Lower Creatinine Concentrations Research Articles

Antioxidant and phytochemical profiling of ethanol leaf extract of Ficus pachyneura and derived fractions

A total of 16, 18-weeks old chickens with mean weight 1.99±0.12 kg (1.85-2.30kg) were used to compare the serum biochemical characteristics of four chicken genotypes (breeds/strains) from south-eastern part of Nigeria. The chickens were grouped based on their genotypes (breeds/strain) in a Completely Randomized Design for the four-week study. The genotypes (breeds) considered were Black Australorp (BA), Isa Brown (IB), Noiler (NOI) and Local chicken (LC) at 4 chickens per genotype. At the end of the experiment, four (4) birds per genotype were drawn and their blood samples analysed for serum biochemical studies. The mean total cholesterol (TC), triaceylglycerol (TAG) and very low density lipoprotein cholesterol (VLDL-C) concentrations of local chicken (LC) were significantly (P < 0.05) higher than the Isa brown (IB) values. Similarly, the mean blood urea nitrogen (BUN) concentrations of LC was significantly (P < 0.05) higher than the Noiler value. The mean high density lipoprotein cholesterol (HDL-C) of black Australorp (BA) was significantly (P < 0.05) higher than the value of Noiler but showed no significant (p > 0.05) difference when compared to the values of IB and LC. There were however no significant (p > 0.05) variations in the mean low density lipoprotein cholesterol (LDL-C), total bilirubin, direct bilirubin, indirect bilirubin and creatinine concentrations among all the breeds investigated. In conclusion, the results obtained in this study will be helpful in creating a baseline data on biochemical profiles of indigenous and exotic chicken breeds in Nigeria which in turn can be used for assessing the health status of these birds, improving desirable breeds/traits and designing appropriate breeding strategies for indigenous poultry birds in the country.

Evaluations of the effect of genetic variations on the serum renal function markers, bilirubin and lipid profile of laying domestic fowls

A total of 16, 18 weeks old chickens with mean weight 1.99±0.12 kg (1.85-2.30kg) were used to compare the serum biochemical characteristics of four chicken genotypes (breeds/strains) from south-eastern part of Nigeria. The chickens were grouped based on their genotypes (breeds/strain) in a Completely Randomized Design for the four-week study. The genotypes (breeds) considered were Black Australorp (BA), Isa Brown (IB), Noiler (NOI) and Local chicken (LC) at 4 chickens per genotype. At the end of the experiment, four (4) birds per genotype were drawn and their blood samples analysed for serum biochemical studies. The mean total cholesterol (TC), triaceylglycerol (TAG) and very low density lipoprotein cholesterol (VLDL-C) concentrations of local chicken (LC) were significantly (P < 0.05) higher than the Isa brown (IB) values. Similarly, the mean blood urea nitrogen (BUN) concentrations of LC was significantly (P < 0.05) higher than the Noiler value. The mean high density lipoprotein cholesterol (HDL-C) of black Australorp (BA) was significantly (P < 0.05) higher than the value of Noiler but showed no significant (p > 0.05) difference when compared to the values of IB and LC. There were however no significant (p > 0.05) variations in the mean low density lipoprotein cholesterol (LDL-C), total bilirubin, direct bilirubin, indirect bilirubin and creatinine concentrations among all the breeds investigated. In conclusion, the results obtained in this study will be helpful in creating a baseline data on biochemical profiles of indigenous and exotic chicken breeds in Nigeria which in turn can be used for assessing the health status of these birds, improving desirable breeds/traits and designing appropriate breeding strategies for indigenous poultry birds in the country..

Avoiding falsely low creatinine concentrations measured in patients treated with N-acetylcysteine for acetaminophen intoxication using enzymo-amperometric method – An in vitro and in vivo study

BackgroundCirculating creatinine is a biomarker of paramount importance in clinical practice. In cases of acetaminophen (APAP) intoxication, the antidote, N-acetylcysteine (NAC), interferes with commonly used creatininase-peroxidase methods. This study aimed to assess whether creatininase-amperometric methods were affected in this context. MethodsThis study includes in vitro interference tests, involving four creatinine assays using NAC-spiked plasma pools and an in vivo retrospective study comparing creatininase-peroxidase and creatininase-amperometric measurements in patients presenting with NAC-treated APAP poisoning. ResultsCreatininase-peroxidase method was impacted by NAC interference in a clinically-significant manner at therapeutic NAC levels (basal value recovery of 80 % and 70 % for 500 and 1000 mg.L-1 of NAC, respectively), surpassing the desirable Reference Change Value (RCV%). Enzymo-amperometric methods were not impacted. Among patients, a mean bias of −45.2 ± 28.0 % was observed for the peroxidase detection method compared to the amperometric in those who received NAC prior plasma sampling and −2.7 ± 5.4 % in those who did not. ConclusionsOur findings indicate that enzymo-amperometric creatinine assays remain unaffected by NAC interference due to the absence of the peroxidase step in the analytical process. Therefore, these methods are suitable to prevent spurious hypocreatininemia in APAP intoxicated patients undergoing NAC therapy.

Variation of eGFR reporting and CKD equations used in the United Kingdom.

UK Clinical laboratories have been routinely reporting an estimated glomerular filtration rate (eGFR) based on creatinine measurements using an eGFR equation since the early 2000s. Though there have been recommendations to use enzymatic based creatinine assays, and a recommendation of which equation to use, there still remains a high degree of variation in calculated eGFR results. Data from the UK NEQAS for Acute and Chronic Kidney Disease Scheme have been reviewed to look at the CKD equations that are currently in use in the UK and the impact on eGFR results reported. The UK NEQAS for Acute and Chronic Kidney Disease has over 400 participants measuring creatinine across all major clinical biochemistry platforms. An audit of EQA registration against results returned showed that in February 2022 at most 44% of registered participants were correctly reporting the 2009 CKD-EPI equation. At higher creatinine concentrations (which give rise to lower eGFR results), the spread of eGFRs is tight and there is little difference between results from different method principles. However, at lower creatinine concentrations, where it is known that there is more variation in creatinine depending on method choice, both method principle and eGFR equation choice can influence calculated eGFR. In some cases, this can impact CKD Stage classification. CKD is a serious public health issue that requires accurate assessment of eGFR. Laboratories should be in constant dialogue with their renal teams about their creatinine assay performance and impact on eGFR reporting across their service.

The anti-tumor and renoprotection study of E-[c(RGDfK)2]/folic acid co-modified nanostructured lipid carrier loaded with doxorubicin hydrochloride/salvianolic acid A

BackgroundPoor in vivo targeting of tumors by chemotherapeutic drugs reduces their anti-cancer efficacy in the clinic. The discovery of over-expressed components on the tumor cell surface and their specific ligands provide a basis for targeting tumor cells. However, the differences in the expression levels of these receptors on the tumor cell surface limit the clinical application of anti-tumor preparations modified by a single ligand. Meanwhile, toxicity of chemotherapeutic drugs leads to poor tolerance to anti-tumor therapy. The discovery of natural active products antagonizing these toxic side effects offers an avenue for relieving cancer patients’ pain during the treatment process. Since the advent of nanotechnology, interventions, such as loading appropriate drug combinations into nano-sized carriers and multiple tumor-targeting functional modifications on the carrier surface to enhance the anti-tumor effect and reduce toxic and side effects, have been widely used for treating tumors.ResultsNanocarriers containing doxorubicin hydrochloride (DOX) and salvianolic acid A (Sal A) are spherical with a diameter of about 18 nm; the encapsulation efficiency of both DOX and salvianolic acid A is greater than 80%. E-[c(RGDfK)2]/folic acid (FA) co-modification enabled nanostructured lipid carriers (NLC) to efficiently target a variety of tumor cells, including 4T1, MDA-MB-231, MCF-7, and A549 cells in vitro. Compared with other preparations (Sal A solution, NLC-Sal A, DOX solution, DOX injection, Sal A/DOX solution, NLC-DOX, NLC-Sal A/DOX, and E-[c(RGDfK)2]/FA-NLC-Sal A/DOX) in this experiment, the prepared E-[c(RGDfK)2]/FA-NLC-Sal A/DOX had the best anti-tumor effect. Compared with the normal saline group, it had the highest tumor volume inhibition rate (90.72%), the highest tumor weight inhibition rate (83.94%), led to the highest proportion of apoptosis among the tumor cells (61.30%) and the lowest fluorescence intensity of proliferation among the tumor cells (0.0083 ± 0.0011). Moreover, E-[c(RGDfK)2]/FA-NLC-Sal A/DOX had a low level of nephrotoxicity, with a low creatinine (Cre) concentration of 52.58 μmoL/L in the blood of mice, and no abnormalities were seen on pathological examination of the isolated kidneys at the end of the study. Sal A can antagonize the nephrotoxic effect of DOX. Free Sal A reduced the Cre concentration of the free DOX group by 61.64%. In NLC groups, Sal A reduced the Cre concentration of the DOX group by 42.47%. The E-[c(RGDfK)2]/FA modification reduced the side effects of the drug on the kidney, and the Cre concentration was reduced by 46.35% compared with the NLC-Sal A/DOX group. These interventions can potentially improve the tolerance of cancer patients to chemotherapy.ConclusionThe E-[c(RGDfK)2]/FA co-modified DOX/Sal A multifunctional nano-drug delivery system has a good therapeutic effect on tumors and low nephrotoxicity and is a promising anti-cancer strategy.Graphical

Biochemical clusters predict mortality and reported inability to work 10 ​years later

BackgroundChronic systemic inflammation has been linked to premature mortality and limited somatic as well as mental health with consequences for capability to work and everyday functioning. We recently identified three biochemical clusters of endocrine and immune parameters (C-reactive protein (CRP), interleukin-6 (IL-6), fibrinogen, cortisol and creatinine) in participants, age 35–81 years, of the open access Midlife in the United States Study (MIDUS) dataset. These clusters have been validated in an independent cohort of Japanese mid-life adults. Among these clusters, the one characterized by high inflammation coupled with low cortisol and creatinine concentrations was associated with the highest disease burden, referred to as high-risk cluster in the following. The current study aims to further examine the nature of this cluster and specifically whether it predicts mortality and the reported inability to work the last 30 days 10 years after the biomarker assessment. Methods and findingsLongitudinally assessed health data from N ​= ​1234 individuals were analyzed in the current study. Logistic regression analyses were performed to predict mortality within one decade after first assessment (T0 ​= ​first assessment; T1 ​= ​second assessment). General linear models were used to predict the number of days study participants were unable to work due to health issues in the last 30 days (assessed at T1, analyses restricted to individuals <70 years of age). Biological sex, disease burden, and age at T0 were used as covariates in all analyses. Individuals in the previously identified high-risk cluster had a higher risk for mortality (22% of individuals deceased between T0 and T1 versus 10% respectively 9% in the two other clusters). Logistic regression models predicting mortality resulted in a significant difference between individuals from the high-risk cluster compared to those from an identified reference cluster (indicator method, p ​= ​.012), independently of age and disease burden. Furthermore, individuals in the high-risk cluster reported a higher number of disability days during the past 30 days (3.4 days in the high-risk cluster versus 1.5 respectively 1.0 days in the reference clusters) assessed at T1. All pairwise comparisons involving the high-risk cluster were significant (all ps ​< ​.001). ConclusionsImmune-endocrine profiles are predictive of mortality within the following decade over and above age and disease burden. The findings thus highlight the importance of biomarker-based risk profiling that may provide new targets for interventions in the context of preventive medicine in the transition from health to disease and disease-related mortality.

Nutritional and Non-Nutritional Predictors of Low Spot Urinary Creatinine Concentration in Patients with Heart Failure.

Low spot urinary creatinine concentration (SUCR) is a marker of muscle wasting and clinical outcome. The risk factors for low SUCR in heart failure (HF) remain poorly understood. We explored the risk factors for low SUCR related to poor outcomes. In 721 HF patients (age: 52.3 ± 11 years, female: 14%, NYHA: 2.7 ± 0.7) SUCR and Dexa body composition scans were performed. BMI prior HF-onset, weight loss, and appendicular muscle mass were obtained. Each patient was classified as malnutrition or normal by GLIM criteria and three other biochemical indices (CONUT, PNI, and GRNI). Sarcopenia index (SI) as creatinine to cystatin C ratio was also calculated. Within 1 year, 80 (11.1%) patients died. In ROC curve we identified a SUCR value of 0.628 g/L as optimally discriminating surviving from dead. In low SUCR group more advanced HF, higher weight loss and catabolic components of weight trajectory (CCWT), more frequent under-nutrition by GLIM, and lower SI were observed. In multivariate analysis the independent predictors of low SUCR were SI, CCWT, and GNRI score. In conclusion: the risk of low SUCR was associated with a worse outcome. Low SUCR was associated with greater catabolism and sarcopenia but not with biochemical indices of malnutrition.

How biomarker patterns can be utilized to identify individuals with a high disease burden: a bioinformatics approach towards predictive, preventive, and personalized (3P) medicine

Prevalences of non-communicable diseases such as depression and a range of somatic diseases are continuously increasing requiring simple and inexpensive ways to identify high-risk individuals to target with predictive and preventive approaches. Using k-mean cluster analytics, in study 1, we identified biochemical clusters (based on C-reactive protein, interleukin-6, fibrinogen, cortisol, and creatinine) and examined their link to diseases. Analyses were conducted in a US American sample (from the Midlife in the US study, N = 1234) and validated in a Japanese sample (from the Midlife in Japan study, N = 378). In study 2, we investigated the link of the biochemical clusters from study 1 to childhood maltreatment (CM). The three identified biochemical clusters included one cluster (with high inflammatory signaling and low cortisol and creatinine concentrations) indicating the highest disease burden. This high-risk cluster also reported the highest CM exposure. The current study demonstrates how biomarkers can be utilized to identify individuals with a high disease burden and thus, may help to target these high-risk individuals with tailored prevention/intervention, towards personalized medicine. Furthermore, our findings raise the question whether the found biochemical clusters have predictive character, as a tool to identify high-risk individuals enabling targeted prevention. The finding that CM was mostly prevalent in the high-risk cluster provides first hints that the clusters could indeed have predictive character and highlight CM as a central disease susceptibility factor and possibly as a leverage point for disease prevention/intervention.

How Routinely Assessed Biomarkers can be Utilized to Identify Individuals with a High Disease Burden: A Bioinformatics Approach

Prevalences of non-communicable diseases such as depression and a range of somatic diseases are continuously increasing requiring simple and inexpensive ways to identify high-risk individuals to target with preventive approaches. Using k-mean cluster analytics, in study 1, we identified biochemical clusters (based on C-reactive protein, interleukin-6, fibrinogen, cortisol, and creatinine) and examined their link to diseases. Analyses were conducted in a U.S. American sample (from Midlife in the United States study, N=1,234) and validated in a Japanese sample (from Midlife in Japan study, N=378). In study 2, we investigated the link of clusters to childhood maltreatment (CM). The three identified biochemical clusters included one cluster (with high inflammatory signaling and low cortisol and creatinine concentrations) indicating the highest disease burden. This high-risk cluster also reported the highest CM exposure. The current study demonstrates how biomarkers can be utilized to identify individuals with a high disease burden and thus, may help to target these high-risk individuals with tailored prevention/intervention. Furthermore, our findings raise the question whether the found biochemical clusters have predictive character; as a tool to identify high-risk individuals. The finding that CM was mostly prevalent in the high-risk cluster provides initial evidence that the clusters could indeed have predictive character and highlight CM as a central disease susceptibility factor and possibly as a leverage point for disease prevention.

Effects of supplemental Bacillus subtilis, injectable vitamin E plus selenium, or both on health parameters during the transition period in dairy cows in a tropical environment.

The objective of this study was to determine the effects of supplemental Bacillus subtilis (BS, 0.5 × 1011 CFU/day), injectable vitamin E and selenium (ES, 1000 mg α-tocopherol acetate and 10 mg sodium selenite), or both during the transition period on health parameters and the incidence of retained fetal membranes (RFM) of dairy cows under tropical conditions (average temperature humidity index = 77.0). Thirty-two crossbred Holstein-Friesian cows were used in a randomized design trial with a 2 × 2 factorial arrangement of treatments. Cows were randomly assigned to one of four treatments, including no supplementation (CON), single intramuscular injection of ES on day - 21 before the expected calving date (ES), daily oral supplementation of BS between day - 21 and day 21 relative to calving, or both ES and BS. Body condition score (BCS) and blood samples were collected on days - 28, - 14, 0, 14, and 28 relative to calving. Mean concentrations of corpuscular hemoglobin were higher (33.12 vs 34.03 g/dL, p = 0.06) and platelets were lower (380.97 vs 302.32 × 103/μL, p = 0.10) with ES than without ES. Cows fed supplemental BS had lower concentrations of creatinine and albumin and tended to have lower AST and β-hydroxybutyrate (BHBA) levels. However, concentrations of glucose were higher for cows fed BS than for those without BS. No differences in the incidence of RFM were observed. In summary, supplemental B. subtilis could reduce indicators of negative energy balance by increasing glucose and lowering BHBA and improve health parameters by keeping WBCs and monocytes in a healthy range during the transition period.

Rapid Quantification of Plasma Creatinine Using a Novel Kinetic Enzymatic Assay.

Enzymatic assays are among the most common diagnostic tests performed in the clinical laboratory. Enzymatic substrate analysis is most commonly measured using endpoint methods; however, modulating the reaction kinetics allows fine control of the reaction rate, which can be adjusted based on specific monitoring technologies. We developed and optimized an enzymatic method for measurement of creatinine in plasma, using commonly paired enzymes of creatininase (Crtnnase), creatinase (Crtase), sarcosine oxidase (SOX), ascorbate oxidase (AOX), and horseradish peroxidase (HRP). The novel aspect of the assay is that it is fast and uses SOX as the limiting enzyme. The assay performance was assessed with respect to precision, accuracy, and interferences. The intrarun %CV (n = 12) was approximately 5% for each concentration tested, with biases ranging from -3 to -9%. The interrun %CV (n = 39) ranged from 5 to 8%, with biases ranging from -2 to -6%. During the accuracy assessment (n = 127), only 4 samples did not meet the minimum acceptability criteria. Minimal interference was observed, except at low creatinine concentrations with elevated creatine. Our novel and versatile enzymatic assay to measure plasma creatinine using kinetic analysis with SOX as the limiting enzyme is rapid (<2 mins), sensitive, and specific and demonstrates excellent concordance with the laboratory standard. We anticipate this rapid kinetic assay to be compatible with emerging technologies in the field of portable diagnostic devices, such as the usage of silicon photonics to monitor biochemical reactions.

Rats with congenital hydronephrosis show increased susceptibility to renal ischemia-reperfusion injury.

Many drug candidates have shown significant renoprotective effects in preclinical models; however, there is no clinically used effective pharmacotherapy for acute kidney injury. The failure to translate from bench to bedside could be due to misleading results from experimental animals with undetected congenital kidney defects. This study was performed to assess the effects of congenital hydronephrosis on the functional capacity of tubular renal transporters as well as kidney sensitivity to ischemia‐reperfusion (I‐R)‐induced injury in male Wistar rats. Ultrasonography was used to distinguish healthy control rats from rats with hydronephrosis. L‐carnitine or furosemide was administered, and serial blood samples were collected and analyzed to assess the effects of hydronephrosis on the pharmacokinetic parameters. Renal injury was induced by clamping the renal pedicles of both kidneys for 30 min with subsequent 24 hr reperfusion. The prevalence of hydronephrosis reached ~30%. The plasma concentrations after administration of L‐carnitine or furosemide were similar in both groups. I‐R induced more pronounced renal injury in the hydronephrotic rats than the control rats, which was evident by a significantly higher kidney injury molecule‐1 concentration and lower creatinine concentration in the urine of the hydronephrotic rats than the control rats. After I‐R, the gene expression levels of renal injury markers were significantly higher in the hydronephrotic kidneys than in the kidneys of control group animals. In conclusion, our results demonstrate that hydronephrotic kidneys are more susceptible to I‐R‐induced damage than healthy kidneys. Unilateral hydronephrosis does not affect the pharmacokinetics of substances secreted or absorbed in the renal tubules.

A Mysteriously Low Creatinine Concentration.

A Mysteriously Low Creatinine Concentration.

Effects of calcium dobesilate (CaD) interference on serum creatinine measurements: a national External Quality Assessment (EQA)-based educational survey of drug-laboratory test interactions

Drug-laboratory test interactions (DLTIs) are one of the major sources of laboratory errors. Calcium dobesilate (CaD) interference on serum creatinine testing is a widespread problem that has long been ignored in China. A national EQA-based survey was launched to investigate the current status of CaD interference on creatinine routine methods used in China and enhance the education of CaD interference in clinical laboratories. A descriptive survey was developed to characterize the status quo of Chinese laboratory professionals' cognition to CaD interference. Four of survey samples which were spiked with/without interference additive were shipped to 175 participant laboratories. The target reference values from a reference measurement procedure were compared against the results from participating laboratories to evaluate the CaD interference on serum creatinine measurements using enzymatic method or Jaffé method. The lack of knowledge of DLTIs and the barriers to collect information from pharmacological and laboratory data systems had become the main problems on implementing DLTIs education in China. A significant negative influence of CaD on enzymatic method was observed regardless of measurement platforms. Jaffé method was generally free from interaction with CaD but showed poor precision and accuracy at low creatinine concentrations. More efforts should be made to enhance the education of DLTIs in clinical laboratories in China.

Sensitive determination of ethyl glucuronide in serum and whole blood: detection time after alcohol exposure compared with urine

Abstract Objectives Ethyl glucuronide (EtG) is a conjugated, minor ethanol metabolite used as a biomarker for recent alcohol intake. EtG is commonly measured in urine as part of a drug testing service but has also attracted attention for measurement in blood. However, due to lower EtG concentrations in blood, the detection time is expected to be shorter. The present work aimed to improve the analytical sensitivity of EtG in blood, to prolong the detection time. Methods A liquid chromatography-tandem mass spectrometry method was developed for EtG in whole blood and serum, using protein precipitation with methanol, a deuterated internal standard, and selected reaction monitoring mode with negative electrospray ionization. No significant matrix effect was observed. The method generated linear results in the measuring range 1.0–50 μg/L, the accuracy was within ±10% and the imprecision &lt;15%. Results In 46 patients followed with daily blood and urine sampling during alcohol detoxification, the mean (median) time to first negative serum EtG sample was 112 (111) h. This was slightly longer than for EtG in urine, using 100 μg/L as cutoff. The detection rate was 76% for serum EtG and 68% for urine EtG. In cases where serum EtG was positive but urine EtG negative, the urine samples tended to be more dilute as indicated by lower creatinine concentrations. On admission to hospital, the whole-blood and serum EtG concentrations correlated with the breath ethanol concentration (p = 0.012 and p = 0.027, respectively). In 100 patients sampled at admission to hospital for other reasons than substance abuse and with no ethanol detected in breath, 40% tested positive for EtG in serum and 43% in urine. In 79 paired urine and serum EtG measurements, the median urine/serum concentration ratio was 155. Conclusions A sensitive method was developed for EtG measurement in whole-blood and serum specimens, offering similar detection time for recent alcohol exposure compared with routine EtG measurement in urine.

Macronutrient Intake And Blood Markers Concentrations In Mexican University Athletes.

PURPOSE: To analyze the association between the concentration of different blood markers and macronutrient intake by sex in university athletes. METHODS: 242 (139 males, 103 females) athletes of different sports were evaluated on their food habits. We administered 24-hour dietary recalls of a training day by standardized staff. Then, we estimated the absolute (g/day) and relative (g/kg/day) macronutrient intake. Also, we obtained uric acid, urea, creatinine, cholesterol, triacylglycerides, glucose, hemoglobin, and hematocrit concentrations from blood analysis. We only analyzed the data of subjects who had their blood samples and dietary recall within a period of no more than 30 days apart. The analysis was divided by sex. RESULTS: Subjects` age, body weight, and height were: 21.4 ±3.0 and 20.7 ±2.0 years, 73.6 ±14.1 and 61.7 ±11.6 kg; and 175.8 ±6.8 and 163.6 ±6.9 cm, for men and women respectively. For males, there were significant associations between relative (beta [95% CI], -0.328 [-0.037 to -0.619]; p = 0.027) and absolute (-0.005 [-0.001 to -0.009]; p = 0.027) protein intake and uric acid concentrations; similarly, absolute protein intake was significantly associated with lower creatinine concentrations (-0.014 [-0.001 to -0.027]; p = 0.031). For females, there was a significant association between relative carbohydrate intake and blood glucose (1.912 [0.259 to 3.566]; p = 0.024). No other significant association was found. CONCLUSIONS: In this study, protein intake was associated with lower blood creatinine and uric acid concentrations in males, and carbohydrate intake with higher blood glucose concentrations in females.

P1144ODORIBACTER AND ANAEROTRUNCUS: GUT MICROBIOME SIGNATURE MIGHT BE RELATED TO COGNITIVE IMPAIRMENT IN PATIENTS ON PERITONEAL DIALYSIS

Abstract Background and Aims Cognitive impairment is very common in dialysis patients, with negative effects on quality of life and mortality. In neurodegenerative conditions (Alzheimer, Parkinson) a gut-brain axis has been identified; however, there is no information about the relationship of gut microbiota alterations and presence of cognitive impairment in chronic kidney disease. The aim was to associate the gut microbiota profile with the cognitive function in patients on automated peritoneal dialysis (APD). Method Cross-sectional study in 39 APD patients; those with visual or mental disabilities, psychiatric or neurodegenerative diseases, inflammatory causes of ESRD, with active infections (including peritonitis), on anti-inflammatory drugs or antibiotics, were excluded. All patients had a clinical, biochemical, nutritional and dialysis adequacy evaluation, and were classified according to the presence of cognitive impairment using the Montreal Cognitive Assessment (MoCA) test. Fecal samples were collected and immediately stored at -80 ºC. DNA extraction was performed with Quick-DNA Fecal/Soil Microbe Miniprep Kit (Zymo Research). Subsequently, V3 and V4 regions of 16S rRNA were sequenced using illumina platform. Statistical analysis: Student t test and χ2 were used to compare quantitative and qualitative variables, respectively. Quantitative Insights Into Microbial Ecology (QIIME) pipeline and Linear Discriminant Analysis Effect Size (LEfSe) were employed for bioinformatic analysis. Results Eighty-two percent of subjects were male, mean age 47 ± 24 years, and dialysis vintage 11 (7-48) months. Sixty-four percent of patients had cognitive impairment. Patients with cognitive impairment were significantly older (53 ± 16 vs 38 ± 14, p=0.006), had higher frequency of diabetes mellitus (56% vs 21%, p=0.04), and had lower creatinine concentrations (11.3 ± 3.7 vs 14.9 ± 5.4, p=0.02) compared to patients with normal cognitive function. No differences were found in other biochemical, nutritional or dialysis adequacy variables. A total of 38,083 sequences per patient were obtained after the microbiome analysis. LEfSe analysis showed a preponderance of S24_7, Rikenellaceae, Odoribacteraceae, Odoribacter, and Anaerotruncus in patients with cognitive impairment. In contrast, patients without cognitive impairment were characterized by Dorea, Ruminococcus, Sutterella and Fusobacteria (LDA score (Log10) &amp;gt; 2.5; p &amp;lt; 0.05). Conclusion Cognitive impairment was present in two-thirds of these APD patients. Odoribacter and Anaerotruncus were significantly more abundant in patients with cognitive impairment than in those with normal function. Such gut bacteria might enhance cognitive impairment as have been described to increase the uremic toxin production and activation of inflammatory pathways in the central nervous system. This is the first study providing evidence than brain and behavior might be influenced by the gut-brain axis in dialysis patients.

Pseudohypercalcemia in a patient with multiple myeloma and acute kidney injury; a case report

Here in this paper, we present a 60-year-old man admitted for generalized pain in his limbs and was finally diagnosed with multiple myeloma. He also underwent evaluation and treatments for his hypercalcemia (15 mg/dL). His calcium concentration did not respond well to different modalities and was along with a low parathyroid hormone (PTH) and elevated creatinine concentration (12 mg/dL). Further evaluations revealed normal ionized calcium which confirmed the diagnosis of pseudohypercalcemia. Multiple myeloma is a plasma cell neoplasm in which 10% of the patients suffer from true-hypercalcemia at the time of diagnosis. Pseudohypercalcemia is described as an elevated serum calcium concentration along with normal ionized calcium concentration and the absence of clinical symptoms of hypercalcemia. The cause of pseudohypercalcemia in multiple myeloma is due to the binding of calcium to increased abnormal immunoglobulins. The importance of this issue lies in the low PTH levels along with hypercalcemia and azotemia which is suggestive of pseudohypercalcemia.

373. Evaluation of the StatSensor Xpress for the point of care determination of capillary creatinine concentration in a pregnant population

Introduction Early identification of Acute Kidney Injury during pregnancy (P-AKI) is critical to reduce adverse maternal and fetal outcomes. The StatSensor Xpress (Nova Biomedical) is a handheld device that may improve feasibility of rapid, serial creatinine concentration measurement, especially in low resource settings with a high incidence of P-AKI. Prior to implementation the device requires validation in a pregnant population. Objective To evaluate the performance of the StatSensor Xpress creatinine analyser in capillary blood compared to an enzymatic serum assay, in a pregnant population. Methods Serum and capillary blood samples were obtained prospectively from pregnant participants at antenatal obstetric clinics, and non-pregnant controls. Repeatability was assessed in quality control lots and venous blood from three participants at low (50 μmol/L), mid (90 μmol/L) and high (200 μmol/L) concentrations. Creatinine concentration was determined using an enzymatic reference method in serum samples and StatSensor in capillary blood, as per manufacturer’s specifications. Agreement was assessed by concordance and construction of Bland–Altman plots. A retrospective adjustment factor was separately applied to evaluate the inbuilt offset function. Results Coefficients of variation (CV) from repeatability analysis, ranged from 2.1 to 3.0%CV in aqueous solution and 4.0%CV, 3.0%CV and 4.1%CV in whole blood samples of low, mid and high creatinine concentrations respectively. Lin’s concordance correlation coefficients between the methods were 0.95 (n = 15), and 0.96 (n = 11) when non-pregnant participants were excluded. The median difference between methods was +12 μmol/L. Discussion The StatSensor met desirable criteria for precision and accuracy. 95% limits of agreement were adequate once systematic bias was corrected for by retrospective application of an adjustment factor, which can be used for future analysis. Device performance may be superior in pregnancy due to the lower serum creatinine concentration observed secondary to glomerular hyperfiltration. Findings require replication in a larger population with prospective evaluation of the offset function.

Measured glomerular filtration rate does not improve prediction of mortality by cystatin C and creatinine.

Cystatin C may add explanatory power for associations with mortality in combination with other filtration markers, possibly indicating pathways other than glomerular filtration rate (GFR). However, this has not been firmly established since interpretation of associations independent of measured GFR (mGFR) is limited by potential multicollinearity between markers of GFR. The primary aim of this study was to assess associations between cystatin C and mortality, independent of mGFR. A secondary aim was to evaluate the utility of combining cystatin C and creatinine to predict mortality risk. Cox regression was used to assess the associations of cystatin C and creatinine with mortality in 1157 individuals referred for assessment of plasma clearance of iohexol. Since cystatin C and creatinine are inversely related to mGFR, cystatin C - 1 and creatinine - 1 were used. After adjustment for mGFR, lower cystatin C - 1 (higher cystatin C concentration) and higher creatinine - 1 (lower creatinine concentration) were independently associated with increased mortality. When nested models were compared, avoiding the potential influence of multicollinearity, the independence of the associations was supported. Among models combining the markers of GFR, adjusted for demographic factors and comorbidity, cystatin C - 1 and creatinine - 1 combined explained the largest proportion of variance in associations with mortality risk ( R 2 = 0.61). Addition of mGFR did not improve the model. Our results suggest that both creatinine and cystatin C have independent associations with mortality not explained entirely by mGFR and that mGFR does not offer a more precise mortality risk assessment than these endogenous filtration markers combined.