Insights into the Relationship Between Hypertension and Albuminuria

Hilliard, Lucinda M; Russo, Leileata M.; Comper, Wayne D.

doi:10.2174/157340207779815563

Cited by 7 publications

(5 citation statements)

References 126 publications

(132 reference statements)

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“…In membranous nephropathy, subepithelial immune-complex deposition is present along the glomerular basement membrane. There is also some evidence suggesting that albuminuria is caused by defective tubular trafficking and degradation of albumin 1,2. It may be that in HCT patients, inflammatory damage to the tubules from GVHD leads to albuminuria and the latter is a manifestation of renal GVHD.…”

Section: Discussionmentioning

confidence: 99%

“…Newer work postulates that albuminuria results from tubular dysfunction in the trafficking and degradation of albumin 1,2. In both the general population and in cohorts of patients with specific diseases (hypertension, diabetes, inflammatory bowel disease and critically ill patients), albuminuria is a marker for adverse events and poor outcomes.…”

Section: Introductionmentioning

confidence: 99%

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Albuminuria in Hematopoietic Cell Transplantation Patients: Prevalence, Clinical Associations, and Impact on Survival

Hingorani

Seidel

Lindner

et al. 2008

Biology of Blood and Marrow Transplantation

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Chronic kidney disease is common after hematopoietic cell transplant. We prospectively measured urinary albumin to creatinine ratios (ACR) in 142 patients. Total (intact) monomeric albumin was determined by liquid chromatography of untreated urine samples collected weekly to day 100 after transplant. Albuminuria was defined as ACR (mg/g creatinine) >30 and proteinuria as ACR >300. Cox and logistic regressions analyses evaluated ACR as a risk factor for clinical events. The prevalence of albuminuria at baseline, day 100 and 1 year was 37%, 64% and 50%, respectively. Proteinuria occurred in 4% of patients at baseline, 15% at day 100 and 4% at 1 year. Characteristics associated with albuminuria include age, gender, donor type, hypertension and sinusoidal obstruction syndrome. Albuminuria was associated with an increased risk of acute GVHD and bacteremia, but not acute kidney injury. Albuminuria at day 100 was associated with chronic kidney disease at 1 year (OR= 4.0; 95%CI 1.1–14.6). Non-relapse mortality risk was elevated (HR=6.8; 95%CI 1.1–41.5) among patients with overt proteinuria at day 100. Albuminuria occurs frequently after HCT and correlates with acute GVHD, bacteremia, hypertension and progression of renal disease. Proteinuria at day 100 is associated with an 6-fold increased risk of non-relapse mortality by one year post transplant.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Albuminuria in Hematopoietic Cell Transplantation Patients: Prevalence, Clinical Associations, and Impact on Survival

Hingorani

Seidel

Lindner

et al. 2008

Biology of Blood and Marrow Transplantation

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“…The detailed evidence for the existence of the degradation pathway has been reviewed elsewhere (26,48,93). Briefly, the degradation pathway is proposed to be a high-affinity/low-capacity pathway, associated with the megalin/cubilin receptor, transporting the relatively small quantities of unretrieved filtered albumin to lysosomes.…”

Section: Major Albumin Processing Pathways In the Proximal Tubular Cellmentioning

confidence: 99%

Disease-dependent mechanisms of albuminuria

Comper

Hilliard²,

Nikolic‐Paterson

et al. 2008

American Journal of Physiology-Renal Physiology

138

116

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The mechanism of albuminuria is perhaps one of the most complex yet important questions in renal physiology today. Recent studies have directly demonstrated that the normal glomerulus filters substantial amounts of albumin and that charge selectivity plays little or no role in preventing this process. This filtered albumin is then processed by proximal tubular cells by two distinct pathways; dysfunction in either one of these pathways gives rise to discrete forms of albuminuria. Most of the filtered albumin is returned to the peritubular blood supply by a retrieval pathway. Albuminuria in the nephrotic range would arise from retrieval pathway dysfunction. The small quantities of filtered albumin that are not retrieved undergo obligatory lysosomal degradation before urinary excretion as small peptide fragments. This degradation pathway is sensitive to metabolic factors responsible for hypertrophy and fibrosis, particularly molecules such as angiotensin II and transforming growth factor-beta1, whose production is stimulated by hyperglycemic and hypertensive environments. Dysfunction in this degradation pathway leads to albuminuria below the nephrotic range. These new insights into albumin filtration and processing argue for a reassessment of the role of podocytes and the slit diaphragm as major direct determinants governing albuminuria, provide information on how glomerular morphology and "tubular" albuminuria may be interrelated, and offer a new rationale for drug development.

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“…The detailed evidence for the existence of the degradation pathway has been reviewed elsewhere [20,46]. The degradation pathway is proposed to be a high affi nity/low capacity pathway, associated with the megalin/cubilin receptors [47], transporting the relatively small quantities (compared to that fi ltered) of unretrieved fi ltered albumin to lysosomes.…”

Section: Degradation Pathwaymentioning

confidence: 99%

“…Studies by Gekle et al [70] and Russo et al [71] have further demonstrated in PTC cultures that the addition of TGF-β can disrupt albumin uptake and degradation. Studies have demonstrated that quantitative effects of ACEIs in reducing albuminuria can be explained by their ability to activate lysosomal processing [46,72]. In other words, ACEI treatment activates lysosomal activity by inhibiting Ang II production.…”

Section: Albuminuria Derived From Altered Lysosomal Processing Refl Ementioning

confidence: 99%

Where does albuminuria come from in diabetic kidney disease?

Comper

Russo²

2008

Curr Diab Rep

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The classic mechanism to explain albumin excretion in diabetes has been permeability defects in the glomerular fi lter. However, a new concept has emerged that albuminuria can be explained by the two major pathways the proximal tubular cell uses to process fi ltered albumin. Specifi cally, albumin permeability through the glomerular fi lter is only governed by size selectivity. Most of the fi ltered albumin is retrieved by the proximal tubular cell and returned to the peritubular blood supply. Albuminuria in the nephrotic range would arise from retrieval pathway dysfunction. The small quantities of fi ltered albumin that are not retrieved undergo obligatory lysosomal degradation before urinary excretion as small peptide fragments. This pathway is sensitive to metabolic factors responsible for hypertrophy and fi brosis, particularly molecules such as angiotensin II and transforming growth factor-β1, whose production is stimulated by hyperglycemic environments. Dysfunction in this degradation pathway may lead to albuminuria below the nephrotic range.

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Insights into the Relationship Between Hypertension and Albuminuria

Cited by 7 publications

References 126 publications

Albuminuria in Hematopoietic Cell Transplantation Patients: Prevalence, Clinical Associations, and Impact on Survival

Albuminuria in Hematopoietic Cell Transplantation Patients: Prevalence, Clinical Associations, and Impact on Survival

Disease-dependent mechanisms of albuminuria

Where does albuminuria come from in diabetic kidney disease?

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