Assessment of Tumor Markers in Renal Transplant Recipients.

Background/Aim: Malignant tumors are diagnosed using various methods, including diagnostic imaging methods. The measurement of tumor markers is commonly used because of its noninvasiveness and convenience. Furthermore, it is known that the excretion and metabolism of some tumor markers are affected by impaired renal function. In the present study, we investigated the effect of improved renal function on pre-and post-transplantation changes in tumor marker levels [carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), and prostate-specific antigen (PSA)] in renal transplant recipients. Patients and Methods: A total of 116 renal transplant recipients, who had not been diagnosed with malignancies between January 2012 and December 2019, were included, and tumor markers were investigated. Results: CEA showed a significant decrease after kidney transplantation, regardless of the dialysis type (3.6→2.6 ng/ml, p<0.001), while other tumor markers showed a significant increase (AFP: 3.6→3.7 ng/ml; CA19-9: 16.2→19.5 U/ml; PSA: 0.95→1.05 ng/ml; all p<0.05). Pre- and postoperative eGFR ratios and postoperative liver function were identified as factors influencing the postoperative CEA and CA19-9 values, while PSA was influenced by the duration of dialysis. No statistically significant factors were found for AFP levels. Conclusion: Caution should be exercised when investigating tumor markers in patients with renal dysfunction, as tumor marker levels may vary depending on the pathophysiology of each patient.

Associations of calcium, phosphate and intact parathyroid hormone levels with mortality, residual kidney function and technical failure among patients on peritoneal dialysis.

Background: Associations of calcium, phosphate and intact parathyroid hormone (iPTH) levels with outcomes may be different between patients on peritoneal dialysis (PD) and hemodialysis (HD). The aim of the study is to evaluate these associations among PD patients. Methods: In this prospective cohort study on the Japan Renal Data Registry, adults on PD at the end of 2009 were included. The observation period was until the end of 2018 and the data were censored at the time of transplantation or transition to HD. Exposures were time-averaged or time-dependent albumin-corrected calcium (cCa), phosphate and iPTH levels. Outcomes were all-cause and cardiovascular mortality, transition to HD and urine output. Data were analyzed using Cox regression models or linear mixed-effects models and the results were shown as cubic spline curves. Results: Among 7393 patients, 590 deaths and 211 cardiovascular deaths were observed during a median follow-up of 3.0 years. Higher cCa and phosphate levels were associated with higher mortality. Lower cCa levels were associated with a faster decline, whereas lower phosphate was associated with a slower decline in urine output. Lower phosphate and iPTH levels were associated with a lower incidence of transition to HD. Conclusions: Among PD patients, the observed associations of cCa, phosphate and iPTH with mortality, residual kidney function and technical failure suggest that avoiding high cCa, phosphate and iPTH levels might improve outcomes.

Association between serum iron markers, iron supplementation and cardiovascular morbidity in pre-dialysis chronic kidney disease.

BACKGROUND: The optimal range of serum iron markers and usefulness of iron supplementation are uncertain in patients with pre-dialysis chronic kidney disease (CKD). We investigated the association between serum iron indices and risk of cardiovascular disease (CVD) events and the effectiveness of iron supplementation using Chronic Kidney Disease Japan Cohort data. METHODS: We included 1416 patients ages 20-75 years with pre-dialysis CKD. The tested exposures were serum transferrin saturation and serum ferritin levels and the outcome measures were any cardiovascular event. Fine-Gray subdistribution hazard models were used to examine the association between serum iron indices and time to events. The multivariable fractional polynomial interaction approach was used to evaluate whether serum iron indices were effect modifiers of the association between iron supplementation and cardiovascular events. RESULTS: The overall incidence rate of CVD events for a median of 4.12 years was 26.7 events/1000 person-years. Patients with serum transferrin saturation <20% demonstrated an increased risk of CVD [subdistribution hazard ratio (HR) 2.13] and congestive heart failure (subdistribution HR 2.42). The magnitude of reduction in CVD risk with iron supplementation was greater in patients with lower transferrin saturations (P = .042). CONCLUSIONS: Maintaining transferrin saturation >20% and adequate iron supplementation may effectively reduce the risk of CVD events in patients with pre-dialysis CKD.

Association of Four Types of Vascular Access Including Arterial Superficialization with Mortality in Maintenance Hemodialysis Patients: A Nationwide Cohort Study in Japan.

INTRODUCTION: Vascular access usage varies widely across countries. Previous studies have evaluated the association of clinical outcomes with the three types of vascular access, namely, arteriovenous fistula (AVF), arteriovenous graft (AVG), and tunneled and cuffed central venous catheter (TC-CVC). However, little is known regarding the association between arterial superficialization (AS) and the mortality of patients. METHODS: A nationwide cohort study was conducted using data from the Japanese Society for Dialysis Therapy Renal Data Registry (2006-2007). We included patients aged ≥20 years undergoing hemodialysis with a dialysis vintage ≥6 months. The exposures of interest were the four types of vascular access: AVF, AVG, AS, and TC-CVC. Cox proportional hazard models were used to evaluate the associations of vascular access types with 1-year all-cause and cause-specific mortality. RESULTS: A total of 183,490 maintenance hemodialysis patients were included: 90.7% with AVF, 6.9% with AVG, 2.0% with AS, and 0.4% with TC-CVC. During the 1-year follow-up period, 13,798 patients died. Compared to patients with AVF, those with AVG, AS, and TC-CVC had a significantly higher risk of all-cause mortality after adjustment for confounding factors: adjusted hazard ratios (95% confidence intervals) - 1.30 (1.20-1.41), 1.56 (1.39-1.76), and 2.15 (1.77-2.61), respectively. Similar results were obtained for infection-related and cardiovascular mortality. CONCLUSION: This nationwide cohort study conducted in Japan suggested that AVF usage may have the lowest risk of all-cause mortality. The study also suggested that the usage of AS may be associated with better survival rates compared to those of TC-CVC in patients who are not suitable for AVF or AVG.

Excess risk of cardiovascular events in patients in the United States vs. Japan with chronic kidney disease is mediated mainly by left ventricular structure and function.

While patients receiving dialysis therapy in the United States are more likely to develop cardiovascular disease (CVD) than those in Japan, direct comparisons of patients with predialysis chronic kidney disease (CKD) are rare. To study this, we compared various outcomes in patients with predialysis CKD using data from the Chronic Renal Insufficiency Cohort (CRIC) and CKD Japan Cohort (CKD-JAC) studies and determined mediators of any differences. Candidate mediators included left ventricular (LV) indices assessed by echocardiography. Among 3125 CRIC and 1097 CKD-JAC participants, the mean LV mass index (LVMI) and ejection fraction (EF) were 55.7 and 46.6 g/m2 and 54% and 65%, respectively (both significant). The difference in body mass index (32 and 24 kg/m2, respectively) largely accounted for the differences in LVMI and C-reactive protein levels across cohorts. Low EF and high LVMI were significantly associated with subsequent CVD in both cohorts. During a median follow-up of five years, CRIC participants were at higher risk for CVD (adjusted hazard ratio [95% confidence interval]: 3.66 [2.74-4.89]) and death (4.69 [3.05-7.19]). A three-fold higher C-reactive protein concentration and higher phosphate levels in the United States cohort were moderately strong mediators of the differences in CVD. However, echocardiographic parameters were stronger mediators than these laboratory measures. LVMI, EF and their combination mediated the observed difference in CVD (27%, 50%, and 57%, respectively) and congestive heart failure (33%, 62%, and 70%, respectively). Thus, higher LV mass and lower EF, even in the normal range, were found to be predictive of CVD in CKD.

Biopsy-proven CKD etiology and outcomes: the Chronic Kidney Disease Japan Cohort (CKD-JAC) study.

BACKGROUND: The Kidney Disease: Improving Global Outcomes guidelines advocate the cause-glomerular filtration rate (GFR)-albuminuria (CGA) classification for predicting outcomes. However, there is a dearth of data supporting the use of the cause of chronic kidney disease. This study aimed to address how to incorporate a prior biopsy-proven diagnosis in outcome prediction. METHODS: We examined the association of biopsy-proven kidney disease diagnoses with kidney failure with replacement therapy (KFRT) and all-cause death before KFRT in patients with various biopsy-proven diagnoses (n = 778, analysis A) and patients with diabetes mellitus labeled with biopsy-proven diabetic nephropathy (DN), other biopsy-proven diseases and no biopsy (n = 1117, analysis B). RESULTS: In analysis A, adding biopsy-proven diagnoses to the GFR-albuminuria (GA) classification improved the prediction of 8-year incidence of KFRT and all-cause death significantly regarding integrated discrimination improvement and net reclassification index. Fine-Gray (FG) models with KFRT as a competing event showed significantly higher subdistribution hazard ratios (SHRs) for all-cause death in nephrosclerosis {4.12 [95% confidence interval (CI) 1.11-15.2)], focal segmental glomerulosclerosis [3.77 (95% CI 1.09-13.1)]} and membranous nephropathy (MN) [2.91 (95% CI 1.02-8.30)] than in immunoglobulin A nephropathy (IgAN), while the Cox model failed to show significant associations. Crescentic glomerulonephritis had the highest risk of all-cause death [SHR 5.90 (95% CI 2.05-17.0)]. MN had a significantly lower risk of KFRT than IgAN [SHR 0.45 (95% CI 0.24-0.84)]. In analysis B, other biopsy-proven diseases had a lower risk of KFRT than biopsy-proven DN in the FG model, with death as a competing event [SHR 0.62 (95% CI 0.39-0.97)]. CONCLUSIONS: The CGA classification is of greater value in predicting outcomes than the GA classification.

Parathyroidectomy vs Cinacalcet Among Patients Undergoing Hemodialysis.

CONTEXT: Parathyroidectomy (PTx) and cinacalcet are both effective treatments for secondary hyperparathyroidism in hemodialysis patients, but limited data exist comparing the long-term outcomes of these interventions. OBJECTIVE: We aimed to compare the risk of mortality among hemodialysis patients who underwent PTx and those who started treatment with cinacalcet. METHODS: In this prospective cohort study, comprising patients from the Japanese Society for Dialysis Therapy Renal Data Registry, patients who had intact parathyroid hormone (PTH) levels ≥ 300 pg/mL in late 2007 and underwent PTx or started treatment with cinacalcet in 2008 to 2009 were matched by propensity score at 1:3. PTx and cinacalcet were compared for all-cause mortality within 6 years. RESULTS: Among eligible patients, 894 patients who underwent PTx were matched with 2682 patients who started treatment with cinacalcet. The median baseline intact PTH levels were 588 pg/mL and 566 pg/mL in the PTx and cinacalcet groups, respectively. PTx resulted in greater reductions in intact PTH, calcium, and phosphorus levels compared with cinacalcet. During the 6-year follow-up period, 201 patients (22.5%) in the PTx group and 736 patients (27.4%) in the cinacalcet group died. PTx was associated with a lower risk of mortality compared with cinacalcet (hazard ratio, 0.78 [95% CI, 0.67-0.91]; P = 0.002). This association was more pronounced in patients with intact PTH levels ≥ 500 pg/mL and in patients with serum calcium levels ≥ 10.0 mg/dL (both P for interaction < 0.001). CONCLUSION: PTx compared with cinacalcet is associated with a lower risk of mortality, particularly among patients with severe secondary hyperparathyroidism.

A Comparative Study of Serum Phosphate and Related Parameters in Chronic Kidney Disease between the USA and Japan.

INTRODUCTION: Recent studies have suggested a higher incidence of cardiovascular disease (CVD) among patients with chronic kidney disease (CKD) in the USA than in Japan. Hyperphosphatemia, a possible risk for CVD, may explain this difference; however, international differences in phosphate parameters in CKD have not been well elaborated. METHODS: By using the baseline data from the USA and the Japanese nation-wide, multicenter, CKD cohort studies; the Chronic Renal Insufficiency Cohort Study (CRIC, N = 3,870) and the Chronic Kidney Disease-Japan Cohort Study (CKD-JAC, N = 2,632), we harmonized the measures and compared clinical parameters regarding phosphate metabolism or serum phosphate, fibroblast growth factor-23 (FGF23), and parathyroid hormone (PTH), in the cross-sectional model. RESULTS: Multivariable linear regression analyses revealed that serum phosphate levels were significantly higher in CRIC across all levels of estimated glomerular filtration rate (eGFR) with the greatest difference being observed at lower levels of eGFR. Serum FGF23 and 25-hydroxy vitamin D (25OHD) levels were higher in CRIC, while PTH levels were higher in CKD-JAC at all levels of eGFR. Adjustments for demographics, 25OHD, medications, dietary intake or urinary excretion of phosphate, PTH, and FGF23 did not eliminate the difference in serum phosphate levels between the cohorts (0.43, 0.46, 0.54, 0.64, and 0.78 mg/dL higher in CRIC within eGFR strata of >50, 41-50, 31-40, 21-30, and ≤20 mL/min/1.73 m2, respectively). These findings were consistent when only Asian CRIC participants (N = 105) were included in the analysis. CONCLUSION: Serum phosphate levels in CRIC were significantly higher than those of CKD-JAC across all stages of CKD, which may shed light on the international variations in phosphate parameters and thus in cardiovascular risk among CKD patients. The key mechanisms for the substantial differences in phosphate parameters need to be elucidated.

Cardiovascular disease history and ß-blocker prescription patterns among Japanese and American patients with CKD: a cross-sectional study of the CRIC and CKD-JAC studies.

Cardiovascular disease (CVD) is a major complication in individuals with chronic kidney disease (CKD). In Japan, the incidence of CVD among persons with CKD is lower than that in the United States. Although various classes of antihypertensive agents are prescribed to prevent CVD, the proportion varies between the United States and Japan. Until now, few studies have compared clinical practices and CVD prevalence among patients with CKD in the United States vs. Japan. In this study, we performed a cross-sectional comparison of the prevalence of CVD and the prescription of ß-blockers at study entry to the Chronic Kidney Disease Japan Cohort (CKD-JAC) Study and the Chronic Renal Insufficiency Cohort (CRIC) Study. The mean patient age was 58.2 and 60.3 years, the mean estimated glomerular filtration rate (eGFR) was 42.8 and 28.9 (mL/min/1.73 m2), and the median urinary albumin:creatinine ratio was 51.9 and 485.9 (mg/g) among 3939 participants in the CRIC Study and 2966 participants in the CKD-JAC Study, respectively. The prevalence of any CVD according to a self-report (CRIC Study) was 33%, while that according to a medical chart review (CKD-JAC Study) was 24%. These findings were consistent across eGFR levels. Prescriptions for ß-blockers differed between the CRIC and CKD-JAC Studies (49% and 20%, respectively). The odds ratios for the association of any history of CVD and ß-blocker prescription were 3.0 [2.6-3.5] in the CRIC Study and 2.0 [1.6-2.5] in the CKD-JAC Study (P < 0.001 for the interaction). In conclusion, the prevalence of CVD and treatment with ß-blockers were higher in the CRIC Study across eGFR levels.

Changes in 3-month mineral and bone disorder patterns were associated with all-cause mortality in prevalent hemodialysis patients with secondary hyperparathyroidism.

BACKGROUND: There is limited evidence on the association between short-term changes in mineral and bone disorder parameters and survival in maintenance hemodialysis patients. METHODS: We investigated the association between changing patterns of phosphorus, calcium and intact parathyroid hormone levels and all-cause mortality in hemodialysis patients with secondary hyperparathyroidism. Each parameter was divided into three categories (low [L], middle [M] and high [H]), and the changing patterns between two consecutive visits at 3-month intervals were categorized into nine groups (e.g., L-L and M-H). The middle category was defined as 4.0-7.0 mg/dL for phosphorous, 8.5-9.5 mg/dL for calcium and 200-500 pg/mL for intact parathyroid hormone. Adjusted incidence rates and rate ratios were analyzed by weighted Poisson regression models accounting for time-dependent exposures. RESULTS: For phosphorus, shifts from low/high to middle category (L-M/H-M) were associated with a lower mortality compared with the L-L and H-H groups, whereas shifts from middle to low/high category (M-L/M-H) were associated with a higher mortality compared with the M-M group. For calcium, shifts from low/middle to high category (L-H/M-H) were associated with a higher mortality compared with the L-L and M-M groups, whereas shifts from high to middle category (H-M) were associated with a lower mortality compared with the H-H group. For intact parathyroid hormone, shifts from low to middle category (L-M) were associated with a lower mortality compared with the L-L group. CONCLUSIONS: Changes in the 3-month patterns of phosphorus and calcium toward the middle category were associated with lower mortality. Our study also suggests the importance of avoiding hypercalcemia.

Serum phosphate levels modify the impact of parathyroid hormone levels on renal outcomes in kidney transplant recipients.

Separate assessment of mineral bone disorder (MBD) parameters including calcium, phosphate, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D (1,25D) predict renal outcomes in kidney transplant recipients (KTRs), with conflicting results. To date, data simultaneously evaluating these parameters and interwoven relations on renal outcomes are scarce. We conducted a prospective long-term follow-up cohort study included 263 KTRs with grafts functioning at least 1 year after transplantation. The outcome was a composite of estimated GFR halving and graft loss. Cox regression analyses were employed to evaluate associations between a panel of six MBD parameters and renal outcomes. The outcome occurred in 98 KTRs during a median follow-up of 10.7 years. In a multivariate Cox analysis, intact PTH (iPTH), phosphate, and 1,25D levels were associated with the outcome (hazard ratio, 1.60 per log scale; 95% confidence interval, 1.19-2.14, 1.60 per mg/dL; 1.14-2.23 and 0.82 per 10 pg/mL; 0.68-0.99, respectively). Competing risk analysis with death as a competing event yielded a similar result. After stratification into four groups by iPTH and phosphate medians, high risks associated with high iPTH was not observed in KTRs with low phosphate levels (P-interaction < 0.1). Only KTRs not receiving active vitamin D, poor 1,25D status predicted the worse outcome (P-interaction < 0.1). High iPTH, phosphate, and low 1,25D, but not FGF23, levels predicted poor renal outcomes. Simultaneous evaluation of PTH and phosphate levels may provide additional information regarding renal allograft prognosis.

New selectivity index calculated using protein fraction as a substitute for the conventional selectivity index.

BACKGROUND: Selectivity index (SI) of proteinuria, calculated using the clearance ratio of immunoglobulin G to transferrin, predicts the response to glucocorticoids in patients with nephrotic syndrome. However, there is disagreement regarding the suitability of SI. Therefore, alternate indices should be considered. This study investigated whether or not selectivity index protein fraction (SIPF) was inferior to SI for the prediction of the response to glucocorticoids. METHODS: Forty-nine patients with nephrotic syndrome were evaluated. On the basis of molecular weight and protein fraction, as an inexpensive substitute for SI, the clearance ratio of the albumin to γ fractions measured in serum and urine protein fractions was defined as SIPF. The quality of SIPF was examined. Moreover, the best cutoff value of SIPF was determined; and SIPF distribution, according to histopathological diagnosis by renal biopsy, was examined. RESULTS: SIPF was strongly correlated with SI (r = 0.79, P < 0.001). The area under the receiver operating characteristic (ROC) curve of SIPF and SI was not significantly different (P = 0.18). The best cutoff value of SIPF was 0.45. In the group with SIPF > 0.45, only two patients with minimal change disease (MCD) achieved complete remission. In the group with SIPF ≤ 0.45, all patients with MCD achieved complete remission, although eight patients with other histopathological diagnoses did not achieve complete remission. CONCLUSIONS: Analysis of protein fractions as a substitute for SI may be useful for predicting response to glucocorticoids in patients with nephrotic syndrome.

Variations in 24-Hour BP Profiles in Cohorts of Patients with Kidney Disease around the World: The I-DARE Study.

BACKGROUND AND OBJECTIVES: Ambulatory BP is increasingly recognized as a better measure of the risk for adverse outcomes related to hypertension, an important comorbidity in patients with CKD. Varying definitions of white-coat and masked hypertension have made it difficult to evaluate differences in prevalence of these BP patterns across CKD cohorts. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The International Database of Ambulatory BP in Renal Patients collaborative group established a large database of demographic, clinical, and ambulatory BP data from patients with CKD from cohorts in Italy, Spain, the Chronic Renal Insufficiency Cohort (CRIC) and the African American Study of Kidney Disease and Hypertension Cohort Study (AASK) in the United States, and the CKD Japan Cohort (CKD-JAC). Participants (n=7518) with CKD were included in the present analyses. Cutoffs for defining controlled BP were 140/90 mm Hg for clinic and 130/80 mm Hg for 24-hour ambulatory BP. RESULTS: Among those with controlled clinic BP, compared with CKD-JAC, AASK participants were more likely to have masked hypertension (prevalence ratio [PR], 1.21; 95% confidence interval [95% CI], 1.04 to 1.41) whereas CRIC (PR, 0.82; 0.72 to 0.94), Italian (PR, 0.73; 0.56 to 0.95), and Spanish participants (PR, 0.75; 0.64 to 0.88) were less likely. Among those with elevated clinic BP, AASK participants were more likely to have sustained hypertension (PR, 1.22; 95% CI, 1.13 to 1.32) whereas Italian (PR, 0.78; 0.70 to 0.87) and Spanish participants (PR, 0.89; 0.82 to 0.96) were less likely, although CRIC participants had similar prevalence as CKD-JAC. Prevalence of masked and sustained hypertension was elevated in males, patients with diabetes, participants on four or more antihypertensives, and those with moderate-to-severe proteinuria. CONCLUSIONS: In a large, multinational database, the prevalence of masked and sustained hypertension varied across cohorts independent of important comorbidities.

[Bone and Mineral Metabolism in Hemodialysis Patients. Fragility Fractures in Hemodialysis Patients.]

Due to the population aging and improved prognosis of hemodialysis patients, fracture has become one of important clinical outcomes that often degrade patients' quality of life and indirectly increase mortality. As Japanese hemodialysis patients have five to six-fold higher incidence of hip fracture than general population, risk factors and prophylactic interventions for fracture should be investigated. Being one of the eldest countries in the world, Japan should conduct more researches and publish more evidences in this field. The Japanese Renal Data Registry has been playing an important role in generating new evidences on non-classical risk factors of hip fracture that are specific to hemodialysis patients. Yet, the preventative intervention has not been established even in the newly-updated KDIGO CKD-MBD guideline. Notable finding is that the incidence rate of hip fracture has been decreased in Japanese females despite aging. The investigation of the reason may shed light on undetermined therapeutic approaches to hip fracture in hemodialysis patients.

Red cell distribution width and renal outcome in patients with non-dialysis-dependent chronic kidney disease.

Higher red cell distribution width (RDW) has been reported to predict mortality among patients with various diseases, including chronic kidney disease (CKD). However, whether RDW is associated with renal outcome remains unclear. We investigated the relationship between RDW and renal outcome in patients with non-dialysis-dependent CKD (NDD-CKD). This prospective, observational study of patients with CKD was conducted at a single nephrology department. First, we performed regression analyses for the decline in estimated glomerular filtration rate (eGFR) during the first 3 months of observation to determine its short-term association with RDW. Next, we categorized baseline RDW into two groups by its median (13.5%) and performed Cox regression analyses to investigate whether higher RDW was an independent predictor of renal outcomes defined as a composite of the initiation of dialysis and doubling of the serum creatinine concentration. Furthermore, we repeated the analyses to confirm whether the transition of the RDW category during the first 3 months would also predict renal outcomes. We enrolled 703 patients. Baseline RDW showed a non-linear association with the eGFR decline during the first 3 months, with a greater negative correlation at the lower end of the RDW distribution. Over a median follow-up of 1.8 years, 178 patients (25.3%) reached the renal endpoint. Multivariable Cox regression analyses showed that patients with higher RDW had a higher risk of developing renal outcomes (adjusted hazard ratio [HR]: 1.47, 95% confidence interval [CI]: 1.05-2.07) than did those with lower RDW. Furthermore, patients with sustained, higher RDW demonstrated a significantly higher risk than did those with consistently lower RDW (adjusted HR: 1.65, 95% CI: 1.02-2.67). In conclusion, higher RDW was independently associated with worse renal outcome in patients with NDD-CKD. RDW could be an additional prognostic marker of the progression of CKD.

Hematuria as a risk factor for progression of chronic kidney disease and death: findings from the Chronic Renal Insufficiency Cohort (CRIC) Study.

BACKGROUND: Hematuria is associated with chronic kidney disease (CKD), but has rarely been examined as a risk factor for CKD progression. We explored whether individuals with hematuria had worse outcomes compared to those without hematuria in the CRIC Study. METHODS: Participants were a racially and ethnically diverse group of adults (21 to 74 years), with moderate CKD. Presence of hematuria (positive dipstick) from a single urine sample was the primary predictor. Outcomes included a 50% or greater reduction in eGFR from baseline, ESRD, and death, over a median follow-up of 7.3 years, analyzed using Cox Proportional Hazards models. Net reclassification indices (NRI) and C statistics were calculated to evaluate their predictive performance. RESULTS: Hematuria was observed in 1145 (29%) of a total of 3272 participants at baseline. Individuals with hematuria were more likely to be Hispanic (22% vs. 9.5%, respectively), have diabetes (56% vs. 48%), lower mean eGFR (40.2 vs. 45.3 ml/min/1.73 m2), and higher levels of urinary albumin > 1.0 g/day (36% vs. 10%). In multivariable-adjusted analysis, individuals with hematuria had a greater risk for all outcomes during the first 2 years of follow-up: Halving of eGFR or ESRD (HR Year 1: 1.68, Year 2: 1.36), ESRD (Year 1: 1.71, Year 2: 1.39) and death (Year 1:1.92, Year 2: 1.77), and these associations were attenuated, thereafter. Based on NRIs and C-statistics, no clear improvement in the ability to improve prediction of study outcomes was observed when hematuria was included in multivariable models. CONCLUSION: In a large adult cohort with CKD, hematuria was associated with a significantly higher risk of CKD progression and death in the first 2 years of follow-up but did not improve risk prediction.

High Titer of Acquired Factor V Inhibitor Presenting with a Pseudo-deficiency of Multiple Coagulation Factors.

Acquired coagulation factor inhibitor is a rare coagulation disorder. We herein report a patient with acquired factor V inhibitor showing a decrease in multiple coagulation factor activities. A high titer of factor V inhibitor presumably led to a marked inhibition of factor V activity in the specific factor-deficient plasma used in coagulation factor activity assays based on either an activated partial thromboplastin time (APTT) or prothrombin time (PT) clotting assay, resulting in false low values of the coagulation activity. We re-examined the coagulation factor activity using several dilutions of the patient's plasma and confirmed that the high factor V inhibitor titer had caused an apparent decrease in multiple coagulation factor activities.

Clinical features of CKD-MBD in Japan: cohort studies and registry.

Randomized controlled trials (RCTs) are essential for evidence-based medicine; however, cohort studies and registries provide an important information about risk factors and, hence, shed light on the target of laboratory parameters. The uniqueness of the current Japanese CKD-MBD guidelines lies in the lower target range of intact parathyroid hormone levels than those used in other countries, which is based on analyses of the nationwide Japan Renal Data Registry. Cohort studies were also useful in exploring risk factors of renal outcome in predialysis patients. It was revealed that low vitamin D status (very prevalent in Japan) and high fibroblast growth factor 23 (FGF23) levels predict poor renal outcome. The reported association of FGF23 levels with left ventricular hypertrophy (LVH) and heart failure observed in cohort studies may support the idea of adding the 4th component of CKD-MBD, namely, "LVH" to the three original components. When it is not feasible to conduct RCTs regarding intervention, we have no choice but to rely on observational studies with sophisticated analysis methods, such as facility-level analysis and marginal structural model minimizing indication bias. Observational studies conducted in Japan revealed that the side effects of medications for CKD-MBD, resultant compliance, and effective doses in terms of hard outcome in Japanese patients were found to be different from those in other countries. For example, the MBD-5D study confirmed the benefit of cinacalcet in terms of mortality despite its median dose of only 25 mg/day. These data are very helpful for future guidelines specific to Japanese patients with CKD.