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The present study was designed to provide information on the ability of several different anthropometric markers to reflect the renal impairment associated with body weight increase and to predict the development of renal alterations linked to overweight and obesity. In 574 subjects representative of the general population of the Pressioni Arteriose Monitorate e Loro Associazioni (PAMELA) study, with an age range between 57 and 73 years, we investigated the association between different anthropometric markers of body fat, as alternative to body mass index, and renal failure, to obtain information useful for determining their potential predictive value. Renal dysfunction was significantly associated with almost all anthropometric markers of adiposity related to body weight and body shape. After adjustment for confounders, such as age, sex, office blood pressure, serum glucose, antihypertensive drugs and smoking habit, association remained significant only for waist-to-hip ratio (WHR), lipid accumulation product (LAP) and visceral adiposity index (VAI). These 3 markers also displayed at the receiver operating curves (ROC) analysis the best ability to detect subjects with or without kidney dysfunction. The results of the present study provide evidence that WHR, LAP and VAI represent the best markers of renal dysfunction associated with visceral body fat accumulation.

Patellar tendon rupture and patellar apex rupture are established complications in patients with end stage kidney disease, however, little to no literature describes bilateral patellar avulsion. This is a case presentation of bilateral knee avulsion due to bilateral patellar tendon rupture at the level of the apexes in a patient with end stage kidney disease on dialysis. A 52 year old female presented to the emergency department for low energy traumatic event. On physical exam patient had bilateral patella alta with limited range of motion. On imaging, bilateral knee MRI was diagnostic of bilateral avulsion of patellar apexes. In light of the clinical and radiological findings, patient was admitted for surgical repair, in which a free tendon graft was placed. Post operation radiography showed good patellar placement and fixation. Upon discharge, patient was allowed partial weight bearing for the first 6 weeks, followed by full weight bearing. 1 year post surgery, patient was pain free and able to ambulate comfortably. We conclude that, patellar apex avulsion should be suspected in patients with renal dysfunction presenting for unilateral or bilateral chronic knee pain even if no severe mechanism of injury was present.

BACKGROUND Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. However, the number of patients with chronic kidney disease (CKD) is on the rise because of the increase in lifestyle-related diseases. AIM To establish a tailored management strategy for HCC patients, we evaluated the impact of comorbid renal dysfunction (RD), as stratified by using the estimated glomerular filtration rate (EGFR), and assessed the oncologic validity of hepatectomy for HCC patients with RD. METHODS We enrolled 800 HCC patients who underwent hepatectomy between 1997 and 2015 at our university hospital. We categorized patients into two (RD, EGFR < 60 mL/min/1.73 m(2); non-RD, EGFR >= 60 mL/min/1.73 m(2)) and three groups (severe CKD, EGFR < 30 mL/min/1.73 m(2); mild CKD, 30 <= EGFR < 60 mL/min/1.73 m(2); control, EGFR >= 60 mL/min/1.73 m(2)) according to renal function as defined by the EGFR. Overall survival (OS) and recurrence-free survival (RFS) were compared among these groups with the log-rank test, and we also analyzed survival by using a propensity score matching (PSM) model to exclude the influence of patient characteristics. The mean postoperative observation period was 64.7 +/- 53.0 mo. RESULTS The RD patients were significantly older and had lower serum total bilirubin, aspartate aminotransferase, and aspartate aminotransferase levels than the non-RD patients (P < 0.0001, P < 0.001, P < 0.05, and P < 0.01, respectively). No patient received maintenance hemodialysis after surgery. Although the overall postoperative complication rates were similar between the RD and non-RD patients, the proportions of postoperative bleeding and surgical site infection were significantly higher in the RD patients (5.5% vs 1.8%; P < 0.05, 3.9% vs 1.8%; P < 0.05, respectively), and postoperative bleeding was the highest in the severe CKD group (P < 0.05). Regardless of the degree of comorbid RD, OS and RFS were comparable, even after

BACKGROUND Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. However, the number of patients with chronic kidney disease (CKD) is on the rise because of the increase in lifestyle-related diseases. AIM To establish a tailored management strategy for HCC patients, we evaluated the impact of comorbid renal dysfunction (RD), as stratified by using the estimated glomerular filtration rate (EGFR), and assessed the oncologic validity of hepatectomy for HCC patients with RD. METHODS We enrolled 800 HCC patients who underwent hepatectomy between 1997 and 2015 at our university hospital. We categorized patients into two (RD, EGFR < 60 mL/min/1.73 m(2); non-RD, EGFR >= 60 mL/min/1.73 m(2)) and three groups (severe CKD, EGFR < 30 mL/min/1.73 m(2); mild CKD, 30 <= EGFR < 60 mL/min/1.73 m(2); control, EGFR >= 60 mL/min/1.73 m(2)) according to renal function as defined by the EGFR. Overall survival (OS) and recurrence-free survival (RFS) were compared among these groups with the log-rank test, and we also analyzed survival by using a propensity score matching (PSM) model to exclude the influence of patient characteristics. The mean postoperative observation period was 64.7 +/- 53.0 mo. RESULTS The RD patients were significantly older and had lower serum total bilirubin, aspartate aminotransferase, and aspartate aminotransferase levels than the non-RD patients (P < 0.0001, P < 0.001, P < 0.05, and P < 0.01, respectively). No patient received maintenance hemodialysis after surgery. Although the overall postoperative complication rates were similar between the RD and non-RD patients, the proportions of postoperative bleeding and surgical site infection were significantly higher in the RD patients (5.5% vs 1.8%; P < 0.05, 3.9% vs 1.8%; P < 0.05, respectively), and postoperative bleeding was the highest in the severe CKD group (P < 0.05). Regardless of the degree of comorbid RD, OS and RFS were comparable, even after

BACKGROUND Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. However, the number of patients with chronic kidney disease (CKD) is on the rise because of the increase in lifestyle-related diseases. AIM To establish a tailored management strategy for HCC patients, we evaluated the impact of comorbid renal dysfunction (RD), as stratified by using the estimated glomerular filtration rate (EGFR), and assessed the oncologic validity of hepatectomy for HCC patients with RD. METHODS We enrolled 800 HCC patients who underwent hepatectomy between 1997 and 2015 at our university hospital. We categorized patients into two (RD, EGFR < 60 mL/min/1.73 m(2); non-RD, EGFR >= 60 mL/min/1.73 m(2)) and three groups (severe CKD, EGFR < 30 mL/min/1.73 m(2); mild CKD, 30 <= EGFR < 60 mL/min/1.73 m(2); control, EGFR >= 60 mL/min/1.73 m(2)) according to renal function as defined by the EGFR. Overall survival (OS) and recurrence-free survival (RFS) were compared among these groups with the log-rank test, and we also analyzed survival by using a propensity score matching (PSM) model to exclude the influence of patient characteristics. The mean postoperative observation period was 64.7 +/- 53.0 mo. RESULTS The RD patients were significantly older and had lower serum total bilirubin, aspartate aminotransferase, and aspartate aminotransferase levels than the non-RD patients (P < 0.0001, P < 0.001, P < 0.05, and P < 0.01, respectively). No patient received maintenance hemodialysis after surgery. Although the overall postoperative complication rates were similar between the RD and non-RD patients, the proportions of postoperative bleeding and surgical site infection were significantly higher in the RD patients (5.5% vs 1.8%; P < 0.05, 3.9% vs 1.8%; P < 0.05, respectively), and postoperative bleeding was the highest in the severe CKD group (P < 0.05). Regardless of the degree of comorbid RD, OS and RFS were comparable, even after PSM between the RD and non-RD groups t

The inodilator levosimendan, in clinical use for over two decades, has been the subject of extensive clinical and experimental evaluation in various clinical settings beyond its principal indication in the management of acutely decompensated chronic heart failure. Critical care and emergency medicine applications for levosimendan have included postoperative settings, septic shock, and cardiogenic shock. As the experience in these areas continues to expand, an international task force of experts from 15 countries (Austria, Belgium, China, Croatia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Spain, Sweden, Switzerland, and the USA) reviewed and appraised the latest additions to the database of levosimendan use in critical care, considering all the clinical studies, meta-analyses, and guidelines published from September 2019 to November 2021. Overall, the authors of this opinion paper give levosimendan a “should be considered” recommendation in critical care and emergency medicine settings, with different levels of evidence in postoperative settings, septic shock, weaning from mechanical ventilation, weaning from veno-arterial extracorporeal membrane oxygenation, cardiogenic shock, and Takotsubo syndrome, in all cases when an inodilator is needed to restore acute severely reduced left or right ventricular ejection fraction and overall haemodynamic balance, and also in the presence of renal dysfunction/failure., SCOPUS: re.j, info:eu-repo/semantics/published

We have reported that a strict denosumab administration management system with oral calcium/ vitamin D supplementation attenuates denosumab-induced hypocalcemia in 158 cancer patients with bone metastasis. In this report, 27.8% of the patients experienced hypocalcemia, including 0.6% with grade 2. So far, the risk factors for >= grade 2 hypocalcemia incidence have been identified in denosumab- treated cancer patients, including patients without calcium/vitamin D supplementation. Therefore, the present study aimed to reveal the factors that affect all-grade hypocalcemia incidence with calcium/vitamin D supplementation and team medical care according to the management system. A receiver operating characteristic curve analysis suggested that the cutoff of baseline serum calcium level for all-grade hypocalcemia incidence was 9.3 mg/dL. Multivariate analysis revealed that age >= 65 years (odds ratio, 95% confidence interval: 2.57, 1.11- 5.95, p = 0.03), grade 1 or higher serum alkaline phosphatase elevation (3.70, 1.71- 8.00, p < 0.01), an adjusted serum calcium level of less than 9.3 mg/dL (3.21. 1.25-8.24, p = 0.02) at baseline, and co-administration of cytotoxic agents (2.33, 1.06-7.11, p = 0.03) are risk factors for the incidence of allgrade hypocalcemia. However, renal dysfunction, which has been suggested to be a risk factor in previous reports, was not a factor. In conclusion, we revealed the risk factors for all-grade hypocalcemia in calcium/vitamin D supplementation and awareness, as demonstrated by the management system. Moreover, renal dysfunction was not a risk factor in our strict denosumab administration management system. Our results support the value of early detection of hypocalcemia incidence to guide the selection of an appropriate management strategy.

Renal dysfunction is a recognized risk factor for mortality after allogeneic hematopoietic cell transplantation (alloHCT), yet our understanding of the effect of different levels of renal dysfunction at time of transplantation on outcomes remains limited. This study explores the impact of different degrees of renal dysfunction on HCT outcomes and examines whether the utilization of incremental degrees of renal dysfunction based on estimated glomerular filtration rate (eGFR) improve the predictability of the hematopoietic cell transplantation comorbidity index (HCT-CI). The study population included 2 cohorts: cohort 1, comprising patients age >= 40 years who under went alloHCT for treatment of hematologic malignancies between 2008 and 2016 (n = 13,505; cohort selected given a very low incidence of renal dysfunction in individuals age <40 years), and cohort 2, comprising patients on dialysis at the time of HCT (n = 46). eGFR was measured using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) method. The patients in cohort 1 were assigned into 4 categories-eGFR >= 90 mL/min (n = 7062), eGFR 60 to 89 mL/min (n = 5264), eGFR 45 to 59 mL/min (n = 897), and eGFR <45 mL/min (n=282)-to assess the impact of degree of renal dysfunction on transplantation outcomes. Transplantation outcomes in patients on dialysis at the time of alloHCT were analyzed separately. eGFR <60 mL/min was associated with an increased risk for nonrelapse mortality (NRM) and requirement for dialysis post-HCT. Compared with the eGFR >= 90 group, the hazard ratio (HR) for NRM was 1.46 (P = .0001) for the eGFR 45 to 59 mL/min group and 1.74 (P = .004) for the eGFR <45 mL/min group. Compared with the eGFR >= 90 mL/min group, the eGFR 45 to 59 mL/min group (HR, 2.45; P < .0001) and the eGFR <45 mL/min group (HR, 3.09; P < .0001) had a higher risk of renal failure necessitating dialysis after alloHCT. In addition, eGFR <45 mL/min was associated with an increa

Per- and polyfluoroalkyl substances (PFAS) are highly persistent synthetic organic contaminants that can cause serious human health concerns such as obesity, liver damage, kidney cancer, hypertension, immunotoxicity and other human health issues. Integrated crop-livestock systems combine agricultural crop production with milk and/or meat production and processing. Key sources of PFAS in these systems include firefighting foams near military bases, wastewater sludge and industrial discharge. Per- and polyfluoroalkyl substances regularly move from soils to nearby surface water and/or groundwater because of their high mobility and persistence. Irrigating crops or managing livestock for milk and meat production using adjacent waters can be detrimental to human health. The presence of PFAS in both groundwater and milk have been reported in dairy production states (e.g., Wisconsin and New Mexico) across the United States. Although there is a limit of 70 parts per trillion of PFAS in drinking water by the U.S. EPA, there are not yet regional screening guidelines for conducting risk assessments of livestock watering as well as the soil and plant matrix. This systematic review includes (i) the sources, impacts and challenges of PFAS in integrated crop-livestock systems, (ii) safety measures and protocols for sampling soil, water and plants for determining PFAS concentration in exposed integrated crop-livestock systems and (iii) the assessment, measurement and evaluation of human health risks related to PFAS exposure.

We have reported that a strict denosumab administration management system with oral calcium/ vitamin D supplementation attenuates denosumab-induced hypocalcemia in 158 cancer patients with bone metastasis. In this report, 27.8% of the patients experienced hypocalcemia, including 0.6% with grade 2. So far, the risk factors for >= grade 2 hypocalcemia incidence have been identified in denosumab- treated cancer patients, including patients without calcium/vitamin D supplementation. Therefore, the present study aimed to reveal the factors that affect all-grade hypocalcemia incidence with calcium/vitamin D supplementation and team medical care according to the management system. A receiver operating characteristic curve analysis suggested that the cutoff of baseline serum calcium level for all-grade hypocalcemia incidence was 9.3 mg/dL. Multivariate analysis revealed that age >= 65 years (odds ratio, 95% confidence interval: 2.57, 1.11- 5.95, p = 0.03), grade 1 or higher serum alkaline phosphatase elevation (3.70, 1.71- 8.00, p < 0.01), an adjusted serum calcium level of less than 9.3 mg/dL (3.21. 1.25-8.24, p = 0.02) at baseline, and co-administration of cytotoxic agents (2.33, 1.06-7.11, p = 0.03) are risk factors for the incidence of allgrade hypocalcemia. However, renal dysfunction, which has been suggested to be a risk factor in previous reports, was not a factor. In conclusion, we revealed the risk factors for all-grade hypocalcemia in calcium/vitamin D supplementation and awareness, as demonstrated by the management system. Moreover, renal dysfunction was not a risk factor in our strict denosumab administration management system. Our results support the value of early detection of hypocalcemia incidence to guide the selection of an appropriate management strategy.

Background and aims: The alteration of kidney function in adolescents with anorexia nervosa (AN) is a frequent, but still poorly investigated, consequence of AN. In this study, we analyzed glomerular filtration rate with the Cockroft-Gault formula in a group of 148 adolescents with Anorexia Nervosa and correlated it to clinical and biochemical data collected at admission. Methods: A retrospective study was conducted on 148 patients hospitalized from 2016 to 2019 for severe malnutrition due to restrictive AN. We measured glomerular filtration rate and correlated it with the patients’ anamnestic history, nutritional status and biochemical data. Results: For the 148 AN patients, 40 (27%) resulted at admission at stage 1 of kidney damage (GFR>90 mL/min), 88 patients (59%) at stage 2 (GFR 89-60 mL/min), 17 patients (11%) at stage 3A (GFR 59-45 mL/min) and 3 patients (2%) at stage 3B (GFR 44-30 mL/min). Results outlined a correlation between the entity of kidney damage and BMI at admission and before illness onset, but not with the rapidity and entity of weight loss. Further, more severe renal damages corresponded to major biochemical and hormonal alterations. Conclusions: Results of our study confirm that kidney damage is a frequent condition in adolescents with restrictive-type AN and support making kidney functionality tests part of routine care in patients with AN.

Background We hypothesized that the transition from bare-metal stents (BMS) to newer generation drug-eluting stents (n-DES) in clinical practice may have reduced the risk also in patients with kidney dysfunction. Methods: Observational study in the national SWEDEHEART registry, that compared the 1-year risk of in-stent restenosis (RS) and stent thrombosis (ST) in all percutaneous coronary intervention treated patients(n = 92 994) during 2007-2013. Results: N-DES patients were younger than BMS, but had more often diabetes, previous myocardial infarction, previous revascularization and were more often treated with potent platelet inhibition. N-DES versus BMS, was associated with lower 1-year risk of RS in patients with estimated glomerular filtration rate (eGFR) >60 with a cumulative probability of 2.1% versus 5.3%, adjusted hazard ratio 0.30, 95% CI (0.27-0.34) and with eGFR 30-60: 3.0% versus 4.9%; hazard ratio 0.46 (0.36-0.60) but not in patients with eGFR <30: 8.1% versus 6.0%; hazard ratio 1.32 (0.71-2.45) (pinteraction = 0.009) as well as lower risk of ST for eGFR >60 and eGFR 30-60: 0.5% versus 0.9%; hazard ratio 0.52 (0.40-0.68) and 0.6% versus 1.3%; hazard ratio 0.54 (0.54-0.72) but not for eGFR <30; 2.1% versus 1.1%; hazard ratio 1.49 (0.56-3.98) (p(interaction)= 0.027). Conclusion: N-DES is associated with lower 1-year risk of in-stent restenosis and stent thrombosis in patients with normal or moderately reduced kidney function but not in patients with severe kidney dysfunction, where stenting is associated with worse outcomes regardless of stent type.

Background Patients with chronic kidney disease (CKD) have poor outcomes following myocardial infarction (MI). We performed an untargeted examination of 175 biomarkers to identify those with the strongest association with CKD and to examine the association of those biomarkers with long-term outcomes. Methods A total of 175 different biomarkers from MI patients enrolled in the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry were analysed either by a multiple reaction monitoring mass spectrometry assay or by a multiplex assay (proximity extension assay). Random forests statistical models were used to assess the predictor importance of biomarkers, CKD and outcomes. Results A total of 1098 MI patients with a median estimated glomerular filtration rate of 85 mL min(-1)/1.73 m(2)were followed for a median of 3.2 years. The random forests analyses, without and with adjustment for differences in demography, comorbidities and severity of disease, identified six biomarkers (adrenomedullin, TNF receptor-1, adipocyte fatty acid-binding protein-4, TNF-related apoptosis-inducing ligand receptor 2, growth differentiation factor-15 and TNF receptor-2) to be strongly associated with CKD. All six biomarkers were also amongst the 15 strongest predictors for death, and four of them were amongst the strongest predictors of subsequent MI and heart failure hospitalization. Conclusion In patients with MI, a proteomic approach could identify six biomarkers that best predicted CKD. These biomarkers were also amongst the most important predictors of long-term outcomes. Thus, these biomarkers indicate underlying mechanisms that may contribute to the poor prognosis seen in patients with MI and CKD.

AIM: To map voiding patterns, degree of continence, use of drugs for voiding disorders, kidney function and surgical interventions but also the bowel function in a near-total regional cohort of adults with spina bifida aged more than or equal to 18 years. METHODS: All individuals more than or equal to 18 years of age with spina bifida registered at a regional outpatient clinic (n = 219) were invited to participate, of which 196 persons were included. Bladder and bowel function were assessed according to questions used by the Nordic Spinal Cord Injury Registry by structured interviews and questionnaires in combination with review of patient charts including kidney function. RESULTS: Twenty percent of the patients voided spontaneously. Fifty-four percent used clean intermittent catherization (CIC) and of these, 14% had also undergone augmentation of the bladder and/or implantation of an artificial sphincter or sling, 23% had undergone major urological surgery, and 3% had an indwelling catheter. Seventeen percent of patients voiding spontaneously or using CIC reported total continence but as many as 36% reported daily leakage. Anticholinergics was the most common drug, used by 21% in the total cohort. About 13% of the patients had a reduced kidney function but only 1.5% had end stage renal failure. Seventy-three percent had problems emptying the bowel and 18% experienced fecal leakage weekly or even daily. CONCLUSION: We found a large variation in problems with bladder and bowel function in this adult group of persons with spina bifida. A structured customized program for follow-up seems necessary to optimize their health status in these areas., Funding Agencies:- Caroline Montgomery Foundation - Foundation of Linnea and Josef Carlsson - Foundation of Neuro Sweden - Norrbacka Eugenia Foundation

AIM: To map voiding patterns, degree of continence, use of drugs for voiding disorders, kidney function and surgical interventions but also the bowel function in a near-total regional cohort of adults with spina bifida aged more than or equal to 18 years. METHODS: All individuals more than or equal to 18 years of age with spina bifida registered at a regional outpatient clinic (n = 219) were invited to participate, of which 196 persons were included. Bladder and bowel function were assessed according to questions used by the Nordic Spinal Cord Injury Registry by structured interviews and questionnaires in combination with review of patient charts including kidney function. RESULTS: Twenty percent of the patients voided spontaneously. Fifty-four percent used clean intermittent catherization (CIC) and of these, 14% had also undergone augmentation of the bladder and/or implantation of an artificial sphincter or sling, 23% had undergone major urological surgery, and 3% had an indwelling catheter. Seventeen percent of patients voiding spontaneously or using CIC reported total continence but as many as 36% reported daily leakage. Anticholinergics was the most common drug, used by 21% in the total cohort. About 13% of the patients had a reduced kidney function but only 1.5% had end stage renal failure. Seventy-three percent had problems emptying the bowel and 18% experienced fecal leakage weekly or even daily. CONCLUSION: We found a large variation in problems with bladder and bowel function in this adult group of persons with spina bifida. A structured customized program for follow-up seems necessary to optimize their health status in these areas., Funding Agencies:Caroline Montgomery Foundation Foundation of Linnea and Josef Carlsson Foundation of Neuro Sweden Norrbacka Eugenia Foundation

OBJECTIVE: Tenofovir disoproxil fumarate (TDF) is a nucleotide analogue recommended in international HIV treatment guidelines. Purpose of this study was to estimate the long term effects of TDF on renal profile in a cohort of HIV patients in Ghana. Three hundred (300) consecutive HIV-positive patients who initiated TDF-based antiretroviral treatment in 2008 at the Korle-Bu Teaching Hospital were sampled. Creatinine clearance (CrCl) was calculated using the Cockcroft-Gault equation at baseline and renal impairment was defined as CrCl values of 30.0-49.9 mL/min (moderate renal impairment) and < 30 mL/min (severe renal impairment) as per institutional guidelines for renal function test.RESULTS: Median follow up time was 2.9 years (IQR 2.3-3.4 years). At study endpoint, 63 participants (21.0% [95% CI 6.5-26.1]) recorded CrCl rate below 50 mL/min indicating incident renal impairment, made up of 18.3% moderate renal impairment and 2.3% severe renal impairment. Factors associated with incidence of renal impairment were increasing age, decrease in creatinine clearance rate at baseline, WHO HIV stage III/IV and participants with BMI of < 18.5 kg/m2. Patients with identified renal impairment risk factors at ART initiation should be targeted and monitored effectively to prevent renal injury.

OBJECTIVE: The effect of dual renin-angiotensin system (RAS) inhibition in heart failure (HF) is still controversial. Systematic reviews have shown that dual RAS blockade may reduce mortality and hospitalizations, yet it has been associated with the increased risk of renal dysfunction (RD). Surprisingly, although RD in patients with HF is frequent, the effect of combining RAS inhibitors in HF patients with RD has never been studied in a meta-analysis. METHODS: A systematic review and meta-analysis of randomized clinical trials involving HF patients with RD who received dual blockade analyzing death, cardiovascular (CV) death or HF hospitalization, and adverse events. RESULTS: Out of 2258 screened articles, 12 studies were included (34,131 patients). Compared with monotherapy, dual RAS inhibition reduced hazard ratio of death to 0.94 (p=0.07) and significantly reduced CV death or HF hospitalization to 0.89 (p=0.0006) in all individuals, and to 0.86 (p=0.005) in patients with RD and to 0.91 (p=0.04) without RD. Nevertheless, dual RAS blockade significantly increased the risk of renal impairment (40%), hyperkalemia (44%), and hypotension (42%), although discontinuation of treatment occurs only in 3.68% versus 2.19% (p=0.00001). CONCLUSIONS: Dual RAS inhibition therapy reduces the risk of CV death or HF hospitalization. However, cautions monitoring for specific adverse events may be warranted.

Background & aimsRenal dysfunction increases risk of death for patients with cirrhosis. We investigated whether mortality differs significantly among patients with acute kidney injury (AKI), chronic kidney disease (CKD), and both.MethodsWe performed a retrospective analysis of all non-status 1 adults on the waitlist for liver transplantation for at least 90 days, collected from the Organ Procurement and Transplantation Network registry from July 1, 2007 through July 1, 2014. We assigned patients to groups of AKI (an increase of ≥0.3 mg/dL or ≥50% in serum creatinine in the last 7 days or fewer than 72 days of hemodialysis), CKD (an estimated glomerular filtration rate <60 ml/min/1.73 m2 for 90 days with a final rate ≥30 ml/min/1.73 m2 or ≥72 days of hemodialysis), AKI and CKD (meet both definitions), or normal (meet neither definition). We performed competing risk analyses to associate patterns of renal dysfunction with waitlist mortality, accounting for liver transplantation, with renal pattern as a time-dependent covariate. Logistic regression for 6-month mortality determined the added benefit of including renal function pattern in the assessment.ResultsThere were 22,680 patients in the cohort; they spent a median 1.6 years (range, 0.7-3.1 years) on the waitlist and a median 5 years (range, 2-9 years) undergoing assessments of renal function. In competing risk analysis, even after adjusting for confounders including final model for end-stage liver disease sodium (MELD-Na) scores, the pattern of renal function was significantly associated with waitlist mortality: AKI and CKD (subhazard ratio [SHR], 2.86; 95% CI, 2.65-3.10), AKI (SHR, 2.42; 95% CI 2.22-2.64), CKD (SHR, 1.56; 95% CI, 1.45-1.67) compared with normal. The area under the curve values, based on MELD-Na score at time of placement on the waitlist, were 0.80 with renal function pattern and 0.71 without (P < .001).ConclusionIn competing risk analysis, even after adjusting for confounders including

Background and Aims: Tenofovir disoproxil fumarate (TDF) is recommended for chronic hepatitis B (CHB) treatment, but it may induce kidney dysfunction whose management is not yet known. This Italian, multicentre, retrospective study aimed to assess the efficacy and safety of switching to entecavir (ETV) patients who developed TDF-associated glomerular and/or tubular dysfunction. Methods: A total of 103 TDF-treated patients were included as follows: age 64 years, 83% male, 49% cirrhotics, 98% with undetectable HBV DNA, 47% with previous lamivudine resistance (LMV-R) and 71% previously treated with adefovir. Twenty-nine (28%) were switched to ETV because estimated glomerular filtration rate (eGFR MDRD ) was <60 mL/min, 37 (36%) because blood phosphate (P) levels were <2.5 mg/dL and 37 (36%) for both reasons. Kidney, liver and virological parameters were recorded every 4 months thereafter. Results: During 46 (4-115) months of ETV treatment, all patients’ renal parameters significantly improved as follows: creatinine from 1.30 to 1.10 mg/dL (P < 0.0001), eGFR MDRD from 54 to 65 mL/min (P = 0.002), P from 2.2 to 2.6 mg/dL (P < 0.0001) and maximal tubule phosphate reabsorption (TmPO4/eGFR) from 0.47 to 0.62 mmol/L (P < 0.0001). Thirteen patients (52%) improved their eGFR MDRD class, P levels were normalised in 13 (35%), and eight (22%) showed improvements in both parameters. Viral suppression was maintained in all but five patients (5%), all of whom had been LMV-R. The 5-year cumulative probability of ETV-R was 0% in LMV-naïve patients, and 11% in LMV-R patients (P = 0.018). Conclusions: Entecavir is an effective and safe rescue strategy for CHB patients who develop renal dysfunction during long-term TDF treatment.

Producción Científica, We aimed to assess the influence of impairment in renal function over the high-sensitivity cardiac troponin T (hs-cTnT) accuracy to diagnose perioperative myocardial infarction (MI) after heart valve surgery. Heart valve surgery was performed in 805 patients from June 2012 to January 2016. Patients with enzymatic curves of hs-cTnT suggestive of myocardial necrosis and electrocardiogram and/or transthoracic echocardiogram criteria were identified as patients with perioperative MI. Impairment in renal function was defined as a postoperative creatinine clearance <50 ml/min at 16 h after surgery and for at least 48 h. Patients included were divided into 2 groups at 16 h: (i) patients with normal renal function (creatinine clearance >50 ml/min) and (ii) patients with impairment in renal function (creatinine clearance <50 ml/min). From a total of 805 patients undergoing heart valve surgery, 88 patients developed perioperative MI. When comparing receiver operating characteristic curves in patients with perioperative MI according to renal function, the optimal threshold of hs-cTnT at 16 h differed in patients with impairment in renal function (1303 vs 1095 pg/ml, P < 0.001). The diagnostic accuracy of hs-cTnT at 16 h was 93.4% [95% confidence interval (CI) 89.98–96.86], with an area under receiver operating characteristic curve (0.993, 95% CI 0.988–0.999 vs 0.972, 95% CI 0.952–0.992; P < 0.001). Renal function might influence in hs-cTnT levels. However, a hs-cTnT threshold of 1303 pg/ml at 16 h may be applied according to renal function to diagnose perioperative MI after cardiac surgery.

Microglobulin (UBMG) were measured. The median UCd, BCd, SZn, and HZn were 2.8 and 13.6 μg/g cr, 1.3 and 12.2 μg/L, 1.31 and 1.12 mg/L, and 0.14 and 0.12 mg/g in subjects living in control and polluted areas. The UBMG level of subjects living in the polluted area was significantly higher than that of the control (0.27 vs 0.11 mg/g cr, p < 0.01). SZn, HZn, and Zn/Cd ratios were negatively correlated with UBMG (p < 0.05 or 0.01). Subjects with high SZn concentrations (≥ 1.62 mg/L) had reduced risks of elevated UBMG [(odds ratio (OR) = 0.26, 95% confidence interval (CI) 0.07-0.99)] after controlling for multiple covariates compared with those with lower zinc levels. A similar result was observed in subjects with high HZn (OR = 0.09, 95% CI 0.02-0.48). The ORs of the second, third, and fourth quartiles of Zn/Cd ratio were 0.40 (95% CI 0.19-0.84), 0.14 (95% CI 0.06-0.37), and 0.01 (95% CI 0.02-0.18) for renal dysfunction compared with those of the first quartile, respectively. For those subjects with high level of UCd, high level of SZn and HZn also had reduced risks of elevated UBMG. The results of the present study show that high zinc body burden is associated with a decrease risk of renal tubular dysfunction induced by cadmium. Zinc nutritional status should be considered in evaluating cadmium-induced renal damage., Correction: Chen, X., Wang, Z., Zhu, G. et al. Correction to: The Association Between Renal Tubular Dysfunction and Zinc Level in a Chinese Population Environmentally Exposed to Cadmium. Biol Trace Elem Res (2020). https://doi.org/10.1007/s12011-020-02403-5

The tolerable dietary intake of cadmium was recommended at provisional tolerable monthly intake of 25gkg(-1) body weight. However, several studies indicated that this tolerable level should be re-evaluated for sufficient health protection. In this study, we show the reference levels of dietary cadmium intake for renal dysfunction by using a benchmark dose (BMD) approach. A total of 790 subjects (302 men and 488 women) living in control and cadmium-polluted areas were included. The dietary cadmium intake was estimated by a food survey. Blood cadmium, urinary cadmium and renal function markers (microalbuminuria, N-acetyl--d-glucosaminidase [NAG] and its isoform B [NAGB], (2)-microglobulin and retinol binding protein) in urine were measured. We calculated the 95% lower confidence bounds of BMD (BMDLs) of cumulative cadmium intake. In control and two polluted areas, the median cumulative cadmium intake was 0.5, 2.1 and 11.1g. The odds ratio of the intermediate (1.0-3.0g), second highest (3.0-11.0g) and the highest cumulative cadmium intake (>11.0g) compared with the lowest cumulative cadmium intake (<1.0g) were 2.8 (95% CI: 1.4-5.8), 8.1 (95% CI: 3.8-17.2) and 11.4 (95% CI: 6.5-26.4) for urinary NAG and 6.6 (95% CI: 3.2-13.8), 14.8 (95% CI: 6.8-32.2) and 22.5 (95% CI: 10.7-47.5) for urinary NAGB. The BMDLs of cumulative cadmium intake were 1.1-1.2g (benchmark response [BMR]=5%) for urinary NAG, and were 0.7-0.9g (BMR=5%) for urinary NAGB, and were 1.3-1.4g (BMR=5%) for urinary (2)-microglobulin. The BMDLs of cumulative cadmium intake in a Chinese population were lower than the critical standard previously reported. Further evaluations are needed for sufficient health protection. Several studies indicated that the tolerable dietary intake of cadmium should be re-evaluated for sufficient health protection. In this study, we show the reference levels of dietary cadmium intake for renal dysfunction by using benchmark dose (BMD) approach. The lowest BMD lower bound con

Introduction Dose reductions are often required to avoid toxicity in combination therapy for advanced cancers, but information on appropriate dose reductions in renal dysfunction is lacking. This study assessed dose reductions of renally cleared oncology agents given in combination therapy in the setting of renal dysfunction. Methods A database of 1,072 patients was screened to identify patients with renal dysfunction (glomerular filtration rate < 60 mL/min) receiving oncology combination therapy with at least one agent requiring dose reduction for renal insufficiency. The dose of the renal agent was compared to the single-agent renal dosing recommendations to calculate a dose percentage. Tolerability was determined from electronic medical records review. Results Thirty-three regimens (n = 25 patients) were identified: 11 included at least one targeted agent (n = 8 patients) and 22 had only cytotoxic chemotherapy (n = 18 patients). The renal agent was given at the recommended single-agent renal dose in ~50% of combinations; ~50% of all regimens were tolerated, and only six combinations had dose reductions for toxicity. The median final dose percentage was 100% of the recommended renal dose (range: 25% - 333%); no significant differences were seen between groups (cytotoxic - tolerated, cytotoxic - not tolerated, targeted - tolerated, targeted - not tolerated; p = 0.38). No significant differences were observed between tolerated vs. non-tolerated (p = 0.97) or targeted vs. cytotoxic (p = 0.80) regimens. Conclusions Dose reductions of renally cleared agents are highly variable in oncology patients with renal dysfunction. Additional studies are needed to determine appropriate dosing adjustments in this population.

Мета. Розробити математичну модель прогнозування ренальної дисфункції у доношених новонароджених дітей з урахуванням ступеня тяжкості патологічного перебігу ранньої неонатальної адаптації. Матеріали і методи. Проведено ретроспективне дослідження, у ході якого здійснено аналіз чинників ризику ренальної дисфункції у 80 доношених новонароджених дітей з проявами перинатальної патології різного ступеня тяжкості з подальшим покроковим дискримінантним аналізом індексованих факторів (віку матері ≥ 35 років, наявності/відсутності хронічної патології сечовидільної системи, гестаційного пієлонефриту у матері, оцінки гострої адаптації новонародженого за шкалою Апгар наприкінці першої та п’ятої хвилин життя, наявності/ відсутності синдрому артеріальної гіпотензії, оцінки за шкалою NTISS, рівнів погодинного діурезу та сироваткового креатиніну у новонародженої дитини). Результати дослідження. Координати центроїдів за основними функціями, отримані за даними дискримінантного аналізу, для дітей з відсутністю ренальної дисфункції склали F1=4,84; F2=-0,36; для дітей з порушеннями легкого ступеня – F1=0,42; F2=0,60; для дітей з порушеннями помірного ступеня – F1=-1,94; F2=0,51; для дітей з порушеннями тяжкого ступеня – F1=-3,31; F2=-0,75. Висновки. Запропонована математична модель прогнозування порушень функціонального стану нирок у хворих новонароджених дітей надає змогу передбачити розвиток ренальної дисфункції тяжкого ступеня з точністю 75,0%, помірного ступеня – 80,0%, легкого ступеня – 85,0%, відсутності ренальної дисфункції – 100,0%., Новорожденные дети, получающие лечение в отделениях интенсивнойтерапии новорожденных, составляют группу высокого риска по формированию почечной дисфункции, наиболее серьезным проявлением которой является острое повреждение почек. Цель. Разработать математическую модель прогнозирования ренальной дисфункции у доношенных новорождённых детей с учётом степени тяжести патологического течения ранней неонатальной адаптации. Материалы и методы. Проведено ретроспективное исследование, в ходе которого проанализированы факторы риска ренальной дисфункции у 80 доношенных новорождённых детей с проявлениями перинатальной патологии разной степени тяжести с дальнейшим пошаговым дискриминантным анализом индексированных факторов (возраста матери ≥ 35 лет, наличия/отсутствия хронической патологии мочевыделительной системы, гестационного пиелонефрита у матери, оценки острой адаптации новорождённого по шкале Апгар в конце первой и пятой минут жизни, наличия/отсутствия синдрома артериальной гипотензии, оценки по шкале NTISS, уровней почасового диуреза и сывороточного креатинина у новорождённого). Результаты исследования. Координаты центроидов по основным функциям, которые получены в результате дискриминантного анализа, для детей с отсутствием ренальной дисфункции составили F =4,84; F =-0,36; для детей с арушениями легкой степени – F 22 2 1 =0,42; F =0,60; для детей с нарушениями умеренной степени тяжести – F 2 1 =-1,94; F =0,51; для детей с нарушениями тяжёлой степени – F 2 1 =-3,31; F =-0,75. Выводы. Предложенная математическая модель прогнозирования нарушений функционального состояния почек у больных новорождённых детей позволяет предположить развитие ренальной дисфункции тяжёлой степени с точностью 75,0%, умеренной степени – 80,0%, лёгкой степени – 85,0%, отсутствие ренальной дисфункции – 100,0%., Newborns getting treatment in the intensive care units constitute a high risk group concerning formation of renal dysfunction which serious sign is acutekidney injury. Objective: to develop a mathematical model toprognosticate renal dysfunction of term newborns considering degree of severity of pathological course of early neonatal adaptation. Materials and methods. A retrospective study was carried out including the analysis of risk factors ofrenal dysfunction in 80 term newborns with signs of perinatal pathology of different degree of severity with further step-by-step discriminant analysis of indexed factors (mother’s age ≥ 35 years, presence/absence ofchronic pathology of the urinary system, gestational pyelonephritis in mother, assessment of acute adaptation of a newborn by Apgar scale at the end of the first and fifth minute of life, presence/absence of arterial hypotension syndrome, assessment by NTISS, levels of diuresis by the hour and serum creatinine in a newborn). Results of the study. Coordinates of centroids by the main functions obtained by the findings of discriminant analysis for children without renal dysfunction were the following: F 1 =4,84; F =-0,36; for children with mild disorders – F 1 =0,42; F 2 2 =0,60; for children with moderate disorders – F 1 =-1,94; F =0,51; and for children with severe disorders – F 1 2 =-3,31; F =-0,75. Conclusion. The suggested mathematical model 2 to prognosticate disorders of the renal functional state in sick newborns enables to predict development of severe renal dysfunction to within 75,0%, moderate degree – 80,0%, mild degree – 85,0%, absence of renal dysfunction – 100,0%.

Producción Científica, We aimed to assess the influence of impairment in renal function over the high-sensitivity cardiac troponin T (hs-cTnT) accuracy to diagnose perioperative myocardial infarction (MI) after heart valve surgery. Heart valve surgery was performed in 805 patients from June 2012 to January 2016. Patients with enzymatic curves of hs-cTnT suggestive of myocardial necrosis and electrocardiogram and/or transthoracic echocardiogram criteria were identified as patients with perioperative MI. Impairment in renal function was defined as a postoperative creatinine clearance <50 ml/min at 16 h after surgery and for at least 48 h. Patients included were divided into 2 groups at 16 h: (i) patients with normal renal function (creatinine clearance >50 ml/min) and (ii) patients with impairment in renal function (creatinine clearance <50 ml/min). From a total of 805 patients undergoing heart valve surgery, 88 patients developed perioperative MI. When comparing receiver operating characteristic curves in patients with perioperative MI according to renal function, the optimal threshold of hs-cTnT at 16 h differed in patients with impairment in renal function (1303 vs 1095 pg/ml, P < 0.001). The diagnostic accuracy of hs-cTnT at 16 h was 93.4% [95% confidence interval (CI) 89.98–96.86], with an area under receiver operating characteristic curve (0.993, 95% CI 0.988–0.999 vs 0.972, 95% CI 0.952–0.992; P < 0.001). Renal function might influence in hs-cTnT levels. However, a hs-cTnT threshold of 1303 pg/ml at 16 h may be applied according to renal function to diagnose perioperative MI after cardiac surgery.

Introduction Dose reductions are often required to avoid toxicity in combination therapy for advanced cancers, but information on appropriate dose reductions in renal dysfunction is lacking. This study assessed dose reductions of renally cleared oncology agents given in combination therapy in the setting of renal dysfunction. Methods A database of 1,072 patients was screened to identify patients with renal dysfunction (glomerular filtration rate < 60 mL/min) receiving oncology combination therapy with at least one agent requiring dose reduction for renal insufficiency. The dose of the renal agent was compared to the single-agent renal dosing recommendations to calculate a dose percentage. Tolerability was determined from electronic medical records review. Results Thirty-three regimens (n = 25 patients) were identified: 11 included at least one targeted agent (n = 8 patients) and 22 had only cytotoxic chemotherapy (n = 18 patients). The renal agent was given at the recommended single-agent renal dose in ~50% of combinations; ~50% of all regimens were tolerated, and only six combinations had dose reductions for toxicity. The median final dose percentage was 100% of the recommended renal dose (range: 25% - 333%); no significant differences were seen between groups (cytotoxic - tolerated, cytotoxic - not tolerated, targeted - tolerated, targeted - not tolerated; p = 0.38). No significant differences were observed between tolerated vs. non-tolerated (p = 0.97) or targeted vs. cytotoxic (p = 0.80) regimens. Conclusions Dose reductions of renally cleared agents are highly variable in oncology patients with renal dysfunction. Additional studies are needed to determine appropriate dosing adjustments in this population.

Producción Científica, We aimed to assess the influence of impairment in renal function over the high-sensitivity cardiac troponin T (hs-cTnT) accuracy to diagnose perioperative myocardial infarction (MI) after heart valve surgery. Heart valve surgery was performed in 805 patients from June 2012 to January 2016. Patients with enzymatic curves of hs-cTnT suggestive of myocardial necrosis and electrocardiogram and/or transthoracic echocardiogram criteria were identified as patients with perioperative MI. Impairment in renal function was defined as a postoperative creatinine clearance <50 ml/min at 16 h after surgery and for at least 48 h. Patients included were divided into 2 groups at 16 h: (i) patients with normal renal function (creatinine clearance >50 ml/min) and (ii) patients with impairment in renal function (creatinine clearance <50 ml/min). From a total of 805 patients undergoing heart valve surgery, 88 patients developed perioperative MI. When comparing receiver operating characteristic curves in patients with perioperative MI according to renal function, the optimal threshold of hs-cTnT at 16 h differed in patients with impairment in renal function (1303 vs 1095 pg/ml, P < 0.001). The diagnostic accuracy of hs-cTnT at 16 h was 93.4% [95% confidence interval (CI) 89.98–96.86], with an area under receiver operating characteristic curve (0.993, 95% CI 0.988–0.999 vs 0.972, 95% CI 0.952–0.992; P < 0.001). Renal function might influence in hs-cTnT levels. However, a hs-cTnT threshold of 1303 pg/ml at 16 h may be applied according to renal function to diagnose perioperative MI after cardiac surgery.

We report a successful ultrasound-guided transversus abdominis plane (TAP) block as an analgesic option for minor abdominal surgery in a 66-year-old patient with cardiac, respiratory, and renal dysfunction caused by primary systemic amyloidosis. Bilateral TAP blocks with 120 mg (1.8 mg/kg) of ropivacaine provided sufficient intra- and postoperative analgesia for insertion of a continuous ambulatory peritoneal dialysis catheter. However, the plasma concentration of ropivacaine reached a maximum of 2.5 mu g/mL at 15 minutes after the TAP block, a concentration that was potentially neurotoxic. Although apparent signs of local anesthetic systemic toxicity (LAST) such as convulsion or changes in an electrocardiogram were not observed, the patient became drowsy after the TAP block, which might be one of the mild symptoms of LAST. A TAP block by itself can thus be an anesthetic option for patients undergoing minor abdominal surgery. However, cardiac and renal dysfunction might influence the pharmacokinetics of a local anesthetic used, and attention should he paid to the possibility of LAST even with a low dose of a local anesthetic for patients with cardiac and renal failure., Article, LOCAL AND REGIONAL ANESTHESIA.11:57-60(2018)

We showed recently that increasing kidney epoxyeicosatrienoic acids (EETs) by blocking soluble epoxide hydrolase (sEH), an enzyme responsible for EETs degradation, retarded the development of renal dysfunction and progression of aorto-caval fistula(ACF)-induced congestive heart failure (CHF) in Ren-2 transgenic hypertensive rats (TGR). In that study the final survival rate of untreated ACF TGR was only 14 % but increased to 41 % after sEH blockade. Here we examined if sEH inhibition added to renin-angiotensin system (RAS) blockade would further enhance protection against ACF-induced CHF in TGR. The treatment regimens were started one week after ACF creation and the follow-up period was 50 weeks. RAS was blocked using angiotensin-converting enzyme inhibitor (ACEi, trandolapril, 6 mg/l) and sEH with an sEH inhibitor (sEHi, c-AUCB, 3 mg/l). Renal hemodynamics and excretory function were determined two weeks post-ACF, just before the onset of decompensated phase of CHF. 29 weeks post-ACF no untreated animal survived. ACEi treatment greatly improved the survival rate, to 84 % at the end of study. Surprisingly, combined treatment with ACEi and sEHi worsened the rate (53 %). Untreated ACF TGR exhibited marked impairment of renal function and the treatment with ACEi alone or combined with sEH inhibition did not prevent it. In conclusion, addition of sEHi to ACEi treatment does not provide better protection against CHF progression and does not increase the survival rate in ACF TGR: indeed, the rate decreases significantly. Thus, combined treatment with sEHi and ACEi is not a promising approach to further attenuate renal dysfunction and retard progression of CHF.

Producción Científica, We aimed to assess the influence of impairment in renal function over the high-sensitivity cardiac troponin T (hs-cTnT) accuracy to diagnose perioperative myocardial infarction (MI) after heart valve surgery. Heart valve surgery was performed in 805 patients from June 2012 to January 2016. Patients with enzymatic curves of hs-cTnT suggestive of myocardial necrosis and electrocardiogram and/or transthoracic echocardiogram criteria were identified as patients with perioperative MI. Impairment in renal function was defined as a postoperative creatinine clearance <50 ml/min at 16 h after surgery and for at least 48 h. Patients included were divided into 2 groups at 16 h: (i) patients with normal renal function (creatinine clearance >50 ml/min) and (ii) patients with impairment in renal function (creatinine clearance <50 ml/min). From a total of 805 patients undergoing heart valve surgery, 88 patients developed perioperative MI. When comparing receiver operating characteristic curves in patients with perioperative MI according to renal function, the optimal threshold of hs-cTnT at 16 h differed in patients with impairment in renal function (1303 vs 1095 pg/ml, P < 0.001). The diagnostic accuracy of hs-cTnT at 16 h was 93.4% [95% confidence interval (CI) 89.98–96.86], with an area under receiver operating characteristic curve (0.993, 95% CI 0.988–0.999 vs 0.972, 95% CI 0.952–0.992; P < 0.001). Renal function might influence in hs-cTnT levels. However, a hs-cTnT threshold of 1303 pg/ml at 16 h may be applied according to renal function to diagnose perioperative MI after cardiac surgery.

Oxidative stress is considered a central pathophysiological event in cardiovascular disease, including hypertension. Early age reduction in renal mass is associated with hypertension and oxidative stress in later life, which is aggravated by increased salt intake. The aim of the present study was to examine if renal sympathetic denervation can exert blood pressure lowering effects in uninephrectomized (UNX) rats (3-week old) fed with high salt (HS, 4%; w/w) diet for 4 weeks. Moreover, we investigated if renal denervation is associated with changes in NADPH and xanthine oxidase-derived reactive oxygen species. Rats with UNX + HS had reduced renal function, elevated systolic and diastolic arterial pressures, which was accompanied by increased heart weight, and cardiac superoxide production compared to sham operated Controls. UNX + HS was also associated with higher expression and activity of NADPH and xanthine oxidase in the kidney. Renal denervation in rats with UNX + HS attenuated the development of hypertension and cardiac hypertrophy, but also improved glomerular filtration rate and reduced proteinuria. Mechanistically, renal de nervation was associated with lower expression and activity of both NADPH oxidase and xanthine oxidase in the kidney, but also reduced superoxide production in the heart. In conclusion, our study shows for the first time that renal denervation has anti-hypertensive, cardio- and reno-protective effects in the UNX + HS model, which can be associated with decreased NADPH oxidase- and xanthine oxidase-derived reactive oxygen species (i.e., superoxide and hydrogen peroxide) in the kidney.

Oxidative stress is considered a central pathophysiological event in cardiovascular disease, including hypertension. Early age reduction in renal mass is associated with hypertension and oxidative stress in later life, which is aggravated by increased salt intake. The aim of the present study was to examine if renal sympathetic denervation can exert blood pressure lowering effects in uninephrectomized (UNX) rats (3-week old) fed with high salt (HS, 4%; w/w) diet for 4 weeks. Moreover, we investigated if renal denervation is associated with changes in NADPH and xanthine oxidase-derived reactive oxygen species. Rats with UNX + HS had reduced renal function, elevated systolic and diastolic arterial pressures, which was accompanied by increased heart weight, and cardiac superoxide production compared to sham operated Controls. UNX + HS was also associated with higher expression and activity of NADPH and xanthine oxidase in the kidney. Renal denervation in rats with UNX + HS attenuated the development of hypertension and cardiac hypertrophy, but also improved glomerular filtration rate and reduced proteinuria. Mechanistically, renal de nervation was associated with lower expression and activity of both NADPH oxidase and xanthine oxidase in the kidney, but also reduced superoxide production in the heart. In conclusion, our study shows for the first time that renal denervation has anti-hypertensive, cardio- and reno-protective effects in the UNX + HS model, which can be associated with decreased NADPH oxidase- and xanthine oxidase-derived reactive oxygen species (i.e., superoxide and hydrogen peroxide) in the kidney.

Oxidative stress is considered a central pathophysiological event in cardiovascular disease, including hypertension. Early age reduction in renal mass is associated with hypertension and oxidative stress in later life, which is aggravated by increased salt intake. The aim of the present study was to examine if renal sympathetic denervation can exert blood pressure lowering effects in uninephrectomized (UNX) rats (3-week old) fed with high salt (HS, 4%; w/w) diet for 4 weeks. Moreover, we investigated if renal denervation is associated with changes in NADPH and xanthine oxidase-derived reactive oxygen species. Rats with UNX + HS had reduced renal function, elevated systolic and diastolic arterial pressures, which was accompanied by increased heart weight, and cardiac superoxide production compared to sham operated Controls. UNX + HS was also associated with higher expression and activity of NADPH and xanthine oxidase in the kidney. Renal denervation in rats with UNX + HS attenuated the development of hypertension and cardiac hypertrophy, but also improved glomerular filtration rate and reduced proteinuria. Mechanistically, renal de nervation was associated with lower expression and activity of both NADPH oxidase and xanthine oxidase in the kidney, but also reduced superoxide production in the heart. In conclusion, our study shows for the first time that renal denervation has anti-hypertensive, cardio- and reno-protective effects in the UNX + HS model, which can be associated with decreased NADPH oxidase- and xanthine oxidase-derived reactive oxygen species (i.e., superoxide and hydrogen peroxide) in the kidney.

Cibenzoline succinate (Cibenzoline, CZ) may cause hypoglycemia as a side effect. Because CZ is mainly excreted by kidney, it is contraindicated in patients who are on hemodialysis. We experienced a case of prolonged hypoglycemia induced by CZ in a dialysis patient. He was prescribed CZ as medication to be taken as needed for palpitations related to atrial fibrillation attacks. Approximately 9 months later, he was brought to our hospital by ambulance due to chest oppression and general fatigue. He developed hypoglycemic coma on the third hospital day. The high serum concentration of immunoreactive insulin and serum C-peptide immunoreactivity suggested enhanced insulin secretion. The toxic plasma concentration of CZ (2,140 ng/ml) indicated that his hypoglycemic coma was induced by CZ. He needed intravenous hypertonic glucose injection for about 20 days to prevent the recurrence of hypoglycemia. The hypoglycemia induced by CZ may be prolonged over a few weeks in patients with reduced renal function, including patients on hemodialysis.

BACKGROUND: Although recent large-scale clinical studies have shown that preoperative renal insufficiency is associated with increased risk of postoperative complications after pancreatoduodenectomy (PD), it is unknown whether asymptomatic renal dysfunction has an impact on postoperative course after PD. METHODS: Two hundred and fifty-four patients who underwent PD between 2007 and 2013 were enrolled. Renal function was evaluated by the preoperative estimated glomerular filtration rate (eGFR). Patients were divided into two groups according to the cutoff value of 55 of eGFR. RESULTS: Thirty-five patients were classified as the low eGFR group, while 219 were classified as the normal group. There were differences between groups in age, comorbidity and pancreatic texture. The incidence of overall postoperative complication, grade B/C pancreatic fistula and severe complication in the low eGFR group was significantly higher than that in the normal group. Multivariate analysis identified low eGFR as an independent risk factor for severe postoperative complications and grade B/C pancreatic fistula after PD. However, there were no differences in mortality and survival between the low and normal eGFR groups. CONCLUSIONS: We have demonstrated for the first time that preoperative asymptomatic renal dysfunction may be a significant risk factor for severe morbidity and clinically relevant pancreatic fistula after PD., 博士（医学）・乙第1394号・平成29年3月15日, © 2015 Japanese Society of Hepato-Biliary-Pancreatic Surgery., This is the peer reviewed version of the following article: http://dx.doi.org/10.1002/jhbp.286, which has been published in final form at http://dx.doi.org/10.1002/jhbp.286. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.

A 62-year-old female patient with renal dysfunction and pulmonary adenocarcinoma developed postoperative recurrence and received carboplatin/pemetrexed and maintenance pemetrexed. As an anaplastic lymphoma kinase (ALK) gene translocation was identified, the therapy was changed to crizotinib. However, the patient’s blood creatinine level increased, and her physical status worsened. Alectinib also induced exacerbation of renal dysfunction but was controlled by dose reduction of 140 mg twice daily for 2 weeks treatment and 2 weeks break were repeated, and exhibited a partial response for 16 months. Here, we describe the case in which alectinib treatment had beneficial clinical effects on ALK-positive lung adenocarcinoma, which controlled the adverse renal effects by dose reduction and drug breaks., OncoTargets and Therapy, 10, pp.3211-3214; 2017

Recombinant human soluble thrombomodulin (ART-123) is a novel anticoagulant for patients with disseminated intravascular coagulation (DIC). It is widely used in clinical settings throughout Japan. Furthermore, a global Phase 3 study is currently being conducted. In healthy subjects, ART-123 is excreted mainly via the kidneys. Therefore, ART-123 dose decrease was recommended in DIC patients with severe renal dysfunction. However, the pharmacokinetics of ART-123 in DIC patients with severe acute renal dysfunction has not been elucidated. In an open-label, multicentre, prospective, clinical pharmacological study, we investigated the pharmacokinetics and safety of ART-123 upon repeated administration to DIC patients. ART-123 was administered to patients at a dose of 130 or 380 U/kg/day for six consecutive days. Plasma concentrations of ART-123 were measured at 21 time points until eight days after the final administration. Urinary ex-cretion rates during the first 24 hours (h) were calculated. Patient renal functions were evaluated by measuring 24-h creatinine clearance (Ccr). Forty-three patients were enrolled in the present study. The urinary excretion rates of ART-123 correlated closely with 24-h Ccr. Total body clearance of ART-123 was also weakly related with 24-h Ccr. However, the plasma concentrations of ART-123 were not considerably different among patients with different renal function. Two patients had subcutaneous haemorrhage as an adverse event related to ART-123. In conclusion, plasma concentrations of ART-123 may not be different among patients with different renal functions. ART-123 was well tolerated in these patients.

Oxidative stress is considered a central pathophysiological event in cardiovascular disease, including hypertension. Early age reduction in renal mass is associated with hypertension and oxidative stress in later life, which is aggravated by increased salt intake. The aim of the present study was to examine if renal sympathetic denervation can exert blood pressure lowering effects in uninephrectomized (UNX) rats (3-week old) fed with high salt (HS, 4%; w/w) diet for 4 weeks. Moreover, we investigated if renal denervation is associated with changes in NADPH and xanthine oxidase-derived reactive oxygen species. Rats with UNX + HS had reduced renal function, elevated systolic and diastolic arterial pressures, which was accompanied by increased heart weight, and cardiac superoxide production compared to sham operated Controls. UNX + HS was also associated with higher expression and activity of NADPH and xanthine oxidase in the kidney. Renal denervation in rats with UNX + HS attenuated the development of hypertension and cardiac hypertrophy, but also improved glomerular filtration rate and reduced proteinuria. Mechanistically, renal de nervation was associated with lower expression and activity of both NADPH oxidase and xanthine oxidase in the kidney, but also reduced superoxide production in the heart. In conclusion, our study shows for the first time that renal denervation has anti-hypertensive, cardio- and reno-protective effects in the UNX + HS model, which can be associated with decreased NADPH oxidase- and xanthine oxidase-derived reactive oxygen species (i.e., superoxide and hydrogen peroxide) in the kidney.

Recombinant human soluble thrombomodulin (ART-123) is a novel anticoagulant for patients with disseminated intravascular coagulation (DIC). It is widely used in clinical settings throughout Japan. Furthermore, a global Phase 3 study is currently being conducted. In healthy subjects, ART-123 is excreted mainly via the kidneys. Therefore, ART-123 dose decrease was recommended in DIC patients with severe renal dysfunction. However, the pharmacokinetics of ART-123 in DIC patients with severe acute renal dysfunction has not been elucidated. In an open-label, multicentre, prospective, clinical pharmacological study, we investigated the pharmacokinetics and safety of ART-123 upon repeated administration to DIC patients. ART-123 was administered to patients at a dose of 130 or 380 U/kg/day for six consecutive days. Plasma concentrations of ART-123 were measured at 21 time points until eight days after the final administration. Urinary ex-cretion rates during the first 24 hours (h) were calculated. Patient renal functions were evaluated by measuring 24-h creatinine clearance (Ccr). Forty-three patients were enrolled in the present study. The urinary excretion rates of ART-123 correlated closely with 24-h Ccr. Total body clearance of ART-123 was also weakly related with 24-h Ccr. However, the plasma concentrations of ART-123 were not considerably different among patients with different renal function. Two patients had subcutaneous haemorrhage as an adverse event related to ART-123. In conclusion, plasma concentrations of ART-123 may not be different among patients with different renal functions. ART-123 was well tolerated in these patients.

Oxidative stress is considered a central pathophysiological event in cardiovascular disease, including hypertension. Early age reduction in renal mass is associated with hypertension and oxidative stress in later life, which is aggravated by increased salt intake. The aim of the present study was to examine if renal sympathetic denervation can exert blood pressure lowering effects in uninephrectomized (UNX) rats (3-week old) fed with high salt (HS, 4%; w/w) diet for 4 weeks. Moreover, we investigated if renal denervation is associated with changes in NADPH and xanthine oxidase-derived reactive oxygen species. Rats with UNX + HS had reduced renal function, elevated systolic and diastolic arterial pressures, which was accompanied by increased heart weight, and cardiac superoxide production compared to sham operated Controls. UNX + HS was also associated with higher expression and activity of NADPH and xanthine oxidase in the kidney. Renal denervation in rats with UNX + HS attenuated the development of hypertension and cardiac hypertrophy, but also improved glomerular filtration rate and reduced proteinuria. Mechanistically, renal de nervation was associated with lower expression and activity of both NADPH oxidase and xanthine oxidase in the kidney, but also reduced superoxide production in the heart. In conclusion, our study shows for the first time that renal denervation has anti-hypertensive, cardio- and reno-protective effects in the UNX + HS model, which can be associated with decreased NADPH oxidase- and xanthine oxidase-derived reactive oxygen species (i.e., superoxide and hydrogen peroxide) in the kidney.

A 73-year-old man who had complained of right chest pain was found to have a nodule, measuring 4×2 cm in a diameter at the base of the right lung. A bronchoscopic examination revealed adenocarcinoma. Metastasis to the right fourth rib rapidly manifested 2 weeks later.....

A 73-year-old man who had complained of right chest pain was found to have a nodule, measuring 4×2 cm in a diameter at the base of the right lung. A bronchoscopic examination revealed adenocarcinoma. Metastasis to the right fourth rib rapidly manifested 2 weeks later.....

Background: Tenofovir disoproxil fumarate (TDF) has been associated with kidney tubular dysfunction and reduced renal function. Limited studies were performed in Europe and Asia that related plasma tenofovir (TFV) concentration with renal function; no such studies to date have been performed on Africans. Objective: To investigate the correlation between plasma tenofovir (TFV) concentration and certain renal function markers in HIV-infected women on TDF antiretroviral therapy (ART). These markers were also compared to a HIV-uninfected control group. Methods: HIV-infected women (n = 30) on TDF-based ART were matched with 30 controls for age and body mass index. Renal markers analysed were estimated glomerular filtration rate (eGFR), creatinine clearance (CrCl), serum creatinine, albuminuria, glucosuria, serum urea, serum uric acid, urine sodium and maximum tubular reabsorption of phosphate. Baseline eGFR and CrCl data were obtained retrospectively for the HIV-infected women. Plasma TFV was assayed using a validated HPLC-MS/MS method. Stepwise regression, Mann–Whitney test, unpaired and paired t-tests were applied in the statistical analyses. Results: TFV concentration was independently associated with albuminuria (adjusted r2 = 0.339; p = 0.001) in HIV-infected women. In the adjusted (weight) analysis, eGFR (p = 0.038), CrCl (p = 0.032) and albuminuria (p = 0.048) were significantly higher in HIV-infected compared to the uninfected women, but eGFR was abnormally high in HIV-infected women. Both eGFR (p < 0.001) and CrCl (p = 0.008) increased from baseline to follow-up in HIV-infected women. Conclusion: Plasma TFV concentration was associated with increased albuminuria in HIVinfected women in this sub-study. Both eGFR and CrCl were increased in HIV-infected women from baseline. These findings should be confirmed in larger studies, and hyperfiltration in HIV-infected women warrants further investigation

Background: Tenofovir disoproxil fumarate (TDF) has been associated with kidney tubular dysfunction and reduced renal function. Limited studies were performed in Europe and Asia that related plasma tenofovir (TFV) concentration with renal function; no such studies to date have been performed on Africans. Objective: To investigate the correlation between plasma tenofovir (TFV) concentration and certain renal function markers in HIV-infected women on TDF antiretroviral therapy (ART). These markers were also compared to a HIV-uninfected control group. Methods: HIV-infected women (n = 30) on TDF-based ART were matched with 30 controls for age and body mass index. Renal markers analysed were estimated glomerular filtration rate (eGFR), creatinine clearance (CrCl), serum creatinine, albuminuria, glucosuria, serum urea, serum uric acid, urine sodium and maximum tubular reabsorption of phosphate. Baseline eGFR and CrCl data were obtained retrospectively for the HIV-infected women. Plasma TFV was assayed using a validated HPLC-MS/MS method. Stepwise regression, Mann–Whitney test, unpaired and paired t-tests were applied in the statistical analyses. Results: TFV concentration was independently associated with albuminuria (adjusted r2 = 0.339; p = 0.001) in HIV-infected women. In the adjusted (weight) analysis, eGFR (p = 0.038), CrCl (p = 0.032) and albuminuria (p = 0.048) were significantly higher in HIV-infected compared to the uninfected women, but eGFR was abnormally high in HIV-infected women. Both eGFR (p < 0.001) and CrCl (p = 0.008) increased from baseline to follow-up in HIV-infected women. Conclusion: Plasma TFV concentration was associated with increased albuminuria in HIVinfected women in this sub-study. Both eGFR and CrCl were increased in HIV-infected women from baseline. These findings should be confirmed in larger studies, and hyperfiltration in HIV-infected women warrants further investigation