Plasma B-type natriuretic peptide is independently associated with cardiovascular events and mortality in patients with chronic kidney disease.

The association between B-type natriuretic peptide (BNP) and cardiovascular (CV) events and mortality has not been well characterized in patients with chronic kidney disease (CKD). We prospectively investigated whether BNP was associated with CV events or mortality beyond cardiac alterations in 1078 patients with CKD. Participants were divided into the following 3 groups according to circulating BNP concentration: < 40 pg/mL, low; 40-100 pg/mL, middle; and > 100 pg/mL, high. Primary outcome was fatal or nonfatal CV events, and alternative outcome was a composite of fatal or nonfatal CV events, or non-CV deaths. During a median follow-up of 2.6 years, CV and composite events occurred in 158 and 248 participants, respectively. Cox analyses after adjustment for covariates, including cardiac parameters, showed that the hazard ratios (HRs) (95% confidence intervals [CIs]) for CV events of middle and high groups were 1.00 (0.63, 1.58) and 1.72 (1.06, 2.79), respectively, compared with low group. Additionally, similar results were obtained for composite events; the HRs (95% CIs) of middle and high groups were 1.10 (0.77, 1.57) and 1.54 (1.04, 2.27), respectively, compared with low group. Thus, in CKD, high BNP concentrations were independently associated with CV events and mortality, independent of cardiac alterations.

Association between iron status markers and kidney outcome in patients with chronic kidney disease.

Several studies conducted in patients with various stages of chronic kidney disease (CKD) have investigated the association of iron status markers, such as transferrin saturation (TSAT) and serum ferritin, with kidney outcomes. However, the associations were inconsistent and remain strongly debated. Therefore, we aimed to investigate whether TSAT and serum ferritin levels were associated with kidney outcome in such a population. In this study, 890 patients who were admitted for the evaluation of and education for CKD were prospectively followed. Primary kidney outcome was a composite of doubling of serum creatinine, end-stage kidney disease, or death due to kidney failure. Participants were divided into quartiles (Q1-Q4) according to TSAT or serum ferritin levels. During a median follow-up period of 2.8 years, kidney events occurred in 358 patients. In the multivariable Cox analyses, compared with Q3 of TSAT, the hazard ratios (95% confidence intervals) for Q1, Q2, and Q4 were 1.20 (0.87, 1.66), 1.38 (1.01, 1.87), and 1.14 (0.82, 1.59), respectively. Compared with Q2 of serum ferritin, lower and higher quartiles had a significantly increased risk for kidney outcome; hazard ratios (95% confidence intervals) for Q1, Q3, and Q4 were 1.64 (1.18, 2.27), 1.71 (1.24, 2.37), and 1.52 (1.10, 2.10), respectively. A Fine-Gray model with death before kidney events as a competing risk showed results similar to the above. In CKD, lower and higher ferritin levels were independent risk factors for kidney disease progression.

Sex differences in the association between urate metabolism and kidney outcomes in patients with chronic kidney disease.

BACKGROUND: The association between serum uric acid (SUA) concentration and kidney outcomes in patients with chronic kidney disease (CKD) is controversial. Furthermore, there are no reports regarding the association of clearance of uric acid (CUA) with kidney outcomes. We aimed to determine whether SUA or CUA was associated with kidney outcomes in patients with CKD stratified by sex. METHODS: The present prospective study was conducted in 815 patients (523 men and 292 women) with CKD. The participants were divided into quartiles (Q1-Q4) of SUA or CUA for each sex. Endpoints were defined as a composite of doubling of serum creatinine (SCr), end-stage kidney disease (ESKD), or death (outcome 1) and a composite of doubling of SCr or ESKD (outcome 2). RESULTS: During a median follow-up of 2.5 years, outcomes 1 and 2 occurred in 363 and 321 patients, respectively. Multivariable-adjusted Cox analyses showed that in men, the hazard ratios (95% confidence intervals) for outcome 1 of Q1, Q2, and Q3 of CUA were 2.08 (1.18-3.70), 2.03 (1.22-3.39), and 1.85 (1.17-2.95), respectively, compared with Q4. Additionally, there were similar associations between lower CUA quartiles and outcome 2 in men. However, no associations between SUA and either outcome were observed in men. Conversely, in women, neither SUA nor CUA was associated with an outcome. CONCLUSION: In CKD, lower CUA was independently associated with poor kidney outcomes only in men, and in both sexes, there was no association of SUA with kidney outcomes.

The Association of Controlling Nutritional Status Score and Prognostic Nutritional Index with Cardiovascular Diseases: the Fukuoka Kidney Disease Registry Study.

AIM: The Controlling Nutritional Status (CONUT) score and the Prognostic Nutritional Index (PNI) reflect the immunonutritional status of patients. However, the associations of these two indices with cardiovascular disease (CVD) have not been characterized in patients with chronic kidney disease (CKD). Therefore, the current study aimed to determine whether the CONUT score or PNI was associated with prior CVD in patients with CKD. METHODS: A cross-sectional study of 2,751 patients with CKD who were not on dialysis was performed. The patients were grouped into tertiles (T1-T3) of PNI and placed into three groups following their CONUT score: low- (CONUT score, 0), mild- (CONUT score, 1-2), and moderate-to-high- (CONUT score, ≥ 3) risk groups. RESULTS: Prior CVD was present in 655 (24%) of the participants. Multivariable logistic regression analyses, with adjustment for potential confounders, showed that high CONUT score was associated with prior CVD than the low score (mild-risk group: odds ratio [OR]=1.35, 95% confidence interval [CI]=1.04-1.76; moderate-to-high-risk group: OR=1.66, 95% CI=1.19-2.30). In addition, the lower PNI tertiles were independently associated with prior CVD compared with T3 of PNI (T1: OR=1.45, 95% CI=1.09-1.92; T2: OR=1.32, 95% CI=1.01-1.72). CONCLUSIONS: Both CONUT score and PNI were found to be independently associated with prior CVD in patients with CKD in the present cross-sectional study. A longitudinal study is needed to elucidate whether these two indices are associated with subsequent cardiovascular events.

Low plasma renin activity is independently associated with kidney disease progression in patients with type 2 diabetes and overt nephropathy, including those with impaired kidney function: a 2-year prospective study.

Plasma renin activity (PRA) is lower in patients with diabetic nephropathy (DN) than in healthy individuals. However, the association, if any, between PRA and renal outcomes in patients with DN remains uncertain. In a 2-year prospective observational study, we aimed to investigate the association of PRA with the decline in kidney function in patients with DN. We studied 97 patients with DN who were categorized according to tertile (T1-T3) of PRA. The annual changes in estimated glomerular filtration rate (eGFR) (mL/min/1.73 m2/year) were determined from the slope of the linear regression curve for eGFR. The secondary endpoint was defined as a composite of the doubling of serum creatinine or end-stage renal disease. Results showed that kidney function rapidly declined with lower tertiles of PRA (median value [interquartile range] of the annual eGFR changes: -8.8 [-18.5 to -4.2] for T1, -8.0 [-14.3 to -3.2] for T2, and -3.1 [-6.3 to -2.0] for T3; p for trend <0.01). Multivariable linear regression analyses showed that, compared with T3, T1 was associated with a larger annual change in eGFR (coefficient, -4.410; 95% confidence interval [CI], -7.910 to -0.909 for T1). Composite renal events occurred in 46 participants. In multivariable Cox analysis, the lower tertiles of PRA (T1 and T2) were associated with higher incidences of the composite renal outcome (T2: hazard ratio [HR], 4.78; 95% CI, 1.64-13.89; T1: HR, 4.85; 95% CI 1.61-14.65) than T3. In conclusion, low PRA is independently associated with poor renal outcomes in patients with DN.

Association between the urinary sodium-to-potassium ratio and renal outcomes in patients with chronic kidney disease: a prospective cohort study.

A higher urinary sodium-to-potassium (UNa/K) ratio has been reported to be associated with high blood pressure and subsequent cardiovascular events. However, the association between the UNa/K ratio and renal outcomes remains uncertain. We prospectively investigated the association between the UNa/K ratio and renal outcomes in patients with chronic kidney disease (CKD). We enrolled 716 patients with CKD, and 24-h urinary sodium and potassium excretion were measured. Patients were divided into UNa/K ratio tertiles (T1-T3). Endpoints were defined as a composite of doubling of serum creatinine (SCr), end-stage kidney disease (ESKD), or death and a composite of doubling of SCr or ESKD (added as an alternative outcome). We investigated the association between the UNa/K ratio and renal outcomes using a Cox proportional hazards model. During a median follow-up of 2.3 years, doubling of SCr, ESKD, or death and doubling of SCr or ESKD occurred in 332 and 293 patients, respectively. After adjustment for covariates including potentially confounding variables such as plasma renin activity, plasma aldosterone concentration, and B-type natriuretic peptide, the hazard ratios (HRs) (95% confidence intervals [CIs]) for the composite of doubling of SCr, ESKD, or death for T2 and T3 were 1.44 (1.06-1.96) and 1.59 (1.14-2.21), respectively, compared with T1. Additionally, compared with T1, the highest tertile (T3) of the UNa/K ratio was associated with a composite of doubling of SCr or ESKD (HR 1.55, 95% CI 1.09-2.20). A higher UNa/K ratio was independently associated with poor renal outcomes in patients with CKD.

Subclinical hypothyroidism is independently associated with poor renal outcomes in patients with chronic kidney disease.

PURPOSE: It remains unclear whether subclinical hypothyroidism (SCH) is associated with renal prognosis in patients with chronic kidney disease (CKD). Therefore, we prospectively investigated the association of SCH with renal outcomes in CKD. METHODS: We conducted a prospective observational study of 480 euthyroid patients and 89 patients with SCH. The endpoints were defined as a composite of doubling of serum creatinine (SCr), end-stage renal disease (ESRD), or death, and a composite of doubling of SCr or ESRD was added as an alternative outcome. Logistic regression analyses were used to identify the factors associated with SCH. In addition, a Cox proportional hazards model was performed to determine whether SCH was associated with poor renal outcomes. RESULTS: During a median follow-up period of 26.1 months, doubling of SCr, ESRD, or death and doubling of SCr or ESRD occurred in 244 and 213 patients, respectively. In univariable logistic regression analyses, SCH was significantly associated with older age, lower hemoglobin, higher proteinuria, lower estimated glomerular filtration rate (eGFR), and higher log B-type natriuretic peptide (BNP). Multivariable Cox analyses showed that SCH was associated with poorer renal outcomes after adjustment for covariates, including eGFR and log BNP [doubling of SCr, ESRD, or death: hazard ratio (HR) 1.61, 95% confidence interval (CI), 1.16-2.23; doubling of SCr or ESRD: HR 1.53, 95% CI 1.07-2.20], compared with euthyroidism. CONCLUSIONS: In CKD, SCH is independently associated with poor renal outcomes, suggesting that screening for SCH might be needed to accurately predict renal prognosis.

Association between urinary salt excretion and albuminuria in Japanese patients with chronic kidney disease: the Fukuoka kidney disease registry study.

BACKGROUND: Several large population-based studies have demonstrated that urinary salt excretion (USALT) is associated with albuminuria. However, this relationship has not been assessed in a large cohort study of patients with chronic kidney disease (CKD). Thus, the present study aimed to elucidate whether USALT was independently associated with albuminuria in a large cohort of patients with CKD. METHODS: This cross-sectional study was conducted in 4075 patients with CKD not on dialysis. USALT (g/day) was estimated from spot urine. Patients were divided into quartiles (Q1-Q4) according to estimated USALT. Multivariable regression models were used to determine whether USALT was independently related to urinary albumin-to-creatinine ratio (UACR) or the presence of macroalbuminuria. RESULTS: In multivariable linear regression analyses, 1-g/day increment in USALT was significantly associated with log UACR [coefficient 0.098, 95% confidence interval (CI) 0.075-0.121]. In addition, compared with the first USALT quartile, the third and fourth quartiles exhibited significant associations with log UACR (Q3: coefficient 0.305, 95% CI 0.154-0.456; Q4: coefficient 0.601, 95% CI 0.447-0.756). Furthermore, multivariable logistic regression analyses showed that USALT (1-g/day increment) was significantly associated with the presence of macroalbuminuria [odds ratio (OR) 1.11, 95% CI 1.07-1.14]; the third and fourth USALT quartiles exhibited significantly greater risks of macroalbuminuria, compared with the first quartile (Q3: OR 1.33, 95% CI 1.09-1.62; Q4: OR 1.89, 95% CI 1.54-2.32). CONCLUSIONS: This significant association of USALT with UACR and macroalbuminuria suggests that higher USALT may cause increased albuminuria, thereby contributing to kidney disease progression.

Association of aortic valve calcification with carotid artery lesions and peripheral artery disease in patients with chronic kidney disease: a cross-sectional study.

BACKGROUND: Patients with chronic kidney disease (CKD) reportedly have a high prevalence of aortic valve calcification (AVC). In population-based studies, AVC is considered a manifestation of systemic atherosclerosis. The association of AVC with atherosclerotic lesions has not been fully investigated in predialysis patients. The present study was performed to determine whether carotid artery lesions and peripheral artery disease (PAD) are associated with AVC in patients with CKD not on dialysis. METHODS: In total, 749 patients were included in this cross-sectional study. AVC was evaluated using echocardiography. Carotid artery lesions including carotid artery plaque (CAP) and PAD were simultaneously examined in each patient. A logistic regression analysis was applied to determine the factors associated with AVC. RESULTS: AVC, CAP, and PAD were found in 201, 583, and 123 patients, respectively. In the multivariable analyses adjusted for covariates including the estimated glomerular filtration rate and makers of mineral metabolism (serum calcium, serum phosphorus, parathyroid hormone, 1,25-dihydroxyvitamin D, and fibroblast growth factor 23), AVC was significantly associated with the presence of CAP [odds ratio (OR), 3.37; 95% confidence interval (CI), 1.43-7.95], the presence of PAD (OR, 1.76; 95% CI, 1.10-2.81), the CAP score (per 1.0-point increase) (OR, 1.06; 95% CI, 1.02-1.11), and the ankle-brachial blood pressure index (per 0.1-point increase) (OR, 0.83; 95% CI, 0.72-0.95). CONCLUSIONS: AVC was associated with atherosclerotic lesions independent of kidney function and mineral metabolism. We consider that this association between AVC and atherosclerosis might reflect the burden of shared atherosclerotic risk factors.

High neutrophil/lymphocyte ratio is associated with poor renal outcomes in Japanese patients with chronic kidney disease.

BACKGROUND: Several studies have shown that the neutrophil/lymphocyte ratio (NLR) is a marker that reflects the state of systemic inflammation. A high NLR was reported to be associated with cardiovascular events and mortality. However, little is known about the association between NLR and kidney disease progression in patients with chronic kidney disease (CKD). Therefore, the aim of the present study was to determine whether NLR is associated with renal outcomes in CKD patients. METHODS: This prospective observational study included 350 consecutive patients with stage 1-4 CKD treated between June 2009 and November 2016. Data were collected until June 2017. The endpoint was the composite of end-stage renal disease requiring dialysis or death. Subjects were divided into two groups according to high and low NLR levels. A Cox proportional hazards model was used to determine the risk factors for composite outcomes. RESULTS: The composite endpoint was observed in 83 patients during the median follow-up period of 31.8 months: 29 in the low NLR group and 54 in the high NLR group. Multivariable analysis showed that the high NLR group had a significant increase in the hazard ratio (HR) for composite outcomes (HR 1.67, 95% confidence interval 1.02-2.77) compared with the low NLR group. CONCLUSION: The present study demonstrated that a high NLR was associated with poor renal outcomes, suggesting that NLR may be a useful marker for prognostic prediction in patients with CKD.

Blood urea nitrogen is independently associated with renal outcomes in Japanese patients with stage 3-5 chronic kidney disease: a prospective observational study.

BACKGROUND: Blood urea nitrogen (BUN) is one of the substances that affects the calculated serum osmolality (cSosm). A previous study demonstrated that BUN and cSosm were independently associated with the development of chronic kidney disease (CKD) in patients with preserved kidney function. In advanced CKD stages, there is a concomitant increase in cSosm and BUN levels. However, it remains unclear whether BUN or cSosm levels are related to renal outcomes in patients with moderate to severe kidney dysfunction. The aim of this study was to clarify whether the BUN or cSosm level is associated with kidney disease progression in patients with advanced CKD. METHODS: In this prospective study, we enrolled 459 patients with CKD (stages 3-5). The composite renal endpoint was end-stage renal disease (ESRD) or death, and ESRD alone was added as an alternative outcome. A Cox proportional hazards model was utilized to determine the risk factors for a poor renal outcome. We adjusted for covariates including estimated glomerular filtration rate (eGFR). The cSosm (mOsm/kg) was calculated using the following formula: (2 × sodium) + (BUN/2.8) + (glucose/18). RESULTS: During a median follow-up of 25.8 months, the renal endpoint was observed in 210 patients. Multivariable Cox analysis determined the hazard ratio (HR) [95% confidence interval (CI)] for the composite renal outcome in the second, third, and fourth BUN quartiles were 1.36 (0.72-2.58), 1.87 (0.95-3.66), and 2.66 (1.23-5.76) (P for trend < 0.01), respectively compared with the first BUN quartile. Conversely, by multivariable Cox analysis, the HRs (95% CIs) for poor outcomes in the second, third, and fourth cSosm quartiles, compared with the first cSosm quartile, were 1.13 (0.69-1.87), 0.95 (0.58-1.55), and 1.26 (0.78-2.03), respectively (P for trend = 0.39). In addition, with regard to the renal outcome of ESRD alone, higher BUN quartiles had a significantly increased risk for the outcome, but cSosm levels were not associated with the outcome. CONCLUSIONS: Higher BUN levels, but not cSosm levels, were associated with adverse renal outcomes independent of the eGFR, suggesting that BUN may be a useful marker for predicting kidney disease progression.

Modified Creatinine Index and the Risk of Bone Fracture in Patients Undergoing Hemodialysis: The Q-Cohort Study.

BACKGROUND: Hemodialysis patients are at increased risk for bone fracture and sarcopenia. There is close interplay between skeletal muscle and bone. However, it is still unclear whether lower skeletal muscle mass increases the risk for bone fracture. STUDY DESIGN: Cross-sectional study and prospective longitudinal cohort study. SETTING & PARTICIPANTS: An independent cohort of 78 hemodialysis patients in the cross-sectional study and 3,030 prevalent patients undergoing maintenance hemodialysis prospectively followed up for 4 years. PREDICTOR: Skeletal muscle mass measured by bioelectrical impedance analysis (BIA) and modified creatinine index, an estimate of skeletal muscle mass based on age, sex, Kt/V for urea, and serum creatinine level. OUTCOMES: Bone fracture at any site. RESULTS: In the cross-sectional study, modified creatinine index was significantly correlated with skeletal muscle mass measured by BIA. During a median follow-up of 3.9 years, 140 patients had bone fracture. When patients were divided into sex-specific quartiles based on modified creatinine index, risk for bone fracture estimated by a Fine-Gray proportional subdistribution hazards model with all-cause death as a competing risk was significantly higher in the lower modified creatinine index quartiles (Q1 and Q2) compared to the highest modified creatinine index quartile (Q4) as the reference value in both sexes (multivariable-adjusted HRs for men were 7.81 [95% CI, 2.63-23.26], 5.48 [95% CI, 2.08-14.40], 2.24 [95% CI, 0.72-7.00], and 1.00 [P for trend < 0.001], and for women were 4.44 [95% CI, 1.50-13.11], 2.33 [95% CI, 0.86-6.31], 1.96 [95% CI, 0.82-4.65], and 1.00 [P for trend = 0.007] for Q1, Q2, Q3, and Q4, respectively). LIMITATIONS: One-time assessment of modified creatinine index; no data for residual kidney function and fracture sites and causes. CONCLUSIONS: Modified creatinine index was correlated with skeletal muscle mass measured by BIA. Lower modified creatinine index was associated with increased risk for bone fracture in male and female hemodialysis patients.

Comparison of Prognostic Values of Daytime and Night-Time Systolic Blood Pressures on Renal Outcomes in Patients With Chronic Kidney Disease.

BACKGROUND: Differences in the predictive value of daytime systolic blood pressure (SBP) and night-time SBP by ambulatory blood pressure monitoring on renal outcomes have not been fully investigated in chronic kidney disease (CKD) patients. This study compared the prognostic value between daytime and night-time SBP on renal outcomes in CKD.Methods and Results:This prospective observational study included 421 patients. The composite renal endpoint was endstage renal disease (ESRD) or death. Cox models were used to determine associations of daytime and night-time SBP with renal outcomes. There were 150 renal events (ESRD, 130; death, 20). Multivariable Cox analyses demonstrated that hazard ratios (HRs) [95% confidence interval (CI)] for composite renal outcomes of every 10-mmHg increase in daytime and night-time SBP levels were 1.13 (1.02-1.26) (P=0.02) and 1.15 (1.05-1.27) (P<0.01), respectively. In addition, compared with the 1st daytime or night-time SBP quartile, HRs (95% CI) for outcomes in the 2nd, 3rd, and 4th quartiles were: daytime SBP, 1.25 (0.70-2.25), 1.09 (0.61-1.94), and 1.58 (0.88-2.85; P=0.13) (P for trend=0.16); night-time SBP, 1.09 (0.61-1.96), 1.31 (0.76-2.28), and 1.82 (1.00-3.30; P=0.049) (P for trend=0.03), respectively. CONCLUSIONS: Night-time SBP appeared superior to daytime SBP for predicting renal outcomes in this population of patients.

Associations of fibroblast growth factor 23 with urate metabolism in patients with chronic kidney disease.

OBJECTIVE: In patients with preserved kidney function, a positive association of fibroblast growth factor 23 (FGF23) with serum uric acid (SUA) has been reported; however, the relationship in overall chronic kidney disease (CKD) patients has not been investigated. No report has examined the relationship between FGF23 and uric acid clearance (CUA). The aim of the present study was to determine whether FGF23 is independently associated with urate metabolism in patients with CKD stages 1-5. MATERIALS AND METHODS: In this cross-sectional study, 537 CKD patients were enrolled. SUA, CUA, FGF23, parathyroid hormone (PTH), and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured. Multivariable linear regression analysis was applied to determine independent factors associated with SUA or CUA. RESULTS: In all patients, both SUA and CUA were independently associated with male sex, use of diuretics, use of uric acid-lowering agents, estimated glomerular filtration rate, and log FGF23 (ß=0.29, P<0.01 for SUA; ß=-0.11, P<0.01 for CUA), but not with log PTH or log 1,25(OH)2D. Dyslipidemia and diabetes were also independent factors for SUA and CUA, respectively. In multivariable analyses by sex, log FGF23 was associated with SUA in both sexes (ß=0.32, P<0.01 in males vs. ß=0.20, P=0.02 in females). Conversely, log FGF23 was independently associated with CUA in males (ß=-0.15, P<0.01), but not in females (ß=-0.09, P=0.17). CONCLUSIONS: FGF23 was independently associated with urate metabolism in this population of CKD patients. FGF23 might also have a stronger association with urate metabolism in males compared with females.

Plasma B-type natriuretic peptide concentration is independently associated with kidney function decline in Japanese patients with chronic kidney disease.

BACKGROUND AND OBJECTIVE: The relationship between B-type natriuretic peptide (BNP) concentration and renal outcomes in patients with chronic kidney disease (CKD) remains unclear; therefore, it has not been determined whether BNP is related to renal outcomes, independent of cardiac parameters. This study was designed to clarify whether BNP concentration is associated with renal outcomes in CKD patients, independent of cardiac functional and structural alterations. METHODS: This prospective observational study included 372 consecutive patients with CKD. The renal endpoint was the composite of doubling of serum creatinine concentration and end-stage renal disease requiring dialysis. BNP concentrations were divided into quartiles. A Cox proportional hazards model was utilized to determine the risk factors for poor renal outcomes. RESULTS: During a median follow-up of 23.1 months, the renal endpoint was observed in 124 patients, including 14, 18, 37 and 55 patients in the first through fourth BNP quartiles, respectively. After adjustment for covariates, including cardiac parameters such as left atrial diameter, left ventricular mass index, left ventricular ejection fraction, and left ventricular hypertrophy, the hazard ratios (HRs) for renal outcomes became progressively higher for the second [HR, 1.50; 95% confidence interval (CI), 0.70-3.30), third (HR, 2.29; 95% CI, 1.11-4.91), and fourth (HR, 4.29; 95% CI, 2.05-9.39) BNP quartiles when compared with the lowest BNP quartile. CONCLUSION: Higher BNP levels were associated with adverse renal outcomes, independent of cardiac structure and function, suggesting that BNP may be a useful biomarker for exploring factors associated with kidney disease progression.

Association of serum total bilirubin with renal outcome in Japanese patients with stages 3-5 chronic kidney disease.

OBJECTIVE: Serum bilirubin has been reported to be associated with the progression of kidney disease in patients with diabetic nephropathy. Less is known, however, about the relationship between bilirubin and chronic kidney disease (CKD) of other etiologies. This study was designed to clarify whether serum total bilirubin concentration is associated with kidney disease progression in patients with CKD independent of etiology. MATERIALS AND METHODS: This prospective observational study enrolled 279 consecutive patients with stages 3-5 CKD. The renal endpoint was the composite of the doubling of serum creatinine or end-stage renal disease requiring dialysis. Patients were divided into three groups by their serum total bilirubin concentrations: ≤0.3 (lowest), 0.4-0.5 (middle), and ≥0.6 (highest) mg/dL. A Cox proportional hazards model was applied to determine the risk factors for poor renal outcome. RESULTS: The median follow-up period was 21months. One-hundred and three patients reached renal end points. After multivariable adjustment, a 0.1mg/dL increase in serum bilirubin was associated negatively with poor renal outcome (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.60-0.87). In addition, after adjustment for confounding factors, including traditional and nontraditional cardiovascular risk factors, the middle (HR 3.14, 95% CI 1.36-8.57) and lowest (HR 4.22, 95% CI 1.81-11.59) bilirubin groups had significantly higher HRs for renal outcome than the highest bilirubin group. CONCLUSIONS: Lower serum bilirubin concentration was independently associated with adverse renal outcomes, suggesting that the measurement of serum bilirubin is useful for predicting kidney disease progression in patients with moderate to severe CKD.

Ankle-brachial blood pressure index predicts cardiovascular events and mortality in Japanese patients with chronic kidney disease not on dialysis.

The ankle-brachial blood pressure index (ABPI) has been recognized to have a predictive value for cardiovascular (CV) events and mortality in general or dialysis populations. However, the associations between ABPI and those outcomes have not been fully investigated in predialysis patients. The present study aimed to clarify the relationships between ABPI and both CV events and mortality in Japanese chronic kidney disease (CKD) patients not on dialysis. In this prospective observational study, we enrolled 320 patients with CKD stages 3-5 who were not on dialysis. At baseline, ABPI was examined and a low ABPI was defined as <0.9. CV events and all-cause deaths were examined in each patient. A Cox proportional hazards model was applied to determine the risk factors for CV events, as well as for mortality from CV and all causes. The median follow-up period was 30 months. CV events occurred in 56 patients and all-cause deaths occurred in 48, including 20 CV deaths. Multivariate analysis showed that age and low ABPI were risk factors for CV events. It was demonstrated that age, a history of cerebrovascular disease and low ABPI were determined as independent risk factors for CV mortality. In addition, age, body mass index and low ABPI were independently associated with all-cause mortality. In patients with CKD, low ABPI during the predialysis period is independently associated with poor survival and CV events, suggesting the usefulness of measuring ABPI for predicting CV events and patient survival in CKD.

Sex differences in the association between serum uric acid levels and cardiac hypertrophy in patients with chronic kidney disease.

Several studies have documented an association between serum uric acid (SUA) concentration and cardiac hypertrophy in hypertensive patients; however, the association remains unclear in chronic kidney disease (CKD) patients. If there is an association between SUA and hypertrophy in these patients, it is unknown whether the association is different between men and women. Our aim in this study is to determine whether SUA is associated with cardiac hypertrophy in CKD patients, focusing on any sex differences. Two hundred sixteen CKD patients (117 men and 99 women) were enrolled in this cross-sectional study. Patients prescribed uric acid-lowering agents and those with congestive heart failure, valvular heart disease, or ischemic heart disease were excluded from this study. Left ventricular mass index (LVMI) and left ventricular hypertrophy (LVH) were assessed using echocardiography. The prevalence of LVH was 58% in men and 47% in women. In multivariate linear regression analysis, SUA levels did not correlate with LVMI in men, whereas SUA was independently associated with LVMI in women (ß=0.27, P=0.02). Multivariate logistic regression analysis also revealed that diabetes mellitus (odds ratio (OR), 4.41; P=0.01) was associated with LVH in men, whereas age (OR, 1.13; P<0.01), hypertension (OR, 7.38; P=0.03) and SUA (OR, 1.91; P=0.03) were associated with LVH in women. In female CKD patients, SUA levels were associated with LVMI and LVH, whereas there was no association in male patients. These observations suggest that an association between SUA levels and the development of cardiac hypertrophy is more likely in women than in men.

Pandemic (H1N1) 2009-associated ARDS rescued by neuraminidase inhibitors with emergency use of extracorporeal membrane oxygenation.

A 36-year-old man with underlying systemic lupus erythematosus complicated by autoimmune hemolytic anemia underwent immunosuppressive treatment. After showing a low-grade fever for two days, his fever spiked. He was confirmed to have pandemic (H1N1) 2009 by real-time reverse transcription polymerase chain reaction (PCR). His condition deteriorated to acute respiratory distress syndrome (ARDS), and mechanical ventilation became necessary. The lowest PaO(2)/FIO(2) ratio was 77, and he was placed on extracorporeal membrane oxygenation (ECMO). Based on our observation, the emergency use of ECMO in addition to peramivir might be useful. A noteworthy point is that once ARDS deteriorates due to pandemic (H1N1) 2009, intensive supportive care should be started.

[Ratio of serum levels of 1,25-dihydroxyvitamin D3 and parathyroid hormone for the diagnosis and treatment of tuberculous peritonitis in a chronic kidney disease patient: a case report].

An 80-year-old man was admitted to our hospital because of exacerbation of preexisting chronic kidney disease (CKD). On admission, he showed elevated levels of serum creatinine (6.37 mg/dL) and corrected calcium (13.7 mg/dL). Although the serum levels of intact parathyroid hormone (I-PTH) and parathyroid hormone-related peptide(PTITH-rP)were low, the serum 1,25-dihydroxyvitamin D3 (1,25 (OH)2D3)levels were high. Computed tomography (CT) revealed ascites, and the ascitic fluid was exudative and serous with predominance of lymphocytes. The levels of adenosine deaminase (ADA) in the ascitic fluid were also elevated, and the results of QuantiFERON-TB2G (QFT-2G)assay were positive, indicating tuberculous peritonitits. Ascites resolved rapidly after initiation of the antituberculosis therapy. The elevated levels of serum calcium and 1,25 (OH) 2D3 returned to below-normal levels; however, serum i-PTH levels increased from 8.9 pg/ mL to 432 pg/mL. Diagnosis of extrapulmonary tuberculosis is often difficult in CKD patients. CKD patients show abnormal vitamin D activation, so these patients usually have low levels of serum 1,25(OH)2D3. On the other hand, in our patient, 1,25(OH)2D3 was extrarenally produced from tuberculous granuloma and therefore, he showed high levels of serum 1,25(OH)2D3 and correspondingly, low levels of serum i-PTH. We observed that the ratio of 1,25 (OH) 2D3:i-PTH decreased due to antituberculosis therapy. This ratio facilitated the diagnosis and evaluation of treatment for this condition.