Amplified Association Between Blood Pressure and Albuminuria in Overweight Patients With Biopsy-Proven Hypertensive Nephrosclerosis.

BACKGROUND: An overweight person is at high risk for hypertensive renal damage. The effect of weight on the association between systolic blood pressure (SBP) and albuminuria remains unknown in patients with histologically diagnosed hypertensive nephrosclerosis. METHODS: A total of 97 patients with biopsy-confirmed hypertensive nephrosclerosis were recruited from 13 centers throughout Japan. We examined the relationship between SBP and proteinuria among those who were overweight, which is defined as a body mass index ≥25 kg/m2, and those who were not. We examined the interaction of weight and SBP with albuminuria at baseline and with the changes in estimated glomerular filtration rate (eGFR) during the observational period. RESULTS: Our results included mean age (54 years old), blood pressure (138/80), eGFR (53 ml/min/1.73 m2), and urine albumin levels (0.2 g/day). SBP was significantly correlated with log-transformed urine albumin levels (r = 0.4, P = 0.01) in patients who were overweight (n = 38) compared with patients who were not overweight (n = 59). Multiple regression analysis revealed that the interaction between being overweight and SBP with respect to albuminuria was significantly correlated with the log-transformed urine albumin level (ß = 0.39, P = 0.047) and was independent of age, sex, and potential confounding factors. The interaction between weight and SBP ≥140 mm Hg was significantly associated with a greater decrease in eGFR in the following 3 years. CONCLUSIONS: Being overweight may enhance susceptibility to hypertensive glomerular damage and may eventually lead to renal progression in patients with hypertensive nephrosclerosis.

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.

Interrelationship between brachial artery function and renal small artery sclerosis in chronic kidney disease.

Chronic kidney disease (CKD), characterized by senile inflammation, is a risk factor for cardiovascular disease. Conduit artery function and small artery structure relate to cardiovascular disease. We examined the correlations, determinants and interrelationships of arterial indices in association with CKD in a cross-sectional study of 139 patients (60% male; mean age 44 years) with CKD (stages 3-5, 39%) who underwent a renal biopsy. Conduit artery function and small artery sclerosis were assessed by brachial artery flow-mediated dilatation (FMD) and semiquantitative evaluation of small artery intimal thickening (SA-IT), respectively. The estimated glomerular filtration rate correlated with FMD (r=0.31, P=0.0002) and inversely correlated with SA-IT (r=-0.54, P<0.0001). Multiple regression analysis showed that FMD was inversely correlated with SA-IT and vice versa. In addition, high-sensitivity C-reactive protein (hs-CRP) was significantly correlated with SA-IT, but not FMD. Multiple logistic analysis revealed that higher hs-CRP concomitant with decreased FMD was further associated with the risk of severe SA-IT compared with their individual effects. These findings suggest that both conduit artery and small artery disease develop with mutual interaction in parallel with decreased kidney function. Coexistence of inflammation and conduit artery dysfunction may be closely related to renal small artery sclerosis in patients with CKD.

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.