Use my Search Websuite to scan PubMed, PMCentral, Journal Hosts and Journal Archives, FullText. Kick-your-searchterm to multiple Engines kick-your-query now !>

A dictionary by aggregated review articles of nephrology, medicine and the life sciences Your one-stop-run pathway from word to the immediate pdf of peer-reviewed on-topic knowledge.

10.2215/CJN.09900915 http://scihub22266oqcxt.onion/10.2215/CJN.09900915 C4858487!4858487 !26912555     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\26912555 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Clin+J+Am+Soc+Nephrol 2016 ; 11 (5 ): 785-794 Nephropedia Template TP {{tp|p=26912555 |t=2016. Effect of Sirolimus on Disease Progression in Patients with Autosomal Dominant Polycystic Kidney Disease and CKD Stages 3b-4 |pdf=|usr=}}{{26912555 }} gab.com Text Effect of Sirolimus on Disease Progression in Patients with Autosomal Dominant Polycystic Kidney Disease and CKD Stages 3b-4 JO: Clin J Am Soc Nephrol http://www.kidney.de/pget.php?&tw=1&pmid=26912555 #FOAvip BACKGROUND AND OBJECTIVES: The effect of mammalian target of rapamycin (mTOR) inhibitors has never been tested in patients with autosomal dominant polycystic kidney disease (ADPKD) and severe renal insufficiency. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this academic, prospective, randomized, open label, blinded end point, parallel group trial (ClinicalTrials.gov no. NCT01223755), 41 adults with ADPKD, CKD stage 3b or 4, and proteinuria ?0.5 g/24 h were randomized between September of 2010 and March of 2012 to sirolimus (3 mg/d; serum target levels of 5-10 ng/ml) added on to conventional therapy (n=21) or conventional treatment alone (n=20). Primary outcome was GFR (iohexol plasma clearance) change at 1 and 3 years versus baseline. RESULTS: At the 1-year preplanned interim analysis, GFR fell from 26.7±5.8 to 21.3±6.3 ml/min per 1.73 m(2) (P<0.001) and from 29.6±5.6 to 24.9±6.2 ml/min per 1.73 m(2) (P<0.001) in the sirolimus and conventional treatment groups, respectively. Albuminuria (73.8±81.8 versus 154.9±152.9 ?g/min; P=0.02) and proteinuria (0.3±0.2 versus 06±0.4 g/24 h; P<0.01) increased with sirolimus. Seven patients on sirolimus versus one control had de novo proteinuria (P=0.04), ten versus three patients doubled proteinuria (P=0.02), 18 versus 11 patients had peripheral edema (P=0.04), and 14 versus six patients had upper respiratory tract infections (P=0.03). Three patients on sirolimus had angioedema, 14 patients had aphthous stomatitis, and seven patients had acne (P<0.01 for both versus controls). Two patients progressed to ESRD, and two patients withdrew because of worsening of proteinuria. These events were not observed in controls. Thus, the independent data and safety monitoring board recommend early trial termination for safety reasons. At 1 year, total kidney volume (assessed by contrast-enhanced computed tomography imaging) increased by 9.0% from 2857.7±1447.3 to 3094.6±1519.5 ml on sirolimus and 4.3% from 3123.4±1695.3 to 3222.6±1651.4 ml on conventional therapy (P=0.12). On follow-up, 37% and 7% of serum sirolimus levels fell below or exceeded the therapeutic range, respectively. CONCLUSIONS: Finding that sirolimus was unsafe and ineffective in patients with ADPKD and renal insufficiency suggests that mTOR inhibitor therapy may be contraindicated in this context. Twit Text FOAVip Effect of Sirolimus on Disease Progression in Patients with Autosomal Dominant Polycystic Kidney Disease and CKD Stages 3b-4 ????Clin J Am Soc Nephrol http://www.kidney.de/pget.php?&tw=1&pmid=26912555 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26912555 #FOAvip English Wikipedia <ref>{{Cite pmid|26912555 }}</ref> Effect of Sirolimus on Disease Progression in Patients with Autosomal Dominant Polycystic Kidney Disease and CKD Stages 3b-4 #MMPMID26912555 Ruggenenti P ; Gentile G ; Perico N ; Perna A ; Barcella L ; Trillini M ; Cortinovis M ; Ferrer Siles CP ; Reyes Loaeza JA ; Aparicio MC ; Fasolini G ; Gaspari F ; Martinetti D ; Carrara F ; Rubis N ; Prandini S ; Caroli A ; Sharma K ; Antiga L ; Remuzzi A ; Remuzzi G Clin J Am Soc Nephrol 2016[May]; 11 (5 ): 785-794 PMID26912555 show ga BACKGROUND AND OBJECTIVES: The effect of mammalian target of rapamycin (mTOR) inhibitors has never been tested in patients with autosomal dominant polycystic kidney disease (ADPKD) and severe renal insufficiency. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this academic, prospective, randomized, open label, blinded end point, parallel group trial (ClinicalTrials.gov no. NCT01223755), 41 adults with ADPKD, CKD stage 3b or 4, and proteinuria ?0.5 g/24 h were randomized between September of 2010 and March of 2012 to sirolimus (3 mg/d; serum target levels of 5-10 ng/ml) added on to conventional therapy (n=21) or conventional treatment alone (n=20). Primary outcome was GFR (iohexol plasma clearance) change at 1 and 3 years versus baseline. RESULTS: At the 1-year preplanned interim analysis, GFR fell from 26.7±5.8 to 21.3±6.3 ml/min per 1.73 m(2) (P<0.001) and from 29.6±5.6 to 24.9±6.2 ml/min per 1.73 m(2) (P<0.001) in the sirolimus and conventional treatment groups, respectively. Albuminuria (73.8±81.8 versus 154.9±152.9 ?g/min; P=0.02) and proteinuria (0.3±0.2 versus 06±0.4 g/24 h; P<0.01) increased with sirolimus. Seven patients on sirolimus versus one control had de novo proteinuria (P=0.04), ten versus three patients doubled proteinuria (P=0.02), 18 versus 11 patients had peripheral edema (P=0.04), and 14 versus six patients had upper respiratory tract infections (P=0.03). Three patients on sirolimus had angioedema, 14 patients had aphthous stomatitis, and seven patients had acne (P<0.01 for both versus controls). Two patients progressed to ESRD, and two patients withdrew because of worsening of proteinuria. These events were not observed in controls. Thus, the independent data and safety monitoring board recommend early trial termination for safety reasons. At 1 year, total kidney volume (assessed by contrast-enhanced computed tomography imaging) increased by 9.0% from 2857.7±1447.3 to 3094.6±1519.5 ml on sirolimus and 4.3% from 3123.4±1695.3 to 3222.6±1651.4 ml on conventional therapy (P=0.12). On follow-up, 37% and 7% of serum sirolimus levels fell below or exceeded the therapeutic range, respectively. CONCLUSIONS: Finding that sirolimus was unsafe and ineffective in patients with ADPKD and renal insufficiency suggests that mTOR inhibitor therapy may be contraindicated in this context. |Adult [MESH] |Albuminuria/etiology [MESH] |Disease Progression [MESH] |Early Termination of Clinical Trials [MESH] |Female [MESH] |Glomerular Filtration Rate [MESH] |Humans [MESH] |Immunosuppressive Agents/*adverse effects/pharmacokinetics/therapeutic use [MESH] |Male [MESH] |Middle Aged [MESH] |Polycystic Kidney, Autosomal Dominant/complications/*drug therapy/*physiopathology [MESH] |Prospective Studies [MESH] |Proteinuria/chemically induced/*etiology [MESH] |Renal Insufficiency, Chronic/*etiology [MESH]Effect of Sirolimus on Disease Progression in Patients with Autosomal (epmc).pdf DeepDyve Pubget Overpricing