Micaela Gentile

Diabetic kidney disease (DKD) is increasingly recognized as a heterogeneous condition encompassing distinct clinical and pathological phenotypes. Albuminuria and estimated glomerular filtration rate may follow divergent trajectories, with non-albuminuric kidney function decline representing a common and clinically relevant phenotype. Importantly, clinical features do not always reflect the underlying renal pathology, as patients with diabetes may present with diabetic kidney disease, non-diabetic kidney disease (NDKD), or mixed lesions. Conventional clinical markers, including diabetic retinopathy, hematuria, proteinuria, and eGFR decline, modify but do not reliably establish the underlying diagnosis. Kidney biopsy therefore retains a selective but important role in patients with atypical or rapidly evolving presentations, particularly when histological findings may alter treatment or prognosis. Beyond diagnostic classification, biopsy can provide prognostic information through assessment of glomerular, tubulointerstitial, and vascular injury. Future approaches should integrate longitudinal clinical trajectories with histopathology and molecular profiling, positioning kidney biopsy as a bridge toward mechanism-based classification and precision medicine in DKD.

Granulomatosis with polyangiitis (GPA) is a systemic vasculitis frequently associated with serum anti-neutrophil cytoplasmic antibodies (ANCAs), particularly anti-proteinase 3 (PR3). Multisystem involvement is typical, although disease onset with simultaneous manifestations affecting both the ocular and otorhinolaryngologic systems is rare and poorly reported in the literature. We describe a 65-year-old woman with renal impairment with microscopic hematuria and proteinuria and PR3-positive who developed bilateral otitis leading to sensorineural hearing loss and severe anterior scleritis, with a high suspicion of ANCA-associated vasculitis. Despite immunosuppression therapy, persistently elevated serum anti-PR3 levels in the absence of overt clinical activity prompted further diagnostic evaluation, which revealed previously unrecognized subglottic stenosis (SGS), confirmed by MRI, and fully resolved after anti-CD20 therapy. Concurrent involvement of the upper airways and ocular district as the initial presentation of GPA is unusual and may precede renal involvement by several months. Persistent elevation of PR3 levels in an apparent state of clinical remission may indicate ongoing active disease in other anatomical sites. The integration of laboratory tests, imaging studies, and multidisciplinary assessment is essential for early diagnosis and effective therapeutic management.

Diabetes mellitus represents a global health concern, which is expected to worsen over the years. The prevalence is estimated to increase up to 642 million people by 2040. Almost half of diabetic patients are at a high risk of developing kidney involvement up to dialysis; moreover, macrovascular complication could be an obstacle to kidney transplant. Besides the classic albuminuric phenotype, non-albuminuric diabetic kidney disease was also discovered recently. Fortunately, compared with classic therapy with diet, oral hypoglycemic drugs, and insulin, current clinicians can rely on several new drugs that act with different pathways characterized by kidney and heart protection, as shown by several clinical trials and confirmed in clinical practice. Herein, we will review the therapies that nephrologist and diabetologist have available today and the future perspective.

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.