GnRH agonist
Leuprolide
Lupron · Leup
GnRH agonist · approved 1985 · 5 references
GnRH agonist whose kidney risk is indirect — metabolic syndrome, bone loss and cardiovascular strain.
- Signature injury
- Hypertension
- Severity
- Mild
- Reversibility
- Variable
- Onset
- Months to years (metabolic/cardiovascular and skeletal).
Signature kidney injury & incidence
Hypertension — representative incidence ~14.6%.
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
Reported injury signatures: Hypertension.
Onset timing & rechallenge
Delayed (>6 weeks / cumulative) — Metabolic/cardiovascular and skeletal effects emerge over months to years.
Mechanism of kidney injury
Clinical presentation
Management
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
Renal dose adjustment
Dialyzability & ESKD dosing
Differential diagnosis
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.
Anticancer mechanism
Note
Guidelines & consensus
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.
- ADQI (2026) — The nephrotoxic effects of anti-cancer therapies: consensus report of the 34th Acute Disease Quality Initiative workgroupProvides 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.Nat Rev Nephrol · PMID 41361704
- SIRM (2022) — SIRM-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)Recommends 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.Radiol Med · PMID 35303246
- KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancerIdentifies 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.Kidney Int · PMID 33126977
- KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantationAddresses 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.Kidney Int · PMID 33276867
- ADDIKD (2025) — Integrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practiceProvides 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.EClinicalMedicine · PMID 40290844
- ADDIKD (2025) — Aligning kidney function assessment in patients with cancer to global practices in internal medicineThree 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.EClinicalMedicine · PMID 40290845
- ADDIKD (2025) — A methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney functionEstablishes 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.EClinicalMedicine · PMID 40290846
- KDIGO (2013) — Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)Defines/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.Crit Care · PMID 23394211
- KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknownsEvaluate 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.Kidney Int · PMID 38519239
- KDIGO (2021) — Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular DiseasesProvides 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.Kidney Int · PMID 34556300
- KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated VasculitisUpdates 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.Kidney Int · PMID 38388147
- KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus NephritisUpdates 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.Kidney Int · PMID 38182299
- KDIGO (2025) — Executive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)Encourages 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.Kidney Int · PMID 40975525
References
5 peer-reviewed references. Citation metadata via PubMed / NLM.
- 1.A phase 3, open-label, multicenter study of a 6-month pre-mixed depot formulation of leuprolide mesylate in advanced prostate cancer patients.Shore N et al. · World Journal of Urology · 2020 · PMID 30941562
- 2.GnRH antagonist associates with less adiposity and reduced characteristics of metabolic syndrome and atherosclerosis compared with orchiectomy and GnRH agonist in a preclinical mouse model.Hopmans SN et al. · Urol Oncol · 2014 · PMID 25242517
- 3.The Cardiovascular Toxicity of Abiraterone and Enzalutamide in Prostate Cancer.Iacovelli R et al. · Clin Genitourin Cancer · 2017 · PMID 29339044
- 4.Cardiovascular Events and Androgen Receptor Signaling Inhibitors in Advanced Prostate Cancer: A Systematic Review and Meta-Analysis.El-Taji O et al. · JAMA Oncol · 2024 · PMID 38842801
- 5.Conventional Chemotherapy Nephrotoxicity.Gupta S et al. · Adv Chronic Kidney Dis · 2021 · PMID 35190107
Case reports & series (3)
The weakest rung of clinical evidence — single-patient and small-series reports, strongest first. Each carries a heuristic strength grade (A Strong / B Moderate / C Limited) inferred from its abstract and journal, not a formal appraisal. Weigh well below the primary references above.
- C1.[B · Moderate]Successful recovery from multiple organ failure associated with bicalutamide and leuprorelin acetate for prostate cancer.Saito S · Urol Case Rep · 2020 · PMID 31934548
- C2.[C · Limited]Tumor lysis syndrome in anti-androgen-treated metastatic prostate cancer.Mazzoni S · Int Urol Nephrol · 2016 · PMID 27417133
- C3.[C · Limited]Fatal spontaneous tumor lysis syndrome in a patient with metastatic, androgen-independent prostate cancer.Lin CJ et al. · South Med J · 2007 · PMID 17902299