Patients with renal dysfunction require a longer duration until blood pressure dips during the night.

We have postulated that the diminished renal capacity to excrete sodium causes nocturnal blood pressure (BP) elevation, which enhances pressure natriuresis in compensation for impaired daytime natriuresis. If such a mechanism holds, high BP during sleep at night may continue until excess sodium is sufficiently excreted into urine. This study examined whether the duration, defined as "dipping time," until nocturnal mean arterial pressure began to fall to <90% of daytime average became longer as renal function deteriorated. Ambulatory BP measurements and urinary sodium excretion rates were evaluated for daytime and nighttime to estimate their circadian rhythms in 65 subjects with chronic kidney disease. Dipping time showed an inverse relationship with creatinine clearance (C(cr); rho=-0.61; P<0.0001) and positive relationships with night/day ratios of mean arterial pressure (rho=0.84; P<0.0001) and natriuresis (rho=0.61; P<0.0001), both of which were also inversely correlated with C(cr) (mean arterial pressure: r=-0.58, P<0.0001; natriuresis: r=-0.69, P<0.0001). When divided into tertiles by C(cr) (mL/min), hazard ratios of nocturnal BP dip adjusted for age, gender, and body mass index were 0.37 (95% CI: 0.17 to 0.79; P=0.01) for the second tertile (C(cr): 50 to 90) and 0.20 (95% CI: 0.08 to 0.55; P=0.002) for the third tertile (C(cr): 5 to 41) compared with the first tertile (C(cr): 91 to 164). These findings demonstrate that patients with renal dysfunction require a longer duration until BP falls during the night. The prolonged duration until BP dip during sleep seems an essential component of the nondipper pattern of the circadian BP rhythm.

Angiotensin II type 1 receptor blocker, olmesartan, restores nocturnal blood pressure decline by enhancing daytime natriuresis.

OBJECTIVE: We have shown that as renal function deteriorated, night-time fall in both blood pressure and urinary sodium excretion were diminished. We have also reported that sodium intake restriction and diuretics both normalized circadian blood pressure rhythm from nondipper to dipper patterns. In this study, we investigated whether an angiotensin II receptor blocker, olmesartan, could restore night-time blood pressure fall. METHODS: Twenty patients with chronic kidney disease (13 men, seven women; mean age 44.8 +/- 18.1 years; BMI 22.9 +/- 3.5 kg/m2) were studied. At baseline and 8 weeks after the treatment with olmesartan medoxomil (10-40 mg/day), 24-h blood pressure monitoring and urinary sampling for both daytime (0600-2100 h) and night-time (2100-0600 h) were repeated to compare the circadian rhythms of blood pressure and urinary sodium excretion. RESULTS: The 24-h mean arterial pressure was lowered by olmesartan, while urinary sodium excretion remained unchanged. On the other hand, daytime urinary sodium excretion was increased from 4.8 +/- 2.2 to 5.7 +/- 2.1 mmol/h, while night-time urinary sodium excretion tended to be reduced from 3.9 +/- 1.7 to 3.4 +/- 1.6 mmol/h. Night/day ratios of mean arterial pressure (0.98 +/- 0.1 to 0.91 +/- 0.08; P = 0.01) and urinary sodium excretion (0.93 +/- 0.5 to 0.68 +/- 0.4; P = 0.0006) were both decreased. Olmesartan enhanced night-time falls more in mean arterial pressure (r = 0.77; r2 = 0.59; P < 0.0001) and urinary sodium excretion (r = 0.59; r2 = 0.34; P = 0.007), especially in patients whose baseline night-time falls were more diminished. CONCLUSIONS: These findings demonstrated that olmesartan could restore night-time blood pressure fall, as seen with diuretics and sodium restriction, possibly by enhancing daytime sodium excretion. Since nocturnal blood pressure is a strong predictor of cardiovascular events, olmesartan could relieve cardiorenal load through normalization of circadian blood pressure rhythm besides having powerful ability to block the renin-angiotensin system.

Regional differences in end-stage renal disease and amount of protein intake in Japan.

OBJECTIVE: We recently showed regional differences in the incidence of end-stage renal disease (ESRD) within Japan, which is generally ethnically homogenous, suggesting that factors other than genetic may contribute to the difference. We examined regional differences in the amounts of dietary nutrient intake, especially protein in our search for an explanation. DESIGN AND SETTING: Annually, the Japanese Society for Dialysis Therapy reports the numbers of patients entering maintenance dialysis in each prefecture of Japan. We used these numbers from 1984 to 2002 to calculate the annual ESRD incidence in each of 12 regions of Japan. The regional differences were analyzed in relation to the amounts of nutrient intake reported annually by National Nutrition Survey in corresponding regions for these 19 years. Each year, approximately 15,000 subjects from 5000 households in randomly selected 300 districts were included to obtain a representative sample of the entire population of Japanese in a manner of age, sex, and body mass matched. RESULTS: There were marked regional differences in the annual ESRD incidence and small regional differences in dietary intake of each nutrient. Multiple regression analysis showed that the annual ESRD incidence was negatively correlated with energy intake (r = -0.65, F = 240, n = 228) and positively correlated with animal protein intake (r = 0.25, F = 30). Across 12 regions in the values averaged for 19 years in each region, however, the incidence of ESRD was negatively correlated only with the amounts of energy intake (r = -0.74, F = 12, n = 12), but not with animal protein (r = 0.07, F = 0.04). CONCLUSION: The present study, relating regional differences between ESRD dynamics and the amounts of nutrient intake in a nationwide population of Japan, revealed that the renal protective effects of dietary restriction of protein, suggested by animal models of progressive nephropathies but yet unproved by large-scale clinical trials, remained unestablished even on a macro level of whole Japan through mapping approaches.

Polynocturia in chronic kidney disease is related to natriuresis rather than to water diuresis.

BACKGROUND: Nocturnal polyuria has been well known in renal insufficiency. Recently, we found that as renal function deteriorated in chronic kidney disease (CKD), natriuresis was enhanced during the night with nocturnal blood pressure elevation. In the present study, we investigated whether nocturnal polyuria in CKD was due to the inability to concentrate urine, as previously proposed, or based on osmotic diuresis mainly by natriuresis. METHODS: In 27 CKD patients, circadian rhythms of urinary sodium, potassium, urea and osmolar excretion rates (U(Na)V, U(K)V, U(urea)V, U(osm)V) as well as of urinary volume (V) and free-water clearance (C(H(2)O)) were estimated during both daytime (6:00 to 21:00) and nighttime (21:00 to 6:00). Then, the night/day ratios of these parameters were analysed in relation to creatinine clearance (C(cr)) as a marker of glomerular filtration rate. RESULTS: C(cr) had significantly negative relationships with night/day ratios of V (R = -0.69; P < 0.0001), U(osm)V (R = -0.54; P = 0.004) and U(Na)V (R = -0.63; P = 0.0005), but no correlation with night/day ratios of C(H(2)O) (R = -0.33; P = 0.1), U(K)V (R = -0.29; P = 0.1) or U(urea)V (R = -0.31; P = 0.1). Linear and multiple regression analysis identified nocturnal natriuresis rather than urea excretion as an independent determinant of nocturia. CONCLUSION: As renal function deteriorated, nocturnal polyuria was seen, being consistent with classical recognition. Furthermore, this increase in nocturnal urine volume seemed related to osmotic diuresis mainly by natriuresis rather than to water diuresis or urea excretion.

Different regional dynamics of end-stage renal disease in Japan by different causes.

BACKGROUND: We recently showed that there were clear regional differences in the dynamics of end-stage renal disease (ESRD) within Japan, which has an ethnically homogenous population. We speculate on the reason for these regional differences by correlating the regional distributions in the incidence of ESRD due to each of the following individual causes of ESRD: chronic glomerulonephritis (CGN), diabetic nephropathy (DMN) and polycystic kidney disease (PKD). METHODS: The number of ESRD patients entering maintenance dialysis therapy due to individual causes of renal disease in each prefecture was reported annually for a 6-year period by the Japanese Society for Dialysis Therapy. After combining data from several prefectures into 11 geopolitical regions in Japan, the mean annual incidence of ESRD across the 11 regions was correlated among the three causes of ESRD. RESULTS: There were significant regional differences in the incidence of ESRD due to CGN (P<0.0001) and DMN (P=0.0015), the distributions of which were similar to each other across the 11 regions. In contrast, no regional differences were found in the incidence of ESRD due to PKD (P=0.6) as the major genetic disorder of the kidneys, suggesting that genetic backgrounds are relatively uniform throughout Japan. The regional distributions due to PKD were not correlated with those due to other causes: CGN and DMN. CONCLUSION: Risk factors common to nephropathy progression, rather than an underlying disease incidence and genetic predisposition, might contribute to regional differences in the overall ESRD incidence in Japan. Other possibilities such as the prevalence of underlying diseases, and acceptance or rejection rates into treatment programmes must be considered further for better explanations.