Landmark evidence
The seminal studies of anti-cancer-drug kidney injury, each reduced to the single figure that made it matter — the incidence that named a syndrome, the effect size that proved a link, the trial that set a standard of care. Every number is quoted from a real PubMed record and was checked against that paper's own abstract; none is invented or estimated.
42 studies across 12 fields. Educational reference, not medical advice — see methods for how the atlas sources its citations.
Showing 42 of 42 landmark studies.
The podocyte-VEGF axis: proteinuria, hypertension, and thrombotic microangiopathy.
Podocyte-specific VEGF-A heterozygosity (~50% loss) caused proteinuria + glomerular endotheliosis by 2.5 weeks of age
The founding mechanistic paper of the field. Years before anti-VEGF drug nephrotoxicity was recognized, it showed that glomerular VEGF is dose-critical for the filtration barrier, predicting why pharmacologic VEGF blockade would injure the podocyte-endothelial axis and cause proteinuria/endotheliosis.
Deleting VEGF from mouse podocytes reproduced 'a profound thrombotic glomerular injury' matching 6 bevacizumab-treated patients
The paper that named 'VEGF inhibition and renal thrombotic microangiopathy,' establishing anti-VEGF kidney injury as a direct, on-target podocyte-VEGF effect. It is the mechanistic bedrock the entire anti-VEGF nephrotoxicity literature builds on.
Relative risk 4.79 (95% CI 2.71 to 8.46) for high-grade proteinuria; nephrotic syndrome RR 7.78 (95% CI 1.80 to 33.62)
The definitive quantification of bevacizumab proteinuria risk — the reference meta-analysis clinicians cite for the magnitude of severe proteinuria and nephrotic syndrome on anti-VEGF therapy, and evidence of dose- and tumor-dependence.
High-grade hypertension RR 5.28 (95% CI 4.15-6.71); all-grade hypertension incidence 23.6% (95% CI 20.5-27.1)
The large-scale reference meta-analysis for bevacizumab-induced hypertension — the numbers routinely quoted for both the incidence and the magnitude of anti-VEGF hypertension, cementing blood-pressure monitoring as standard of care.
Immune-mediated acute interstitial nephritis and its steroid response.
Acute tubulointerstitial nephritis in 12 of 13 biopsied patients, at a median of 91 days after checkpoint-inhibitor initiation
The founding description of checkpoint-inhibitor nephritis. It established acute interstitial nephritis as the signature lesion and set the diagnostic-and-steroid template that every subsequent multicenter cohort was built upon.
30 of 1016 (3%) had potential checkpoint-inhibitor-related AKI; 169 (17%) developed any AKI and 82 (8%) sustained AKI within 12 months
It anchored the field's incidence estimates by separating the frequent, heterogeneous 'any AKI' signal from the smaller ICI-attributable fraction across a complete single-center population of 1016 recipients, and first flagged PPIs as a modifiable risk factor.
ICI rechallenge occurred in 22% of patients, of whom 23% developed recurrent associated AKI; tubulointerstitial nephritis was the dominant lesion in 93% of the 60 patients biopsied
It turned single-center description into generalizable, independently associated risk factors and provided the first real rechallenge estimate: most patients rechallenged did NOT recur, reframing ICI-AKI as frequently not an absolute contraindication to resuming immunotherapy.
Corticosteroids within 14 days of ICPi-AKI diagnosis associated with renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41); recovery in 276 of 429 patients (64.3%)
This is the definitive evidence base for treating ICI-AKI with corticosteroids and treating early; its effect size is the figure guidelines cite for steroid management, and it also showed rechallenge did not worsen survival.
Cisplatin acute tubular necrosis and magnesium wasting.
Hypomagnesemia in 23 of 44 evaluable patients (~52%) receiving cisplatin
The founding systematic clinical description of cisplatin renal magnesium wasting. It defined a signature electrolyte lesion of platinum therapy and created the enduring standard of routine magnesium monitoring and repletion during cisplatin chemotherapy.
Cisplatin-AKI in 13.6% (development cohort) and 11.6% (validation cohort) after the first course
The first validated bedside risk score for cisplatin AKI. It notably found that baseline kidney function did not predict risk, shifting risk stratification toward age, dose, hypertension and albumin, and became the reference model later cohorts were benchmarked against.
Severe CP-AKI incidence 5.2% (608/11,766) derivation and 3.3% (421/12,951) validation across 24,717 patients at six centers
The definitive modern incidence and risk-stratification study for cisplatin nephrotoxicity, spanning 24,717 adults across six US cancer centers, and it linked greater CP-AKI severity to markedly worse 90-day survival (adjusted HR 4.63 for stage 3).
CP-AKI or death in 2.7% (104/3893) with IV magnesium vs 5.3% (520/9826) without; adjusted odds ratio 0.80
The largest study to date supporting magnesium prophylaxis for cisplatin nephrotoxicity, connecting Schilsky's 1979 observation of renal magnesium wasting to a concrete, low-cost renoprotective intervention.
Anti-EGFR magnesium wasting and cancer electrolyte disorders.
8 of the 154 cetuximab-treated patients reviewed had grade 3-4 hypomagnesemia (6 grade 3, 2 grade 4) — but only 34 (22%) had a serum magnesium drawn at all, so 8/34 overstates the rate and 8/154 understates it; testing was not systematic and the series yields no true incidence
The index report that put anti-EGFR hypomagnesemia on the clinical map, prompting routine serum-magnesium monitoring and supplementation on cetuximab and framing the renal-reabsorption hypothesis that later work confirmed.
EGF identified as a magnesiotropic hormone that activates TRPM6 via the EGFR — the molecular basis explaining cetuximab-induced hypomagnesemia
The founding mechanistic paper of the field: it supplies the EGF to EGFR to TRPM6 pathway that explains the entire anti-EGFR-antibody class effect on magnesium, connecting a rare Mendelian disorder to an on-target drug toxicity.
Hyponatremia in 47% of admissions (36% mild, 10% moderate, 1% severe); 90-day mortality HR 2.04 / 4.74 / 3.46
The landmark cohort quantifying how common hyponatremia is on a cancer ward and tying it to 90-day mortality, making sodium a prognostic marker in oncology. Two limits travel with it: the study stratified admissions by sodium band and adjudicated no causes, so it says nothing about which mechanism dominates; and the mortality signal is not a clean gradient — the hazard ratio peaks at moderate hyponatremia (4.74) rather than severe (3.46).
All-grade hypomagnesemia incidence 34.0% across 16,411 patients in 25 RCTs
The broadest quantitative estimate of the electrolyte-disorder burden of the anti-EGFR-antibody class, anchoring the ~one-third all-grade hypomagnesemia figure across 16,000-plus randomized patients and formalizing the monitoring imperative.
High-dose methotrexate crystal nephropathy and glucarpidase rescue.
1.8% (68 of 3,887 osteosarcoma patients) developed grade ≥2 nephrotoxicity; 4.4% (3 of 68) of those died
The foundational cohort that put a hard number on how often HD-MTX injures the kidney and how lethal it can be; it is the incidence figure the field still cites and it made the case that carboxypeptidase-G2 (glucarpidase), not hemodialysis, is the rescue of choice for delayed MTX excretion.
Plasma methotrexate fell 98.7% within 15 minutes of glucarpidase
The pivotal clinical/pharmacologic dataset behind glucarpidase's use in HD-MTX renal failure — it proved both the speed/magnitude of MTX clearance and, critically, that outcome hinges on giving the enzyme early rather than late.
Acute kidney injury occurs in 2%–12% of patients receiving high-dose methotrexate
The most widely used practical reference for HD-MTX toxicity; its 2%–12% AKI figure and management framework became the default teaching and protocol basis for administering HD-MTX safely across adult and pediatric cancers.
Pamidronate collapsing FSGS and zoledronate acute tubular necrosis.
7 patients (the first reported series)
The founding paper of the field. Until this series, collapsing FSGS was a diagnosis of young African-American, HIV-positive, or idiopathic patients; Markowitz established the first drug etiology for it, putting high-dose IV aminobisphosphonate on the nephrotoxicity map and creating the entity 'pamidronate-associated collapsing FSGS' that every later description references.
serum creatinine rose from a mean baseline of 1.4 mg/dL to 3.4 mg/dL (n=6)
Founded the second, distinct bisphosphonate kidney injury and — crucially — showed it was NOT collapsing FSGS despite all six patients' prior pamidronate exposure. This established the drug-specific dichotomy (zoledronate → toxic ATN, pamidronate → collapsing FSGS). Its reversibility half is what underpins checking creatinine before each dose: all six improved after withdrawal. It demonstrates no dose or infusion-rate gradient and cannot — every patient received the identical labeled 4 mg over at least 15 minutes, so the injury occurred at correct dosing.
two distinct, drug-specific injury patterns: toxic ATN (zoledronate) vs collapsing FSGS (pamidronate)
The reference review that fused the two founding biopsy descriptions into the single clinical framework clinicians and this atlas use. It made the entity-per-drug dichotomy the standard teaching and articulated why oral and osteoporosis-dose bisphosphonates are largely spared (lower dose, longer intervals).
Which anti-cancer drugs cause thrombotic microangiopathy, and by what evidence.
risk of cancer-associated HUS after mitomycin between 4% and 15% (85 registry cases, mitomycin in 84, >50% mortality)
The landmark registry that defined mitomycin-associated HUS/TMA as a distinct, dose-dependent, frequently fatal syndrome — the founding cohort for chemotherapy-induced thrombotic microangiopathy and the reason cumulative-dose monitoring entered mitomycin practice.
crude overall incidence 0.015% (range, 0.008-0.078%) among 78,800 gemcitabine-exposed patients
The founding quantification of gemcitabine HUS/TMA risk; the ~0.015% figure remains the anchor incidence clinicians cite when weighing gemcitabine's renal danger, and it converted case-report suspicion into a defensible denominator.
22 of 78 drugs had definite causal evidence for TMA (20 more probable)
The reference drug-induced-TMA systematic review: its definite/probable/possible evidence-grading framework became the field standard for adjudicating whether a given anti-cancer agent truly causes TMA, replacing scattered anecdote with a reproducible causal threshold that every later cohort is measured against.
The defining classification, risk model, and rasburicase trials.
86% vs 12% reduction in plasma uric acid 4 hours after the first dose (rasburicase vs allopurinol); uric-acid AUC(0–96) 128±70 vs 329±129 mg/dL·h, P < .0001
The landmark pediatric RCT that established recombinant urate oxidase as superior to allopurinol and drove FDA approval of rasburicase — the practice-changing trial that redefined hyperuricemia prophylaxis in high-risk malignancy.
Unifies the 5 metabolic derangements of TLS (hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia, uremia) into a single laboratory + graded clinical (grade 0–V) classification
Before this paper there was no standardized definition; the Cairo–Bishop classification became the reference definition used in essentially every subsequent TLS guideline, trial, and cohort, making outcomes comparable across studies.
Three-tier risk model (high / intermediate / low) driving prophylaxis — high-risk = hydration + prophylactic rasburicase; low-risk = monitoring
The Coiffier et al. consensus became the internationally cited practice standard for TLS prevention, codifying rasburicase for high-risk patients and settling the alkalinization debate — the guideline clinicians reference at the bedside.
Plasma uric-acid response 87% with rasburicase vs 66% with allopurinol (P = .001); 90% vs 53% in baseline-hyperuricemic patients
The pivotal adult phase III RCT that extended the pediatric rasburicase evidence to adults and underpinned adult guideline recommendations and regulatory use of rasburicase in high-risk TLS.
Acute kidney injury after CAR-T and its link to cytokine release.
30% cumulative incidence of any-grade AKI by day 100 (95% CI 16.9–43.9%); grade 2–3 in only 8.7%, no renal replacement therapy
The founding cohort that put AKI after CAR-T on the map. Its 'low incidence and rapid recovery' framing plus the explicit CRS link became the reference point for essentially every subsequent onco-nephrology discussion of cellular therapy.
154 of 694 patients (22%) developed AKI across 15 studies; of those 154, stage 1 in 89 (57.8%), stage 2/3 in 59 (38.3%), and renal replacement therapy in 16 (10.4%) — most recovered with symptomatic treatment
The reference synthesis clinicians cite for how often AKI complicates CAR-T and how severe it tends to be, pulling the scattered single-center cohorts into one field-level figure. Read it as a crude sum, not a pooled estimate: the counts are simple totals across the 15 studies with no random-effects model and no confidence interval, and PubMed indexes the record as a Review rather than a Meta-Analysis.
Severe CRS associated with AKI: OR 16.4 (95% CI 1.9–138.5), p=0.01; severe AKI predicted worse survival (HR 18.2, 95% CI 2.6–27.3)
Pins the CRS→AKI link to a striking effect size and closes the loop to survival, cementing severe CRS as the dominant driver of kidney injury after CAR-T rather than an incidental association.
Treating the myeloma kidney and the concept of MGRS.
Renal response in 62% of patients (renal CR 31%, renal PR 7%, renal MR 24%); median GFR rose from 20.5 to 48.4 mL/min
One of the first prospective demonstrations that a bortezomib-based regimen can rapidly reverse severe light-chain AKI, cementing bortezomib as the chemotherapy backbone for myeloma kidney and showing renal impairment is often reversible with the right anti-clone therapy.
Introduced the term 'monoclonal gammopathy of renal significance' (MGRS) — a new disease category carved out of MGUS
The field-founding paper that separated MGRS from 'benign' MGUS, establishing that the nephrotoxic monoclonal immunoglobulin itself — not tumor burden — is the treatment indication. It reframed how nephrologists and hematologists approach paraprotein kidney disease.
Dialysis independence at 3 months: 41.3% (n=19) with high-cutoff hemodialysis vs 33.3% (n=16) with conventional hemodialysis — not statistically significant
The definitive randomized trial testing whether aggressive extracorporeal free-light-chain removal adds anything to bortezomib-based chemotherapy. Its negative primary endpoint moved cast-nephropathy management away from the dialysis membrane and back to rapid, effective anti-myeloma therapy as the true lever on renal recovery.
Acute kidney injury and dialysis in the oncologic ICU.
309 of 975 (32%) developed acute renal dysfunction; 98 (32% of those) received dialysis
One of the first large prospective cohorts to quantify AKI frequency, dialysis requirement, and outcomes across BOTH solid and hematologic cancers in the ICU — and to document high renal recovery among survivors, key early evidence that intensive organ support is justified in cancer patients.
6-month complete remission 39.4% vs 68.3% with vs without AKI (P<0.01)
The landmark study linking AKI directly to CANCER outcomes rather than survival alone — by showing AKI compromised delivery of optimal chemotherapy and lowered remission, it reframed renal protection in the oncologic ICU as protection of oncologic efficacy.
671 of 1,009 (66.5%) developed AKI; adjusted OR for hospital death 1.65 (95% CI 1.19–2.29)
The definitive GRRR-OH primary dataset behind the field's canonical 'two-thirds develop AKI' figure. It showed hospital mortality in these patients now approaches that of the general ICU population, directly undercutting the historic therapeutic nihilism about dialyzing cancer patients.
How common kidney disease is in cancer, and what it costs in survival.
57.4% (Cockcroft-Gault) / 52.9% (aMDRD) had abnormal renal function, yet only 7.2% had an elevated serum creatinine (n=4,684)
The IRMA study was the first large (~5,000-patient) national prevalence survey of kidney function in cancer, and it reframed the field: most cancer patients with impaired GFR have a 'normal' creatinine, so GFR must be estimated, not assumed. It also exposed the downstream dosing crisis — over half of anticancer prescriptions required dose adaptation for renal function — making it the founding reference for renal dose-adjustment in oncology.
1-year AKI risk 17.5% (95% CI 17.1-17.9%); 5-year risk 27.0%; incidence 258 (95% CI 252-264) per 1,000 person-years in the first year
The population-based cohort that put a hard number on how often cancer patients develop AKI, using unselected registry linkage rather than a single center. It anchored the modern understanding that AKI is a common, cancer-type-dependent complication and became a reference incidence figure for the field. Regional rather than nationwide: Northern Denmark, about 1.2 million of the country's population, with AKI ascertained from a laboratory database covering that area.
12% of the 3,558 PATIENTS admitted over the 3-month window had AKI (RIFLE Risk 68%, Injury 21%, Failure 11%); dialysis in 4%; AKI carried 4.7-fold greater odds of death, with length of stay and cost each roughly doubled
A landmark single-center inpatient study that linked AKI incidence directly to a hard mortality signal in cancer patients, moving the field beyond 'AKI happens' to 'AKI kills.' Its RIFLE-based severity gradient and modifiable risk factors (IV contrast OR 4.55, chemotherapy OR 1.61) made it a cornerstone reference for onco-nephrology risk assessment.
AKI rate 27 per 1,000 person-years; overall cumulative incidence 9.3% (5-year incidence 26.0% in myeloma)
The definitive population-based cohort tying AKI to active systemic cancer treatment. It demonstrated both a treatment-proximate risk window and a rising secular trend, framing therapy-associated AKI as a growing, measurable public-health burden as more patients receive systemic therapy.