**Case 6:**

204 Basic Nephrology and Acute Kidney Injury

In the nursing home his vancomycin level was not monitored. On re-admission, the vancomycin level (77 mg/L) was found to be in toxic range. Vancomycin was thus discontinued. 5 days later serum creatinine was 6.6mg/dl and it continued to climb to a

peak level of 10.3 mg/dl on hospital day 7 (Fig 5A).

Fig. 5. B

Fig. 5. C

This patient was a 65 year old man hospitalized for hand osteomyelitis. He had a significant and complicated past and ongoing medical history due to uncontrolled type 2 diabetes mellitus, hypertension, hyperlipidemia, atrial fibrillation, previous stroke, degenerative joint disease of his left hip and knee, status-post knee replacement, gastroesophageal reflux disease, diabetic neuropathy, and a chronic but recently resolved MRSA diabetic left foot ulcer.

His present illness related to his left thumb pain that was initially treated with local steroid injections by his outside doctor. Subsequently, he had a draining ulcer at the first metacarpal joint of his left hand. Four days prior to his transfer from a local hospital to our medical center, MRI showed first metacarpal osteomyelitis and tendonitis. He was started on vancomycin, initially at a dose of 1.5 g every 18 hours three days before the transfer. On the 2nd hospital day with us, gram stain and culture from the left thumb wound showed MRSA. MRSA was also confirmed by intra-operative bone biopsy culture on the 3rd hospital day. Vancomycin was continued targeting 24-h trough levels ≥ 15 mg/L.

The patient was discharged on the 5th hospital day to complete a prolonged course of vancomycin at a dose of 1.5 g daily at the recommendation of ID consultants. Blood for vancomycin levels and basic metabolic profile was drawn and checked by home health nurse once weekly. After two weeks, his vancomycin dose was increased to 2.0 g daily. Four more weeks later, it was further raised to 2.5 g daily to keep level >15 mg/L (Fig 6C). Three weeks after the last dose increase, although the 24-h trough levels finally reached 17-19 mg/L (Fig 6C), his serum creatinine had also risen from 1.3 to 2.3 mg/dl (Fig 6 A). This represented a further hike from initial baseline of 0.8 at the start of vancomycin therapy.

Meloxicam, an NSAID, and lisinopril, which he had taken for years, were temporarily stopped, along with holding his vancomycin for 3 days. When his serum creatinine appeared to stop rising and seemed to stabilize at ~ 2.1 mg/dl, vancomycin was resumed albeit at a reduced dose of 1 g daily. This was however stopped completely due to the persistent elevation of his serum creatinine at 2 mg/dl (Fig 6A). By having excluded obstruction with renal ultrasound, pre-renal or hemodynamic factors, bacteremic or septic etiologies and other intra-renal insults, we believe his subacute decline in renal function (Fig

Vancomycin-Induced Nephrotoxicity 207

detection by most physicians if evaluated simply based on examining the absolute values at one point in time or judged by the modest rise in creatinine from ~ 0.8 to 1.3 mg/dl (Fig 6A), the latter typically attributed to pre-renal or volume-related issues. Only when serum creatinine exceeded the rather arbitrary upper limit of normal of 1.2 mg/dl and only when it remained elevated was the concern of AKI raised in this patient. This issue of renal failure had finally become unequivocal and unmistakable when the entire course was reviewed longitudinally. After 10 weeks of vancomycin exposure, there was a 3-fold elevation in his serum creatinine (0.8 to 2.2 mg/dl) (Fig 6A), or more dramatically though more meaningfully in clinical nephrology, a corresponding 60 % decrease in creatinine clearance

**Lessons learned and insights deduced from the published literature and our case** 

To generate a typical profile of patients suffering from Van-AKI, we attempted to generalize from the group of our six patients on whom we have a complete set of clinical and laboratory data. When the serial renal function data and vancomycin levels for all 6 patients were plotted as group means on the same figure as a function of the time of vancomycin treatment, a clinical profile of Van-AKI and its recovery become apparent (Fig 7). Table 6 summarizes the group data as mean ± SE on their demographic and hematologic data (Table 6A), serial renal function through the 60th and last day of follow-up (Table 6B), vancomycin dosages (cumulative and average daily dose), duration of treatment, and serial vancomycin levels (Table 6 C). The following statistical statements could thus be made, providingsome

1. For our cohort of 6 patients, the mean duration of vancomycin administration was 28.2 ± 12.7 [SE] days (Table 6 C). Our group of patients, with more delayed diagnosis and

Fig. 6. C

(from 125 to 50 ml/min). **Results on objective 2:** 

insights and lessons on the issue of Van-AKI.

**experience** 

6B), at least in retrospect, was best explained by the protracted vancomycin exposure with unmeasured peak levels which could have inflicted steady but sustained chronic damage.

Fig. 6. A

#### Fig. 6. B

The most informative was the marked drop in his creatinine clearance 2 weeks into vancomycin therapy (from ~ 125 to ~ 80 ml/min) (Fig 6B), which had easily escaped clinical

6B), at least in retrospect, was best explained by the protracted vancomycin exposure with unmeasured peak levels which could have inflicted steady but sustained chronic damage.

The most informative was the marked drop in his creatinine clearance 2 weeks into vancomycin therapy (from ~ 125 to ~ 80 ml/min) (Fig 6B), which had easily escaped clinical

Fig. 6. A

Fig. 6. B

#### Fig. 6. C

detection by most physicians if evaluated simply based on examining the absolute values at one point in time or judged by the modest rise in creatinine from ~ 0.8 to 1.3 mg/dl (Fig 6A), the latter typically attributed to pre-renal or volume-related issues. Only when serum creatinine exceeded the rather arbitrary upper limit of normal of 1.2 mg/dl and only when it remained elevated was the concern of AKI raised in this patient. This issue of renal failure had finally become unequivocal and unmistakable when the entire course was reviewed longitudinally. After 10 weeks of vancomycin exposure, there was a 3-fold elevation in his serum creatinine (0.8 to 2.2 mg/dl) (Fig 6A), or more dramatically though more meaningfully in clinical nephrology, a corresponding 60 % decrease in creatinine clearance (from 125 to 50 ml/min).
