Outcomes of brachial artery transposition in hemodialysis patients.

OBJECTIVE: In hemodialysis patients with a difficult access extremity who are not suitable for an arteriovenous fistula or arteriovenous graft creation, the concept of cannulating a superficialized artery for arterial outflow in dialysis sessions has been adopted as a tertiary alternative. However, its long-term patency and complications have not been recognized widely. We report our 16-year experience with hemodialysis access creation using the brachial artery transposition (BAT) technique. METHODS: This single-center retrospective study included consecutive patients who underwent BAT for hemodialysis vascular access between June 1, 2006, and December 31, 2022. The patency of the whole access circuit and the transposed brachial artery itself was evaluated independently. RESULTS: In total, 193 surgical procedures were included. The success rate was 93.2%. The mean operative time was 128 minutes. The median interval from access placement to first cannulation was 21 days. The primary patency rates for BAT were 92.3%, 91.3%, 90.3%, 86.1%, and 71.9% at 1, 2, 3, 5, and 10 years, respectively. The secondary patency rates for BAT were 96.3%, 96.3%, 95.0%, 90.1%, and 74.9% at 1, 2, 3, 5, and 10 years, respectively. The primary patency rates for the whole access circuit were 61.4%, 49.2%, 45.8%, and 26.9% at 1, 2, 3, and 5 years, respectively. The secondary patency rates for the whole access circuit were 85.1%, 83.3%, 82.0%, and 68.6% at 1, 2, 3, and 5 years, respectively. The overall patient survival rates were 79.6%, 69.6%, 54.6%, 36.5%, and 13.4% at 1, 2, 3, 5 and 10 years, respectively. The abandonments of BAT were brachial artery thrombosis (n = 6), pseudoaneurysm (n = 2), aneurysmal change (n = 1), and other reasons (n = 1). The abandonments of the whole access circuit were exhaustion of venous return (n = 26), abandonment of BAT (n = 7), and other reasons (n = 2). Complications were exhaustion of venous return (n = 26), aneurysmal change (n = 12), pseudoaneurysm (n = 6), brachial artery thrombosis (n = 7), impaired wound healing (n = 19), lymphorrhea (n = 9), skin infection (n = 5), hematoma on cannulation (n = 3), and reduced peripheral blood flow (n = 2). CONCLUSIONS: The patency of BAT was excellent, and that of the whole access circuit was adequate, with a few complications. BAT is an effective alternative from a long-term perspective for patients who are unsuitable for conventional hemodialysis access creation.

Serum Cytokeratin 18 as a Metastatic and Therapeutic Marker for Extramammary Paget's Disease.

Extramammary Paget's disease (EMPD) is a rare cutaneous adenocarcinoma with unfavourable prognosis once it becomes invasive. A tumour marker that reflects disease progression is required for adequate management of EMPD. Cytokeratin 18 is highly expressed in many types of cancer and its soluble forms are detected by M30 (for caspase-cleaved form) and M65 (for both caspase-cleaved and intact forms) assays. We report here that tumour cells of EMPD in both lesional skin and lymph node metastasis are immunohistochemically positive for CK18, and the baseline serum M30 and M65 levels in patients with metastatic EMPD are significantly higher than those in non-metastatic patients. In addition, serial serum M30 and M65 levels might reflect recurrence of EMPD and response to chemotherapy. These results suggest that serum CK18 levels may be a useful tumour marker for advanced EMPD.

Deep learning analysis of clinical course of primary nephrotic syndrome: Japan Nephrotic Syndrome Cohort Study (JNSCS).

BACKGROUND: Prognosis of nephrotic syndrome has been evaluated based on pathological diagnosis, whereas its clinical course is monitored using objective items and the treatment strategy is largely the same. We examined whether the entire natural history of nephrotic syndrome could be evaluated using objective common clinical items. METHODS: Machine learning clustering was performed on 205 cases from the Japan Nephrotic Syndrome Cohort Study, whose clinical parameters, serum creatinine, serum albumin, dipstick hematuria, and proteinuria were traceable after kidney biopsy at 5 measured points up to 2 years. The clinical patterns of time-series data were learned using long short-term memory (LSTM)-encoder-decoder architecture, an unsupervised machine learning classifier. Clinical clusters were defined as Gaussian mixture distributions in a two-dimensional scatter plot based on the highest log-likelihood. RESULTS: Time-series data of nephrotic syndrome were classified into four clusters. Patients in the fourth cluster showed the increase in serum creatinine in the later part of the follow-up period. Patients in both the third and fourth clusters were initially high in both hematuria and proteinuria, whereas a lack of decline in the urinary protein level preceded the worsening of kidney function in fourth cluster. The original diseases of fourth cluster included all the disease studied in this cohort. CONCLUSIONS: Four kinds of clinical courses were identified in nephrotic syndrome. This classified clinical course may help objectively grasp the actual condition or treatment resistance of individual patients with nephrotic syndrome.

Supportive Effects of Online Hemodiafiltration Therapy on the Nutritional State and Lipid Profile in Very Elderly Dialysis Patients.

INTRODUCTION: Online hemodiafiltration (HDF) therapy has been recognized as one of the potential dialysis modalities. However, the long-term effects of online HDF therapy on very elderly dialysis patients older than 75 years have yet to be fully elucidated. METHODS: Seventy-four very elderly patients older than 75 years undergoing maintenance dialysis therapy were studied retrospectively. Twenty-four (mean ± SE, 81.5 ± 1.0 years) were treated by predilution online HDF, and fifty (81.2 ± 0.6 years) were treated by conventional hemodialysis (HD) for 3 years. Laboratory data related to the nutritional state and lipid profile were collected. Body composition was measured by a bioelectrical impedance method. RESULTS: Dry weight and body mass index decreased in HD patients (2.9%, p = 0.003 and 3.1%, p = 0.001, respectively), while no significant changes were found in online HDF patients. Serum albumin levels reduced in both HD and online HDF groups (3.5%, p = 0.003 and 2.9%, p = 0.026, respectively). The geriatric nutritional risk index decreased in HD patients (3.0%, p < 0.001), while no significant change was shown in online HDF patients. Body composition analysis demonstrated a significant decrease in intracellular water and increases in extracellular water and edema ratio in both groups. Fat mass and %fat showed significant decreases in HD patients (8.1%, p = 0.003 and 7.3%, p = 0.003, respectively), but no significant changes in online HDF patients. Among laboratory data, serum high-density lipoprotein cholesterol levels did not change in HD patients. However, the levels elevated significantly (10.6%, p = 0.03) in online HDF patients. DISCUSSION/CONCLUSION: These results indicated that the time-dependent deterioration of the nutritional state in very elderly dialysis patients was inevitable; however, such deterioration was not prominent in online HDF patients. Moreover, the lipid profile showed unique changes in online HDF patients. In order to treat very elderly dialysis patients, online HDF should preferentially be taken into consideration because the maintenance of general condition seems to be a practical goal against the natural time-dependent deterioration.

Dual disruption of eNOS and ApoE gene accelerates kidney fibrosis and senescence after injury.

The relationship between cellular senescence and fibrosis in the kidney is being elucidated and we have identified it as therapeutic target in recent studies. Chronic kidney disease has also become a lifestyle disease, often developing on the background of hypertension and dyslipidemia. In this study, we clarify the effect of interaction between these two conditions on kidney fibrosis and senescence. Wild type mice (WT), apolipoprotein E-/- mice (ApoEKO), and endothelial nitric oxide synthase (eNOS)-/- ApoE-/- mice (DKO) were obtained by breeding. Unilateral ureteral obstruction (UUO) was performed on 8-10 week old male mice and the degree of renal tubular injury, fibrosis and kidney senescence were evaluated. DKO manifested elevated blood pressure, higher total cholesterol and lower HDL than WT. DKO showed sustained kidney injury molecule-1 protein expression. Kidney fibrosis was significantly higher in ApoEKO and DKO. mRNA expression of genes related to kidney fibrosis was the highest in DKO. The mRNA expression of Zinc-α2-Glycoprotein and heme oxygenase-1 were significantly decreased in DKO. Furthermore, mRNA expression of p53, p21 and p16 were increased both in ApoEKO and DKO, with DKO being the highest. Senescence associated ß-gal positive tubule area was significantly increased in DKO. Increased DNA damage and target of rapamycin-autophagy spatial coupling compartments (TASCCs) formation was found in DKO. Mice with endothelial dysfunction and dyslipidemia developed kidney fibrosis and accelerated senescence even in young mice after injury. These data highlight the fact managing lifestyle-related diseases from a young age is important for CKD prevention.

Incidence of remission and relapse of proteinuria, end-stage kidney disease, mortality, and major outcomes in primary nephrotic syndrome: the Japan Nephrotic Syndrome Cohort Study (JNSCS).

BACKGROUND: Despite recent advances in immunosuppressive therapy for patients with primary nephrotic syndrome, its effectiveness and safety have not been fully studied in recent nationwide real-world clinical data in Japan. METHODS: A 5-year cohort study, the Japan Nephrotic Syndrome Cohort Study, enrolled 374 patients with primary nephrotic syndrome in 55 hospitals in Japan, including 155, 148, 38, and 33 patients with minimal change disease (MCD), membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), and other glomerulonephritides, respectively. The incidence rates of remission and relapse of proteinuria, 50% and 100% increases in serum creatinine, end-stage kidney disease (ESKD), all-cause mortality, and other major adverse outcomes were compared among glomerulonephritides using the Log-rank test. Incidence of hospitalization for infection, the most common cause of mortality, was compared using a multivariable-adjusted Cox proportional hazard model. RESULTS: Immunosuppressive therapy was administered in 339 (90.6%) patients. The cumulative probabilities of complete remission within 3 years of the baseline visit was ≥ 0.75 in patients with MCD, MN, and FSGS (0.95, 0.77, and 0.79, respectively). Diabetes was the most common adverse events associated with immunosuppressive therapy (incidence rate, 71.0 per 1000 person-years). All-cause mortality (15.6 per 1000 person-years), mainly infection-related mortality (47.8%), was more common than ESKD (8.9 per 1000 person-years), especially in patients with MCD and MN. MCD was significantly associated with hospitalization for infection than MN. CONCLUSIONS: Patients with MCD and MN had a higher mortality, especially infection-related mortality, than ESKD. Nephrologists should pay more attention to infections in patients with primary nephrotic syndrome.

Better remission rates in elderly Japanese patients with primary membranous nephropathy in nationwide real-world practice: The Japan Nephrotic Syndrome Cohort Study (JNSCS).

BACKGROUND: The aim of the present study was to clarify the prevalence of immunosuppressive drug use and outcomes in elderly and non-elderly patients with primary membranous nephropathy (MN) in nationwide real-world practice in Japan. PATIENTS AND METHODS: Between 2009 and 2010, 374 patients with primary nephrotic syndrome were enrolled in the cohort study (The Japan Nephrotic Syndrome Cohort Study, JNSCS), including 126 adult patients with MN. Their clinical characteristics were compared with those of nephrotic patients with primary MN registered in a large nationwide registry (The Japan Renal Biopsy Registry, J-RBR). Outcomes and predictors in the elderly (≥ 65 years) and non-elderly groups were identified. RESULTS: Similar clinical characteristics were observed in JNSCS patients and J-RBR patients (n = 1808). At the early stage of 1 month, 84.1% of patients were treated with immunosuppressive therapies. No significant differences were observed in therapies between age groups. However, elderly patients achieved complete remission (CR) more frequently than non-elderly patients, particularly those treated with therapies that included corticosteroids. No significant differences were noted in serum creatinine (sCr) elevations at 50 or 100%, end-stage kidney disease, or all-cause mortality between age groups. Corticosteroids were identified as an independent predictor of CR (HR 2.749, 95%CI 1.593-4.745, p = 0.000) in the multivariate Cox's model. sCr levels, hemoglobin levels, immunosuppressants, clinical remission, and relapse after CR were independent predictors of sCr × 1.5 or × 2.0. CONCLUSION: Early immunosuppressive therapy including corticosteroids for primary MN showed better remission rates in elderly patients in a nationwide cohort study.

All-trans retinoic acid suppresses bone morphogenetic protein 4 in mouse diabetic nephropathy through a unique retinoic acid response element.

Diabetic nephropathy (DN) causes mesangial matrix expansion, which results in glomerulosclerosis and renal failure. Collagen IV (COL4) is a major component of the mesangial matrix that is positively regulated by bone morphogenetic protein 4 (BMP4)/suppressor of mothers against decapentaplegic (Smad1) signaling. Because previous studies showed that retinoids treatment had a beneficial effect on kidney disease, we investigated the therapeutic potential of retinoids in DN, focusing especially on the regulatory mechanism of BMP4. Diabetes was induced with streptozotocin in 12-wk-old male Crl:CD1(ICR) mice, and, 1 mo later, we initiated intraperitoneal injection of all-trans retinoic acid (ATRA) three times weekly. Glomerular matrix expansion, which was associated with increased BMP4, phosphorylated Smad1, and COL4 expression, worsened in diabetic mice at 24 wk of age. ATRA administration alleviated DN and downregulated BMP4, phosopho-Smad1, and COL4. In cultured mouse mesangial cells, treatment with ATRA or a retinoic acid receptor-α (RARα) agonist significantly decreased BMP4 and COL4 expression. Genomic analysis suggested two putative retinoic acid response elements (RAREs) for the mouse Bmp4 gene. Chromatin immunoprecipitation analysis and reporter assays indicated a putative RARE of the Bmp4 gene, located 11,488-11,501 bp upstream of exon 1A and bound to RARα and retinoid X receptor (RXR), which suppressed BMP4 expression after ATRA addition. ATRA suppressed BMP4 via binding of a RARα/RXR heterodimer to a unique RARE, alleviating glomerular matrix expansion in diabetic mice. These findings provide a novel regulatory mechanism for treatment of DN.

Influence of albumin leakage on glycated albumin in patients with type 2 diabetes undergoing hemodialysis.

Glycated albumin (GA) is recommended as a better glycemic indicator than HbA1c in patients undergoing hemodialysis, because the red blood cell lifespan is generally faster than that in normal subjects. However, GA can be also affected by protein loss in urine and hemodialysis fluid. Therefore, in this study, we investigated the effect of albumin leakage induced by hemodialysis on GA. Nine patients undergoing hemodialysis with a large or small amount of albumin leakage were observed for 9 months in a crossover manner. As a result, it was shown that albumin leakage could affect GA, but the effect was practically small considering the prescription of diabetic drugs. The correlations between HbA1c and blood glucose levels and between GA and blood glucose levels were similar in our study. In conclusion, GA was a reliable indicator, even with the change of hemodialysis modality. The influence of albumin leakage induced by hemodialysis on GA was negligible practically. We should recognize that the preferable glycemic indicator in patients undergoing hemodialysis depends on the hemoglobin and albumin metabolism of each patient.

Regional variations in immunosuppressive therapy in patients with primary nephrotic syndrome: the Japan nephrotic syndrome cohort study.

BACKGROUND: The lack of high-quality clinical evidences hindered broad consensus on optimal therapies for primary nephrotic syndromes. The aim of the present study was to compare prevalence of immunosuppressive drug use in patients with primary nephrotic syndrome across 6 regions in Japan. METHODS: Between 2009 and 2010, 380 patients with primary nephrotic syndrome in 56 hospitals were enrolled in a prospective cohort study [Japan Nephrotic Syndrome Cohort Study (JNSCS)], including 141, 151, and 38 adult patients with minimal change disease (MCD), membranous nephropathy (MN), and focal segmental glomerulosclerosis (FSGS), respectively. Their clinical characteristics were compared with those of patients registered in a large nationwide registry of kidney biopsies [Japan Renal Biopsy Registry (J-RBR)]. The regional prevalence of use of each immunosuppressive drug was assessed among adult MCD, MN, and FSGS patients who underwent immunosuppressive therapy in the JNSCS (n = 139, 127, and 34, respectively). Predictors of its use were identified using multivariable-adjusted logistic regression models. RESULTS: The clinical characteristics of JNSCS patients were comparable to those of J-RBR patients, suggesting that the JNSCS included the representatives in the J-RBR. The secondary major immunosuppressive drugs were intravenous methylprednisolone [n = 33 (24.6%), 24 (19.7%), and 9 (28.1%) in MCD, MN, and FSGS, respectively] and cyclosporine [n = 25 (18.7%), 62 (50.8%), and 16 (50.0%), respectively]. The region was identified as a significant predictor of use of intravenous methylprednisolone in MCD and MN patients. CONCLUSION: Use of intravenous methylprednisolone for MCD and MN differed geographically in Japan. Its efficacy should be further evaluated in a well-designed trial.

Prognostic factors for mortality in middle-aged and older hemodialysis patients: a 5-year observational study.

Clinical guidelines for hemodialysis therapy have been described in an evidence-based manner with most evidence from randomized control trials or retrospective studies in which all generations of the hemodialysis patients were enrolled. Therefore, the question still remains whether these guidelines can be applied to increasing older patients. This study is an observational study, including 735 patients who received maintenance hemodialysis in April 2006. At baseline, the participants' age was 62.1 ± 12.8 years (mean ± SD). Hemodialysis duration was 103.7 ± 89.3 months. In a 5-year observation period (actual follow-up period: 1551 ± 499 days), 175 patients died. Prognostic factors were investigated by multivariate analysis with Cox proportional hazard model. Next, we stratified the patients according to their age. 363 patients were included in the middle-aged patient's category between 40 and 64 years, and 314 were involved in the older patient's category between 65 and 84 years old. As a subanalysis, significant predictors of 5-year survival were examined in the age-stratified cohort. Then, Kt/V, serum ß2-microglobulin and calcium concentration were significant predictors in our entire cohort, as well as body mass index, neutrophil count, and serum sodium concentration even after adjustment for age, gender, diabetic status and hemodialysis duration. However, Kt/V, serum ß2-microglobulin and calcium concentration controlled by hemodialysis prescriptions were independent risk factors especially in older patients, not in middle-aged patients. In conclusion, hemodialysis prescriptions for lowering uremic toxins and managing mineral-bone disorder are important to decrease the risk of death even in older hemodialysis patients.

Mesangial Cell Mammalian Target of Rapamycin Complex 1 Activation Results in Mesangial Expansion.

Human glomerular diseases can be caused by several different diseases, many of which include mesangial expansion and/or proliferation followed by glomerulosclerosis. However, molecular mechanisms underlying the pathologic mesangial changes remain poorly understood. Here, we investigated the role of the mammalian target of rapamycin complex 1 (mTORC1)-S6 kinase pathway in mesangial expansion and/or proliferation by ablating an upstream negative regulator, tuberous sclerosis complex 1 (TSC1), using tamoxifen-induced Foxd1-Cre mice [Foxd1ER(+) TSC1 mice]. Foxd1ER(+) TSC1 mice showed mesangial expansion with increased production of collagen IV, collagen I, and α-smooth muscle actin in glomeruli, but did not exhibit significant mesangial proliferation or albuminuria. Furthermore, rapamycin treatment of Foxd1ER(+) TSC1 mice suppressed mesangial expansion. Among biopsy specimens from patients with glomerular diseases, analysis of phosphorylated ribosomal protein S6 revealed mesangial cell mTORC1 activation in IgA nephropathy and in lupus mesangial proliferative nephritis but not in the early phase of diabetic nephropathy. In summary, mesangial cell mTORC1 activation can cause mesangial expansion and has clinical relevance for human glomerular diseases. This report also confirms that the tamoxifen-induced mesangium-specific Cre-loxP system is useful for studies designed to clarify the role of the mesangium in glomerular diseases in adults.

Successful treatment of highly advanced immunoglobulin G4-related kidney disease presenting renal mass-like regions with end-stage kidney failure: a case study.

BACKGROUND: Immunoglobulin G4-related kidney disease characterized by immunoglobulin G4-positive plasma cell-rich tubulointerstitial nephritis has distinctive serological and radiological findings. Renal prognosis is good because of a good response to glucocorticoids. Here we report a case of successful treatment of highly advanced immunoglobulin G4-related kidney disease presenting renal mass-like regions with end-stage kidney failure. CASE PRESENTATION: A 59-year-old Japanese man was referred to our hospital because of uremia with a creatinine level of 12.36 mg/dL. Urinalysis revealed mild proteinuria and hyperß2microglobulinuria, and blood tests showed hyperglobulinemia with an IgG level of 3243 mg/dL and an IgG4 level of 621 mg/dL. Non-contrast computed tomography revealed renal mass-like regions. Based on the findings, immunoglobulin G4-related kidney disease was suspected, however, further radiological examination showed unexpected results. Ga-67 scintigraphy showed no kidney uptake. T2-weighted magnetic resonance imaging revealed high-intensity signals which corresponded to mass-like regions and multiple patchy low-intensity signals in kidney cortex. Finally, the patient was diagnosed with immunoglobulin G4-related kidney disease by renal pathology of severe immunoglobulin G4-positive plasma cell-rich tubulointerstitial nephritis and characteristic fibrosis. He received 50 mg oral prednisolone, which was tapered with a subsequent decrease of serum creatinine and IgG4 levels. One year after initiation of treatment, he achieved normalization of serum IgG4 level and proteinuria, and remained off dialysis with a creatinine level of 3.50 mg/dL. After treatment with steroids, repeat imaging suggested bilateral severe focal atrophy. However, mass-like regions did not show atrophic change although renal atrophy was evident in patchy low-intensity lesions on T2-weighted magnetic resonance imaging. These findings suggest that multiple patchy low-intensity signals and high-intensity mass-like regions were mildly atrophic lesions of immunoglobulin G4-related kidney disease due to severe fibrosis and normal parts of kidney, respectively. CONCLUSIONS: In immunoglobulin G4-related kidney disease with severe kidney failure, radiological findings should be carefully examined. In addition, renal prognosis may be good despite highly advanced tubulointerstitial nephritis and fibrosis.

Henoch-Schönlein purpura nephritis occurring postpartum in a patient with anti-PL-7 anti-synthetase syndrome.

A 37-year-old pregnant woman developed purpura which was subsequently diagnosed as Henoch-Schönlein purpura (HSP). After childbirth, the patient developed proteinuria and hematuria. Further examination revealed that the HSP nephritis (HSPN) was associated with anti-threonyl-tRNA synthetase anti-synthetase syndrome. The onset of HSPN during pregnancy or after childbirth is rare. Moreover, to our knowledge, this is the first case to describe renal involvement in anti-synthetase syndrome.

The effect of albumin leakage in hemodialysis patients on redox status of serum albumin.

Human mercaptoalbumin (HMA) is a reduced form of albumin that is associated with cardiovascular disease in dialysis patients. Albumin-leaky hemodialysis (HD) is increasingly recognized as a gold standard therapy because it is correlated with better prognosis compared to conventional HD. However, albumin-leaky HD induces low serum albumin concentration because of albumin leakage, which is a classical risk factor for mortality. The aim of this study was to explain the preferable prognosis in patients undergoing albumin-leaky HD with low serum albumin concentration. Ten HD patients were enrolled. They were preconditioned with albumin-non-leaky HD (mean albumin leakage: 1.0 g) for 2 months. Subsequently, albumin-leaky HD (9.1 g) was performed for 6 months, followed by relatively non-leaky HD (within 3.0 g). The ratio and level of HMA were evaluated. The amount of albumin leakage was related to the ratio of HMA, and inversely correlated with serum albumin concentration. The level of HMA was maintained regardless of albumin leakage. Regarding HMA level, a moderate amount of albumin leakage was acceptable. A stably maintained HMA level in albumin-leaky HD patients can contribute to preferable prognosis even if they have low serum albumin concentration.

Re-evaluation of Pre-pump Arterial Pressure to Avoid Inadequate Dialysis and Hemolysis: Importance of Prepump Arterial Pressure Monitoring in Hemodialysis Patients.

Prepump arterial pressure (PreAP) is monitored to avoid generating excessive negative pressure. The National Kidney Foundation K/DOQI clinical practice guidelines for vascular access recommend that PreAP should not fall below -250 mm Hg because excessive negative PreAP can lead to a decrease in the delivery of blood flow, inadequate dialysis, and hemolysis. Nonetheless, these recommendations are consistently disregarded in clinical practice and pressure sensors are often removed from the dialysis circuit. Thus far, delivered blood flow has been reported to decrease at values more negative than -150 mm Hg of PreAP. These values have been analyzed by an ultrasonic flowmeter and not directly measured. Furthermore, no known group has evaluated whether PreAP-induced hemolysis occurs at a particular threshold. Therefore, the aim of this study was to clarify the importance of PreAP in the prediction of inadequate dialysis and hemolysis. By using different diameter needles, human blood samples from healthy volunteers were circulated in a closed dialysis circuit. The relationship between PreAP and delivered blood flow or PreAP and hemolysis was investigated. We also investigated the optimal value for PreAP using several empirical monitoring methods, such as a pressure pillow. Our investigation indicated that PreAP is a critical factor in the determination of delivered blood flow and hemolysis, both of which occured at pressure values more negative than -150 mm Hg. With the exception of direct pressure monitoring, commonly used monitoring methods for PreAP were determined to be ineffective. We propose that the use of a vacuum monitor would permit regular measurement of PreAP.

Bioelectrical Impedance Phase Angle Value and Prolongations of PR and Corrected QT Intervals in Patients Undergoing Dialysis.

INTRODUCTION: Phase angle value, derived from bioelectrical impedance analysis, represents the body cell mass and nutritional status of patients undergoing hemodialysis. Although the phase angle value has clinical significance in these patients, its relationship with electrocardiogram (ECG), another clinically relevant bioelectrical examination, has not yet been well clarified. METHODS: Two hundred and twenty-four patients undergoing dialysis (80 females and 144 males; mean ± SD, 72.2 ± 12.0 years old; 117 diabetic and 107 nondiabetic patients) were studied retrospectively. Multifrequency bioelectrical impedance analysis was performed immediately after the end of dialysis therapy. The phase shift was geometrically converted into a phase angle value. The ECG was recorded simultaneously, and the upper limits of the PR interval, QRS width, and corrected QT interval (QTc) were set at 0.20, 0.12, and 0.44 s, respectively. The geriatric nutritional risk index (GNRI), a representative nutritional index, was also determined. In addition, we examined the incidence of cardiac events, including heart failure, myocardial infarction, cardiac revascularization procedure, cardiac arrhythmia, and cardiac death, or all-cause death. RESULTS: Of 224 patients undergoing dialysis, the prolongation of the PR interval, QRS width, and QTc was found in 30.7, 17.4, and 62.1%, respectively. The prevalence of QTc prolongation was higher in females and diabetic patients than in males and nondiabetic patients. An inverse relationship between phase angle value and QTc was observed only in males and nondiabetic patients. The relationships of GNRI both with phase angle value and QTc were stronger in males and nondiabetic patients. In addition, PR interval was inversely correlated with a phase angle value only in nondiabetic patients. No significant correlation was found between phase angle value and QRS width. Five-year survival probability for the composite endpoints was significantly worse in patients with lower phase angle values. QTc prolongation was associated with survival in males and nondiabetic patients. Prolonged PR was associated with survival in nondiabetic patients. DISCUSSION: Relationships between phase angle value and ECG findings were demonstrated in patients undergoing dialysis, especially in males and nondiabetic patients. Although the phase angle value has been considered as an index for evaluating nutritional status, another clinical application of phase angle value in predicting cardiac complications seems to be useful.

Coexistence of systemic sclerosis and cryopyrin-associated periodic syndrome.

Systemic sclerosis (SSc) and cryopyrin-associated periodic syndrome (CAPS) are distinct clinical entities belonging to the autoimmune and autoinflammatory diseases, respectively. The coexistence of the two entities has rarely been reported and is poorly characterized. Here, we described a case of a 38-year-old Japanese woman diagnosed with anti-centromere antibody-positive SSc and CAPS carrying the pathogenic mutation in the NLRP3 gene, with a detailed autoantibody profile by a high-throughput comprehensive protein array covering approximately 90% of the human transcriptome. The clinical manifestations of the patient were typical of both SSc and CAPS. Comprehensive autoantibody profiling identified 65 autoantibodies in the patient's serum and 78 autoantibodies in the serum of her daughter with CAPS, who carried the same NLRP3 mutation as the patient. SSc-associated autoantibodies (anti-DBT, anti- CENP-B, and anti-CENP-A) and anti-CD320 antibody were detected at high levels only in the patient's serum, while autoantibodies to the following four proteins were detected in the sera of both the patient and her daughter: TRIM21, LIMS1, CLIP4, and KAT2A. The TRRUST enrichment analysis identified NF-κB1 and RelA as overlapping key transcription factors that regulate the genes encoding proteins to which autoantibodies were detected in the patient and her daughter, therefore the autoantibody profile of the patient cannot be solely attributed to SSc, but may also be influenced by CAPS. Although autoimmune and autoinflammatory diseases are considered to be at opposite ends of the immunological spectrum, detailed autoantibody profiling may reveal a unique immunological landscape in an overlapping case of the two entities.

Evidence of tosufloxacin deposition in the kidneys of a patient presenting with crystal nephropathy.

Tosufloxacin tosilate is classified as a new quinolone antibacterial agent, which has been reported to cause crystal nephropathy. However, the origin of these crystal deposits has not yet been elucidated. We encountered a case of renal failure that progressed slowly owing to crystal-forming interstitial nephritis after long-term exposure to tosufloxacin. Mass spectrometry of the renal specimens revealed that tosufloxacin was deposited in the kidneys. The patient's renal function improved slowly with the withdrawal of tosufloxacin and steroid therapy. This is the first case to demonstrate the presence of crystal deposits consisting of tosufloxacin.