Mark Anthony Perazella

Lithium remains a mainstay of therapy for bipolar disease and refractory depression with future potential for expanded use on the basis of novel data demonstrating its immunomodulatory and neuroprotective effects. This drug accumulates intracellularly via sodium transport pathways, and its effects on complex cellular signaling mechanisms, including glycogen synthase kinase-3 β inhibition, form the basis of its therapeutic efficacy and toxicity. Increased intracellular levels disrupt cellular processes and trigger injury via mitochondrial dysfunction and oxidative stress. Lithium has a narrow therapeutic index and causes dose-dependent nephrotoxicity. A tubulointerstitial pattern of kidney injury is typical; however, lithium can rarely cause glomerular injury as well. An acute rise in serum lithium levels can result in severe volume depletion from lithium-induced natriuresis and aquaresis and cause AKI. Changes in kidney function and various drug interactions can acutely affect serum lithium levels further increasing the risk of toxicity. Arginine vasopressin resistance is the most common complication of chronic lithium use and can be an early manifestation. CKD occurs after a longer latency of over 10 years with a variable slope of GFR decline. Progression to ESKD is relatively low but is affected by the presence of other nephrotoxic risk factors. Epithelial sodium channel blockers such as amiloride can be helpful in mitigating lithium nephrotoxicity by reducing cellular accumulation. Hypercalcemia secondary to lithium-induced hyperparathyroidism is associated with a higher risk of nephrolithiasis and CKD progression. Kidney microcystic changes are common in lithium-induced CKD, and distal renal tubular acidosis can also be seen. Using the lowest effective lithium dose, close monitoring of kidney function and serum lithium levels and early diagnosis of lithium nephrotoxicity is critical in preventing irreversible kidney injury. The decision to discontinue lithium is challenging, and the benefits versus risks must be carefully weighed. This comprehensive review provides a pathogenetic basis and practical clinical framework for diagnosis and management of lithium nephrotoxicity.

In the past few decades, advances in understanding of cancer biology have led to the development of highly effective conventional chemotherapies, targeted therapies that act on specific pathways that are critical to cancer growth, immune-based therapies, and cellular therapies such as haematopoietic cell transplantation and chimeric antigen receptor T cell therapy. However, the nephrotoxic effects of these therapies continue to pose substantial challenges, with many unanswered questions regarding the prevention, diagnosis and management of this nephrotoxicity. Further, a lack of consensus and precise guidance on kidney function estimation and drug dosing for patients with acute kidney disease or chronic kidney disease and for patients receiving kidney replacement therapy limits access to life-saving therapies and jeopardizes outcomes. In this Consensus Statement, we present guidance on the prevention, diagnosis and management of anticancer therapy nephrotoxicity for adult patients that was developed at the 34th Acute Disease Quality Initiative meeting, which convened an international panel of experts in nephrology, haematology, oncology, nephropathology, critical care, paediatric care and pharmacology. We also define a research agenda focused on preventing and mitigating anticancer therapy toxicity, maximizing early detection of nephrotoxicity and enabling optimal drug dosing in patients with kidney disease, with the goal of advancing cancer care and fulfilling the potential of these ground-breaking treatments.

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.

Key Points: Needle selection in kidney biopsy requires balancing risk of complications with benefit of obtaining diagnostic tissue. Our data show that higher needle gauge provides more tissue for diagnosis but might be associated with greater risk of complications. Background: While a larger needle gauge can provide additional kidney tissue for diagnosis, it might also predispose to greater complication risk. Here, we evaluate the safety and diagnostic adequacy of kidney biopsies in patients who underwent a biopsy with various needle sizes. Methods: We evaluated rates of biopsy-related complications and adequacy between participants who underwent biopsy with 16 versus 18 G needles. We assessed safety using a composite outcome of blood transfusion, angiographic intervention, hemoglobin drop of at least 2 g/dl, or at least a medium sized hematoma after kidney biopsy. We defined adequacy as the number of glomeruli available for diagnosis. Results: Among 781 participants included in the analysis, 665 biopsies (85%) were performed using a 16 G needle and 116 (15%) were performed using an 18 G needle. We observed similar odds of complications in the 16 G group as compared with the 18 G group in univariable analysis (odds ratio, 1.56 [95% confidence interval, 0.81 to 3.01]); however, there were higher odds of complications in the 16 G group in both multivariable analysis adjusting for prebiopsy bleeding risk factors (2.40 [1.16 to 4.93]) and propensity score weighted analysis (2.92 [1.28 to 6.67]). As compared with 18 G needle, 16 G biopsy needle was associated with more glomeruli obtained (13 [9–19] versus 11 [6–15], P < 0.001). The higher number of glomeruli in 16 G group persisted after multivariable adjustment (5.06 [2.52 to 7.59]) and propensity score weighted (4.39 [0.37 to 8.42]) analyses. Conclusions: Participants with kidney biopsies performed with a 16 G needle tended to sample more glomeruli and had similar complications on univariable analysis but higher complications when adjusting for prebiopsy risk factors. This indicates that larger needle gauge provided more tissue for diagnosis, but clinicians appropriately avoided its use in those at higher risk of complications. Our findings suggest that the use of a 16 G needle improves diagnostic yield but carries a higher adjusted risk of complications, underscoring the importance of individualized needle gauge selection.

Introduction: Adverse drug reactions are a significant problem in modern society, stemming from the increase in prescribed medications, over-the-counter drugs, and overall polypharmacy. Glomerular disorders are one of the frequently reported renal conditions associated with medication use. VigiBase is a significant tool for evaluating events associated with drug use, and, to the authors’ knowledge, no study has yet assessed this database to identify the primary medications associated with glomerular disorders. Materials and Methods: We collected data from VigiBase for 54 years and evaluated data based on global frequencies, disproportionality (IC₀₂₅ values), nephrotoxic potential, and physiopathological mechanisms. Results: Over the evaluation period, 33.932.051 spontaneous notifications of adverse drug reactions reported in VigiBase were assessed, from which 106.775 notifications of drug-associated glomerular disorders were extracted. The isolated medications were classified as ‘potential nephrotoxins’ (47.0%), with 40% of the medications lacking scientific references to report any association with the development of glomerular disorders. Among the evaluated medications, Inotersen (IC₀₂₅ of 8.3), Penicillamine (IC₀₂₅ 6.8), Bevacizumab (IC₀₂₅ 5.9) and Lenvatinib (IC₀₂₅ 5.4) were identified as having the strongest association with these glomerular disorders. For medications classified as ‘non-nephrotoxic’, a high disproportionality index was observed, suggesting drugs that might be considered as new potential nephrotoxins. Conclusions: Drug-induced glomerular disorders were significantly associated with medications that had no established nephrotoxic role but demonstrated a high disproportionality index in VigiBase. These newly alleged nephrotoxic drugs warrant further evaluation in dedicated studies to assess their true nephrotoxic potential.

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