Albuminuria: all you need to predict outcomes in chronic kidney disease?

Gansevoort, Ron T.; Nauta, Ferdau L.; Bakker, Stephan J. L.

doi:10.1097/mnh.0b013e32833e4ce1

Cited by 36 publications

(26 citation statements)

References 53 publications

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“…32,[36][37][38] If microcirculatory remodeling and damage are both involved in renal disease progression, the interaction of both factors (narrow arterioles and albuminuria) is proposed. 39 In the case of narrow arterioles and albuminuria combined in patients with CKD, a synergistic risk for developing renal end points may be suggested.…”

Section: Discussionmentioning

confidence: 99%

Microcirculatory Marker for the Prediction of Renal End Points

2014

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T he prevalence of chronic kidney disease (CKD) has increased during the past years worldwide, 1 imposing a major burden on health-care systems. It is important to prevent CKD, thereby to reduce the need for renal replacement therapy and the rising morbidity and mortality associated with end-stage renal disease.2 Therefore, an efficient individual prediction of CKD progression is warranted.Several factors are involved in CKD progression, including baseline renal function, age, ethnicity, diabetes mellitus, blood pressure, use of renin-angiotensin system (RAS) blocker, and albuminuria.3-9 Despite these single predictive factors, an individual prediction of CKD progression remains difficult. Interestingly, all of the factors described above additionally influence the microcirculation and contribute to intraglomerular pressure.10-16 Thus, it is not surprising that renal microvascular pathology has been considered an important factor in CKD progression. 17 One pathophysiological aspect of the microcirculation is vascular remodeling in small arteries, including microvascular narrowing. 18,19 The latter can be assessed by noninvasive retinal vessel analysis.20,21 Narrow retinal arterioles are associated with age, black race, hypertension, and albuminuria. Ooi et al 22 and our group described narrow retinal arteries in patients with advanced CKD. 23,24 Similar to systemic arteriolar narrowing, the retinal and preglomerular arterioles could show the same effects.25 Narrow preglomerular arterioles increase intraglomerular pressure and contribute to the glomerular defect, determined by albuminuria, as has been demonstrated in spontaneously hypertensive rats and in patients with diabetes mellitus. [25][26][27][28] We hypothesize that retinal arteriolar narrowing predicts CKD progression and subsequently renal end points. Moreover and of importance to clinical practice, we hypothesize that Abstract-Retinal arteriolar narrowing reflects aging, hypertension, chronic kidney disease (CKD), and other vascular processes. We examined the predictive value of retinal arteriolar narrowing alone and in combination with albuminuria on renal disease progression in CKD. A white CKD stage 2 to 4 cohort of 164 men and women (60.8±13.8 years) underwent retinal photography and determination of albuminuria. The calibers of all retinal arterioles were measured after digital conversion of the photographs. Cases of incident renal end points defined as 50% renal function loss and start of renal replacement therapy were identified and validated by case record reviews. Over an average period of 1410 (range, 106-1606) days, 25 patients with CKD had incident renal end points. Kaplan-Meier analysis revealed that patients with CKD within the tertile of narrowest arterioles had more renal end points (log-rank P<0.001). Cox regression analysis confirmed this before (β=1.183±0.411) and after adjusting for age and baseline renal function (β=1.204±0.416). With respect to renal end points, a significant interaction was present between narrow arterioles and a...

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Section: Discussionmentioning

confidence: 99%

Microcirculatory Marker for the Prediction of Renal End Points

2014

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“…Diabetes is one of the leading causes of blindness and end-stage renal failure which is due to changes in the microvasculature [Burrows et al 2010]. But even early in the development of end-organ damages we see changes in the microvasculature, for example by measurement of the urinary excretion of albumin which is a well established marker of glomerular damage and an accepted risk factor for cardiovascular disease and progression of renal disease [Gansevoort et al 2010]. Recent findings indicate that the development of organ damage in patients with type 2 diabetes is dependent in part on the accumulation of tissue macrophages [Gustafson, 2010].…”

Section: Introductionmentioning

confidence: 99%

Serum myeloid-related protein 8/14 complex is associated with microalbuminuria in patients with type 2 diabetes

Schmaderer

Kemmner

Burkhardt³

et al. 2014

Therapeutic Advances in Cardiovascular Disease

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Objectives: Microalbuminuria (MA) is associated independently with cardiovascular risk and progression of renal disease in patients with diabetes and the normal population. MA is an accepted factor for microvascular defects, in particular in patients with diabetes, and is associated with inflammation. Activated transmigrating macrophages are key cells in these inflammatory processes. Based on the theory that myeloid-related protein 8/14 complex (MRP8/14) is secreted by transmigrating macrophages, we hypothesized that MA was accompanied by elevated MRP8/14 and investigated whether MA predicts MRP8/14 in patients with type 2 diabetes. Methods: A total of 86 men with type 2 diabetes were grouped according to urinary albumin excretion in normoalbuminuria and MA. Serum MRP8/14 levels were measured by enzymelinked immunosorbent assay. Established cardiovascular risk factors were quantified in both groups and compared with urinary albumin excretion. Results: Albuminuria (mg/day) was positively associated with MRP8/14 (r = 0.34) and systemic blood pressure (r = 0.33). Patients with type 2 diabetes and MA demonstrated significantly higher MRP8/14 levels than patients with normoalbuminuria [median (interquartile range), 1.24 (0.97-2.28) µg/ml versus 0.97 (0.67-1.35) µg/ml, p < 0.05]. Serum creatinine levels, systolic blood pressure (SBP), very low density lipoprotein levels and the incidence of hypertension and coronary artery disease were significantly higher in the group with MA. Both groups did not differ significantly in other cardiovascular risk factors. MA was an independent predictor of serum MRP8/14 levels (β = 0.454) as well as SBP (β = 0.625) and haemoglobin A1c (β = 0.322). Conclusion: Our data demonstrate that albumin excretion is associated with the process of macrophage activation determined by MRP8/14 levels. These data not only suggest tissue inflammation as a factor for elevated cardiovascular risk in patients with type 2 diabetes, they further point to a role of macrophage activation in this process.

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“…[6][7][8][9] CKD represents as expected a major risk factor for the progression to end-stage renal disease but associates also with an increased risk of cardiovascular morbidity and mortality. 10,11 In addition to the assessment of impaired renal function or glomerular filtration rate, urinary albumin excretion rate (albuminuria) represents another important clinical marker for the evaluation of CKD and cardiovascular risk of patients. [10][11][12][13][14][15] These renal disease phenotypes are also inherited in several inbred rat strains many of which are hypertensive.…”

Section: Introductionmentioning

confidence: 99%

“…10,11 In addition to the assessment of impaired renal function or glomerular filtration rate, urinary albumin excretion rate (albuminuria) represents another important clinical marker for the evaluation of CKD and cardiovascular risk of patients. [10][11][12][13][14][15] These renal disease phenotypes are also inherited in several inbred rat strains many of which are hypertensive. 16 During the last decades, genetic mapping studies by genome-wide linkage analysis followed by fine mapping of selected quantitative trait loci (QTL) for renal disease phenotypes were reported.…”

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Mapping genetic determinants of kidney damage in rat models

Schulz

Kreutz

2012

Hypertens Res

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During the last two decades, significant progress in our understanding of the development of kidney diseases has been achieved by unravelling the mechanisms underlying rare familial forms of human kidney diseases. Due to the genetic heterogeneity in human populations and the complex multifactorial pathogenesis of the disease phenotypes, the dissection of the genetic basis of common chronic kidney diseases (CKD) remains a difficult task. In this regard, several inbred rat models provide valuable complementary tools to uncover the genetic basis of complex renal disease phenotypes that are related to common forms of CKD. In this review, data obtained in nine experimental rat models, including the Buffalo (BUF), Dahl salt-sensitive (SS), Fawn-hooded hypertensive (FHH), Goto-Kakizaki (GK), Lyon hypertensive (LH), Munich Wistar Frömter (MWF), Sabra hypertension-prone (SBH), spontaneously hypertensive rat (SHR) and stroke-prone spontaneously hypertensive rat (SHRSP) inbred strains, that contributed to the genetic dissection of renal disease phenotypes are presented. In this panel of inbred strains, a large number of quantitative trait loci (QTL) linked to albuminuria/proteinuria and other functional or structural kidney abnormalities could be identified by QTL mapping analysis and follow-up studies including consomic and congenic rat lines. The comprehensive exploitation of the genotype-renal phenotype associations that are inherited in this panel of rat strains is suitable for making a significant contribution to the development of an integrated approach to the systems genetics of common CKD. INTRODUCTIONCommon forms of chronic kidney diseases (CKD) represent complex disease phenotypes that are influenced by both environmental and genetic factors. [1][2][3][4][5] Both arterial hypertension and type-2 diabetes mellitus are major contributors to complex CKD, which has a high prevalence in the general human population worldwide affecting B11-15% of individuals in Europe and United States. 6-9 CKD represents as expected a major risk factor for the progression to end-stage renal disease but associates also with an increased risk of cardiovascular morbidity and mortality. 10,11 In addition to the assessment of impaired renal function or glomerular filtration rate, urinary albumin excretion rate (albuminuria) represents another important clinical marker for the evaluation of CKD and cardiovascular risk of patients. [10][11][12][13][14][15] These renal disease phenotypes are also inherited in several inbred rat strains many of which are hypertensive. 16 During the last decades, genetic mapping studies by genome-wide linkage analysis followed by fine mapping of selected quantitative trait loci (QTL) for renal disease phenotypes were reported. Subsequently, studies in consomic and congenic rats were performed to further unravel the genetics of kidney injury in inbred rat strains. For QTL confirmation, consomic strains were generated by transfer of an entire chromosome carrying a QTL from a donor strain into the disease backgro...

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Albuminuria: all you need to predict outcomes in chronic kidney disease?

Cited by 36 publications

References 53 publications

Microcirculatory Marker for the Prediction of Renal End Points

Microcirculatory Marker for the Prediction of Renal End Points

Serum myeloid-related protein 8/14 complex is associated with microalbuminuria in patients with type 2 diabetes

Mapping genetic determinants of kidney damage in rat models

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