|
AFMR - Biomarkers of acute kidney injury- early diagnosis, pathogenesis and recovery
Back to Experimental Biology 2007
Title of symposium presentation: Biomarkers of acute kidney injury- early diagnosis, pathogenesis and recovery
Organizer Name: Chirag Parikh, MD, PhD
Institution: Yale University and VAMC
Address: 950 Campbell Ave, Mail Code 151B, West Haven –CT- 06492
Abstract:
Tremendous progress has been made in our understanding of the molecular mechanisms of renal diseases such as acute kidney injury (AKI). However, a translation of these findings to diagnostics and therapeutics used in clinical practice remains challenging. Despite significant technical advances in therapeutics, the mortality and morbidity rates associated with AKI remain dismally high and have not appreciably improved during the last four decades. The lack of significant progress in the prevention and management of AKI has been attributed, in part, to the failure to identify suitable physiologic surrogate endpoints for use in research studies testing the efficacy of new interventions. For example, the standardized use of serum cardiac enzyme concentrations and electrocardiographic criteria has facilitated rapid progress in the management of coronary insufficiency, markedly decreasing the morbidity and mortality of acute myocardial infarction. By contrast, AKI prevention and therapy studies using variables such as urine output and serum and urine chemistries have not yielded interventions proven to decrease the morbidity (requirement for dialysis) and mortality. In fact, very few AKI studies have demonstrated a beneficial effect on the most commonly used physiologic surrogate endpoints, the serum urea nitrogen and creatinine concentrations.
The diagnosis of AKI is usually based on either the elevation of serum creatinine or the detection of oliguria. Serum creatinine, however, is a poor marker of early renal function because the serum concentration is greatly influenced by changes in muscle mass and tubular secretion. Hence, the normal reference interval is relatively wide, and the use of serum creatinine alone to follow disease progression is fraught with imprecision. There are numerous non-renal factors influencing the serum creatinine concentration such as body weight, race, age, gender, total body volume, drugs, muscle metabolism and protein intake. In AKI, serum creatinine is an even poorer reflection of kidney function, because the patients are not in steady state; hence, serum creatinine lags far behind renal injury. Furthermore, significant renal disease (e.g., fibrosis) can exist with minimal or no change in creatinine because of renal reserve, enhanced tubular secretion of creatinine, or other factors. Possibly, the interventions would have been successful if they could be initiated at the onset of AKI rather than waiting several days for creatinine to rise. The issues discussed above increase the risk of failure in drug development. These issues also increase the variability in the outcomes and magnify the size and cost of clinical studies.
Biomarkers and surrogate endpoint markers have many uses in laboratory and clinical investigations and in drug discovery. Biomarkers are useful for diagnosing, classifying, or grading the severity of disease in both laboratory and clinical settings. They may be able to provide efficacy, toxicity, and mechanistic information for the preclinical and clinical phases of drug discovery. Because biomarkers and surrogate endpoint markers can accelerate the speed and decrease the risk of drug discovery, they are highly sought after. A troponin-like biomarker of acute kidney injury that is easily measured, unaffected by other biological variables, and capable of both early detection and risk stratification would be a tremendous advance for clinical medicine.
Session Chairperson(s)*:
Chairperson, Chirag Parikh, MD, PhD
| Presenters/Discussants*: |
| Chirag Parikh, MD, PhD |
| | “Role of Biomarkers in early diagnosis of Acute Kidney Injury” |
| Lloyd Cantley, MD |
| | “Stem Cells as Biomarkers of Recovery of Acute Kidney Injury” |
| Devaraj Prasad, MD |
| | “Biomarkers of Injury after cadaveric kidney transplantation” |
| Charles Edelstein, MD, PhD |
| | “Systemic effect of Acute Kidney Injury- A case for biomarkers” |
Back to Experimental Biology 2007
|
