Acute Tubulointerstitial Nephritis Research Articles

Urinary soluble PD-1 as a biomarker of Checkpoint Inhibitor induced acute tubulointerstitial nephritis

Abstract Background Acute interstitial nephritis (AIN) related to Immune Checkpoint Inhibitors (ICI-AIN) has a not completely understood pathophysiology. Our objectives were to analyze possible biomarkers for the differentiation between acute tubular necrosis (ATN) and AIN, especially in cancer patients, and to study the participation of the immune checkpoint pathway in ICI-AIN. Methods We performed an observational study. We recruited patients with incident diagnosis of ICI-AIN (n=19). We measured soluble PD-1 (sPD-1), sPD-L1 and sPD-L2 in serum and urine at diagnosis and compared to patients with non ICI-related AIN (non-ICI AIN) (n=18) and ATN (n=21). The findings were validated in an independent cohort from another institution (n=30). Besides, we performed PD-L1 and PD-L2 immunostaining of kidney biopsies from patients with ICI-AIN and compared to patients with non-ICI AIN. Results Urinary sPD-1 (usPD-1) was higher in patients with AIN compared to ATN (p=0.03). Patients with AIN also showed higher serum sPD-1 (ssPD-1) than patients with ATN (p=0.021). In cancer patients, usPD-1 <129.3 pg/ml had a 71.43% sensitivity and 94.44% specificity to differentiate ATN from ICI-AIN, with a likelihood ratio of 12.86. In the external validation cohort, the same cutoff showed a sensitivity of 80%. In kidney biopsies, patients with ICI-AIN showed higher density of PD-L1 positive tubules than patients with non-ICI AIN (p=0.02). The proportion of patients having more than 2.64/mm2 PD-L2 positive tubules was higher among patients with ICI-AIN compared to non-ICI AIN (p=0.034). There was a positive correlation (p=0.009, r=0.72) between usPD-1 and the number of PD-L1 positive tubules. Conclusions UsPD-1 and ssPD-1 are higher in AIN than ATN. Moreover, there was a strong correlation between usPD-1 and renal tubular PD-L1 expression. Our findings suggest a role of usPD-1 as non-invasive biomarker to differentiate ICI-AIN from ATN, especially in cancer patients, which has been confirmed in an external validation cohort.

Diet and risk for acute tubulointerstitial nephritis

Diet and risk for acute tubulointerstitial nephritis

#622 Baseline inflammatory indexes and clinicopathological features to predict the outcome of acute interstitial nephritis

Abstract Backgrounds-and-aims Acute tubulointerstitial nephritis(AIN) is a rare cause of acute kidney injury(AKI). We aimed to investigate the characteristics of AIN patients and predictive factors for treatment response. Method 31 patients diagnosed with AIN by biopsy between 2006-2021 were included in this retrospective study. Baseline clinical, pathological, and laboratory findings, including CBC(complete blood count), creatinine, serum-immune-inflammation-index(SII), neutrophil-to-lymphocyte ratio(NLR), and platelet-to-lymphocyte ratio(PLR) were evaluated. Also, treatment response and creatinine levels at the last follow-up were noted. Results Median age was 46 years, and 80.6% of the patients were female. Median baseline creatinine and proteinuria levels were 4.1 mg/dL and 0.84 g/g or g/day. Median follow-up was 14 months. 93.5% of patients received immunosuppressives. End-stage-kidney-disease(ESKD) developed in five patients. Renal recovery(creatinine < 1.4 mg/dL) was observed in 17 (54.8%) patients. Global glomerulosclerosis percentage, interstitial fibrosis(IF), tubular atrophy(TA), granuloma formation, and higher baseline hemoglobin levels were associated with poor renal outcomes(non-responder). Also, ESKD-developed patients had higher baseline hemoglobin(p = 0.033) and lymphocyte(p = 0.044) and lower PLR levels(p = 0.016), as well as higher degrees of global glomerulosclerosis(p = 0.014), IF(p = 0.042), and TA(p = 0.030). Conclusion Treatment rates are low for AIN, which may lead to ESKD. Besides chronicity in pathology specimens, higher baseline hemoglobin levels and lower PLR might be prognostic for AIN. Further studies should be conducted on new markers for AIN.

#1671 Prevalence and factors predicting non diabetic kidney disease in type 2 diabetic patients

Abstract Background and Aims Renal involvement in type 2 diabetes is mostly presumed to be due to diabetic nephropathy, however a significant majority of diabetic patients can have pure non diabetic kidney disease (NDKD) or NDKD superimposed on diabetic kidney disease (DKD). Kidney biopsy cannot be routinely performed for all diabetic patients and hence short of conclusive biomarkers we need to explore various factors that can predict the occurrence of NDKD. Method We conducted a retrospective review of all native kidney biopsies conducted in patients with type 2 diabetes at our institute to identify the prevalence and factors that predict NDKD. The demographic data, clinical data, laboratory parameters, and histological results of the patients were obtained from their medical records. Binary logistic regression analysis was performed to evaluate the predictive factors for NDKD. Patients were categorized into 3 groups-DKD alone (presence of Kimmelstiel-Wilson nodules, capsular drops, fibrin caps and absence of any other NDKD features), NDKD along (presence of vasculopathy, interstitial fibrosis and specific glomerular changes in absence of classical DKD changes) and lastly DKD+NDKD (presence of histological changes of both DKD+NDKD). Results We analyzed a total of 69 patients. The mean (SD) age of the cohort was 51.94 ± 12.7 years and males constituted the majority (68%). Around 2/3rd of the entire cohort had hypertension, with no significant differences among the groups. Mean 24-hour urinary proteinuria was 6.6 ± 4.9 g/TV and 15.9% patients had microscopic hematuria. The mean (SD) duration of diabetes was 6.9 ± 6.2 years. Patients with pure DKD, pure NDKD and NDKD superimposed on DKD constituted 46.3%, 33.3% and 20% respectively of the cohort. The most common indication for renal biopsy in our cohort was rapid GFR decline in 38 patients (54.2%), followed by massive proteinuria in 27 (38.5%) and lastly positive serological work up for multiple myeloma in 5 patients (7.1%). Around 2/3rd of pure DKD patients in our cohort had diabetic retinopathy (DR), whereas only around 1/5th (26%) of pure NDKD patients had DR (p=0.005). DR was absent in around 74% of our diabetic patients who had pure NDKD. Non diabetic kidney disease in our cohort was seen in 46.3% patients and combined with DKD in 20% of patients. Among patients with NDKD, the most common cause was membranous glomerulonephritis (MGN) (43.4%) followed by acute tubulointerstitial nephritis (ATIN) (17.3%). Among combined DKD and NDKD, most common histological diagnosis was MGN (32.4%) followed by ATIN (16.2%). Independent factors predicting NDKD were shorter duration of diabetes (OR 0.74, CI 0.59–0.94, P=0.01) and absence of diabetic retinopathy (OR 0.15, 95% CI 0.09–0.26, P = 0.01). Conclusion Judicious use of kidney biopsy revealed NDKD in nearly half of T2DM patients especially in those with short duration of diabetes and absence of diabetic retinopathy (DR). Kidney biopsy is strongly recommended for T2DM patients with atypical presentation and in absence of DR.

#1187 Acute kidney injury and tubulointerstitial nephritis following prescription of anticancer drugs: VigiBase analysis

Abstract Background and Aims Anticancer drugs can have varying effects on the kidneys, depending on their characteristics. Various anticancer drugs may be nephrotoxic and can potentially cause renal impairment. We aimed to analyze the risk of renal adverse reactions according to different types of anticancer drugs using a global reporting system. Method We conducted an analysis on VigiBase, the World Health Organization pharmacovigilance database from Dec 1967 to Jul 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) compares observed and expected values to find the associations of each category of anticancer drugs with acute kidney injury (AKI) and tubulointerstitial nephritis (TIN). Results We observed 32,722 AKI and 2,056 TIN reports which were reported as anticancer drug-related renal adverse reactions. Noteworthy trends emerged in AKI reports following anticancer drugs: cytotoxic therapies consistently dominated with 13,925 cases, while AKI cases related to targeted therapies and immunotherapies surged to 14,236 and 3,816 cases over three decades, respectively. Notably, TIN exhibited a significant increase, particularly after the popular usage of immunotherapy between 2015 and 2020, surpassing other categories of anticancer drugs. The highest disproportionality signal for AKI was associated with immunotherapies (ROR, 8.92; confidence interval [CI], 8.63–9.21, followed by cytotoxic therapies (ROR, 7.14; 95% CI, 7.01–7.26), targeted therapies (ROR, 5.83; 95% CI, 5.73–5.93), and hormone therapies (ROR, 2.59; 95% CI, 2.41–2.79). In the case of TIN, a significantly higher disproportionality signal was found for immunotherapies (ROR, 21.74; 95% CI, 20.39–23.18), followed by cytotoxic therapies (ROR, 2.60; 95% CI, 2.40–2.82), and targeted therapies (ROR, 1.54; 95% CI, 1.40–1.69). Hormone therapies did not exhibit a significant disproportionality signal. Separate analyses were also conducted for the ROR of AKI and TIN for each individual anticancer drug. Conclusion AKI and TIN were substantially observed following the administration of anticancer drugs. Noticeably, renal adverse reactions following immunotherapy, which have been experiencing an increase in utilization, were more prominent than other types of anticancer drugs. Clinicians should consider the increased risk of renal adverse reactions after specific anticancer drugs.

#2989 Superposition of atypical hemolytic syndrome and tubulointerstitial nephritis, a case report

Abstract Background and Aims Hemolytic uremic syndrome is a heterogeneous group of diseases that have in common the development of thrombotic microangiopathy with diffuse endothelial damage, resulting in the classic triad composed of microangiopathic hemolytic anemia, thrombocytopenia and acute kidney injury, on the other hand, tubulointerstitial nephritis is characterized by the presence of inflammatory infiltrates and edema and of the interstitial compartment that causes deterioration of renal function. Method The following is the case of a patient with acute kidney injury of etiology composed of thrombotic microangiopathy and tubulointerstitial nephritis. Results 27-year-old female patient without significant history, began 3 weeks prior to admission with fever, chills, asthenia, nausea and vomiting of food content, approximately 5 episodes per day for 3 days, presenting intermittent episodes of jaundice of the mucous membranes and conjunctivae, with progressive increase of the symptoms to the point of preventing daily activities, she was admitted for study, detecting hemolytic anemia, thrombocytopenia and severe acute kidney injury, so she was referred to our center was decided for evaluation by Nephrology and Hematology. In our institution, urinary sediment with dysmorphic erythrocytes was documented, peripheral blood smear without the presence of schistocytes, positive Coombs 4 crosses, renal ultrasound with data compatible with acute kidney injury, and supportive management with hemodialysis was initiated. Due to suspicion of autoimmune glomerulopathy, an autoantibody panel was indicated with negative antinuclear antibodies, anti-double-stranded DNA, anti-Sm, anti-B2 glycoproteins, and lupus anticoagulant, with normal complement values, stool culture, and negative stool Shiga protein assay, angiotomography of the abdomen where the integrity of renal circulation is verified, so renal biopsy with immunohistochemical study is performed, finding data compatible with thrombotic microangiopathy and acute tubulointerstitial nephritis. The patient is maintained with supportive care, steroids and hemodialysis as required with progressive recovery of renal function until renal replacement therapy is weaned, she is discharged with a steroid regimen and clinical nephrology and hematology follow-up. Conclusion Acute kidney injury is a complex and multifactorial entity, which requires a comprehensive approach in order to identify the best therapeutic option and to offer a better outcome in the renal function of these patients. The case of our patient presented a sudden deterioration of renal injury composed of two entities with different pathophysiology, demonstrating that, although the approach to these two entities converge in certain etiologies, it is imperative that the clinician does not forget the wide variety of factors that contribute to the development of renal injury.

#1153 Short course of steroids as a treatment for immune checkpoint inhibitors-associated acute kidney injury

Abstract Background and Aims Immune checkpoint inhibitors (ICPi) have been a revolution in oncology. Due to their mechanism of action they can produce inflammatory adverse events, called “immune related adverse events” (IrAEs). Immune-mediated renal toxicity appears to be infrequent (2.2-5%), with acute tubulointerstitial nephritis being the most common form, clinically manifested as acute kidney injury (AKI). Corticosteroids are a highly effective treatment. However, the most suitable regimen has not been established. Method Retrospective multicenter study to evaluate the efficacy and safety of a short course of steroids (Group A) versus a long course (Group B) in patients with a clinical or histologic diagnosis of ICPi-associated acute kidney injury (ICPi-AKI). Short-duration regimen was considered to be that with a duration ≤3 months. Renal response was assessed 3 months after initiation of steroid therapy. Partial and complete renal response rates were compared in both groups, as well as relapses of ICPi-AKI with the lowering or suspension of steroid treatment. The development of adverse effects attributable to corticosteroids and the evolution of the oncologic disease were also evaluated. Results Sixty-three patients were included, 30 (48%) of whom received a short course of corticosteroids. Type of malignancy and oncologic treatment were similar in both groups. Baseline serum creatinine (1.1 mg/dL Group A and 0.9 mg/dL Group B; p = 0.53) and at ICPi-AKI diagnosis (3.0 mg/dL in Group A and 2.8 mg/dL in Group B; p = 0.43) were comparable. As shown in the table below, cumulative prednisone dose was lower in Group A than in Group B (1654 mg vs 4030 mg; p = 0.001). The overall renal response was 92% (87% Group A and 97% Group B; p = 0.2). There were no differences in complete response (40% Group A and 40% Group B; p = 1) or partial response (47% Group A and 57% Group B; p = 0.4). There were no recurrences of AKI after rechallenge of ICPi treatment. Adverse events related to corticosteroids were similar. There was a trend towards greater progression of oncologic disease in group B (64% versus 40%; p = 0.08). Conclusion A short course of steroids (< 3 months) is equally effective as a treatment for ICPi-AKI as longer courses, both in terms of renal response and relapse rate of ICPi-AKI. Adverse events related to steroid treatment were comparable in both groups. There appeared to be greater oncologic progression in the prolonged steroid treatment group.

#410 Novel renal pathology and treatment of TIN with monoclonal plasma cells invasion in a patient with Sjögren's syndrome and IgA monoclonal gammopathy

Abstract Background and Aims Patients with Sjögren's syndrome (SS) may occasionally present with monoclonal gammopathy of undetermined significance (MGUS), of the rare IgA type. Additionally, they may present with tubulointerstitial nephritis (TIN) infiltrated by polyclonal plasmacytes and lymphocytes. Previous reports indicate the development of IgA-type MGUS and TIN with monoclonal plasma cells in some SS patients, which are considered distinct from monoclonal gammopathy of renal significance (MGRS) because there is no evidence that monoclonal gammopathy affects nephropathy. Although treatment with prednisolone (PSL) has shown beneficial effects, the influence of monoclonal plasma cells on nephropathy remains unclear and a standardized treatment approach is lacking. Here we present a new renal pathological insight through a case of such a patient as described above, who underwent renal biopsy before and after PSL treatment. The aim is to propose a treatment strategy based on the findings of the second renal biopsy. Method and Results (Case Presentation) A 75-year-old Japanese man with primary complaint of dry mouth was diagnosed with SS by lip biopsy and anti-Ro/SSA and La/SSB antibody tests. Monoclonal proteins were found in both blood and urine. After immunoelectrophoresis, bone marrow puncture, and 18F-FDG PET/CT, we identified it as IgA kappa-type MGUS. At the same time, he developed renal dysfunction and was admitted to our hospital (week 1, Fig. 1) for a renal biopsy. The biopsy revealed severe and diffuse TIN infiltrated by lymphocytes with abundant interstitial plasma cell invasion (Fig. 2a). Minimal changes were observed in the glomeruli. Periodic acid–Schiff staining revealed Dutcher bodies in the nucleus of plasma cells. Immunohistochemical staining for immunoglobulins and light chains showed predominantly positive results for IgA and kappa (Fig. 2b). Monoclonality was confirmed by in situ hybridization. The infiltrates were positive for CD 45, CD 79a, and CD 138, partially positive for CD 19 and CD 20, and negative for CD 5, CD 10, and CD 23. Congo-red staining showed no evidence of amyloid. Immunofluorescence and electron microscopy revealed no detectable immunological deposits in the glomeruli and tubules. Mutations in the myeloid differentiation primary response gene 88 were not detected in the kidney. We diagnosed the condition as acute TIN by lymphocytes with IgA kappa-positive monoclonal plasma cells, distinct from MGRS. Considering the lack of evidence from previous reports on the impact of monoclonal plasma cells on nephropathy, we decided to treat the patient primarily for TIN with SS, initiating PSL at 30 mg/day (0.5 mg/kg/day). Renal function improved rapidly with the treatment, allowing for a gradual reduction in the dose of PSL; however, a low dose of PSL (10 mg/day) was required to prevent relapse. As a complication of PSL, the patient eventually developed a lumbar compression fracture, prompting us to evaluate the effect of PSL on renal function by a renal re-biopsy. The re-biopsy revealed significant recovery of TIN by lymphocytes (Fig. 2c). Other findings, including abundant interstitial plasma cells invasion were comparable to the initial biopsy. We diagnosed the condition as recovered TIN by lymphocytes with IgA kappa-positive monoclonal plasma cells. We concluded that TIN by lymphocytes, rather than monoclonal plasma cell invasion, primarily affected the nephropathy, and PSL mainly improved the former. The Nudix hydrolase 15 codon139 in blood was identified as Cys/Cys, indicating a high risk of severe adverse reactions to azathioprine in Asians. Therefore, we decided to concurrently administer mycophenolate mofetil, proven effective in the treatment of TIN with SS. Conclusion In the management patients with SS and IgA monoclonal gammopathy, the focus should be on TIN by lymphocytes rather than monoclonal plasma cell invasion. This case, considering similar cases, suggests that it should be defined as a new disease category. We demonstrate new renal pathology and treatment insights based on renal re-biopsy in a patient treated with PSL.

#2910 Renal toxicities in oncology at a secondary level hospital within the first 6 months of outpatient consultation establishment

Abstract Background and Aims In recent years the discovery of targeted therapies in oncology have been a revolution with spectacular results for patients with advanced neoplasia and metastasis. Representing a more precise approach to interfering with tumorigenesis, these therapies exhibit superior tolerability profile in terms of toxicity and have significantly improved overall survival (1). Numerous studies have demonstrated the increased risk of cancer patients developing acute renal failure and progressing to chronic kidney disease, both contributing to higher mortality. The use of these novel drugs, alongside traditional chemotherapy, coupled with the extended survival of patients with neoplasms has led to a rise in kidney pathologies (2.3). Addressing the need to provide a comprehensive and optimized treatment to this group of patients, the field of Onconephrology has emerged. Its primary objective is to assist in the diagnosis and management of kidney diseases associated with the underlying oncological condition and/or oncotherapeutics. While well-established Onconephrology Clinics predominantly operate in tertiary hospitals worldwide, acknowledging the growing significance of this field, we established an Onconephrology outpatient consultation at our secondary level hospital. In this study, we aim to delineate the incidence of renal toxicities secondary to oncotherapeutics within the first six months of initiating our Onconephrology outpatient consultation. Method Forty-six patients were retrospectively included, and an analysis of oncological and renal variables was conducted to determine the incidence of renal toxicities. Results Out of the forty-six patients evaluated, 12 exhibited renal toxicity secondary to oncotherapeutics, with a mean age of 73.3 years. The most frequent malignancy was lung cancer (n = 6), followed by gastrointestinal tract cancer (n = 2). Most patients presented with metastatic disease (n = 9), and their malignant disease was either in remission (n = 4) or stable (n = 5). Reasons for referral included acute kidney injury (n = 7), acute kidney injury over chronic kidney disease (n = 3), proteinuria (n = 1), and electrolyte abnormalities (n = 1). The diagnoses included acute immune-mediated tubulointerstitial nephritis secondary to checkpoint inhibitors (n = 5), cisplatin renal toxicity (n = 3), acute tubular necrosis secondary to tyrosine kinase inhibitors (n = 2), hypomagnesemia induced by EGFR inhibitor (n = 1), and nephrotic syndrome related to anti-VEGF. Following multidisciplinary intervention, most patients experienced recovery of kidney function (n = 9), while some progressed to chronic kidney disease (n = 2), and other maintained electrolyte imbalances (n = 1). Conclusion This study describes 12 patients with renal toxicities secondary to oncotherapeutics over a 6-month period at a secondary hospital. Most patients exhibited recovery of kidney function, emphasizing the positive outcomes achievable through multidisciplinary care, particularly in the context of the Onconephrology outpatient consultation, even in institutions with limited resources.

Causal association of plasma circulating metabolites with nephritis: a Mendelian randomization study.

Nephritis is a pivotal catalyst in chronic kidney disease (CKD) progression. Although epidemiological studies have explored the impact of plasma circulating metabolites and drugs on nephritis, few have harnessed genetic methodologies to establish causal relationships. Through Mendelian randomization (MR) in two substantial cohorts, spanning large sample sizes, we evaluated over 100 plasma circulating metabolites and 263 drugs to discern their causal effects on nephritis risk. The primary analytical tool was the inverse variance weighted (IVW) analysis. Our bioinformatic scrutiny of GSE115857 (IgA nephropathy, 86 samples) and GSE72326 (lupus nephritis, 238 samples) unveiled anomalies in lipid metabolism and immunological characteristics in nephritis. Thorough sensitivity analyses (MR-Egger, MR-PRESSO, leave-one-out analysis) were undertaken to verify the instrumental variables' (IVs) assumptions. Unique lipoprotein-related molecules established causal links with diverse nephritis subtypes. Notably, docosahexaenoic acid (DHA) emerged as a protective factor for acute tubulointerstitial nephritis (ATIN) (OR1 = 0.84, [95% CI 0.78-0.90], p1 = 0.013; OR2 = 0.89, [95% CI 0.82-0.97], p2 = 0.007). Conversely, multivitamin supplementation minus minerals notably increased the risk of ATIN (OR = 31.25, [95% CI 9.23-105.85], p = 0.004). Reduced α-linolenic acid (ALA) levels due to lipid-lowering drugs were linked to both ATIN (OR = 4.88, [95% CI 3.52-6.77], p < 0.001) and tubulointerstitial nephritis (TIN) (OR = 7.52, [95% CI 2.78-20.30], p = 0.042). While the non-renal drug indivina showed promise for TIN treatment, the use of digoxin, hydroxocobalamin, and liothyronine elevated the risk of chronic tubulointerstitial nephritis (CTIN). Transcriptome analysis affirmed that anomalous lipid metabolism and immune infiltration are characteristic of IgA nephropathy and lupus nephritis. The robustness of these causal links was reinforced by sensitivity analyses and leave-one-out tests, indicating no signs of pleiotropy. Dyslipidemia significantly contributes to nephritis development. Strategies aimed at reducing plasma low-density lipoprotein levels or ALA supplementation may enhance the efficacy of existing lipid-lowering drug regimens for nephritis treatment. Renal functional status should also be judiciously considered with regard to the use of nonrenal medications.

Case Report: A rare renal manifestation of Acute intermittent porphyria

Acute porphyria is a group of metabolic disorders characterized by a deficiency in enzymes involved in heme biosynthesis. A 21-year-old female with abdominal pain and an altered sensorium, eventually leading to a diagnosis of acute porphyria. Glucose treatment and supportive measures improved her general condition. Renal biopsy showed persistent renal dysfunction, which revealed acute tubulointerstitial nephritis with 5-10% interstitial fibrosis and tubular atrophy. This highlights a unique manifestation of acute porphyria involving the kidney and emphasizes the importance of considering acute tubulointerstitial nephritis as a cause of renal dysfunction in acute porphyria.

Acute Interstitial Nephritis Associated with Smilax Consumption: Case Report

The cocolmeca herb (Smilax) belongs to the smilacaceae family, comprising around 350 species of tropical and subtropical distribution, used as popular medicine in Central America and the Caribbean islands. In Mexico it has been used mainly for weight loss. Case presentation: A 52-year-old man with a history of systemic arterial hypertension and grade I obesity, with consumption of smilax for at least two months, presented deterioration in renal function, with initial studies with urea 90 mg/dl and serum creatinine 3.6. mg/dl, infectious and systemic causes were ruled out, acute tubulointerstitial nephritis was confirmed by percutaneous biopsy, management was given with methylprednisolone boluses and renal function improved. The use of traditional remedies is common throughout the world, with use rates exceeding 80% in some populations. It is considered that approximately 2% of chronic kidney disease (CKD) is due to AIN.

PPI-related acute tubulointerstitial nephritis

PPI-related acute tubulointerstitial nephritis

Differentiation Syndrome Presenting as Acute Kidney Injury in a Patient of Acute Promyelocytic Leukemia on All-trans Retinoic Acid and Arsenic Trioxide Regimen: A Case Report

Introduction: Acute promyelocytic leukemia (APL), classified as Subtype M3 of acute myeloid leukemia, is known for its relatively favorable prognosis, primarily due to the high effectiveness of all-trans retinoic acid (ATRA) in treating the maturation block. However, it is essential to be aware of potential complications such as ATRA syndrome, which can affect 5%–25% of patients and manifest with symptoms such as fever, interstitial pulmonary infiltration, pleural/pericardial effusion, and acute renal failure. Methods: We present the case of a 47-year-old female with a history of hypertension, who experienced rash, fever, and reduced urine output during the induction phase with ATRA. Her serum creatinine levels exhibited a rapid increase from 2.63 mg/dL on October 07, 2022, to 7 mg/dL on October 18, 2022, despite having normal-sized kidneys and normal corticomedullary differentiation. A renal biopsy conducted on October 20, 2022, revealed features consistent with active tubulointerstitial nephritis, with direct immunofluorescence showing no significant glomerular immune deposits. A total of 17 hemodialysis sessions were performed. Results: A subsequent bone marrow examination conducted on October 26, 2022, demonstrated a hypercellular aspirate with normal morphology. However, due to the persistence of renal failure, a repeat biopsy was performed, revealing severe acute tubular injury. Pulse steroids were initiated, and ATRA was discontinued, resulting in an improvement in renal function. Conclusion: This case highlights an instance of acute, early, and severe differentiation syndrome (DS) occurring after induction therapy in a patient with APL. The DS in this case was particularly severe, leading to renal failure necessitating hemodialysis. The prompt initiation of pulse steroids and discontinuation of ATRA proved to be effective in managing this complication. Clinicians should remain vigilant for DS and its potential complications, including acute kidney injury and acute tubulointerstitial nephritis, when treating patients with APL.

Pediatric Cases Diagnosed with Drug-Related Acute Tubulointerstitial Nephritis: A Single-Center Experience

Aim: Acute tubulointerstitial nephritis (TIN) is inflammation of the renal interstitium. It is also a common cause of acute kidney injury (AKI). The aim is to contribute to the literature by evaluating patients diagnosed with drug-induced TIN.&#x0D; Material methods: 29 Turkish children aged between 3 and 217 months, 5 of whom had undergone a biopsy, were retrospectively analyzed in terms of clinical and laboratory findings.&#x0D; Results: 29 patients, 19 of whom were girls, were evaluated. The mean age at diagnosis was 138.6(3-217) ± 67.4 months. Nausea-vomiting complaint of 12 cases, 6 under treatment during hospitalization, 4 with headache, 2 with isolated fatigue, and the remaining 5 patients with incidentally detected renal function test disorder, oligo-anuria, urinary incontinence, red urination, and uveitis. At the time of diagnosis, 4 patients had hypertension and 26 patients had AKI. Two of these cases were anuric. The low eGFR values at the time of diagnosis were observed to improve at the end of the follow-up. Hematuria was detected in 18 cases and of them were macroscopic hematuria. 4 patients had pyuria, 19 patients had proteinuria, and 2 of them were nephrotic. FeNa was the most common abnormality of the tubular tests with 4.5%. Biopsy was performed in 5 cases. While one of the patients presented with uveitis, uveitis developed in 1 patient during the 3rd month of follow-up.&#x0D; Conclusion: Consequently, although TIN is a reversible disease, its recognition is important in terms of treatment and follow-up.

Two acute kidney injury episodes after ICI therapy: a case report.

A 74-year-old Japanese male with lung squamous cell carcinoma received his first dose of immune checkpoint inhibitors (ICIs): ipilimumab and nivolumab. He developed acute kidney injury (AKI) and was admitted to our department. We diagnosed kidney immune-related adverse effects (irAE), and a kidney biopsy revealed acute tubulointerstitial nephritis. We started oral prednisolone (PSL) and his AKI immediately improved. The patient maintained stable findings after PSL was tapered off. However, seven months after the ICI administration, he developed rapid progressive glomerular nephritis and was admitted to our department again. The second kidney biopsy showed findings consistent with anti-glomerular basement membrane glomerulonephritis. Although the patient was treated with pulse methylprednisolone followed by oral PSL and plasma exchange, he became dependent on maintenance hemodialysis. To our knowledge, no case report has described two different types of biopsy-proven nephritis. In cases of suspected relapsing kidney irAEs, both a relapse of previous nephritis and the development of another type of nephritis should be considered.

Vancomycin nephrotoxicity: A comprehensive clinico-pathological study.

Vancomycin, a commonly prescribed antibiotic particularly in the setting of multi-drug resistant infections, is limited by its nephrotoxicity. Despite its common occurrence, much remains unknown on the clinicopathologic profile as well as the pathogenesis of vancomycin nephrotoxicity. Clinical studies included patients often with severe comorbidities and concomitant polypharmacy confounding the causal pathogenesis. Animal models cannot recapitulate this complex clinical situation. Kidney biopsy was not commonly performed. To address this limitation, we studied 36 patients who had renal biopsies for acute kidney injury (AKI) for suspicion of vancomycin nephrotoxicity. Detailed renal biopsy evaluation, meticulous evaluation of clinical profiles, and up-to-date follow-up allowed for a diagnostic categorization of vancomycin nephrotoxicity (VNT) in 25 patients and absence of vancomycin nephrotoxicity (NO-VNT) in 11 patients. For careful comparison of these two groups, we proceeded to compile a clinicopathologic and morphologic profiles characteristic for each group. Patients with VNT had a characteristic clinical profile including a common clinical background, a high serum trough level of vancomycin, a rapidly developed and severe acute kidney injury, and a recovery of renal function often shortly after discontinuation of vancomycin. This clinical course was correlated with characteristic renal biopsy findings including acute tubulointerstitial nephritis of allergic type, frequent granulomatous inflammation, concomitant and pronounced acute tubular necrosis of nephrotoxic type, and vancomycin casts, in the absence of significant tubular atrophy and interstitial fibrosis. This clinico-pathologic profile was different from that of patients with NO-VNT, highlighting its role in the diagnosis, management and pathogenetic exploration of vancomycin nephrotoxicity. Vancomycin nephrotoxicity has a distinctive morphologic and clinical profile, which should facilitate diagnosis, guide treatment and prognostication, and confer pathogenetic insights.

Investigation of renal perfusion and pathological changes in patients with acute kidney disease and tubulointerstitial nephritis using intravoxel incoherent motion and arterial spin labelling MRI: a prospective, observational study protocol

IntroductionAcute kidney injury (AKI) is a critical condition with a complex aetiology and different outcomes, where haemodynamic dysfunction, renal hypoperfusion and inflammation serve as key contributors to its development and...

Immune checkpoint inhibitors and acute kidney injury.

As a new type of anti-tumor immunotherapy, immune checkpoint inhibitors (ICIs) have improved the prognosis of multiple malignancies. However, renal complications are becoming more frequent. Nephrotoxicity often manifests as acute kidney injury (AKI), and the most common histopathological type is acute tubulointerstitial nephritis (ATIN). Based on previous studies of the incidence and potential risk factors for nephrotoxicity, in this review, we describe the mechanism of AKI after ICIs treatment, summarize the incidence, risk factors, and outcomes of AKI, and discuss the diagnosis and management of immune checkpoint inhibitors-associated acute kidney injury (ICI-AKI). In addition, we review the current status of ICIs rechallenge and the therapeutic strategies of ICIs applied in kidney transplant recipients. Finally, we emphasize the importance of collaboration between nephrologists and oncologists to guide the treatment of ICIs and the management of renal complications.

Renal Injury During Viral Infections

Renal pathologies following viral infections have become an emerging public health problem in both developed and developing countries. Diagnostic criteria are complex. In most cases, they involve correlation between clinical, biological and histological data, with occasional recourse to molecular biology techniques. Several mechanisms are involved in the pathogenesis of virus-related nephropathy, including virus tropism in the kidney, formation of immune complexes in situ or in the bloodstream, direct cytopathogenic effects, and multiple organ failure. The hepatitis C virus is responsible for three main types of kidney disease: membranoproliferative glomerulnephritis, cryoglobulinemia and membranous nephropathy. Hepatitis B virus is associated with membranous nephropathy, membranoproliferative glomerulnethritis, and IgA nephropathy. HIV (human immunodeficiency virus) infection is associated with several glomerular and tubular kidney damage. HIVAN (HIV-associated nephropathy), a specific entity mainly affecting Africans and African-Americans, presents as a rapidly progressive glomerulonephritis rapidly progressing to the terminal stage. Infections secondary to adenovirus, cytomegalovirus, epstein-barr virus, poliomavirus and coronavirus are often responsible for acute or chronic tubulointerstitial nephritis. Treatment is mainly symptomatic, based on nephroprotection measures, rarely combined with antiviral therapy. Prophylaxis with vacci-nation, when available, remains the best means of preventing viral nephropathy.