Correlation between Aortic Calcification Score and Biochemical Parameters in Hemodialysis Patients.

BACKGROUND: The purpose of this study was to determine the correlation between aortic calcification and demographic and biochemical parameters in hemodialysis patients. SUMMARY: Calcification scores of the aortic arch and abdominal aorta were determined from multi-slice computed tomography scans and evaluated according to the Agatston score. The associations between demographic and biochemical parameters and aortic calcification score were determined. In total, 190 patients were included in the study. There was a significant positive correlation between aortic calcification scores and age, duration of hemodialysis, cardiothoracic ratio, normalized protein catabolic rate, brachial-ankle pulse wave velocity (baPWV), serum markers of mineral metabolism, and inflammation. A significant negative correlation was found between aortic calcification scores and platelet count. Multivariate analysis showed that age, duration of hemodialysis, baPWV, phosphate, calcium and phosphate (Ca×P) product, parathyroid hormone, and C-reactive protein levels were independent risk factors for calcification of the aortic arch, while baPWV and Ca×P product were independent risk factors for calcification of the abdominal aorta. Key Messages: Aortic calcification scores correlate with age, duration of hemodialysis, and several biochemical parameters of inflammation and mineral metabolism.

Efficacy of L-carnitine supplementation for improving lean body mass and physical function in patients on hemodialysis: a randomized controlled trial.

BACKGROUND: Carnitine deficiency is common in patients on hemodialysis. However, the efficacy of L-carnitine supplementation for improving lean body mass (LBM) and physical function has not yet been evaluated. METHODS: In this multicenter, prospective, parallel, randomized, controlled trial, 91 patients on hemodialysis who developed carnitine deficiency were randomly assigned to receive injections of 1,000 mg L-carnitine 3 times per week after each hemodialysis session (L-carnitine group) or no injections (control group) with monitoring for 12 months. RESULTS: The data for 84 of the 91 patients were available for analysis (L-carnitine group, n = 42; control group, n = 42). Dry weight and body mass index did not significantly change in the L-carnitine group, but significantly decreased in the control group. Arm muscle area (AMA) did not change significantly in the L-carnitine group but decreased significantly in the control group; the difference in mean AMA between the groups was 6.22% (95% confidence interval [CI] 1.90-10.5; P = 0.037). Hand grip strength did not change significantly in the L-carnitine group, but decreased significantly in the control group. The difference in change in hand grip strength between the groups was 4.27% (95% CI 0.42-8.12; P = 0.030). Furthermore, LBM did not change significantly in the L-carnitine group but decreased significantly in the control group; the difference in mean LBM between the groups was 2.92 % (95% CI 1.28-4.61; P = 0.0007). CONCLUSIONS: L-carnitine supplementation is useful in patients who develop carnitine deficiency on hemodialysis because it maintains physical function and LBM.

Effect of Sucroferric Oxyhydroxide on Fibroblast Growth Factor 23 Levels in Hemodialysis Patients.

OBJECTIVE: This study investigated the effects of sucroferric oxyhydroxide on fibroblast growth factor (FGF)-23 and dose reduction of erythropoiesis-stimulating agents (ESA) and intravenous saccharated ferric oxide in hemodialysis patients. METHODS: In this prospective, open-label, parallel-group, multicenter trial involving patients receiving lanthanum carbonate hydrate, eligible patients were randomized to a sucroferric oxyhydroxide group or a control group. Hemoglobin, serum phosphate, FGF-23, iron, and ferritin levels, as well as transferrin saturation, doses of intravenous saccharated ferric oxide and ESA administered, and the erythropoietin responsiveness index (ERI) were monitored for 24 weeks. RESULTS: Sixty-eight eligible patients were allocated to receive sucroferric oxyhydroxide (n = 34) or serve as controls (n = 34). Data for 31 patients in the sucroferric oxyhydroxide group and 32 in the control group were analyzed. Serum phosphate was equally well controlled in both groups. In the sucroferric oxyhydroxide group, intact FGF-23 levels decreased significantly from baseline at the end of the study (p = 0.01) and there was a significant difference compared with the control group (p = 0.035). Required doses of ESA and ERI were significantly reduced in the sucroferric oxyhydroxide group decreased significantly. The dose of intravenous saccharated ferric oxide required in the sucroferric oxyhydroxide group was significantly lower than that at baseline (p = 0.006) and in the control group (p = 0.003). CONCLUSIONS: Treatment of hyperphosphatemia with sucroferric oxyhydroxide was effective in patients on hemodialysis, resulting in decreased serum FGF-23 levels and a reduction in the required dose of saccharated ferric oxide.

Targets and Therapeutics for Glycemic Control in Diabetes Patients on Hemodialysis.

BACKGROUND: For diabetes patients without nephropathy, glycemic control is important to reduce the risk or delay the progression of diabetes complications, including nephropathy. In diabetes patients on hemodialysis, good glycemic control is necessary to improve prognosis. Many factors influence the blood glucose level of diabetes patients on hemodialysis, such as factors associated with end-stage kidney disease and factors related to hemodialysis. Therefore, since glucose metabolism in diabetes patients on hemodialysis has unique characteristics, it is necessary to manage blood glucose in these patients with specific guidelines. Here, we describe the targets and therapeutics for glycemic control in diabetes patients on hemodialysis. SUMMARY: According to the guidelines of the Japanese Society for Dialysis Therapy (JSDT) regarding the treatment of diabetes in hemodialysis patients, the target casual plasma glucose level (predialysis blood glucose level) is less than 180-200 mg/dL, the target glycated albumin value is less than 20.0% (less than 24.0% in patients at risk of hypoglycemia). When glycemic control is poor and the plasma glucose level before dialysis is high, hemodialysis-induced hyperglycemia may occur, in which plasma glucose decreases during hemodialysis and appears to rise after hemodialysis. On the other hand, hemodialysis patients with diabetes tend to develop hypoglycemia due to various factors. In addition, autonomic nervous system disorders may complicate the manifestation of hypoglycemia so that these patients may not exhibit symptoms. Thus, particular caution is necessary to prevent hypoglycemia. Key Messages: The plasma glucose level of hemodialysis patients with diabetes may fluctuate under the influence of many factors, such as the state of kidney function, delay in metabolism and excretion of diabetes medicine, and hemodialysis parameters. In particular, patients with poor glycemic control are susceptible to various influences, leading to a wider fluctuation in plasma glucose, with increased risk of both hyperglycemia and hypoglycemia. Since hypoglycemia may lead to a poorer prognosis and quality of life, it is necessary to control plasma glucose levels with the aim of improving the prognosis while avoiding hypoglycemia.

Renoprotective effects of canagliflozin, a sodium glucose cotransporter 2 inhibitor, in type 2 diabetes patients with chronic kidney disease: A randomized open-label prospective trial.

BACKGROUND: To evaluate the renoprotective effects of canagliflozin, we assessed the albuminuria-lowering effect in Japanese type 2 diabetes patients with chronic kidney disease (CKD). METHODS: In this prospective, open-label, parallel-group study, type 2 diabetes patients with CKD were randomized to receive either oral canagliflozin (100 mg/day) or usual care (control group) for 52 weeks. Endpoints included changes in urinary albumin-to-creatinine ratio (UACR), other urinary biomarkers, laboratory parameters, and adverse events. RESULTS: Both groups included 20 patients in the analysis. Mean changes in UACR was -83 (-266 to -31) mg/gCr and 27 (-11 to 131) mg/gCr, in the canagliflozin and control groups, respectively ( p = 0.004). Urinary liver-type free acid binding protein, N-acetyl-ß-d-glucosaminidase, and ß2-microglobulin levels were also significantly decreased in the canagliflozin group, but not in the control group. Mean change in estimated glomerular filtration rate at the end of the study was 0.7 and -3.4 mL/min/1.73 m2 in the canagliflozin and control group, respectively ( p = 0.024). Canagliflozin treatment led to improvement of glycaemic control and reduction in body weight, blood pressure, and liver transaminase. There were no adverse events associated with canagliflozin. CONCLUSION: Canagliflozin was associated with slower progression of kidney disease and reduction in albuminuria and tubulointerstitial markers in diabetes patients with CKD.

Ferric Citrate Decreases Fibroblast Growth Factor 23 and Improves Erythropoietin Responsiveness in Hemodialysis Patients.

BACKGROUND: Serum phosphate and vitamin D receptor activator regulate fibroblast growth factor 23 (FGF23), and iron may modulate FGF23 metabolism. The aim of the present study was to elucidate the effects of ferric citrate hydrate and lanthanum carbohydrate on serum FGF23 levels in hemodialysis patients. METHODS: This prospective, open-label, multicenter study enrolled 60 patients on hemodialysis treated with lanthanum carbonate. Patients were randomly assigned to 2 groups: those switching from lanthanum carbonate to ferric citrate hydrate (ferric citrate group, n = 30) or those continuing lanthanum carbonate (control group, n = 30). Patients were monitored for 24 weeks. Endpoints included changes in FGF23, phosphate, and the dose of erythropoiesis stimulating agent (ESA), erythropoietin responsiveness index (ERI), and adverse events. RESULTS: FGF-23 levels were significantly lower in the ferric citrate group compared with the levels in the control group (change from baseline -6,160 vs. -1,118 pg/mL; p = 0.026). There were no significant changes in serum calcium, phosphate, and intact parathyroid hormone levels in either group. The ferric citrate group had significantly increased serum iron, ferritin, and transferrin saturation. Hemoglobin levels were significantly elevated, and the dose of ESA was significantly decreased in the ferric citrate group but not in the control group. ERI and the dose of intravenous saccharated ferric oxide were significantly lower in the ferric citrate group compared with those of the control group (p = 0.015 and p = 0.002). CONCLUSION: In patients on hemodialysis, 24-week treatment with ferric citrate hydrate resulted in significant reduction in FGF23 and ERI independently of serum phosphate level.

Glycated Albumin versus Glycated Hemoglobin as a Glycemic Indicator in Diabetic Patients on Peritoneal Dialysis.

Compared with glycated hemoglobin (HbA1c), glycated albumin (GA) is superior in estimating glycemic control in diabetic patients on hemodialysis (HD). However, the better index for assessment of glycemic control in diabetic patients on peritoneal dialysis (PD) and the impact of protein loss on GA are unknown. Twenty diabetic patients on HD were matched by age, sex, and baseline postprandial plasma glucose (PG) levels to 20 PD patients. PG, HbA1c, GA, and serum albumin levels were measured for six months. Protein loss in PD patients was estimated by measuring the protein concentration in the peritoneal dialysate and by 24 h urine collection. Although PG and HbA1c did not differ significantly between the groups, the PD group had significantly lower GA (17.8% versus 20.8%, p < 0.001) and GA/HbA1c ratio (2.95% versus 3.45%, p < 0.0001) than the HD group. Although the PG level correlated significantly with the GA levels in both groups, it was not correlated with the HbA1c levels in both groups. HbA1c level was negatively associated with erythropoiesis-stimulating agent (ESA) dose in both groups, whereas GA was not significantly associated with serum albumin, hemoglobin concentration, ESA dose, and protein loss. Multiple regression analysis identified GA as the only independent factor associated with PG in PD patients. Our results suggested that GA was not significantly associated with protein loss, hemoglobin, serum albumin, and ESA dose. Although GA might underestimate glycemic status, it provided a significantly better measure for estimating glycemic control than HbA1c, even in PD patients.

Comparison of Clinical Trajectories before Initiation of Renal Replacement Therapy between Diabetic Nephropathy and Nephrosclerosis on the KDIGO Guidelines Heat Map.

This study investigated differences between the clinical trajectories of diabetic nephropathy and nephrosclerosis using the Kidney Disease: Improving Global Outcomes (KDIGO) heat map and the clinical characteristics between the two diseases at RRT initiation. This single-center, retrospective study enrolled 100 patients whose estimated glomerular filtration rate (eGFR) was ≥45 mL/min/1.73 m(2) at their first visit and who were initiated on RRT. Fifty consecutive patients were assigned to each of the diabetic nephropathy and nephrosclerosis groups. All data for simultaneously measured eGFR and urinary albumin to creatinine ratio (UACR) were collected from first visit to RRT initiation and were plotted on the KDIGO heat map. Diabetic nephropathy was characterized by higher blood pressure and UACR and lower age, eGFR, and serum albumin levels compared with nephrosclerosis at RRT initiation. The vast majority of patients with diabetic nephropathy and eGFR < 60 mL/min/1.73 m(2) had concomitant macroalbuminuria, whereas for patients with nephrosclerosis, even when eGFR was <45 mL/min/1.73 m(2), many still had normoalbuminuria or microalbuminuria. The rate of decline of eGFR was significantly faster in the diabetic nephropathy group than that in the nephrosclerosis group. The clinical trajectories of diabetic nephropathy and nephrosclerosis differed markedly on the KDIGO heat map.

Randomized Controlled Trial of Darbepoetin α Versus Continuous Erythropoietin Receptor Activator Injected Subcutaneously Once Every Four Weeks in Patients with Chronic Kidney Disease at the Pre-Dialysis Stage.

Continuous erythropoietin receptor activator (CERA) seems to maintain a stable hemoglobin (Hb) level because its half-life is longer than darbepoetin α (DA). Twenty chronic kidney disease (CKD) patients at the pre-dialysis stage who had been administered DA for over 24 weeks were randomly assigned to receive subcutaneous CERA or DA once every four weeks during 48 weeks. In both groups, the rate of achievement of target Hb level changed from 70% to 100% in weeks 0 to 48, with no significant difference between the groups. Compared with week 0, the Hb level was significantly increased from week 24 in the DA group and from week 8 in the CERA group. In addition, the reticulocyte count was significantly increased from week 4 in the CERA group compared with the DA group. There was no significant difference in the levels of estimated glomerular filtration rate and iron status between both groups. Because of the small number of patients in this study, only limited conclusions can be drawn. However, the results suggest that subcutaneous administration of DA or CERA once every four weeks to predialysis patients has similar effects on achievement of target Hb levels.

A Trial of Pitavastatin Versus Rosuvastatin for Dyslipidemia in Chronic Kidney Disease.

AIM: To determine the lipid lowering effectiveness, cost effectiveness, and safety of rosuvastatin compared with pitavastatin in dyslipidemic patients with concurrent renal disorders. METHODS: This single-center, prospective, open-label, randomized, 12-month study evaluated rosuvastatin (2.5 mg) and pitavastatin (1 or 2 mg) in 134 dyslipidemic patients with concurrent chronic kidney disease (CKD; rosuvastatin group, n=68; pitavastatin group, n=66). Lipid parameters [i.e., low density lipoprotein cholesterol (LDL-C), etc.], renal function parameters [i.e., estimated glomerular filtration rate (eGFR), etc.], glycated hemoglobin (HbA1c), and high-sensitivity C-reactive protein (hs-CRP) were measured at enrollment (baseline), month 6, and month 12. RESULTS: The mean daily dose of rosuvastatin and pitavastatin was 2.5 mg and 1.4 mg, respectively. All lipid parameters were significantly more improved in the rosuvastatin group. eGFR improved from baseline in the rosuvastatin group (p ＜ 0.0001) and showed no tendency to worsen in the pitavastatin group (p=0.2232). In multiple regression analysis (n=134), it was significantly associated with a percent change in total cholesterol (ß=0.2296; p=0.0112), smoking (ß=0.1927; p=0.0224), and HbA1c (ß=-0.1606; p=0.0585). Hs-CRP was significantly improved in both groups. An analysis eliminating the influence of antidiabetic medication showed a significant difference between groups in the change of HbA1c at month 6 from baseline (p=0.0016). No subjects in either group had new onset of diabetes mellitus. The cost of statin medication required to reduce LDL-C by 10 mg/dL was significantly lower for 2.5 mg of rosuvastatin (p=0.0116). CONCLUSIONS: Rosuvastatin 2.5 mg had superior lipid lowering and cost effectiveness in dyslipidemic patients with concurrent CKD.(UMIN ID: UMIN000005812).

Urinary ACE2 is associated with urinary L-FABP and albuminuria in patients with chronic kidney disease.

AIM: Angiotensin-converting enzyme 2 (ACE2) is expressed in the kidney and may be a renoprotective enzyme since it converts angiotensin (Ang) II to Ang-(1-7). In addition, ACE2 has been detected in urine from patients with chronic kidney disease (CKD). The aim of this study was to determine the urinary ACE2 levels in patients with various stages of CKD and to identify the factors associated with the presence of ACE2. METHODS: We assessed 152 patients with CKD stage G1-G4. The patients were classified according to the presence or absence of diabetes mellitus (DM) (DM group, n = 72; non-DM group, n = 80) and according to the estimated glomerular filtration rate (CKD stage G1/2 group, n = 40; CKD stage G3 group, n = 74; and CKD stage G4 group, n = 38). Parameters were urinary ACE2, urinary albumin/ creatinine ratio (UACR), urinary liver-type fatty acid binding protein (L-FABP), estimated glomerular filtration rate, and other factors determined to be associated with elevated urinary ACE2. RESULTS: Urinary ACE2 was significantly higher in patients with diabetes (p = 0.01) and in patients with CKD stage G4 compared with stages G1-G3 (p < 0.0001). Multivariable regression analysis revealed that urinary L-FABP and UACR were significantly associated with urinary ACE2 levels, indicating that urinary ACE2 is increased in patients with diabetes and advanced stage CKD. CONCLUSION: ACE2 might continuously protect from both glomerular and tubulointerstitial injury during CKD progression. Taken together, urinary ACE2 might be a marker of kidney renin-angiotensin system activation in such patients.

Oral zinc supplementation reduces the erythropoietin responsiveness index in patients on hemodialysis.

BACKGROUND: In hemodialysis (HD) patients, zinc depletion caused by inadequate intake, malabsorption, and removal by HD treatment leads to erythropoiesis-stimulating agent (ESA) hyporesponsiveness. This study investigated the effects of zinc supplementation in HD patients with zinc deficiency on changes in the erythropoietin responsiveness index (ERI). METHODS: Patients on HD with low serum zinc levels (<65 µg/dL) were randomly assigned to two groups: The polaprezinc group (who received daily polaprezinc, containing 34 mg/day of zinc) (n = 35) and the control group (no supplementation) (n = 35) for 12 months. All the 70 patients had been taking epoetin alpha as treatment for renal anemia. ERI was measured with the following equation: Weekly ESA dose (units)/dry weight (kg)/hemoglobin (g/dL). RESULTS: There were no significant changes in hemoglobin levels within groups or between the control and polaprezinc groups during the study period. Although reticulocyte counts were increased immediately after zinc supplementation, this change was transient. Serum zinc levels were significantly increased and serum copper levels were significantly decreased in the polaprezinc group after three months; this persisted throughout the study period. Although there was no significant change in the serum iron or transferrin saturation levels in the polaprezinc group during the study period, serum ferritin levels significantly decreased following polaprezinc treatment. Further, in the polaprezinc group, ESA dosage and ERI were significantly decreased at 10 months and nine months, respectively, as compared with the baseline value. Multiple stepwise regression analysis revealed that the change in the serum zinc level was an independent predictor of lowered ERI. CONCLUSIONS: Zinc supplementation reduces ERI in patients undergoing HD and may be a novel therapeutic strategy for patients with renal anemia and low serum zinc levels.

Randomized trial of frequent low-efficiency and short hemodialysis/hemofiltration in hemodialysis patients with acute brain injury.

PURPOSE: The aim of the study was to compare effects of frequent low-efficiency and short hemodialysis (FLESHD) and frequent low-efficiency and short hemofiltration (FLESHF) in hemodialysis (HD) patients with acute brain injury (ABI).
 METHODS: We randomly divided 13 HD patients with ABI into FLESHD (n = 6) or FLESHF (n = 7) groups. Conditions for the first to third sessions were as follows. FLESHD: intravenous administration of glycerol 400 ml/session, blood flow rate (QB) 100 ml/min, dialysate flow rate 300 ml/min, and treatment duration 2 h (HD-1). FLESHF: intravenous administration of glycerol 400 ml/session, QB 150 ml/min, substitution flow rate 10 l/session, and treatment duration 4 h (HF-1). After the fourth session, we gradually changed the conditions and stopped glycerol administration (HD-2 and HF-2).
 RESULTS: There were no significant differences in survival rate, consciousness level, or adverse effects during hospitalization in either group. In mixed model analysis, the level of HCO3- post FLESHF was significantly (p<0.0001) increased compared with the level post FLESHD. However, no significant differences were seen in the levels of osmolality, in blood pressure before and after either dialysis method, or in the level of HCO3- pre dialysis. The variation in the relative ratio of BUN before FLESHF was significantly higher (p<0.05) than the relative ratio before FLESHD in the sixth session. In the FLESHD groups, serum sodium was higher and serum potassium was lower than in the FLESHF groups.
 CONCLUSIONS: FLESHD with glycerol under these conditions may be a better therapeutic option for managing patients with ABI, although the short-term survival rate is similar.

Changes to prothrombin international normalized ratio in patients receiving hemodialysis.

BACKGROUND: The clinical utility of factor Xa inhibitors (xabans) has been demonstrated, but these inhibitors are contraindicated in patients undergoing dialysis therapy. Therefore, warfarin remains the mainstay for oral anticoagulation treatment of patients receiving hemodialysis (HD). OBJECTIVE: This study investigated the changes in international normalized ratio (INR) during HD treatment of patients receiving warfarin. METHODS: Changes in INR and serum albumin levels were determined before (pre-) and after (post-) HD in six consecutive HD sessions. 30 patients (23 males, 7 females; mean age, 72 ± 8 years) were enrolled, and a total of 180 measurements were performed. RESULTS: Post-HD INR levels were significantly decreased compared with pre-HD levels (2.07 ± 0.52 to 1.99 ± 0.50, p < 0.0001), while serum albumin levels were significantly increased post-HD compared with pre-HD (p < 0.0001). There was a significant negative correlation between changes in INR and serum albumin during HD (r = -0.383, p = 0.0002). CONCLUSION: INR is significantly decreased post-HD compared with pre-HD. Although the therapeutic range of INR differs according to the disease, close monitoring of the degree of anticoagulation in patients receiving warfarin is recommended to minimize the risk of thrombosis and hemorrhagic complications.

The dipeptidyl peptidase-4 inhibitor alogliptin improves glycemic control in type 2 diabetic patients undergoing hemodialysis.

OBJECTIVES: The potent and selective dipeptidyl peptidase-4 (DPP-4) inhibitor alogliptin improves glycemic control in patients with type 2 diabetes through incretin hormone-mediated increases in both α- and ß-cell responsiveness to glucose. In this study, the efficacy and safety of alogliptin in type 2 diabetic patients undergoing hemodialysis (HD) were evaluated. METHODS: A prospective, open-label study of 30 patients (male/female: 24/6; mean age: 69.7 ± 1.7 years) with type 2 diabetes who were undergoing HD without insulin injection therapy was conducted. Patients were administered 6.25 mg/day alogliptin and efficacy and safety were determined by monitoring clinical and laboratory parameters during the 48-week study period. RESULTS: After 48 weeks, alogliptin had decreased postprandial plasma glucose levels from 212 ± 8 mg/dL baseline to 156 ± 7 mg/dL, hemoglobin A1c levels from 7.1 ± 0.2% baseline to 6.3 ± 0.2% and glycated albumin (GA) levels from 25.6 ± 0.6% baseline to 20.7 ± 0.4% (all p < 0.0001). Alogliptin efficacy did not differ according to median age or body mass index, but the GA reduction was significantly greater in the antidiabetic agents-naïve group. The magnitude of GA reduction was baseline GA-dependent, being greater at higher baseline GA levels. No serious adverse effects, such as hypoglycemia or liver impairment, were observed in any patient. CONCLUSION: Alogliptin as monotherapy or in combination with other oral antidiabetic agents improved glycemic control and was generally well tolerated in patients with HD over a 48-week period.

L/N-type calcium channel blocker cilnidipine reduces plasma aldosterone, albuminuria, and urinary liver-type fatty acid binding protein in patients with chronic kidney disease.

Cilnidipine inhibits both L- and N-type calcium channels and has been shown to dilate efferent arterioles as effectively as afferent arterioles. We conducted an open-label, randomized trial to compare the effects of cilnidipine against those of amlodipine on blood pressure (BP), albuminuria, and plasma aldosterone concentration in hypertensive patients with mild- to moderate-stage chronic kidney disease. Patients with BP ≥130/80 mmHg, an estimated glomerular filtration rate of 90-30 ml/min/1.73 m(2), and albuminuria ≥30 mg/g, despite treatment with the maximum recommended dose of angiotensin II receptor blockers, were randomly assigned to two groups. Patients received either 10 mg/day cilnidipine (increased to 20 mg/day; n = 35) or 2.5 mg/day amlodipine (increased to 5 mg/day; n = 35). After 48 weeks of treatment, a significant and comparable reduction in systolic and diastolic BP was observed in both groups. The percent reduction in the urinary albumin to creatinine ratio and liver-type fatty acid binding protein (L-FABP) in the cilnidipine group was significantly greater than in the amlodipine group. Although plasma renin activity did not differ between the two groups, the plasma aldosterone level was significantly decreased in the cilnidipine group. Cilnidipine therefore appears to reduce albuminuria, urinary L-FABP, and plasma aldosterone levels more than amlodipine, and these effects are independent of BP reduction.

Efficacy analysis of the renoprotective effects of aliskiren in hypertensive patients with chronic kidney disease.

We aimed to assess the effect of aliskiren treatment on blood pressure, albuminuria, and kidney function in patients with chronic kidney disease (CKD). We conducted a prospective, open-label study of 67 patients with CKD who were already being treated with other antihypertensives. Inclusion criteria were blood pressure (BP) ≥130/80 mmHg, albuminuria ≥30 mg/g, and estimated glomerular filtration rate (eGFR) >30 ml/min/1.73 m(2). Subjects were treated with 150 mg/day aliskiren, which was increased to 300 mg/day for the 24-week study period. Aliskiren effectively reduced both systolic and diastolic BP, plasma renin activity (PRA), serum aldosterone concentration, albuminuria, urinary N-acetyl-glucosaminidase, and urinary ß2-microglobulin levels. Although eGFR was significantly decreased after 4 weeks of aliskiren treatment, it recovered to a pretreatment level within 12 weeks of treatment initiation. There were no significant differences in the percent reduction of albuminuria or changes of eGFR levels when the subjects were divided into three groups on the basis of baseline eGFR (stages 1/2, 3, and 4) and the presence or absence of diabetes mellitus (DM group and non-DM group). Furthermore, in patients not treated with renin-angiotensin-aldosterone-system (RAAS) inhibitors, including angiotensin receptor blockers or angiotensin-converting enzyme inhibitors at baseline, changes in eGFR were significantly increased compared with those already treated with RAAS inhibitors at baseline. Aliskiren administration reduced BP, PRA, serum aldosterone levels, and albuminuria, while maintaining eGFR, regardless of the presence or absence of DM or the degree of eGFR.

Aliskiren reduces home blood pressure and albuminuria in patients with hypertensive nephrosclerosis.

BACKGROUND: The aim of this study was to investigate the antialbuminuric and antihypertensive effects of aliskiren by monitoring home blood pressure (BP) in comparison with the effects of the angiotensin receptor blocker (ARB) valsartan in patients with hypertensive nephrosclerosis and albuminuria. METHODS: We conducted an open-label, randomized trial to compare the effects of aliskiren with those of valsartan. Patients with BP <150/90 mmHg, an estimated glomerular filtration rate of 90-30 mL/min/1.73 m(2), and albuminuria >30 mg/g, despite treatment with a 160 mg daily dose of valsartan, were randomly assigned to the following two groups: the aliskiren group, who switched from 160 mg/day valsartan to 150 mg/day aliskiren, which was later increased to 300 mg/day (n = 20); and the valsartan group, who continued with 160 mg/day valsartan (n = 20). RESULTS: After 12 weeks of treatment, although there was no significant difference in clinic BP between groups, a significant reduction in morning and evening systolic BP was observed in the aliskiren group. The decrease in albuminuria in the aliskiren group was significantly better than that in the valsartan group, and a significant correlation was noted between the change in morning systolic BP and the change in albuminuria in the aliskiren group (r = 0.564, P = 0.0084). CONCLUSION: We showed that aliskiren treatment leads to a greater reduction in albuminuria and home systolic BP values than valsartan in patients with nephrosclerosis. We propose that aliskiren therapy should be considered as a therapeutic modality to complement ARBs in hypertensive patients with nephrosclerosis.

International normalized ratio decreases after hemodialysis treatment in patients treated with warfarin.

This study determined the changes in international normalized ratio (INR) that occur during hemodialysis (HD) treatment of patients receiving warfarin. Twenty patients were enrolled in the study (15 males, 5 females; mean age, 71 ± 7 years). We investigated changes in INR and R-isomer and S-isomer of warfarin concentrations before (pre-) and after (post-) HD. Post-HD INR levels were significantly decreased compared with pre-HD levels (P < 0.01), whereas plasma concentrations of both R-isomer and S-isomer of warfarin were significantly increased post-HD compared with pre-HD (P < 0.01). There was a negative correlation between INR changes and changes in warfarin concentration or changes in serum albumin levels during HD. Multivariate analysis revealed that change of serum albumin was the only factor that was significantly related to the change of INR (P = 0.0051, R = 0.501). We suggest that the free fraction of plasma warfarin decreased with increases in serum albumin levels because the protein-binding rate of warfarin is very high and free fractions were bound to albumin during HD sessions. The INR depletion was therefore dependent on circulating plasma volumes and serum albumin concentrations. Caution should be taken for those HD patients who have absolute indications of anticoagulation therapy with warfarin.