Endothelial activation syndrome (EAS) is an increasingly recognized complication of hematopoietic stem cell transplantation (HSCT) and includes transplant-associated thrombotic microangiopathy (TA-TMA), sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD), capillary leak syndrome, idiopathic pneumonia syndrome, and engraftment syndrome. Kidney involvement is common and may be an early marker of systemic endothelial dysfunction. We report a 53-year-old man with high-risk TP53-mutated B-cell acute lymphoblastic leukemia who underwent matched sibling donor allogeneic HSCT. Nine months after transplant, he developed persistent thrombocytopenia, microangiopathic hemolytic anemia, proteinuria, and declining kidney function, fulfilling criteria for high-risk TA-TMA. He initially improved with narsoplimab and supportive care, but his course was complicated by extramedullary leukemia relapse, inotuzumab exposure, progressive SOS/VOD with portal hypertension and ascites, and severe acute kidney injury superimposed on chronic kidney disease. Serum creatinine rose from 1.57 to 6.04 mg/dL with persistent proteinuria, requiring intermittent hemodialysis followed by continuous renal replacement therapy because of hemodynamic instability. He subsequently developed invasive pulmonary aspergillosis with septic shock and progressive respiratory failure. Despite intensive multidisciplinary care, multiorgan dysfunction progressed, and he was discharged for home palliative care. This case highlights the kidney as a sentinel organ of endothelial injury after HSCT and supports EAS as a unifying framework for TA-TMA, SOS/VOD, and severe kidney injury, characterized by complement-mediated endothelial dysfunction and microvascular thrombosis.
Hypokalaemia is a common finding in oncological patients, with a wide range of potential aetiologies. We present the case of a 64-year-old female patient, with a history of breast invasive carcinoma with positive hormonal receptors and negative HER2, and lymph node metastasis. She underwent neoadjuvant chemotherapy with adriamycine, cyclophosphamide, and docetaxel (subsequently switched to paclitaxel), followed by mastectomy, lymph node dissection, radiotherapy, and hormone therapy. During chemotherapy, she developed mild hypokalaemia, attributed to taxanes. Later on, she presented severe hypokalaemia, hyperchloremic metabolic acidaemia, and mildly elevated creatinine. She was admitted for supplementation, but the disturbances persisted despite the absence of gastrointestinal losses. A 24-h urine anion gap revealed renal tubular acidosis (RTA), and a random urine sample showed a high urine pH, suggestive of distal RTA. Autoimmune study revealed a decreased C3, a high titre of rheumatoid factor, antinuclear, anti-Ro52, anti-SSA, and SSB antibodies. The patient mentioned sicca symptoms and, after exclusion of other causes, the presumptive diagnosis of Sjögren syndrome was made. The patient’s blood workup is currently stable on potassium citrate, and sicca complaints are controlled with symptomatic treatment. Sjögren syndrome often presents with sicca symptoms, but rarely with renal manifestations, mostly as tubulointerstitial involvement. It may manifest with electrolyte disturbances (the most significant features in this patient), but these are normally associated with overt tubulointerstitial involvement. In conclusion, hypokalaemia is a common disturbance in oncological patients, requiring prompt study and correction. In this population, uncommon aetiologies must not be forgotten and may pose significant challenges.
Tumor lysis syndrome (TLS) is a life-threatening oncologic emergency characterized by hyperuricemia, hyperphosphatemia, hyperkalemia, hypocalcemia, and acute kidney injury (AKI). Although TLS most commonly occurs following initiation of cytotoxic therapy, it may rarely develop spontaneously in rapidly proliferating hematologic malignancies. Chronic myeloid leukemia (CML) is generally considered a low-risk malignancy for TLS; however, blast transformation can markedly increase tumor turnover and precipitate catastrophic metabolic complications. We report a 46-year-old woman with CML who defaulted treatment and follow-up for approximately 5 months and subsequently presented with decreased appetite, abdominal distension, and bilateral pedal edema. Prior molecular monitoring demonstrated disease progression with BCR-ABL transcript levels increasing from 2.5% to 40%. Laboratory evaluation revealed leukocytosis (174.3 × 10 9 /L), severe anemia (41 g/L), thrombocytopenia (26 × 10 9 /L), and 28% circulating blasts consistent with blast-phase transformation. She had severe metabolic derangements including serum creatinine 1379 µmol/L, blood urea nitrogen 64.0 mmol/L, uric acid 2718 µmol/L, potassium 5.8 mmol/L, phosphorus 1.84 mmol/L, calcium 1.85 mmol/L, lactate dehydrogenase 897 U/L, and arterial pH 7.0. The patient fulfilled Cairo–Bishop criteria for both laboratory and clinical TLS with dialysis-requiring AKI. Despite aggressive management with intravenous hydration, rasburicase, febuxostat, correction of electrolyte abnormalities, and urgent hemodialysis, progressive metabolic acidosis and renal failure culminated in death within 48 h of admission. This case highlights the potential for blast-phase CML to present with fulminant TLS-associated AKI and demonstrates the devastating consequences of extreme hyperuricemia, emphasizing the importance of early recognition and prompt intervention in patients with progressive CML.
Monoclonal gammopathy of renal significance (MGRS) encompasses renal lesions caused by nephrotoxic monoclonal immunoglobulins produced by small B-cell or plasma cell clones that do not meet criteria for overt hematologic malignancy. Diagnosis may be challenging when immune deposits are masked on routine immunofluorescence. We report a 63-year-old woman with hypertension, chronic kidney disease, peripheral neuropathy, venous thromboembolism, and progressive proteinuria who underwent kidney biopsy for worsening urinary abnormalities. Routine immunofluorescence on frozen tissue was negative; however, repeat immunofluorescence on protease-digested paraffin-embedded tissue demonstrated focal and segmental granular staining for IgG and kappa light chain with essentially negative lambda staining, consistent with proliferative glomerulonephritis with masked IgG-kappa dominant deposits. Congo red stain was negative. Bone marrow biopsy subsequently showed approximately 8% plasma cells with an abnormal kappa-excess plasma cell population, and serum immunofixation identified IgG-kappa monoclonal protein, supporting MGRS. Due to baseline peripheral neuropathy, bortezomib-based therapy was deferred, and the patient was treated with daratumumab, lenalidomide, and dexamethasone. Kidney function remained preserved, and proteinuria improved markedly from nephrotic-range level of 8.5–0.22 g/g. This case highlights the diagnostic importance of paraffin immunofluorescence when MGRS is suspected despite negative routine studies and illustrates that early clone-directed therapy can produce substantial renal response in masked monoclonal proliferative glomerulonephritis.
Background: Immune checkpoint inhibitors (ICI) have transformed outcomes for patients with advanced melanoma but are associated with acute kidney injury (AKI), including immune-related (IR) nephritis, which may lead to treatment interruption, immunosuppression, and adverse kidney and oncological outcomes. Objective: To describe incidence, clinical characteristics, management, and outcomes of AKI, including IR nephritis, in patients with melanoma treated with ICIs in an Australian cancer centre. Design: Retrospective single-centre cohort study. Setting: Melbourne, Australia. Participants: All adults (⩾18 years) with stage II–IV melanoma who received ⩾1cycle of ICI therapy between 1 August 2020 and 1 November 2024. Main outcomes: Incidence of AKI and IR nephritis; clinical characteristics; management; kidney recovery; treatment interruption; rechallenge; overall survival. Results: Among 633 patients with melanoma receiving ICIs, 86 (13.6%) developed AKI. Fifteen (2.4%) were classified as IR nephritis (seven biopsy-confirmed). Compared with non-immune AKI ( n = 71), IR nephritis occurred earlier after ICI initiation (median 43 vs 192 days; p = 0.009) and with more severe AKI (IR nephritis Stage 3 = 53%, versus non-immune AKI Stage 3 = 15%, p = 0.003). Concurrent IR-adverse events were common in both groups (64% vs 45%). Systemic corticosteroids were administered in all IR nephritis cases, and additional immunosuppression in 26%. Complete kidney recovery occurred in 80% of IR nephritis cases and 75% of non-immune AKI ( p = 0.92). Among patients with metastatic or unresectable melanoma ( n = 407), in a multivariate time-dependent Cox regression analysis, AKI was independently associated with a 2.71 fold higher hazard of death (adjusted hazard ratio 2.71, 95% CI 1.72–4.26; p < 0.001). Seven patients were rechallenged with ICIs after IR nephritis; none developed recurrent nephritis (median follow-up 13.9 months, IQR 7. 2–22.9 months). Conclusions: In this Australian study of patients with melanoma, AKI occurred in 13.6% treated with ICIs. IR nephritis was uncommon but often severe; however, kidney recovery was frequent with immunosuppression. AKI of any cause was associated with worse survival, and disrupted cancer treatment. Selected patients with IR nephritis may be safely rechallenged, highlighting the importance for individualised, multidisciplinary patient care.
