Clinical effects of the new phosphorus binder, bixalomer in hemodialysis patients switched from sevelamer hydrochloride.

It has been reported that sevelamer hydrochloride, which is often used as a polymer phosphorus (P) binder for managing serum P concentration in dialysis patients, causes gastrointestinal adverse effects such as constipation, etc. The reason for this is thought to be that sevelamer hydrochloride has high water absorption, causing it to absorb water and swell in the gastrointestinal tract. In June 2012, the new polymer P binder bixalomer was launched in Japan. Since bixalomer has low swelling due to water absorption, it can be expected to alleviate adverse effects in the gastrointestinal system. In our study, for 21 cases of maintenance hemodialysis patients undergoing treatment with sevelamer hydrochloride at our hospital, the P binder was switched from sevelamer hydrochloride to the same dosage of bixalomer, and the concentrations of serum P, corrected calcium (Ca) and whole parathyroid hormone (PTH) before and one month after the switch were compared. In addition, gastrointestinal symptoms (acid reflux, abdominal pain, indigestion, diarrhea and constipation) were evaluated before and after the switch using a questionnaire based on the Japanese version of the Gastrointestinal Symptom Rating Scale (GSRS). By switching to bixalomer, serum P concentration was significantly reduced (P=0.024), but there were no significant changes observed for serum corrected Ca and whole PTH. Furthermore, there were no significant changes observed for all five of the evaluation items of the GSRS, before and after the switch. These results suggest that although bixalomer can more potently reduce the serum P concentration than sevelamer hydrochloride, there were no significant differences in the effects of both P binders on the gastrointestinal symptoms.

Aliskiren reduces morning blood pressure in hypertensive patients with diabetic nephropathy on hemodialysis.

Our previous study indicated that the exchange from an angiotensin receptor blocker (ARB) to aliskiren reduced morning blood pressure and albuminuria in hypertensive patients with diabetic nephropathy. We extended the above study and assessed the effects of exchanging from an ARB to aliskiren on home blood pressure in hypertensive patients with diabetic nephropathy on chronic hemodialysis. The patients who were persistently hypertensive despite antihypertensive therapy, including ARB, were considered as candidates for the exchange from the ARB to aliskiren. Patients' age and durations of diabetes and hemodialysis were averaged as 62 ± 9 years old, 15 ± 8 and 7 ± 3 years, respectively. Aliskiren decreased morning systolic blood pressure (149 ± 14 to 144 ± 13 mm Hg, n = 30, P < .01) and plasma renin activity (3.5 ± 1.1 to 1.2 ± 0.6 ng/mL/h, P < .01) without changes in serum potassium. Aliskiren also reduced interdialytic weight gain (2.7 ± 0.6 to 2.5 ± 0.5 kg/interval, P < .05) and attenuated the magnitude of intradialytic declines in systolic (-20 ± 11 to -17 ± 10 mm Hg, P < .05) and diastolic blood pressure (-9 ± 6 to -5 ± 5 mm Hg, P < .01). The exchange from an ARB to aliskiren is safe and useful to control home blood pressure in hypertensive hemodialysis patients with diabetic nephropathy. Aliskiren reduced both intradialytic blood pressure drops and interdialytic weight gain in patients with DN.

Aliskiren reduces morning blood pressure in hypertensive patients with diabetic nephropathy.

Diabetic nephropathy (DN) is a leading disease that requires renal replacement therapy. The progression of renal dysfunction in DN is faster than the other renal diseases. While antihypertensive therapy reduces albuminuria, a good indicator for the progression, hypertension in DN is treatment resistant. Among patients with DN who took angiotensin receptor blockers (ARBs), 27 patients who exhibited poor control of albuminuria were enrolled into the study. Angiotensin receptor blocker was exchanged to aliskiren (150-300 mg/d) and clinical parameters were followed for 6 months. Exchange to aliskiren decreased albuminuria (1.57 ± 0.68 to 0.89 ± 0.45 g/gCr, P < .01) without changes in estimated glomerular filtration rate and office blood pressure (BP). Body weight and hemoglobin A1c were not altered. Aliskiren also reduced plasma renin activity (2.0 ± 0.9 to 1.2 ± 0.6 ng/mL/h, P < .01). While evening BP was unchanged, morning systolic BP (139 ± 8 to 132 ± 7 mm Hg, P < .01) and diastolic BP (81 ± 7 to 76 ± 6 mm Hg, P < .05) were decreased significantly after 6 months. Our results indicated that aliskiren decreased BP, especially morning BP in hypertensive patients with DN. The present data suggest that aliskiren exerts renoprotective actions including reduction in albumin excretion for patients with DN.

Long-term effects of calcium antagonists on augmentation index in hypertensive patients with chronic kidney disease: a randomized controlled study.

BACKGROUND: Our previous retrospective study showed that benidipine was superior to amlodipine (AM) for reducing proteinuria and preserving the augmentation index (AI) in patients with chronic kidney disease (CKD). METHODS: The present study enrolled CKD patients whose blood pressure was not well controlled by an angiotensin receptor blocker (ARB) and a calcium channel blocker other than AM or azelnidipine (AZ). Either AM (5 mg) or AZ (16 mg) was prescribed randomly. Clinical parameters, including proteinuria, serum creatinine, and AI, were measured before initiation of AM or AZ and 1 year later to assess the long-term effect on renal function and central blood pressure. RESULTS: Brachial and central blood pressures were similarly reduced in both groups. However, pulse rate increased in the AM group, but decreased in the AZ group (+3 ± 1 vs. -2 ± 1 bpm, p < 0.0001). The reduction of proteinuria was greater in the AZ group (-29 ± 2 vs. -38 ± 3%, p < 0.01). Improvement of AI adjusted for a pulse rate of 75 bpm was larger in the AZ group than in the AM group (-4 ± 1 vs. -9 ± 1%, p < 0.05). In both groups, estimated GFR remained unchanged throughout the observation period. CONCLUSION: In hypertensive patients with CKD, combined treatment with AZ and an ARB decreases proteinuria and preferentially improves arterial reflection.

Aging is an important risk factor for peritoneal dialysis-associated peritonitis.

Peritonitis remains a leading complication of peritoneal dialysis (PD). The aim of this observational retrospective cohort study, conducted at our single center, was to determine the risk factors for peritonitis. A Cox proportional hazards model was used for the multivariate analysis. The event investigated was peritonitis, and the variables studied were sex, age, diabetes mellitus, use of statins, and several laboratory values including albumin and total cholesterol. All PD patients who visited our clinic from January 2005 to September 2011 and who had complete medical records for at least 3 years were included. Among the 82 patients who met the criteria (mean period of observation: 1086 +/- 752 days; mean age: 62.0 +/- 12.3 years), 47 had experienced at least 1 episode of peritonitis. Aging was a significant risk factor for peritonitis, with a relative risk of 1.04 per year (p = 0.014). In our study, aging--rather than diabetes mellitus, efficiency of PD, or nutrition status--was an important risk factor for PD-associated peritonitis. Poor PD technique because of advanced age might be one of the reasons for this result.

Continuous ambulatory Peritoneal dialysis beyond a decade: cases from a single center.

A broad consensus has not been reached on the appropriate timing for cessation of peritoneal dialysis (PD). Decreasing urine volume, repeated and refractory peritonitis, and deterioration of the peritoneal membrane are major reasons to stop PD. Also, the link between length of time on PD and encapsulating peritoneal sclerosis (EPS) should be an additional concern. The aim of the present study was to investigate patients who had been on continuous ambulatory PD (CAPD) for a long time. All patients undergoing CAPD at our kidney center for more than a decade from January 1990 to September 2011 were included in the study. Among more than 436 CAPD patients, 11 met the inclusion criteria. Their mean PD duration was 12.3 +/- 3.1 years. Mean age at CAPD introduction had been 46.0 +/- 10.1 years. All patients had nondiabetic nephropathy as the underlying cause of their end-stage renal disease. At least 2 of the 11 had developed EPS, and 1 had subsequently died from EPS. Patients on prolonged CAPD for more than a decade are still rare. The CAPD modality may be continued if it is efficiently maintained within an acceptable level, but EPS remains a serious complication of prolonged PD.

Close association of vascular and valvular calcification and prognosis of patients on continuous ambulatory peritoneal dialysis.

In the present study, we examined the association between vascular and valvular calcification and the prognosis of patients on continuous ambulatory peritoneal dialysis (CAPD). Data were collected from the records of patients introduced onto CAPD therapy during 1999 - 2006 at the Department of Nephrology, Saitama Medical University. At the start of CAPD, cardiac and vascular echography were used to examine 162 patients (average age: 56 +/- 5 years; 58 men, 104 women; 43 with and 119 without diabetes) for evaluation of vascular and valvular calcification. Both vascular and valvular calcification were found in 32 patients. Vascular calcification was found in 16, and valvular calcification in 11. Over 5 years, 11 patients suffered from cardiovascular disease (7 with stroke, 4 with myocardial infarction). All of these patients had vascular or valvular calcification at the start of CAPD therapy. We also used Cox hazard analysis to examine values for Ca, P, Ca x P, intact parathyroid hormone (iPTH), and lipids. None of these values were independent contributory factors for incidence of cardiovascular disease in patients on CAPD. These data suggest the importance of vascular and valvular echography to evaluate patients on CAPD, especially at the start of CAPD therapy. Vascular and valvular calcification are important factors for determining the prognosis of patients on CAPD.

Risk factors and cause of removal of peritoneal dialysis catheter in patients on continuous ambulatory peritoneal dialysis.

In the present study, we examined the risk factors and causes for removal of the peritoneal dialysis (PD) catheter in patients on continuous ambulatory PD (CAPD). Data were collected from the records of patients who received CAPD therapy from 1995 to 2007 in the Department of Nephrology, Saitama Medical University. During that time, 473 patients were introduced onto CAPD therapy and the PD catheter was removed from 63 patients. Catheters were removed in 30 patients (47%) because of peritoneal infection, in 11 (17%) because of dialysis failure, in 8 (13%) because of neoplasm of the gastrointestinal tract, in 6 (10%) because of perforation of the gastrointestinal tract, in 2 (3%) because of laceration of PD catheter, and in 3 each (5%) because of transplantation and home hemodialysis therapy. Duration of CAPD was 5.6 +/- 1.2 years. In patients who experienced peritoneal infection, causative organisms were Staphylococcus (mainly methicillin-resistant S. aureus), Candida, Pseudomonas, and non tuberculous Mycobacterium. Failure to continue PD therapy related to dialysis deficiency. All patients were examined for encapsulating peritoneal sclerosis (EPS) by computed tomography (CT) enhanced using contrast material. In 9 cases in which the CT findings indicated EPS, treatment with oral prednisolone (20 mg daily) was started; the dose was then gradually reduced over 1 year. After removal of the PD catheter, no patient developed EPS. All removed catheters were examined using electron microscopy. The catheters from patients who experienced PD peritonitis revealed biofilm formation; however, no biofilm formation was found in PD catheters removed from patients without infection. Despite appropriate antibiotic therapy, peritoneal infection remains the major cause of PD catheter removal. Biofilm formation might be an obstacle to PD continuation.