Urinary Albumin Concentration Research Articles

Associations of serum uric acid and urinary albumin with the severity of diabetic retinopathy in individuals with type 2 diabetes

BackgroundDiabetic retinopathy (DR) is a serious microvascular complication of type 2 diabetes mellitus (T2DM). The aim of this retrospective study was to reveal the risk factors for the severity of DR in individuals with T2DM. Demographic data and biochemical parameters were collected and analyzed.MethodsA total of 518 individuals with type 2 diabetes were included. These individuals were classified into three groups according to the severity of diabetic retinopathy: non-diabetic retinopathy (NDR) group (N = 172), non proliferative diabetic retinopathy (NPDR) group (N = 184), and proliferative diabetic retinopathy (PDR) group (N = 162). Demographic and clinical measurement data of the individuals were collected by reviewing medical records and direct interview. The demographic data and biochemical parameters between groups were compared using Student’s t-test. Moreover, the factors related to severity of diabetic retinopathy were identified by using the multivariate logistic regression analysis.ResultsNo significant difference in age, gender, body mass index (BMI), and diabetes duration was found among these three groups. The serum uric acid (SUA), total cholesterol (TC), low density lipoprotein cholesterol (LDL-c), homocysteine, and urinary albumin levels were significantly higher in the NPDR and PDR group than those in the NDR group (P < 0.05). The individuals in the PDR group had obviously higher levels of SUA, homocysteine, and urinary albumin than individuals in the NPDR group (P < 0.05). The multivariate logistic regression analysis revealed that high SUA, homocysteine, TC, LDL-c, and urinary albumin levels were associated with more serious diabetic retinopathy (OR > 1; P < 0.05).ConclusionThe concentrations of SUA and urinary albumin are associated with the severity of DR in individuals with T2DM.

Effects of Hydroxyurea and Renin-Angiotensin Blockade on Kidney Function in Sickle Cell Disease

Kidney disease is a common complication that leads to increased morbidity and early mortality in patients with sickle cell disease (SCD). Vaso-occlusion, hyperfiltration, hypertension, and cell-free hemoglobin/heme-mediated toxicity may contribute to the pathophysiology of kidney disease. Treatments for SCD-related kidney disease have been adopted from therapies used to treat other SCD-related complications (hydroxyurea [HU]) or diabetic nephropathy (angiotensin converting enzyme [ACE]-inhibitors or angiotensin receptor blockers [ARBs]), although their effects on kidney function are not clear. We evaluated the effects of HU and ACE-inhibitors or ARBs on kidney function in a longitudinal cohort of 439 SCD patients enrolled into a prospective registry between 2011 and 2019. Patients were considered for the analysis if they had 6 months of kidney function values pre-therapy and remained on therapy for 6 months or longer. Changes in the estimated glomerular filtration rate (eGFR) and urine albumin concentration were compared prior to and after starting therapy using a mixed effects model. The effects of HU on kidney function were evaluated in 49 SCD patients. The mean age was 38 years (standard deviation [SD] 11 years), 43% were male, and 80% were Hb SS/Sβ0-thalassemia genotype. The eGFR improved from an average decline of -3.3 mL/min/1.73m2 in the 6 months prior to starting HU to an increase of +9.5 mL/min/1.73m2 during HU therapy (P = 0.0002) (Table). The average change in albuminuria also improved from an increase of +1.2 mg/g creatinine pre-HU therapy to a decline of -1.2 mg/g creatinine during HU therapy, although the difference was not statistically significant (P = 0.17). In 47 SCD patients started on ACE-inhibitors or ARBs, the mean age was 45 years (SD 11 years), 43% were male, and 87% were Hb SS/Sβ0-thalassemia genotype. During ACE-inhibitor or ARB therapy, there was no observed difference in the change in eGFR pre- versus during therapy (P = 0.9) (Table). Albuminuria improved from an average change of -1.0 mg/g creatinine pre-therapy to -1.6 mg/g creatinine during therapy (P = 0.009). Because clinical data are limited, current American Society of Hematology guidelines have conditional recommendations with low levels of certainty for the use of HU and ACE-inhibitors or ARBs to treat sickle cell nephropathy. In a longitudinal cohort of SCD patients, we demonstrate that during 6 months of therapy, there may be a benefit of HU in improving eGFR and of ACE-inhibitors or ARBs in reducing albuminuria. Larger and longer follow up studies of HU, ACE-inhibitors and ARBs as well as new targeted therapies to treat sickle cell nephropathy are urgently needed. Figure Disclosures Gordeuk: Novartis: Consultancy; Ironwood: Research Funding; CSL Behring: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; Imara: Research Funding. Saraf:Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Other: Advisory Boards, Speakers Bureau; Novartis, Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Pfizer, Global Blood Therapeutics, Novartis: Research Funding.

ASIAN PACIFIC SOCIETY OF NEPHROLOGY CLINICAL PRACTICE GUIDELINE ON DIABETIC KIDNEY DISEASE - EXECUTIVE SUMMARY.

Introduction: COVID-19 is now a global pandemic affecting millions of people Patients on dialysis are at an increased risk to COVID-19 infection due to their exposure in the health care setting Strategies for infection control and prevention are also being implemented in the dialysis units because of the increased risk of virus transmission within the unit Objective: Describe the different measures and strategies done to mitigate the spread of COVID-19 outbreak in a hospital based dialysis centre Methods: Review of the epidemic course with contact tracing was done from March 14 to May 14, 2020 in the dialysis unit of a tertiary hospital Results: Of 167 haemodialysis patients, 20 were considered COVID-19 suspects Eight tested positive-2 were traced to be exposed with the first confirmed case, 2 were handled by a COVID-19 infected healthcare worker (HCW) who was asymptomatic at time of contact while 2 asymptomatic patients tested positive during mass screening Two of 67 HCWs tested positive were exposed to patients Key interventions during the course of the outbreak included: mass testing of patients and HCWs after identifying 6 patients and 2 HCWs infected with COVID-19 using nasopharyngeal/oropharyngeal swabs by RT-PCR;dialysis of COVID-19 confirmed and suspected cases in isolation rooms separate from the dialysis unit (instead of cohorting);provision of adequate protective personal equipment for HCWs and surgical masks for all patients, environmental disinfection especially in the waiting area with strict social distancing and screening for signs and symptoms at the entrance of the unit Conclusion: Infection control strategies are needed to manage the spread of COVID-19 in dialysis centres These infection prevention measures should be implemented at the first indication of transmission in the area and should be maintained for the duration of the pandemic and until the area show no more reports of transmission

ASIAN PACIFIC SOCIETY OF NEPHROLOGY CLINICAL PRACTICE GUIDELINE ON DIABETIC KIDNEY DISEASE.

ASIAN PACIFIC SOCIETY OF NEPHROLOGY CLINICAL PRACTICE GUIDELINE ON DIABETIC KIDNEY DISEASE.

Proof-of-concept study: Evaluation of plasma and urinary electrolytes as markers of response to L-asparaginase therapy in dogs with high-grade lymphoma.

Response to chemotherapy is one of the most important prognostic factors in dogs with lymphoma. The objective of this feasibility study was to evaluate if clinical responses to a specific cytotoxic agent (L-asparaginase) could be anticipated by measuring analyte concentrations in plasma and urine concentrations of lymphoma-bearing dogs. We hypothesized that potassium and phosphate concentrations in plasma and urine would be higher in dogs that completely responded to therapy. Plasma and urine samples of dogs with lymphoma were obtained before 12 and 24hours after intramuscular L-asparaginase injections. Peripheral lymph node volumes were evaluated according to the Veterinary Cooperative Oncology Group standardized criteria. Plasma and urine electrolyte, calcium, phosphate, creatinine, urea, total protein, and albumin concentrations were measured, and the fractional excretions of each electrolyte were calculated. Statistical analyses compared complete vs partial responders using a linear regression model. Contrast analyses were also performed to differentiate the mean of each group, with adjustments made with the Benjamini-Hochberg procedure. Fourteen dogs were included, eight with complete responses, and six with partial responses. Plasma phosphate concentrations were significantly higher at 12hours (P=.0003) and 24hours (P=.009) after complete responses to therapy. This study demonstrates the potential use of plasma and urine analyte monitoring after chemotherapy induction. Plasma phosphate measurements represent a potential indicator of early responses to L-asparaginase therapy. Larger population studies are warranted to confirm these preliminary results.

A Novel Near Infrared Spectroscopy Based Device for Albumin Estimation.

In this paper we have proposed a fluorescence based spectroscopy device which can be used to quantitatively estimate the amount of albumin that gets excreted out of our body. Albumin is a significant protein in bio-fluids and performs a wide range of metabolic functions. The dye that has been used as a fluorescent indicator for the presence of albumin in this study has been earlier tested with bovine serum albumin (BSA) and human serum albumin (HSA) with satisfactory results. The method is based on principle of fluorescence in near infrared range (NIR) of 700 to 850 nm by using a novel dye with the test mixture. The chosen near infrared range has a benefit of absence of the auto fluorescence of the bio-molecules present in urine other than the albumin molecules. The system consists of: light source, spectroscopic chamber, sensing and computational unit. The study shows the stability and reproducibility of device so as to avoid fluctuations of voltage and other undesirables. The optimization with bovine serum albumin and human serum albumin has been done and the device can sense as low as 100 nM concentration precisely and accurately.Clinical Relevance-The system being presented is intended for developing a low cost point of care testing device for determining albumin concentration in urine.

P0133INCREASED INTRA-ABDOMINAL PRESSURE DURING LAPARASCOPIC PNEUMOPERITONEUM ENHANCES ALBUMINURIA VIA RENAL VENOUS CONGESTION, ILLUSTRATING PATHOPHYSIOLOGICAL ASPECTS OF HIGH OUTPUT PREECLAMPSIA

Abstract Background and Aims Intra-abdominal hypertension (IAH) causes severe organ dysfunction. Our aim is to evaluate the effect of increased intra-abdominal pressure (IAP) on renal function, hypothesizing that venous congestion may increase proteinuria and fluid retention without endothelial dysfunction. Method Three urine samples were collected from 32 non-pregnant women undergoing laparoscopic assisted vaginal hysterectomy (LAVH) and from 10 controls placed in Trendelenburg position for 60 minutes. Urine sampling was done before (PRE), during or immediately after (PER), and two hours after (POST) the procedure. Urinary albumin, protein and creatinine concentrations were measured in each sample, ratios were calculated and compared within and between groups. Results During LAVH, the albumin/creatinine ratio (ACR) increased and persisted POST-procedure, which was not observed in controls. A positive correlation existed between the LAVH duration and the relative change in both ACR and protein/creatinine ratio (PCR) PER- and POST-procedure. Conclusion Iatrogenic IAH increases urinary ACR and PCR in non-pregnant women via a process of venous congestion. This mechanism might explain the presentation of one specific subtype of late-onset preeclampsia, where no drop of maternal cardiac output is observed.

Whey Protein and Its Components Lactalbumin and Lactoferrin Affect Energy Balance and Protect against Stroke Onset and Renal Damage in Salt-Loaded, High-Fat Fed Male Spontaneously Hypertensive Stroke-Prone Rats

Whey protein (WH)-enriched diets are reported to aid in weight loss and to improve cardiovascular health. However, the bioactive components in whey responsible for causing such effects remain unidentified. We determined the effects of whey and its components [α-lactalbumin (LA) and lactoferrin (LF)] on energy balance, glucose tolerance, gut hormones, renal damage, and stroke onset in rats. Male spontaneously hypertensive stroke-prone (SHRSP) rats (age 8 wk) were fed isocaloric high-fat (40%kcal) and high-salt (4%wt/wt) diets (n=8-10/group) and randomized for 8 wk to diets enriched as follows: control (CO): 15%kcal from egg albumin, 45%kcal from carbohydrate; WH: 20%kcal WH isolate+15%kcal egg albumin; LA: 20%kcal LA +15%kcal egg albumin; or LF: 20%kcal lactoferrin+15%kcal egg albumin. Measurements included energy balance (food intake, energy expenditure, and body composition), stroke-related behaviors, brain imaging, glucose tolerance, metabolic hormones, and tissue markers of renal damage. Data were analyzed by linear mixed models with repeated measures or 1-way ANOVA. Diets enriched with WH, LA, or LF increased survival, with 25% of rats fed these diets exhibiting stroke-associated morbidity, whereas 90% of CO rats were morbid by 8 wk (P<0.05). The nephritis scores of rats fed WH-, LA-, or LF-enriched diets were 80%, 92%, and 122% lower than those of COs (P=0.001). The mRNA abundances of renin and osteopontin were 100-600% lower in rats fed WH-, LA-, or LF-enriched diets than in COs (P<0.05). Urine albumin concentrations and albumin-to-creatinine ratios were 200% lower in rats fed LF-enriched diets than in COs (P<0.05). Compared with COs, rats fed LF-enriched diets for 2-3 wk had food intake decreased by 29%, body weight decreased by 13-19%, lean mass decreased by 12-19%, and fat mass decreased by 20% (P<0.001). Relative to COs, rats fed WH and LA had food intake decreased by 10% (P<0.1), but COs had 12-45% lower weight than rats fed LA- and WH-enriched diets by 3 wk (P<0.01). Compared with COs, rats fed WH-enriched diets increased energy expenditure by 7%, whereas, rats fed LA-enriched diets had energy expenditure acutely decreased by 7% during the first 4 d, and rats fed LF-enriched diets had energy expenditure decreased by 7-17% throughout the first week ( P<0.001). Rats fed LA- and LF-enriched diets had blood glucose decreased by 14-19% (P<0.05) and WH by 9% (P=0.1), relative to COs. Compared with COs, rats fed LF had GIP decreased by 90% and PYY by 87% (P<0.05). Together, these findings indicate that whey and its components α-lactalbumin and lactoferrin improved energy balance and glycemic control, and protected against the onset of neurological deficits associated with stroke and renal damage in male SHRSP rats.

Effect of a Single Intravitreal Bevacizumab Injection on Proteinuria in Patients With Diabetes.

PurposeProteinuria is the second most common complication after hypertension after systemic administration of bevacizumab. Therefore we aimed to analyze the effect of intravitreal bevacizumab (IVB) injection on proteinuria in patients with diabetes.MethodsPatients scheduled to receive IVB injection from May 1, 2018, to December 31, 2018, were prospectively enrolled. In total, 53 patients with diabetes (26 with nonproliferative diabetic retinopathy and 27 with proliferative diabetic retinopathy) and 37 patients without diabetes were included. Urine tests were performed within 1 month of and 7 ± 1 days after IVB injection. Urinary protein, creatinine, and albumin concentrations were quantitatively measured, and urinary protein-to-creatinine ratio and urinary albumin-to-creatinine ratio (UACR) were calculated from these data before and after IVB injection.ResultsThe mean urinary microalbumin concentrations and urinary protein-to-creatinine ratio were significantly higher in patients with diabetes, both before and after IVB injection. There were no differences between patients with nonproliferative diabetic retinopathy and proliferative diabetic retinopathy. About 80% of patients with diabetes showed improved albuminuria or at least no harmful effect in terms of albuminuria. Patients with deteriorated baseline UACR showed more residual increase in UACR after IVB injection (P < 0.05 in all groups).ConclusionsClose monitoring of renal function after IVB might be needed in patients with diabetes according to the severity of nephropathy.Translational RelevanceOur results may provide information regarding the renal function of IVB-treated patients with diabetes.

Novel Assessment of Urinary Albumin Excretion in Type 2 Diabetes Patients by Raman Spectroscopy.

Urinary albumin excretion remains the key biomarker to detect renal complications in type 2 diabetes. As diabetes epidemy increases, particularly in low-income countries, efficient and low-cost methods to measure urinary albumin are needed. In this pilot study, we evaluated the performance of Raman spectroscopy in the assessment of urinary albumin in patients with type 2 diabetes. The spectral Raman analysis of albumin was performed using artificial urine, at five concentrations of albumin and 24 h collection urine samples from ten patients with Type 2 Diabetes. The spectra were obtained after removing the background fluorescence and fitting Gaussian curves to spectral regions containing features of such metabolites. In the samples from patients with type 2 diabetes, we identified the presence of albumin in the peaks of the spectrum located at 663.07, 993.43, 1021.43, 1235.28, 1429.91 and 1633.91 cm−1. In artificial urine, there was an increase in the intensity of the Raman signal at 1450 cm−1, which corresponds to the increment of the concentrations of albumin. The highest concentration of albumin was located at 1630 cm−1. The capability of Raman spectroscopy for detection of small concentrations of urinary albumin suggests the feasibility of this method for the screening of type 2 diabetes renal complications.

Increased Intra-Abdominal Pressure During Laparoscopic Pneumoperitoneum Enhances Albuminuria via Renal Venous Congestion, Illustrating Pathophysiological Aspects of High Output Preeclampsia.

Intra-abdominal hypertension (IAH) causes severe organ dysfunction. Our aim is to evaluate the effect of increased intra-abdominal pressure (IAP) on renal function, hypothesizing that venous congestion may increase proteinuria and fluid retention without endothelial dysfunction. Three urine samples were collected from 32 non-pregnant women undergoing laparoscopic-assisted vaginal hysterectomy (LAVH) and from 10 controls placed in Trendelenburg position for 60 min. Urine sampling was done before (PRE), during or immediately after (PER), and two hours after (POST) the procedure. Urinary albumin, protein and creatinine concentrations were measured in each sample, and ratios were calculated and compared within and between groups. During LAVH, the albumin/creatinine ratio (ACR) increased and persisted POST-procedure, which was not observed in controls. A positive correlation existed between the LAVH duration and the relative change in both ACR and protein/creatinine ratio (PCR) PER- and POST-procedure. Iatrogenic IAH increases urinary ACR and PCR in non-pregnant women via a process of venous congestion. This mechanism might explain the presentation of one specific subtype of late-onset preeclampsia, where no drop of maternal cardiac output is observed.

Incremental short maximal exercise increases urinary liver-type fatty acid-binding protein in adults without CKD.

Exercise-induced redistribution of tissue blood flow decreases the renal blood flow in an exercise intensity-dependent manner. However, the acute effects of incremental short maximal exercise on renal tubular conditions remain unknown. The purpose of this study was to investigate the acute effects of incremental short maximal exercise on the urinary liver-type fatty acid-binding protein, which is a highly sensitive tubular biomarker that correlates excellently with peritubular capillary blood flow. A total of 116 adults (aged 24-83years) without chronic kidney disease performed the incremental short maximal exercise using a cycling ergometer, wherein the exercise sequence consisted of commencing with a 2-min workout period at 20W (as a warm-up period) and then followed by a 10-20W increase every 1minute until termination criteria were reached. Urinary samples were gathered before and immediately after the exercise to evaluate the concentrations of urinary creatinine, albumin, and liver-type fatty acid-binding protein. Urinary excretion levels of albumin and liver-type fatty acid-binding protein were significantly increased post-exercise (P<.001 and P=.008, respectively). Furthermore, the %change in urinary liver-type fatty acid-binding protein levels after exercise was found to correlate independently with age, estimated glomerular filtration rate at baseline, and the %change in urinary albumin (Model R2 =0.451, P<.001). Our findings suggest that incremental short maximal exercise may lead to acute slightly adverse effects on tubular conditions, especially in young adults or adults with lower renal function, even without chronic kidney disease.

Podocyte Damage in Acute Hypertensive Mice; Involvement of TRPC6

In order to study the effect of changes in TRPC6 protein pathway on podocyte injury in hypertensive mice, 20 WT mice were randomly divided into the control group and the experimental group. Acute hypertension model was established by ligating abdominal aorta for 15 min in the experimental group mice. After successful establishment of the mouse model, in vivo freezing technology is used in all mice to prepare tissue samples for the experiment. H and E staining, SABC-DAB immunohistochemical staining, Western blot and calcium ion detections were made on kidney tissue samples of mice. Urine samples of mice were collected to test urinary albumin. The results showed that compared to the control group, the glomerular tubules and Bowman capsules in the experimental group were swollen, the expression of TRPC6 channels in podocytes increased, the concentration of calcium increased sharply and the concentration of albumin in urine also increased sharply. These results showed that hypertension could cause opening of TRPC6 channel to increase the calcium ion concentration leading to podocyte damage. The ability of damaged podocytes to deal with albumin is weakened and a large increase of albumin would cause further increase of Ca2+ concentration, that aggravated damage to podocytes this initiated a vicious circle. This study thus laid a foundation for exploring the mechanism of podocyte injury caused by hypertensions

Albuminuria detection using graphene oxide-mediated fluorescence quenching aptasensor

A simple and sensitive graphene oxide-mediated fluorescence quenching aptasensor is developed to quantify albuminuria in urine samples. The developed aptasensor used the specific target binding property of aptamer and fluorescence quenching property of graphene oxide to determine the concentration of human serum albumin in urine. The limit of detection of the developed platform is 0.05 µg.mL−1 and the detection range is 0.1–600 µg.mL−1, which covers the albuminuria concentration range present in normal human urine and the urine of the patient with chronic kidney disease. This approach can be modified to measure albuminuria using a high-throughput quantification platform and portable point of care testing. In addition, the production cost for one reaction is cheaper than those for the standard automated method. Therefore, this aptasensor has significant potential for commercialization and public use.•Our protocol is customized by using the fluorescence quenching property of graphene oxide and specific binding property of human serum albumin aptamer to detect human serum albumin in urine sample•The limit of detection of our developed platform is 0.05 µg.mL−1•The detection range of our aptasensor is 0.1–600 µg.mL−1

Risk Factors for Kidney Disease in Hb SC and Hb Sβ+-Thalassemia Sickle Cell Disease

Sickle cells disease (SCD) is an inherited red blood disorder that leads to acute and chronic organ complications. The kidneys are among the most commonly affected organ systems and chronic kidney disease (CKD) predicts increased morbidity and early mortality in SCD (PMID 1892333). Risk factors for CKD have been primarily investigated in patients with homozygous inheritance of the hemoglobin (Hb) S mutation but are not as well understood in other SCD variants, such as in those with Hb SC or Hb SB+-thalassemia. We investigated clinical, laboratory, and genetic predictors (α-thalassemia and the APOL1 G1 and G2 kidney disease risk variants) for CKD in a combined analysis of non-Hb SS patients from the University of Illinois at Chicago and the multi-center Walk-PHaSST cohort. Clinical and laboratory variables were obtained at the time of enrolment. Estimated glomerular filtration (eGFR) rate was calculated using the CKD-EPI formula and CKD stage was defined according to the KDIGO guidelines. Univariate analysis for the association of variables with eGFR, albuminuria, and CKD stage were conducted using the linear trend test and Cochran's test for linear trend. Variables with a P &lt; 0.1 were entered into linear and ordinal logistic regression models adjusting for age and sex. Median and interquartile ranges (IQR) are provided. Two hundred and forty-seven patients were included in this analysis. The median age of this cohort was 39 years (IQR, 24 - 50 years), 62% were female, 16% were on hydroxyurea, and 72% were Hb SC genotype. Albuminuria data was available in 174 patients; microalbuminuria (albuminuria 30 - 300 mg/g creatinine) was present in 24% and macroalbuminuria (albuminuria &gt; 300 mg/g creatinine) in 5% of patients. Patients with higher urine albumin concentration were older, had higher systolic blood pressures and LDH concentrations, and lower hemoglobin concentrations (P ≤ 0.03). On multivariate analysis, the urine albumin concentration was independently associated with a higher systolic blood pressure (log transformed β +3.08 ± 1.09; P = 0.005) and a lower hemoglobin concentration (β -0.17 ± 0.09; P = 0.05). Patients with lower eGFR were older, had higher body mass indexes and systolic blood pressures, lower hemoglobin concentrations, and were more frequently female (P ≤ 0.04). No variables were independently associated with eGFR on multivariate analysis after adjusting for age and sex. When applying the KDIGO CKD staging criteria, 67% were classified as not having CKD (urine albumin &lt; 30mg/g creatinine and eGFR &gt; 60 mL/min/1.73m2), 23% had stage 1 or 2 CKD (urine albumin ≥ 30mg/g creatinine and eGFR &gt; 60 mL/min/1.73m2), and 10% had stage 3 or greater CKD (eGFR &lt; 60 mL/min/1.73m2). Patients with increasing CKD stage were older, had higher systolic blood pressures and LDH concentrations, and lower hemoglobin concentrations (Table 1) (P ≤ 0.005). On multivariate analysis, incremental CKD stage was independently associated with lower hemoglobin (OR 0.91, 95%CI: 0.88 - 0.94; P = 0.002) and higher LDH (natural log OR 1.43, 95% CI: 1.27 - 1.61; P = 0.004) concentrations. We did not observe an association between coinheritance of α-thalassemia or the APOL1 G1/G2 risk variants with urine albumin concentration, eGFR, or CKD stage. In conclusion, we demonstrate that CKD is a common comorbidity that is observed in approximately one third of SCD patients with the Hb SC or Hb Sβ+-thalassemia genotypes. A lower hemoglobin concentration and higher systolic blood pressure were independently associated with greater urine albumin concentration. This may reflect anemia causing reduced oxygen delivery to the renal cortex and hypertension-mediated vascular and glomerular damage. The association of worsening CKD stage with lower hemoglobin and higher LDH concentrations, consistent with increased hemolysis, is similar to what has been observed in the Hb SS genotypes. The potential effects of hemolysis on kidney function in the Hb SC and Sβ+-thalassemia genotypes will need to be explored further. Disclosures Gladwin: Bayer Pharmaceuticals: Other: Co-investigator; United Therapeutics: Patents &amp; Royalties: Co-inventor on an NIH government patent for the use of nitrite salts in cardiovascular diseases ; Globin Solutions, Inc: Patents &amp; Royalties: Provisional patents for the use of recombinant neuroglobin and heme-based molecules as antidotes for CO poisoning. Gordeuk:Novartis: Consultancy, Honoraria, Research Funding; Global Blood Therapeutics: Consultancy, Honoraria, Research Funding; Emmaus: Consultancy, Honoraria; Modus Therapeutics: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Research Funding; Modus Therapeutics: Consultancy, Honoraria; Pfizer: Research Funding; Inctye: Research Funding; Inctye: Research Funding; CSL Behring: Consultancy, Honoraria, Research Funding; CSL Behring: Consultancy, Honoraria, Research Funding; Ironwood: Research Funding; Ironwood: Research Funding; Imara: Research Funding; Imara: Research Funding. Saraf:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding.

Discovery of a Potent and Selective TRPC5 Inhibitor, Efficacious in a Focal Segmental Glomerulosclerosis Model.

The nonselective Ca2+-permeable transient receptor potential (TRP) channels play important roles in diverse cellular processes, including actin remodeling and cell migration. TRP channel subfamily C, member 5 (TRPC5) helps regulate a tight balance of cytoskeletal dynamics in podocytes and is suggested to be involved in the pathogenesis of proteinuric kidney diseases, such as focal segmental glomerulosclerosis (FSGS). As such, protection of podocytes by inhibition of TRPC5 mediated Ca2+ signaling may provide a novel therapeutic approach for the treatment of proteinuric kidney diseases. Herein, we describe the identification of a novel TRPC5 inhibitor,GFB-8438, by systematic optimization of a high-throughput screening hit, pyridazinone 1. GFB-8438 protects mouse podocytes from injury induced by protamine sulfate (PS) in vitro. It is also efficacious in a hypertensive deoxycorticosterone acetate (DOCA)-salt rat model of FSGS, significantly reducing both total protein and albumin concentrations in urine.

Assessment of the degree of adherence of medical laboratories to KDIGO 2012 guideline for evaluation and management of CKD in Czechia and Slovakia.

IntroductionThe aim of the study is to assess the degree of adherence of medical laboratories to Kidney Disease Improving Global Outcomes (KDIGO) 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD) in laboratory practice in Czechia and Slovakia.Materials and methodsAn electronic questionnaire on adherence to KDIGO 2012 guideline was designed by an external quality assessment (EQA) provider SEKK spol. s.r.o. The questionnaire was placed and distributed through website to all medical biochemistry laboratories in Czechia and Slovakia (N = 396).ResultsA total of 212 out of 396 laboratories responded to the questions, though some laboratories only answered some questions, those applicable to their practice. A total of 48 out of 212 laboratories adopted the KDIGO 2012 guideline in full extent. The metrological traceability of creatinine measurement to standard reference material of SRM 967 was declared by 180 out of 210 laboratories (two of the responding laboratories did not measure creatinine). Thirty laboratories are not well educated on traceability of creatinine measurement and seven laboratories do not calculate estimated glomerular filtration rate (eGFR). Both urinary albumin concentration and albumin to creatinine ratio are reported by 144 out of 175 laboratories (37 of the responding laboratories did not measure urinary albumin).ConclusionMajority of laboratories in Czechia and Slovakia adopted some parts of the KDIGO 2012 guideline in their practice, but only 23% of the laboratories apply them completely. Thus, further education and action should be conducted to improve its implementation.

Changes in albuminuria during the spontaneous breathing trial: A prospective observational study

We hypothesized urine albumin concentration may detect the early increasing cardiac load during the spontaneous breathing trial (SBT). The purpose of our study is to determine whether the changes in urine albumin concentration before and after the SBT correlate with SBT outcome. This prospective observational study was conducted from January 2013 to September 2013. Patients receiving endotracheal tube intubation due to acute respiratory failure were included. Urine albumin concentration was measured upon admission to the intensive care unit, before and after the SBT. A total of 211 patients with respiratory failure were screened. Finally, 69 patients were included for analysis. Among the 69 patients received the SBT, 61 patients passed the SBT while 8 patients didn't. Urine albumin concentration upon admission was 251.00±108.21mg/g in the SBT success group and 260.87±77.95mg/g in the SBT failure group (p=0.97). The mean percent change in urine albumin concentration during the SBT was significantly higher in the SBT failure group (+58.44%) than in the SBT success group (+13.11%) (p=0.02). Univariable and multivariable logistic regression model showed that the difference of urine albumin concentration before and after the SBT correlated significantly with SBT failure (adjusted OR:1.04, p=0.01). This open label pilot study demonstrates the significant association of the changes in urine albumin concentration with SBT outcome. Further study is warranted to investigate the predictive value of urine albumin concentration.

MON-293 NEUTROPHIL-LYMPHOCYTE RATIO IN PATIENTS WITH DIABETIC KIDNEY DISEASE

A major complication of diabetes is diabetic kidney disease (DKD) which is currently the leading cause of end-stage renal disease worldwide. Furthermore, DKD has been shown to be an independent risk factor for cardiovascular disease morbidity and mortality. Hence, DKD places a huge burden on healthcare systems. Therefore, early detection of DKD is hoped to reduce morbidity and mortality and to improve patient quality of life. Considering the inflammatory pathways involved in the development of the DKD, markers of inflammation could be potentially used for detecting the disease at early stages. Given that the neutrophil-to-lymphocyte ratio (NLR) is a reliable measure of systemic inflammation, we hypothesized that higher NLR would be associated with an increased risk of having DKD with albuminuria. In a cross-sectional study, 535 patients with type 1 or type 2 diabetes attending Austin Health Diabetes Clinics were recruited. NLR was calculated by dividing the total neutrophil count by total lymphocyte count from a full blood examination. The Albumin excretion rate (AER) was calculated using urine albumin concentration, total urine volume and total collection time. Serum creatinine was run on the Roche Cobas C800 and then measured using the kinetic colorimetric assay based on the Jaffe method. Estimated glomerular filtration rate (eGFR) was calculated using the creatinine-based CKD-EPI equation. Multivariate logistic regression models adjusted for age, HbA1c, fasting cholesterol and CRP were run for the following three outcomes: 1) eGFR <60ml/min/1.73m2 and AER ≥20 µg/min, 2) eGFR <60ml/min/1.73m2 and AER <20 µg/min 3) eGFR <60ml/min/1.73m2. Analysis of 535 patients with a full set of observations for 1,202 visits (mean visit per patient =2.2) demonstrated that one unit increase in NLR was associated with 44% increased risk of having eGFR <60ml/min/1.73m2 along with an AER ≥20µg/min [ odds ratio (OR), 95% confidence interval (CI): 1.44 (1.01-2.05); p= 0.046]. However, there was no statistically significant association between NLR and having eGFR <60ml/min/1.73m2 and an AER <20µg/min [OR (95% CI): 0.87 (0.63-1.20); p=0.39] as well as having eGFR <60ml/min/1.73m2 alone [OR (95% CI): 0.75 (0.53-1.05); p= 0.096]. Higher NLR values are independently associated with stage 3-5 chronic kidney disease with albuminuria (AER≥20µg/min). These data support the potential association of inflammation in the development of diabetic kidney disease and support the need for future studies.

Albuminuria: population epidemiology and concordance in Australian children aged 11–12 years and their parents

ObjectivesTo describe the distribution of albuminuria among Australian children aged 11–12 years and their parents, and assess its intergenerational concordance within parent–child dyads.DesignPopulation-based cross-sectional study (the Child Health CheckPoint), nested within the Longitudinal Study of Australian Children.SettingAssessment centres (seven Australian cities and eight regional towns) and home visits across Australia, February 2015 to March 2016.ParticipantsOf all participating CheckPoint families (n=1874), 1557 children (46.2% girls) and 1454 parents (85.5% mothers) provided random urine samples at the visit; samples from menstruating females were excluded.Outcome measuresUrine albumin-to-creatinine ratio (ACR) and its components (urine albumin and creatinine concentration); albuminuria was defined as an ACR ≥3.4 mg/mmol. Pearson’s correlation coefficients and multivariable linear regression models assessed parent–child concordance, using log-transformed data due to skewing. Survey weights and methods were applied to account for the complex sample design.ResultsThe median ACR for children was 1.03 mg/mmol (IQR 0.65–1.97) and 1.01 mg/mmol (IQR 0.60–2.09) for adults. The median ACR was higher in girls (1.20, IQR 0.71–2.65) than boys (0.90, IQR 0.61–1.65) and in mothers (1.13, IQR 0.63–2.33) than fathers (0.66, IQR 0.41–1.05). Albuminuria was detected in 15.1% of children (girls 20.8%, boys 10.1%) and 13.5% of adults (15.1% mothers, 4.0% fathers) had albuminuria. There was a small correlation between parent and child ACR (Pearson correlation coefficient 0.06, 95% CI 0.01 to 0.12).ConclusionsAlbuminuria is common among Australian children and adults, which is of concern because it predicts risk for kidney and cardiovascular disease, and mortality. The weak concordance among intergenerational pairs for urine ACR suggests either that genetic heritability is low or that it becomes evident only at later offspring life stages.