Levels Of Urine Albumin Excretion Research Articles

Periostin deficiency attenuates kidney fibrosis in diabetic nephropathy by improving pancreatic β-cell dysfunction and reducing kidney EMT

Diabetic nephropathy (DN) is associated with kidney fibrosis. A previous study revealed that periostin (POSTN) contributes to kidney fibrosis. This study examined the role of POSTN in DN. The urinary concentrations of POSTN and TNC increased according to the severity of DN in human samples. Streptozotocin (STZ) was administered after unilateral nephrectomy (UNXSTZ) to induce DN in wild-type and Postn-null mice. Four experimental groups were generated: wild-typeham (WT Sham), wild-type UNXSTZ (WT STZ), Postn-null Sham (KO Sham), and Postn-null UNXSTZ (KO STZ). After 20 weeks, the KO STZ group had lower levels of urine albumin excretion, glomerular sclerosis, and interstitial fibrosis than those of the WT STZ group. Additionally, the KO STZ group had lower expression of fibrosis markers, including TNC. The KO STZ group showed better glucose regulation than the WT STZ model. Furthermore, the KO STZ group exhibited significantly preserved pancreatic islet integrity and insulin expression. HK-2 cells were used to observe the aggravation of fibrosis caused by POSTN under TGF-β conditions. We stimulated INS-1 cells with streptozotocin and evaluated the viability of these cells. The anti-POSTN antibody treatment of INS-1 cells with streptozotocin resulted in higher cell viability than that with treatment with streptozotocin alone. The absence of POSTN in DN contributes to renal fibrosis alleviation by improving pancreatic β-cell function. Additionally, there is an association between POSTN and TNC.

Progression of Albuminuria Among Patients with Type 1 Diabetes Mellitus: A Long Term Observational Follow-up Study.

The purpose of the present study was to determine whether patients with DM1 have shown improvement, stabilization or deterioration of their urine albumin excretion levels during a close follow-up. A cohort of 84 patients, 18-76 years of age, a median duration of diabetes of 24 years (1-50 years) and a median follow-up duration of 12 years (1-37 years) were included in the study. Among the 84 patients for whom we had UAE levels at the beginning and by the end of the study, mean glycosylated hemoglobin was statistically significantly decreased during the follow-up period, from 8.02±2.04-7.06±1.05% (p=0.036). Normoalbuminuria was present in 66 patients and remained so in 56 patients while 9 patients progressed to microalbuminuria and one patient to macroalbuminuria by the end of the study. Microalbuminuria was present in 15 patients: regression was observed in 8 patients, and progression in one patient. Regression of macroalbuminuria to microalbuminuria was noted in one patient and to normoalbuminuria was noted in one participant, too. Improvement of glycemic control with close monitoring of DM1 patients together with the appropriate use ACE or AT2 inhibitors and statins, seems to exert nephron-protective potential and to delay or even reverse the presence of micro/macroalbuminuria. This long term follow-up study has demonstrated a statistically significant increase in serum HDLcholesterol levels. The study also revealed that intensively treated diabetes patients may show reductions in serum ALP levels. Whether this finding is related to diabetic nephropathy, NAFLD, or diabetic hepatosclerosis remains to be assessed in future trials.

Medical Nutrition Therapy for Patients with Non–Dialysis-Dependent Chronic Kidney Disease: Barriers and Solutions

Medical Nutrition Therapy for Patients with Non–Dialysis-Dependent Chronic Kidney Disease: Barriers and Solutions

Comparative effectiveness of sitagliptin and vildagliptin in the management of patients with type 2 diabetes mellitus undergoing haemodialysis: an Indian rural tertiary care centre experience

Background: The prevalence of chronic kidney disease is increasing with diabetic nephropathy as the common underlying cause. Although numerous drugs are being used to improve glycaemic control, evidence in patients with diabetic nephropathy is sparse. The aim of the present was to evaluate the effectiveness of sitagliptin or vildagliptin addition on glycaemic control in patients with T2DM undergoing haemodialysis as part of their routine care in a rural tertiary care setting.Methods: Type 2 diabetic patients on maintenance haemodialysis as part of routine care and whose glycaemia was not controlled adequately and prescribed one of the oral gliptins once daily in addition to existing therapy for a period of 24 weeks were included in the present study. Effectiveness was assessed in terms of glycaemic control as measured by the change over time in glycated haemoglobin. Data analysis included glycated haemoglobin, body weight, serum creatinine, urine albumin creatinine ratio and the occurrence of hypoglycaemia.Results: Significant reduction in glycated haemoglobin values were noted after 24 weeks of therapy with gliptins similar to insulin glargine with a small weight loss. There was an insignificant decrease in the serum creatinine and urine albumin excretion levels after treatment with vildagliptin with Vildagliptin producing a slightly higher decrease but there was no correlation with changes in A1c levels. The overall incidence of adverse experiences was low and generally mild in both groups.Conclusions: In a group of Asian Indian patients with diabetic nephropathy due to T2DM undergoing haemodialysis in whom glycaemia was not controlled adequately, addition of gliptins helped to achieve glycaemic control to a similar extent as insulin glargine but with a marginal weight advantage.

Monitoring of patients with type 2 diabetes and nephropathy in a specialized diabetic nephropathy clinic seems to be beneficial

BackgroundThe purpose of this study was to evaluate the outcome of DM2 patients with nephropathy when they are under surveillance of a joined clinic run by endocrinologists & nephrologists. Patients and methodsA cohort of 106 patients with DM2, 42–83 years of age, and eGFR < 60 ml/min/m2 were included. Age, sex, duration of diabetes, duration of attending our clinic, smoking habits, BMI, data regarding ischemic heart disease and induction of hemodialysis, urine albumin excretion (UAE) levels, eGFR (MDRD equation) and values of various biochemical parameters were recorded too. Follow-up period ranged from one to 25 years. Paired samples t-test and non-parametrical Kruskal–Wallis test were used for the analyses of the data. ResultsFifty percent of patients had no further progression, 25.9% improvement, while 24.1% had worsening of the UAE levels. During the follow-up in the joined clinic, there was a smaller than the expected from the medical literature decrease in median eGFR, i.e. 2,3 ml/min/m2 and a statistically significant improvement in glycosylated hemoglobin levels from 8.0% to 7.4% (p = 0.016). Time in years of follow-up in the joined clinic of our hospital appeared to be the most significant factor in the improvement or stabilization against deterioration of the UAE levels (p = 0.018). ConclusionsClose follow-up of DM2 patients with eGFR < 60 ml/min/m2 has resulted in a minor annual eGFR decrease. Monitoring of these patients in a specialized diabetic nephropathy clinic is beneficial for this group of patients for delaying the occurrence of end-stage renal disease.

Abstract 569: Albuminuria, the HDL Proteome, and Prevalent Coronary Artery Calcium in Type 1 Diabetes

Patients with type 1 diabetes (T1D) are at high risk of atherosclerotic cardiovascular disease (CVD). Albuminuria is strongly associated with CVD risk and fully accounts for the excess overall mortality risk in some T1D cohorts. One important contributor might be alterations of the HDL proteome. In the current study, we tested the hypotheses that albuminuria is associated with alterations in the HDL proteome in T1D, and that these alterations are associated with prevalent CVD. We performed a cross-sectional study of 191 Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) participants selected according to levels of urine albumin excretion (67 persistent normoalbuminuria, 64 persistent microalbuminuria, and 60 persistent macroalbuminuria). We used targeted proteomics and isotope dilution tandem-mass spectrometry to quantify the concentration of 47 proteins in HDL. Adjusting for age, sex, DCCT treatment group, duration of diabetes, lipid-lowering medications, renin-angiotensin system inhibitors, smoking, BMI, and HbA1c, and after accounting for multiple comparisons, six proteins in HDL were significantly associated with albuminuria (2 increased and 4 decreased). For example, compared to normoalbuminuria, macroalbuminuria was associated with 57% and 177% higher AMBP ( P =0.0003) and PTGDS ( P =0.0006), respectively, and 28% and 27% lower PON1 ( P =0.002) and PON3 ( P =0.008), respectively. Furthermore, PON1 and PON3 in HDL were strongly and negatively associated with the presence of coronary artery calcium, with odds ratios per 1-SD difference of 0.63 (0.43-0.92, 95% CI, P =0.02) for PON1 and 0.59 (0.40-0.87, 95% CI, P =0.008) for PON3. Our observations indicate that the HDL proteome is remodeled in albuminuric patients with T1D, and that these alterations in HDL’s protein cargo may mediate, in part, the relationship of albuminuria with CVD. Because PON1 and PON3 are anti-atherogenic in hypercholesterolemic mice, our data suggest that low levels of PON1 and PON3 in HDL increase the risk of atherosclerosis in diabetic humans. In future studies, it will be important to determine whether reductions of PON1 and PON3 in HDL predict the risk of future CVD in subjects with T1D.

Urine Albumin/Creatinine Ratio Below 30mg/g is a Predictor of Incident Hypertension and Cardiovascular Mortality.

BackgroundMicroalbuminuria is associated with cardiovascular disease (CVD) mortality, but whether lower levels of urine albumin excretion similarly predict CVD is uncertain. We investigated associations between urine albumin:creatinine ratio (UACR) <30 mg/g, and incident hypertension, incident diabetes mellitus, and all‐cause and CVD mortality, during a maximum of 11 years of follow‐up.Methods and ResultsIndividuals (37 091) in a health screening program between 2002 and 2012 with baseline measurements of UACR were studied. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for incident hypertension, incident diabetes mellitus, and mortality outcomes (lowest UACR quartile as reference) at follow‐up. For linear risk trends, the quartile rank was used as a continuous variable in regression models. Nine‐hundred sixty‐three cases of incident hypertension, 511 cases of incident diabetes mellitus, and 349 deaths occurred during follow‐up. In the fully adjusted models, there was a significant HR for the association between UACR and incident hypertension (highest UACR quartile HR 1.95 [95% CI 1.51, 2.53], P‐value for trend across UACR quartiles P<0.001). In contrast, the association between UACR and incident diabetes mellitus was not significant (highest UACR quartile, HR 1.15 [95% CI 0.79, 1.66], P‐value for trend P=0.20). For CVD mortality, with increasing UACR quartiles, there was a significant increase in HR across quartiles, P=0.029, (for all‐cause mortality, P=0.078).ConclusionsLow levels of albuminuria, UACR below 30 mg/g, are associated with increased risk of incident hypertension and CVD mortality at follow‐up, but are not associated with increased risk of incident diabetes mellitus.

Linkage disequilibrium analysis reveals an albuminuria risk haplotype containing three missense mutations in the cubilin gene with striking differences among European and African ancestry populations

BackgroundA recent meta-analysis described a variant (p.Ile2984Val) in the cubilin gene (CUBN) that is associated with levels of albuminuria in the general population and in diabetics.MethodsWe implemented a Linkage Disequilibrium (LD) search with data from the 1000 Genomes Project, on African and European population genomic sequences.ResultsWe found that the p.Ile2984Val variation is part of a larger haplotype in European populations and it is almost absent in west Africans. This haplotype contains 19 single nucleotide polymorphisms (SNPs) in very high LD, three of which are missense mutations (p.Leu2153Phe, p.Ile2984Val, p.Glu3002Gly), and two have not been previously reported. Notably, this European haplotype is absent in west African populations, and the frequency of each individual polymorphism differs significantly in Africans.ConclusionsGenotyping of these variants in existing African origin sample sets coupled to measurements of urine albumin excretion levels should reveal which is the most likely functional candidate for albuminuria risk. The unique haplotypic structure of CUBN in different populations may leverage the effort to identify the functional variant and to shed light on evolution of the CUBN gene locus.

Diabetic nephropathy in type 1 diabetes: has the outlook improved since the 1980s?

This edition of Then and Now discusses three papers published in Diabetologia in the 1980s relating to diabetic nephropathy. Two epidemiological papers by Andersen et al (1983; 25:496-501) and Borch-Johnsen et al (1985; 28:590-596) described in graphic detail the ravages of diabetic nephropathy in type 1 diabetes. After 40 years of diabetes, 41% of their cohort had developed persistent proteinuria. The median time from first appearance of proteinuria to death was 7-8 years, the majority dying of uraemia or cardiovascular disease. The third paper, by Mathiesen et al (1984; 26:406-410), identified individuals with microalbuminuria, a much earlier stage of diabetic nephropathy, and analysed the risk of progression to persistent proteinuria at various levels of urine albumin excretion. Since the description of microalbuminuria, clinicians have hoped that earlier identification of individuals at high risk of end-stage kidney disease, coupled with aggressive use of reno-protective therapies, would prevent, or at the very least significantly delay, the development of end-stage renal disease. Recent data suggest that the outlook has indeed improved since the 1980s, at least in some populations. However, we may be delaying rather than preventing the development of microalbuminuria, proteinuria and kidney failure. Whilst a delay of 10 or more years in the appearance of end-stage renal disease is very welcome, further work is needed to understand why rates of chronic kidney disease vary substantially between cohorts and to develop novel therapies.

Production of a new transgenic mouse (Jtmt) that specifically overexpresses the antioxidant metallothionein in endothelial cells

Diabetes mellitus increases the risk for cardiovascular disease due, in part, to hyperglycemia‐induced oxidative stress. To investigate the potential for antioxidant protection of the vasculature, a transgenic mouse (Jtmt) that overexpresses the antioxidant metallothionein (MT) specifically in endothelial cells (EC) was produced. A 16kb transgene consisting of the murine Tie2 promoter and enhancer ligated to the human MTII gene was microinjected into FVB mouse embryos. Five Jtmt(1–5) founder mice were identified by PCR using human MTII primers. Two of these founder mice, Jtmt1 and Jtmt4, have generated numerous transgenic progeny. Further characterization of the Jtmt1 line showed that at 60 days of age heart, kidney and body weights as well as blood glucose, HbA1c, and urine albumin excretion levels were normal. Importantly, MT overexpression in EC in the micro‐ and macrovasculature of kidney, heart, and tail tissues was confirmed by immunohistochemical studies. Ongoing studies are assessing the amount of MT overexpression in renal, hepatic and myocardial tissues by competitive ELISA and Western blot analyses as well as the effect of MT overexpression on EC cytological features by TEM. Future studies include crossing Jtmt1 and OVE26 transgenic diabetic mice in an effort to determine the potential benefits of endothelial‐specific antioxidant protection of the diabetic vasculature.Grant Funding Source: North Dakota Lions Foundation

Relationship between blood inflammatory factor, urinary MCP-1 and urinary albumin excretion rate in type 2 diabetic patients

The different levels and clinical significance of high sensitivity C reactive protein(hs-CRP) , tumor necrosis factor-a ( TNF-α) , erythrocyte sedimentation rate ( ESR) , and urinary monocyte chemoattractant protein-1 (uMCP-1) in 84 type 2 diabetic patients with different urine albumin excretion (UAE) were observed. The results indicated that the levels of hs-CRP,TNF-α,urinary MCP-1 ,and ESR in diabetic patients were significantly higher than those in control group,and the first three indexes increased with the levels of UAE. The results suggest that diabetic nephropathy seems to be correlated with inflammatory reactions. Key words: Diabetic nephropathies; High sensitivity C reactive protein; Tumor necrosis factor a; Monocvte chemoattractant protein-1: Erythrocyte sedimentation rate

Microvascular rarefaction precedes the decline in renal function in the streptozotocin (STZ)‐induced diabetic rat

Diabetic nephropathy is a generalized vasculopathic condition associated with abnormal angiogenesis. The aim of the study was to correlate changes in the 3‐dimensional renal microvasculature density (MV) with changes in renal function and vascular endothelial growth factor (VEGF).The study was performed in male non‐diabetic (ND) or STZ‐induced diabetic (D) Sprague‐Dawley rats followed for 4 (4w) or 12 (12w) weeks. Renal MV density was quantified ex vivo using a 3D micro‐CT reconstruction of the kidney. Urine albumin excretion (UAE) and renal VEGF levels were measured by ELISA and glomerular filtration rate (GFR) by 125I‐[iothalamate] clearance. 4w of diabetes was associated with a 34% reduction in MV density, no changes in UAE and augmented renal VEGF levels. At 12w, the reduction in MV density was even more pronounced (75%) and correlated with increased UAE; however, renal VEGF remained unchanged. ND D P value 4w 12w 4w 12w MV density/cm2 69.3±8.8 210±40.2* 45.5±12.3 52.7±15.6# *0.05 vs ND at 4w #0.05 vs ND at 12w $0.05 vs D at 4w UAE (mg/day) 1.2±0.2 2.3±1.3 2.9±0.3* 6.0±1.0#,$ GFR (ml/min/kidney) 1.4±0.2 1.3±0.2 2.1±0.3* 2.2±0.4# VEGF (ml/min/kidney) 1.5±0.07 1.7±0.2 1.9±0.2* 1.7±0.2 The study suggests a novel concept of MV rarefaction preceding the decline in renal function in STZ‐induced diabetic rats. This effect may be related to changes in renal VEGF bioavailability with progression of diabetic renal injury.

Early renal and vascular changes in ADPKD patients with low-grade albumin excretion and normal renal function

Autosomal dominant polycystic kidney disease (ADPKD) shows an increase in both urine monocyte chemoattractant protein-1 (MCP-1) and carotid intima-media thickness (CIMT) before changes in serum creatinine concentration. Although microalbuminuria is an index of disease progression, data on whether renal alterations and vascular remodelling are already present at normal or minimally increased levels of urine albumin excretion in early stages of the disease are lacking. Forty-eight ADPKD patients (24.8 +/- 0.8 years) with normal renal function (MDRD 108.1 +/- 3.1 ml/min) and 21 age-matched controls were studied in a cross-sectional study. The urine albumin/creatinine ratio (UACR) above the upper range of controls (6.8 mg/g) was taken as the predictor of renal alterations and vascular remodelling. Urine MCP-1, MCP-1 fractional excretion (FE(MCP-1)), endothelial-dependent vascular relaxation (EDVR), aortic pulse-wave velocity (Ao-PWV) and CIMT were chosen as biological markers. No differences between ADPKD with UACR <or=6.8 mg/g and controls were observed in urine MCP-1 (77.7 +/- 13.9 versus 57.8 +/- 6.3 ng/g), FE(MCP-1) (91 +/- 19 versus 74 +/- 8%) and CIMT (0.47 +/- 0.06 versus 0.44 +/- 0.07 mm), respectively. Conversely, ADPKD with UACR >6.8 mg/g showed values that were different from the two other groups. In addition, patients with UACR >6.8 and <20 mg/g showed greater values for urine MCP-1, FE(MCP-1) and CIMT (131.8 +/- 21.7 ng/g, 159 +/- 31% and 0.55 +/- 0.05 mm, respectively), as compared with patients with UACR <or=6.8 mg/g. The same pattern was found in a subset of normotensive ADPKD patients. No differences were found in EDVR and Ao-PWV. In young ADPKD patients, normal levels of UACR suggest that renal interstitium is comparable to that in healthy subjects and indicate an absence of subtle atherosclerotic changes in the carotid arteries. Likewise, early renal and vascular changes may be present at UACR below the levels defined as microalbuminuria.

Importance of Low-Grade Albuminuria

The well-described association between chronic kidney disease and cardiovascular disease is typically thought to originate from loss of renal function, as estimated by the glomerular filtration rate. However, recent data suggest that urinary albumin excretion has an important role in this association. Albuminuria is a marker of underlying vascular dysfunction and has been correlated with structural and functional integrity of the vasculature. Although the traditional upper limit of normal daily albumin excretion has been 30 mg/d, recent epidemiologic data suggest that levels in the general population are actually much lower. Further, within this range of low-grade albuminuria (LGA), increasing excretion rates are associated with increasing risk of cardiovascular disease. This association is independent of renal function, and in the earliest stages of chronic kidney disease, LGA seems to be a more important determinant than the glomerular filtration rate. This emerging association underscores the complexity of albumin excretion, in which subtle changes in albumin excretion reflect widespread vascular processes. Using the key words albuminuria, low-grade albuminuria, and microalbuminuria in a PubMed search of literature from January 1, 1995, to February 29, 2008, this review summarizes the most recent data on LGA and its association with cardiovascular and renal disease.

Abstract 385: Endothelial Vasomotor Dysfunction in Brachial Artery Predicts Early Renal Dysfunction in Patients with Coronary Artery Disease

There is an intimate relation between coronary artery disease (CAD) and chronic kidney disease. Endothelial function in renal vasculature plays an important role in regulation of renal hemodynamics in normal and pathological states. Endothelial dysfunction is a systemic disorder, and there may be possible relation of endothelial function between brachial artery and renal vasculature. We examined whether endothelial vasomotor dysfunction in brachial artery may predict early renal dysfunction in patients with CAD. Methods and Results: Flow-mediated endothelium-dependent dilation (FMD, % increase in diameter from baseline) in brachial artery was measured by ultrasound in 558 consecutive patients with CAD. Patients with advanced renal failure (glomerular filtration rate [GFR] &lt; 50 mL/min/1.73 m 2 ) were not included. A subgroup of 402 patients with normal renal function at the enrollment (normo-albuminuria [&lt; 30 mg/day] and normal serum creatinine levels [&lt; 1.0 mg/dL]) were prospectively followed up for 1 year. The end point was the occurrence of either microalbuminuria (≥ 30 mg/day) or serum creatinine levels &gt; 1.5 mg/dL. At the enrollment, patients with impaired FMD (≤ 4.4%, 50 th percentile of the distribution in all study patients) had higher levels of urine albumin excretion (24 ± 2 vs. 17 ± 1 mg/day, p &lt; 0.05) and serum creatinine (0.8 ± 0.1 vs. 0.5 ± 0.1 mg/dL, p &lt;0.05), and lower GFR (72 ± 3 vs. 80 ± 2 mL/min/1.73 m 2 , p &lt; 0.05) than patients with preserved FMD (&gt; 4.4%). Over 1 year follow up, 30 (17%) patients with impaired FMD had an end point (12 patients, increase in serum creatinine levels; 18, microalbuminuria), while 15 (6.7%) patients with preserved FMD had an end point (6, increase in serum creatinine levels; 9, microalbuminuria) (p &lt; 0.01). Using multivariate logistic analysis, impaired FMD was the most strongest predictor of occurrence of either increase in serum creatinine levels or microalbuminuria during 1 year follow up (OR; 2.8, 95% CI; 1.5 – 5.5, p &lt; 0.01) among covariates including hypertension, diabetes, age. Conclusion: Endothelial vasomotor dysfunction in brachial artery is an independent predictor of development of early renal dysfunction in patients with CAD. Measurement of FMD is useful for stratification of risk for future renal dysfunction.

Metabolic Risk Factors and Markers of Cardiovascular and Renal Damage in Overweight Subjects

The prevalence of overweight and obesity in the United States has dramatically increased. Obesity clusters with a variety of hemodynamic and metabolic disturbances that increase the risk of cardiovascular disease. In this study we evaluated whether overweight subjects with hypertension also manifest hemodynamic and metabolic abnormalities compared with individuals of normal weight. In a cohort of 129 patients with essential hypertension we measured the relationship between body mass index (BMI), blood pressure (BP), insulin sensitivity, lipid profile, and markers of organ damage including thickness of the carotid artery (IMT) and urine albumin excretion (UAE). A total of 41 normotensive, age-matched, healthy individuals served as control subjects. Hypertensive individuals showed higher levels of serum triglycerides, insulin area-under-the-curve (AUC), UAE, and greater IMT than normotensive subjects. Overweight hypertensive subjects showed higher levels of serum triglycerides, LDL cholesterol, glucose AUC, insulin AUC, UAE, and IMT than hypertensive subjects with normal body weight (BMI <25). Night-time systolic BP was higher and night-time fall in BP was lower among overweight than among normal-weight hypertensive patients. Simple regression analysis showed that BMI was correlated with age, UAE, BP, insulin and glucose AUC, serum triglycerides, cholesterol, and IMT in hypertensive subjects. However multiple regression analyses showed that BMI significantly correlated only with UAE. The study results show that increased body weight clusters with a variety of hemodynamic and metabolic abnormalities in hypertensive subjects. However multiple regression analyses showed a significant correlation only between BMI and UAE, a marker and predictor of cardiovascular and renal disease.

Screening for Kidney Disease in Adults With Diabetes

Screening programs are generally aimed at conditions with a substantial public health impact and which benefit from early interventions. Chronic kidney disease (CKD), especially CKD attributed to diabetes, certainly fits this criterion. Diabetes remains the leading cause of end-stage renal disease (ESRD) in most countries in the world, accounting for 40–50% of incident ESRD cases (1–4). Due to the epidemic of diabetes secondary to obesity and the aging of the population, rates of kidney disease secondary to diabetes are on the rise. Within the past 2 decades, the incidence of ESRD secondary to diabetes in the U.S. has doubled while the prevalence of CKD among general Medicare patients diagnosed with both diabetes and hypertension has increased fourfold (1). Annual expenditures are highest for patients with ESRD secondary to diabetes compared with all other primary ESRD diagnoses (1). Thus, the epidemic of diabetes will certainly drive up health care costs for ESRD, which in the U.S. are projected to exceed $28 billion by 2010 (5). To prevent ESRD in individuals with diabetes, we must first do an adequate job of screening and detecting CKD. Unfortunately, the enormous burden of CKD remains undetected among adults with diabetes. The early detection of CKD among patients with diabetes has primarily involved the measurement of urinary albumin excretion. A timed urine collection confirmed on at least two of three occasions over a 6-month period was the initial method of screening. The acceptance of the use of the albumin (in milligrams)-to-creatinine (in grams) ratio measured in a random urine specimen has greatly expanded screening efforts due to the test’s convenience for both patients and physicians. Persistently increased levels of urine albumin excretion ≥30–299 mg/24 h or spot urine albumin-to-creatinine ratios ≥30–299 mg/g indicate the presence of microalbuminuria while urine albumin excretion levels higher than …