Medical treatment for diabetic acute kidney disease from 2012 to 2024: advances, prescription trends, and future directions

Heng-Chih Pan; Chung-An Wang; Jui-Yi Chen; Vin-Cent Wu

doi:10.23876/j.krcp.25.126

Kidney Res Clin Pract > Volume 45(3); 2026 > Article

Pan, Wang, Chen, and Wu: Medical treatment for diabetic acute kidney disease from 2012 to 2024: advances, prescription trends, and future directions

Review Article

Kidney Research and Clinical Practice 2026;45(3):327-342.

Published online: February 6, 2026

DOI: https://doi.org/10.23876/j.krcp.25.126

Medical treatment for diabetic acute kidney disease from 2012 to 2024: advances, prescription trends, and future directions

Heng-Chih Pan^1,^2,^3,^4,^5,⁶

, Chung-An Wang⁷

, Jui-Yi Chen^8,⁹

, Vin-Cent Wu^10,^11,^12,¹³

¹Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan

²Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan

³Division of Nephrology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan

⁴Community Medicine Research Center, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan

⁵Division of Nephrology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

⁶Kidney Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

⁷Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan

⁸Division of Nephrology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan

⁹Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, Tainan, Taiwan

¹⁰Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

¹¹PAC (Primary Aldosteronism Center), National Taiwan University Hospital, Taipei, Taiwan

¹²NSARF (National Taiwan University Hospital Study Group of Acute Renal Failure), Taipei, Taiwan

¹³CAKs (Taiwan Consortium for Acute Kidney Injury and Renal Diseases), Taipei, Taiwan

Correspondence: Vin-Cent Wu Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei 100, Taiwan. E-mail: q91421028@ntu.edu.tw

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial and No Derivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/) which permits unrestricted non-commercial use, distribution of the material without any modifications, and reproduction in any medium, provided the original works properly cited.

Abstract

Diabetic acute kidney disease (AKD) represents a pivotal transitional phase between acute kidney injury (AKI) and chronic kidney disease (CKD), carrying a high risk of progression to end-stage kidney disease. Effective medical management is crucial during this phase. Renin-angiotensin-aldosterone system inhibitors remain the foundation of therapy, and newer agents have expanded the armamentarium. Sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists have been shown to confer significant nephroprotective and cardioprotective effects, including decreased risks of AKD progression, heart failure, and mortality. Finerenone, a novel nonsteroidal mineralocorticoid receptor antagonist, has also been shown to reduce kidney disease progression and cardiovascular events in patients with established diabetic CKD, although its role in AKD remains uncertain. However, real-world data indicate the suboptimal utilization of these therapies, highlighting barriers related to clinical inertia, safety concerns after AKI, and socioeconomic disparities. Future strategies should emphasize the timely initiation and combination of treatments to maximize renoprotection, while exploring emerging agents such as endothelin receptor antagonists and aldosterone synthase inhibitors. Integrating evidence-based therapies, improving adherence to guideline-directed care, and leveraging real-world data to inform clinical practice are necessary to optimize kidney and cardiovascular outcomes in patients with diabetic AKD.

Keywords: Acute kidney disease, Diabetic kidney disease, Finerenone, Glucagon-like peptide-1 receptor agonists, Prescribing trendsr, Real-world data, Sodium–glucose cotransporter-2 inhibitors

Introduction

Type 2 diabetes mellitus (T2DM) is a leading cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) worldwide [1,2]. In addition to causing progressive diabetic kidney disease (DKD), diabetes mellitus (DM) predisposes patients to acute kidney injury (AKI) during acute illnesses or cardiovascular events [3]. People with DM have a higher risk of AKI than those without [1,4], and when AKI occurs in these patients, it often accelerates the progression of renal dysfunction [2,5]. The term acute kidney disease (AKD) describes kidney dysfunction lasting from 7 to 90 days after an acute kidney insult, bridging the gap between AKI and CKD [6,7]. In practice, AKD encompasses patients with persistent AKI beyond 7 days or new-onset kidney impairment within 90 days that has not yet returned to baseline [6–8]. Patients with DM and classified as having AKD, essentially those with recent AKI on a background of DM, are at high risk of poor outcomes, including further loss of kidney function, cardiovascular events, and mortality [2,9]. Optimizing medical management during this vulnerable period is therefore critical to improving long-term outcomes.

Fig. 1 illustrates the historical introduction and subsequent evolution of diabetic kidney care, from the foundational role of renin-angiotensin-aldosterone system (RAAS) blockade first established in 2001 to the introduction of sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) (2010s), approval of finerenone (2021), and next-generation therapies (e.g., endothelin antagonists and novel incretin co-agonists). The relative efficacy of each drug class on CKD progression, AKI recurrence, heart failure hospitalization, and major adverse cardiovascular events is shown in Fig. 2. Because diabetic AKD is an emerging disease entity distinct from stable CKD, these agents warrant reconsideration in an acute-to-chronic transitional context. Ongoing efforts are investigating the combination of these agents to achieve a maximum effect while also exploring precision medicine (e.g., biomarker-driven therapy) [10].

This review addresses the pathophysiology of AKD in the context of DM and examines current medical treatment strategies. Key pharmacological interventions—including RAAS inhibitors, SGLT2is, GLP-1 RAs, and other medications such as finerenone, dipeptidyl peptidase-4 inhibitors (DPP-4is), and thiazolidinediones (TZDs)—are reviewed in terms of their potential efficacy and practical use in patients with diabetic AKD [11–13]. We also explore real-world prescription trends (with insights from TriNetX platform), and discuss future directions for research and clinical care in this field [14,15].

Pathophysiology of diabetic acute kidney disease

Long-standing T2DM leads to structural and functional changes in the kidneys that not only cause chronic dysfunction but also increase susceptibility to acute injury [1,2,16]. Hyperglycemia-driven glomerular hyperfiltration, the accumulation of advanced glycation end-products, oxidative stress, and upregulation of the renin-angiotensin system all contribute to diabetic kidney damage [10,17]. These factors cause glomerular basement membrane thickening, mesangial expansion, and arteriolar sclerosis, which reduce renal functional reserve. As a result, the kidneys of a diabetic patient are less able to compensate during an acute insult—such as volume depletion, sepsis, or cardiorenal decompensation—resulting in a higher likelihood of kidney injury [1,2,4,9]. Moreover, acute injuries in the context of DM tend to cause more severe damage that does not completely recover. Sepsis and cardiorenal complications are among the most common precipitants of AKI in T2DM patients [18,19]. Ongoing pathophysiological processes during AKD include sustained inflammation, oxidative stress, and fibrosis that can further impair renal function [8,17].

No specific pharmacologic therapies are currently available to reverse established AKI, and management remains largely supportive [6,20]. Consequently, the post-AKI period is a crucial window in which to provide therapies that support renal recovery and prevent additional injury. Identifying risk factors for incomplete recovery after AKI—such as pre-existing CKD (often present in patients with DM), older age, and severe initial injury—can help to identify patients who need especially close monitoring and aggressive risk factor control [5,6]. Fig. 3 provides an overview of how hyperglycemia and increased glomerular pressure lead to RAAS activation and oxidative stress.

Pharmacological treatment strategies

The management of diabetic AKD builds on the foundational treatments for chronic DKD, with adjustments for the acute context. The goal is to slow or halt kidney disease progression, reduce cardiovascular risk, and ideally improve the likelihood of renal recovery after AKI (Fig. 3). Table 1 summarizes the pivotal trials evaluating kidney outcomes in patients with DM, whereas Table 2 summarizes the key studies focusing on pharmacologic management in diabetic AKD.

Renin-angiotensin-aldosterone system inhibitors (angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers)

RAAS blockade with angiotensin-converting enzyme inhibitors (ACEis) or angiotensin II receptor blockers (ARBs) is the cornerstone of therapy for DKD, particularly in patients with significant albuminuria [21–23]. By dilating the efferent arterioles and reducing intraglomerular pressure, these agents’ lower proteinuria and confer long-term renoprotective and cardioprotective effects. Landmark trials have demonstrated that RAAS blockade slows nephropathy progression in patients with DM. For example, the RENAAL study of patients with T2DM nephropathy reported that losartan reduced the incidence of the composite outcome of doubling of serum creatinine, ESKD, or death by 16% (p = 0.022, mainly the risk of progression to ESKD by 28%–29%) [22]. Similarly, the IDNT trial showed that irbesartan significantly reduced the risk of kidney function decline or ESKD compared to placebo [21].

Accordingly, clinical guidelines uniformly recommend an ACEi or ARB in diabetic patients with hypertension and albuminuria, unless contraindicated (e.g., persistent hyperkalemia). In AKD, once hemodynamics and renal function stabilize, RAAS inhibitors should be restarted; otherwise, the long-term renoprotective benefit is diminished [24,25]. A recent study suggested that reinitiating ACEis/ARBs as soon as possible after AKI was associated with lower risks of mortality and CKD progression [26]. The close monitoring of blood pressure, creatinine, and potassium is critical as renal function recovers. RAAS blockade remains the foundational therapy upon which newer treatments such as SGLT2is, GLP-1 RAs, and finerenone are added for diabetic AKD.

Sodium-glucose cotransporter-2 inhibitors

SGLT2is have emerged in the past decade as transformative therapies for diabetic kidney and cardiovascular diseases. Landmark outcome trials—including CANVAS, DECLARE-TIMI 58, CREDENCE, and DAPA-CKD showed that these agents not only improve glycemic control but also confer substantial cardiorenal protection [27–30]. Drugs in this class reduce renal tubular glucose reabsorption, leading to glycosuria. This mechanism not only lowers blood glucose but also alleviates glomerular hyperfiltration and helps reduce blood pressure. SGLT2 inhibition also restores tubuloglomerular feedback, reduces intraglomerular hypertension, and mitigates the hemodynamic stress and inflammatory signaling that drive DKD progression [27,29,31–34]. Despite early concerns about hypovolemia and transient reductions in estimated glomerular filtration rate (eGFR) in acute settings, a previous meta-analysis found an overall lower incidence of AKI in patients receiving SGLT2i treatment [31]. In addition, recent real-world AKD-focused cohort studies have reported significant reductions in mortality and major kidney events [18,35]. Hence, once stable from an acute insult, resuming or introducing an SGLT2i may confer substantial benefits in patients with AKD. We thus consider SGLT2i to be a cornerstone therapy even in post-AKI recovery to prevent further decline in diabetic patients [31,36].

Glucagon-like peptide-1 receptor agonists

GLP-1 RAs are another class of agents originally developed for glycemic control in patients with T2DM that have demonstrated cardiovascular and renal benefits. GLP-1 RAs enhance glucose-dependent insulin secretion, suppress glucagon, promote weight loss, and have mild blood pressure-lowering effects [37,38]. Beyond glucose control, GLP-1 RAs appear to exert organ-protective effects through anti-inflammatory and anti-atherosclerotic mechanisms. In the kidneys, GLP-1 RAs have been shown to reduce the risk of developing or worsening CKD, mainly by reducing the progression to overt albuminuria [39,40]. Potential renoprotective mechanisms include attenuation of oxidative stress, fibrosis, and apoptosis in kidney tissues [41–45].

Several large cardiovascular outcome trials have shown renal benefits. The LEADER trial found that liraglutide lowered the composite renal outcome by 22% [39,46], and the SUSTAIN-6 and REWIND trials reported that semaglutide and dulaglutide slowed CKD progression and decreased the amount of proteinuria [40,47]. In addition, the ongoing dedicated renal outcome trial, FLOW, will clarify hard kidney endpoints in T2DM with CKD [48]. Guidelines now recommend GLP-1 RAs as an add-on to metformin/SGLT2is, especially for patients with T2DM and CKD or concomitant atherosclerotic cardiovascular disease [24,25]. In diabetic AKD, real-world TriNetX data suggest a 43% reduction in mortality, 12% fewer cardiovascular events, and 27% fewer major adverse kidney events with the use of GLP-1 RAs [19]. Given these benefits, GLP-1 RAs should be considered once AKI stabilizes, even in patients with a low eGFR. Close monitoring for gastrointestinal side effects and volume changes is essential [25,43].

Dipeptidyl peptidase-4 inhibitors and thiazolidinediones

While SGLT2is and GLP-1 RAs are important medications, some real-world data suggest that the post-AKI use of DPP-4is may further reduce adverse outcomes [49,50]. TZDs have also been shown to have potential benefits in patients with diabetic AKD, improving both survival and renal endpoints despite fluid retention concerns [51]. Hence, DPP-4is and TZDs remain alternative or adjunct options for specific AKD patients, possibly enhancing post-AKI renal recovery via insulin sensitivity and anti-inflammatory effects [49–51].

Finerenone and emerging therapies

Finerenone is a nonsteroidal mineralocorticoid receptor antagonist that has recently emerged as an important therapy for diabetic CKD. By blocking the effects of aldosterone in the kidneys and heart, finerenone reduces pro-fibrotic and pro-inflammatory pathways. In the FIDELIO-DKD trial (patients with T2DM and advanced CKD receiving RAAS blockade therapy), finerenone was shown to reduce the composite kidney outcome (kidney failure, sustained eGFR decline, or renal death) by 18%, and also to reduce the key secondary cardiovascular outcome by 14% (hazard ratio, 0.86) [52]. The FIGARO-DKD trial enrolled patients with earlier-stage CKD and demonstrated a 13% reduction in cardiovascular events with finerenone treatment and a trend toward kidney benefits consistent with the FIDELIO-DKD trial [11].

Based on these results, finerenone is now approved for patients with T2DM and CKD (eGFR ≥25 mL/min/1.73 m² and urinary albumin-to-creatinine ratio ≥30 mg/g) to reduce the risks of kidney function decline, kidney failure, and heart failure hospitalization [53,54].

Although no randomized trial has yet enrolled patients with diabetic AKD, the recent CONFIDENCE study showed that starting finerenone together with the SGLT2i empagliflozin in stable CKD produced an additional 29% to 32% reduction in albuminuria over either agent alone, without new safety signals [55]. These data imply that early combination therapy is feasible, but AKD-specific trials remain a major unmet need. Until such evidence emerges, finerenone use during AKD should be individualized.

Practical reinitiation in partially recovered AKD—incomplete renal recovery amplifies finerenone-associated hyperkalemia. We therefore suggest restarting treatment only after eGFR has remained stable for ≥2 weeks and baseline serum potassium is <4.8 mmol/L [11,52]. When eGFR has improved from <15 mL/min/1.73 m² into the 25–30 mL/min/1.73 m² range, begin at 10 mg once daily, repeat potassium and creatinine on days 7 and 28, and up-titrate to 20 mg only if potassium stays ≤5.0 mmol/L [52]. Concomitant loop or thiazide diuretics, a low-potassium diet, and early use of potassium binders help maintain normokalemia [24,56]. An analysis across FIDELIO and FIGARO indicates that with these safeguards, the cardiorenal benefits of finerenone persist down to an eGFR of approximately 25 mL/min/1.73 m², while the absolute excess risk of severe hyperkalemia remains low [53].

Other emerging therapies are under investigation for DKD, although none have yet become standard in AKD management. These include endothelin-1 receptor antagonists (e.g., atrasentan), which have been shown to reduce albuminuria in trials but have not advanced due to side effects, anti-inflammatory drugs such as pentoxifylline (which can modestly reduce proteinuria), and novel metabolic agents such as dual GLP-1/ glucose-dependent insulinotropic polypeptide agonists and SGLT1/2 co-inhibitors [57–60]. While these are promising in concept, robust evidence of improved hard outcomes in patients with diabetic AKD is still lacking. For now, the mainstay pharmacologic therapies for diabetic AKD remain RAAS inhibitors, SGLT2is, and GLP-1 RAs [24,25], as shown in Figs. 3, 4.

Timing of (re-)initiation of kidney-protective agents in acute kidney disease

• RAAS inhibitors (ACEi/ARB): restart as soon as hemodynamics are stable; early resumption is linked to lower mortality and slower CKD progression after AKI [24,26].

• SGLT2is and finerenone

- De-novo use: initiate only after eGFR has stabilized ≥25 mL/min/1.73 m² for ≥1 to 2 weeks, reflecting the lower enrolment boundary of CREDENCE, DAPA-CKD, EMPA-KIDNEY, FIDELIO, and FIGARO-DKD trials [11,24,29,32,33,52].

- Patients previously on therapy:

* eGFR of 20–25 mL/min/1.73 m²: restart at half of the prior dose once renal function has plateaued [24].

* eGFR <20 mL/min/1.73 m²: withhold; reconsider once eGFR rises into 20–25 mL/min/1.73 m² and remains steady for ≥14 days [24].

Check serum creatinine (and potassium for finerenone) at day 7 and week 4; up-titrate only if eGFR is stable and K⁺ ≤5.0 mmol/L [52].

• GLP-1 RAs

- De-novo use: May be added once oral intake and hemodynamics are stable (typically weeks 3–4 post-AKI); they exert minimal hemodynamic stress and have shown cardiorenal safety even at eGFR 15–30 mL/min/1.73 m² [24,45,61].

-Patients previously on therapy: GLP-1 RA therapy can be resumed near discharge or at the first outpatient review, using the pre-AKI dose unless gastrointestinal intolerance mandates adjustment [24].

Practical guidance on when to (re)introduce these kidney-protective agents during AKD recovery is shown in Supplementary Fig. 1 (available online).

Prescription trends and real-world utilization

Fig. 5 illustrates the real-world prescribing patterns of DM and hypertension medications based on data from the TriNetX global database, a collaborative health research network widely used in numerous prominent epidemiological studies (Supplementary materials, available online) [14,62], with this analysis focusing on prescription data from 2012 to 2024. Among patients with T2DM and AKD, aggregated prescription patterns reveal consistently high ACEi/ARB usage (approximately 25%–35%) but also notable increases in the use of SGLT2is and GLP-1 RAs (Fig. 5A). Metformin remains widely prescribed, whereas the use of sulfonylureas has declined. Prescription rates for TZDs and DPP-4is have remained relatively stable. Fig. 5B underscores the relatively modest utilization of SGLT2is and GLP-1 RAs, indicating persistent reliance on older therapeutic regimens. Despite accumulating evidence supporting their renoprotective and cardioprotective benefits, a substantial proportion of eligible patients have not received these therapies, even in recent years.

Beyond these trends, real-world utilization in patients with DKD, particularly those recovering from AKI, remains suboptimal. Historically, RAAS inhibitors have been underused [24]. Despite the proven benefits of SGLT2is and GLP-1 RAs, early adoption has been reported to face barriers such as safety concerns, lack of familiarity, and cost. In patients with AKD, clinicians are often cautious about initiating new medications during renal recovery, which can further delay the use of these therapies [13,36]. In two separate cohort studies of T2DM patients with AKD spanning 2002–2022, only 2.3% received SGLT2is in the first study and 4.5% received GLP-1 RAs in the second, underscoring notable underutilization [18,19]. Further studies have revealed significant disparities in prescribing patterns based on geographic region and socioeconomic status, underscoring the need for guideline-driven multidisciplinary strategies to optimize equitable access and the implementation of renoprotective therapies [63–65].

Several factors contribute to the underutilization of SGLT2is and GLP-1 RAs in practice:

•Historical CKD contraindications

For years, many DM medications were contraindicated once CKD reached a moderate stage, which made clinicians hesitant to use newer agents in patients with low eGFR. This mindset has only recently begun to shift as trials and guidelines have expanded the indications into lower eGFR ranges [24,25].

• Safety concerns post-AKI

Physicians may fear that starting an ACEi, SGLT2i, or other agent soon after AKI could cause another decline in kidney function or other complications. In reality, careful introduction with monitoring can mitigate these risks, and data suggest net benefits (e.g., no increase in recurrent AKI with SGLT2is) [31].

• Cost and access

SGLT2is, GLP-1 RAs, and finerenone are newer, brand-name medications that can be expensive. Limited insurance coverage or high co-payments may prevent some patients from using them [63,65].

• Provider awareness and inertia

There is often a delay between published evidence and widespread clinical practice; a recently published viewpoint underscored this evidence-to-practice gap [66]. Some providers may not be fully aware of the latest guideline recommendations or may be uncomfortable managing potential side effects (such as diuresis or hyperkalemia), leading to a “wait and see” approach [67,68].

Encouragingly, prescription trends are improving as awareness grows. The inclusion of SGLT2is and finerenone in CKD guidelines (e.g., KDIGO [Kidney Disease: Improving Global Outcomes] 2020 and ADA [American Diabetes Association] Standards of Care) and the endorsement of GLP-1 RAs for those with diabetic CKD and cardiovascular disease have spurred greater adoption [24,25,36]. Nonetheless, there remains a clear gap between evidence and practice, and many patients with diabetic AKD are still only receiving old regimens [8,13,34]. Bridging this gap requires concerted efforts in provider education and system-level support. Ensuring early post-AKI follow-up (for example, arranging nephrology visits a few weeks after hospital discharge) can help in reassessing medications and starting these therapies when appropriate. Multidisciplinary collaboration between nephrologists, endocrinologists, and primary care providers can also facilitate comprehensive management. In summary, improving the real-world utilization of these proven therapies in patients with diabetic AKD is a key opportunity to enhance patient outcomes [34,64,65,69].

Discussion and future directions

Stepwise sequencing of pharmacotherapy during acute kidney disease recovery

Recent advances in medical therapy for DKD have greatly expanded the options to improve renal and cardiovascular outcomes, and this is particularly relevant in the AKD period following AKI. Current evidence supports a multifactorial approach, and combining RAAS inhibition, SGLT2 inhibition, and GLP-1 RA therapy addresses hemodynamic, hyperglycemic, and inflammatory mechanisms in patients with diabetic AKD. The addition of finerenone may provide further anti-fibrotic and anti-inflammatory effects; however, its role in AKD still requires confirmation.

In AKD, where renal function remains labile, we favor a stepwise rather than simultaneous introduction of reno-protective agents. Recent viewpoints in stable CKD have urged accelerated or rapid-sequence implementation of guideline therapy; our proposed 0 to 4-week algorithm adapts this concept to the higher-risk AKD recovery phase [66]. This sequencing serves two purposes: 1) it allows clear attribution if serum creatinine rises or an adverse effect emerges, and 2) it avoids cumulative hemodynamic or electrolyte stress during the vulnerable recovery phase. Our recommended timetable is as follows (Supplementary Fig. 2, available online):

1. Restart ACEi/ARB as soon as blood pressure is stable and serum creatinine has plateaued, because RAAS blockade is the cornerstone of long-term reno-protection [26].

2. Add an SGLT2i within 1 to 2 weeks if eGFR ≥25 mL/min/1.73 m²; emerging observational data suggest early use accelerates functional recovery and lowers recurrent-AKI risk [18,31].

3. Introduce a GLP-1 receptor agonist in weeks 3 to 4 once oral intake has normalized; its cardiometabolic benefits accrue early, and it carries minimal hemodynamic penalty [24,45].

4. Layer finerenone last—typically ≥4 weeks post-AKI—after eGFR and potassium have demonstrated stability and residual albuminuria persists despite steps 1 to 3, noting that the CKD-focused CONFIDENCE trial supports the biological rationale for earlier dual therapy, but AKD-specific safety remains untested [11,52,55].

Thus, for drugs with putative pro-recovery effects (chiefly SGLT2is and, to a lesser extent, GLP-1 RAs), we advocate early but staggered initiation to capture benefit while preserving clinical clarity. Supplementary Fig. 2 (available online) summarizes this sequential algorithm for the AKD convalescent period.

Monitoring AKI/AKD recovery is equally important. A recent study stressed the significance of tracking post-dialysis AKI recovery, indicating that nearly half of patients with acute kidney injury requiring dialysis had poor outcomes [70]. Guidelines emphasize the importance of tracking kidney health after acute insults. AKD clinics or interdisciplinary models could ensure timely medication titration, detect recurrent injury, and promote patient education [71]. To avoid misinterpreting an early “functional dip” in eGFR as true AKI recurrence, we recommend the following bedside checklist (Supplementary Fig. 3, available online) [7,21,24,27,32,52]: 1) confirm that any eGFR decline occurs within 3 to 14 days of drug initiation and remains ≤20% to 30% of baseline; 2) verify stable hemodynamics and absence of new nephrotoxin exposure; 3) examine urine output and sediment for oliguria or active casts; 4) confirm that blood urea nitrogen and serum potassium remain stable; and 5) repeat chemistry at day 7 and week 4, continuing therapy if the dip plateaus.

Ultimately, it is important to implement proven treatment (RAAS blockade, SGLT2is, GLP-1 RAs in indicated patients) and refine therapy for AKD. Future research should explore optimal combination strategies and the timing of initiating therapy post-AKI.

Acute kidney disease heterogeneity and future precision strategies

We concur that AKD is unlikely to represent single-entity syndrome; therapeutic responsiveness may vary by biological subtype. Future research should therefore pursue three complementary avenues:

1. Phenotype-driven classification. Early data point to at least three recurring AKD patterns: 1) a persistent-AKI phenotype (prolonged creatinine elevation after a documented AKI), 2) a de-novo AKD phenotype (subacute eGFR decline ± new albuminuria without an overt AKI trigger), and 3) an acute-on-CKD phenotype (AKD superimposed on established CKD with incomplete recovery). Each category likely differs in dominant pathobiology—tubular necrosis, microvascular congestion, or maladaptive repair—and therefore in drug sensitivity [7,8].

2. Biomarker-guided enrichment. Emerging panels (e.g., NGAL and KIM-1 for tubular injury; CCL14 and L-FABP for maladaptive inflammation) should be integrated with plasma/urine proteomics, metabolomics, and single-cell transcriptomics in large AKD cohorts. Machine-learning clustering of these multidimensional data could yield biologically coherent subgroups that transcend clinical labels [72].

3. Subtype-specific trials. Once phenotypes are validated, interventional studies ought to move from “all-comer” AKD designs toward enrichment or adaptive platform trials randomizing within a single biomarker-defined stratum. Such precision frameworks could test, for example, whether early SGLT2 inhibition accelerates recovery specifically in the persistent-AKI phenotype [34], whereas anti-fibrotic strategies (e.g., finerenone) might target de-novo AKD with high profibrotic signatures [52].

Recognizing and interrogating AKD heterogeneity will be essential to shift from empiric, one-size-fits-all treatment toward truly tailored kidney-rescue strategies.

Conclusion

Diabetic AKD represents an important window for intervention, where timely therapy can alter disease trajectory. Current evidence supports a combination of RAAS inhibitors, SGLT2is, and GLP-1 RAs to address hemodynamic, metabolic, and fibrotic mechanisms, and potentially the additional use of finerenone. However, despite strong guideline recommendations, real-world adoption remains inadequate. Bridging this gap requires improved education, cost-effective strategies, and integrated post-AKI management to optimize renal and cardiovascular outcomes. Through ongoing research and interdisciplinary collaboration, optimizing renal and cardiovascular outcomes in patients with diabetic AKD remains achievable.

Supplementary Materials

Supplementary data are available at Kidney Research and Clinical Practice online (https://doi.org/10.23876/j.krcp.25.126).

j-krcp-25-126-Supplementary-materials.pdf

j-krcp-25-126-Supplementary-Figure-1.pdf

j-krcp-25-126-Supplementary-Figure-2.pdf

j-krcp-25-126-Supplementary-Figure-3.pdf

Notes

Conflicts of interest

All authors have no conflicts of interest to declare.

Funding

This work was supported by competitive grants from the Ministry of Science and Technology (MOST), Taiwan (106-2314-B-182A-064, 106-2314-B-400-015, 106-2321-B-182-002, 107-2321-B-182-004, 107-2314-B-002-026-MY3, 107-2314-B-182A-138, 108-2314-B-182A-027, 108-2314-B-002-058, 110-2314-B-002-124-MY3, 110-2314-B-002-241, 110-2314-B-002-239, 111-2314-B-182A-074-MY3); the National Science and Technology Council (NSTC), Taiwan (111-2314-B-002-046, 111-2314-B-002-058, 111-2314-B-002-232-MY3, 112-2314-B-002-029, 112-2314-B-002-040, 112-2628-B-002-026-MY3, 113-2314-B-002-294-MY3); the Chang Gung Medical Foundation (CGRPG-2Q0011, CGRPG-2Q0021, CMRPG-2G0361-3, CMRPG-2J0261, CMRPG-2K0091-3, CORPG-2N0141, CORPG-2P0101, CORPG-2P0191, CORPG-2P0231, CRRPG-2H0161-5); National Taiwan University Hospital (109-S4634, PC-1246, PC-1309, VN109-09, UN109-041, UN110-030, 111-FTN0011); the Ministry of Health and Welfare (PMRPG-2L0011, 110-TDU-B-212-124005); intramural funding from the National Health Research Institutes; and the Mrs. Hsiu-Chin Lee Kidney Research Fund.

Acknowledgments

We gratefully acknowledge the Second Core Laboratory, National Taiwan University Hospital, for its technical assistance. We also thank all NSARF (National Taiwan University Hospital Study Group of Acute Renal Failure) and CAKs (Taiwan Consortium for Acute Kidney Injury and Renal Diseases) participants, the National Health Research Institute and Harvard Statistics teams, and the Taiwan Clinical Trial Consortium (TCTC) staff for their invaluable support. A full list of CAKs collaborators is available at http://links.lww.com/MD/B298.

Data sharing statement

The data presented in this study are available from the corresponding author upon reasonable request.

Authors’ contributions

Conceptualization, Funding acquisition: HCP, VCW

Data curation: HCP

Formal analysis: HCP, CAW

Investigation, Methodology, Project administration, Resources, Validation: JYC, VCW

Software: CAW, JYC, VCW

Supervision: VCW

Visualization: CAW, JYC

Writing–original draft: HCP, CAW

Writing–review & editing: JYC, VCW

All authors read and approved the final manuscript.

Figure 1.

Evolution of pharmacologic treatments for DM and kidney disease.

The timeline illustrates key milestones in the development of pharmacologic therapies for DM and kidney disease. In 2001, the first clinical role of renin-angiotensin-aldosterone system (RAAS) blockers was established. The emergence of sodium-glucose cotransporter-2 inhibitors (SGLT2is) followed, with major cardiovascular and renal trials conducted between 2017 and 2022. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been under investigation since 2016, with ongoing trials evaluating their efficacy. In 2021, the introduction of finerenone, a nonsteroidal mineralocorticoid receptor antagonist, marked another advancement in renal and cardiovascular protection. Future directions involve the exploration of novel therapeutic approaches to further enhance DM and kidney disease management.

DM, diabetes mellitus.

Figure 2.

Efficacy of diabetes mellitus medications on CKD progression.

This figure compares the effectiveness of different diabetes mellitus-related medications in slowing CKD progression, expressed as hazard ratio (HR). Renin-angiotensin-aldosterone system (RAAS) blockers, despite being effective, have a relatively weaker impact on CKD progression (HR, 0.80–0.87). Sodium-glucose cotransporter-2 inhibitors (SGLT2is) demonstrate the strongest protective effect (HR, 0.56–0.72), providing benefits in CKD, heart failure, and reducing major adverse cardiovascular events (MACEs), mortality, and acute kidney injury (AKI) risk. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) effectively lower MACEs and mortality, particularly benefiting patients with atherosclerotic cardiovascular disease (ASCVD), with an HR of 0.78–0.85. Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, is beneficial for CKD and heart failure (HF) and offers modest MACE reduction and potential AKI benefits (HR, 0.82–0.87). These data highlight the relative efficacy of different classes of medications in CKD progression management.

CKD, chronic kidney disease.

Figure 3.

Pathophysiology of diabetic glomerular hyperfiltration and pharmacologic interventions.

This figure illustrates the mechanisms underlying diabetic glomerular hyperfiltration and the pharmacologic interventions targeting different pathways. Hyperglycemia and increased glomerular pressure lead to activation of the renin-angiotensin-aldosterone system (RAAS) and oxidative stress, contributing to hyperfiltration. Sodium-glucose cotransporter-2 inhibitors (SGLT2is) reduce proximal tubular sodium-glucose reabsorption, restoring tubuloglomerular feedback and mitigating afferent arteriole dilation. RAAS blockers counteract efferent arteriole constriction by promoting vasodilation, thereby reducing glomerular pressure. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) exert systemic anti-inflammatory and metabolic benefits. Finerenone, a nonsteroidal mineralocorticoid receptor (MR) antagonist, blocks MR-mediated fibrosis and inflammation, further mitigating kidney injury. These agents collectively modulate glomerular hemodynamics and systemic pathways to reduce chronic kidney disease progression in diabetic patients.

Figure 4.

Mechanistic pathways in diabetic AKD.

This figure illustrates the mechanistic pathways of key pharmacologic agents in the management of diabetic AKD. Renin-angiotensin-aldosterone system (RAAS) blockers inhibit angiotensin II-mediated efferent arteriole constriction, reducing intraglomerular pressure. Sodium-glucose cotransporter-2 inhibitors (SGLT2is) decrease proximal tubular glucose and sodium reabsorption, restoring tubuloglomerular feedback. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improve glycemic control, reduce weight, and provide anti-inflammatory and endothelial benefits. Finerenone, a nonsteroidal mineralocorticoid receptor antagonist (MRA), blocks aldosterone-driven fibrotic and inflammatory pathways. These mechanisms collectively contribute to nephroprotection in diabetic AKD.

AKD, acute kidney disease.

Figure 5.

Annual prescription trends of DM and hypertension medications (2012–2024) in diabetic patients with acute kidney disease.

(A) Annual prescription trends of DM medications from 2012 to 2024. The utilization of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been increasing, while that of metformin and sulfonylureas (SUs) has exhibited a declining trend. The prescription rates of thiazolidinediones (TZDs) and dipeptidyl peptidase-4 inhibitors (DPP-4is) have remained relatively stable, with a modest decline for DPP-4is. The use of angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs) has been increasing. (B) Summary of key prescription trends for DM medications between 2012 and 2024. The utilization of GLP-1 RAs and SGLT2is have markedly increased, while the use of metformin and SUs has shown a decreasing trend. These data were derived from the TriNetX global database, covering the period of 2012–2024.

DM, diabetes mellitus.

Table 1.

Clinical trials evaluating kidney outcomes in patients with diabetes mellitus

Trial (year)	Drug	Study population	Study period (year)	Primary outcome	Secondary outcomes
RAAS blockers (ACEi/ARB)
RENAAL (2001)	Losartan	T2DM + CKD (eGFR >30, UACR >300)	1996–2001	16% reduction in ESKD risk (HR, 0.84; p = 0.0023)	28% reduction in proteinuria (p < 0.001)
IDNT (2001)	Irbesartan	T2DM + CKD (eGFR >30, UACR >300)	1996–2001	20% reduction in CKD progression (HR, 0.80; p = 0.02)	33% reduction in proteinuria (p < 0.001)
SGLT2 inhibitors
CANVAS (2017)	Canagliflozin	T2DM + CV risk (no CKD)	2009–2017	14% reduction in MACE (HR, 0.86; p = 0.02)	40% reduction in albuminuria progression (p < 0.001)
DECLARE-TIMI 58 (2019)	Dapagliflozin	T2DM + CV risk (no CKD)	2013–2018	17% reduction in CV death or HF hospitalization (HR, 0.83; p = 0.005)	24% ↓ sustained ≥40% eGFR decline, ESKD or renal death (exploratory; HR, 0.76)
CREDENCE (2019)	Canagliflozin	T2DM + CKD (eGFR 30–90, UACR >300)	2014–2018	30% reduction in CKD progression (HR, 0.70; p < 0.001)	25% reduction in AKI (HR, 0.75; p = 0.01)
DAPA-CKD (2020)	Dapagliflozin	CKD (T2DM and non-T2DM, eGFR 25–75, UACR >200)	2017–2020	39% reduction in CKD progression (HR, 0.61; p < 0.001)	36% reduction in AKI (HR, 0.64; p = 0.003)
EMPA-KIDNEY (2022)	Empagliflozin	CKD (T2DM and non-T2DM, eGFR 20–45 or UACR >200)	2019–2022	28% reduction in CKD progression (HR, 0.72; p < 0.001)	14% reduction in hospitalization risk (HR, 0.86; p = 0.003)
GLP-1 receptor agonists
LEADER (2016)	Liraglutide	T2DM + CV risk (no CKD)	2010–2016	13% reduction in MACE (HR, 0.87; p < 0.001)	22% reduction in nephropathy progression (HR, 0.78; p < 0.001)
SUSTAIN-6 (2016)	Semaglutide	T2DM + CV risk (no CKD)	2013–2016	26% reduction in MACE (HR, 0.74; p = 0.02)	36% reduction in nephropathy progression (HR, 0.64; p = 0.002)
AWARD-7 (2018)	Dulaglutide	T2DM + CKD (eGFR 15–60)	2014–2018	Slower eGFR decline (p = 0.0004) vs. insulin	No significant CV outcome difference
REWIND (2019)	Dulaglutide	T2DM + CV risk (no CKD)	2011–2019	12% reduction in MACE (HR, 0.88; p = 0.026)	15% reduction in composite renal endpoint (HR, 0.85; p = 0.02)
FLOW (ongoing, 2024)	Semaglutide	T2DM + CKD (eGFR 25–75, UACR 200–5,000)	2019–2024	Time to composite kidney outcome (ESRD, eGFR decline ≥50%, renal or CV death)	Pending AKI outcomes
Finerenone (selective MRA)
FIDELIO-DKD (2020)	Finerenone	T2DM + CKD (eGFR 25–75, UACR 30–5,000)	2015–2020	18% reduction in CKD progression (HR, 0.82; p < 0.001)	14% reduction in CV events (HR, 0.86; p = 0.03)
FIGARO-DKD (2021)	Finerenone	T2DM + CKD (eGFR ≥ 25, albuminuria)	2015–2021	13% reduction in CV death or HF hospitalization (HR, 0.87; p = 0.03)	23% reduction in albuminuria progression (p < 0.001)
Combined therapy
CONFIDENCE (2025)	Finerenone + empagliflozin	T2DM + CKD (eGFR 30–90, UACR 100–5,000) already on ACEi/ARB	2022–2024	29% greater UACR reduction vs. finerenone; 32% vs. empagliflozin at 6 months	No unexpected ↑AKI, hyper-kalaemia <2% discontinuation

ACEi, angiotensin-converting enzyme inhibitor; AKI, acute kidney injury; ARB, angiotensin II receptor blocker; CKD, chronic kidney disease; CV, cardiovascular; ESKD, end-stage kidney disease; eGFR, estimated glomerular filtration rate (mL/min/1.73 m²); GLP-1, glucagon-like peptide-1; HF, heart failure; HR, hazard ratio; MACE, major adverse cardiovascular events; MRA, mineralocorticoid receptor antagonist; RAAS, renin-angiotensin-aldosterone system; SGLT2, sodium-glucose cotransporter-2; T2DM, type 2 diabetes mellitus; UACR, urinary albumin-to-creatinine ratio (mg/g).

Table 2.

Key studies focusing on pharmacologic management in diabetic AKD

Study (year)	Design and data source	Population	Intervention vs. Comparator	Primary kidney end-point^a	Key findings (adjusted)	Median follow-up (yr)
Menne et al. [31] (2019)	Meta-analysis (46 RCTs and cohorts)	34,879 diabetic patients; AKD subgroup	Any SGLT2i vs. placebo/ other GLD	AKI/AKI recurrence	↓ AKI events by 36% (OR, 0.64); benefit preserved in AKD subgroup	Up to 4
Su et al. [8] (2023)	Systematic review and meta-analysis (12 cohorts)	>150,000 AKD	NA (observational synthesis)	CKD progression, mortality	AKD associated with 2.5-fold ↑ risk of CKD; emphasizes need for targeted therapy	NA
Pan et al. [19] (2024)	Multicenter real-world cohort, TriNetX database	165,860 T2DM-AKD	GLP-1 RA users vs. non-users	MAKE	↓ MAKE by 27% (aHR, 0.73)	2.3
Pan et al. [19] (2024)	Multicenter real-world cohort, TriNetX database	165,860 T2DM-AKD	GLP-1 RA users vs. non-users	MAKE	↓ All-cause mortality by 43% (aHR, 0.57)	2.3
Pan et al. [18] (2024)	Multicenter real-world cohort, TriNetX database	103,180 T2DM-AKD	SGLT2i users vs. non-users	MAKE	↓ MAKE by 35% (aHR, 0.65); ↓ mortality by 29% (aHR, 0.71)	2.0
Murphy et al. [35] (2024)	Veterans’ Health Administration cohort	13,860 T2DM post AKI	Post-AKI SGLT2i vs. standard care	eGFR <30 or ≥40% decline	↓ CKD progression by 20% (HR, 0.80); neutral for hyperkalemia	1.9
Chang et al. [51] (2025)	Multicenter hospital registry	9,812 T2DM-AKD	TZD users vs. non-users	MAKE	↓ MAKE by 22% (aHR, 0.78); neutral for HF hospital	2.0
Liao et al. [50] (2025)	National Health Insurance Research Database (Taiwan)	41,220 T2DM-AKD	DPP-4i users vs. non-users	MAKE	↓ MAKE by 18% (aHR, 0.82); ↓ mortality 15%	2.6

aHR, adjusted hazard ratio; AKD, acute kidney disease; AKI, acute kidney injury; CKD, chronic kidney disease; DPP-4i, dipeptidyl-peptidase-4 inhibitor; eGFR, estimated glomerular filtration rate; GLD, glucose-lowering drug; GLP-1 RA, glucagon-like peptide-1 receptor agonist; HF, heart failure; HR, hazard ratio; MAKE, major adverse kidney events; NA, not applicable; OR, odds ratio; RCT, randomized controlled trial; SGLT2i, sodium-glucose cotransporter-2 inhibitor; T2DM, type 2 diabetes mellitus; TZD, thiazolidinedione.

^aPrimary kidney endpoints varied by study.

References

1. Thomas MC, Cooper ME, Zimmet P. Changing epidemiology of type 2 diabetes mellitus and associated chronic kidney disease. Nat Rev Nephrol 2016;12:73–81.

2. Alicic RZ, Rooney MT, Tuttle KR. Diabetic kidney disease: challenges, progress, and possibilities. Clin J Am Soc Nephrol 2017;12:2032–2045.

3. Svensson AM, McGuire DK, Abrahamsson P, Dellborg M. Association between hyper- and hypoglycaemia and 2 year all-cause mortality risk in diabetic patients with acute coronary events. Eur Heart J 2005;26:1255–1261.

4. Hsu CY, Ordoñez JD, Chertow GM, Fan D, McCulloch CE, Go AS. The risk of acute renal failure in patients with chronic kidney disease. Kidney Int 2008;74:101–107.

5. Coca SG, Singanamala S, Parikh CR. Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis. Kidney Int 2012;81:442–448.

6. Forni LG, Darmon M, Ostermann M, et al. Renal recovery after acute kidney injury. Intensive Care Med 2017;43:855–866.

7. Chawla LS, Bellomo R, Bihorac A, et al. Acute kidney disease and renal recovery: consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup. Nat Rev Nephrol 2017;13:241–257.

8. Su CC, Chen JY, Chen SY, et al. Outcomes associated with acute kidney disease: a systematic review and meta-analysis. EClinicalMedicine 2023;55:101760.

9. Kaur A, Sharma GS, Kumbala DR. Acute kidney injury in diabetic patients: a narrative review. Medicine (Baltimore) 2023;102:e33888.

10. Chaudhary K, Phadke G, Nistala R, Weidmeyer CE, McFarlane SI, Whaley-Connell A. The emerging role of biomarkers in diabetic and hypertensive chronic kidney disease. Curr Diab Rep 2010;10:37–42.

11. Pitt B, Filippatos G, Agarwal R, et al. Cardiovascular events with finerenone in kidney disease and type 2 diabetes. N Engl J Med 2021;385:2252–2263.

12. Kung CW, Chou YH. Acute kidney disease: an overview of the epidemiology, pathophysiology, and management. Kidney Res Clin Pract 2023;42:686–699.

13. Giugliano D, Esposito K, De Nicola L. Management of acute kidney disease in type 2 diabetes: the potential role of GLP-1 RAs and SGLT2-Is. J Nephrol 2024;37:2347–2350.

14. Topaloglu U, Palchuk MB. Using a federated network of real-world data to optimize clinical trials operations. JCO Clin Cancer Inform 2018;2:1–10.

15. King A, Tan X, Dhopeshwarkar N, et al. Recent trends in GLP-1 RA and SGLT2i use among people with type 2 diabetes and atherosclerotic cardiovascular disease in the USA. BMJ Open Diabetes Res Care 2024;12:e004431.

16. Tuttle KR, Bakris GL, Bilous RW, et al. Diabetic kidney disease: a report from an ADA Consensus Conference. Am J Kidney Dis 2014;64:510–533.

17. Ruiz-Ortega M, Rayego-Mateos S, Lamas S, Ortiz A, Rodrigues-Diez RR. Targeting the progression of chronic kidney disease. Nat Rev Nephrol 2020;16:269–288.

18. Pan HC, Chen JY, Chen HY, et al. Sodium-glucose cotransport protein 2 inhibitors in patients with type 2 diabetes and acute kidney disease. JAMA Netw Open 2024;7:e2350050.

19. Pan HC, Chen JY, Chen HY, et al. GLP-1 receptor agonists’ impact on cardio-renal outcomes and mortality in T2D with acute kidney disease. Nat Commun 2024;15:5912.

20. Himmelfarb J, Ikizler TA. Acute kidney injury: changing lexicography, definitions, and epidemiology. Kidney Int 2007;71:971–976.

21. Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001;345:851–860.

22. Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001;345:861–869.

23. Parving HH, Lehnert H, Bröchner-Mortensen J, Gomis R, Andersen S, Arner P. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 2001;345:870–878.

24. Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int 2022;102:S1–S127.

25. ElSayed NA, Aleppo G, Aroda VR, et al. 11. Chronic kidney disease and risk management: standards of care in diabetes-2023. Diabetes Care 2023;46:S191–S202.

26. Chen JJ, Lee CC, Yen CL, et al. Impact of different angiotensin-converting enzyme inhibitors or angiotensin receptor blocker resumption timing on post acute kidney injury outcomes. Kidney Int Rep 2024;9:3290–3300.

27. Perkovic V, de Zeeuw D, Mahaffey KW, et al. Canagliflozin and renal outcomes in type 2 diabetes: results from the CANVAS Program randomised clinical trials. Lancet Diabetes Endocrinol 2018;6:691–704.

28. Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2019;380:347–357.

29. Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 2019;380:2295–2306.

30. Cherney DZI, Verma S. DAPA-CKD: the beginning of a new era in renal protection. JACC Basic Transl Sci 2021;6:74–77.

31. Menne J, Dumann E, Haller H, Schmidt BM. Acute kidney injury and adverse renal events in patients receiving SGLT2-inhibitors: a systematic review and meta-analysis. PLoS Med 2019;16:e1002983.

32. Heerspink HJ, Stefánsson BV, Correa-Rotter R, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med 2020;383:1436–1446.

33. Fernández-Fernandez B, Sarafidis P, Soler MJ, Ortiz A. EMPA-KIDNEY: expanding the range of kidney protection by SGLT2 inhibitors. Clin Kidney J 2023;16:1187–1198.

34. Alicic RZ, Neumiller JJ, Tuttle KR. Combination therapy: an upcoming paradigm to improve kidney and cardiovascular outcomes in chronic kidney disease. Nephrol Dial Transplant 2025;40:i3–i17.

35. Murphy DP, Wolfson J, Reule S, Johansen KL, Ishani A, Drawz PE. A cohort study of sodium-glucose cotransporter-2 inhibitors after acute kidney injury among Veterans with diabetic kidney disease. Kidney Int 2024;106:126–135.

36. Yau K, Dharia A, Alrowiyti I, Cherney DZ. Prescribing SGLT2 inhibitors in patients with CKD: expanding indications and practical considerations. Kidney Int Rep 2022;7:1463–1476.

37. Müller TD, Finan B, Bloom SR, et al. Glucagon-like peptide 1 (GLP-1). Mol Metab 2019;30:72–130.

38. Tommerdahl KL, Kendrick J, Bjornstad P. The role of glucagon-like peptide 1 (GLP-1) receptor agonists in the prevention and treatment of diabetic kidney disease: insights from the AMPLITUDE-O Trial. Clin J Am Soc Nephrol 2022;17:905–907.

39. Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2016;375:311–322.

40. Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 2016;375:1834–1844.

41. Vitale M, Haxhi J, Cirrito T, Pugliese G. Renal protection with glucagon-like peptide-1 receptor agonists. Curr Opin Pharmacol 2020;54:91–101.

42. Diz-Chaves Y, Mastoor Z, Spuch C, González-Matías LC, Mallo F. Anti-inflammatory effects of GLP-1 receptor activation in the brain in neurodegenerative diseases. Int J Mol Sci 2022;23:9583.

43. Marx N, Husain M, Lehrke M, Verma S, Sattar N. GLP-1 receptor agonists for the reduction of atherosclerotic cardiovascular risk in patients with type 2 diabetes. Circulation 2022;146:1882–1894.

44. Pandey S, Mangmool S, Parichatikanond W. Multifaceted roles of GLP-1 and its analogs: a review on molecular mechanisms with a cardiotherapeutic perspective. Pharmaceuticals (Basel) 2023;16:836.

45. Lin Y, Wang TH, Tsai ML, et al. The cardiovascular and renal effects of glucagon-like peptide 1 receptor agonists in patients with advanced diabetic kidney disease. Cardiovasc Diabetol 2023;22:60.

46. Kalra S. Follow the LEADER-liraglutide effect and action in diabetes: evaluation of cardiovascular outcome results trial. Diabetes Ther 2016;7:601–609.

47. Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet 2019;394:121–130.

48. Gragnano F, De Sio V, Calabrò P. FLOW trial stopped early due to evidence of renal protection with semaglutide. Eur Heart J Cardiovasc Pharmacother 2024;10:7–9.

49. Chao CT, Wang J, Wu HY, Chien KL, Hung KY. Dipeptidyl peptidase 4 inhibitor use is associated with a lower risk of incident acute kidney injury in patients with diabetes. Oncotarget 2017;8:53028–53040.

50. Liao HW, Cheng CY, Chen HY, et al. Dipeptidyl peptidase 4 inhibitors reduce the risk of adverse outcomes after acute kidney injury in diabetic patients. Clin Kidney J 2025;18:sfae385.

51. Chang LY, Liao HW, Chen JY, Wu VC. Enhanced outcomes in type 2 diabetes patients with acute kidney disease through thiazolidinedione. J Clin Endocrinol Metab 2025;110:2205–2214.

52. Bakris GL, Agarwal R, Anker SD, et al. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med 2020;383:2219–2229.

53. Rossing P, Agarwal R, Anker SD, et al. Finerenone in patients across the spectrum of chronic kidney disease and type 2 diabetes by glucagon-like peptide-1 receptor agonist use. Diabetes Obes Metab 2023;25:407–416.

54. Rana A, Sahu JK. Finerenone: a novel drug discovery for the treatment of chronic kidney disease. Curr Drug Discov Technol 2024;21:e290124226291.

55. Agarwal R, Anker SD, Bakris G, et al. Investigating new treatment opportunities for patients with chronic kidney disease in type 2 diabetes: the role of finerenone. Nephrol Dial Transplant 2022;37:1014–1023.

56. Kovesdy CP. Management of hyperkalaemia in chronic kidney disease. Nat Rev Nephrol 2014;10:653–662.

57. Navarro-González JF, Mora-Fernández C, Muros de Fuentes M, et al. Effect of pentoxifylline on renal function and urinary albumin excretion in patients with diabetic kidney disease: the PREDIAN trial. J Am Soc Nephrol 2015;26:220–229.

58. Heerspink HJL, Parving HH, Andress DL, et al. Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial. Lancet 2019;393:1937–1947.

59. Scheen AJ. Dual GIP/GLP-1 receptor agonists: new advances for treating type-2 diabetes. Ann Endocrinol (Paris) 2023;84:316–321.

60. Bantounou MA, Sardellis P, Thuemmler R, et al. Effect of the dual sodium-glucose co-transporter-1 and -2 inhibitor sotagliflozin on renal outcomes in type 1 diabetes and type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Diabetes Obes Metab 2024;26:710–720.

61. Tuttle KR, Lakshmanan MC, Rayner B, et al. Dulaglutide versus insulin glargine in patients with type 2 diabetes and moderate-to-severe chronic kidney disease (AWARD-7): a multicentre, open-label, randomised trial. Lancet Diabetes Endocrinol 2018;6:605–617.

62. Wu VC, Chen JY, Lin YH, Wang CY, Lai CC. Assessing the cardiovascular events and clinical outcomes of COVID-19 on patients with primary aldosteronism. J Microbiol Immunol Infect 2023;56:1158–1168.

63. Eberly LA, Yang L, Essien UR, et al. Racial, ethnic, and socioeconomic inequities in glucagon-like peptide-1 receptor agonist use among patients with diabetes in the US. JAMA Health Forum 2021;2:e214182.

64. Eberly LA, Yang L, Eneanya ND, et al. Association of race/ethnicity, gender, and socioeconomic status with sodium-glucose cotransporter 2 inhibitor use among patients with diabetes in the US. JAMA Netw Open 2021;4:e216139.

65. Mittman BG, Le P, Payne JY, Ayers G, Rothberg MB. Sociodemographic disparities in GLP-1RA and SGLT2i use among US adults with type 2 diabetes: NHANES 2005-March 2020. Curr Med Res Opin 2024;40:377–383.

66. Neuen BL, Tuttle KR, Bakris G, Vaduganathan M. Reframing chronicity with urgency in chronic kidney disease management. Clin J Am Soc Nephrol 2024;19:1209–1211.

67. Inker LA, Grams ME, Guðmundsdóttir H, et al. Clinical trial considerations in developing treatments for early stages of common, chronic kidney diseases: a scientific workshop cosponsored by the National Kidney Foundation and the US Food and Drug Administration. Am J Kidney Dis 2022;80:513–526.

68. Hirsch JS, Danna SC, Desai N, et al. Optimizing care delivery in patients with chronic kidney disease in the United States: proceedings of a multidisciplinary roundtable discussion and literature review. J Clin Med 2024;13:1206.

69. DeFronzo RA. Combination therapy with GLP-1 receptor agonist and SGLT2 inhibitor. Diabetes Obes Metab 2017;19:1353–1362.

70. Pan HC, Chen HY, Teng NC, et al. Recovery dynamics and prognosis after dialysis for acute kidney injury. JAMA Netw Open 2024;7:e240351.

71. Ostermann M, Zarbock A, Goldstein S, et al. Recommendations on acute kidney injury biomarkers from the Acute Disease Quality Initiative Consensus Conference: a consensus statement. JAMA Netw Open 2020;3:e2019209.

72. Koyner JL, Chawla LS, Bihorac A, et al. Performance of a standardized clinical assay for urinary C-C motif chemokine ligand 14 (CCL14) for persistent severe acute kidney injury. Kidney360 2022;3:1158–1168.