Approximation of Glomerular Filtration Rate after 1 Year Using Annual Medical Examination Data.

Background: This cohort study was conducted to devise an approximation formula for predicting the glomerular filtration rate (GFR) after 1 year using annual medical examination data from the general population. Methods: Consecutive annual medical examination data were obtained for 41,337 inhabitants. Machine learning with the random forest method was used to assess the importance of each clinical parameter in terms of its association with estimated GFR (eGFR) after 1 year. An approximation formula was developed by multiple linear regression analysis based on the four most important clinical parameters. The relationship between the GFR after 1 year approximated by our formula and the eGFR after 1 year was analyzed using Pearson's correlation coefficient. Results: The following approximation formula was obtained by multiple linear regression analysis: approximate GFR after 1 year (mL/min/1.73 m2) = -0.054 × age + 0.162 × hemoglobin - 0.085 × uric acid + 0.849 × eGFR + 11.5. The approximate GFR after 1 year was significantly and strongly correlated with the eGFR at that time (r = 0.884; p < 0.001). Conclusions: An approximation formula including age, hemoglobin, uric acid, and eGFR may be useful for predicting GFR after 1 year among members of the general population.

Effects to cerebral oxygenation by arteriovenous fistula creation in patients with chronic kidney disease.

BACKGROUND: Vascular access, including arteriovenous fistula (AVF), is essential in patients undergoing hemodialysis (HD). However, the presence of AVF is non-physiological in humans and could pose a burden to the systemic circulation or tissue microcirculation, potentially affecting tissue oxygenation, including in the brain. Recently, near-infrared spectroscopy has been used to measure regional oxygen saturation (rSO2) as a marker of cerebral oxygenation in various settings, including in patients undergoing HD. Thus far, no studies have reported changes in cerebral rSO2 before and after AVF creation. This study aimed to monitor the differences in cerebral oxygenation before and after AVF creation and to clarify the clinical factors affecting the changes in cerebral rSO2. METHODS: Forty-eight patients (34 men, 14 women) with chronic kidney disease (CKD) who were not undergoing dialysis and newly created AVF were recruited. Cerebral rSO2 values before and after AVF creation were evaluated using near-infrared spectroscopy (INVOS 5100c). RESULTS: Cerebral rSO2 values were significantly changed from 60.3% ± 7.5% to 58.4% ± 6.8% before and after AVF creation in all patients (p < 0.001). Cerebral rSO2 were also lower in patients with diabetes mellitus (DM) than in those without DM (57.5 ± 7.1 vs 63.7 ± 6.5, p = 0.003) before surgery; however, no differences of changes in cerebral rSO2 were observed between the two groups after AVF creation. Additionally, multivariate regression analysis identified changes in HR (standardized coefficient: 0.436) as independent factors associated with changes in cerebral rSO2. CONCLUSION: Surgically created AVF was associated with the deterioration of cerebral rSO2 in patients with CKD not undergoing dialysis. Notably, AVF could cause cerebral hypoxia, and thus further studies are needed to clarify the clinical factors influencing changes in cerebral oxygenation after AVF creation.

Hepatic Oxygenation Changes and Symptomatic Intradialytic Hypotension.

INTRODUCTION: Clinical studies on differences among changes in cerebral and hepatic oxygenation during hemodialysis (HD) in patients with and without intradialytic hypotension (IDH) are limited. We investigated changes in intradialytic cerebral and hepatic oxygenation before systolic blood pressure (SBP) reached the nadir during HD and compared these differences between patients with and without symptomatic IDH. METHODS: We analyzed data from 109 patients with (n = 23) and without (n = 86) symptomatic IDH who were treated with HD. Cerebral and hepatic regional oxygen saturation (rSO2), as a marker of tissue oxygenation and circulation, was monitored during HD using an INVOS 5100c oxygen saturation monitor. Changes in cerebral or hepatic rSO2 when SBP reached the nadir during HD were compared between the groups of patients. RESULTS: The cerebral rSO2 before HD in patients with and without symptomatic IDH was 49.7 ± 11.2% and 51.3 ± 9.1% (p = 0.491). %Changes in cerebral rSO2 did not significantly differ between the two groups from 60 min before the SBP nadir during HD. Hepatic rSO2 before HD in patients with and without symptomatic IDH was 58.5 ± 15.4% and 57.8 ± 15.9% (p = 0.869). The %changes in hepatic rSO2 were significantly lower in patients with symptomatic IDH than in those without throughout the observational period (p < 0.001). We calculated the area under the receiver operating characteristic curve (AUC) and estimated cutoff values for changes in hepatic rSO2 as a symptomatic IDH predictor. The predictive ability at 5 and 40 min before symptomatic IDH onset was excellent, with AUCs and cutoff values of 0.847 and 0.841, and -10.9% and -5.0%, respectively. CONCLUSIONS: Hepatic oxygenation significantly decreased more in patients with symptomatic IDH before its onset, than in those without symptomatic IDH, whereas changes in cerebral oxygenation did not differ. Evaluating changes in hepatic oxygenation during HD might help to predict symptomatic IDH.

Factors Affecting Psoas Muscle Mass Index in Patients Undergoing Peritoneal Dialysis.

INTRODUCTION: Many patients with chronic kidney disease (CKD), including peritoneal dialysis (PD), have sarcopenia. It is important to evaluate muscle mass to prevent sarcopenia in the field of CKD management. Recently, muscle mass assessment using psoas muscle evaluated by computed tomography (CT) has been reported in patients undergoing hemodialysis. However, few clinical studies have investigated the clinical factors associated with the evaluation of psoas muscle in patients undergoing PD. METHODS: Psoas muscle mass index (PMI) was measured in cross-sectional areas of the bilateral psoas muscles at the third lumbar spine level to evaluate psoas muscle status. The associations between PMI and possible clinical factors were investigated in 68 patients undergoing PD. RESULTS: The mean PMI was 6.3 ± 2.0 cm2/m2, and the PMI was higher in men than in women (p < 0.001). In a multivariable linear regression analysis of the factors associated with PMI, male gender (standardized coefficient: 0.331), body mass index (standardized coefficient: 0.283), serum creatinine concentration (standardized coefficient: 0.289), serum albumin concentration (standardized coefficient: 0.235), and the use of vitamin D (standardized coefficient: 0.195) were independently identified. CONCLUSION: PMI was independently and significantly associated with gender, BMI, serum creatinine concentration, serum albumin concentration and the use of vitamin D. Further prospective studies are needed to clarify whether the maintenance of nutritional status or vitamin D administration could affect muscle mass in patients undergoing PD.

Steroid-resistant minimal change nephrotic syndrome associated with thymoma treated effectively with rituximab following thymectomy and cyclosporine: a case report.

BACKGROUND: Minimal change nephrotic syndrome (MCNS) can be complicated by thymoma; however, no standard therapy for thymoma-associated MCNS has yet been established. We herein describe a case of steroid-resistant MCNS associated with thymoma, treated effectively with rituximab. CASE PRESENTATION: A 71-year-old Japanese man was referred to our department with severe proteinuria (20 g/gCr). Renal biopsy showed minimal change disease and computed tomography revealed an anterior mediastinal mass. Based on these findings, he was diagnosed with thymoma-associated MCNS. He was treated with oral prednisolone (50 mg/day) and cyclosporine, and underwent thymectomy and plasma exchange. However, no improvement in proteinuria was observed. He therefore received intravenous rituximab 500 mg, resulting in a marked decrease in proteinuria from 5328 to 336 mg/day after 1 week. CONCLUSIONS: This case suggests that rituximab might be an effective therapy in patients with steroid-resistant MCNS associated with thymoma.

The Efficacy and Safety of Dotinurad on Uric Acid and Renal Function in Patients with Hyperuricemia and Advanced Chronic Kidney Disease: A Single Center, Retrospective Analysis.

Objective: We investigated the efficacy and safety of dotinurad, a selective urate reabsorption inhibitor, in hyperuricemic patients with advanced chronic kidney disease (CKD) (stage G3-5). Patients and Methods: We retrospectively analyzed the cases of 34 patients (mean age, 68.6 ± 13.3 years; 17 men and 17 women) after 12 months of dotinurad treatment based on the changes in uric acid (UA) and the urine protein-to-creatinine ratio (UPCR) plus the annual change in estimated glomerular filtration rate (eGFR). Hyperuricemia (UA ≥6.0 mg/dL) and advanced CKD (mean eGFR: 32.0 ± 13.3 mL/min/1.73m2; stage G3, n=17; G4, n=13; G5, n=4) were present in all of the patients. The cases of 34 matched individuals with similar propensity scores (who were not taking dotinurad) were analyzed as a control group. Results: UA values decreased significantly in the dotinurad group (7.1 ± 0.8 mg/dL to 5.9 ± 1.0 mg/dL, p<0.05) but those did not change in the control group. UPCR did not change in either group. Low-density lipoprotein cholesterol also decreased significantly in the dotinurad group (98.8 ± 43.4 mg/dL to 82.9 ± 33.1 mg/dL, p<0.05). With the 12-month dotinurad treatment, the annual change in the patients' eGFR was significantly improved from -6.0 ± 12.9 mL/min/1.73 m2/year to -0.9 ± 4.6 mL/min/1.73 m2/year (p<0.05), but there was no change in the control group. Conclusion: Dotinurad can decrease UA levels and might attenuate renal function decline in individuals with hyperuricemia and advanced CKD.

A case of renal vein thrombosis associated with autoimmune hemolytic anemia and eosinophilic granulomatous polyangiitis.

Only a few cases of renal vein thrombosis (RVT) occurring in patients with vasculitis have been reported. RVT associated with vasculitis and hemolytic anemia has not been reported yet. We describe here a patient with RVT complicated by pulmonary embolism, autoimmune hemolytic anemia, and eosinophilic granulomatous polyangiitis. A 69-year-old Japanese man who had been treated with corticosteroids was referred to our department for severe proteinuria (4.32 g/gCr). Abdominal ultrasonography showed bilateral RVT, and contrast-enhanced computed tomography showed bilateral pulmonary embolism. Therefore, the patient was diagnosed with RVT complicated by pulmonary embolism. Anticoagulation therapy with heparin followed by apixaban was started. Thereafter, the D-dimer concentration decreased from 8.3 to 1.2 µg/mL, and urinary protein excretion improved to 0.62 g/gCr. Renal function was unchanged with an estimated glomerular filtration rate of 68.8 mL/minute/1.73 m2. The thrombi in both renal veins and pulmonary arteries gradually regressed. Clinicians should be aware of this complication when worsening proteinuria is observed during steroid therapy in patients with autoimmune hemolytic anemia and eosinophilic granulomatous polyangiitis.

Differences between Hepatic and Cerebral Regional Tissue Oxygen Saturation at the Onset of Intradialytic Hypotension.

BACKGROUND: Intradialytic hypotension (IDH) is a critical pathological condition associated with all-cause mortality in patients undergoing hemodialysis (HD). However, few studies have investigated IDH-related changes in hepatic and cerebral regional tissue oxygen saturation (rSO2). This study investigated IDH-induced changes in hepatic and cerebral rSO2. METHODS: Hepatic and cerebral rSO2 during HD were measured using an INVOS 5100C oxygen saturation monitor, and their percentage (%) changes during the development of IDH were analyzed. Ninety-one patients undergoing HD were investigated, including twenty with IDH. RESULTS: In patients with IDH, % changes in hepatic and cerebral rSO2 decreased at the onset of IDH. Additionally, the % change in hepatic rSO2 was significantly larger than that in cerebral rSO2 (p < 0.001). In patients without IDH, no significant differences were found between the % changes in hepatic and cerebral rSO2 at the time of the lowest systolic blood pressure during HD. Multivariable linear regression analysis showed that the difference between the % changes in cerebral and hepatic rSO2 was significantly associated with the development of IDH (p < 0.001) and the ultrafiltration rate (p = 0.010). CONCLUSIONS: Hepatic and cerebral rSO2 significantly decreased during the development of IDH, and hepatic rSO2 was more significantly decreased than cerebral rSO2 at the onset of IDH.

Whole Blood Spermine/Spermidine Ratio as a New Indicator of Sarcopenia Status in Older Adults.

Early diagnosis and therapeutic intervention improve the quality of life and prognosis of patients with sarcopenia. The natural polyamines spermine and spermidine are involved in many physiological activities. Therefore, we investigated blood polyamine levels as a potential biomarker for sarcopenia. Subjects were Japanese patients >70 years of age who visited outpatient clinics or resided in nursing homes. Sarcopenia was determined based on muscle mass, muscle strength, and physical performance according to the criteria of the Asian Working Group for Sarcopenia (2019). The analysis included 182 patients (male: 38%, age: 83 [76-90] years). Spermidine levels were higher (p = 0.002) and the spermine/spermidine ratio was lower (p < 0.001) in the sarcopenia group than in the non-sarcopenia group. Polyamine concentration analysis showed that the odds ratios for age and spermidine changed in parallel with sarcopenia progression, and the odds ratio for the spermine/spermidine ratio changed inversely with the degree of sarcopenia progression. Additionally, when the odds ratio was analyzed with spermine/spermidine instead of polyamine concentrations, only for spermine/spermidine, the odds ratio values varied in parallel with the progression of sarcopenia. Based on the present data, we believe that the blood spermine/spermidine ratio may be a diagnostic indicator of risk for sarcopenia.

Factors affecting intradialytic hepatic oxygenation: Associations between ultrafiltration rate and changes in systemic blood pressure.

INTRODUCTION: Hepato-splanchnic circulation influences the oxygenation of abdominal organs and is important in preventing a reduction in intradialytic blood volume. However, the association between changes in intradialytic hepato-splanchnic circulation and clinical factors remain unknown. METHODS: We enrolled 91 hemodialysis (HD) patients (20 with intradialytic hypotension (IDH) and 71 without IDH). During HD, hepatic regional oxygen saturation (rSO2), a marker of hepatic oxygenation reflecting hepato-splanchnic circulation and oxygenation, was monitored. Changes in hepatic rSO2 at the lowest systolic blood pressure (BP) during HD were analyzed to identify associations with clinical factors. RESULTS: Hepatic rSO2 levels were 55.8 ± 15.3% before HD and 53.8 ± 14.9% at the lowest systolic BP; therefore, % changes in hepatic rSO2 were -2.7 ± 11.3%. These values were significantly lower in patients with IDH than in those without IDH (-13.8 ± 9.3% vs 0.4 ± 9.8%, p < 0.001). Multivariable regression analysis showed that % changes in hepatic rSO2 were independently associated with % changes in systolic BP (standardized coefficient: 0.416) and ultrafiltration rate (-0.206). Furthermore, % changes in mean BP (0.304) were identified as affecting % changes in hepatic rSO2 instead of those in systolic BP. CONCLUSIONS: Changes in intradialytic hepatic oxygenation is associated with ultrafiltration rate and changes in systemic BP. Further studies are required to clarify the directionality of the association between changes in hepatic oxygenation and changes in systemic BP during HD.

Effects of roxadustat on anemia, iron metabolism, and lipid metabolism in patients with non-dialysis chronic kidney disease.

Background: We determined the effects of roxadustat on the values of anemia, iron metabolism, renal function, proteinuria, and lipid metabolism and identified the associated factors of the change in hemoglobin levels after roxadustat administration in non-dialysis chronic kidney disease (CKD) patients who were receiving an erythropoietin-stimulating agent (ESA). Methods: We conducted retrospective analysis of the changes in hemoglobin, serum ferritin, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride levels; transferrin saturation; the estimated glomerular filtration rate; and the urinary protein/creatinine ratio over 24 weeks after the change from an ESA to roxadustat in 50 patients with non-dialysis CKD and anemia (roxadustat group). Seventy-two patients with non-dialysis CKD and anemia who proceeded ESA therapy were used as the control (ESA) group. Results: We observed no significant between-group differences in clinical parameters at baseline except for the significantly lower hemoglobin concentration and lower proportion of diabetes mellitus in the roxadustat group. The hemoglobin concentration was significantly higher in the roxadustat group after 24 weeks (11.3 ± 1.2 versus 10.3 ± 1.0 g/dL; value of p < 0.05), whereas the transferrin saturation, ferritin concentration, estimated glomerular filtration rate, and urinary protein/creatinine ratio were not different between the two groups. TC (135.9 ± 40.0 versus 165.3 ± 38.4 mg/dL; value of p < 0.05), LDL-C (69.1 ± 28.3 versus 87.2 ± 31.5 mg/dL; value of p < 0.05), HDL-C (41.4 ± 13.5 versus 47.2 ± 15.3 mg/dL; value of p < 0.05), and triglyceride concentrations (101.5 ± 52.7 versus 141.6 ± 91.4 mg/dL, value of p < 0.05) were significantly lower in the roxadustat group compared with the ESA group at 24 weeks. Multiple linear regression analysis showed that the roxadustat dose at baseline (standard coefficient [ß] = 0.280, value of p = 0.043) was correlated with the change in the hemoglobin levels during the first 4 weeks of roxadustat treatment, whereas age (ß = 0.319, value of p = 0.017) and the roxadustat dose at 24 weeks (ß = -0.347, value of p = 0.010) were correlated with the hemoglobin concentration after 24 weeks of roxadustat administration. Conclusion: Roxadustat can improve anemia and reduce serum cholesterol and triglyceride levels in non-dialysis CKD patients after the patients' treatment was switched from an ESA without affecting renal function or proteinuria. These results indicate that roxadustat has superior effects to ESAs regarding anemia and lipid metabolism at the dose selected for the comparison in patients with non-dialysis CKD.

Positive Correlation between Relative Concentration of Spermine to Spermidine in Whole Blood and Skeletal Muscle Mass Index: A Possible Indicator of Sarcopenia and Prognosis of Hemodialysis Patients.

Several mechanisms strictly regulate polyamine concentration, and blood polyamines are excreted in urine. This indicates polyamine accumulation in renal dysfunction, and studies have shown increased blood polyamine concentrations in patients with renal failure. Hemodialysis (HD) may compensate for polyamine excretion; however, little is known about polyamine excretion. We measured whole-blood polyamine levels in patients on HD and examined the relationship between polyamine concentrations and indicators associated with health status. Study participants were 59 hemodialysis patients (median age: 70.0 years) at Minami-Uonuma City Hospital and 26 healthy volunteers (median age: 44.5 years). Whole-blood spermidine levels were higher and spermine/spermidine ratio (SPM/SPD) was lower in hemodialysis patients. Hemodialysis showed SPD efflux into the dialysate; however, blood polyamine levels were not altered by hemodialysis and appeared to be minimally excreted. The skeletal muscle mass index (SMI), which was positively correlated with hand grip strength and serum albumin level, was positively correlated with SPM/SPD. Given that sarcopenia and low serum albumin levels are reported risk factors for poor prognosis in HD patients, whole blood SPM/SPD in hemodialysis patients may be a new indicator of the prognosis and health status of HD patients.

Effects of percutaneous transluminal angioplasty and associated factors in access hand oxygenation in patients undergoing hemodialysis.

In hemodialysis (HD) patients with arteriovenous fistula (AVF), changes in systemic or peripheral tissue circulation occur non-physiologically via the presence of AVF; however, associations between blood flow and tissue oxygenation in the brain and access hand are uncertain. In this study, 85 HD patients with AVF were included and evaluated for changes in flow volume (FV) and regional oxygen saturation (rSO2) in the brain and hands with AVF before and after percutaneous transluminal angioplasty (PTA). Furthermore, we evaluated the factors that determine access hand rSO2 without stenosis after PTA. Brachial arterial FV increased after PTA (p < 0.001), and carotid FV decreased (p = 0.008). Access hand rSO2 significantly decreased after PTA (p < 0.001), but cerebral rSO2 did not significantly change (p = 0.317). In multivariable linear regression analysis of factors associated with access hand rSO2, serum creatinine (standardized coefficient: 0.296) and hemoglobin (standardized coefficient: 0.249) were extracted as independent factors for access hand rSO2. In conclusion, a decrease in access hand oxygenation and maintenance of cerebral oxygenation were observed throughout PTA. To maintain access hand oxygenation, it is important to adequately manage Hb level and maintain muscle mass, in addition to having an AVF with appropriate blood flow.

Cerebral oxygenation changes in response to post-hemodialysis standing.

Few reports have examined the association between changes in cerebral oxygenation and clinical factors, including blood pressure (BP), upon standing after hemodialysis (HD). This study aimed to clarify the factors affecting the changes in cerebral regional oxygen saturation (rSO2) upon standing after HD and monitor the differences in cerebral rSO2 changes that occur upon standing after HD in patients with and without diabetes mellitus (DM). Changes in mean BP and cerebral rSO2 were tracked in 43 HD patients during 120 s of standing after HD using an INVOS 5100c oxygen saturation monitor. The post-HD cerebral rSO2 at rest was 55.8 ± 10.2%, while that at 120 s of standing decreased to 51.9 ± 9.6%; therefore, the percentage change in cerebral rSO2 at 120 s of standing was - 6.8 ± 6.4%, which was significantly lower than before HD (p < 0.001). This change was significantly correlated with the presence of DM, HD duration, mean BP at 120 s of standing, and percentage change in mean BP at 120 s of standing. A multivariable linear regression analysis showed that percentage change in cerebral rSO2 at 120 s of standing was independently associated with the percentage change in mean BP at 120 s of standing (standardized coefficient: 0.432; p = 0.004). Furthermore, there were significant decreases in percentage changes in cerebral rSO2 throughout the standing period in HD patients with versus without DM. Therefore, cerebral oxygenation deterioration upon standing after HD should receive attention, particularly in HD patients with DM.

Cell-Free and Concentrated Ascites Reinfusion Therapy during Hemodialysis for Intradialytic Hypotension and Intractable Ascites.

A 60-year-old woman with POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome and intractable ascites presented with acute renal failure and received hemodialysis (HD) therapy. Due to frequent intradialytic hypotension, ultrafiltration with cell-free and concentrated ascites reinfusion therapy (CART) was performed to adequately manage the body fluid status and massive ascites. During HD with CART, her blood pressure was maintained compared with that during HD without CART, and an ultrafiltration volume of 3.7 L was achieved after HD with CART. In HD patients with intradialytic hypotension and massive ascites, the combination of CART and ultrafiltration during HD may be an effective therapeutic option for body-fluid management.

Changes in cerebral oxygenation during hemodialysis before and after carotid artery stenting.

A 68-year-old man received hemodialysis (HD) for the treatment of end-stage renal failure for 6 years. Five years prior to carotid artery stenting (CAS), a neck ultrasound performed to screen for carotid atherosclerosis revealed an asymptomatic right internal carotid artery stenosis. One month prior, the stenotic lesion progressed to 74% by cerebral angiography; therefore, CAS was performed. To evaluate the influence of right internal carotid artery stenosis on the intradialytic cerebral circulation and oxygenation, cerebral regional oxygen saturation (rSO2) at bilateral forehead was measured using the INVOS 5100c oxygen saturation monitor (Covidien Japan, Japan) during HD before and after CAS. Before CAS, right cerebral rSO2 was maintained during HD, whereas left cerebral rSO2 gradually increased from the initiation to end of HD. However, the differences of intradialytic cerebral rSO2 changes between bilateral sides disappeared after CAS. In the present case, before CAS, the intradialytic increase in left cerebral rSO2 might reflect the increase in the left cerebral blood flow to compensate for the ultrafiltration-associated decreases in the right cerebral blood flow and perfusion pressure. Furthermore, the preserved right cerebral rSO2 before CAS might reflect the mechanism maintaining the right cerebral blood flow from the collateralized circle of Willis during HD. Throughout our experience, cerebral oxygenation monitoring during HD might disclose intradialytic changes in cerebral blood flow distribution between the ipsilateral and contralateral side in HD patients with carotid artery stenosis.

Cerebral oxygenation and body mass index association with cognitive function in chronic kidney disease patients without dialysis: a longitudinal study.

In chronic kidney disease (CKD) patients, the prevalence of cognitive impairment increases with CKD progression; however, longitudinal changes in cognitive performance remain controversial. Few reports have examined the association of cerebral oxygenation with cognitive function in longitudinal studies. In this study, 68 CKD patients were included. Cerebral regional oxygen saturation (rSO2) was monitored. Cognitive function was evaluated using mini-mental state examination (MMSE) score. Clinical assessments were performed at study initiation and 1 year later. MMSE score was higher at second measurement than at study initiation (p = 0.022). Multivariable linear regression analysis showed that changes in MMSE were independently associated with changes in body mass index (BMI, standardized coefficient: 0.260) and cerebral rSO2 (standardized coefficient: 0.345). This was based on clinical factors with p < 0.05 (changes in BMI, cerebral rSO2, and serum albumin level) and the following confounding factors: changes in estimated glomerular filtration rate, hemoglobin level, proteinuria, salt and energy intake, age, presence of diabetes mellitus, history of comorbid cerebrovascular disease, and use of renin-angiotensin system blocker. Further studies with a larger sample size and longer observational period are needed to clarify whether maintaining BMI and cerebral oxygenation improve or prevent the deterioration of cognitive function.

MicroRNA expression profiling in acute kidney injury.

The aim of this study was to identify miRNAs that regulate AKI and develop their applications as diagnostic biomarkers and therapeutic agents. First, kidney tissues from two different AKI mouse models, namely, AKI induced by the administration of lipopolysaccharide (LPS) causing sepsis (LPS-AKI mice) and AKI induced by renal ischemia-reperfusion injury (IRI-AKI mice), were exhaustively screened for their changes of miRNA expression compared with that of control mice by microarray analysis followed by quantitative RT-PCR. The initial profiling newly identified miRNA-5100, whose expression levels significantly decreased in kidneys in both LPS-AKI mice and IRI-AKI mice. Next, the administration of miRNA-5100-mimic conjugated with a nonviral vector, polyethylenimine nanoparticles (PEI-NPs), via the tail vein significantly induced miRNA-5100 overexpression in the kidney and prevented the development of IRI-AKI mice by inhibiting several apoptosis pathways in vivo. Furthermore, serum levels of miRNA-5100 in patients with AKI were identified as significantly lower than those of healthy subjects. ROC analysis showed that the serum expression level of miRNA-5100 can identify AKI (cut-off value 0.14, AUC 0.96, sensitivity 1.00, specificity 0.833, p<0.05). These results suggest that miRNA-5100 regulates AKI and may be useful as a novel diagnostic biomarker and therapeutic target for AKI.