Hepatorenal syndrome acute kidney injury (HRS–AKI) is a highly fatal complication of decompensated cirrhosis. While liver transplant is the only curative option for HRS, there are supportive care therapies with demonstrated benefit that are commonly utilized, including terlipressin, a V1a receptor agonist that received FDA approval for the treatment of HRS–AKI in 2022. Despite increasing utilization of terlipressin in the treatment of HRS–AKI in recent years, it does not appear that it has previously been used in the context of a patient with concurrent HRS–AKI and active malignancy. We report a case of a 58-year-old patient with a history of cirrhosis in the setting of pancreatic adenocarcinoma with liver metastasis who was successfully treated for HRS–AKI with terlipressin on three separate occasions. To our knowledge, this is the first report of terlipressin use in a patient with malignant hepatorenal syndrome. While little is known about the use of this agent in onco-nephrology patients, this case highlights the potential for terlipressin use in HRS–AKI in cirrhotic patients with underlying malignancy.
Persistent nephrotic-range proteinuria in cancer patients can compromise ongoing cancer therapy and prognosis. Although renin-angiotensin-aldosterone system (RAAS) blockade and sodium–glucose cotransporter 2 (SGLT2) inhibitors are mainstays of therapeutic management, proteinuria often persists. Patients who present with this clinical picture require a unique therapeutic approach. Pentoxifylline, a non-selective phosphodiesterase inhibitor with anti-inflammatory and anti-fibrotic properties, has shown proteinuria-lowering potential, but is not widely utilized in the United States for proteinuria management. We present a case of persistent proteinuria despite maximum-dose losartan and empagliflozin in a patient with AL amyloidosis and multiple myeloma not in remission. This patient demonstrated a reduction in proteinuria to modest levels (<1 g/g) following the addition of pentoxifylline 400 mg twice daily, allowing uninterrupted cancer treatment. Notably, there was an 86% decrease in urine protein/creatinine ratio (UPCR). This case illustrates the potential role of pentoxifylline as an adjunctive agent for refractory proteinuria in the onconephrology setting. Wider awareness and consideration of this inexpensive oral therapy may help optimize renal and oncologic outcomes in this vulnerable population.
High-dose Methotrexate (MTX) is commonly used in the treatment of hematologic malignancies but can be complicated by acute kidney injury (AKI), most often due to MTX-induced crystal nephropathy. Direct visualization of MTX crystals on urine microscopy is rarely reported and likely underrecognized. We describe a case of an elderly woman with diffuse large B-cell lymphoma (DLBCL) and central nervous system metastasis who developed AKI after receiving high-dose MTX as part of the MTX, Cytarabine, Thiotepa, Rituximab (MATRIX) chemotherapy regimen. This was followed by significant supratherapeutic levels of MTX with progressive decline in kidney function reflecting AKI, which was attributed to intratubular crystal precipitation. Management consisted of high dose leucovorin, aggressive intravenous hydration, and urinary alkalinization with sodium bicarbonate and acetazolamide, resulting in gradual MTX clearance. The diagnosis was supported by delayed drug clearance, worsening kidney function, and the direct visualization of MTX crystals on urine microscopy, a finding that makes this case unique.
Immune checkpoint inhibitor-associated podocytopathies are rare but clinically relevant renal immune-related adverse events (irAEs). Herein, we describe the case of a recurrent head and neck squamous cell carcinoma (HNSCC) of the tongue that developed refractory nephrotic syndrome following pembrolizumab therapy. A renal biopsy showed severe injury consistent with podocytopathy likely secondary to immune checkpoint inhibitor (ICI) use. Management strategies typically include the use of corticosteroids and permanent discontinuation of the ICI. Despite initial improvements, the patient experienced a course of steroid-resistant nephrotic syndrome (SRNS) requiring therapy with rituximab and ultimately obinutuzumab, eventually resulting in sustained remission. This case underscores the diagnostic ambiguity and management challenges of ICI-associated podocytopathy and suggests a potential role for advanced anti-CD20 therapy in refractory cases.
Introduction: Hematopoietic stem cell transplantation (HSCT) is a treatment for hematopoietic malignancies and certain immune disorders. Although rare, nephrotic syndrome is a significant complication of HSCT, often linked to graft-versus-host disease (GvHD) and frequently manifesting as membranous nephropathy. This case aims to highlight the rare detection of PLA2R antibodies in a patient with nephrotic syndrome following HSCT. Case presentation: A 52-year-old man with acute myeloid leukemia underwent allogeneic HSCT. Six months after discontinuation of immunosuppressants, he experienced two episodes of GvHD, requiring further immunosuppressive therapy. One year later, he presented with lower limb edema and anorexia. Investigations revealed nephrotic-range proteinuria (24-h urine protein 13 g; urine ACR 7004 mg/g), severe hypoalbuminemia (1.97 g/dL), and hyperlipidemia. Complement levels (C3, C4) were normal. Renal biopsy demonstrated membranous nephropathy with positive anti-PLA2R staining. Treatment with corticosteroids and rituximab was initiated. The patient subsequently achieved complete remission. Literature review: A Review of 11 reported cases (mean age 53.4 years; 8 (72.7%) allogeneic, 3 (27.3%) autologous) showed membranous nephropathy as the predominant pathology (9, 81.8%), followed by minimal change disease and focal segmental glomerulosclerosis (1, 9.1% each). IgG and/or C3 deposition occurred in 9 (81.8%). GvHD was present in 7 (63.6%). Treatment commonly included corticosteroids and immunosuppressants, including rituximab. Clinical improvement occurred in all cases, with complete or partial remission in 9 (81.8%). Conclusion: This case highlights the rare occurrence of nephrotic syndrome post-HSCT. The detection of anti-PLA2R antibody positivity on tissue immunofluorescence of the renal biopsy suggests a complex immune mechanism potentially overlapping with primary membranous nephropathy pathways. Corticosteroids and rituximab proved effective, reinforcing their role in management.
Background: Hyponatremia is a common electrolyte disturbance among hospitalized cancer patients and is associated with increased morbidity and mortality. Optimal correction rates for severe hyponatremia remain debated, particularly in oncology populations where comorbidities and treatment-related factors complicate management. Methods: We conducted a retrospective cohort study of adult cancer patients admitted to Shaukat Khanum Memorial Cancer Hospital & Research Centre (SKMCH&RC), Lahore, Pakistan, between January 2011 and March 2023 with severe hyponatremia (serum sodium ⩽120 mEq/L). Patients were categorized based on 24-h sodium correction rates: <6 mEq/L, 6–10 mEq/L, and >10 mEq/L. Outcomes included in-hospital mortality, 30-day mortality, and length of stay. Multivariable logistic regression models were used to assess associations between correction rates and mortality. Results: Among 939 patients, 45.5% had correction <6 mEq/L/24 h, 24.7% had 6–10 mEq/L/24 h, and 29.8% had >10 mEq/L/24 h. In-hospital and 30-day mortality were significantly higher in the slow correction group compared with rapid correctors (in-hospital: 54.1% vs 20.4%; p = 0.003; 30-day: 55.3% vs 20.6%; p < 0.001). On multivariable analysis, a correction >10 mEq/L/24 h was independently associated with lower in-hospital mortality (adjusted OR = 0.58; 95% CI: 0.36–0.92; p = 0.021). One case of osmotic demyelination was identified. Conclusions: In hospitalized cancer patients with severe hyponatremia, slow correction (<6 mEq/L/24 h) was associated with significantly higher mortality, whereas rapid correction (>10 mEq/L/24 h) was linked to improved survival without significant neurological complications. Prospective multicenter studies are warranted to investigate the associations between the different etiologies of hyponatremia and mortality.
Background: Hispanic adults comprise approximately 19.1% (63.6 million) of the U.S. population yet remain yet only 2%–4% of therapeutic oncology trial participants are Hispanic/Latinx. Renal cell carcinoma (RCC) is one of the most rapidly increasing cancers in this group, accounting for nearly 8000 new cases and over 1300 deaths annually among Hispanic Americans. Despite this burden, the inclusion, reporting, and analysis of Hispanic participants in RCC drug trials have not been systematically evaluated. Objective: To assess Hispanic inclusion, demographic reporting, and subgroup analysis in Phase III and IV systemic therapy trials for RCC conducted between 2005 and 2025. Methods: A scoping review was conducted following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. Systematic searches were performed using PubMed, Embase, and ClinicalTrials.gov for trials registered or published between January 1, 2005, and January 1, 2025. The search strategy combined terms for RCC, clinical trial phase (III and IV), Hispanic or Latino identity, and human subjects. Trials were eligible if they evaluated systemic therapies for RCC and enrolled at least 50 adult participants. Trials were excluded if they were Phase I or II, observational, lacked accessible results, or omitted any demographic reporting. Data extracted from each trial included total sample size, percentage of Hispanic participants (if reported), presence or absence of a Hispanic ethnicity option, and whether subgroup analyses by ethnicity were performed. Results: After removing duplicates, and studies that did not meet inclusion criteria, 31 trials involving 20,550 participants met inclusion criteria. Only eight trials (25.8%) reported Hispanic participant percentages, which ranged from 0% to 12.9% (mean 4.95%), significantly below their national population share. Six trials (19.4%) collected demographic data but did not list Hispanic/Latino as an ethnicity category. 17 trials (54.8%) failed to report any race or ethnicity data. None conducted Hispanic-specific subgroup efficacy or toxicity analyses. Conclusion: Although Hispanic individuals represent nearly one-fifth of the U.S. population and face a growing RCC burden, they are notably underrepresented or omitted in RCC systemic phase III and IV therapy trials of the last 20 years. Many trials neglect ethnicity data collection or structurally exclude Hispanic identity, and none perform ethnicity-stratified analyses. To foster equitable and generalizable oncologic research, future RCC trials must standardize ethnicity reporting, proactively recruit Hispanic participants, and incorporate race- and ethnicity-stratified outcome analyses.
Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR–TKI), including osimertinib, have been reported to cause nephrotoxicity. However, distinguishing true renal impairment from pseudo-renal dysfunction due to transporter inhibition (pseudo-AKI) remains challenging, particularly in patients with chronic kidney disease (CKD). We report a case of a 76-year-old man with pre-existing CKD stage G3bA3 who developed a rapid increase in serum creatinine levels 8 days after initiating osimertinib for EGFR L858R mutation-positive non-small cell lung cancer (NSCLC). Anticancer therapy was subsequently modified by switching to dose-adjusted afatinib, allowing for continued EGFR–TKIs treatment without further renal deterioration. Renal function remained stable for more than 2 years under joint oncological and nephrological management. This case highlights the clinical utility of an integrated renal assessment using cystatin C and tubular injury markers in differentiating true renal injury from pseudo-AKI. This approach supports the clinical decision to switch to an alternative EGFR–TKI in patients with CKD, thereby enabling the safe continuation of targeted cancer therapy.
Immune effector cell (IEC) therapies including chimeric antigen receptor (CAR)-modified T-cell therapy have shown efficacy in pediatric B-cell acute lymphoblastic leukemia (B-ALL) and are being investigated for other malignancies. A common toxicity associated with IEC therapy is cytokine release syndrome (CRS), which can lead to organ dysfunction due to systemic inflammation causing capillary vasodilation and hypoperfusion. Data is limited regarding acute and chronic renal toxicities in children receiving these therapies. This study describes our institutional experience with renal adverse effects after IEC therapy in pediatric patients. We retrospectively review patients who received IECs directed toward various antigens in patients with hematologic, solid, and central nervous system malignancies, from January 2014 to June 2023 at Texas Children’s Hospital. The primary endpoint was defined as major adverse kidney events within 90 days acute kidney injury (MAKE90). Two hundred and three patients with a median age of 13 years and 57% male met inclusion criteria. Any grade AKI occurred in 28 patients, all of whom had concurrent CRS. Four patients had AKI-D, two of whom died of disease progression and two of whom recovered. Patients with history of pre-existing renal disease ( p = 0.023) with hematologic malignancy ( p = 0.025) or who received CART products ( p = 0.05) were more likely to have AKI. Most patients had recovery to their pretreatment baseline, with only one patient progressing to new diagnosis of CKD and none needing dialysis at 90-day follow-up. One patient developed biopsy confirmed collapsing variant focal segmental glomerulosclerosis (FSGS) after infusion of CD19 CART product. Significant compromise of renal function including AKI or dialysis occurred in a minority of patients treated with IEC therapy, with most having recovery of renal function within 90 days.
Severe cholestasis may induce renal tubular injury via bile pigment toxicity, leading to bile cast nephropathy (BCN) or, rarely, a Fanconi-like syndrome. We report the case of an 87-year-old man with pancreatic adenocarcinoma and profound hyperbilirubinemia who developed partial proximal tubular dysfunction, characterized by hypouricemia, hypophosphatemia, and hyperchloremic metabolic acidosis, without glucosuria or bicarbonaturia. Fractional excretion studies confirmed proximal tubulopathy. This case represents, to our knowledge, the first description of Fanconi-like syndrome secondary to obstructive jaundice in pancreatic cancer, highlighting the importance of screening for tubular dysfunction in cholestatic states.
Light chain cast nephropathy, the most common cause of acute kidney injury (AKI) in multiple myeloma, is triggered by the overproduction of free light chains and the resultant generation of obstructing and pro-inflammatory casts in the renal tubules. Plasma cell-directed chemotherapies form the mainstay of management. At initial presentation some individuals have severe kidney injury requiring dialysis. High-cutoff haemodialysis (HCO-HD), which effectively filters circulating free light chains, has been posited as an adjunctive treatment for multiple myeloma patients with dialysis-dependent AKI. While standard haemodialysis, and indeed plasmapheresis, in the absence of a dialysis indication have shown no benefit in randomised trials, one randomised study using HCO-HD in patients requiring dialysis did suggest longer term benefit in terms of dialysis independence. Herein we describe three cases of multiple myeloma with severe AKIs treated with a shortened version of the MYRE study HCO-HD protocol and standard chemotherapy. All three cases demonstrated renal recovery; two within weeks and one within months of commencing HCO-HD. Treatment refractory multiple myeloma cases were excluded and cast nephropathy was not biopsy-confirmed. In cases of myeloma kidney requiring dialysis and receiving plasma cell-directed chemotherapy, use of HCO dialysis membranes should be considered over standard cut off membranes, to maximise potential for long term renal recovery.
Advances in cancer therapies have allowed for improved cancer outcomes; however, with the benefits of novel treatments, clinicians must recognize associated side effects, including acute kidney injury (AKI). AKI and associated changes in kidney function are particularly consequential in patients with cancer, as these may lead to ineligibility for treatments, delays and dose reductions in therapy as well as exclusion from clinical trials. This in turn has a negative impact on cancer outcomes. In this review, we address anticancer drug-induced AKI, with specific focus on conventional cytotoxic chemotherapies and targeted therapies chemotherapies. We discuss frequently nephrotoxic chemotherapies, including: platinum-based agents (cisplatin, carboplatin, oxaliplatin); methotrexate and its derivative, pemetrexed; gemcitabine; and other systemic therapies frequently complicated by AKI. With respect to targeted therapies, we review both AKI and pseudo-AKI (i.e. serum creatinine elevation related to drug-mediated impairment of tubular creatinine secretion) from multiple classes, including: anaplastic lymphoma kinase (ALK) inhibitors; cyclin-dependent kinase-4/6 (CDK4/6) inhibitors poly-ADP ribose polymerase (PARP) inhibitors; vascular endothelial growth factor (VEGF) and multi-target tyrosine kinase inhibitors, among others. For each therapy, we review mechanisms of injury and associated renal lesions and preventive strategies, where available. Both oncology and nephrology clinicians must be aware of, promptly recognize, and appropriately manage AKI associated with cancer therapies to allow for optimal cancer outcomes.
Hyponatremia in patients with cancer is common and often multifactorial, complicating the management of heart failure and anticancer therapies. Sacubitril/valsartan, a combined neprilysin inhibitor and angiotensin receptor blocker, is a cornerstone therapy for heart failure with reduced ejection fraction, but it may have adverse effects that are clinically significant. We present a case of a 54-year-old woman with poor-risk acute myeloid leukemia in remission after allogeneic hematopoietic stem cell transplantation who developed recurrent hyponatremia temporally associated with sacubitril/valsartan use. Cessation of the medication led to sodium improvement. This case highlights the need for increased clinical suspicion for drug-induced hyponatremia in onconephrology patients treated with neprilysin inhibitors.
Background:Plasma cell dyscrasia (PCD) is a rare but important cause of end stage kidney disease (ESKD). Kidney transplant is the treatment of choice in patients with ESKD. However, the complexity of PCD care and risk of disease recurrence poses challenges to kidney transplant candidacy and outcomes. We examined the current clinical practice patterns of clinicians who care for patients with PCD and identified barriers to kidney transplantation for patients with PCD. Methods:A web-based survey was developed and distributed from January to July 2024 to kidney transplant clinicians (American Society of Transplant (AST) members), hematologists (PCD experts), and onco-nephrologists. Results:Seventy clinicians (50 transplant nephrologists, 18 hematologists, and two surgeons) from 42 transplant centers in the US participated in the survey. Clinical practice patterns pre and post kidney transplant for patients with PCD are highly variable among institutions, and only 36% reported having a protocol for pre- and post-transplant management for patients with PCD. Particularly, the requirement for pre-transplant hematologic remission criteria, induction and maintenance immunosuppression regimens and protocols for prophylaxis and screening for opportunistic infection are areas of future study. Clinicians listed lack of data and practice guidance as well as communication challenges among multiple specialties especially hematology and kidney transplant clinicians as notable barriers. Conclusions:Our study identified the highly variable current practice patterns when evaluating and managing patients with PCD for kidney transplant. Our findings emphasize the need for collecting and sharing clinical data to support standardized practices and serve as a basis for the upcoming multi-societal management recommendation for kidney transplant for patients with PCD.
Targeted cancer therapies have revolutionized oncology, offering improved survival for many malignancies. However, these treatments are associated with significant renal complications, including acute kidney injury (AKI), chronic kidney disease (CKD), proteinuria, hypertension, and thrombotic microangiopathy (TMA). This review summarizes the nephrotoxic effects of various targeted agents, such as vascular endothelial growth factor VEGF inhibitors, tyrosine kinase inhibitors (TKIs), cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, and poly (ADP-ribose) polymerase (PARP) inhibitors, while providing evidence-based management strategies. Special emphasis is placed on distinguishing true AKI from “pseudo-AKI” caused by tubular creatinine secretion inhibition. A multidisciplinary approach, including renal function monitoring, drug dose adjustments, and antihypertensive management, highlight the importance of multidisciplinary collaboration between nephrologists and oncologists as well as shows how crucial it is for optimizing outcomes in cancer patients with kidney disease.
A third-generation anaplastic lymphoma kinase (ALK) inhibitor, lorlatinib, plays a crucial role in the management of ALK-rearranged non-small cell lung cancer. The renal effects of the drug are not yet clear. Herein we report the first case of focal segmental glomerulosclerosis (FSGS) associated with lorlatinib in a 64-year-old male diagnosed with stage IV ALK-rearranged lung adenocarcinoma. This is the first case of FSGS, confirmed by kidney biopsy, described in literature in patient treated with lorlatinib. This case shows a potential kidney effect of lorlatinib, suggesting the importance of monitoring proteinuria and kidney function during therapy, to perform a kidney biopsy in these patients to understand the underlying mechanisms of damage and highlight the importance of close cooperation between oncologist and nephrologist in the clinical management of these frail patients.
Magnesium plays a vital role in numerous cellular and enzymatic functions, yet it tends to be neglected or undervalued. Hypomagnesemia, a prevalent medical concern, significantly impacts the morbidity and mortality rates of cancer patients. This review provides an overview of magnesium physiology and accentuates the mechanisms involved in magnesium inbalances resulting from cancer and its treatment, seeking to emphasize the importance of monitoring magnesium levels in cancer patients to healthcare providers and serve as a practical resource. Future clinical research should prioritize investigations into magnesium monitoring’s effects on cancer advancement.
Hematopoietic stem cell transplantation (HSCT) and chimeric antigen receptor (CAR) T-cell therapy have transformed the treatment of hematologic malignancies, with expanding applications in selected solid tumors and nonmalignant hematologic conditions, but are frequently complicated by kidney dysfunction. Acute and chronic kidney disease after HSCT are often multifactorial, with several unique causes such as capillary leak syndrome, sinusoidal obstruction syndrome, transplant-associated thrombotic microangiopathy, and post-transplant nephrotic syndrome playing important roles. Key drivers of CAR T-cell therapy-related kidney disease include sepsis, cytokine release syndrome, and tumor lysis syndrome. Understanding of these injury mechanisms is critical to optimizing prevention, early detection, and management of kidney complications in these populations, with the overall goals of improving kidney and overall outcomes.
Hyponatremia is a common electrolyte abnormality in patients with malignancy, and recent investigations into the off-label use of SGLT 2 inhibitors for syndrome of inappropriate antidiuretic hormone (SIADH) have shown promising short-term results. We report the case of an 84-year-old woman with history of relapsed metastatic uterine carcinosarcoma with chronic hyponatremia who failed standard therapy. The patient was initiated on empagliflozin 11 months ago and has had sustained normalization of serum sodium levels. While less is known about the long-term use of these agents, this case highlights the potential for SGLT 2 inhibitors to be used as a low-burden therapeutic option for cancer-associated chronic hyponatremia.
The subfield of onco-nephrology has evolved significantly since its inception, with the term itself emerging in the nephrology world nearly two decades ago. There has been significant growth and interest in this field in past decade. This growing interest was recently highlighted when the University of Turin in Italy hosted the second onco-nephrology meeting on April 11–12, 2025, titled: “The New Challenge for Nephrologists and Oncologists.” Here we briefly summarize the history of onco-nephrology and the lectures from Turin meeting which will be highlighted in this issue of JON.
