Pamidronate

Glomerular Injury / Proteinuria — representative incidence ~7.7%.

Not well quantified; the histopathologic pattern comes from case series, notably at higher-than-approved doses. Reported rate: renal deterioration in 7.7% — Patients with multiple myeloma or metastatic breast cancer receiving 1-hour intravenous pamidronate infusions, British… (de 2006, PMID 17156591).

Source: de Lemos et al., J Oncol Pharm Pract 2006

Reported injury signatures: Glomerular Injury / Proteinuria.

Delayed (>6 weeks / cumulative) — Develops over months to years of therapy (15–48 months in the Markowitz 2001 series).

• High dose
• Prolonged use
• Pre-existing CKD

• Use approved doses

• Check serum creatinine before each pamidronate dose and hold the next dose for any deterioration from baseline (label-recommended interruption threshold).
• Screen for proteinuria (urine protein/creatinine ratio or dipstick) at baseline and serially — new nephrotic-range proteinuria is the hallmark of collapsing FSGS and warrants stopping the drug and nephrology referral.
• Monitor serum calcium, phosphate, magnesium, and potassium, since correcting hypercalcemia can unmask hypocalcemia and electrolyte shifts.
• Verify infusion duration and dose against the order each cycle — rapid or supratherapeutic infusion is the dominant modifiable nephrotoxicity risk.

• Markowitz et al. (J Am Soc Nephrol 2001, PMID 11373339) — the landmark clinicopathologic case series establishing high-dose pamidronate as the first drug definitively linked to collapsing focal segmental glomerulosclerosis with nephrotic-range proteinuria and podocyte injury.
• Berenson 'Aredia' pivotal myeloma/bone-metastasis trial (Berenson et al., N Engl J Med 1996) — the registrational randomized trial of 90 mg pamidronate that established efficacy for skeletal events and the labeled dose/infusion that nephrotoxicity recommendations are anchored to.

• Pamidronate was the first drug ever causally linked to collapsing FSGS — a true sentinel association in drug-induced nephrotoxicity.
• Patients in the landmark series presented already in renal failure — mean creatinine 3.6 mg/dL and 12.4 g/d of protein after 15-48 months of therapy — so prevention (correct dose, slow infusion, hydration) outweighs rescue.
• New or rising proteinuria — not just a creatinine bump — is the earliest actionable signal; a falling albumin with edema should prompt discontinuation rather than dose continuation.
• In patients needing antiresorptive therapy with established glomerular injury or advanced CKD, the RANKL antibody denosumab is the kidney-sparing alternative (watch for hypocalcemia instead).

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.

• ASCO / CCO (2017) — Role of Bone-Modifying Agents in Metastatic Breast Cancer: An American Society of Clinical Oncology-Cancer Care Ontario Focused Guideline UpdateEndorses denosumab 120 mg SC q4w, pamidronate 90 mg IV q3-4w, or zoledronic acid 4 mg IV q12w or q3-4w; nitrogen bisphosphonates require renal function monitoring and dose/interval adjustment for impaired clearance, whereas denosumab needs no renal dose adjustment (with hypocalcemia risk in CKD).J Clin Oncol · PMID 29035643
• 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