Albuminuria High Quality
Albuminuria is a pathological condition wherein the protein albumin is abnormally present in the urine. It is a type of proteinuria. Albumin is a major plasma protein (normally circulating in the blood); in healthy people, only trace amounts of it are present in urine, whereas larger amounts occur in the urine of patients with kidney disease. For a number of reasons, clinical terminology is changing to focus on albuminuria more than proteinuria.
The kidneys normally do not filter large molecules into the urine, so albuminuria can be an indicator of damage to the kidneys or excessive salt intake. It can also occur in patients with long-standing diabetes, especially type 1 diabetes. Recent international guidelines (KDIGO 2012) reclassified chronic kidney disease (CKD) based on cause, glomerular filtration rate category, and albuminuria category (A1, A2, A3).
Also a urine dipstick test for proteinuria can give a rough estimate of albuminuria. This is because albumin is by far the dominant plasma protein, and bromophenol blue the agent used in the dipstick is specific to albumin.
Though there is some evidence that dietary interventions (to lower red meat intake) can be helpful in lowering albuminuria levels, there is currently no evidence that low protein interventions correlate to improvement in kidney function. Among other measures, blood pressure control, especially with the use of inhibitors of the renin-angiotensin-system, is the most commonly used therapy to control albuminuria.
It may be an early sign of kidney disease, but your doctor will check you again to make sure albuminuria is not caused by something else, like not drinking enough water. If your doctor suspects that you have kidney disease, the test for albumin will be repeated. Three positive results over three months or more is a sign of kidney disease.
Context: Kidney disease in type 2 diabetes mellitus (DM) is more heterogeneous than in type 1 DM. Reduced glomerular filtration rate (GFR) among individuals with type 2 DM may not always be due to classic diabetic glomerulosclerosis, which is associated with albuminuria and retinopathy.
Objective: To determine the prevalence of chronic renal insufficiency (CRI), defined as a GFR less than 60 mL/min per 1.73 m2 body surface area (BSA) in the absence of microalbuminuria or macroalbuminuria and diabetic retinopathy among adults with type 2 DM.
Main outcome measures: The GFR per 1.73 m2 BSA, calculated with serum creatinine, urea nitrogen, and serum albumin levels using the Modification of Diet in Renal Disease Study prediction equation; albuminuria, assessed using spot urine albumin/creatinine ratio; and presence of retinopathy, determined with fundus photography.
Results: Overall, 13% (sampled n = 171) of adults with type 2 DM (n = 1197) had CRI with a population estimate of 1.1 million. Among these adults with CRI, diabetic retinopathy was noted in 28% (n = 58), while the frequencies of microalbuminuria and macroalbuminuria were 45% (n = 64) and 19% (n = 47), respectively. Retinopathy and albuminuria (microalbuminuria or macroalbuminuria) were both absent in 30% (n = 51) of adults with type 2 DM and CRI. The population estimate of adults with type 2 DM and CRI in the absence of diabetic retinopathy or albuminuria was approximately 0.3 million.
There are limited data regarding whether albuminuria and reduced estimated GFR (eGFR) are separate and independent risk factors for cardiovascular and renal events among individuals with type 2 diabetes. The Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) study examined the effects of routine BP lowering on adverse outcomes in type 2 diabetes. We investigated the effects of urinary albumin-to-creatinine ratio (UACR) and eGFR on the risk for cardiovascular and renal events in 10,640 patients with available data. During an average 4.3-yr follow-up, 938 (8.8%) patients experienced a cardiovascular event and 107 (1.0%) experienced a renal event. The multivariable-adjusted hazard ratio for cardiovascular events was 2.48 (95% confidence interval 1.74 to 3.52) for every 10-fold increase in baseline UACR and 2.20 (95% confidence interval 1.09 to 4.43) for every halving of baseline eGFR, after adjustment for regression dilution. There was no evidence of interaction between the effects of higher UACR and lower eGFR. Patients with both UACR >300 mg/g and eGFR
Background: Albuminuria is an established risk marker for both cardiovascular and renal outcomes. Albuminuria can be reduced with drugs that block the renin-angiotensin system (RAS). We questioned whether the short-term drug-induced change in albuminuria would predict the long-term cardioprotective efficacy of RAS intervention.
Methods and results: We analyzed data from Reduction in Endpoints in Non-insulin dependent diabetes mellitus with the Angiotensin II Antagonist Losartan (RENAAL), a double-blind, randomized trial in 1513 type 2 diabetic patients with nephropathy, focusing on the relationship between the prespecified cardiovascular end point (composite) or hospitalization for heart failure and baseline or reduction in albuminuria. Patients with high baseline albuminuria (> or =3 g/g creatinine) had a 1.92-fold (95% CI, 1.54 to 2.38) higher risk for the cardiovascular end point and a 2.70-fold (95% CI, 1.94 to 3.75) higher risk for heart failure compared with patients with low albuminuria (
Conclusions: Albuminuria is an important factor predicting cardiovascular risk in patients with type 2 diabetic nephropathy. Reducing albuminuria in the first 6 months appears to afford cardiovascular protection in these patients.
Objectives: To estimate the risk of CV events in high-risk individuals with diabetes mellitus (DM) and without DM who have microalbuminuria and to determine whether levels of albuminuria below the microalbuminuria threshold increase CV risk.
Results: Microalbuminuria was detected in 1140 (32.6%) of those with DM and 823 (14.8%) of those without DM at baseline. Microalbuminuria increased the adjusted relative risk (RR) of major CV events (RR, 1.83; 95% confidence interval [CI], 1.64-2.05), all-cause death (RR, 2.09; 95% CI, 1.84-2.38), and hospitalization for congestive heart failure (RR, 3.23; 95% CI, 2.54-4.10). Similar RRs were seen for participants with or without DM, even after adjusting for other CV risk factors (eg, the adjusted RR of the primary aggregate end point was 1.97 [95% CI, 1.68-2.31] in those with DM and 1.61 [95% CI, 1.36-1.90] in those without DM). Compared with the lowest quartile of ACR (1.62 mg/mmol) (P for trend
Conclusions: Our results indicate that any degree of albuminuria is a risk factor for CV events in individuals with or without DM; the risk increases with the ACR, starting well below the microalbuminuria cutoff. Screening for albuminuria identifies people at high risk for CV events.
Participants received, in random order, 4 weeks of treatment with an angiotensin-receptor blocker (ARB; telmisartan 80 mg daily), an SGLT2i (empagliflozin 10 mg daily), a DPP4i (linagliptin 5 mg daily), and a JAK-STAT inhibitor (baricitinib 2 mg daily) with 4-week washout periods in between. At the end of the four-way rotation schedule, participants were re-exposed to a 4-week treatment period with the drug that induced the strongest albuminuria-lowering response for each participant.
We observed significant variability in the albuminuria response to four drugs with different mechanisms of action among individuals with type 1 and type 2 diabetes and elevated albuminuria. We found variability to the four drugs within an individual such that many participants had only one treatment that reached the criteria for good response of 30% reduction in albuminuria. We also observed marked variability in response between participants such that for a given drug, some individuals had a large reduction in albuminuria, whereas others did not. We confirmed that this response variability is, in part, reproducible upon re-exposure. The clinical consequences of these findings are that for approximately one-third of participants, the first drug of the rotation scheme was the best-performing treatment, whereas for nearly 75% of participants, a >30% reduction in albuminuria was achieved with their best-performing drug supporting the need for systemic rotation. There were no baseline clinical characteristics that predicted the response to these drugs except that participants receiving diuretic treatment were more likely to respond to telmisartan.
A key aspect of the trial design was the re-exposure of participants to their best-performing drug to confirm the individual treatment response. We observed a statistically significant correlation between the first and confirmatory exposures, indicating that the individual response is reproducible and unlikely to be a chance finding. This notion is supported by the finding that the albuminuria change during treatment inversely correlated with the change in albuminuria during the washout period. Nevertheless, because of the large, biological, day to day variation in albuminuria (36,37), we had not expected that the individual response to the first exposure would be completely reproducible at re-exposure. Indeed, there was considerable residual variation. Many other factors could have influenced the reproducibility in response, including variation in dietary patterns and differences in disease activity. Moreover, the interval between the first and confirmatory exposures could be up to 28 weeks, during which participants were treated with different interventions that may have introduced random variations. In addition, the albuminuria reduction during the confirmation period was less compared with the at first exposure. This may be explained, in part, by regression to the mean. These aspects should be considered in the design of clinical trials focused on individual drug response. 041b061a72