Fluid administration strategies for the prevention of contrast-associated acute kidney injury.

PURPOSE OF REVIEW: The known timing of contrast media exposure in patients identified as high-risk for contrast-associated acute kidney injury (CA-AKI) enables the use of strategies to prevent this complication of intravascular contrast media exposure. Although multiple preventive strategies have been proposed, periprocedural fluid administration remains as the primary preventive strategy. This is a critical review of the current evidence evaluating a variety of fluid administration strategies in CA-AKI. RECENT FINDINGS: Fluid administration strategies to prevent CA-AKI include comparisons of intravenous (i.v.) to no fluid administration, different fluid solutions, duration of fluid administration, oral hydration, left ventricular end diastolic-pressure guided fluid administration and forced diuresis techniques. SUMMARY: Despite an abundance of fluid administration trials, it is difficult to make definitive recommendations about preventive fluid administration strategies due to low scientific quality of published studies. The literature supports use of i.v. compared with no fluid administration, especially in high-risk patients undergoing intra-arterial contrast media exposure. Use of isotonic saline is recommended over 0.45% saline or isotonic sodium bicarbonate. Logistical considerations support shortened over longer i.v. fluid administration strategies, despite an absence of evidence of equivalent efficacy. Current literature does not support oral hydration for high-risk patients. The use of tailored fluid administration in heart failure patients and forced diuresis with matching fluid administration are promising new fluid administration strategies.

Risks and Options With Gadolinium-Based Contrast Agents in Patients With CKD: A Review.

Gadolinium-based contrast agents (GBCAs) improve the diagnostic capabilities of magnetic resonance imaging. Although initially believed to be without major adverse effects, GBCA use in patients with severe chronic kidney disease (CKD) was demonstrated to cause nephrogenic systemic fibrosis (NSF). Restrictive policies of GBCA use in CKD and selective use of GBCAs that bind free gadolinium more strongly have resulted in the virtual elimination of NSF cases. Contemporary studies of the use of GBCAs with high binding affinity for free gadolinium in severe CKD demonstrate an absence of NSF. Despite these observations and the limitations of contemporary studies, physicians remain concerned about GBCA use in severe CKD. Concerns of GBCA use in severe CKD are magnified by recent observations demonstrating gadolinium deposition in brain and a possible systemic syndrome attributed to GBCAs. Radiologic advances have resulted in several new imaging modalities that can be used in the severe CKD population and that do not require GBCA administration. In this article, we critically review GBCA use in patients with severe CKD and provide recommendations regarding GBCA use in this population.

Finding a common language for patient safety in CKD.

Improving patient safety has become a primary objective of health systems; however, the frequency of adverse safety events continues to be unacceptable despite the attention and dedicated efforts of many stakeholders. CKD that does not require dialysis increases the risk for adverse safety events, and adverse safety events can account for a substantial portion of the poor outcomes typical of CKD. Because much of CKD care occurs outside the typical health care setting, systems designed to detect and reduce adverse safety events are not necessarily effective in this population. Underrecognition (or underappreciation) of CKD and the associated impairment of renal function contribute to the high risk for adverse safety events. Medication errors are common in CKD and account for many lapses in patient safety, but a wide range of other potentially modifiable care processes in CKD also contribute to the high rate of observed adverse safety events. This review describes the spectrum of safety concerns specific to CKD and the need for a common set of standards to improve on current general constructs and to reduce adverse safety events in this chronic disease. An accepted set of disease-specific indicators is necessary to gauge the extent of the disease-specific patient safety problem and to design means to reduce adverse safety events and improve outcomes in CKD.

Acute kidney injury due to pulmonary embolism: the case for 'congestive renal failure'.

The development of acute kidney injury in patients with pulmonary embolism (PE) has not been well documented. We report a patient who developed acute oliguria in the setting of massive PE. Catheter embolectomy followed by ultrafiltration resulted in an immediate and dramatic improvement in urine output. Uncharacteristically, serum creatinine did not rise during the oliguric phase for several days until after embolectomy, and there were no metabolic derangements. Our observation that embolectomy and ultrafiltration helped with hemodynamics and renal perfusion despite decreased cardiac output suggests that right ventricular failure from both pressure and volume overload may have been central to this process. We review the older and recent literature in support of our observations.

Obesity and obesity-initiated metabolic syndrome: mechanistic links to chronic kidney disease.

There is an epidemic of obesity and the metabolic syndrome in the United States and across the world. Both entities are associated with high mortality, mainly as a result of cardiovascular disease. The epidemic of obesity has been paralleled by an increase in the incidence of chronic kidney disease (CKD). Several recent epidemiologic studies have shown that obesity and the metabolic syndrome are independent predictors of CKD. In addition to diabetes and hypertension, several other mechanisms have been postulated to initiate and maintain kidney injury in patients with obesity and the metabolic syndrome. This article reviews the recent epidemiologic data linking obesity and the metabolic syndrome to CKD and summarizes the potential mechanisms of renal injury in this setting, with a focus on the role of inflammation, lipotoxicity, and hemodynamic factors. Potential preventive and therapeutic modalities based on the limited evidence available are discussed.

Administration of tobramycin in the beginning of the hemodialysis session: a novel intradialytic dosing regimen.

BACKGROUND: Aminoglycoside antibiotic efficacy is related to peak concentration (C(max)) and postantibiotic effect, whereas toxicity is directly related to body exposure as measured by area under the serum concentration versus time curve (AUC). On the basis of pharmacokinetic simulation models, tobramycin administration during the first 30 min of high-flux hemodialysis achieves similar C(max) but significantly lower AUC and prehemodialysis concentrations compared with conventional dosing in the last 30 min of hemodialysis. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: To test this hypothesis, a pilot study in which five adult chronic hemodialysis patients who were undergoing high-flux dialysis received one dose of tobramycin 1.5 mg/kg intravenously during the first or last 30 min of hemodialysis was conducted. After a 1-mo washout period, patients crossed over to the other treatment schedule. Tobramycin serum concentrations were measured to determine C(max), interdialytic and intradialytic elimination rate constants and half-lives, AUC, and clearance. RESULTS: Tobramycin administration during the first and last 30 min of hemodialysis resulted in similar C(max) of 5.63 +/- 0.49 and 5.83 +/- 0.67 mg/L (P > 0.05) but significantly lower prehemodialysis concentrations of 0.16 +/- 0.09 and 2.44 +/- 0.43 mg/L (P < 0.001) and AUC of 21.06 and 179.23 +/- 25.84 mg/h per L (P < 0.001), respectively. CONCLUSIONS: Tobramycin administration during the first 30 min of hemodialysis results in similar C(max) but lower AUC to conventional dosing, which may translate into comparable efficacy but lower toxicity.

Expression of apoptosis-related genes in chronic cyclosporine nephrotoxicity in mice.

To define the mechanism of cyclosporine (CsA)-induced apoptosis, we investigated the expression of apoptosis-related genes in experimental chronic CsA nephrotoxicity. Mice on a low-salt (0.01%) diet were given vehicle (VH, olive oil, 1 mg/kg/day), or CsA (30 mg/kg/day), and sacrificed at 1 and 4 weeks. Apoptosis was detected with deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) stain, and the expressions of apoptosis-related genes were evaluated by reverse transcription-polymerase chain reaction, immunoblot or immunohistochemistry. The activity of caspase 1 and 3 was also evaluated. The CsA group showed increases in apoptotic cells compared with the VH group (54 +/- 41 vs. 3 +/- 3, p < 0.05), and the number of apoptotic cells correlated well with interstitial fibrosis scores (r = 0.83, p < 0.01). The CsA group showed a significant increase in Fas-ligand mRNA (0.20 vs. 0.02 amol/microgram total RNA, p < 0.05) and Fas protein expression (146% vs. 95%, p < 0.05), compared with the VH group. The CsA group showed significant increases in ICE mRNA (0.21 vs. 0.03 amol/microgram total RNA at 4 weeks, p < 0.05) and CPP32 mRNA (0.18 vs. 0.03 amol/microgram total RNA at 4 weeks, p < 0.05), compared with the VH group. The enzymatic activity of ICE (16.6 vs. 7.9 rho mol/microgram/h, p < 0.05) and CPP32 protease (15.6 vs. 2.7 rho mol/microgram/h, p < 0.05) proteases were increased in the CsA group, compared with the VH group. The ratio between bax and bcl-2 protein increased significantly in the CsA group (5.3-fold), compared with the VH group. Levels of p53 protein also increased in the CsA group. Immunohistochemical detection of Fas, Fas-ligand, ICE and CPP32 revealed strong immunoreactivity in renal tubular cells in areas of structural injury. These findings suggest that local activation of the apoptosis-related genes is associated with CsA-induced apoptotic cell death.