Tachycardia and Acute Kidney Injury among Critically Ill Patients with Sepsis: A Prospective Observational Study.

INTRODUCTION: Tachycardia caused by sympathetic overactivity impairs myocardial function and raises septic patients' mortality. This study examined whether tachycardia is associated with acute kidney injury (AKI) period-prevalence among critically ill patients with and without sepsis. METHODS: In 328 patients (119 sepsis and 209 non-sepsis) admitted to our intensive care unit (ICU), we assessed heart rate at ICU admission, plasma neutrophil gelatinase-associated lipocalin (NGAL) and N-terminal pro-B-type natriuretic peptide, and urinary L-type fatty acid-binding protein and N-acetyl-ß-d-glucosaminidase (NAG) at 0 and 48 h after admission. Tachycardia was defined as a heart rate above 100 beats/min. RESULTS: Tachycardia was independently correlated with AKI prevalence during the first week after ICU admission in the septic patients, but not in the non-septic patients. A dose-dependent increase in AKI period-prevalence was observed across ascending heart rate ranges. Furthermore, we discovered a dose-dependent increase in renal biomarker-positive patients regarding plasma NGAL and urinary NAG over increasing heart rate ranges 48 h after admission. CONCLUSION: The findings revealed an independent relationship between tachycardia and AKI prevalence during the first week of ICU in septic patients. Heart rate was found to have a dose-dependent effect on AKI prevalence and renal insult monitored by biomarkers.

Acute tubulointerstitial nephritis in a patient with early bronchial tuberculosis.

Patients with chronic kidney disease (CKD) are commonly at high risk of tuberculosis (TB). Conversely, TB rarely causes tubulointerstitial nephritis. A 75-year-old Japanese man who was undergoing periodic follow-ups for CKD stage G3aA3 with membranous nephropathy was diagnosed with acute kidney injury (AKI) (estimated glomerular filtration rate [eGFR]: 15 mL/min/1.73 m2) without prerenal AKI. He reported developing recent-onset cough 3 weeks prior to presenting to us. Renal biopsy revealed acute tubulointerstitial nephritis along with known membranous nephropathy. CD4+ helper T cells comprised most lymphocytes in the tubulointerstitium. Results of the interferon-gamma release assay, sputum smear test, polymerase chain reaction (PCR), and culture test were positive for TB. Chest computed tomography revealed thickening of the left bronchial wall; therefore, a diagnosis of early bronchial TB was made; his urine culture and PCR were negative for TB. At four months after TB treatment with no immunosuppressive therapy, his eGFR improved to 50 mL/min/1.73 m2, and based on this progress, the AKI was diagnosed as tuberculosis-associated tubulointerstitial nephritis (TATIN). Although TATIN typically occurs with chronic or miliary tuberculosis, it is very rare in early bronchial TB. Identification of TATIN is important in kidney diseases of unknown etiology, and treatment with anti-TB drugs is necessary.

Anti-neutrophil cytoplasmic antibody-associated vasculitis accompanied by type II heparin-induced thrombocytopenia resulting in asymptomatic cerebral infarction: a case report.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) involves platelet activation and aggregation caused by heparin or HIT antibodies associated with poor survival outcomes. We report a case of HIT that occurred after hemodialysis was started for rapidly progressive glomerulonephritis (RPGN), which was caused by anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), and ultimately resulted in asymptomatic cerebral infarction. CASE PRESENTATION: A 76-year-old Japanese man was urgently admitted to our hospital for weight loss and acute kidney injury (serum creatinine: 12 mg/dL). Hemodialysis therapy was started using heparin for anticoagulation. Blood testing revealed elevated titers of myeloperoxidase anti-neutrophil cytoplasmic antibodies, and renal biopsy revealed crescentic glomerulonephritis with broad hyalinization of most of the glomeruli and a pauci-immune staining pattern. These findings fulfilled the diagnostic criteria for microscopic polyangiitis, and the patient was diagnosed with RPGN caused by AAV. Steroid pulse therapy, intermittent pulse intravenous cyclophosphamide, and oral steroid therapy failed to improve the patient's renal function, and maintenance dialysis was started. However, on day 15, his platelet count had decreased to 47,000/µL, with clotting observed in the hemodialysis catheter. Magnetic resonance imaging of the head identified acute asymptomatic brain infarction in the left occipital lobe, and a positive HIT antibody test result supported a diagnosis of type II HIT. During hemodialysis, the anticoagulant treatment was changed from heparin to argatroban. Platelet counts subsequently normalized, and the patient was discharged. A negative HIT antibody test result was observed on day 622. CONCLUSIONS: There have been several similar reports of AAV and HIT co-existence. However, this is a rare case report on cerebral infarction with AAV and HIT co-existence. Autoimmune diseases are considered risk factors for HIT, and AAV may overlap with other systemic autoimmune diseases. To confirm the relationship between these two diseases, it is necessary to accumulate more information from future cases with AAV and HIT co-existence. If acute thrombocytopenia and clotting events are observed when heparin is used as an anticoagulant, type II HIT should always be considered in any patient due to its potentially fatal thrombotic complications.

Seasonality of acute kidney injury incidence and mortality among hospitalized patients.

Background: Understanding disease seasonality is important for improving clinical practice, hospital resource utilization and community-based preventive care. However, no studies have investigated the seasonality of acute kidney injury (AKI). Methods: In the Tokushukai Medical Database, which includes 38 Japanese community hospitals, we identified hospitalized patients with AKI based on the Kidney Disease: Improving Global Outcomes serum creatinine criteria from January 2012 to December 2014. We plotted the number and proportion of patients with AKI among hospitalized patients by month of hospital admission. Subgroup analyses were conducted by the admission diagnosis category, timing of AKI diagnosis and age. We also examined the association between month of hospital admission and AKI, adjusting for patient characteristics and AKI risk factors. Finally, we assessed seasonal variations in disease severity and 30-day mortality of patients with AKI. Results: We identified 81 279 (14.6%) patients with AKI among 555 940 hospitalized patients. The proportion of patients with AKI was highest in January (16.7%) and lowest in June (13.4%). Subgroup analyses suggested that the seasonality of AKI incidence was driven by community-acquired AKI associated with the admission diagnosis of cardiovascular and pulmonary diseases among older patients. The adjusted odds ratio for AKI (January versus June) was 1.24 (95% confidence interval, 1.17-1.31). Patients with AKI showed a larger number of failing organs in winter, and their 30-day mortality was 16.4% in spring, 14.5% in summer, 15.6% in autumn and 18.4% in winter. Conclusion: AKI is more common among hospitalized patients and patients with AKI are more severely ill in winter.

Mortality prediction by acute kidney injury biomarkers in comparison with serum creatinine.

OBJECTIVES: To investigate the performance of acute kidney injury (AKI) biomarkers for mortality prediction. MATERIALS AND METHODS: Cutoff values of urinary L-type fatty acid-binding protein (L-FABP) and N-acetyl-ß-d-glucosaminidase (NAG) for AKI diagnosis in ICU were determined in the derivation cohort. The performance of these AKI biomarkers for mortality prediction was evaluated in the validation cohort with stratification of serum-creatinine based AKI diagnosis. RESULTS: Mortality in the AKI patients diagnosed by serum creatinine was increased remarkably when urinary L-FABP and NAG were positive. CONCLUSIONS: These AKI biomarkers can specifically detect high-risk patients among creatinine-base diagnosed AKI.

Sarpogrelate hydrochloride, a selective 5-HT(2A) receptor antagonist, improves skin perfusion pressure of the lower extremities in hemodialysis patients with peripheral arterial disease.

BACKGROUND: Peripheral arterial disease (PAD) frequently occurs in patients on hemodialysis (HD); however, little is known about the effectiveness of drugs. We compare the effects of sarpogrelate and cilostazol in HD patients with PAD. METHODS: We conducted a prospective, randomized, open-label, and multicenter trial for 24 weeks in HD patients with PAD. Thirty-five patients were divided into two groups: sarpogrelate (n = 17) and cilostazol (n = 18). We analyzed changes in skin perfusion pressure (SPP), levels of oxidative stress biomarkers, and adverse events. RESULTS: At 24 weeks, SPP was increased in both groups (sarpogrelate, 43 ± 17 to 55 ± 15 mmHg; cilostazol, 49 ± 21 to 66 ± 29 mmHg; p < 0.05), and no difference was observed between the groups. Plasma pentosidine levels decreased in both groups (sarpogrelate, 0.65 ± 0.24 to 0.48 ± 0.12 mg/mL; cilostazol, 0.58 ± 0.22 to 0.47 ± 0.17 mg/mL; p < 0.05), and there were no differences between the groups. Serum malondialdehyde-modified low-density lipoprotein (MDA-LDL) levels significantly increased only in cilostazol group (p < 0.05). There were no clinically significant safety concerns linked to the both drugs. Although blood pressure did not differ in both groups, heart rate increased only in cilostazol group from 77 ± 13 to 83 ± 16 beats per minute (p < 0.05). CONCLUSION: Sarpogrelate improves SPP in HD patients with PAD without increasing heart rate and serum MDA-LDL levels. We demonstrated that sarpogrelate is an effective and safe drug for the treatment of HD patients with PAD.

Application of urinary biomarkers for diagnosing acute kidney injury in critically ill patients without baseline renal function data.

PURPOSE: Estimating the baseline renal function of patients without prior creatinine measurement is crucial for diagnosing acute kidney injury (AKI). This study aimed to incorporate AKI biomarkers into a new AKI diagnosis rule when no premorbid baseline is available. METHODS: This prospective observational study was conducted in an adult intensive care unit (ICU). Urinary neutrophil gelatinase-associated lipocalin (NGAL) and L-type fatty acid-binding protein (L-FABP) were measured at ICU admission. An AKI diagnostic rule was composed by classification and regression tree (CART) analysis. RESULTS: A total of 243 patients were enrolled. In the development cohort, CART analysis composed a decision tree for AKI diagnosis selecting serum creatinine and urinary NGAL at ICU admission as predictors. In the validation cohort, the novel decision rule was superior to the imputation strategy based on Modification of Diet in Renal Disease (MDRD) equation regarding misclassification rate (13.0% vs. 29.6%, p = 0.002). Decision curve analysis demonstrated that the net benefit of the decision rule exceeded the MDRD approach in a threshold probability range of 25% and higher. CONCLUSIONS: The novel diagnostic rule incorporating serum creatinine and urinary NGAL at ICU admission showed superiority to the MDRD approach in AKI diagnosis without baseline renal function data.

Relationship Between Helicobacter pylori Infection and Arteriosclerosis.

It is reported that Helicobacter pylori (H. pylori) infection may be linked to non-digestive tract diseases, such as arteriosclerosis including dyslipidemia, diabetes, obesity, hypertension, and cardiovascular disease. Therefore, we reviewed recent studies available in PubMed dealing with the mechanisms of arteriosclerosis due to H. pylori infection and the effects of H. pylori eradication. Conventional studies suggested that H. pylori infection may increase the risk of arteriosclerosis. A large interventional study is required to clarify the causal relationships and the effects of bacterial eradication.

Modest Impact of Serial Measurements of Acute Kidney Injury Biomarkers in an Adult Intensive Care Unit.

BACKGROUND/AIMS: Acute kidney injury (AKI) biomarkers have been developed with the aim of being able to detect kidney damage earlier than the detection process based on serum creatinine levels. However, single time-point measurements appear to furnish insufficient information for detecting and predicting AKI in intensive care unit patients who are frequently affected by multiple and transient/persistent renal insults. We evaluated whether serial measurements enable the prediction of AKI outcomes in such patients. METHODS: Serial measurements of AKI biomarkers, including plasma and urinary neutrophil gelatinase-associated lipocalin, urinary L-type fatty acid-binding protein, and urinary N-acethyl-ß-D-glucosaminidase, at intensive care unit (ICU) admission (d1) and 24 h later (d2) were performed for critically ill adult patients in a mixed ICU. We assessed whether each biomarker could predict newly developed AKI, recovery from AKI, worsening of AKI, and hospital mortality. RESULTS: Among the enrolled 272 patients, 33 were determined to show newly developed AKI after ICU admission, 58 showed worsening of AKI, 57 recovered from AKI, and 38 died in the hospital. ROC analysis showed that biomarkers at day 2 provided no significant additional benefit in predicting the above-mentioned AKI outcomes compared with those at day 1. However, net reclassification improvement analysis demonstrated that adding day 2 biomarkers to the clinical model comprising clinical variables along with day 1 biomarkers significantly improved the prediction of these AKI outcomes. CONCLUSION: Serial measurement of AKI biomarkers used in clinical models could contribute to the prediction of AKI outcomes in a heterogeneous cohort of adult mixed ICU patients, although its reliability seemed to be modest.

Response to different furosemide doses predicts AKI progression in ICU patients with elevated plasma NGAL levels.

BACKGROUND: Furosemide responsiveness (FR) is determined by urine output after furosemide administration and has recently been evaluated as a furosemide stress test (FST) for predicting severe acute kidney injury (AKI) progression. Although a standardized furosemide dose is required for FST, variable dosing is typically employed based on illness severity, including renal dysfunction in the clinical setting. This study aimed to evaluate whether FR with different furosemide doses can predict AKI progression. We further evaluated the combination of an AKI biomarker, plasma neutrophil gelatinase-associated lipocalin (NGAL), and FR for predicting AKI progression. RESULTS: We retrospectively analyzed 95 patients who were treated with bolus furosemide in our medical-surgical intensive care unit. Patients who had already developed AKI stage 3 were excluded. A total of 18 patients developed AKI stage 3 within 1 week. Receiver operating curve analysis revealed that the area under the curve (AUC) values of FR and plasma NGAL were 0.87 (0.73-0.94) and 0.80 (0.67-0.88) for AKI progression, respectively. When plasma NGAL level was < 142 ng/mL, only one patient developed stage 3 AKI, indicating that plasma NGAL measurements were sufficient to predict AKI progression. We further evaluated the performance of FR in 51 patients with plasma NGAL levels > 142 ng/mL. FR was associated with AUC of 0.84 (0.67-0.94) for AKI progression in this population with high NGAL levels. CONCLUSIONS: Although different variable doses of furosemide were administered, FR revealed favorable efficacy for predicting AKI progression even in patients with high plasma NGAL levels. This suggests that a combination of FR and biomarkers can stratify the risk of AKI progression in a clinical setting.

Association of Heart Rate with N-Terminal Pro-B-Type Natriuretic Peptide in Septic Patients: A Prospective Observational Cohort Study.

BACKGROUND: Excessive sympathetic stress has multiple adverse effects during critical illness including sepsis. Recent studies showed that heart rate control had a significant effect on reducing mortality in septic shock patients. Furthermore, elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in septic patients were reportedly associated with adverse outcome. However, no study has evaluated the relationship between hemodynamic profiles of septic patients and the circulating cardiac biomarker. Our objective was to determine whether hemodynamic profiles, specifically tachycardia and new-onset atrial fibrillation (AF), were associated with NT-proBNP elevation in septic patients. METHODS: We consecutively enrolled patients admitted to our intensive care unit (ICU). NT-proBNP levels, heart rate, and rhythm at ICU admission were measured, and all clinical and laboratory data were prospectively collected. Tachycardia was defined as a heart rate of above 100 bpm. RESULTS: Ninety-five patients out of 267 patients (35.6%) were diagnosed as sepsis. Of these septic patients, 47 presented with tachycardia and 6 developed new-onset AF. Multivariate Cox regression analysis revealed that tachycardia was an independent predictor of 28-day overall survival in septic patients (hazard ratio, 4.22; 95% confidence interval, 1.10-27.72; P < 0.05), but not in nonseptic patients. Multivariate linear regression analysis demonstrated that the presence of tachycardia was an independent determinant of NT-proBNP elevation (P < 0.05) in septic patients, but not in nonseptic patients. CONCLUSIONS: Tachycardia was significantly and independently associated with NT-proBNP elevation and lower survival rate in septic patients, although no association was observed in nonseptic patients. Increased NT-proBNP in sepsis with tachycardia might predict poor outcomes in ICU.

Association of Urinary Neutrophil Gelatinase-Associated Lipocalin With Long-Term Renal Outcomes in ICU Survivors: A Retrospective Observational Cohort Study.

BACKGROUND: Epidemiological studies recently suggested that acute kidney injury (AKI) in intensive care units (ICUs) increases the risk of chronic kidney disease development and progression. However, whether any AKI biomarker can predict long-term renal outcomes in ICU survivors remains unclear. This study was undertaken to elucidate the role of urinary biomarkers for long-term renal outcome prediction after ICU discharge. METHODS: This retrospective observational study examined 495 adult patients who had been admitted to the ICU of the University of Tokyo Hospital. Major adverse kidney events (MAKE): death, incident end-stage renal disease (ESRD), and halving of estimated glomerular filtration rate (eGFR), at hospital discharge and long-term renal outcomes of 30% reduction of eGFR or incident ESRD were evaluated. RESULTS: Among all the enrolled 495 patients, 393 patients were discharged from the hospital without MAKE. Data of eGFR up to two years after ICU discharge were available for 173 patients; 63 patients (36.4%) were positive for long-term renal outcomes. Step-wise logistic regression analysis demonstrated that male sex and urinary neutrophil gelatinase-associated lipocalin (NGAL) measured at ICU admission showed significant associations with long-term renal outcomes. Receiver operating characteristic curve analysis showed the area under the curve of 0.66 (95% confidence interval 0.57-0.74) for prediction of long-term renal outcome by urinary NGAL. CONCLUSION: Urinary NGAL measured at ICU admission was significantly associated with long-term renal outcomes after hospital discharge in MAKE-free ICU survivors. Urinary NGAL measurements at ICU might be useful to identify a high risk population of kidney disease progression after intensive care.

Impact of clinical context on acute kidney injury biomarker performances: differences between neutrophil gelatinase-associated lipocalin and L-type fatty acid-binding protein.

Application of acute kidney injury (AKI) biomarkers with consideration of nonrenal conditions and systemic severity has not been sufficiently determined. Herein, urinary neutrophil gelatinase-associated lipocalin (NGAL), L-type fatty acid-binding protein (L-FABP) and nonrenal disorders, including inflammation, hypoperfusion and liver dysfunction, were evaluated in 249 critically ill patients treated at our intensive care unit. Distinct characteristics of NGAL and L-FABP were revealed using principal component analysis: NGAL showed linear correlations with inflammatory markers (white blood cell count and C-reactive protein), whereas L-FABP showed linear correlations with hypoperfusion and hepatic injury markers (lactate, liver transaminases and bilirubin). We thus developed a new algorithm by combining urinary NGAL and L-FABP with stratification by the Acute Physiology and Chronic Health Evaluation score, presence of sepsis and blood lactate levels to improve their AKI predictive performance, which showed a significantly better area under the receiver operating characteristic curve [AUC-ROC 0.940; 95% confidential interval (CI) 0.793-0.985] than that under NGAL alone (AUC-ROC 0.858, 95% CI 0.741-0.927, P = 0.03) or L-FABP alone (AUC-ROC 0.837, 95% CI 0.697-0.920, P = 0.007) and indicated that nonrenal conditions and systemic severity should be considered for improved AKI prediction by NGAL and L-FABP as biomarkers.

Cerebral blood flow in patients with peritoneal dialysis by an easy Z-score imaging system for brain perfusion single-photon emission tomography.

Cognitive impairment has long been recognized as a complication of chronic kidney disease. However, there is little information available regarding regional cerebral blood flow (rCBF) in patients with peritoneal dialysis (PD). Therefore, we evaluated rCBF using brain single photon emission computed tomography (SPECT). We conducted a cross-sectional study in our hospital. Eighteen consecutive PD patients who could visit the hospital by themselves without any history of stroke were examined by Technetium-99 m-labeled ethylcrysteinate dimer brain SPECT. An easy Z-score imaging system (eZIS) was used to compare rCBF in PD patients with those in age-matched healthy controls. We also evaluated cognitive dysfunction with the mini-mental state examination (MMSE) questionnaire. Only one patient showed an MMSE score of 18 points, and the remaining 14 patients were considered as normal (MMSE ≥ 27), and three patients were considered to have mild cognitive impairment (24 ≤ MMSE ≤ 26). In all patients, rCBF in the posterior cingulated gyri, precunei, and parietal cortices was significantly decreased. The ratio of the reduction of rCBF in each region relative to that of rCBF across the whole brain correlated positively with the PD duration (r = 0.559; P < 0.05). The serum ß2-microglobulin level was significantly higher in patients who had a higher ratio of rCBF reduction compared with those with lower ratios. In conclusion, all PD patients in the present study had decreased rCBF irrespective of MMSE scores.