Pranav Garimella, MBBS, MPH, is chief medical officer of the American Kidney Fund.

Pranav Garimella, MBBS, MPH

Recent trial data have broadened the case for GLP-1 receptor agonists in kidney disease, pointing to a possible role beyond the drug class's original diabetes indication. 

Translating that evidence into everyday practice hasn't necessarily kept pace, says Pranav Garimella, MD, chief medical officer at the American Kidney Fund, who points to cost, clinician unfamiliarity, and gaps in patient identification as ongoing barriers to access.

GLP-1s Move Beyond Diabetes as Core Kidney-Protective Therapy

What Does the Evidence Show for GLP-1 Receptor Agonists in Kidney Disease?

 In more than 3,500 participants with type 2 diabetes and CKD, semaglutide cut kidney-specific outcomes by 21% and slowed annual eGFR decline versus placebo.[1]

 A 22% reduction in the composite kidney endpoint among non-diabetic participants with cardiovascular disease and obesity.[1]

 Semaglutide cut a marker of kidney protein loss by roughly half over 24 weeks in people with overweight or obesity.[1]

"GLP-1 [receptor agonists] no longer belong just in the treatment of diabetes," Garimella has said, describing them as integral to preventing both heart failure and kidney disease progression. He frames them as complementary to RAS inhibitors, SGLT2 inhibitors, and nonsteroidal mineralocorticoid receptor antagonists (MRAs)—and, in select patients without significant proteinuria who have obesity, sleep apnea, or elevated heart failure risk, as a potential alternative to nonsteroidal MRAs. His approach broadly tracks the 2024 KDIGO CKD guideline, which pairs RAS/SGLT2 inhibitor therapy with emerging support for nonsteroidal MRAs and GLP-1 receptor agonists.

What Barriers Limit GLP-1 Receptor Agonist Use in Kidney Disease?

Garimella pointed to four first-line barriers still limiting access:

 "The ability to get these for all patients across all payers remains a challenge," he told HCPLive, noting that coverage criteria can differ by indication—diabetic kidney disease, heart failure, or obesity—so documenting the specific indication at prescribing matters.

 GLP-1s were historically viewed as diabetes-only drugs prescribed mainly by primary care and endocrinology. "Now we know that these medications can prevent kidney disease progression [and] heart disease progression, and so cardiologists and nephrologists are using them more often," Garimella said.

 Clinicians need to correctly flag patients with CKD alongside diabetes, obesity, or heart failure—including as a complementary option for patients who need to come off a drug class that's raising their potassium levels.

 Not every patient tolerates the maximal dose. "We may need to back off to the best-tolerated dose, or even take patients off of it," Garimella said, adding that setting this expectation early keeps patients on therapy long enough to see benefit.

How Should Clinicians Discuss Weight Loss With GLP-1 Patients?

Garimella pushes back on the stigma that can surround weight-loss discussions in clinic. Central adiposity drives cardiac, kidney, and metabolic dysfunction, he said, so he frames GLP-1 therapy around long-term outcomes rather than the scale: "I show patients that this is doing more than just changing the numbers on the scale... The overarching goal is to connect that medication with the outcomes—not just the weight loss in the short term, but really those long-term outcomes that we're trying to prevent."

What's Next for GLP-1 Receptor Agonists in Kidney Disease?

GLP-1 receptor agonists are approaching standard therapy in the CKD toolkit, Garimella said, with wider use across disease states and combination therapies likely as data accumulates and FDA indications expand. Open questions remain: which patients benefit most versus those where risk outweighs benefit, how long therapy should continue, and how to manage patients who regain weight after stopping. Evidence is also thin in medically complex populations. "We don't know what the true benefits of GLP-1 receptor agonists are in patients who've received kidney transplants," he said, noting many still have diabetes, proteinuria, obesity, heart failure, or sleep apnea. "That is an area that is ripe for research still in the GLP-1 space."

: Garimella reports no relevant disclosures.

Cooper ME, van Raalte DH. GLP-1 agonists in the treatment of chronic kidney disease in type 2 diabetes and obesity. J Clin Invest. 2025;135(21):e194749. doi:10.1172/JCI194749

GLP-1 Receptor Agonists Reshape CKD Treatment Sequencing, With Pranav Garimella, MD. HCPLive. Published July 30, 2026. Accessed July 31, 2026. 

https://www.hcplive.com/view/glp-1-receptor-agonists-reshape-ckd-treatment-sequencing-with-pranav-garimella-md

Videos

Pranav Garimella, MD, on how nephrologists and cardiologists can apply GLP-1 receptor agonist evidence to CKD treatment decisions.

a nephrologist and the Director of Acute Dialysis Services and the Polycystic Kidney Disease (PKD) Center of Excellence at UC San Diego Health and Chief Medical Officer of the American Kidney Fund

a nephrologist at Florida Kidney Physicians and Director of the FKP Glomerulonephritis Center of Excellence in Boca Raton, Florida.

an assistant Professor in the Division of Nephrology at the University of California, San Francisco (UCSF) and the medical director of the nephrology-based kidney stone prevention center at UCSF.

 care has entered a new era, but what does this mean for nephrologists managing patients today?

After decades with few disease-modifying options beyond blood pressure control and renin-angiotensin system blockade, clinicians now have multiple therapies targeting different pathways involved in kidney disease progression. The challenge in 2026 is no longer simply whether effective treatments exist, but how best to identify patients who need them and implement them in practice.

“I think a lot of nephrologists have been sort of swayed to sleep by 20 to 25 years of really no groundbreaking developments in how we manage chronic kidney disease,” said Marc Richards, MD. “We've gone from that to now potentially 3 new classes of agents on the market, and potentially more, that can delay progression of kidney disease in our patients and prevent progression to end-stage kidney disease.”

Historically, CKD care focused largely on controlling blood pressure, managing diabetes, and slowing kidney damage with renin-angiotensin system (RAS) blockade. However, the treatment landscape has expanded with therapies targeting multiple pathways involved in kidney disease progression, proteinuria, cardiovascular risk, and metabolic dysfunction.

“The modern management of CKD relies on the integration of foundational and newer nephroprotective therapies,” Richards said.

From Supportive Care to Disease-Modifying Therapy

The expanding CKD treatment landscape reflects a shift toward evidence-based therapies that target specific mechanisms involved in disease progression.

CKD Treatment Toolbox: Key Kidney-Protective Therapies in 2026


Longstanding foundational therapy, particularly for patients with proteinuric CKD and hypertension.


Reduce kidney disease progression and cardiovascular risk and are now considered foundational therapy across broad CKD populations.

Nonsteroidal mineralocorticoid receptor antagonists (MRAs)


Target aldosterone-related pathways and are particularly used in patients with proteinuric CKD, with evidence expanding beyond diabetic kidney disease.

 semaglutide, liraglutide, tirzepatide (dual GIP/GLP-1 agonist)



Provide cardiovascular and metabolic benefits and are increasingly incorporated into cardio-kidney-metabolic risk reduction strategies.

“Now our data is exploding,” Richards said. “We have evidence with ACE inhibitors and ARBs for proteinuric kidney disease states. We have SGLT2 inhibitors becoming a standard of care. We now have the nonsteroidal MRAs that are on the market, both in diabetic and—now we're learning—non-diabetic kidney disease, that could benefit our patients. Data is emerging with GLP-1 agonists.”

RAS inhibitors, including angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), remain foundational therapies for patients with CKD, particularly those with proteinuric disease.

“RAS inhibitors such as ACE inhibitors or angiotensin receptor blockers have a long and safe history of being the first-line therapy for treatment of diabetes and kidney disease, and even high blood pressure,” Richards said. “That remains unchanged.”

Over the past decade, sodium-glucose cotransporter-2 (SGLT2) inhibitors have become another cornerstone of CKD management, with evidence supporting kidney and cardiovascular benefits across broad patient populations.

“Over the last decade, we've now added SGLT2 inhibitors that have the added benefit of preventing heart failure and cardiovascular disease, and even progression of kidney disease,” Richards said. “They now form the cornerstone of treating all chronic kidney disease.”

Nonsteroidal mineralocorticoid receptor antagonists (MRAs), including finerenone, have further expanded treatment options, particularly among patients with proteinuric kidney disease.

“The nonsteroidal mineralocorticoid receptor antagonists are added on, especially in people who have proteinuric kidney disease,” Richards said.

The Cardio-Kidney-Metabolic Connection Expands CKD Care

Another major shift in CKD management has been the recognition that kidney disease cannot be treated independently from cardiovascular and metabolic health.

Glucagon-like peptide-1 (GLP-1) receptor agonists, once primarily viewed as glucose-lowering therapies, are increasingly being incorporated into CKD care because of their cardiovascular and metabolic benefits.

“Over the last few years, the biggest shift is that GLP-1 agonists have gone from being viewed as just glucose-lowering drugs to drugs that now treat the broader cardio, kidney, metabolic syndrome,” said Pranav Garimella, MD.

“That’s really critical because we’ve come to realize that we can’t treat these organs in silos anymore,” he continued. “The kidneys, the heart, and the metabolic system are intricately tied together.”

Garimella said GLP-1 receptor agonists should now be considered part of the broader CKD treatment toolkit.

“GLP-1s no longer belong just in the treatment of diabetes, but they are integral to preventing heart failure and kidney disease progression,” he said.

However, he emphasized that GLP-1 receptor agonists should be viewed as complementary to existing kidney-protective therapies rather than replacements for foundational treatments.

For example, a patient with CKD, hypertension, diabetes, and proteinuria may benefit from RAS blockade followed by an SGLT2 inhibitor and potentially a nonsteroidal MRA. In contrast, a patient with CKD, obesity, sleep apnea, and increased cardiovascular risk may derive additional benefit from GLP-1 receptor agonist therapy.

“The GLP-1s are seen now as complementary,” Garimella said.

Emerging Targets: The Role of Aldosterone in CKD

Beyond currently established therapies, researchers continue to investigate additional pathways involved in CKD progression, including aldosterone signaling.

Richards said aldosterone has become an increasingly important therapeutic target because of its effects on cardiovascular and kidney health.

“Now we have a focus on targeting aldosterone as a way of trying to help limit stress on the kidney or limit stress on the heart,” Richards said. “With older drugs like spironolactone and eplerenone, newer medicines like finerenone, and even looking into novel agents like aldosterone synthase inhibitors to even prevent aldosterone from being released in the first place.”

Aldosterone contributes to processes including hypertension, electrolyte abnormalities, and organ stress over time, making it an important pathway of interest for future CKD therapies.

Beyond eGFR: Moving Toward Personalized CKD Management

While the expansion of treatment options has changed CKD care, experts emphasized that effective management still depends on understanding the individual patient and their underlying disease drivers.

Matthew Breeggemann, MD, said evaluating CKD requires looking beyond a single kidney function measurement.

“I think for me it’s really helpful to get a really detailed history when you first meet them, and this would include the patient and the patient’s family, and just trying to fit those pieces of the puzzle together,” Breeggemann said.

A patient with diabetes may have straightforward diabetic kidney disease, he explained, while another patient may have diabetes along with hypertension, kidney stones, or other contributors that require a different management approach.

When assessing CKD severity, Breeggemann said clinicians should focus on trends over time rather than isolated values.

“I really want to see the trend,” he said.

He explained that one patient may have an eGFR of 50 mL/min/1.73 m² that remains stable for years, while another patient with the same baseline value may experience a rapid decline over a short period of time.

Beyond laboratory values, Breeggemann highlighted the growing role of precision approaches, including genetic testing and kidney biopsy.

“Our center also does perform a substantial amount of genetic testing for kidney disorders, and these findings have definitely led to a change in how we approach and manage some patients with CKD,” he said.

He also emphasized the importance of incorporating patient preferences into treatment decisions.

“We want to ensure that patients understand why we recommend what we recommend, and importantly, lastly, take into account the patient’s priorities for their own care to really make sure we’re working with them and honoring their treatment preferences,” Breeggemann said.

Recognizing AKI as a Driver of Long-Term Kidney Health

Another shift in kidney care has been the recognition that acute kidney injury (AKI) may have long-term consequences for kidney health.

Breeggemann said AKI should not be viewed simply as a temporary event that resolves once creatinine improves.

“An episode of acute kidney injury should not really be viewed as a simple transient condition, even when perhaps labs may improve and then thus suggest so,” he said.

AKI episodes can contribute to structural changes in the kidney, inflammation, cellular injury, and vascular damage, potentially increasing the risk of future CKD development or progression.

“It would be a mistake to just say, okay, great, nothing, no additional evaluation or monitoring is needed,” Breeggemann said.

He added that many patients who experience AKI may not receive consistent follow-up after discharge, despite their increased risk.

The Remaining Challenge: Translating Evidence Into Practice

Despite major advances in CKD treatment, experts said a significant challenge remains: ensuring that evidence-based therapies reach the patients who could benefit.

Breeggemann noted that implementation of new therapies often takes years.

“It takes approximately 17 years following a new medical intervention or therapy to be routinely used in clinical practice,” he said.

Barriers include delayed diagnosis, delayed referral to nephrology, insurance challenges, clinician familiarity, and coordination between specialties.

Garimella also highlighted clinician familiarity as an ongoing challenge as GLP-1 receptor agonists expand beyond diabetes care.

“Historically we viewed these medications as being exclusively diabetic medications,” he said. “However, now we know that these medications can prevent kidney disease progression; they can prevent heart disease progression.”

Looking ahead, Richards said continued research will be essential to further improve CKD care.

“Potentially the next great treatment is out there, but we just need to get patients into clinical trials to see if we can establish new standards of care to optimize management of our patients,” he said.

Editor’s Note: Richards reports no relevant disclosures; Garimella has relevant disclosures with Otsuka and the PKD Foundation.

Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group.
Kidney Disease: Improving Global Outcomes (KDIGO) 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. 

 2024;105(4S):S117-S314. doi:10.1016/j.kint.2023.10.018

Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al.
Dapagliflozin in patients with chronic kidney disease. 

 2020;383(15):1436-1446. doi:10.1056/NEJMoa2024816 

The EMPA-KIDNEY Collaborative Group.
Empagliflozin in patients with chronic kidney disease. 

 2023;388(2):117-127. doi:10.1056/NEJMoa2204233 

Bakris GL, Agarwal R, Anker SD, et al.
Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. 

 2020;383(23):2219-2229. doi:10.1056/NEJMoa2025845 

Perkovic V, Tuttle KR, Rossing P, et al.
Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes. 

 2024;391:109-121. doi:10.1056/NEJMoa2403347 

Agarwal R, Green JB, Heerspink HJL, et al.
Finerenone with empagliflozin in chronic kidney disease and type 2 diabetes. 

 2025;393:533-543. doi:10.1056/NEJMoa2410659

Articles

Chronic kidney disease management has shifted from supportive measures toward multi-pathway, disease-modifying therapy. RAS blockade remains foundational for proteinuric disease, with SGLT2 inhibitors now broadly nephroprotective and cardioprotective across CKD populations. Nonsteroidal MRAs such as finerenone add incremental benefit, particularly in proteinuria, while GLP-1 receptor agonists are increasingly positioned within cardio-kidney-metabolic risk reduction as complementary agents. Optimal care emphasizes individualized phenotyping beyond single eGFR values, attention to AKI as a progression driver, and faster implementation of evidence into routine practice.

Nephrology experts discuss how CKD care has evolved in 2026, including SGLT2 inhibitors, finerenone, GLP-1 receptor agonists, and personalized treatment.

Where Are We Now? Treating Chronic Kidney Disease in 2026

management continues to evolve beyond glucose control alone, GLP-1 receptor agonists are increasingly being incorporated into treatment strategies aimed at reducing both kidney and cardiovascular risk.

According to Pranav Garimella, MD, of the American Kidney Fund, the drug class is no longer viewed solely as a diabetes therapy but as an important component of comprehensive CKD management alongside renin-angiotensin system (RAS) inhibitors, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and nonsteroidal mineralocorticoid receptor antagonists (MRAs).

GLP-1 Receptor Agonists Reshape CKD Treatment Sequencing, With Pranav Garimella, MD

"GLP-1 [receptor agonists] no longer belong just in the treatment of diabetes, but they are integral to preventing heart failure and kidney disease progression," Garimella said.

GLP-1 Receptor Agonists and the Cardiovascular-Kidney-Metabolic Model

Garimella described a shift away from treating the heart, kidneys, and metabolic system as separate entities, instead emphasizing their overlapping risk factors and interconnected disease pathways.

"We're no longer thinking about these as isolated organ systems," Garimella said. "They're all connected."

This perspective aligns with the growing emphasis on cardiovascular-kidney-metabolic (CKM) syndrome in contemporary cardiovascular and kidney care.

Supporting this evolving treatment paradigm, the FLOW trial demonstrated semaglutide reduced the composite risk of major kidney outcomes, cardiovascular events, and death from any cause by 24% compared with placebo among patients with type 2 diabetes and CKD. Secondary analyses also showed an 18% reduction in major adverse cardiovascular events and a 20% reduction in all-cause mortality, reinforcing the cardiorenal benefits of GLP-1 receptor agonists beyond glycemic control alone.

Identifying Patients Most Likely to Benefit

According to Garimella, patients with type 2 diabetes, obesity, albuminuria, and elevated cardiovascular risk are among those most likely to benefit from GLP-1 receptor agonist therapy because of the class’s established cardiovascular and kidney protective effects.

However, he emphasized that careful patient selection remains essential.

"If you have patients who have a history of diabetic gastroparesis and maybe cannot stay hydrated, GLP-1 receptor agonists may not be the best drugs as first-line therapy," Garimella said.

He noted that gastrointestinal adverse effects, including appetite suppression, nausea, vomiting, and dehydration, may increase the risk of acute kidney injury in susceptible patients. While these individuals may still benefit from treatment, he said clinicians should weigh the potential benefits against tolerability and safety on a case-by-case basis.

Sequencing GLP-1 Therapy in Contemporary CKD Care

Asked where GLP-1 receptor agonists fit within current CKD management, Garimella described an approach that begins with RAS inhibition for patients with diabetes, hypertension, and albuminuria, followed by SGLT2 inhibitors as foundational kidney-protective therapy. For patients with persistent proteinuria despite optimized treatment, nonsteroidal MRAs may then be added.

Garimella described GLP-1 receptor agonists as complementary to these therapies and, in selected patients, a potential alternative to nonsteroidal MRAs—particularly among individuals with obesity, obstructive sleep apnea, or elevated heart failure risk who do not have substantial proteinuria.

His approach generally aligns with the 2024 KDIGO Clinical Practice Guideline for CKD, which recommends RAS inhibition and SGLT2 inhibitor therapy for appropriate patients with CKD while incorporating emerging evidence supporting nonsteroidal MRAs and GLP-1 receptor agonists for kidney protection.

Perkovic V, Tuttle KR, Rossing P, et al. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes. 

 2024;391(2):109-121. doi:10.1056/NEJMoa2403347.

Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. 

KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease.

Pranav Garimella, MD, discusses how GLP-1 receptor agonists are reshaping CKD treatment sequencing alongside SGLT2 inhibitors, RAS inhibitors, and finerenone.

APOL1-Mediated Kidney Disease: From Genetic Discovery to the Edge of Precision Medicine


A decade and a half after APOL1 was linked to kidney disease, clinicians are still grappling with misdiagnosis, unpredictable progression, and uneven access to genetic insight, just as targeted therapies begin to emerge.

Kirk Campbell, MD, Professor of Medicine and Chief of the Renal Division at the University of Pennsylvania Perelman School of Medicine.

Pranav Garimella, MD, Chief Medical Officer of the American Kidney Fund,

Kristin Meliambro, MD, is an Associate Professor in the Department of Medicine, Division of Nephrology at the Icahn School of Medicine at Mount Sinai.

Katalin Susztak, MD, PhD, is a Professor of Medicine and Genetics at the University of Pennsylvania

John Cijan He, MD, PhD, Professor of Medicine and Pharmacological Sciences and Chief of the Division of Nephrology at the Icahn School of Medicine at Mount Sinai

A Genetic Discovery That Reshaped Kidney Disease Risk

In the span of roughly 16 years, APOL1 has moved from evolutionary curiosity to one of the most important genetic risk factors in nephrology.

The G1 and G2 variants, enriched in populations with West and Central African ancestry, rose in frequency because they confer protection against 

 infection. Today, they are recognized as among the strongest common genetic risk factors for kidney disease.

Approximately one-third of African Americans carry at least one high-risk APOL1 variant, and about 14% carry the high-risk genotype—two risk alleles in combinations such as G1/G1, G2/G2, or G1/G2. Globally, more than 100 million people in sub-Saharan Africa are estimated to carry two risk variants, with frequencies reaching 37% in parts of Ghana and 50% in southeastern Nigeria.

“It is a long time,” said Campbell. “But the fact that it took 13 years from the discovery of APOL1 kidney disease genetic association to the first proof-of-concept APOL1 inhibitor efficacy report should be celebrated.”

At the same time, Campbell emphasized ongoing uncertainty:

“There are still no approved APOL1-specific therapies, no consensus on population screening, limited ability to predict who among carriers will progress, and unresolved questions about ‘second hits,’” he said.

Rethinking a Default Diagnosis: Hypertension as Explanation — or Misclassification

Before APOL1 can be treated, it must be recognized—and that remains a persistent challenge.

Hypertensive nephrosclerosis has long served as a default diagnosis for chronic kidney disease in patients with hypertension, particularly Black patients. But emerging evidence suggests this label often obscures more specific and potentially treatable disease.

One biopsy-based study found that clinical criteria for nephrosclerosis had a sensitivity of just 0.13. Even optimized algorithms only reached 0.19, and roughly 40% of clinically diagnosed cases were found to have alternative diagnoses such as glomerulonephritis or interstitial nephritis.

Clinicians increasingly caution against treating hypertension as the primary explanation by default. “Hypertensive nephrosclerosis is often a diagnosis of exclusion,” Garimella noted. “Some patients labeled that way actually have APOL1-associated kidney disease, FSGS, or another primary kidney disorder.”

The reframing has clinical and psychological implications. Elevated blood pressure may in some cases be a consequence rather than a cause of kidney disease.

“Sometimes patients feel that explanation doesn’t fully make sense, especially if their hypertension hasn’t seemed severe,” Meliambro observed. “Recognizing that there may have been more going on can be validating rather than implying they did something wrong.”

The data on blood pressure management remain nuanced. Some studies show intensive blood pressure control does not necessarily slow progression in high-risk APOL1 carriers, while other data suggest a survival benefit with more intensive control compared with standard targets.

The introduction of a dedicated ICD code for APOL1-mediated kidney disease represents an important structural shift, enabling more precise diagnosis, counseling, and trial referral.

The Core Problem: Risk Without Prediction

While identifying APOL1 risk variants is now straightforward, predicting outcomes remains the central clinical challenge.

Carriers of two high-risk alleles face an estimated 15%–20% lifetime risk of kidney disease—meaning roughly 80% will never develop kidney failure.

“This represents a major knowledge gap,” Susztak explained. “If you receive a genotype result, you start asking: should I be doing something specific to prevent disease?”

Traditional risk models have not resolved this. Polygenic risk scores have failed to improve prediction in APOL1 high-risk individuals. Clinical risk scores based on eGFR, proteinuria, age, and sex perform well in established disease but are not clinically meaningful in preserved kidney function, she said.

“Some work has suggested that the G1/G1 genotype might be associated with a higher risk of decline in GFR and also a younger age of developing kidney disease,” Meliambro noted, adding that this requires further validation. High-risk genotype is still defined as any two risk alleles.

To address this gap, researchers turned to proteomics.

In a study of approximately 1,400 African American individuals from the Penn Medicine Biobank—many with preserved kidney function and no proteinuria at baseline—researchers analyzed roughly 7,700 circulating proteins.

Using machine learning, they identified nine proteins that, combined with clinical variables, formed the APOL1 Proteomic Risk Score (APRS), achieving a time-dependent AUC of 86.5%.

Individuals in the highest-risk quintile had approximately a 60% probability of progressing to dialysis or transplant over 10 years, while those in the lowest-risk quintile had less than a 1% risk. The score outperformed both the Kidney Failure Risk Equation and polygenic risk scores.

“Some of these proteins are related to tissue damage in the kidney that is not reflected in creatinine levels or urinary protein,” Susztak said. “For example, markers like MMP7 and matrix proteins may reflect fibrosis or injury that isn’t detected with standard tests.”

Others reflect inflammatory and endothelial pathways.

The score has been validated in external cohorts, including UK Biobank and NIH-supported data, but remains a research tool.

“We need to incorporate this biomarker into clinical trials and demonstrate that it is actionable,” she said. “Currently, we can treat the disease but not cure it.”

What APOL1 Biology Is Revealing About Early Kidney Injury

Beyond prediction, APOL1 research is reshaping understanding of early disease biology.

“In African American patients, we know the APOL1 gene is a high-risk gene for what we call APOL1-mediated glomerular disease, which is essentially like FSGS,” said He. “When this gene is highly expressed, it can cause podocyte injury through specific cellular pathways.”

“Some of these proteins are related to tissue damage in the kidney that is not reflected in creatinine levels or urinary proteins,” Susztak said.

“Other proteins are linked to inflammation. APOL1 is strongly regulated by inflammation, so individuals with higher inflammatory states may be at greater risk.”

“And there are a few proteins related to endothelial injury that we are still working to understand.”

Together, these findings suggest injury may precede traditional clinical markers such as proteinuria or eGFR decline.

From Biology to Therapy: Precision Medicine Takes Shape

Mechanistic insight has enabled targeted drug development.

“Based on that mechanism, therapies have been developed to block the pathways activated by APOL1,” He said. “These inhibitors have shown promising results in reducing proteinuria in phase 2 studies, with ongoing phase 3 trials.”

Inaxaplin directly targets APOL1 pore formation in podocytes.

“This is a very specific, targeted therapy that inhibits the pore-forming function of the APOL1 protein,” Meliambro said. “It represents a true example of precision medicine in nephrology.”

Other approaches include antisense oligonucleotides and anti-inflammatory strategies.

Despite therapeutic advances, management remains standard CKD care.

“A two-risk-variant APOL1 genotype raises concern for progressive disease,” Garimella explained. “But the treatment backbone remains standard CKD care.”

That includes RAAS blockade, SGLT2 inhibitors when appropriate, blood pressure control, statins, and avoidance of nephrotoxins.

“APOL1 testing is worth considering when the result can change follow-up, trial eligibility, transplant donor counseling, or future targeted-treatment decisions,” Campbell said. “But it should come with counseling, and it should never replace a full kidney-disease workup.”

“Awareness only matters if it changes decisions such as diagnosis, counseling, testing, referral, or follow-up,” Garimella said.

The ICD code for APOL1-mediated kidney disease may help translate awareness into action.

Barriers to Integration and Uneven Adoption

Despite availability of testing, adoption remains inconsistent.

“It’s not necessarily ordering the test—it’s interpreting and explaining the results,” Meliambro said.

Barriers include lack of guidelines, limited genetic counseling infrastructure, and patient concerns about privacy and discrimination.

Equity Will Define the Impact of Precision Medicine

“Equitable access would require more than drug approval,” Campbell said. “It would require payer coverage for testing, counseling, nephrology referral, and medication.”

“Otherwise, we risk repeating the same inequities,” he said. “Patients with better access get tested and treated, while underserved populations remain underdiagnosed.”

The decision to hold a major consensus meeting in Accra reflects the field’s shifting center of gravity.

“This is a rapidly evolving field,” Meliambro said. “There has been substantial research progress. But there are still many unresolved questions—especially around predicting disease progression and translating this knowledge into improved patient outcomes.”

“There is significant investment and enthusiasm,” she added. “Hopefully that will lead to meaningful breakthroughs in the near future.”

Campbell reports relevant disclosures with NIH, National Kidney Foundation. Garimella reports relevant disclosures with NIH. Meliambro reports no relevant disclosures identified. Susztak reports relevant disclosures with NIH. He reports no relevant disclosures identified.

APOL1 G1/G2 variants, selected for trypanosome resistance, are prevalent in people with West/Central African ancestry and drive substantial CKD and FSGS risk, yet progression remains poorly predictable. Hypertensive nephrosclerosis frequently misclassifies underlying glomerular or interstitial disease, prompting calls for more precise workups and use of the new APOL1-mediated kidney disease ICD code. A nine-protein APOL1 Proteomic Risk Score stratifies 10-year kidney failure risk far better than existing models. Targeted APOL1 inhibitors (eg, inaxaplin) and other modalities are advancing, while equitable access to testing, counseling, and therapy lags.

APOL1 research is driving precision nephrology, but prediction gaps and equity challenges still limit clinical impact.