Where does albuminuria come from in diabetic kidney disease?

Abstract

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.

Treatment of db/db diabetic mice with triptolide: a novel therapy for diabetic nephropathy

“…In our previous study, triptolide reduced proteinuria in puromycin aminonucleoside (PAN) nephrosis rats without influencing GFR [10]. It has been accepted that not only abnormal haemodynamics but also metabolic factors are responsible for glomerular hypertrophy [29]. The alleviated glomerular hypertrophy by triptolide in db/db diabetic mice may be related to improved metabolic disturbance.…”

Impaired Albumin Uptake and Processing Promote Albuminuria in OVE26 Diabetic Mice

“…Podocyte effacement, mutations in podocyte genes, or loss of podocytes results in increased glomerular permeability and leakage of albumin [19]. However Russo et al [17] and Comper and Russo [20] have proposed that impaired tubular reabsorption of albumin is the primary cause of diabetic albuminuria. Our results in diabetic OVE mice show that both glomerular leakage and impaired tubular reabsorption contribute to the severity of OVE diabetic proteinuria.…”

Lipokaina związana z żelatynazą neutrofilii i katepsyna L jako wczesne markery uszkodzenia nerek u dzieci z cukrzycą typu 1

“…This may indicate glomerular involvement in the pathogenesis of DKD. However, some authors claim that in diabetes, albumin excretion is caused by tubular dysfunction and PRACE ORYGINALNE reduced lysosomal albumin degradation in proximal tubule cells [24].…”

“…In rats, the activity of Cathepsins L and B was shown to be significantly decreased, which may be associated with renal hypertrophy in early diabetes [28]. Decreased activity of uCathL in diabetes may result from the inhibition by transforming growth factor beta (TGF-β) [24] and may lead to albumin loss resulting from the dysfunction of the degradation pathway and altered lysosomal processing in renal tubules. However, the potential importance of uCathL in DKD needs further investigation.…”