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Drug-Induced Kidney Injury: Renal Safety Assessment in Clinical Development and Pharmacovigilance

Understand how drug-induced kidney injury is identified and medically evaluated, why kidney function and kidney injury are not the same, how renal biomarkers support clinical-trial safety assessment, and how pharmacovigilance teams evaluate potential nephrotoxicity.

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Drug-Induced Kidney Injury: Renal Safety Assessment in Clinical Development and Pharmacovigilance

Introduction

The kidneys are major targets for drug-related toxicity because they receive a high proportion of cardiac output, concentrate substances during urine formation and contain specialized cellular transport systems that can expose renal tissues to relatively high concentrations of medicines and their metabolites.

Drug-induced kidney injury can therefore arise through multiple mechanisms. These include direct tubular toxicity, glomerular injury, interstitial inflammation, crystal deposition, obstruction, vascular injury and changes in renal haemodynamics.

Renal safety assessment is consequently more complicated than simply monitoring serum creatinine.

Serum creatinine is an important marker of kidney function, but a change in serum creatinine does not necessarily mean that structural kidney injury has occurred. Conversely, clinically important kidney injury can sometimes occur before a substantial change in serum creatinine becomes apparent.

This distinction is central to renal safety assessment.

A drug may produce a reversible functional change in renal filtration without causing structural injury. Another drug may cause tubular cellular injury while the measurable decline in kidney function is initially small.

For pharmacovigilance professionals, the important question is therefore not simply:

"Did creatinine increase?"

It is:

"What happened to kidney function, is there evidence of kidney injury, what mechanism is most plausible, and is the medicinal product responsible?"

This article describes the principles used to answer those questions during clinical development and post-marketing pharmacovigilance.

The approach is complementary to the assessment of other organ toxicities such as drug-induced liver injury. However, there is no single universally accepted renal equivalent of Hy's Law.

Instead, renal safety assessment integrates measures of kidney function, structural injury, urine findings, clinical events, exposure, competing causes and, where appropriate, emerging biomarkers.

Learning Objectives

After reading this article, the reader should be able to:

Understanding Drug-Induced Kidney Injury

What Is Drug-Induced Kidney Injury?

Drug-induced kidney injury refers to impairment or damage to the kidneys caused by exposure to a medicinal product.

The term encompasses several biological processes.

A drug can alter renal function without directly damaging renal cells.

A drug can also produce structural injury that eventually leads to impaired kidney function.

The clinical presentation can therefore range from a small laboratory abnormality to severe acute kidney injury requiring kidney replacement therapy.

Potential manifestations include:

The same laboratory abnormality can arise through very different mechanisms.

An increase in serum creatinine, for example, can result from reduced glomerular filtration, altered tubular secretion of creatinine, changes in creatinine production or other non-structural mechanisms.

The medical evaluation must therefore establish the likely mechanism rather than treating every laboratory change as structural nephrotoxicity.

Why the Kidney Is Vulnerable to Drug Toxicity

The kidneys perform several functions that make them susceptible to drug-related effects.

They receive substantial renal blood flow.

They filter large volumes of plasma.

They actively secrete and reabsorb many substances.

They concentrate certain compounds within the tubular fluid.

Renal epithelial cells also contain transporters and metabolic systems that can influence intracellular exposure to drugs and metabolites.

Consequently, potentially toxic substances may reach concentrations within particular nephron segments that are substantially different from their concentrations in systemic circulation.

Different drugs can therefore injure different parts of the nephron.

This produces different clinical phenotypes.

Mechanisms of Drug-Induced Kidney Injury

Drug-induced kidney injury can arise through several broad mechanisms:

A single medicine may also produce more than one mechanism depending on dose, duration, patient characteristics and concomitant treatments.

Understanding mechanism is therefore an important part of medical causality assessment.

Kidney Function Versus Kidney Injury

The Fundamental Distinction

The most important concept in renal safety assessment is the distinction between kidney function and kidney injury.

Kidney function describes how effectively the kidneys perform functions such as filtration and regulation of fluid and electrolytes.

Kidney injury refers to structural or cellular damage.

These concepts overlap but are not identical.

A patient can have evidence of kidney injury before a major decline in filtration occurs.

Conversely, kidney function can change without structural kidney damage.

This distinction explains why serum creatinine alone cannot provide a complete picture of renal safety.

Functional Changes Without Structural Injury

Some medicines alter renal haemodynamics.

For example, a drug can reduce glomerular filtration through a change in intrarenal haemodynamics without causing direct tubular cell death.

Other medicines can alter the tubular secretion of creatinine.

The resulting increase in serum creatinine may appear similar to an injury-related increase even though the underlying mechanism is different.

This is sometimes described as pseudo-nephrotoxicity or a creatinine-based apparent decline in renal function without corresponding structural injury.

The distinction is particularly important during drug development because an apparent renal safety signal can otherwise be misclassified.

Structural Injury Without an Immediate Large Functional Change

The reverse situation is also possible.

Tubular cellular injury may occur before sufficient functional loss develops to produce a large serum creatinine increase.

This is one reason why renal injury biomarkers have attracted interest in clinical development.

A biomarker that reflects cellular stress or injury may potentially provide information that differs from a conventional filtration marker.

However, biomarkers should not automatically be interpreted as diagnostic proof of clinically meaningful drug-induced kidney injury.

Their interpretation depends on the biomarker, indication, assay, timing, clinical context and regulatory status.

Serum Creatinine and eGFR

Serum Creatinine

Serum creatinine remains one of the most important conventional markers used in renal safety assessment.

Creatinine is produced from creatine metabolism and is eliminated predominantly through the kidneys.

When glomerular filtration decreases, serum creatinine generally increases.

However, serum creatinine is influenced by factors other than kidney filtration.

These include:

Therefore, a change in serum creatinine should be interpreted in clinical context.

Why Serum Creatinine Is an Imperfect Injury Marker

Serum creatinine is primarily a marker of kidney function rather than a direct marker of cellular injury.

It may change relatively late in the course of kidney injury.

The relationship between serum creatinine and filtration is also not instantaneous.

A patient can therefore have meaningful renal injury before serum creatinine reaches a predefined threshold.

This limitation has been one of the major drivers for the development and evaluation of additional renal biomarkers.

Estimated Glomerular Filtration Rate

eGFR provides an estimate of glomerular filtration based on serum creatinine and other demographic or laboratory variables, depending on the equation used.

eGFR is useful for describing baseline kidney function and chronic kidney disease.

However, rapidly changing kidney function creates challenges for interpreting eGFR because conventional equations generally assume a relatively stable creatinine concentration.

For acute changes, the absolute serum creatinine trajectory and clinical context may therefore be more informative than treating a calculated eGFR value as a precise real-time measurement of filtration.

Baseline Kidney Function

Baseline renal function is essential for interpreting a potential drug-related change. [7]

A clinical-trial subject may enter a study with:

The same absolute creatinine value can have different clinical implications depending on baseline status.

Longitudinal baseline information can therefore be more informative than a single screening result.

Cystatin C and Alternative Measures of Kidney Function

Cystatin C

Cystatin C is a low-molecular-weight protein produced by nucleated cells and filtered by the glomerulus.

Because its biological determinants differ from those of creatinine, cystatin C can provide complementary information about kidney filtration.

It can be particularly useful when serum creatinine is potentially misleading.

The 2026 KDIGO AKI/AKD public-review draft includes serum cystatin C within its proposed framework for identifying AKI and suggests using it when serum creatinine is less accurate.

Because this is a public-review draft rather than a finalized guideline, its recommendations should be described accordingly.

When Alternative Markers May Help

Alternative markers may be particularly useful when creatinine production is unusual or when creatinine-based estimates are difficult to interpret.

Examples include patients with:

No alternative biomarker should be interpreted in isolation.

The objective is to improve the characterization of kidney function and injury rather than to replace clinical assessment with a single laboratory result.

Urine Output

Why Urine Output Matters

Urine output provides a different dimension of renal function from serum biomarkers.

A substantial reduction in urine output can indicate acute deterioration in kidney function even before serum creatinine has changed substantially.

Urine output can also provide information about the severity and clinical trajectory of an acute kidney injury episode.

However, urine output is influenced by:

Therefore, it must also be interpreted in context.

Acute Kidney Injury Criteria

KDIGO criteria have historically defined AKI using changes in serum creatinine and urine output. [5]

The 2026 KDIGO public-review draft proposes an expanded framework incorporating functional and structural criteria and includes serum creatinine, cystatin C, urine output and qualified kidney-damage biomarkers. [6]

Because the 2026 document remains a draft, safety professionals should verify which criteria are specified by the relevant clinical protocol, regulatory analysis plan or medical-review framework.

The broader principle remains unchanged:

AKI is a clinical syndrome defined by a change in kidney function and/or evidence of kidney injury over a defined time period, rather than by one isolated laboratory value.

Proteinuria and Albuminuria

Proteinuria

Proteinuria refers to increased urinary protein excretion.

It can occur through several mechanisms.

Proteinuria may reflect:

The type and magnitude of proteinuria therefore matter.

Albuminuria

Albuminuria is particularly informative for glomerular barrier abnormalities.

Increased urinary albumin can indicate altered glomerular permeability.

However, albuminuria can also be influenced by:

Consequently, a treatment-emergent increase in albuminuria should be evaluated against baseline and clinical context.

Why Urinary Protein Can Complement Serum Creatinine

Serum creatinine primarily describes filtration.

Urinary protein and albumin provide information about the integrity and function of the nephron and glomerular filtration barrier.

A patient may therefore develop significant proteinuria without an immediate major increase in serum creatinine.

This is particularly important for medicines associated with glomerular injury.

Patterns of Drug-Induced Kidney Injury

Tubular Injury

The renal tubules are important targets for drug toxicity. [8]

Tubular injury can result from:

Clinical manifestations can include:

The specific pattern depends on the nephron segment affected.

Glomerular Injury

Glomerular injury affects the filtration barrier.

Potential manifestations include:

Glomerular injury may require specialist evaluation because the causal mechanisms and clinical consequences differ substantially from tubular toxicity.

Acute Interstitial Nephritis

Acute interstitial nephritis is an inflammatory injury involving the renal interstitium and tubules.

Medicines are an important cause.

Potential features include:

The classic triad is not present in every patient.

Therefore, absence of rash, fever or eosinophilia does not exclude drug-induced interstitial nephritis.

Hemodynamic Kidney Injury

Some medicines can alter renal blood flow or intraglomerular pressure.

The resulting reduction in filtration may produce an increase in serum creatinine without direct structural toxicity.

This distinction is important because the clinical implications and management can differ from those of direct tubular injury.

Vascular Injury

Drug-related vascular effects can produce renal injury through:

The renal findings may occur together with abnormalities in other organ systems.

Crystal and Obstructive Nephropathy

Some medicines or metabolites can precipitate within the urinary tract.

This can cause:

Imaging and urine findings can be particularly useful in evaluating these mechanisms.

Renal Safety Biomarkers

Why Biomarkers Are Needed

The limitations of serum creatinine have encouraged the development and evaluation of biomarkers that may detect kidney injury earlier or provide mechanistic information.

FDA has supported exploratory development of urinary biomarkers for drug-induced renal tubular injury, including:

These biomarkers should be understood as complementary tools.

FDA's Letter of Support describes their exploratory use in early clinical development and emphasizes that they should be interpreted alongside traditional renal safety measures and other clinical and nonclinical findings.

Kidney Injury Molecule-1

Kidney Injury Molecule-1, or KIM-1, is associated with renal tubular injury, particularly proximal tubular injury.

Urinary KIM-1 has therefore attracted substantial interest as a marker of tubular injury.

Its potential value is that it may provide information about cellular injury that differs from serum creatinine.

However, detection of an elevated biomarker does not automatically establish that a medicinal product has caused clinically important kidney injury.

NGAL

Neutrophil gelatinase-associated lipocalin, or NGAL, can increase in association with kidney injury.

NGAL has been studied extensively as an early marker of tubular injury.

However, NGAL can also be influenced by conditions outside a narrowly defined drug-induced tubular injury phenotype.

Its interpretation therefore requires clinical context.

Cystatin C

Cystatin C can be used as a marker of kidney filtration and may provide complementary information to creatinine.

Urinary cystatin C has also been studied as a marker of tubular dysfunction.

These are conceptually different uses and should not be conflated.

Clusterin, NAG and Other Biomarkers

Other biomarkers investigated in renal safety include:

Different biomarkers may reflect different nephron segments or mechanisms of cellular stress.

A biomarker panel can therefore potentially provide more information than one biomarker alone.

However, biomarker panels introduce additional analytical, interpretative and regulatory considerations.

Biomarker Qualification Versus Exploratory Use

One of the most important distinctions for pharmacovigilance professionals is between:

These categories should not be treated as interchangeable.

FDA's Letter of Support for the renal biomarker panel explicitly encouraged exploratory use and noted that the performance characteristics and sensitivity and specificity of the biomarkers were not fully established for broad nephrotoxicity detection.

Therefore, an article about renal biomarkers should avoid describing every candidate biomarker as a validated diagnostic test for drug-induced kidney injury.

The Problem of Pseudo-Nephrotoxicity

Creatinine Transporter Effects

Some drugs can increase serum creatinine by interfering with renal tubular secretion of creatinine.

This can create the appearance of reduced kidney function without structural kidney injury.

The distinction is important because an apparent decline in eGFR may otherwise be misclassified as nephrotoxicity.

Why This Matters in Clinical Trials

If a drug causes a reversible creatinine increase through transporter inhibition, the clinical-development team may observe:

The total pattern may therefore suggest a functional or pharmacological effect rather than structural renal injury.

This is one reason why FDA's Kidney Injury Targeted Analysis Guide recommends considering additional data such as proteinuria, albuminuria and cystatin C when evaluating potential renal signals.

Hemodynamic Effects

A similar issue arises when a medicine changes renal haemodynamics.

The resulting reduction in filtration may be pharmacologically expected rather than evidence of direct tubular toxicity.

This does not mean that the effect is clinically irrelevant.

A functional change can still be important in patients with limited renal reserve or when combined with other nephrotoxic exposures.

The correct conclusion is therefore not simply "not nephrotoxic."

The reviewer should characterize the mechanism and clinical significance accurately.

Medical Evaluation of a Potential Drug-Induced Kidney Injury Case

Confirm the Laboratory Data

The first step is to confirm:

Laboratory reference ranges and units should also be confirmed.

Establish the Time Course

The reviewer should determine:

Temporal association is necessary for many causality assessments but does not establish causality by itself.

Review Baseline Kidney Status

The reviewer should determine whether the subject had:

The baseline should ideally include more than one measurement when renal function is known to fluctuate.

Review Concomitant Medicines

Potentially nephrotoxic or renal-function-altering medicines should be considered.

The review may include:

The purpose is not to label every concomitant medicine as causal.

The purpose is to determine whether another exposure provides a more plausible explanation.

Evaluate Volume and Hemodynamic Status

The reviewer should consider:

These factors can materially affect renal function.

Evaluate the Urine

Where available, review:

The pattern can provide important clues about the underlying mechanism.

Consider Imaging

Imaging may be appropriate when obstruction, stones or other structural abnormalities are suspected.

Renal ultrasound and other imaging modalities can help distinguish obstructive or structural causes from purely functional changes.

Assess Dechallenge

Improvement after drug discontinuation can support a causal relationship.

However, the interpretation depends on:

Assess Rechallenge

A recurrence after re-exposure may provide strong causal evidence.

However, deliberate rechallenge is generally inappropriate when a serious renal reaction could recur.

An inadvertent or clinically necessary rechallenge should be documented and evaluated carefully.

Kidney Safety in Clinical Development

Individual-Subject Review

Individual subjects may require medical review when they develop:

The medical reviewer should integrate laboratory, clinical and treatment information.

Population-Level Review

At the population level, clinical-development teams may examine [2]:

The purpose is to determine whether there is a consistent treatment-related pattern.

Treatment Versus Control

A renal laboratory abnormality occurring in both treatment and control groups may have a different interpretation from an abnormality concentrated in the investigational treatment group.

The reviewer should consider:

Control data are therefore essential for interpreting population-level renal signals.

Exposure-Response Assessment

If renal abnormalities increase with increasing exposure, this may support a drug-related mechanism.

Exposure-response assessment can be particularly informative when:

However, exposure-response association does not by itself prove structural nephrotoxicity.

FDA Targeted Kidney Safety Analyses

The Kidney Injury Targeted Analysis Guide

FDA's Standard Safety Tables and Figures programme includes a dedicated Kidney Injury Targeted Analysis Guide for deeper evaluation of potential renal safety signals.

The guide reflects an important principle:

routine laboratory tables may identify a signal, but targeted analyses may be required to understand the signal.

What the Targeted Analysis Can Explore

Depending on the clinical-development context, analyses may examine:

FDA also notes that additional information may be needed to determine whether an apparent renal signal represents true injury, an early change in kidney function, or a drug effect on creatinine handling.

Risk-Factor Subgroups

Relevant subgroups may include patients with:

Subgroup analysis can help determine whether the signal is concentrated in a population with particular susceptibility.

Narrative Review

Laboratory data alone may not explain a renal signal.

Narratives can provide information about:

This is why medical review remains essential even when large-scale automated analyses are available.

Post-Marketing Pharmacovigilance

Sources of Renal Safety Information

Potential drug-induced kidney injury may be identified through:

Post-marketing cases often contain less complete laboratory information than clinical-trial cases.

The absence of creatinine or urine data therefore does not necessarily mean that a renal adverse event did not occur.

It means that the available evidence may be insufficient to characterize the renal phenotype fully.

Case-Level Medical Review

A safety physician should distinguish between:

  1. a case with documented AKI and a plausible drug relationship;
  2. a case with creatinine elevation but insufficient clinical information;
  3. a case with a renal diagnosis but no supporting laboratory data;
  4. a case with a strong alternative explanation;
  5. a case with multiple potentially nephrotoxic exposures.

This avoids over-attribution.

Aggregate Safety Assessment

At the aggregate level, the safety team may examine:

The analysis should consider reporting patterns, exposure, background disease and concomitant medicines.

Worked Examples

Example 1: Creatinine Increase With No Other Evidence of Injury

A subject has:

Baseline creatinine = 0.9 mg/dL

After treatment:

Creatinine = 1.2 mg/dL

The subject is clinically well.

There is no proteinuria.

Urinalysis is unchanged.

There is no evidence of dehydration or hypotension.

A drug-specific assessment suggests inhibition of creatinine tubular secretion.

This case warrants evaluation but should not automatically be labelled structural nephrotoxicity.

The most appropriate conclusion may be a treatment-related functional effect on creatinine handling, depending on the complete evidence.

Example 2: Acute Kidney Injury With Volume Depletion

A subject develops:

The investigational medicine was also administered during this period.

The temporal relationship alone does not establish drug causality.

The medical reviewer should evaluate whether volume depletion and hypotension provide a more plausible explanation.

If renal function improves rapidly with restoration of volume and treatment of the underlying illness, this may support a hemodynamic or pre-renal mechanism.

Example 3: Tubular Injury Pattern

A subject develops:

The combination provides stronger evidence for potential drug-related tubular injury than an isolated creatinine increase.

The biomarker result still requires interpretation in the context of the specific assay and its regulatory status.

Example 4: Proteinuria With Preserved Filtration

A subject develops substantial new albuminuria while serum creatinine remains close to baseline.

This should not be dismissed simply because eGFR has not changed substantially.

The pattern may indicate an alteration in the glomerular filtration barrier.

Further clinical assessment may be required to determine:

This illustrates why kidney safety cannot be reduced to serum creatinine.

Limitations of Renal Safety Assessment

Serum Creatinine Is Not a Direct Injury Biomarker

Serum creatinine is primarily a marker of kidney filtration.

It can be affected by non-renal factors and may respond relatively slowly to acute injury.

eGFR Has Limitations During Rapid Change

eGFR equations are useful for describing kidney function but have limitations when creatinine is changing rapidly.

The calculated value should therefore not be treated as an exact real-time measurement of filtration during acute kidney injury.

Biomarkers Are Not Interchangeable

Different biomarkers reflect different biological processes.

KIM-1, NGAL, cystatin C and other biomarkers should not be treated as interchangeable indicators of "kidney toxicity."

Each requires appropriate interpretation.

Background Kidney Disease Is Common

Patients entering clinical trials or post-marketing surveillance may have:

These conditions increase background renal event rates and complicate causality assessment.

Multiple Drugs May Affect the Kidney

Patients frequently receive multiple medicines that can influence:

Attribution therefore requires careful consideration of the complete exposure history.

Practical Medical Review Framework

Step-by-Step Renal Safety Review

A structured medical review can proceed through the following sequence:

  1. Confirm the laboratory values.
  2. Confirm units and reference ranges.
  3. Establish baseline kidney function.
  4. Review the longitudinal creatinine trajectory.
  5. Assess eGFR where appropriate.
  6. Assess urine output.
  7. Review urinalysis.
  8. Assess proteinuria and albuminuria.
  9. Review relevant renal biomarkers.
  10. Determine the likely renal phenotype.
  11. Review treatment timing and dose.
  12. Review concomitant medicines.
  13. Assess hydration and hemodynamic status.
  14. Review relevant medical history.
  15. Evaluate infection, obstruction and systemic illness.
  16. Consider imaging where appropriate.
  17. Assess dechallenge.
  18. Assess rechallenge if it occurred.
  19. Determine the most plausible mechanism.
  20. Assess causality.
  21. Assess seriousness and outcome.
  22. Document the medical rationale.

Medical Documentation

A medically useful renal safety assessment should make the reasoning reconstructable.

Documentation should address, where relevant:

The objective is not simply to document that "creatinine increased."

The objective is to explain what the increase means.

Pharmacovigilance and Inspection Considerations

Inspection Perspective

During an inspection, an organisation should be able to demonstrate that important renal safety signals were identified, evaluated and followed appropriately.

Evidence may include:

An inspector may reasonably ask how the organisation distinguishes:

Common Documentation Weaknesses

Potential weaknesses include:

Good documentation should allow an independent reviewer to reconstruct how the medical conclusion was reached.

Common Mistakes in Renal Safety Assessment

Common errors include:

What an Experienced Safety Physician Looks For

An experienced safety physician does not start with:

"Did creatinine increase?"

The first question is:

"What changed in kidney function or kidney structure, and what is the most plausible mechanism?"

The reviewer then asks:

Only after these questions have been addressed should the reviewer decide whether the event represents a convincing potential drug-induced kidney injury signal.

The key principle is the same one that applies across organ systems:

A laboratory abnormality is a signal requiring interpretation, not automatically a diagnosis of drug-induced organ injury.

Kidney Safety Compared With Liver Safety

Hy's Law provides a useful conceptual comparison.

In liver safety, a relatively recognizable combination of aminotransferase elevation and bilirubin elevation can identify a population-level signal of concern.

Renal safety is more heterogeneous.

There is no single renal laboratory pattern that captures all clinically important drug-induced kidney injury.

Instead, renal assessment may require integration of:

This difference should be preserved rather than forcing renal safety into the framework of Hy's Law.

The appropriate lesson from Hy's Law is not that every organ should have an equivalent rule.

The lesson is that organ-specific safety assessment works best when biological injury, functional consequence, clinical phenotype and drug causality are evaluated together.

Key Takeaways

Drug-induced kidney injury is an important component of clinical development and pharmacovigilance.

The most important principle is that kidney function and kidney injury are not synonymous.

Serum creatinine and eGFR provide important information about kidney function, but they do not directly measure structural renal injury.

Renal safety assessment may therefore require consideration of:

Renal injury can occur through multiple mechanisms, including tubular toxicity, glomerular injury, interstitial nephritis, vascular injury, crystal deposition, obstruction and hemodynamic effects.

FDA has supported exploratory use of several urinary biomarkers, including KIM-1, NGAL, clusterin, cystatin C, osteopontin and alpha-GST, for monitoring drug-induced renal tubular injury in early clinical development [3][4] These biomarkers should be interpreted in conjunction with conventional measures and their specific regulatory context. [3]

A particularly important issue is pseudo-nephrotoxicity, in which a drug changes serum creatinine through effects on renal handling without causing structural kidney injury.

FDA's Kidney Injury Targeted Analysis Guide provides a framework for deeper clinical-trial evaluation of potential renal safety signals, including analysis of creatinine, eGFR, proteinuria, albuminuria, cystatin C and relevant clinical factors. [1]

There is no single renal equivalent of Hy's Law.

Instead, the strongest renal safety assessment integrates function, injury, phenotype, mechanism, exposure and competing causes.

The central principle is:

Renal safety assessment should explain what changed in the kidney, why it changed, and whether the medicinal product is the most plausible cause.

References

  1. U.S. Food and Drug Administration. Standard Safety Tables and Figures: Kidney Injury Targeted Analysis Guide. Center for Drug Evaluation and Research.

  2. U.S. Food and Drug Administration. Standard Safety Tables and Figures (ST&Fs). Center for Drug Evaluation and Research.

  3. U.S. Food and Drug Administration. Letter of Support for Drug-Induced (DIKI) Renal Tubular Injury Biomarker(s). November 23, 2016.

  4. U.S. Food and Drug Administration. Reviews: Qualification of Biomarker: clusterin (CLU), Cystatin-C (CysC), Kidney Injury Molecule-1 (KIM-1), N-acetyl-beta-D-glucosaminidase (NAG), Neutrophil Gelatinase-Associated Lipocalin (NGAL), and osteopontin (OPN).

  5. Kidney Disease: Improving Global Outcomes (KDIGO). KDIGO 2012 Clinical Practice Guideline for Acute Kidney Injury.

  6. Kidney Disease: Improving Global Outcomes (KDIGO). KDIGO 2026 Clinical Practice Guideline for Acute Kidney Injury (AKI) and Acute Kidney Disease (AKD): Public Review Draft. 2026.

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

  8. U.S. Food and Drug Administration. Drug-Induced Renal Injury List (DIRIL) Dataset. Center for Drug Evaluation and Research.

Revision History

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