Tokumi Ishii

Carvedilol protects tubular epithelial cells from ischemia–reperfusion injury by inhibiting oxidative stress

Objectives:  Renal ischemia–reperfusion injury (IRI), leading to acute kidney injury, is a frequent complication with renal transplantation and it is associated with graft function. Its pathogenesis involves ischemia, vascular congestion and reactive oxygen metabolites. Carvedilol is an antihypertensive drug with potent anti‐oxidant properties. In this study we investigated the protective effects of carvedilol in a rat renal IRI model.

Efficacy of Carvedilol for Ischemia/Reperfusion-Induced Oxidative Renal Injury in Rats

In renal transplantation, ischemia/reperfusion (I/R) injury is related to production of reactive oxygen species. In addition to its antihypertensive action due to nonselective beta-adrenergic blocking activity, carvedilol has potent antioxidant activity. This study was designed to investigate the effects of carvedilol on I/R injury in rats. On postoperative days 2 and 4, serum creatinine levels were higher among the control and the metoprolol treatment groups compared with the carvedilol treatment group (P < .005). However, there were no significant differences on postoperative day 7. In conclusion, increased antioxidant modulation by carvedilol attenuated renal I/R injury.

Efficacy of Ramelteon in Patients with Insomnia and Nocturia.

Objectives: To study the efficacy of ramelteon for patients with insomnia and nocturia.

Survey on lower urinary tract symptoms and sleep disorders in patients treated at urology departments

Objectives This study examined the association between sleep disorders and lower urinary tract symptoms in patients who had visited urology departments. Methods This was an independent cross-sectional, observational study. Outpatients who had visited the urology departments at the Kinki University School of Medicine or the Sakai Hospital, Kinki University School of Medicine, between August 2011 and January 2012 were assessed using the Athens Insomnia Scale and the International Prostate Symptom Score. Results In total, 1174 patients (mean age, 65.7 ± 13.7 years), with 895 men (67.1 ± 13.2 years old) and 279 women (61.4 ± 14.6 years old), were included in the study. Approximately half of these patients were suspected of having a sleep disorder. With regard to the International Prostate Symptom Score subscores, a significant increase in the risk for suspected sleep disorders was observed among patients with a post-micturition symptom (the feeling of incomplete emptying) subscore of ≥1 (a 2.3-fold increase), a storage symptom (daytime frequency + urgency + nocturia) subscore of ≥5 (a 2.7-fold increase), a voiding symptom (intermittency + slow stream + hesitancy) subscore of ≥2 (a 2.6-fold increase), and a nocturia subscore of ≥2 (a 1.9-fold increase). Conclusion The results demonstrated that the risk factors for sleep disorders could also include voiding, post-micturition, and storage symptoms, in addition to nocturia.

Efficacy and safety of treatment with low-dose Fluvastatin in hypercholesterolemic renal transplant recipients

HYPERCHOLESTEROLEMIA is one of the major risk factors for long-term patient survival of renal transplant recipients maintained with cyclosporin (CYA). When combined with CYA, HMG-CoA reductase inhibitors (HMG-CoARIs, statins) are known to induce rhabdomyolysis through the elevation of plasma statin concentration, and they also affect CYA trough level. The purpose of this study was to investigate the efficacy and safety of antihypercholesterolemic agent fluvastatin (FLU) at a low dose in recipients treated with CYA.

Therapeutic efficacy and anti-inflammatory effect of ramelteon in patients with insomnia associated with lower urinary tract symptoms

Objectives This study was conducted to examine the therapeutic efficacy and anti-inflammatory effect of ramelteon in elderly patients with insomnia associated with lower urinary tract symptoms (LUTS), who visited our urology department. Methods The study included 115 patients (102 men, 13 women) who scored ≥4 on the Athens Insomnia Scale and who wished to receive treatment. The assessment scales for therapeutic efficacy included the International Prostate Symptom Score (IPSS) for LUTS and the Insomnia Severity Index (ISI) for sleep disorders. The high-sensitivity C-reactive protein (hs-CRP) test was used to an objective assessment. The patients were treated with ramelteon (8 mg/day) for an average of 10 weeks and were then reexamined using the questionnaires and hs-CRP test to evaluate therapeutic efficacy. Results IPSS total scores declined significantly from 11.39 ± 8.78 to 9.4 ± 7.72. ISI total scores improved significantly from 11.6 ± 5.2 to 9.2 ± 5.3 (P < 0.0001). The levels of hs-CRP decreased significantly from 0.082 (standard deviation [SD] upper limit, 0.222; SD lower limit, −0.059) to 0.06 (SD upper limit, 0.152; SD lower limit, −0.032). The ISI scores ≥ 10 (n = 51) showed a weak correlation with the hs-CRP levels. Conclusion Ramelteon had a systemic anti-inflammatory effect and improved sleep disorders and LUTS, suggesting that it may be a useful treatment for patients with LUTS-associated insomnia.

Long-Term Renoprotective Effect of Candesartan in Renal Transplant Patients

BACKGROUND The renoprotective effects of angiotensin II type 1 receptor blockers (ARBs) have been demonstrated in a number of clinical studies, but there are few evaluations of long-term ARB treatment. We measured blood pressure, urine protein, and estimated glomerular filtration rate (eGFR) among patients under long-term (up to 9 years) treatment with candesartan cilexetil to evaluate its safety and effectiveness to protect renal graft function. METHODS This study of 41 patients (31 male and 10 female) who presented with proteinuria and hypertension (blood pressure >140/90 mm Hg) after receiving a renal graft. Their serum creatinine level at baseline was 1.51 ± 0.53 mg/dL. Cyclosporine or tacrolimus were concomitantly prescribed for 18 (43.9%) and 22 (53.7%) subjects, respectively. The ARB treatment period was ≥12 months (up to 9 years, mean 4.8 years). Combination with other antihypertensive drugs (calcium antagonists) was necessary in 14/41 subjects (34.1%). RESULTS Significant declines in blood pressure were observed during the treatment period; blood pressure reduction target (blood pressure <130/80 mm Hg) was met in 56.1% for systolic and 68.3% for diastolic pressure. No significant increase in serum creatinine level or eGFR was observed. Urinary protein was reduced to negative or marginal in 63.4% of the subjects, demonstrating a significant decrease. CONCLUSIONS Candesartan cilexetil was considered to be safe even for long-term treatment in renal transplant patients, and effective to protect renal graft function.

Clinicopathological Study on End-Stage Reflux Nephropathy in Renal-Transplanted Children

Five children with end-stage reflux nephropathy underwent kidney transplantation at our clinic. Reflux nephropathy was studied clinically and histologically. All children had proteinuria before starting hemodialysis, and hypertension was present in 2 cases. Three children underwent antireflux operations prior to transplantation. The original kidneys exhibiting reflux were removed during renal transplantation. All original kidneys exhibited atrophy and scarring. Focal and segmental glomerulosclerosis was found in 4 cases. PAS deposition in the interstitium, suggestive of Tamm-Horsfall glycoprotein, was found in all cases. No recurrent signs of focal and segmental glomerulosclerosis have been found in the children who have been followed up from 1 to 6 years after transplantation.

Examination of the Effect of Changing to Azilsartan From Candesartan in Renal Transplant Patients

BACKGROUND Azilsartan, an angiotensin receptor blocker (ARB), was administered to renal transplant recipients to investigate the safety and antihypertensive effect in addition to its ARB-characteristic organ-protective effect. METHODS The subjects were 20 patients (18 males, 2 females; baseline serum creatinine 2.39 ± 1.33 mg/dL) responding poorly to candesartan, who suffered albuminuria (>0.3 g/g creatinine) and hypertension (>140/90 mm Hg) following renal transplantation. Three months after candesartan was switched to azilsartan 20 mg/d, blood pressure, creatinine-corrected urinary albumin excretion, urinary L-type acid binding protein, urinary 8-hydroxydeoxyguano-sine, serum creatinine, and estimated glomerular filtration rate were evaluated. Thirteen patients received cyclosporine (65.0%) and 7 received tacrolimus (35.0%). Another hypertensive (calcium antagonist) agent was combined in 7 (35.0%). RESULTS Systolic blood pressure significantly decreased from 139.5 mm Hg (baseline) from 128.7 mm Hg (at 3 months), whereas no significant changes were observed for diastolic blood pressure. The percentage of patients achieving the target level of antihypertensive effect (blood pressure < 130/80 mm Hg) significantly improved from 30.0% (baseline) to 70.0% (at 3 months). No significant changes were observed in renal graft function, oxidative stress marker level, or biochemical examination findings. CONCLUSION Sufficient antihypertensive effect was demonstrated soon after switching to azilsartan. However, no significant change was found in renal damage markers. Long-term study must be conducted to confirm the protective effect azilsartan on the transplanted kidney, as found with candesartan. The safety of azilsartan was demonstrated. If the transplanted kidney protection is demonstrated, this drug is expected to contribute to the improved long-term prognosis of renal transplant recipients.

Editorial Comment from Dr Ishii to Recent topics related to nephrogenic systemic fibrosis associated with gadolinium-based contrast agents

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