Taro Hoshino

The value of QuantiFERON®TB-Gold in the diagnosis of tuberculosis among dialysis patients

BACKGROUND It is difficult to diagnose tuberculosis (TB) in dialysis patients because of the high rate of extrapulmonary TB in these patients compared with the general population. Recently, a new diagnostic test called QuantiFERON (QFT) has been developed and shown promise as a diagnostic tool for active TB diseases and latent TB infection. METHODS We examined 162 dialysis patients admitted to a single institute, including 8 patients with active TB, and evaluated the utility of this test in dialysis patients. RESULTS Among 162 dialysis patients, positive QFT results occurred in 28 (17.3%), negative QFT results occurred in 95 (58.6%) and indeterminate QFT results occurred in 39 (24.1%). All eight active TB patients had positive QFT results, and none of the 95 patients with negative results had active TB. Among 23 patients with a history of active TB, 10 (43.5%) had positive results. Although the indeterminate rate was relatively high, no patient with an indeterminate result had active TB. Factors such as shorter duration of dialysis, lower lymphocyte count and higher white blood cell count were associated with indeterminate results. Among 105 cases after excluding the patients with previous TB or indeterminate results, the sensitivity of the QFT is 100% (8 of 8) and the specificity is 89.7% (87 of 97 cases). CONCLUSIONS Our data suggest that the QFT test is a useful supplementary tool for the diagnosis of active TB even in dialysis patients. Negative and indeterminate results on this test may be used to exclude the presence of active TB.

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.

Antiepoetin antibody-related pure red cell aplasia: successful remission with cessation of recombinant erythropoietin alone

An elderly patient with pure red cell aplasia (PRCA) with antierythropoietin (anti-EPO) antibodies is described. PRCA due to alloimmunization is a rare and severe complication of recombinant human erythropoietin (rHu-EPO) therapy. Most reported patients with PRCA were cured primarily by immunosuppressive drug therapy. The patient in this case, however, did not want to receive any immunosuppressive drugs. Therefore, rHu-EPO injection was simply discontinued, the severe anemia gradually improved, and the hemoglobin approached normal range. This case is very rare and significant in that there have been few such elderly patients with rHu-EPO-induced PRCA in whom PRCA remission was achieved, with decreasing antibody titers, after cessation of rHu-EPO alone. Further cases are needed to assess how PRCA should be treated in patients with anti-EPO antibodies.

A case of sarcoidosis with severe acute renal failure requiring dialysis.

We report here a 79-year-old male having sarcoidosis without presentation of typical findings, such as respiratory symptoms, ocular signs, or skin lesions. Two weeks prior to admission to our hospital, he presented to a different hospital with acute renal failure, with blood urea nitrogen (BUN) and serum creatinine (Cr) levels of 67.9 mg/dl and 7.97 mg/dl, respectively, and was initiated on hemodialysis. The patient also exhibited fever, severe anorexia, and fatigue. We initially experienced difficulty in performing kidney biopsy due to a thrombocytopenia complication and severe general debility. Tuberculosis and other malignancies were not found. However, bone marrow biopsy revealed noncaseating granuloma with multinucleated giant cells, and the patients serum angiotensin converting enzyme (ACE) level was slightly elevated at 24.3 U/l. We informed the patient and his family of the risk of a kidney biopsy and subsequently received informed consent for the procedure. The biopsy showed many epitheloid granulomas with multinucleated giant cells in the interstitium, from which we diagnosed sarcoidosis. The thrombocytopenia was subsequently found to be due to heparin-induced thrombocytopenia (HIT). After administering 20 mg/day of oral prednisolone, the patients general condition improved rapidly. Therefore, it is important to take sarcoidosis into account as a differential diagnosis of acute renal failure, and kidney biopsy offers useful information in these cases.

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 associated with recovery of renal function in patients with multiple myeloma who were treated with hemodialysis.

Background: The presence of renal failure in patients with multiple myeloma (MM) has been considered an ominous prognostic factor associated with a significantly decreased life expectancy. The prognostic factors have seldom been analyzed to predict discontinuation of hemodialysis (HD) therapy in MM patients with renal failure after HD initiation. It is clinically very important to predict whether HD can be discontinued after introducing HD in such patients. Methods: All medical and HD records were reviewed in MM patients who underwent HD in the National Center for Global Health and Medicine Hospital between January 1995 and May 2009. Thirty-two patients with MM had undergone HD. The clinical features and the factors that might be associated with recovery of renal function leading to discontinuation of HD in MM patients with severe renal failure were examined. Results: The factors associated with recovery of renal function and discontinuation of HD were: low International Staging System (ISS) score (p = 0.0034); high response to chemotherapy (p = 0.036); low serum Ca (p = 0.006); low Cr (p = 0.019), and low serum β2-microglobulin (sβ2M) (p = 0.002). On multivariate analysis, low serum Ca and sβ2M were significantly associated with HD discontinuation. Moreover, discontinuing HD was the significant factor associated with improved overall survival in MM patients who required HD at least once. Conclusion: sβ2M and Ca were the laboratory parameters that were significant, independent prognostic factors for predicting the probability of recovery from severe renal failure and discontinuation of HD in MM patients who needed HD at least once.

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.