change as the ultrafiltration volume decreased. Fibrin degradation products and vascular endothelial growth factor in the drained dialysate decreased while the interleukin level increased. These results suggest that bicarbonate/lactate-buffered neutral PDF may have beneficial effects in terms of peritoneal preservation and can be safely used in patients undergoing PD.

We herein report a case of ureter rupture with severe oliguric acute renal injury due to benign prostatic hypertrophy. After insertion of an indwelling urinary catheter, the patient’s urine output immediately increased. His symptoms and renal function also rapidly improved to the normal range without a surgical operation. Clinicians should note this complication in patients with oliguria.

Background A decline in estimated glomerular filtration rate (eGFR) is reportedly associated with increased prevalence rates of cognitive impairment. However, data concerning the association between the cerebral saturation of oxygen (rSO 2 ) and cognitive function of patients with chronic kidney disease (CKD) is limited. This study aimed to (i) elucidate the clinical factors associating with cerebral rSO 2 and (ii) investigate the association between cerebral rSO2 and cognitive assessment in CKD patients. Methods A total of 40 CKD patients not requiring dialysis (26 men and 14 women mean age, 61.0 ± 2.7 years) were recruited. The numbers of patients at each CKD stage were as follows: G1, 5 G2, 8 G3a, 6 G3b, 5 G4, 11 and G5, 5. Cerebral rSO 2 was monitored at the forehead using the oxygen saturation monitor INVOS 5100C. The cognitive function of each patient was confirmed using the Mini-Mental State Examination (MMSE). Results Cerebral rSO 2 levels were significantly higher in CKD patients than in hemodialysis patients (63.8 ± 1.5% vs. 44.9 ± 2.2%, p &lt 0.001). Multiple regression analysis showed that cerebral rSO 2 was independently associated with eGFR (standardized coefficient: 0.530), serum albumin concentration (standardized coefficient: 0.365), and serum sodium concentration (standardized coefficient: 0.224). Furthermore, MMSE showed a significantly positive correlation with cerebral rSO 2 (r = 0.624, p &lt 0.001). Conclusions Cerebral rSO 2 was affected by eGFR and serum albumin and sodium concentrations in CKD patients. Furthermore, cerebral rSO 2 monitoring, which reflected MMSE scores, might be a useful method for assessing cognitive function in CKD patients.

Near-infrared spectroscopy has been used to measure regional saturation of oxygen (rSO2) based on the total hemoglobin (t-Hb) signal strength. To date, few studies have investigated the changes of systemic oxygenation and t-Hb signal strength during hemodialysis (HD). This study aimed to (1) monitor rSO2 and t-Hb signal strength in the brain, liver, and lower-limb muscle during HD and (2) clarify the differences in rSO2 and t-Hb signal strength in each compartment. Fifty-three patients receiving 4-h HD were included and divided into three groups according to the compartments in which tissue oxygenation was measured as follows: brain (n = 44), liver (n = 42), and lower-limb muscle (n = 40). The rSO2 and t-Hb signal strength was monitored using an INVOS 5100c (Covidien Japan, Tokyo, Japan). The rSO2 levels were significantly lower in the brain than in the liver from HD initiation to the end (HD initiation: rSO2 in the brain and liver, 46.5 ± 1.3 and 52.4 ± 1.7%, respectively, p = 0.031). Furthermore, compared to the t-Hb signal strength ratio [value at t (min) during HD/initial value before HD] in the brain during HD, there were significant increases in the liver and lower-limb muscle, respectively. In conclusion, deterioration of cerebral oxygenation was remarkable.

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 &lt 0.001), and cerebral rSO2 values significantly improved after HD (from 42.4 ± 9.9 to 46.3 ± 9.0%, p &lt 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 &lt 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.

Background. Near-infrared spectroscopy revealed that the regional saturation of oxygen (rSO2) in cerebral tissue is lower in hemodialysis (HD) patients than in healthy subjects. However, no study has examined the changes in cerebral oxygenation by aortic arch calcification (AAC) progression in HD patients. Methods. A total of 104 HD patients were divided into four groups by AAC grade determined using chest radiography: 23 patients at grade 0, 24 at grade 1, 30 at grade 2, and 27 at grade 3. Differences in clinical parameters, including cerebral rSO2, among AAC grades were investigated and atherosclerotic parameters affecting cerebral rSO2 values were identified. Results. Cerebral rSO2 significantly decreased as AAC progressed (AAC grade 3 versus grade 0, p&lt 0.01 versus grade 1, p&lt 0.05). Multivariate logistic regression analysis was performed using parameters with p values &lt 0.20 in univariate analysis between cerebral rSO2 values less than the mean and atherosclerotic parameters. AAC grades 2 and 3, serum phosphate level, and history of smoking were factors associated with the cerebral rSO2 decrease. Conclusions. Cerebral rSO2 significantly decreased as AAC progressed and was independently associated with higher AAC grade, serum phosphate level, and history of smoking.

BACKGROUND: We investigated the effects and safety of linagliptin as an add-on therapy in patients with advanced-stage diabetic nephropathy (DMN) taking renin-angiotensin-aldosterone system (RAAS) blockers. METHOD: Twenty advanced-stage DMN patients (estimated glomerular filtration rate (eGFR): 24.5 ± 13.4 mL/min/1.73 m2) taking RAAS blockers were administered 5 mg/day linagliptin for 52 weeks. Changes in glucose and lipid metabolism and renal function were evaluated. RESULTS: Linagliptin decreased glycosylated hemoglobin levels (from 7.32 ± 0.77% to 6.85 ± 0.87%, P, 0.05) without changing fasting blood glucose levels, and significantly decreased total cholesterol levels (from 189.6 ± 49.0 to 170.2 ± 39.2 mg/dL, P, 0.05) and low-density lipoprotein cholesterol levels (from 107.1 ± 32.4 to 90.2 ± 31.0 mg/dL, P, 0.05) without changing high-density lipoprotein cholesterol and triglyceride levels. Urine protein/creatinine ratio and annual change in eGFR remained unchanged. No adverse effects were observed. CONCLUSION: Linagliptin as an add-on therapy had beneficial effects on glucose and lipid metabolism without impairment of renal function, and did not have any adverse effects in this population of patients with advanced-stage DMN taking RAAS blockers.

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 (%δBV) were measured with intradialytic exercise (n = 12). After confirming the linearity of %δBV 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 lowintensity exercise. Baseline %δBV (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, %δBV in the exercise group was significantly higher than the assumed baseline (measured - assumed baseline %δBV: 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.

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≥8.4mg/dL and≤10.4mg/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.

Background: The highly concentrated lactate in peritoneal dialysis fluid (PDF) has been considered to contribute to peritoneal failure in patients undergoing PD. A new PDF containing a lower lactate concentration, physiological bicarbonate concentration, and neutral pH (bicarbonate/lactate-buffered neutral PDF) was recently developed. We compared the clinical effects of this bicarbonate/lactate-buffered neutral PDF and a lactate-buffered neutral PDF. Methods and Design: Patients undergoing PD were changed from a lactate-buffered neutral PDF to a bicarbonate/lactate-buffered neutral PDF. We then investigated the changes in peritoneal functions as estimated by a peritoneal equilibration test (PET) and the following surrogate markers of peritoneal membrane failure in the drained dialysate: Fibrin degradation products (FDP), vascular endothelial growth factor (VEGF), cancer antigen 125 (CA125), interleukin-6 (IL-6), and transforming growth factor beta 1 (TGF-β1). Results: Fourteen patients undergoing PD were enrolled. The PET results were not different before and after use of the bicarbonate/lactate-buffered neutral PDF. The FDP concentration significantly decreased from 15.60 ± 13.90 to 6.04 ± 3.49 μg/mL (p = 0.02) and the VEGF concentration significantly decreased from 37.83 ± 15.82 to 27.70 ± 3.80 pg/mL (p = 0.02), while the CA125 and IL-6 concentrations remained unchanged before and after use of the bicarbonate/lactate-buffered neutral PDF. TGF-β1 was not detected in most patients. Conclusion: The bicarbonate/lactate-buffered neutral PDF decreased the FDP and VEGF concentrations in the drained dialysate. These results suggest that the decreased lactate level achieved by administration of bicarbonate with a neutral pH in PDF may contribute to decreased peritoneal membrane failure in patients undergoing PD.

Type 2 diabetic kidney disease (DKD) is frequently accompanied by uncontrollable hypertension due to the sodium sensitivity inherent in DKD and to diuretic-resistant edema. In general, diuretics are effective in treating this condition, but thiazide diuretics are thought to be innocuous in advanced chronic kidney disease (CKD). We examined the renoprotective effects of combination therapy with thiazides and loop diuretics in type 2 DKD patients with CKD stage G4 or G5. This study included 11 patients with type 2 DKD and an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m(2) who were suffering from severe edema even with loop diuretics. Each patient received additional hydrochlorothiazide (HCTZ) therapy, which was continued for more than 12 months. We examined clinical parameters including blood pressure (BP), proteinuria, and eGFR before and after the addition of HCTZ. Patients received a 13.6 +/- A 3.8 mg/day dose of HCTZ in addition to loop diuretics (azosemide: 120 mg/day in 6 cases, 60 mg/day in 3 cases and furosemide: 80 mg/day in 1 case, 120 mg/day in 1 case). Side effects of HCTZ were not observed in all patients. After the addition of HCTZ therapy, systolic and diastolic blood pressures (S-BP, D-BP) as well as proteinuria significantly decreased (S-BP: at 6 months, p < 0.05 and 12 months, p < 0.01 vs. 0 month, D-BP: at 12 months, p < 0.05 vs. 0 month, proteinuria: at 6 months, p < 0.05 and 12 months, p < 0.01 vs. 0 month). The annual decline in eGFR was not significantly different before and after HCTZ therapy (-7.7 +/- A 8.5 and -8.4 +/- A 4.8 mL/min/1.73 m(2)/year, respectively). Our findings suggest that the combination of HCTZ and loop diuretics improves BP levels, and decreases proteinuria even in advanced stage type 2 DKD patients with severe edema. The addition of HCTZ therapy was not found to negatively affect the change in eGFR in the present study.

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.

A high cardiothoracic ratio (CTR) is indicative of a cardiac disorder. However, few reports have revealed an association between the CTR and mortality in patients starting hemodialysis (HD). Methods: Patients with HD initiation (n = 387 mean age, 66.7 ± 12.7 years) were divided into the following three groups according to their CTR at HD initiation: CTR &lt 50%, 50% ≤ CTR &lt 55%, and CTR ≥55%. Kaplan-Meier analysis was performed to compare 2-year all-cause mortality among these groups. Furthermore, we investigated the factors affecting their 2-year mortality using a Cox proportional hazard regression analysis. Results: Sixty-five patients (17%) died within 2 years after HD initiation. Kaplan-Meier analysis showed that patients with CTR ≥55% had a higher mortality rate than those in the other groups. Cox proportional hazard regression analysis was performed using parameters with p values &lt 0.1 among these three groups [sex, age, presence or absence of ischemic heart disease, hemoglobin levels, serum albumin levels, CTR, body mass index (BMI)] and confounding factors [presence or absence of diabetes mellitus, and estimated glomerular filtration rate (eGFR)]. Age, eGFR, BMI, and CTR ≥55% at HD initiation were identified as factors influencing 2-year mortality. Conclusion: CTR &gt 55% is one of the most important independent factors to affect 2-year all-cause mortality. Thus, confirming the cardiac condition of patients at HD initiation with a CTR &gt 55% may improve their survival.

Epstein-Barr virus (EBV) infection is common in adolescence, but fulminant infection is very rare. A 40-year-old man presented with high fever and sore throat. Symptoms, including cervical lymphadenopathy, jaundice, atypical lymphocytosis, respiratory distress and oliguria, suggested infectious mononucleosis with multiple organ failure that required mechanical ventilation and renal replacement therapy. Virus markers were consistent with primary EBV infection. Renal function was gradually improved by corticosteroid therapy. Renal biopsy revealed acute tubulointerstitial nephritis. In situ hybridizaion EBV-encoded RNA 1 did not show the presence of virus in the kidney, but acute kidney injury may be explained by cytotoxic/suppressor T lymphocyte infiltration,