Chronic kidney disease (CKD) and other nephrology conditions are a major global health challenge. With rising prevalence and persistent unmet medical needs, there is an urgent need for safer, more effective and innovative treatments for renal disease, encouraging many biotech and pharmaceutical companies to enter the field with different strategic and tactical approaches.

Over the last decade, new nephrology trials have grown consistently. As disease understanding has improved, better classification of kidney diseases and patient subgroups have led to tailored drug development efforts. At the same time, sponsors are showing increased interest in rare kidney indications such as glomerular diseases and those with a genetic driver like Alport syndrome. The volume of new glomerulonephritis studies has tripled in the last six years, with 37 new studies in 2019 versus 111 in 2025.

Why earlier insights are needed

Like many other major therapy areas, nephrology is becoming increasingly crowded and competitive. But in contrast to some fields, renal trials can be particularly time-intensive. According to GlobalData analysis, Phase III CKD studies have an average duration of 34.7 months, while enrollment periods take 21.9 months on average. Trials are often event-driven, meaning they conclude only after a specific number of primary endpoints, typically kidney failure or death, has been reached. And kidney disease progresses very slowly, with early stages often lasting a decade or more with stable kidney function and no symptoms.

Modern trials require investigative medicines to be employed with both the newer as well as existing standards of care such as SGLT-2 or RAAS inhibitors. This heightened “placebo” group” can be intimidating for sponsors of new IP. When both trial arms offer benefit, it may take lengthier trials – and more patients – to separate their effects, further extending trial duration. Safety concerns and comorbidities are a key risk as trials continue, while recruitment and enrollment challenges often hinder proceedings right from the beginning. In slow-moving studies, new therapies or guidelines may emerge before the trial’s results are available, potentially weakening or invalidating the findings and requiring additional trials to align with updated care standards.

All of this has made renal research risky for sponsors, who rely on prolonged trials that provide clarity only after capital has been spent. As lengthy studies go on, costs multiply. According to GlobalData estimates, the average cost to run a Phase II nephrology trial is $20.57 million, and this increases to $29.82 million in Phase III. The financial stakes of failure are high, meaning sponsors desperately need faster decision-making tools to identify failing programs early and accelerate promising ones sooner.

Fortunately, there is a solution: biomarkers.

Biomarkers in kidney studies

Predictive biomarkers are biological indicators that forecast the likelihood of a drug leading to therapeutic benefit or harm, enabling sponsors to anticipate outcomes during treatment. Biomarkers have been used in approximately 47% of all nephrology trials in the GlobalData database. Usage is highest in Phases II and III, with just 17% of Phase I trials using biomarkers.

“Biomarker use has lagged in nephrology,” notes Dr Henry Cremisi, MD, FACP, an accomplished nephrologist who now serves as Executive Medical Director of Medical Affairs at Caidya. “It is starting to tick up, but we are 20 years behind where oncology is. In order for us to provide a true value proposition, not just for sponsors but for all stakeholders, including patients and families living with significant medical disease with profound unmet need, biomarkers are a critical part of getting this right.”

According to analysis by GlobalData, the majority of the biomarkers deployed in nephrology trials have been used for evaluating efficacy, followed by patient screening and stratification, then safety monitoring. This focus on efficacy is logical given the amount of time it takes for traditional clinical endpoints to be reached. With efficacy biomarkers indicating positive or negative responses to a drug well before these outcomes, sponsors can terminate or adjust their program early if the biomarker shows little or no change in early studies, saving significant time and resources from going to waste. Conversely, there may be the opportunity for a drug to be approved on efficacy biomarkers – known as surrogate endpoints – alone, significantly shortening the time to regulatory approval.

Yet early development decisions are less binary than simply whether a drug works or not, and the value biomarkers can bring stretches far beyond that. The under-utilization of biomarkers in Phase I is one part of this missed opportunity for nephrology sponsors. In early-phase studies, biomarkers can be used to confirm whether the drug hits its intended molecular target and whether it provides any benefit before functional change is observed. There is also a safety component for early studies, with biomarkers helping researchers assess how well kidneys are processing a drug and how the drug is affecting kidney function in the short term, detecting early signs of stress or injury that can be addressed in Phase II rather than Phase III. In earlier studies, the information gleaned from biomarkers can be instrumental for determining the optimal dose of a medication and generating broader insights about other potential indications that the drug may benefit, either renal or extrarenal. This might help justify the use of basket trials in Phase III, enabling simultaneous, efficient evaluation of multiple indications.

The chart below shows the most common biomarkers used to monitor treatment response in nephrology-related trials since 2014. Serum creatinine is the most widely used marker for estimating glomerular filtration rate (eGFR) – a standardized, globally used tool for diagnosing and staging CKD. Proteinuria, often measured via the albumin-to-creatinine ratio in the urine, is another hallmark, with recent studies emphasizing a strong link between proteinuria and cardiovascular risk.

While creatinine, albumin, and albumin/creatinine ratios (ACR) have been used heavily in nephrology studies, these traditional biomarkers have several limitations. Lacking sensitivity, serum creatinine and eGFR may struggle to detect kidney dysfunction in its earliest stages. Creatinine is a byproduct of muscle metabolism, meaning levels are also influenced by external factors such as age, sex, diet, and muscle mass, potentially leading to inaccurate or false readings in certain subgroups. Proteinuria is also variable, with levels fluctuating in the urine based on hydration status, exercise, and other factors.  

In the future, novel, emerging biomarkers will reshape kidney disease research, offering significant benefits over creatinine and proteinuria. Key advancements include neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and cystatin-C. Cystatin-C can be thought of as a functional biomarker for GFR estimation that may be more accurate and sensitive than creatinine, especially in early disease or patients with low muscle mass or atypical diets. On the other hand, NGAL and KIM-1 are closer to injury biomarkers. Both are expressed in tubular cells after kidney injury occurs, making them particularly useful in acute kidney injury (AKI) trials. According to Dr Cremisi, a key benefit is the ability to distinguish true structural injury from temporary hemodynamic effects such as changes in blood pressure and renal blood flow.

“This allows us to better understand what is actually happening and to differentiate between changes in the numbers versus changes that truly reflect safety and injury outcomes, so that we don’t stop medications or study drugs simply because a number goes up or down,” he explains.

Since 2022, 13% of new clinical trials for AKI have used NGAL as a biomarker, while KIM-1 has been used in just 5% of those trials. These novel biomarkers are still largely considered exploratory by regulators, which means they are not yet accepted as primary endpoints and usage is uneven across regions, with significantly stronger adoption in the US than Europe. Limitations include low specificity; NGAL, for example, is produced during inflammation or infection of various tissue types, not just the kidneys, raising concerns about false positives.

Nevertheless, these important biomarkers already provide insight into mechanisms that traditional measures cannot capture, such as podocyte injury, complement activity, inflammation, oxidative stress, and repair/resilience. While Dr Cremisi believes they are “not going to be accepted as being more than exploratory from the regulatory perspective”, they do help to better understand and explain the mechanism of action of a new medicine, and such insights are vital for building a forward-looking differentiation narrative in a competitive space.

Most importantly, biomarkers provide these insights early on, helping sponsors predict the trajectory of their trials and guiding rapid yet well-informed decisions about whether to continue, modify, or stop development at lower cost and risk. As novel biomarkers with improved sensitivity for detecting early stages of kidney disease or injury emerge, this potential is only strengthening. As the evidence base matures and these markers are used more consistently, they are expected to move from “nice-to-have” exploratory tools to central components of clinical trials.