GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    Induction of kidney injury molecule-1 in homozygous Ren2 rats is attenuated by blockade of the renin-angiotensin system or p38 MAP kinase
    American Physiological Society ; 2007
    In:  American Journal of Physiology-Renal Physiology Vol. 292, No. 1 ( 2007-01), p. F313-F320
    Details
    In: American Journal of Physiology-Renal Physiology, American Physiological Society, Vol. 292, No. 1 ( 2007-01), p. F313-F320
    Abstract: Kidney injury molecule-1 (Kim-1) is associated with ischemic and proteinuric tubular injury; however, whether dysregulation of the renin-angiotensin system (RAS) can also induce Kim-1 is unknown. We studied Kim-1 expression in homozygous Ren2 rats, characterized by renal damage through excessive RAS activation. We also investigated whether antifibrotic treatment (RAS blockade or p38 MAP kinase inhibition) would affect Kim-1 expression. At 7 wk of age, homozygous Ren2 rats received a nonhypotensive dose of candesartan (0.05 mg·kg −1 ·day −1 sc) or the p38 inhibitor SB-239063 (15 mg·kg −1 ·day −1 sc) for 4 wk; untreated Ren2 and Sprague-Dawley (SD) rats served as controls. Kim-1 mRNA and protein expression were determined by quantitative PCR and immunohistochemistry, respectively, and related to markers of prefibrotic renal damage. Urinary Kim-1 was measured in 8-wk-old Ren2 and SD rats with and without angiotensin-converting enzyme inhibition (ramipril, 1 mg·kg −1 ·day −1 in drinking water for 4 wk). Untreated Ren2 rats showed a 〉 20-fold increase in renal Kim-1 mRNA (expressed as Kim-1-to-GAPDH ratio): 75.5 ± 43.6 vs. 3.1 ± 1.0 in SD rats ( P 〈 0.01). Candesartan and SB-239063 strongly reduced Kim-1 mRNA: 3.1 ± 1.5 ( P 〈 0.01) and 9.8 ± 4.2 ( P 〈 0.05), respectively. Kim-1 protein expression in damaged tubules paralleled mRNA expression. Kim-1 expression correlated with renal osteopontin, α-smooth muscle actin, and collagen III expression and with tubulointerstitial fibrosis. Damaged tubular segments expressing activated p38 also expressed Kim-1. Urinary Kim-1 was increased in Ren2 vs. SD (458 ± 70 vs. 27 ± 2 pg/ml, P 〈 0.01) rats and abolished in Ren2 rats treated with ramipril (33 ± 5 pg/ml, P 〈 0.01). Kim-1 is associated with development of RAS-mediated renal damage. Antifibrotic treatment through RAS blockade or p38 MAP kinase inhibition reduced Kim-1 in the homozygous Ren2 model.
    Type of Medium: Online Resource
    ISSN: 1931-857X , 1522-1466
    URL: Article
    DOI: 10.1152/ajprenal.00180.2006
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2007
    detail.hit.zdb_id: 1477287-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Profiling of the renal kinome: a novel tool to identify protein kinases involved in angiotensin II-dependent hypertensive renal damage
    American Physiological Society ; 2007
    In:  American Journal of Physiology-Renal Physiology Vol. 293, No. 1 ( 2007-07), p. F428-F437
    Details
    In: American Journal of Physiology-Renal Physiology, American Physiological Society, Vol. 293, No. 1 ( 2007-07), p. F428-F437
    Abstract: Regulation of protein kinase activities is crucial in both physiology and disease, but analysis is hampered by the multitude and complexity of kinase networks. We used novel peptide array chips containing 1,152 known kinase substrate sequences to profile different kinase activities in renal lysates from homozygous Ren2 rats, a model characterized by hypertension and angiotensin II (ANG II)-mediated renal fibrosis, compared with Sprague-Dawley (SD) control rats and Ren2 rats treated with an angiotensin-converting enzyme inhibitor (ACEi). Five-wk-old homozygous Ren2 rats were left untreated or treated with the ACEi ramipril (1 mg·kg −1 ·day −1 ) for 4 wk; age-matched SD rats served as controls ( n = 5 each). Peptide array chips were incubated with renal cortical lysates in the presence of radioactively labeled ATP. Radioactivity incorporated into the substrate motifs was measured to quantify kinase activity. A number of kinases with modulated activities, which might contribute to renal damage, were validated by Western blotting, immunoprecipitation, and immunohistochemistry. Relevant kinases identified by the peptide array and confirmed using conventional techniques included p38 MAP kinase and PDGF receptor-β, which were increased in Ren2 and reversed by ACEi. Furthermore, insulin receptor signaling was reduced in Ren2 compared with control rats, and G protein-coupled receptor kinase (GRK) activity decreased in Ren2 + ACEi compared with untreated Ren2 rats. Array-based profiling of tissue kinase activities in ANG II-mediated renal damage provides a powerful tool for identification of relevant kinase pathways in vivo and may lead to novel strategies for therapy.
    Type of Medium: Online Resource
    ISSN: 1931-857X , 1522-1466
    URL: Article
    DOI: 10.1152/ajprenal.00367.2006
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2007
    detail.hit.zdb_id: 1477287-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Tubular maximum phosphate reabsorption capacity in living kidney donors is independently associated with one-year recipient GFR
    American Physiological Society ; 2018
    In:  American Journal of Physiology-Renal Physiology Vol. 314, No. 2 ( 2018-02-01), p. F196-F202
    Details
    In: American Journal of Physiology-Renal Physiology, American Physiological Society, Vol. 314, No. 2 ( 2018-02-01), p. F196-F202
    Abstract: The donor glomerular filtration rate (GFR) measured before kidney donation is a strong determinant of recipient graft outcome. No tubular function markers have been identified that can similarly be used in donors to predict recipient outcomes. In the present study we investigated whether the pre-donation tubular maximum reabsorption capacity of phosphate (TmP-GFR), which may be considered a functional tubular marker in healthy kidney donors, is associated with recipient GFR at 1 yr after transplantation, a key determinant of long-term outcome. We calculated the pre-donation TmP-GFR from serum and 24-h urine phosphate and creatinine levels in 165 kidney donors, and recipient 125 I-iothalamate GFR and eGFR (CKD-EPI) at 12 mo after transplantation. Kidney donors were 51 ± 10 yr old, 47% were men, and mean GFR was 118 ± 26 ml/min. The donor TmP-GFR was associated with recipient GFR 12 mo after transplantation (GFR 6.0 ml/min lower per 1 mg/dl decrement of TmP-GFR), which persisted after multivariable adjustment for donor age, sex, pre-donation GFR, and blood pressure and other potential confounders. Results were highly similar when eGFR at 12 mo was taken as the outcome. Tubular damage markers kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin were low and not associated with recipient GFR. A lower donor TmP-GFR before donation, which may be considered to represent a functional measure of tubular phosphate reabsorption capacity, is independently associated with a lower recipient GFR 1 yr after transplantation. These data are the first to link donor tubular phosphate reabsorption with recipient GFR post-transplantation.
    Type of Medium: Online Resource
    ISSN: 1931-857X , 1522-1466
    URL: Article
    DOI: 10.1152/ajprenal.00287.2017
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2018
    detail.hit.zdb_id: 1477287-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Overweight young female kidney donors have low renal functional reserve postdonation
    American Physiological Society ; 2018
    In:  American Journal of Physiology-Renal Physiology Vol. 315, No. 3 ( 2018-09-01), p. F454-F459
    Details
    In: American Journal of Physiology-Renal Physiology, American Physiological Society, Vol. 315, No. 3 ( 2018-09-01), p. F454-F459
    Abstract: Maintenance of adequate renal function after living kidney donation is important for donor outcome. Overweight donors, in particular, may have an increased risk for end-stage kidney disease (ESKD), and young female donors have an increased preeclampsia risk. Both of these risks may be associated with low postdonation renal functional reserve (RFR). Because we previously found that higher body mass index (BMI) was associated with lower postdonation RFR, we now studied the relationship between BMI and RFR in young female donors. RFR, the rise in glomerular filtration rate (GFR) ( 125 I-iothalamate clearance) during dopamine, was measured in female donors ( 〈 45 yr) before and after kidney donation. Donors who are overweight (BMI 〉 25) and nonoverweight donors were compared by Studentʼs t-test; the association was subsequently explored with regression analysis. We included 105 female donors [age 41 (36–44) median(IQR)] with a BMI of 25 (22–27) kg/m 2 . Predonation GFR was 118 (17) ml/min [mean(SD)] rising to 128 (19) ml/min during dopamine; mean RFR was 10 (10) ml/min. Postdonation GFR was 76 (13) ml/min, rising to 80 (12); RFR was 4 (6) ml/min ( P 〈 0.001 vs. predonation). In overweight donors, RFR was fully lost after donation (1 ml/min vs. 10 ml/min predonation, P 〈 0.001), and BMI was inversely associated with RFR after donation, independent of confounders (standardized β 0.37, P = 0.02). Reduced RFR might associate with the risk of preeclampsia and ESKD in kidney donors. Prospective studies should explore whether RFR is related to preeclampsia and whether BMI reduction before conception is of benefit to overweight female kidney donors during and after pregnancy.
    Type of Medium: Online Resource
    ISSN: 1931-857X , 1522-1466
    URL: Article
    DOI: 10.1152/ajprenal.00492.2017
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2018
    detail.hit.zdb_id: 1477287-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    SLC22A2 is associated with tubular creatinine secretion and bias of estimated GFR in renal transplantation
    American Physiological Society ; 2013
    In:  Physiological Genomics Vol. 45, No. 6 ( 2013-03-15), p. 201-209
    Details
    In: Physiological Genomics, American Physiological Society, Vol. 45, No. 6 ( 2013-03-15), p. 201-209
    Abstract: Genome-wide association studies reported SLC22A2 variants to be associated with serum creatinine. As SLC22A2 encodes the organic cation transporter 2 (OCT2), the association might be due to an effect on tubular creatinine handling. To test this hypothesis we studied the association of SLC22A2 polymorphisms with phenotypes of net tubular creatinine secretion: fractional creatinine excretion (FE creat ) and bias of estimated glomerular filtration rate (eGFR). We also studied the association with end-stage renal disease (ESRD) and graft failure (GF) in renal transplant recipients. SLC22A2 single nucleotide polymorphisms (SNPs), rs3127573 and rs316009, were genotyped in 1,142 ESRD patients receiving renal transplantation and 1,186 kidney donors as controls. GFR was measured with 125 I-iothalamate clearance. Creatinine clearance was also assessed. FE creat was calculated from the simultaneous clearances of creatinine and 125 I-iothalamate. Donor rs316009 was associated with FE creat (beta −0.053, P = 0.024) and with estimated [modification of diet in renal disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)] but not measured GFR. In line with this, donor rs316009 was associated with bias of the MDRD and CKD-EPI but not the Cockroft-Gault equation. Both SNPs were associated with ESRD: odds ratios [95% CI] 1.39 [1.16–1.67], P = 0.00065, and 1.23 [1.02–1.48] , P = 0.042, for rs3127573 and rs316009, respectively. Neither SNP was associated with GF. Thus, SLC22A2 is associated with phenotypes of net tubular creatinine secretion and ESRD.
    Type of Medium: Online Resource
    ISSN: 1094-8341 , 1531-2267
    URL: Article
    DOI: 10.1152/physiolgenomics.00087.2012
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2013
    detail.hit.zdb_id: 2031330-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Renal functional reserve capacity before and after living kidney donation
    American Physiological Society ; 2018
    In:  American Journal of Physiology-Renal Physiology Vol. 315, No. 6 ( 2018-12-01), p. F1550-F1554
    Details
    In: American Journal of Physiology-Renal Physiology, American Physiological Society, Vol. 315, No. 6 ( 2018-12-01), p. F1550-F1554
    Abstract: Compensatory gomerular filtration rate (GFR) increase after kidney donation results in a GFR above 50% of the predonation value. The renal functional reserve (RFR) assessed by the renal response to dopamine infusion (RFR dopa ) is considered to reflect functional reserve capacity and is thought to be a tool for living donor screening. However, it is unknown if the RFR dopa predicts long-term kidney function. Between 1984 and 2017, we prospectively measured GFR ( 125 I-iothalamate) and RFR by dopamine infusion in 937 living kidney donors. We performed linear regression analysis of predonation RFR dopa and postdonation GFR. In donors with 5-yr follow-up after donation we assessed the association with long-term GFR. Mean donor age was 52  yr (SD 11); 52% were female. Mean predonation GFR was 114  ml/min (SD 22), GFR dopa was 124 ml/min (SD 24), resulting in an RFR of 9 ml/min (SD 10). Three months postdonation, GFR was 72 ml/min (SD 15) and GFR dopa was 75 ml/min (SD 15), indicating that donors still had RFR dopa [3 ml/min (SD 6), P 〈 0.001]. Predonation RFR dopa was not associated with predonation GFR [standardized (st.) β −0.009, P = 0.77] but was positively associated with GFR 3 mo after donation (st. β 0.12, P 〈 0.001). In the subgroup of donors with 5-yr follow-up data ( n = 383), RFR dopa was not associated with GFR at 5 yr postdonation (st. β 0.05, P = 0.35). In conclusion, RFR dopa is a predictor of short-term GFR after living kidney donation but not of long-term kidney function. Therefore, measurement of the RFR dopa is not a useful tool for donor screening. Studies investigating long-term renal adaptation are warranted to study the effects of living kidney donation and improve donor screening.
    Type of Medium: Online Resource
    ISSN: 1931-857X , 1522-1466
    URL: Article
    DOI: 10.1152/ajprenal.00064.2018
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2018
    detail.hit.zdb_id: 1477287-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Neonatal dexamethasone administration causes progressive renal damage due to induction of an early inflammatory response
    American Physiological Society ; 2008
    In:  American Journal of Physiology-Renal Physiology Vol. 294, No. 4 ( 2008-04), p. F768-F776
    Details
    In: American Journal of Physiology-Renal Physiology, American Physiological Society, Vol. 294, No. 4 ( 2008-04), p. F768-F776
    Abstract: Glucocorticoids (GCs) are widely used to prevent chronic lung disease in immature newborns. Emerging evidence indicates that GC exposure in early life may interfere with kidney function and is associated with hypertension in later life. In this study, we have investigated the effect of neonatal dexamethasone (DEX) administration on renal function in rats. Male rats were treated with DEX in the first 3 days after birth, controls received saline (SAL). Severe renal damage associated with premature death was found at 50 wks upon DEX treatment, while renal function and morphology were normal in controls. A subsequent time-course study was performed from 2 days to 32 wks. Compared with controls, neonatal DEX administration led to significant and persistent growth retardation. Progressive proteinuria and increased systolic blood pressure were found from 8 wks onwards in DEX-treated animals. Renal α-SMA gene expression was elevated from wk 24 onwards and morphological fibrosis was noted at 32 wks of age following DEX treatment. Markedly increased renal gene expression of TNF-α and MCP-1 in DEX -treated rats was observed at day 7, probably contributing to the permanent increase in interstitial macrophage numbers that started at 14 days. Permanently elevated renal TGF-β gene expression was induced by DEX administration from 4 wks onwards. Our data indicate that neonatal DEX administration in rats leads to renal failure in later life, presumably due to an early inflammatory trigger that elicits a persistent pro-fibrotic process that eventually results in progressive renal deterioration.
    Type of Medium: Online Resource
    ISSN: 1931-857X , 1522-1466
    URL: Article
    DOI: 10.1152/ajprenal.00163.2007
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2008
    detail.hit.zdb_id: 1477287-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...