Urinary Albumin Concentration Research Articles

The Human Phospholipase B-II Precursor (HPLBII-P) in Urine as a Novel Biomarker of Glomerular Activity in COVID-19 and Diabetes Mellitus.

Background: The human phospholipase B-II precursor (HPLBII-P) was originally purified from white blood cells but is also found in other cellular structures, such as kidney glomeruli and tubuli. The objective of this report was to investigate the relationship of HPLBII-P in urine to acute kidney injury in patients with COVID-19. Methods: Urine was collected at admission from 132 patients with COVID-19 admitted to the intensive care units (ICUs) because of respiratory failure. HPLBII-P was measured using a sensitive ELISA. For comparison, human neutrophil lipocalin (HNL) was measured in urine, using the ELISA configured with the monoclonal antibody 763/8F, as a sign of tubular affection in addition to routine biomarkers of kidney disease. Results: Overall, the concentrations of urinary HPLBII-P were almost 3-fold higher in patients with COVID-19 compared to healthy controls (p < 0.0001) and with significantly higher concentrations even in patients with COVID-19 without signs of acute kidney injury (AKI) (p < 0.001). HPLBII-P was further increased in patients with AKI (p < 0.02). HPLBII-P was significantly increased in patients with diabetes mellitus (p = 0.0008) and correlated to plasma glucose (r = 0.29, p = 0.001) and urine albumin concentrations (r = 0.55, p < 0.001). Conclusions: Urine concentrations of HPLBII-P are highly raised in the urine of patients with COVID-19 and relate to AKI and diabetes mellitus. HPLBII-P may reflect glomerular injury and/or increased glomerular cell activity in SARS-CoV-2 infections.

Abstract 14347: Albuminuria, N-Terminal Pro-Brain Natriuretic Peptide and Incident Congestive Heart Failure in High-Risk Adults With Hypertension: A Post Hoc Analysis of the Systolic Blood Pressure Intervention Trial

Introduction: Abnormal levels of urinary albumin concentration (UAC) and N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) have each been independently associated with an increased risk of congestive heart failure (CHF). It remains unknown whether the concomitant presence of abnormal UAC and NT-proBNP increases an individual’s risk for future CHF beyond that contributed by each biomarker. Objective: To examine the joint association between abnormal UAC and NT-ProBNP with incident CHF in participants from the SPRINT (Systolic Blood Pressure Intervention Trial) study. Methods: This analysis included 8,176 participants from SPRINT with available data on baseline UAC and NT-proBNP. UAC was measured by urine albumin-creatinine ratio (UACR). Albuminuria was defined as UACR ≥30 mg/g. Abnormal NT-proBNP was defined as levels ≥125 pg/ml. Cox proportional hazard models were used to examine the association of UAC and NT-proBNP, as well as albuminuria and abnormal NT-proBNP, with incident CHF. Results: Over a median follow-up of 3.2 years, 179 incident cases of CHF were observed. In adjusted models, the risk of incident CHF (HR 95% CI) associated with each 1 (one) unit standard deviation increase in the levels of UAC and NT-proBNP was 1.10 (1.04-1.16; p &lt;0.001) and 1.13 (1.10-1.16; p &lt;0.0001), respectively. A statistically significant multiplicative interaction between UAC*NT-proBNP was observed in the fully adjusted model (p &lt;0.0001). The risk associated with the presence of abnormal UAC +/- abnormal NT-proBNP in the SPRINT cohort is depicted in the figure. Conclusions: Among SPRINT participants, we found a significant multiplicative interaction between UAC and NT-proBNP as predictors of incident CHF. Also, the risk of future CHF was over six times higher in individuals with abnormal UAC and NT-proBNP, compared with those with normal levels of both biomarkers. More studies are needed to further explore this interaction and the implications on CHF prevention.

Relationship of cardiorenal risk factors with albuminuria based on age, smoking, glycaemic status and BMI: a retrospective cohort study of the UK Biobank data

IntroductionSmoking is harmful, and its cessation is recommended to prevent chronic kidney disease, which often begins with abnormal leakage of albumin in the urine, called albuminuria. Smoking cessation’s effect on...

Refractometric Sensing of Protein in Urine by the Photonic Crystal Fiber Biosensor in THz Regime

The presence of albumin in human urine is one of the confirmed early symptoms of kidney dysfunction. A precise urine protein identification process is very important to monitor the kidney’s proper functioning. To identify the presence of albumin in urine, a refractometric protein sensing approach in the photonic crystal fiber (PCF) environment has been introduced here. A PCF geometry with suspended cladding and a circular hollow core has been proposed and investigated in the terahertz (THz) spectrum for protein identification in the liquid samples. Three levels of albumin concentrations in urine (7–125 mg/dl, 250–500 mg/dl, and 1000 mg/dl) are considered to evaluate the sensing performances of the proposed PCF. The numerical investigations are performed on the COMSOL Multiphysics platform where the finite element method (FEM) figures out the numerical outcomes. The performances of the proposed PCF exhibit highly sensitive characteristics for albumin identification in the different albumin concentration levels of urine. The sensitivity shows more than 98.5% for all the tested concentration levels due to the strategic selection of geometrical parameters and proper optimization. Alongside, negligible confinement loss of 10−16 cm−1 is attained at the same operating point of 4.3 THz. Furthermore, dispersion profiles and practical implementation strategies are also investigated and discussed in detail.

Colorimetry-based and smartphone-assisted machine-learning model for quantification of urinary albumin

The presence of albumin in the urine is indicative of kidney damage and can occur due to several underlying conditions, such as diabetes. The concentration of albumin in urine is used for the diagnosis and staging of chronic kidney disease (CKD). In clinical samples, the detection of albumin at lower concentrations is crucial for the early diagnosis and monitoring of CKD. Current urine analyzers precisely quantify albumin but are expensive and difficult to use in point-of-care (PoC) settings. Here, we demonstrate the quantification of albumin concentration in a urine sample using colorimetry. This model presents an accessory-free urine analyzer that uses a smartphone and customized machine-learning algorithms. Here, a urine sample is introduced onto a chemically impregnated dipstick that exhibits a change in color with the amount of albumin. Images of the urine dipsticks are captured using a smartphone camera under different illumination/experimental conditions and are processed to extract changes in the color values arising due to changes in the concentration of urinary albumin. Albumin concentrations are estimated from changes in color values. We used customized machine-learning algorithms to classify albumin concentrations and mitigate the effect of ambient light conditions. The k-nearest neighbor algorithm yielded an average classification accuracy of 96% with a detection limit of 4 mg l−1. The proposed scheme can be extensively used to monitor albumin concentration in PoC settings.

Renalase regulates renal tubular injury in diabetic nephropathy via the p38MAPK signaling pathway.

Diabetic nephropathy (DN) is an important complication of diabetes and the leading cause of end-stage renal disease globally. Renal tubular damage occurs to varying degrees in the early stages of DN prior to glomerular damage. Renalase (RNLS) is an amine oxidase, which is produced and secreted by the renal tubular epithelial cells. RNLS is reportedly closely related to renal tubular injury in acute and chronic kidney diseases. Herein, we aimed to evaluate the changes in tubular RNLS expression in DN and its correlation with DN-associated renal tubular injury. Conditional permanent renal tubular epithelial rat-cell line NRK-52E was transfected with pcDNA3-RNLS plasmid or administered recombinant rat RNLS protein and high glucose (HG) dose. A total of 22 adult Sprague-Dawley rats were randomly divided into the control (CON, n = 10) or diabetic nephrology (DN, n = 12) group. Random blood glucose levels of the rats were measured by sampling of the caudal vein weekly. After 8 weeks, the rat's body weight, 24-h urinary albumin concentration, and right kidney were evaluated. Our study suggested the decreased expression levels of RNLS in renal tissue and renal tubular epithelial cells in DN rats, accompanied by renal tubulointerstitial fibrosis, apoptosis of renal tubular epithelial cells, and activation of the p38MAPK signal pathway. Reversing the low RNLS expression can reduce the level of p38MAPK phosphorylation and delay renal tubular injury. Thus, the reduction of renal tubular RNLS expression in DN mediates tubulointerstitial fibrosis and cell apoptosis via the activation of the p38MAPK signal pathway. RNLS plays a key mediating role in DN-associated tubular injury via p38MAPK, which provides new therapeutic targets and a theoretical basis for early prevention and treatment of DN.

Intraindividual variations of urinary biomarkers in hospitalized children with glomerular diseases: a prospective observational study

This study aimed to assess the intraindividual variations of urinary biomarkers in hospitalized children with glomerular diseases. Hospitalized children with glomerular diseases participated in the study. For each patient, an overnight (9:00 p.m.–7:00 a.m.) urine was collected, followed by a 24-h urine (classified into four distinct periods: morning 7:00 a.m.–12:00 p.m., afternoon 12:00 p.m.–4:00 p.m., evening 4:00 p.m.–9:00 p.m., and overnight 9:00 p.m.–7:00 a.m.). The concentrations of protein, albumin, N-acetyl-beta-D-glucosaminidase, and epidermal growth factor (EGF) were measured and normalized by three correction factors (creatinine, osmolality, or specific gravity, respectively). Additionally, the 2nd overnight urine sample was grouped into different aliquots according to centrifugation, additives, storage temperature, or delayed processing. Twenty (14 boys, 6 girls) children were enrolled, with an average age of 11.3 years. Among the three correction factors, creatinine-normalized biomarkers provided the best agreements among different periods over 24 h. There were significant diurnal variations during 24 h in the concentrations of urinary protein, albumin, N-acetyl-beta-D-glucosaminidase, and EGF (p = 0.001, p = 0.003, p = 0.003, and p = 0.003, respectively). Evening urine overestimated 24-h urinary protein and albumin, while overnight urine underestimated 24-h urinary albumin. Urinary EGF showed low variability within a day or between the 2 days (coefficients of variation 10.2% and 10.6%, respectively) and excellent agreements (intraclass correlation coefficients > 0.9) with 24-h urinary concentration. Furthermore, urinary EGF was not affected by centrifugation, additives, storage temperature, or delayed processing of urine samples (all p > 0.05). Conclusion: Given the diurnal variations of urinary biomarkers, urine samples should be collected during the same time period in clinical practice if possible. The results also extend the evidence for urinary EGF as a relatively stable biomarker applied in the future clinical practice.What is Known:• Urinary biomarkers have been widely used or discussed in making diagnoses and therapy regimens and estimating the prognosis of pediatric glomerular diseases. It remains unclear whether their levels would be affected by the time of sample collection, processing methods, and storage conditions in hospitalized children with glomerular diseases.What is New:• The levels of both commonly used biomarkers and novel biomarkers exhibited diurnal variations in hospitalized children with glomerular diseases.• Our results extend the evidence for urinary EGF as a relatively stable biomarker applied in the future clinical practice.

Prevalence of Microalbuminuria among Diabetic Patients Attending Federal Medical Centre Gusau, Nigeria

Microalbuminuria is persistent albumin excretion between 30 and 300 mg/day. In patients with diabetes, it is usually indicative of diabetic nephropathy which is the most common cause of end-stage renal disease; it is also associated with cardiovascular disease. The main objective was to determine the prevalence of microalbuminuria and its association with glycemic control, blood pressure, and duration of diabetes in type-1 and type-2 diabetic patients attending Federal Medical Center Gusau, Nigeria. This study evaluated the level of microalbuminuria among 150 diabetic patients and 50 control subjects. The urinary albumin concentration was measured by immunoturbidimetric assay. From both the control and diabetic subjects, fasting blood sugar was estimated and blood pressure was measured with an automated manometer. Prevalence of microalbuminuria (MAL) according to demographic, the incidence of variables was detected in 12 males 28 females, and &lt; 40 years of age 10 and &gt; 40 years of age 31. The Mean of Fasting Blood Glucose (FBG) was slightly higher in patients with Non-insulin Dependent Diabetes Mellitus (NIDDM) when compared to IDDM patients. There was no significant (p&gt;0.05) difference between males and females, within the group regarding age, blood pressure, and glycemic status. However, there is a statistically significant difference (p&gt;0.05) in FBG and MAL between the patients and the control. The results suggest that there is a high prevalence of microalbuminuria in patients attending Federal Medical Center Gusau which is an independent risk factor for renal and cardiovascular diseases.

Renal Disturbances during and after Radioligand Therapy of Neuroendocrine Tumors-Extended Analysis of Potential Acute and Chronic Complications.

Neuroendocrine tumors (NEN) are a group of neoplasms that arise from hormonal and neural cells. Despite a common origin, their clinical symptoms and outcomes are varied. They are most commonly localized in the gastrointestinal tract. Targeted radioligand therapy (RLT) is a treatment option which has proven to be successful in recent studies. However, the possible outcomes and true safety profile of the treatment need to be fully determined, especially by new, more sensitive methods. Our study aimed to present an extended analysis of acute and chronic renal complications during and after radioligand therapy using, for the first time in the literature, innovative and complex renal parameters. Forty patients with neuroendocrine tumors underwent four courses of radioligand therapy with [177Lu]Lu-DOTATATE or [177Lu]Lu/[90Y]Y-DOTATATE. Radioisotopes were administrated in intervals of 8-12 weeks, with concurrent intravenous nephroprotection. New detailed and sensitive renal parameters were used to determine the renal safety profile during and after radioisotope therapy for standard treatment of NEN. During the first and fourth courses of RLT, no change in the glomerular filtration rate (GFR) was observed. However, long-term observations one year after the treatment showed a 10% reduction in the GFR. During the first course of treatment, the fractional urea and calcium excretions increased, while the fractional potassium concentration decreased. The fractional calcium excretion remained highly increased in long-term observations. Decreases in urine IL-18, KIM-1 and albumin concentrations were observed during RLT. The concentrations of IL-18 and KIM-1 remained low even a year after therapy. The ultrasound parameters of renal perfusion changed during treatment, before partially returning to the baseline one year after therapy, and were correlated with the biochemical parameters of renal function. A permanent increase in diastolic blood pressure was correlated with the decrease in the GFR observed during the study. In this innovative and complex renal assessment during and after RLT, we found a permanent 10% per year decrease in the GFR and noticeable disturbances in renal tubule function. The diastolic blood pressure also increased.

Rapid identification of chronic kidney disease in electronic health record database using computable phenotype combining a common data model.

Rapid identification of chronic kidney disease in electronic health record database using computable phenotype combining a common data model.

A diet supplemented with cholic acid elevates blood pressure accompanied by albuminuria in rats.

A diet supplemented with cholic acid (CA), the primary 12α-hydroxylated bile acid, can induce hepatic lipid accumulation in rats without obesity. This study examined the effects of a CA-supplemented diet on blood pressure (BP). After acclimation, WKAH/HkmSlc rats (3 weeks old) were divided into two groups and fed with a control AIN-93-based diet or a CA-supplemented diet (0.5g CA/kg) for 13 weeks. The CA diet increased systolic and diastolic BP as well as hepatic lipid concentrations in the rats. No changes were found in the blood sodium concentration. Urinary albumin concentration increased in CA-fed rats. An increase was observed in the hepatic expression of ATP-binding cassette subfamily B member 1B that correlated BPs and urinary albumin concentration accompanied by an increase in portal taurocholic acid concentration. These results suggest that 12α-hydroxylated bile acids are involved in increased BP and albuminuria via alteration of hepatic function.

Long-Term Complications of Radioligand Therapy with Lutetium-177 and Yttrium-90 in Patients with Neuroendocrine Neoplasms

Neuroendocrine neoplasms are a group of tumors deriving from neural crest. They can be located in every tissue, but most commonly in gastrointestinal tract. Targeted therapy with use of radionuclides is an available and acceptable way of treatment, but its long-term safety is still to be determined, especially with sensitive methods. Study was performed on a group of 42 patients. They underwent full cycle (4 courses; 8-12 weekly intervals) of radioligand therapy with [177Lu]Lu-DOTATATE alone or tandem therapy with [177Lu]Lu-DOTATATE+[90Y]Y-DOTATATE. Late and long-term marrow and renal complications were assessed. Analysis focused on comparing data before first, fourth, and one year after the last course of RLT. Study showed decreasing of all blood parameters in long-term observation, especially in lymphocytes line. Type of radioisotope, other diseases, primary tumor location, BMI, gender or age did not affect results. The only factor that had influence on hemoglobin and erythrocytes was decreased renal filtration. In long-term observation almost 10% decrease of renal filtration was observed. Type of isotope, gender, age, BMI did not affect these results. Moreover, reduction of urine IL-18, KIM-1, and albumin concentration has been observed. Though low-grade complications of radioligand therapy are possible, it stay a safe method of NEN treatment where benefits outweigh the risk.

Commutability assessment of human urine certified reference materials for albumin and creatinine on multiple clinical analyzers using different statistical models.

Urine albumin concentration and albumin-creatinine ratio are important for the screening of early-stage kidney damage. Commutable urine certified reference materials (CRMs) for albumin and creatinine are necessary for standardization of urine albumin and accurate measurement of albumin-urine ratio. Two urine CRMs for albumin and creatinine with certified values determined using higher-order reference measurement procedures were evaluated for their commutability on five brands/models of clinical analyzers where different reagent kits were used, including Roche Cobas c702, Roche Cobas c311, Siemens Atellica CH, Beckman Coulter AU5800, and Abbott Architect c16000. The commutability study was conducted by measuring at least 26 authentic patient urine samples and the human urine CRMs using both reference measurement procedures and the routine methods. Boththe linear regression model suggested by the Clinical and Laboratory Standard Institute (CLSI) guidelines and log-transformed model recommended by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Commutability Working Group were used to evaluate the commutability of the human urine CRMs. The commutability of the human urine CRMs was found to be generally satisfactory on all five clinical analyzers for both albumin and creatinine, suggesting that they are suitable to be used routinely by clinical laboratories as quality control or for method validation of urine albumin and creatinine measurements.

Association of Eating Patterns and Diabetic Kidney Disease in Type 2 Diabetes: A Cross-Sectional Study

The aim of this cross-sectional study was to evaluate the relationship between eating patterns and diabetic kidney disease in patients with type 2 diabetes. Outpatients underwent clinical and nutritional evaluation. Dietary information was obtained through a validated quantitative food frequency questionnaire, and eating patterns were identified by cluster analysis. Diabetic kidney disease was defined as an estimated glomerular filtration rate <60mL/min/1.73m2 and/or persistently elevated urinary albumin concentration (albuminuria ≥ 14mg/L). Procedures involving patients were approved by the Hospital's Ethics Committee. Patients with type 2 diabetes treated at university hospital and tertiary referral center, southern Brazil. A total of 329 patients were evaluated: mean age 62±10years, body mass index 30.9±4.2kg/m2, glycated hemoglobin 8.7%±2.0, and 10 (5 to 19) years of diabetes duration. Four eating patterns were identified based on cluster analysis: healthy= dairy products, fruits, and vegetables; snacks= dairy products, whole breads, vegetables, and low-calorie products; processed foods= refined carbohydrates and processed meat, and red meat= red meat. Poisson regression models confirmed that snack eaters (PR=1.48, 95% CI 1.10, 1.99; P=.010) and red meat eaters (PR=1.93, 95% CI 1.29, 2.89; P=.001) were associated with diabetic kidney disease. In this sample of outpatients with type 2 diabetes, the patterns of snacks and red meat were associated with diabetic kidney disease as compared to a healthy pattern.

P-020: IMPLICATIONS OF SOCIOECONOMIC DISTRESS ON NUTRITIONAL STATUS AND KIDNEY FUNCTION IN PEOPLE WITH SICKLE CELL ANEMIA

Purpose: Sickle cell anemia (SCA) is characterized by a myriad of acute and chronic complications. These complications negatively impact the ability to achieve educational and occupational goals making this group a particularly vulnerable population to socioeconomic challenges (PMID 30540112). In the general population, indices of socioeconomic distress are associated with poor nutrition and kidney disease risk (PMID 25573510). The association of socioeconomic distress with nutritional status and kidney function in people with SCA is unknown. Materials and methods: We conducted a cross-sectional study to describe the burden of socioeconomic distress and its impact on nutritional status and kidney function in an SCA cohort (n=332) treated at an urban academic institution. The distressed community index (DCI), a composite of socioeconomic indicators that estimate the economic well-being of a community, was determined for each individual using the following website: https://eig.org/dci/interactive-map. A higher DCI score indicates a more distressed community. The associations of DCI with measures of nutritional status (serum albumin, body mass index [BMI], vitamin D 25-OH) and kidney function (estimated glomerular filtration rate [eGFR]; albuminuria; serum bicarbonate, potassium, and erythropoietin levels), were determined using linear or logistic regression. The analyses were adjusted for age, sex, and hydroxyurea use for nutritional status as well as for APOL1 G1 and G2 risk status for kidney function. The beta coefficients provided are based on increments of 10 for DCI. Median and interquartile ranges (IQR) are provided. Results: The median age of the cohort was 31 years (IQR, 24 – 41 years), 55% were female, and 53% were on hydroxyurea therapy. The median DCI in this cohort was 87 (IQR, 61 – 96) with 61% of SCA patients living in a distressed tier (DCI≥ 80) and only 5% living in a prosperous tier (DCI< 20). The DCI tiers for SCA patients trended towards more socioeconomically distressed communities compared to the general African American population (P=0.1) (Figure 1A). A higher DCI, reflecting an increase in socioeconomic distress, was associated with a trend for a lower odds ratio (OR) of being on hydroxyurea therapy (OR 0.93, 95% CI: 0.86 – 1.01; P=0.08). An increasing DCI was significantly associated with lower serum albumin (β= -0.02; P=0.016) (Figure 1B), BMI (β= -0.01; P=0.045), and vitamin D 25-OH levels (β= -0.7; P=0.001) (Figure 1C). A higher DCI was associated with a trend for a lower eGFR (β= -0.6; P=0.09) (Figure 1D) while no association was observed with urine albumin concentration (P=0.8). Lower serum bicarbonate (β= -0.1; P=0.02) and lower erythropoietin (β= -0.9; P=0.1) levels, but not serum potassium concentration (P=0.9), were also associated with higher DCI. Conclusion: In conclusion, we demonstrate that a high proportion of patients with SCA treated at an urban academic institution live in distressed socioeconomic communities. Furthermore, higher distressed community indices are associated with lower measures of nutritional status and with some markers of impaired kidney function. Future studies investigating the effects of socioeconomic distress on access to healthy foods and kidney disease risk may guide public health strategies to improve health disparities in the SCA population.Figure 1. The authors do not declare any conflict of interest

Clopidogrel delays and can reverse diabetic nephropathy pathogenesis in type 2 diabetic db/db mice.

BACKGROUNDDiabetic nephropathy (DN) is the principal cause of end-stage renal disease. Previous studies have shown that clopidogrel can prevent the early progression of renal injury.AIMTo elucidate whether clopidogrel is beneficial against DN by using a db/db mouse model.METHODS db/db mice with a higher urinary albumin/creatinine ratio (ACR) relative to age- and sex-matched wild-type control mice were randomly allocated to clopidogrel and vehicle treatment groups. Clopidogrel was administered at doses of 5, 10, and 20 mg/kg by gavage for 12 wk. Body mass, blood glucose level, and urinary creatinine and albumin concentrations in each group were measured before and after the intervention. Renal fibrosis was evaluated using periodic acid-Schiff and Masson’s trichrome staining. The renal protein expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and F4/80 was assessed using immunohistochemistry. Urinary TNF-α, monocyte chemoattractant protein-1 (MCP-1), and IL-6 levels were analyzed using enzyme-linked immunosorbent assay; TNF-α and IL-1β mRNA expression was measured using real-time quantitative polymerase chain reaction. The protein expression of fibronectin (FN) and collagen I was assessed using immunohistochemistry.RESULTSClopidogrel treatment did not affect the body mass or blood glucose level of the db/db mice; however, it increased bleeding time and reduced urinary ACR in a dose-dependent manner. Immunohistochemical staining revealed an amelioration of renal fibrosis, significantly lower deposition of FN and collagen I, and significantly lower expression of the proinflammatory cytokines TNF-α and IL-1β and lower levels of urinary TNF-α and MCP-1 in the clopidogrel-treated db/db mice (P < 0.05). Furthermore, clopidogrel significantly reduced macrophage infiltration into the glomeruli of the db/db mice.CONCLUSIONClopidogrel significantly reduced renal collagen deposition and fibrosis and prevented renal dysfunction in db/db mice, most likely through inhibition of renal macrophage infiltration and the associated inflammation.

A New Method for Albuminuria Measurement Using a Specific Reaction between Albumin and the Luciferin of the Firefly Squid Watasenia scintillans.

This study demonstrates that the luciferin of the firefly squid Watasenia scintillans, which generally reacts with Watasenia luciferase, reacted with human albumin to emit light in proportion to the albumin concentration. The luminescence showed a peak wavelength at 540 nm and was eliminated by heat or protease treatment. We used urine samples collected from patients with diabetes to quantify urinary albumin concentration, which is essential for the early diagnosis of diabetic nephropathy. Consequently, we were able to measure urinary albumin concentrations by precipitating urinary proteins with acetone before the reaction with luciferin. A correlation was found with the result of the immunoturbidimetric method; however, the Watasenia luciferin method tended to produce lower albumin concentrations. This may be because the Watasenia luciferin reacts with only intact albumin. Therefore, the quantification method using Watasenia luciferin is a new principle of urinary albumin measurement that differs from already established methods such as immunoturbidimetry and high-performance liquid chromatography.

Predictors and determinants of albuminuria in people with prediabetes and diabetes based on smoking status: A cross-sectional study using the UK Biobank data.

SummaryBackgroundSmoking is attributed to both micro- and macrovascular complications at any stage of metabolic deregulation including prediabetes. Current global diabetes prevention programmes appear to be glucocentric, and do not fully acknowledge the ramifications of cardiorenal risk factors in smokers and ex-smokers. A more holistic approach is needed to prevent vascular complications in people with prediabetes and diabetes before and after quitting.MethodsA cross-sectional study was carried out on participants who agreed to take part in the UK Biobank dataset at the time of their first attendances between March 01, 2006, and December 31, 2010. Those who had their urinary albumin concentration (UAC) data available were included, and those who did not have this data, were excluded. A logistic regression model was fitted to explore the relationship between cardiorenal risk factors and albuminuria in people with prediabetes and diabetes, based on smoking status.FindingsA total of 502,490 participants were included in the UK Biobank dataset. Of them, 30.4% (n=152,896) had their UAC level recorded. Compared with non-smokers, the odds of albuminuria in smokers with prediabetes and diabetes were 1.21 (95% CI 1.05 – 1.39, p=0.009), and 1.26 (95% CI 1.10 – 1.44, p=0.001), respectively. The odds declined after quitting in both groups, but it was not statistically significant (p>0.05). Each unit increase in HbA1c was associated with equivalent increased odds of albuminuria in current and ex-smokers, OR 1.035 (95% CI 1.030 – 1.039, p<0.001), and 1.026 (95% CI 1.023 – 1.028, p <0.001), respectively. Compared to females, male ex-smokers were at 15% increased odds of albuminuria. In ex-smokers, each unit increase in waist circumference was associated with 1% increased risk of albuminuria. Compared with the least deprived quintiles, the odds of albuminuria in the most deprived quintiles, in current and ex-smokers were identical, OR 1.18 (95% CI 1.04–1.324, p=0.010), and 1.19 (95% CI 1.11 – 1.27, p<0.001), respectively.InterpretationMale smokers are at a higher risk of albuminuria after smoking cessation. Monitoring waist circumference in quitters may identify those who are at a higher risk of albuminuria. Combining smoking cessation intervention in smokers with prediabetes in the current diabetes prevention programmes may offset post-cessation weight gain and reduce the risk of albuminuria.FundingUniversity of Sheffield.

Urinary Transthyretin as a Biomarker in ATTRv Val50Met Amyloidosis

Transthyretin (TTR), the precursor protein for amyloidogenic TTR (ATTR) amyloidosis, forms tetramers and escapes glomerular filtration by binding with thyroxine and retinol-binding protein. However, variant TTRs are unstable as tetramers, so monomeric TTR has become the precursor protein of amyloid deposits, via protein misfolding. The aim of the study was to evaluate the utility of urinary TTR in the diagnosis of ATTRv amyloidosis. Urinary samples from healthy volunteers, ATTRv V50M amyloidosis patients, and asymptomatic carriers of the ATTRv V50M gene were analysed using ELISA. To analyse the different forms of TTR secreted to the urine, we performed Western blotting and mass spectrometry. Urinary TTR concentrations were significantly higher in the ATTRv V50M amyloidosis patients than they were in the healthy volunteers and asymptomatic carriers of the gene. Although the TTR concentrations were negligible in the healthy volunteers, they were correlated with disease progression and urinary albumin concentrations in the ATTRv V50M amyloidosis patients. The Western blotting and mass spectrometry revealed the presence of monomeric wild-type and variant TTRs in the urine. Urinary TTR concentrations may become a more sensitive biomarker of ATTRv progression than albumin.

Relationship Between IL-2, IL-17 Concentrations, and Serum Creatinine Levels in Men with Chronic Kidney Diseases

Chronic kidney disease (CKD), is a major public health challenge worldwide. It is more prevalent in developed countries compared with the rest of the world, due to the higher rates of life expectancy and unhealthy lifestyle related factors. This aim of the current study is to evaluate the relationship between interleukins IL-2 and IL-17 concentrations and kidney function markers in men with CKD. Forty-five men with CKD and seventy controls were enrolled in the current study to assess the relationship between interleukin-2 (IL-2), interleukin-17 (IL-17), and CKD parameters. Fasting blood samples were collected from patients with CKD and their controls at same time. Serum IL-2, and IL-17 were measured in patients with CKD and their controls, and then the relationship between these interleukins and serum creatinine, serum urea, serum uric acid and urine albumin were evaluated. A significant relationship was detected between IL-2 (p< 0.001), IL-17 (p< 0.001) levels and serum creatinine concentrations. The significant increase of IL-2 and IL-17 levels were also paralleled with a significant increase in serum urea (p< 0.001), and urine albumin (p< 0.001) concentrations respectively. IL-2 and IL-17 may play a critical role in the pathophysiology of CKD. The significant increase of IL-2 and IL-17 is associated with significantly high concentrations of creatinine, serum urea and urine albumin suggesting that these interleukins may be used as targets for future biomarkers and molecular therapy. However, due to limited sample size of the current study, larger prospective cohorts are needed to confirm these observations.