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Uromodulin, also known as Tamm–Horsfall protein, is the most abundant protein in urine. It has recently been reported that uromodulin exists in a small amount in blood and that its concentration correlates with the estimated glomerular filtration rate (eGFR). First, we generated anti-human uromodulin mouse monoclonal antibodies (mAb(s)) and established a specific enzyme-linked immunosorbent assay (ELISA) for uromodulin. We then performed an observational clinical study to determine if there was a correlation between serum uromodulin concentration and estimates of kidney function and whether the serum uromodulin value could be a biomarker in clinical nephrology. The clinical study included 308 patients with and without chronic kidney disease and healthy volunteers. Serum concentrations of creatinine, cystatin C, and uromodulin were measured and correlations were sought between the eGFR calculated from the creatinine and cystatin C levels and the serum uromodulin concentration. There was a good correlation between the serum uromodulin concentration and the eGFR value calculated from the creatinine (r = 0.76) and cystatin C (r = 0.79) levels. The mean serum uromodulin level in the group with an eGFR > 90 mL/min/1.73 m2 calculated using cystatin C was significantly higher than that in the group with an eGFR of 80–89 mL/min/1.73 m2. The serum uromodulin measurement could be a useful biomarker for identification of patients with early deterioration of kidney function.

The validity of the Birmingham Vasculitis Activity Score (BVAS) as an index of disease activity and a predictor of the prognosis and outcome in patients with MPA has not yet been established in Japan. We conducted a retrospective study of the data of 73 patients with MPA who were followed up for at least 2 years. We divided the patients into two groups according to the BVAS, namely, the high-BVAS group (≥16) and the low-BVAS group (

An observational cohort study was conducted to compare the performance of the RIFLE (risk, injury, failure, loss and end-stage kidney disease), AKIN (acute kidney injury network) and conventional graded criteria to identify acute kidney injury (AKI) following SCT and to predict long-term mortality in 141 myeloablative allogeneic SCT (m-allo), 60 non-myeloablative allogeneic SCT (nm-allo) and 48 autologous SCT (auto) cases. The AKIN criteria had less ability to identify patients as having the lowest category, stage 1 (analogous to RIFLE risk): 33% (37%) in m-allo, 23% (32%) in nm-allo and 8.3% (16.7%) in auto. Cox regression showed that categories higher than the intermediate stage were independent predictors of mortality in all three definitions. The areas under receiver operating characteristic curves showed that both definition systems had similar and significant ability to predict mortality (0.643-0.649 in m-allo and 0.734-0.766 in nm-allo, respectively). These abilities of the conventional graded criteria were comparable with those of the RIFLE criteria. The RIFLE criteria have greater sensitivity than the AKIN criteria to identify patients with AKI and therefore are more favorable as a uniform definition system for post-SCT AKI. However, the RIFLE criteria do not improve on the clinical relevance of the conventional graded criteria.

Background Chronic kidney disease (CKD) seems to be common in long-term survivors of haematopoietic cell transplantation (HCT). However, the range of its frequency is very wide, likely due to variability in the definitions of CKD and the periods of follow-up. Methods We conducted a cross-sectional and retrospective study in 158 adults who received myeloablative allogeneic HCT for lymphohaematologic malignancies at least 3 years ago and are alive today. The mean survival time was 6.15 +/- 4.88 years (range: 3-16 years). CKD was defined as a sustained decrease in glomerular filtration rate (GFR) or persistent proteinuria for a period more than 3 months. GFR was calculated based on serum creatinine (Cr) using the Modification of Diet in Renal Disease formula. Serum Cr and proteinuria were measured at least on three occasions separated by one or more months before the investigation. CKD was classified according to the National Kidney Foundation CKD staging. Proteinuria was defined as positive dipstick test > or =1+. The factors associated with the presence of CKD with a decrease of GFR (CKD > or = stage 3) were examined using multivariate logistic regression analysis, adjusted for demographic and clinical characteristics. Results The prevalence of proteinuria was found in 36 out of 158 patients (22.8%). The prevalence of each CKD stage was as follows: Stage 0 (no CKD), 98 patients (62.0%); Stage 1, 18 patients (11.4%); Stage 2, 15 patients (9.5%); Stage 3, 8 patients (5.1%); Stage 4, 10 patients (6.3%) and Stage 5, 9 patients (5.7%). Initiation of chronic dialysis treatment or transplant was performed in seven CKD stage-5 patients (4.4%) at a mean of 10.9 +/- 3.72 years after HCT. Multivariate analysis identified acute kidney injury with HCT [odds ratio (OR), 9.920; 95% confidence interval (CI), 2.084-39.68; P = 0.0051], hypertension after HCT (OR, 4.031; 95% CI, 1.044-13.06; P = 0.0346) and survival time after HCT (OR, 4.275; 95% CI, 2.823-23.04; P = 0.0481) as significant factors associated with the presence of CKD > or = stage 3. Conclusions A remarkably high percentage of long-term survivors had evidence of proteinuria and all stages of CKD. CKD in transplant recipients may result from incomplete recovery from acute renal insults, hypertension and increasing longevity. The CKD cohort should be at a great risk for end-stage renal disease and cardiovascular morbidity and mortality. The burden of CKD should be recognized as a significant public health problem.

Background/Aims: S100A12 induces vascular inflammation contributing to the development of atherosclerosis. Serum S100A12 concentration is shown to be elevated in patients with chronic kidney disease (CKD), however the reason remains unclear. Methods: Transcriptional levels of S100A12 and RAGE (receptor for advanced glycation end products) were measured in peripheral leukocytes by quantitative real-time RT-PCR. Subjects were 40 patients with CKD stage 4-5, 20 of whom were affected with cardiovascular disease (CVD), and 20 healthy subjects. Serum concentrations of S100A12 and soluble RAGE were measured using enzyme-linked immunosorbent assay. Results: The serum concentration of S100A12 was significantly higher in CKD patients than in healthy subjects (78.5 ± 70.5 vs. 23.7 ± 19.2 ng/ml, p = 0.0035), but that of soluble RAGE was not. The relative quantity of S100A12 mRNA was significantly greater in leukocytes from CKD patients than in those from healthy subjects [mean (95% confidence interval of the mean): 3.1 (2.2-3.9) vs. 1.2 (0.8-1.7), p = 0.0001], however that of RAGE mRNA was not. The serum concentration of S100A12 was significantly correlated with the relative quantity of S100A12 mRNA among uremic CKD patients (r2 = 0.656, p < 0.0001). Both the serum concentration and gene expression of S100A12 were significantly higher in patients who had CVD than in those who did not. Conclusion: Excessive expression of the S100A12 gene in uremic leukocytes is relevant to its increased serum concentration, particularly in those affected with CVD.

Myeloablative (m-allo) hematopoietic stem cell transplantation (SCT) involves a great risk of acute kidney injury (AKI). We assessed whether or not early elevation of urinary biomarkers is useful for identifying high-risk patients for AKI.A prospective cohort study was conducted in 40 patients (46.0+/-12.5 years, eGFR 96.1 +/- 25.3 mL/min/1.73 m2) who received m-allo SCT in our hospital. We measured urinary biomarkers such as N-acetyl-beta -glucosaminidase (NAG), beta2 microglobulin (beta 2M), alpha microglobulin ( alpha1M) before conditioning therapy, on the day of SCT and both days 7 and 14 after SCT. AKI was defined as a decrease in eGFR within 100 days after SCT, and classified based on the RIFLE criteria. Discriminative sensitivity of urinary biomarkers was estimated using area under receiver operating characteristic (AuROC) curve analysis.AKI occurred in 28 cases(70 %): risk was 25.0 %, injury was 17.5 %, failure was 22.5 % and loss was 5.0 %, respectively. Only 4 cases with AKIor = injury that occurred less than 40 days after SCT died within 100 days after SCT. Thus, this level of AKI was denoted as"severe AKI"and targeted for early identification. Values of all urinary biomarkers increased gradually after the conditioning therapy, and both NAG and alpha 1M values at day 7 became significantly higher in the severe AKI group than in the opposite group. The AuROC showed that both NAG and alpha 1M values at day 7 had moderate discriminative sensitivity for predicting severe AKI (NAG : 0.783, 95 % confidence interval [CI] 0.611-0.966 ; and alpha 1M: 0.807, 95 % CI 0.647-0.956, respectively). Multivariate logistic regression showed that only alpha 1M at day 7 was significantly associated with the occurrence of severe AKI(odds ratio 18.4, 95 % CI 1.210-736, p=0.035).Consecutive monitoring of urinary alpha 1M after SCT is likely to be useful for early identification of patients at risk for severe AKI, leading to early death.

A 38-year-old male with impaired renal function and serious anemia was admitted to our hospital. He had suffered from a disorder of urination since early childhood and been diagnosed as having neurogenic bladder by an urologist when he was 20 years old. Since February 2007, general fatigue emerged and gradually worsened. In addition, he began to feel nauseous around February 2008. He visited a family doctor and was diagnosed with renal failure and anemia both of which were serious. H e was referred t o our office and admitted immediately because his blood test showed a serum creatinine level of 4.4 mg/dL and hemoglobin of 3.1 g/dL. The initial study with ultrasonograhy suggested that both kidneys contained multiple cysts for the most part, likely due to hereditary polycystic kidney disease. However, a subsequent series of diagnostic imaging tests, including computed tomography and magnetic resonance urography, determined that the cause of renal failure was most likely reflux nephropathy due to secondary vesicouretral reflux induced by the chronic neurogenic bladder. Moreover, the upper gastrointestinal endoscopic examination showed that the cause of anemia was probably the persistent bleeding from gastric antral vascular ectasia. Reflux nephropathy emerges in early childhood and slowly progresses to chronic renal failure in some cases. According to the literature, it is not rare as a cause of end-stage kidney failure even among adult populations. Diagnostic imaging of severe reflux nephropathy is apparently similar to that of polycystic kidney disease. We herein present an adult male with chronic renal failure due to reflux nephropathy, the images of which were similar to polycystic kidney disease.

Stem cell transplantation (SCT) involves a great risk of acute kidney injury (AKI). Urinary liver-type fatty acid-binding protein (uL-FABP) is a sensitive biomarker to detect kidney damage before an increase in serum creatinine (Cr); however, the utility of uL-FABP is not fully understood in the platform of SCT. A prospective study was conducted in 84 allogeneic SCT recipients to ascertain a link between the uL-FABP level before preparative procedures and AKI incidence after SCT. The association between them was analyzed using Gray's method and a multivariate Fine-Gray proportional hazards regression model. The recipients were stratified into high and low uL-FABP groups, according to the reference value for healthy subjects (8.4 μg/g Cr). AKI developed more frequently in the high (n = 20) than low (n = 64) group (55.0% versus 26.6% at day 30, P = .005), and high uL-FABP was an independent risk for the emergence of AKI (hazard ratio, 2.78; 95% confidence interval, 1.24 to 6.22, P = .01). In conclusion, increased baseline uL-FABP, which may indicate previous incipient kidney injury, is linked with a high risk of AKI after allogeneic SCT.