-
1.
Cardiovascular risk prediction in people with chronic kidney disease.
Matsushita, K, Ballew, SH, Coresh, J
Current opinion in nephrology and hypertension. 2016;(6):518-523
-
-
Free full text
-
Abstract
PURPOSE OF REVIEW Clinical guidelines are not consistent regarding whether or how to utilize information on measures of chronic kidney disease (CKD) for predicting the risk of cardiovascular disease (CVD). This review summarizes recent literature regarding CVD prediction in the context of CKD. RECENT FINDINGS Previous studies used different definitions of CKD measures and CVD outcomes, and applied distinct statistical approaches. A recent individual-level meta-analysis from the CKD Prognosis Consortium is of value as it has uniformly investigated creatinine-based estimated glomerular filtration rate (eGFR) and albuminuria as CKD measures and applied the same statistical approach across 24 cohorts with more than 630 000 participants. In this meta-analysis, eGFR and albuminuria improve CVD risk prediction beyond traditional CVD risk factors, particularly for CVD mortality and heart failure. Albuminuria demonstrates more evident improvement than eGFR. Moreover, several recent studies have shown that other filtration markers, for example, cystatin C and β2-microglobulin, and measures of atherosclerosis or cardiac damage (e.g., coronary artery calcium and cardiac troponins) can further improve CVD prediction in the CKD population. SUMMARY Future clinical guidelines may require updates regarding whether/how to incorporate CKD measures and other biomarkers in CVD prediction, depending on the CVD outcomes of interest, target population, and availability of those measures/biomarkers in that population.
-
2.
Oxidative Stress in Diabetic Nephropathy with Early Chronic Kidney Disease.
Miranda-Díaz, AG, Pazarín-Villaseñor, L, Yanowsky-Escatell, FG, Andrade-Sierra, J
Journal of diabetes research. 2016;:7047238
Abstract
The increase in the prevalence of diabetes mellitus (DM) and the secondary kidney damage produces diabetic nephropathy (DN). Early nephropathy is defined as the presence of microalbuminuria (30-300 mg/day), including normal glomerular filtration rate (GFR) or a mildly decreased GFR (60-89 mL/min/1.73 m(2)), with or without overt nephropathy. The earliest change caused by DN is hyperfiltration with proteinuria. The acceptable excretion rate of albumin in urine is <30 mg/day. Albuminuria represents the excretion of >300 mg/day. Chronic kidney disease (CKD) is characterized by abnormalities in renal function that persist for >3 months with health implications. Alterations in the redox state in DN are caused by the persistent state of hyperglycemia and the increase in advanced glycation end products (AGEs) with ability to affect the renin-angiotensin system and the transforming growth factor-beta (TGF-β), producing chronic inflammation and glomerular and tubular hypertrophy and favoring the appearance of oxidative stress. In DN imbalance between prooxidant/antioxidant processes exists with an increase in reactive oxygen species (ROS). The overproduction of ROS diminishes expression of the antioxidant enzymes (manganese superoxide dismutase, glutathione peroxidase, and catalase). The early detection of CKD secondary to DN and the timely identification of patients would permit decreasing its impact on health.
-
3.
Diabetic Kidney Disease: A Syndrome Rather Than a Single Disease.
Piccoli, GB, Grassi, G, Cabiddu, G, Nazha, M, Roggero, S, Capizzi, I, De Pascale, A, Priola, AM, Di Vico, C, Maxia, S, et al
The review of diabetic studies : RDS. 2015;(1-2):87-109
Abstract
The term "diabetic kidney" has recently been proposed to encompass the various lesions, involving all kidney structures that characterize protean kidney damage in patients with diabetes. While glomerular diseases may follow the stepwise progression that was described several decades ago, the tenet that proteinuria identifies diabetic nephropathy is disputed today and should be limited to glomerular lesions. Improvements in glycemic control may have contributed to a decrease in the prevalence of glomerular lesions, initially described as hallmarks of diabetic nephropathy, and revealed other types of renal damage, mainly related to vasculature and interstitium, and these types usually present with little or no proteinuria. Whilst glomerular damage is the hallmark of microvascular lesions, ischemic nephropathies, renal infarction, and cholesterol emboli syndrome are the result of macrovascular involvement, and the presence of underlying renal damage sets the stage for acute infections and drug-induced kidney injuries. Impairment of the phagocytic response can cause severe and unusual forms of acute and chronic pyelonephritis. It is thus concluded that screening for albuminuria, which is useful for detecting "glomerular diabetic nephropathy", does not identify all potential nephropathies in diabetes patients. As diabetes is a risk factor for all forms of kidney disease, diagnosis in diabetic patients should include the same combination of biochemical, clinical, and imaging tests as employed in non-diabetic subjects, but with the specific consideration that chronic kidney disease (CKD) may develop more rapidly and severely in diabetic patients.
-
4.
Angiotensin-converting enzyme (ACE) inhibitors for proteinuria and microalbuminuria in people with sickle cell disease.
Sasongko, TH, Nagalla, S, Ballas, SK
The Cochrane database of systematic reviews. 2015;(6):CD009191
-
-
Free full text
-
Abstract
BACKGROUND Sickle cell disease is a group of disorders characterized by deformation of erythrocytes. Renal damage is a frequent complication in sickle cell disease as a result of long-standing anemia and disturbed circulation through the renal medullary capillaries. Due to the improvement in life expectancy of people with sickle cell disease, there has been a corresponding significant increase in the incidence of renal complications. Microalbuminuria and proteinuria are noted to be a strong predictor of subsequent renal failure. There is extensive experience and evidence with angiotensin-converting enzyme (ACE) inhibitors over many years in a variety of clinical situations for patients who do not have sickle cell disease, but their effect in people with this disease is unknown. It is common practice to administer ACE inhibitors for sickle nephropathy due to their renoprotective properties; however, little is known about their effectiveness and safety in this setting. This is an update of a Cochrane Review first published in 2013. OBJECTIVES To determine the effectiveness of ACE inhibitor administration in people with sickle cell disease for decreasing intraglomerular pressure, microalbuminuria and proteinuria and to to assess the safety of ACE inhibitors as pertains to their adverse effects. SEARCH METHODS The authors searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Hameoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search: 03 June 2015. SELECTION CRITERIA Randomized or quasi-randomized controlled trials of ACE inhibitors designed to reduce microalbuminuria and proteinuria in people with sickle cell disease compared to either placebo or standard treatment regimen. DATA COLLECTION AND ANALYSIS Three authors independently applied the inclusion criteria in order to select studies for inclusion in the review. Two authors assessed the risk of bias of studies and extracted data and the third author verified these assessments. MAIN RESULTS Five studies were identified through the searches, only one met our inclusion criteria. The included study randomized 22 participants (seven males and 15 females) having proteinuria or microalbuminuria with sickle cell disease and treated the participants for six months (median length of follow up of three months) with captopril or placebo. The overall quality of the outcomes reported was high, since most aspects that may contribute to bias were regarded to be of low risk, although allocation concealment was not reported. At six months, the study reported no significant difference in urinary albumin excretion between the captopril group and the placebo group, although the mean urinary albumin excretion in the captopril group was lower by a mean difference of -49.00 (95% confidence interval -124.10 to 26.10) compared to that of placebo. However, our analysis on the absolute change score showed significant changes between the two groups by a mean difference of -63.00 (95% confidence interval -93.78 to -32.22). At six months albumin excretion in the captopril group was noted to decrease from baseline by a mean of 45 ± 23 mg/day and the placebo group was noted to increase by 18 ± 45 mg/day. Serum creatinine and potassium levels were reported constant throughout the study. The potential for inducing hypotension should be highlighted; the study reported a decrease of 8 mmHg in systolic pressure and 5 mmHg in diastolic and mean blood pressure. AUTHORS' CONCLUSIONS There is not enough evidence to show that the administration of ACE inhibitors is associated with a reduction of microalbuminuria and proteinuria in people with sickle cell disease, although a potential for this was seen. More long-term studies involving multiple centers and larger cohorts using a randomized-controlled design are warranted, especially among the pediatric age group. Detailed reporting of each outcome measure is necessary to allow a clear cut interpretation in a systematic review. One of the difficulties encountered in this review was the lack of detailed data reported in the included study.
-
5.
Glomerular filtration rate and albuminuria for detection and staging of acute and chronic kidney disease in adults: a systematic review.
Levey, AS, Becker, C, Inker, LA
JAMA. 2015;(8):837-46
-
-
Free full text
-
Abstract
IMPORTANCE Because early-stage kidney disease is asymptomatic and is associated with both morbidity and mortality, laboratory measurements are required for its detection. OBJECTIVE To summarize evidence supporting the use of laboratory tests for glomerular filtration rate (GFR) and albuminuria to detect and stage acute kidney injury, acute kidney diseases and disorders, and chronic kidney disease in adults. EVIDENCE REVIEW We reviewed recent guidelines from various professional groups identified via the National Guideline Clearing House and author knowledge, and systematically searched MEDLINE for other sources of evidence for selected topics. FINDINGS The KDIGO (Kidney Disease Improving Global Outcomes) guidelines define and stage acute and chronic kidney diseases by GFR and albuminuria. For initial assessment of GFR, measuring serum creatinine and reporting estimated GFR based on serum creatinine (eGFRcr) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 equation is recommended. If confirmation of GFR is required because of conditions that affect serum creatinine independent of GFR (eg, extremes of muscle mass or diet), or interference with the assay, cystatin C should be measured and estimated GFR should be calculated and reported using cystatin C (eGFRcys) and serum creatinine (eGFRcr-cys) or GFR should be measured directly using a clearance procedure. Initial assessment of albuminuria includes measuring urine albumin and creatinine in an untimed spot urine collection and reporting albumin-to-creatinine ratio. If confirmation of albuminuria is required because of diurnal variation or conditions affecting creatinine excretion, such as extremes of muscle mass or diet, the albumin excretion rate should be measured from a timed urine collection. CONCLUSIONS AND RELEVANCE Detection and staging of acute and chronic kidney diseases can be relatively simple. Because of the morbidity and mortality associated with kidney disease, early diagnosis is important and should be pursued in at-risk populations.
-
6.
Vascular and metabolic properties of manidipine.
Buset Ríos, N, Rodríguez Esparragón, F, Fernández-Andrade Rodríguez, C, Rodríguez Pérez, JC
Nefrologia : publicacion oficial de la Sociedad Espanola Nefrologia. 2011;(3):268-74
Abstract
The combination of renin-angiotensin system blockers with calcium channel blockers appears to be one of the most effective options for treating hypertension and diabetes.Nevertheless, not all calcium blockers behave in the same manner. Manidipine, unlike other third-generation dihydropyridine derived drugs, blocks T-type calcium channels present in the efferent glomerular arterioles, reducing intraglomerular pressure and microalbuminuria. In addition,T-type channels are related to proliferation, inflammation,fibrosis, vasoconstriction and activation of the renin-angiotensin system. The inhibition of these factors could explain the non-haemodynamic effects of manidipine as compared to other blockers.
-
7.
'Hypertension' and 'microalbuminuria': the bell tolls for thee.
Forman, JP, Brenner, BM
Kidney international. 2006;(1):22-8
-
-
Free full text
-
Abstract
Since the terms 'hypertension' and 'microalbuminuria' were first defined, data from numerous studies have documented the continuous, rather than dichotomous, relation between blood pressure, albumin excretion, and cardiovascular disease. Lower blood pressures, down to at least 115/75 mmHg, and lower albumin excretions, below an estimated 2 mg/day, are associated with less cardiovascular risk. We hypothesize that the abundances of modern civilization superimposed on the Paleolithic genotype of humans, which has not substantially changed in the last 10 000 years, have considerably shifted the 'normal' values for blood pressure and various biochemical indices such as albuminuria still found in today's stone-aged cultures to the 'neo-normal' values observed today in the rest of the modern world. Defining a large portion of the population as 'normal' based upon these dichotomous 'neo-normal' standards is not supported by the data, and therefore seems unjustifiable. We propose that the medical community consider abandoning the terms 'hypertension' and 'microalbuminuria' in favor of 'blood pressure-associated' and 'albuminuria-associated' disease.
-
8.
Systematic review on urine albumin testing for early detection of diabetic complications.
Newman, DJ, Mattock, MB, Dawnay, AB, Kerry, S, McGuire, A, Yaqoob, M, Hitman, GA, Hawke, C
Health technology assessment (Winchester, England). 2005;(30):iii-vi, xiii-163
Abstract
OBJECTIVES To determine whether microalbuminuria is an independent prognostic factor for the development of diabetic complications and whether improved glycaemic or blood pressure control has a greater influence on the development of diabetic complications in those with microalbuminuria than in those with normoalbuminuria. DATA SOURCES Electronic databases up until January 2002. REVIEW METHODS A protocol for peer review by an external expert panel was prepared that included selection criteria for data extraction and required two independent reviewers to undertake article selection and review. Completeness was assessed using hand-searching of major journals. Random effects meta-analysis was used to obtain combined estimates of relative risk (RR). Funnel plots, trim and fill methods and meta-regression were used to assess publication bias and sources of heterogeneity. RESULTS In patients with type 1 or type 2 DM and microalbuminuria there is a RR of all-cause mortality of 1.8 [95% confidence interval (CI) 1.5 to 2.1] and 1.9 (95% CI 1.7 to 2.1) respectively. Similar RRs were found for other mortality end-points, with age of cohort being inversely related to the RR in type 2 DM. In patients with type 1 DM, there is evidence that microalbuminuria or raised albumin excretion rate has only weak, if any, independent prognostic significance for the incidence of retinopathy and no evidence that it predicts progression of retinopathy, although strong evidence exists for the independent prognostic significance of microalbuminuria or raised albumin excretion rate for the development of proliferative retinopathy (crude RR of 4.1, 95% CI 1.8 to 9.4). For type 2 DM, there is no evidence of any independent prognostic significance for the incidence of retinopathy and little, if any, prognostic relationship between microalbuminuria and the progression of retinopathy or development of proliferative retinopathy. In patients with type 1 DM and microalbuminuria there is an RR of developing end-stage renal disease (ESRD) of 4.8 (95% CI 3.0 to 7.5) and a higher RR (7.5, 95% CI 5.4 to 10.5) of developing clinical proteinuria, with a significantly greater fall in glomerular filtration rate (GFR) in patients with microalbuminuria. In patients with type 2 DM, similar RRs were observed: 3.6 (95% CI 1.6 to 8.4) for developing ESRD and 7.5 (95% CI 5.2 to 10.9) for developing clinical proteinuria, with a significantly greater decline in GFR in the microalbuminuria group of 1.7 (95% CI 0.1 to 3.2) ml per minute per year compared with those who were normoalbuminuric. In adults with type 1 or type 2 DM and microalbuminuria at baseline, the numbers progressing to clinical proteinuria (19% and 24%, respectively) and those regressing to normoalbuminuria (26% and 18%, respectively) did not differ significantly. In children with type 1 DM, regression (44%) was significantly more frequent than progression (15%). In patients with type 1 or type 2 DM and microalbuminuria, there is scarce evidence as to whether improved glycaemic control has any effect on the incidence of cardiovascular disease (CVD), the incidence or progression of retinopathy, or the development of renal complications. However, among patients not stratified by albuminuria, improved glycaemic control benefits retinal and renal complications and may benefit CVD. In the effects of angiotensin-converting enzyme (ACE) inhibitors on GFR in normotensive microalbuminuric patients with type 1 DM, there was no evidence of a consistent treatment effect. There is strong evidence from 11 trials in normotensive type 1 patients with microalbuminuria of a beneficial effect of ACE inhibitor treatment on the risk of developing clinical proteinuria and on the risk of regression to normoalbuminuria. Patients with type 2 DM and microalbuminuria, whether hypertensive or not, may obtain additional cardiovascular benefit from an ACE inhibitor and there may be a beneficial effect on the development of retinopathy in normotensive patients irrespective of albuminuria. There is limited evidence that treatment of hypertensive microalbuminuric type 2 diabetic patients with blockers of the renin--angiotensin system is associated with preserved GFR, but also evidence of no differences in GFR in comparisons with other antihypertensive agents. The data on GFR in normotensive cohorts are inconclusive. In normotensive type 2 patients with microalbuminuria there is evidence from three trials (all enalapril) of a reduction in risk of developing clinical proteinuria; in hypertensive patients there is evidence from one placebo-controlled trial (irbesartan) of a reduction in this risk. Intensive compared with moderate blood pressure control did not affect the rate of progression of microalbuminuria to clinical proteinuria in the one available study. There is inconclusive evidence from four trials of any difference in the proportions of hypertensive patients progressing from microalbuminuria to clinical proteinuria when ACE inhibitors are compared with other antihypertensive agents, and in one trial regression was two-fold higher with lisinopril than with nifedipine. CONCLUSIONS The most pronounced benefits of glycaemic control identified in this review are on retinal and renal complications in both normoalbuminuric and microalbuminuric patients considered together, with little or no evidence of any greater benefit in those with microalbuminuria. Hence, microalbuminuric status may be a false boundary when considering the benefits of glycaemic control. Classification of a person as normoalbuminuric must not serve to suggest that they will derive less benefit from optimal glycaemic control than a person who is microalbuminuric. All hypertensive patients benefit from blood pressure lowering and there is little evidence of additional benefit in those with microalbuminuria. Antihypertensive therapy with an ACE inhibitor in normotensive patients with microalbuminuria is beneficial. Monitoring microalbuminuria does not have a proven role in modulating antihypertensive therapy while the patient remains hypertensive. Recommendations for microalbuminuria research include: determining rate and predictors of development and factors involved in regression; carrying out economic evaluations of different screening strategies; investigating the effects of screening on patients; standardising screening tests to enable use of common reference ranges; evaluating the effects of lipid-lowering therapy; and using to modulate antihypertensive therapy.
-
9.
Framingham score and microalbuminuria: combined future targets for primary prevention?
Asselbergs, FW, Hillege, HL, van Gilst, WH
Kidney international. Supplement. 2004;(92):S111-4
-
-
Free full text
-
Abstract
BACKGROUND Risk assessment is the cornerstone of primary prevention of cardiovascular disease. Our objective was to evaluate the prognostic value of the Framingham score in microalbuminuric subjects without a history of cardiovascular disease and whether this risk score can predict the benefit of treatment with fosinopril or pravastatin. METHODS Subjects were randomized to fosinopril 20 mg or matching placebo, and to pravastatin 40 mg or matching placebo (mean age 51 +/- 12 years, 65% men, N = 830). Prediction of 10-year risk for coronary heart disease by the Framingham score was performed using the risk factor categories with LDL cholesterol. RESULTS Albuminuria was correlated with Framingham score at baseline (P < 0.001). In the population with a Framingham risk score <20%, both albuminuria and Framingham risk score were independent predictors of the primary end point. A two-fold increase of albuminuria or the Framingham risk score was associated with a hazard ratio of 1.60 (95% CI 1.10-2.31), P = 0.013 and 3.00 (95% CI 1.40-6.44), P = 0.005, respectively. In contrast to fosinopril, pravastatin showed a significant beneficial effect on Framingham risk score after 4 years of follow-up (P < 0.001). Furthermore, the observed absolute risk reduction in cardiovascular events was greater than calculated by the Framingham risk score. CONCLUSION The Framingham score is useful in microalbuminuric subjects as a prognostic tool. In addition, when considering the risk score as a target of intervention, the beneficial effects of therapies might be underestimated. Combining the Framingham score with the level of urinary albumin excretion is suggested as a primary prevention strategy with higher efficiency.
-
10.
Microalbuminuria and hypertension with focus on type 1 and type 2 diabetes.
Mogensen, CE
Journal of internal medicine. 2003;(1):45-66
-
-
Free full text
-
Abstract
UNLABELLED Microalbuminuria and hypertension with Over the past decade, there has been considerable focus on the concept of microalbuminuria, not only because it predicts renal disease in type 1 and type 2 diabetes, but also because it relates to premature mortality in the diabetic and in the general population. More importantly, intervention at this stage is now possible with the perspective of preserving glomerular filtration rate (GFR) and ameliorating cardiovascular disease and ensuing strong end-points. INITIAL STUDIES The concept of microalbuminuria was introduced about 20 years ago and since then there has been a multitude of studies and papers on this subject using the original definition, but not always, in the US. Before that time it was suggested, mainly from the US, that diabetic renal disease was an untreatable relentlessly progressive condition. GENETIC STUDIES There is an overwhelming number of studies on genetics and diabetes and also covering the genetics of diabetic complications including nephropathy. However, so far the results are extremely disappointing. Patients at risk cannot be identified and genetic analyses are of no value as a guide to treatment. The notion that the development of complications is controlled mainly by a special genetic pattern is increasingly doubtful. In genetic studies, it is rather phenotypic well-accepted risk factors that dominate. STRUCTURAL BASIS OF MICROALBUMINURIA Patients with microalbuminuria have significant abnormalities in the kidney, including glomeruli. This is quite clear in patients with type 1 diabetes, but is also seen in type 2 diabetes, where on the other hand, other risk factors such as hypertension and dyslipidaemia also seem to be of importance, including loss of autoregulation. Renal biopsies are generally not indicated in the management of diabetic patients. MICROALBUMINURIA AND EARLY MORTALITY It is quite clear that microalbuminuria predicts early mortality both in type 1 and type 2 diabetes. The association to other risk factors may partly explain this--but this does not account for the whole picture. Endothelial dysfunction as well as inflammatory and arteriosclerotic abnormalities in blood vessels may be a relevant hypothesis that needs to be further explored along with other possibilities. CLINICAL COURSE AND ASSOCIATED ABNORMALITIES The risk factor for progression in normoalbuminuric patients to microalbuminuria is higher than normal albumin excretion (strongest factor), poor glycaemic control, elevated blood pressure, and to some extent smoking. The clinical course of microalbuminuria is usually progressive, but with the more effective intervention now available we encounter that the so-called natural history (without intervention) is increasingly difficult to study. Microalbuminuria is clearly associated with a number of abnormalities, almost in all organs, but GFR is generally well preserved in spite of more advanced structural lesions. Therefore, microalbuminuria is an important marker for more pronounced diabetic vascular disease in general as well as for nephropathy. Regression to normoalbuminuria only rarely occurs during standard unchanged nonintensive treatment. TREATMENT STRATEGIES The best possible glycaemic control is important in preventing and ameliorating the course of normo- and micro-albuminuria. Another major treatment strategy, especially in microalbuminuric patients, is antihypertensive treatment including inhibition of the renal angiotensin aldosterone system. Numerous new studies are available, both in type 1 and type 2 diabetes, documenting that not only microalbuminuria but also renal and cardiovascular complications in these patient are also far better controlled by early detection and treatment. Therefore, screening for microalbuminuria should be a strategy in all diabetes management followed by effective intervention as outlined in this paper.