ReviewNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association2024
How can inhibition of glucose and sodium transport in the early proximal tubule protect the cardiorenal system?
Review in Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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
18 citing papers in PubMed, 25 citations in OpenAlex.
- Uncoupling Erythropoiesis from Cardiorenal Effects: SGLT2 Inhibition in Non-Diabetic Heart Failure.Medicina (Kaunas, Lithuania) · 2026Observational
- Mitochondrial Dysfunction at the Intersection of CKM Syndrome: Molecular Mechanisms and Path-to-Target Therapies.International journal of molecular sciences · 2026Review
- Lipid droplets beyond storage: Cellular metabolic modulator in the diabetic heart (Review).International journal of molecular medicine · 2026Review
- Chronic Kidney Disease in Metabolic Disease: Regulation of SGLT2 and Transcriptomic-Epigenetic Effects of Its Pharmacological Inhibition.International journal of molecular sciences · 2026Review
- Association Between Gliflozins Use and Outcomes in Adults with Sepsis: A Multicenter Retrospective Cohort Study Among Veterans.Annals of intensive care · 2026Article
- Clinical and genetic features of Gitelman syndrome patients with hyperuricemia.Clinical kidney journal · 2025Article
- Risk of End-Stage Kidney Disease and Topiramate Use.Kidney international reports · 2025Article
- ASK1 limits kidney glucose reabsorption, growth, and mid-late proximal tubule KIM-1 induction when diabetes and Western diet are combined with SGLT2 inhibition.American journal of physiology. Renal physiology · 2025Article
- Not Just an Alternative Energy Source: Diverse Biological Functions of Ketone Bodies and Relevance of HMGCS2 to Health and Disease.Biomolecules · 2025Review
- Beyond SGLT2: proximal tubule transporters as potential drug targets for chronic kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Review
- Genetic deletion of the kidney sodium/proton exchanger-3 (NHE3) does not alter calcium and phosphate balance due to compensatory responses.Kidney international · 2025Article
- Chronic kidney disease.Nature reviews. Disease primers · 2025Review
- Transcriptomics of SGLT2-positive early proximal tubule segments in mice: response to type 1 diabetes, SGLT1/2 inhibition, or GLP1 receptor agonism.American journal of physiology. Renal physiology · 2025Article
- Impact of SGLT2 inhibitors on blood pressure among kidney transplant recipients: insights from a French multicentric cohort (GREAT ASTRE).Clinical hypertension · 2025Article
- Randomized, Placebo-Controlled Trial on the Renal and Systemic Hemodynamic Effects of Empagliflozin.Kidney international reports · 2025Article
- State-of-the-Art-Review: Mechanisms of Action of SGLT2 Inhibitors and Clinical Implications.American journal of hypertension · 2024Review
- Proximal tubule hypertrophy and hyperfunction: a novel pathophysiological feature in disease states.Clinical kidney journal · 2024Review
- Sodium-Glucose Cotransporter 2 Inhibitor Combined with Conventional Diuretics Ameliorate Body Fluid Retention without Excessive Plasma Volume Reduction.Diagnostics (Basel, Switzerland) · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
What mechanisms can link the inhibition of sodium-glucose cotransporter 2 (SGLT2) in the early proximal tubule to kidney and heart protection in patients with and without type 2 diabetes? Due to physical and functional coupling of SGLT2 to other sodium and metabolite transporters in the early proximal tubule (including NHE3, URAT1), inhibitors of SGLT2 (SGLT2i) reduce reabsorption not only of glucose, inducing osmotic diuresis, but of other metabolites plus of a larger amount of sodium than expected based on SGLT2 inhibition alone, thereby reducing volume retention, hypertension and hyperuricemia. Metabolic adaptations to SGLT2i include a fasting-like response, with enhanced lipolysis and formation of ketone bodies that serve as additional fuel for kidneys and heart. Making use of the physiology of tubulo-glomerular communication, SGLT2i functionally lower glomerular capillary pressure and filtration rate, thereby reducing physical stress on the glomerular filtration barrier, tubular exposure to albumin and nephrotoxic compounds, and the oxygen demand for reabsorbing the filtered load. Together with reduced gluco-toxicity in the early proximal tubule and better distribution of transport work along the nephron, SGLT2i can preserve tubular integrity and transport function and, thereby, glomerular filtration rate in the long-term. By shifting transport downstream, SGLT2i may simulate systemic hypoxia at the oxygen sensors in the deep cortex/outer medulla, which stimulates erythropoiesis and, together with osmotic diuresis, enhances hematocrit and thereby improves oxygen delivery to all organs. The described SGLT2-dependent effects may be complemented by off-target effects of SGLT2i on the heart itself and on the microbiome formation of cardiovascular-effective uremic toxins.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.