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.

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.

Short- and Long-term Effects of Dialysate Calcium Concentrations on Mineral and Bone Metabolism in Hemodialysis Patients: The K4 Study.

RATIONALE & OBJECTIVE: The short- and long-term impact of conversion of dialysate calcium concentration from either 2.5 or 3.0 mEq/L to 2.75 mEq/L on mineral and bone metabolism remains unknown in hemodialysis patients. STUDY DESIGN: Nonrandomized intervention study. SETTING & POPULATION: 12 hemodialysis patients treated at baseline with a 2.5-mEq/L dialysate calcium concentration and another 12 hemodialysis patients treated with a 3.0-mEq/L dialysate calcium concentration. INTERVENTION: Use of 2.75-mEq/L dialysate calcium concentration. OUTCOMES: Changes in intradialytic calcium and phosphate clearance and changes in predialysis and intradialytic serum and ionized mineral and biochemical parameters over the 24 weeks following dialysate calcium conversion. RESULTS: Conversion of dialysate calcium concentration from 2.5 to 2.75 mEq/L increased intradialytic calcium loading and serum total and ionized calcium levels, whereas conversion of dialysate calcium from 3.0 to 2.75 mEq/L decreased intradialytic calcium loading and serum total and ionized calcium levels. Dialysate calcium concentration conversion did not affect intradialytic serum parathyroid hormone level, intradialytic phosphate elimination, or predialysis serum calcium, phosphate, parathyroid hormone, and fibroblast growth factor 23 levels. Intradialytic calcium influx was determined by dialysate calcium concentration and predialysis serum calcium levels, whereas intradialytic phosphate elimination was determined by predialysis serum phosphate levels. LIMITATIONS: Small sample size and no control groups treated with 2.5- and 3.0-mEq/L dialysate calcium concentrations during the 24 weeks of the observation period. CONCLUSIONS: Conversion of dialysate calcium concentration from either 3.0 or 2.5 to 2.75 mEq/L results in expected changes in calcium loading based on predialysis calcium concentration. The dialysate calcium concentration should be personalized based on clinical factors. FUNDING: None. TRIAL REGISTRATION: University Hospital Medical Information Network, www.umin.ac.jp/english/, R000040105, UMIN000035184.

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.