My Healthcare News & Research — May 11, 2026

Anatomical cross-section of a human kidney with luminescent azure-blue methylene blue flowing through the renal vasculature and nephrons
Methylene blue moving through the renal vasculature. About 40% of an IV dose is excreted unchanged in urine, which is why kidney function determines drug exposure.
Microscopic view of mitochondria inside a renal tubule cell glowing electric blue, with methylene blue shuttling electrons to cytochrome c and one mitochondrion glowing orange-red from oxidative overload
Mitochondrial electron-transport bypass at the cellular level. Methylene blue shuttles electrons to cytochrome c; the orange mitochondrion shows oxidative overload at the high-dose end of the hormetic curve.
Anatomical cross-section of a human kidney showing azure-blue methylene blue dye flowing through the renal vasculature and into the proximal tubules
Kidney with proximal tubules highlighted. The proximal tubule is the site of most methylene blue nephroprotective effects and most dose-related toxicity.

Table of Contents

Methylene Blue and the Kidneys: A Double-Edged Story

Methylene blue (methylthioninium chloride, MB) is one of the oldest synthetic drugs in continuous medical use — first synthesized in 1876 as a textile dye, formally approved by the United States Food and Drug Administration as an antidote for acquired methemoglobinemia, and increasingly used off-label as a mitochondrial cofactor in cognitive, longevity, and critical-care medicine. Over the past two decades, a substantial and largely underappreciated body of literature has examined its effects specifically on the kidneys: in sepsis, in transplantation, in ischemia–reperfusion injury, in chemotherapy-induced nephrotoxicity, in cyclosporine toxicity, and — importantly — in case reports of acute kidney injury (AKI) produced by methylene blue itself.

Taken as a set, the literature does not tell a clean “methylene blue is kidney-protective” story. It tells a more nuanced one. In specific injury models — sepsis-driven endothelial dysfunction, reperfusion after ischemia, cisplatin-induced tubular toxicity, cyclosporine-induced calcineurin damage — methylene blue measurably reduces biochemical and histological markers of renal injury. In other contexts — pre-existing renal impairment, high doses, and certain drug combinations — it can cause AKI, contribute to methemoglobinemia-related ischemic injury, or accumulate to toxic levels because the kidneys excrete roughly 40 percent of an administered dose unchanged in urine. This edition pulls those threads together: ten papers the user surfaced, plus mechanism, plus practical dosing guidance from the current ProvayBlue (methylene blue 0.5% injection) label.

For readers tracking the broader methylene blue story, this edition is the kidney complement to the existing Methylene Blue hub, which covers mitochondrial bioenergetics, cognitive enhancement, the serotonin-syndrome warning, G6PD deficiency, and the pharmaceutical-grade-versus-industrial-dye distinction. None of that is repeated here. Everything below is about the kidney.

Why Kidneys Are Central to Methylene Blue Pharmacology

Before the studies, the pharmacology. Three points anchor every kidney finding that follows.

First, methylene blue is heavily renally excreted. The current ProvayBlue prescribing information from the FDA reports that roughly 40 percent of an intravenous dose is eliminated unchanged in urine, with the remainder excreted as the reduced metabolite leucomethylene blue (also predominantly in urine), bile, and feces. This is why methylene blue urine — bright blue-green, fluorescent under UV — is one of the most recognizable pharmacologic phenomena in medicine, and why kidney function determines drug exposure. In patients with moderate-to-severe renal impairment, plasma concentrations rise; the FDA label specifically recommends dose adjustment in those populations.

Second, methylene blue acts on every major pathway the kidney is sensitive to. It inhibits inducible nitric oxide synthase (iNOS) and soluble guanylate cyclase, restoring vascular tone in distributive shock and thereby protecting renal perfusion. It accepts electrons from NADH and shuttles them directly to cytochrome c in the mitochondrial electron transport chain, bypassing damaged Complexes I and III in proximal tubular cells whose energy demand is exceptional. It induces the Nrf2 antioxidant defense pathway, raising glutathione and superoxide dismutase capacity in renal tissue. And it appears to participate in mitochondrial DNA (mtDNA) repair, an emerging mechanism in tubular cell recovery. The kidney is, in effect, an organ on which methylene blue has multiple simultaneous handles — some helpful, some potentially harmful depending on dose and context.

Third, the kidney is a redox-sensitive organ. The proximal tubule is one of the most oxygen-demanding tissues in the body, and oxidative stress is a final common pathway for sepsis-, ischemia-, contrast-, cisplatin-, cyclosporine-, and aminoglycoside-induced AKI. A small-molecule electron carrier with documented antioxidant effects at low doses and pro-oxidant effects at high doses — the classic hormetic bell curve that dominates methylene blue’s pharmacology — will inevitably show different effects on the kidney depending on where on that curve a given dose lands. Most of the disagreement in the literature is explained by this single fact.

1. Septic Shock — The First Human Kidney Signal

Heemskerk and colleagues at Erasmus Medical Center reported in 2008 (study originally posted online October 2007, hence its 17926021 PubMed identifier) the first carefully measured human renal data on methylene blue in distributive shock. The team enrolled nine patients with septic shock and gave each a continuous intravenous infusion of methylene blue at 0.25 mg/kg/h for four hours, followed by a 0.5 mg/kg loading and a maintenance phase, and measured urinary nitric oxide metabolites, tubular injury markers, and 24-hour creatinine clearance before and after.

Three findings stand out. Urinary nitric oxide metabolite excretion fell sharply, consistent with methylene blue’s inhibition of iNOS at the renal vascular endothelium. Markers of tubular injury — including urinary alpha-1 microglobulin and N-acetyl-beta-D-glucosaminidase (NAG), both proximal-tubule damage signals — declined. And 24-hour creatinine clearance improved, suggesting at least partial restoration of glomerular filtration, although it remained well below normal at study end. No serious adverse events were observed at this dose, and methemoglobin remained within acceptable limits.

The trial is small, uncontrolled, and short-term, and its authors are appropriately cautious in framing methylene blue as anything more than a candidate adjunct to standard septic shock care. But it provides what every later study has relied on: a clean human biochemical demonstration that methylene blue, infused in shock at modest doses, reduces the specific kidney signals that distributive shock produces. Subsequent meta-analyses of methylene blue in sepsis (Kwok & Howes 2006; Pasin et al. 2013 in cardiac surgery vasoplegia, where renal perfusion is a critical secondary outcome) have built on this scaffold without invalidating it.

2. Living Donor Liver Transplant AKI (2026)

The newest paper in this set is a 2026 single-center retrospective cohort analysis examining whether intravenous methylene blue administered before graft reperfusion during living donor liver transplantation (LDLT) reduces postoperative acute kidney injury. The mechanistic premise is straightforward: graft reperfusion is one of the most reliable triggers of distributive vasoplegia in modern surgery, the resulting systemic vasodilation drops renal perfusion pressure, and the proximal tubule — already vulnerable from intraoperative hypoperfusion and inflammatory cytokine release — is at high risk. If methylene blue can blunt the vasoplegic response by inhibiting NO–cGMP signaling, the kidney should benefit.

The investigators report a lower incidence of postoperative AKIN Stage 1 AKI in patients who received pre-reperfusion methylene blue compared with matched controls who did not. The effect did not reach statistical significance for higher AKI stages, where the underlying renal insult is harder to overcome with any single intervention, and the study is retrospective rather than randomized. Nonetheless, it is the first contemporary clinical paper to translate the Heemskerk septic-shock signal into a planned surgical setting where the timing of methylene blue administration is controlled by the surgical team rather than dictated by the onset of unmeasured organ injury.

For readers in or near the transplant world — or for clinicians thinking about prophylactic vasoplegia prevention in cardiac and abdominal surgery generally — this study is the proof-of-concept that the kidney signal observed in septic shock can be reproduced when methylene blue is given before the predictable insult rather than after it. Larger prospective randomized trials are the obvious next step.

3. Renal Ischemia–Reperfusion Injury (Animal Models)

Two of the most cited mechanistic papers on methylene blue and the kidney come from rodent models of renal ischemia–reperfusion injury (IRI) — the experimental analog of what happens during transplant cold ischemia, prolonged surgical cross-clamping, and certain cardiac arrest survivors. In these models, the renal artery is clamped for a defined interval, then released; the resulting tissue captures the dual injury of oxygen deprivation followed by a violent reoxygenation burst.

In a 2018 mouse study from the Chinese University of Hong Kong (PMID 29771438), intraperitoneal methylene blue administered before reperfusion reduced renal tubular apoptosis, lowered pro-inflammatory cytokine release (TNF-α, IL-6), and preserved tubular architecture on histology compared to vehicle controls. The mechanism the authors emphasize is mitochondrial: methylene blue stabilizes the mitochondrial membrane potential during the reperfusion oxidative burst, reducing cytochrome c release into the cytosol and therefore reducing the apoptotic trigger that drives so much of post-ischemic tubular cell death.

An older rat study using urinary proton magnetic resonance spectroscopy (PMID 9815837) examined early metabolic perturbations after renal ischemia and the modifying effect of methylene blue. The technique — 1H-MRS of urine — captures non-invasive snapshots of organic-acid and amino-acid signatures characteristic of tubular injury. Methylene blue administration shifted those signatures back toward baseline more rapidly than untreated ischemia, providing a complementary biochemical line of evidence to the histological story.

Together these papers describe a recurring pattern: methylene blue, given before or at the time of reperfusion, reduces the apoptotic and inflammatory consequences of renal ischemia in animal models. Whether that effect translates to humans — in transplantation, in cardiac arrest, in cardiopulmonary bypass — is the question the 2026 LDLT cohort begins to answer affirmatively.

4. Cisplatin-Induced Nephrotoxicity

Cisplatin is one of the most effective antineoplastic drugs in oncology — and one of the most reliably nephrotoxic. Dose-limiting kidney injury affects roughly a third of patients receiving standard regimens for testicular, ovarian, head-and-neck, and bladder cancers, and the underlying mechanism is multifactorial: direct proximal-tubule cell toxicity, mitochondrial DNA damage, oxidative stress, and inflammatory infiltration. Decades of nephroprotection research have looked for adjunctive agents that preserve antitumor efficacy while reducing renal injury, and methylene blue has emerged as one of the more promising candidates.

A 2022 animal toxicity study (PMID 35483196) administered methylene blue alongside cisplatin and examined renal histology, function, and apoptosis/fibrosis markers. Methylene blue improved serum creatinine and blood urea nitrogen (BUN), reduced apoptosis on TUNEL staining, and lowered fibrosis-promoting markers including TGF-β. Tubular architecture on histology was substantially better preserved.

A 2023 mechanistic study (PMID 37047089) went further and asked how. The authors document that methylene blue induces Nrf2-dependent antioxidant defense — Nrf2 is the master transcription factor controlling the expression of glutathione synthesis enzymes, superoxide dismutases, and other antioxidant proteins — and that it appears to participate in the repair of mitochondrial DNA (mtDNA) damage induced by cisplatin. Because mtDNA damage is one of the molecular hallmarks of cisplatin nephrotoxicity, this is a particularly direct mechanistic link.

The clinical translation, however, has not yet happened. There are no published randomized trials of methylene blue as a cisplatin nephroprotectant in humans, and the existing standard-of-care nephroprotection — aggressive saline hydration, magnesium repletion, dose modification, and in some protocols amifostine — remains in place. The animal data are consistent and mechanistically coherent enough to make methylene blue a credible candidate for a future Phase 2 trial. They are not, today, a recommendation for oncology patients to add methylene blue to their regimen.

5. Cyclosporine-Induced Renal Injury

Cyclosporine A, the calcineurin inhibitor that revolutionized organ transplantation in the 1980s, has a well-characterized dose-related nephrotoxicity profile. Chronic cyclosporine causes afferent arteriolar vasoconstriction, ischemic tubular injury, and ultimately interstitial fibrosis — the same kind of injury pattern that ultimately limits transplant graft longevity for many recipients.

A 2001 animal study (PMID 11598398) examined whether methylene blue could protect kidney parenchyma from cyclosporine-induced injury. The authors found preservation of tubular structure and reduction in biochemical injury markers in methylene-blue-treated animals compared with cyclosporine-alone controls. The hypothesized mechanism overlaps with the cisplatin and IRI literature: mitochondrial preservation, antioxidant defense, and possibly improvement in afferent arteriolar tone via interaction with the NO–cGMP axis.

This is older work, and it has not been replicated in modern transplant cohorts. Its current value is conceptual: it tells us that the methylene-blue-protective phenotype seen in cisplatin and IRI models extends to a third, mechanistically distinct nephrotoxin. Whether transplant nephrology should be looking at methylene blue as an adjunct to calcineurin-inhibitor therapy — particularly in patients already showing early signs of chronic allograft nephropathy — is an open question.

6. The Dark Side — AKI and Toxicity Case Reports

No honest review of methylene blue and the kidneys can stop at the protective studies. Two case reports anchor the cautionary side of the literature.

The first (PMID 29217886) describes methylene-blue-induced methemoglobinemia complicated by acute kidney injury after treatment for nitrobenzene poisoning. Nitrobenzene is one of the classic causes of severe methemoglobinemia — the iron in hemoglobin is oxidized from Fe2+ to Fe3+, which cannot bind or release oxygen — and methylene blue is its standard antidote. The paradox: at therapeutic doses (1–2 mg/kg), methylene blue reduces methemoglobin back to functional hemoglobin via NADPH-methemoglobin reductase. At higher doses, or in the setting of G6PD deficiency, it causes methemoglobinemia and hemolysis. The case report documents AKI in a patient who experienced exactly this iatrogenic cascade: prolonged tissue hypoxia from persistent methemoglobinemia, hemoglobinuria from intravascular hemolysis, and resulting acute tubular injury.

The second (PMID 3487723) is older and more general: a clinical observation that methylene blue can produce direct toxicity when administered to patients with pre-existing renal failure. The mechanism is straightforward: 40 percent renal excretion plus reduced glomerular filtration equals drug accumulation, and accumulated methylene blue crosses from the therapeutic range into the pro-oxidant, methemoglobinemia-inducing range without the dose ever being formally increased. The implication for current practice is direct: methylene blue dosing must be reduced in moderate-to-severe renal impairment, a recommendation now formalized in the ProvayBlue label.

Beyond these two specific reports, the broader literature documents additional kidney-related concerns worth knowing. Methylene blue can interfere with pulse oximetry, falsely lowering SpO2 readings for tens of minutes after administration — clinically important in postoperative monitoring of patients with marginal renal perfusion. It can produce refractory hypoxemia in patients with G6PD deficiency through massive hemolysis, which both deprives the kidney of oxygen-carrying capacity and floods the tubules with cell-free hemoglobin. And in critically ill patients, the drug’s urinary discoloration can mask the visible darkening of myoglobinuric urine in rhabdomyolysis, delaying recognition of a separate AKI driver.

7. Vasoplegia, Cardiac Surgery, and the Renal-Perfusion Question

The longest-running clinical use of methylene blue in modern critical care is for vasoplegic syndrome after cardiopulmonary bypass — a refractory distributive shock state in which systemic vascular resistance falls precipitously and conventional vasopressors fail. The mechanism implicates the same NO–cGMP axis described above, and methylene blue’s inhibition of soluble guanylate cyclase has made it a frequent second- or third-line rescue agent. Although the primary indication is hemodynamic, the renal stakes are large: post-cardiopulmonary-bypass AKI is one of the most common and most morbid complications of cardiac surgery, and its risk rises sharply with the duration and depth of intraoperative hypotension.

A 2004 randomized trial (Levin et al., Annals of Thoracic Surgery) reported that methylene blue rescue of vasoplegic post-bypass patients was associated with reduced mortality and morbidity, including a lower incidence of postoperative renal dysfunction. A 2013 systematic review and meta-analysis by Pasin and colleagues, and a 2016 narrative review by Hosseinian et al. in the Journal of Cardiothoracic and Vascular Anesthesia, both reach similar conclusions while emphasizing the methodological limitations of the underlying evidence base. The largest take is consistent: methylene blue, used at vasoplegia rescue doses (1–2 mg/kg IV), preserves renal perfusion pressure long enough for tubular cells to survive the immediate post-bypass window.

This is not the same as “methylene blue protects the kidney through a direct molecular effect.” In vasoplegia, the renal benefit is largely a consequence of restored systemic hemodynamics. But for the purposes of a patient in the cardiothoracic ICU at 0200 with refractory low blood pressure and dropping urine output, the distinction is academic. The kidney is preserved because the perfusion is preserved — and that is what methylene blue does in this setting.

Mechanism: Why Methylene Blue Acts on the Kidney at All

Pulling the seven preceding sections together, methylene blue’s renal pharmacology has four converging mechanistic strands.

The NO–cGMP–vascular tone strand. Inducible nitric oxide synthase (iNOS) is upregulated in sepsis and after reperfusion, and the resulting NO production activates soluble guanylate cyclase, raises cGMP, and produces vasodilation. Methylene blue inhibits both iNOS and soluble guanylate cyclase, restoring vascular tone and renal perfusion pressure. This is the dominant mechanism in septic shock, vasoplegia rescue, and at least part of the LDLT pre-reperfusion benefit.

The mitochondrial electron-transport strand. In proximal tubule cells — among the most mitochondria-dense cells in the body — methylene blue accepts electrons from NADH and shuttles them directly to cytochrome c, bypassing damaged Complexes I and III. The result is preserved ATP production and reduced reactive oxygen species (ROS) leakage during the moments of greatest oxidative stress. This is the dominant mechanism in ischemia–reperfusion injury, cisplatin nephrotoxicity, and the cyclosporine model.

The Nrf2 antioxidant strand. Methylene blue activates the Nrf2 transcription factor, which drives expression of glutathione synthesis enzymes, superoxide dismutases, catalase, and heme oxygenase-1 — the body’s endogenous antioxidant defense system. The 2023 cisplatin mechanism paper places Nrf2 induction at the center of the renal-protective effect.

The mitochondrial DNA repair strand. An emerging finding from the same 2023 cisplatin paper is that methylene blue appears to facilitate repair of mitochondrial DNA damage. mtDNA, unlike nuclear DNA, lacks histones and has limited repair capacity; in proximal tubule cells under cisplatin or ischemic stress, mtDNA damage is a key contributor to cell death. If methylene blue accelerates mtDNA repair — the mechanism is incompletely characterized but appears to involve mitochondrial transcription factor A (TFAM) stabilization — that is a novel and clinically interesting capacity.

The four mechanisms overlap and reinforce one another. Restoring perfusion buys time. Preserving ATP buys tubular cell survival. Activating Nrf2 reduces ongoing oxidative damage. Repairing mtDNA restores the long-term replicative capacity of the recovering nephron. No other small molecule currently in clinical use acts simultaneously through all four of these pathways — which is both the appeal of methylene blue and the reason that more is not better: pushing any one of these pathways past its hormetic optimum produces pro-oxidant, pro-apoptotic, pro-methemoglobinemia harm.

Dosing in Renal Impairment — What the FDA Label Says

The current ProvayBlue prescribing information (Provayblue, methylthioninium chloride 0.5% injection, NDA 204630), available at FDA Drugs@FDA, makes three explicit statements relevant to kidney function.

  1. Approximately 40 percent of an administered dose is excreted unchanged in urine. The remainder is excreted as the reduced leucomethylene blue metabolite, predominantly in urine as well, with bile and feces accounting for a minority.
  2. Plasma exposure rises in patients with renal impairment. The label recommends caution and dose adjustment in patients with moderate-to-severe renal impairment (estimated glomerular filtration rate below 60 mL/min/1.73 m2).
  3. Methylene blue is contraindicated in patients with severe hypersensitivity reactions, in patients taking serotonergic drugs, and in patients with G6PD deficiency — the latter because of catastrophic hemolysis risk that, when it occurs, can itself precipitate pigment-induced AKI through cell-free hemoglobin tubular toxicity.

For the standard acquired-methemoglobinemia indication, the FDA-approved dose is 1 mg/kg administered IV over 5 to 30 minutes, with a second dose at 30 to 60 minutes if methemoglobin level does not adequately decline. In patients with renal impairment, conservative practice is to reduce the second-dose threshold, monitor methemoglobin levels closely, and avoid cumulative dosing above 4 mg/kg over 24 hours unless the alternative is loss of life. Off-label nootropic doses (0.5–4 mg/kg/day oral) are not formally addressed by the label, but the same renal-elimination math applies: a patient with eGFR of 30 will accumulate methylene blue at roughly twice the rate of a patient with eGFR of 90, all else equal, and the cumulative pro-oxidant exposure rises accordingly.

For patients with end-stage renal disease on hemodialysis, the situation is more complex. Methylene blue is a small, water-soluble cationic dye that should in principle be partially dialyzable, but published pharmacokinetic data in dialysis populations are sparse. The conservative clinical posture is to treat any methylene blue dose in dialysis as if it will accumulate, dose at the low end of the methemoglobinemia indication, and monitor methemoglobin levels and clinical hemolysis markers closely.

Bottom Line: How to Think About This Body of Evidence

The ten papers the user surfaced, plus the wider methylene-blue critical-care literature, do not say methylene blue is “kidney-protective” in any general or supplement-shelf sense. They say something more interesting and more clinically useful.

  1. In well-defined injury models — sepsis, ischemia–reperfusion, cisplatin, cyclosporine, post-bypass vasoplegia — methylene blue reduces measurable kidney injury through converging molecular pathways. The animal data are consistent; the human data are early but pointing the same direction.
  2. The protective effect is dose-dependent and context-dependent. Low-to-moderate doses, given early in the injury cascade, are where the benefit lives. Higher doses cross into pro-oxidant territory; the same molecule that protected the proximal tubule at 1 mg/kg may damage it at 7 mg/kg.
  3. Renal impairment changes the dosing math. Forty percent renal excretion means that a kidney patient receives effectively more drug than a normal-kidney patient at the same nominal dose, with cumulative effects that can flip the risk-benefit balance.
  4. Two iatrogenic harms dominate the cautionary literature: dose-related methemoglobinemia (paradoxically, since methylene blue is the antidote at correct doses), and G6PD-related hemolysis with secondary AKI. Both are predictable, both are screenable, and both are formally addressed in the FDA label.
  5. No human randomized trial currently supports oral methylene blue supplementation as a standalone kidney-protective strategy. The off-label nootropic use of methylene blue at modest doses (5–25 mg daily) has not been shown to either help or harm kidney function in healthy adults. Anyone with established CKD considering off-label use should treat the renal-elimination data as the primary safety constraint.

The most useful framing, for both clinicians and curious lay readers, is this: methylene blue is a tool, not a treatment. Used in narrow clinical windows where the renal threat is real and the dose is calibrated, it has measurable benefit. Used carelessly — in dialysis patients without dose reduction, in G6PD-deficient patients without screening, in combination with serotonergic drugs that are far more common than the methemoglobinemia presentation it is approved to treat — it can cause exactly the kind of kidney injury the protective papers describe averting. The literature does not, on balance, recommend either reflexive enthusiasm or reflexive avoidance. It rewards careful reading.

References & Further Reading

Primary Studies (User-Surfaced)

  1. Heemskerk S, Pickkers P, Bouw MPWJM, et al. Short-Term Beneficial Effects of Methylene Blue on Kidney Damage in Septic Shock Patients. Intensive Care Medicine. 2008;34(2):350–354. PMID 17926021. doi:10.1007/s00134-007-0867-9
  2. Methylene Blue Administration Reduces Acute Kidney Injury After Living Donor Liver Transplantation. 2026. PMID 41804495 (retrospective human cohort, pre-reperfusion methylene blue and postoperative AKIN Stage 1 AKI).
  3. Methylene Blue Attenuates Renal Ischemia–Reperfusion Injury. Mouse model. 2018. PMID 29771438 (apoptosis and inflammatory cytokine reduction).
  4. Urinary Proton Magnetic Resonance Spectroscopy of Early Methylene Blue Effects in Renal Ischemia–Reperfusion in Rats. 1998. PMID 9815837 (non-invasive metabolic markers of tubular protection).
  5. Evaluation of Protective Effects of Methylene Blue on Cisplatin-Induced Nephrotoxicity. 2022. PMID 35483196 (creatinine, BUN, apoptosis, fibrosis markers).
  6. Methylene Blue Induces Antioxidant Defense and Reparation of Mitochondrial DNA in Cisplatin-Induced Renal Toxicity. 2023. PMID 37047089 (Nrf2 induction and mtDNA repair mechanism).
  7. Does Methylene Blue Protect Kidney Tissues from Cyclosporine A Toxicity? 2001. PMID 11598398 (animal nephroprotection model).
  8. Methylene Blue–Induced Methemoglobinemia with Acute Kidney Injury. 2017. PMID 29217886 (iatrogenic AKI case report after nitrobenzene poisoning).
  9. Possible Toxicity of Methylene Blue Administration in Renal Failure. 1986. PMID 3487723 (cautionary clinical report).
  10. ProvayBlue (Methylene Blue) 0.5% Injection — FDA Prescribing Information, NDA 204630. accessdata.fda.gov (40% renal excretion; dose adjustment in renal impairment).

Additional Renal & Critical-Care Literature

  1. Kwok ESH, Howes D. Use of Methylene Blue in Sepsis: A Systematic Review. Journal of Intensive Care Medicine. 2006;21(6):359–363. doi:10.1177/0885066606290671
  2. Levin RL, Degrange MA, Bruno GF, et al. Methylene Blue Reduces Mortality and Morbidity in Vasoplegic Patients After Cardiac Surgery. Annals of Thoracic Surgery. 2004;77(2):496–499. doi:10.1016/S0003-4975(03)01510-8
  3. Pasin L, Umbrello M, Greco T, et al. Methylene Blue as a Vasopressor: A Meta-Analysis of Randomised Trials. Critical Care & Resuscitation. 2013;15(1):42–48. PMID 23432501
  4. Hosseinian L, Weiner M, Levin MA, Fischer GW. Methylene Blue: Magic Bullet for Vasoplegia? Journal of Cardiothoracic and Vascular Anesthesia. 2016;30(6):1684–1691. doi:10.1053/j.jvca.2016.06.009
  5. Donati A, Conti G, Loggi S, et al. Does Methylene Blue Administration to Septic Shock Patients Affect Vascular Permeability and Blood Volume? Critical Care Medicine. 2002;30(10):2271–2277. doi:10.1097/00003246-200210000-00015
  6. Memis D, Karamanlioglu B, Yuksel M, et al. The Effect of Methylene Blue on Lung Injury in Septic Patients. Surgery Today. 2002;32(9):752–755. doi:10.1007/s005950200143
  7. Mayer B, Brunner F, Schmidt K. Inhibition of Nitric Oxide Synthesis by Methylene Blue. Biochemical Pharmacology. 1993;45(2):367–374. doi:10.1016/0006-2952(93)90072-5
  8. Salaris SC, Babbs CF, Voorhees WD III. Methylene Blue as an Inhibitor of Superoxide Generation by Xanthine Oxidase. Biochemical Pharmacology. 1991;42(3):499–506. doi:10.1016/0006-2952(91)90311-R
  9. Ginimuge PR, Jyothi SD. Methylene Blue: Revisited. Journal of Anaesthesiology Clinical Pharmacology. 2010;26(4):517–520. PMID 21547182
  10. Bistas E, Sanghavi DK. Methylene Blue. StatPearls Publishing. Updated 2023. NCBI Bookshelf NBK557593
  11. Ramsay RR, Dunford C, Gillman PK. Methylene Blue and Serotonin Toxicity: Inhibition of Monoamine Oxidase A (MAO A) Confirms a Theoretical Prediction. British Journal of Pharmacology. 2007;152(6):946–951. doi:10.1038/sj.bjp.0707430
  12. Tucker D, Lu Y, Zhang Q. From Mitochondrial Function to Neuroprotection — An Emerging Role for Methylene Blue. Molecular Neurobiology. 2018;55(6):5137–5153. doi:10.1007/s12035-017-0712-2
  13. Wischik CM, Staff RT, Wischik DJ, et al. Tau Aggregation Inhibitor Therapy: An Exploratory Phase 2 Study in Mild or Moderate Alzheimer’s Disease. Journal of Alzheimer’s Disease. 2015;44(2):705–720. doi:10.3233/JAD-142874
  14. Atamna H, Nguyen A, Schultz C, et al. Methylene Blue Delays Cellular Senescence and Enhances Key Mitochondrial Biochemical Pathways. FASEB Journal. 2008;22(3):703–712. doi:10.1096/fj.07-9610com
  15. Schirmer RH, Adler H, Pickhardt M, Mandelkow E. “Lest We Forget You — Methylene Blue…” Neurobiology of Aging. 2011;32(12):2325.e7–2325.e16. doi:10.1016/j.neurobiolaging.2010.12.012

Live PubMed Searches

  1. PubMed: methylene blue acute kidney injury
  2. PubMed: methylene blue nephrotoxicity
  3. PubMed: methylene blue septic shock kidney
  4. PubMed: methylene blue vasoplegia cardiac surgery
  5. PubMed: methylene blue renal ischemia reperfusion
  6. PubMed: methylene blue cisplatin nephroprotection
  7. PubMed: methylene blue cyclosporine kidney
  8. PubMed: methylene blue Nrf2 antioxidant
  9. PubMed: methylene blue mitochondrial DNA repair
  10. PubMed: methylene blue pharmacokinetics renal impairment
  11. PubMed: methylene blue methemoglobinemia G6PD
  12. PubMed: methylene blue liver transplantation AKI

Back to Table of Contents