Removal performance of pre- and post-dilution online hemodiafiltration using identical hemodiafilters in the same patients.

Online hemodiafiltration (OHDF) for renal replacement therapy has two modes: pre- (pre-OHDF) and post-dilution OHDF (post-OHDF). To elucidate the precise differences between the two modes, a clinical study was performed using the same polysulfone hemodiafilters in the same patients. Eight patients were treated with ABH™-22PA for 6 weeks: 3 weeks of pre-OHDF (with substitution volumes of 24, 36, and 48 L) and 3 weeks of post-OHDF (6, 8, and 10 L). The reduction ratios of urea, uric acid (UA), creatinine (CRE), inorganic phosphorus (iP), beta-2-microglobulin (ß2-MG), and alpha-1-microglobulin (α1-MG) were evaluated. The removal amounts of ß2-MG, α1-MG, and albumin were also evaluated by analyzing the spent dialysis fluids. The types and numbers of adverse events (AEs) and device malfunctions were recorded. The reduction ratios of urea, UA, CRE, iP, and ß2-MG were comparable among all conditions, while that of α1-MG tended to be slightly higher in post-OHDF than in pre-OHDF. The removal amounts of α1-MG and albumin in pre-OHDF and post-OHDF were significantly greater with the maximum substitution volume than with the minimum volume. However, the selective removal indices, which were obtained by dividing the amount of α1-MG removed by the albumin level, tended to be slightly higher in pre- than in post-OHDF. No device-related AEs or device malfunctions occurred in either mode. No significant differences in inflammatory responses, evaluated by high-sensitivity C-reactive protein and interleukin-6, were observed. This study provides removal performance and safety data regarding the application of ABH-22PA for pre- and post-OHDF.

Circulating FGF23 is not associated with cardiac dysfunction, atherosclerosis, infection or inflammation in hemodialysis patients.

Fibroblast growth factor (FGF) 23 is a bone-derived hormone regulating serum inorganic phosphate (Pi) concentration. FGF23 is also involved in the development of chronic kidney disease (CKD)-mineral and bone disorder. Serum FGF23 concentration begins to increase early in the progression of CKD and can be remarkably high in hemodialysis patients with end-stage renal disease. It has been reported that high FGF23 concentration is a risk factor for cardiac dysfunction, atherosclerosis, infection or systemic inflammation in CKD patients. FGF23 was also shown to induce cardiac hypertrophy directly acting on cardiomyocytes. However, it is still controversial whether high FGF23 is causing cardiac dysfunction, atherosclerosis, infection or systemic inflammation in CKD patients. In the current study, we investigated whether FGF23 concentration is associated with cardiac dysfunction, atherosclerosis, infection or systemic inflammation in Japanese hemodialysis patients. We recruited 119 hemodialysis patients and examined the association between serum FGF23 concentration and several parameters concerning mineral metabolism, cardiac dysfunction, atherosclerosis, infection, and systemic inflammation. Serum FGF23 concentration was independently associated with serum calcium and Pi concentration (ß = 0.276, p < 0.001; ß = 0.689, p < 0.001). However, serum FGF23 concentration was not associated with parameters of cardiac dysfunction, atherosclerosis, infection, and systemic inflammation, either. Our results do not support the hypothesis that high FGF23 in dialysis patients is the cause of cardiac dysfunction, atherosclerosis, infection or systemic inflammation.

Pulmonary sarcoidosis as a cause of intermittent fever of unknown origin in a hemodialysis patient with renal cell carcinoma: A case report and literature review.

Hemodialysis patients have weakened immune systems and can exhibit fever due to various causes. Herein, we describe the case of a 61-year-old hemodialysis patient who exhibited intermittent low-grade fever after a pacemaker had been implanted 2 months before due to sick sinus syndrome. She had a medical history of subcutaneous sarcoidosis and uveitis. Active pulmonary sarcoidosis was diagnosed based on elevated soluble interleukin-2 receptor, elevated lysozyme level, and gallium-67 scintigraphy uptake in hilar and mediastinal lymph nodes. She was also diagnosed with renal cell carcinoma via contrast computed tomography. However, because her C-reactive protein level remained normal, the possibility of neoplastic fever was considered low. After the initiation of prednisolone administration, her fever gradually disappeared. Her serum soluble interleukin-2 receptor and lysozyme level improved in parallel with the enlargement of the mediastinal lymph node and gallium-67 scintigraphy uptake.

Alogliptin-Induced Minimal Change Nephrotic Syndrome and Interstitial Nephritis.

Alogliptin is one of the dipeptidyl peptidase-4 inhibitors used to treat patients with type 2 diabetes. Little is known about the nephrotoxicity associated with alogliptin, such as nephrotic syndrome or interstitial nephritis. We report a biopsy-proven rare case of minimal change nephrotic syndrome and interstitial nephritis induced by alogliptin. A 68-year-old man who had been prescribed alogliptin was hospitalized for nephrotic syndrome. On admission, serum creatinine level was elevated with increased urinary ß2-microglobulin and N-acetyl-ß-d-glucosaminidase excretion. Kidney biopsy revealed minor glomerular abnormalities and interstitial nephritis, and gallium-67 scintigraphy showed uptake in both kidneys. A drug lymphocyte stimulation test for alogliptin was positive. With discontinuation of alogliptin treatment alone, serum creatinine level normalized in parallel with urine ß2-microglobulin and N-acetyl-ß-d-glucosaminidase levels. In addition, complete remission of nephrotic syndrome was observed. Drug-induced dual pathology has not been previously reported with alogliptin. In summary, clinicians should keep in mind that alogliptin can induce minimal change nephrotic syndrome and interstitial nephritis.

Sucroferric oxyhydroxide decreases serum phosphorus level and fibroblast growth factor 23 and improves renal anemia in hemodialysis patients.

OBJECTIVE: Sucroferric oxyhydroxide, a novel iron-based phosphate-binder, has been shown to have beneficial effects in lowering serum phosphorus levels and improving renal anemia in clinical studies. Although an effect of this agent on fibroblast growth factor 23 (FGF23) has been reported in an animal study, there is little clinical data supporting this finding. This study aimed to evaluate the effect on chronic kidney disease-mineral and bone disorder, FGF23, renal anemia, iron-related parameters, adverse events of sucroferric oxyhydroxide in hemodialysis patients. RESULTS: Hemodialysis patients, receiving existing hyperphosphatemia drugs with insufficient benefit, were administered sucroferric oxyhydroxide with/without calcium carbonate for 16 weeks. Serum phosphorus level declined rapidly in Week 8 (p < 0.0001) and this decrease persisted until Week 16 (p < 0.0001). FGF23 decreased (p = 0.0412, Week 16), and hemoglobin increased (p < 0.0001, Week 16). Cumulative dose of erythropoiesis-stimulating agents (p = 0.0122, Week 16), and intravenous iron (p = 0.0233, Week 12) decreased. All adverse reactions were mild, and diarrhea was the most frequently observed adverse reaction (16.7%). Therefore, hyperphosphatemia treatment with sucroferric oxyhydroxide may safely improve serum phosphorus level, renal anemia, FGF23, and other factors that affect the prognosis of hemodialysis patients.

Intestinal perforation by a peritoneal dialysis catheter in which fungal peritonitis led to diagnosis: a rare case report.

Intestinal perforation by a peritoneal catheter is an uncommon, but serious, complication that has a high mortality rate. Intestinal perforation in peritoneal dialysis (PD) patients is difficult to diagnose using symptoms and radiological findings, which may result in a delay in diagnosis. Moreover, intestinal perforation complicated with fungal peritonitis is reportedly a severe condition with a poor prognosis. Herein, we report the case of a 78-year-old man on PD, whose diagnosis of perforative peritonitis was difficult to diagnose preoperatively. He was transferred to our hospital complaining of relapsing PD-related peritonitis due to Klebsiella oxytoca infection 2 months after the insertion of the PD catheter. He had been treated with various antibiotics in the previous hospital. Over the course of treatment, he complained of diarrhea, which was diagnosed as acute enteritis. Upon admission to our hospital, he had no abnormal clinical signs except for a cloudy PD effluent. Blood examination showed a high C-reactive protein level (8.41 mg/dL), a white blood cell count in the PD fluid of 367 cell/µL (neutrophils 55.1%), and the presence of Candida parapsilosis. We initiated antifungal therapy and, during catheter removal, found evidence of intestine perforations by the PD catheter, which were successfully repaired. After catheter removal and intestine repair, he recovered and was discharged to continue undergoing hemodialysis. Based on our case, we recommend that intestine perforations should be considered as a cause of relapsing PD-related peritonitis with abdominal symptoms, particularly watery diarrhea. Furthermore, catheter removal and antifungal administration should be initiated earlier after the diagnosis of fungal peritonitis.

Cilostazol-induced acute tubulointerstitial nephritis accompanied by IgA nephropathy: a case report.

BACKGROUND: Cilostazol is an antiplatelet drug that is widely prescribed for the prevention of secondary stroke. Adverse reactions to cilostazol include headaches, palpitations, and diarrhea. Little is known about the nephrotoxicity of cilostazol, such as acute kidney injury. We report a biopsy-proven case of diffuse tubulointerstitial nephritis induced by cilostazol. CASE PRESENTATION: A 69-year-old woman prescribed cilostazol was hospitalized for acute kidney injury. On admission, her renal function deteriorated, with an increased serum creatinine level. Urinalysis showed hematuria, proteinuria, and hyper-beta2-microglobulinuria. A renal biopsy revealed diffuse tubulointerstitial nephritis associated with IgA nephropathy, and gallium-67 scintigraphy showed uptake in the bilateral kidneys. A drug lymphocyte stimulation test for cilostazol was positive, and the patient was diagnosed with cilostazol-induced acute tubulointerstitial nephritis. Despite discontinuation of cilostazol, her renal function rapidly worsened and steroid pulse therapy was initiated, followed by oral high-dose glucocorticoid therapy. After steroid treatment, her serum creatinine level normalized in parallel with urine beta2-microglobulin. CONCLUSION: Cilostazol can induce acute tubulointerstitial nephritis.

Aldosterone and Insulin Resistance: Vicious Combination in Patients on Maintenance Hemodialysis.

Recently, we demonstrated that plasma aldosterone contributed to insulin resistance in chronic kidney disease. The aim of this study is the clinical impact of this relationship in hemodialysis patients. In a cross section study using a total of 128 hemodialysis patients, multiple regression analysis revealed that plasma aldosterone levels were independently associated with HOMA-IR, insulin resistance index. This association was found to be more stringent in diabetic patients than in non-diabetic patients. Aldosterone levels were associated with cardiac hypertrophy and carotid artery stenosis. HOMA-IR was associated with cardiac hypertrophy. The patients whose aldosterone and HOMA-IR were above the top tertile of each parameter in this cohort showed more severe cardiac hypertrophy and lower contractile function as compared with the patients whose aldosterone levels and HOMA-IR are below the lowest tertile of each parameter. In conclusion, in hemodialysis patients, aldosterone levels and insulin resistance are closely interrelated and the constellation of the two is related to severe cardiovascular tissue damages.

Nutritional counseling regulates interdialytic weight gain and blood pressure in outpatients receiving maintenance hemodialysis.

Maintenance hemodialysis outpatients must limit salt and water intake to maintain electrolyte balance and blood pressure. In Kawashima Hospital, nationally registered dietitians provide hemodialysis patients with monthly nutritional counseling. We investigated whether nutritional counseling affects interdialytic weight gain (IDWG) and blood pressure. We investigated 48 hemodialysis patients whose monthly average IDWG ratio to dry weight exceeded 5.1% and who had not had a long-term hospital admittance of > 1 month. After the 48-month nutritional counseling period, the IDWG ratio had improved in 37 of the patients (77.1%), significantly decreasing from 6.0±0.7 to 5.3±0.9%. Estimated salt and water intake decreased significantly from 13.3±2.7 to 11.8±2.4 g/day and 2528±455 to 2332±410 ml/day, respectively. During the intervention period, normalized protein catabolic rate and body mass index did not change substantially. Pre-hemodialysis systolic and diastolic blood pressures had significantly decreased from 149±19 to 134±18 mmHg, and 82±13 to 75±10 mmHg for 48 months after study initiation, respectively. The dosage of antihypertensive drugs had significantly decreased in the group that experienced improvement in the IDWG ratio. Long-term nutritional counseling by nationally registered dietitians may improve the IDWG ratio and blood pressure of hemodialysis patients by decreasing their salt and water intake. J. Med. Invest. 64: 129-135, February, 2017.

Impact of Lanthanum Carbonate on Prognosis of Chronic Hemodialysis Patients: A Retrospective Cohort Study (Kawashima Study).

In hemodialysis patients, mineral and bone disorder is an important risk factor for cardiovascular disease and subsequent death through the progression of vascular calcification. Serum phosphorus plays a major role in this process. In the present study, we retrospectively analyzed the effects of oral phosphate binder, lanthanum carbonate (LC), on the mortality in hemodialysis patients. Among a total of 841 patients who underwent maintenance hemodialysis on 1 July 2010, patients who were treated with LC (LC group, N = 324) and those who were treated without LC (NLC group, N = 517) were compared with respect to their all-cause mortality for a long-term observation period of up to 36 months. The mortality rate was compared using the Cox proportional hazard model adjusted by the propensity score. The adjusted hazard ratio for mortality in the LC group versus NLC group was 0.515 (95% confidence interval, 0.328-0.807), suggesting that the use of LC is associated with an almost 50% reduction in the mortality rate. The present retrospective study including all hemodialysis patients demonstrated, for the first time, an association between the use of LC and improved prognosis in hemodialysis patients. Randomized controlled trials should be done in the future to validate our present findings.

Association between periodontal condition and kidney dysfunction in Japanese adults: A cross-sectional study.

Recent studies have demonstrated that chronic kidney disease (CKD) may be associated with the progression of periodontal disease. Diabetes mellitus (DM) is a major risk factor for CKD. The objective of this study was to clarify the relationship between periodontal condition and kidney dysfunction in patients who had kidney failure with or without DM. One hundred sixty-four patients with kidney dysfunction were enrolled (male: N = 105; female: N = 59), and the relationship between periodontal condition and kidney dysfunction was analyzed in a cross-sectional study. The subjects were divided into three groups: (a) patients with DM, (b) dialysis patients with nephropathy due to various kidney diseases, and (c) dialysis patient with nephropathy due to DM (diabetic nephropathy). Then, the effect of DM on the periodontal condition was analyzed. The patients were also stratified by CKD stage (into G1-G5) using the estimated glomerular filtration rate (eGFR), and the G5 group was divided in patients with or without DM. Correlations between eGFR and parameters of periodontal condition were calculated in patients from G1 to G4. The number of missing teeth was significantly higher in dialysis patients with diabetic nephropathy than in patients with DM, whereas alveolar bone loss did not show a significant difference among the three groups. In addition, the G5 patients with DM had a significantly higher number of missing teeth than the other CKD groups, whereas alveolar bone loss did not show a significant difference. In G5 patients with DM, Community Periodontal Index and Oral Hygiene Index scores were significantly higher than in G1-4 patients with DM. There was a significant negative correlation between eGFR and the number of missing teeth. Patients with diabetic nephropathy have a higher rate of periodontal problems such as missing teeth in Japanese adults.

Treatment of renal anaemia with erythropoiesis-stimulating agents in predialysis chronic kidney disease patients: Haemoglobin profile during the 6 months before initiation of dialysis.

AIM: Erythropoiesis-stimulating agents (ESAs) are all effective for renal anaemia in patients with chronic kidney disease (CKD). However, it was reported that the haemoglobin (Hb) concentration decreases to 8.4 g/dL during the initial phase of dialysis despite treatment with recombinant human erythropoietin (rHuEPO). This study compared Hb at the initiation of dialysis among patients treated with three different ESAs (rHuEPO, darbepoetin alfa [DA], and a continuous erythropoietin receptor activator [CERA]). METHODS: The subjects were 82 CKD patients who started dialysis at Kawashima Hospital between 1 January 2009 and 28 February 2015 and who received only one kind of ESA for at least 6 months before initiation of dialysis. Baseline characteristics and laboratory data at initiation of dialysis were compared among the three groups. Then changes of the Hb, ESA dose, and erythropoiesis resistance index were assessed over time during the 6 months before initiation of dialysis. Differences of Hb at the initiation of dialysis were also assessed. RESULTS: Among the 82 patients, 36 received rHuEPO, 13 received DA, and 33 received CERA. Baseline characteristics and laboratory data of the patients showed no significant differences among the three groups. The monthly Hb decreased gradually during the 6-month period before initiation of dialysis in all three groups. Hb was significantly higher in the CERA group than the rHuEPO group at the initiation of dialysis. CONCLUSION: Long-acting ESAs may be more useful for predialysis patients with CKD because they do not attend hospital frequently, unlike haemodialysis patients.

Vascular access for long-term hemodialysis/hemodiafiltration patients in Japan.

BACKGROUND: Many patients are receiving long-term hemodialysis (HD) or hemodiafiltration (HDF) treatment in Japan. Vascular access is a lifeline for patients on HD or HDF, and proper maintenance of vascular access is one of the key factors that make long-term HD and HDF possible. We investigated the conditions of vascular access in patients undergoing chronic HD or HDF in our hospital group in Japan to assess the relationship between the type of vascular access and long-term treatment. PATIENTS AND METHODS: We studied the conditions of vascular access in 899 patients who were on chronic HD or HDF, including patients who had been on dialysis for over 20 years as of December 2014. RESULTS: There were 125 patients who had been on dialysis treatment for over 20 years, with the longest dialysis vintage being 37 years, and they accounted for 13.9% of the total number of subjects. The primary disease was diabetes in two cases and chronic glomerulonephritis in the rest. There were 105 patients with an arteriovenous fistula and only 20 with an arteriovenous graft (AVG) (16.0%), whereas 91 had an AVG (11.7%) among the 774 patients who had been on dialysis treatment for less than 20 years, which indicated that the percentage of patients with an AVG increased with dialysis vintage. CONCLUSIONS: An arteriovenous fistula was the main type of vascular access used in patients who had been on dialysis treatment for over 20 years, which is very rare, even on the global scale. However, switching to an AVG is unavoidable in cases of vein deterioration due to long-term use. Access via an AVG is expected to increase further in long-term patients in the future.

Present status of Japanese ethics committees: a survey in Tokushima Prefecture.

Clinical research is important to improve medical quality, and ethics review is essential to conduct clinical research. Since the establishment of the first Japanese ethics committee at the University of Tokushima in 1982, Japanese ethics committees have increased. In this study, we surveyed the status of clinical studies and ethics committees in one Japanese region. The survey was conducted in collaboration with the Tokushima Medical Association. A questionnaire was established and mailed to all medical institutions (n=737) registered to the Tokushima Medical Association in 2012. Among 737, 223 (30.3%) questionnaires were returned and 221 were completed and are included in this analysis (respondents). Among respondents, 51 (23.1%) had performed clinical research, and of these, 17 had established ethics committees (though one was omitted from the following analysis due to an unsatisfactory response). Among 16 ethics committees, review of protocol amendments, review of serious adverse events, annual follow-up of approved protocols, and education for committee members were active in 10 (62.5%), 9 (56.3%), 6 (37.5%) and 4 (25.0%), respectively. Research ethics education was active in 4 (25.0%). Based on the results, we attempt to establish an appropriate system for ethical conduct of health-related research in Tokushima Prefecture.

Stringent glycaemic control prolongs survival in diabetic patients with end-stage renal disease on haemodialysis.

AIM: No suitable index or optimal target for diabetic control has been established for diabetic patients with end-stage renal disease (ESRD) undergoing haemodialysis. To address these issues, the single-centre observational study was conducted. METHODS: Two hundred and forty-five diabetic ESRD patients (23.3% female; age at initiation of haemodialysis 61.7 ± 10.7 years) at start of haemodialysis between 1 January 1995 and 31 December 2004 were enrolled. Subjects were grouped according to glycaemic control level throughout the observational period as follows: mean postprandial plasma glucose (PPG) <8.9 mmol/L, 8.9 mmol/L ≤ PPG < 10.0 mmol/L, 10.0 mmol/L ≤ PPG < 11.1 mmol/L, 11.1 mmol/L ≤ PPG < 12.2 mmol/L and PPG ≥ 12.2 mmol/L; and HbA1c < 6.0%, 6.0-6.4%, 6.5-6.9% and ≥ 7.0%. Survival was then followed until 31 December 2005. RESULTS: Cumulative survival of groups of 10.0 mmol/L ≤ PPG < 11.1 mmol/L, 11.1 ≤ PPG < 12.2 and PPG ≥ 12.2 mmol/L was significantly lower than that for PPG < 8.9 mmol/L as determined by Kaplan-Meier estimation (P = 0.016, 0.009 and 0.031, respectively; log-rank test). In both uni- and multivariate Cox proportional hazard models, mortality hazard ratios were significantly higher for PPG ≥ 10.0 mmol/L than for PPG < 8.9 mmol/L (P = 0.002-0.021). Kaplan-Meier survival curves grouped by HbA1c levels showed no correlation between HbA1c and survival during the observational period. No significant difference in mortality hazard ratios was seen for any HbA1c groups evaluated by Cox proportional hazard model. CONCLUSION: Intensive management of diabetic control at a stringent mean on-study PPG < 10.0 mmol/L will improve the life expectancy in diabetic dialysis patients. However, no range of HbA1c values obtained in this study showed any clear difference in clinical outcomes.

Effect of protein and energy intakes on body composition in non-diabetic maintenance-hemodialysis patients.

This cross sectional study was performed to find the adequate amount and combination of dietary protein and energy for maintaining better nutritional status for stable non-diabetic maintenance hemodialysis (MHD) patients. The body composition including body fat, total body water, body cell mass and body protein were measured by multi-frequency bioelectrical impedance analysis in 200 stable MHD patients without diabetes (124 men, 76 women). Dietary energy intake (DEI) and dietary protein intake (DPI) were assessed by a brief self-administered diet history questionnaire (BDHQ), the DPI value being confirmed by calculating the normalized protein equivalent of total nitrogen appearance (nPNA). The nutritional status and the body composition were compared among 4 groups of patients in each gender that were divided by the combination of DEI and DPI; high energy (HE)/high protein (HP), HE/low protein (LP), low energy (LE)/HP and LE/LP groups. The mean DPI ranged between 1.17-1.23 and 0.89-0.95 g/kg IBW/d in the HP and LP groups, respectively for both genders, and the mean DEI was 35-37 and 24-25 kcal/kg IBW/d in HE and LE groups, respectively. BMI and serum albumin concentration were not different among the 4 groups. Body cell mass index (BCMI) was maintained in the HE groups regardless of DPI, and it was significantly higher in the HE/HP group than in the LE/LP group. Multiple regression analysis also showed that the BCMI was more greatly affected by DEI than DPI. These results indicated that a DPI of 0.89-0.95 g/kg IBW/d could be sufficient for maintaining BCMI, if DEI is kept over 35 kcal/kg IBW/d in stable non-diabetic MHD patients. This DPI level is lower than the recommended DPI proposed by dietary guidelines in the US and Japan.

[Mass screening for prostate cancer in Tokushima City: the results of 2001].

PURPOSE: Screening with prostate specific antigen (PSA) only to detect prostate cancer was started in Tokushima City from 2001 as one of health check lists. We evaluated the first year result. MATERIALS AND METHODS: Fifty-five years old or elder men living in Tokushima City who wants to measure serum PSA level to screen for prostate cancer were entered to screening program. The men whose PSA levels detected as over normal; range were recommended to visit to urologists for further examination to detect prostate cancer include prostate biopsy. The results of further examination were reported to Tokushima City and evaluated. RESULTS: The population of fifty-five or elder men in Tokushima City was 25,416 and 9,019 (35.5%) men were measured serum PSA levels. In 801 (8.9%) men, PSA levels were over normal range, and recommended further examination to detect prostate cancer. 451 (56.3%) men visited to urologists for further examination, and prostate biopsy was performed in 231 (51.2%) men. Finally, 121 men were diagnosed as prostate cancer, 52.1% of 231 men performed prostate biopsy, 26.7% of 451 men visited to urologist for further examination, 1.34% of 9,019 men measured serum PSA levels. Patient number for each clinical stages were 49 in B0, 16 in B1, 16 in B2, 29 in C, one in D1, and 10 in D2. Patients number in each age range were 3 in 55-59, 11 in 60-64, 22 in 65-69, 37 in 70-74, 33 in 75-79, 15 in 80 or elder. Patient number of Stage B and 74 years old or younger was 48 (39.7%). CONCLUSION: Prostate cancer was detected in 1.34% of 9,019 men who measured serum PSA levels, and early stage B was two thirds. PSA screening to detect prostate cancer as one of health check-lists in Tokushima City was useful to detect early prostate cancer.