What kind of kidney injury does Leuprolide cause?

Hypertension — Raised blood pressure — archetypally on-target loss of endothelial nitric oxide from VEGF-pathway blockade, studied as a pharmacodynamic marker of drug exposure. Other agents raise it too: vascular effects of BCR-ABL, BTK and RET inhibitors and of copanlisib; abiraterone's mineralocorticoid excess; androgen suppression or blockade.

Is kidney injury from Leuprolide reversible?

Variable. Typical onset: Months to years (metabolic/cardiovascular and skeletal)..

How should kidney function be monitored during Leuprolide therapy?

Blood pressure, fasting lipids and glucose/HbA1c periodically; Weight/waist circumference; Bone density (DXA) and vitamin D; Cardiovascular risk reassessment.

How can kidney injury from Leuprolide be prevented?

Cardiovascular and metabolic risk-factor management Lifestyle modification; consider intermittent ADT where appropriate

Who is at higher risk of kidney injury from Leuprolide?

Pre-existing metabolic syndrome or diabetes; Established cardiovascular disease; Prolonged/continuous androgen deprivation; Older age; Baseline CKD.

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Printable monograph

GnRH agonist

Leuprolide

Lupron · Leup

GnRH agonist · approved 1985 · 8 citations

Recent· through 2024

Fairly sourced6/9 · 5 signals

Met: 8 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 17y)
Met: Beyond single case reports
Not met: Peer-reviewed sources
Met: Landmark reference
Met: Current through 2024
Not met: Real-world FAERS signal

Describes how this page is sourced, not how dangerous the drug is. Thinly sourced means fewer of the sourcing signals are met — not that the agent is kidney-safe. A rule-based summary, not a formal certainty appraisal.

GnRH agonist whose kidney risk is indirect — metabolic syndrome, bone loss and cardiovascular strain.

MildGnRH agonist (androgen deprivation)

Prostate cancerOther hormone-responsive tumors

§01

Signature kidney injury

Signature lesion

Hypertension

Representative incidence14.6%

No characteristic direct nephrotoxicity. Androgen-deprivation therapy is associated with metabolic syndrome, insulin resistance, dyslipidemia and increased cardiovascular disease, which raise long-term renovascular risk; a systematic review/meta-analysis confirms excess cardiovascular events with androgen-pathway therapy, and preclinical models show GnRH-agonist-induced metabolic syndrome and atherosclerosis. Reported rate: hypertension in 14.6% — 137 subjects with advanced prostate cancer indicated for androgen ablation, receiving leuprolide mesylate subcutaneous… (Shore 2020, PMID 30941562).Source: Shore et al., World J Urol 2020

Onset & rechallenge

Time to injuryDelayed (>6 weeks / cumulative)

Metabolic/cardiovascular and skeletal effects emerge over months to years.

Distilled from: “Months to years (metabolic/cardiovascular and skeletal).”

§02

Renal toxicities, ranked

This agent's defining kidney lesion — its #1 signature. Cited incidence is shown where a citable figure exists; otherwise the tier stands qualitatively.

Hypertension#1 · Signaturequalitative — no citable incidence
Raised blood pressure — archetypally on-target loss of endothelial nitric oxide from VEGF-pathway blockade, studied as a pharmacodynamic marker of drug exposure. Other agents raise it too: vascular effects of BCR-ABL, BTK and RET inhibitors and of copanlisib; abiraterone's mineralocorticoid excess; androgen suppression or blockade.

§03

Kidney injury

Mechanism of kidney injury

Profound testosterone suppression promotes visceral adiposity, dyslipidemia, insulin resistance and hypertension (a metabolic-syndrome phenotype), accelerating atherosclerosis and chronic renovascular and cardiovascular injury rather than acute tubular damage. The renal effect is therefore indirect and longitudinal — driven by the cardiometabolic consequences of hypogonadism, not by a tubular toxin. The initial testosterone flare is a tumor/symptom concern, not a renal one.

Clinical presentation

Weight gain, new dyslipidemia, rising blood pressure and impaired glucose tolerance over months to years; accelerated bone loss. No specific acute renal lesion; any GFR change is mediated through cardiometabolic disease.

Management

Manage hypertension, dyslipidemia and hyperglycemia per guideline targets; multidisciplinary cardiovascular risk reduction and bone protection. No drug-specific renal therapy.Lesion-level management framework

Risk factors

Pre-existing metabolic syndrome or diabetes
Established cardiovascular disease
Prolonged/continuous androgen deprivation
Older age
Baseline CKD

Prevention

Cardiovascular and metabolic risk-factor management
Lifestyle modification; consider intermittent ADT where appropriate

Anticancer mechanism· how it treats cancer

GnRH (LHRH) agonist that after an initial gonadotropin surge downregulates and desensitizes pituitary GnRH receptors, suppressing LH/FSH and gonadal sex-steroid production (medical castration). Used for prostate cancer and other hormone-responsive conditions.

Note · GnRH antagonists may carry a somewhat smaller cardiometabolic signal than agonists in some data.

§04

Clinical depth

Renal dose adjustment

No renal dose adjustment; leuprolide is a peptide cleared by peptidase/tissue metabolism and is dosed by depot interval, not renal function.

Dialyzability & ESKD dosing

Peptide depot formulation; not relevant to dialyzability and no ESKD dose change needed. The clinical focus in ESKD is cardiometabolic and bone management.

Differential diagnosis

Distinguish ADT-driven metabolic-syndrome hypertension/CKD from primary renovascular or diabetic kidney disease; an acute creatinine change is not expected from the drug and warrants an alternative explanation.

Monitoring

Blood pressure, fasting lipids and glucose/HbA1c periodically
Weight/waist circumference
Bone density (DXA) and vitamin D
Cardiovascular risk reassessment

Key trials & series

El-Taji JAMA Oncol 2024 systematic review/meta-analysis of cardiovascular events with androgen-pathway therapy
Hopmans Urol Oncol 2014 preclinical metabolic-syndrome/atherosclerosis model

Clinical pearls

Leuprolide injures the kidney only indirectly — through years of ADT-induced metabolic syndrome and atherosclerosis.
There is no acute renal lesion and no renal dose adjustment; the management is cardiometabolic and skeletal.
Screen for and treat hypertension, dyslipidemia, hyperglycemia and bone loss proactively in men on long-term ADT.
Pay extra attention to bone health in CKD patients on long-term ADT, who already carry a heightened fracture burden.

Where it strikes· nephron segments & injury signatures

Nephron segments

Vasculature / Endothelium

Glomerular & peritubular capillaries

Injury signatures

Hypertension

Beyond the kidney — non-renal toxicities· 3 organ systems

Class-level context for the major non-renal toxicities of the GnRH agonist class.

Cardiac

Cardiomyopathy, QT, ischemia, myocarditis

QT, hypertension, fluid retention

Musculoskeletal

Myalgia, myositis, rhabdomyolysis, ONJ

Bone loss, fatigue, hot flashes

Hepatic / Liver

Transaminitis, hepatitis, VOD/SOS

Transaminitis (abiraterone)

§05

References

5 primary references — trials, cohorts, mechanism, and reviews. Single-patient case reports are listed separately below, graded by strength. Citation metadata via PubMed / NLM.

Evidence accrual

5 references · 2014–2024 · 1 since 2022

Primary (non–case-report) references per year — a proxy for how actively the agent's renal literature is accruing. Recent years are highlighted. Reflects curation depth, not a systematic bibliometric count.

Case reports — ranked by strength· 3

Single-patient and small-series reports, graded by evidentiary strength — A Strong (biopsy-proven plus a series and/or positive rechallenge), B Moderate, and C Limited (a single clinically-diagnosed case). Strongest first. Grades are inferred automatically from each report's abstract and journal — a heuristic ranking aid, not a formal quality appraisal.

CaseB · ModerateSuccessful recovery from multiple organ failure associated with bicalutamide and leuprorelin acetate for prostate cancer.Saito S · Urol Case Rep 2020 · PMID 31934548Case of acute kidney injury with biopsy-proven drug-induced tubulointerstitial nephritis during combined androgen blockade with leuprorelin (leuprolide) plus bicalutamide, requiring hemodialysis and drug withdrawal.CaseC · LimitedTumor lysis syndrome in anti-androgen-treated metastatic prostate cancer.Mazzoni S · Int Urol Nephrol 2016 · PMID 27417133Case report of tumor lysis syndrome with consequent acute renal involvement in a metastatic prostate cancer patient on leuprolide-based anti-androgen therapy.CaseC · LimitedFatal spontaneous tumor lysis syndrome in a patient with metastatic, androgen-independent prostate cancer.Lin CJ et al. · South Med J 2007 · PMID 17902299Case report of fatal tumor lysis syndrome with acute renal failure in a leuprolide-treated metastatic prostate cancer patient.

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 78,546 of them for this agent. Nobody counts the patients who were fine, so none of these numbers is an incidence, a risk, or a rate: they describe what gets reported, shaped by a drug's fame, its indication, and who was watching. How these numbers work.

Reporting odds ratio (ROR) — is kidney injury named in this agent's reports more often than in every other drug's? Above 1 means yes, disproportionately.
Renal phenotypes — the same question asked separately for each kind of kidney injury, so the ratios differ from the overall one and from each other.
Outcomes — a share of this agent's own reports, not of patients: how many were filed as involving a death or a hospitalization. Not a case-fatality rate.

FAERS reported renal phenotypes· 2 signals

Only significant signals appear (95% CI lower bound above 1) — a phenotype missing here was tested and did not reach significance, except Prerenal / Hemodynamic AKI, Pseudo-AKI, Renal Cysts, Chronic Interstitial Nephropathy — outside the clinician-reviewed MedDRA term map, never queried — and ATN and AIN, queried but biopsy-bound: real cases are filed as generic “acute kidney injury”, so their absence is not a negative. As of 2026-10-01.

What reporting says about this profile's documented lesions

HypertensionNo disproportionate reporting — This phenotype IS reportable and this agent has enough reports, yet the reporting is not disproportionate — the one genuinely informative negative of the four.

Hemorrhagic Cystitis

ROR 1.9595% CI 1.79–2.13· 504 reports

Crystal / Obstructive Nephropathy

ROR 1.5795% CI 1.41–1.75· 327 reports

FAERS outcomes & reporting trend· 15.5% of reports w/ death · 15.6% w/ hospitalization

15.5%

Reported with a death outcome

12,171 of 78,546 reports

15.6%

Reported with hospitalization

12,254 of 78,546 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 7 systems · 78,546 reports

Bars rank systems by summed reaction-term mentions (a report counts once per term it names) — an ordinal “more vs less reported” cue, not a tally of distinct reports. Renal & urinary first. As of 2026-10-01.

Disproportionality (acute kidney injury):ROR 0.4095% CI 0.35–0.46· 230 AKI reports ·AKI is reported less often than for other drugs (CI entirely below 1) — no disproportionate signal.

General / constitutional

Fatigue5,182Injection Site Pain4,891Asthenia2,441Fall2,021Pain1,972

Vascular

Hot Flush9,599

Nervous system

Headache1,969Dizziness1,803

Musculoskeletal

Arthralgia1,982Pain In Extremity1,222

Gastrointestinal

Nausea1,798Abdominal Pain1,193

Psychiatric

Insomnia1,234

Respiratory

Dyspnoea1,185

Guidelines & consensus· 13

Each recommendation below is this atlas's faithful summary of the source, not a quotation from it — follow the PubMed link for the wording the society published. Summaries may be superseded; consult the current full text and individualize to the patient.

General onco-nephrology references

ADQIThe nephrotoxic effects of anti-cancer therapies: consensus report of the 34th Acute Disease Quality Initiative workgroupNat Rev Nephrol 2026 · PMID 41361704Provides expert-based statements (modified Delphi) on preventing and managing cisplatin/platinum-associated AKI, including isotonic IV hydration, attention to volume status and concomitant nephrotoxins, and incorporates evidence that IV magnesium supplementation may reduce cisplatin-associated AKI; emphasizes risk stratification and standardized AKI definitions.SIRMSIRM-SIN-AIOM: appropriateness criteria for evaluation and prevention of renal damage in the patient undergoing contrast medium examinations-consensus statements from Italian College of Radiology (SIRM), Italian College of Nephrology (SIN) and Italian Association of Medical Oncology (AIOM)Radiol Med 2022 · PMID 35303246Recommends eGFR-based renal risk assessment and pre/post-contrast isotonic saline or sodium bicarbonate hydration; advises maintaining a 5-7 day interval between iodinated contrast administration and cisplatin in cancer patients to reduce additive nephrotoxicity.KDIGOKDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancerKidney Int 2020 · PMID 33126977Identifies platinum compounds (especially cisplatin) as leading cytotoxic causes of acute tubular injury, AKI, and electrolyte/magnesium wasting; calls for interdisciplinary onco-nephrology care, accurate GFR estimation, and individualized drug dosing in patients with reduced kidney function.KDIGOKDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantationKidney Int 2020 · PMID 33276867Addresses chemotherapy-associated AKI/CKD in hematologic cancer, GFR estimation and chemotherapy dosing in patients with reduced kidney function, and management priorities and research gaps for onco-nephrology care.ADDIKDIntegrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practiceEClinicalMedicine 2025 · PMID 40290844Provides GRADE-based, drug-specific dose-adjustment recommendations for anticancer agents in kidney dysfunction (illustrated for methotrexate, cisplatin, carboplatin and nivolumab); the recommendations build on Part 1's standardised CKD-EPI eGFR assessment rather than Cockcroft-Gault creatinine clearance.ADDIKDAligning kidney function assessment in patients with cancer to global practices in internal medicineEClinicalMedicine 2025 · PMID 40290845Three consensus recommendations: assess kidney function by GFR (measured GFR or CKD-EPI eGFR), classify it using KDIGO categories, and use this uniform approach to dose anticancer drugs — moving cancer medicine away from Cockcroft-Gault estimated creatinine clearance.ADDIKDA methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney functionEClinicalMedicine 2025 · PMID 40290846Establishes that, where RCT evidence is lacking, anticancer drug dosing recommendations in kidney dysfunction should be derived by critically appraising observational literature via GRADE combined with structured international multidisciplinary consensus voting.KDIGODiagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)Crit Care 2013 · PMID 23394211Defines/stages AKI by serum creatinine and urine output; emphasizes avoiding nephrotoxins, maintaining euvolemia/perfusion, dose-adjusting drugs to kidney function, and monitoring high-risk patients — the framework applied to nephrotoxic anti-cancer agents.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknownsKidney Int 2024 · PMID 38519239Evaluate and risk-stratify CKD, manage to delay progression and its complications, and practise explicit medication management and drug stewardship — the framework the atlas's G1–G5 eGFR banding and every renal dose-adjustment recommendation sit inside. Because the guideline excludes dialysis and transplant recipients by its own statement of scope, its recommendations do not carry to those settings, where this atlas's dialyzability and post-transplant guidance rests on other sources.KDIGOExecutive summary of the KDIGO 2021 Guideline for the Management of Glomerular DiseasesKidney Int 2021 · PMID 34556300Provides the staging/treatment framework for drug-associated glomerular lesions (e.g., bisphosphonate- and interferon-related collapsing FSGS, VEGF-inhibitor podocytopathy/proteinuria), including immunosuppression and supportive RAAS-blockade strategies.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated VasculitisKidney Int 2024 · PMID 38388147Updates immunosuppressive induction (rituximab/cyclophosphamide), incorporates avacopan and lower-dose or glucocorticoid-sparing regimens — the management framework for drug- and checkpoint-inhibitor-associated ANCA/pauci-immune glomerulonephritis.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus NephritisKidney Int 2024 · PMID 38182299Updates first-line lupus nephritis therapy to combination immunosuppression with the addition of belimumab or a calcineurin inhibitor (voclosporin) — informs management of immune-complex/lupus-like glomerulonephritis encountered with immunotherapy.KDIGOExecutive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)Kidney Int 2025 · PMID 40975525Encourages liberal kidney biopsy and stricter proteinuria control (<0.5 g/d, ideally <0.3 g/d) with RAAS blockers, SGLT2 inhibitors, and targeted-release budesonide — the framework for IgA-dominant glomerular lesions, including those triggered by immune-modulating cancer therapy.

Where Leuprolide sits in nephrotoxicity space — each dot is an anti-cancer agent, positioned so neighbors share a kidney-injury phenotype. Its 6 closest are filled and lead to a numbered marker, matching the numbered cards below.

Position is a 2-D projection (MDS) of each agent's injury signature, nephron target, severity, and class, so two dots can sit close on the page while differing on an axis the projection flattened — the numbered ranking is computed from the full metric, not from the distance you see. Open the full map.

Phenotype-similar agents· the numbered markers on the map above

Ripretinib

Qinlock · KIT switch-control inhibitor

Profile

Hypertension and alopecia in GIST.

HTN

Mild#1 · 86% phenotype match

Copanlisib

Aliqopa · Pan-PI3K inhibitor

Profile

Transient infusion-related hypertension and hyperglycemia.

HTN

Moderate#2 · 81% phenotype match

Enzalutamide

Xtandi · Androgen-receptor inhibitor

Profile

Hypertension; rare electrolyte effects.

HTNLYTE

Mild#3 · 76% phenotype match

Asciminib

Scemblix · BCR-ABL STAMP inhibitor

Profile

Hypertension and pancreatitis; allosteric BCR-ABL inhibitor.

HTNPRE

Mild#4 · 62% phenotype match

Acalabrutinib

Calquence · BTK inhibitor

Profile

Tumor lysis; lower hypertension than ibrutinib.

HTNPREXTAL

Mild#5 · 57% phenotype match

Niraparib

Zejula · PARP inhibitor

Profile

Hypertension and creatinine rise.

HTNPSEUDO

Mild#6 · 54% phenotype match

Compare Leuprolide with its nearest agents

Nearest agents by kidney-injury phenotype (shared injuries, nephron target, severity, class) — a similarity approximation, not a claim of shared drug identity or mechanism.

Kidney risk across Hormonal / endocrine

Same-class agents ordered by their documented kidney-injury profile — atlas severity, an acute-kidney-injury FAERS signal, and how many injury types each is documented to cause. Agents nearer the top carry the lighter documented renal profile.

A comparison of documented kidney-injury data within one drug class — not a substitution recommendation. Efficacy, indication, and non-renal toxicity differ between these agents and are out of scope here. Educational only, not medical advice.