Kunitoshi Iseki

A slight increase within the normal range of serum uric acid and the decline in renal function: associations in a community-based population

BACKGROUNDnHyperuricemia is a risk factor for adverse renal outcomes in patients with chronic kidney disease. This study investigated the effect of uric acid on renal function in a community-based population.nnnMETHODSnWe used a nationwide database of 165 847 subjects (aged 29-74, male 40%) who participated in the annual Specific Health Check and Guidance in Japan checkup between 2008 and 2010; we examined the relationship between serum uric acid levels at baseline and 2-year change in the estimated glomerular filtration rate (eGFR) obtained by using the Japanese equation.nnnRESULTSnAfter adjusting for possible confounders, the eGFR change was inversely correlated with uric acid at baseline. In the multivariable analysis, the decline in eGFR was significantly more rapid in subjects with the slight increase in uric acid (males ≥5.7 mg/dL, females ≥4.4 mg/dL), and the risk for incidental renal insufficiency (eGFR <60 mL/min/1.73 m(2)) was increased at uric acid of ≥6.3 mg/dL in males and ≥5.5 mg/dL in females, compared with the lowest quintile. The multiple linear regression analysis revealed that the effect of uric acid on eGFR changes was significant, especially in females, those with proteinuria and diabetes and those without alcohol consumption.nnnCONCLUSIONnThis study showed that serum uric acid is independently associated with a more rapid decline of eGFR and incident renal insufficiency, and that a slight increase within the normal range of serum uric acid might be a risk for renal damage in the general population.

Blood Pressure, Proteinuria, and Renal Function Decline: Associations in a Large Community-Based Population

BACKGROUNDnHypertension and proteinuria are risk factors for adverse renal outcomes in patients with chronic kidney disease. This study investigated the associations of blood pressure and proteinuria on renal function in a community-based population.nnnMETHODSnWe analyzed data from a nationwide database of 141,514 subjects who participated in the annual Specific Health Check and Guidance in Japan checkup in 2008 and 2010. The study subjects were aged between 29 and 74 years, and the cohort comprised 40% men. We examined relationships between blood pressure levels, proteinuria at baseline, and the 2-year change in the estimated glomerular filtration rate (eGFR), which was determined using the Japanese equation.nnnRESULTSnAfter adjusting for possible confounders, the change in the eGFR was inversely correlated with systolic blood pressure (SBP), but not diastolic blood pressure (DBP), at baseline, irrespective of the presence of proteinuria. Compared with the lowest SBP sixtile (≤118mm Hg), eGFRs declined significantly at SBPs ≥ 134mm Hg in subjects with proteinuria, while eGFRs declined significantly at SBPs ≥ 141mm Hg in those without proteinuria. At the same SBPs, renal function decline was faster and the risk for incident renal insufficiency was higher in subjects with proteinuria compared with those without proteinuria.nnnCONCLUSIONSnThis study showed that a difference in SBP, but not DBP, is independently associated with a rapid eGFR decline in the general Japanese population, and that the association of SBP on the decline of renal function was greater in subjects with proteinuria compared with those without proteinuria.

Inflammation as a Risk of Developing Chronic Kidney Disease in Rheumatoid Arthritis

Objective The relationship between chronic inflammation and the incidence of chronic kidney disease (CKD) remained not-clear in patients with rheumatoid arthritis (RA). This study aims to examine the relationship between persistently high C-reactive protein (CRP), a marker of inflammation, and the incidence of CKD in RA. Methods We retrospectively examined the relationship between the levels of CRP and incidence of CKD in 345 RA patients. The outcome of interest was incidence of CKD, defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 and/or positive dipstick testing for proteinuria for ≥3 months. We defined high CRP, as >3.0 mg/L. On the basis of three measurements of CRP for 6-months period, patients were divided into three groups: group 1, including patients with no high CRP values; group 2, patients with transient high CRP values (once or twice) and group 3, patients with persistently high CRP values. Results During a median follow-up period of 89 months, 14% of all patients developed CKD. The cumulative incidence of CKD was 7% in group 1, 14% in group 2 and 22% in group 3 (P = 0.008, log-rank test). In a multivariate analysis, including classical risk factors for CKD, persistently high CRP was an independent predictor of the incidence of CKD (hazard ratio, 3.00; 95% confidence interval, 1.23–8.53; P = 0.01). Conclusions Persistently high CRP was a significant risk factor for the incidence of CKD. Results suggest that persistent inflammation is a marker for the high risk of CKD in RA.

Observation period for changes in proteinuria and risk prediction of end-stage renal disease in general population

Proteinuria is known to be an independent risk factor of end‐stage renal disease (ESRD). But the associations between changes in dipstick proteinuria and the risk of ESRD in the general population and its appropriate observation period to predict incident ESRD are unknown.

Importance of glomerular filtration rate change as surrogate endpoint for the future incidence of end-stage renal disease in general Japanese population: community-based cohort study

BackgroundBecause of the necessity for extended period and large costs until the event occurs, surrogate endpoints are indispensable for implementation of clinical studies to improve chronic kidney disease (CKD) patients’ prognosis.MethodsSubjects with serum creatinine level for a baseline period over 1–3xa0years were enrolled (nxa0=xa069,238) in this community-based prospective cohort study in Okinawa, Japan, and followed up for 15xa0years. The endpoint was end-stage renal disease (ESRD). The percent of estimated glomerular filtration rate (%eGFR) change was calculated on the basis of the baseline period.ResultsSubjects had a meanxa0±xa0SD age, 55.59xa0±xa014.69xa0years; eGFR, 80.15xa0±xa021.15xa0ml/min/1.73xa0m2. Among the subjects recruited, 15.81% had a low eGFR (<60xa0ml/min/1.73xa0m2) and 36.1/100,000 person years developed ESRD. Cox proportional hazards models adjusted for baseline characteristics showed that the risk of ESRD tended to be high with high rates of decrease in %eGFR changes over 2 or 3xa0years in the high- and low-eGFR groups. The specificities and positive predictive values for ESRD based on a cutoff value of %eGFR change of less than −30% over 2 or 3xa0years were high in the high- and low-eGFR groups.Conclusions%eGFR change tends to be associated with the risk of ESRD. %eGFR change of less than −30% over 2 or 3xa0years can be a candidate surrogate endpoint for ESRD in the general Japanese population.

Chronic kidney disease, inflammation, and cardiovascular disease risk in rheumatoid arthritis

BACKGROUNDnRheumatoid arthritis (RA), a prototypic systemic autoimmune inflammatory condition, confers an increased risk of cardiovascular disease (CVD). Recently, chronic kidney disease (CKD) was suggested to increase the risk of CVD in RA patients, and inflammation was identified as a critical, nontraditional CKD-associated risk factor for CVD. This study aimed to examine the combined effects of CKD and CVD in RA patients.nnnMETHODSnIn this retrospective evaluation of 428 RA patients, the outcome of interest was the incidence of CVD. CKD was defined as an estimated glomerular filtration rate of <60mL/min/1.73m2 and/or positive dipstick tests for proteinuria of ≥3 months duration. C-reactive protein (CRP) was used as an inflammation marker, and a high CRP level was defined as a mean CRP value of ≥0.57mg/dL during the first 6 months of follow-up. Patients were categorized as follows: non-CKD with low CRP, non-CKD with high CRP, CKD with low CRP, and CKD with high CRP.nnnRESULTSnDuring a median follow-up of 89 months, 67 patients (16%) had CKD, and 38 (9%) developed CVD. Using patients with non-CKD and low CRP as a reference group, the adjusted hazard ratios (HR, 95% confidence interval) for CVD were 1.88 (0.25-9.44) for patients with CKD/low CRP and 9.71 (3.27-31.97) for those with CKD/high CRP.nnnCONCLUSIONSnThe coexistence of CKD and inflammation was associated with a higher risk of CVD than either condition alone in RA patients. Inflammation might increase the risk of CVD especially in patients with CKD.

Nephrology and Nutrition Leaders Coming to Hawaii for the World Renal Nutrition Week: Why is the 16th Congress in Renal Nutrition and Metabolism in Honolulu, Hawai’i, June 2012, Worth Attending?

RECENT ADVANCES IN our understanding of, and approach to, caring for patients with kidney disease and their nutritional and dietary management are expected to have unprecedented impact on the current and future status of nephrology and nutrition practice throughout the world. To this end, the International Society of Renal Nutrition and Metabolism (ISRNM, www.RenalNutrition.com) and the Council of Renal Nutrition (CRN) of the National Kidney Foundation (NKF), in collaboration with several professional societies in different countries, have joined together to expand the 16th International Congress in Renal Nutrition and Metabolism into the 1st World Renal Nutrition Week during June 26 to 30, 2012. The beautiful Hawaiian main island is the location of the World Renal Nutrition Week upon gracious agreement of the NKF of Hawaii to serve as the local host of the

Association of dipstick hematuria with all-cause mortality in the general population: results from the specific health check and guidance program in Japan

BackgroundnDipstick urine tests are used for general health screening in Japan. The effects of this screening on mortality have not been examined, especially with regard to hematuria.nnnMethodsnSubjects were those who participated in the 2008 Tokutei-Kenshin (nationwide specific health check and guidance program) in six districts in Japan. Using the national database of death certificates from 2008 to 2012, we identified subjects who might have died. We verified the candidates in collaboration with the regional National Health Insurance agency and public health nurses. Data were released to the research team supported by the Ministry of Health, Labor, and Welfare of Japan. Dipstick results of 1+ and higher were defined as hematuria (+). Hazard ratio (HR) [95% confidence interval (CI)] was calculated using the Cox proportional hazard analysis.nnnResultsnAmong 112u2009115 subjects, we identified that 1290 had died by the end of 2012. In hematuria (-) subjects, the crude mortality rates were 1.2% (1.8% in men, 0.7% in women), whereas in hematuria (+) subjects, they were 1.1% (2.9% in men, 0.7% in women). After adjusting for age, body mass index, estimated glomerular filtration rate, proteinuria, comorbid condition (diabetes mellitus, hypertension and dyslipidemia), past history (stroke, heart disease and kidney disease) and lifestyle (smoking, drinking, walking and exercise), the HR (95% CI) for dipstick hematuria (+) in men was 1.464 (1.147-1.846; Pu2009=u20090.003), whereas that for hematuria (-) was 0.820 (0.617-1.073; Pu2009=u20090.151).nnnConclusionsnDipstick hematuria is significantly associated with mortality in men among Japanese community-based screening participants.

Glucosuria and all-cause mortality among general screening participants

BackgroundDipstick urine tests are used for general health screening in Japan, but how the test results (e.g., glucosuria) relate to mortality is unknown.MethodsSubjects participated in a nationwide screening in 2008 in six districts in Japan. We identified those who might have died using the national database of death certificates from 2008 to 2012 (total registeredu2009~u20096xa0million) and verified candidates with the regional National Health Insurance Agency and public health nurses. Diabetes mellitus (DM) was defined as HbA1cu2009≥u20096.5%, fasting blood glucoseu2009≥u2009126xa0mg/dl, or medicated for DM. Hazard ratio (HR) and 95% confidence interval (CI) were calculated by Cox proportional hazard analysis. Glucosuria was defined as dipsticku2009≥u20091xa0+.ResultsAmong 209,060 subjects, we identified 2714 fatalities (median follow-up 3.57xa0years). Crude mortality rates were 1.2% for those without glucosuria and 3.4% for those with glucosuria. After adjusting for sex, age, body mass index, comorbidity (DM, hypertension, and dyslipidemia), history (stroke, heart disease, and kidney disease), and lifestyle (smoking, drinking, walking, and exercise), the HR (95% CI) for dipstick glucosuria was 1.475 (1.166–1.849, Pu2009<u20090.001). DM subjects with glucosuria (Nu2009=u20094655) had a higher HR [1.302 (1.044–1.613, Pu2009=u20090.020)] than DM subjects without glucosuria (Nu2009=u200920,245), and non-DM subjects with glucosuria (Nu2009=u2009470) had a higher HR [2.511 (1.539–3.833, Pu2009<u20090.001)] than non-DM subjects without glucosuria (Nu2009=u2009183,690).ConclusionDipstick glucosuria significantly affected mortality in Japanese community-based screening participants.

Comparison of albuminuria test and urine test strip in Japanese hypertensive patients: AVA-E study.

BACKGROUNDnAlbuminuria is thought to reflect generalized endothelial dysfunction. In hypertensive patients, albuminuria is related to the risk for cardiovascular disease (CVD) events. Thus, screening for albuminuria is critical for risk stratification in hypertensive patients. However, the actual state of albuminuria in Japanese patients without diabetes remains unclear due to insurance coverage.nnnMETHODSnThe CLINITEK microalb creatinine test® is a urine test paper that can assess albumin excretion corrected for urine creatinine levels in only 60 seconds without any special equipment. The semi-quantitative albuminuria test and urine proteinuria test were performed on 8,181 Japanese hypertensive patients, and the clinical significance of the test was evaluated by comparison with the urine test strip method.nnnRESULTSnAlbumin creatinine ratio (ACR) < 30 mg/g creatinine, ACR 30 - 299 mg/g creatinine, and ACR ≥ 300 mg/g creatinine on the albuminuria test were present in 70.0%, 25.7%, and 4.3%, respectively, of patients with a negative urine protein test strip result. Furthermore, in patients with a negative urine protein test strip result, ACR ≥ 30 mg/g creatinine was independently associated with previous CVD (odds ratio: 1.25, 95% confidence interval: 1.00 - 1.57, p < 0.05) after adjustment for estimated glomerular filtration rate, age, sex, BMI, smoking, dyslipidemia, diabetes, and blood pressure categories on multivariate logistic regression analysis.nnnCONCLUSIONSnWe considered that urine test strip was inadequate test to evaluate albuminuria. Easy and quick albuminuria test on the CLINITEK MICROALB CREATININE TEST might be useful test to risk stratification of hypertensive patients compared to urine test strip.