1. Endothelin Receptor Antagonist for Anti-Vascular Endothelial Growth Factor signaling pathway inhibitor Induced hypertension and/or proteinuria 
 

Author: Jaya Kala, MD​

Affiliation: Division of Renal Diseases and Hypertension, University of Texas Health Science Center, Houston, Texas

​

Background: Anti-angiogenic drugs targeting VEGF (bevacizumab) and its receptors (sunitinib, sorafenib, pazopanib, axitinib) are standard treatment for renal cell, non–small cell lung, colorectal carcinoma, and gastrointestinal stromal tumors. However, VEGF signaling pathway inhibitors (VSPIs) frequently cause hypertension and proteinuria leading to dose interruption or discontinuation. Proposed mechanisms include reduced nitric oxide and prostacyclin production,increased endothelin-1 (ET-1), microvascular rarefaction, renin–angiotensin activation, oxidative stress, and arterial stiffness. Sunitinib-induced hypertension is partially reversed by ETA/ETB antagonism with macitentan, supporting an ET-1–driven "preeclampsia-like syndrome." Current management (ACEi, ARBs, CCBs, diuretics, β-blockers) is nonspecific. These therapies are nonspecific and do not target the underlying endothelin-1 (ET-1)–driven pathophysiology. We propose the use of Aprocitentan, an endothelin receptor antagonist, approved by FDA foruncontrolled hypertension, to treat hypertension and or proteinuria caused by VSPI.

 

Methods: We extracted data from patients who were referred to Onco-nephrology clinic for uncontrolled hypertension and or proteinuria while on VSPI agents. Among patients who were referred, 4 patients were started on Aprocicentan (while continuing their other antihypertensives). The patients are currently being closely followed for hypertension, proteinuria, cancer treatment and prognosis.

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Results: Of the 4 patients who were started on treatment with Aprocicentan, two patients showed response with improved proteinuria, and all patients showed improvement in their hypertension. Due to hyperkalemia, three patients had to stop their ACEi. Three patients continued VSPI treatment while on Aprocicentan, except one who had TMA on kidney biopsy.

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Conclusion: Our limited data set indicates feasibility of using Aprocitentan, to specifically target the underlying ET-1 pathophysiology of VSPI-induced hypertension and proteinuria. Use of Aprocicentan allows for continuation of VSPI cancer treatment while taking care of hypertension and proteinuria.

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2. Unmasking the Brush Border: Anti-LRP2 (Megalin) Nephropathy in the Setting of Immune Checkpoint Inhibitor Therapy
 

Authors: Chenyang Yu(1), Arley F Diaz(2,3), Cherry Starling(4), Sujal I Shah(1,5)
Affiliations:
1. Department of Pathology, Brigham and Women's Hospital, Boston, MA
2. Department of Nephrology, Cooley Dickinson Hospital, Northampton, MA
3. UMass Chan Medical School - Baystate, Springfield, MA
4. Arkana Laboratories, Little Rock, AR
5. Harvard Medical School, Boston, MA

​

Introduction: Anti-brush border antibody (ABBA) disease is an exceedingly rare autoimmune tubulopathy driven by autoantibodies against low-density lipoprotein receptor-related protein 2 (LRP2/megalin), or less frequently, cubilin and amnionless protein, all being components of the proximal tubular brush border. The etiology is poorly understood, but ABBA has been reported in setting of autoimmune and neoplastic conditions. Immune checkpoint inhibitors (ICIs) typically trigger acute interstitial nephritis (AIN), though there are increasing reports of glomerular immune complex disease. Here, we report a patient who developed anti-LRP2-mediated ABBA disease in the setting of combination ICI and Tyrosine Kinase Inhibitor (TKI) therapy for renal cell carcinoma (RCC).

 

Case Description: An 82-year-old male with metastatic papillary RCC developed severe acute kidney injury (peak serum creatinine 11.2mg/dL) three weeks after initiating pembrolizumab and lenvatinib. Kidney biopsy was performed. Light microscopy (Figure 1A) revealed severe chronic-active interstitial nephritis alongside acute tubular injury with focal necrosis. Glomeruli showed mild mesangial expansion but otherwise appeared unremarkable. Direct immunofluorescence (Figure 1B) demonstrated prominent, granular polytypic IgG deposits, with IgG4 and weaker IgG1 staining, along the proximal tubular basement membranes (TBM) and segmentally along glomerular capillary loops. LRP2 staining (Figure 1C) showed granular reactivity along the TBM. Electron microscopy revealed dense deposits in the TBM and glomeruli. The findings were consistent with ABBA disease. Both oncologic agents were held and steroids were initiated, with complete renal recovery to baseline without requiring renal replacement therapy. The patient was subsequently treated with TKI monotherapies (cabozantinib, then tivozanib) without evidence of renal relapse.

 

Discussion: While separating paraneoplastic from drug-induced nephrotoxicity is challenging, the tight temporal onset following immunotherapy and complete renal recovery upon treatment cessation strongly implicate the ICI as a key immunologic catalyst. This case further supports the possibility of immunotherapy-related immune complex-mediated diseases and suggests that deposition may not be limited to glomeruli.​​

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3. Severe Acute Kidney Injury Following Liver Ablation – A Case Series
 

Authors: Michelle E. Madden, MBBCh, MA(*1), Ivan Cancarevic, MD(*1), Mia B. Rubman, BS(1), Ava Kim(1) Sujal I. Shah, MD(2), Abdullah Jalal, MD(1,3), Raad Chowdhury, MD(1,3,4), Jiping Wang MD, PhD (3,5,6), Paul B. Shyn, MD(3,7), Shruti Gupta, MD, MPH (1,3,4)
Affiliations:
1. Department of Medicine, Division of Renal Medicine, Mass General Brigham, Boston, MA
2. Department of Pathology, Mass General Brigham, Boston, MA
3. Harvard Medical School, Boston, MA
4. Adult Survivorship Program, Dana Farber Cancer Institute, Boston, MA
5. Department of Surgery, Division of Surgical Oncology, Mass General Brigham, Boston, MA
6. Department of Surgery, Division of Surgical Oncology, Dana-Farber Cancer Institute, Boston, MA
7. Department of Radiology, Division of Abdominal Imaging and Intervention, Mass General Brigham, Boston, MA
*These authors contributed equally

​

BACKGROUND: Cryoablation is a procedure that utilizes extreme cold to destroy tumor cells in the setting of both primary and metastatic liver tumors; however, it has been associated with a broad spectrum of complications, ranging from fever and tachycardia to multi-organ failure, coagulopathy, and acute kidney injury (AKI). In comparison, histotripsy is a novel focused ultrasound technique that mechanically disrupts tumor tissue while sparing surrounding structures, thus potentially reducing systemic toxicity.

 

METHODS AND CASE DESCRIPTIONS: We retrospectively reviewed three cases of severe, stage 3 AKI following liver tumor ablation: two after histotripsy and one after cryoablation. All patients were women, aged 58-68 years, with normal baseline eGFRcr who developed AKI within 24 hours of their procedures. Two required kidney replacement therapy (KRT). Kidney biopsies in all three patients demonstrated acute tubular injury with features of pigment nephropathy, inflammatory infiltrates, hypoperfusion-related changes, and oxalate crystals. Hemoglobin-positive, myoglobin-negative casts were observed in two of the cases (Figure 1). Laboratory findings included elevated creatine kinase, lactate dehydrogenase, and myoglobin levels. Additionally, in two patients, cystatin C-based estimates of eGFR were consistently higher than those derived from serum creatinine values. Treatment of all three cases involved corticosteroids, and complete recovery of kidney function occurred in all patients, including those requiring KRT.

 

CONCLUSION: Both cryoablation and histotripsy may precipitate severe AKI, potentially through shared mechanisms involving cytokine release, pigment-mediated tubular injury, and hemodynamic perturbations. The inflammatory features and response to corticosteroids in select cases support a contributory immune-mediated component. Our findings emphasize the importance of identifying biomarkers that could shed light on the pathophysiology of AKI following liver ablation and potentially explain the discordant serum creatinine/cystatin C measurements. Larger studies with detailed risk profiling and phenotyping are needed to clarify risk factors and clinical features of AKI following cryoablation and histotripsy.
 

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4. AKI Following Bispecific T-Cell Engager Therapy in Hematologic Malignancies: A Multicenter Cohort Study
 

Authors: Carolina Saldanha Neves Horta Lima(*1), Rajesh Krishna Anumolu(*1), Motohiko
Adomi(2), Mia B. Rubman(1), Rafaella Litvin(3), Junglee Kim(4), Paolo F. Caimi(3), Api Chewcharat(1), Abdullah Jalal(1,2,3), Raad Chowdhury(1,2,3), Shruti Gupta (1,2,3)
Affiliations:
1. Division of Renal Medicine, Mass General Brigham, Boston, MA
2. Adult Survivorship Program, Dana-Farber Cancer Institute, Boston, MA
3. Harvard Medical School
4. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA
5. Department of Hematology and Oncology, Cleveland Clinic Foundation, Cleveland, OH
6. Department of Kidney Medicine, Cleveland Clinic Foundation, Cleveland, OH
*co-first authors

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Background: Bispecific antibodies (BsAbs) have transformed the therapeutic landscape for blood cancers, including multiple myeloma (MM) and non-Hodgkin’s Lymphomas (NHL), offering highly effective, off-the-shelf immunotherapy options for relapsed and refractory disease. Despite the expanding use of BsAbs in real-world populations, the renal safety profile of BsAbs remains poorly characterized.

 

Methods: We retrospectively reviewed all patients with MM and NHL treated with BsAbs across two major academic cancer centers between December 2022 and January 2026. We examined the incidence of a composite outcome of AKI (defined as rise in serum creatinine ≥1.5-fold from pre-BsAb baseline and/or need for renal replacement therapy), or death in the 30 days following the first dose of BsAbs, compared to a contemporaneous control cohort treated with CAR-T. We used multivariable logistic regression to examine risk factors for AKI. We also examined the incidence and severity of cytokine release syndrome (CRS) in the 30 days following treatment initiation.

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Results: Of 476 eligible patients who received BsAb, 91 (18.9%) developed the composite outcome of AKI (n=60), death (n=41) or both (n=11). In the CAR-T cohort, of 213 eligible patients, 50 (23.5%) had the composite outcome of AKI (n=48), death(n=4) or both (n=2). AKI severity in each group is shown in Figure 1A. In multivariable analyses, serum albumin <3 g/dL (OR 2.94, 95% CI, 1.35-6.41), platelets <150 K/uL (OR 2.15, 95% CI, 1.15-4), and serum free light chains ≥1000 mg/L (OR 2.99, 95% CI, 1.54-5.83), each assessed at the time of the first dose of BsAbs, were associated with an increased odds of AKI or death (Figure 1B). CRS grade ≥ 2 occurred in 67 (14.9%) patients treated with BsAbs compared to 65 (30.5%) receiving CAR-T (Figure 1C). Patients with AKI after bispecific therapy were more likely to have CRS grade 2 or higher than those without AKI (35 vs. 11%).

 

Conclusion: We identified key risk factors for AKI in patients treated with BsAbs, and also found that the incidence of AKI or death was lower in this cohort compared to CAR-T -treated patients. Patients with AKI were also more likely to have concurrent CRS. Prospective studies are needed to further evaluate the safety of BsAbs.
 

5. Prevalence of Malignancies Among Adult Kidney Transplant Recipients in Colombia: Analysis of the National Health Registry, 2019–2023
 

Authors: Andrea Zapata-Arango(1), Kateir Contreras-Villamizar(1,2,3), Diana Vargas-Angel (2,3),
Valentina Camacho-López(4), Paola García-Padilla(1,2,3), Diego Rosselli(5)
Affiliations:
1. Department of Internal Medicine, Pontificia Universidad Javeriana, Bogotá, Colombia
2. Nephrology Unit, Hospital Universitario San Ignacio, Bogotá, Colombia
3. Kidney Transplant Unit, Hospital Universitario San Ignacio, Bogotá, Colombia
4. Nephrology Research Group, Pontificia Universidad Javeriana, Bogotá, Colombia
5. Department of Epidemiology and Biostatistics, Pontificia Universidad Javeriana, Bogotá, Colombia
​

Background: Kidney transplant recipients have an increased risk of malignancy related to chronic immunosuppression. However, population-based data from Latin America remain scarce. We evaluated the prevalence of malignancies among kidney transplant recipients in Colombia using the national mandatory health registry.
 

Methods: We conducted a cross-sectional prevalence study using secondary data from the Colombian Integrated Social Protection Information System (SISPRO). Adults (>20 years) registered between January 2019 and December 2023 were included. Kidney transplant recipients and malignancies were identified using ICD-10 codes. Cancer prevalence per 1,000 individuals and prevalence ratios (PR) with 95% confidence intervals (CI) were calculated comparing transplant recipients with the non-transplanted population.
 

Results: The study included 17,405 kidney transplant recipients and 38,832,056 individuals from the general population. Overall cancer prevalence was significantly higher among transplant recipients (185.1 vs. 38.1 per 1,000 individuals; PR 4.86, 95% CI 4.73–5.04). The highest prevalence ratios by organ system were observed for genitourinary malignancies (PR 12.95, 95% CI 11.41–14.68), otorhinolaryngologic cancers (PR 7.61, 95% CI 6.92–8.32), and hematologic malignancies (PR 6.67, 95% CI 6.02–7.39). The greatest excess risks were identified for anal canal carcinoma (PR 50.38, 95% CI 42.84–59.26), esophageal cancer (PR 28.56, 95% CI 23.87–34.18), native kidney renal cell carcinoma (PR 21.92, 95% CI 18.96–25.35), and acute lymphoblastic leukemia (PR 20.07, 95% CI 15.73–25.61).
 

Conclusions: Kidney transplant recipients in Colombia experience an almost fivefold higher prevalence of malignancy compared with the general population. These findings support the implementation of tailored cancer surveillance strategies in this high-risk population and provide a foundation for future studies evaluating transplant-specific screening approaches in Latin America.

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6. Overall survival with sequential systemic anticancer therapy and first-line response in metastatic renal cell carcinoma with ESKD: a real-world analysis
 

Authors: Tomaž Milanez (1˒2), Vinay Srinivasan(3), Boštjan Seruga(2˒4), Miha Arnol(1˒4), Janja Ocvirk(2), Edgar A. Jaimes(5˒6)
Affiliations:
1. University Medical Centre Ljubljana, Ljubljana, Slovenia
2. Institute of Oncology Ljubljana, Division of Medical Oncology, Ljubljana, Slovenia
3. Cooper Medical School of Rowan University, Division of Nephrology, New Jersey, United States of America
4. University of Ljubljana, Ljubljana, Slovenia
5. Weil Cornell Medicine, New York, United States of America
6. Memorial Sloan Kettering Cancer Center, Memorial Sloan Kettering Cancer Center, New York, United States of America
​

Background: Sequential systemic anticancer therapy (SACT) improves overall survival (OS) in mRCC, with more lines associated with longer OS. Real-world data supports ICI benefit across lines, and first-line ORR per RECIST is associated with OS.

Methods: We retrospectively included patients with mRCC and ESKD treated with VEGFR TKIs, ICIs, and/or mTOR inhibitors at the Institute of Oncology Ljubljana, Slovenia, between January 2009 and December 2025. OS was defined from cohort entry to death from any cause and censored at last known vital status or 31 December 2025. Median time to next treatment (TTNT; IQR,Range) was calculated for first-line SACT. OS was analyzed by IMDC risk group, and best response (CR, PR, SD, PD) was physician-assessed per RECIST v1.1.
 

Results: Among 41 patients with mRCC and ESKD, median age was 70 years; 80.5% were male, 92.7% had clear-cell histology, and 34% had favorable-risk disease (IMDC). Median SACT lines: 2 (range, 1–5). In 28 patients receiving first-line VEGFR-TKI SACT, PR was 46.4%. In 10 patients treated with first-line ICI-based therapy, PR was 50%. Of three patients receiving VEGFR-TKI plus ICI, two achieved ORR, including one CR. Overall ORR was 54% in patients treated with ICIs or ICI plus VEGFR-TKI. Median TTNT was 8 months (IQR, 3–8; range, 0–47). Median OS for all histologies across IMDC risk groups was 32 months (95% CI, 13–51). In patients receiving ≥1 ICI cycle, median OS was 47 months (95% CI, 30–63), versus 16 months (95% CI, 7–25) in those treated with VEGFR-TKIs, mTOR inhibitors, or combination SACT sequences (n=20).
 

Conclusion: In mRCC with ESKD, ORR with first-line ICI or ICI+VEGFR-TKI SACT was ~8% higher across IMDC groups (~34% favorable risk), with CR observed in the ICI+VEGFR-TKI group. Median OS was longer in patients receiving ≥1 ICI cycle during sequential SACT.

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7. Safety of kidney biopsy in the oncologic populations: a single center experience

 

Authors: Mehmood M(1), Ali S(1), Chen Z(2), Azar N(3), Rashidi A(1)
Affiliations:
1. Department of Medicine, Division of Nephrology and Hypertension, University Hospitals Cleveland Medical
Center, Cleveland, OH
2. Case Western Reserve University School of Medicine, Cleveland OH
3. Department of Radiology, University Hospitals Cleveland Medical Center, Cleveland, OH
​

Introduction: Safety of the biopsy in native kidneys is well established, with bleeding, pain, infection, AV fistula, and urine leak being the main complications. History of cancer within the preceding year before biopsy has been mentioned as one of the risk factors for major bleeding. Data on biopsy safety in cancer patients remain limited. This study aims to evaluate the safety of renal biopsy in cancer patients.

 

Methods: A retrospective single center observational study was performed on cancer patients who underwent a kidney biopsy from Jan 2018- May 2026. Clinical and laboratory data were obtained from medical charts. Primary outcomes were minor and major complications categorized according to the need for intervention. Firth penalized logistic regression was used to reduce small‐sample bias and address potential separation.

 

Results: A study population consisted of 115 patients. The cohort comprised of 57% males, 81.7% White and Hispanics having mean age of 65.24 ± 12.59 years at the time of biopsy. A total of four patients in the cohort had a solitary kidney. Overall, there were a total of 18 events (15.6%) out of which 4 were categorized as major complications (3.47%). Three patients had platelet level below 50,000/μL out of which one of them had major complication. Warfarin use was the only variable significantly associated with major complications (OR 30.15, 95% CI 1.55–588.3). Male sex was associated with 68% lower odds of post biopsy complications (OR 0.32, 95% CI 0.11–0.91).

 

Conclusion: The findings of this study demonstrated that kidney biopsy is generally safe in cancer patients with a low incidence of major complications. This is comparable with kidney biopsy complications in general nephrology population. Warfarin use emerged as the significant predictor of major adverse events, underscoring the importance of careful anticoagulation management in this population.

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8. Subclinical Glomerular Pathology in Patients with Solid Tumors: An Ongoing Multicenter Histopathological, Immunofluorescence and Electron Microscopy Study
 

Authors: Manya Karamyan(1), Armen Mkhitaryan(2), Katya Baydyuk(4), Karen Tsarukyan(1), Vardan
Arakelyan(1), Nelli Grigoryan(1), Arevik Stepanyan(1), Arthur Grabski(3)
Affiliations:
1. National Center of Oncology, Yerevan, Armenia
2. Histogen Pathology Center, Armenian-German Scientific-Practical Center of Pathology, Yerevan, Armenia
3. Izmirlian Medical Center, Yerevan, Armenia
4. Institute of Physiology, National Academy of Sciences of the Republic of Armenia, named after Academician L.
A. Orbeli, Yerevan, Armenia
​

Background: Cancer-associated glomerular diseases represent an important component of onconephrology; however, current knowledge is largely derived from clinically overt nephrotic or nephritic syndromes. Subclinical glomerular abnormalities in patients with solid tumors remain poorly characterized. Advanced pathological techniques, particularly transmission electron microscopy (TEM), may reveal occult glomerular lesions undetectable by routine clinical evaluation, light microscopy, or immunofluorescence alone.
 

Aim: To determine the prevalence and spectrum of subclinical glomerular abnormalities in patients with solid tumors using light microscopy, immunofluorescence (IF), and TEM, and to compare findings with age-matched non-neoplastic controls.
 

Methods: This ongoing multicenter cross-sectional case-control study will enroll adults undergoing nephrectomy or partial renal resection for renal or extrarenal solid tumors, together with controls undergoing nephrectomy for non-neoplastic conditions. Non-tumorous renal tissue will be evaluated by light microscopy, IF (IgG, IgA, IgM, C3, C1q), Congo red staining, and TEM. Clinical data including proteinuria, kidney function, circulating immune complexes, tumor markers, and viral serology will be collected and correlated with pathological findings.

Primary Outcome: Prevalence and morphological spectrum of subclinical glomerular lesions identified by combined histopathological modalities.
 

Expected Results: We anticipate identifying a broader and previously underrecognized spectrum of glomerular abnormalities, including ultrastructural podocyte injury, immune complex–related changes, and other lesions detectable only by TEM. Novel histopathological patterns associated with malignancy may improve understanding of early cancer-associated kidney injury.
 

Conclusions: This study aims to define the true burden of occult glomerular disease in patients with solid tumors and provide new insights into the immunopathological mechanisms of cancer-associated kidney injury. The findings may support earlier renal surveillance in oncology patients and help establish a rationale for routine nephropathological assessment, including ultrastructural evaluation, of nephrectomy and renal resection specimens.

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9. Biomarkers of Kidney Injury and Recovery in Patients with Multiple Myeloma Receiving Daratumumab
 

Authors: Poy Theprungsirikul, MD(*1); Api Chewcharat, MD, MPH(*2˒3); Ayumi Takakura, PhD, (2); Shahrier Hossain, PharmD(4); Ava Kim,(2); Mia B. Rubman, BS,(2); Sophia L. Wells, BS,(2); Kiana M. Zargari, MMSc,(2); Robert S. Rider, MMSc,(2); Raad B. Chowdhury, MD,(2˒3˒5); Abdullah Jalal, MD, (2); Tarek H. Mouhieddine, MD, (1); Joseph V. Bonventre, MD, PhD, (2); Paul G. Richardson, MD, (1^); Shruti Gupta, MD, MPH, (2˒3˒5^)
Affiliations:
1. Department of Medical Oncology, Division of Hematologic Malignancies, Dana Farber Cancer Institute, Boston,
MA
2. Department of Medicine, Division of Renal Medicine, Mass General Brigham, Boston, MA
3. Harvard Medical School, Boston, MA
4. Department of Pharmacy, Dana Farber Cancer Institute, Boston, MA
5. Adult Survivorship Program, Dana Farber Cancer Institute, Boston, MA
*PT and AC contributed equally
^SG and PR contributed equally​

​

BACKGROUND: Kidney impairment is a common complication of multiple myeloma (MM) and is associated with worse treatment response and outcomes. Daratumumab, an anti-CD38 monoclonal antibody, has demonstrated efficacy across MM disease states and has been associated with improved kidney function. Novel biomarkers reflecting distinct nephron injury and repair pathways have recently been validated, but their utility in monitoring kidney responses in MM remains unclear.
 

METHODS: We prospectively enrolled 20 adults with newly diagnosed MM at high risk for acute kidney injury initiating subcutaneous daratumumab between September 2024 and November 2025. Blood and urine samples were collected before treatment and approximately 30 days after initiation. Prespecified biomarkers included plasma dickkopf-3 (DKK-3; primary biomarker), soluble urokinase plasminogen activator receptor (suPAR), monocyte chemoattractant protein-1 (MCP-1), kidney injury molecule-1 (KIM-1), and urinary DKK-3, KIM-1, neutrophil gelatinase-associated lipocalin (NGAL), and clusterin (CLU).
 

RESULTS: Paired plasma (n=20) and urine (n=19) samples were analyzed. Following daratumumab initiation, plasma DKK-3, plasma suPAR, and urinary suPAR/creatinine increased significantly, with median rises of 19.8% (p=0.01), 22.1% (p=0.008), and 26.0% (p=0.01), respectively (Figure 1A). Increased plasma DKK-3 was associated with greater odds of early kidney recovery and showed a borderline association with improved 90-day eGFR slope. Several secondary biomarkers demonstrated nominal associations with kidney outcomes, including baseline urine KIM-1/creatinine, plasma MCP-1, urine NGAL/creatinine, and change in urine CLU/creatinine; however, none remained significant after false-discovery-rate correction.
 

CONCLUSIONS: Although DKK-3 is traditionally viewed as a marker of tubular stress and progressive kidney injury, rising plasma DKK-3 after daratumumab initiation was associated with improved kidney recovery. These findings suggest that transient biomarker elevations may reflect adaptive tubular stress-response and remodeling during renal recovery rather than irreversible injury. Larger prospective studies are needed to validate these observations.

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10. Cancer Associated Kidney Alterations: Assessing Current and Identifying Novel Biomarkers
 

Authors: Theresa Weis (1˒3), Dianet Sanchez Vega (2), Barbara O’Steen (3), Timothy Cummins (5), Levi Beverly (3˒4), and Leah J. Siskind (3˒4)
 

Affiliations:
1. Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, USA
2. Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, USA
3. Division of Medical Oncology and Hematology, Department of Medicine, University of Louisville School of Medicine, Louisville, KY, USA
4. Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA
5. Department of Nephrology, University of Louisville School of Medicine, Louisville, KY, USA
​

Abstract: Over 60% of cancer patients present with reduced kidney function at diagnosis, suggesting that remote cancer may alter renal function and induce kidney injury, with important implications for treatment. Accurate assessment of kidney function and injury in cancer patients is essential to optimize therapy and reduce acute kidney injury (AKI). Our lab has established the concept of cancer-kidney crosstalk, in which remote cancer alters kidney function, increases markers of kidney injury, and induces interstitial fibrosis through yet unidentified mechanisms. These alterations also increase susceptibility to cisplatin-induced AKI, highlighting the need to define both reliable biomarkers and mechanisms of cancer-associated kidney dysfunction. Here, we evaluated tumor effects on kidney function using transdermal glomerular filtration rate (tdGFR) and surrogate markers, serum creatinine (SCr) and blood urea nitrogen (BUN), in syngeneic mouse models of lung cancer. tdGFR declined early during tumor development, before detectable changes in SCr or BUN. Although tdGFR strongly correlated with tumor size, SCr and BUN did not. For kidney injury markers, lung tumors secreted NGAL and may falsely elevate serum and urinary NGAL; thus, urinary NGAL may be an unreliable marker of kidney injury in the setting of lung cancer. We performed targeted and unbiased serum proteomics in control and tumor-bearing mice to identify candidate biomarkers and mediators of tumor-induced kidney dysfunction. Cross-validation with cytokines and chemokines secreted by lung cancer cells in vitro identified several candidates, of which GDF15, CCL8, and osteoprotegerin have been validated thus far. Serum levels positively correlate with tumor size and tdGFR, supporting their potential as biomarkers of cancer-induced kidney dysfunction. Future studies will determine the clinical relevance of GDF15, CCL8, and osteoprotegerin and test whether they mediate remote cancer-induced kidney dysfunction.

 

 

11. IgA Nephropathy in cancer patients: either tumor-related or immunotherapy induced immune dysregulation
 

Authors: Mariem Borcheni (1), Majd Shaarani (2), Jaya Kala (1)
Affiliations:
1. Division of Renal Diseases and Hypertension, McGovern Medical School, Houston, Tx
2. Department of Pathology and Laboratory Medicine

​

Introduction: IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and usually follows a slow, chronic course. In cancer patients, it arises in two distinct scenarios: paraneoplastic (secondary) IgAN, and IgAN induced by cancer therapies, particularly immune checkpoint inhibitors (ICIs). Paraneoplastic IgAN may precede, coincide with, or follow the cancer diagnosis, and malignant relapse can trigger glomerulonephritis recurrence; treatmenttargets the underlying tumor. ICI-induced IgAN is far rarer than acute tubulointerstitial nephritis.
 

We report two cases: one paraneoplastic and one ICI-induced.
Case 1: A 48-year-old woman with metastatic peritoneal mesothelioma, having failed multiple chemotherapy lines since 2018, began atezolizumab and bevacizumab for disease progression. After two months, she developed nephrotic-range proteinuria (4.7g), prompting nephrology referral. Biopsy performed to distinguish ICI-nephritis from antiangiogenic induced renal limited thrombotic microangiopathy revealed secondary IgAN due to ICI (M0E1S1, NOS) with moderate arteriosclerosis and mild arteriolosclerosis. Immunotherapy was held and losartan replaced with sparsentan.
 

Case 2: A 66-year-old man with papillary thyroid cancer (diagnosed 2015, thyroidectomy 2016) was treated with sunitinib, then lenvatinib, stopped after 15 months for proteinuria and hypertension despite normal kidney function. Biopsy showed IgAN (M0E1S). For persistent disease, therapy was switched to dabrafenib and trametinib, with good response. Cancer response was accompanied by reduced proteinuria, and this parallel improvement supports a paraneoplastic etiology for the IgAN.
 

Conclusion: These cases underscore the value of kidney biopsy in cancer patients with proteinuria. ICIs rarely induce secondary IgAN as an immune-related adverse event, typically presenting with hematuria, proteinuria, and sometimes acute kidney injury. Our ICI case was unusual in lacking both hematuria and acute kidney injury. The paraneoplastic patient's proteinuria improved alongside cancer response to therapy.

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12. Bladder Cancer Mortality in Alabama (1999–2020): A County-Level Analysis of Racial and Sex-Based Disparities

​

Authors: Milan Regmi1, Maheem Jawaid1, Bibek Man Shrestha3, Ahmed Al Sharie1, Om
Prakash Bhatta2, Abinaya Sivakumar1
Affiliations:
1. Southeast Health Medical Center, Dothan, AL
2. University of Toledo Medical Center, Toledo, OH
3. University of Maryland Medical Center Midtown Campus, Baltimore, Maryland

 

Background: Bladder cancer is the 10th leading cause of Death in the USA (1,2), which is the most urologically significant malignancy with direct implications for kidney and urinary tract health. Population-level mortality data stratified by race and sex can reveal structural inequities that inform both clinical care and health policy, but data from Alabama are very scarce from Alabama. The goal of this study is to evaluate the county-level bladder cancer mortality across Alabama over 21 years.
 

Methods: Death certificate data were obtained from the CDC WONDER Underlying Cause of Death database (ICD-10 codes C67.0–C67.9) for the state of Alabama from 1999 to 2020. Data encompassing 51 counties were stratified by race (White; African American) and sex, with crude mortality rates and age-adjusted rates (AAR) calculated per 100,000 population. Counties with fewer than 10 deaths were classified as statistically unreliable per CDC suppression standards.
 

Results: We found total of 4,053 bladder cancer deaths recorded across a cumulative population of approximately 79.9 million person years. The overall crude mortality rate was 5.07 per100,000. Men accounted for 73.2% of all deaths, representing a male-to-female ratio of 2.7:1.White individuals comprised 90.3% of total deaths (n=3,659), while African American individuals accounted for 9.7% (n=394). However, age-adjusted mortality rates revealed a more complex picture: White males carried the highest AAR (7.92), while African American males demonstrated markedly elevated rates relative to African American females (AAR 5.03 vs. 2.10), suggesting significant sex-based vulnerability within this group. Jefferson County recorded the highest county-level burden (623 deaths).
 

Conclusions: Bladder cancer mortality in Alabama Countys showed pronounced sex and racial disparities, with White males bearing the greatest absolute burden and African American males showing disproportionate age-adjusted risk, with possible unreliable data given the disproportionate burden. These findings suggested the need for targeted urological screening protocols in high-risk communities and individuals. Also, further research studies should be done to find out if any specific risk factors contribute to this high number of disparities.

 

References:

1. SEER Preliminary Cancer Incidence Rate Estimates for diagnosis years 2000 to 2023, National Cancer Institute, Bethesda, MD, https://seer.cancer.gov/statistics/preliminary-estimates/ , based on the February 2025 SEER data submission. Posted to the SEER web site and SEER Explorer, July 2025.
2. American Cancer Society. 2026. "Key Statistics for Bladder Cancer." American Cancer Society.
https://www.cancer.org/cancer/types/bladder-cancer/about/key-statistics.html .
 

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13. Resolution of Bevacizumab-Associated Hypertension and Proteinuria After Drug Cessation In Patients with OBGYN Cancers: A Real-World Cohort Study
 

Authors: Paul E. Hanna1, Gregory Nelson2, Vinay Srinivasan2, Abhijat Kitchlu3, Shruti Gupta4
Affiliations:
1. Medical College of Wisconsin, Milwaukee, WI, USA
2. Cooper University Hospital, Camden, NJ, USA
3. Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada
4. Brigham and Women’s Hospital, Boston, MA, USA

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Background: Bevacizumab is associated with hypertension (HTN) and proteinuria in patients
with gynecologic cancers. The natural history of resolution of these toxicities after drug cessation has not been well-characterized.
 

Methods: We used the TriNetX US Collaborative Network to identify adult female patients with
gynecologic malignancies who received and subsequently discontinued bevacizumab. Drug cessation was defined at 21 days after the last noted administration. Primary endpoints were time to resolution of de novo Grade 3+ HTN (SBP ≥160 or DBP ≥100 mmHg) and de novo Grade 2+proteinuria (UPCR ≥1.0 g/g, UACR ≥300 mg/g, or dipstick ≥2+). A secondary composite renal outcome (dialysis initiation, new CKD Stage 5, or ≥40% sustained eGFR decline confirmed ≥30 days apart) was assessed using Fine-Gray hazard models with death as a competing event, applying a 90-day survivor landmark post-cessation.
 

Results: Of 6,960 patients, 1,255 met inclusion criteria (median age 63 years [IQR 54–71]. During active treatment, 339/1,255 (27.0%) developed de novo Grade 3+ HTN (median 105 days) and 574/1,255 (45.7%) developed de novo Grade 2+ proteinuria (median 104 days). Among patients with Grade 3+ HTN, 138 (40.7%) achieved full resolution (median 124 days), 106 (31.3%) achieved BP normalization requiring antihypertensive class escalation (improved to Grade 1), and 95 (28.0%) had persistent uncontrolled BP at last follow-up. Among 574 patients with Grade 2+ proteinuria, only 100/574 (17.4%) achieved full resolution (median 172 days), while 474/574 (82.6%) had proteinuria at final follow-up. De novo Grade 3+ HTN was associated with the composite renal outcome (sHR 1.37, 95% CI 1.12–1.67, p=0.002), while de novo Grade 2+ proteinuria was not (sHR 1.10, 95% CI 0.91–1.33, p=0.314).

 

Conclusion: In this real-world cohort, de novo Grade 3+ HTN resolved in ~72% of patients within 12 months of cessation. In contrast, de novo Grade 2+ proteinuria was largely refractory
 

14. IgG1 Heavy Chain Deposition Disease with Fibrillary Glomerulonephritis as a Manifestation of MGRS
 

Authors: Muhammad Khuram Nouman, MD1; Gunjan Garg, MD1; Ali S. Zaidi, MA2
Affiliations:
1. University of Louisville, Louisville, Kentucky, USA
2. Brown University, Providence, RI.

 

Introduction: Monoclonal gammopathy of renal significance (MGRS) refers to kidney diseases caused by pathogenic monoclonal immunoglobulins. Heavy chain deposition disease (HCDD) with fibrillary glomerulonephritis (FGN) is an exceedingly rare MGRS variant.

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Case Description: A 67yo F with HTN and HFpEF presented with AKI on CKD & nephrotic syndrome. Evaluation revealed an IgG lambda monoclonal gammopathy with markedly elevated serum free lambda light chains (2742 mg/L, K/L ratio 0.00) and a minimal M-spike (0.09g/dL). Kidney biopsy demonstrated mesangial expansion and segmental sclerosis on light microscopy. IF showed mesangial and capillary wall staining for IgG (2–3+), lambda light chain restriction, and IgG1 subclass positivity, with C3 and C1q 1+ staining. EM revealed powdery electron-dense deposits along glomerular and tubular basement membranes with associated mesangial fibrillary deposits, consistent with HCDD with FGN. Bone marrow biopsy revealed 15–25% plasma cells without evidence of amyloidosis & with intermediate-risk cytogenetics. There was paucity of heavy chain production, but she still had heavy chain renal disease. She was started on daratumumab-based CyBorD therapy with improvement in K/L ratio to 0.86, Cr down from 2.6mg/dL to 1.6 mg/dL and proteinuria down from 3.5g/g to 2.2g/g within 6 weeks.
 

Discussion: This case highlights a rare overlap of HCDD and FGN and underscores the discordance between hematologic burden and severity of renal involvement in MGRS. This case emphasizes the importance of timely kidney biopsy and early clone-directed therapy. Early recognition of rare MGRS variants is critical to guide prompt treatment and potentially preserve kidney function.

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15. Mortality from Multiple Myeloma and Plasma Cell Neoplasms in Alabama: A 22-Year County-Level Disparity Analysis

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Authors: Milan Regmi1, Maheem Jawaid1, Om Prakash Bhatta2, Bibek Man Shrestha3, Ahmed
Al Sharie1, Abinaya Sivakumar1
Affiliations:
1. Southeast Health Medical Center, Dothan, AL
2. University of Maryland Medical Center Midtown Campus, Baltimore, Maryland
3. University of Toledo Medical Center, Toledo, OH

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Background: Multiple myeloma (MM)/plasma cell neoplasm is a group of malignant neoplasms that affects African Americans and older adults disproportionately, among which MM represents around 1.3% of total cancer in the USA (1). With its racially diverse rural population and significant healthcare access barriers, Alabama represents a critical state for examining county-level mortality and disparities. Our study analyzes the geographic distribution of MM deaths across Alabama counties from 1999 to 2020 using CDC WONDER national mortality surveillance data.

Methods: Mortality records were extracted from the CDC WONDER Underlying Cause of Death database (ICD-10 codes C90.0–C90.2) for all Alabama counties over the 22 years 1999–2020. Outcome measures included total deaths, crude mortality rates, and age-adjusted mortality rates (AAR) per 100,000 persons. County-level data were analyzed to identify geographic clustering and high-burden areas. Counties with fewer than 20 deaths were flagged as unreliable per CDC suppression criteria and excluded from rate comparisons.
 

Results: In our analysis, we found a total of 4612 deaths, which were recorded across 64 of Alabama's 67 counties. Age-adjusted mortality rates ranged from 2.4 per 100,000 (DeKalb County) to 6.0 per 100,000 (Choctaw County). Notably, the five counties with the highest AARs are Choctaw (6.0), Pickens (5.6), Conecuh (5.2), Marengo (5.1), and Chambers (5.0), which are rural, predominantly African American counties concentrated in the Alabama Black Belt region. Jefferson County recorded the highest absolute death count (752), reflecting its large population. Eleven counties had unreliable or suppressed rates due to small death counts, which is a limitation of our analysis.

 

Conclusions: We found marked geographic variation in MM mortality across Alabama counties, with rural counties bearing disproportionate burden. We believe these findings are suggestive of racial composition, rurality, and healthcare access as key drivers of MM mortality inequity in Alabama, warranting policy targeting these specific populations and easy access to oncology care in underserved areas.

 

References:
1. Albagoush SA, Shumway C, Azevedo AM. Multiple Myeloma. [Updated 2023 Jan 30]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK534764/