ReviewNature reviews. Nephrology2020
The tubular hypothesis of nephron filtration and diabetic kidney disease.
Review in Nature reviews. Nephrology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 278 papers, 8 of them syntheses that pooled it.
What it found
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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
278 citing papers in PubMed, 8 syntheses or guidelines pooled it, 408 citations in OpenAlex.
- Blood pressure effects of SGLT2 inhibitors in kidney transplant recipients: a systematic review and meta-analysis.International urology and nephrology · 2026Pooled it
- Cardiovascular and renal outcomes of combined SGLT2 inhibitors and GLP-1 receptor agonists versus monotherapy in patients with type 2 diabetes mellitus: a network meta-analysis.CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne · 2026Pooled it
- The impact of SGLT2 inhibitors on renal outcomes in patients with type 2 diabetes and chronic kidney disease: systematic review and meta-analysis.Frontiers in endocrinology · 2026Pooled it
- Efficacy and safety of GLP-1RAs, SGLT2is, and nsMRAs for cardiovascular and renal outcomes in T2DM with CKD: a systematic review and network meta-analysis.Frontiers in endocrinology · 2026Pooled it
- Update on the Efficacy and Safety of Sodium-Glucose Co-Transporter 2 Inhibitors in Patients with Chronic Diseases: A Systematic Review and Meta-Analysis.Medicina (Kaunas, Lithuania) · 2025Pooled it
- Evaluation of N-acetyl-β-D-glucosaminidase as a prognostic marker for diabetic nephropathy in type 2 diabetics: systematic review and meta-analysis.International urology and nephrology · 2024Pooled it
- Abrupt Decline in Estimated Glomerular Filtration Rate after Initiating Sodium-Glucose Cotransporter 2 Inhibitors Predicts Clinical Outcomes: A Systematic Review and Meta-Analysis.Diabetes & metabolism journal · 2024Pooled it
- American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update.Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists · 2022Guideline
- Short-term effects of empagliflozin on preventing contrast induced acute kidney injury in patients undergoing percutaneous coronary intervention, a randomised trial.Scientific reports · 2025Trial
- Separate and combined effects of semaglutide and empagliflozin on kidney oxygenation and perfusion in people with type 2 diabetes: a randomised trial.Diabetologia · 2023Trial
- Association between time in range and incident early diabetic kidney disease in patients with type 2 diabetes: a retrospective cohort study.International urology and nephrology · 2026Article
- Irisin upregulation as a contributory mechanism for the therapeutic benefits of SGLT-2 inhibitors.Pharmacology & therapeutics · 2026Review
- Metabolic control by liver-kidney crosstalk and glucagon in health and disease.Nature reviews. Nephrology · 2026Review
- Low Nephron Number and Kidney Disease.International journal of molecular sciences · 2026Review
- S100A1 Promotes MDM2-Mediated KLF15 Ubiquitination to Regulate ID1-Driven Tubular Injury in Diabetic Kidney Disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Berberine attenuates diabetic kidney injury via FOXO1/SP1-associated regulation of renal SGLT-2 expression.Chinese medicine · 2026Article
- The Cardio-Renal-Hepatic Axis in MASLD. Role of BDNF, NGF, and Metabolic Cross-Talk.Current hypertension reports · 2026Review
- Dual roles of renal tubular mitochondrial Akt1 in protecting against diabetic nephropathy and improving body glucose metabolism.The Journal of endocrinology · 2026Article
- Polyphenol-Rich Mangosteen Pericarp Extract Attenuates Metabolic and Reproductive Dysfunction in High-fat Diet and Streptozotocin-induced Obese-Diabetic Male Rats: A Preliminary Study.Applied biochemistry and biotechnology · 2026Article
- Amino acid homeostasis in the kidney: Physiological roles and pathological dysregulation.Physiological reports · 2026Review
218 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Kidney size and glomerular filtration rate (GFR) often increase with the onset of diabetes, and elevated GFR is a risk factor for the development of diabetic kidney disease. Hyperfiltration mainly occurs in response to signals passed from the tubule to the glomerulus: high levels of glucose in the glomerular filtrate drive increased reabsorption of glucose and sodium by the sodium-glucose cotransporters SGLT2 and SGLT1 in the proximal tubule. Passive reabsorption of chloride and water also increases. The overall capacity for proximal reabsorption is augmented by growth of the proximal tubule, which (alongside sodium-glucose cotransport) further limits urinary glucose loss. Hyperreabsorption of sodium and chloride induces tubuloglomerular feedback from the macula densa to increase GFR. In addition, sodium-glucose cotransport by SGLT1 on macula densa cells triggers the production of nitric oxide, which also contributes to glomerular hyperfiltration. Although hyperfiltration restores sodium and chloride excretion it imposes added physical stress on the filtration barrier and increases the oxygen demand to drive reabsorption. Tubular growth is associated with the development of a senescence-like molecular signature that sets the stage for inflammation and fibrosis. SGLT2 inhibitors attenuate the proximal reabsorption of sodium and glucose, normalize tubuloglomerular feedback signals and mitigate hyperfiltration. This tubule-centred model of diabetic kidney physiology predicts the salutary effect of SGLT2 inhibitors on hard renal outcomes, as shown in large-scale clinical trials.
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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.