A candidate panel of eight urinary proteins shows potential of early diagnosis and risk assessment for diabetic kidney disease in type 1 diabetes.

Diabetic kidney disease (DKD) poses a significant health challenge for individuals with diabetes. At its initial stages, DKD often presents asymptomatically, and the standard for non-invasive diagnosis, the albumin-creatinine ratio (ACR), employs discrete categorizations (normal, microalbuminuria, macroalbuminuria) with limitations in sensitivity and specificity across diverse population cohorts. Single biomarker reliance further restricts the predictive value in clinical settings. Given the escalating prevalence of diabetes, our study uses proteomic technologies to identify novel urinary proteins as supplementary DKD biomarkers. A total of 158 T1D subjects provided urine samples, with 28 (15 DKD; 13 non-DKD) used in the discovery stage and 131 (45 DKD; 40 pDKD; 46 non-DKD) used in the confirmation. We identified eight proteins (A1BG, AMBP, AZGP1, BTD, RBP4, ORM2, GM2A, and PGCP), all of which demonstrated excellent area-under-the-curve (AUC) values (0.959 to 0.995) in distinguishing DKD from non-DKD. Furthermore, this multi-marker panel successfully segregated the most ambiguous group (microalbuminuria) into three distinct clusters, with 80% of subjects aligning either as DKD or non-DKD. The remaining 20% exhibited continued uncertainty. Overall, the use of these candidate urinary proteins allowed for the better classification of DKD and offered potential for significant improvements in the early identification of DKD in T1D populations.

Estimated health economic impact of conducting urine albumin-to-creatinine ratio testing alongside estimated glomerular filtration rate testing in the early stages of chronic kidney disease in patients with type 2 diabetes.

AIM: To estimate the health economic impact of undertaking urine albumin-to-creatinine ratio (UACR) testing versus no UACR testing in early stages of chronic kidney disease (CKD) progression in patients with type 2 diabetes (T2D). METHODS: An economic model, taking a UK healthcare system perspective, estimated the impact of UACR testing on additional costs, clinical benefits measured as prevented dialyses and cardiovascular-related deaths, life years gained (LYg), LYg before kidney failure, and incremental cost-effectiveness ratio (ICER). Sixteen of the 18 Kidney Disease: Improving Global Outcomes (KDIGO) heatmap categories were considered separately, and grouped in health states according to CKD risk. Results were derived for current standard-of-care and emerging CKD therapies. RESULTS: The cohort that adhered to both UACR and estimated glomerular filtration rate (eGFR) testing guidelines in early stages of CKD (n = 1000) was associated with approximately 500 LYg before kidney failure onset; costing approximately £2.5 M. ICERs across the KDIGO heatmap categories were approximately £5,000. LIMITATIONS: This model used data from a comprehensive meta-analysis that was initiated more than 10 years ago (2009). While this was the most comprehensive source identified, recent changes in the treatment landscape, patient population and social determinants of CKD will not be captured. Furthermore, a narrow approach was taken, aligning included costs with UK NHS reference materials. This means that some direct and indirect drivers of costs in late-stage disease have been excluded. CONCLUSIONS: UACR testing in the early stages of CKD is cost effective in T2D patients. Emerging therapies with the potential to slow CKD progression, mean that optimal monitoring through UACR/eGFR testing will become increasingly important for accurate identification and timely treatment initiation, particularly for the highest-risk A3 category.

Prospective urinary albumin/creatinine ratio for diagnosis, staging, and organ response assessment in renal AL amyloidosis: results from a large cohort of patients.

OBJECTIVES: Quantification of 24 h-proteinuria is the gold standard for diagnosing, staging, and monitoring of patients with renal AL amyloidosis. However, 24 h-urine collection is cumbersome and may result in preanalytical error. In this prospective study, we investigated the role of urinary albumin/creatinine ratio (UACR) (cut-off: 300 mg/g) identifying renal involvement, evaluated a UACR-based staging system (UACR cut-off: 3,600 mg/g) and assessed whether UACR response (UACR decrease >30% without worsening in eGFR >25%) predicts renal outcome in 531 patients with newly-diagnosed AL amyloidosis. METHODS: From October 2013 paired 24 h-proteinuria and UACR (on first morning void) were measured in all newly-diagnosed patients with AL amyloidosis. Correlation between 24 h-proteinuria and UACR at baseline was assessed by Pearson's r test. Impact of UACR response on renal outcome was assessed in randomly created testing (n=354) and validation (n=177) cohorts. RESULTS: A strong linear correlation was found between 24 h-proteinuria and UACR at baseline (r=0.90; p<0.001). After a median follow-up of 31 months, 57 (11%) patients required dialysis. A UACR-based renal staging system identified three stages with significantly higher dialysis rate at 36 months comparing stage I with stage II and stage II with stage III. Achieving a renal response, according to a UACR-based criterion, resulted in lower dialysis rate in both testing and validation cohorts. CONCLUSIONS: UACR is a reliable marker for diagnosis, prognosis, and organ response assessment in renal AL amyloidosis and can reliably replace 24 h-proteinuria in clinical trials and individual patients' management.

Polydopamine-based quantitation of albuminuria for the assessment of kidney damage.

Proteinuria is considered indicative of kidney damage that can be related to various adverse outcomes. Nowadays, there is a huge demand for routine urine screening methods to assess health risks in clinical setting without expensive procedures and long pretreatment of the sample. To address this issue, a polydopamine-based colorimetric assay to determine urinary albumin concentration in real samples is proposed here. The core of this approach relies on the established competitive adsorption of polydopamine film and human serum albumin onto the polystyrene surface of ELISA plates. Herein, we investigated the influence of temperature and the Tris-HCl buffer concentration on the polydopamine film growth. The absorbance of polydopamine film, after 24 h at 25 °C, decreases with the increase of HSA concentration, allowing the selective detection of HSA down to 0.036 ± 0.001 g L-1 in untreated urine. This simple and low-cost bioanalytical assay exhibited very good reproducibility, %CVmean = 2 in human urine, and was superior in terms of analytical performances to some standard methods available on the market, especially in comparison to the Bradford assay, for early screening and assessment of kidney damage.

Guía de práctica clínica para el tamizaje, diagnóstico y manejo de la enfermedad renal crónica en los estadios 1 al 3 / Clinical practice guideline for the screening, diagnosis and management of chronic kidney disease in stages 1 to 3

La enfermedad renal crónica (ERC) consiste en la pérdida progresiva de la función renal a través de cinco estadios (1, 2). Esta condición es un problema de salud pública que ocasiona daños en la calidad de vida y pérdidas socioeconómicas por la mortalidad, discapacidad y costos asociados que genera (3). Se estima que la ERC afecta al 8% a 16% de la población mundial y tanto la incidencia como mortalidad van en aumento (4). La carga de enfermedad de la ERC se ve incrementada por las comorbilidades asociadas a esta enfermedad, de tal manera que la diabetes mellitus e hipertensión arterial son condiciones frecuentemente asociadas (1, 4). En Perú, un estudio realizado en Lima y Tumbes reportó que la prevalencia de ERC fue de 20.7% y 12.9%, respectivamente, en el año 2011 (5). En adición, un estudio realizado con datos del Ministerio de Salud de Perú, evidenció que durante el periodo del 2010 al 2017, se han registrado 188686 casos de ERC, y que en el 2017 se encontró una prevalencia de 1.51%. Una encuesta nacional realizada a los asegurados del seguro social de salud, EsSalud (ENSSA2015), encontró que el 1.7% de asegurados mayores de 60 años reportó padecer de enfermedad renal crónica en el año 2015 (7). En contraste, un estudio realizado con datos del registro nacional de defunciones de Perú reportó que la incidencia de fallecimientos por ERC se incrementó entre el año 2003 y 2015, siendo Puno la región más afectada (4.1% de muertes por ERC). La tendencia creciente tanto en la incidencia como en la mortalidad de la ERC, dan cuenta que a pesar de contar con estrategias terapéuticas para su manejo, los pacientes son captados en estadios avanzados (9). Ante ello, se ha propuesto que la evaluación y el manejo oportuno y adecuado de los casos de ERC, principalmente en estadios tempranos (1 al 3), reducirían la morbimortalidad y las complicaciones de esta condición, evitando que esta enfermedad impacte en la calidad de vida de las personas que la padecen (1, 9, 10). En consecuencia, el Seguro Social de Salud (EsSalud) priorizó la realización de la presente guía de práctica clínica (GPC) para establecer lineamientos basados en evidencia y gestionar de la mejor manera los procesos y procedimientos asistenciales de la presente condición. Esta GPC fue realizada por la Dirección de Guías de Práctica Clínica, Farmacovigilancia y Tecnovigilancia del Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI) de EsSalud.

Microalbuminuria assessment after thoracic surgery: Early identification of complication risks.

INTRODUCTION: Microalbuminuria (MA) is considered a reflection of systemic capillary leak and an early marker of acute stress reaction to the surgical insult, proportional to the severity of the initiating condition and predictive of the individual response to surgical stress. OBJECTIVES: We conducted a prospective study to assess for the variation of MA within 4 days after thoracic surgery. We correlated observed MA levels with both their respective PaO2 /FiO2 respiratory ratio and the onset of postoperative complications. METHODS: This single-centre study enrolled 255 consecutive patients having an American Society of Anaesthesiologists (ASA) score ≤ 3. The mean age was 62 years with 67% male. All patients were scheduled for elective pulmonary resection. MA was measured in urine samples as the albumin-to-creatinine ratio (A/C), prior to, at and after extubation up to 96 hours. PaO2 /FiO2 was measured at extubation and on the first postoperative day. RESULTS: Overall, preoperative A/C levels resulted normal, with a significant average increase at extubation which peaked 6 hours later (P < 0.001). Larger postoperative A/C increases were observed in patients who developed postoperative complications, compared to those without these complications (P < 0.019). Moreover, patients undergoing major open pulmonary resections had larger postoperative A/C increases, compared to those undergoing minor video-assisted thoracic surgery resections (P < 0.006). At the time of extubation, A/C was inversely related to the PaO2 /FiO2 ratio (r = -0.25; P = 0.038). Peak A/C > 61 mg/g (P = 0.0003) was associated with postoperative cardio-pulmonary complications (OR 3.85; P = 0.003). CONCLUSION: Within 6 hours after extubation, MA assessment may be a rapid and relatively inexpensive method for better predicting perioperative risk in an ASA score ≤ 3 population.

Can a semi-quantitative method replace the current quantitative method for the annual screening of microalbuminuria in patients with diabetes? Diagnostic accuracy and cost-saving analysis considering the potential health burden.

OBJECTIVES: Diabetes is a global epidemic, and the high cost of annually and quantitatively measuring urine albumin excretion using the turbidimetric immunoassay is challenging. We aimed to determine whether a semi-quantitative urinary albumin-creatinine ratio test could be used as a screening tool for microalbuminuria in diabetic patients. METHODS: We assessed the diagnostic accuracy of the semi-quantitative method. The costs of false results in the semi-quantitative method were calculated based on the annual probability of disease progression analyzed through a systematic literature review and meta-analysis. The pooled long-term cost-saving effect of the semi-quantitative method compared with the quantitative test was assessed using a Markov model simulating a long-term clinical setting. Diagnostic accuracy and the cost-saving effect were also validated in an independent external cohort. RESULTS: Compared with the quantitative test, the semi-quantitative method had sensitivities of 93.5% and 81.3% and specificities of 61.4% and 63.1% in the overall sample of diabetic patients (n = 1,881) and in diabetic patients with eGFR ≥60 ml/min/1.73 m2 and a negative dipstick test (n = 1,110), respectively. After adjusting for direct and indirect medical costs, including the risk of disease progression, which was adjusted by the meta-analyzed hazard ratio for clinical outcomes, it was determined that using the semi-quantitative method could save 439.4 USD per person for 10 years. Even after adjusting the result to the external validation cohort, 339.6 USD could be saved for one diabetic patient for 10 years. CONCLUSIONS: The semi-quantitative method could be an appropriate screening tool for albuminuria in diabetic patients. Moreover, it can minimize the testing time and inconvenience and significantly reduce national health costs.

Laboratory intervention to improve the request of urinary albumin in primary care patients with arterial hypertension and financial implications.

INTRODUCTION: The request of Urinary albumin in primary care in Spain is insufficient to monitor patients with diabetes and hypertension (HTN). Our aim was to evaluate a strategy designed in consensus with general practitioners (GPs) to improve the request of urinary albumin in primary care patients with HTN according to guidelines, and to study its financial implications. MATERIALS AND METHODS: In a meeting with GPs, we decided that the Laboratory Information System (LIS) would automatically register the albumin-to-creatinine ratio (ACR) test in patients with HTN when the former had not been requested in the previous year. We counted the number of ACRs requested by the GPs, those that were automatically added through the intervention, and if they were measured through the strip assay or additionally through quantification. We calculated the economic cost of the additional registered ACR based on reagent cost. RESULTS: In the 6 months study period, the laboratory received 48,075 requests for primary care patients. For 3816 (7.9%), HTN was the indication that prompted the request. 386 ACR were automatically registered through the intervention. Use of strip analysis cost of 275.8 € but resulted in savings of 1450.3€ in albumin reagent. CONCLUSIONS: By making use of the laboratory technology, the strategy achieved a better adherence to the guidelines at no additional cost.

A cost-effective method for purification and characterization of human urinary albumin.

We describe a simplified approach for the purification and characterization of urinary albumin, a key biomarker currently used for understanding the onset and prognosis of microalbuminuria. Urinary albumin was purified from human urine collected from diabetic kidney disease patients by using 2-stage tangential flow filtration process and set of column chromatography steps. The relative molecular mass of urinary albumin is 66,871 Da (SYNAPT G2 High Definition Mass Spectrometry System). Isolated urinary albumin was analyzed by SDS-PAGE, Western blotting, immunoelectrophoresis, Ouchterlony double-immunodiffusion, single radial immunodiffusion, size-exclusion HPLC and peptide mass fingerprint analysis. The size-exclusion HPLC elution profile of the purified urinary albumin was similar to that of a reference form of native albumin. Peptide mass fingerprint analysis of the purified urinary albumin yielded peptides that partially matched with known sequence of ALBU_HUMAN (P02768). This is the first report of purification and validation of immunochemically reactive form of urinary albumin from a large volume of urine of diabetic kidney disease patients. In this purification approach, the cost of the purified albumin is significantly lower.

Assessment of Vitamin D-Binding Protein and Early Prediction of Nephropathy in Type 2 Saudi Diabetic Patients.

Early detection of diabetic nephropathy (DN) represents a great challenge in an attempt to reduce the burden of chronic kidney diseases in diabetic patients. This study aimed to investigate the potential early prediction role of urinary vitamin D-binding protein (uVDBP) for the diagnosis of DN and to examine the possible correlation to serum VDBP, high-sensitivity C-reactive protein (hs-CRP), and insulin resistance in these patients. Serum and urine samples were obtained from 40 healthy volunteers and 120 patients with type 2 diabetes divided into 3 groups: normoalbuminuria, microalbuminuria, and macroalbuminuria (urinary albumin excretion rate < 30, 30-300, and >300 µg/mg, resp.); n = 40/group. Serum and urinary VDBP levels were quantified by ELISA. Insulin resistance has been assessed by homeostasis model assessment index (HOMAI). Correction for urine creatinine concentration was applied for urinary quantitative measurements. uVDBP levels were significantly elevated in micro- and macroalbuminuria patient groups compared with those of the normoalbuminuria patient group and controls (820.4 ± 402.8 and 1458.1 ± 210.0 compared with 193.1 ± 141.0 and 127.7 ± 21.9 ng/mg, resp.) (P < 0.001). There was significant correlation between serum and urinary levels of VDBP in total patient group. Receiver operating characteristic analysis of uVDBP levels showed optimum cut-off value of 216.0 ng/mg corresponding to 98.8% sensitivity and 80.0% specificity and an area under the curve of 0.973 to discriminate the normoalbuminuria from the microalbuminuria groups. In multivariate analysis, ordination plot showed obvious demarcation between the study groups caused by the higher levels of uVDBP and albumin/creatinine ratio among other variables. The study findings suggested a possible clinical application of uVDPB as an early and a good marker for the detection of early renal disease in type 2 DM Saudi patients. Large-scale validation studies are warranted to confirm the results before including uVDBP with the available list of other conventional biomarkers.

Performance Verification of Alternative Quality Control Materials for Urine Albumin Assessment.

BACKGROUND: Accurate detection of urine albumin is important for evaluating the progression of diabetic kidney disease. However, two levels of daily quality control may not be practically feasible in some small clinical laboratories owing to a small number of patient samples and high costs. We aimed to prepare homemade quality control material (HQM) to measure urine albumin and then verify its performance. METHODS: Normal saline solution and fresh mixed urine samples from five donors with serious kidney disease were used to prepare two levels of HQM (HQM1 and HQM2). Anhydrous ethylene glycol and sodium azide were used as antifreeze and as a preservative, respectively. RESULTS: Before being separated into Eppendorf tubes, 20 tests for HQM1 and HQM2 were performed, resulting in mean ± SD of 19.52 ± 0.91 mg/L and 105.28 ± 3.71 mg/L, respectively. After having been divided, the vial-to-vial variations of HQM1 and HQM2 were small (4.93% and 3.70%, respectively). The stability of HQM1 and HQM2 stored at 2 - 8°C was about 2 months and 80 days, respectively, and when stored at -20°C, remained stable for more than 8 months. After 1 - 8 months of cryopreservation at -20°C, once opened, the HQM in every Eppendorf tube could be kept for at least five days (CV < 6.1%). CONCLUSIONS: Our HQM stored at -20°C remained stable for a long time, and so could be considered as an alternative to standard QMs in the clinical laboratory.

[Assessment of kidney function : Creatinine is not the whole story]. / Beurteilung der Nierenfunktion : Kreatinin ist nicht alles.

Chronic renal insufficiency has a high prevalence and leads not only to a severe impairment in the quality of life but also to a higher mortality, mainly due to cardiovascular complications; however, in the early stages where there is still a chance for a therapeutic intervention, it is often underestimated because depending on endogenous factors (e.g. age and muscle mass), serum creatinine could falsely remain in the normal range while kidney function is already impaired. An exact measurement of the glomerular filtration rate (GFR) using radionuclide techniques is cumbersome and usually confined to rare cases, such as in clinical studies. Creatinine clearance measurement by 24-h urine collection requires good patient instructions and is error prone, thus it is limited to special circumstances. In routine clinical practice, estimation of the GFR by calculation algorithms provides the best approach. In recent years the chronic kidney disease epidemiology collaboration (CKD-EPI) formula has become established as the most accurate method. This should be used for screening and continuous surveillance. In addition, urinalysis including dipstick tests and urinary microscopy represent non-invasive, technically simple and economic screening tools. Due to its semiquantitative nature, the results of urinalysis should only to be interpreted after comprehensive consideration of the diagnostic and technical limitations, which are reviewed in this article.

The Effectiveness of the Semi-quantitative Assessment of Microalbuminuria Using Routine Urine Dipstick Screening in Patients with Diabetes.

Objective The early diagnosis and treatment of microalbuminuria is important for preventing the progression of diabetic kidney disease in patients with diabetes. In this study, we assessed the accuracy of the semi-quantitative measurement of microalbuminuria by urine dipstick screening in patients with diabetes. Methods The semi-quantitative urinary albumin-to-creatinine ratio (QUACR) was used for microalbuminuria screening. A total of 291 diabetes patients with normoalbuminuria [urine albumin-to-creatinine ratio (UACR) <30 mg/g・Cre; n=205] or microalbuminuria (UACR 30-299 mg/g・Cre; n=86) were enrolled as study participants. Both the qualitative test of albumin (QUA) and the QUACR of early-morning or spot urine samples were performed at the same time. A receiver operating characteristic (ROC) analysis was performed to compare the diagnostic utility of the QUACR to that of the QUA in the detection of microalbuminuria. Results The sensitivity and specificity values of the QUACR were 84.9% and 76.6%, respectively. Those of the QUA were 53.5% and 84.4%, respectively. In the ROC analysis, the area under the curve values of the QUACR and QUA for the diagnosis of microalbuminuria were 0.807 (95% confidence interval: 0.752-0.863) and 0.689 (0.618-0.760), respectively. Conclusion These results suggest that the QUACR is a simple and efficient test-with high levels of sensitivity and specificity-for the detection of microalbuminuria in patients with diabetes.

Spot protein-creatinine ratio and spot albumin-creatinine ratio in the assessment of pre-eclampsia: a diagnostic accuracy study with decision-analytic model-based economic evaluation and acceptability analysis.

BACKGROUND: The National Institute for Health and Care Excellence (NICE) guidelines highlighted the need for 'large, high-quality prospective studies comparing the various methods of measuring proteinuria in women with new-onset hypertensive disorders during pregnancy'. OBJECTIVES: The primary objective was to evaluate quantitative assessments of spot protein-creatinine ratio (SPCR) and spot albumin-creatinine ratio (SACR) in predicting severe pre-eclampsia (PE) compared with 24-hour urine protein measurement. The secondary objectives were to investigate interlaboratory assay variation, to evaluate SPCR and SACR thresholds in predicting adverse maternal and fetal outcomes and to assess the cost-effectiveness of these models. DESIGN: This was a prospective diagnostic accuracy cohort study, with decision-analytic modelling and a cost-effectiveness analysis. SETTING: The setting was 36 obstetric units in England, UK. PARTICIPANTS: Pregnant women (aged ≥ 16 years), who were at > 20 weeks' gestation with confirmed gestational hypertension and trace or more proteinuria on an automated dipstick urinalysis. INTERVENTIONS: Women provided a spot urine sample for protein analysis (the recruitment sample) and were asked to collect a 24-hour urine sample, which was stored for secondary analysis. A further spot sample of urine was taken immediately before delivery. MAIN OUTCOME MEASURES: Outcome data were collected from hospital records. There were four index tests on a spot sample of urine: (1) SPCR test (conducted at the local laboratory); (2) SPCR test [conducted at the central laboratory using the benzethonium chloride (BZC) assay]; (3) SPCR test [conducted at the central laboratory using the pyrogallol red (PGR) assay]; and (4) SACR test (conducted at the central laboratory using an automated chemistry analyser). The comparator tests on 24-hour urine collection were a central test using the BZC assay and a central test using the PGR assay. The primary reference standard was the NICE definition of severe PE. Secondary reference standards were a clinician diagnosis of severe PE, which is defined as treatment with magnesium sulphate or with severe PE protocol; adverse perinatal outcome; one or more of perinatal or infant mortality, bronchopulmonary dysplasia, necrotising enterocolitis or grade III/IV intraventricular haemorrhage; and economic cost and outcomes. Health service data on service use and costs followed published economic models. RESULTS: In total, 959 women were available for primary analysis and 417 of them had severe PE. The diagnostic accuracy of the four assays on spot urine samples against the reference standards was similar. The three SPCR tests had sensitivities in excess of 90% at prespecified thresholds, with poor specificities and negative likelihood ratios of ≥ 0.1. The SACR test had a significantly higher sensitivity of 99% (confidence interval 98% to 100%) and lower specificity. Receiver operating characteristic (ROC) curves were similar (area under ROC curve between 0.87 and 0.89); the area under the central laboratory's SACR curve was significantly higher (p = 0.004). The central laboratory's SACR test was the most cost-effective option, generating an additional 0.03 quality-adjusted life-years at an additional cost of £45.07 compared with the local laboratory's SPCR test. The probabilistic analysis showed it to have a 100% probability of being cost-effective at the standard willingness-to-pay threshold recommended by NICE. LIMITATIONS: Implementation of NICE guidelines has led to an increased intervention rate in the study population that affected recruitment rates and led to revised sample size calculations. CONCLUSIONS: Evidence from this clinical study does not support the recommendation of 24-hour urine sample collection in hypertensive pregnant women. The SACR test had better diagnostic performance when predicting severe pre-eclampsia. All four tests could potentially be used as rule-out tests for the NICE definition of severe PE. FUTURE WORK: Testing SACR at a threshold of 8 mg/mmol should be studied as a 'rule-out' test of proteinuria. TRIAL REGISTRATION: Current Controlled Trials ISRCTN82607486. FUNDING: This project was funded by the National Institute Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 61. See the NIHR Journals Library website for further project information.

Point-of-care testing improves diabetes management in a primary care clinic in South Africa.

INTRODUCTION: Diabetes is a major health problem in South Africa. DiabCare Africa found just 47% of diabetes patients had a hemoglobin A1c (HbA1c) test for their management in the previous year. METHODS: Patients attending an urban diabetes clinic near Johannesburg, run by Project HOPE, accessed HbA1c (and urine albumin:creatinine ratio) point-of-care testing (POCT) as part of a quality-assured international program called ACE (Analytical and Clinical Excellence). Patients who had two or more HbA1c POC tests from 2012 to 2014 were assessed to determine their change in glycaemic control. RESULTS: The mean (±SD) HbA1c in this group of diabetes patients (n=131) fell significantly from 9.7%±2.4 (83mmol/mol) at their first POCT measurement to 8.4%±2.4 (68mmol/mmol/mol) at their most recent POCT measurement (paired t-test p<0.01). The average time between first and most recent HbA1c test was 15 months. The number of diabetes patients achieving optimal glycaemic control (HbA1c≤6.5-7.5% [48-58mmol/mol) increased by 125%, while the number with very poor glycaemic control (HbA1c>10% [86mmol/mol]) halved. An association was observed between degree of glycaemic control and increasing albuminuria in this cohort. DISCUSSION: POCT has promoted change in clinical practice by facilitating greater accessibility to HbA1c testing.

Assessment of urinary microparticles in normotensive patients with type 1 diabetes.

AIMS/HYPOTHESIS: Assessment of urinary extracellular vesicles including exosomes and microparticles (MPs) is an emerging approach for non-invasive detection of renal injury. We have previously reported that podocyte-derived MPs are increased in diabetic mice in advance of albuminuria. Here, we hypothesised that type 1 diabetes and acute hyperglycaemia would increase urinary podocyte MP levels in uncomplicated diabetes. METHODS: In this post hoc exploratory analysis, we examined archived urine samples from normoalbuminuric patients with uncomplicated type 1 diabetes studied under clamped euglycaemia and hyperglycaemia and compared with healthy controls. Urinary vesicles were assessed by electron microscopy and nanoparticle tracking while podocyte MPs were assessed by flow cytometry. RESULTS: Neither vesicle size nor total number were significantly altered in type 1 diabetes or acute hyperglycaemia. By contrast, urinary podocyte MP levels were higher in type 1 diabetes (0.47 [0.00-3.42] MPs/µmol creatinine [Cr]) compared with healthy controls (0.00 [0.00-0.00] MPs/µmol Cr, p < 0.05) and increased under hyperglycaemic clamp (0.36 [0.00-4.15] MPs/µmol Cr during euglycaemia vs 2.70 [0.00-15.91] MPs/µmol Cr during hyperglycaemia, p < 0.05). Levels of urinary albumin to creatinine ratio and nephrin (surrogates of podocyte injury) were unchanged by type 1 diabetes or acute hyperglycaemia. CONCLUSION/INTERPRETATION: Taken together, our data show that urinary podocyte MP levels are higher in patients with type 1 diabetes in advance of changes in other biomarkers (albuminuria, nephrin). Examination of podocyte MPs may serve as an early biomarker of glomerular injury in uncomplicated type 1 diabetes.

Urinary Biomarkers in the Assessment of Early Diabetic Nephropathy.

Diabetic nephropathy (DN) is a frequent and severe complication of diabetes mellitus (DM). Its diagnosis in incipient stages may allow prompt interventions and an improved prognosis. Towards this aim, biomarkers for detecting early DN can be used. Microalbuminuria has been proven a remarkably useful biomarker, being used for diagnosis of DN, for assessing its associated condition-mainly cardiovascular ones-and for monitoring its progression. New researches are pointing that some of these biomarkers (i.e., glomerular, tubular, inflammation markers, and biomarkers of oxidative stress) precede albuminuria in some patients. However, their usefulness is widely debated in the literature and has not yet led to the validation of a new "gold standard" biomarker for the early diagnosis of DN. Currently, microalbuminuria is an important biomarker for both glomerular and tubular injury. Other glomerular biomarkers (transferrin and ceruloplasmin) are under evaluation. Tubular biomarkers in DN seem to be of a paramount importance in the early diagnosis of DN since tubular lesions occur early. Additionally, biomarkers of inflammation, oxidative stress, podocyte biomarkers, and vascular biomarkers have been employed for assessing early DN. The purpose of this review is to provide an overview of the current biomarkers used for the diagnosis of early DN.

Comparison of urine collection methods for albuminuria assessment in young children.

Cotton wool or pantyliners placed in a diaper can be used as urine collection devices for albuminuria measurements in young, not continent children. We tested a new collection method (PeeSpot(R)) for its analytical performance, and compared it with the pantyliner technique. Eighty-one urine samples with a wide range of albuminuria were pipetted on the pantyliner and PeeSpot in duplicate. These were incubated for 3h at 37°C (simulating the time a toddler wears a diaper), and subsequently 72h at room temperature (simulating transport to a central laboratory). Urine was extracted by centrifugation and albumin concentration (UAc) was measured. UAC measured by the two methods was compared with UAC in an unprocessed reference aliquot stored for 75h at 4°C. Bias (mean percentage UAC difference between test and reference), precision (interquartile range of the UAC difference) and accuracy (proportion of samples within 30% of reference UAC) were calculated. Median UAC in the reference aliquot was 66.0mg/L [IQR 25.0-211.0], pantyliner 32.0mg/L [4.7-165.0; P<0.001 vs reference], and PeeSpot 61.0mg/L [27.0-216.0; P=0.84 vs reference]. Bias, precision and accuracy in pantyliner were -34.2%, 31.3mg/L and 48.1%; in PeeSpot 3.3%, 5.0mg/L and 96.3%. Passing-Bablok regression and Bland-Altman plot showed an underestimation for the pantyliner but not for the PeeSpot. The PeeSpot is an accurate and precise tool for collecting urine for albumin measurement in young children and should be preferred over the alternative cotton wool collection technique.

Association of Reduced eGFR and Albuminuria with Serious Fall Injuries among Older Adults.

BACKGROUND AND OBJECTIVES: Falls are common and associated with adverse outcomes in patients on dialysis. Limited data are available in earlier stages of CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We analyzed data from 8744 Reasons for Geographic and Racial Differences in Stroke Study participants ≥65 years old with Medicare fee for service coverage. Serious fall injuries were defined as a fall-related fracture, brain injury, or joint dislocation using Medicare claims. Hazard ratios (HRs) for serious fall injuries were calculated by eGFR and albumin-to-creatinine ratio (ACR). Among 2590 participants with CKD (eGFR<60 ml/min per 1.73 m(2) or ACR≥30 mg/g), cumulative mortality after a serious fall injury compared with age-matched controls without a fall injury was calculated. RESULTS: Overall, 1103 (12.6%) participants had a serious fall injury over 9.9 years of follow-up. The incidence rates per 1000 person-years of serious fall injuries were 21.7 (95% confidence interval [95% CI], 20.3 to 23.2), 26.6 (95% CI, 22.6 to 31.3), and 38.3 (95% CI, 31.2 to 47.0) at eGFR levels ≥60, 45-59, and <45 ml/min per 1.73 m(2), respectively, and 21.3 (95% CI, 20.0 to 22.8), 31.7 (95% CI, 27.5 to 36.5), and 42.2 (95% CI, 31.3 to 56.9) at ACR levels <30, 30-299, and ≥300 mg/g, respectively. Multivariable adjusted HRs for serious fall injuries were 0.91 (95% CI, 0.76 to 1.09) and 1.09 (95% CI, 0.86 to 1.37) for eGFR=45-59 and <45 ml/min per 1.73 m(2), respectively, versus eGFR≥60 ml/min per 1.73 m(2) and 1.31 (95% CI, 1.11 to 1.54) and 1.81 (95% CI, 1.30 to 2.50) for ACR=30-299 and ≥300 mg/g, respectively, versus ACR<30 mg/g. Among participants with CKD, cumulative 1-year mortality rates among patients with a serious fall and age-matched controls were 21.0% and 5.5%, respectively. CONCLUSIONS: Elevated ACR but not lower eGFR was associated with serious fall injuries. Evaluation for fall risk factors and fall prevention strategies should be considered for older adults with elevated ACR.

The prevalence of albuminuria among diabetic patients in a primary care setting in Singapore.

INTRODUCTION: Microalbuminuria is an early sign of kidney damage. The prevalence of microalbuminuria in Singapore has been reported to be 36.0%-48.5%. However, the prevalence of microalbuminuria reported in these studies was determined with one urine sample using a qualitative urine test. The aim of this study was to determine the prevalence of micro- and macroalbuminuria using a more stringent criterion of two positive quantitative urine albumin-creatinine ratio (ACR) tests. METHODS: We conducted a cross-sectional study of patients with type 2 diabetes mellitus (T2DM) who were followed up at a primary care clinic in Singapore. Patients were diagnosed to have albuminuria if they had two positive ACR tests within a seven-month period. RESULTS: A total of 786 patients with T2DM met the study's inclusion criteria. 55.7% were already on an angiotensin-converting enzyme inhibitor (ACEI) and/or angiotensin receptor blocker (ARB). The prevalence rates of micro- and macroalbuminuria were 14.2% and 5.7%, respectively. Patients with albuminuria were more likely to have hypertension (odds ratio [OR] 3.47, 95% confidence interval [CI] 1.55-7.80). Diabetics with poorer diabetic control (OR 1.88, 95% CI 1.26-2.79), and higher systolic (OR 1.69, 95% CI 1.14-2.49) and diastolic (OR 1.96, 95% CI, 1.20 to 3.22) blood pressures were more likely to have albuminuria. CONCLUSION: In the present study, the prevalence of microalbuminuria is significantly lower than that previously reported in Singapore. The presence of hypertension, poor diabetic control and suboptimal blood pressure control are possible risk factors for albuminuria in patients with T2DM.