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Research Article Details

Article ID: A00177
PMID: 30422235
Source: JAMA
Title: Effect of Lanreotide on Kidney Function in Patients With Autosomal Dominant Polycystic Kidney Disease: The DIPAK 1 Randomized Clinical Trial.
Abstract: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst formation in both kidneys and loss of renal function, eventually leading to a need for kidney replacement therapy. There are limited therapeutic management options. To examine the effect of the somatostatin analogue lanreotide on the rate of kidney function loss in patients with later-stage ADPKD. An open-label randomized clinical trial with blinded end point assessment that included 309 patients with ADPKD from July 2012 to March 2015 at 4 nephrology outpatient clinics in the Netherlands. Eligible patients were 18 to 60 years of age and had an estimated glomerular filtration rate (eGFR) of 30 to 60 mL/min/1.73 m2. Follow-up of the 2.5-year trial ended in August 2017. Patients were randomized to receive either lanreotide (120 mg subcutaneously once every 4 weeks) in addition to standard care (n = 153) or standard care only (target blood pressure <140/90 mm Hg; n = 152). Primary outcome was annual change in eGFR assessed as slope through eGFR values during the 2.5-year treatment phase. Secondary outcomes included change in eGFR before vs after treatment, incidence of worsening kidney function (start of dialysis or 30% decrease in eGFR), change in total kidney volume and change in quality of life (range: 1 [not bothered] to 5 [extremely bothered]). Among the 309 patients who were randomized (mean [SD] age, 48.4 [7.3] years; 53.4% women), 261 (85.6%) completed the trial. Annual rate of eGFR decline for the lanreotide vs the control group was -3.53 vs -3.46 mL/min/1.73 m2 per year (difference, -0.08 [95% CI, -0.71 to 0.56]; P = .81). There were no significant differences for incidence of worsening kidney function (hazard ratio, 0.87 [95% CI, 0.49 to 1.52]; P = .87), change in eGFR (-3.58 vs -3.45; difference, -0.13 mL/min/1.73 m2 per year [95% CI, -1.76 to 1.50]; P = .88), and change in quality of life (0.05 vs 0.07; difference, -0.03 units per year [95% CI, -0.13 to 0.08]; P = .67). The rate of growth in total kidney volume was lower in the lanreotide group than the control group (4.15% vs 5.56%; difference, -1.33% per year [95% CI, -2.41% to -0.24%]; P = .02). Adverse events in the lanreotide vs control group included injection site discomfort (32% vs 0.7%), injection site papule (5.9% vs 0%), loose stools (91% vs 6.6%), abdominal discomfort (79% vs 20%), and hepatic cyst infections (5.2% vs 0%). Among patients with later-stage autosomal dominant polycystic kidney disease, treatment with lanreotide compared with standard care did not slow the decline in kidney function over 2.5 years of follow-up. These findings do not support the use of lanreotide for treatment of later-stage autosomal dominant polycystic kidney disease. ClinicalTrials.gov Identifier: NCT01616927.
DOI: 10.1001/jama.2018.15870

Strategy ID Therapy Strategy Synonyms Therapy Targets Therapy Drugs

Target ID Target Name GENE Action Class UniProtKB ID Entry Name
T47 Sialin SLC17A5 Target is a single protein chain Q9NRA2 SLC17A5_HUMAN Details
T15 Steryl-sulfatase STS INHIBITOR Hydrolase P08842 STS_HUMAN Details

Diseases ID DO ID Disease Name Definition Class
I02 1184 nephrotic syndrome "A nephrosis characterized by marked increase in glomerular protein permeability resulting in marked elevation of urine protein levels, hypoalbuminemia, hyperlipidemia, and hypercoagulability." [url:https\://en.wikipedia.org/wiki/Nephrotic_syndrome, url:https\://www.niddk.nih.gov/health-information/kidney-disease/nephrotic-syndrome-adults] Details
I07 9352 type 2 diabetes mellitus "A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin." [url:http\://en.wikipedia.org/wiki/Diabetes, url:http\://en.wikipedia.org/wiki/Diabetes_mellitus_type_2] Details

Drug ID Drug Name Type DrugBank ID Targets Category Latest Progress
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D004 Pyridoxal phosphate small molecule DB00114 Details
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D007 Biotin small molecule DB00121 Details
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D009 L-Lysine small molecule DB00123 Details
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D015 Serine small molecule DB00133 Details
D016 Methionine small molecule DB00134 Details
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D021 Glutamic acid small molecule DB00142 Details
D022 Phosphatidyl serine small molecule DB00144 Details
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D026 Creatine small molecule DB00148 Details
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D028 Tryptophan small molecule DB00150 Details
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D046 Bortezomib small molecule DB00188 Details
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D181 Prednisone small molecule DB00635 Details
D182 Inulin small molecule DB00638 Details
D183 Adenosine small molecule DB00640 Details
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D186 Trazodone small molecule DB00656 Details
D187 Verapamil small molecule DB00661 Details
D188 Epinephrine small molecule DB00668 Details
D189 Pirenzepine small molecule DB00670 Details
D190 Cefixime small molecule DB00671 Details
D191 Chlorpropamide small molecule DB00672 Details
D192 Losartan small molecule DB00678 Details
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D194 Warfarin small molecule DB00682 Details
D195 Midazolam small molecule DB00683 Details
D196 Tobramycin small molecule DB00684 Details
D197 Fludrocortisone small molecule DB00687 Details
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D201 Amprenavir small molecule DB00701 Details
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D205 Ibandronate small molecule DB00710 Details
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D209 Lisinopril small molecule DB00722 Details
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D211 Rocuronium small molecule DB00728 Details
D212 Risperidone small molecule DB00734 Details
D213 Esomeprazole small molecule DB00736 Details
D214 Pentamidine small molecule DB00738 Details
D215 Hydrocortisone small molecule DB00741 Details
D216 Mannitol small molecule DB00742 Details
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D218 Prilocaine small molecule DB00750 Details
D219 Isoflurane small molecule DB00753 Details
D220 Clopidogrel small molecule DB00758 Details
D221 Methimazole small molecule DB00763 Details
D222 Clavulanic acid small molecule DB00766 Details
D223 Alprostadil small molecule DB00770 Details
D224 Mefenamic acid small molecule DB00784 Details
D225 Perindopril small molecule DB00790 Details
D226 Alfentanil small molecule DB00802 Details
D227 Pentoxifylline small molecule DB00806 Details
D228 Indapamide small molecule DB00808 Details
D229 Tropicamide small molecule DB00809 Details
D230 Ribavirin small molecule DB00811 Details
D231 Fentanyl small molecule DB00813 Details
D232 Propofol small molecule DB00818 Details
D233 Acetazolamide small molecule DB00819 Details
D234 Tadalafil small molecule DB00820 Details
D235 Fosfomycin small molecule DB00828 Details
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D239 Tolazamide small molecule DB00839 Details
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D241 Donepezil small molecule DB00843 Details
D242 Nalbuphine small molecule DB00844 Details
D243 Levamisole small molecule DB00848 Details
D244 Perphenazine small molecule DB00850 Details
D245 Pseudoephedrine small molecule DB00852 Details
D246 Aminolevulinic acid small molecule DB00855 Details
D247 Terbinafine small molecule DB00857 Details
D248 Prednisolone small molecule DB00860 Details
D249 Diflunisal small molecule DB00861 Details
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D251 Guaifenesin small molecule DB00874 Details
D252 Eprosartan small molecule DB00876 Details
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D255 Quinapril small molecule DB00881 Details
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D259 Remifentanil small molecule DB00899 Details
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D261 Cocaine small molecule DB00907 Details
D262 Repaglinide small molecule DB00912 Details
D263 Phenformin small molecule DB00914 Details
D264 Amantadine small molecule DB00915 Details
D265 Metronidazole small molecule DB00916 Details
D266 Dinoprostone small molecule DB00917 Details
D267 Buprenorphine small molecule DB00921 Details
D268 Azacitidine small molecule DB00928 Details
D269 Misoprostol small molecule DB00929 Details
D270 Mesoridazine small molecule DB00933 Details
D271 Oxymetazoline small molecule DB00935 Details
D272 Salicylic acid small molecule DB00936 Details
D273 Acetylsalicylic acid small molecule DB00945 Details
D274 Phenprocoumon small molecule DB00946 Details
D275 Fexofenadine small molecule DB00950 Details
D276 Isoniazid small molecule DB00951 Details
D277 Norgestimate small molecule DB00957 Details
D278 Methylprednisolone small molecule DB00959 Details
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D281 Bromfenac small molecule DB00963 Details
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D289 Isotretinoin small molecule DB00982 Details
D290 Nandrolone phenpropionate small molecule DB00984 Details
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D304 Bethanechol small molecule DB01019 Details
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D316 Melatonin small molecule DB01065 Details
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D325 Benzocaine small molecule DB01086 Details
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D426 Methaqualone small molecule DB04833 Details
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D433 Voglibose small molecule DB04878 Details
D434 Iloperidone small molecule DB04946 Details
D435 Lobeline small molecule DB05137 Details
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D469 Triclosan small molecule DB08604 Details
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D477 Tofacitinib small molecule DB08895 Details
D478 Dimethyl fumarate small molecule DB08908 Details
D479 Sofosbuvir small molecule DB08934 Details
D480 Dexetimide small molecule DB08997 Details
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D482 Aliskiren small molecule DB09026 Details
D483 Ledipasvir small molecule DB09027 Details
D484 Acipimox small molecule DB09055 Details
D485 Ciprofibrate small molecule DB09064 Details
D486 Olaparib small molecule DB09074 Details
D487 Benzoyl peroxide small molecule DB09096 Details
D488 Coenzyme M small molecule DB09110 Details
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D491 Methylene blue small molecule DB09241 Details
D492 Moxonidine small molecule DB09242 Details
D493 Ubidecarenone small molecule DB09270 Details
D494 Silibinin small molecule DB09298 Details
D495 Glycerin small molecule DB09462 Details
D496 Methyl salicylate small molecule DB09543 Details
D497 Ixazomib small molecule DB09570 Details
D498 Hydrogen peroxide small molecule DB11091 Details
D499 Lycopene small molecule DB11231 Details
D500 Medetomidine small molecule DB11428 Details
D501 Lesinurad small molecule DB11560 Details
D502 Carbon monoxide small molecule DB11588 Details
D503 Curcumin small molecule DB11672 Details
D504 Pyridoxamine small molecule DB11673 Details
D505 Equol small molecule DB11674 Details
D506 Mosapride small molecule DB11675 Details
D507 Ebastine small molecule DB11742 Details
D508 Rifamycin small molecule DB11753 Details
D509 Imidapril small molecule DB11783 Details
D510 Angiotensin II small molecule DB11842 Details
D511 Verinurad small molecule DB11873 Details
D512 2,4-thiazolidinedione small molecule DB11898 Details
D513 Zuretinol acetate small molecule DB12112 Details
D514 Bradykinin small molecule DB12126 Details
D515 Sarpogrelate small molecule DB12163 Details
D516 Secoisolariciresinol small molecule DB12179 Details
D517 Bexagliflozin small molecule DB12236 Details
D518 Benzbromarone small molecule DB12319 Details
D519 Nitroaspirin small molecule DB12445 Details
D520 Piperine small molecule DB12582 Details
D521 Isoquercetin small molecule DB12665 Details
D522 Cicletanine small molecule DB12766 Details
D523 Gallopamil small molecule DB12923 Details
D524 Lactitol small molecule DB12942 Details
D525 Daidzein small molecule DB13182 Details
D526 Camostat small molecule DB13729 Details
D527 Fenofibric acid small molecule DB13873 Details
D528 Candesartan small molecule DB13919 Details
D529 Testosterone enanthate small molecule DB13944 Details
D530 Ferric cation small molecule DB13949 Details
D531 Palmidrol small molecule DB14043 Details
D532 Cianidanol small molecule DB14086 Details
D533 Tenofovir small molecule DB14126 Details
D534 Cinnamaldehyde small molecule DB14184 Details
D535 Cobaltous cation small molecule DB14205 Details
D536 Chromic cation small molecule DB14525 Details
D537 Zinc cation small molecule DB14532 Details
D538 Cupric cation small molecule DB14552 Details
D539 Bismuth cation small molecule DB14572 Details
D540 Calcium cation small molecule DB14577 Details
D541 Cortisone small molecule DB14681 Details
D542 Dabigatran small molecule DB14726 Details
D543 Remdesivir small molecule DB14761 Details
D544 Venglustat small molecule DB14966 Details
D545 Abrocitinib small molecule DB14973 Details
D546 Ursolic acid small molecule DB15588 Details