Primary results of the randomized trial of metformin administration in polycystic kidney disease (TAME PKD)
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by growth of kidney cysts and glomerular filtration rate (GFR) decline. Metformin was found to impact cystogenesis in preclinical models of polycystic disease, is generally considered safe and may be a promising candidate for clin...
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| Veröffentlicht in: | Kidney international Jg. 100; H. 3; S. 684 |
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| Sprache: | Englisch |
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01.09.2021
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| Abstract | Autosomal dominant polycystic kidney disease (ADPKD) is characterized by growth of kidney cysts and glomerular filtration rate (GFR) decline. Metformin was found to impact cystogenesis in preclinical models of polycystic disease, is generally considered safe and may be a promising candidate for clinical investigation in ADPKD. In this phase 2 two-year trial, we randomly assigned 97 patients, 18-60 years of age, with ADPKD and estimated GFR over 50 ml/min/1.73 m
, in a 1:1 ratio to receive metformin or placebo twice daily. Primary outcomes were medication safety and tolerability. Secondary outcomes included estimated GFR decline, and total kidney volume growth. Thirty-eight metformin and 39 placebo participants still received study product at 24-months. Twenty-one participants in the metformin arm reduced drug dose due to inability to tolerate, compared with 14 in the placebo arm (not significant). Proportions of participants experiencing serious adverse events was similar between the groups. The Gastrointestinal Symptoms Rating Scale score was low at baseline and did not significantly change over time. The annual change for estimated GFR was -1.71 with metformin and -3.07 ml/min/1.73m
per year with placebo (mean difference 1.37 {-0.70, 3.44} ml/min/1.73m
), while mean annual percent change in height-adjusted total kidney volume was 3.87% in metformin and 2.16% per year in placebo, (mean difference 1.68% {-2.11, 5.62}). Thus, metformin in adults with ADPKD was found to be safe and tolerable while slightly reducing estimated GFR decline but not to a significant degree. Hence, evaluation of efficacy requires a larger trial, with sufficient power to detect differences in endpoints. |
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| AbstractList | Autosomal dominant polycystic kidney disease (ADPKD) is characterized by growth of kidney cysts and glomerular filtration rate (GFR) decline. Metformin was found to impact cystogenesis in preclinical models of polycystic disease, is generally considered safe and may be a promising candidate for clinical investigation in ADPKD. In this phase 2 two-year trial, we randomly assigned 97 patients, 18-60 years of age, with ADPKD and estimated GFR over 50 ml/min/1.73 m2, in a 1:1 ratio to receive metformin or placebo twice daily. Primary outcomes were medication safety and tolerability. Secondary outcomes included estimated GFR decline, and total kidney volume growth. Thirty-eight metformin and 39 placebo participants still received study product at 24-months. Twenty-one participants in the metformin arm reduced drug dose due to inability to tolerate, compared with 14 in the placebo arm (not significant). Proportions of participants experiencing serious adverse events was similar between the groups. The Gastrointestinal Symptoms Rating Scale score was low at baseline and did not significantly change over time. The annual change for estimated GFR was -1.71 with metformin and -3.07 ml/min/1.73m2 per year with placebo (mean difference 1.37 {-0.70, 3.44} ml/min/1.73m2), while mean annual percent change in height-adjusted total kidney volume was 3.87% in metformin and 2.16% per year in placebo, (mean difference 1.68% {-2.11, 5.62}). Thus, metformin in adults with ADPKD was found to be safe and tolerable while slightly reducing estimated GFR decline but not to a significant degree. Hence, evaluation of efficacy requires a larger trial, with sufficient power to detect differences in endpoints.Autosomal dominant polycystic kidney disease (ADPKD) is characterized by growth of kidney cysts and glomerular filtration rate (GFR) decline. Metformin was found to impact cystogenesis in preclinical models of polycystic disease, is generally considered safe and may be a promising candidate for clinical investigation in ADPKD. In this phase 2 two-year trial, we randomly assigned 97 patients, 18-60 years of age, with ADPKD and estimated GFR over 50 ml/min/1.73 m2, in a 1:1 ratio to receive metformin or placebo twice daily. Primary outcomes were medication safety and tolerability. Secondary outcomes included estimated GFR decline, and total kidney volume growth. Thirty-eight metformin and 39 placebo participants still received study product at 24-months. Twenty-one participants in the metformin arm reduced drug dose due to inability to tolerate, compared with 14 in the placebo arm (not significant). Proportions of participants experiencing serious adverse events was similar between the groups. The Gastrointestinal Symptoms Rating Scale score was low at baseline and did not significantly change over time. The annual change for estimated GFR was -1.71 with metformin and -3.07 ml/min/1.73m2 per year with placebo (mean difference 1.37 {-0.70, 3.44} ml/min/1.73m2), while mean annual percent change in height-adjusted total kidney volume was 3.87% in metformin and 2.16% per year in placebo, (mean difference 1.68% {-2.11, 5.62}). Thus, metformin in adults with ADPKD was found to be safe and tolerable while slightly reducing estimated GFR decline but not to a significant degree. Hence, evaluation of efficacy requires a larger trial, with sufficient power to detect differences in endpoints. Autosomal dominant polycystic kidney disease (ADPKD) is characterized by growth of kidney cysts and glomerular filtration rate (GFR) decline. Metformin was found to impact cystogenesis in preclinical models of polycystic disease, is generally considered safe and may be a promising candidate for clinical investigation in ADPKD. In this phase 2 two-year trial, we randomly assigned 97 patients, 18-60 years of age, with ADPKD and estimated GFR over 50 ml/min/1.73 m , in a 1:1 ratio to receive metformin or placebo twice daily. Primary outcomes were medication safety and tolerability. Secondary outcomes included estimated GFR decline, and total kidney volume growth. Thirty-eight metformin and 39 placebo participants still received study product at 24-months. Twenty-one participants in the metformin arm reduced drug dose due to inability to tolerate, compared with 14 in the placebo arm (not significant). Proportions of participants experiencing serious adverse events was similar between the groups. The Gastrointestinal Symptoms Rating Scale score was low at baseline and did not significantly change over time. The annual change for estimated GFR was -1.71 with metformin and -3.07 ml/min/1.73m per year with placebo (mean difference 1.37 {-0.70, 3.44} ml/min/1.73m ), while mean annual percent change in height-adjusted total kidney volume was 3.87% in metformin and 2.16% per year in placebo, (mean difference 1.68% {-2.11, 5.62}). Thus, metformin in adults with ADPKD was found to be safe and tolerable while slightly reducing estimated GFR decline but not to a significant degree. Hence, evaluation of efficacy requires a larger trial, with sufficient power to detect differences in endpoints. |
| Author | Abebe, Kaleab Z Miskulin, Dana C Lalama, Christina M Tao, Cheng Althouse, Andrew D Watnick, Terry J Perrone, Ronald D Bae, Kyongtae Ty Hallows, Kenneth R Seliger, Stephen L Harris, Peter C |
| Author_xml | – sequence: 1 givenname: Ronald D surname: Perrone fullname: Perrone, Ronald D email: rperrone@tuftsmedicalcenter.org organization: Division of Nephrology, Department of Medicine, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA. Electronic address: rperrone@tuftsmedicalcenter.org – sequence: 2 givenname: Kaleab Z surname: Abebe fullname: Abebe, Kaleab Z organization: Division of General Internal Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA – sequence: 3 givenname: Terry J surname: Watnick fullname: Watnick, Terry J organization: Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA – sequence: 4 givenname: Andrew D surname: Althouse fullname: Althouse, Andrew D organization: Division of General Internal Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA – sequence: 5 givenname: Kenneth R surname: Hallows fullname: Hallows, Kenneth R organization: USC/UKRO Kidney Research Center and Division of Nephrology and Hypertension, Department of Medicine, University of Southern California Keck School of Medicine, Los Angeles, California, USA – sequence: 6 givenname: Christina M surname: Lalama fullname: Lalama, Christina M organization: Division of General Internal Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA – sequence: 7 givenname: Dana C surname: Miskulin fullname: Miskulin, Dana C organization: Division of Nephrology, Department of Medicine, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA – sequence: 8 givenname: Stephen L surname: Seliger fullname: Seliger, Stephen L organization: Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA – sequence: 9 givenname: Cheng surname: Tao fullname: Tao, Cheng organization: Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA – sequence: 10 givenname: Peter C surname: Harris fullname: Harris, Peter C organization: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA – sequence: 11 givenname: Kyongtae Ty surname: Bae fullname: Bae, Kyongtae Ty organization: Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA |
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| Keywords | clinical trial total kidney volume metformin autosomal dominant polycystic kidney disease estimated glomerular filtration rate |
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| Title | Primary results of the randomized trial of metformin administration in polycystic kidney disease (TAME PKD) |
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