FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2320190694> ?p ?o ?g. }

• W2320190694 endingPage "271" @default.
• W2320190694 startingPage "269" @default.
• W2320190694 abstract "In the present issue of the journal, Russo et al. [1] investigated the effect of the angiotensin I-converting enzyme inhibitor ramipril on urinary albumin excretion in spontaneously hypertensive rats (SHR) and normotensive Wistar–Kyoto (WKY) rats with or without diabetes. For induction of diabetes, the classic method of intravenous streptozotocin injection was used. Although this model is well standardizable, it should be noted that it only exhibits some of the typical aspects of human diabetic nephropathy [2]. Thus, as in all studies using rat renal damage models, the results obtained can only be extrapolated to the situation in humans with caution. The novel aspect of the study of Russo et al. [1] is the measurement of total urinary albumin excretion, which takes into account the excretion of albumin-derived fragments. These fragments are not detectable by standard immunohistochemical methods, because the latter only detect intact albumin [3–6]. The determination of the amount of these albumin-derived fragments in addition to intact urinary albumin concentration has already been successfully performed by the authors in previous studies [3,4,7–11]. The fact that degradation of filtered proteins in the kidney occurs through lysosomal or endosomal activity in proximal tubular cells was recognized decades ago [12,13]. Degradation occurs for all larger proteins including immunoglobulins [14]. The degradation of proteins consists exclusively of lysosomal protein uptake from the tubular fluid and subsequent exocytosis of the peptide products back into the urine [3,4,7,8,14]. The contribution of albumin fragments generated from proteolytic activity on the luminal surface of tubular cells [15–17], from extrarenal sources [7], or from contraluminal uptake of albumin with subsequent degradation [15], is negligable. Consequently, degradation products are found in the urine but not in the blood [18]. In the kidney of rodents and humans, filtered albumin is fragmented to small peptides (< 10–15 kDa) within minutes [3,4,7,8,14,18,19]. In the urine of healthy rat or human kidneys, the albumin-derived fragments constitute > 90–95% of urinary albumin compared with < 5–10% of intact albumin [3,7,8,10,14,19]. Although the exact physiological role of this degradation pathway is unknown [10], it has become apparent that the pathway is impaired in the diseased kidney, leading to a reduction in the fragmentation ratio (fragmented : intact) of urinary albumin [8,14,18]. Thus, at least a part of a pathological urinary albumin loss may be due to tubular dysfunction in the state of disease, a fact which challenges the paradigm of glomerular capillary leakage as the primary cause of albuminuria/proteinuria [20–28]. The intratubular processing of albumin may be regulated by mediators of progressive renal damage, such as transforming growth factor-β (TGF-β) and angiotensin II [29]. Therefore, Russo et al. [1] also investigated whether changes in the amounts of renal TGF-β1 mRNA and its inducible gene transforming growth factor-β inducible gene (big-h3) mRNA, as well as renal angiotensinogen mRNA, correlated with changes in renal lysosomal activity. The latter was assessed by a direct method allowing estimation of lysosomal processing in vivo (i.e. masurement of the degree of desulphation of tritium-labelled dextran sulphate, [3H]DSO4, during renal passage) [30,31]. In a previous study [11], the authors reported that albuminuria in SHR rats is due to a malfunction of the lysosomal processing of albumin in tubular cells. Of importance, the authors demonstrated that the glomerular capillary wall permeability was unaltered. Thus, the increase of urinary albumin concentration in hypertensive rats appears to be a consequence of tubular dysfunction and not of glomerular damage. They were able to show that the same is true for rat models of glomerular injury (i.e. puromycin aminonucleoside nephrosis and anti-glomerular basement membrane glomerulonephritis) [32]. In a series of studies [3,4,8], it was shown that the proximal tubular processing of albumin in diabetes is similarly altered. In patients with type 1 diabetes [8], the reduction of the fragmentation ratio of albumin was proportional to the level of albuminuria, indicating that the tubular handling of albumin is progressively impaired as diabetic nephropathy advances. In the present study, Russo et al. [1] showed that the reduction of total urinary albumin concentration by ramipril in normotensive diabetic WKY rats and SHR rats with or without diabetes differed with regard to reduction of fragmented and intact urinary albumin. In the renal high-risk group of diabetic SHR, ramipril increased the rate of fragmented albumin excretion in the urine, which implicates that angiotensin-converting enzyme (ACE) inhibition improves tubular processing of albumin. This could indeed be documented by the measurement of the desulfation of [3H]DSO4 as a marker of in-vivo renal lysosomal activity: in the SHR but not the WKY rats ramipril prevented the increase of intact [3H]DSO4 concentration in the urine. Furthermore, treated diabetic SHR animals exhibited a marked reduction of intact urinary albumin excretion, which may partly be due to the above-mentioned increased fragmentation in proximal tubular cells. It is likely that the reduction of systemic and intraglomerular pressures as well as a beneficial effect on glomerular permselectivity also participate in the reduction of intact albuminuria in ramipril-treated diabetic SHR animals. Concerning diabetic WKY rats, which exhibit a lesser degree of renal damage due to the lack of an additional renal risk factor (i.e. hypertension), ramipril treatment did not influence intact albumin excretion rate. In contrast, ramipril prevented the increase of urinary albumin fragment excretion in these animals. The method for the measurement of renal lysosomal activity [30,31] deserves some comment. Because it is indirect and a ‘whole body method', it may over- or, less likely, underestimate lysosomal activity in proximal tubular cells, which are presumably the most important cells for the processing of urinary protein. Concerning the contraintuitive finding of the lack of any significant effect of ramipril on the amount of renal TGF-β1 mRNA, it should be acknowledged that the measurements were performed using the whole kidney. Thus, varying effects of ramipril on TGF-β1 mRNA in different segments of the nephron cannot be detected. Gilbert et al. [33] were able to document that ramipril attenuates the increase of both TGF-β1 and α1 (IV) collagen mRNA in renal tubules of streptozotocin diabetic Sprague–Dawley rats by means of in situ hybridization. The fact that the increase in the amount of renal TGF-β inducible gene (big-h3) mRNA in the study of Russo et al. [1] was inhibited by ramipril, at least in the diabetic and non-diabetic SHR animals, is more in line with previous reports about the effect of ACE inhibition on TGF-β1 expression in the diseased kidney of animals [33–39] and humans [40]. Concerning the levels of renal angiotensinogen mRNA, which were unaffected by ramipril both in diabetic and non-diabetic WKY and SHR, the finding of increased renal allograft angiotensinogen mRNA levels in ACE inhibitor-treated rats with chronic transplant nephropathy [39] is noteworthy. However, these different findings may be due to the different ACE inhibitors and animal models used. For example, enalapril but not captopril normalized renal angiotensinogen expression in a model of heart failure in rats [41]. In conclusion, Russo et al. [1] provide further evidence that the state of albuminuria may not only be due to changes in glomerular permselectivity. Conversely, the nephroprotective effect of ACE inhibition, which is mainly due to a reduction of albuminuria/proteinuria [42], cannot only be explained by an improvement of glomerular permselectivity and a reduction of intraglomerular pressure, but also by beneficial effects on the function of the transtubular pathway of albumin/protein transport [43] and albumin/protein degradation [1,8,9]. Further studies will be necessary to gain more insights into the ‘tubular degradation pathway’ [6], especially with regard to the specific mechanisms leading to its malfunction in the diseased kidney. As an ultimate goal, specific therapeutic approaches to restore the function of this pathway have to be developed. This may result in a new therapeutic option in the treatment of progressive renal damage." @default.
• W2320190694 created "2016-06-24" @default.
• W2320190694 creator A5052396006 @default.
• W2320190694 creator A5075578189 @default.
• W2320190694 date "2003-02-01" @default.
• W2320190694 modified "2023-09-24" @default.
• W2320190694 title "Altered tubular albumin degradation in the pathogenesis of albuminuria" @default.
• W2320190694 cites W120112492 @default.
• W2320190694 cites W1572048900 @default.
• W2320190694 cites W1579144739 @default.
• W2320190694 cites W1928017893 @default.
• W2320190694 cites W1966766282 @default.
• W2320190694 cites W1967880713 @default.
• W2320190694 cites W1969009295 @default.
• W2320190694 cites W1991631571 @default.
• W2320190694 cites W2005482739 @default.
• W2320190694 cites W2018392587 @default.
• W2320190694 cites W2018680608 @default.
• W2320190694 cites W2036563690 @default.
• W2320190694 cites W2037715793 @default.
• W2320190694 cites W2039013303 @default.
• W2320190694 cites W2043340584 @default.
• W2320190694 cites W2046303640 @default.
• W2320190694 cites W2048129659 @default.
• W2320190694 cites W2056725555 @default.
• W2320190694 cites W2056923835 @default.
• W2320190694 cites W2060705706 @default.
• W2320190694 cites W2061885821 @default.
• W2320190694 cites W2063189982 @default.
• W2320190694 cites W2066538838 @default.
• W2320190694 cites W2066690419 @default.
• W2320190694 cites W2067799385 @default.
• W2320190694 cites W2078060833 @default.
• W2320190694 cites W2082728934 @default.
• W2320190694 cites W2082888430 @default.
• W2320190694 cites W2083152534 @default.
• W2320190694 cites W2083693708 @default.
• W2320190694 cites W2101728431 @default.
• W2320190694 cites W2108307703 @default.
• W2320190694 cites W2116364231 @default.
• W2320190694 cites W2136992489 @default.
• W2320190694 cites W2140285167 @default.
• W2320190694 cites W2156379999 @default.
• W2320190694 cites W2299528224 @default.
• W2320190694 cites W2324490186 @default.
• W2320190694 cites W2344469084 @default.
• W2320190694 cites W4255638556 @default.
• W2320190694 doi "https://doi.org/10.1097/00004872-200302000-00016" @default.
• W2320190694 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/12569255" @default.
• W2320190694 hasPublicationYear "2003" @default.
• W2320190694 type Work @default.
• W2320190694 sameAs 2320190694 @default.
• W2320190694 citedByCount "6" @default.
• W2320190694 countsByYear W23201906942013 @default.
• W2320190694 crossrefType "journal-article" @default.
• W2320190694 hasAuthorship W2320190694A5052396006 @default.
• W2320190694 hasAuthorship W2320190694A5075578189 @default.
• W2320190694 hasBestOaLocation W23201906941 @default.
• W2320190694 hasConcept C126322002 @default.
• W2320190694 hasConcept C2776125364 @default.
• W2320190694 hasConcept C2776174234 @default.
• W2320190694 hasConcept C2780091579 @default.
• W2320190694 hasConcept C2780942790 @default.
• W2320190694 hasConcept C71924100 @default.
• W2320190694 hasConceptScore W2320190694C126322002 @default.
• W2320190694 hasConceptScore W2320190694C2776125364 @default.
• W2320190694 hasConceptScore W2320190694C2776174234 @default.
• W2320190694 hasConceptScore W2320190694C2780091579 @default.
• W2320190694 hasConceptScore W2320190694C2780942790 @default.
• W2320190694 hasConceptScore W2320190694C71924100 @default.
• W2320190694 hasIssue "2" @default.
• W2320190694 hasLocation W23201906941 @default.
• W2320190694 hasLocation W23201906942 @default.
• W2320190694 hasOpenAccess W2320190694 @default.
• W2320190694 hasPrimaryLocation W23201906941 @default.
• W2320190694 hasRelatedWork W1905619768 @default.
• W2320190694 hasRelatedWork W2011861071 @default.
• W2320190694 hasRelatedWork W2055045862 @default.
• W2320190694 hasRelatedWork W2057384529 @default.
• W2320190694 hasRelatedWork W2140285167 @default.
• W2320190694 hasRelatedWork W2146378459 @default.
• W2320190694 hasRelatedWork W2320190694 @default.
• W2320190694 hasRelatedWork W2428300499 @default.
• W2320190694 hasRelatedWork W2530854055 @default.
• W2320190694 hasRelatedWork W2767673896 @default.
• W2320190694 hasVolume "21" @default.
• W2320190694 isParatext "false" @default.
• W2320190694 isRetracted "false" @default.
• W2320190694 magId "2320190694" @default.
• W2320190694 workType "article" @default.