Measurement Of Urinary Albumin Excretion Research Articles

Podocyte Geranylgeranyl Transferase Type-I Is Essential for Maintenance of the Glomerular Filtration Barrier.

A tightly regulated actin cytoskeleton attained through balanced activity of RhoGTPases is crucial to maintaining podocyte function. However, how RhoGTPases are regulated by geranylgeranylation, a post-translational modification, has been unexplored. The authors found that loss of the geranylgeranylation enzyme geranylgeranyl transferase type-I (GGTase-I) in podocytes led to progressive albuminuria and foot process effacement in podocyte-specific GGTase-I knockout mice. In cultured podocytes, the absence of geranylgeranylation resulted in altered activity of its downstream substrates Rac1, RhoA, Cdc42, and Rap1, leading to alterations of β1-integrins and actin cytoskeleton structural changes. These findings highlight the importance of geranylgeranylation in the dynamic management of RhoGTPases and Rap1 to control podocyte function, providing new knowledge about podocyte biology and glomerular filtration barrier function. Impairment of the glomerular filtration barrier is in part attributed to podocyte foot process effacement (FPE), entailing disruption of the actin cytoskeleton and the slit diaphragm. Maintenance of the actin cytoskeleton, which contains a complex signaling network through its connections to slit diaphragm and focal adhesion proteins, is thus considered crucial to preserving podocyte structure and function. A dynamic yet tightly regulated cytoskeleton is attained through balanced activity of RhoGTPases. Most RhoGTPases are post-translationally modified by the enzyme geranylgeranyl transferase type-I (GGTase-I). Although geranylgeranylation has been shown to regulate activities of RhoGTPases and RasGTPase Rap1, its significance in podocytes is unknown. We used immunofluorescence to localize GGTase-I, which was expressed mainly by podocytes in the glomeruli. To define geranylgeranylation's role in podocytes, we generated podocyte-specific GGTase-I knockout mice. We used transmission electron microscopy to evaluate FPE and measurements of urinary albumin excretion to analyze filtration barrier function. Geranylgeranylation's effects on RhoGTPases and Rap1 function were studied in vitro by knockdown or inhibition of GGTase-I. We used immunocytochemistry to study structural modifications of the actin cytoskeleton and β1 integrins. Depletion of GGTase-I in podocytes in vivo resulted in FPE and concomitant early-onset progressive albuminuria. A reduction of GGTase-I activity in cultured podocytes disrupted RhoGTPase balance by markedly increasing activity of RhoA, Rac1, and Cdc42 together with Rap1, resulting in dysregulation of the actin cytoskeleton and altered distribution of β1 integrins. These findings indicate that geranylgeranylation is of crucial importance for the maintenance of the delicate equilibrium of RhoGTPases and Rap1 in podocytes and consequently for the maintenance of glomerular integrity and function.

PS-C27-2: RISK OF PSEUDO-MICROALBUMINURIA DURING MENSTRUAL SITUATION IN APPARENTLY HEALTHY WORKERS

Background: Measurement of urinary albumin excretion (UAE) is useful for the prediction of future cardiovascular event and is now used not only in clinical but also in health-check up or industrial settings. Especially, microalbuminuria (MA) is an important category of early vascular marker to alert lifestyle modification and/or pharmacological treatment. In the working female population, however, examination of urine in above settings could encounter menstrual situation. Contamination of menstrual blood into urine could induce pseudo-microalbuminuria. However, it has never been studied in apparently healthy women how much of contamination of menstrual blood could increase the risk of pseudo-microalbuminuria. To address this issue, we examined the relationship between urine occult blood level and UAE or frequency of MA cases during menstrual and non-menstrual situation in apparently healthy workers. Subjects and method: We studied 735 female school workers who participated in the Miyagi Karoshi Prevention study. Urinary albumin excretion adjusted for creatinine (UAE) from morning spot urine sample was examined together with annual health check-up in 2019 and 2020. Menstrual situation was confirmed by a questionnaire at the time of examination. One hundred and forty-four non-diabetic, non-hypertensive women without chronic kidney disease (36.9 ± 9.2yrs) were studied either during menstrual or non-menstrual situation in the 2 consecutive years. We compared clinical data during menstrual and non-menstrual situation and then examined the dose-response relationship between urine occult blood category (negative to three plus) and UAE or frequency of MA cases at menstrual and non-menstrual situation. Results: Menstrual situation was associated with significantly higher UAE (4.6 vs. 3.4 mg/gCr, p < 0.001), systolic BP (113.6 ± 13.1 vs. 111.3 ± 12mmHg, p = 0.015) and uric acid level (4.3 ± 0.8 vs. 4.10.9 ± mg/dl, p = 0.004) and was associated with significantly lower high density lipoprotein cholesterol (70.0 ± 14.4 vs. 72.7 ± 16.3 mg/dl, p < 0.001) and eGFR(85.0 ± 14.6 vs, 87.7 ± 16.9 ml/min/1.73m2, p = 0.003) as compared with non-menstrual situation. In menstrual situation, UAE was dose-dependently increased with an increase in urine occult blood category (p < 0.001). Frequency of MA in each urine blood category was 0, 0, 4.5, 0 and 17% (p = 0.001), respectively. UAE was not correlated with systolic BP or other parameters during menstrual situation. In non-menstrual situation, there was no correlation with UAE and urine occult blood level. Conclusion: Risk of pseudo-microalbuminuria could abruptly rise if urine occult blood level reach three plus in menstruated women.

Urinary Albumin to Creatinine Ratio to Predict Diabetic Retinopathy: The Eyes Have It!

IntroductionThe Coronavirus disease 2019 (COVID-19) pandemic has provided a push in the search for alternative screening methods to replace annual fundoscopic examination of patients with type 2 diabetes mellitus (T2DM) to detect diabetic retinopathy (DR).Materials and methodsThis retrospective study was conducted using the data of T2DM patients from their routine follow-up hospital visits. The details from their history and physical examination were extracted. As part of their routine follow-up visit, they had undergone a panel of investigations that included blood glucose measurements and urinary albumin excretion measurements. Univariate and logistic multivariate regression analyses were applied to identify the potential clinical and laboratory parameters associated with the presence of DR in them.ResultsAnalysis of the medical records of 272 T2DM patients revealed that 147 patients had DR while 125 did not. Furthermore, 135 had non-proliferative DR (64 mild, 53 moderate, and 18 severe grades), whereas the remaining 12 had proliferative DR. On sequential univariate and multiple regression analysis, urinary albumin creatinine ratio (UACR), known duration of T2DM, and history of ischemic heart disease were seen to be independently associated with the presence of DR. Median UACR for those without DR was 42.6 mg/g (range 18.21-183.3 mg/g) while for those with retinopathy it was 214 mg/g (range 45.4-1260 mg/g) (p<0.001). The receiver operating characteristics curve analysis provided an area under the curve of 70% for UACR. UACR value of 140 mg/g could predict the presence of DR with a sensitivity of 60.5% & specificity of 72%, as well as had positive and negative likelihood ratios of 2.16 and 0.54, respectively.ConclusionUACR has the potential to be used as a screening tool for DR until the easing of social restrictions due to the COVID-19 pandemic.

Impact of salt intake on urinary albumin excretion in patients with type 2 diabetic nephropathy: a retrospective cohort study based on a generalized additive model.

Diabetic kidney disease is an important and common cause of end-stage renal disease. Measurement of urinary albumin excretion (UAE) requires the diagnosis of the stage of diabetic nephropathy and the prognosis of renal function. We aimed to analyze the impact of lifestyle modification on UAE in patients with stage 2 and 3 type 2 diabetic nephropathy who received comprehensive medical care, using a generalized additive model (GAM), an explanatory machine learning model. In this retrospective observational study, we used changes in HbA1c, systolic blood pressure (SBP), and diastolic blood pressure (DBP) levels; body mass index (BMI); and daily salt intake as factors contributing to changes in UAE. In total, 269 patients with type 2 diabetic nephropathy were enrolled (stage 2, 217 patients; stage 3, 52 patients). The rankings that contributed to changes in UAE over 6 months by permutation importance were the changes in daily salt intake, HbA1c, SBP, DBP, and BMI. GAM, which predicts the change in UAE, showed that with increase in the changes in salt intake, SBP, and HbA1c, the delta UAE tended to increase. Salt intake was the most contributory factor for the changes in UAE, and daily salt intake was the best lifestyle factor to explain the changes in UAE. Strict control of salt intake may have beneficial effects on improving UAE in patients with stage 2 and 3 diabetic nephropathy.

The Role of Telenephrology in the Management of CKD.

CKD is a common illness across societies, affecting an estimated 13% of the population worldwide (1). The prevalence of CKD is thought to be rising, likely due to a combination of an aging population and increases in comorbid chronic conditions—such as obesity, diabetes, and hypertension—that contribute to its pathogenesis. In the United States, the prevalence of CKD is estimated at nearly 15%, and Medicare spent $114 billion on CKD and ESKD in 2018 (2). Whereas studies indicate that early referral to nephrologists may improve outcomes in CKD, many patients do not see nephrologists until late in the course of their disease. Barriers to early referral include geographic remoteness, with patients living far from available nephrologic care, and difficulties in traveling due to the burden of comorbidities (3⇓⇓–6). Rural patients with CKD have been found to have poorer quality-of-care markers, including timely measurement of urinary albumin excretion and appropriate use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and experience a greater risk for hospitalization and all-cause mortality than urban patients with CKD (5,6). Telemedicine, a video-based healthcare delivery technology, has the potential to attenuate these disparities and has been used in multiple chronic illnesses, including heart failure, diabetes mellitus, and chronic obstructive pulmonary disease. Although the approach is not appropriate for all encounters, nephrology is, in many ways, particularly suited for telemedicine. The longitudinal follow-up of patients with CKD is heavily dependent on repeat laboratory evaluations and detailed history taking. Although questions regarding changes in weight or edema can be critical, the majority of visits do not center on extensive physical examinations. Similarly, patient appointments for the management of hypertension are typically focused on reviews of BP logs and office measurements of vital signs, whereas encounters for nephrolithiasis involve appraisal of laboratory evaluations …

Thiamine Supplementation is Beneficial as Adjunctive Therapy to ACE Inhibitors to Improve the Course of Nephrogenic Complications of Type II Diabetes Mellitus: Possible Involvement of the Inflammatory Cascade as a Mechanism of this Effect

AbstractBackground: Diabetic nephropathy is one of the most common complications of type II diabetes mellitus. Different recent researches investigated the therapeutic effects of different medications and therapeutic agents on the progression of diabetic nephropathy.Aim of Study: Compare the reno-protective effects of thiamine in addition to ACE inhibitors in type 2 diabetic kidneys.Material and Methods: A total of 50 male albino rats were were divided into 5 groups:Group 1: Control group.Group 2: Type 2 diabetic rats.Group 3: Type 2 diabetic nephropathy rats.Group 4: Lisinopril-treated type 2 diabetic nephropathy rats. Group 5: Thiamine mononitrate-treated type 2 diabetic neph-ropathy rats.Blood samples were collected for the measurements of fasting blood glucose, fasting blood insulin, blood urea, and blood albumin-creatinine ratio. Urine samples were collected for measurement of urinary albumin excretion. Systolic and diastolic blood pressure were measured. Nuclear factor kappa-B gene expression was estimated.Results: Treatment with ACE inhibitors reduced fasting blood glucose, fasting blood insulin, blood urea, urinary albumin excretion, nuclear factor kappa B gene expression, systolic blood pressure and diastolic blood pressure. While treatment with thiamine mononitrate reduced fasting blood glucose, blood urea, urinary albumin excretion and systolic blood pressure.Conclusion: The use of ACE inhibitors and thiamine in the treatment of kidney disease with type 2 diabetes significantly offered renal protection and improved the diabetic condition and may postpone the onset of renal injury in type 2 diabetic person.

77 Choline supplementation during pregnancy protects against lipopolysaccharide-induced preeclampsia symptoms

Introduction Pre-eclampsia is characterized by new-onset hypertension and proteinuria at ⩾20 weeks of gestation. Our previous study demonstrated that the cholinergic anti-inflammatory pathway may contribute to the relief of Pre-eclampsia through α7 nicotinic acetylcholine receptor (α7 nAChR). Choline, a selective α7 nAChR agonist, has recently been established as a promising treatment for inflammation. Objectives In order to examine the effects of gestational choline supplementation on LPS-induced pre-eclampsia symptoms in rats. Methods Pre-eclampsia model was induced by lipopolysaccharide (1.0 μ g/kg) via tail vein injection on gestational day (GD) 14. Pregnant SD rats were placed on a supplemented (5.0 g/kg diet) or normal (1.1 g/kg diet) choline diet throughout gestation. All the rats were divided into 4 groups (P = normal pregnant + 1.1 g/kg choline diet; P-CHOLINE = normal pregnant + 5.0 g/kg choline diet; LPS = LPS + 1.1 g/kg choline diet; LPS-CHOLINE = LPS +5.0 g/kg choline diet). Systolic blood pressure (SBP) was measured on GD 6,11,14,16 and 18. On GD 7, 12, 17, and 19, urine is collected for 24 h urinary albumin excretion measurements. On GD 20, dams were all sacrificed. Pups were then removed, counted and weighed. Percent of resorbed and malformation fetuses were also counted. Placental weights were measured. Results An injection with LPS on GD 14 resulted in higher blood pressure (GD 14 = 105 ± 1.5 mmHg VS GD 16 = 127 ± 0.9 mmHg; GD 18 = 130 ± 1.1 mmHg, P Conclusions Thus, choline supplementation during pregnancy protects against LPS-induced pre-eclampsia. This may provide a new potential prevention strategy for pre-eclampsia.

Measuring glomerular filtration rate by iohexol clearance on filter paper is feasible in adolescents with type 1 diabetes in the ambulatory setting.

The American Diabetes Association recently recommended routine screening of glomerular filtration rate (GFR) in adolescents with type 1 diabetes, although this is not routinely performed clinically [1]. Current estimates of GFR lack precision and accuracy before stage 3 of chronic kidney disease (GFR \60 mL/min/1.73 m). Also, measurement of urinary albumin excretion, currently recommended as part of routine screening, does not directly measure kidney function. This is of particular concern in adolescents and young adults with type 1 diabetes, in whom renal hyperfiltration may promote renal injury, or rapid change in GFR may be missed due to the lack of acceptable screening methods for GFR. Perrin and Berg [2] recently reported that estimated GFR cannot accurately replace measured GFR to defect hyperfiltration in young patients with type 1 diabetes. We recently reported that iohexol clearance measured with dried blood spots (DBS) on filter paper performed better than the estimates of GFR using the CKD-EPI equations and was comparable to gold-standard iohexol plasma clearance in adults with type 1 diabetes [3]. GFR measured by iohexol clearance on DBS has also been evaluated in adults with a wide range of GFRs showing strong agreement to gold-standard measurements [4]. Standard iohexol GFR (iGFR) measurement requires more than 4 h in a research center, making it impractical for routine clinical monitoring of GFR. Here, we present data from a pilot study in youth with type 1 diabetes (n = 8, 70 % female, 17 ± 4 years, type 1 diabetes duration of 6.3 ± 5.0 years, HbA1c 8.9 ± 2.5 %) with the goal of demonstrating feasibility of translating this method to an ambulatory setting. Kidney function was measured by iGFR with DBS and estimated by Bouvet (cystatin C and creatinine-based GFR equation) and Schwartz (creatinine-based GFR equation). The participants had blood drawn, then iohexol injected intravenously prior to their regular diabetes visit and were sent home with filter paper to collect DBS at 120, 150, 180, 210 and 240 min after iohexol injection followed by mailing the filter paper back to our laboratory. There appeared to be less variability of GFR with the iGFR than the estimated GFR methods (Bouvet and Schwartz) (Fig. 1). As this study was performed on an outpatient basis to determine feasibility, we did not perform an in-patient gold-standard iGFR study to serve as a comparator for these three GFR measurements. However, our previous publication in adults with type 1 diabetes demonstrated that iGFR measured in DBS on filter paper was significantly less biased and more comparable to a gold-standard iGFR measurement than estimated GFR [3]. Moreover, using two spots at 120 and 240 min was comparable to using five spots [3], which if validated would further decrease burden to the patient and cost of this method. The adolescents also rated eight statements on a 7-point non-validated Likert scale (Fig. 2). All participants agreed or strongly agreed that the procedure was preferable Managed by Massimo Federici.

Biomarkers of progression in diabetic nephropathy: The past, present and future.

More than 380 million people are currently suffering from diabetes. The International Diabetes Federation estimated that this would rise to 592 million within a generation. Despite this relentless increase in the prevalence of type 2 diabetes worldwide, with the advent of potent statins, there has been a gradual decline in mortality from macrovascular complications, such as stroke and coronary heart disease. However, this is not the situation in diabetic nephropathy, which remains a leading cause of end-stage renal disease (ESRD) globally, with its incidence being still on a rising trend. Notably, once nephropathy develops, approximately 20–40% of patients inevitably progress to ESRD. Therefore, we need biomarkers that would enable early risk stratification in diabetic nephropathy (Figure​(Figure1),1), so that those at higher risk of progression to ESRD are identified at early stages of nephropathy development. Long-term follow up of interventional studies, such as STENO-2, have clearly shown that, even at the stage of microalbuminuria, intensive multifactorial management targeting blood pressure (particularly with blockade of the renin–angiotensin system), glucose, cholesterol and lifestyle issues could reduce the progression to ESRD as well as the associated cardiovascular mortality. The availability of sensitive and well-validated biomarkers for nephropathy progression would allow targeted intensive management to be provided to those who would derive the most cost-effective benefits from such intervention.

Diabetic kidney disease: from physiology to therapeutics.

Diabetic kidney disease (DKD) defines the functional, structural and clinical abnormalities of the kidneys that are caused by diabetes. This complication has become the single most frequent cause of end-stage renal disease. The pathophysiology of DKD comprises the interaction of both genetic and environmental determinants that trigger a complex network of pathophysiological events, which leads to the damage of the glomerular filtration barrier, a highly specialized structure formed by the fenestrated endothelium, the glomerular basement membrane and the epithelial podocytes, that permits a highly selective ultrafiltration of the blood plasma. DKD evolves gradually over years through five progressive stages. Briefly they are: reversible glomerular hyperfiltration, normal glomerular filtration and normoalbuminuria, normal glomerular filtration and microalbuminuria, macroalbuminuria, and renal failure. Approximately 20-40% of diabetic patients develop microalbuminuria within 10-15 years of the diagnosis of diabetes, and about 80-90% of those with microalbuminuria progress to more advanced stages. Thus, after 15-20 years, macroalbuminuria occurs approximately in 20-40% of patients, and around half of them will present renal insufficiency within 5 years. The screening and early diagnosis of DKD is based on the measurement of urinary albumin excretion and the detection of microalbuminuria, the first clinical sign of DKD. The management of DKD is based on the general recommendations in the treatment of patients with diabetes, including optimal glycaemic and blood pressure control, adequate lipid management and abolishing smoking, in addition to the lowering of albuminuria.

Low birthweight and risk of albuminuria in living kidney donors.

Low birthweight is linked to hypertension, chronic kidney disease and even end-stage renal disease. We hypothesized that living kidney donors born with lower birthweight may be at increased risk of hypertension, albuminuria, or reduced GFR beyond what is typical following uninephrectomy. Two hundred fifty-seven living kidney donors who donated at the University of Minnesota between 1967 and 2005 underwent iohexol GFR and urinary albumin excretion measurements. Predictors of iohexol GFR <60 mL/min/1.73 m(2), albuminuria, and hypertension were examined using logistic regression. Predictors examined include age at GFR measurement, time since donation, BMI, gender, serum creatinine level (at donation and GFR measurement), systolic and diastolic blood pressure, race, and birthweight. The latter was obtained through self-report and verified through birth certificates and family members. Older age, higher BMI, and time from donation were associated with reduced GFR. Older age and higher BMI were also associated with hypertension. Birthweight was not associated with GFR <60 mL/min/1.73 m(2): OR=0.70, 95% CI (0.28, 1.74), p = 0.45 or hypertension: OR=0.92, 95% CI (0.46, 1.84), p = 0.82 but was associated with albuminuria: OR=0.37, 95% CI (0.15, 0.92), p = 0.03. These data further strengthen the link between low birthweight and potential adverse renal outcomes.

Quality of care of patients with type 1 diabetes: Population-based results in a French region

Although the incidence of type 1 diabetes (T1D) has been increasing, little is known of its quality of care. Thus, our survey was designed to retrospectively evaluate this issue in French patients. Patients with T1D living in northeastern France were identified thanks to the healthcare system (CPAM) database, and the resulting list reviewed by local diabetes specialists. All of the listed patients and their primary physicians were asked to fill in a questionnaire including clinical data, laboratory results and follow-up habits. The 'optimized results' included CPAM-based results plus any specialized care provided during hospitalizations in diabetes and non-diabetes units, according to questionnaire data. A total of 227 individuals, for whom CPAM data were available, were identified as having T1D. From these patients, 174 questionnaires were answered, and optimized results (having both CPAM data and a completely filled-in questionnaire) were available for 149 patients. Of the 169 patients who responded, 71.3% reported at least a yearly visit with a diabetologist. This number reached 77.9% when optimized results were considered. Patients who received specialized care were younger, underwent HbA(1c) tests more often and were more frequently on optimal treatment; however, there was no difference in HbA(1c) values or in the prevalence of complications. Eye examinations and kidney tests had been performed at least once over the 2-year period in more than 87% of the patients, whereas around 30%, 21% and 23% had an eye exam, creatinine test and urinary albumin excretion measurement, respectively, only once over the same time period. This is the first large-scale study of the quality of care in patients with T1DM in France, and it could serve as a preliminary survey for a national study. Although the follow-up was better than previously reported, there is still considerable room for improvement.

Relation of Reduction in Urinary Albumin Excretion to Ten-Year Cardiovascular Mortality in Patients With Type 2 Diabetes and Systemic Hypertension

Microalbuminuria is one of the strongest predictors of both adverse renal and cardiovascular disease (CVD) outcomes in patients with type 2 diabetes mellitus. Although measurement of urinary albumin excretion (UAE) is widely recommended, limited data are available to suggest that reducing UAE translates into a reduction in long-term cardiovascular mortality, particularly among patients without overt nephropathy, who constitute most patients with type 2 diabetes worldwide. We assessed whether changes in the UAE at 1 year were associated with cardiovascular mortality in 393 patients with hypertension and type 2 diabetes during a 10-year period. On univariate analysis, CVD history, age, diabetes duration, and change in UAE at 1 year were associated with cardiovascular mortality risk (hazard ratio 2.60 for those with CVD history, 95% confidence interval [CI] 1.47 to 4.62; hazard ratio 1.59 per 10 years of diabetes duration, 95% CI 1.12 to 2.25; and hazard ratio 1.49 per log UAE increase, 95% CI 1.13 to 1.96). In a stepwise Cox regression model that included baseline UAE and CVD history, the 10-year predicted mortality of those with a decrease in UAE of 2 logs at 1 year was 4.7% (95% CI 1.4% to 7.8%). For those with an increase in UAE of 2 logs at 1 year, it was 24.5% (95% CI 10.1% to 36.5%). In conclusion, these data support current guideline recommendations to screen for UAE in all patients with type 2 diabetes, even in the absence of nephropathy, and suggest that serial UAE measurements even after the initiation of antihypertensive therapy has prognostic value independent of traditional cardiovascular risk factors.

Microalbuminuria in children with primary and white-coat hypertension

Microalbuminuria serves as an early marker of hypertension-related renal damage in adults. However, data on the prevalence of microalbuminuria in paediatric hypertensive patients in general and in children with white-coat hypertension (WCH) specifically are lacking. The aim of our study was to investigate the prevalence of microalbuminuria in children with primary hypertension (PH) and WCH, respectively. This was a retrospective case review of children with PH and WCH treated at three paediatric nephrology centres. Untreated children with either form of hypertension for whom measurements of urinary albumin excretion (UAE) had been performed were enrolled in the study. The study cohort comprised 52 children (39 boys) with hypertension (26 children with PH, 26 with WCH). Microalbuminuria (>3.2 mg/mmol creatinine) was present in 20% of children with PH and none of the children with WCH (p < 0.01). Children with PH had a higher median UAE than those with WCH (1.27 ± 1.92 vs. 0.66 ± 0.46 mg/mmol creatinine, p < 0.05). Based on these results, we suggest that children with PH have an increased prevalence of microalbuminuria, while children with WCH show no signs of hypertension-related renal damage.

Clinical impact of albuminuria in diabetic nephropathy

Patients suffering from diabetic nephropathy, resulting in end-stage renal failure, are increasing in number. The pathophysiology of diabetic nephropathy remains to be fully investigated. In the clinical setting, the presence of albuminuria/overt proteinuria and a low glomerular filtration rate may predict poor renal prognosis, but the prognosis of the normoalbuminuric renally insufficient diabetic patient remains controversial. In addition to the measurement of urinary albumin excretion, biomarker studies to detect diabetic nephropathy more specifically at the early stage have been performed worldwide. There is a growing body of evidence for remission and/or regression of diabetic nephropathy, which may be an indicator for cardiovascular and renal risk reduction. Deeper insights into the pathological characteristics as well as the clinical impact of albuminuria on renal and cardiovascular outcome are required.

Association of two glyoxalase I gene polymorphisms with nephropathy and retinopathy in Type 2 diabetes.

Glyoxalase I (GLO1), which is the major enzyme that catalyzes the metabolism of methylglyoxal (MG), may play an important role in the pathogenesis of diabetic microvascular complications. To investigate whether the C-7T and A419C polymorphisms of the GLO1 gene are associated with nephropathy and retinopathy in Chinese Type 2 diabetic patients. A total of 364 Type 2 diabetic patients and 301 healthy controls were enroled in the study. Diabetic microvascular complications were determined by urinary albumin excretion measurements and ophthalmological examinations. Genetic analyses were performed using either Taqman PCR or direct sequencing. The effect of C-7T polymorphism on promoter activity was measured by reporter gene assays. The albumin/ creatinine ratio (ACR) and prevalence of nephropathy and retinopathy were significantly higher in diabetic patients with GLO1 -7CC genotype than in patients with -7CT and -7TT genotypes (p=0.02, p=0.02, and p=0.04, respectively). The - 7CC genotype is independently associated with ACR (β=0.13, p=0.01) and the risk for retinopathy [odds ratio (OR): 2.30, 95% confidence interval (CI): 1.25-4.24, p<0.01]. The luciferase activity of the -7T promoter was higher than that of the -7C promoter (13.2±0.2 vs 11.7±0.8, p=0.04). No differences were found between ACR and the prevalence of nephropathy and retinopathy for A419C polymorphism in Type 2 diabetic patients. GLO1 C-7T polymorphism alters promoter activity and confers susceptibility to nephropathy and retinopathy to Type 2 diabetic patients.

Reproducibility of albuminuria in type 2 diabetic subjects. Findings from the Renal Insufficiency And Cardiovascular Events (RIACE) study

Measurement of urinary albumin excretion (UAE) shows important intra-individual variability suggesting the need for multiple assessments. This study aimed at investigating the reproducibility of UAE in type 2 diabetes. UAE was obtained from two to three samples collected in a 3- to 6-month period from 4062 of the 15 773 type 2 diabetic subjects participating in the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicentre Study in 2007-08. UAE was assessed as albumin excretion rate (AER) in 24-h urine collections from 833 subjects and albumin:creatinine ratio (A/C) in early-morning urine samples from 3229 patients. Albuminuria was measured by immunonephelometry or immunoturbidimetry. The median coefficient of variation (CV) was 32.5% (interquartile range: 14.3-58.9). Concordance rate between a single UAE and the geometric mean of multiple measurements was 94.6% for normoalbuminuria, 83.5% for microalbuminuria, 91.1% for macroalbuminuria and 90.6% for albuminuria (micro + macro). CV was significantly higher (P < 0.01) for AER measurement than for A/C and with immunoturbidimetry than with immunonephelometry, whereas concordance rates were similar between the two modalities of urine collection and the two assay methods. Receiver-operating characteristic (ROC) plots demonstrated a good performance of single UAE in predicting the geometric mean of multiple measures at the cut-off level of both microalbuminuria (ROC(AUC) 0.926; 95% confidence interval: 0.915-0.937) and macroalbuminuria (ROC(AUC) 0.950; 95% confidence interval: 0.927-0.973). Data from this large cohort indicate that, in type 2 diabetic subjects, a single UAE value, thought to be encumbered with high intra-individual variability, is an accurate predictor of nephropathy stage for clinical and epidemiological purposes.

A population-based survey of Chronic REnal Disease In Turkey--the CREDIT study

Background. Chronic kidney disease (CKD) is a growing health problem worldwide that leads to end-stage kidney failure and cardiovascular complications. We aimed to determine the prevalence of CKD in Turkey, and to evaluate relationships between CKD and cardiovascular risk factors in a population-based survey.Methods. Medical data were collected through home visits and interviews. Serum creatinine, blood glucose, total cholesterol, triglycerides, HDL, LDL and uric acid were determined from 12-h fasting blood samples, and spot urine tests were performed for subjects who gave consent to laboratory evaluation.Results. A total of 10 872 participants were included in the study. The final analysis was performed on 10 748 subjects (mean age 40.5 ± 16.3 years; 55.7% women) and excluded 124 pregnant women. A low glomerular filtration rate (GFR) (< 60 mL/min/1.73 m2) was present in 5.2% of the subjects who were evaluated for GFR, while microalbuminuria and macroalbuminuria were observed in 10.2% and 2% of the subjects, respectively. The presence of CKD was assessed in subjects who gave consent for urinary albumin excretion measurement (n = 8765). The overall prevalence of CKD was 15.7%; it was higher in women than men (18.4% vs. 12.8%, P < 0.001) and increased with increasing age of the subjects. The prevalence of hypertension (32.7% in the general population), diabetes (12.7%), dyslipidaemia (76.3%), obesity (20.1%) and metabolic syndrome (31.3%) was significantly higher in subjects with CKD than subjects without CKD (P < 0.001 for all).Conclusions. The prevalence of CKD in Turkey is 15.7%. Cardiovascular risk factors were significantly more prevalent in CKD patients.

Selection on albuminuria enhances the efficacy of screening for cardiovascular risk factors

As many subjects with a cardiovascular (CV) risk factor are undiagnosed, guidelines to prevent cardiovascular disease argue for case finding on those risk factors. Such an approach is, however, labour and cost intensive. An elevated urinary albumin loss is an early marker of vascular damage and is associated with an increased CV risk. As albuminuria is easy to measure, we tested whether a screening approach in which detailed risk factor measurement is done only after selection of subjects with an elevated albuminuria results in a higher yield of subjects at risk. A random sample of the general population as investigated in the Prevention of Renal and Vascular End-Stage Disease study was used. Plasma glucose, blood pressure, serum cholesterol and renal function were measured in an overall random sample of the population, in subgroups according to their urinary albumin concentration (UAC) of one first morning urine void and in subgroups in whom the elevated albuminuria level was confirmed with two 24 h urine collections for measurement of urinary albumin excretion (UAE). In the overall population, the number of subjects with any newly found CV risk factor was higher than the number of subjects already known with any CV risk factor (n = 1331 versus 370; 39.2 versus 10.9%). The prevalence of subjects with any newly diagnosed CV risk factor was higher in the group of 267 subjects with a first morning UAC of ≥ 20 mg/L (61.0%; P < 0.05) compared to the overall population (39.2%). Although the sensitivity of a UAC ≥ 20 mg/L to detect a subject with at least one CV risk factor was relatively low (12%), the specificity was very high (96%). The positive predictive value was 70%. When the elevated UAC could be confirmed in two subsequent 24-h urine collections, the diagnostic yield still further improved. The prevalence of undiagnosed CV risk factors in the general population is much higher than the prevalence of known risk factors. After a selection of subjects with an elevated albuminuria, the relative prevalence of subjects with newly diagnosed CV risk factors increases while the number of subjects to test for presence of CV risk factors is smaller. Such an approach facilitates a more effective and simple strategy for risk factor screening.

First Morning Voids Are More Reliable Than Spot Urine Samples to Assess Microalbuminuria

Measurement of urinary albumin excretion (UAE) in a 24-h collection is the gold standard method to determine the presence of microalbuminuria. We sought to compare more practical alternatives--measurement of urinary albumin concentration (UAC) or albumin:creatinine ratio (ACR)--in a first morning void or in a spot urine sample with this gold standard. We asked 241 participants of a prospective cohort study to make three 24-h urine collections, a first morning void, and a spot urine sample. Regression analysis showed that the ACR in a first morning void best agreed with 24-h UAE. The prevalence of microalbuminuria determined by data from a first morning void (7.5%, whether by UAC or ACR) nearly equaled the prevalence of microalbuminuria determined by 24-h UAE (10.0%), whereas the prevalence was higher when determined by spot urine samples (25.4% for UAC and 22.4% for ACR; both P < 0.001 versus 24-h UAE). The intraindividual coefficients of variation of the ACR in a first morning void and 24-h UAE were similar (19%). Intraindividual coefficients of variations of all other measurements of albuminuria were significantly greater. In conclusion, measurement of albuminuria in a first morning void, preferably as the ACR, is more reliable than a spot urine sample to diagnose and monitor microalbuminuria.