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Competing Interests: The authors have no conflicts of interest to declare.

Amyloidosis is a rare cause of inherited kidney disease, with most variants responsible for prominent glomerular involvement. In this issue, Kmochová et al. reported the first description of autosomal dominant medullary amyloidosis due to apolipoprotein A4 variants, resulting in slowly progressive chronic kidney disease with minimal proteinuria. Combining next-generation sequencing with histopathological studies incorporating Congo red staining and mass spectrometry should be considered in the diagnostic workup of hereditary tubulointerstitial disorders not identified after routine genetic testing., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Sporadic cases of apolipoprotein A-IV medullary amyloidosis have been reported. Here we describe five families found to have autosomal dominant medullary amyloidosis due to two different pathogenic APOA4 variants. A large family with autosomal dominant chronic kidney disease (CKD) and bland urinary sediment underwent whole genome sequencing with identification of a chr11:116692578 G>C (hg19) variant encoding the missense mutation p.L66V of the ApoA4 protein. We identified two other distantly related families from our registry with the same variant and two other distantly related families with a chr11:116693454 C>T (hg19) variant encoding the missense mutation p.D33N. Both mutations are unique to affected families, evolutionarily conserved and predicted to expand the amyloidogenic hotspot in the ApoA4 structure. Clinically affected individuals suffered from CKD with a bland urinary sediment and a mean age for kidney failure of 64.5 years. Genotyping identified 48 genetically affected individuals; 44 individuals had an estimated glomerular filtration rate (eGFR) under 60 ml/min/1.73 m 2 , including all 25 individuals with kidney failure. Significantly, 11 of 14 genetically unaffected individuals had an eGFR over 60 ml/min/1.73 m 2 . Fifteen genetically affected individuals presented with higher plasma ApoA4 concentrations. Kidney pathologic specimens from four individuals revealed amyloid deposits limited to the medulla, with the mutated ApoA4 identified by mass-spectrometry as the predominant amyloid constituent in all three available biopsies. Thus, ApoA4 mutations can cause autosomal dominant medullary amyloidosis, with marked amyloid deposition limited to the kidney medulla and presenting with autosomal dominant CKD with a bland urinary sediment. Diagnosis relies on a careful family history, APOA4 sequencing and pathologic studies., (Copyright © 2023 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Purpose: Tubulointerstitial nephritis and uveitis (TINU) syndrome is an uncommon disease. We present a confirmed case of TINU syndrome, and a systematic review of epidemiological characteristics, clinical manifestations, management, and outcomes in Chinese patients., Methods: A systematic search was carried out using defined terms and updated up to September 2022, in PubMed, Web of Science, Wanfang, CNKI, and VIP, to identify reported cases of TINU in China, according to PRISMA guidelines., Results: An 18-year-old boy presented with elevated serum creatinine and 24-h urine protein level of > 2 g. Inspection result revealed acute tubulointerstitial nephritis, and bilateral uveitis. The patient was diagnosed with TINU syndrome and received treatment with methylprednisolone sodium succinate, which resulted in a significant decrease in creatinine and urinary protein levels. Systematic review identified 35 publications that met the inclusion criteria. A total of 71 cases were included in this article, of which 70 were from publications and 1 was from our hospital. The median age at onset was 42 years and was significantly lower in males than females (P < 0.05). The symptoms of uveitis often occurred after kidney injury (54%) and most uveitis was anterior (55%) and bilateral (75%). Among the 51 patients who were followed up for more than 6 months, 24 had recurrent ocular symptoms or progression to chronic uveitis. Twenty patients experienced chronic or progressive kidney disease., Conclusion: TINU syndrome is prone to misdiagnosis because kidney damage may not occur simultaneously with uveitis. The incidence of kidney sequelae in children is lower than that in adults, and glucocorticoids are the preferred treatment., Inplasy Registration Number: INPLASY202350050., (© 2023. The Author(s).)

IgG4-related kidney disease (IgG4-RKD) encompasses all forms of kidney disease that are part of IgG4-related disease (IgG4-RD). First recognized as IgG4-related tubulointerstitial nephritis (IgG4-TIN), and then IgG4-related membranous glomerulonephritis (IgG4-MGN), we now recognize additional patterns of interstitial nephritis, glomerular disease, and vascular disease that can be seen as part of IgG4-RKD. The clinical presentation is variable and can include acute or chronic kidney injury, proteinuria or nephrotic syndrome, mass lesion(s), and obstruction. While usually associated with other organ involvement by IgG4-RD, kidney-alone involvement is present in approximately 20 % of IgG4-RKD. Compared to IgG4-RD overall, patients with IgG4-RKD are more likely to show increased serum IgG4 or IgG, and more likely to have hypocomplementemia. In this review, we extensively cover other types of autoimmune and plasma cell-rich interstitial nephritis, mass forming inflammatory diseases of the kidney, and other mimics of IgG4-TIN, in particular ANCA-associated disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and IgG4-related disease (IgG4-RD) are distinct immune disorders with overlapping clinical and laboratory features. While ANCA positivity excludes IgG4-RD in the 2019 ACR/EULAR classification, this criterion is not uniformly applied, and AAV can form inflammatory masses in various organs and show increase in IgG4 + plasma cells, similar to IgG4-RD., Case Diagnosis/treatment: A 5-year-old female with history of orbital mass diagnosed as IgG4-RD presents with acute kidney injury. She has a myeloperoxidase ANCA, and kidney biopsy shows pauci-immune crescentic glomerulonephritis and acute tubulointerstitial nephritis with increased IgG4 + plasma cells and tubular basement membrane (TBM) deposits., Conclusion: In isolation, TBM deposits and increased IgG4 + plasma cells are suggestive of IgG4-RD. In the context of a positive ANCA and pauci-immune crescentic glomerulonephritis, however, increased IgG4 + plasma cells due to AAV are favored. In cases with features of IgG4-RD, ANCA positivity suggests an alternate diagnosis of AAV to be more likely., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: IgG4-related disease (IgG4-RD) is a fibroinflammatory disease that affects multiple organs, including the pancreas, lacrimal glands, salivary glands, periaortic/retroperitoneum, and kidney. Interstitial nephritis is a typical renal disorder associated with IgG4-RD, but membranous nephropathy is also seen in some cases., Case Presentation: Herein we report on the case of a 77-year-old male patient with nephrotic syndrome and IgG4-related lung disease. His serum phospholipase A2 receptor (PLA2R) antibody was positive. His renal biopsy specimen was also positive for PLA2R. The renal biopsy specimen showed membranous nephropathy with equal IgG3 and IgG4 immunofluorescence staining and no interstitial nephritis, suggesting IgG4-RD manifesting as membranous nephropathy., Conclusions: Nephrotic syndrome caused by membranous nephropathy is sometimes associated with IgG4-RD. In such cases, even if serum PLA2R antibody is positive, it should be considered that the membranous nephropathy may be secondary to IgG4-RD., (© 2024. The Author(s).)

Background: Recent studies have focused on immune checkpoint inhibitors. Renal complications associated with the use of immune checkpoint inhibitors are uncommon compared with other immune-related adverse events. Acute interstitial nephritis accounts for most of these renal complications, with nephrotic syndrome quite rare. We herein report a case of nephrotic syndrome associated with immune checkpoint inhibitors that was more severe than that in previous cases. By comparing this case with previous reports, the possible reasons for the particular severity of this case are discussed., Case Presentation: A 75-year-old man developed nephrotic syndrome with acute kidney injury after the first combination therapy of nivolumab and ipilimumab for malignant pleural mesothelioma. The results of a kidney biopsy indicated minimal change disease with mild atherosclerosis, acute interstitial nephritis, and fusion of nearly all podocyte foot processes. Nivolumab and ipilimumab therapy were stopped, and treatment with corticosteroids was initiated. We investigated previously reported cases of nephrotic syndrome using immune checkpoint inhibitors. Seventeen cases of immune checkpoint inhibitor-related nephrotic syndrome, including ours, have been reported. Two of the 17 patients with immune checkpoint inhibitor-related nephrotic syndrome required hemodialysis treatment for acute kidney injury. Unlike many previously reported cases, the present patient was administered two different immune checkpoint inhibitors, which may be one of the reasons for the development of severe nephrotic syndrome., Conclusions: In addition to previously reported risk factors, immune checkpoint inhibitor combination therapy can exacerbate nephrotic syndrome compared to immune checkpoint inhibitor monotherapy., (© 2024. The Author(s).)

Objectives: BK polyomavirus-associated nephropathy is a clinicopathological entity that negatively affects graft function in kidney transplant recipients. We compared the efficacy of leflunomide and cidofovir to treat BK polyomavirus-associated nephropathy in pediatric kidney transplant recipients., Materials and Methods: Medical records of pediatric recipients with BK viremia for the period 2004 through 2019 were reviewed retrospectively, and patients diagnosed with BK polyomavirusassociated nephro-pathy were included in the study. A serum BK virus level above 104 copies/mL was accepted as BK viremia. We defined BK polyomavirusassociated nephropathy as detection of BK virus SV40 antigen on immunochemistry staining of renal graft tissue accompanied by signs of tubulointerstitial nephritis or elevated serum creatinine in addition to BK viremia., Results: Of 304 kidney transplant recipients, 53 had persistent BK viremia; 36 of these patients (61.1% male) were included in the study with the diagnosis of BK polyomavirus-associated nephropathy. Twelve patients (33.3%) received cidofovir, and 14 (38.8%) received leflunomide. Results were similar between the cidofovir and leflunomide groups for serum creatinine level at last follow-up (0.91 ± 0.29 vs 0.94 ± 0.37 mg/dL, respectively; P = .843) and graft failure rate (8.3% vs 14.2%, respectively; P = .632). Graft failure was observed in 8.3% of patients with BK polyomavirus-associated nephropathy., Conclusions: Leflunomide and cidofovir showed similar efficacy for treatment of BK polyomavirus-associated nephropathy.

Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) predominantly affects small vessels. Almost all AAV patients are positive for myeloperoxidase- or proteinase 3-ANCA, and ANCA plays a crucial role in the pathogenesis of AAV. We herein report an ANCA-negative AAV patient with pauci-immune necrotizing glomerulonephritis and plasma cell-rich tubulointerstitial nephritis who was complicated with pleuritis and digital ischemia. ANCA-negative AAV is a rare clinical entity that is difficult to diagnose, and pleuritis and digital ischemia are rare manifestations of AAV. An early diagnosis and appropriate treatment are important, as any delay in the diagnosis may worsen the prognosis.

Background: Sarcoidosis affects multiple organs and exhibits diverse clinical manifestations. Although tubulointerstitial nephritis is a known feature of renal involvement, necrotizing vasculitis is rare. Furthermore, prostate involvement with urinary retention is unusual in patients with sarcoidosis. Here, we report a case of systemic sarcoidosis with a rare combination of manifestations and different acute kidney injuries., Case Presentation: A 66-year-old man developed sudden urinary retention and fever. He was diagnosed with prostatitis and admitted to our hospital. An indwelling urethral catheter was inserted, and antimicrobial therapy was initiated; however, the prostatitis was refractory. Computed tomography revealed enlarged mediastinal lymph nodes. Analysis of transbronchoscopic lymph node and prostate biopsies showed epithelioid cell granulomas, suggesting systemic sarcoidosis. During the clinical course, the serum creatinine level rapidly increased to 2.36 mg/dL without oliguria. A kidney biopsy revealed tubulointerstitial injury with moderate lymphohistiocytic infiltration and small-vessel vasculitis in the interstitium. Following oral administration of 60 mg/day prednisolone, the patient's renal function immediately improved, and urinary retention did not recur., Conclusions: To the best of our knowledge, this is the first reported case of sarcoidosis with two unusual complications. Given its clinical course and pathology, this case is clinically valuable., (© 2023. The Author(s).)

Objectives: The incidence and prevalence of inflammatory bowel disease (IBD), mainly including ulcerative colitis (UC) and Crohn's disease (CD), are increasing globally. We aimed to evaluate the potential association between IBD and nephrolithiasis, tubulointerstitial nephritis, and chronic kidney disease (CKD)., Methods: Data of hospitalized adults ≥20 years of age were extracted from the U.S. National Inpatient Sample (NIS) during 2016-2018. Patients with UC, CD, or CKD were identified through the International Classification of Diseases, Tenth Revision (ICD-10) codes. Propensity score matching (PSM) analysis (1:1) was conducted to balance the characteristics between groups. Logistic regression analyses were performed to determine the relationships between UC or CD and kidney conditions., Results: Three cohorts were included for analysis after PSM analysis. Cohorts 1, 2 and 3 contained 235 262 subjects (117 631 with CD or without IBD), 140 856 subjects (70 428 with UC or without IBD), and 139 098 subjects (69 549 with CD or UC), respectively. Multivariate analysis revealed that compared to non-IBD individuals, CD patients were significantly associated with greater odds for nephrolithiasis (adjusted odds ratio [aOR] 2.25, 95% confidence interval [CI] 2.08-2.43), tubulointerstitial nephritis (aOR 1.31, 95% CI 1.24-1.38), CKD at any stage (aOR 1.28, 95% CI 1.24-1.32), and moderate-to-severe CKD (aOR 1.22, 95% CI 1.17-1.26), while UC was associated with a higher rate of nephrolithiasis. Compared to UC, CD was associated with higher odds for all such kidney conditions., Conclusions: Patients with CD are more likely to have nephrolithiasis, tubulointerstitial nephritis, CKD at any stage, and moderate-to-severe CKD compared to non-IBD individuals., (© 2023 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Acute interstitial nephritis (AIN) is a cause of acute kidney injury and characterized by an inflammation of the tubulointerstitial space, leading to a decline in kidney function. Multiple etiologies can cause AIN including medications, autoimmune diseases and infections. A multiplicity of drugs is associated with AIN, while antibiotics (especially beta-lactams), proton-pump inhibitors (PPI) and non-steroidal anti-inflammatory agents (NSAIDs) are the most common. The pathognomonic triad of exanthema, fever and eosinophilia is rarely present in AIN patients. Treatment of medication-associated AIN is based upon the discontinuation of the provoking drug. Glucocorticoids can be considered in severe cases.Nephropathia epidemica (NE) is a disease caused by an infection with the Puumula-virus (PUUV) in northern and central Europe. Small rodents (mostly mice) are the host of the virus accountable for a rising number of infections during spring and summer. It is causing a syndrome consisting of AIN, fever and often thrombocytopenia. There is a good chance of complete recovery of kidney function following NE., Competing Interests: Erklärung zu finanziellen Interessen Forschungsförderung erhalten: ja, von einer anderen Institution (Pharma- oder Medizintechnikfirma usw.); Honorar/geldwerten Vorteil für Referententätigkeit erhalten: ja, von einer anderen Institution (Pharma- oder Medizintechnikfirma usw.); Bezahlter Berater/interner Schulungsreferent/Gehaltsempfänger: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an im Bereich der Medizin aktiven Firma: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an zu Sponsoren dieser Fortbildung bzw. durch die Fortbildung in ihren Geschäftsinteressen berührten Firma: nein Erklärung zu nichtfinanziellen Interessen Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Introduction: Spanish Lavender is an herbal from the lavender family and is widely used among people for the belief that it cures various diseases. Acute interstitial nephritis (AIN) is one of the common causes of acute kidney injury (AKI). Although drugs are the most common cause of AIN, the frequency of reporting AIN cases due to various herbals has been increasing in recent years., Case Presentation: We present a 24-year-old male patient who developed AKI after consuming Spanish lavender tea to treat upper respiratory tract infection symptoms and was diagnosed with AIN., Aim and Discussion: With this case report, we wanted to explain the fact that medicinal herbs, which are used frequently and carelessly today, can have serious consequences, as in acute interstitial nephritis associated with Spanish lavender., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Infection-related glomerulonephritis (IRGN) is one of the most common causes of acute kidney injury (AKI). Positive glomerular staining of the nephritis-associated plasmin receptor (NAPlr) has been reported as a useful biomarker of IRGN. Although the infection can provoke acute tubulointerstitial nephritis (AIN), there are few reports of positive staining for NAPlr with AIN. We report a case of methicillin-sensitive Staphylococcus aureus (MSSA) infection-related nephritis complicated with AIN, which showed positive staining for tubulointerstitial NAPlr. The patient developed AKI and nephrotic syndrome during an intraperitoneal MSSA infection. A diagnosis of IRGN complicated by infection-related acute tubulointerstitial nephritis (IRAIN) was made based on glomerular endocapillary proliferation with tubulointerstitial infiltrating cells and tubular atrophy. Tubulointerstitial infiltrating cells were positive for NAPlr staining and plasmin activity. Treatment of the infection by antibiotics and drainage did not improve the AKI, but steroid administration improved that. NAPlr evaluation is a helpful tool for identifying causes of AIN during infection., (© 2023. The Author(s) under exclusive licence to The Japan Society of Nephrology.)

Background: Tubulointerstitial nephritis and uveitis (TINU) syndrome is an uveits characterized by complications of idiopathic acute tubulointerstitial nephritis, and most cases present only anterior uveitis. We report a case of TINU syndrome in which the presence of choroiditis was revealed by multimodal imaging., Case Presentation: A 12-year-old male visited our hospital with a 6-day history of ocular pain and hyperemia. Conjunctival and ciliary injections, 1 + flare and 3 + cells of anterior chamber inflammation with mutton fat keratic precipitates were observed in both eyes (OU), together with redness and swelling of the optic disc OU. Laboratory tests showed slightly high levels of soluble IL-2R and serum β2 microglobulin and markedly high levels of urinary β2 microglobulin. The diagnosis of probable TINU syndrome was established on the basis of bilateral uveitis and urinalysis results in accordance with a clinical criteria of tubulointerstitial nephritis. With treatment with oral prednisolone (PSL) at 20 mg/day, ocular findings improved, and the dose of PSL was gradually reduced and withdrawn 6 months later. However, 1 month later from the withdrawal, ocular inflammation recurred with the presence of retinal exudates and snowball vitreous opacities in the peripheral retina OU. Fluorescein angiography showed leakages from peripheral retinal vessels and staining corresponding to retinal exudates. Indocyanine green angiography showed hypofluorescent dots scattered over the ocular fundus. Optical coherence tomography revealed the presence of choroidal thickening. Laser speckle flowgraphy color map showed a relatively cooler color. Findings from these multimodal images indicated the presence of subclinical choroiditis; therefore, oral PSL was administered again, and ocular inflammatory findings were improved., Conclusions: TINU syndrome can exhibit subclinical choroiditis detected with multimodal imaging. Further studies are necessary to determine the frequency of subclinical choroiditis in TINU syndrome., (© 2023. BioMed Central Ltd., part of Springer Nature.)

We performed 3 kidney biopsies in a 71-year-old man. At the first biopsy, we made the diagnosis of immunoglobulin G4 (IgG4)-related interstitial nephritis characterized by the simultaneous presence of IgG4-positive plasma cells and characteristic fibrosis with a bird's-eye pattern. At the second biopsy, rather than finding fibrosis as a post-inflammatory scar, we noted that steroid treatment had caused the simultaneous disappearance of IgG4-positive plasma cells and fibrosis and had restored the normal tubular structure. The third biopsy showed the recurrence of the disease with inflammatory cells accompanied by fibrosis. These findings suggest that IgG4-positive plasma cells and fibrosis occur simultaneously.

Background: Renal tubular acidosis is the principal clinical feature associated with tubulointerstitial nephritis in patients with primary Sjögren's syndrome. Renal tubular dysfunction due to interstitial nephritis has been considered the underlying pathophysiology connecting renal tubular acidosis and primary Sjögren's syndrome. However, the detailed mechanisms underlying the pathophysiology of renal tubular acidosis in primary Sjögren's syndrome is not fully understood., Case Presentation: A 30-year-old woman was admitted with complaints of weakness in the extremities. The patient was hospitalized thirteen years earlier for similar issues and was diagnosed with hypokalemic paralysis due to distal renal tubular acidosis with primary Sjögren's syndrome. This diagnosis was based on a positive Schirmer's test. Besides, anti-Sjögren's syndrome-related antigen A was also detected. Laboratory tests indicated distal RTA; however, a renal biopsy showed no obvious interstitial nephritis. Laboratory tests conducted during the second admission indicated distal renal tubular acidosis. Therefore, a renal biopsy was performed again, which revealed interstitial nephritis. Histological analysis of acid-base transporters revealed the absence of vacuolar type H + -ATPases in the collecting duct. The vacuolar type H + -ATPase was also absent in the past renal biopsy, suggesting that the alteration in acid-base transporters is independent of interstitial nephritis., Conclusions: This case study demonstrates that vacuolar-type H + -ATPases are associated with distal renal tubular acidosis, and distal renal tubular acidosis precedes interstitial nephritis in patients with primary Sjögren's syndrome., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Tubulointerstitial nephritis with IgM-positive plasma cells (IgMPC-TIN) is a newer disease about which there are many unclear points. Glucocorticoid therapy is effective in many cases of IgMPC-TIN; however, relapse during glucocorticoid tapering has been reported. Relapse and its treatment are poorly defined., Case Presentation: Case 1 was a 61-year-old man with renal dysfunction and proteinuria. Tubulointerstitial nephritis and IgM-positive plasma cells were observed in a renal biopsy. He was diagnosed with IgMPC-TIN accompanied by Fanconi syndrome and distal renal tubular acidosis (d-RTA). Prednisolone (PSL; 30 mg daily, 0.45 mg/kg/day) treatment was highly effective, and PSL was gradually tapered and discontinued after 1 year. However, 1 month after PSL discontinuation, therapeutic markers were elevated. Therefore, PSL (10 mg daily, 0.15 mg/kg/day) was administered, and the markers indicated improvement. Case 2 was a 43-year-old woman referred for renal dysfunction and proteinuria. Laboratory data revealed that she had primary biliary cholangitis (PBC), d-RTA, and Fanconi syndrome. A renal biopsy showed accumulation of IgM-positive plasma cells in the tubulointerstitium without any glomerular changes. A diagnosis of IgMPC-TIN was made and the patient was started on PSL (35 mg daily, 0.6 mg/kg/day). Therapeutic markers decreased immediately and PSL was discontinued after 1 year. Three months later, the proteinuria and Fanconi syndrome worsened. PSL treatment was restarted (20 mg daily, 0.35 mg/kg/day) and markers indicated improvement. Case 3 was a 45-year-old woman with renal dysfunction and proteinuria. Tubulointerstitial nephritis and IgM-positive plasma cells were observed in a renal biopsy. The patient had PBC, Sjögren syndrome, d-RTA, and Fanconi syndrome, and the diagnosis of IgMPC-TIN was made. The patient was started on PSL (30 mg daily, 0.4 mg/kg/day) and disease markers decreased immediately. However, when PSL was tapered to 15 mg daily (0.2 mg/kg/day), the patient's serum IgM levels increased; therefore, we maintained the PSL at 15 mg daily (0.2 mg/kg/day)., Conclusion: We report three cases of relapsed IgMPC-TIN associated with reduction or discontinuation of glucocorticoid therapy. In these cases, elevation of serum IgM preceded that of other markers such as urinary β 2 -microglobulin, proteinuria, and glycosuria. We recommend monitoring serum IgM levels while tapering glucocorticoids; a maintenance dose of glucocorticoid should be considered if relapse is suspected or anticipated., (© 2023. The Author(s).)

The field of nephrology has been slow in moving beyond the utilization of creatinine as an indicator for chronic kidney disease and acute kidney injury (AKI). Early diagnosis and establishment of etiology, in particular, are important for treatment of AKI. In the setting of hospital-acquired AKI, tubular injury is more common, but acute interstitial nephritis (AIN) has a more treatable etiology. However, it is likely that AIN is under- or misdiagnosed due to current strategies that largely rely on clinical gestalt. In this issue of the JCI, Moledina and colleagues made an elegant case for the chemokine called C-X-C motif ligand 9 (CXCL9) as a biomarker of AIN. The authors used urine proteomics and tissue transcriptomics in patients with and without AIN to identify CXCL9 as a promising, noninvasive, diagnostic biomarker of AIN. These results have clinical implications that should catalyze future research and clinical trials in this space.

Tuberculosis is a common etiology of granulomatous interstitial nephritis (GIN). However, the absence of evidence of lung involvement and lack of mycobacterial isolation in cultures make the etiological diagnosis and treatment decision challenging. We herein report a 46-year-old man with severe renal failure, a persistent fever, and a history of lymphoma. A renal biopsy exhibited GIN. Despite no evidence of tuberculosis except for a positive interferon-gamma release assay (IGRA), the patient was successfully treated with anti-tuberculosis drugs. Our case suggests that anti-tuberculosis therapy should be considered for patients with IGRA-positive GIN after excluding other etiologies.

Karyomegalic interstitial nephritis (KIN) is a rare cause of chronic interstitial nephritis characterized by enlarged renal tubular epithelial nuclei. The first case of KIN reported in a kidney graft was in 2019. Here, we report the first case of KIN in 2 brothers receiving kidneys from 2 different unrelated living donors. A male kidney transplant recipient with focal segmental glomerulosclerosis as the original kidney disease presented with graft impairment and proteinuria, and graft biopsy revealed KIN. This patient had a brother who was also a kidney transplant recipient and had one episode of graft impairment and was diagnosed with KIN as well., (© 2023. The Author(s).)

This is a case report of a 69-year-old Japanese man who has been undergoing treatment for primary Sjögren's syndrome (pSS) since he was 62 years. A renal biopsy, which revealed diffuse and severe mononuclear cell infiltration in the tubulointerstitium, was performed because of progressive renal dysfunction. Immunostaining demonstrated most of the infiltrating cells to be IgA, kappa, CD38, and CD138 positive. Immunofixation blood test revealed IgA kappa-type M protein; however, bone marrow abnormalities or lymph node enlargements on examination or imaging, respectively, were not observed. Tubulointerstitial nephritis caused by monotypic plasmacytic infiltration in pSS, accompanied with a monoclonal gammopathy of undetermined significance (MGUS), was diagnosed. A treatment of prednisolone 40 mg/day was initiated, promptly improving the patient's serum creatinine levels from 3.0 to 1.5 mg/dl. The infiltrating cells in pSS-associated tubulointerstitial nephritis are generally polytypic plasmacytes and lymphocytes, but in the present case, monotypic plasmacytes were predominant. This case is remarkable and rare and can be considered a complication of pSS or MGUS. Since it may become a new disease entity, it is important to accumulate similar cases., (© 2022. The Author(s) under exclusive licence to The Japan Society of Nephrology.)

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a relatively rare form of autoimmune disease. Diabetes insipidus (DI) is characterized by diluted polyuria and thirstiness, and is clinically categorized into central and nephrogenic DI depending on damaged organs. In most previously reported cases, ANCA-related disorders have been implicated in central DI, which is attributed to impaired secretion of arginine vasopressin (AVP) from the posterior pituitary. However, no previous case of AAV-related nephrogenic DI has been reported in the English literature. Herein, we report a case of nephrogenic DI likely caused by AAV. A 76-year-old man was admitted to our hospital for acute kidney injury. He showed dehydration, polyuria, and polydipsia. Laboratory tests demonstrated elevated levels of serum urea and creatinine and a high myeloperoxidase ANCA titer. In the present case, both plasma AVP concentration and response of AVP secretion to 5% saline load test were normal. In addition, 1-desmino-8-arginine vasopressin administration could not increase urinary osmolarity. Kidney biopsy specimen revealed tubulointerstitial nephritis with findings that appeared to indicate peritubular capillaritis. Therefore, the patient was diagnosed with nephrogenic DI likely owing to ANCA-associated tubulointerstitial nephritis. Immediately after prednisolone administration, urinary volume decreased, urinary osmolarity increased, and kidney function was improved. This case demonstrates that AAV that extensively affects the tubulointerstitial area can result in nephrogenic DI., (© 2022. The Author(s) under exclusive licence to The Japan Society of Nephrology.)

Immune checkpoint inhibitors (ICIs) have become the standard treatment for many types of cancer and have improved patient prognosis. However, ICIs upregulate the immune system against tumors, leading to immune-related adverse events (irAEs). Kidney irAEs are less common, and most of them are acute tubulointerstitial nephritis (ATIN). However, there has been a recent increase in recognition of glomerular disease related to ICI therapies. We report the case of a 65-year-old man with lung adenocarcinoma who was treated with pembrolizumab (a monoclonal antibody targeting programmed cell death protein-1 [PD-1]). Pembrolizumab was discontinued after seven cycles due to the development of destructive thyroiditis. Within three months of discontinuing the pembrolizumab treatment, the patient developed rapid progressive glomerulonephritis (RPGN), liver dysfunction, and dysgeusia. The patient underwent renal biopsy and was diagnosed with crescentic glomerulonephritis due to anti-glomerular basement membrane (GBM) antibodies complicated with membranous nephropathy (MN) and ATIN. Treatment with systemic corticosteroids resulted in a favorable clinical response. Various ICI-associated glomerular diseases have been described; however, this is the first reported case of anti-GBM glomerulonephritis associated with MN and ATIN following ICI treatment., (© 2022. The Author(s) under exclusive licence to The Japan Society of Nephrology.)

Because of some similarities in organ involvement, clinical manifestations, and histopathological features, IgG4-related disease (IgG4-RD) may occur concurrently with some clinicopathologic variants of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). An overlap syndrome of IgG4-RD and AAV has recently been proposed in clinical and/or histopathological studies, indicating that there may be some potential pathophysiological associations between the two disease entities; however, the mechanisms underlying these are incompletely understood. Here, we describe a rare case of a 63-year-old man with IgG4-related tubulointerstitial nephritis (IgG4-TIN) and microscopic polyangiitis-associated glomerulonephritis (MPA-GN) overlap syndrome. The clinical diagnosis of MPA was based on the 2022 American College of Rheumatology (ACR)/European League Against Rheumatology (EULAR) classification criteria. Remission induction therapy with intravenous methylprednisolone was initiated, followed by oral prednisone maintenance therapy with gradual tapering. The patient remained asymptomatic and his renal function was essentially normalized within 3.5 months of follow-up. The serum IgG4 levels decreased to 5 g/L. We also conducted a literature review to identify clinical findings, treatment options, and outcomes of patients with concurrent IgG4-RD and MPA and briefly discussed the potential pathophysiological association between IgG4-RD and MPA. Our findings enrich the database of this rare overlap syndrome and provide a basis for the diagnosis and early intervention in both diseases. These results provide some insights for clinicians to recognize and treat this overlap syndrome., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Background: IgG4-related disease (IgG4-RD) is a newly discovered systemic disease that can affect any organ or tissue in the body. IgG4-related kidney disease (IgG4-RKD) is relatively rare but essential to IgG4-RD. However, there are few reports of IgG4-RD mimicking malignant ureteral tumors leading to hydronephrosis. We report here a rare case of IgG4-RD involving the ureter., Case Presentation: An 87-year-old man presented to our nephrology department with anorexia, nausea, and acute kidney injury in November 2020. Urinary computed tomography (CT) examination revealed a right lower ureter mass with right renal and ureter hydronephrosis. The serum level of IgG4 was 1890 mg/dL, and the concurrently renal biopsy revealed extensive infiltration of IgG4-positive plasma cells in renal interstitium, which was diagnosed as IgG4-associated tubule-interstitial nephritis(IgG4-TIN). The renal function improved significantly after double-J tube implantation of the right ureter and moderate-dose hormone therapy. The serum IgG4 decreased to the normal range, and the right lower ureter mass almost disappeared after one year of low-dose hormone maintenance therapy., Conclusion: IgG4-RD can present as a mass in the renal pelvis and (or) ureter, leading to hydronephrosis. Therefore, early recognition of this disease is significant. Most patients respond well to hormonal therapy to avoid surgical treatment due to misdiagnosis as malignant tumors, causing secondary harm to patients., (© 2023. The Author(s).)

Background: Microscopic polyangiitis (MPA), a kind of antineutrophil cytoplasmic autoantibody associated vasculitis (AAV), predominantly affects small-sized vessels. MPA is a significant cause of the pulmonary-renal syndrome. Pauci-immune necrotizing and crescentic glomerulonephritis is the typical renal histological feature of AAV. Tubulointerstitial lesions may occur and mostly form with inflammatory cell infiltration in the interstitium. However, a few cases reported only tubulointerstitial involvement without glomerular lesions in patients with MPA., Case Presentation: We present an MPA case, a 70-year-old male patient diagnosed with acute kidney injury accompanying the dialysis requirement. Only acute tubulointerstitial nephritis was revealed in kidney biopsy without evidence of glomerular injury. Also, interstitial pulmonary fibrosis was determined on computerized tomography, and myeloperoxidase antineutrophil cytoplasmic autoantibody was positive. Consequently, we have considered the main diagnosis as MPA. We did not prefer a standard tubulointerstitial nephritis treatment regimen due to the presence of life-threatening systemic vasculitis. Treatment was established like crescentic glomerulonephritis. Induction therapy consisted of pulse steroid, cyclophosphamide, and plasmapheresis. Unfortunately, severe SARS-CoV-2 infection caused death during induction therapy in this case., Conclusions: The lack of glomerular injury and solely interstitial inflammation is atypical regarding AAV involvement in the kidney. This diversity might be initially considered as only a simple histological elaboration. However, it is a significant entity for guiding the treatment of AAV., (© 2023. The Author(s).)

Background: Oxaliplatin is an anticancer therapy for pancreatic, gastric, and colorectal cancers. It is also used in patients with carcinomas of unknown primary sites. Oxaliplatin is associated with less frequent renal dysfunction than other conventional platinum-based drugs such as cisplatin. Albeit, there have been several reports of acute kidney injury with frequent use. In all cases, renal dysfunction was temporary and did not require maintenance dialysis. There have been no previous reports of irreversible renal dysfunction after a single dose of oxaliplatin., Case Presentation: Previous reports of oxaliplatin-induced renal injury occurred after patients received multiples doses. In this study, a 75-year-old male with unknown primary cancer and underlying chronic kidney disease developed acute renal failure after receiving the first dose of oxaliplatin. Suspected of having drug-induced renal failure through an immunological mechanism, the patient was treated with steroids; however, treatment was ineffective. Renal biopsy ruled out interstitial nephritis and revealed acute tubular necrosis. Renal failure was irreversible, and the patient subsequently required maintenance hemodialysis., Conclusions: We provide the first report of pathology-confirmed acute tubular necrosis after the first dose of oxaliplatin which led to irreversible renal dysfunction and maintenance dialysis., (© 2023. The Author(s).)

Background: BK virus (BKV)-associated nephropathy (BKVN) is one of the leading causes of renal dysfunction and graft loss in renal transplant recipients. Early monitoring of BKV in urine is crucial to minimize the deleterious effects caused by this virus on preservation of graft function., Methods: We report a simple, rapid, sensitive loop-mediated isothermal amplification (LAMP) assay using an HFman probe for detecting BKV in urine. To evaluate the performance of the assay, a comparison of the HFman probe-based LAMP (HF-LAMP) assay with two qPCR assays was performed using urine samples from 132 HIV-1 infected individuals. We further evaluated the performance of HF-LAMP directly using the urine samples from these HIV-1 infected individuals and 30 kidney transplant recipients without DNA extraction. Furthermore, we combined the HF-LAMP assay with a portable finger-driven microfluidic chip for point-of-care testing (POCT)., Results: The assay has high specificity and sensitivity with a limit of detection (LOD) of 12 copies/reaction and can be completed within 30 min. When the DNA was extracted, the HF-LAMP assay showed an equivalent and potentially even higher sensitivity (93.5%) than the qPCR assays (74.2-87.1%) for 132 urine samples from HIV-1 infected individuals. The HF-LAMP assay can be applied in an extraction-free format and can be completed within 45 min using a simple heat block. Although some decreased performance was seen on urine samples from HIV-1 infected individuals, the sensitivity, specificity, and accuracy of the extraction-free BKV HF-LAMP assay were 95%, 100%, and 96.7% for 30 clinical urine samples from kidney transplant recipients, respectively., Conclusion: The assay has high specificity and sensitivity. Combined with a portable finger-driven microfluidic chip for easy detection, this method shows great potential for POCT detection of BKV., Competing Interests: The authors declare there are no competing interests., (©2023 Zhao et al.)

BK virus DNAemia (BKPyV) and nephropathy are common after kidney transplant; however, there are limited data on BK infections in nonrenal solid organ transplant recipients. We examined the frequency, clinical and pathologic features, and kidney and lung outcomes of BKPyV and BK virus native kidney nephropathy (BKVN) in lung transplant recipients at our center. Among 878 recipients transplanted from 2003 to 2019, 56 (6%) developed BKPyV at a median of 30.1 months after transplant (range, 0.6-213) and 11 (1.3%) developed BKVN at a median of 46 months after transplant (range, 9-213). The incidence of end-stage kidney disease was significantly higher in patients with peak viral load ≥10 000 copies/mL (39% vs 8%, P < .001). All cases of BKVN were in patients with peak viral load of ≥10 000 copies/mL, and 55% of these patients developed end-stage kidney disease. Despite the reduction of immunosuppression to treat BKVN, only 1 patient developed acute rejection, and lung function was stable >1 year. BKPyV and nephropathy are more common after lung transplantation than previously reported. Routine screening for BKPyV should be considered in all lung transplant recipients., (Copyright © 2022 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Nephronophthisis type 12 (NPHP 12) is a rare cilia-related cystic kidney disease, caused by TTC21B mutation, mainly involving the kidneys, which generally occurs in children. Our study aimed to illustrate its clinical, pathological and genetic characteristics by reporting an adult-onset case of NPHP 12 caused by a single heterozygous nonsense mutation of TTC21B confirmed by renal histology and whole exome sequencing and reviewing related literature with a comparative analysis of the clinical features of each case. It will further increase the recognition of this rare kidney genetic disease, which sometimes can manifest as an adult disease., Results: A 33-years-old man showed a chronic disease course, and he exhibited slight renal dysfunction (CKD stage 3, eGFR = 49 ml/[min* 1.73 m2]) with renal tubular proteinuria, without any extrarenal manifestations, congenital malformation history of kidney disease, or family hereditary disease. Renal histological findings showed substantial interstitial fibrosis with some irregular and tortuous tubules with complex branches and segmental thickening and splitting of the tubular basement membrane. The patient was diagnosed with chronic interstitial nephritis for an unknown reason clinically. Further genetic analysis revealed a single heterozygous nonsense mutation in the TTC21B gene and NPHP 12 was diagnosed finally., Conclusion: A single heterozygous mutation in the TTC21B gene may cause atypical NPHP12, which had a relatively later onset and milder clinical symptoms without developmental abnormalities. Therefore, for unexplained adult-onset chronic interstitial nephritis with unusual changes of renal tubules and interstitial fibrosis, even without a clear history of hereditary kidney disease, genetic testing is still recommended. The correct diagnosis of this rare adult-onset hereditary nephropathy can avoid unnecessary treatment., (© 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

A 50-year-old man was admitted to our hospital with the complaints of fever and general malaise. He had no history of human immunodeficiency virus (HIV) infection or treatment with immunosuppressive agents. We performed renal biopsy to investigate possible acute kidney injury. Pathological findings showed inflammatory cell infiltration, including granulomatous lesions in the interstitium. We diagnosed the patient with acute granulomatous tubulointerstitial nephritis. We initiated prednisolone (PSL) 40 mg/day (0.6 mg/kg), in combination with isoniazid for a latent tuberculosis infection, because of positive results in interferon-γ release assays. The patient's fever and malaise promptly disappeared, and his renal function improved. After the patient had been discharged, Mycobacterium intracellulare grew in cultures of his renal tissue and urine. We gradually reduced the dose of PSL; we initiated combination therapy with ethambutol, clarithromycin, and rifampin. After 2 years of follow-up, the patient continued treatment for chronic kidney disease; it has since enabled him to avoid renal replacement therapy. This report describes a rare instance of nontuberculous mycobacteria-associated tubulointerstitial nephritis in a patient without a history of HIV infection or organ transplantation. In differential diagnosis of granulomatous tubulointerstitial nephritis, clinicians should consider drugs, sarcoidosis, tubulointerstitial nephritis and uveitis syndrome, vasculitis, and infections (e.g., involving mycobacteria). Prompt microbiological examinations, especially of urine or biopsy cultures, are vital for diagnosis., (© 2022. The Author(s) under exclusive licence to The Japan Society of Nephrology.)

Introduction: Lenalidomide is an immunomodulatory drug widely used in the treatment of multiple myeloma. Several cases of nephrotoxicity have been reported, but few have been documented histologically., Case Presentation: We report a case of acute interstitial nephritis to lenalidomide in a 62-year-old patient with multiple myeloma after administration of the second course of chemotherapy according to the protocol combining bortezomib, lenalidomide and dexamethasone. The outcome was quickly favorable after stopping lenalidomide, with corticosteroid therapy., Conclusion: Lenalidomide may be responsible for acute interstitial nephritis. When acute kidney injury occurs in myeloma, the nephrotoxicity of therapeutic agents should be considered in addition to the common causes of kidney failure. The chronology of events and the histological data are essential and guide the specific management., (Copyright © 2022 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.)

Anabolic-androgenic steroids (AAS) have been widely used by young people to enhance performance and increase muscle mass. The use of AAS can affect the kidneys and lead to a myriad of presentations, ranging from mildly elevated serum creatinine and blood urea nitrogen to irreversible chronic kidney disease and focal segmental glomerulosclerosis (FSGS). To the best of our knowledge, the coexistence of interstitial nephritis and the cellular variant of FSGS [Immunoglobulin M (IgM)] secondary to AAS abuse has not been previously reported in the literature. Here, we report the case of a 40-year-old bodybuilder who developed simultaneous interstitial nephritis and the cellular variant of FSGS (IgM) after short-term use of AAS and other dietary supplements., (Copyright © 2022 Copyright: © 2022 Saudi Journal of Kidney Diseases and Transplantation.)

Bovine polyomavirus-1 (BoPyV-1, Epsilonpolyomavirus bovis ) is widespread in cattle and has been detected in commercialized beef at supermarkets in the USA and Germany. BoPyV-1 has been questioned as a probable zoonotic agent with documented increase in seropositivity in people exposed to cattle. However, to date, BoPyV-1 has not been causally associated with pathology or disease in any animal species, including humans. Here we describe and illustrate pathological findings in an aborted bovine fetus naturally infected with BoPyV-1, providing evidence of its pathogenicity and probable abortigenic potential. Our results indicate that: (i) BoPyV-1 can cause severe kidney lesions in cattle, including tubulointerstitial nephritis with cytopathic changes and necrosis in tubular epithelial cells, tubular and interstitial inflammation, and interstitial fibroplasia; (ii) lesions are at least partly attributable to active viral replication in renal tubular epithelial cells, which have abundant intranuclear viral inclusions; (iii) BoPyV-1 large T (LT) antigen, resulting from early viral gene expression, can be detected in infected renal tubular epithelial cells using a monoclonal antibody raised against Simian Virus-40 polyomavirus LT antigen; and (iv) there is productive BoPyV-1 replication and virion assembly in the nuclei of renal tubular epithelial cells, as demonstrated by the ultrastructural observation of abundant arrays of viral particles with typical polyomavirus morphology. Altogether, these lesions resemble the "cytopathic-inflammatory pathology pattern" proposed in the pathogenesis of Human polyomavirus-1 -associated nephropathy in immunocompromised people and kidney allograft recipients. Additionally, we sequenced the complete genome of the BoPyV-1 infecting the fetus, which represents the first whole genome of a BoPyV-1 from the Southern Hemisphere. Lastly, the BoPyV-1 strain infecting this fetus was isolated, causing a cytopathic effect in Madin-Darby bovine kidney cells. We conclude that BoPyV-1 is pathogenic to the bovine fetus under natural circumstances. Further insights into the epidemiology, biology, clinical relevance, and zoonotic potential of BoPyV-1 are needed.

One of the common causes of acute kidney injury (AKI) is drug nephrotoxicity. A large group of drugs associated with AKI includes a considerable number of antimicrobials. Clinical manifestations range from mild forms of tubular damage to significant deterioration of renal function requiring renal replacement therapy. Several mechanisms have been described, although the most common are acute interstitial nephritis, acute tubular necrosis, crystalic nephropathy or proximal/distal tubulopathy with electrolyte abnormalities. General risk factors for antimicrobial-induced AKI include pre-existing chronic kidney disease and concomitant use of drugs with nephrotoxic potential. Prevention and early recognition of AKI are the standard approach to mitigate AKI and avoid morbidity.

Acute granulomatous tubulointerstitial nephritis (GTIN) is a rare finding in renal biopsy. Differential diagnosis is facilitated when GTIN is associated with granulomatous bilateral anterior uveitis (GBAU). Nevertheless, differentiation between a rare form of granulomatous tubulointerstitial nephritis and uveitis syndrome (TINU) and sarcoidosis can be challenging. We report a case of biopsy-proven GTIN with concomitant GBAU, leading to a dead-end diagnosis. We discuss workup and propose a diagnostic algorithm based on a literature review. We also report a successful treatment of ophthalmologic and renal relapse using mycophenolate mofetil.

In this case report, we describe the case of a 50-year-old woman referred by her general practitioner to a pulmonologist in order to investigate persistent fever and elevation of C-reactive protein despite antibiotic treatment following a respiratory infection. The patient was examined extensively, during which rheumatology, gastroenterology, nephrology, ophthalmology, laboratory and imaging tests were performed. Due to a rapid progression of renal insufficiency with active urinary sediment, the patient was referred for a renal biopsy, which confirmed tubulointerstitial nephritis, followed by a diagnosis of bilateral anterior uveitis two months later - genetic testing was also conducted, which confirmed the diagnosis of tubulointerstitial nephritis with uveitis syndrome. Steroid treatment brought about a gradual reduction of proteinuria and a stabilisation of renal function.

BK polyomavirus (BKPyV) often reactivates after kidney transplantation, causing BKPyV-associated nephropathy (BKPyVAN) in 1%-10% of cases with a potential detrimental effect on allograft survival. Kidney transplant recipients are regularly screened for BKPyV DNA in plasma. As this strategy may not always reduce the risk of BKPyVAN, other predictive markers are needed. To evaluate the role of pretransplant BKPyV-specific antibody, 210 kidney transplant recipients and 130 donors were screened for BKPyV DNA and BKPyV-specific antibodies. We found that the donor BKPyV immunoglobulin G (IgG) seroprevalence and antibody level were strongly associated with BKPyV-DNAemia and BKPyVAN, although multivariant analysis found the presence of anti-BKPyV-specific antibodies as a predictive factor only for BKPyV-DNAemia. The pretransplant recipient status had no effect on posttransplant BKPyV-DNAemia and BKVAN. BKPyV IgG levels remained stable in BKPyV-negative recipients during 1-year follow-up, while a considerable increase was observed in BKPyV-positive patients. The presence of anti-BKPyV-specific antibodies in kidney allograft donors is a good and reliable predictive marker for posttransplant BKPyV replication with relevance to risk stratification in transplant recipients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Saláková, Ludvíková, Hamšíková, Kolářová, Šroller, Viklický and Wohlfahrtová.)

Background: Urinary tract tuberculosis (UTTB) is a common form of extrapulmonary tuberculosis (TB) which can infrequently present as renal carcinoma, leading to serious errors in the diagnosis and treatment of UTTB., Case Presentation: A 76-year-old Syrian man presented with gross hematuria as the main symptom. A urinary endoscopic examination and pelvic multi-slice computed tomography imaging increased the suspicion of a speared renal mass in the right urinary tract. The patient was treated for renal cancer. After nephrectomy and ureterctomy, the histopathology of the resected mass confirmed the diagnosis of UTTB and interstitial nephritis., Conclusion: This case should serve to increase the attention of clinicians to perform an accurate diagnosis step by step. This is especially important if they have a patient similar to the case described here who presents with a renal mass, to avoid serious results such as the loss of an essential organ system., (© 2022. The Author(s).)

A 70-year-old man received pembrolizumab as a second-line treatment for squamous cell lung cancer of the lower right lobe. After three courses, proteinuria and hematuria were observed, which worsened after seven courses. He was diagnosed with a combination of IgA nephropathy and active interstitial nephritis. Steroid pulse therapy was started, and the dose of prednisolone was gradually reduced from 60 mg/day. Renal dysfunction as an immune-related adverse event of pembrolizumab monotherapy for non-small cell lung cancer has been reported previously. Therefore, establishing a system for the early detection and treatment that distinguishes immune-related glomerular diseases is essential.

A 39-year-old woman was hospitalized for nephrotic syndrome. Laboratory test results showed increased serum creatinine levels and urinary excretions of beta-2-microglobulin, and N-acetyl-beta-D-glucosaminidase. A renal biopsy revealed collapsing focal segmental glomerulosclerosis (FSGS) and acute interstitial nephritis. Despite treatment with pulse steroid followed by oral high-dose glucocorticoids and cyclosporines, heavy proteinuria persisted. After low-density lipoprotein apheresis (LDL-A) therapy was initiated, her proteinuria gradually decreased, leading to complete remission. A repeat renal biopsy after treatment revealed no collapsing glomeruli. Immediate LDL-A should be performed to treat cases of collapsing FSGS poorly responding to other treatments.

Drug-induced kidney injury has historically been associated with renal tubule injury related to small molecule pharmaceuticals such as nonsteroidal anti-inflammatory drugs, antineoplastic agents, or antibiotics, but as a greater number of alternative classes of medicines such as biotherapeutics, molecular-targeted antineoplastic drugs, chimeric antigen receptor T-cell therapies, antibody-drug conjugates, oligonucleotide therapies, or other immunomodulatory drugs come to market, the presentation of drug-induced nephrotoxicity is changing. This review article describes the potential rare clinical events in drug-induced kidney injury that might be noted with these new therapies and their potential impact on patients. Potential pathogenic mechanisms related to immunogenicity, immune complex formation, and stimulation of downstream proinflammatory pathways with some of these alternative medicine classes have resulted in the potential for glomerulonephritis, acute interstitial nephritis, renal vasculitis, and other immune-mediated renal disorders in humans. This contrasts with nonclinical toxicity studies, where biologic therapies more often result in vasculitis and glomerulonephritis associated with antidrug antibodies and immunomodulatory pharmacology, and which are not always predictive of clinical effects. While nonclinical antidrug antibody-related renal disease is generally not clinically relevant, other immune-mediated nephrotoxicities associated with immunomodulatory drugs may be predictive of clinical adverse events. Fortunately, these conditions are still rare and account for a small percentage of serious adverse events in kidneys of patients.

Ingestion of toxic trace elements in the human body has been considered one of the major reasons for renal dysfunction. Chronic kidney disease with uncertain etiological factors (CKDu) is a recently described clinical entity in which the disease is found in geographically isolated pockets in the dry zone of Sri Lanka. In CKDu regions, an increasing number of cases are reported with acute interstitial nephritis without any known reason (AINu). However, recent exposure to certain risk behaviors or nephrotoxins, or both, is suspected for the AINu. Consumption of foods that are contaminated with trace elements is one of the main pathways of human exposure to environmental toxins. The current study was carried out to assess the possibility of trace element-contaminated rice consumption on the etiopathogenesis of AINu. Samples of rice consumed by 32 clinically diagnosed AINu cases were collected and analyzed for possible nephrotoxic trace elements. Out of 32 patients, 26 were histologically confirmed with tubulointerstitial disease. The results revealed that the mean values of Cd, As, and Pb were 0.18, 0.055, and 0.135 mg/kg, with ranges of 0.020-1.06, 0.012-0.222, and 0.003-0.744 mg/kg (on dry weight basis), respectively. This study indicated that the investigated toxic trace element levels of rice consumed by AINu were reasonably below the recommended levels of the Codex Alimentarius Commission of FAO and WHO. Hence, it is less likely that rice consumption is to be a risk factor for the etiology of AINu., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)