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RENAL SYSTEM: Edited by Marlies Ostermann

New drugs for acute kidney injury

Côté, Jean-Maximea,b,c; Murray, Patrick T.a,b; Rosner, Mitchell H.d

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Current Opinion in Critical Care: December 2020 - Volume 26 - Issue 6 - p 525-535
doi: 10.1097/MCC.0000000000000778
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Acute kidney injury (AKI) is a syndrome with multiple short-term and long-term deleterious effects [1,2]. The past decade was marked by an improvement in the understanding of the cellular and molecular mechanisms involved in AKI [3]. However, there is currently no Food and Drug Administration (FDA)-approved drug for the treatment or prevention of AKI [4]. Barriers to translation of our extensive knowledge of AKI pathogenesis into effective therapeutics are well detailed in the literature [4–6]. This review aims to summarize recent promising agents for the prevention or therapy of AKI (Fig. 1), which include novel agents (Table 1), repurposed drugs (Table 2) and cell-based therapies (Table 3; not further discussed) [7–29]. The detailed pathogenesis of AKI and drug targets still in preclinical development are beyond the scope of this review. Several excellent recent reviews of these topics are referenced [3–9]. 

Potential therapeutics for acute kidney injury according to their principal mechanisms of action. Angiotensin II and levosimendan affect intraglomerular pressure. Natriuretic peptide agonists (carperitine and nesiritide) increase glomerular filtration rate and natriuresis. Heme arginate and propofol have antioxidant properties. Oral nicotinamide increases nicotinamide adenine dinucleotide+ availability, affecting cellular metabolism. Teprasiran inhibits p53 pathways temporarily. Toxic reactive oxygen species and mitochondrial stress are reduced by MitoQ, MitoTEMPO, elamipretide and ASP1128. Alkaline phosphatase has luminal enzymatic activity, by dephosphorylation of ATP to adenosine, a potent anti-inflammatory. Bone-morphogenetic-protein-7 and propofol decrease levels of transforming growth factor-β reducing fibrosis and local inflammation. Relticimob is a CD28 modulator, reducing T-cell activation and proinflammatory cytokines and chemokines. ANG-3777 activates hepatocyte growth factor repair pathways, affecting tubular regeneration and cellular function. Sphingosine-1-phosphate, ∝-melanocortin-stimulating hormone and dexmedetomidine have various anti-inflammatory effects. EA-230 is an active fragment of human chorionic gonadotrophin hormone having pleiotropic immunotolerance effects.
Table 1
Table 1:
List of potential pharmacologic agents for acute kidney injury
Table 2
Table 2:
List of promising repurposed drugs for acute kidney injury
Table 3
Table 3:
List of cell-based therapies for acute kidney injury
Box 1
Box 1:
no caption available

Vasoactive drugs: vasopressors, inotropes, vasodilators

Decreased kidney perfusion and microvascular blood flow are critical, well recognized factors in the development of AKI. Sustained, severe kidney hypoperfusion may result in endothelial injury by oxidative stress, alteration to the glycocalyx and reduced capillary blood flow [30]. Several mediators and hormones are implicated in this circulatory dysfunction – including adenosine, nitric oxide and the renin–angiotensin–aldosterone system (RAAS). These mechanisms have led to the development of several therapeutics whose objective is to maintain oxygen and nutrient availability to sustain organ function [31].


Angiotensin II: Angiotensin II (AII) is a potent vasoconstrictor [32]. In the kidney, it leads to preferential constriction of the efferent arteriole, increasing intraglomerular pressure and filtration fraction. Severe inflammatory states may lead to dysfunction of the RAAS, resulting in a relative lack of AII [33]. Animal models of sepsis demonstrated that AII levels are diminished, which may lead to a decreased transcapillary glomerular pressure gradient and, consequently to AKI. Exogenous infusion of AII increases urine output and improves kidney function [4,34]. Recently, in patients with catecholamine-resistant shock, a phase 3 trial, ‘Angiotensin II for the Treatment of High-Output Shock’ (ATHOS-3), showed that it effectively increased blood pressure, with a trend toward improved survival at 28 days and no increase in AKI-related adverse events [35]. The FDA approved AII for the treatment of vasodilatory shock in 2017. A similar study is underway in a pediatric population (NCT03623529). To date, no study aiming to specifically study the potential renoprotective effects of AII has been published. However, a post-hoc analysis of the ATHOS-3 trial, in patients with AKI requiring renal replacement therapy (RRT), showed a higher 28-day survival and improved day-7 dialysis-free survival in the AII group compared with placebo [36]. The ongoing phase 2 Angiotensin in Septic Kidney Injury Trial evaluates the hemodynamics and urine output in patients with sepsis and AKI exposed to AII (NCT00711789). Another trial is assessing the efficacy of AII in hepatorenal syndrome (ANTHEM Trial, NCT04048707).


Levosimendan: Levosimendan is a calcium sensitizer with inotropic and vasodilatory effects (inodilator). Recently approved for decompensated heart failure in patients with low cardiac output, it improved cardiac contractility without increasing oxygen consumption [37]. However, three large randomized controlled trials (RCTs) and a recent meta-analysis did not demonstrate an improvement in clinical outcomes with levosimendan over conventional inotropic drugs, limiting its routine clinical use [38]. Theoretically, an improvement in cardiac function following its administration could lead to improved renal perfusion and function. In addition, it appears that afferent renal arteriolar vasodilation also plays a role in the potential renoprotective effects of levosimendan [4,37]. Animal models of ischemia-reperfusion and endotoxemia supported this hypothesis [39]. Furthermore, a meta-analysis combining 13 small RCTs on the efficacy of levosimendan in 1345 patients shown a reduction in postoperative AKI, need for RRT, postoperative mortality, days of mechanical ventilation and length of ICU stay [40]. However, a small RCT with primary renal hemodynamic outcomes showed no benefit of levosimendan over dobutamine in patients with cardiorenal syndrome [41]. Two larger RCTs are underway to specifically assess the impact of levosimendan on renal outcomes. The phase 4 ‘Effects of Levosimendan in Acute Kidney Injury after Cardiac Surgery trial’ (LEVOAKI) measures the effect of 210 min infusion of levosimendan versus placebo on renal hemodynamics and glomerular filtration rate (GFR) following cardiac surgeries (NCT02531724). A second RCT is assessing its efficacy on nonsurgical AKI in the ICU (LAKIS, 2012-004979-39).


Atrial natriuretic peptide agonists: Natriuretic peptides (atrial natriuretic peptide – ANP and brain natriuretic peptide – BNP) are endogenous hormones released in response to myocardial stretch and overload, inducing various actions such as natriuresis, kaliuresis, vasodilation and suppression of the RAAS [42]. Currently, nesiritide (a recombinant BNP) is approved for acute heart failure treatment in the USA, while carperitide (a recombinant ANP) is approved in Japan [43]. Renal benefits may also include protective effects on podocytes and arteriolar vasodilation by local RAAS blockade [44,45]. A recent meta-analysis of 1471 patients treated with low-dose carperitide found a trend towards a lower incidence of AKI and RRT initiation in patients at risk of AKI [46]. Ularitide, another recombinant ANP peptide, is currently under investigation in a phase 2 proof-of-concept trial for AKI treatment following cardiovascular surgery (TRUST, 2018-004871-11).

Anti-inflammatory therapies

Kidney injury is associated with the release of inflammatory cytokines that attract neutrophils, macrophages and lymphocytes. Inflammation plays a key role in the pathogenesis of AKI and its prognosis. No immunomodulatory interventions have been found effective and approved for the prevention or treatment of AKI to date.


The T-cell costimulatory receptor CD28 is critical to the adaptive immune response. Bacterial toxins may act as superantigens to hyperstimulate the response, inducing a cytokine storm [47]. Reltecimob (formerly AB103) is an immunomodulator that may attenuate the systemic inflammatory response to severe infection [48,49]. As a CD28-mimetic peptide, reltecimob is able to selectively inhibit the direct binding of superantigen to the CD28 receptor on T-helper lymphocytes [50]. Preliminary studies on toxic shock in animal models are associated with improved survival. A phase 2 trial in patients with necrotizing soft tissue infections, showed significantly less global organ dysfunction at 14 days without safety concerns [50]. A phase 3 trial is underway to confirm these results, and secondary outcomes include recovery from AKI by day 28 (ACCUTE, NCT02469857). Another large phase 2 RCT, Reltecimob Efficacy for Acute Kidney Injury Trial, will assess the efficacy and safety of this C28 modulator in patients with abdominal sepsis and AKI. The primary endpoint is complete recovery from KDIGO stage 2 or 3 AKI (NCT03403751; 2018-002547-29).

Alkaline phosphatase

Alkaline phosphatase is an enzyme expressed along the brush border of the proximal tubule. It has the capacity to reduce inflammation via the dephosphorylation and de-toxification of endotoxin (Lipopolysaccharide), and by dephosphorylation of ATP (which is a proinflammatory mediator) to produce adenosine, which has anti-inflammatory properties [51,52]. A recombinant chimeric alkaline phosphatase (recAP) could potentially exert anti-inflammatory effects and improve kidney function in sepsis, as shown in animal models and early phase trials using a bovine-derived form [53]. Recently, the STOP-AKI trial, using recAP in 301 patients with septic AKI randomized from 53 international sites, confirmed safety. While recAP did not significantly improve short-term (7-day) kidney function (the primary outcome) or need for RRT [54▪▪], there were signals of beneficial effects on both renal function and mortality (dose-dependent) [55]. A large phase 3 RCT of recap in septic AKI is currently in development [56].


Sphingosine-1-phosphate (S1p) analogues might mitigate endothelial damage and lymphocyte effects in AKI [57]. S1p-receptor activation improves cell survival by a reversible redistribution of lymphocytes, leading to temporary anti-inflammatory and tissue-protective effects [58]. Two analogues have been studied in renoprotection: fingolimod (FTY720) and SEW2871. In animal models exposed to cisplatin and ischemia-reperfusion, FTY720 was found to decrease renal injury biomarkers [57] and SEW2871 was associated with reduced tubular necrosis, lower serum creatinine and less leukocyte infiltration [59]. Fingolimod was also tested in several small RCTs to prevent acute rejection and delayed graft function [60] in kidney transplantation, with conflicting results; a meta-analysis is currently underway [61]. Despite potential benefits in renal ischemia-reperfusion injuries, no clinical trial involving S1p analogues on patients at risk of AKI has been registered to date.

∝ Melanocortin stimulating hormone

An ∝-melanocortin stimulating hormone (MSH) agonist, ABT-719 (formerly AP214) also has anti-inflammatory effects. It decreases nitric oxide production, neutrophil adhesion molecule expression and inflammatory cytokines [62]. Small and large animal models showed a protective effect of ∝-MSH agonist in septic and ischemia-reperfusion AKI models [62]. A phase 2 trial of 77 patients undergoing cardiac surgery showed a reduced incidence of AKI when receiving ABT-719 (unpublished, NCT01256372). However, a phase 2b study using ABT-719 in 231 chronic kidney disease (CKD) patients who underwent cardiac surgeries did not lower AKI incidence or kidney injury biomarkers [63]. Potential explanations for these discordant results include the lack of preclinical studies with CKD and other risk factors for AKI [64], and potentially a ‘U-shaped’ dose–effect relationship, with benefit at moderate doses, but harm at higher doses.


Some hormones play a pivotal role in the mechanism behind the pregnancy-associated immune tolerance. Human chorionic gonadotrophin has been shown to exert these immunomodulatory effects [65]. EA-230, a small tetrapeptide, was developed to replicate these properties. It improved survival in mice and in monkeys with experimental septic shock [66], and preserved renal function in models of renal ischemia-reperfusion and transplantation [67,68]. A phase 2 RCT is currently being conducted in 180 patients undergoing elective cardiac surgery [69]. The primary outcome is comprised of changes in inflammatory mediators, but secondary outcomes will include serum creatinine and tubular injury biomarkers (EASI-Study, NCT03145220).

Old agents: new trials: dexmedetomidine

Dexmedetomidine, an alpha-2 adrenoreceptor agonist used for its sedative effect, also has hemodynamic and anti-inflammatory properties. Animal studies showed a renoprotective effect in ischemia-reperfusion injuries that may be explained, at least in part, by a reduction of Toll-like receptor 4 and other proinflammatory signals in tubular cells [70]. A similar effect was described in sepsis models, where exposure to dexmedetomidine reduced IL-6, IL-18, TNF∝ as well as serum creatinine and tubular injury biomarkers like kidney injury molecule-1 (KIM-1) [71]. Several single-center RCTs have addressed this question in humans. A recent meta-analysis focusing in postcardiac surgery AKI prevention, including 10 trials and 1575 patients, concluded that dexmedetomidine might reduce the incidence of AKI [72], but time and dosage must be further evaluated. Other perioperative RCTs aiming to reduce incidence of AKI with this sedative are ongoing in kidney transplantation (NCT03522688) and following vascular surgery (NCT02607163).


Free radical oxygen species (ROS) play a significant role in AKI. Oxidative stress may have deleterious effects on the kidney on several levels: oxidation of proteins, peroxidation of lipids, damage to DNA and even induction of apoptosis [73]. Various disease states associated with AKI may result in free radical formation, including ischemia-reperfusion, contrast nephropathy, sepsis and drug toxicity [74]. Some potential therapies and repurposed drugs that directly target free radicals might prevent or ameliorate AKI.

Heme arginate

Iron is critical to the transport of oxygen and a variety of enzymatic reactions. Although iron is essential for life, in its ferrous form it can catalyze conversion of hydrogen peroxide to the toxic hydroxyl radical. A way of restricting this reaction is to favor the passage of free iron, after heme degradation, to ferritin, its protein-bound form. Heme oxygenase-1 (HO-1) can rapidly breakdown toxic free heme to generate three protective antioxidant products: carbon monoxide, biliverdin and ferritin [75]. In animal models of AKI, in addition to reducing oxidative stress, HO-1 also modulates autophagy, inflammations and apoptosis [76]. Heme arginate is a potent inducer of HO-1. In a proof-of-concept phase 2b study, 40 recipients were randomized to receive heme arginate versus placebo during the first 48 h following kidney transplantation. Upregulation of HO-1 was achieved as the primary endpoint, but the study was not powered to assess renal outcomes, despite a trend toward less biomarker-defined tubular injury [77]. A confirmatory phase 3 multicenter RCT recruiting 600 kidney transplant recipients is looking at reduction in delayed graft function (HOT 2 Trial, NCT03646344). Another phase 2 trial aiming to reduce AKI incidence in the context of cardiac surgery is still ongoing (2013-004607-39).

Old agents: new trials: propofol

Propofol is one of the most commonly used medications for induction and maintenance of anesthesia. With its structural resemblance to vitamin E, propofol has been shown to have anti-inflammatory properties [78]. Propofol can also increase levels of bone morphogenetic protein-7 (BMP-7), a potential tubular repair agent discussed below [79]. Indeed, abundant proliferation and a decreased rate of apoptosis was described in human tubular cells treated with propofol in vitro[80,81]. A large retrospective cohort of 4320 patients who underwent colorectal surgeries demonstrated that anesthesia with sevoflurane was associated with a modest increase in AKI incidence when compared with propofol anesthesia [82]. In addition, a prospective RCT conducted in 112 patients who underwent valvular heart surgery using either sevoflurane or propofol reported surprising results: a large reduction of AKI incidence in the group receiving propofol (10.7 versus 37.5%, P = 0.007) [83]. Another small RCT in abdominal aortic aneurysm repair found similar results [84]. Although prior larger prospective studies [85,86] did not show benefit with propofol over volatile anesthetics for AKI in the past, the large treatment effect observed in these both recent studies supports current active research on various surgical populations, including renal transplantation (VAPOR-2 Trial, NCT02727296), orthopedic procedures (NCT03336801) and partial nephrectomies [87].

Apoptosis inhibitors


P53 is implicated in cell cycle regulation, apoptosis and genomic stability. This pro-apoptotic transcription factor is activated in various AKI causes, including ischemia-reperfusion and cisplatin nephrotoxicity [88,89]. Teprasiran (formerly named QPI-1002), a small interfering RNA (siRNA) developed by Quark Pharmaceuticals, demonstrated rapid and temporary reduction (24–48 h) in p53 gene expression in AKI animal models. The synthetic siRNA was found to be associated with lower serum creatinine and less histological signs of mitochondria disruption and tubular injury [90]. A phase 2 RCT evaluating the efficacy and safety of teprasiran in patients at high risk of AKI following cardiovascular surgery was recently completed. In 341 patients, treatment with a single dose of teprasiran, versus placebo, reduced the primary endpoint of developing AKI within 5 days by 29%, and the duration of AKI [91]. These results were initially presented in 2017 but remain unpublished. However, based on these positive results, a large phase 3 RCT in 1088 patients at risk of AKI following cardiac surgery is ongoing (QRK309, NCT03510897).

Targeting mitochondrial stress

Mitochondria provide energy that is critical to normal kidney functions such as tubular transport and urinary concentration [92]. In the setting of ischemic injury and sepsis, mitochondria undergo changes including alterations in energy metabolism, and increases in ROS with peroxidation of the critical mitochondrial protein, cardiolipin [93,94]. This critical role of mitochondria dysfunction in AKI has led to potential therapies including [95]: first, Targeting antioxidant therapies to the mitochondria using triphenylphosphonium ion conjugated to lipophilic antioxidant molecules, such as MitoQ, TEMPO (MitoTEMPO) or plastoquinone (SkQR1); second, Cardiolipin-targeting peptides such as Szeto-Schiller peptides that stabilize mitochondrial cristae and can prevent apoptosis, ROS and inflammation (elamipretide, discussed below); third, Mitochondrial homing agents such as mitochonic acid-5 that may increase cellular ATP content; fourth, Drugs that promote fatty acid oxidation, including carnitine or acetyl-l-carnitine supplements and peroxisome proliferator-activated receptor (PPAR) α activators such as fenofibrate. Recently, ASP1128, a selective PPARδ modulator received fast-track designation by the FDA for patients at risk of AKI after cardiac surgery (NCT03941483); fifth, Drugs that promote mitochondrial biogenesis such as the PPARγ agonist pioglitazone and the β2-adrenergic agonist formoterol; and sixth, Activators of the major energy-sensing enzyme adenosine monophosphate kinase kinase such as elamipretide.


Cardiolipin is critical in regulating electron transport in the mitochondria as well as in maintenance of mitochondrial structures that support ATP production. Oxidation of cardiolipin leads to mitochondrial damage, impairment of ATP production, ROS production, inflammation and, consequently, initiation of apoptosis [95]. Elamipretide (also known as SS31, MTP-131 or Bendavia) is a mitochondrially targeted tetrapeptide that reduces the production of toxic ROS and stabilizes cardiolipin [96]. In animal models, elamipretide improves energetics and decreases ROS, possibly by stabilizing the mitochondrial membrane and cytochrome-c [97]. Much of the focus on elamipretide has been in neuromuscular diseases due to inherited mitochondrial deficiencies. However, in an early trial in mitochondrial myopathies, elamipretide was not effective in improving muscle function [98]. Elamipretide has also demonstrated potential for attenuating ischemia-reperfusion injury in AKI models, and improving kidney outcomes after experimental percutaneous renal artery angioplasty in renal artery stenosis models [99]. A phase 2a study was performed in patients undergoing stent revascularization for atherosclerotic renal vascular disease where the drug attenuated renal hypoxia developing 24 h after contrast imaging and stent revascularization. Cortical blood flow and estimated GFR (eGFR) increased in the elamipretide group when measured 3 months later suggesting a role of the drug in minimizing procedure-associated ischemic injury [100]. At this time, there are no current registered trials of elamipretide in AKI.

Cell metabolism

Oral nicotinamide

Nicotinamide is incorporated into nicotinamide adenine dinucleotide (NAD)+ and NADP+. NAD+ and NADP+ are coenzymes in a wide variety of enzymatic oxidation-reduction reactions, most notably glycolysis, the citric acid cycle, and the electron transport chain. Recent studies have shown that chronic deficiency of NAD+ can negatively affect several organ systems, while supplementation of NAD+ can extend longevity [101]. Using a metabolomic screen on the urine of mice with AKI induced by ischemia, defects in de novo biosynthesis of NAD+ and elevations of a precursor substance in the pathway of NAD+ biosynthesis, quinolinate were identified [101]. As a marker for defects in this metabolic pathway, elevated urinary levels of quinolinate/tryptophan were a biomarker for prediction of AKI. Following these observations on the importance of NAD+ biosynthesis, a phase I placebo-controlled study using oral nicotinamide to supplement NAD+ levels in patients undergoing cardiac surgery was performed [102▪▪]. Oral nicotinamide was well tolerated, and administration was associated a lower frequency of AKI events. These results will require additional study but suggest that targeting metabolic pathways involved in cellular protection may be a beneficial strategy. A single-center phase II clinical trial to evaluate the efficacy of ‘NAD+ supplementation’ with Basis (Nicotinamide Riboside and Pterostilbene) to prevent AKI in patients undergoing complex aortic aneurysm repair and open aortic arch reconstruction is now recruiting (NCT04342975).

Tubular repair agents

Ischemia-reperfusion models are extensively used to study AKI that may occur in diverse settings. Extensive studies have suggested that renal ischemia-reperfusion triggers a pro-inflammatory cascade that culminates in a tubular epithelial cell response with tubular apoptosis and acute tubular necrosis, resulting in a fall in GFR and AKI [103,104]. Identifying an effective strategy to promote tubular survival and repair is essential for minimizing damage and accelerating functional recovery after AKI.

Hepatocyte growth factor

Hepatocyte growth factor (HGF) is a pleiotropic growth factor with diverse biological roles [105,106]. In models of AKI secondary to various insults including ischemia-reperfusion, cold preservation/transplantation or toxin exposure, administration of recombinant human HGF attenuates injury and augments kidney function [107,108]. These biological actions of HGF are mediated by the tyrosine kinase receptor cMet. HGF administration in the setting of AKI promotes tubular regeneration, mitigates acute tubular necrosis and reduces kidney dysfunction via activation of the cMet-Akt axis and upregulation of cell survival proteins, including Bcl-2 [109–111]. HGF is an attractive target in the development of therapeutics for AKI. However, the short biological half-life of HGF necessitates continuous exogenous administration to achieve a therapeutic effect. Furthermore, administration of HGF, as gene or protein therapy, is impractical in a clinical setting. Thus, there has been a concerted effort to discover HGF-like molecules which would be practical and safe to administer in a clinical setting. BB3 is an HGF-like peptide which emulates the biological activity of HGF and when first administered at 24 h after renal ischemia in rats, improved survival, augmented urine output and reduced increases in serum creatinine and blood urea nitrogen. The kidneys of BB3-treated animals exhibited reduced levels of KIM-1, Neutrophil gelatinase-associated lipocalin and reduced tubular apoptosis and acute tubular necrosis but enhanced tubular regeneration [112].

BB3 has been renamed ANG-3777 (Angion Biomedica Corporation, San Francisco, California, USA) and is being developed as a potential therapy to activate HGF-related repair pathways post-AKI. In a phase 2 RCT, ANG-3777 was administered to patients with oliguria or slow creatinine reduction (<30% pretransplantation values) over the first 24 h postkidney transplantation [113]. The 19 patients treated with ANG-3777 were more likely to achieve the primary outcome of oliguria resolution by 28 days postkidney transplantation (78.9 versus 44.4% in the placebo group, P = 0.09). In addition, those patients treated with ANG-3777 had lower serum creatinine values and higher eGFRs, and fewer dialysis sessions and hospital days. Further trials of ANG-3777 are ongoing in transplant-associated AKI (NCT02474667) and for postcardiopulmonary bypass AKI (NCT02771509).

Bone morphogenetic protein-7 agonist

Research into the mechanisms of AKI has identified TGF-β and bone morphogenetic protein-7 as key mediators in the processes of kidney fibrosis, inflammation and tubular apoptosis. In these pathways, TGF-β has a primary role in injury, and BMP-7 inhibits TGF-β signaling, thereby protecting the kidney from transforming growth factor-mediated injury [114]. BMP-7 has anti-inflammatory and antifibrotic effects and has been found to be nephroprotective and to promote regeneration of kidney tubules [115,116]. Thus, pharmacological stimulation of the BMP-7 pathway is promising as a therapy for AKI. The compound THR-184 was developed as a synthetic positive modulator of the BMP-7 pathway and in preclinical studies showed promise in exerting anti-inflammatory and antiapoptotic effects in the kidney [117–119]. THR-184 was studied in a multidose RCT in 452 patients scheduled for nonemergent cardiac surgery requiring cardiopulmonary bypass [120▪▪]. The primary endpoint was the proportion of patients developing AKI within 7 days. However, in this study, THR-184 failed to reduce the incidence, severity and duration of AKI postcardiac surgery.


Translation of preclinical candidates into effective pharmacotherapies for the prevention and treatment of AKI has proven challenging. However, several promising candidates with a variety of targets are progressing through early-phase clinical trials, which we anticipate will yield successful therapies soon.



Financial support and sponsorship

Fellowship support for J-.M.C was provided by ’la Société québécoise de Néphrologie’, ’ l’Académie CHUM’ and ’le Fonds de Recherche en Santé du Québec.

Conflicts of interest

J.-M.C and M.H.R have no conflict of interest. P.T.M has received scientific advisory board consultancy fees from AM-Pharma, FAST Biomedical, and Renibus Therapeutics.


Papers of particular interest, published within the annual period of review, have been highlighted as:


1. Heung M, Steffick DE, Zivin K, et al. Acute kidney injury recovery pattern and subsequent risk of CKD: an analysis of veterans health administration data. Am J Kidney Dis 2016; 67:742–752.
2. Chawla LS. Acute kidney injury leading to chronic kidney disease and long-term outcomes of acute kidney injury: the best opportunity to mitigate acute kidney injury? Contrib Nephrol 2011; 174:182–190.
3. Agarwal A, Dong Z, Harris R, et al. Cellular and molecular mechanisms of AKI. J Am Soc Nephrol 2016; 27:1288–1299.
4. Hulse M, Rosner MH. Drugs in development for acute kidney injury. Drugs 2019; 79:811–821.
5. Jo SK, Rosner MH, Okusa MD. Pharmacologic treatment of acute kidney injury: why drugs haven’t worked and what is on the horizon. Clin J Am Soc Nephrol 2007; 2:356–365.
6. Zuk A, Palevsky PM, Fried L, et al. Overcoming translational barriers in acute kidney injury: a report from an NIDDK workshop. Clin J Am Soc Nephrol 2018; 13:1113–1123.
7. Prowle JR, Bellomo R. Sepsis-associated acute kidney injury: macrohemodynamic and microhemodynamic alterations in the renal circulation. Semin Nephrol 2015; 35:64–74.
8. Perico N, Casiraghi F, Remuzzi G. Clinical translation of mesenchymal stromal cell therapies in nephrology. J Am Soc Nephrol 2018; 29:362–375.
9. Lee KH, Tseng WC, Yang CY, Tarng DC. The anti-inflammatory, anti-oxidative, and anti-apoptotic benefits of stem cells in acute ischemic kidney injury. Int J Mol Sci 2019; 20:3529.
10. Deferrari G, Bonanni A, Bruschi M, et al. Remote ischaemic preconditioning for renal and cardiac protection in adult patients undergoing cardiac surgery with cardiopulmonary bypass: systematic review and meta-analysis of randomized controlled trials. Nephrol Dial Transplant 2018; 33:813–824.
11. Saito K, Uchino S, Fujii T, et al. Effect of low-dose atrial natriuretic peptide in critically ill patients with acute kidney injury: a retrospective, single-center study with propensity-score matching. BMC Nephrol 2020; 21:31.
12. Wei XB, Jiang L, Liu XR, et al. Brain natriuretic peptide for prevention of contrast-inducednephropathy: a meta-analysis of randomized controlled trials. Eur J Clin Pharmacol 2016; 72:1311–1318.
13. Pickkers P, Heemskerk S, Schouten J, et al. Alkaline phosphatase for treatment of sepsis-induced acute kidney injury: a prospective randomized double-blind placebo-controlled trial. Crit Care 2012; 16:R14.
14. Zeng Z, Fu X, Zhang X, Fu N. Comparison of double-dose vs. usual dose of nicorandil for the prevention of contrast-induced nephropathy after cardiac catheterization. Int Urol Nephrol 2019; 51:1999–2004.
15. Zhao M, Zhou Y, Liu S, et al. Control release of mitochondria-targeted antioxidant by injectable self-assembling peptide hydrogel ameliorated persistent mitochondrial dysfunction and inflammation after acute kidney injury. Drug Deliv 2018; 25:546–554.
16. Bove T, Zangrillo A, Guarracino F, et al. Effect of fenoldopam on use of renal replacement therapy among patients with acute kidney injury after cardiac surgery: a randomized clinical trial. JAMA 2014; 312:2244–2253.
17. Zangrillo A, Biondi-Zoccai GG, Frati E, et al. Fenoldopam and acute renal failure in cardiac surgery: a meta-analysis of randomized placebo-controlled trials. J Cardiothorac Vasc Anesth 2012; 26:407–413.
18. Ring A, Morris T, Wozniak M, et al. A Phase I study to determine the pharmacokinetic profile, safety and tolerability of sildenafil (Revatio(®)) in cardiac surgery: the REVAKI-1 study. Br J Clin Pharmacol 2017; 83:709–720.
19. Aslanabadi N, Afsar Gharebagh R, Moharramzadeh S, Entezari-Maleki T. Pentoxifylline for the prevention of contrast-induced nephropathy in diabetic patients undergoing angioplasty: a randomized controlled trial. Int Urol Nephrol 2019; 51:699–705.
20. Zhai M, Kang F, Han M, et al. The effect of dexmedetomidine on renal function in patients undergoing cardiac valve replacement under cardiopulmonary bypass: a double-blind randomized controlled trial. J Clin Anesth 2017; 40:33–38.
21. Cho JS, Shim JK, Soh S, et al. Perioperative dexmedetomidine reduces the incidence and severity of acute kidney injury following valvular heart surgery. Kidney Int 2016; 89:693–700.
22. Cho MH, Kim SN, Park HW, et al. Could vitamin E prevent contrast-induced acute kidney injury? A systematic review and meta-analysis. J Korean Med Sci 2017; 32:1468–1473.
23. Rezaei Y, Khademvatani K, Rahimi B, et al. Short-term high-dose vitamin E to prevent contrast medium-induced acute kidney injury in patients with chronic kidney disease undergoing elective coronary angiography: a randomized placebo-controlled trial. J Am Heart Assoc 2016; 5:e002919.
24. Chen F, Liu F, Lu J, et al. Coenzyme Q10 combined with trimetazidine in the prevention of contrast-induced nephropathy in patients with coronary heart disease complicated with renal dysfunction undergoing elective cardiac catheterization: a randomized control study and in vivo study. Eur J Med Res 2018; 23:23.
25. Amini S, Robabi HN, Tashnizi MA, Vakili V. Selenium, vitamin C and N-acetylcysteine do not reduce the risk of acute kidney injury after off-pump CABG: a randomized clinical trial. Braz J Cardiovasc Surg 2018; 33:129–134.
26. Garg AX, Devereaux PJ, Hill A, et al. Oral curcumin in elective abdominal aortic aneurysm repair: a multicentre randomized controlled trial. CMAJ 2018; 190:E1273–E1280.
27. Swaminathan M, Stafford-Smith M, Chertow GM, et al. Allogeneic mesenchymal stem cells for treatment of AKI after cardiac surgery. J Am Soc Nephrol 2018; 29:260–267.
28. Yun CW, Lee SH. Potential and Therapeutic Efficacy of Cell-based Therapy Using Mesenchymal Stem Cells for Acute/chronic Kidney Disease. Int J Mol Sci 2019; 20:1619–1635.
29. De Chiara L, Fagoonee S, Ranghino A, et al. Renal cells from spermatogonial germline stem cells protect against kidney injury. J Am Soc Nephrol 2014; 25:316–328.
30. Guerci P, Ergin B, Ince C. The macro- and microcirculation of the kidney. Best Pract Res Clin Anaesthesiol 2017; 31:315–329.
31. Matejovic M, Ince C, Chawla LS, et al. Renal hemodynamics in AKI: in search of new treatment targets. J Am Soc Nephrol 2016; 27:49–58.
32. Basso N, Terragno NA. History about the discovery of the renin-angiotensin system. Hypertension 2001; 38:1246–1249.
33. Correa TD, Jeger V, Pereira AJ, et al. Angiotensin II in septic shock: effects on tissue perfusion, organ function, and mitochondrial respiration in a porcine model of fecal peritonitis. Crit Care Med 2014; 42:e550–e559.
34. Wan L, Langenberg C, Bellomo R, May CN. Angiotensin II in experimental hyperdynamic sepsis. Crit Care 2009; 13:R190.
35. Khanna A, English SW, Wang XS, et al. Angiotensin II for the treatment of vasodilatory shock. N Engl J Med 2017; 377:419–430.
36. Tumlin JA, Murugan R, Deane AM, et al. Outcomes in patients with vasodilatory shock and renal replacement therapy treated with intravenous angiotensin II. Crit Care Med 2018; 46:949–957.
37. Farmakis D, Alvarez J, Gal TB, et al. Levosimendan beyond inotropy and acute heart failure: evidence of pleiotropic effects on the heart and other organs: an expert panel position paper. Int J Cardiol 2016; 222:303–312.
38. Faisal SA, Apatov DA, Ramakrishna H, Weiner MM. Levosimendan in cardiac surgery: evaluating the evidence. J Cardiothorac Vasc Anesth 2019; 33:1146–1158.
39. Zager RA, Johnson AC, Lund S, et al. Levosimendan protects against experimental endotoxemic acute renal failure. Am J Physiol Renal Physiol 2006; 290:F1453–F1462.
40. Zhou C, Gong J, Chen D, et al. Levosimendan for prevention of acute kidney injury after cardiac surgery: a meta-analysis of randomized controlled trials. Am J Kidney Dis 2016; 67:408–416.
41. Lannemyr L, Ricksten SE, Rundqvist B, et al. Differential effects of levosimendan and dobutamine on glomerular filtration rate in patients with heart failure and renal impairment: a randomized double-blind controlled trial. J Am Heart Assoc 2018; 7:e008455.
42. Vesely DL. Natriuretic peptides and acute renal failure. Am J Physiol Renal Physiol 2003; 285:F167–F177.
43. Lee CY, Burnett JC Jr. Natriuretic peptides and therapeutic applications. Heart Fail Rev 2007; 12:131–142.
44. Mitaka C, Ohnuma T, Murayama T, et al. Effects of low-dose atrial natriuretic peptide infusion on cardiac surgery-associated acute kidney injury: a multicenter randomized controlled trial. J Crit Care 2017; 38:253–258.
45. Ogawa Y, Mukoyama M, Yokoi H, et al. Natriuretic peptide receptor guanylyl cyclase-A protects podocytes from aldosterone-induced glomerular injury. J Am Soc Nephrol 2012; 23:1198–1209.
46. Yamada H, Doi K, Tsukamoto T, et al. Low-dose atrial natriuretic peptide for prevention or treatment of acute kidney injury: a systematic review and meta-analysis. Crit Care 2019; 23:41.
47. Kaempfer R, Arad G, Levy R, et al. CD28: direct and critical receptor for superantigen toxins. Toxins (Basel) 2013; 5:1531–1542.
48. Arad G, Hillman D, Levy R, Kaempfer R. Broad-spectrum immunity against superantigens is elicited in mice protected from lethal shock by a superantigen antagonist peptide. Immunol Lett 2004; 91:141–145.
49. Arad G, Levy R, Nasie I, et al. Binding of superantigen toxins into the CD28 homodimer interface is essential for induction of cytokine genes that mediate lethal shock. PLoS Biol 2011; 9:e1001149.
50. Bulger EM, Maier RV, Sperry J, et al. A novel drug for treatment of necrotizing soft-tissue infections: a randomized clinical trial. JAMA Surg 2014; 149:528–536.
51. Peters E, Geraci S, Heemskerk S, et al. Alkaline phosphatase protects against renal inflammation through dephosphorylation of lipopolysaccharide and adenosine triphosphate. Br J Pharmacol 2015; 172:4932–4945.
52. Peters E, Heemskerk S, Masereeuw R, Pickkers P. Alkaline phosphatase: a possible treatment for sepsis-associated acute kidney injury in critically ill patients. Am J Kidney Dis 2014; 63:1038–1048.
53. Peters E, Masereeuw R, Pickkers P. The potential of alkaline phosphatase as a treatment for sepsis-associated acute kidney injury. Nephron Clin Pract 2014; 127:144–148.
54▪▪. Pickkers P, Mehta RL, Murray PT, et al. Effect of human recombinant alkaline phosphatase on 7-day creatinine clearance in patients with sepsis-associated acute kidney injury: a randomized clinical trial. JAMA 2018; 320:1998–2009.
55. Tang W, Huang J, Huang X, et al. Effect of alkaline phosphatase on sepsis-associated acute kidney injury patients: a systematic review and meta-analysis. Medicine (Baltimore) 2020; 99:e18788.
56. AM_Pharma. Acute kidney injury. 2020; Available from: [Accessed 19 May 2020].
57. Bajwa A, Rosin DL, Chroscicki P, et al. Sphingosine 1-phosphate receptor-1 enhances mitochondrial function and reduces cisplatin-induced tubule injury. J Am Soc Nephrol 2015; 26:908–925.
58. Mandala S, Hajdu R, Bergstrom J, et al. Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists. Science 2002; 296:346–349.
59. Lien YH, Yong KC, Cho C, et al. S1P(1)-selective agonist, SEW2871, ameliorates ischemic acute renal failure. Kidney Int 2006; 69:1601–1608.
60. Tedesco-Silva H, Lorber MI, Foster CE, et al. FTY720 and everolimus in de novo renal transplant patients at risk for delayed graft function: results of an exploratory one-yr multicenter study. Clin Transplant 2009; 23:589–599.
61. Gholamnezhadjafari R, Falak R, Tajik N, et al. Effect of FTY720 (fingolimod) on graft survival in renal transplant recipients: a systematic review protocol. BMJ Open 2016; 6:e010114.
62. Doi K, Hu X, Yuen PS, et al. AP214, an analogue of alpha-melanocyte-stimulating hormone, ameliorates sepsis-induced acute kidney injury and mortality. Kidney Int 2008; 73:1266–1274.
63. McCullough PA, Bennett-Guerrero E, Chawla LS, et al. ABT-719 for the Prevention of Acute Kidney Injury in Patients Undergoing High-Risk Cardiac Surgery: A Randomized Phase 2b Clinical Trial. J Am Heart Assoc 2016; 5:e003549.
64. de Caestecker M, Harris R. Translating knowledge into therapy for acute kidney injury. Semin Nephrol 2018; 38:88–97.
65. Khan NA, Benner R. Human chorionic gonadotropin: a model molecule for oligopeptide-based drug discovery. Endocr Metab Immune Disord Drug Targets 2011; 11:32–53.
66. Khan NA, Vierboom MP, van Holten-Neelen C, et al. Mitigation of septic shock in mice and rhesus monkeys by human chorionic gonadotrophin-related oligopeptides. Clin Exp Immunol 2010; 160:466–478.
67. Gueler F, Shushakova N, Mengel M, et al. A novel therapy to attenuate acute kidney injury and ischemic allograft damage after allogenic kidney transplantation in mice. PLoS One 2015; 10:e0115709.
68. Khan NA, Susa D, van den Berg JW, et al. Amelioration of renal ischaemia-reperfusion injury by synthetic oligopeptides related to human chorionic gonadotropin. Nephrol Dial Transplant 2009; 24:2701–2708.
69. van Groenendael R, Beunders R, Hofland J, et al. The safety, tolerability, and effects on the systemic inflammatory response and renal function of the human chorionic gonadotropin hormone-derivative EA-230 following on-pump cardiac surgery (the EASI study): protocol for a randomized, double-blind, placebo-controlled phase 2 study. JMIR Res Protoc 2019; 8:e11441.
70. Gu J, Sun P, Zhao H, et al. Dexmedetomidine provides renoprotection against ischemia-reperfusion injury in mice. Crit Care 2011; 15:R153.
71. Tan F, Chen Y, Yuan D, et al. Dexmedetomidine protects against acute kidney injury through downregulating inflammatory reactions in endotoxemia rats. Biomed Rep 2015; 3:365–370.
72. Liu Y, Sheng B, Wang S, et al. Dexmedetomidine prevents acute kidney injury after adult cardiac surgery: a meta-analysis of randomized controlled trials. BMC Anesthesiol 2018; 18:7.
73. Tomsa AM, Alexa AL, Junie ML, et al. Oxidative stress as a potential target in acute kidney injury. PeerJ 2019; 7:e8046.
74. Chen H, Busse LW. Novel therapies for acute kidney injury. Kidney Int Rep 2017; 2:785–799.
75. Walker VJ, Agarwal A. Targeting iron homeostasis in acute kidney injury. Semin Nephrol 2016; 36:62–70.
76. Bolisetty S, Zarjou A, Agarwal A. Heme oxygenase 1 as a therapeutic target in acute kidney injury. Am J Kidney Dis 2017; 69:531–545.
77. Thomas RA, Czopek A, Bellamy CO, et al. Hemin preconditioning upregulates heme oxygenase-1 in deceased donor renal transplant recipients: a randomized, controlled, phase IIB trial. Transplantation 2016; 100:176–183.
78. Murphy PG, Myers DS, Davies MJ, et al. The antioxidant potential of propofol (2,6-diisopropylphenol). Br J Anaesth 1992; 68:613–618.
79. Hsing CH, Chou W, Wang JJ, et al. Propofol increases bone morphogenetic protein-7 and decreases oxidative stress in sepsis-induced acute kidney injury. Nephrol Dial Transplant 2011; 26:1162–1172.
80. Wang H, Peng X, Huang Y, et al. Propofol attenuates hypoxia/reoxygenation-induced apoptosis and autophagy in HK-2 cells by inhibiting JNK activation. Yonsei Med J 2019; 60:1195–1202.
81. Feng Y, Bai T, Ma H, Wang JK. Propofol attenuates human proximal renal tubular epithelial cell injury induced by anoxia-reoxygenation. Lab Med 2008; 39:356–360.
82. Bang JY, Lee J, Oh J, et al. The influence of propofol and sevoflurane on acute kidney injury after colorectal surgery: a retrospective cohort study. Anesth Analg 2016; 123:363–370.
83. Yoo YC, Shim JK, Song Y, et al. Anesthetics influence the incidence of acute kidney injury following valvular heart surgery. Kidney Int 2014; 86:414–422.
84. Ammar AS, Mahmoud KM. Comparative effect of propofol versus sevoflurane on renal ischemia/reperfusion injury after elective open abdominal aortic aneurysm repair. Saudi J Anaesth 2016; 10:301–307.
85. Story DA, Poustie S, Liu G, McNicol PL. Changes in plasma creatinine concentration after cardiac anesthesia with isoflurane, propofol, or sevoflurane: a randomized clinical trial. Anesthesiology 2001; 95:842–848.
86. Lorsomradee S, Cromheecke S, Lorsomradee S, De Hert SG. Effects of sevoflurane on biomechanical markers of hepatic and renal dysfunction after coronary artery surgery. J Cardiothorac Vasc Anesth 2006; 20:684–690.
87. Lee HJ, Bae J, Kwon Y, et al. General Anesthetic Agents and Renal Function after Nephrectomy. J Clin Med 2019; 8:1530–1544.
88. Kelly KJ, Plotkin Z, Vulgamott SL, Dagher PC. P53 mediates the apoptotic response to GTP depletion after renal ischemia-reperfusion: protective role of a p53 inhibitor. J Am Soc Nephrol 2003; 14:128–138.
89. Wei Q, Dong G, Yang T, et al. Activation and involvement of p53 in cisplatin-induced nephrotoxicity. Am J Physiol Renal Physiol 2007; 293:F1282–F1291.
90. Fujino T, Muhib S, Sato N, Hasebe N. Silencing of p53 RNA through transarterial delivery ameliorates renal tubular injury and downregulates GSK-3beta expression after ischemia-reperfusion injury. Am J Physiol Renal Physiol 2013; 305:F1617–F1627.
91. American_Society_Nephrology. Efficacy and safety of QPI-1002 (QPI) for prevention of AKI following cardiac surgery (QRK209 AKI). 2017; Available from: [Accessed 19 May 2020].
92. Mount PF, Power DA. Balancing the energy equation for healthy kidneys. J Pathol 2015; 237:407–410.
93. Paradies G, Petrosillo G, Paradies V, Ruggiero FM. Role of cardiolipin peroxidation and Ca2+ in mitochondrial dysfunction and disease. Cell Calcium 2009; 45:643–650.
94. Sun J, Zhang J, Tian J, et al. Mitochondria in sepsis-induced AKI. J Am Soc Nephrol 2019; 30:1151–1161.
95. Szeto HH. Pharmacologic approaches to improve mitochondrial function in AKI and CKD. J Am Soc Nephrol 2017; 28:2856–2865.
96. Kloner RA, Shi J, Dai W. New therapies for reducing postmyocardial left ventricular remodeling. Ann Transl Med 2015; 3:20.
97. Zhao K, Zhao GM, Wu D, et al. Cell-permeable peptide antioxidants targeted to inner mitochondrial membrane inhibit mitochondrial swelling, oxidative cell death, and reperfusion injury. J Biol Chem 2004; 279:34682–34690.
98. Mitochondrial_Disease_News. Elimipretide failed to meet promose of earlier trial results for primary mitochondrial myopathy. 2020; Available from: [Accessed 19 May 2020]
99. Eirin A, Li Z, Zhang X, et al. A mitochondrial permeability transition pore inhibitor improves renal outcomes after revascularization in experimental atherosclerotic renal artery stenosis. Hypertension 2012; 60:1242–1249.
100. Saad A, Herrmann SMS, Eirin A, et al. Phase 2a Clinical Trial of Mitochondrial Protection (Elamipretide) During Stent Revascularization in Patients With Atherosclerotic Renal Artery Stenosis. Circ Cardiovasc Interv 2017; 10:e005487.
101. Mouchiroud L, Houtkooper RH, Auwerx J. NAD(+) metabolism: a therapeutic target for age-related metabolic disease. Crit Rev Biochem Mol Biol 2013; 48:397–408.
102▪▪. Poyan Mehr A, Tran MT, Ralto KM, et al. De novo NAD(+) biosynthetic impairment in acute kidney injury in humans. Nat Med 2018; 24:1351–1359.
103. Linkermann A, De Zen F, Weinberg J, et al. Programmed necrosis in acute kidney injury. Nephrol Dial Transplant 2012; 27:3412–3419.
104. Pefanis A, Ierino FL, Murphy JM, Cowan PJ. Regulated necrosis in kidney ischemia-reperfusion injury. Kidney Int 2019; 96:291–301.
105. Jiang WG, Hiscox S. Hepatocyte growth factor/scatter factor, a cytokine playing multiple and converse roles. Histol Histopathol 1997; 12:537–555.
106. Nakamura T, Sakai K, Nakamura T, Matsumoto K. Hepatocyte growth factor twenty years on: much more than a growth factor. J Gastroenterol Hepatol 2011; 26: (Suppl 1): 188–202.
107. Fiaschi-Taesch NM, Santos S, Reddy V, et al. Prevention of acute ischemic renal failure by targeted delivery of growth factors to the proximal tubule in transgenic mice: the efficacy of parathyroid hormone-related protein and hepatocyte growth factor. J Am Soc Nephrol 2004; 15:112–125.
108. Dai C, Yang J, Liu Y. Single injection of naked plasmid encoding hepatocyte growth factor prevents cell death and ameliorates acute renal failure in mice. J Am Soc Nephrol 2002; 13:411–422.
109. Homsi E, Janino P, Biswas SK, et al. Attenuation of glycerol-induced acute kidney injury by previous partial hepatectomy: role of hepatocyte growth factor/c-met axis in tubular protection. Nephron Exp Nephrol 2007; 107:e95–e106.
110. Kamimoto M, Mizuno S, Matsumoto K, Nakamura T. Hepatocyte growth factor prevents multiple organ injuries in endotoxemic mice through a heme oxygenase-1-dependent mechanism. Biochem Biophys Res Commun 2009; 380:333–337.
111. Kawaida K, Matsumoto K, Shimazu H, Nakamura T. Hepatocyte growth factor prevents acute renal failure and accelerates renal regeneration in mice. Proc Natl Acad Sci U S A 1994; 91:4357–4361.
112. Narayan P, Duan B, Jiang K, et al. Late intervention with the small molecule BB3 mitigates postischemic kidney injury. Am J Physiol Renal Physiol 2016; 311:F352–F361.
113. Bromberg JS, Weir MR, Gaber AO, et al. Renal function improvement following ANG-3777 treatment in patients at high risk for delayed graft function after kidney transplantation. Transplantation 2020; [Online First April 14, 2020].
114. Meng XM, Chung AC, Lan HY. Role of the TGF-beta/BMP-7/Smad pathways in renal diseases. Clin Sci (Lond) 2013; 124:243–254.
115. Chen D, Zhao M, Mundy GR. Bone morphogenetic proteins. Growth Factors 2004; 22:233–241.
116. Vukicevic S, Basic V, Rogic D, et al. Osteogenic protein-1 (bone morphogenetic protein-7) reduces severity of injury after ischemic acute renal failure in rat. J Clin Invest 1998; 102:202–214.
117. Sugimoto H, LeBleu VS, Bosukonda D, et al. Activin-like kinase 3 is important for kidney regeneration and reversal of fibrosis. Nat Med 2012; 18:396–404.
118. Zeisberg M, Bottiglio C, Kumar N, et al. Bone morphogenic protein-7 inhibits progression of chronic renal fibrosis associated with two genetic mouse models. Am J Physiol Renal Physiol 2003; 285:F1060–F1067.
119. Zeisberg M, Hanai J, Sugimoto H, et al. BMP-7 counteracts TGF-beta1-induced epithelial-to-mesenchymal transition and reverses chronic renal injury. Nat Med 2003; 9:964–968.
120▪▪. Himmelfarb J, Chertow GM, McCullough PA, et al. Perioperative THR-184 and AKI after cardiac surgery. J Am Soc Nephrol 2018; 29:670–679.

acute kidney injury; antioxidant; clinical trials; drugs; inflammation; repair

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