Drug-induced Crystalline Nephropathy, Drug-induced Crystalluria, Infections Treated With Sulfamethoxazole, High Dose Ciprofloxacin or High Dose iv Amoxicillin
Conditions
Keywords
crystalluria, drug-induced acute kidney injury, drug-induced crystalline nephropathy, amoxicillin, sulfamethoxazole, ciprofloxacin
Brief summary
This study examines in hospitalized patients, treated with sulfamethoxazole, high dose ciprofloxacin or high dose iv amoxicillin, the incidence of drug-induced urinary crystal formation and its association with acute kidney injury development.
Detailed description
This is a prospective study which evaluates in hospitalized patients treated with sulfamethoxazole (po or iv), high dose ciprofloxacin (po or iv) or high dose iv amoxicillin, regardless the indication of the antibiotic treatment, the incidence of development of drug-induced urinary crystal formation. In addition, the association between development of AKI and the development of drug-induced crystalluria will be assessed for each of these antibiotics. Moreover, demographic, clinical and biochemical factors associated with the development of drug-induced crystalluria will be evaluated, as well as the timing of crystalluria development and potential AKI development. In eligible patients who have provided informed consent first voided morning urine samples will be evaluated for the presence of drug-induced crystals by crystalluria examination at predefined moments, depending on the specific antibiotic treatment (day 2, 4, 6, 8 and 11 after start of antibiotic treatment for amoxicillin treatment, day 3 and 7 after start of antibiotic treatment for ciprofloxacin treatment, day 3, 7 and 11 after start of antibiotic treatment for sulfamethoxazole treatment). Renal function determination by serum creatinine in case of amoxicillin and ciprofloxacin treatment and by serum creatinine and serum urea in case of sulfamethoxazole treatment will be performed at baseline and other predefined moments after the start of antibiotic treatment, depending on the specific antibiotic treatment ( day 1-3, 4-7, 8-11 and 12-14 after the start of antibiotic treatment for amoxicillin treatment, day 3-7 and 8-12 after the start of antibiotic treatment for ciprofloxacin treatment, day 1-4, 5-9, 10-14 after the start of antibiotic treatment for sulfamethoxazole treatment). Occurrence of acute kidney injury will be evaluated. Demographic, clinical and biochemical data will be collected from the electronic medical records, including data on demographics, medical history, medical treatment, data on the antibiotic treatment including dosing and biochemical parameters, including baseline renal function renal function (serum creatinine and eGFR (CKD-EPI), serum urea), CRP. Patients will remain included up to 14 days of antibiotic treatment or until discharge, whatever comes first.
Interventions
DIAGNOSTIC_TESTCrystalluria examination
Crystalluria examination
Sponsors
Universitair Ziekenhuis Brussel
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Able to give informed consent without the intervention of a legal representative * Treatment with * sulfamethoxazole/trimethoprim, with minimum dose of * ≥ 800/160 mg q12h oral administration (PO) or intravenous administration (IV) for eGFR ≥ 30 ml/min * ≥ 400/80 mg q12h OR or IV for eGFR \< 30 ml/min OR * high dose ciprofloxacin, defined as * ≥ 750 mg q12h PO or ≥ 400 mg q8h IV for eGFR ≥ 60 ml/min * ≥ 750 mg q24h PO or ≥ 400 mg q12h IV for eGFR 15-59 m/min * ≥ 750 mg q24h PO OR ≥ 400 mg q24h IV for eGFR \< 15 ml/min OR * high dose amoxicillin, defined as * ≥ 2g q6h IV for eGFR ≥ 30 ml/min * ≥ 2g q8h IV for eGFR 15-29 ml/min * ≥ 2g q12h IV for eGFR \< 15 ml/min * Treatment for min 24 hours and sufficiently long to perform one crystalluria investigation as defined in the protocol * Baseline renal function up to 72 hours prior to the start of antibiotic treatment available (evaluated by serum creatinine and eGFR (CKD-EPI)) for all study groups and additional serum urea for the sulfamethoxazole group).
Exclusion criteria
* Unable to give informed consent without the intervention of a legal representative * No baseline renal function up to 72 hours prior to the start of antibiotic treatment available, evaluated by serum creatinine and eGFR (CKD-EPI)) for all study groups and additional serum urea for the sulfamethoxazole group. * Treatment duration \< 24 hours or insufficiently long to perform one crystalluria inves-tigation as defined in the protocol * Patients treated with hemodialysis or peritoneal dialysis, anuric patients before start of antibiotic treatment * Patients with urinary diversions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of drug-induced crystalluria in patients treated with sulfamethoxazole | Up to 11 days after start of treatment | The presence of sulfamethoxazole-induced crystalluria will be evaluated by microscopic crystalluria examination in first voided morning urine samples on day 3, 7 and 11 after start of treatment and will be reported as a dichotomous parameter (present/absent). |
| Incidence of drug-induced crystalluria in patients treated with high dose ciprofloxacin | Up to day 7 after start of treatment | The presence of ciprofloxacin-induced crystalluria will be evaluated by microscopic cyrstalluria examination in first voided morning urine samples on day 3 and 7 after start of treatment and will be reported as a dichotomous parameter (present/absent). |
| Incidence of drug-induced crystalluria in patients treated with high dose iv amoxicillin | Up to 11 days after start of treatment | The presence of amoxicillin-induced crystalluria will be evaluated by microscopic cyrstalluria examination in first voided morning urine samples on day 2, 4, 6, 8 and 11 after start of treatment and will be reported as a dichotomous parameter (present/absent). |
| Incidence of AKI in patients treated with high dose iv amoxicillin | Up to 14 days after start of treatment | Acute kidney injury is defined as an increase in serum creatinine by ≥ 0.3 mg/dl within 48 hours or ≥ 1.5 times baseline within the prior 7 days. The occurrence of acute kidney injury will be performed by calculating the difference between serum creatinine at baseline and during antibiotic treatment at 4 different moments after start of antibiotic treatment, namely day 1-3, day 4-7, day 8-11 and day 12-14. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of AKI in patients treated with sulfamethoxazole | Up to 14 days after start of treatment | Acute kidney injury is defined as an increase in serum creatinine by ≥ 0.3 mg/dl within 48 hours or ≥ 1.5 times baseline in association with a concomitant rise of serum urea of 22 mg/dl within 48 hours or ≥ 1.5 times base-line within the prior 7 days. The occurrence of acute kidney injury will be performed by calculating the difference between serum creatinine and serum urea at baseline and during antibiotic treatment at 3 different moments after start of antibiotic treatment, namely day 1-4, day 5-9, day 8-11 and day 10-14. |
| Incidence of AKI in patients treated with high dose ciprofloxacin | Up to 12 days after start of treatment | Acute kidney injury is defined as an increase in serum creatinine by ≥ 0.3 mg/dl within 48 hours or ≥ 1.5 times baseline within the prior 7 days. The occurrence of acute kidney injury will be performed by calculating the difference between serum creatinine at baseline and during antibiotic treatment at 2 different moments after start of antibiotic treatment, namely day 3-7 and day 8-12. By this we will evaluated if the occurrence of ciprofloxacin-induced crystalluria is associated with an increased risk of incident AKI development in patients treated with high dose ciprofloxacin. |
| Identification of demographic, clinical and biochemical factors associated with the development of drug-induced crystalluria | Up to 11 days after start of treatment for sulfamethoxazole, up to 7 days after start of treatment for ciprofloxacin, up to 11 days after start of treatment for high dose iv amoxicillin | Identification of demographic, clinical and biochemical factors associated with the development of drug-induced crystalluria by means of repeated measures logistic regression modelling |
| Time interval between start of antibiotic treatment and development of sulfamethoxazole, ciprofloxacin and amoxicillin crystalluria | up to 11 days after start of treatment for sulfamethoxazole, up to 7 days after start of treatment for ciprofloxacin, up to 11 days after start of treatment for high dose iv amoxicillin | — |
| Time interval between development of drug-induced crystalluria and development of AKI for each antibiotic | up to 14 days after start of treatment for sulfamethoxazole and high dose iv amoxicillin, up to 12 days after start of treatment for ciprofloxacin | — |
| Premature dose reduction of antibiotic or premature stopping of antibiotic treatment for each antibiotic | Up to 14 days of treatment | — |
| Evolution of drug-induced crystalluria over time for each antibiotic | Up to 11 days after start of treatment for sulfamethoxazole and high dose iv amoxicillin and up to 7 days after start of treatment for ciprofloxacin | The evolution of drug-induced crystalluria (resolution, persistance) will be evaluated in a descriptive manner |
Countries
Belgium
Contacts
CONTACTEls Van de Perre, MD
Outcome results
None listed