Increase In Serum Creatinine Concentration Research Articles

#475 Association between hospital-acquired acute kidney injury and the risk of kidney cancer

Abstract Background and Aims The effects of hospital-acquired acute kidney injury (HA-AKI) on kidney cancer remain unclear. The study aimed to investigate the association between HA-AKI and kidney cancer by a large multicenter cohort study. Method The real-world cohort study included Chinese adults with at least two serum creatinine (SCr) tests within 7 days during hospitalization from 24 regional central hospitals between January 2000 and December 2022. AKI was defined as a ≥26.5 μmol/l increase in serum creatinine concentration within 48 hours or a ≥50% increase over the baseline within 7 days. The primary outcome was a new diagnosis of kidney cancer, while the secondary outcomes included death attributed to kidney cancer and new diagnoses of other cancers of the urinary system. The Cox proportional hazard model was employed for analyses. Results Of the 342861 patients (median age, 57.06 [43.68, 68.54] yr; men, 179096 [52.2%]), 9337 patients experienced HA-AKI. During a mean follow-up of 2.03 years, 195 (0.57‰) patients with a new diagnosis of kidney cancer were detected. After multivariable adjustment, HA-AKI was significantly associated with a higher risk of kidney cancer (adjusted hazard ratio [HR], 2.39; 95% confidence interval [CI], 1.37-4.17, P = 0.003) and kidney cancer-specific death (adjusted HR, 3.19; 95% CI, 1.90-5.37, P < 0.001). We also found that relationships between HA-AKI and cancers of the urinary system, excluding kidney cancer, such as bladder cancer, prostate cancer, were not statistically significant. Conclusion HA-AKI was significantly associated with increased risk of kidney cancer and death attributed to kidney cancer. Our findings highlight the importance of monitoring HA-AKI patients for early detection of kidney cancer.

The model of functional disorders in rats with kidney nephrectomy ¾ in comparison with a high-salt diet

BACKGROUND. Modeling of chronic kidney disease using nephrectomy of 5/6 kidney parenchyma is actively used in experimental nephrology. However, the remaining 17 % of the organ parenchyma is associated with severe renal fibrosis in humans. A high-salt diet has traditionally been considered as a systemic hemodynamic model for the development of chronic kidney disease.THE AIM: to compare the functional disorders that occur in rats with nephrectomy of ¾ of the kidneys and when using only a high-salt diet.MATERIAL AND METHODS. The study was performed on 30 male Wistar rats. The animals were randomly divided into 3 equal groups: control (falsely operated, L), high-salt diet (falsely operated, LVD), nephrectomy ¾ renal parenchyma (NE). The rats received a balanced laboratory feed daily, differing only in the content of sodium chloride (NaCl). In the L and NE groups, rats received a feed containing 0.34 % NaCl, and in the VD group – 4 % NaCl. The duration of follow-up was 16 weeks. Systolic blood pressure (SBP) was measured on the tail by the cuff method. The serum and urine concentrations of creatinine, urea, potassium, sodium, chlorine, as well as the degree of proteinuria and albuminuria were determined.RESULTS. During the observation, the SBP in group L did not change. In the LVD group, SBP increased from 120 [120; 125] mmHg to 130.0 [125.0; 140.0] mmHg, p=0.011. In the NE group, SBP also increased from 120 [120; 125] mmHg to 135.0 [132.5; 137.5] mmHg, p=0.011. In the LVD group, there was an increase in serum creatinine concentration compared to the control to 52.5 [50.0; 56.0] mmol/l, p=0.0001; urea to 6.0 [5.6; 6.6] mmol/l, p=0.0001; potassium to 5.6 [5.3; 5.8] mmol/l, p=0.0001; chlorine up to 87.5 [86.6; 87.9] mmol/l, p= 0.0001. At the same time, creatinine clearance decreased from 187.5 [160.0; 205.0] ml/min in the L group to 92.0 [81.2; 99.0] ml/min, p=0.0003 in the LVD group and to 83.9 [65.7; 85.9] ml/min p=0.0001 in the NE group. The value of albuminuria before the end of the experiment was statistically significantly higher compared to the control in both the LVD group of 12.12 [6.36;18.41] mg/g creatinine, p= 0.0001, and in the NE group of 72.5 [61.6; 92.9] mg/g creatinine, p= 0.0001. When conducting a nonparametric correlation analysis (all three observation groups were combined), a statistically significant relationship was noted between the level of SBP after 1 month from the start of the experiment and the amount of albuminuria at its completion (Rs=0.583 p=0.001). A statistically significant relationship between the value of SBP and creatinine clearance was revealed before the end of the experiment (Rs=-0.700 p=0.005). Also, before the end of the experiment, a statistically significant relationship between albuminuria and creatinine clearance was revealed (Rs=-0.671 p=0.006).CONCLUSION. The NE model of the renal parenchyma is expected to be accompanied by the development of less severe functional changes compared to NE 5/6 of the renal parenchyma. In this regard, we assume that its use may be useful in studying the effectiveness of nephroprotective measures at the initial stages of CKD development. The negative effects of a high-salt diet are comparable in a number of indicators to nephrectomy of the renal parenchyma. Traditionally, an increase in salt intake is associated with an increase in blood pressure, which could result in an increase in albuminuria. However, we could not identify any relationships between albuminuria and the value of SAD. We assume that the model of a high-salt diet can be considered as a variant of a local, rather than a systemic hemodynamic model of the development of chronic kidney disease. In the future, we will present the results of nephrobiopsy in the experimental groups described above.

LC/MS-MS quantification of myo-inositol: a novel biomarker for kidney disease

Abstract Creatinine is the primary biomarker used for assessing kidney function in patients with suspected acute and chronic kidney injury. However, creatinine, a product of muscle creatine metabolism, is an imperfect proxy for renal function because it is subject to non-renal interferences including muscle mass, diet, and medications. Creatinine is particularly problematic as a biomarker of acute kidney injury (AKI) due to relatively high renal function reserve, requiring considerable kidney damage and time for a clinically significant change in creatinine to be detected. Given that AKI and chronic kidney injury (CKD) are associated with high mortality, morbidity, and contribute significantly to health care costs, there is an unmet need for highly sensitive and specific biomarkers for assessing renal function in patients. Myo-inositol oxygenase (MIOX) is a novel biomarker limitedly expressed in the proximal renal tubules. MIOX concentrations are elevated in mice with renal injury and in critically ill patients with AKI. Our previously published studies have demonstrated that elevation in MIOX concentrations precedes changes in creatinine concentrations by approximately 54 hours. Importantly, MIOX facilitates the conversion of myo-inositol to glucuronic acid. We developed a robust LC-MS/MS method to quantify myo-inositol in human plasma, hypothesizing that following renal injury (acute and chronic), plasma concentrations of myo-inositol will increase, and will correlate with increases in serum creatinine concentrations. A healthy outpatient cohort was identified from samples obtained from out-patients with normal plasma creatinine, eGFR>60, as well as normal urine protein: creatinine ratio, albumin: creatinine ratio, or urinalysis results that were pan-negative/pan-normal. Remnant samples from out-patients with clinically staged CKD who have not initiated dialyses were selected for the CKD group. In healthy adult out-patients with stable renal function, the central 95th% distribution of plasma myo-inositol concentrations was 16.61 - 44.2 uM (Median 27.7uM, 95% CI: 26.7-28-7). No sex-based differences in plasma myo-inositol were observed. We also observed excellent correlation between plasma myo-inositol and serum creatinine concentrations (r=0.84, 95% CI: 80-88), as well as excellent sensitivity (99%) and specificity (100%) at a myo-inositol concentration of 50.22uM for differentiating patients with stable kidney function from those with CKD. Patients with CKD exhibited higher plasma myo-inositol concentrations (p value <0.0001) with a central 95% percentile of 51.2-309.1 uM (Median 104.1 uM, 95% CI: 92.3- 113.6). These results imply that myo-inositol concentrations increase in accord with renal injury and MIOX buildup in patients with kidney dysfunction, making it a potential biomarker for renal impairment.

Usefulness of the N-Terminal of the Prohormone Brain Natriuretic Peptide in Predicting Acute Kidney Injury Requiring Renal Replacement Therapy in Patients Undergoing Heart Valve Surgery.

Background and Objectives: By definition, acute kidney injury (AKI) is a clinical syndrome diagnosed when the increase in serum creatinine concentration is >0.3 mg/dL in 48 h or >1.5-fold in the last seven days or when diuresis < 0.5 mL/kg/h for a consecutive 6 h. AKI is one of the severe complications that may occur in the early postoperative period in patients undergoing heart valve surgery, significantly increasing the risk of death. Early implementation of renal replacement therapy increases the chances of improving treatment results in patients with postoperative AKI. The study assessed the predictive ability of selected preoperative and perioperative parameters for the occurrence of postoperative AKI requiring renal replacement therapy in the early postoperative period in a group of patients with severe valvular heart disease. Materials and Methods: A prospective study was conducted on a group of patients undergoing consecutive heart valve surgeries. The primary endpoint was postoperative AKI requiring renal replacement therapy. AKI was diagnosed with an increase in serum creatinine > 0.3 mg/dL in 48 h or >1.5-fold in the previous 7 days and/or a decrease in diuresis < 0.5 mL/kg/h for 6 h. The observation period was until the patient was discharged home or death occurred. Logistic regression analysis was used to assess which variables were predictive of primary endpoint, and odds ratios (OR) were calculated with a 95% confidence interval (CI). Multivariate analysis was based on the result of single factor logistic regression, i.e., to further steps, all statistically significant variables were taken into consideration. Results: A total of 607 patients were included in the study. The primary endpoint occurred in 50 patients. At multivariate analysis: NT-proBNP (OR 1.406; 95% CI 1.015-1.949; p = 0.04), CRP (OR 1.523; 95% CI 1.171-1.980; p = 0.001), EuroSCORE II (OR 1.090; 95% CI 1.014-1.172; p = 0.01), age (OR 1.037; 95% CI 1.001-1.075; p = 0.04) and if they stayed in the intensive care unit longer than 2 days (OR 9.077; 95% CI 2.026-40.663; p = 0.004) remained the independent predictors of the primary endpoint. The mean preoperative NT-proBNP level was 2063 pg/mL (±1751). Thirty-eight patients with AKI requiring renal replacement therapy died in intrahospital follow-up. Conclusions: The results of the presented study indicate that a high preoperative level of NT-proBNP and postoperative hemodynamic instability may be associated with a significant risk of a postoperative AKI requiring renal replacement therapy. The results of the study may also suggest that qualifying for heart valve surgery earlier may be associated with improved prognosis in this group of patients.

Preliminary evaluation of hepatitis A virus cell receptor 1/kidney injury molecule 1 in healthy horses treated with phenylbutazone.

To investigate if hepatitis A virus cell receptor 1/kidney injury molecule 1 (HAVCR1/KIM1) in urine is detectable concurrently with increases in serum creatinine concentrations in horses receiving a recommended dose of phenylbutazone (PBZ) for 7days. Preliminary study. Ten clinically healthy horses with normal physical examination and laboratory work were randomly assigned to PBZ or placebo groups (5 each). The PBZ group received PBZ at 4.4mg/kg mixed with corn syrup orally every 12hours. The placebo group received corn syrup orally every 12hours. Both groups were treated for 7days. Kidney ultrasonography was performed, and venous blood and urine samples were collected prior to commencement and at the end of treatment. Samples from 1 additional healthy horse, 3 horses with acute kidney failure, and 1 horse with chronic kidney failure were also evaluated. None of the 10 horses had detectable HAVCR1/KIM1 in urine at baseline. Serum creatinine concentrations in placebo group did not increase, and HAVCR1/KIM1 was undetectable in urine. At the end of treatment, 3 of 5 horses receiving PBZ developed increases in serum creatinine of >26.5μmol/L (>0.3mg/dL), and HAVCR1/KIM1 was detectable in urine, despite normal findings on kidney ultrasonography in all horses. HAVCR1/KIM1 is detectable in urine and is associated with increases in serum creatinine concentrations of >26.5 μmol/L in horses following treatment with PBZ for 7 consecutive days. Thus, HAVCR1/KIM1 might aid in the early detection of acute kidney injury in horses.

Prepubertal to adulthood exposure to low doses of glyphosate-based herbicide increases the expression of the Havcr1 (Kim1) biomarker and causes mild kidney alterations

Glyphosate is a nonselective and postemergent herbicide used to combat weeds in several crops, which raises concerns about risks to human health since residues are detected in urine, human milk, surface water and several types of food. Feces and urine are the major routes of elimination of glyphosate, making the kidney a sensitive target for the development of toxicity. In fact, farmers are at high risk of developing chronic kidney disease. In this sense, this study aims to investigate kidney function by measuring the serum levels of urea and creatinine, examining the histological morphology, and analyzing the mRNA expression of genes related to tubular transport of ions, urea and urates and the biomarker of kidney disease Kim1, and the levels of lead in the kidney in male Wistar rats orally exposed to low levels of glyphosate-based herbicide (GBH: 0, 0.5 or 5 mg/kg) from weaning to adult life by gavage. GBH0.5 showed reduced serum urea concentration, presence of tubulointerstitial swelling and mononuclear cell infiltration into the interstitium, increased gene expression of Kim1 and reduced gene expression of Slc14a1. GBH5 showed reduced serum urea and increased serum creatinine concentrations, tubulointerstitial swelling, interstitial fibrosis, and reduced expression of Trpm6 and Trpv5. Exposure to GBH did not affect the levels of Pb in the kidneys of animals. In conclusion, glyphosate at low doses may cause mild kidney damage. It is necessary to evaluate whether the long-term effects of this constant injury may contribute to the development of chronic kidney disease of uncertain etiology.

Ренальна дисфункція у пацієнток із післяпологовими кровотечами

The purpose of the study was to assess the influence of the hematocrit level on the frequency of development of renal dysfunction in massive obstetric bleeding. Materials and methods. For the study, we selected 33 women in labor in whom low hematocrit values were determined as a result of blood loss. The examined group had no risk factors and signs of renal dysfunction in the prenatal period. The average age of the women in labor was 32.5 ± 6.4 years, the average weight was 76.5 ± 12.4, and the average gestational age was 39.5 ± 1.5 weeks. Postpartum blood loss averaged 1830.5 ± 622.7 ml (from 1200 to 2500 ml). All bleeding was stopped according to current protocols. Results and discussion. Despite improvements in prenatal and delivery care, postpartum acute kidney injury, associated with massive postpartum blood loss and blood transfusions, currently remains a serious problem. A lot of factors play a role in kidney damage and the development of postpartum acute kidney injury, but it is largely related to hemodilution and low values of hematocrit and hemoglobin. At the same time, there are currently no reliable data on hematocrit threshold values in patients undergoing infusion therapy against the background of postpartum blood loss. Acute kidney injury was defined according to the Kidney Disease: Improving Global Outcomes 2012 recommendations as the presence of at least one of the following criteria: an increase in serum creatinine concentration ≥0.3 mg/dl (≥26.5 μmol/l) within 48 hours, or an increase in serum creatinine concentration ≥1.5 times from the baseline, which is known or assumed to have occurred within 7 days, or a diuresis rate &lt;0.5 ml/kg/h within 6 hours. Conclusion. As a result of the research, it was established that the following pathological conditions and nosologies were the most frequent causes of postpartum acute kidney injury: HELLP syndrome (75% of cases), preeclampsia (70.8% of cases), postpartum hemorrhage (58.3% of cases) and gestational hypertension (45.8% of cases). At the same time, the most frequent clinical manifestation of acute kidney injury occurred with the development of oliguria/anuria (45.8%), hypertension more than 140/90 mm Hg (37.5%) and eclampsia (29.2%). The functional state of the kidneys (namely, the glomerular filtration rate) depended on the hematocrit level, and when its values decreased, the glomerular filtration rate decreased significantly. The obtained dependence was statistically reliable, which was indicated by the value of p=0.0000132 and corresponded to a strong positive correlation, which was indicated by the value r = 0.9449 and r2 = 0.8928. Hematocrit values in the range of 19.57 ± 2.18% and below are a risk factor for the development of postpartum renal dysfunction

Acute kidney injury in snake bite patients

Background: In India, large proportion of snake bites occur when people are working barefoot in fields or while walking at night. Objectives: To study i) clinical profile of renal involvement in snake bite patients. ii) in-hospital outcome of acute kidney injury in snake bite patients Methodology: Patients are classified into three stages of acute kidney injury proposed by Acute Kidney Injury Network which defines AKI as an abrupt increase in serum creatinine concentration of ≥0.3 mg/dl from baseline, a percentage increase in the serum creatinine concentration ≥50% or oliguria of 0.5 ml/kg/hr &gt;6 hours. Results: Mean age of patients was 43.8±12.63 years. Male to female ratio was 1.63:1 with male preponderance. Mean interval between snakebite and presentation to hospital was 15.37 hours. All snake bites were inflicted to lower limbs and 48% of snake bites were due to Viper as identified by patients. 98% patients presented with local signs of inflammation. 52% patients presented with coagulation abnormality and 60% with decreased urine output which were associated with increase severity of AKI and need for haemodialysis in 12% of patients.Conclusion: Common manifestations of poisonous snake bite include cellulitis, abnormal Coagulation profile and decreased urine output.

Advances in the study of subclinical AKI biomarkers.

Acute kidney injury (AKI) is a prevalent and serious illness in all clinical departments, with a high morbidity and death rate, particularly in intensive care units, where prevention and treatment are crucial. As a result, active prevention, early detection, and timely intervention for acute kidney injury are critical. The current diagnostic criteria for acute kidney injury are an increase in serum creatinine concentration and/or a decrease in urine output, although creatinine and urine output merely reflect changes in kidney function, and AKI suggests injury or damage, but not necessarily dysfunction. The human kidney plays a crucial functional reserve role, and dysfunction is only visible when more than half of the renal mass is impaired. Tubular damage markers can be used to detect AKI before filtration function is lost, and new biomarkers have shown a new subset of AKI patients known as “subclinical AKI.” Furthermore, creatinine and urine volume are only marginally effective for detecting subclinical AKI. As a result, the search for new biomarkers not only identifies deterioration of renal function but also allows for the early detection of structural kidney damage. Several biomarkers have been identified and validated. This study discusses some of the most promising novel biomarkers of AKI, including CysC, NGAL, KIM-1, lL-18, L-FABP, IGFBP7, TIMP-2, Clusterin, and Penkid. We examine their performance in the diagnosis of subclinical AKI, limitations, and future clinical practice directions.

Incidence and Risk Factors for Acute Kidney Injury After Chimeric Antigen Receptor T-Cell Therapy

ObjectiveTo evaluate the association of baseline and postinfusion patient characteristics with acute kidney injury (AKI) in the month after chimeric antigen receptor T-cell (CAR-T) therapy. MethodsWe retrospectively reviewed records of 83 patients with non-Hodgkin lymphoma undergoing CAR-T therapy (axicabtagene ciloleucel) between June 2016 and November 2020. Patients were followed up to 1 month after treatment. Post–CAR-T AKI was defined as a more than 1.5-fold increase in serum creatinine concentration from baseline (on the day of CAR-T infusion) at any time up to 1 month after CAR-T therapy. ResultsOf 83 patients, 14 (17%) developed AKI during follow-up. At 1 month after CAR-T infusion, 10 of 14 (71%) AKI events had resolved. Lower baseline estimated glomerular filtration rate, use of intravenous contrast material, tumor lysis prophylaxis, higher peak uric acid and creatine kinase levels during follow-up, and change in lactate dehydrogenase from baseline to peak level within 1 month after initiation of CAR-T therapy were significantly associated with AKI incidence during follow-up. Incidence of AKI was also higher in patients who received higher doses of corticosteroids and tocilizumab. ConclusionAcute kidney injury occurred in approximately 1 in 6 patients who received axicabtagene ciloleucel for non-Hodgkin lymphoma. Patients with high tumor burden receiving higher total doses of corticosteroids or tocilizumab should be closely monitored for development of AKI. Lower baseline kidney function at CAR-T initiation, exposure to contrast material, and progressive increase in levels of tumor lysis markers (uric acid, lactate dehydrogenase, creatine kinase) after CAR-T infusion may predict risk of AKI during the 1 month after infusion.

Impact of trimethoprim on serum creatinine, sodium, and potassium concentrations in patients taking trimethoprim-sulfamethoxazole without changes in glomerular filtration rate.

Trimethoprim (TMP) inhibits the Na+ /K+ -ATPase present in the basement membrane of distal tubular epithelial cells. However, hyponatremia and hyperkalemia may develop in patients taking TMP-sulfamethoxazole (SMX). In addition, because TMP inhibits drug transporters, such as organic cation transporter 2 and multidrug and toxin extrusion protein 2-K in proximal tubules, reversible increases in the concentration of serum creatinine (SCr), the substrate of these transporters, may occur. Here, we investigated variability in SCr, serum sodium (Na+ ), and serum potassium (K+ ) concentrations after initiation of TMP-SMX treatment and evaluated the risk of hyponatremia and hyperkalemia in patients with increased SCr concentrations without changes in the glomerular filtration rate (GFR). In this retrospective study, all patients aged 20 years or older who received oral TMP-SMX during hospitalization were enrolled. The patients with estimated creatinine (Cr) clearance (eCCr) lower than 30 mL/min were excluded, as were patients taking drugs that were likely to induce renal dysfunction, drugs other than glucocorticoids that were likely to induce electrolyte imbalances, or drugs other than TMP that inhibit tubular Cr secretion. Additionally, those with SCr concentrations elevated more than 30% from baseline or serum blood urea nitrogen concentration levels above 20 mg/dL during follow-up were also excluded. In total, 111 patients were enrolled in the study. The common independent variable affecting the change rate in SCr, Na+ , and K+ concentrations (ΔSCr, ΔNa+ , and ΔK+ ) from baseline to the highest value during the follow-up period (14 days after initiation of TMP-SMX treatment) was the daily dose of TMP. There were significant correlations between ΔSCr and ΔNa+ or ΔK+ (ρ=-0.199, p=0.036 and ρ=0.244, p=0.010, respectively). Kaplan-Meier curves for hyponatremia and hyperkalemia with greater than or equal to grade 1 severity showed different profiles when the TMP dose varied (≤ 160 vs. > 160 mg/day; p=0.005 and 0.008). The cumulative incidences of both adverse effects were 64.7% (median: 7 days) and 29.4% in patients taking more than 160 mg/day TMP and 35.2% and 6.7% in patients taking 160 mg/day TMP or less. Thus, TMP may affect the kinetics of Cr, Na+ , and K+ in the proximal and distal tubules in a dose-dependent without changing the GFR. This study is the first report to demonstrate the degree of changes in SCr, Na+ , and K+ concentrations after initiation of TMP-SMX treatment. If SCr is elevated after initiation of TMP-SMX treatment, clinicians should be aware of decreased Na+ and increased K+ concentrations. TMP may increase the risks of hyponatremia and hyperkalemia in a dose-dependent manner without altering GFR.

Telmisartan as an add-on treatment for dogs with refractory idiopathic epilepsy: a nonrandomized, uncontrolled, open-label clinical trial.

To evaluate the effect on seizure frequency of add-on telmisartan treatment in dogs with refractory idiopathic epilepsy. 11 client-owned dogs with idiopathic epilepsy and ≥ 2 generalized seizures/mon that were currently being treated with ≥ 2 antiepileptic drugs. Telmisartan was administered at a dosage of 0.25 to 1 mg/kg, PO, every 12 hours for 4 to 16 months. Seizure frequencies before and during telmisartan treatment were recorded. 10 dogs completed the 4-month treatment protocol. One dog was excluded owing to a transient increase in serum creatinine concentration; no adverse effects of telmisartan were observed in the remaining 10 dogs. A reduction in seizure frequency greater than an estimated expected placebo effect of 30% was evident in 7 of the 10 dogs. Long-term (12 to 16 months) follow-up information was available for 6 dogs, of which 4 had a further reduction in seizure frequency. Differences in seizure frequency were not statistically significant. No significant difference was found in serum phenobarbital concentration throughout the treatment period in the 7 dogs that were tested. Telmisartan has the potential to reduce seizure frequency when administered as an add-on antiepileptic drug in dogs with refractory idiopathic epilepsy. A randomized, double-blind, placebo-controlled trial is needed to determine the true efficacy of telmisartan. On the basis of our results, a sample size of 54 dogs with refractory idiopathic epilepsy would be needed.

Enhanced external counterpulsation: A new method to alleviate contrast-induced acute kidney injury

BackgroundContrast-induced acute kidney injury (CI-AKI) is a common complication after exposure to contrast media. Renal ischaemia occurs in the initial stage of CI-AKI, however, there are very few effective measures to improve renal perfusion. MethodsA total of 114 patients with an estimated glomerular filtration rate (eGFR) of 60–89 ml/min/1.73m2 were randomly assigned to two groups: enhanced external counterpulsation (EECP) group (N = 57) and control group (N = 57). Two hours after contrast exposure, EECP group received EECP treatment for 1 h while no intervention was performed control group. The primary outcome was the incidence of serum cystatin C concentration to 10% above the baseline concentration at 24 h after contrast administration. The secondary outcomes were the incidence of CI-AKI (defined as an increase in serum creatinine concentration to ≥0.5 mg/dl or by 25% compare to the baseline after contrast exposure), contrast clearance and adverse clinical events. ResultsThe primary outcome was observed in 26 patients (6 EECP and 20 control; 11% vs. 35%; P = 0.002). CI-AKI occurred in four patients (0 EECP and 4 control; 0% vs. 7%; P = 0.042). The clearance rate of iopromide in the initial 3 h was significantly different between EECP and control group (59.92 ± 8.84 vs 46.80 ± 9.26 ml/min/1.73 m2; P < 0.001). No adverse clinical events were observed in this study. ConclusionsThis study demonstrates that EECP increases the contrast clearance and may have an effect in reducing the risk of CI-AKI.The study has been registered in Chinese Clinical Trial Registry (ChiCTR 2,000,039,190).

Effect of a Perioperative Hypotension-Avoidance Strategy Versus a Hypertension-Avoidance Strategy on the Risk of Acute Kidney Injury: A Clinical Research Protocol for a Substudy of the POISE-3 Randomized Clinical Trial.

Background:Most patients who take antihypertensive medications continue taking them on the morning of surgery and during the perioperative period. However, growing evidence suggests this practice may contribute to perioperative hypotension and a higher risk of complications. This protocol describes an acute kidney injury substudy of the Perioperative Ischemic Evaluation-3 (POISE-3) trial, which is testing the effect of a perioperative hypotension-avoidance strategy versus a hypertension-avoidance strategy in patients undergoing noncardiac surgery.Objective:To conduct a substudy of POISE-3 to determine whether a perioperative hypotension-avoidance strategy reduces the risk of acute kidney injury compared with a hypertension-avoidance strategy.Design:Randomized clinical trial with 1:1 randomization to the intervention (a perioperative hypotension-avoidance strategy) or control (a hypertension-avoidance strategy).Intervention:If the presurgery systolic blood pressure (SBP) is <130 mmHg, all antihypertensive medications are withheld on the morning of surgery. If the SBP is ≥130 mmHg, some medications (but not angiotensin receptor blockers [ACEIs], angiotensin receptor blockers [ARBs], or renin inhibitors) may be continued in a stepwise manner. During surgery, the patients’ mean arterial pressure (MAP) is maintained at ≥80 mmHg. During the first 48 hours after surgery, some antihypertensive medications (but not ACEIs, ARBs, or renin inhibitors) may be restarted in a stepwise manner if the SBP is ≥130 mmHg.Control:Patients receive their usual antihypertensive medications before and after surgery. The patients’ MAP is maintained at ≥60 mmHg from anesthetic induction until the end of surgery.Setting:Recruitment from 108 centers in 22 countries from 2018 to 2021.Patients:Patients (~6800) aged ≥45 years having noncardiac surgery who have or are at risk of atherosclerotic disease and who routinely take antihypertensive medications.Measurements:The primary outcome of the substudy is postoperative acute kidney injury, defined as an increase in serum creatinine concentration of either ≥26.5 μmol/L (≥0.3 mg/dL) within 48 hours of randomization or ≥50% within 7 days of randomization.Methods:The primary analysis (intention-to-treat) will examine the relative risk and 95% confidence interval of acute kidney injury in the intervention versus control group. We will repeat the primary analysis using alternative definitions of acute kidney injury and examine effect modification by preexisting chronic kidney disease, defined as a prerandomization estimated glomerular filtration rate <60 mL/min/1.73 m2.Results:Substudy results will be analyzed in 2022.Limitations:It is not possible to mask patients or providers to the intervention; however, objective measures will be used to assess acute kidney injury.Conclusions:This substudy will provide generalizable estimates of the effect of a perioperative hypotension-avoidance strategy on the risk of acute kidney injury.

Synbiotics Easing Renal Failure by Improving Gut Microbiology II (SYNERGY II): A Feasibility Randomized Controlled Trial.

Synbiotics have emerged as a therapeutic strategy for modulating the gut microbiome and targeting novel cardiovascular risk factors, including uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (PCS). This study aims to evaluate the feasibility of a trial of long-term synbiotic supplementation in adults with stage 3–4 chronic kidney disease (CKD). Adult participants with CKD and estimated glomerular filtration rate (eGFR) of 15–60 mL/min/1.73 m2) were recruited between April 2017 and August 2018 to a feasibility, double-blind, placebo-controlled, randomized trial of synbiotic therapy or matched identical placebo for 12 months. The primary outcomes were recruitment and retention rates as well as acceptability of the intervention. Secondary outcomes were treatment adherence and dietary intake. Exploratory outcomes were evaluation of the cardiovascular structure and function, serum IS and PCS, stool microbiota profile, kidney function, blood pressure, and lipid profile. Of 166 potentially eligible patients, 68 (41%) were recruited into the trial (synbiotic n = 35, placebo n = 33). Synbiotic and placebo groups had acceptable and comparable 12-month retention rates (80% versus 85%, respectively, p = 0.60). Synbiotic supplementation altered the stool microbiome with an enrichment of Bifidobacterium and Blautia spp., resulting in a 3.14 mL/min/1.73 m2 (95% confidence interval (CI), −6.23 to −0.06 mL/min/1.73 m2, p < 0.01) reduction in eGFR and a 20.8 µmol/L (95% CI, 2.97 to 38.5 µmol/L, p < 0.01) increase in serum creatinine concentration. No between-group differences were observed in any of the other secondary or exploratory outcomes. Long-term synbiotic supplementation was feasible and acceptable to patients with CKD, and it modified the gastrointestinal microbiome. However, the reduction in kidney function with synbiotics warrants further investigation.

Glomerular Filtration Rate Decline and increased Serum Creatinine Concentration in Abia State University Teaching Hospital Aba

Glomerular filtration Rate (GFR) is essentially the most reliable index of kidney function in health. A decrease in GFR is a pointer to decline in Kidney function and persistent or progressive GFR decline is a specific diagnostic criterion for chronic kidney disease (CKD). In defining CKD, we consider GFR of less than 60ml/min/1.73m 2 for three months or more. Markers of Kidney function test assess the normal function of kidneys. These markers may be biochemical or even radioactive. They assist in measuring GFR, as well as the concentrating and diluting property (tubular function) of kidneys. One of such biochemical markers is Serum Creatinine. An increase or decrease in the serum level of these biomarkers can be of help in determining the efficiency of kidney function. Endogenously produced creatinine is an accepted biomarker of kidney function. It is produced from the metabolism of skeletal muscle creatine. It is released into the plasma in a stable rate in normal subjects, and freely filtered at the glomerulus. However, creatinine is secreted into the urine in the proximal tubule which can occasionally overestimate GFR by 10- 20 %.A number of GFR estimating equations have been developed to overcome some of the limitations of estimating GFR from serum creatinine. The CG equation (Cockcroft Gault) was developed in 1973 and is used widely. A new equation Modification of diet in renal disease (MDRD) study equation was developed in 1999 and has since been validated in a number of populations. The MDRD equation was used in estimating GFR in this study.

In vivo treatment with varespladib, a phospholipase A2 inhibitor, prevents the peripheral neurotoxicity and systemic disorders induced by Micrurus corallinus (coral snake) venom in rats

In this study, we investigated the action of varespladib (VPL) alone or in combination with a coral snake antivenom (CAV) on the local and systemic effects induced by Micrurus corallinus venom in rats. Adult male Wistar rats were exposed to venom (1.5 mg/kg – i.m.) and immediately treated with CAV (antivenom:venom ratio 1:1.5 ‘v/w’ – i.p.), VPL (0.5 mg/kg – i.p.), or both of these treatments. The animals were monitored for 120 min and then anesthetized to collect blood samples used for haematological and serum biochemical analysis; after euthanasia, skeletal muscle, renal and hepatic tissue samples were collected for histopathological analysis. M. corallinus venom caused local oedema without subcutaneous haemorrhage or apparent necrosis formation, although there was accentuated muscle morphological damage; none of the treatments prevented oedema formation but the combination of CAV and VPL reduced venom-induced myonecrosis. Venom caused neuromuscular paralysis and respiratory impairment in approximately 60 min following envenomation; CAV alone did not prevent the neurotoxic action, whereas VPL alone prevented neurotoxic symptoms developing as did the combination of CAV and VPL. Venom induced significant increase of serum CK and AST release, mostly due to local and systemic myotoxicity, which was partially prevented by the combination of CAV and VPL. The release of hepatotoxic serum biomarkers (LDH and ALP) induced by M. corallinus venom was not prevented by CAV and VPL when individually administered; their combination effectively prevented ALP release. The venom-induced nephrotoxicity (increase in serum creatinine concentration) was prevented by all the treatments. VPL alone or in combination with CAV significantly prevented the venom-induced lymphocytosis. In conclusion, VPL shows to be effective at preventing the neurotoxic, nephrotoxic, and inflammatory activities of M. corallinus venom. In addition, VPL acts synergistically with antivenom to prevent a number of systemic effects caused by M. corallinus venom.

Metabolic Effects of Vitamin B1 Therapy under Overnutrition and Undernutrition Conditions in Sheep.

As a precursor for a universal metabolic coenzyme, vitamin B1, also known as thiamine, is a vital nutrient in all living organisms. We previously found that high-dose thiamine therapy prevents overnutrition-induced hepatic steatosis in sheep by enhancing oxidative catabolism. Based on this capacity, we hypothesized that thiamine might also reduce whole-body fat and weight. To test it, we investigated the effects of high-dose thiamine treatment in sheep under overnutrition and calorie-restricted undernutrition to respectively induce positive energy balance (PEB) and negative energy balance (NEB). Eighteen mature ewes were randomly assigned to three treatment groups (n = 6 each). The control group (CG) was administered daily with subcutaneous saline, whereas the T5 and T10 groups were administered daily with equivoque of saline containing 5 mg/kg and 10 mg/kg of thiamine, respectively. Bodyweight and blood biochemistry were measured twice a week for a period of 22 days under PEB and for a consecutive 30 days under NEB. Surprisingly, despite the strong effect of thiamine on liver fat, no effect on body weight or blood glucose was detectable. Thiamine did, however, increase plasma concentration of non-esterified fatty acids (NEFA) during NEB (575.5 ± 26.7, 657.6 ± 29.9 and 704.9 ± 26.1 µEqL−1 for CG, T5, and T10, respectively: p < 0.05), thereby favoring utilization of fatty acids versus carbohydrates as a source of energy. Thiamine increased serum creatinine concentrations (p < 0.05), which paralleled a trending increase in urea (p = 0.09). This may indicate an increase in muscle metabolism by thiamine. Reduction of fat content by thiamine appears more specific to the liver than to adipose tissue. Additional studies are needed to evaluate the potential implications of high-dose vitamin B1 therapy in muscle metabolism.

German S3-Guideline on the treatment of Psoriasis vulgaris, adapted from EuroGuiDerm - Part 2: Treatment monitoring and specific clinical or comorbid situations.

German S3-Guideline on the treatment of Psoriasis vulgaris, adapted from EuroGuiDerm - Part 2: Treatment monitoring and specific clinical or comorbid situations.

Relationships between creatinine increase and mortality rates in patients given vancomycin in 76 hospitals: The increasing role of infectious disease pharmacists.

Vancomycin is a commonly used antimicrobial with the potential for renal toxicity. We evaluated vancomycin duration, changes in renal function after vancomycin initiation ("post-vancomycin" renal function changes), and associated mortality risk among hospitalized patients. We analyzed data from 76 hospitals and excluded patients with a baseline serum creatinine concentration (SCr) of >3.35 mg/dL. We estimated mortality risk relative to vancomycin duration and the magnitude of post-vancomycin SCr change, controlling for demographics, baseline SCr, underlying diseases, clinical acuity, and comorbidities. Among 128,993 adult inpatients treated with vancomycin, 49.0% did not experience SCr elevation. Among the remaining patients, 26.0%, 11.4%, 8.8% and 4.8% experienced increases in post-vancomycin SCr of 1% to 20%, 21% to 40%, 41% to 100%, and greater than 100%, respectively. Compared to mortality risk among patients with a vancomycin therapy duration between 4 and 5 days (the lowest-mortality group), longer vancomycin therapy duration was not independently associated with higher mortality risk after adjusting for confounders. In contrast, there was a graded relationship between post-vancomycin SCr elevation and mortality. Multivariable adjusted mortality odds ratios ranged from 1.60 to 13.66, corresponding to SCr increases of 10% and greater than 200%, respectively. Half of patients given vancomycin did not experience SCr elevation and had the lowest mortality, suggesting that vancomycin can be used safely if renal function is stabilized. In the large study cohort, vancomycin duration itself was not an independent predictor of mortality. Post-vancomycin SCr elevation appeared to be a driver of in-hospital mortality. Even a 10% post-vancomycin SCr increase was associated with an increased mortality risk. This finding stresses the importance of closely monitoring renal function and may support the value of pharmacokinetic dosing.