N-acetylcysteine effect on serum creatinine and cystatin C levels in CKD patients.
Clin J Am Soc Nephrol. 2008 Nov;3(6):1610-4
Authors: Rehman T, Fought J, Solomon R
BACKGROUND AND OBJECTIVES: N-acetylcysteine (NAC) has been widely used as a prophylactic therapy for contrast-induced nephropathy (CIN). Its efficacy is controversial because of heterogeneity in study results and because of evidence that NAC can alter serum creatinine levels without affecting glomerular filtration rate. This confounding effect of N-acetylcysteine on serum creatinine has not been rigorously tested, however, in a population at risk for CIN and following doses of NAC currently recommended for prophylaxis of CIN. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: "Double-dose" NAC was administered in the absence of iodinated contrast media to 29 stage 3 to 5 stable chronic kidney disease patients. Serum creatinine and cystatin C were measured before and 4 h and 48 h after the last dose of NAC. RESULTS: There was no effect of NAC on either serum creatinine or cystatin C levels. CONCLUSION: NAC, in doses currently recommended for prophylaxis of CIN, has no effect on serum creatinine or cystatin C levels. It is therefore unlikely that the heterogeneity seen in clinical trials of NAC prophylaxis for CIN is related to a confounding effect on serum creatinine.
PMID: 18667743 [PubMed - indexed for MEDLINE]Link to Article at PubMed
Elevations in serum creatinine with RAAS blockade: why isn't it a sign of kidney injury?
Curr Opin Nephrol Hypertens. 2008 Sep;17(5):443-9
Authors: Ryan MJ, Tuttle KR
PURPOSE OF REVIEW: The aim of this article is to review the pertinent physiology and pathophysiology of the renin-angiotensin-aldosterone system (RAAS), summarize the proven beneficial cardiovascular and renal effects of RAAS blockade, examine clinical situations in which RAAS blockade may induce reductions in glomerular filtration rate, and explore why increases in serum creatinine in the setting of angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) therapy do not necessarily signify the presence of clinically relevant kidney failure. RECENT FINDINGS: RAAS inhibition appears to reduce the likelihood of atrial fibrillation. RAAS inhibition leads to improved insulin sensitivity and glycemic control, but does not appear to prevent diabetes. The beneficial effects of ACEi/ARB therapy extend to those with significant renal disease. Combination ACEi/ARB is safe, and reduces proteinuria more than either agent alone in patients with macroalbuminuric nephropathy. Acute deteriorations in renal function that result from RAAS inhibition are usually reversible. SUMMARY: RAAS blockade exerts potent hemodynamic, antihypertensive, and antiinflammatory effects, and slows progression of kidney disease beyond that due to lowering of blood pressure. The benefit extends to those with advanced disease. In spite of established benefit, ACEi and ARB therapy remains underutilized, in part due to concerns about acute deteriorations in renal function that result from interruption of the RAAS.
PMID: 18695383 [PubMed - indexed for MEDLINE]Link to Article at PubMed
Do thiazides worsen metabolic syndrome and renal disease? The pivotal roles for hyperuricemia and hypokalemia.
Curr Opin Nephrol Hypertens. 2008 Sep;17(5):470-6
Authors: Reungjui S, Pratipanawatr T, Johnson RJ, Nakagawa T
PURPOSE OF REVIEW: The aims of this article are to review the current controversies related to the use of thiazide diuretics as first-line treatment of hypertension and to discuss the causal roles for hyperuricemia and hypokalemia on the adverse consequences of thiazide usage. RECENT FINDINGS: Thiazides significantly reduce morbidity and mortality in hypertensive subjects. There remains, however, debate about thiazide usage as first-line treatment of hypertension. This negative impact of thiazides may be partially attributed to the ability of thiazides to exacerbate features of metabolic syndrome or increase the risk for developing diabetes. Several clinical trials suggest that thiazide-induced hyperuricemia and hypokalemia may account for some of these negative effects. Thiazide treatment is also associated with a decline of renal function in spite of a lowering blood pressure. In this review, we discuss the clinical and experimental evidence supporting a potential role of hyperuricemia and hypokalemia on the development of renal injury and worsening of the metabolic syndrome. SUMMARY: Hyperuricemia and hypokalemia may have pivotal roles in the exacerbation of the metabolic syndrome in response to thiazides. We propose that controlling serum uric acid and serum potassium could improve thiazide efficacy and also reduce its risk for inducing metabolic syndrome or diabetes.
PMID: 18695387 [PubMed - indexed for MEDLINE]Link to Article at PubMed
Comparison of dosing recommendations for antimicrobial drugs based on two methods for assessing kidney function: cockcroft-gault and modification of diet in renal disease.
Pharmacotherapy. 2008 Sep;28(9):1125-32
Authors: Golik MV, Lawrence KR
STUDY OBJECTIVES: To quantify the difference between glomerular filtration rates (GFRs) estimated by using the Cockcroft-Gault and Modification of Diet in Renal Disease (MDRD) equations, and to determine whether dosing recommendations for four commonly prescribed antimicrobial agents are discordant when determined by using these equations. DESIGN: Prospective, observational study. SETTING: Tertiary-care medical center. PATIENTS: Two hundred seven consecutive adults without normal renal function but not receiving dialysis who were admitted to a non-intensive-care ward and had two consecutive serum creatinine concentration (S(cr)) values measured 20-24 hours apart. MEASUREMENTS AND MAIN RESULTS: The patients' mean +/- SD S(cr) was 1.41 +/- 0.95 mg/dl. Kidney function was estimated by using two versions of the four-variable MDRD equation and four versions of the Cockcroft-Gault equation. Mean estimated GFRs ranged from 52.3-73.1 ml/minute. Dosing for cefepime, levofloxacin, meropenem, and piperacillin-tazobactam was determined using the two equations that had the highest level of correlation; these were the MDRD equation unadjusted for body surface area and the Cockcroft-Gault equation adjusted for ideal body weight and S(cr). When the total daily doses based on these two equations for the four antimicrobials were compared, the discordance rate was 22.8-36.3%, and statistically significant differences were observed for most of the discordant doses. When discordance was present, the MDRD equation resulted in a higher dose of the drug. CONCLUSION: Discordance rates for drug dosing ranged from 22.8-36.3% between the MDRD and Cockcroft-Gault methods for estimating GFR. Although use of the MDRD equation is a well-accepted and accurate method of estimating GFR to stage chronic kidney disease, our results demonstrated a significant difference in drug dosing regimens between the MDRD method and the Cockcroft-Gault method.
PMID: 18752383 [PubMed - indexed for MEDLINE]Link to Article at PubMed
Definition and classification of acute kidney injury.
Nephron Clin Pract. 2008;109(4):c182-7
Authors: Kellum JA, Bellomo R, Ronco C
Changes in urine output and glomerular filtration rate are neither necessary nor sufficient for the diagnosis of renal pathology. Yet no simple alternative for the diagnosis currently exists. Until recently, there has been no consensus as to diagnostic criteria or clinical definition of acute renal failure. Depending on the definition used, acute renal failure has been reported to affect from 1 to 25% of ICU patients and has led to mortality rates from 15 to 60%. The RIFLE criteria were developed to standardize the diagnosis of acute renal failure and in the process the term acute kidney injury (AKI) has been proposed to encompass the entire spectrum of the syndrome from minor changes in renal function to requirement for renal replacement therapy. Thus, AKI is not acute renal failure but a more general description. Small changes in kidney function in hospitalized patients are important and are associated with significant changes in short and possibly long-term outcomes. The RIFLE criteria provide a uniform definition of AKI and have now been validated in numerous studies.
PMID: 18802365 [PubMed - indexed for MEDLINE]Link to Article at PubMed