Atsuhiro Yoshida

Angiotensin receptor blockers shift the circadian rhythm of blood pressure by suppressing tubular sodium reabsorption

Recently, we found that an angiotensin II receptor blocker (ARB) restored the circadian rhythm of the blood pressure (BP) from a nondipper to a dipper pattern, similar to that achieved with sodium intake restriction and diuretics (Fukuda M, Yamanaka T, Mizuno M, Motokawa M, Shirasawa Y, Miyagi S, Nishio T, Yoshida A, Kimura G. J Hypertens 26: 583-588, 2008). ARB enhanced natriuresis during the day, while BP was markedly lower during the night, resulting in the dipper pattern. In the present study, we examined whether the suppression of tubular sodium reabsorption, similar to the action of diuretics, was the mechanism by which ARB normalized the circadian BP rhythm. BP and glomerulotubular balance were compared in 41 patients with chronic kidney disease before and during ARB treatment with olmesartan once a day in the morning for 8 wk. ARB increased natriuresis (sodium excretion rate; U(Na)V) during the day (4.5 ± 2.2 to 5.5 ± 2.1 mmol/h, P = 0.002), while it had no effect during the night (4.3 ± 2.0 to 3.8 ± 1.6 mmol/h, P = 0.1). The night/day ratios of both BP and U(Na)V were decreased. The decrease in the night/day ratio of BP correlated with the increase in the daytime U(Na)V (r = 0.42, P = 0.006). Throughout the whole day, the glomerular filtration rate (P = 0.0006) and tubular sodium reabsorption (P = 0.0005) were both reduced significantly by ARB, although U(Na)V remained constant (107 ± 45 vs. 118 ± 36 mmol/day, P = 0.07). These findings indicate that the suppression of tubular sodium reabsorption, showing a resemblance to the action of diuretics, is the primary mechanism by which ARB can shift the circadian BP rhythm into a dipper pattern.

PR3-ANCA-positive crescentic necrotizing glomerulonephritis accompanied by isolated pulmonic valve infective endocarditis, with reference to previous reports of renal pathology.

Patients with infective endocarditis (IE) often have renal complications which may include infarcts, abscesses and glomerulonephritis (GN). Furthermore, it is generally accepted that there is an association between IE and anti-neutrophil cytoplasmic antibody (ANCA). Here, we report the case of a 24-year-old man who developed rapidly progressive GN in the course of IE due to infection with alpha-streptococcus. The initial clinical manifestation of the condition was severe sacroiliitis without fever. Sandwich ELISA showed that the patient was positive for PR3-ANCA at low titer, and the classical complement pathway was also activated. Renal biopsy demonstrated several lesions: focal embolic GN, GN with immune deposits and focal and segmental crescentic necrotizing GN. Treatment with antibiotics and steroids led to eradication of the infection, and resolution of the renal disease was accompanied by immediate disappearance of PR3-ANCA and hypocomplementemia. During a 4-year follow-up period, no recurrence was observed. There have only been 7 case reports of GN associated with IE and PR3-ANCA in which the renal pathology has been described, and the current report is the first to document renal pathology in a patient with isolated pulmonic valve IE and PR3-ANCA. Moreover, this report is the first to show a change in renal biopsy findings in response to treatment. A review of the 7 literature cases and that of our patient showed that none involved pauci-immune GN. Hence, further studies are needed to clarify the prevalence of pauci-immune GN in ANCA-positive IE patients.

Angiotensin receptor blockers regulate the synchronization of circadian rhythms in heart rate and blood pressure.

Objective: The sympathetic nervous system plays an important role in blood pressure regulation even in the early stages of chronic kidney disease (CKD). Methods: To understand the role of the sympathetic system, we examined the relationship between day/night ratios of both heart rate (HR) and mean arterial pressure (MAP) as well as HR variability (HRV, SD) before and during an 8-week treatment with the angiotensin II receptor blocker (ARB), olmesartan, in 45 patients with CKD. Results: The day/night HR ratio strongly correlated with the day/night MAP ratio before and during ARB treatment. The ratio of [day/night HR ratio] over [day/night MAP ratio] was increased as renal function deteriorated at baseline (r = −0.31, P = 0.04), and it was attenuated (1.10 ± 0.10 to 1.06 ± 0.10; P = 0.04) and became independent of renal function during ARB treatment (r = −0.04, P = 0.8). ARB increased both the day/night HR ratio (1.17 ± 0.09 to 1.21 ± 0.13; P = 0.04) and HRV (10.6 ± 2.9 to 11.7 ± 4.2; P = 0.04), which were lower when baseline renal function deteriorated. Conclusion: The present study indicates that there exists a close correlation in circadian rhythms between HR and MAP in CKD. Synchronization between the two rhythms was progressively lost as renal function deteriorated, and ARB partly restored the synchronization. These findings suggest that the sympathetic nervous system is activated as renal function deteriorates, and ARB may suppress its activation.

Morning hypertension in chronic kidney disease is sustained type, but not surge type.

ObjectiveWe have shown that as renal function deteriorates, the circadian blood pressure (BP) rhythm shifts to a nondipper pattern and the duration until nocturnal BP decline [dipping time (DT)] is prolonged. We investigated whether or not morning hypertension (BP 2 h after awakening >135/85 mmHg) in chronic kidney disease (CKD) was sustained type with a prolonged DT. Materials and methodsTwenty-four-hour BP was monitored in 104 patients with CKD. Fifty-one of 104 participants (group A) did not exhibit morning hypertension. The patients with morning hypertension (group B, n=53) were classified into three groups: group C (n=23), participants who exhibited morning hypertension but did not meet the criteria for the surge or sustained type; group D (n=29), the sustained type (with no night-time BP readings <120/70 mmHg); and group E (n=1), the surge type (systolic BP rises >25 mmHg after awakening). ResultsThe night/day BP ratio and DT were compared among groups A, C, and D because there was only one participant in group E. Night/day ratio of BP and DT were both significantly higher in group D compared with groups A and C. The prevalence of nondippers tended to be higher in group D compared with the other groups (A, 65%; C, 57%; D, 86%, P=0.09). Creatinine clearance was significantly lower in group D compared with groups A and C. ConclusionSustained elevation of night-time BP until the early morning and high night/day ratio of BP may contribute to the high frequency of morning hypertension, which is generally the sustained rather than the surge type in CKD.

Circadian rhythm of urinary potassium excretion in patients with CKD.

AIMS We previously reported in patients with chronic kidney disease (CKD) that the circadian rhythms of blood pressure (BP) and urinary sodium excretion were both impaired into non-dipper pattern as renal function deteriorated. However, the circadian rhythm of urinary potassium excretion has not been studied in relation to renal dysfunction. METHODS BP and urinary excretion rates of sodium (UNaV) and potassium (UKV) were evaluated for daytime and nighttime to estimate their circadian rhythms in 83 subjects with CKD. RESULTS As renal function deteriorated, night/day ratios of UNaV and UKV were both increased. Night/day ratio of UKV was positively correlated with night/day ratio of UNaV (r = 0.60, p < 0.0001). Multiple regression analysis (R2 = 0.37, p < 0.0001) revealed that night/day ratio of UKV was determined independently by the night/day ratio of UNaV (r = -0.55, p < 0.0001), rather than renal function or night/day ratio of BP. CONCLUSIONS Circadian rhythm of natriuresis was regulated by renal function and night/day ratio of BP. On the other hand, the circadian rhythm of urinary potassium excretion was primarily determined by neither renal function nor BP, but was correlated with that of urinary sodium excretion.

Immunotactoid glomerulopathy with microtubular deposits, with reference to the characteristics of Japanese cases.

We present the case of a 69-year-old man with nephrotic syndrome and renal insufficiency, who developed lobular glomerulonephritis. An electron microscopy examination of a renal biopsy showed microtubular structures of 24 nm in diameter in the subendothelial space and the paramesangial area. These deposits were PAS-positive and Congo red-negative, and revealed predominantly positive staining for kappa light chain. There was no evidence of diseases with highly organized glomerular deposits, such as amyloidosis, cryoglobulinemia, systemic lupus erythematosus or paraproteinemia. Therefore, the patient was diagnosed to have immunotactoid glomerulopathy (ITG). During a seven-year course he has not developed any disease known to be associated with organized glomerular immune deposits. Hence, we believe ITG occurred as a primary glomerular disease in this case. We also highlight cases of ITG with microtubular deposits that have been reported in Japan, compare these cases to previous reports, and show that the characteristics of the Japanese cases are male predominance; a high incidence of membranoproliferative glomerulonephritis (MPGN); a low incidence of monoclonal gammopathy and hematological malignancies and a higher incidence of hypocomplementemia.