Immune checkpoint inhibitors have improved cancer prognosis, but are associated with immune-related adverse events, including rare renal complications. Here, we report the case of a 68-year-old Japanese man with unresectable advanced non-small cell lung cancer who developed nephrotic syndrome and organizing pneumonia associated with durvalumab therapy. The patient developed significant proteinuria during glucocorticoid treatment for organizing pneumonia. Renal biopsy led to a diagnosis of durvalumab-associated nephrotic syndrome. Histological examination revealed complex features, characterized by lesions resembling focal segmental glomerulosclerosis, marked foot process effacement and detachment, and prominent tubulointerstitial nephritis. Notably, his proteinuria improved following discontinuation of durvalumab and treatment with losartan potassium, dapagliflozin, and finerenone, without a substantial increase in the glucocorticoid dose. The clinical course highlights the heterogeneity of durvalumab-associated nephrotic syndrome.
Drug-induced thrombotic microangiopathy (TMA) is an important cause of kidney injury in patients receiving anticancer therapy, although kidney-limited forms without systemic manifestations are often difficult to recognize. Pegylated liposomal doxorubicin (PLD)-associated TMA remains under-recognized, particularly in patients receiving concomitant vascular endothelial growth factor (VEGF) inhibitors. We report a case of biopsy-proven kidney-limited TMA associated with bevacizumab and PLD in a 52-year-old woman with metastatic ovarian serous adenocarcinoma, characterized by a biphasic clinical course. She developed progressive kidney dysfunction and proteinuria during treatment with bevacizumab followed by PLD. Despite discontinuation of bevacizumab, kidney dysfunction persisted. Kidney biopsy demonstrated findings consistent with TMA, including mesangiolysis, glomerular basement membrane duplication, and focal PAS-positive pseudothrombi suggestive of VEGF inhibitor–associated endothelial injury. Electron microscopy further revealed endothelial detachment, accompanied by a substance containing liposome-like particles, suggestive of the characteristic ultrastructural findings previously reported in PLD-associated TMA. The patient had no evidence of microangiopathic hemolytic anemia or thrombocytopenia, and no alternative cause of TMA was identified. Following discontinuation of PLD, kidney function improved markedly with complete resolution of proteinuria. This case highlights the importance of kidney biopsy and careful clinicopathological correlation in diagnosing drug-induced kidney-limited TMA.
Kidney transplantation (KT) for adenine phosphoribosyltransferase (APRT) deficiency is performed using the xanthine dehydrogenase (XDH) inhibitor allopurinol to prevent the recurrence of dihydroxyadenine (DHA) nephropathy. However, there are few reports on the use of febuxostat after pediatric KT for APRT deficiency. Herein, we report the case of a 12-year-old boy with congenital kidney and urinary tract abnormalities who underwent deceased-donor KT for end-stage kidney disease caused by APRT deficiency. The patient developed acute kidney injury during infancy due to urinary tract stones and was diagnosed with APRT deficiency based on stone analysis and genetic testing. Treatment with allopurinol was initiated. However, the patient had persistent renal dysfunction and required peritoneal dialysis at the age of 9 years. Grade IV left vesicoureteral reflux (VUR) and a large bladder diverticulum were observed. Although the VUR resolved, the patient underwent bladder diverticulectomy and ureteroneocystostomy before KT due to recurrent complicated urinary tract infections associated with an enlarged bladder diverticulum and residual urine. Subsequently, the patient underwent KT, and the XDH inhibitor was switched from allopurinol to febuxostat. Transplant renal biopsy at 4 months post-KT showed no recurrence of DHA nephropathy; graft function remained stable. This case demonstrated that pediatric patients with APRT deficiency undergoing KT could be successfully managed with febuxostat.
Variants in the inverted formin-2 (INF2) gene are a known cause of hereditary focal segmental glomerulosclerosis (FSGS) and Charcot–Marie–Tooth disease. We report a case of rapidly progressive FSGS associated with a rare INF2 variant. A 12-year-old boy developed proteinuria and was diagnosed with FSGS at age 14 following a renal biopsy. Steroid therapy and subsequent immunosuppressive treatments, including plasma exchange, were ineffective. At age 15, a heterozygous missense variant in exon 6 of the INF2 gene (c.763G>A, p.Asp255Asn) was identified. Despite conservative management, the patient progressed to end-stage kidney disease at age 17. Although exon 6 variants are rarely reported, the present case showed a relatively aggressive renal course.
Ethylene glycol (EG) poisoning typically causes severe metabolic acidosis and acute kidney injury (AKI), characterized by urinary calcium oxalate (CaOx) crystals. Although needle-shaped calcium oxalate monohydrate (COM) crystals are a recognized diagnostic marker in the acute phase, sequential changes in urinary crystal morphology during recovery have not been well characterized in human cases. We present a 32-year-old man who developed profound metabolic acidosis (pH 6.747) and AKI (serum creatinine 1.56 mg/dL) after ingesting a lethal dose of EG. Following emergency hemodialysis and fomepizole treatment, urinalysis showed a sequential transition of urinary CaOx crystals from abundant needle-shaped COM in the acute phase to dumbbell-shaped COM and octahedral calcium oxalate dihydrate (COD) by day 14. This transition was observed during recovery, and renal function fully recovered by day 68 (serum creatinine 0.78 mg/dL). Low-vacuum scanning electron microscopy (LV-SEM) provided detailed three-dimensional visualization of these recovery-phase crystals after simple cytospin preparation, without chemical fixation or conductive coating. This report provides the first human LV-SEM visualization and characterization of recovery-phase urinary calcium oxalate crystals in ethylene glycol poisoning. These morphological changes may reflect recovery-related changes in the intratubular environment and offer pathophysiological insight into the transition from the acute toxic phase to recovery.
Anti-glomerular basement membrane (anti-GBM) disease is a rare autoimmune disorder characterized by rapidly progressive glomerulonephritis, with or without pulmonary hemorrhage. Central nervous system (CNS) involvement is exceedingly uncommon, and intracranial subarachnoid hemorrhage (SAH) has rarely been described in association with anti-GBM disease. We report a rare case of anti-GBM disease complicated by intracranial SAH and subsequent cerebral infarction. A 53-year-old woman presented with fever and headache and rapidly developed acute kidney injury with markedly elevated anti-GBM antibody titers. Renal biopsy confirmed anti-GBM disease. Despite treatment with plasma exchange and high-dose corticosteroids, renal function deteriorated, and the patient became dialysis-dependent. Rituximab was added to achieve serological control after an insufficient response to conventional therapy. During the clinical course, the patient developed a generalized seizure and was diagnosed with intracranial SAH, followed later by a subacute cerebral infarction. Cerebral angiography revealed no aneurysms or vascular malformations. Blood pressure had remained stable prior to the neurological event. Following intensive management, including continued plasma exchange, rituximab, corticosteroids, and strict blood pressure control, no neurological sequelae were observed. Anti-GBM antibody titers gradually declined, although renal function did not recover. This case illustrates a rare occurrence of intracranial subarachnoid hemorrhage as a central nervous system complication in anti-GBM disease and highlights the importance of careful neurological monitoring.
Lysozyme-induced nephropathy (LyN) is a rare kidney complication associated with chronic myelomonocytic leukemia (CMML). This condition is characterized by distinctive pathological features, including granules within proximal tubular cells that stain positively with periodic acid-Schiff or lysozyme staining, and granular deposits identified as high-electron-density deposits under electron microscopy. Although CMML is the most common cause of LyN, previous reports have suggested that its occurrence may be associated with the myelodysplastic syndrome (MDS). This report describes cases of LyN in a patient with MDS and CMML. Although both the LyN cases, caused by either MDS or CMML, exhibited similar kidney pathological findings, there was a clinical difference in the occurrence of peripheral blood monocytosis. The MDS-induced LyN showed no persistent peripheral blood monocytosis and, when the bone marrow biopsy specimens were stained with lysozyme, numerous positive cells were observed. Thus, hematologic disorders wherein the bone marrow comprises lysozyme-producing cells may induce LyN, even without peripheral blood monocytosis.
To describe a pediatric case of aHUS triggered by influenza A(H1N1) infection in a patient with a homozygous pathogenic variant in CD46, successfully treated with ravulizumab. A previously healthy 12-year-old girl presented with a four-day history of fever, diarrhea, abdominal pain, mucosal bleeding, jaundice, and acute kidney injury. Initial evaluation confirmed microangiopathic hemolytic anemia and thrombocytopenia. ADAMTS13 activity was preserved. Nasopharyngeal polymerase chain reaction testing detected influenza A virus subtype H1N1, and a multiplex gastrointestinal polymerase chain reaction panel identified enteropathogenic Escherichia coli; Shiga toxin was not detected. Despite therapeutic plasma exchange and hemodialysis, there was no hematologic or renal improvement, and multi-organ involvement persisted, including respiratory failure and elevated pancreatic enzyme levels. Terminal complement inhibition with ravulizumab was initiated, leading to rapid hematologic normalization and full renal recovery by day 106. Genetic testing revealed a homozygous splice-site variant in CD46 (c.286 + 1G > C), consistent with atypical hemolytic uremic syndrome. This case underscores the importance of early C5 inhibition in complement-mediated thrombotic microangiopathy associated with defects in membrane-bound complement regulators, in which therapeutic plasma exchange may have limited efficacy. It also highlights how infections can act as triggers that unmask underlying genetic susceptibility.
Anti-glomerular basement membrane (anti-GBM) disease typically presents as rapidly progressive glomerulonephritis, however an atypical anti-GBM nephritis with various light microscopic findings without crescentic formation has been reported in recent years. The findings reported including cases with membranoproliferative glomerulonephritis (MPGN) pattern. Few reports have been able to follow the course of the disease over a long period of time. We report a case of MPGN associated with the spectrum of atypical anti-GBM nephritis that showed a slowly progressive course over more than eight years. A 49-year-old man underwent kidney biopsy because of hypertension, proteinuria, and mild renal insufficiency. The findings on kidney biopsy showed the findings of MPGN. Immunofluorescence microscopy revealed bright linear staining of IgG on the GBM. Electron microscopy showed subepithelial, intra-basement membrane, subendothelial, and paramesangial electron-dense deposits. Serum anti-GBM antibodies were negative. Proteinuria had been present for 4 years prior to the renal biopsy, however no worsening of renal function was observed. Because of worsening proteinuria and the presence of endocapillary hypercellularity in the tissues, the intravenous and oral steroids were started. Although the proteinuria showed slight improvement, the serum creatinine level was stable around 1.5–1.7 mg/dl. Although some indolent cases of atypical anti-GBM syndrome were reported previously, compared with these cases, our patient had more stable renal function for a long time. This is a rare case of resembling atypical anti–GBM disease that shows MPGN with linear IgG staining having a long-term indolent course and without secondary etiology.
Pathogenic variants in the WDR72 gene are known to cause hypoplastic amelogenesis imperfecta (AI) and have recently been linked to distal renal tubular acidosis (dRTA). This case report highlights an unusual presentation of WDR72-associated dRTA with renal cysts. A 12-year-old boy presented with difficulty walking, lower limb deformities, and significant growth retardation. On examination, hypoplastic AI, rickets, and short stature were present. Biochemical investigations showed hypokalemia, hypophosphatemia, elevated alkaline phosphatase, and hypercalciuria. Imaging revealed medullary nephrocalcinosis and renal cysts. Clinical exome sequencing identified a homozygous pathogenic nonsense variant in WDR72 (NM_182758.4): c.2934G > A (p.Trp978Ter), consistent with autosomal recessive inheritance. He was diagnosed with dRTA and managed with potassium citrate and phosphate supplementation. Over two years, the patient showed improved growth velocity and reduced hypercalciuria, though nephrocalcinosis and renal cysts persisted. This case of WDR72-associated dRTA complicated by renal cyst formation is an underrecognized phenotype of this rare disorder. It further highlights that delayed diagnosis and prolonged, uncorrected tubulopathy may result in structural renal injury that is not fully reversible with treatment. Systematic renal evaluation, including biochemical assessment and renal ultrasonography, is strongly warranted in all children presenting with AI, particularly in the presence of concurrent growth failure, electrolyte disturbances, or rachitic changes, to facilitate early diagnosis and mitigate the risk of long-term renal sequelae.
Rhabdomyolysis in children is frequently attributed to viral myositis or trauma; however, severe or recurrent episodes precipitated by febrile illnesses often indicate an underlying genetic myopathy. Variants in the LPIN1 gene, which encodes the phosphatidic acid phosphatase Lipin-1, have recently emerged as a major cause of early-onset, life-threatening rhabdomyolysis (Autosomal Recessive Acute Recurrent Myoglobinuria). We present the case of a 5-year-old female who presented with acute onset profound lethargy, generalized muscle weakness, and cola-colored urine following a viral prodrome, on a background of previous similar milder episodes. The patient’s family history was significant for consanguinity and the unexplained deaths of two siblings at similar ages. Laboratory investigations revealed massive rhabdomyolysis with a creatine phosphokinase (CPK) level of 59,679 U/L and significant myoglobinuria, though renal function remained initially preserved. Given the severity of the presentation and family history, comprehensive genetic investigation was pursued. Whole Exome Sequencing (WES) of a similarly affected younger sibling, followed by targeted familial screening, identified a homozygous variant in the LPIN1 gene; NM_001349206.2: c.2360_2361delinsGA p.(Pro787Arg) in our patient. The patient was managed conservatively with vigorous hydration and alkalinization of urine, resulting in clinical improvement without the development of acute renal failure. LPIN1 deficiency is a critical differential diagnosis in pediatric patients presenting with unexplained, massive rhabdomyolysis, particularly in the context of consanguinity or a history of sibling mortality preceded by muscle weakness. This case highlights the utility of Whole Exome Sequencing post-stabilization to establish a strong molecular basis for the diagnosis, which terminates the diagnostic odyssey and is essential for providing genetic counseling to affected families.
Tubulointerstitial nephritis (TIN) with IgM-positive plasma cells (IgMPC-TIN) is an inflammatory disease characterized by the infiltration of IgM and CD138 dual-positive plasma cells into the renal interstitium. Steroid treatment is effective for many cases of IgMPC-TIN. However, the optimal dose and duration of steroid therapy remain poorly understood. In the present case, IgMPC-TIN was diagnosed in a 36-year-old woman with femoral head osteonecrosis. After administration of prednisolone (PSL, 20 mg/day), several markers of disease activity gradually decreased. The PSL dose was tapered to 5 mg/day for one year without TIN recurrence. To avoid exacerbation of bone lesions due to prolonged administration of PSL, cyclosporine was added to PSL. Combination treatment with 5 mg/day PSL and 100–125 mg/day cyclosporine stabilized the TIN. The patient remained stable without recurrence after further reduction and discontinuation of PSL. This case provides original evidence regarding the optimal treatment regimen for patients with IgMPC-TIN who are unsuitable for prolonged PSL administration.
A 19-year-old male with end-stage renal disease caused by vesicoureteral reflux, hypertension, and type 2 diabetes mellitus underwent preemptive kidney transplantation using his mother’s left kidney. This was an ABO-incompatible kidney transplant between a recipient with blood type O and a donor with blood type B. Therefore, plasma exchange and rituximab administration were performed preoperatively as desensitization therapy. Immediately after vascular anastomosis, blood flow in the transplanted renal cortex was assessed using ultrasonography, which was deemed adequate. Nonetheless, the urine output did not increase. Ultrasound re-evaluation revealed an elevated vascular resistance index in the transplanted renal cortex, raising hyperacute rejection suspicion. Rejection therapy was initiated before vesicoureteral anastomosis. Because concomitant de novo thrombotic microangiopathy (dnTMA) was also suspected, anticoagulant therapy was initiated. By the end of the surgery, the velocity of the renal cortical blood flow had decreased, prompting immediate plasma exchange. Hemodialysis was performed on postoperative day (POD) 0 but was not required thereafter. Serum creatinine levels remained at around 5–6 mg/dL for some time; nevertheless, they began to decrease on POD15, finally improving to 1.36 mg/dL on POD 65. A renal biopsy performed 1 h after reperfusion revealed fibrin thrombi and inflammatory cell infiltrates in the glomerular capillaries (g1), resulting in the diagnosis of dnTMA due to hyperacute rejection. The cause of hyperacute rejection was possibly HLA-DP donor-specific antibody. This report describes a case in which the prompt treatment for dnTMA due to hyperacute rejection preserved graft function.
AL amyloidosis is characterized by extracellular deposition of immunoglobulin light-chain fibrils, frequently leading to kidney involvement and progressive organ dysfunction. We report a case of kidney AL amyloidosis secondary to multiple myeloma in which daratumumab-based chemotherapy combined with autologous peripheral blood stem cell transplantation resulted in marked improvement, as confirmed by sequential kidney biopsy. The initial biopsy revealed vascular-dominant amyloid deposition, whereas the second biopsy obtained 2 years later demonstrated a marked reduction in amyloid burden, particularly within the vascular compartments. This histopathological improvement corresponded with hematologic remission and stabilization of kidney function. The observed reduction in tissue amyloid deposits was presumed to result from suppression of amyloidogenic light chains, leading to inhibition of new fibril formation and subsequent tissue remodeling. Our findings provide direct pathological evidence that daratumumab-based combination therapy, through immune-mediated plasma cell depletion, may indirectly promote the regression of amyloid deposits and contribute to functional recovery.
Lymphomatoid granulomatosis (LYG) is a rare Epstein–Barr virus-associated B-cell lymphoproliferative disorder. While LYG mainly causes pulmonary lesions, it is also known to cause extrapulmonary lesions involving the kidney; however, there are limited reports describing the pathology of extrapulmonary lesions in detail. We report the case of an 82-year-old woman who presented with fever and multiple pulmonary nodules, along with elevated urinary β2-microglobulin and proteinuria. A renal biopsy revealed granuloma-like interstitial infiltrates consisting predominantly of CD3+ and CD4+ T lymphocytes with scattered CD20+ B cells and histiocytes. Similar findings on CT-guided lung biopsy raised the possibility of Grade 1 LYG, although a definitive diagnosis could not be established. Following transient clinical improvement with corticosteroids, pulmonary lesions recurred. Subsequent video-assisted thoracoscopic surgery confirmed the presence of Epstein–Barr virus-encoded small (EBER)-RNA positive cells, establishing a final diagnosis of LYG. Detailed descriptions of the renal pathology of LYG are scarce. This case adds to the limited number of reported cases and highlights the value of renal biopsy in excluding alternative diagnoses, particularly when a definitive diagnosis cannot be made using transbronchial or CT-guided lung biopsy.
Renal arcuate vein thrombosis (RAVT) is a rare and often underrecognized cause of acute kidney injury (AKI) that typically requires renal biopsy for diagnosis. We report a 29-year-old man who developed AKI following heavy alcohol intake, an upper respiratory tract infection, and exposure to multiple medications including repeated nonsteroidal anti-inflammatory drugs and traditional Chinese patent medicines. Laboratory tests showed mild proteinuria without hematuria and negative autoimmune serology, with normal renal imaging. Renal biopsy revealed acute tubular injury and thrombus-like material within arcuate veins, accompanied by mild medullary hemorrhage and focal vascular necrosis, findings suggestive of arcuate venous thrombosis. Renal function recovered completely after supportive therapy within eight days. This case highlights that an arcuate venous lesion suggestive of thrombosis may be an underrecognized finding in patients with multifactorial, biopsy-proven AKI, even when the clinical presentation and imaging findings are nonspecific. Awareness of this possibility may broaden the differential diagnosis in selected patients with unexplained or disproportionate AKI and multiple renal risk factors, and kidney biopsy may help identify otherwise unrecognized vascular involvement.
Immunoglobulin A (IgA) nephropathy (IgAN) with superimposed minimal change disease (MCD) is a rare but increasingly recognized clinicopathological phenotype that is generally associated with a favorable renal prognosis. We present a case of IgAN with MCD complicated by severe acute kidney injury (AKI) during the clinical course and requiring temporary renal replacement therapy. A 38-year-old man presented with acute nephrotic syndrome. Renal biopsy showed mesangial IgA deposition, and anti-galactose-deficient IgA1 antibody (KM55) staining demonstrated co-localization with IgA deposits, supporting the diagnosis of IgAN with superimposed MCD. Electron microscopy revealed foot process effacement, leading to a diagnosis of IgAN with MCD. High-dose prednisolone therapy was initiated; however, the patient subsequently developed severe AKI requiring hemodialysis (HD). Concurrent treatment with cyclosporine A and steroid pulse therapy was administered, ultimately allowing successful discontinuation of HD. This rare case was diagnosed as IgAN with MCD based on mesangial IgA deposition supported by KM55 staining and characteristic electron microscopic findings, and this case demonstrates that severe AKI requiring temporary HD may occur during the clinical course of IgAN with MCD. Although IgAN with MCD has been increasingly recognized, reports of cases complicated by severe AKI requiring HD remain limited in the literature. This patient showed subsequent improvements in renal function and proteinuria, suggesting that this condition may be reversible. These findings highlight the importance of careful clinical management with attention to the potential risk of AKI even in patients with IgAN with MCD.
Denosumab is increasingly used to treat osteoporosis in patients with advanced kidney disease, but clinically significant disturbances in calcium homeostasis remain a major concern. We report a peritoneal dialysis (PD) case in which denosumab administration was followed by pronounced calcium fluctuations requiring medication management. A 56-year-old woman with end-stage kidney disease due to lupus nephritis, receiving prednisolone (5 mg/day), had been on continuous ambulatory PD (1.5-L exchanges three times daily) for 5 years. Baseline intact parathyroid hormone was 176 pg/mL. Osteoporosis was confirmed by dual-energy X-ray absorptiometry (lumbar spine 68
Pregnancy induces vascular, coagulation, and immune alterations that predispose to thrombotic microangiopathy (TMA). Within this spectrum—preeclampsia/ hemolysis, elevated liver enzymes, and low platelets syndrome (HELLP) and complement-mediated TMA (CM-TMA)—overlapping features complicate diagnosis, whereas management and prognosis diverge. A 39-year-old woman developed severe hypertension at 35 weeks’ gestation, underwent emergency cesarean section for preeclampsia, and subsequently became anuric. She had schistocytic hemolysis, thrombocytopenia, elevated lactate dehydrogenase (LDH), and transaminitis. One plasma exchange, hemodialysis, and supportive care were provided; urine output recovered and dialysis ceased. Atypical complement tests results persisted for 1 month (undetectable serum CH50 with elevated C3/C4), with normal functional assays and no pathogenic variants in complement-regulatory genes. On subsequent testing with Ethylenediaminetetraacetic acid (EDTA) plasma, preserved at − 80 °C, showed a normal CH50, suggesting that ex vivo complement activation may have contributed to the low serum CH50. In the acute setting, HELLP versus CM-TMA remained indeterminate, so management was guided by the clinical trajectory: brief plasma exchange during TTP evaluation, close monitoring, and deferral of complement inhibition as platelets, LDH, and urine output improved. This case supports a “trend-first” approach to peripartum TMA, and underscores ex vivo complement activation as a key pitfall when interpreting complement assays in the peripartum setting.
