Ciprofloxacin-Induced Granulomatous Interstitial Nephritis and Localized Elastolysis

doi:10.1016/S0272-6386(12)80936-X

American Journal of Kidney Diseases

Volume 22, Issue 4, October 1993, Pages 598-602

https://doi.org/10.1016/S0272-6386(12)80936-X Get rights and content

Ciprofloxacin is known to cause acute interstitial nephritis. We report the first case of ciprofloxacin-induced granulomatous interstitial nephritis and localized elastolysis. The patient presented with acute renal failure and skin lesions following a 14-day course of ciprofloxacin administered for cellulitis. The patient had symmetric, palm-sized, tender violaceous plaques on both axillae. The renal biopsy revealed granulomatous interstitial disease. A skin biopsy revealed an elastolytic process with histocytic infiltration and calcification. After discontinuing ciprofloxacin and starting a short course of steroid therapy, the skin lesion and renal function improved promptly. The nephritis relapsed after prednisone was discontinued and responded to a second course of steroid therapy. Ciprofloxacin, like penicillin, can cause granulomatous interstitial nephritis and elastolysis. A prolonged course of steroid therapy may be indicated in patients with ciprofloxacin-induced granulomatous interstitial nephritis to avoid early relapse.

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Cited by (36)

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The mechanism of quinolone antibiotics is generally considered to be that quinolones interact with bacterial DNA gyrase, inhibiting DNA synthesis and replication and leading to bacterial death. Unfortunately, the overdose of CIP can lead to many side effects, such as central nervous system disorders [25], cholestatic jaundice [26], hepatotoxicity [27–29], interstitial nephritis [30] and eosinophilia [31]. Delightfully, the β-diketone moiety in CIP can sensitive the lanthanide ions through the antenna effect [32,33], in which process the energy absorbed by CIP under excitation can be transferred to Ln3+.
Lanthanide-functionalized porous organic materials have been the promising candidates in the chemical and biological sensing. Considering the superior thermal and solvent stability of covalent organic frameworks (COFs), the development of lanthanide ions-functionalized COFs based sensing platform is meaningful, while remains to be a challenge. In this work, a new imine-linked COF which provides suitable coordination sites for Tb³⁺ was constructed via the Schiff base reaction between P-phenylenediamine (Pda) and 2,6-Diformylpyridine (Dfp). Benefiting from its high signal-to-noise, the COF@Tb shows excellent ability to determinate ciprofloxacin (CIP) with a detection limit of 3.01 nM. The measurement can maintain good stability in the presence of potential interference or in actual sample. Being washed with ethanol after each measurement, COF@Tb can be recycled for five times. This work provides a novel alternative strategy for efficient construction of lanthanide-grafted COFs and may promote the development of porous organic materials based chemical sensing.
Metal organic framework based fluorescence sensor for detection of antibiotics
2021, Trends in Food Science and Technology
Citation Excerpt :
However, they are often stable and not fully metabolized in the body (Kümmerer, Al-Ahmad, & Mersch-Sundermann, 2000; Vasconcelos, Henriques, König, Martins, & Kümmerer, 2009). It should be noted that high levels of CIP can lead to serious side effects such as eosinophilia (Mösges, Nematian-Samani, & Eichel, 2011), interstitial nephritis (Lien et al., 1993), central nervous system disorders (Gui, Bu, He, & Jin, 2018), cholestasis jaundice (Labowitz & Silverman, 1997) and hepatotoxicity (Jalal, Madrakian, Afkhami, & Ghamsari, 2019). In addition, antibiotic residues can be harmful to the environment and lead to undesirable biological processes, including decoding genetic information, protein synthesis (Pioletti, Schlünzen, Harms, Zarivach, Glühmann, Avila, et al., 2001), anaphylactic reactions, and the risk of certain infections such as endocrine disorders (Daghrir & Drogui, 2013; Ramezani, Danesh, Lavaee, Abnous, & Taghdisi, 2015).
Metal-Organic Frameworks (MOFs) are multidimensional coordination polymeric materials formed by coordinating half-filled d-/f-block metal ions with mono-/multi-dentate organic ligands. Due to their structural flexibility, porosity, adsorption sites and controllable synthesis have gained significant attention in gas storage, chemical sensing, heterogeneous catalysis and biological applications. The individual metal ion-ligand interaction mechanisms observed in coordination complexes of d-/f-block metal ions like Metal Centered (MC), Ligand-to-Metal Charge Transfer (LMCT) and Metal-to-Ligand Charge Transfer (MLCT) are also applicable to these coordination polymers and, that makes them more interesting in their applications.
MOFs are very promising for fabricating fluorescent or luminescent sensors because the fluorescence can be generated from the metal and the ligand units and can also be tuned by the interplay/interactions among the building components. The energy is transferred through a fluorescence resonance energy transfer (FRET) mechanism that is important for applying MOFs for antibiotic detection. The excess dosage of antibiotics is transmitted to the environment and the human body resulting in a serious threat to mankind. The frequently used conventional methods for the analysis of antibiotics residue, especially detection in clinical, environment and food products, biological complex matrices are time-consuming, non-specific, poor sensitivity, complex and requires skilled personnel. Immunologic and high-performance liquid chromatography (HPLC) based methods are expensive, lack specificity, and yield false results.
As outlined in this review, MOFs based fluorescent sensors have now become effective alternative tools for rapid and routine detection for clinical and environmental analysis, as well as for food safety control. We provide an overview regarding the uses of MOFs based materials sensors in the development of fluorescence with special emphasis on underlying detection principles, sensitivity, specificity, and their capability of multiplexed analysis. The diverse MOFs based materials are used for antibiotics detection, which is critically analyzed concerning their advantages and limitations for future applications in the diagnosis of antibiotics in the environment.
A turn-on fluorescence probe Eu<sup>3+</sup> functionalized Ga-MOF integrated with logic gate operation for detecting ppm-level ciprofloxacin (CIP) in urine
2020, Talanta
Citation Excerpt :
As the result of bacteriological terrorists’ attack threats lately, CIP significance increased as specific drug in Bacillus anthracis infection treatment [13]. However, it is worth noting that an overdose of CIP can have severe side effects such as hepatotoxicity [14–16], central nervous system disorders [17], interstitial nephritis [18], cholestatic jaundice [19] and eosinophilia [20]. Up to now, several efforts have been undertaken to efficiently determine the CIP, containing high performance liquid chromatography (HPLC) [21–23], capillary electrophoresis (CE) [24–27], spectrophotometry [28]，liquid chromatography–tandem mass spectrometry (LC-MS/MS) [29,30].
The threatening of antibiotic drugs for human and environment is being paid more and more attention. Ciprofloxacin (CIP), a strong quinolone antibiotic drug widely used in therapeutic treatments, is the most frequently detected in surface waters among the fluoroquinolones, which represents animal and human health risks. A novel highly fluorescent Ga-based hybrid (Eu³⁺@1) has been synthesized based on metal-organic framework (MOF) by encapsulating lanthanide cations Eu³⁺ in its channels. The as-synthesized compound possesses excellent water and pH-independent stability. It displays week red luminescence of Eu³⁺ in itself and can sense the CIP concentration as turn-on fluorescent probe in the human urine. With addition of CIP, the evident luminescence enhancement is clearly observed from the Eu³⁺@1. Linear correlation between the fluorescence intensity and the concentration of CIP is investigated, proving the excellent performance of Eu³⁺@1 in the detection of CIP with linear range (0.01–0.2 mg/mL) and low detection limit (2.4 ppm or 2.4 μg/mL). The response time is also very quick, less than 3 min. Based on these findings, we introduce AND logic gate strategy to the probe. The input of the logic gates (0, 1), (0, 1, 1), (1, 1, 1) cause the different outputs of CIP determination “LOW” (<25 ppm),“NORMAL” (25–76 ppm), “HIGH” (>76 ppm), respectively. The novel strategy can be applied for a real-time CIP concentration evaluation by intelligent discrimination.
Clinical Manifestations and Outcomes of Fluoroquinolone-Related Acute Interstitial Nephritis
2018, Mayo Clinic Proceedings
Citation Excerpt :
This represented 10% of all biopsy-proven AIN cases during this time period at our institution. Another 22 patients with biopsy-proven FQ-related AIN were identified from the literature search from January 1, 1987, to December 31, 2016.8-10,12,18-31 Clinical characteristics and outcomes of these patients are summarized in the Table. (
To describe the clinical presentation, diagnosis, and outcomes of patients with biopsy-proven acute interstitial nephritis (AIN) related to fluoroquinolone (FQ) therapy.
We conducted a retrospective review of biopsy-proven AIN attributed to FQ use at Mayo Clinic's campus in Rochester, Minnesota, from January 1, 1993, through December 31, 2016. Cases were reviewed by a renal pathologist and attributed to FQ use by an expert nephrologist. We also reviewed and summarized all published case reports of biopsy-proven AIN that were attributed to FQ use.
We identified 24 patients with FQ-related biopsy-proven AIN at our institution. The most commonly prescribed FQ was ciprofloxacin in 17 patients (71%), and the median antibiotic treatment duration was 7 days (interquartile range [IQR], 5-12 days). The median time from the initiation of FQ to the diagnosis of AIN was 8.5 days (IQR, 3.75-20.75 days). Common clinical manifestations included fever (12; 50%), skin rash (5; 21%), and flank pain (2; 8%), and 9 (38%) had peripheral eosinophilia. However, 4 (17%) of the patients were asymptomatic at the time of diagnosis and AIN was suspected on the basis of routine laboratory monitoring. Most patients (17; 71%) recovered after the discontinuation of antibiotic therapy, and renal function returned to baseline at a median of 20.5 days (IQR, 11.75-27.25 days). Six patients (25%) required temporary hemodialysis, and 14 patients (58%) received corticosteroid therapy.
The onset of FQ-related AIN can be delayed, and a high index of suspicion is needed by physicians evaluating these patients. Overall outcomes are favorable, with recovery to baseline renal function within 3 weeks of discontinuing the offending drug.
Histopathologic review of granulomatous inflammation
2017, Journal of Clinical Tuberculosis and Other Mycobacterial Diseases
Granulomatous inflammation is a histologic pattern of tissue reaction which appears following cell injury. Granulomatous inflammation is caused by a variety of conditions including infection, autoimmune, toxic, allergic, drug, and neoplastic conditions. The tissue reaction pattern narrows the pathologic and clinical differential diagnosis and subsequent clinical management. Common reaction patterns include necrotizing granulomas, non necrotizing granulomas, suppurative granulomas, diffuse granulomatous inflammation, and foreign body giant cell reaction. Prototypical examples of necrotizing granulomas are seen with mycobacterial infections and non-necrotizing granulomas with sarcoidosis. However, broad differential diagnoses exist within each category. Using a pattern based algorithmic approach, identification of the etiology becomes apparent when taken with clinical context.
The pulmonary system is one of the most commonly affected sites to encounter granulomatous inflammation. Infectious causes of granuloma are most prevalent with mycobacteria and dimorphic fungi leading the differential diagnoses. Unlike the lung, skin can be affected by several routes, including direct inoculation, endogenous sources, and hematogenous spread. This broad basis of involvement introduces a variety of infectious agents, which can present as necrotizing or non-necrotizing granulomatous inflammation. Non-infectious etiologies require a thorough clinicopathologic review to narrow the scope of the pathogenesis which include: foreign body reaction, autoimmune, neoplastic, and drug related etiologies. Granulomatous inflammation of the kidney, often referred to as granulomatous interstitial nephritis (GIN) is unlike organ systems such as the skin or lungs. The differential diagnosis of GIN is more frequently due to drugs and sarcoidosis as compared to infections (fungal and mycobacterial).
Herein we discuss the pathogenesis and histologic patterns seen in a variety of organ systems and clinical conditions.
Granulomatous interstitial nephritis: A retrospective study of 44 cases
2010, Revue de Medecine Interne
Les granulomatoses rénales (GR) sont des maladies rares dont la fréquence est estimée entre 0,5 à 1,3 % des ponctions biopsies rénales (PBR) réalisées. Les GR restent peu étudiées dans la littérature et les modalités thérapeutiques et évolutives sont mal connues.
Nous avons analysé 44 observations de GR identifiées sur l’ensemble des PBR réalisées entre 1984 et 2005 dans la région Rhône-Alpes.
Notre population était composée de 25 hommes et 19 femmes. L’âge moyen au diagnostic était de 56 ans. Le délai diagnostic moyen était de 11 mois. L’insuffisance rénale était sévère avec une clairance de la créatinine moyenne de 24 mL/min, associée à une protéinurie dans 77 % des cas (taux moyen de 0,9 g/24 heures), et à une hématurie microscopique et une leucocyturie aseptique chez respectivement 30 et 25 % des patients. La sarcoïdose était la principale étiologie, dans 25 % des cas (n = 11), suivie par l’origine immunoallergique (9 %, n = 4), la tuberculose (6,8 %, n = 3), les hémopathies (6,8 %, n = 3), l’infection par le virus de l’immunodéficience humaine (n = 1) et le rejet chronique chez un transplanté rénal (n = 1). La GR était qualifiée d’idiopathique dans 48 % des cas (n = 21). La sévérité de l’atteinte rénale expliquait le recours fréquent à l’épuration extra rénale (34 %, n = 15). Trois patients ont justifié une greffe rénale. L’évolution était cependant plutôt favorable : la fonction rénale s’est finalement améliorée dans 41 % (n = 18) et stabilisée dans 34 % des cas (n = 15).
La sarcoïdose, les causes médicamenteuses et infectieuses sont les causes les plus fréquentes de GR. L’enquête diagnostique est compliquée par l’absence de données histologiques pathognomoniques sur la PBR. La corticothérapie est le traitement de référence des GR sarcoïdosiques, immunoallergiques et idiopathiques. Autant que possible, le traitement est étiologique.
Granulomatous interstitial nephritis (GIN) are identified in 0.5 to 1,3% of all renal biopsies. Renal outcome and treatment modalities are not clearly established in the literature.
We retrospectively analyzed a case series of 44 GIN identified among all renal biopsies performed between 1984 and 2005 in the Rhône-Alpes area.
The study population included 25 men and 19 women with a mean age of 56 years, and mean diagnostic delay was 11 months. Renal function was severely impaired (mean creatinine clearance 24 mL/min). Proteinuria was observed in 77% (mean value 0,9 g/24 h) of the patients and associated with microscopic hematuria and leukocyturia in 30% and 25%, respectively. The most common diagnosis was sarcoidosis (25%, n = 11), followed by drug-induced GIN (9%, n = 4), tuberculosis (6,8%, n=3), hemopathy-related paraneoplastic GIN (6,8%, n = 3), HIV infection (n = 1) and chronic renal allograft rejection (n = 1). In other patients, no aetiology was found (48%, n = 21). Severity of renal failure justified hemodialysis in 34% (n = 15) of the patients. Three patients underwent renal transplantation. Nonetheless, renal outcome was generally favorable: renal function improved in 41% (n = 18) and stabilized in 34% (n = 15) of patients.
Sarcoidosis, drug-induced and infections represent the main causes of GIN. Histologic features are not specific enough to determine the aetiology. Corticosteroids is the gold standard in sarcoidosis, drug-induced, and idiopathic GIN. Treatment is etiologic in the other cases.

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View full text

Ciprofloxacin-Induced Granulomatous Interstitial Nephritis and Localized Elastolysis

Hum Pathol

Ciprofloxacin: An update on clinical experience

Am J Med

Ciprofloxacin and allergic interstitial nephritis

Ann Intern Med

Ciprofloxacin-induced interstitial nephritis

Clin Pharm

Acute renal failure due to Ciprofloxacin

Arch Intern Med

111, Daly JS: Acute renal failure after an overdose of Ciprofloxacin

Arch Intern Med

Alteration in elastic fibers