IgG4-related disease is a fibroinflammatory condition characterized by dense lymphoplasmacytic infiltrates rich in IgG4-positive plasma cells affecting multiple organs. Though the most common renal manifestation of IgG4-related disease is tubulointerstitial nephritis, it can rarely present as secondary membranous nephropathy. We present a case of a 75-year-old male with phospholipase A2 receptor-negative membranous nephropathy as an atypical manifestation of IgG4-related disease. The patient presented with nephrotic syndrome and was found to have elevated serum IgG4 levels and IgG4-positive plasma cells in the kidney biopsy. He was successfully treated with corticosteroids and rituximab, resulting in significant improvement in proteinuria and normalization of IgG4 levels. This case highlights the importance of considering IgG4-related disease in patients with phospholipase A2 receptor-negative membranous nephropathy, especially in those with a history of other organ involvement. Early recognition and treatment of IgG4-related disease are crucial to prevent progressive kidney damage and improve patient outcomes.

UNASSIGNED: IgG4-related disease (IgG4-RD) is a systemic immune-mediated disease that can involve nearly any organ. IgG4-RD can affect the kidney in different disease patterns, collectively referred to as IgG4-related kidney disease (IgG4-RKD).
UNASSIGNED: We conducted a tissue-based cohort study with clinicopathological correlation in 125 patients with IgG4-RKD.
UNASSIGNED: The mean age at biopsy (n = 120) or nephrectomy (n = 5) was 63 years; 80% were male. One hundred eighteen patients (94%) had IgG4-related tubulointerstitial nephritis (IgG4-TIN); 20 patients (16%) had IgG4-related membranous glomerulonephritis (IgG4-MGN; 13 with concurrent IgG4-TIN). The primary clinical indication for biopsy/nephrectomy was acute or chronic renal failure in 78%, proteinuria in 17%, and mass lesion(s) in 15% (with overlap in primary indication). Fifty-two percent patients (41/79) had abnormal radiographic findings, including masses in 30% (24/79). All patients with IgG4-MGN had proteinuria. Extrarenal involvement by IgG4-RD was present in 79%. Median serum creatinine at presentation was 2.5 mg/dl (range 0.7-12). Serum IgG and/or IgG4 was increased in 91% (53/58); hypocomplementemia was present in 56% (43/77). Light microscopy showed plasma cell-rich interstitial nephritis in all cases of IgG4-TIN. Ninety-two percent of patients showed increased IgG4+ plasma cells. Seven percent showed an acute interstitial nephritis (AIN) pattern, and 5% showed non-necrotizing arteritis. Tubular basement membrane immune deposits were present in 83% of IgG4-TIN. Treatment information was available for 71 patients; 62 were treated with immunosuppression. Of those with elevated creatinine, 72% (41/57) showed a treatment response.
UNASSIGNED: This largest tissue-based series more clearly defines the disease phenotype of IgG4-RKD.

Chronic beryllium disease (CBD), or berylliosis, is an interstitial lung disease caused by the chronic inhalation of finely particulate beryllium, frequently mistaken for sarcoidosis. It is rarely associated with skin nodular lesions, asymptomatic granulomatous hepatitis or calcium nephrolithiasis. To date, it has never been reported as a diffused multi-organ granulomatous disease. A 60-year-old Pakistani man, a former excavation worker with ancient history of suspected sarcoidosis, underwent a left nephroureterectomy for suspected papillary kidney carcinoma. The histopathological analysis showed a benign non-necrotic granulomatous infiltration of the renal pelvis and ureter. Six months later, he suffered from two consecutive episodes of acute kidney failure. Bladder biopsies found similar noncaseous granulomatosis and kidney biopsies showed interstitial nephritis. Known for suspected asthma, sleep apnea, and usual interstitial pneumonia, the patient would regularly consult for episodes of pyrexia, chills, nocturnal coughing, and wheezing. As kidney function gradually worsened, he ultimately started hemodialysis and was transferred to our facility. A positive blood beryllium lymphocyte proliferation test confirmed the diagnosis of CBD. This original report is the first description of multi-organ berylliosis with diffused urothelial granulomatosis and pseudo-tumor. The patient\'s pulmonary disease is minimal compared with renal and urinary tract involvement, eventually responsible for end-stage kidney disease. Berylliosis usually responds to glucocorticoids. This case report highlights the importance of evoking the diagnosis of CBD in the presence of any granulomatosis, even extra-thoracic, especially if associated with pulmonary symptoms, however atypical.

Dichlorvos, an organophosphate compound, has the potential to cause acute kidney injury (AKI) besides its well-known neuromuscular complications. We report a case of severe-recurrent AKI that progressed to end-stage-renal-disease (ESRD) following accidental exposure to Dichlorvos. A 52-year-old male farmer presented with breathlessness after accidental exposure while spraying in the field. He required mechanical ventilation due to allergic pneumonitis and developed anuric AKI, requiring renal replacement therapy (RRT). Biopsy revealed severe acute tubulointerstitial nephritis (ATIN), which responded to steroids, and the patient became dialysis-independent by 4 weeks. Two weeks later, the patient had recurrent AKI requiring RRT. A repeat biopsy revealed severe ATIN. However, despite steroid treatment, he progressed to ESRD. Organophosphate compounds can cause renal injury with a wide spectrum of presentations, ranging from subclinical AKI to severe dialysis-dependent renal failure, which may eventually progress to end-stage renal disease.

This study aims to figure out the worldwide prevalence of anticancer therapy-associated acute kidney injury (AKI) and tubulointerstitial nephritis (TIN) and the relative risk of each cancer drug. We conducted an analysis of VigiBase, the World Health Organization pharmacovigilance database, 1967-2023 via disproportionate Bayesian reporting method. We further categorized the anticancer drugs into four groups: cytotoxic therapy, hormone therapy, immunotherapy, and targeted therapy. Reporting odds ratio (ROR) and information component (IC) compares observed and expected values to investigate the associations of each category of anticancer drugs with AKI and TIN. We identified 32,722 and 2056 reports (male, n = 17,829 and 1,293) of anticancer therapy-associated AKI and TIN, respectively, among 4,592,036 reports of all-drug caused AKI and TIN. There has been a significant increase in reports since 2010, primarily due to increased reports of targeted therapy and immunotherapy. Immunotherapy exhibited a significant association with both AKI (ROR: 8.92; IC0.25: 3.06) and TIN (21.74; 4.24), followed by cytotoxic therapy (7.14; 2.68), targeted therapy (5.83; 2.40), and hormone therapy (2.59; 1.24) for AKI, and by cytotoxic therapy (2.60; 1.21) and targeted therapy (1.54; 0.61) for TIN. AKI and TIN were more prevalent among individuals under 45 years of age, with a female preponderance for AKI and males for TIN. These events were reported in close temporal relationship after initiation of the respective drug (16.53 days for AKI and 27.97 days for TIN), and exhibited a high fatality rate, with 23.6% for AKI and 16.3% for TIN. These findings underscore that kidney-related adverse drug reactions are of prognostic significance and strategies to mitigate such side effects are required to optimize anticancer therapy.

5-Amino salicylic acid (5-ASA) is a known culprit for the development of tubulointerstitial nephritis. Together with impaired kidney function, tubulointerstitial nephritis can lead to specific tubular malfunctions including distal renal tubular acidosis. Distal renal tubular acidosis is an acid-base disorder in which acid secretion in the distal part of the renal tubular system is decreased. Patients with distal renal tubular acidosis are predisposed to recurrently form calcium phosphate kidney stones. This results from the inability to acidify the urine properly as well as from a decreased citrate concentration in the urine, which is another pathognomonic feature of distal renal tubular acidosis. We present the case of a man in his late 40s with Crohn\'s disease who developed tubulointerstitial nephritis associated with 5-ASA leading to the development of distal renal tubular acidosis and recurrent calcium phosphate nephrolithiasis. After steroid therapy and partial recovery of kidney function, we observed an increase of citraturia in response to treatment with dapagliflozin, potentially indicating beneficial effects of sodium/glucose cotransporter 2 inhibition on the recurrence of calcium phosphate stone disease in interstitial nephritis-induced distal tubular acidosis.

UNASSIGNED: IgG4-associated kidney disease (IgG4-RKD) encompasses a spectrum of disorders, predominantly featuring tubulointerstitial nephritis (TIN) and membranous glomerulonephropathy (MGN). The limited understanding of the co-occurrence of IgG4-RD-TIN with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) poses a diagnostic and therapeutic challenge.
UNASSIGNED: We examined 49 cases, comprising 21 cases of IgG4-RD-TIN (group A), 10 cases of IgG4-RD-TIN accompanied with MGN (group B), and 18 cases of IgG4-RD-TIN concurrent with AAV (group C), at the First Affiliated Hospital of Zhejiang University, China, from June 2015 to December 2022.
UNASSIGNED: The mean age and gender of the three IgG4-RKD subtypes were not statistically significant. IgG4-RD-TIN exhibited higher serum creatinine and a higher incidence of hypocomplementemia (group A 47.6%, group B 30%, group C 16.7%). IgG4-RD-TIN-MGN was characterized by proteinuria (group A 0.3 g/d, group B 4.0 g/d, group C 0.8 g/d, P < 0.001) and hypoalbuminemia. IgG4-RD-TIN-AAV exhibited hypohemoglobinemia (group A 103.45 g/l, group B 119.60 g/l, group C 87.94 g/l, P < 0.001) and a high level of urine erythrocytes. The primary treatment for IgG4-RD-TIN was steroids alone, whereas IgG4-RD-TIN-MGN and IgG4-RD-TIN-AAV necessitated combination therapy. Group A experienced two relapses, whereas groups B and C had no relapses. There was no significant difference in patient survival among the three groups, and only two cases in group C suffered sudden death.
UNASSIGNED: This study provides valuable insights into clinical manifestations, auxiliary examination features, pathological characteristics, and prognosis of IgG4-RD-TIN, IgG4-RD-TIN-MGN, and IgG4-RD-TIN concurrent AAV. Large-scale studies are required to validate these findings.

The monocyte-macrophage lineage of inflammatory cells is characterized by significant morphologic and functional plasticity. Macrophages have broad M1 and M2 phenotype subgroups with distinctive functions and dual reno-toxic and reno-protective effects. Macrophages are a major contributor to injury in immune-complex-mediated, as well as pauci-immune, glomerulonephritis. Macrophages are also implicated in tubulointerstitial and vascular disease, though there have not been many human studies. Patrolling monocytes in the intravascular compartment have been reported in auto-immune injury in the renal parenchyma, manifesting as acute kidney injury. Insights into the pathogenetic roles of macrophages in renal disease suggest potentially novel therapeutic and prognostic biomarkers and targeted therapy. This review provides a concise overview of the macrophage-induced pathogenetic mechanism as a background for the latest findings about macrophages\' roles in different renal compartments and common renal diseases.

A 66-year-old male presented with renal dysfunction. At the time of presentation, his serum creatinine (sCr) was 2.55 mg/dL, estimated glomerular filtration rate (eGFR) was 20.93 ml/min/1.73 m2, urinary red blood cell (RBC) was 30-49/high power field, and urine protein-creatinine ratio was 0.43 g/gCr. The patient had no urinalysis abnormalities or renal dysfunction within the year prior to presentation but had gross hematuria after the third and fourth coronavirus disease 2019 (COVID-19) vaccinations. Therefore, immunoglobulin A nephropathy (IgAN) was suspected and a percutaneous renal biopsy was performed. Renal pathology confirmed IgAN and interstitial nephritis and glucocorticoid therapy was initiated. Glucocorticoids improved renal function, and microscopic hematuria resolved. Although previous reports have shown that the COVID-19 vaccine induces various renal diseases, complications associated with these two renal diseases are rare. In this case, while IgAN was suspected based on episodes of gross hematuria after vaccination, renal biopsy confirmed it and also revealed interstitial nephritis.

OBJECTIVE: Tubulointerstitial nephritis (TIN) has various etiologies, including IgG4-related disease (IgG4-RD), autoimmune diseases, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), and others. IgG4-positive plasma cell infiltration can occasionally be found in TIN unrelated to IgG4-RD. Therefore, there may be problems with usage of IgG4 immunostaining to differentiate between TIN with and TIN without IgG4-RD. This study aimed to compare the proportion of plasma cells that are positive for each IgG subclass and to clarify the predominant IgG subclass trends and clinical characteristics associated with IgG4-RD and non-IgG4-related interstitial nephritis.
METHODS: The study enrolled 44 cases of TIN: 6 of IgG4-RD, 8 of autoimmune disease, 9 of AAV, and 21 of unknown disease group. In addition to clinical characteristics, IgG subclass composition of interstitial plasma cells was evaluated among 4 groups by immunohistochemistry.
RESULTS: IgG1 was the predominant IgG subclass in TIN unrelated to IgG4-RD. In the IgG4-RD group, the IgG subclass rate was high in both IgG1 and IgG4. The rate of average IgG4-positive cells was significantly lower in the autoimmune disease group and unknown disease group compared with the IgG4-RD group.
CONCLUSIONS: The present study revealed IgG1-dominant immune profiles of TIN unrelated to IgG4-RD. Further investigation is required to elucidate the clinicopathological differences between IgG1-dominant and IgG4-dominant groups in IgG4-RD.