Albuminuria, Wherefore Art Thou?

Jarad, George; Miner, Jeffrey H.

doi:10.1681/asn.2009010075

Cited by 14 publications

(18 citation statements)

References 11 publications

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“…Microalbuminuria is an important early clinical indicator of progressive kidney disease in association with the metabolic syndrome and diabetes [1,2,3]. PTCs normally reabsorb most of the glomerular-filtered protein, so only 30 mg or less appears in the urine [7,8,9,10,11,12,13,14]. Further, there is increasing evidence that growth factors such as angiotensin II (Ang II), in conjunction with filtered proteins, can exert direct injury to the PTC resulting in tubulointerstitial fibrosis.…”

Section: Introductionmentioning

confidence: 99%

“…Albumin and other small molecular proteins filtered through the glomerulus are processed by PTC by at least two distinct pathways and most of the filtered albumin is returned to the peritubular blood by a retrieval pathway [11,12,13,14,15]. Compelling evidence for the importance of this retrieval pathway has been provided by two-photon microscopy [16].…”

Section: Introductionmentioning

confidence: 99%

“…This process is disrupted by elevated tissue levels of Ang II. Albumin retrieval can be restored through Ang II blockade [7,9,10,11,12,13,14,15,16,17,18,19,20]. Smaller quantities of filtered proteins that are not retrieved undergo lysosomal degradation before urinary excretion as small peptide fragments [17,21].…”

Section: Introductionmentioning

confidence: 99%

“…Smaller quantities of filtered proteins that are not retrieved undergo lysosomal degradation before urinary excretion as small peptide fragments [17,21]. This degradation pathway is especially susceptible to metabolic and growth factors such as Ang II, responsible for maladaptive changes in the PTC and consequent tubulointerstitial fibrosis [10,11,12,13,14,15,16,17,18,19,20]. …”

Section: Introductionmentioning

confidence: 99%

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Nebivolol Attenuates Maladaptive Proximal Tubule Remodeling in Transgenic Rats

Hayden

Habibi²,

Whaley‐Connell³

et al. 2010

Am J Nephrol

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Background/Aims: The impact of nebivolol therapy on the renal proximal tubular cell (PTC) structure and function was investigated in a transgenic (TG) rodent model of hypertension and the cardiometabolic syndrome. The TG Ren2 rat develops nephropathy with proteinuria, increased renal angiotensin II levels and oxidative stress, and PTC remodeling. Nebivolol, a β₁-antagonist, has recently been shown to reduce albuminuria, in part, through reductions in renal oxidative stress. Accordingly, we hypothesized that nebivolol therapy would attenuate PTC damage and tubulointerstitial fibrosis. Methods: Young Ren2 (R2-N) and SD (SD-N) rats were treated with nebivolol (10 mg/kg/day) or vehicle (R2-C; SD-C) for 3 weeks. PTC structure and function were tested using transmission electron microscopy and functional measurements. Results: Nebivolol treatment decreased urinary N-acetyl-β-D-glucosaminidase, tubulointerstitial ultrastructural remodeling and fibrosis, NADPH oxidase activity, 3-nitrotyrosine levels, and increased megalin and lysosomal-associated membrane protein-2 immunostaining in PTCs. Ultrastructural abnormalities that were improved with therapy included altered canalicular structure, reduced endosomes/lysosomes and PTC vacuoles, basement membrane thickening, and mitochondrial remodeling/fragmentation. Conclusion: These observations support the notion that nebivolol may improve PTC reabsorption of albumin and other glomerular filtered small molecular weight proteins in association with the attenuation of oxidative stress, tubulointerstitial injury and fibrosis in this rat model of metabolic kidney disease.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Nebivolol Attenuates Maladaptive Proximal Tubule Remodeling in Transgenic Rats

Hayden

Habibi²,

Whaley‐Connell³

et al. 2010

Am J Nephrol

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show abstract

“…Jared and Miner 13 have asked for the definitive experiment and data to settle the matter. However, we doubt there can be a single experiment or that the necessary data can be obtained easily with the available techniques.…”

mentioning

confidence: 99%