[Investigation of Improvement Items Based on Students' Perspectives on Practical Training for Raising Pharmaceutical Problem-solving Capability at Pharmacies].

Experience-based clinical training has been introduced in long-term practical training at pharmacies in Japan. Satisfaction and motivation of pharmacy students differs among pharmacies; however, the underlying causes of the differences are unclear. The purpose of this study was to investigate items for improvement for long-term practical training for raising pharmaceutical problem-solving capability at pharmacies based on students' perspectives. We performed a questionnaire survey to evaluate student satisfaction in clinical education and learning environments. The results were analyzed using customer satisfaction (CS) analysis. After long-term practical training at pharmacies, questionnaires were distributed to 126 pharmacy students at Fukuyama University between November 2021 and March 2022. Ninety-eight students responded. "The practice hours per prescription or pharmacotherapy screening and intervention (improvement factor: 14.954)", "the discussion hours for optimization of prescribing and rational medication use, or patient education with pharmacist (9.493)", and "the self-learning place (3.490)" were identified as items requiring improvement. Our findings suggest that the university should work together with pharmacies to improve the learning strategy and environments to increase direct and continuous interaction with pharmacists at pharmacies. Such interventions may result in improvement of students' satisfaction and a wide variety of practical pharmacy skills.

Population Pharmacodynamic Analysis of Uric Acid-Lowering Effects of Febuxostat Based on Electronic Medical Records in Two Hospitals.

The aim of this study was to develop a population pharmacodynamic (PPD) model to describe uric acid (UA)-lowering effects in patients treated with febuxostat based on electronic medical records in 2 independent hospitals (university and city hospitals). Interhospital differences in the PPD model were also evaluated. We conducted the following 2 approaches to build the PPD models. A PPD model was developed separately using individual hospital data, and structural models and covariates between the two hospitals were compared (approach A). Another PPD model was developed using all available data from both hospitals, and differences between the 2 hospitals were evaluated by performing a covariate analysis on all PPD parameters (approach B). PPD analyses were performed by NONMEM using data from 358 patients. In both approaches, one indirect response model was established. In approach A, 2 diuretics (loops and thiazides) and renal function tests (Scr or BUN) were selected as covariates for the UA baseline level (serum UA levels just before the febuxostat treatment), whereas 2 diuretics and BUN were selected in approach B. A covariate analysis indicated that loops and thiazides increased UA baseline levels by 7%-14% and 6%-11%, respectively. In approach B, "hospital" was identified as a significant covariate for the UA baseline level; the baseline level was 7% higher in the city hospital. A PPD analysis may provide a precise description of the time course of the UA-lowering effects of febuxostat and quantitatively detect an interhospital difference in the UA baseline level.

Successful Plasma Exchange for Acute Pancreatitis Complicated With Hypertriglyceridemia: A Case Report.

A 33-year-old male with acute pancreatitis induced by hypertriglyceridemia had problems during treatment with plasma exchange. The hypercoagulable state was prevented by introducing innovative methods for cleaning and warming of the circuit and dialyzer. This enabled successful therapy, and the patient fully recovered from life-threatening acute pancreatitis.

Long-term survival benefits of combined hemodialysis and peritoneal dialysis.

Recently, it was reported that concomitant hemodialysis (HD) in peritoneal dialysis (PD) patients facilitated continuation of PD treatment and mitigated the deterioration of peritoneal function in patients with uremic symptoms and excess body fluid associated with loss of residual renal function. To determine the effect of combined HD and PD on patient and technique survival, we undertook a retrospective cohort study of patients who underwent PD at Saitama Medical University Hospital between 1995 and 2010. We compared patients who started PD during 1995 2002 with those who started during 2003- 2010. Because our center started a new strategy of supplementing PD with once-weekly HD in 2000, the effects of combination therapy could be determined by comparing the data obtained during the two periods. The 440 patients (274 men, 166 women) who started PD during the study period had a mean age of 60.2 +/- 73 years. The mean age was significantly higher in the 2003 - 2010 group than in the 1995 - 2002 group. Using a Kaplan-Meier plot, we observed a significant difference in technique survival (p < 0.001). The technique survival rate at 3 and 5 years was, respectively, 89% and 74% in the 2003-2010 group and 68% and 35% in the 1995 - 2002 group (p < 0.05). Cumulative patient survival at 3 and 5 years was, respectively, 87% and 72% in the 2003 - 2010 group and 69% and 51% in the 1995 - 2003 group (p < 0.01). Patient and technique survival were significantly improved in PD patients receiving the combination of HD and PD.

Blood glucose levels in peritoneal dialysis are better reflected by HbA1c than by glycated albumin.

A recent study indicated that, compared with glycated hemoglobin (HbA1c), glycated albumin (GA) provides a more accurate assessment of glycemic control in diabetic patients on hemodialysis. However, the suitability of GA for this purpose in peritoneal dialysis (PD) patients is questionable. We measured blood glucose, GA, HbA1c, serum albumin, protein losses in urine and dialysate, protein catabolic rate, hemoglobin, and dose of erythropoiesis-stimulating agents in 71 PD patients [20 with diabetes (DM), 51 without DM]. In both DM and non-DM patients, blood glucose levels correlated significantly with HbA1c (r = 0.47, p < 0.001), but not with GA (r = 0.18, p = 0.19). In patients with high serum albumin (> 3.2 g/dL), blood glucose levels correlated significantly with GA (r = 0.32, p = 0.047). Further, low protein losses in urine and dialysate (< 5.9 g daily) also significantly correlated with GA (r = 0.37, p = 0.041). In PD patients, HbA1c is better than GA as an indicator of blood glucose levels. Glycated albumin can be used as an indicator of glycemic control in PD patients with normal serum albumin and low protein losses in urine and dialysate.

Home hemodialysis and conventional in-center hemodialysis in Japan: a comparison of health-related quality of life.

Health-related quality of life (HRQOL) is an important measure of how disease affects patients' daily life. Conventional in-center hemodialysis (CHD) patients have been found to have decreased HRQOL. Recent study reported that at-home hemodialysis (HHD) improved the long-term HRQOL compared with CHD; however, there have been no data from Japanese HHD patients. A sample of 80 Japanese hemodialysis patients (46 HHD and 34 CHD) was matched for age, sex, and cause of end-stage renal disease. Patient HRQOL was measured using two health surveys: Medical Outcomes Study 36 Item Short Form Health Survey-Version 2 and Kidney Disease Quality of Life-Short Form. HHD patients reported better scores on seven out of eight domains (all domains except general heath) of the Medical Outcomes Study 36 Item Short Form Health Survey-Version 2, as well as better Kidney Disease Quality of Life-Short Form scores with respect to symptoms and problems, effect of kidney disease, and work status. No significant differences were observed for burden of kidney disease, cognitive function, quality of social interaction, sexual function, or sleep. More than 65% of HHD patients stated that they were not bothered at all by limitations on food and water intake. Japanese HHD patients demonstrate significantly higher HRQOL scores. However, while their HRQOL and employment rate were high and they were able to enjoy fewer dietary restrictions, kidney disease remained a great burden.

Calcium channel blockers suppress daily variations of blood pressure in hypertensive patients with end-stage renal diseases.

Hypertension is a well-known cardiovascular risk. Patients with end-stage renal diseases frequently suffer hypertension. Furthermore, daily variations of blood pressure are relatively large in patients treated with hemodialysis, partly due to ultrafiltration. Twenty hypertensive patients with end-stage renal diseases whose blood pressure was controlled by a single antihypertensive agent, either angiotensin receptor antagonist (ARB) or calcium channel blocker (CCB), were enrolled into the study. Home blood pressure measurements were also performed. Average systolic and diastolic blood pressures were similar between two agents. However, variations of systolic blood pressure during ARB treatment were greater than those of CCB, and maximal differences in daily systolic blood pressure during treatment with ARB (19±7 mmHg) were greater than those with CCB (14±6 mmHg, p<0.01). Systolic blood pressure measured after hemodialysis under ARB therapy (110±6 mmHg) was lower than that of CCB (118±6 mmHg, p<0.05). Daily variations of diastolic blood pressure were similar between ARB and CCB periods. Our results indicate that variations of systolic blood pressure during ARB treatment are larger than CCB, and suggest that CCB is useful to obtain the better quality of blood pressure control, improving blood pressure stability by preventing substantial drops in blood pressure in hypertensive patients with end-stage renal diseases.

Association between DNA methylation in the miR-328 5'-flanking region and inter-individual differences in miR-328 and BCRP expression in human placenta.

MicroRNA (miRNA) are non-coding small RNA that regulate gene expression. MiR-328 is reported to influence breast cancer resistance protein (BCRP) expression in cancer cells. As a large inter-individual difference in BCRP levels is observed in various human tissues, the contribution of miR-328 to these differences is of interest. We hypothesized that DNA methylation in the miR-328 promoter region is responsible for the difference in miR-328 levels, leading to inter-individual variability in BCRP levels in human placenta. The association between placental miR-328 and BCRP levels was analyzed, and then DNA methylation in the miR-328 5'-flanking region and regulatory mechanisms causing inter-individual differences in miR-328 and BCRP levels were examined. MiR-328 expression was significantly correlated with BCRP mRNA (Rs = -0.560, P < 0.01) and protein (Rs = -0.730, P < 0.01) levels. It was also up-regulated by the demethylating agent 5-aza-2'-deoxycytidine in BCRP-expressing cells. Luciferase assays with differentially methylated reporter constructs indicated that methylation in the miR-328 5'-flanking region including a predicted CpG island remarkably decreased transcriptional activity compared to that in unmethylated constructs. We selected CCAAT/enhancer binding protein α (C/EBPα), located within the predicted CpG island, by in silico analysis. To elucidate the role of C/EBPα in miR-328 expression, a chromatin immunoprecipitation assay, promoter deletion analysis, and electrophoretic mobility shift assay (EMSA) were performed. C/EBPα-binding site-truncated constructs showed significantly decreased promoter activity, and EMSA indicated that the C/EBPα-binding sites were located in the CpG island. Finally, the methylation patterns of several CpG dinucleotides proximal to two C/EBPα-binding sites in the miR-328 5'-flanking region were correlated negatively with miR-328 levels, and positively with BCRP levels in human placental samples. These results suggest that methylation patterns in the miR-328 5'-flanking region are involved in the inter-individual difference in BCRP levels in human placenta.

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.

Statin improves flow-mediated vasodilation in chronic kidney diseases.

Background. Numbers of drugs are required to manage patients with chronic kidney disease (CKD). Drug adherence is relatively poor in this population. Methods. In 36 CKD patients with hypertension and dyslipidemia, who were prescribing amlodipine 5 mg and atorvastatin 10 mg daily, the influences of exchanging to a combination drug containing equivalent doses of amlodipine and atorvastatin were observed for 6 months. Results. At the baseline, flow-mediated dilation (FMD) was reduced (2.4 ± 0.3%), and proteinuria was significantly contributed to decrements of FMD (R (2) = 0.38, F = 3.7, df (6,29), and P < 0.01). Six months later from exchanging to combination drug, total cholesterol (TC, 197 ± 5 to 183 ± 3 mg/dL, P < 0.01) and triglycerides (142 ± 14 to 129 ± 10 mg/dL, P < 0.05) were decreased, but high density lipoprotein cholesterol (53 ± 3 to 56 ± 3 mg/dL, P < 0.05) was increased. FMD was slightly albeit significantly improved to 2.7 ± 0.3% (P < 0.05). No serious adverse effects were seen by the combination drug. Subanalysis for the patients with considerable reductions of TC demonstrated that the combination drug decreased proteinuria and high sensitive CRP (P < 0.05 for both). Conclusion. Our data indicate that proteinuria constitutes a determinant of a reduced FMD. The present results implicate that combination drug is useful to improve adherence and suggest that atorvastatin refines endothelium function as well as lipid profiles in CKD patients.

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.

Dihydropyrimidine dehydrogenase (DPD) expression is negatively regulated by certain microRNAs in human lung tissues.

Dihydropyrimidine dehydrogenase (DPD) is important to the antitumor effect of 5-fluorouracil (5-FU). DPD gene (DPYD) expression in tumors is correlated with sensitivity to 5-FU. Because the 5-FU accumulated in cancer cells is also rapidly converted into inactivated metabolites through catabolic pathways mediated by DPD, high DPD activity in cancer cells is an important determinant of the response to 5-FU. DPD activity is highly variable and reduced activity causes a high risk of 5-FU toxicity. Genetic variation in DPYD has been proposed as the main factor responsible for the variation in DPD activity. However, only a small proportion of the activity of DPD can be explained by DPYD mutations. In this study, we found that DPYD is a target of the following microRNAs (miRNA): miR-27a, miR-27b, miR-134, and miR-582-5p. In luciferase assays with HepG2 cells, the overexpression of these miRNAs was associated with significantly decreased reporter activity in a plasmid containing the 3'-UTR of DYPD mRNA. The level of DPD protein in MIAPaca-2 cells was also significantly decreased by the overexpression of these four miRNAs. The results suggest that miR-27a, miR-27b, miR-134, and miR-582-5p post-transcriptionally regulate DPD protein expression. The levels of miRNAs in normal lung tissue and lung tumors were compared; miR-27b and miR-134 levels were significantly lower in the tumors than normal tissue (3.64 ± 4.02 versus 9.75 ± 6.58 and 0.64 ± 0.75 versus 1.48 ± 1.39). DPD protein levels were significantly higher in the tumors. Thus, the decreased expression of miR-27b would be responsible for the high levels of DPD protein. This study is the first to show that miRNAs regulate the DPD protein, and provides new insight into 5-FU-based chemotherapy.

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.

Clinical presentation in patients more than 80 years of age at the start of peritoneal dialysis.

The age of new dialysis patients is rapidly increasing. In the present study, we examined clinical presentation in new peritoneal dialysis (PD) patients 80 years of age or older at our hospital. Data were collected from the records of patients newly starting continuous ambulatory PD (CAPD) therapy between January 2005 and July 2010. During that period, 11 patients 80 years of age or older (average age: 83.1 +/- 3.8 years) were introduced to PD therapy. The reason for dialysis was hypertensive nephrosclerosis in 8 patients, and chronic glomerulonephritis, chronic tubulointerstitial nephritis, and an unknown primary disease in 1 patient each; there were no cases of diabetic nephropathy. At dialysis start, average serum creatinine was 6.1 +/- 1.4 mg/dL, arterial wall calcification was found by computed tomography or chest radiography in 10 of 11 patients (90.9%), and aortic or mitral valve calcification, or both, was found by echocardiography in 3 patients (27.3%). By the end of January 2011, 8 patients had died. Average survival after the start of PD was 31.9 +/- 22.3 months. Hypertensive nephrosclerosis, a cause less often seen in younger patients, was the most common primary disease among our elderly dialysis patients. As we previously reported, vascular and valvular calcification are important factors for determining prognosis; however, no significant relationships were observed in the present study, probably because almost all the patients had such calcifications.

Removal of the peritoneal dialysis catheter because of gastrointestinal disease in patients on continuous ambulatory peritoneal dialysis: a single-center case series.

We previously reported that peritoneal dialysis (PD)-associated peritonitis is a major cause of PD catheter removal. Another major cause is disease of the gastrointestinal tract, including neoplasm and perforation. In the present study, we reviewed the records of patients who underwent catheter removal at our hospital for reasons other than peritoneal infection--and for gastrointestinal disease in particular. Data were collected from the records of patients who received continuous ambulatory PD (CAPD) therapy between 2004 and 2010 at the Department of Nephrology, Saitama Medical University. Mean duration of CAPD was 6.2 +/- 4.7 years, and mean age at onset was 64.5 +/- 9.6 years. During the investigation period, catheters were removed from 13 patients (4 men, 9 women) because of gastrointestinal disease: gastric cancer in 3 cases, colon cancer in 3 cases, perforation of the lower gastrointestinal tract in 3 cases, and other reasons in 4 cases. Examination of pathology specimens obtained from 6 patients-including 1 in whom contrast-enhanced computed tomography indicated the presence of encapsulating peritoneal sclerosis (EPS)-revealed mild fibrosis in the subserous layer. No patient died of infection after a surgical procedure. Moreover, throughout the observation period, no patient developed new EPS or postoperative ileus. The present study suggests that CAPD itself seems to be free of untoward effects during the postoperative course in these patients.

[Genetic polymorphisms of SLCO1B1 for drug pharmacokinetics and its clinical implications].

Various drug transporters are selectively expressed in single or multiple tissues, such as the intestine, liver and kidney, where these transporters play various roles in drug absorption, distribution and excretion. Genetic polymorphisms in drug transporters as well as drug-metabolizing enzymes are associated with interindividual differences in drug disposition, efficacy and toxicity. Organic anion transporting polypeptide 1B1 (OATP1B1, gene SLCO1B1) is expressed on the basolateral membrane of hepatocytes and can facilitate hepatic uptake of certain clinically relevant drugs such as statins except for fluvastatin, angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, antidiabetic drug (repaglinide) and anticancer drugs (SN-38 and methotrexate). Some single nucleotide polymorphisms or haplotypes of the SLCO1B1 gene have been identified and demonstrated to have functional significance for transporter activity. For examples, the SLCO1B1*15 haplotype (or 521T>C genotype) results in decreased uptake activity of SN-38 from systemic circulation, leading to increased plasma concentration of SN-38 and an enhanced risk of neutropenia. This review focuses on the impact of genetic polymorphisms of the SLCO1B1 gene on transport activity, and implications for the clinical efficacy and toxicity of clinically useful drugs.

Amlodipine and loop diuretics as the second anti-hypertensive medication for the treatment of hypertension with chronic kidney diseases.

Renoprotective effects of renin-angiotensin system inhibitors are well known. However, hypertension with chronic kidney diseases (CKDs) is usually hard to manage with a single agent, and requires the addition of either a calcium antagonist or diuretics to achieve the goal of blood pressure (BP) lowering. Retrospective study was performed among the patients who regularly visited our office, and whose BP had not reached the goal of BP despite of treatment with an angiotensin receptor blocker. Clinical parameters were observed for 6 months. Comparisons of home BP and proteinuria were made between 16 patients prescribed additional calcium antagonists and 15 patients with diuretics. Patient background including age, sex BP, augmentation index, and renal function were similar between the two groups. Both calcium antagonists and diuretics considerably decreased BP. An addition of either agent resulted in similar control of home BP. While both agents reduced augmentation index (AI), calcium antagonist exerted greater improvements in AI (-7 ± 5 vs. -4 ± 3%, p < 0.01). Although urinary protein excretion in both groups was decreased, the degree of these decreases was greater among the patients treated with a calcium antagonist (-28 ± 15 vs. -11 ± 15%, p < 0.01). During observation periods, eGFR in both groups did not show any significant changes from the base line. Under the inhibition of a renin-angiotensin system, calcium antagonists elicited a greater decrease in urinary protein excretion than diuretics when BP similarly controlled. Calcium antagonists also improved AI more strongly than diuretics. Calcium antagonists appear suited for adding on renin angiotensin system inhibitors to treat hypertension with CKDs.