Cryoglobulinemia (CG) is a rare disease characterized by the presence of circulating immunoglobulins that precipitate at low temperatures and may lead to systemic manifestations. We report the case of a 73-year-old woman who met the diagnostic criteria for type I cryoglobulinemic vasculitis, presenting with ulceronecrotic, partly purpuric lesions. Skin biopsy revealed vasculitis, and laboratory evaluation revealed an IgG kappa monoclonal gammopathy, leading to multiple myeloma (MM) as the underlying etiology. Clone-directed therapy resulted in marked clinical improvement, with significant regression of cutaneous lesions within two months. Given its rarity and potential for severe complications, this case highlights the importance of systematically investigating an underlying monoclonal gammopathy in patients presenting with type I cryoglobulinemic vasculitis.

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a form of monoclonal gammopathy of renal significance (MGRS) in which monoclonal immunoglobulin deposits are found within the glomerulus, without involvement of other renal compartments. This condition can result in kidney dysfunction and ultimately kidney failure. It most commonly presents in the native kidney and has a high risk of recurrence in renal allografts, typically within a few months post-transplantation. PGNMID rarely presents as de novo in a transplanted kidney; if so, it usually manifests within 3 years. Early treatment is required to prevent further deterioration and reduce the risk of allograft loss. We present a case of a patient who presented with progressive kidney function decline 10.5 years after simultaneous pancreas-kidney (SPK) transplantation. The patient had a prior diagnosis of an immune complex-mediated glomerulonephritis on the pre-transplant native renal biopsy. The subsequent allograft biopsy showed electron-dense, glomeruli-limited deposits on electron microscopy, with immunofluorescence showing a nonspecific full-house pattern of staining. Immunofluorescence performed following protease (pronase) digestion on FFPE tissue showed the deposits to be IgG3 lambda light chain restricted, with no plasma cell or lymphoid clone identified in the bone marrow, resulting in a diagnosis of MGRS with a PGNMID pattern in the renal biopsy. This prompted treatment with prednisone and rituximab, with subsequent ongoing improvement in proteinuria and kidney function. To our knowledge, this is the latest presentation of post-transplantation de novo PGNMID with survival reported to date.

Immunoglobulin A-dominant infection-related glomerulonephritis (IgA-DIRGN) is a rare variant of acute postinfectious glomerulonephritis, typically seen in elderly individuals with comorbid conditions. IgA-DIRGN is characterized by diffuse endocapillary proliferation and the formation of mesangial deposits of IgA and C3, leading to inflammation and subsequently resulting in acute kidney injury, proteinuria, hematuria, and hypocomplementemia. In this report, we describe an immunocompromised 68-year-old man who developed acute kidney injury, nephrotic-range proteinuria, and microscopic hematuria following a splenic Mycobacterium avium abscess. Kidney biopsy showed endocapillary proliferative glomerulonephritis with IgA and C3-dominant granular deposits, consistent with IgA-DIRGN. Progression of kidney dysfunction during antimycobacterial therapy prompted the use of glucocorticoids 1 month after the initial presentation and eventually a splenectomy 1 month later, followed by renal recovery. To our knowledge, this is the first case to report the association between a nontuberculous mycobacterial infection and IgA-DIRGN, emphasizing the importance of source control and illustrating the usefulness of steroids in this patient.

Cryoglobulinemia is an immune complex-mediated disorder that can be associated with autoimmune diseases, lymphoproliferative disorders, and chronic infections. Renal involvement can be a prominent manifestation and may occasionally be the initial clue to an underlying systemic condition. Here, we describe a 33-year-old woman who presented with pedal edema, intermittent arthralgia, hematuria, and impaired renal function. Kidney biopsy demonstrated characteristic intraluminal pseudothrombi with dominant immunoglobulin M deposition, consistent with cryoglobulinemic glomerulonephritis. Subsequently, serologic testing confirmed mixed cryoglobulinemia. Further evaluation revealed strong positivity for anti-Sjögren syndrome-related antigen-A and anti-Sjögren syndrome-related antigen-B antibodies, and a labial salivary gland biopsy fulfilled the 2016 American College of Rheumatology European Alliance of Associations for Rheumatology criteria for Sjögren syndrome, despite the absence of sicca symptoms. Treatment with corticosteroids and rituximab led to significant improvement in renal function. The clinical course was complicated by secondary thrombotic microangiopathy, which responded to plasma exchange. This report highlights the diagnostic value of kidney biopsy in uncovering occult systemic autoimmune disease and emphasizes that Sjögren syndrome may initially present with isolated renal manifestations. Early recognition is essential for the timely initiation of appropriate immunomodulatory therapy.

Resolving T cell clonality at single-cell spatial resolution remains a major challenge. Here, we developed an in situ hybridization panel comprising probes for immune and tissue cell types alongside comprehensive coverage of TRAV, TRBV, TRGV, and TRDV gene segments, enabling unbiased spatial mapping of T cell clones in situ. As a proof of principle, we applied this approach to human kidney biopsies from patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis and controls. Combinatorial T cell receptor variable (TRV) gene expression allowed identification of T cell clones and their spatial organization. Confined clusters of clonally related αβ T cells were found in proximity to increased numbers of antigen-presenting cells, consistent with local immune activation, while γδ T cells occupied distinct peripheral niches. Although paired αβ chain detection is currently limited, this method establishes a scalable framework for spatially resolved clonotype analysis and provides a broadly applicable tool to investigate tissue-level immune organization across diseases.

Crescentic renal amyloidosis is a rare complication of light-chain (AL) amyloidosis. We report the case of a 73-year-old man with AL amyloidosis involving the kidney and heart. At diagnosis, his creatinine was 0.94 mg/dL and proteinuria was 3.1 g/d. He achieved a hematologic very good partial response with ixazomib, cyclophosphamide, and dexamethasone. Creatinine briefly increased to 1.4 mg/dL after a coronavirus disease-2019 (COVID-19) infection but returned to baseline and remained stable for 11 months until receiving a COVID-19 vaccine. Following vaccination, creatinine progressively increased, and proteinuria increased to 8.5 g/d. Owing to worsening kidney function, therapy was switched first to daratumumab and subsequently to bortezomib. Although these agents further reduced lambda free light chains, creatinine continued to increase to 2.68 mg/dL, accompanied by a 25-pound weight loss. A kidney biopsy demonstrated diffuse amyloid deposition, cellular crescents, and fibrinoid necrosis in 2 glomeruli. Serologies for vasculitis were negative. Creatinine initially improved with dexamethasone, but treatment was discontinued owing to steroid myopathy. Cyclophosphamide was initiated, but creatinine increased further to 3.3 mg/dL. After switching to mycophenolate mofetil, creatinine steadily improved to 2.5 mg/dL. In this case, crescentic glomerulonephritis likely developed secondary to the COVID-19 vaccine, as evidenced by its lack of response to therapy targeting AL amyloidosis. This case emphasizes the importance of kidney biopsy in patients whose kidney function declines unexpectedly during successful treatment of systemic diseases such as AL amyloidosis.

Lipin-1 deficiency is a rare inherited metabolic disorder and a major genetic cause of severe, recurrent rhabdomyolysis in early childhood, carrying a significant risk of acute kidney injury and mortality if unrecognized. We report the case of a male toddler who first presented at 19 months of age with dark urine and intercurrent viral illness. Initial investigations demonstrated hematuria/myoglobinuria, proteinuria, and markedly elevated transaminases, leading to a presumptive diagnosis of glomerulonephritis. Creatine kinase (CK) was not measured at that time, and the episode was retrospectively felt to represent missed rhabdomyolysis. The patient subsequently presented similarly with abdominal pain and dark urine when profound rhabdomyolysis was identified by checking CK (CK >120,000 U/L). Aggressive hyperhydration led to biochemical improvement, and genetic testing confirmed a homozygous pathogenic LPIN1 exon 18 deletion. Since diagnosis, he has experienced multiple recurrent episodes of rhabdomyolysis, predominantly triggered by viral infections, requiring repeated admissions and intensive metabolic management. Notably, this patient also has a background of global developmental delay (GDD). To our knowledge, this represents the first reported case describing an association between LPIN1 deficiency and developmental delay. Emerging experimental and clinical evidence suggests a potential biological link between LPIN1 dysfunction, impaired myelination, and abnormal neurodevelopment, raising the possibility that developmental delay may be an under-recognized phenotypic feature of this condition. This case highlights the importance of considering rhabdomyolysis in children presenting with dark urine and intercurrent illness and the critical role of early CK measurement in preventing missed diagnoses. Prompt recognition of LPIN1 deficiency is essential, as delayed treatment may result in life-threatening complications and avoidable morbidity.

Distinguishing autoimmune glomerulonephritis from hereditary nephropathy is critical to avoid unnecessary immunosuppression and ensure appropriate long-term renal monitoring. A 31-year-old Hispanic female patient with a complex medical history, including proteinase 3 (PR3)-positive granulomatosis with polyangiitis (GPA), rheumatoid arthritis, Raynaud phenomenon, seizure disorder, autism spectrum disorder, bipolar disorder with psychotic features, and cochlear implantation in childhood, was found to have genetically confirmed Alport syndrome through Natera testing (Natera, Inc., Austin, Texas, United States). Despite preserved renal function (estimated glomerular filtration rate (eGFR) 107 mL/minute/1.73m²), urinalysis demonstrated persistent proteinuria. Her history of early-onset hearing loss requiring cochlear implantation raised suspicion for hereditary nephropathy. Elevated anti-PR3 antibodies were present without clinical evidence of active vasculitis. The coexistence of autoimmune disease and hereditary collagen IV nephropathy complicated the attribution of urinary abnormalities. This case highlights the importance of genetic evaluation in patients with multisystem disease and urinary abnormalities, particularly when clinical features such as early-onset sensorineural hearing loss are present. Recognition of Alport syndrome in patients with coexisting autoimmune vasculitis has significant implications for renal surveillance, immunosuppressive stewardship, and multidisciplinary management.

The kidney is a primary target organ in systemic lupus erythematosus (SLE) and ANCA-associated vasculitis (AAV), which frequently manifest as lupus nephritis (LN) and renal AAV, respectively. A severe acute presentation of both diseases is rapidly progressive glomerulonephritis (RPGN), leading to rapid loss of renal function. However, the shared molecular mechanisms underlying this aggressive phenotype remain poorly defined. This study aimed to identify key biomarkers and pathological processes in acute autoimmune-related glomerulonephritis, with a focus on LN and AAV presenting as RPGN. Through comparative transcriptomic analysis of glomerular samples from patients with LN, AAV, and RPGN against healthy controls, we identified a total of 180 common differentially expressed genes, comprising 33 upregulated and 147 downregulated genes. Pathway analysis revealed enhanced immune and inflammatory responses, including neutrophil extracellular trap (NET) formation, accompanied by significant impairments in amino acid and fatty acid metabolism. A core set of 12 hub genes was identified, and network analysis suggested specific transcriptional and post-transcriptional regulatory axes. Immune infiltration analysis demonstrated a common pattern characterized by decreased resting immune cells and increased activated cells-including memory CD4 [+] T cells, NK cells, and mast cells-along with elevated monocyte levels, particularly in LN. Notably, epidermal growth factor (EGF) was significantly downregulated and strongly correlated with impaired renal function, demonstrating good diagnostic performance. These findings suggest that EGF may serve as a potential biomarker for LN and RPGN. This study provides the first systematic transcriptomic analysis of LN and AAV presenting as RPGN, highlighting enhanced inflammation (including NETosis) and dysregulated amino acid/fatty acid metabolism as key glomerular pathological features. Targeting EGF signaling and monocyte differentiation may offer novel therapeutic strategy for LN and AAV presenting as RPGN.