Acute kidney injury

Summary

Acute kidney injury (MONDO:0002492) is a disease with 1 cohort gene (13 GWAS associations across 14 studies) and 1,261 clinical trials. Top therapeutic interventions include sodium bicarbonate, iopamidol, and aminophylline.

At a glance

• Cohort genes: 1
• GWAS associations: 13
• ClinVar variants: 1
• Clinical trials: 1,261

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	acute kidney injury
Mondo ID	MONDO:0002492
MeSH	D058186
DOID	DOID:3021
ICD-10-CM	N17
ICD-11	476391827
NCIT	C26808
UMLS	C2609414
MedGen	388570
Is cancer (heuristic)	no

Also known as: acute kidney failure · acute renal failure · AKI · ARF · kidney failure, acute

Data availability: 1 ClinVar variant · 13 GWAS associations (14 studies).

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › urinary system disorder › kidney disorder › kidney failure › acute kidney injury

Related subtypes (2): uremia, chronic renal failure syndrome

Subtypes (1): acute kidney tubular necrosis

Genetics & variants

GWAS landscape

13 GWAS associations across 14 studies. Top hits map to 1 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
chr9:5073770	1e-18		T	1.19
rs113993960	2e-12	CFTR	?	1.71
chr17:76736877	3e-10		T	1.58
chr17:8227000	6e-10		CGG	1.85
chr15:90088702	9e-10		T	1.96
chr15:57104435	7e-09		CTT	0.11
chr2:466003	1e-08		A	0.13
chr7:131412073	2e-08		C	1.95
chr2:197402110	2e-08		C	1.72
chr12:60124253	4e-08		T	2.37
chr12:61228433	4e-08		T	2.37
chr6:81925832	4e-08		T	1.43
rs377402665	3e-07	GNAI2P1 - RPL30P11	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90474172	UK Biobank Whole-Genome Sequencing Consortium	2025	24,174	434,266	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90667780	UK Biobank Whole-Genome Sequencing Consortium	2025	24,174	434,266	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90446417	Chen Y	2024	22,385	420,797	The performance of AlphaMissense to identify genes influencing disease.
GCST90446418	Chen Y	2024	22,385	420,797	The performance of AlphaMissense to identify genes influencing disease.
GCST90080580	Backman JD	2021	7,925	379,873	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084566	Backman JD	2021	7,925	379,873	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90080579	Backman JD	2021	7,852	380,074	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084565	Backman JD	2021	7,852	380,074	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90652060	Liu TY	2025	4,026	202,534	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90044221	Jiang L	2021	1,199	455,149	A generalized linear mixed model association tool for biobank-scale data.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	1
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	12

MAF distribution

Bucket	Variants
common (>=0.05)	1
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	12

Functional consequences

Consequence	Count
unknown	11
inframe_insertion	1
intergenic_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
chr9:5073770							1e-18	Tier 4: intronic/intergenic
rs113993960	7	117559591	ATCT>A,ATCTTCT	0.05	inframe_insertion	CFTR	2e-12	Tier 1: coding
chr17:76736877							3e-10	Tier 4: intronic/intergenic
chr17:8227000							6e-10	Tier 4: intronic/intergenic
chr15:90088702							9e-10	Tier 4: intronic/intergenic
chr15:57104435							7e-09	Tier 4: intronic/intergenic
chr2:466003							1e-08	Tier 4: intronic/intergenic
chr7:131412073							2e-08	Tier 4: intronic/intergenic
chr2:197402110							2e-08	Tier 4: intronic/intergenic
chr12:60124253							4e-08	Tier 4: intronic/intergenic
chr12:61228433							4e-08	Tier 4: intronic/intergenic
chr6:81925832							4e-08	Tier 4: intronic/intergenic
rs377402665	12	14340062	T>C		intergenic_variant	GNAI2P1 - RPL30P11	3e-07	Tier 4: intronic/intergenic

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
986742	NM_003680.4(YARS1):c.611A>C (p.Tyr204Ser)	YARS1	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
YARS1	Orphanet:100045	Autosomal dominant intermediate Charcot-Marie-Tooth disease type C

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
YARS1	HGNC:12840	ENSG00000134684	P54577	Tyrosine–tRNA ligase, cytoplasmic	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
YARS1	Tyrosine–tRNA ligase, cytoplasmic	Tyrosine–tRNA ligase that catalyzes the attachment of tyrosine to tRNA(Tyr) in a two-step reaction: tyrosine is first activated by ATP to form Tyr-AMP and then transferred to the acceptor end of tRNA(Tyr).

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
YARS1	Enzyme (other)	yes	6.1.1.1	aa-tRNA-synth_Ic, Tyr-tRNA-ligase, tRNA-bd_dom

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
islet of Langerhans	1
left adrenal gland	1
right adrenal gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
YARS1	290	ubiquitous	marker	islet of Langerhans, right adrenal gland, left adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
YARS1	4,793

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
YARS1	P54577	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Cytosolic tRNA aminoacylation	1	439.2×	0.007	YARS1
tRNA Aminoacylation	1	285.5×	0.007	YARS1
Translation	1	62.1×	0.021	YARS1
Metabolism of proteins	1	12.4×	0.081	YARS1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
tyrosyl-tRNA aminoacylation	1	16852.0×	2e-04	YARS1
response to starvation	1	468.1×	0.003	YARS1
apoptotic process	1	28.7×	0.035	YARS1

Therapeutics

Drugs indicated or in trials for this disease

1 approved drug — disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Status
Mannitol	Approved (phase 4)

37 drugs in clinical trials for this disease (phase 2–3, investigational): efficacy not established — a trial record, not an indication.

Drug	Highest phase
Acetylcysteine	Phase 3
Alanyl Glutamine	Phase 3
Dapagliflozin	Phase 3
Deferiprone	Phase 3
Epoetin Beta	Phase 3
Fenoldopam	Phase 3
Heparin Sodium	Phase 3
Irbesartan	Phase 3
Ketanserin	Phase 3
Levocarnitine	Phase 3
Melatonin	Phase 3
Nafamostat	Phase 3
Nesiritide	Phase 3
Nitric Oxide	Phase 3
Oxygen	Phase 3
Sodium Bicarbonate	Phase 3
Sodium Chloride	Phase 3
Spironolactone	Phase 3
Alprostadil	Phase 2
Atorvastatin	Phase 2
Calcitriol	Phase 2
Conestat Alfa	Phase 2
Cyclosporine	Phase 2
Darbepoetin Alfa	Phase 2
Dexmedetomidine	Phase 2
Furosemide	Phase 2
Heme Arginate	Phase 2
Insulin Human	Phase 2
Iohexol	Phase 2
Levosimendan	Phase 2
Nicotinamide Riboside	Phase 2
Pentoxifylline	Phase 2
Relmapirazin	Phase 2
Sevoflurane	Phase 2
Teprasiran	Phase 2
Terevalefim	Phase 2
Vitamin E	Phase 2

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
YARS1	CAPSAICIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
YARS1	2	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CAPSAICIN	4	YARS1
CRENOLANIB	3	YARS1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
YARS1	16	Binding:16

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
YARS1	6.1.1.1	tyrosine-tRNA ligase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

2 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
CAPSAICIN	4	YARS1
CRENOLANIB	3	YARS1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	YARS1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 1,261.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	810
PHASE4	87
PHASE2	82
PHASE3	57
PHASE2/PHASE3	24
PHASE1	20
PHASE1/PHASE2	13
EARLY_PHASE1	7

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04592744	PHASE4	ENROLLING_BY_INVITATION	Angiotensin 2 for AKI After OLT
NCT04705896	PHASE4	RECRUITING	Albumin To Enhance Recovery After Acute Kidney Injury
NCT05429515	PHASE4	NOT_YET_RECRUITING	Effect of HFR-SUPRA in the Treatment of Multiple Myeloma-related Acute Kidney Injury
NCT05590143	PHASE4	ACTIVE_NOT_RECRUITING	proMoting Effective Renoprotection in Cardiac sURgery Patients by Inhibition of SGLT-2
NCT06229990	PHASE4	RECRUITING	A Protocol Based-Furosemide Stress Test to Evaluate Renal Recovery During Continuous Renal Replacement Therapy
NCT06418542	PHASE4	ACTIVE_NOT_RECRUITING	Contrast Nephropathy Associated FFA
NCT06521697	PHASE4	NOT_YET_RECRUITING	Effects of Minimal-Flow Sevoflurane and Multimodal Analgesia in Head and Neck Cancer Surgery
NCT06535945	PHASE4	RECRUITING	Influence of Human Albumin Supplementation on Kidney Dysfunction After Liver Transplantation
NCT06570187	PHASE4	RECRUITING	The Effect of Dexmedetomidine on the Renal Functions in Septic Critically Ill Patients
NCT06696235	PHASE4	RECRUITING	Accelerated vs. Standard Continuous Renal Replacement Therapy for Patients With Cardiogenic Shock Undergoing Veno-arterial ExtraCorporeal Membrane Oxygenator
NCT06802224	PHASE4	RECRUITING	The Choice of Vasopressor to Prevent Postoperative Acute Kidney Injury After Major Non-Cardiac Surgery
NCT06954129	PHASE4	RECRUITING	A Pragmatic Clinical Trial Comparing the Risk of Acute Kidney Injury During Treatment With Vancomycin and Piperacillin-Tazobactam vs. Vancomycin and Cefepime in Hospitalized Patients
NCT07030933	PHASE4	NOT_YET_RECRUITING	Amino Acid Infusion in Cardiac Surgery
NCT07182422	PHASE4	RECRUITING	AST-120 (Kremezin®) for the Renal Protection and Attenuation of Decline in Acute Kidney Disease
NCT07464431	PHASE4	NOT_YET_RECRUITING	Sodium Bicarbonate for Critically Ill Patients With Metabolic Acidosis and Acute Kidney Injury
NCT07518303	PHASE4	NOT_YET_RECRUITING	Nafamostat Mesylate Versus Regional Citrate Anticoagulation for Continuous Renal Replacement Therapy in Sepsis-Associated Acute Kidney Injury
NCT07556107	PHASE4	NOT_YET_RECRUITING	The Vancomycin Piperacillin/Tazobactam (VPT) Patient Safety Trial (VPS)
NCT00221013	PHASE4	COMPLETED	Augmented Vs. Normal Renal Replacement Therapy in Severe Acute Renal Failure (ARF).
NCT00264355	PHASE4	COMPLETED	Metabolic Pattern of Cyclosporine A and Acute Renal Failure
NCT00264368	PHASE4	TERMINATED	Ganciclovir Pharmacokinetics in Patients Undergoing Continuous Renal Replacement Therapy
NCT00286273	PHASE4	COMPLETED	Safety and Efficacy of the Use of Regional Anticoagulation With Citrate in Continuous Venovenous Hemofiltration
NCT00334204	PHASE4	TERMINATED	Does An Abnormal PFA 100 Predict Bleeding After Renal Biopsy?
NCT00384995	PHASE4	TERMINATED	Bicarbonate v Saline to Prevent Contrast Nephropathy
NCT00529139	PHASE4	COMPLETED	Hannover Dialysis Outcome Study
NCT00675818	PHASE4	COMPLETED	The Optimal Mode of Renal Replacement Therapy in Acute Kidney Injury (OMAKI) Study
NCT00816790	PHASE4	TERMINATED	Standard Vs Adjusted Dosing of Piperacillin/Tazobactam in Acute Renal Failure and Septic Shock
NCT00837057	PHASE4	UNKNOWN	Early Continuous Renal Replacement Therapies (CRRT) in Patients With Severe Sepsis or Septic Shock With Acute Kidney Injury
NCT00877370	PHASE4	COMPLETED	Pharmacokinetics of Ertapenem in Continuous Venovenous Hemodialysis
NCT00890214	PHASE4	COMPLETED	Prostacyclin’s Effect on Platelet Responsiveness
NCT00965328	PHASE4	COMPLETED	Nadroparin Anticoagulation for Continuous Venovenous Hemofiltration
NCT01228292	PHASE4	UNKNOWN	Comparison of Slow Efficiency Daily Dialysis (SLEDD) With Unfractionated Heparin Versus Citrasate in Critically Ill Patients.
NCT01269112	PHASE4	COMPLETED	Citrate-based Regional Anticoagulation Versus Heparin for Continuous Renal Replacement Therapy
NCT01318811	PHASE4	TERMINATED	A Comparison of Dilute Versus Concentrated Heparin for CRRT Anticoagulation
NCT01560650	PHASE4	COMPLETED	Effect of the Intensity of Continuous Renal Replacement Therapy in Patients With Acute Kidney Injury
NCT01594489	PHASE4	COMPLETED	Aminophylline and Contrast Induced Nephropathy in Acute Myocardial Infarction
NCT01722513	PHASE4	UNKNOWN	Efficacy and Safety of Alprostadil Prevent Contrast Induced Nephropathy
NCT01761994	PHASE4	COMPLETED	The Effect of Nafamostat Mesilate in Prolonging Filter Patency With Patients on Continuous Renal Replacement Therapy
NCT01866397	PHASE4	COMPLETED	Pharmacokinetics of Cidofovir During Continuous Venovenous Hemofiltration
NCT01886079	PHASE4	UNKNOWN	The Effects of Dexmedetomidine on Postoperative Renal Function in Valvular Heart Surgery
NCT01920126	PHASE4	COMPLETED	The Effect of Sodium Bicarbonate on Postoperative Renal Function in Infective Endocarditis Patients Undergoing Open Heart Surgery

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
SODIUM BICARBONATE	4	10
IOPAMIDOL	4	7
AMINOPHYLLINE	4	6
ANGIOTENSIN II	4	6
FUROSEMIDE	4	6
IOHEXOL	4	6
CILASTATIN	4	5
FENOLDOPAM	4	5
TERLIPRESSIN	4	5
NITRIC OXIDE	4	4
ACETYLCYSTEINE	4	3
ALBUMIN HUMAN	4	3
CITRIC ACID	4	3
DEXMEDETOMIDINE	4	3
EMPAGLIFLOZIN	4	3
HEPARIN	4	3
NIACINAMIDE	4	3
NOREPINEPHRINE	4	3
PIPERACILLIN	4	3
VASOPRESSIN	4	3
AMBRISENTAN	4	2
ASCORBIC ACID	4	2
CIDOFOVIR ANHYDROUS	4	2
CYCLOSPORINE	4	2
DAPAGLIFLOZIN	4	2
DEFEROXAMINE	4	2
IODOHIPPURATE	4	2
MANNITOL	4	2
MIDODRINE	4	2
PANTOPRAZOLE	4	2