**Objective 1: To better document and more firmly establish the existence of Van-AKI**

We approached this objective in two ways. First, we performed a systematic search and a careful review of the existing literature (Tables 1 & 2) using Pub-Med, Web of Science, Medline (OVID), Journal Citation Reports (ISI), Cochrane Database of Systematic Reviews, and Current Contents. Secondary references cited from these primary sources were also considered and reviewed with a focus on the published evidence in support of or against the entity of vancomycin nephrotoxicity. Search terms included acute renal failure (ARF), AKI, acute tubular necrosis, nephrotoxicity, renal insufficiency, renal failure, elevated creatinine, decline or deterioration in renal function or glomerular filtration rate or creatinine clearance, all cross-referenced with vancomycin. All studies with sufficient details on methods that are amendable to critical reviews were considered and only those with conclusions supported by the presented data or results were then included in Tables 1 & 2.

Second, we carefully and objectively analyzed the data from 101 consecutive patients evaluated for ARF (from among a total of 153 cases referred for renal consultation in the course of the month of services (Table 3). The renal consultative service was provided to adult patients admitted to the Hospitals of the University of Oklahoma Health Sciences Center (OUHSC) with a 450-bed capacity for acute or tertiary care. After excluding prerenal and post-renal causes for ARF using the traditional or conventional clinical criteria and renal ultrasound, we found intra-renal insults in 78 patients from among the 101 with ARF (Table 4). Additional diagnostic studies and analyses of the clinical presentation and subsequent course allowed us to assign an etiologic factor accounting for the intra-renal ARF (Table 5). We have identified 6 patients with ARF with clinical and laboratory data and subsequent recovery course that unequivocally support the causal role of vancomycin in the AKI.


Table 3. Indications for Renal Consultations (analysis of the 153 cases seen over a month)

In analyzing the potential etiologies of their AKI, we have vigorously ruled out sepsis, bacteremia, urinary tract obstruction, volume depletion, and any conceivable concomitant nephrotoxic antibiotics or intra-renal or intrinsic insults so that we could convincingly pin down vancomycin as the principal culprit. Based on serial drug levels, daily and

the renal functional profile in the evolution of the ARF and the recovery. We will also outline the lessons that could be learned for safer but equally effective administration of vancomycin. Three, we will recommend some simple practical guidelines designed to

**Objective 1: To better document and more firmly establish the existence of Van-AKI** 

We approached this objective in two ways. First, we performed a systematic search and a careful review of the existing literature (Tables 1 & 2) using Pub-Med, Web of Science, Medline (OVID), Journal Citation Reports (ISI), Cochrane Database of Systematic Reviews, and Current Contents. Secondary references cited from these primary sources were also considered and reviewed with a focus on the published evidence in support of or against the entity of vancomycin nephrotoxicity. Search terms included acute renal failure (ARF), AKI, acute tubular necrosis, nephrotoxicity, renal insufficiency, renal failure, elevated creatinine, decline or deterioration in renal function or glomerular filtration rate or creatinine clearance, all cross-referenced with vancomycin. All studies with sufficient details on methods that are amendable to critical reviews were considered and only those with conclusions supported by the presented data or results were then included

Second, we carefully and objectively analyzed the data from 101 consecutive patients evaluated for ARF (from among a total of 153 cases referred for renal consultation in the course of the month of services (Table 3). The renal consultative service was provided to adult patients admitted to the Hospitals of the University of Oklahoma Health Sciences Center (OUHSC) with a 450-bed capacity for acute or tertiary care. After excluding prerenal and post-renal causes for ARF using the traditional or conventional clinical criteria and renal ultrasound, we found intra-renal insults in 78 patients from among the 101 with ARF (Table 4). Additional diagnostic studies and analyses of the clinical presentation and subsequent course allowed us to assign an etiologic factor accounting for the intra-renal ARF (Table 5). We have identified 6 patients with ARF with clinical and laboratory data and subsequent recovery course that unequivocally support the causal role of vancomycin

1. Inter- or concurrent issues in patients with known end-stage renal diseases (N=41). 2. Issues unrelated to acute kidney injury (AKI), acute renal failure (ARF) or chronic

Table 3. Indications for Renal Consultations (analysis of the 153 cases seen over a month)

In analyzing the potential etiologies of their AKI, we have vigorously ruled out sepsis, bacteremia, urinary tract obstruction, volume depletion, and any conceivable concomitant nephrotoxic antibiotics or intra-renal or intrinsic insults so that we could convincingly pin down vancomycin as the principal culprit. Based on serial drug levels, daily and

prevent and/or ameliorate the emergence of Van-AKI.

**3. Methods** 

in Tables 1 & 2.

in the AKI.

kidney diseases (N=11).

3. AKI or ARF (N=101).

 electrolytes disorders n=4 transplantation issues n=2 fluid management n=4 drug overdose n=1 cumulative administered doses, the temporal relationship between drug administration and changing renal function, the profile of renal failure, and the course of recovery upon stopping vancomycin, we believe other confounding variables could be excluded with a high degree of certainty. As opposed to the previous era when vancomycin was typically and invariably administered to patients along with an aminoglycoside or amphotericin B (typically for overt or presumed sepsis, bacteremia, or neutropenic fever), the recent practice of treating HCAP with triple antibiotics consisting of vancomycin but no other known nephrotoxins has provided a unique opportunity to witness and document AKI in the absence of other nephrotoxic insults. The absence of bacteremia or sepsis also helps eliminate a key confounding variable that previously precluded isolation of vancomycin as the culprit. Similarly, with the heightened detection and increased diagnosis of osteomyelitis by CT or MRI, more and more patients have been treated with long-term antibiotic regimen composed of vancomycin but not aminoglycoside. Since these patients are relatively asymptomatic and generally free of bacteremia on pre-treatment blood cultures, their subsequent development of AKI could reasonably be attributed to the adverse effects of antibiotics like vancomycin. Thus these two groups of patients (vancomycin-treated HCAP or osteomyelitis of undefined pathogens) have unwittingly provided a wonderful chance for clinicians to document the diagnosis of Van-AKI, an entity which had previously been questioned and debated because of the presence of other potential but unexcluded nephrotoxic insults.


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Table 4. Acute Kidney Injury (AKI) or Acute Renal Failure (ARF) (N=101)
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