Augmented Association Between Blood Pressure and Proteinuria in Hyperuricemic Patients With Nonnephrotic Chronic Kidney Disease.

BACKGROUND: Hyperuricemia (HU) may enhance susceptibility to hypertensive renal damage via disrupted autoregulation of glomerular hemodynamics. The effect of HU on the association between blood pressure (BP) and proteinuria remains unknown in patients with chronic kidney disease (CKD). METHODS: In total, 109 patients with nonnephrotic CKD (55 men and 54 females) who underwent renal biopsy were recruited. Arteriolar hyalinosis was semiquantitatively assessed via arteriole grading. Correlation between BP and urine protein (UP) level was examined based on the presence of HU, which was defined as the use of urate-lowering drugs or serum uric acid levels of ≥7 and ≥5 mg/dl in males and females, respectively, which were associated with increased risks of hyalinosis in our previous study. RESULTS: Median age, BP, estimated glomerular filtration rate, and UP level were 38 years, 124/74 mm Hg, 82 ml/min/1.73 m2, and 0.8 g/gCr, respectively. In patients with HU (n = 59), log-transformed systolic BP (SBP) was significantly correlated with log-transformed UP level (r = 0.49, P < 0.0001); this was not observed in patients without HU (n = 50). Multiple regression analysis (R2 = 0.21, P = 0.0001) revealed that the interaction between HU and log-transformed SBP with respect to proteinuria was significantly correlated with log-transformed UP level (ß = 7.0, P = 0.03), independent of age, sex, and potential confounding factors; however, this statistical significance was completely eliminated after adjustment for the arteriolar hyalinosis index. CONCLUSIONS: HU potentiates susceptibility to hypertensive glomerular damage via disrupted autoregulation in patients with nonnephrotic CKD.

Effects of xanthine oxidase inhibitors on renal function and blood pressure in hypertensive patients with hyperuricemia.

Hyperuricemia may promote the progression of hypertension and renal dysfunction. However, the effects of hyperuricemia treatment on blood pressure and renal function in adult hypertensive patients with hyperuricemia remain unclear. A total of 137 hypertensive patients with hyperuricemia (96 men and 41 women; mean age of 67 years) who recently started taking xanthine oxidase inhibitors (allopurinol or febuxostat) as outpatients were recruited. Serum uric acid level, estimated glomerular filtration rate (eGFR, ml min(-1) per 1.73 m(2)) and blood pressure (mm Hg) were retrospectively compared immediately before and shortly after starting treatment with xanthine oxidase inhibitors. The mean blood pressure and the eGFR immediately before starting treatment were 128/71 mm Hg and 44.6 ml min(-1) per 1.73 m(2), respectively. Although the eGFR decreased from 46.6 to 44.6 ml min(-1) per 1.73 m(2) before starting treatment with xanthine oxidase inhibitors, it increased to 46.2 ml min(-1) per 1.73 m(2) (P=0.001, compared with immediately before treatment) without any significant changes in blood pressure after the administration of xanthine oxidase inhibitors. Multiple regression analysis revealed that the increase in eGFR after starting xanthine oxidase inhibitor treatment positively correlated with the changes in systolic blood pressure and negatively correlated with the changes in uric acid levels and the use of renin-angiotensin system inhibitors. These results suggest that xanthine oxidase inhibitors may delay the progression of renal dysfunction in adult hypertensive patients with hyperuricemia.

Associations between serum uric acid levels and the incidence of hypertension and metabolic syndrome: a 4-year follow-up study of a large screened cohort in Okinawa, Japan.

The purpose of this study was to examine the associations between serum uric acid (SUA) levels and the incidences of hypertension and metabolic syndrome (MetS) in a large screened cohort of Japanese men and women. We evaluated 4812 subjects (males, 2528; females, 2284; mean age, 47.5 years) who underwent health checkups between 2006 and 2010 and were free of hypertension and MetS in 2006. After 4 years, 618 (13%), 764 (16%) and 158 (3%) subjects developed hypertension, MetS and hypertension with MetS, respectively. Increased SUA levels were significantly and positively associated with the incidences of hypertension, MetS and hypertension with MetS. Compared with the first quartile of SUA levels, the odds ratios (95% confidence intervals) for the third and fourth quartiles, respectively, were as follows: 1.5 (1.1-2.1; P = 0.0128) and 1.8 (1.2-2.5; P = 0.0022) for hypertension, 1.3 (0.9-1.9; P = 0.1910) and 1.8 (1.2-2.7; P = 0.0039) for MetS and 2.7 (1.1-6.6; P = 0.0276) and 3.2 (1.3-8.0; P = 0.0115) for hypertension with MetS. In conclusion, increased SUA levels were significantly and independently associated with the incidences of hypertension and MetS in subjects without hypertension or MetS at baseline. Increased SUA levels might also be correlated with the incidence of hypertension with MetS.

Hypertriglyceridemia accompanied by increased serum complement component 3 and proteinuria in non-nephrotic chronic kidney disease.

BACKGROUND: Hypertriglyceridemia (hTG) is a risk factor for progression of chronic kidney disease (CKD); however, it remains unknown whether the adipocytokine complement component 3 (C3) is involved in the association between hTG and CKD. METHODS: The study included 138 patients (54 % male) with non-nephrotic (serum albumin ≥3 g/dl) CKD who had undergone a renal biopsy and did not have hypocomplementemic disease. Renal arteriolopathy was assessed semi-quantitatively. We examined the cross-sectional associations between proteinuria and hTG with or without a higher serum C3 level (hC3), defined as equal or above the median value. RESULTS: The mean (SD) age of the patients was 42 (±17) years and urine protein was 1.2 (±1.2) g/gCr. Patients with hTG had a significantly higher urine protein than those without hTG. Subgroup analysis showed that the hTG+/hC3+ group had higher grade arteriolopathy and urine protein levels. Multiple logistic regression analysis adjusted for age, sex, and diabetes mellitus showed that hC3+ alone was associated significantly with higher levels of urine protein [odds ratio (OR), 2.98; 95 % confidence interval (CI) 1.19-7.46, p = 0.02]; however, hTG alone showed no such association. hTG+/hC3+ was a significant factor when hTG-/hC3- was used as the reference (adjusted OR 5.32; 95 % CI 1.40-20.17, p = 0.01), with this OR being decreased by adjustment for arteriolopathy. CONCLUSIONS: hTG accompanied by hC3 was associated with proteinuria in non-nephrotic CKD. Arteriolopathy may influence this association. A prospective study is needed to determine the predictive value of this association in CKD progression.

An association between uric acid levels and renal arteriolopathy in chronic kidney disease: a biopsy-based study.

Uric acid (UA) can induce renal arteriolopathy in animal models. Whether there is an association between UA and renal arteriolopathy in patients with chronic kidney disease (CKD) is unknown. Here, we examined the cross-sectional association of serum UA levels with renal arteriolar hyalinosis and wall thickening. Arteriolar parameters were assessed by semiquantitative grading (max: grade 3) of arterioles in 167 patients with CKD (mean age, 42.4 years; 86 men and 81 women) who underwent renal biopsy. The mean serum UA level was 6.4 mg dl(-1). We observed hyalinosis in 94 patients (56%) and wall thickening in 119 patients (71%). As the UA level tertile increased, the proportion of higher-grade (grade 2 and 3) hyalinosis and wall thickening increased (hyalinosis, P<0.0001 and wall thickening, P=0.0002, for trend). Multiple logistic analysis adjusted for age ≥40 years, sex, hypertension status, diabetes mellitus status and estimated glomerular filtration rate <60 ml min(-1) per 1.73 m(2) showed that hyperuricemia (UA ≥7 mg dl(-1)) was significantly associated with a higher risk of hyalinosis (adjusted odds ratio: 3.13; 95% confidence interval: 1.23-7.94; P=0.02) and higher-grade (equal to or higher than the mean value) wall thickening (adjusted odds ratio: 2.66; 95% confidence interval: 1.11-6.38; P=0.03). Hence, these results suggest that hyperuricemia may be related to renal arteriolar damage in patients with CKD.

Penicillin G-induced hemorrhagic cystitis with hydronephrosis.

Irritable urological symptoms with gross hematuria and bilateral lumbar pain developed when the patient received penicillin G for endocarditis. These symptoms were followed by renal insufficiency. A contrast-enhanced abdominal computed tomography (CT) scan revealed a thickened bladder wall, bilateral hydroureter and hydronephrosis, suggesting hemorrhagic cystitis complicated with urinary tract obstruction. Urine culture was negative. After discontinuation of penicillin G, all symptoms subsided and renal function recovered; hence, penicillin G seems to have been associated with hemorrhagic cystitis and acute kidney injury. Positive findings in the drug lymphocyte stimulation test (DLST) for penicillin G were consistent with this diagnosis.

Hyperuricemia as a predictor of hypertension in a screened cohort in Okinawa, Japan.

Several epidemiological studies have shown a positive association between serum uric acid levels and the risk of hypertension. However, subjects in these studies were mostly men, or were incompletely examined for lifestyle-related variables. We prospectively examined the relation between hyperuricemia and the risk of developing hypertension with consideration for alcohol consumption and smoking habits in a large screened cohort of men and women. A total of 4,489 individuals (2,927 men and 1,562 women) who did not have hypertension and were not currently using antihypertensive medication were examined at the Okinawa General Health Maintenance Association in 1977. Subjects were re-examined in 2000. Hyperuricemia was defined as a serum uric acid level >or=7.0 mg/dl in men and >or=6.0 mg/dl in women. Hypertension was defined as systolic blood pressure (SBP) >or=140 mmHg, and/or diastolic blood pressure (DBP) >or=90 mmHg. A total of 289 subjects (201 men and 88 women) were hypertensive (SBP >or=140 mmHg, and/or DBP >or=90 mmHg) in 2000. Multivariate analysis was performed for development of hypertension in hyperuricemic subjects, adjusted for age, family history of hypertension, alcohol consumption, cigarette smoking, obesity, hypercholesterolemia, hypertriglyceridemia, low high-density lipoprotein cholesterol, and diabetes mellitus. The adjusted odds ratio (95% confidence interval) in men was 1.48 (1.08-2.02) and in women was 1.90 (1.03-3.51) (p <0.05, respectively). The results showed hyperuricemia to be a new predictor of hypertension development in both men and women.

Cardiovascular risk factors associated with pulse pressure in a screened cohort in Okinawa, Japan.

We evaluated the association between pulse pressure (PP) and cardiovascular risk factors in a screened cohort. Individuals who were receiving medications for hypertension or heart disease, who had no ECG record, or who had a record of arrhythmia were excluded. In total, 8,508 subjects (5,299 men and 3,209 women; age range, 18 to 89 years) were studied. Subjects were divided into four PP classes: PP.1 (PP < or = 40 mmHg, n=2,127), PP.2 (40 < or = PP < or = 44 mmHg, n=2,127), PP.3 (44 < or = PP < or = 50 mmHg, n=2,127) and PP.4 (50 mmHg < or = PP, n=2,127). Multiple regression analysis was used for evaluating the association between PP and cardiovascular risk factor or lifestyle. In men, the regression coefficient was 0.27 for age, 2.50 for diabetes mellitus, 0.33 for uric acid, 0.20 for body mass index, 0.07 for heart rate, -0.83 for current smoking habit and 1.23 for habitual drinking. In women, the regression coefficient was 0.37 for age, 4.09 for diabetes mellitus, 0.42 for body mass index, 0.14 for heart rate, and 0.84 for habitual exercise. In both men and women, PP was significantly increased in association with an increase in the number of risk factors (diabetes mellitus, obesity, current drinking status, heart rate, and hyperuricemia). In conclusion, higher PP was associated with cardiovascular risk factors. These associations were similar in both men and women.