Search Results (30)

Salmonella spp. is a major zoonotic pathogen. Although reptiles are mostly considered subclinical carriers, clinical disease may develop following immunosuppression. Clinical salmonellosis in reptiles has been extensively reported; however, the condition has been rarely described in bearded dragons (Pogona vitticeps). We retrospectively analyzed six cases of salmonellosis in bearded dragons and characterized the pathological, immunohistochemical, and bacteriological findings. Clinical signs and gross findings were mostly non-specific. Histological findings mainly consisted of fibrinonecrotizing enterocolitis (83.3%); necrotizing or granulomatous hepatitis (66.7%); pneumonia including bronchopneumonia or interstitial pneumonia in one case each (33.3%); tubulointerstitial nephritis with tubular necrosis (16.7%); and coelomitis (16.7%). Salmonella enterica subsp. houtenae was cultured in three cases (33.3%), whereas S. enterica subsp. enterica serovar Rissen, S. enterica subsp. enterica serovar Cotham, and S. enterica subsp. diarizonae were cultured in one case each. Intralesional bacteria were detected via immunohistochemistry in kidneys and colon in two cases (33.3%). The predominance of lesions in the intestines and liver likely reflects initial intestinal colonization followed by hematogenous dissemination to the liver. Hepatic lesions are thought to represent different stages along a continuum, progressing from acute necrosis to discrete granuloma formation. Renal and respiratory involvement was infrequent, as reported in other reptile species. Some of the isolated Salmonella subspecies (S. diarizonae and S. houtenae) are well-recognized causes of clinical disease in other reptile species but not previously identified in bearded dragons. This study provides a comprehensive pathological, immunohistochemical, and bacteriological characterization of salmonellosis in bearded dragons, thus raising awareness and assisting in the identification of this condition. Full article

Immune checkpoint inhibitors are essential treatments for many oncologic diseases, but with well-known immune-related adverse events, such as acute interstitial nephritis (ICI-AIN). We investigated novel potential biomarkers that could assist in the diagnosis and follow-up of this condition and that are related to the active pathogenic pathways involved. We measured urinary soluble PD-1, PD-L1 and PD-L2, as well as chemokines CXCL5, CXCL9, CXCL10, CXCL11, CCL2, CCL3, CCL5 and cytokines IL-6 and IL-12p70 performing a Luminex assay in urine from patients with ICI-AIN (n = 35) and compared them with patients with AIN from other causes (non-ICI AIN) (n = 29) and ATN (n = 26). We found that CXCL5, CXCL9, CXCL10, CXCL11, CCL5 and IL-6 were higher in patients with ICI-AIN than in those with ATN, and all of them but CXCL9 and IL-6 were also higher in patients with ICI-AIN compared with non-ICI AIN. We also determined these molecules at follow-up for ICI-AIN patients (40 samples from 22 patients) and found that concentrations of CXCL9, CXCL10, CXCL11 and CCL2 decreased after treatment. The decrease of CXCL9 and CXCL10 correlated with greater kidney function recovery at one-year follow-up. These molecules could serve as noninvasive biomarkers and may aid fine patient monitoring. Full article

Background: Immune checkpoint inhibitor therapy (ICI) has greatly changed cancer therapy in recent years. The main side effects are immune-related adverse events (irAEs) that can affect any organ system. With the widespread use of ICIs, even rare irAEs, like acute kidney injury due to ICI-induced nephritis (ICI-AKI), have become a more common complication. Methods: All ICI-treated patients who underwent a kidney biopsy for AKI at a single academic center between January 2020 and December 2023 were analyzed. Results: We identified twelve cases of biopsy-proven ICI-AKI. The median follow up was 11.5 months. All cases showed acute interstitial nephritis (AIN) on the biopsy. Melanoma was the most common cancer, and dual-checkpoint inhibition with Ipilimumab and Nivolumab was the most common regimen. Extrarenal irAEs were present in only 25% of cases. Two-thirds had concomitant medication with proton pump inhibitors (PPIs). Only four patients completely recovered their kidney function, and one patient remained on kidney replacement therapy. Conclusions: AIN is a common cause of AKI in ICI-treated cancer patients. Although they respond well to steroid treatment, full restitution of kidney function occurs in less than half of the subjects. As ICIs are increasingly used in cancer management, more research on the prevention and treatment of ICI-associated AKI is needed. Full article

Background/Objectives: Immune checkpoint inhibitors (ICIs) have generated a revolutionary approach in the treatment of cancer, but their effectiveness has been compromised by immune-related adverse events, including renal damage. Although rare, these effects are relevant because they have been related to poor patient prognoses. The objective of this review was to estimate the current incidence of nephrotoxicity in patients treated with single and double ICI therapies. Methods: A total of 1283 potential articles were identified, which were reduced to 50 after applying the exclusion and inclusion criteria. Results: This study reveals the increase in acute kidney injury associated with these drugs in the last decade and shows that, interestingly, combined therapies with ICIs does not lead to an increase in kidney damage compared with anti-CTLA-4. It also suggests that kidney damage could be underdiagnosed when it comes to interstitial nephritis, because definitive evidence requires a renal biopsy. Conclusions: In perspective, these conclusions could guide clinicians in making decisions for therapy personalization and highlight the need to search for new diagnostic systems that are more sensitive and specific to the type of damage and could replace the biopsy. Full article

Piperacillin/tazobactam (PT), a widely utilized broad-spectrum antibiotic, has been associated with acute kidney injury (AKI). Although the precise mechanism remains uncertain, and most cases of PT-associated AKI are mild, this report describes a rare and severe complication of PT, which manifested as severe AKI with necrotizing glomerulonephritis requiring hemodialysis. A 42-year-old man was transferred to the nephrology clinic due to progressive deterioration of kidney function. Prior to the transfer, the patient had been diagnosed with appendicitis complicated by peritonitis and received intravenous PT for 8 days. Baseline kidney function was normal, but serum creatinine subsequently increased to 7.2 mg/dL. Hemodialysis was initiated to address metabolic acidosis and edema. Kidney biopsy revealed severe acute tubular injury and necrotizing glomerulonephritis. Steroid therapy was initiated based on the biopsy findings, and serum creatinine returned to normal levels after 4 weeks of treatment. This case demonstrates that severe AKI with necrotizing glomerulonephritis can occur after PT use. Prompt kidney biopsy and the timely initiation of immunosuppressive therapy are essential for a favorable outcome. Full article

Background: Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare autoimmune disorder, characterized by acute tubulointerstitial nephritis and uveitis. It poses diagnostic challenges due to the mostly asynchronous onset of renal and ocular manifestations, as well as the variety of differential diagnoses. This review provides an overview of the epidemiology, pathogenesis, clinical features, diagnostic criteria, and management strategies. Methods: A comprehensive review of the peer-reviewed literature, including studies and case reports, was conducted. Results: The etiology of TINU syndrome involves an autoimmune reaction to renal and ocular antigens, leading to interstitial inflammation and tubular damage in the kidneys, and anterior uveitis with acute onset of flares. Diagnostic criteria based on ocular examination, laboratory parameters, and renal biopsy emphasize the need to exclude other systemic diseases. TINU syndrome accounts for approximately 2% of all uveitis cases. Primary treatment consists of corticosteroids, while immunomodulatory therapies (methotrexate, azathioprine, mycophenolate mofetil, or biologic agents) are reserved for refractory cases. Recurrence of uveitis appears to be more common than that of nephritis. Conclusions: TINU syndrome is rare and requires clinical suspicion for accurate diagnosis. Early diagnosis and initiation of treatment are crucial for achieving favorable outcomes. Advances in the understanding of its pathogenesis and treatment have improved patient outcomes. Further research is needed to investigate the underlying triggers and mechanisms in order to develop targeted therapies. Full article

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. Full article

Background: Acute kidney disease (AKD) is a known risk factor for increased mortality and evolution towards chronic kidney disease (CKD) in adults. The data regarding AKD in children are scarce. The purpose of our study was to explore the risk factors for developing AKD based on exposures and susceptibilities in children with AKI doubled by the biological parameters from the first day of identified AKI. In addition, we followed the trajectory of AKD following an acute kidney injury (AKI) episode in children during hospital admission and after discharge with special considerations towards mortality and progression to new-onset CKD. Methods: We retrospectively evaluated 736 children, ages between 2 and 18 years old, with identified AKI during hospital admission in a tertiary care hospital from west Romania over a 9-year period. Results: AKD incidence following an AKI episode was 17%. Patients who developed AKD were older, with higher baseline serum creatinine, urea, C reactive protein and lower proteins, haemoglobin and sodium levels. In the adjusted model, no biological parameters influenced AKD development. Regarding certain exposures and personal susceptibilities in children with AKI, only anaemia independently increased the risk of AKD development by 2.47 times. However, out of the AKI causes, only the intrinsic causes of AKI independently increased the risk of progressing to AKD (glomerulonephritis by 4.94 and acute tubule-interstitial nephritis by 2.76 times). AKD increased the overall mortality by 2.6 times. The factors that independently increased the risk of CKD were AKD, acute tubular necrosis and higher baseline serum creatinine values. Conclusions: Only anaemia, glomerulonephritis and acute tubule-interstitial nephritis increased the risk of AKD development in children with AKI. AKD was an independent risk factor for mortality and new-onset CKD in children. Full article

We report the histological changes over time for a patient with infection-related glomerulonephritis (IRGN) that developed in a transplanted kidney. A 47-year-old man had undergone renal transplantation 3 years ago for end-stage kidney disease (ESKD). After several episodes of acute rejection, the patient was in a stable CKD condition. The abrupt development of severe microscopic hematuria and renal dysfunction was observed approximately 2 weeks after the onset of a phlegmon in his right leg. An allograft biopsy showed prominent glomerular endocapillary proliferation on light microscopy, granular C3 deposition on immunofluorescent microscopy, and subepithelial electron-dense deposits on electron microscopy, suggesting IRGN accompanied by moderate interstitial fibrosis and tubular atrophy (IFTA). Positive glomerular staining for nephritis-associated plasmin receptor (NAPlr) and plasmin activity, which are biomarkers of bacterial IRGN, supported the diagnosis. Although the infection was completely cured with antibiotic therapy, renal dysfunction persisted. A re-biopsy of the allograft 2 months later revealed resolution of the glomerular endocapillary proliferation and negative staining for NAPlr/plasmin activity, with worsening IFTA. We showed, for the first time, the chronological changes in infiltrating cells and histological markers of IRGN in transplanted kidneys. Glomerular changes, including NAPlr/plasmin activity staining, almost disappeared after the cessation of infection, while interstitial changes continuously progressed, contributing to ESKD progression. Full article

Introduction: The combination therapy of platinum and pembrolizumab looks like a promising treatment in advanced non-small-cell lung cancer. However, both platinum-based chemotherapy and pembrolizumab can lead to AKI. AKI can occur due to acute tubular necrosis or interstitial nephritis. It is essential to identify the drug responsible for renal damage. For this purpose, we used new immunohistochemistry markers (p53 and anti-PD1 analysis). Case Description: A 77-year-old female patient with advanced non-small-cell lung cancer received the PD-1 inhibitor pembrolizumab and platinum-based chemotherapy carboplatin. The patient, after 60 days, experienced AKI. A kidney biopsy was performed, and two new immunohistochemical techniques for p53 (experimental markers of ATN from platinum) and anti-PDL1 (experimental markers of PD-1 inhibitors nephritis) were employed. Renal biopsies revealed severe tubular damage. No infiltration was detected, and the immunohistochemical assessment of PDL-1 was negative. The expression of p53 was positive. The renal biopsy suggested platinum-induced acute tubular necrosis. After discontinuing steroids and reducing carboplatin, the patient continued with pembrolizumab, and their renal function returned to normal within two months. Discussion: Combining checkpoint inhibitors and platinum-based therapies may result in AKI. The standard method of examining kidney tissue may not provide sufficient information about the effects of these drugs on the kidneys. To address this issue, we recommend incorporating an assessment of the analysis of the expression of PDL1 and p53. This personalized approach will help identify the best treatment option for the patient while ensuring the best possible cancer treatment plan. Full article

We investigated the polarisation of CD68+ macrophages and perforin and granulysin distributions in kidney lymphocyte subsets of children with IgA vasculitis nephritis (IgAVN). Pro-inflammatory macrophage (M)1 (CD68/iNOS) or regulatory M2 (CD68/arginase-1) polarisation; spatial arrangement of macrophages and lymphocytes; and perforin and granulysin distribution in CD3+ and CD56+ cells were visulaised using double-labelled immunofluorescence. In contrast to the tubules, iNOS+ cells were more abundant than the arginase-1+ cells in the glomeruli. CD68+ macrophage numbers fluctuated in the glomeruli and were mostly labelled with iNOS. CD68+/arginase-1+ cells are abundant in the tubules. CD56+ cells, enclosed by CD68+ cells, were more abundant in the glomeruli than in the tubuli, and co-expressed NKp44. The glomerular and interstitial/intratubular CD56+ cells express perforin and granulysin, respectively. The CD3+ cells did not express perforin, while a minority expressed granulysin. Innate immunity, represented by M1 macrophages and CD56+ cells rich in perforin and granulysin, plays a pivotal role in the acute phase of IgAVN. Full article

Acute interstitial nephritis (AIN) due to helminths is a rare cause of acute kidney injury (AKI). Helminthiases often progresses insidiously, making diagnosis difficult. This was the case of a 72-year-old man, who presented with renal failure, itching and diarrhoea. Urinalysis revealed leukocyturia, microhaematuria and mild proteinuria. A full blood count revealed leucocytosis with eosinophilia. A stool parasitological examination revealed fertilised eggs of Ascaris lumbricoides. Tubulointerstitial nephropathy secondary to A. lumbricoides infection was suspected. A percutaneous renal biopsy was not performed since the patient refused the anti-platelet therapy discontinuation. Mebendazole, albendazole and prednisone therapy was administered. After worm eradiation and discharge, recovery from the parasitosis, absence of pruritus and eosinophilia, and progressive improvement of renal function were observed, strongly suggesting a causal relationship between Ascaris infection and AIN. Parasite infection should be considered in the differential diagnosis of unexplained renal failure because early diagnosis and treatment are necessary to avoid irreversible complications. Full article

(1) Background: Despite increasing recognition of immune checkpoint inhibitors (ICIs) and kidney immune-related adverse events (IRAEs), no large-sample studies have assessed the pathological characteristics and outcomes of biopsy-proven kidney IRAEs. (2) Methods: We comprehensively searched PubMed, Embase, Web of Science, and Cochrane for case reports, case series, and cohort studies for patients with biopsy-proven kidney IRAEs. All data were used to describe pathological characteristics and outcomes, and individual-level data from case reports and case series were pooled to analyze risk factors associated with different pathologies and prognoses. (3) Results: In total, 384 patients from 127 studies were enrolled. Most patients were treated with PD-1/PD-L1 inhibitors (76%), and 95% presented with acute kidney disease (AKD). Acute tubulointerstitial nephritis/acute interstitial nephritis (ATIN/AIN) was the most common pathologic type (72%). Most patients (89%) received steroid therapy, and 14% (42/292) required RRT. Among AKD patients, 17% (48/287) had no kidney recovery. Analyses of pooled individual-level data from 221 patients revealed that male sex, older age, and proton pump inhibitor (PPI) exposure were associated with ICI-associated ATIN/AIN. Patients with glomerular injury had an increased risk of tumor progression (OR 2.975; 95% CI, 1.176, 7.527; p = 0.021), and ATIN/AIN posed a decreased risk of death (OR 0.164; 95% CI, 0.057, 0.473; p = 0.001). (4) Conclusions: We provide the first systematic review of biopsy-proven ICI-kidney IRAEs of interest to clinicians. Oncologists and nephrologists should consider obtaining a kidney biopsy when clinically indicated. Full article

Acute kidney injury (AKI) is a common clinical syndrome characterized by a sudden decline in or loss of kidney function. AKI is not only associated with substantial morbidity and mortality but also with increased risk of chronic kidney disease (CKD). AKI is classically defined and staged based on serum creatinine concentration and urine output rates. The etiology of AKI is conceptually classified into three general categories: prerenal, intrarenal, and postrenal. Although this classification may be useful for establishing a differential diagnosis, AKI has mostly multifactorial, and pathophysiologic features that can be divided into different categories. Acute tubular necrosis, caused by either ischemia or nephrotoxicity, is common in the setting of AKI. The timely and accurate identification of AKI and a better understanding of the pathophysiological mechanisms that cause kidney dysfunction are essential. In this review, we consider various medical causes of AKI and summarize the most recent updates in the pathogenesis of AKI. Full article

Cancer immunotherapy has now entered clinical practice and has reshaped the standard of care for many cancer patients. With these new strategies, specific toxicities have emerged, and renal side effects have been described. In this review, we will describe the causes of acute kidney injury in CAR T cell, immune checkpoint inhibitors and other cancer immuno-therapy recipients. CAR T cell therapy and bispecific T cell engaging antibodies can lead to acute kidney injury as a consequence of cytokine release syndrome, tumor lysis syndrome, sepsis or specific CAR T cell infiltration. Immune checkpoint blockade most often results in acute tubular interstitial nephritis, but glomerular diseases have also been described. Although the pathophysiology remains mostly elusive, we will describe the mechanisms of renal damage in these contexts, its prognosis and treatment. As the place of immunotherapy in the anti-cancer armamentarium is exponentially increasing, close collaboration between nephrologists and oncologists is of utmost importance to provide the best standard of care for these patients. Full article