**2. Objectives**

We have three objectives in writing this chapter. One, we shall draw upon the evidence from a thorough review of the published literature and from the detailed analyses of our own experience to argue for the existence of Van-AKI. Two, based on the insights deduced from these two sources, we will describe and characterize the typical picture of Van-AKI,

Vancomycin-Induced Nephrotoxicity 187

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.

**experience** 

A. Post-renal or obstructive nephropathy

(atrial fibrillation, bleeding, myocardial

C. Intra-renal insults (N=78 or 77% of all AKI).

**Objective 2: To describe and characterize the clinical and renal function profile for a typical Van-AKI, using lessons and insights from the reviewed literature and our own** 

To this end, we examined and tested the validity of the various independent risk factors proposed from the literature, namely serum vancomycin levels, total dose administered, and the duration of administration in our group of 6 patients. We attempted to generate insights from our own experience and that of the literature by doing the following statistical analyses. We first grouped their demographic data and clinical characteristics including hematologic data. We abstracted and tabulated the various parameters and indices of vancomycin therapy and longitudinal renal function, for each patient and also the entire group, using 100/serum creatinine as the estimate of creatinine clearance (CrCl) (Table 6). We analyzed their serial serum creatinine (and the associated CrCl) by calculating group means (and variance as standard errors), throughout the entire course of their AKI (Figure 7), starting from their initial baseline, to the days just before serum vancomycin reached its peak, through the days of peak vancomycin levels, then the days of peak serum creatinine,

 (N=4 or 4% of all AKI). B. Pre-renal (N=19 or 19% of all AKI)

ischemia, or hypotension).

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

 volume depletion, n=8; hemodynamic issues, n=11;

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