Editor’s Note: We asked authors of Original Investigations to provide short plain-language summaries that would briefly summarize what inspired their study, the basic approach taken, what was learned, and why it matters. We hope our readers will find this valuable in helping them keep up with the latest research in the field of nephrology.

Highlights from the June 2025 issue:

Associations of Topiramate and Zonisamide Use With Kidney Stones: A Retrospective Cohort Study by Bassel R. Salka et al. 

Topiramate and zonisamide are increasingly prescribed for uses other than seizure prophylaxis. These agents may cause kidney stones. In this retrospective cohort study of adults with either Medicare or commercial health insurance, we assessed the relationship between use of topiramate or zonisamide and kidney stone events requiring clinical intervention. Between 3 months and 3 years after first use of these drugs, stone events occurred more often among users of topiramate or zonisamide than nonusers. Our analysis also demonstrated a stronger association with stone risk among younger adults receiving either topiramate or zonisamide. These findings are consistent with the magnitude of association reported previously in the literature and the association was independent of treatment indication in younger adults.

DOI:  10.1053/j.ajkd.2024.12.009

EDITORIAL: Do Topiramate and Zonisamide Cause Kidney Stones? by Harshil A. Fichadiya and John C. Lieske [FREE]

Time-Updated Estimated GFR Variability Is Associated With Mortality, Cardiovascular Disease, and End-Stage Kidney Disease in Patients With CKD: Findings From the CRIC Study by Hiroki Nishiwaki et al. 

From the authors: Estimated glomerular filtration rate (eGFR) is a key indicator of kidney function calculated from routine clinical blood test results. It is well established that variability in eGFR over time is associated with poor patient outcomes such as mortality. However, previous analyses have primarily focused on the relationship between the initial eGFR variability observed and future adverse events. In this study, we continuously updated eGFR variability over time and analyzed its association with the development of cardiovascular disease, end-stage kidney disease, and mortality. Our findings demonstrated a stronger association between time-updated eGFR variability and these outcomes compared with the previous analytical methods.

DOI:  10.1053/j.ajkd.2025.01.010

EDITORIAL: Variability in Estimated GFR: When the Signal Is the Noise by Ann M. O’Hare and Ziyad Al-Aly [FREE]

Development of a Patient-Reported Outcome Measure of Side Effects for Patients Taking Calcineurin Inhibitors: The FACIT-CNI-Ntx by Courtney N. Hurt et al. [OPEN ACCESS]

People undergoing kidney transplantation require a lifelong regimen of immunosuppressing medications, including calcineurin inhibitors. Calcineurin inhibitors have side effects that may negatively impact transplant recipients’ lives, sometimes interfering with important daily activities. We created a new survey for kidney transplant recipients to report on their experiences with calcineurin inhibitor side effects that we named the Functional Assessment of Chronic Illness Therapy–Calcineurin Inhibitor–Neurotoxicity (FACIT-CNI-Ntx) and that captures important side effects among patients receiving CNIs.

DOI: 10.1053/j.ajkd.2024.11.012

IgM Variant of Proliferative Glomerulonephritis With Monoclonal Immunoglobulin Deposits: A Case Series by Lihong Bu et al. [OPEN ACCESS]

From the authors: The IgM variant of proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID-IgM) is very rare, and data on its clinicopathologic and outcome characteristics are scanty. This study of 23 patients with PGNMID-IgM identified in the Mayo Clinic pathology archives revealed that most patients were elderly White males who presented with proteinuria, hematuria, and reduced kidney function. The underlying hematologic condition was monoclonal gammopathy of renal significance in all cases, and the detection rate of the circulating nephropathic monoclonal immunoglobulin with serum protein electrophoresis/serum immunofixation was low but was increased using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Pathologically, all cases exhibited nonorganized glomerular monotypic IgM, most with a membranoproliferative glomerulonephritis pattern. Outcome analysis revealed a guarded kidney survival (median, 44 months), a high rate of early recurrence after transplant, and favorable patient survival (158 months).

DOI:  10.1053/j.ajkd.2025.01.009

Association of Estimated GFR Slope and Heart Failure Progression in Older Adults by Karim Kohansal et al. 

From the authors: Heart failure (HF) is a prevalent condition in older people, and its occurrence may be affected by kidney function. This study examined the relationship between changes in kidney function assessed by the slope of estimated glomerular filtration rate (eGFR) and the incidence of clinically diagnosed HF. We monitored more than 5,000 older people who were either at elevated risk for HF (stage A) or had cardiac abnormalities of HF (stage B) but had not yet developed clinical HF. Our findings indicated that among individuals in stage B a more rapid decline in kidney function was associated with a greater risk of developing HF, in particular HF with preserved ejection fraction (HFpEF). These findings highlight the potential value of tracking changes in kidney function to identify people at elevated risk of HF.

DOI:  10.1053/j.ajkd.2025.01.011

AJKDBlog COMMENTARY: One Metric, Two Missions: How eGFR Slope Guides Risk and Research by Benjamin Catanese [FREE]

Perspective in the June 2025 issue:

The Future of Technology-Based Kidney Replacement Therapies: An Update on Portable, Wearable, and Implantable Artificial Kidneys by Fokko P. Wieringa et al. [OPEN ACCESS]

Worldwide, the number of people who need lifesaving kidney replacement therapy (KRT) steadily increases, but approximately two thirds of them lack access to KRT and therefore die. Access to KRT depends on economic, social, infrastructural, ecological, and political factors. Current KRTs include kidney transplant, peritoneal dialysis, and hemodialysis. The field of xenotransplantation has been opening promising new perspectives recently but needs improvement. Unfortunately, not all patients are suitable for transplant. Peritoneal dialysis and hemodialysis will remain important KRTs, but they are expensive and strongly dependent on infrastructure, with few fundamental changes since the 1980s. The KRT field might learn from the “African mobile phone revolution” that beat infrastructural limitations, lowered costs, and increased access. We provide a nonexhaustive overview of promising ways to increase the mobility of technology-based KRTs by dialysate regeneration, chip-based nanoporous filters, bioreactor-enabling technologies, and using the gut as a “third kidney.” In 2018, the Kidney Health Initiative published a road map for innovative KRTs composed by leading innovators, but the pace of innovation is slower than was targeted. Ambitious political statements about realizing this road map can only succeed if the granted funding matches the targeted time scale. Patient-centered international “coopetition” (ie, the act of cooperation between competing entities) seems to offer the quickest pathway to success..

DOI: 10.1053/j.ajkd.2024.10.015

On the Cover:

The Kidney & Gravel Pills advertisement from a century ago reminds us that no pill cures kidney disease and all medications come with some risk, regardless of their indications. In this month’s issue of AJKD, Salka et al examine the associations between topiramate and zonisamide, medications frequently prescribed for seizure prophylaxis and kidney stones. At the same time, modern medicine is progressing rapidly in ways that seem almost as unbelievable as the snake oil promises of yesteryear. Wieringa et al look at one promising innovation the wearable artificial kidney which could revolutionize dialysis and improve patients’ lives.

Special thanks to Editorial Intern Api Chewcharat for curating the cover image and drafting the cover blurb for this issue. The poster “Baldwin’s Kidney & Gravel Pills” is from the Wellcome Collection and is in the public domain.

SPECIAL ANNOUNCEMENT:

The NKF is actively seeking applications for an Editor-in-Chief to manage and lead the American Journal of Kidney Diseases (AJKD) for a 5-year term beginning January 1, 2027. Letters of Intent and a CV must be submitted by July 15, 2025. Please review the Call for Applications for complete details.