Incidence Of Macroalbuminuria Research Articles

Associations of Kidney Tubular Biomarkers With Incident Macroalbuminuria and Sustained Low eGFR in DCCT/EDIC.

Tubulointerstitial injury contributes to diabetic kidney disease (DKD) progression. We tested tubular biomarker associations with DKD development in type 1 diabetes (T1D). We performed a case-cohort study examining associations of tubular biomarkers, measured across seven time points spanning ∼30 years, with incident macroalbuminuria ("severely elevated albuminuria," urinary albumin excretion rate (AER) ≥300 mg/day) and sustained low estimated glomerular filtration rate (eGFR) (persistent eGFR <60 mL/min/1.73 m2) in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study. Biomarkers included KIM-1 and sTNFR1 in serum/plasma, MCP-1 and EGF in urine, and a composite tubular secretion score reflecting secreted solute clearance. We assessed biomarkers using single values, as mean values from consecutive time points, and as change over consecutive time points, each as time-updated exposures. At baseline, mean diabetes duration was 5.9 years, with mean HbA1c 8.9%, eGFR 125 mL/min/1.73 m2, and AER 16 mg/day. There were 4.8 and 3.5 cases per 1,000 person-years of macroalbuminuria and low eGFR, respectively. Assessed according to single biomarker values, KIM-1 was associated with risk of subsequent macroalbuminuria and low eGFR (hazard ratio [HR] per 20% higher biomarker 1.11 [95% CI 1.06, 1.16] and 1.12 [1.04, 1.21], respectively) and sTNFR1 was associated with subsequent macroalbuminuria (1.14 [1.03, 1.25]). Mean KIM-1 and EGF-to-MCP-1 ratio were associated with subsequent low eGFR. In slope analyses, increases in KIM-1 and sTNFR1 were associated with subsequent macroalbuminuria (per 20% biomarker increase, HR 1.81 [1.40, 2.34] and 1.95 [1.18, 3.21]) and low eGFR (2.26 [1.65, 3.09] and 2.94 [1.39, 6.23]). Serial KIM-1 and sTNFR1 are associated with incident macroalbuminuria and sustained low eGFR in T1D.

Correction to: Efpeglenatide and Clinical Outcomes With and Without Concomitant Sodium-Glucose Cotransporter-2 Inhibition Use in Type 2 Diabetes: Exploratory Analysis of the AMPLITUDE-O Trial.

HomeCirculationVol. 147, No. 23Correction to: Efpeglenatide and Clinical Outcomes With and Without Concomitant Sodium-Glucose Cotransporter-2 Inhibition Use in Type 2 Diabetes: Exploratory Analysis of the AMPLITUDE-O Trial Free AccessCorrectionPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessCorrectionPDF/EPUBCorrection to: Efpeglenatide and Clinical Outcomes With and Without Concomitant Sodium-Glucose Cotransporter-2 Inhibition Use in Type 2 Diabetes: Exploratory Analysis of the AMPLITUDE-O Trial Originally published5 Jun 2023https://doi.org/10.1161/CIR.0000000000001157Circulation. 2023;147:e720This article corrects the followingEfpeglenatide and Clinical Outcomes With and Without Concomitant Sodium-Glucose Cotransporter-2 Inhibition Use in Type 2 Diabetes: Exploratory Analysis of the AMPLITUDE-O TrialIn the article by Lam et al, “Efpeglenatide and Clinical Outcomes With and Without Concomitant Sodium-Glucose Cotransporter-2 Inhibition Use in Type 2 Diabetes: Exploratory Analysis of the AMPLITUDE-O Trial,” which was first published on November 14, 2021, and appeared in the February 22, 2022, issue of the journal (Circulation. 2022;145:565–574. doi: 10.1161/CIRCULATIONAHA.121.057934), a correction is needed.The authors determined that there was a formatting error regarding the second half of panel C of the Figure. The absence of an interaction noted for the renal outcome is unchanged, as is our acknowledgment that limited number of events within the subgroup of baseline SGLT2 inhibitor users may have precluded detection of modest interactions.Corrected Figure panel C1 showing hazards plots for the cumulative risk of composite renal outcome of incident macroalbuminuria, a decline in estimated glomerular filtration rate (eGFR) by ≥40% for ≥30 days, renal replacement therapy for ≥90 days, or an eGFR <15 mL·min−1·1.73 m−2 for ≥30 days; among patients receiving and not receiving baseline SGLT2 inhibitors. HR indicates hazard ratio, SGLT2 indicates sodium-glucose cotransporter-2.The Figure has been updated and the authors have stated that this unintended mistake does not affect any results reported or conclusions drawn in their manuscript.The article has been updated and the corrected article is available at https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.057934.Download figureDownload PowerPointFootnotesCirculation is available at www.ahajournals.org/journal/circ Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesEfpeglenatide and Clinical Outcomes With and Without Concomitant Sodium-Glucose Cotransporter-2 Inhibition Use in Type 2 Diabetes: Exploratory Analysis of the AMPLITUDE-O TrialCarolyn S.P. Lam, et al. Circulation. 2022;145:565-574 June 6, 2023Vol 147, Issue 23 Advertisement Article InformationMetrics © 2023 American Heart Association, Inc.https://doi.org/10.1161/CIR.0000000000001157PMID: 37276255 Originally publishedJune 5, 2023 PDF download Advertisement

Kidney outcomes associated with sodium-glucose cotransporter 2 inhibitors versus glucagon-like peptide 1 receptor agonists: A real-world population-based analysis.

SummaryBackgroundKidney benefits have been demonstrated for both sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) compared with placebo in patients with type 2 diabetes. This study aimed to compare the impacts of SGLT2i and GLP1RA on the trend of estimated glomerular filtration rate (eGFR) and other kidney outcomes.MethodsUsing a real-world population-based database, the Hong Kong Hospital Authority (HA) database, of patients with type 2 diabetes between January 2008 and December 2020, patients started on SGLT2i were compared with those started on GLP1RA, with one-to-one propensity-score matching. Primary outcome was a composite of sustained ≥50% eGFR decline, end-stage kidney disease (ESKD), incident macroalbuminuria and kidney-related mortality. Secondary outcome was the rate of eGFR decline.FindingsA total of 2551 SGLT2i and 2551 GLP1RA new users were analyzed. At baseline, mean age was 56·2 years, with mean eGFR 78·0 mL/min/1·73m2 and 11·9% having macroalbuminuria. Upon median follow-up of 13 months (IQR: 5-27), SGLT2i users had a lower risk of composite kidney outcomes (HR=0·77, 95%CI 0·62–0·96, p = 0·02), mainly driven by a reduction in ESKD (HR=0·53, p = 0·01). SGLT2i users also tended to have a lower risk of incident macroalbuminuria (HR=0·74, p = 0·05). Subgroup analyses of the benefits of SGLT2i use on composite kidney outcomes did not reveal interaction by age, sex, baseline eGFR/albuminuria status, hemoglobin A1c (HbA1c) and renin-angiotensin-system inhibitor use. Furthermore, SGLT2i users had a slower eGFR decline than GLP1RA users (SGLT2i: -1·19 mL/min/1·73m2/year, GLP1RA: -1·95 mL/min/1·73m2/year, p < 0·01).InterpretationOur results suggest that SGLT2i might be superior to GLP1RA in reducing kidney outcomes among patients with type 2 diabetes. Future trials are needed to corroborate our findings.FundingNone.

Abstract MP14: White Matter Hyperintensity Progression, Macroalbuminuria, and Intensive Glycemic Control in Diabetics

Introduction: White matter hyperintensity (WMH) is associated with a higher risk of stroke, dementia, and depression. Prior research has suggested that renal impairment and diabetes may predispose to the development of WMH. Here, we evaluated the association between WMH volume (WMHv), macroalbuminuria, and glycemic control in a cohort of diabetic patients. Methods: This is a secondary analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) dataset. The primary outcome is WMH progression in mL, evaluated by fitting linear regression to WMHv on the month 40 MRI and including the WMHv on the baseline MRI in the model. The primary predictors were incident macroalbuminuria, defined as new onset urinary albumin &gt;300mg/day, and the ACCORD glucose randomization arm. Results: We included 502 patients. The mean (SD) WMHv at baseline was 2.1 (3.9) mL and at month 40 was 3.6 (5.7) mL. Twenty-three patients (4.6%) developed macroalbuminuria during the study period, who had a higher mean WMH progression (2.9 vs. 1.4 mL, p=0.012). In a linear regression model adjusted for mean systolic blood pressure during follow-up, macroalbuminuria was a significant predictor of WMH progression (Beta 1.20, 95% CI 0.17-2.22, p=0.022). In the same model, the interaction term between glucose randomization arm and macroalbuminuria was highly significant (Beta 3.38, 95% CI 1.20-5.57, p=0.003). The predicted follow-up WMHv for the interaction term are in Figure 1, showing that macroalbuminuria with intensive glycated hemoglobin reduction (goal A1c&lt;6%) was associated with the most WMH progression. Conclusion: In diabetic patients, the development of macroalbuminuria was associated with WMH progression over 40 months, although only in patients assigned to intensive glycemic control. This finding is consistent with the adverse events seen in ACCORD with intensive glycemic control.

Microvascular and Cardiovascular Outcomes According to Renal Function in Patients Treated With Once-Weekly Exenatide: Insights From the EXSCEL Trial.

To evaluate the impact of once-weekly exenatide (EQW) on microvascular and cardiovascular (CV) outcomes by baseline renal function in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL). Least squares mean difference (LSMD) in estimated glomerular filtration rate (eGFR) from baseline between the EQW and placebo groups was calculated for 13,844 participants. Cox regression models were used to estimate effects by group on incident macroalbuminuria, retinopathy, and major adverse CV events (MACE). Interval-censored time-to-event models estimated effects on renal composite 1 (40% eGFR decline, renal replacement, or renal death) and renal composite 2 (composite 1 variables plus macroalbuminuria). EQW did not change eGFR significantly (LSMD 0.21 mL/min/1.73 m2 [95% CI -0.27 to 0.70]). Macroalbuminuria occurred in 2.2% of patients in the EQW group and in 2.5% of those in the placebo group (hazard ratio [HR] 0.87 [95% CI 0.70-1.07]). Neither renal composite was reduced with EQW in unadjusted analyses, but renal composite 2 was reduced after adjustment (HR 0.85 [95% CI 0.74-0.98]). Retinopathy rates did not differ by treatment group or in the HbA1c-lowering or prior retinopathy subgroups. CV outcomes in those with eGFR <60 mL/min/1.73 m2 did not differ by group. Those with eGFR ≥60 mL/min/1.73 m2 had nominal risk reductions for MACE, all-cause mortality, and CV death, but interactions by renal function group were significant for only stroke (HR 0.74 [95% CI 0.58-0.93]; P for interaction = 0.035) and CV death (HR 1.08 [95% CI 0.85-1.38]; P for interaction = 0.031). EQW had no impact on unadjusted retinopathy or renal outcomes. CV risk was modestly reduced only in those with eGFR ≥60 mL/min/1.73 m2 in analyses unadjusted for multiplicity.

536-P: Association between Uric Acid Level and Incidence of Macroalbuminuria in People with Type 2 Diabetes Mellitus: A 4.5-Year Cohort Study

Background: Using animal models and molecular biology researches, hyperuricemia has been shown to instruct renal arteriolopathy, arterial hypertension, and microvascular injury involving the renin-angiotensin system and resulting in renal function impairment. Nevertheless, the association between uric acid levels and the development of macroalbuminuria has been under-investigated in people with type 2 diabetes mellitus. Methods: Patients with type 2 diabetes and regular outpatient visits were recruited from the Puli Branch of the Taichung Veterans General Hospital in Taiwan since January 2014. Demographics, lifestyle features, and medical history were gathered by well-trained interviewers. All participants underwent comprehensive physical examinations, including a biochemical assay of venous blood specimens and urine samples after an 8-hour overnight fast. Participants were followed until June 2018. The primary outcome was the macroalbuminuria incidence. Univariate and multivariate Cox regression analysis were employed to explore the relation between uric acid and incident macroalbuminuria. Uric acid cutoffs for incident macroalbuminuria were determined with the receiver operator characteristic curve. Results: We included 247 qualified subjects (mean age: 64.78 years old [standard deviation=11.29 years]; 138 [55.87%] men). During a 4.5-year follow-up duration, 20 subjects with incident macroalbuminuria were recognized. Serum uric acid was significantly associated with an increased risk of incident macroalbuminuria (adjusted hazard ratio=2.39; 95% confidence interval: 1.53-3.75; p&amp;lt;0.001) with potential confounders adjustment. The uric acid cutoff point was 6.9 mg/dL (area under the curve 0.708, sensitivity 60.0%, specificity 84.58%) for incident macroalbuminuria. Conclusions: Serum uric acid was associated with incident macroalbuminuria among people with type 2 diabetes. Disclosure Y. Lai: None.

Risk Factors for Kidney Disease in Type 1 Diabetes.

In type 1 diabetes (T1D), the course of microalbuminuria is unpredictable and timing of glomerular filtration rate (GFR) loss is uncertain. Thus, there is a need to identify the risk factors associated with the development of more advanced stages of kidney disease through large, long-term systematic analysis. Multivariable Cox proportional hazards models assessed the association of baseline and time-dependent glycemic and nonglycemic risk factors for incident macroalbuminuria and reduced estimated GFR (eGFR; defined as <60 mL/min/1.73 m2) over a mean of 27 years in the Diabetes Control and Complications Trial (DCCT) cohort. Higher mean HbA1c (hazard ratio [HR] 1.969 per 1% higher level [95% CI 1.671-2.319]) and male sex (HR 2.767 [95% CI 1.951-3.923]) were the most significant factors independently associated with incident macroalbuminuria, whereas higher mean triglycerides, higher pulse, higher systolic blood pressure (BP), longer diabetes duration, higher current HbA1c, and lower mean weight had lower magnitude associations. For incident reduced eGFR, higher mean HbA1c (HR 1.952 per 1% higher level [95% CI 1.714-2.223]) followed by higher mean triglycerides, older age, and higher systolic BP were the most significant factors. Although several risk factors associated with macroalbuminuria and reduced eGFR were identified, higher mean glycemic exposure was the strongest determinant of kidney disease among the modifiable risk factors. These findings may inform targeted clinical strategies for the frequency of screening, prevention, and treatment of kidney disease in T1D.

Long-Term Effects of Intensive Glycemic and Blood Pressure Control and Fenofibrate Use on Kidney Outcomes.

In people with type 2 diabetes, aggressive control of glycemia, BP, and lipids have resulted in conflicting short-term (<5 years) kidney outcomes. We aimed to determine the long-term kidney effects of these interventions. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) was a multifactorial intervention study in people with type 2 diabetes at high risk for cardiovascular disease (n=10,251), to examine the effects of intensive glycemic control (hemoglobin A1c <6.0% versus 7%-7.9%), BP control (systolic BP <120 mm Hg versus <140 mm Hg) or fenofibrate versus placebo added to simvastatin on cardiovascular events and death. The glycemia trial lasted 3.7 years and participants were followed for another 6.5 years in ACCORDION, the ACCORD Follow-On Study. The post hoc primary composite kidney outcome was defined as incident macroalbuminuria, creatinine doubling, need for dialysis, or death by any cause. Cox proportional hazards regression estimated the effect of each intervention on the composite outcome and individual components. In secondary outcome analyses, competing risk regression was used to account for the risk of death in incident kidney outcomes. Analyses were adjusted for sociodemographics, randomization groups, and clinical factors. There were 988 cases of incident macroalbuminuria, 954 with doubling of creatinine, 351 requiring dialysis, and 1905 deaths. Hazard ratios (HRs) for the composite outcome with intensive glycemic, BP control, and fenofibrate use compared with standard therapy were 0.92 (95% confidence interval [95% CI], 0.86 to 0.98), 1.16 (95% CI, 1.05 to 1.28), and 1.16 (95% CI, 1.06 to 1.27). Multivariable, secondary outcome analyses showed that in the glycemia trial, only macroalbuminuria was significantly decreased (HR, 0.68; 95% CI, 0.59 to 0.77). In the BP and lipid trials, only creatinine doubling was affected (HR, 1.64; 95% CI, 1.30 to 2.06 and HR, 2.00; 95% CI, 1.61 to 2.49, respectively). In people with type 2 diabetes at high risk for cardiovascular disease, intensive glycemic control may result in a long-term reduction in macroalbuminuria; however, intensive BP control and fenofibrates may increase the risk for adverse kidney events.

Galectin-3 is independently associated with progression of nephropathy in type 2 diabetes mellitus.

Galectin-3 has been implicated in cardiac and renal fibrosis and serves as a prognostic clinical indicator in heart failure. The aim of the present study was to evaluate whether serum galectin-3 level is associated with progressive kidney disease in type 2 diabetes. Galectin-3 was measured in baseline samples by ELISA in 1320 participants with type 2 diabetes with eGFR ≥30mlmin-1 1.73m-2. The primary outcome was defined as doubling of serum creatinine and/or initiation of renal replacement therapy during follow-up. The secondary outcome was progression to macroalbuminuria in individuals with normo- or microalbuminuria at baseline. Serum galectin-3 levels were significantly increased in a random subgroup of 270 type 2 diabetic individuals with eGFR >60mlmin-1 1.73m-2 compared with an age- and sex-matched non-diabetic control group (7.58 ± 2.29ng/ml vs 6.10 ± 1.91ng/ml, respectively, p < 0.01). In the whole diabetic cohort, after a mean follow-up of 9years, galectin-3 was independently associated with doubling of serum creatinine (HR 1.19; 95% CI 1.14, 1.24, p < 0.001) and incident macroalbuminuria (HR 1.20; 95% CI 1.12, 1.30, p < 0.001), even after adjusting for traditional risk factors, baseline eGFR and albuminuria status. Individuals with galectin-3 levels in the highest quartile had a fourfold risk of renal function loss and threefold risk of incident macroalbuminuria. Serum galectin-3 was independently associated with progressive renal disease in type 2 diabetes. Further mechanistic studies are warranted to determine whether galectin-3 is simply a disease biomarker or is also a mediator of the development and progression of diabetic nephropathy.

High levels of AGE-LDL, and of IgG antibodies reacting with MDA-lysine epitopes expressed by oxLDL and MDA-LDL in circulating immune complexes predict macroalbuminuria in patients with type 2 diabetes

BackgroundCirculating immune complexes (IC) containing modified forms of LDL (mLDL) are strongly pro-inflammatory and when present in high levels are associated with the development of diabetic complications. ObjectiveWe investigated whether levels of oxidized LDL (oxLDL), malondialdehyde-LDL (MDA-LDL) and advanced glycation end products-LDL (AGE-LDL) as well as IgG and IgM antibodies reacting with MDA-lysine epitopes expressed by oxLDL and MDA-LDL isolated from circulating IC were associated with progression to macroalbuminuria in type 2 diabetes (VADT cohort). MethodsLevels of mLDL in IC were measured in 905 patients, a median of two years after entry into the study. Participants were followed for an average of 3.7years for renal outcomes. Generalized logistic regression models were used to quantify the association of increased levels of biomarkers and development of abnormal albuminuria. Normal, persistent micro- (ACR ≥30), incident micro- (ACR ≥30) and incident macroalbuminuria (ACR ≥300) were the outcomes of interest. Results and conclusionsPatients with macro (n=78) or non-persistent microalbuminuria (n=81) at baseline were excluded. Odds ratios for endpoints in relation to high versus low (defined using a median split) biomarker levels are found in Fig. 1. Our study demonstrates that high levels of AGE-LDL as well as of IgG antibodies (but not IgM antibodies) reacting with MDA-LDL lysine epitopes in circulating IC predict the development of macroalbuminuria in patients with type 2 diabetes. These data support the pathogenic role of modified LDL IgG antibodies but not the protective role of modified LDL IgM antibodies.

Identifying the determinants of microalbuminuria in obese patients in primary care units: the effects of blood pressure, random plasma glucose and other risk factors.

The objective of this study is to evaluate the demographic characteristics, blood pressure and blood glucose and the other related factors that affect the microalbuminuria levels in the obese patients aged 40 and above who applied to the primary care for medical evaluation. The population of the research, which was a cross-sectional type, comprised obese patients aged 40 and above who had applied to the community health centers in the center of Malatya. A total of 422 obese patients consisting of 116 males and 306 females were included in the research. The anthropometric measurements of the participants were determined, their blood pressures and their random blood glucoses were evaluated, as well. A microalbuminuria measurement was performed in the urine samples taken from the patients using "Nycocard Reader II" device. The incidence of microalbuminuria in patients was found as 31.5%, whereas the incidence of macroalbuminuria was 6.6%. The incidence of microalbuminuria in female patients was 32.7%, while it was 28.4% in male patients; on the other hand, the incidence of macroalbuminuria in female patients was found as 6.8%, whereas this percentage was determined as 7.8 in male patients (p > 0.05). The probability of the incidence of microalbuminuria increased 2.8 times more in those with the diastolic blood pressure of 90 mmHg and above when compared to those without it (GA: 1.79-4.56), whereas the incidence increased 3.2 times more in those with the random blood glucose of 200 mg/l and above (GA: 1.32-7.84) (p < 0.001). In our study, among the variables predicting the microalbuminuria in obese patients; the cutoff values of the diastolic and systolic blood pressures, the waist circumference were found as >85 mmHg; >130 mmHg; >141 mg/dl, respectively, in male patients and found as >85 mmHg, >114 cm, and 109 cm, respectively, in female patients. The sensitivity and specificity of the tests indicating the cutoff values showed significance (p < 0.05). There was no statistically significant relevance between the microalbumin levels of the obese patients via the anthropometric criteria, except for their waist circumference (p > 0.05). In this study, the blood pressure and blood glucose levels of the patients along with their waist circumference that indicated a central obesity were specified as the determinants of microalbuminuria. While the obese patients are being evaluated in terms of proteinuria, the cutoff values of these variables can be taken into consideration.

Resting heart rate is associated with renal disease outcomes in patients with vascular disease: results of the ONTARGET and TRANSCEND studies.

Resting heart rate (RHR) is associated with cardiovascular disease outcomes in high-risk patients. It is not known whether RHR is predictive of renal outcomes such as albuminuria, end-stage renal disease (ESRD) or doubling of creatinine. We evaluated whether RHR could predict renal endpoints in patients at a high risk of cardiovascular disease. We also tested the effects of RHR at different levels of systolic blood pressure (SBP). We analysed data from 28 757 patients in the ONTARGET and TRANSCEND trials. RHR and SBP were available for a mean of 4.9 ± 0.4 visits (range 3-5) within the first 2 years of the studies. Albuminuria was determined at baseline, at 2 years and at study end. Mean RHR was predictive of incident micro-albuminuria [hazard ratio (HR) for RHR ≥80 vs. <60 beats min(-1) 1.49, 95% confidence interval (CI) 1.29-1.71, P < 0.0001], incident macro-albuminuria (HR 1.84, 95% CI 1.39-2.42, P < 0.0001), doubling of creatinine (HR 1.47, 95% CI 1.00-2.17, P = 0.050) and ESRD (HR 1.78, 95% CI 1.00-3.16, P = 0.050), and the combined renal end-point (HR 1.51, 95% CI 1.32-1.74, P < 0.0001). Associations were robust at SBPs from <120 to ≥150 mmHg, with the lowest risk at a SBP of 130-140 mmHg. Resting heart rate is a potent predictor of these renal outcomes, as well as their combination, in patients with cardiovascular disease. RHR at all SBP levels should be considered as a possible renal disease risk predictor and should be investigated as a treatment target with RHR-reducing agents.

Renal outcomes in patients with type 1 diabetes and macroalbuminuria.

Macroalbuminuria, defined as urine albumin excretion rate (AER)≥300 mg/d, has long been considered a stage of irreversible kidney damage that leads reliably to GFR loss. We examined the long-term renal outcomes of persons with type 1 diabetes who developed incident macroalbuminuria during the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study. One hundred fifty-nine participants developed incident macroalbuminuria and were subsequently followed for a median duration of 9 years (maximum of 25 years). At the time of macroalbuminuria diagnosis, mean (SD) age was 37 (9) years, mean (SD) duration of diabetes was 17 (5) years, median AER was 524 mg/d, and mean (SD) eGFR was 108 (20) ml/min per 1.73 m(2). Ten years after macroalbuminuria diagnosis, the cumulative incidence of a sustained reduction in AER to <300 mg/d was 52%, mostly but not entirely under treatment with renin-angiotensin system inhibitors. The cumulative incidence of impaired GFR (sustained eGFR<60 ml/min per 1.73 m(2)) 10 years after macroalbuminuria diagnosis was 32%, including 16% who developed ESRD. Lower hemoglobin A1c and BP and regression to AER<300 mg/d were associated with reduced risk of developing impaired GFR. In conclusion, people with type 1 diabetes who develop macroalbuminuria are at high risk of progressive kidney disease. However, through at least 10 years of follow-up, AER could often be controlled, and GFR frequently remained in the normal range.

Diabetic retinopathy related to degree of albuminuria and tubular (low molecular weight) proteinuria in insulin‐dependent (Type I) diabetes mellitus

The urinary excretion of albumin (a marker of glomerular damage) and retinol binding protein (a low molecular weight protein marker of tubular dysfunction) was determined by sensitive immunochemical methods in 110 insulin-dependent (Type I) diabetic patients. We observed a statistically significant correlation between the urinary excretion levels of both proteins, in particular albumin, and the degree of retinopathy. The incidence of macroalbuminuria and tubular proteinuria was significantly higher in patients with manifest background retinopathy and proliferative retinopathy as compared to patients with no or slight retinopathy. The duration of diabetes was significantly correlated to the degree of retinopathy, but not to the urinary excretion of albumin and retinol binding protein.