Feasibility of methotrexate discontinuation following tocilizumab and methotrexate combination therapy in patients with long-standing and advanced rheumatoid arthritis: a 3-year observational cohort study.

OBJECTIVES: Methotrexate (MTX) is associated with extensive side effects, including myelosuppression, interstitial pneumonia, and infection. It is, therefore, critical to establish whether its administration is required after achieving remission with tocilizumab (TCZ) and MTX combination therapy in patients with rheumatoid arthritis (RA). Therefore, the aim of this multicenter, observational, cohort study was to evaluate the feasibility of MTX discontinuation for the safety of these patients. METHODS: Patients with RA were administered TCZ, with or without MTX, for 3 years; those who received TCZ+MTX combination therapy were selected. After remission was achieved, MTX was discontinued without flare development in one group (discontinued [DISC] group, n = 33) and continued without flare development in another group (maintain [MAIN] group, n = 37). The clinical efficacy of TCZ+MTX therapy, patient background characteristics, and adverse events were compared between groups. RESULTS: The disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) at 3, 6, and 9 months was significantly lower in the DISC group (P < .05, P < .01, and P < .01, respectively). Further, the DAS28-ESR remission rate at 6 and 9 months and Boolean remission rate at 6 months were significantly higher in the DISC group (P < .01 for all). Disease duration was significantly longer in the DISC group (P < .05). Furthermore, the number of patients with stage 4 RA was significantly higher in the DISC group (P < .01). CONCLUSIONS: Once remission was achieved, MTX was discontinued in patients who responded favorably to TCZ+MTX therapy, despite the prolonged disease duration and stage progression.

Regulatory role of metallothionein-1/2 on development of sex differences in a high-fat diet-induced obesity.

AIMS: To evaluate the role of metallothionein (MT) in sex differences of obesity, we examined the effect of MT on regulation of lipid accumulation in female and male wild type (WT) and MT1/MT2-null (MT-KO) mice. MAIN METHODS: Male and female WT and MT-KO mice fed standard diet (SD) or high-fat diet (HFD) for 35 weeks. Surgical castration in male mice was also performed to examine the effects of androgen on fat accumulation under HFD condition. KEY FINDINGS: The fat mass and size of adipocytes in white adipose tissue (WAT) was greater in adult MT-KO mice than in WT mice after 35 weeks of SD feeding without gender differences, suggesting a role of MT in limiting WAT development during normal growth in both sexes. In female mice fed HFD, weights of WAT and body were greater in MT-KO mice than in WT mice, indicating that MT had a preventive role against excess fat accumulation. In male mice fed HFD, WAT weight hardly increased in MT-KO mice compared to the increase in WT mice. Surgically castrated WT males fed HFD had lower WAT weight compared with sham-treated mice, although castrated MT-KO males fed HFD had greater increases in WAT weight compared with sham-treated mice and castrated WT males. SIGNIFICANCE: These data suggest that MT could enhance the preventive action of estrogen against excess fat accumulation, on the contrary, MT augmented the ability of androgen to increase fat accumulation. MT may act to modify the susceptibility to obesity under sex hormones.

A case of lipoprotein glomerulopathy with a rare apolipoprotein E isoform combined with neurofibromatosis type I.

Lipoprotein glomerulopathy (LPG) is a rare inherited disease characterized by histopathological features of lipoprotein thrombi in dilated glomerular capillaries and type III like hyperlipoproteinemia with heterozygous mutation of the apolipoprotein (apo) E gene. We herein present the case of a 50-year-old woman with LPG complicated by neurofibromatosis type 1 (NF1). To the best of our knowledge, this is the first report of a case of LPG complicated by NF1. On the other hand, she had not only a heterozygous apoE-Sendai mutation, which is one of the most frequent apoE variants in LPG patients, but also a rare isoform of ApoE5 (Glu3Lys). Although apoE mutation has been recognized as having a principal role in the pathogenesis of LPG, some other factors are assumed to be present in the pathogenesis of LPG, because many asymptomatic carriers of apoE variants are recognized. The coexistence of NF1 or apoE5 (Glu3Lys) allele might play a role as an additional factor in the development of LPG.

Clinical and structural remission rates increased annually and radiographic progression was continuously inhibited during a 3-year administration of tocilizumab in patients with rheumatoid arthritis: A multi-center, prospective cohort study by the Michinoku Tocilizumab Study Group.

OBJECTIVE: To evaluate the clinical and structural efficacy of tocilizumab (TCZ) during its long-term administration in patients with rheumatoid arthritis (RA). METHODS: In total, 693 patients with RA who started TCZ therapy were followed for 3 years. Clinical efficacy was evaluated by DAS28-ESR and Boolean remission rates in 544 patients. Joint damage was assessed by calculating the modified total Sharp score (mTSS) in 50 patients. RESULTS: When the reason for discontinuation was limited to inadequate response or adverse events, the 1-, 2-, and 3-year continuation rates were 84.0%, 76.8%, and 72.2%, respectively. The mean DAS28-ESR was initially 5.1 and decreased to 2.5 at 6 months and to 2.2 at 36 months. The Boolean remission rate was initially 0.9% and increased to 21.7% at 6 months and to 32.2% at 36 months. The structural remission rates (ΔmTSS/year ≤ 0.5) were 68.8%, 78.6%, and 88.9% within the first, second, and third years, respectively. The structural remission rate at 3 years (ΔmTSS ≤ 1.5) was 66.0%, and earlier achievement of swollen joint count (SJC) of 1 or less resulted in better outcomes. CONCLUSIONS: TCZ was highly efficacious, and bone destruction was strongly prevented. SJC was an easy-to-use indicator of joint destruction.

Gene expression related to lipid and glucose metabolism in white adipose tissue.

PROBLEM: A number of endogenous and external factors influence the development of obesity. However, the factors responsible for these differences in obesity pathogenesis between males and females are largely unknown. METHODS: We investigated the expression of 35 genes related to lipid and glucose metabolism and to receptors for insulin signaling in white adipose tissue (WAT) of 8-week-old 129/Sv mice and mice fed standard diet (STD) or high fat diet (HFD) for 35 weeks in males and females. RESULTS: At 8 weeks, the expression levels of two genes for fatty acid synthesis, Acaca and Fasn, were higher in females than in males. Female mice fed a STD for 35 weeks also had higher expression levels of an additional four genes related to glucose transporters (Slc2a1 and Slc2a4) and adipokines (Adipoq and Nampt). The expression levels of these six genes were also higher in females than in males fed a HFD for 35 weeks. At 43 weeks old, the female-to-male expression ratio of these six genes was similar for the STD and HFD groups. Furthermore, glucose tolerance testing showed that the half-life for the elimination of elevated blood glucose was shorter in females than males, although blood glucose parameters were generally similar between females and males. CONCLUSIONS: These findings suggest that sex and aging may cause diet-independent differences in gene expression levels in female and male mice, and that higher expression of these genes in females could contribute to higher metabolic activity and resistance to obesity compared with males.

Histological reassessment of the role of bridging fibrosis in the angioarchitectural features associated with lobular distortion of the liver in chronic viral hepatitis.

AIM: To reassess the role of bridging fibrosis in the lobular distortion of the liver from an angioarchitectural aspect. METHODS: Two tissue samples obtained from surgically resected livers with chronic hepatitis and one obtained from an autopsy case with chronic hepatitis were used for the three-dimensional observation of angioarchitecture by histological reconstruction. RESULTS: Samples showed bridging fibrosis with various degrees of severity, without cirrhotic changes. Two different types of portal-portal bridging fibrosis were found. In our samples, the type that developed in the bifurcation region of the portal tracts was more common than the type observed between the distal portions originating from different parent portal tracts. The angioarchitecture tended to be generally maintained in these lesions. Concerning portal-central bridging fibrosis, two types were observed. One type developed in the lesion with partial paucity of the third-step portal branches in the portal tract at a relatively early stage of chronic hepatitis. The other type developed in an advanced lesion with a complete loss of the normal angioarchitecture of the parenchymal portion of the portal veins. The former was likely developed after large-scale necrosis, such as bridging necrosis, while the latter was presumed to be attributable to portal vein damage associated with long standing chronic inflammation. CONCLUSION: As has been previously noted regarding lobular angioarchitecture, portal-central bridging fibrosis clearly affects the lobular structure of the liver more than portal-portal bridging fibrosis. Therefore, portal vein damage may be a critical event in the eventual distortion of the lobular structure.

Leptospirosis in the Tohoku region: re-emerging infectious disease.

Leptospirosis is a zoonotic and disaster-related infectious disease. It is mainly endemic in subtropical or tropical countries and has not been reported since 2009 in the Tohoku region (northern Japan), including the Yamagata and Miyagi Prefectures. However, we experienced four patients with leptospirosis in the Tohoku region from 2012 to 2014; three patients (#1-3) live in the agricultural areas of the Yamagata Prefecture and one patient (#4) was a visitor to the Miyagi Prefecture. Patient 1 (81-year-old female) is a villager, with a rat bite, while Patient 2 (77-year-old male) and Patient 3 (84-year-old female) are farmers and were infected probably during agriculture work. Patient 4 (40-year-old male US citizen) was infected while traveling in Thailand. They had chief complaint of fever, headache, and myalgia and showed manifestations of hyperbilirubinemia (mean, 4.35 mg/dL), thrombocytopenia and acute kidney injury (AKI). All patients were diagnosed by polymerase chain reaction using blood and/or urine samples and a microscopic agglutination test for the anti-Leptospira antibody. All the patients were treated with infused antibiotics, including minocycline. The patients underwent hemodialysis due to severe AKI (mean serum creatinine, 4.44 mg/dL), except for Patient 2 with the normal serum creatinine level (1.12 mg/dL). All the patients recovered and were discharged. The presence of the three patients in the Yamagata Prefecture implies that leptospirosis does re-emerge in the Tohoku region. Therefore, careful survey of the pathogen is necessary for febrile patients with AKI who engage in agriculture or have a recent history of travelling in subtropical or tropical countries.

Macrophage Infiltration into the Glomeruli in Lipoprotein Glomerulopathy.

Lipoprotein glomerulopathy (LPG) is characterized by histopathological features showing intra-glomerular lipoprotein thrombi and type III hyperlipoproteinemia (HLP), with heterozygote mutation of apolipoprotein (apo) E gene. On the other hand, as another renal lipidosis with type III HLP, apoE2 homozygote-related glomerulopathy (apoE2-GN) showing foamy macrophages has been reported. The case of a 25-year-old man who had LPG by clinical behavior and gene analysis, but demonstrated atypical histopathological features with a substantial amount of foamy macrophage infiltration in the glomeruli, is presented. The combination of alleles for apoE Tokyo/Maebashi and classical apoE2 (Arg158Cys) was inferred to be the leading cause of the unique renal pathology with lipoprotein thrombi and foamy macrophages. In addition, foamy macrophages infiltrated some part of the apoE-positive region within the glomerulus, but did not exist in lipoprotein thrombi despite apoE positivity, suggesting that properties of apoE are crucial in the development of LPG rather than macrophage function. This case provides important information related to the pathogenesis of LPG and apoE2-GN.

Kartagener's syndrome and rheumatoid arthritis.

We herein present the case of a 47-year-old woman with rheumatoid arthritis (RA) complicated by Kartagener's syndrome (KS). Although her RA disease activity score (DAS28-CRP) decreased following the administration of periodontitis treatment and etanercept, she did not achieve symptom relief or DAS28-CRP remission. After undergoing surgery for chronic sinusitis, her articular symptoms improved and the DAS28-CRP declined to the level of remission. Patients with KS may develop respiratory infections due to an impaired defense mechanism against microbes in the airway. Therefore, in patients with RA complicated by KS, comprehensive management of infection, including surgical therapy for sinusitis, is needed to reduce the RA disease activity.

In the non-cirrhotic stage of nonalcoholic steatohepatitis, angioarchitecture of portal veins and lobular architecture are maintained.

The morphogenesis of lobular restructuring to liver cirrhosis in nonalcoholic steatohepatitis (NASH) is yet to be clearly understood. Therefore, we observed tissue samples from three biopsies and one autopsy with NASH in the non-cirrhotic stage three-dimensionally to elucidate the evolution of fibrosis and the changes of angioarchitecture. Histologic reconstructions revealed that pericellular fibrosis developed around the central vein in the early stage and gradually progressed to arch-shaped band-like fibrosis connecting the central veins in the neighboring lobules. In contrast, the basic angioarchitecture of the portal vein in the portal tracts tended to be preserved in the non-cirrhotic stage, although the portal vein architecture was slightly altered as the portal tract underwent gradual fibrous expansion. In addition, a striking development of arteries originating from the portal tract was found in the fibrotic area around the central and sublobular veins. In summary, while central-central bridging fibrosis and ectopic arterial development were conspicuous, the lobular architecture was maintained relatively well in the non-cirrhotic stage of NASH because of only mildly damaged angioarchitecture of the portal veins. The process of lobular restructuring in NASH is considered to be different from that in chronic viral hepatitis in the non-cirrhotic stage.

Increases in urinary albumin and beta2-microglobulin are independently associated with blood pressure in the Japanese general population: the Takahata Study.

Essential hypertension is a multifactorial disorder and a risk factor for renal failure and cardiovascular disease. Recently it was hypothesized that subtle acquired renal injury such as renal microvascular and tubulointerstitial damage induces salt-sensitive hypertension. The objective of this study was to examine the relationship between blood pressure and renal abnormalities in the Japanese general population. The participants in this community-based, cross-sectional study were 1,965 subjects over 40 years old, without renal insufficiency and antihypertensive medication. Urine albumin-creatinine ratio (UACR) and beta2-microglobulin-creatinine ratio (UBCR) were measured in single spot urine samples, as markers of renal microvascular and tubulointerstitial damage, respectively. Multiple linear regression analysis showed a significant positive correlation of blood pressure with UACR and UBCR, but not with estimated glomerular filtration rate. In multiple logistic regression analysis, the increases in UACR and UBCR were independently associated with hypertension, after adjustment for possible confounders. Higher levels of UACR (≥ 5.9 mg g(-1)) and UBCR (≥ 145 µg g(-1)) were associated with a significantly higher risk of hypertension, compared with UACR ≤ 5.8 mg g(-1) and UBCR ≤ 84.5 µg g(-1), respectively. Furthermore, there was a positive relationship between urinary sodium excretion and blood pressure in subjects with high UBCR tertile. This study showed that the increases in urinary albumin and beta2-microglobulin were independently associated with blood pressure in a general population. These renal abnormalities may be differentially related to the development of hypertension.

Suppressive effects of valsartan on microalbuminuria and CRP in patients with metabolic syndrome (Val-Mets).

The presence of metabolic syndrome (Mets) increases the risk for cardiovascular disease. There is a significant correlation between the levels of urinary albumin to creatinine ratio (UACR) and high-sensitive C-reactive peptide (hs-CRP), and accumulation of each Mets component. Increasing evidence has shown the importance of blockade of renin-angiotensin-systems (RAS) for reducing urinary albumin excretion and hs-CRP levels in Mets patients. However, the impact of RAS blockade on these effects in hypertensive (HT) Mets patients without diabetes mellitus (DM) has not been evaluated. We prospectively measured the levels of UACR and hs-CRP in 153 HT patients with and without Mets. Body weight; waist circumference; presence of dyslipidemia and DM, and levels of HOMA-R, UACR, and hs-CRP were significantly higher in HT patients with Mets than in those without Mets. After we treated these Mets patients with valsartan for 6 months, blood pressure (BP), UACR, and hs-CRP were decreased, whereas body weight, HOMR-R, and the lipid profile were not changed. In HT Mets patients without DM, 6 months after valsartan administration, levels of UACR and hs-CRP were also significantly decreased by 37.8% (-9.0-56.5%, p < 0.05) and 23.6% (-28.7-73.4%, p < 0.05), respectively. However, the percentage change of UACR and hs-CRP was not correlated with the reduction in BP. Valsartan administration lowered increased levels of chronic inflammation in both HT Mets patients with DM and in those without DM. These results indicate that the anti-inflammatory properties of valsartan might also have beneficial effects in Mets patients without DM.

The association between renal tubular damage and rapid renal deterioration in the Japanese population: the Takahata study.

BACKGROUND: Injury to renal tubules plays an important role in the development of various renal diseases; however, the prevalence and significance of renal tubular damage in the general population are unclear. To clarify this point, we conducted a community-based study, using urinary ß(2)-microglobulin as a marker of tubular damage. METHODS: The subjects studied were 3,444 Japanese over the age of 40 years. The urinary ß(2)-microglobulin-creatinine ratio (UBCR) was assessed in morning spot urine samples. RESULTS: In this population, the distribution of the UBCR among these subjects was skewed towards higher values and a high UBCR (≥300 µg/g) was identified in 438 (12.7%) subjects. However, overlap with macroalbuminuria and renal insufficiency [estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2)] was observed in only 25 (5.7%) and 58 (13.2%) of these subjects, respectively. Multivariate analysis indicated that a high UBCR was positively associated with aging, hypertension, macroalbuminuria and increased urinary sodium excretion. A 5-year longitudinal analysis in 899 subjects indicated a greater decline in eGFR in parallel with the increase in baseline UBCR. After adjustment for possible confounders, a high UBCR was an independent risk factor for rapid decline in eGFR [<-10 mL/min/1.73 m(2); odds ratio 1.79 (95% confidence interval 1.07-2.99), P = 0.026]. CONCLUSION: This study showed that renal tubular damage was common and was an independent risk factor for renal deterioration in the Japanese population. More attention should be paid to occult renal tubular damage in order to prevent end-stage renal disease.

The novel and independent association between single-point SNP of NPHP4 gene and renal function in non-diabetic Japanese population: the Takahata study.

Nephronophthisis (NPHP) 4 gene coding nephrocystin-4 is involved in the development of renal tubules and its congenital mutations cause juvenile end-stage renal disease, NPHP. To investigate the association between single-point single-nucleotide polymorphism (SNP) of NPHP4 gene and renal function, we conducted a cross-sectional study in Japanese population. The subjects of this study were non-diabetic general population consisting of 2604 individuals >40 years in Takahata town, Japan. We genotyped 11 SNPs within NPHP4 gene that displayed frequent minor allele frequencies (>0.1) in Japanese general population. Among 11 SNPs in NPHP4 gene, only rs1287637 that induces amino acid substitution (A (Gln)/T (Leu)), located in the acceptor site of exon 21, showed a significant association with estimated glomerular filtration rate (eGFR; T/T: 81.3±15.6 (n=1886), A/T: 82.0±15.5 (n=652) and A/A: 87.4±21.4 ml min(-1) per 1.73m(2) (n=66); mean±s.d., P=0.006). This SNP was not in linkage disequilibrium with the surrounding SNPs. The multivariate analysis adjusted with possible confounders showed that the A/T+T/T genotype of rs1287637 was independently associated with reduced renal function (eGFR <90 ml min(-1) per 1.73m(2); odds ratio (OR) 1.75, 95% confidence interval (CI) 1.05-2.94, P=0.033). These results indicate the novel and independent association between single-point SNP rs1287637 in NPHP4 gene and renal function in non-diabetic Japanese population.

High variability of albuminuria in nondiabetic population: the Takahata Study.

BACKGROUND: Albuminuria is a risk factor for renal and cardiovascular events and shows a quick change reflecting vascular status. The aim of this study is to examine the frequency and related factors of the short-term change of albuminuria in nondiabetic Japanese population. METHODS: The study subjects were 1,378 individuals (mean age 63.9 years) who attended community-based health checkup in 2004 and 2005 in Takahata town. Albuminuria was evaluated by urine albumin creatinine ratio in morning urine and was categorized into four stages (low normal, high normal, and micro- and macroalbuminuria). RESULTS: At baseline, the prevalence of subjects with low normal, high normal, and micro- and macroalbuminuria was 62.3, 17.3, 18.7, and 1.7%, respectively. During 1 year, progression and remission of albuminuria stages were observed in 23.1 and 14.5% of total subjects, respectively. Both progression and remission of albuminuria were frequently detected at every stage, especially in high normal albuminuria (29% in progression and 39% in remission, respectively). On multivariate analysis, the changes of albuminuria were associated with older age, blood pressures, total protein, estimated glomerular filtration rate (GFR), and urine sodium excretion at baseline, start of antidiabetic drugs, changes in body weight (+/-1 kg), hemoglobin (+/-1 g/dl), and urine sodium excretion (+/-50 mEq/day). CONCLUSION: This study revealed that albuminuria showed high variability associated with age and small changes in modifiable risk factors during 1 year. In the treatment and risk analysis of subjects with albuminuria, the effect of these factors should be considered.

Genetic polymorphisms of paraoxonase-1 are associated with chronic kidney disease in Japanese women.

Paraoxonase-1 (PON1) is an HDL cholesterol-associated antioxidant enzyme, and some of its polymorphisms are linked with systemic oxidative stress and cardiovascular events. In this study, we genotyped seven single nucleotide polymorphisms (SNPs) within the PON1 gene and determined their association with chronic kidney disease in 2,968 individuals from the general Japanese population. We found that a missense SNP (rs662) with a G-to-A substitution leading to an amino acid substitution (G[Arg]/A[Gln]), was significantly associated with albuminuria and estimated glomerular filtration rate (eGFR), especially in women. The A/A genotype in women had the highest prevalence of albuminuria and the lowest values of adjusted eGFR. In contrast, such relationships were not detected in men. Multivariate regression analysis found that the A/A genotype was an independent and significant factor for albuminuria and renal insufficiency (eGFR less than 60 ml/min/1.73 m(2)). The serum PON1 activity was lowest in subjects with the A/A genotype. In biopsy specimens, immunohistochemical analysis found increased PON1 expression on the endothelial surface of sclerotic renal arterioles and glomerular capillaries in patients with hypertension or diabetes. Our study shows that this PON1 G-to-A substitution may be a key player in a common pathway to chronic kidney and cardiovascular diseases in women.

In a non-diabetic Japanese population, the combination of macroalbuminuria and increased urine beta 2-microglobulin predicts a decline of renal function: the Takahata study.

BACKGROUND: Glomerular and tubular damage are important factors in the development of renal insufficiency. However, the interaction of these factors is largely unknown in the non-diabetic Japanese population. To clarify the relationship between renal insufficiency and both glomerular and tubular damage, we conducted a community-based study using albuminuria and urine beta 2-microglobulin as markers of glomerular and tubular damages, respectively. METHODS: Subjects of this study were 2816 non-diabetic individuals >40 years old in Takahata, Japan. The urine albumin-creatinine ratio (UACR) and urine beta 2-microglobulin-creatinine ratio (UBCR) were assessed from single spot urine. The glomerular filtration rate (eGFR) was estimated using the abbreviated MDRD equation with a Japanese coefficient. RESULTS: The prevalence of albuminuria (UACR >20 mg/ g in men and >30 mg/g in women), increased UBCR (>300 microg/g) and renal insufficiency (eGFR <60 mL/ min/1.73 m(2)) were 21.0%, 12.5% and 21.7%, respectively, and there was only a small overlap between the three. The mean eGFR was significantly lower in subjects with macroalbuminuria (UACR >200 mg/g in men and >300 mg/g in women) and increased UBCR. No urinary abnormalities were observed in 71.7% of the 611 subjects with renal insufficiency, and were more common in young, women and the non-hypertensive population. The 1-year decline of eGFR was greatest in subjects with an overlap of macroalbuminuria and increased UBCR. CONCLUSIONS: This study indicated that only a small part of renal insufficiency accompanied increased urine albumin or beta 2-microglobulin in the non-diabetic Japanese population. The combination of macroalbuminuria and increased urine beta 2-microglobulin might predict faster renal deterioration.

Factors correlated with plasma renin activity in general Japanese population.

BACKGROUND: The renin-angiotensin-aldosterone system plays a pivotal role in regulation of blood pressure and electrolyte homeostasis and is a target in the treatment of hypertension and renal diseases. However, the factors correlated with plasma renin activity (PRA) are unclarified in general Japanese population. To examine this point, we conducted a community-based cross-sectional study. METHODS: Subjects of this study were 2,056 individuals (mean age, 61 years; 934 men; 1,122 women) over 40-year-old without antihypertensive medication in Takahata town, Japan. PRA was measured by radioimmunoassay. Estimated 24-h urine sodium (e24hUNa) and potassium excretion were calculated from morning spot urine. RESULTS: The median value of PRA was higher in men compared to women (1.1 ng/ml/h vs. 0.7 ng/ml/h, P < 0.001). The increased PRA (>2.0 ng/ml/h) were detected in 248 men (26.3%) and 142 women (12.7%). One-factor analysis of variance showed that PRA was correlated with blood pressure, uric acid, hemoglobin, total protein, total cholesterol, low-density lipoprotein cholesterol, serum adiponectin and e24hUNa in men. In women, PRA was correlated with age, blood pressure, total protein, high-density lipoprotein cholesterol (HDL-C), serum insulin, e24hUNa and obesity. Multivariate logistic regression analysis showed that high PRA (>2.0 ng/ml/h) was independently associated with low blood pressures, low e24UNa and high serum total protein both in men and women, smoking only in men and high HDL-C only in women, respectively. CONCLUSIONS: This study revealed that PRA was higher in men than women and was associated negatively with blood pressures and urine sodium excretion, and positively with total protein, smoking and HDL-C in Japanese population.

Relationship between antinuclear antibody and microalbuminuria in the general population: the Takahata study.

BACKGROUND: Microalbuminuria, a marker of vascular damage, is associated with increased risk of progressive renal deterioration, cardiovascular disease and mortality. However, the relationship between antinuclear antibody (ANA) and microalbuminuria in the general population is unknown. Thus, we conducted a cross-sectional study to examine the relationship between ANA and microalbuminuria. METHODS: The subjects of this community-based study were individuals over 40 years old in Takahata, Japan. The urine albumin-creatinine ratio (UACR) was calculated from a single-spot urine specimen collected in the morning. ANA was examined by enzyme immunoassay (EIA). RESULTS: Among the 2,875 subjects (mean age 63 years; men 1,276; women 1,599), positive ANA (ANA index >or=20.0) was detected in 16.9% of the total population (men 12.9%, women 20.3%) and the prevalence of positive ANA increased with age. The prevalence of microalbuminuria (UACR 30-300 mg/g), but not macroalbuminuria (UACR > 300 mg/g), was significantly higher in the positive ANA group than the negative ANA group (24.1% vs. 16.0%, respectively, P < 0.001). Along with the increase of the ANA index, the prevalence of microalbuminuria and UACR levels were increased. Multivariate logistic regression analyses showed that ANA was significantly associated with microalbuminuria (odds ratio [OR] 1.63 and 95% confidence interval [95%CI] 1.27-2.10). These associations were significant in women, but not men, when examined separately. CONCLUSIONS: These results indicate that the presence of ANA is associated with microalbuminuria in the general population, especially women.