Acute Brachial Arterial Embolic Occlusion Following Anticoagulant Discontinuation in a Renal Biopsy of a Nephrotic Syndrome Patient.

A 73-year-old woman with atrial fibrillation treated with rivaroxaban was hospitalized for nephrotic syndrome. After discontinuation of rivaroxaban to lower the risk of hemorrhagic events, a renal biopsy was performed. Rivaroxaban was scheduled to resume a week after the biopsy to prevent renal hemorrhaging. However, she developed acute brachial arterial embolic occlusion and mural thrombosis in the abdominal aorta before resuming rivaroxaban. If immune-mediated renal diseases are suspected in anticoagulated patients at a risk of thrombotic events, physicians should consider initiating glucocorticoid therapy without a renal biopsy in order to avoid hemorrhagic and thrombotic events.

Vancomycin Intoxication and Cefepime-induced Encephalopathy Treated by Abdominal Drainage of Massive Ascites in Addition to Online Hemodiafiltration.

A patient with recurrent plasmacytoma with massive ascites exhibited vancomycin intoxication and cefepime-induced encephalopathy due to renal dysfunction. The ascitic accumulation of these drugs was suspected because of the refractory intoxicated state. To remove these drugs that had accumulated in the blood and ascites, abdominal drainage was performed in addition to online hemodiafiltration. If patients with renal dysfunction and massive ascites develop vancomycin intoxication and cefepime-induced encephalopathy that cannot be improved by drug discontinuation, physicians should suspect ascitic accumulation and evaluate the ascitic concentration. Furthermore, if a high accumulation in massive ascites occurs, physicians should perform abdominal drainage along with blood purification.

[A case of thrombotic microangiopathy with glomerular subendothelial IgA deposition due to bevacizumab].

Bevacizumab, an inhibitor of vascular endothelial growth factor, is approved for the treatment of various cancers, but the incidence of proteinuria as a side effect has been reported to be 2-64%. We report a case of renal impairment due to thrombotic microangiopathy (TMA) accompanied with glomerular subendothelial deposition of IgA resulting from bevacizumab administration. A 57-year-old female with advanced breast cancer, to whom bevacizumab had been administered from October 2012, developed proteinuria and epithelial casts in her urine about a month later. Serum creatinine remained at 0.7-0.8 mg/dL until June 2013, but gradually increased to 1.3 mg/dL in September. She was referred to our hospital because her renal function had not improved despite termination of bevacizumab, and a renal biopsy was performed in October. At that time, the levels of proteinuria, serum creatinine and serum IgA were high at 1.3 g/g x Cr, 1.6 mg/dL and 430 mg/dL, respectively. Histological examinations showed prominent IgA deposits in the subendothelial area and glomerular infiltration of CD68 positive cells in addition to features of TMA, such as narrowed glomerular capillary lumina and double contours of the basement membranes. In consideration of her clinical history, a diagnosis of bevacizumab-induced TMA was made. Through follow-up care without readministration of bevacizumab, epithelial casts in her urine disappeared, and proteinuria decreased to 0.62 g/g x Cr in November. Serum creatinine remains high at around 1.3 mg/dL, but has not elevated further. Serum IgA gradually decreased and reached 289 mg/dL in April 2014. TMA due to bevacizumab described in several other reports was also accompanied by glomerular IgA deposition, thus a differential diagnosis of IgA nephropathy is required. TMA was recently added to a section of "significant adverse effects" in the package insert of bevacizumab. Nephrologists should be fully aware of this drug-induced nephropathy.

The evaluation of filtration coefficients of microvasculature for the assessment of fluid status in hemodialysis patients.

PURPOSE: Bioimpedance spectroscopy (BIS) is widely used to assess fluid status in hemodialysis (HD) patients. Our purpose is to evaluate filtration coefficients (Lpst) as an alternative test to assess fluid status by utilizing BIS as a reference test.
 METHODS: 106 HD patients (determined group) were divided into two groups with (EX group: 53) or without excess fluid mass (ExF). ExF calculated from extracellular water and intracellular water measured by BIS. Multiple linear regression equation of Lpst was made using ExF (ExF/DW) and ultrafiltration rate (UFR/DW) to adjust Lpst (AdjLpst). The cut-off values of the tests for detection of EX were determined by receiver-operator characteristic curve analysis. Lpst, AdjLpst, serum atrial natriuretic peptide concentration (ANP), ultrasonically measured inferior vena cava diameter (IVCe/BSA), and blood volume change (Δ BV/TUF/DW) were examined. The detection abilities of these tests were evaluated in the distinct 61 patients (evaluated group).
 RESULTS: Patients of the EX group numbered 29 in the evaluated group. The correlation between AdjLpst and ExF/DW was the highest. The sensitivity of AdjLpst and specificity of Lpst were the highest. The specificity of AdjLpst was equivalent to that of Lpst. Unadjusted and adjusted odds ratios of AdjLpst were the higher (20.80, 95% CI, 5.61-77.10, 16.06, 95% CI 4.00-64.59, respectively) than those of the other tests.
 CONCLUSIONS: AdjLpst can detect patients of the EX group more accurately than other tests. Because AdjLpst is related to plasma refilling, it may indicate removable fluid overload. AdjLpst in conjunction with BIS may contribute to more adequate fluid management.

Evaluation of estimated creatinine clearance before steady state in acute kidney injury by creatinine kinetics.

BACKGROUND: A simple method to calculate estimated creatinine clearance using two serum creatinine concentration (Cr) values in acute kidney injury (AKI) was developed (eCrCl-AKI). We aimed to evaluate its accuracy and to clarify its contribution to the classification of AKI. METHODS: We validated the errors in eCrCl-AKI in a simulation study after various reductions in creatinine clearance (CrCl) at various levels of chronic kidney disease (CKD). We compared the eCrCl-AKI-based classification of RIFLE criteria with the Cr-based classification or that proposed by Waikar and Bonventre. The regression equations of eCrCl-AKI on time were determined and Cr values were reconstructed by creatinine kinetics substituting CrCl with eCrCl-AKI in actual patients. RESULTS: Most errors in eCrCl-AKI were relatively small (from -13.6 to +7.9%) with the exception of two Cr values that straddled the changing trend of Cr. The classification according to RIFLE criteria based on Cr was unstable and did not enable adequate classification, especially in milder reductions of CrCl with advanced CKD. The classification based on eCrCl-AKI was stable and enabled adequate classification. There were good agreements between measured Cr and reconstructed Cr with eCrCl-AKI. The regression equations of eCrCl-AKI revealed changes of renal function that were unexpected only from fluctuations of Cr. CONCLUSIONS: eCrCl-AKI can provide relatively accurate estimates for fluctuating CrCl. eCrCl-AKI enables more stable and earlier classification of AKI than Cr, at least in the simulation study. The more widespread use of eCrCl-AKI in actual clinical settings of AKI is necessary to evaluate this formula.

Discrepancy between cystatin C and creatinine points leading to a diagnosis of postrenal acute kidney injury and its reversibility: three case reports.

We report on three patients with postrenal acute kidney injury (AKI) showing a remarkably low level of cystatin C (CysC) compared with that of creatinine (Cr). The levels of Cr and CysC (Cr/CysC) were respectively as follows: 12.16 mg/dl/1.26 mg/l, 17.92 mg/dl/0.95 mg/l and 18.94 mg/dl/0.55 mg/l. The causes of urinary tract obstruction were benign prostatic hypertrophy, urinary bladder carcinoma and urethral stenosis due to radiation therapy for bladder carcinoma. Renal function was promptly recovered after relief of the obstruction. It is considered that the discrepancy strongly indicated AKI because of urinary tract obstruction and encouraged relief of the obstruction in order to recover renal function. Although the precise mechanism for the discrepancy was not determined, the maintenance of glomerular filtration and proximal tubular reabsorption of CysC long after the cessation of Cr excretion because of urinary tract obstruction seemed to be involved. This finding may be beneficial for the diagnosis and reversal of postrenal AKI and provides new insight into the process of postrenal AKI.

Comparisons of cystatin C with creatinine for evaluation of renal function in chronic kidney disease.

BACKGROUND: Because of the limitations of creatinine (Cr) as a marker for the glomerular filtration rate (GFR), cystatin C (CysC) has been proposed as an alternative substance. The aim here was to clarify the characteristics of CysC compared with Cr. METHODS: CysC and Cr were measured in 199 patients with chronic kidney disease. Regression analysis between CysC and Cr and comparisons of the effect of gender, inflammation, prescription of prednisolone, smoking and diabetes mellitus (DM) on these markers were performed. Sensitivity and specificity of CysC and Cr to discriminate estimated GFR of less than 50 ml/min/1.73 m(2) were computed and evaluated by the receiver-operating characteristic curve (ROC). RESULTS: The correlation coefficient between natural logarithmic Cr [ln(Cr)] and ln(CysC) was higher than that between these variables per se (0.941 vs. 0.906). When Cr was lower than 1.10 mg/dl, CysC rose more sharply than Cr. CysC divided by Cr (CysC/Cr) was higher in females (1.35 +/- 0.33 vs. 1.16 +/- 0.30; p < 0.001), in patients with elevated CRP (1.33 +/- 0.40 vs. 1.21 +/- 0.29; p < 0.001) and in patients prescribed with prednisolone (1.42 +/- 0.33 vs. 1.20 +/- 0.30; p < 0.001). A stepwise multiple linear regression model indicated that ln(CysC) was positively correlated with ln(Cr), age, female gender, prednisolone prescription, elevated CRP and DM (R = 0.964, p < 0.001). The area under the ROC curve of Cr was 0.900 and that of CysC was 0.925. CONCLUSION: CysC is a promising marker for GFR because it was not gender- or age-related. However, inflammation, prednisolone and DM caused CysC to deviate higher than expected from GFR. CysC can rise sensitively in early renal dysfunction.

Evaluation of markers to estimate volume status in hemodialysis patients: atrial natriuretic peptide, inferior vena cava diameter, blood volume changes and filtration coefficients of microvasculature.

Relationships among five markers of volume status - cardio-thoracic ratio (CTR), atrial natriuretic peptide (ANP), inferior vena cava diameter at quiet expiration (IVCe), blood volume change (Delta BV/TUF) during ultrafiltration and filtration coefficients of microvasculature (Lpst) - were investigated. Fifty stable hemodialysis patients were enrolled. The CTR was measured before hemodialysis (HD), and ultrasonic measurement of IVCe and sample collection for ANP were performed shortly after HD. Lpst and Delta BV/TUF were calculated using a CRIT-LINE monitor. Overhydrated patients determined by each marker (OVERctr, OVERivc, OVERanp, OVERlp and OVERbv) were compared. The agreement of volume status determined by each marker was assessed by kappa value, and the sensitivity and specificity of each marker to distinguish overhydrated patients were analyzed by a receiver-operating characteristic (ROC) curve. IVCe, ANP, Delta BV/TUF and Lpst, significantly correlated with each other. The correlation coefficients of Lpst with IVCe, ANP and Delta BV/TUF were higher than the others. The kappa value between ANP and Lpst was the highest. OVERanp was the highest, then OVERlp, OVERivc and OVERbv, in this order. The OVERlp and OVERivc patients were completely included in OVERanp. All patients, except one OVERbv patient, were included in OVERlp. The relatively high distinguishing ability of Lpst was demonstrated by ROC analysis. These results suggest that the determination of overhydration solely by ANP was an overestimation and by Delta BV/TUF was an underestimation. The relatively high correlation coefficients of Lpst with other markers, as well as its distinguishing ability, suggest that Lpst fluctuates in close relation to other markers.

Synergistic growth suppression induced in esophageal squamous cell carcinoma cells by combined treatment with docetaxel and heavy carbon-ion beam irradiation.

Heavy carbon-ion beam therapy has revealed several potential advantages over X-rays. Heavy-ion therapy has been applied for various solid tumors including esophageal squamous cell carcinoma (SCC). Although the local control rate of carbon ion radiotherapy for esophageal cancer has revealed better rates than that of conventional radiotherapy, some patients have shown resistance to the treatment. No study has evaluated whether anti-cancer drugs can enhance the anti-tumor effect of heavy carbon-ion beam irradiation. Therefore, we evaluated the efficacy of docetaxel, fluorouracil, cisplatinum, doxorubicin and gemcitabine to enhance the anti-tumor effects of heavy carbon-ion beam irradiation on human esophageal SCC cells in both in vitro and in vivo experiments. Fluorouracil, cisplatinum, doxorubicin and gemcitabine showed only additive anti-tumor effects. On the other hand, growth suppression was significantly potentiated by the combined treatment with heavy carbon-ion beam and docetaxel as compared to that treated with either agent alone. These data suggest that heavy carbon-ion beam irradiation combined with docetaxel may be a potentially useful therapeutic strategy for locally advanced esophageal SCC.

Chromosomal mapping of hyperserum IgA and glomerular IgA deposition in a high IgA (HIGA) strain of DdY mice.

BACKGROUND: The high IgA (HIGA) strain of ddY mice is an inbred model of IgA nephropathy (IgAN), established by selective mating of outbred ddY mice. HIGA mice show high levels of serum IgA and glomerulonephritis with mesangial IgA deposition. To identify the genetic loci responsible for hyperserum IgA and glomerular IgA deposition in this strain, quantitative trait loci analysis was carried out. METHODS: By crossing HIGA with BALB/c mice, 244 F2 generations were produced. Serum IgA levels and glomerular IgA deposition were examined at 40 weeks of age. Genetic markers were typed at 105 microsatellites and the quantitative trait loci of hyperserum IgA and glomerular IgA deposition were confirmed using Map Manager QTX software. RESULTS: Two significant quantitative trait loci of hyperserum IgA were identified on chromosome 2 [logarithm of odds (LOD) = 5.01] and chromsome 4 (LOD = 4.45), and a suggestive quantitative trait locus of hyperserum IgA was located on chromosome 1 (LOD = 3.49). On chromosome 15, a significant quantitative trait locus of glomerular IgA deposition was identified (LOD = 4.40) without the hyperserum IgA locus. Serum IgA level was weakly correlated with the intensity of glomerular IgA in 244 F2 mice; however, the quantitative trait loci of hyperserum IgA were not significantly associated with glomerular IgA deposition. CONCLUSION: These findings indicate that, in HIGA mice, glomerular IgA deposition is mainly regulated by a quantitative trait locus on chromosome 15, and hyperserum IgA synergistically but weakly affect glomerular IgA deposition. The immune disturbance similar to IgAN was revealed to be under multigenic control in HIGA mice.

Quantitative trait loci (QTL) analysis reveals a close linkage between the hinge region and trimeric IgA dominancy in a high IgA strain (HIGA) of ddY mice.

Polymerization of IgA has been suggested as one of the causes of mesangial deposition in IgA nephropathy. HIGA mice are an inbred model of IgA nephropathy, established by selective mating of ddY mice. This strain is characterized by a unique profile of the IgA molecule that is dominantly polymeric and has high serum levels with intense IgA deposition on the mesangium. We carried out quantitative trait loci (QTL) analysis, using F2 generations by crossing HIGA with BALB/c mice. Significant linkage of polymeric IgA in serum samples was identified around D12Mit263, which is close to the gene of the immunoglobulin heavy chain on chromosome 12. The amino acid sequence of the alpha heavy chain revealed marked differences between BALB/c and HIGA mice. Furthermore, most differences were focussed on the hinge region. The DBA/2J strain, which has the same amino acid sequence in the hinge region as the HIGA strain, also showed polymeric IgA dominance but low IgA levels in sera. Size fraction analysis revealed that these polymeric IgA showed trimer dominance in both DBA/2J and HIGA mice. In conclusion, the hinge region plays a key role in trimeric IgA formation in HIGA mice.