Onconephrology is an emerging subspecialty that encompasses comprehensive kidney management in patients with cancer. Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate composed of trastuzumab linked to the microtubule inhibitor. T-DM1 is widely used in the treatment of human epidermal growth factor receptor 2-positive breast cancer, and glomerular disease arising during T-DM1 therapy remains rarely reported. The present report describes the case of a 50-year-old Japanese woman who developed nephrotic-range proteinuria approximately five months after initiating T-DM1 adjuvant therapy. Kidney biopsy confirmed the diagnosis of cellular variant focal segmental glomerulosclerosis. Other secondary causes, including autoimmune disease and infection, were excluded, and the temporal relationship between symptom onset and T-DM1 administration suggested a possible drug-related etiology. Given the absence of alternative treatment regimens for her breast cancer, we decided to continue T-DM1 without immunosuppressive therapy, with careful monitoring of kidney function and proteinuria. The scheduled anticancer treatment course was successfully completed, and proteinuria improved significantly within 7 weeks of treatment completion. This case highlights the importance of recognizing rare glomerular adverse effects of T-DM1 and underscores the need to carefully balance oncological treatment benefits against renal toxicity, emphasizing the value of multidisciplinary collaboration between oncologists and nephrologists.

A 62-year-old man with biopsy-proven focal segmental glomerulosclerosis presented with nephrotic syndrome and enlarging bilateral perinephric masses. Contrast-enhanced CT showed large low-density lesions surrounding and compressing both kidneys, raising concern for retroperitoneal malignancy. Needle biopsy revealed bland spindle cells with low proliferative activity in myxoid stroma. Because he declined repeat biopsy, dual-tracer PET/CT was performed, showing diffuse mild-to-moderate 18F-FDG uptake (SUVmax, 6.5) and moderate 68Ga-FAPI uptake (SUVmax, 8.5), without focal markedly increased uptake. Integration of these imaging and pathologic findings supported the diagnosis of perinephric myxoid pseudotumor of fat and guided conservative management.

Focal segmental glomerulosclerosis (FSGS) is a major cause of nephrotic syndrome and progression to end-stage renal disease, yet its molecular pathogenesis remains still incompletely defined. While transcriptional alterations in podocytes have been extensively characterized, the contribution of post-transcriptional regulatory mechanisms is poorly understood. Here, we combined a zebrafish podocyte-specific injury model with glomerulus-resolved transcriptomic profiling to dissect RNA regulatory alterations during FSGS progression. Integrated analyses of bulk RNA sequencing, small RNA profiling, and alternative splicing revealed pronounced, time-dependent remodeling of the glomerular transcriptome. We demonstrate that podocyte injury is associated with loss of key podocyte-specific proteins, activation of inflammatory pathways, remodeling of the extracellular matrix, and altered microRNA expression, such as miR-21 and miR-193. Moreover, we found that alternative splicing influences key podocyte gene expression, affecting genes critical for slit diaphragm integrity, actin cytoskeleton organization, and glomerular basement membrane stability. Isoform analyses identified FSGS-associated isoform switches in SRSF3 and EPB41L5. Importantly, these changes were also evident in glomeruli from FSGS patients, demonstrating that the zebrafish model recapitulates key molecular features of human disease and highlighting alternative splicing as a central regulatory mechanism in FSGS.

Collapsing glomerulopathy is a severe form of focal segmental glomerulosclerosis (FSGS) that can occur as a primary or secondary condition, often in the context of infections such as HIV. Multiple myeloma can cause kidney injury through mechanisms such as cast nephropathy, while malaria-associated kidney injury is most often due to acute tubular necrosis. We present the case of a 47-year-old male of African descent with well-controlled HIV infection who became critically ill with severe AKI requiring intensive care and renal replacement therapy. A blood smear confirmed Plasmodium falciparum infection, and the clinical course was further complicated by a previously undiagnosed multiple myeloma. Given the multiple potential etiologies, a kidney biopsy was performed, which ruled out myeloma-associated kidney injury and revealed collapsing glomerulopathy. The temporal association with the malaria infection, together with the well-controlled HIV status, pointed to malaria-associated collapsing glomerulopathy as the most likely diagnosis. This case highlights the diagnostic challenges of AKI in critically ill patients with overlapping comorbidities and underscores the value of kidney biopsy in guiding the differential diagnosis.

Podocytes are key structural components of the glomerular filtration barrier and are essential for maintaining selective protein filtration. Podocyte dysfunction is closely associated with proteinuria and the progression of glomerulosclerosis, constituting the common pathological basis of various chronic kidney diseases such as diabetic nephropathy and focal segmental glomerulosclerosis. While histone post-translational modifications have been extensively studied in podocyte biology, recent attention has shifted toward the regulatory roles of nonhistone post-translational modifications. By modulating protein stability, activity, localization, and interactions, these modifications participate in core biological processes such as apoptosis, cytoskeletal remodeling, inflammatory signaling, and metabolic reprogramming. Nevertheless, the strength of evidence is not uniform across post-translational modification categories. While some mechanisms have been directly demonstrated in podocytes, others are inferred mainly from broader kidney injury models or from studies in non-podocyte cell types. Accordingly, not all reported post-translational modification changes should be interpreted as equally well-established causal drivers of podocyte injury. This review focuses on the molecular regulatory networks and pathophysiological significance of major nonhistone post-translational modifications, including acetylation, phosphorylation, methylation, lactylation, ubiquitination, and SUMOylation. We further propose a hypothesis-generating and integrative conceptual model of podocyte deterioration, linking initiating pathological stimuli to stress transduction and downstream effector decompensation that may culminate in structural collapse. Importantly, this proposed cascade is not intended to represent a universally validated linear sequence or a definitive disease mechanism. Rather, it provides an organizing framework to generate testable hypotheses. We further highlight the therapeutic promise of targeting nonhistone post-translational modification pathways while acknowledging the considerable translational challenges that remain. By synthesizing the mechanistic landscape of nonhistone post-translational modifications, this review provides an integrated framework for advancing our understanding of podocytopathy pathogenesis and fostering the development of precision-targeted therapies.

Podocytes are terminally differentiated visceral epithelial cells that form the outermost layer of the glomerular filtration barrier. Through their foot processes and slit diaphragm structures, podocytes confer selective permeability to the glomerular filtration barrier and play a critical role in maintaining kidney function. Podocyte damage is characterized by foot process effacement, loss of slit diaphragm proteins, reorganization of the actin cytoskeleton, and apoptosis, and plays a central role in the pathogenesis of proteinuric glomerular diseases such as minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and diabetic nephropathy. This narrative review examines podocyte biology, the main molecular pathways of podocyte damage (RhoA/ROCK, TGF-β, mTOR, and oxidative stress), the clinical presentations of podocytopathies, and treatment strategies ranging from RAAS blockade, SGLT2 inhibitors, cytoskeletal stabilizers, gene therapy, to regenerative medicine approaches. By highlighting recent findings and translational challenges, the importance of podocyte-focused therapies in glomerular diseases is emphasized. Future studies aim to preserve podocyte integrity and prevent progressive kidney disease through personalized molecular therapies and multidisciplinary research.

Emerging studies have identified autoantibodies targeting the podocyte protein nephrin in patients with post-transplant recurrent focal segmental glomerulosclerosis (FSGS). These antibodies bind nephrin, directly disrupting its downstream signaling pathways. This disruption profoundly impacts podocyte structure and function, thereby enriching our understanding of antibody-mediated podocytopathies and their classification. The presence of these autoantibodies correlates with disease activity and offers considerable potential as an innovative biomarker for post-transplant recurrent FSGS. However, the precise contribution of these autoantibodies to the development of recurrent FSGS after transplantation remains elusive. In this review, we summarize the current research on anti-nephrin autoantibodies and discuss their applicability as a new biomarker for diagnosing, predicting outcomes, and guiding treatment in post-transplant recurrent FSGS.

Hypothyroidism is a rare cause of rhabdomyolysis and an even less common cause of acute kidney injury (AKI). Because the symptoms may be mild or non-specific, the diagnosis can easily be overlooked. We report the case of a 44-year-old man with no significant past medical history who was admitted after renal impairment was discovered on routine blood testing. On clinical examination, he had sinus bradycardia, puffy facies with bilateral periorbital edema, Hertoghe sign, muffled heart sounds, psychomotor slowing, and constipation. Laboratory investigations showed stage II AKI, severe rhabdomyolysis with creatine phosphokinase levels above 8,450 IU/L (reference range: <171 IU/L), and liver cytolysis. Further evaluation revealed profound hypothyroidism, with markedly elevated thyroid-stimulating hormone, very low free thyroxine, and strongly positive anti-thyroid peroxidase antibodies, consistent with autoimmune thyroiditis. Thyroid ultrasound supported the diagnosis of Hashimoto's thyroiditis, and echocardiography showed a moderate pericardial effusion without hemodynamic compromise. Because nephrotic-range proteinuria was also present, a kidney biopsy was performed and showed mainly tubulointerstitial injury with pigmented casts and tubular atrophy, associated with focal segmental glomerulosclerosis. The patient was treated with intravenous hydration and gradual levothyroxine replacement, with clear clinical improvement and progressive normalization of laboratory abnormalities. This case highlights that severe hypothyroidism may rarely present with rhabdomyolysis and AKI. It also underlines the importance of considering thyroid dysfunction in patients with unexplained rhabdomyolysis, especially when the clinical picture is not very suggestive, since early treatment can lead to a favorable outcome.