ArticleClinical and translational science2017
Does Secretory Clearance Follow Glomerular Filtration Rate in Chronic Kidney Diseases? Reconsidering the Intact Nephron Hypothesis.
Article in Clinical and translational science, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 2 syntheses or guidelines pooled it, 43 citations in OpenAlex.
- Effectiveness of thiazide and thiazide-like diuretics in advanced chronic kidney disease: a systematic review and meta-analysis.Renal failure · 2023Pooled it
- The intact nephron hypothesis as a model for renal drug handling.European journal of clinical pharmacology · 2019Pooled it
- Resilient nanostructured bioanalytic microneedle longitudinally monitors preclinical renal and hepatic drug clearance and dysfunction.Science translational medicine · 2026Article
- A guide to uraemic toxicity.Nature reviews. Nephrology · 2026Review
- Evaluation of Adefovir PBPK Model to Assess Biomarker-Informed OAT1 Drug-Drug Interaction and Effect of Chronic Kidney Disease.CPT: pharmacometrics & systems pharmacology · 2025Article
- Aligning kidney function assessment in patients with cancer to global practices in internal medicine.EClinicalMedicine · 2025Review
- Physiologically Based Pharmacokinetic Model of Cefotaxime in Patients with Impaired Renal Function.Clinical pharmacokinetics · 2025Article
- Challenges of Serum Creatinine Level in GFR Assessment and Drug Dosing Decisions in Kidney Injury.Advanced pharmaceutical bulletin · 2024Review
- Modeling Metformin and Dapagliflozin Pharmacokinetics in Chronic Kidney Disease.The AAPS journal · 2024Article
- Incorporating Uremic Solute-mediated Inhibition of OAT1/3 Improves PBPK Prediction of Tenofovir Renal and Systemic Disposition in Patients with Severe Kidney Disease.Pharmaceutical research · 2023Article
- Medication Management in the Critically Ill Patient with Acute Kidney Injury.Clinical journal of the American Society of Nephrology : CJASN · 2023Review
- Comparison of creatinine-based equations for estimating renal function for digoxin dose adjustment in patients with atrial fibrillation and heart failure.Pharmacology research & perspectives · 2023Article
- Effect of Chronic Kidney Disease on the Renal Secretion via Organic Anion Transporters 1/3: Implications for Physiologically-Based Pharmacokinetic Modeling and Dose Adjustment.Clinical pharmacology and therapeutics · 2022Article
- Determining the Effects of Chronic Kidney Disease on Organic Anion Transporter1/3 Activity Through Physiologically Based Pharmacokinetic Modeling.Clinical pharmacokinetics · 2022Article
- Drug toxicity in the proximal tubule: new models, methods and mechanisms.Pediatric nephrology (Berlin, Germany) · 2022Review
- PBPK Simulation-Based Evaluation of Ganciclovir Crystalluria Risk Factors: Effect of Renal Impairment, Old Age, and Low Fluid Intake.The AAPS journal · 2021Article
- Creatinine-Based Renal Function Assessment in Pediatric Drug Development: An Analysis Using Clinical Data for Renally Eliminated Drugs.Clinical pharmacology and therapeutics · 2021Article
- Physiologically-Based Pharmacokinetic Modelling of Creatinine-Drug Interactions in the Chronic Kidney Disease Population.CPT: pharmacometrics & systems pharmacology · 2020Article
- Novel Mechanistic PBPK Model to Predict Renal Clearance in Varying Stages of CKD by Incorporating Tubular Adaptation and Dynamic Passive Reabsorption.CPT: pharmacometrics & systems pharmacology · 2020Article
- Pharmacokinetics in children with chronic kidney disease.Pediatric nephrology (Berlin, Germany) · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Drug-dose modification in chronic kidney disease (CKD) utilizes glomerular filtration rate (GFR) with the implicit assumption that multiple renal excretory processes decline in parallel as CKD progresses. We compiled published pharmacokinetic data to evaluate if GFR predicts renal clearance changes as a function of CKD severity. For each drug, we calculated ratio of renal clearance to filtration clearance (Rnf). Of 21 drugs with Rnf >0.74 in subjects with GFR >90 mL/min (implying filtration and secretion), 13 displayed significant change in Rnf vs. GFR (slope of linear regression statistically different from zero), which indicates failure of GFR to predict changes in secretory clearance. The dependence was positive (n = 3; group A) or negative (n = 10; group B). Eight drugs showed no correlation (group C). Investigated drugs were small molecules, mostly hydrophilic, and ionizable, with some characterized as renal transporter substrates. In conclusion, dosing adjustments in CKD require refinement; in addition to GFR, biomarkers of tubular function are needed for secreted drugs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.