BackgroundThe study aim was, for the first time, to conduct a multicenter randomized controlled trial to evaluate the effect of tonsillectomy in patients with IgA nephropathy (IgAN).MethodsPatients with biopsy-proven IgAN, proteinuria and low serum creatinine were randomly allocated to receive tonsillectomy combined with steroid pulses (Group A; n = 33) or steroid pulses alone (Group B; n = 39). The primary end points were urinary protein excretion and the disappearance of proteinuria and/or hematuria.ResultsDuring 12 months from baseline, the percentage decrease in urinary protein excretion was significantly larger in Group A than that in Group B (P < 0.05). However, the frequency of the disappearance of proteinuria, hematuria, or both (clinical remission) at 12 months was not statistically different between the groups. Logistic regression analyses revealed the assigned treatment was a significant, independent factor contributing to the disappearance of proteinuria (odds ratio 2.98, 95% CI 1.01–8.83, P = 0.049), but did not identify an independent factor in achieving the disappearance of hematuria or clinical remission.ConclusionsThe results indicate tonsillectomy combined with steroid pulse therapy has no beneficial effect over steroid pulses alone to attenuate hematuria and to increase the incidence of clinical remission. Although the antiproteinuric effect was significantly greater in combined therapy, the difference was marginal, and its impact on the renal functional outcome remains to be clarified.

As the aging of the population progresses in Japan, the nutritional problems in dialysis patients are being highlighted. Frailty is a clinical concept including body weight loss, muscle weakness, fatigability, decreased walking speed, and decreased physical activity, which means an intermediate concept between healthy subjects and disability subjects, indicating that their activities of daily living are not decreased but they cannot smoothly perform housework or exercise. Morbidity of dialysis patients is known to be high, and mortality of dialysis patients with frailty is 3 times higher. Sarcopenia is one of the principal reasons for or triggers of frailty. It is a disease setting showing decreased muscle volume and quality associated with decreased physical function or quality of life. Recent mean age at dialysis therapy induction is getting near to 70 years old in Japan. Japanese dialysis patients who are elderly and present organ failure would have a double risk for sarcopenia. Patients with advanced stages of CKD are generally given protein diet, and it has been reported that a low protein intake in dialysis patients would be a significant risk for developing sarcopenia and increasing mortality. Recently, the focus has been on protein energy wasting (PEW) - an underlying disease condition in sarcopenia or frailty. PEW is an energy wasting condition occurring in dialysis patients, and the cause of PEW is principally decreased food intake and increased catabolism. It has recently been revealed that decreased protein intake would be a risk factor for increased mortality in dialysis patients. The incidence of PEW in dialysis patients is reported to be 14%. To avoid sarcopenia and PEW leading to frailty, we should pay much more attention to an appropriate protein and calorie intake rather than restriction in dialysis patients.

Background/Aims: Pioglitazone (PGZ), one of the thiazolidinediones, has been known to show renoprotective effects. In this study, we focused on the effect of PGZ on glomerular hyperfiltration (GHF), resultant glomerular injury and altered macula densa signaling as a cause of sustained GHF through modified tubuloglomerular feedback in rats with diabetic nephropathy. Methods: Kidneys from 24-week-old male OLETF rats and LET rats, nondiabetic controls, were used for the experiment. PGZ was administered (10 mg/kg/day, p.o.) for 2 weeks from 22 to 24 weeks of age in some of the OLETF rats (OLETF+PGZ). Results: Parameters relating GHF, kidney weight, creatinine clearance, urine albumin/creatinine ratio and glomerular surface were all increased in OLETF rats and partially restored in OLETF+PGZ rats. Expressions of desmin and TGF-β were also increased in OLETF rats and restored in OLETF+PGZ rats. The changes in TGF-β expression were confirmed to be independent of podocyte number. Finally, the immunoreactivity of neuronal nitric oxide synthase (nNOS) and cyclooxygenase 2 (COX-2) in the macula densa was assessed for the evaluation of macula densa signaling. Altered intensities of nNOS and COX-2 in OLETF rats were restored in OLETF+PGZ rats, which agreed with the gene expression analysis (nNOS: 100.2 ± 2.9% in LET, 64.2 ± 2.7% in OLETF, 87.4 ± 12.1% in OLETF+PGZ; COX-2: 100.8 ± 7.4% in LET, 249.2 ± 19.4% in OLETF, 179.9 ± 13.5% in OLETF+PGZ; n = 5) and the semiquantitative analysis of nNOS/COX-2-positive cells. Conclusion: PGZ effectively attenuated the GHF and hyperfiltration-associated glomerular injury in diabetic nephropathy. The restoration of altered macula densa signaling might be involved in the renoprotective effect of PGZ.

Adrenomedullin (AM) is a potent vasodilating peptide secreted from the vasculature of various organs. It is biologically active when its C-terminus is amidated. Recently, an RIA method was developed for measurement of the active form of AM, or mature AM. We here employed this method to investigate the significance of amidation of AM in controlling cardiovascular function. Thirty-six patients under hemodialysis were recruited and divided into hypertensive (n=25; 157186 mmHg) and normotensive (n=11; 116!66 mmHg) groups. Mature AM, immature AM and blood pressure were monitored during hemodialysis in all patients. There was a significant reduction in blood pressure during hemodialysis in both groups, although after hemodialysis blood pressure was still higher in hypertensives than in normotensives (139± 14.8176 ± 2.5 mmHg vs. 110 ± 5.1166.7 ± 3.1 mmHg). Mature AM before hemodialysis were lower in hypertensives than normotensives and it decreased in both groups. Although mature AM decreased more in normotensives than in hypertensives (-27 ± 8% vs. -17 ± 5%), at the end point, its level was still higher in normotensives. The ratio of mature AM/immature AM decreased only in normotensives (-11.4 ± 8.7%), whereas it remained stable in hypertensives (0.2± 5.6%). Both groups showed similar changes in ANP, endothelin, catecholamines, cGMP, and NOx. The low level in mature AM level in hypertensives may have contributed to the higher blood pressure in this group. The attenuation of AM amidation in normotensives indicates that an unspecified amidative enzyme of AM was regulated in order to normalize blood pressure. (Hypertens Res 2000; 23: 167-171)

The purpose of this study was to assess the factors affecting the efficacy of combination therapy with losartan and thiazide, with a focus on the significance of salt excretion, via a multicenter observational study. Adult patients with essential hypertension showing therapy resistance to angiotensin receptor blocker (ARB) as a monotherapy or in combination with Ca channel blockers (CCB) were enrolled, and their previously administered ARBs were replaced with the combination tablet containing losartan (50 mg per day) and hydrochlorothiazide (12.5 mg per day). Blood pressure and biochemical parameters were monitored for a year. The baseline blood pressure (153.4±14.8/86.4±11.3 mm Hg) was significantly lowered at the 3rd month (137.3±17.4/78.2±11.1 mm Hg, n=93) and was maintained at this lower level until the 12th month (135.3±14.0/76.4±11.1 mm Hg, n=74). The baseline value of estimated salt excretion (eSE), calculated using Tanaka's formula, differed significantly between the high and low treatment response groups, which were defined by the average change in mean blood pressure (MBP-C, -11.3 mm Hg; eSE=10.8±2.9 g per day in high responders vs. 9.2±2.3 g per day in low responders, P=0.004). Univariate and multivariate analyses showed a significant correlation between eSE and MBP-C (R=-0.288, P=0.007) and indicated the clinical effectiveness of eSE as a possible predictor for MBP-C (P=0.021). In addition, the urine Na-to-Cr ratio (NCR) demonstrated significant correlations with eSE (R=0.848, P<0.001) and MBP-C (R=-0.344, P<0.001). These results suggest that eSE or NCR could, to a certain extent, predict the efficacy of combination therapy with losartan and low-dose thiazide in patients demonstrating ARB resistance. Combination therapy with losartan and thiazide might thus be suitable for patients with a large amount of salt excretion.

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We report on a case of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with lupus erythematosus in the central nervous system (CNS). A 73-year-old woman with essential hypertension suddenly demonstrated consciousness disturbance. Upon her admission, laboratory data showed significant hyponatremia (114 mEq/L) and a lack of body fluid loss. Diminished free water excretion (urine osmolality 684 mOsm/kg) and normal urine Na excretion (FENa 1.70 %) were consistent with the diagnosis of SIADH, which was confirmed by an inappropriately high concentration of plasma antidiuretic hormone (ADH) (15.3 pg/mL at 256 mOsm/kg of plasma osmolality). The hyponatremia was corrected by a combination of oral water intake restriction and saline infusion with furosemide administration until the 20th hospital day. Simultaneously, the presence of exudative pleural effusion in both chest cavities, suggesting the existence of pleuritis, and high titer of anti-nuclear antibody (ANA, 51209) and anti-doublestrand DNA antibody (6500 IU/mL), indicated the subclinical development of systemic lupus erythematosus (SLE), although the diagnostic criteria were not satisfied at that time. On the 34th hospital day, the sudden onset of unknown consciousness disturbance confirmed the diagnosis of SLE as CNS lupus. In previous case reports on SLE and/or SIADH, a few cases in which SLE and SIADH developed concomitantly regularly showed high immunological activities, as in our case. Some common pathophysiological bases might be involved in the concomitant appearance of those disorders.

Background We conducted the multicenter, prospective, open-label study in type 2 diabetic (T2DM) patients with renal dysfunction, to clarify the efficacy and the safety in relation to renal function and glycemic control, and the economic effect when other dipeptidyl peptidase-4 (DPP-4) inhibitors were switched to a small dose of sitagliptin depending on their renal function. Methods Vildagliptin, alogliptin, or linagliptin received for more than 2 months were changed to sitagliptin at 25 or 12.5 mg/ day depending on their renal function in 49 T2DMs. Renal function and glycemic control, and the drug cost were assessed during 6 months. Results Estimated glomerular filtration rate was not changed in patients not on hemodialysis (n = 29). The HbA1c levels were not altered in all of the patients including those on hemodialysis (n = 20). The active glucagon-like peptide-1 levels or other renal parameters were not altered significantly. There were no adverse events to be related to the drugs. The daily drug expense was reduced by 88.1 yen per patient. Conclusion Switching to a small dose of sitagliptin according to the renal function in T2DM patients with renal dysfunction demonstrated the same efficacy and safety as those with other full-dose DPP-4 inhibitors, indicating a therapeutic option with a high cost performance.