Interstitial Nephritis In Patients Research Articles

P839 Acute interstitial nephritis in patients with Inflammatory Bowel Disease treated with vedolizumab: a systematic review

Abstract Background Acute interstitial nephritis (AIN) is a complication of drugs that may cause permanent kidney injury. AIN has been reported in inflammatory bowel disease (IBD) patients treated with the anti-integrin inbibitor vedolizumab. However, systematically collected data on cases of AIN associated with vedolizumab treatment is lacking. We therefore, through systematic review of existing literature, aimed to identify and describe reported cases of AIN. Methods We searched Medline, Embase, Cochrane, and Web of Science Core Collection between January 1, 2009 and April 25, 2023. The search yielded 1473 publications after deduplication, for which titles and abstracts were screened by two independent reviewers. Of these, 75 publications were reviewed in full-text. Demographics and clinical characteristics of AIN cases were extracted. Case causality assessment was performed according to the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) system and the Naranjo Adverse Drug Reaction Probability Scale. Results were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A prespecified protocol was registered in the PROSPERO database. Results Eight publications met the inclusion criteria and were included in descriptive analysis of AIN in patients with IBD treated with vedolizumab. A total of nine biopsy-confirmed cases of AIN were reported in six patients with ulcerative colitis and three with Crohn’s disease. The mean age at AIN onset was 36 years (range: 19-58). The majority of patients were females (n=6/9). Time from vedolizumab treatment initiation to AIN onset spanned from hours to 12 months. Common symptoms were fever, malaise, and myalgia. Creatinine levels were elevated in all patients (mean: 219 µmol/L; range; 133-410). Rechallenge after pause and treatment with corticosteroids were reported in three cases, where one attempt was successful. Five patients sustained permanent kidney injury. According to the WHO-UMC scale, six of nine cases were assessed as “possible” or “probable”, and the remaining three cases as “unlikely” or “unclassifiable”. Three patients were treated with concomitant mesalazine or proton pump inhibitors, which both are associated with an increased risk of AIN. Conclusion In systematic review of existing literature, we identified nine cases of biopsy-confirmed AIN in patients with IBD treated with vedolizumab. Our findings suggest that vedolizumab, although rarely, could potentially cause AIN in patients with IBD. Awareness of laboratory findings and symptoms consistent with AIN, along monitoring of the kidney function, could be warranted in patients with IBD treated with vedolizumab.

Renal tubular acidosis without interstitial nephritis in Sjögren’s syndrome: a case report and review of the literature

BackgroundRenal 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 presentationA 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.ConclusionsThis 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.

The Anti-Rheumatic Drug, Leflunomide, Induces Nephrotoxicity in Mice via Upregulation of TGFβ-Mediated p53/Smad2/3 Signaling.

Recent studies indicated renal toxicity and interstitial nephritis in patients receiving leflunomide (LEFN), but the exact mechanism is still unknown. The transforming growth factor β (TGFβ)/p53/Smad2/3 pathway crucially mediates renal fibrosis. We aimed to assess the nephrotoxic effect of LEFN in mice and the possible role of TGFβ-stimulated p53/SMAD2/3 signaling. The study design involved distributing sixty male albino mice into four groups: (i) vehicle-treated mice, (ii) LEFN (2.5 mg/kg), (iii) LEFN (5 mg/kg), and (iv) LEFN (10 mg/kg). The drug was given orally every 48 h and continued for 8 weeks. Blood samples were then taken from mice for the determination of kidney function parameters. Right kidneys were used for histopathologic staining and immunohistochemistry, whereas left kidneys were frozen and used for Western blot analysis of the target proteins, p-p53 and Smad2/3. Results indicated that chronic administration of LEFN in mice resulted in a four- and nine-fold increase in serum urea and creatinine levels, respectively. Kidney specimens stained with hematoxylin and eosin or periodic acid–Schiff showed significant histopathological manifestations, such as cellular irregularity, interstitial congestion, and moderate lymphocytic inflammatory infiltrate in mice treated with LEFN. Western blotting indicated upregulation of the p-p53/Smad2/3 proteins. LEFN, especially in the highest dose (10 mg/kg), produced prominent nephrotoxicity in mice. This toxicity is mediated through stimulating fibrotic changes through TGFβ-stimulated p53/Smad2/3 signaling and induction of glomerular and tubular apoptosis. An improved understanding of LEFN-induced nephrotoxicity would have great implications in the prediction, prevention, and management of leflunomide-treated rheumatic patients, and may warrant further clinical studies for following up these toxidromes.

Mortality after acute kidney injury and acute interstitial nephritis in patients prescribed immune checkpoint inhibitor therapy

BackgroundIn patients receiving immune checkpoint inhibitor (ICI) therapy, acute kidney injury (AKI) is common, and can occur either from kidney injury unrelated to ICI use or from immune activation resulting...

Safe and appropriate use of diclofenac in chronic kidney disease: An Indian perspective.

Pain is most common symptom associated with progressive disorder, chronic kidney disease (CKD), and is usually undertreated during the early stages of CKD. So, present review was conducted to evaluate the challenges for the management of pain in CKD patients and addresses the scope for considering Diclofenac as suitable alternative for pain management in CKD patient. The database PubMed and Google Scholar were searched from 1970 to Dec 2020 for literature published in English and all studies, review articles that examined the use of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in pain management in CKD patients were included. Literatures revealed that there is a considerable challenge in appropriate management of pain in CKD patients include understanding the altered pharmacokinetics and pharmacodynamics of analgesics in CKD patients and the risk of acute interstitial nephritis. The shorter duration of analgesics is acceptable and considered to pose a low risk of acute interstitial nephritis in patients. Considering that Diclofenac has a shorter half-life and high efficacy, it may be well tolerated in patients with CKD. The acceptance of Diclofenac is partly attributed to being a potent COX-2 inhibitor with the lowest IC50 and its rapid onset of action at lowest effective dose. In conclusion, diclofenac may be well tolerated in patients of renal impairment when used at lowest effective dose for shortest dose duration. Diclofenac is worthy of consideration in mild to moderate cases of CKD. For effective pain management, it is vital to evaluate the tolerability and efficacy of the available analgesics critically.

S1341 Risk of Acute Interstitial Nephritis in Patients on Acute Proton Pump Inhibitor Therapy

INTRODUCTION: Proton pump inhibitors (PPIs) are commonly prescribed medications. Studies suggest a link between PPI and acute interstitial nephritis (AIN), however data is limited. Our primary aim was to evaluate the prevalence of AIN in patients on short-term PPI therapy. Our secondary aim was to compare the risk of AIN in patients on PPI compared to H2-receptor blockers and compare adverse events (AE) . METHODS: We performed a retrospective analysis in the IBM Explorys database 5 (1999-2020), a pooled, national, de-identified clinical database of over 72 million unique patients from 26 health care networks and 300 hospitals across the United States. Patient populations were identified using SNOMED and ICD codes. PPI included were esomeprazole, omeprazole, pantoprazole and lansoprazole. The development of AIN was evaluated within 8 weeks of PPI initiation. Patients on medications commonly implicated in AIN which included NSAIDs, antibiotics, loops diuretic, H2-blockers, rifampin, and allopurinol were excluded from the study if prescribed within 30 days of initiation of PPI. Additionally, patients with systemic lupus erythematous, sarcoidosis, granulomatosis with polyangiitis, and Sjogren’s disease were also excluded from the study. The control group was defined as patients on H2 blockers with the above exclusion criteria. AE were defined as ICU admission within 7 days, hemodialysis within 2 weeks, new chronic kidney disease within 6 months of diagnosis of AIN, and new end stage renal disease within 1 year for PPI group and control group. Prevalence was reported for each PPI. Odds ratio with 95% CI were calculated for risk of AIN for each PPI compared to control group. Chi-squared test was used to compare the risk of AEs in the combined PPI group vs H2-blockers. RESULTS: Acute PPI-induced AIN comprised 0.56% (n = 1410) of total AIN patients. Prevalence of AIN in esomeprazole and omeprazole was 6 (per 10,000), pantoprazole was 18 (per 10,000) and lansoprazole was 4 (per 10,000). Pantoprazole was the only PPI associated with an increased risk of AIN (OR 1.66, 95% CI 1.51-1.84). There was no difference between risk of CKD and ESRD between PPI and control. Patients in PPI group were more likely to be senior, female, have Medicare insurance, hypertension, hyperlipidemia and heart failure. CONCLUSION: Our study shows that AIN is a rare side effect of acute PPI therapy. Pantoprazole should be used with caution perhaps in patients with underlying CKD however this needs to be validated in future studies.Figure 1Figure 2Table 1

S1340 Risk of Acute Interstitial Nephritis in Patients on Chronic Proton Pump Inhibitor Therapy

INTRODUCTION: Proton pump inhibitors (PPIs) are commonly prescribed medications. Studies suggest a link between PPI use and acute interstitial nephritis (AIN), however data is limited. Our primary aim was to evaluate the prevalence of AIN in patients on chronic PPI therapy. Our secondary aim was to compare the risk of AIN in patients on PPI compared to H2 blockers and compare adverse events (AE). METHODS: We performed a retrospective analysis in the IBM Explorys database 5 (1999-2020), a pooled, national, de-identified clinical database of over 72 million patients from 26 health care networks and 300 hospitals across the United States. Patient populations were identified using SNOMED and ICD codes. PPI included were esomeprazole, omeprazole, pantoprazole and lansoprazole. The development of AIN was evaluated after at least 6 months of PPI therapy. Patients on medications commonly implicated in AIN including NSAIDs, antibiotics, loop diuretic, H2 blockers, rifampin, and allopurinol were excluded from the study if prescribed within 30 days of development of AIN. Patients with systemic lupus erythematosus, sarcoidosis, granulomatosis with polyangiitis, and Sjogren’s were also excluded. The control group was defined as patients on H2 blockers with the above exclusion criteria. AE were defined as ICU admission within 7 days, hemodialysis within 2 weeks, chronic kidney disease within 6 months, and end stage renal disease within 1 year. Odds ratios with 95% CI were calculated for risk of AIN for each PPI compared to the control group. Chi-squared test was used to compare the risk of AEs in the combined PPI group vs H2 blockers. RESULTS: The prevalence of AIN on chronic PPI therapy comprised 6.49% (n = 16130). Prevalence of AIN in lansoprazole was 28 (per 10,000), esomeprazole was 21 (per 10,000), omeprazole was 15 (per 10,000), and pantoprazole was 8 (per 10,000). Esomeprazole, omeprazole, and lansoprazole were associated with an increased risk of AIN when compared to the control. Lansoprazole had the highest associated risk for AIN (OR 2.53, 95% CI 2.38-2.70, followed by esomeprazole (OR 1.9, 95% CI 1.8-2.02), and then omeprazole (OR 1.32, 95% CI 1.26-1.39). Esomeprazole had a higher risk of ICU admission and new-onset CKD. Lansoprazole had a higher risk of ESRD. CONCLUSION: Most PPIs confer a higher risk of AIN compared to H2-blockers. Esomeprazole should be used with caution in patients at high risk for the development of CKD or ESRD. Future prospective studies are needed to validate these findings.Figure 1Figure 2

124 Interstitial Nephritis in Patients Treated with Immune Checkpoint Inhibitors: Risk Factors and Treatment

124 Interstitial Nephritis in Patients Treated with Immune Checkpoint Inhibitors: Risk Factors and Treatment

Acute interstitial nephritis in patients with viperine snake bite: single center experience of a rare presentation.

Acute renal failure following vasculotoxic viperine snake bites is very common in South Asia. Acute tubular necrosis and acute cortical necrosis are the common findings, with acute interstitial nephritis (AIN) being a rare presentation. We conducted renal biopsies in all patients who were admitted in our institute with viperine snake bite-related acute kidney injury (AKI) and who did not improve after three weeks of supportive care. Patients who had findings of AIN on renal histology were included for this study. Of a total of 42 patients, there were five patients (11.9%) with AIN. Our series of five patients is the largest series of this rare presentation in the literature. All of these five patients had features of severe envenomation, severe AKI network stage of AKI and very high antivenom requirements. They had a very prolonged stay in the hospital, and four of the five patients developed chronic kidney disease on follow-up. The overall outcome in this group was worse as compared with those who did not have AIN. AIN following viperine snake bites is not a very rare presentation. The reason for the development of this pathology is unclear, but direct venom-related effects are possible. This presentation portends a poor overall long-term prognosis as demonstrated in our case series.

Light-Chain–Mediated Acute Tubular Interstitial Nephritis: A Poorly Recognized Pattern of Renal Disease in Patients With Plasma Cell Dyscrasia

Acute renal failure may be the first clinical presentation in patients with plasma cell dyscrasia. Recognition of the unusual interstitial inflammatory lesion associated with monoclonal light chains and renal failure described herein is important to guide clinicians in requesting appropriate tests to confirm plasma cell dyscrasia and providing adequate treatment. To describe an unusual pattern of tubular interstitial nephritis in patients with underlying plasma cell dyscrasia characterized by an interstitial inflammatory reaction associated with deposition of light chains along tubular basement membranes. Eight cases of light-chain-mediated acute tubular interstitial nephritis were identified from the archives of 4296 kidney biopsy specimens. In all cases, routine light microscopic examination, direct immunofluorescence, and electron microscopic examination were performed. Ultrastructural immunogold labeling was performed in specimens with inconclusive findings and in specimens from patients with no clinical history of plasma cell dyscrasia. All patients presented with acute renal failure. Light microscopy revealed acute tubular interstitial nephritis. In some of the cases, direct immunofluorescence and electron microscopy failed to show definitive evidence of light-chain deposition along tubular basement membranes. Ultrastructural immunogold labeling aided the demonstration of monotypical light chains along some tubular basement membranes. No light chains were present in other renal compartments. Accumulation of light chains along tubular basement membranes may induce an interstitial process that mimics acute tubular interstitial nephritis. Recognition of this unusual pattern of renal disease in patients with plasma cell dyscrasia requires ancillary diagnostic techniques.

Light-Chain–Mediated Acute Tubular Interstitial Nephritis: A Poorly Recognized Pattern of Renal Disease in Patients With Plasma Cell Dyscrasia

Abstract Context.—Acute renal failure may be the first clinical presentation in patients with plasma cell dyscrasia. Recognition of the unusual interstitial inflammatory lesion associated with monoclonal light chains and renal failure described herein is important to guide clinicians in requesting appropriate tests to confirm plasma cell dyscrasia and providing adequate treatment. Objective.—To describe an unusual pattern of tubular interstitial nephritis in patients with underlying plasma cell dyscrasia characterized by an interstitial inflammatory reaction associated with deposition of light chains along tubular basement membranes. Design.—Eight cases of light-chain–mediated acute tubular interstitial nephritis were identified from the archives of 4296 kidney biopsy specimens. In all cases, routine light microscopic examination, direct immunofluorescence, and electron microscopic examination were performed. Ultrastructural immunogold labeling was performed in specimens with inconclusive findings and in ...

Primary chronic interstitial nephritis in Crohn's disease

Background & Aims: In Crohn's disease, cases of interstitial nephritis with renal failure have been reported in connection with the use of mesalamine. Methods: We observed 4 patients with severe interstitial nephritis proven by examination of kidney biopsy specimens. Renal failure was discovered before or simultaneously with the diagnosis of Crohn's disease, and patients were not treated with mesalamine. Impairment of renal function progressed to end-stage renal failure in 3 of the 4 patients. Results: Our results show that the kidney can be an extraintestinal target of Crohn's disease. Conclusions: Several unanswered questions remain concerning the frequency of interstitial nephritis in patients with Crohn's disease, as well as the exact role of mesalamine in the development of chronic interstitial nephritis.GASTROENTEROLOGY 2002;123:1436-1440

SNAKEBITE INDUCED ACUTE INTERSTITIAL NEPHRITIS: REPORT OF A RARE ENTITY

Snakebite induced acute renal failure continues to occur in many tropical areas of the world. Renal histological lesions other than acute tubular necrosis and acute cortical necrosis as the cause of acute renal failure are rare. Only 3 cases of acute interstitial nephritis in patients with snakebite induced acute renal failure have been previously reported. We report a patient with acute renal failure following viperine snakebite due to acute interstitial nephritis. After a prolonged oliguric phase, there was complete recovery of renal function without institution of steroids. Interstitial nephritis may result from a hypersensitivity reaction to some component of the snake venom.

Limited TCR repertoire of infiltrating T cells in the kidneys of Sjögren's syndrome patients with interstitial nephritis.

To analyze the mechanism of interstitial nephritis in patients with Sjörgren's syndrome (SS), we examined the TCR repertoire of infiltration T cells in kidney, labial salivary glands, and PBLs using a PCR. The repertoire of the TCR V beta gene on infiltrating T cells from the kidneys of SS patients was more restricted than those on infiltrating T cells in labial salivary glands and PBL. The TCR V beta 2 gene was expressed predominantly in six of seven (86%) SS patients. Junctional sequences of cDNAs encoding the V beta 2 gene on infiltrating T cells in the kidneys of five SS patients showed that some of the cells expanded clonally, indicating Ag-driven stimulation rather than superantigen-induced proliferation. The same V beta 2 clones in the kidney were not detected in labial salivary glands of the same SS patients; the conserved amino acid (arginine at position 96) in the CDR3 region of the V beta 2 gene was found at a frequency of 48.0% in the kidney, whereas it was detected in only 15.4% of the clones in lips. In conclusion, these findings suggest the possibility that T cells that infiltrate the kidneys of SS patients with interstitial nephritis might recognize different autoantigens than those that infiltrate labial salivary glands.

Side-effects of anti-inflammatory/ analgesic drugs: renal, hepatic and other systems

Deparanera of Pharmacology, University of Cambridge. Cambridge, UK. Nephropathy Analgesic abuse has been a major came of nephropathy. There has been much concern that the lay public, taking large quantities of combinations of analgesics such as acetyl salicylic acid with phen- acetin or paracetamol, may be at parti- cular risk ~'-'. Also, arthritic patients may be at risk since renal papillary necrosis has been frequently observed at autopsy or following biopsy in these patients who have ;ngested large quantities of non-steroidal, anti-inflammatory (NSAl) drugs 12. The incidence of papillary necrosis and chronic interstitial nephritis in arthritics has been claimed to be 21-28% 2 . Definitive renal papillary necrosis has been reported in man follow- ing the use of alclofenac, aminophena- zone, phenazone, acetyl salicylic acid, fenoprofen, ibuprofen, indometacin, paracetamol and phenyibutazone-'. Pro- teinuria and renal damage also occurs frequently in arthritic patients receiving D-penicillamine and the gold salts 2. Nephropathy from analgesic abuse had its origins in Switzerland about 30 years ago 23. Sptihler and Zollinger ob- served chronic interstitial nephritis in patients abusing analgesic mixtures, such as Saridon' and 'Kafe' (Refs 2 and 3). These studies were followed by reports during the 1960s from Germany, Denmark and other Scandinavian coun- tries showing a high incidence of chronic interstitial nephritis associated witl high intake of analgesics 2'3. The exact ;Lgents responsible for the development of anal- gesic nephropathy observed by Spiihler and Zollinger were not only phenacetin but also diethyl dioxotetrapyridine and isopropylantipyrine, but the pronounce- ment was made then that the principal causative agent was phenacetin L2. Later