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The diagnosis and prognosis of acute kidney injury (AKI) by current clinical means is inadequate. Biomarkers of kidney injury that are easily measured and unaffected by physiological variables could revolutionize the management of AKI. Our objective was to systematically review the diagnostic and prognostic utility of urine and serum biomarkers of AKI in humans. We searched MEDLINE, PubMed and EMBASE databases (January 2000-August 2009) for biomarker studies that could be classified into the following categories: (a) confirmation of the diagnosis of established AKI, (b) early prediction of AKI, and (c) prognostication of AKI. We identified 54 manuscripts published since 2000 that met our inclusion and exclusion criteria. Urinary interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) and N-acetyl-beta-D-glucosaminidase (NAG) are potentially useful biomarkers for the diagnosis of established AKI. Urinary NGAL, IL-18, and liver-type fatty acid binding protein, and serum NGAL and cystatin C represent the most promising biomarkers for early prediction of AKI. Urinary cystatin C, alpha1-microglobulin, NAG and retinol-binding protein may be useful to predict severity and outcomes of AKI. In conclusion, we identified several studies of promising biomarkers for the diagnosis, prediction and prognostication of AKI. However, we note several limitations, including small sample sizes, inadequate gold standard, exclusion of patients with chronic kidney disease, incomplete statistical analyses, utilization of research-based assays and a paucity of studies examining prediction for clinical outcomes. Future studies will need to address these limitations in order for further progress to be made.

Purpose of Review: The goal of this review is to summarize the recent plethora of data that relate to long-term outcomes after acute kidney injury (AKI)., Recent Findings: Surviving patients with AKI are still at high risk for long-term adverse outcomes, even if serum creatinine returns to normal. After adjusting for potential confounders, many recent studies have demonstrated that AKI is independently associated with chronic kidney disease, end-stage renal disease, and premature death. Unfortunately, definitive evidence from randomized controlled trials demonstrating that prevention or treatment of AKI prevents long-term adverse outcomes is not yet available., Summary: AKI is clearly a prognostic marker for poor long-term outcomes, but more studies will be needed to determine whether AKI is truly causal and whether or not the risk is modifiable.

Background and Objectives: Serum creatinine concentration at the time of nephrology consultation is not necessarily indicative of the severity of acute kidney injury (AKI). Although urine microscopy is useful to differentiate AKI, its role in predicting adverse clinical outcomes has not been well described., Design, Setting, Participants, & Measurements: The relationship between urine microscopy findings at the time of nephrology consultation for AKI and clinical outcomes was evaluated prospectively. A urinary sediment scoring system was created on the basis of the number of renal tubular epithelial cells and granular casts. The primary outcome was worsening of AKI (progressing to higher AKI Network stage, dialysis, or death) during hospitalization., Results: Of 249 patients consulted for AKI, 197 had acute tubular necrosis or prerenal AKI and were included in the analysis. At consultation, 80 (40%) had stage 1, 53 (27%) had stage 2, and 66 (33%) had stage 3 AKI. The urinary sediment combined scores were lowest in those with stage 1 and highest in stage 3 AKI. Seventy-nine patients (40%) experienced worsening of AKI from the time of consultation. The urinary scoring system was significantly associated with increased risk of worsening AKI (adjusted relative risk: 7.3; 95% confidence interval: 4.5 to 9.7 for worsening with score of > or =3 versus score of 0) and was more predictive than AKI Network stage at the time of consultation., Conclusions: The urinary sediment score may be a useful tool to predict worsening of AKI due to either acute tubular necrosis or prerenal AKI during hospitalization.

Current methods for predicting graft recovery after kidney transplantation are not reliable. We performed a prospective, multicenter, observational cohort study of deceased-donor kidney transplant patients to evaluate urinary neutrophil gelatinase-associated lipocalin (NGAL), IL-18, and kidney injury molecule-1 (KIM-1) as biomarkers for predicting dialysis within 1 wk of transplant and subsequent graft recovery. We collected serial urine samples for 3 d after transplant and analyzed levels of these putative biomarkers. We classified graft recovery as delayed graft function (DGF), slow graft function (SGF), or immediate graft function (IGF). Of the 91 patients in the cohort, 34 had DGF, 33 had SGF, and 24 had IGF. Median NGAL and IL-18 levels, but not KIM-1 levels, were statistically different among these three groups at all time points. ROC curve analysis suggested that the abilities of NGAL or IL-18 to predict dialysis within 1 wk were moderately accurate when measured on the first postoperative day, whereas the fall in serum creatinine (Scr) was not predictive. In multivariate analysis, elevated levels of NGAL or IL-18 predicted the need for dialysis after adjusting for recipient and donor age, cold ischemia time, urine output, and Scr. NGAL and IL-18 quantiles also predicted graft recovery up to 3 mo later. In summary, urinary NGAL and IL-18 are early, noninvasive, accurate predictors of both the need for dialysis within the first week of kidney transplantation and 3-mo recovery of graft function.

Background: Acute kidney injury (AKI) is common in patients undergoing cardiac surgery and is associated with a high rate of death, long-term sequelae and healthcare costs. We conducted a systematic review of randomized controlled trials for strategies to prevent or treat AKI in cardiac surgery., Methods: We screened Medline, Scopus, Cochrane Renal Library, and Google Scholar for randomized controlled trails in cardiac surgery for prevention or treatment of AKI in adults., Results: We identified 70 studies that contained a total of 5,554 participants published until November 2008. Most studies were small in sample size, were single-center, focused on preventive strategies, and displayed wide variation in AKI definitions. Only 26% were assessed to be of high quality according to the Jadad criteria. The types of strategies with possible protective efficacy were dopaminergic agents, vasodilators, anti-inflammatory agents, and pump/perfusion strategies. When analyzed separately, dopamine and N-acetylcysteine did not reduce the risk for AKI., Conclusions: This summary of all the literature on prevention and treatment strategies for AKI in cardiac surgery highlights the need for better information. The results advocate large, good-quality, multicenter studies to determine whether promising interventions reliably reduce rates of acute renal replacement therapy and mortality in the cardiac surgery setting., (2010 S. Karger AG, Basel.)

Background and Objectives: Identifying patients who may develop acute kidney injury (AKI) remains challenging, as clinical determinants explain only a portion of individual risk. Another factor that likely affects risk is intrinsic genetic variability. Therefore, a systematic review of studies was performed that related the development or prognosis of AKI to genetic variation., Design, Setting, Participants, and Measurements: MEDLINE, EMBASE, HuGEnet, SCOPUS, and Web of Science were searched for articles from 1950 to Dec 2007. Two independent researchers screened articles using predetermined criteria. Studies were assessed for methodological quality via an aggregate scoring system., Results: The 16 included studies were of cohort or case-cohort design and investigated 35 polymorphisms in 21 genes in association with AKI. Fifteen gene-gene interactions were also investigated in four separate studies. Study populations were primarily premature infants or adults who were critically ill or postcardiac bypass patients. Among the studies, five different definitions of AKI were used. Only one polymorphism, APO E e2/e3/e4, had greater than one study showing a significant impact (P < 0.05) on AKI incidence. The mean quality score of 5.8/10 (range four to nine), heterogeneity in the studies, and the dearth of studies precluded additional meta-analysis of the results., Conclusions: Current association studies are unable to provide definitive evidence linking genetic variation to AKI. Future success will require a narrow consensus definition of AKI, rigorous epidemiologic techniques, and a shift from a priori hypothesis-driven to genome-wide association studies.

Background: Acute kidney injury (AKI) is common in hospitalized patients. The impact of AKI on long-term outcomes is controversial., Study Design: Systematic review and meta-analysis., Setting & Participants: Persons with AKI., Selection Criteria for Studies: MEDLINE and EMBASE databases were searched from 1985 through October 2007. Original studies describing outcomes of AKI for patients who survived hospital discharge were included. Studies were excluded from review when participants were followed up for less than 6 months., Predictor: AKI, defined as acute changes in serum creatinine level or acute need for renal replacement therapy., Outcomes: Chronic kidney disease (CKD), cardiovascular disease, and mortality., Results: 48 studies that contained a total of 47,017 participants were reviewed; 15 studies reported long-term data for patients without AKI. The incidence rate of mortality was 8.9 deaths/100 person-years in survivors of AKI and 4.3 deaths/100 patient-years in survivors without AKI (rate ratio [RR], 2.59; 95% confidence interval, 1.97 to 3.42). AKI was associated independently with mortality risk in 6 of 6 studies that performed multivariate adjustment (adjusted RR, 1.6 to 3.9) and with myocardial infarction in 2 of 2 studies (RR, 2.05; 95% confidence interval, 1.61 to 2.61). The incidence rate of CKD after an episode of AKI was 7.8 events/100 patient-years, and the rate of end-stage renal disease was 4.9 events/100 patient-years., Limitations: The relative risk for CKD and end-stage renal disease after AKI was unattainable because of lack of follow-up of appropriate controls without AKI., Conclusions: The development of AKI, defined as acute changes in serum creatinine level, characterizes hospitalized patients at increased risk of long-term adverse outcomes.

Background: Delayed graft function (DGF) is a common complication of renal transplantation. The short-term consequences of DGF are well known, but the long-term relationship between DGF and patient and graft survival is controversial in the published literature. We conducted a systematic review and meta-analysis to precisely estimate these relationships., Methods: We performed a literature search for original studies published through March 2007 pertaining to long-term (>6 months) outcomes of DGF. The primary outcome was graft survival. Secondary outcomes were patient survival, acute rejection and kidney function., Results: When compared to patients without DGF, patients with DGF had a 41% increased risk of graft loss (RR 1.41, 95% CI 1.27-1.56) at 3.2 years of follow-up. There was no significant relationship between DGF and patient survival at 5 years (RR 1.14, 95% CI 0.94-1.39). The mean creatinine in the non-DGF group was 1.6 mg/dl. Patients with DGF had a higher mean serum creatinine (0.66 mg/dl, 95% CI 0.57-0.74) compared to patients without DGF at 3.5 years of follow-up. DGF was associated with a 38% relative increase in the risk of acute rejection (RR 1.38, 95% CI 1.29-1.47)., Conclusion: The results of this meta-analysis emphasize and quantify the long-term detrimental association between DGF and important graft outcomes like graft survival, acute rejection and renal function. Efforts to prevent and treat DGF should be aggressively investigated in order to improve graft survival given the deficit in the number of kidney donors.

Background: Contrast-induced nephropathy (CIN) is a common cause of acute kidney injury. Several preventive therapies for this injury have been tested; however, there is still no consensus on the optimal protocol., Methods: We performed a systematic search of the National Library of Medicine and the Cochrane Library databases from January 1985 to November 2008 to identify randomized controlled studies examining sodium bicarbonate as a preventive measure for CIN in humans. We also reviewed conference abstracts from cardiology nephrology and radiology meetings from 2004 to 2008. A change in serum creatinine levels defined by an absolute (>or=0.5 mg/dl) or percentage (>or=25%) increase in the serum creatinine level is defined as CIN. The primary outcome measure was the incidence of CIN, and the secondary outcome measures were: change in serum creatinine from baseline, requirement for renal replacement therapy and death., Results: Seventeen randomized controlled trials have investigated the role of sodium bicarbonate for prophylaxis of CIN. The overall incidence of CIN was 11.3%. Using the results from all 17 studies that compared bicarbonate versus saline, the pooled relative risk of developing CIN was 0.54 (95% CI, 0.36-0.83) in the intervention arm, indicating a significant benefit from sodium bicarbonate. The pooled relative risk of CIN was 0.57 (95% CI, 0.35-0.95) when we analyzed for the studies that compared the effects sodium bicarbonate to NAC on development of CIN. There was no difference in the rates of requirement for renal replacement therapy and death., Conclusions: The use of sodium bicarbonate appears to reduce the incidence of CIN when compared to other preventive strategies for CIN without a significant difference in the requirement of renal replacement therapy and mortality. There are study heterogeneity and publication biases. Further adequately powered randomized controlled studies are needed to determine whether sodium bicarbonate will reduce the clinically meaningful outcomes (e.g., need for dialysis or death) and optimal hydration strategy in high-risk patients.

Background and Objectives: Urine microscopy is the oldest and one of the most commonly used tests for differential diagnosis of acute kidney injury (AKI), but its performance has not been adequately studied in the setting of AKI., Design, Setting, Participants, & Measurements: Fresh urine samples were obtained from 267 consecutive patients with AKI, and urinary sediment was examined. The cause of AKI was assessed at two time points: (1) Before urine microscopy diagnosis and (2) after patient discharge or death (final diagnosis). A urinary scoring system also was created on the basis of casts and renal tubular epithelial cells (RTEC) to differentiate acute tubular necrosis (ATN) from prerenal AKI., Results: The urinary sediment scoring system was highly predictive of the final diagnosis of ATN. In patients with a high pretest probability of ATN (initial diagnosis of ATN), any casts or RTEC (score > or =2) resulted in very high positive predictive value and low negative predictive value for a final diagnosis of ATN. In patients with a low pretest probability of ATN (initial diagnosis of prerenal AKI), lack of casts or RTEC on urinary sediment examination had a sensitivity of 0.73 and specificity of 0.75 for a final diagnosis of prerenal AKI. The negative predictive value of lack of casts or RTEC in patients with low pretest probability of disease was 91%., Conclusions: Urine sediment examination is a valuable diagnostic tool for confirming the diagnosis of ATN. A score of > or =2 on an ATN urinary sediment scoring system is an extremely strong predictor of ATN.

Background: In the era of antiretroviral therapy, non-AIDS complications such as kidney disease are important contributors to morbidity and mortality., Objective: To estimate the impact of hepatitis C coinfection on the risk of kidney disease in HIV patients., Design and Methods: Two investigators identified English-language citations in MEDLINE and Web of Science from 1989 through 1 July 2007. References of selected articles were reviewed. Observational studies and clinical trials of HIV-related kidney disease and antiretroviral nephrotoxicity were eligible if they included at least 50 subjects and reported hepatitis C status. Data on study characteristics, population, and kidney disease outcomes were abstracted by two independent reviewers., Results: After screening 2516 articles, 27 studies were eligible and 24 authors confirmed or provided data. Separate meta-analyses were performed for chronic kidney disease outcomes (n = 10), proteinuria (n = 4), acute renal failure (n = 2), and indinavir toxicity (n = 5). The pooled incidence of chronic kidney disease was higher in patients with hepatitis C coinfection [6.2 versus 4.0%; relative risk 1.49, 95% confidence interval (CI) 1.08-2.06]. In meta-regression, prevalence of black race and the proportion of patients with documented hepatitis C status were independently associated with the risk of chronic kidney disease. The relative risk associated with hepatitis C coinfection was significantly increased for proteinuria (1.15; 95% CI 1.02-1.30) and acute renal failure (1.64; 95% CI 1.21-2.23), with no significant statistical heterogeneity. The relative risk of indinavir toxicity was 1.59 (95% CI 0.99-2.54) with hepatitis C coinfection., Conclusion: Hepatitis C coinfection is associated with a significant increase in the risk of HIV-related kidney disease.

Background: The term delayed graft function (DGF) is commonly used to describe the need for dialysis after receiving a kidney transplant. DGF increases morbidity after transplantation, prolongs hospitalization and may lead to premature graft failure. Various definitions of DGF are used in the literature without a uniformly accepted technique to identify DGF., Methods: We performed a systematic review of the literature to identify all of the different definitions and diagnostic techniques to identify DGF., Results: We identified 18 unique definitions for DGF and 10 diagnostic techniques to identify DGF., Conclusions: The utilization of heterogeneous clinical criteria to define DGF has certain limitations. It will lead to delayed and sometimes inaccurate diagnosis of DGF. Hence a diagnostic test that identifies DGF reliably and early is necessary. Heterogeneity, in the definitions used for DGF, hinders the evolution of a diagnostic technique to identify DGF, which requires a gold standard definition. We are in need of a new definition that is uniformly accepted across the kidney transplant community. The new definition will be helpful in promoting better communication among transplant professionals and aids in comparing clinical studies of diagnostic techniques to identify DGF and thus may facilitate clinical trials of interventions for the treatment of DGF.

Background: Acute kidney injury (AKI) is a common complication during hospitalization and is an accepted risk factor for in-hospital mortality. However, the association of severity of AKI with the long-term risk of death is not well defined., Methods: To examine the independent effect of the severity of AKI on long-term risk of death following acute myocardial infarction (AMI), we performed an observational study of 147007 elderly Medicare patients admitted for AMI from January 1994 through February 1996 as a part of the Cooperative Cardiovascular Project. We evaluated the association between AKI and all-cause mortality. We defined AKI as absolute changes in serum creatinine level, categorized as none (creatinine level increase, < or =0.2 mg/dL), mild (0.3-0.4 mg/dL increase), moderate (0.5-0.9 mg/dL increase), and severe (> or =1.0 mg/dL increase)., Results: Overall, 19.4% of the patients had AKI, including 7.1% with mild AKI, 7.1% with moderate AKI, and 5.2% with severe AKI. Less than 10% of patients who had severe AKI were alive at 10 years compared with 12.2%, 21.1%, and 31.7% patients with moderate, mild, and no AKI, respectively. The adjusted hazard ratio for death for in-hospital survivors at 10 years was 1.15 (95% confidence interval [CI], 1.12-1.18) for mild AKI, 1.23 (95% CI, 1.20-1.26) for moderate AKI, and 1.33 (95% CI, 1.28-1.38) for severe AKI. Similar results were obtained in several secondary analyses that included inpatient mortality, excluded mortality in the first 3 years, and stratified by some specified high-risk groups. Moderate or severe AKI were comparable in strength with other known correlates of cardiovascular mortality., Conclusions: Acute kidney injury has an independent and graded association with long-term mortality. These results should stimulate additional mechanistic and interventional studies and plans for follow-up of patients with AKI after discharge.

Acute kidney injury (previously known as acute renal failure) is a common complication in hospitalized patients, and its incidence has risen significantly in the past 15 yr. Despite significant technical advances in therapeutics, the mortality and morbidity rates associated with acute kidney injury remain dismally high and have not appreciably improved during the past four decades. Although the serum creatinine concentration performs fairly well for estimating kidney function in patients with stable chronic kidney disease, it performs poorly in the setting of acute disease. An ideal biomarker for acute kidney injury would help clinicians and scientists diagnose the most common form of acute kidney injury in hospitalized patients, acute tubular necrosis, early and accurately and may aid to risk-stratify patients with acute kidney injury by predicting the need for renal replacement therapy, the duration of acute kidney injury, the length of stay, and mortality. Herein is reviewed the diagnostic and prognostic performance of several types of urinary biomarkers for the diagnosis and risk stratification of acute kidney injury. The major types of urinary biomarkers fall into three classes: (1) Inflammatory, (2) renal tubular proteins that are excreted into the urine after injury, and (3) surrogate markers of tubular injury. Also discussed are statistical issues in evaluating the accuracy of biomarkers as diagnostic tests. It is likely that a panel of biomarkers, rather than a single biomarker, will be needed to perform extremely well in these three situations.

Background: Recently, acute kidney injury defined by small changes in serum creatinine levels was associated with worse short-term outcomes; however, the precision and variability of this association was not fully explored., Study Design: Systematic review and meta-analysis., Setting & Participants: Hospitalized patients., Selection Criteria for Studies: MEDLINE and EMBASE databases were searched for observational cohort studies and randomized controlled trials published from 1990 through February 2007 that provided information for small changes in serum creatinine levels., Predictor: Small acute changes in serum creatinine levels by absolute and percentage of changes in serum creatinine levels (lower threshold for increase in serum creatinine <0.5 mg/dL or <25%)., Outcome: Short-term mortality (or=50%) had the greatest RR of death (RR, 6.9; 95% CI, 2.0 to 24.5). Results were similar when absolute changes in creatinine levels were considered and when pooled estimates of adjusted RR were used., Limitations: Individual patient data were unavailable; thus, only group-level data were pooled for meta-analysis. Results showed a significant degree of statistical heterogeneity that was only partially ameliorated by separating studies into subsets based on clinical setting., Conclusions: Short-term mortality and acute decreases in renal function are associated through a graded relationship such that even mild changes in serum creatinine levels portend worse outcome in a variety of clinical settings and patient-types.

Background: Severe acute kidney injury (AKI) that requires dialytic support, a relatively uncommon complication in severely burned adults, is associated with a substantially increased mortality rate. It is not known whether milder forms of AKI have prognostic importance in burns., Methods: We performed an observational cohort analysis of consecutive patients with major burns admitted to the burn care unit of a tertiary-care center from 1998 to 2003. Our main outcome measures were AKI stratified by the Risk of renal dysfunction, Injury to the kidney, Failure of kidney function, Loss of kidney function, and End-stage kidney disease (RIFLE) classification and mortality., Results: AKI occurred in 81 of 304 patients (26.6%) with burns on 10% or greater total-body surface area. Risk factors for AKI on multivariate analysis were inhalational injury, catheter infection, and sepsis. Patients with AKI stratified by using the RIFLE classification had greater mortality, greater requirement of artificial ventilation, and longer durations of intensive care unit and hospital stays. Mortality was not significantly different among those with the "Risk" and "Injury" strata of RIFLE AKI compared with those without AKI, but mortality increased significantly with the "Failure" (60%) strata. In multivariate analysis, age, greater total-body surface area, inhalational injury, and the RIFLE classification of Failure were each independent predictors of death., Conclusion: In conclusion, the mortality of patients with burns with severe AKI remains high and unchanged in the modern era of critical care medicine. The RIFLE classification added prognostic information regarding morbidity in patients with milder forms of AKI.

Background: Little is known about the impact of chronic kidney disease (CKD) on health-related quality-of-life outcomes after coronary artery bypass grafting (CABG)., Methods: Our objective was to examine the changes in physical function (PF) and mental health (MH) 6 months after CABG in 1055 patients with and without CKD. The primary end points were mean change in score and status of "improved" or "worsened" in both PF and MH subscales of the Medical Outcomes Trust Short Form 36-Item Health Survey from baseline to 6 months after CABG, stratified by CKD stage (0-5)., Results: Absolute PF and MH scores at baseline and at 6 months varied by renal impairment level. Patients with severe CKD (stages 4-5) had a mean (SD) decrease in PF score at 6 months of 3 (3) compared with increases in the rest of the cohort (P<.001). After adjustment for baseline score, 21% of patients with advanced CKD experienced worsened PF scores, compared with 0% of patients with stages 0 to 2 and stage 3 CKD (P<.001). In contrast to PF scores, patients with and without CKD had similar improvements in mean MH scores at 6 months, and patients with stages 4 to 5 CKD had the highest frequency of those with improved MH scores (77%). After adjustment, no patients experienced worsened MH scores., Conclusions: After 6 months, patients with severe CKD who underwent CABG had improvement in MH but not improvement in PF and may have had worsened PF compared with those without severe CKD. Comparable evidence regarding quality-of-life outcomes in the absence of CABG is needed to more fully inform decision making regarding patients with severe CKD and coronary artery disease.

Context: Patients with renal disease are at high risk for cardiovascular mortality. Determining which interventions best offset this risk remains a health priority., Objective: To quantify the representation of patients with renal disease in randomized controlled trials for interventions proven efficacious for cardiovascular disease., Data Sources: We searched MEDLINE for trials published from 1985 through 2005 in 11 major medical and subspecialty journals., Study Selection: Randomized controlled trials for chronic congestive heart failure and acute myocardial infarction of treatments that are currently listed as class I or II recommendations in the current American College of Cardiology/American Heart Association guidelines were included., Data Extraction: Two reviewers independently abstracted data on study and patient characteristics, renal measurements, outcomes, and prognostic features., Data Synthesis: A total of 153 trials were reviewed. Patients with renal disease were reported as excluded in 86 (56%) trials. Patients with renal disease were more likely to be excluded from trials that were multicenter; of moderate enrollment size; North American; that tested renin-angiotensin-aldosterone system antagonists and anticoagulants; and that tested chronic congestive heart failure. Only 8 (5%) original articles reported the proportion of enrolled patients with renal disease, and only 15 (10%) reported mean baseline renal function. While 81 (53%) trials performed subgroup analyses of some baseline characteristic in the original article, only 4 (3%) subgroup analyses of treatment stratified by renal disease were performed., Conclusion: Major cardiovascular disease trials frequently exclude patients with renal disease and do not provide adequate information on the renal function of enrollees or the effect of interventions on patients with renal disease.

The neurohormonal model of congestive heart failure (CHF) has replaced the previously accepted hemodynamic model. A shift in this paradigm has allowed alterations in therapy of CHF such that agents that target the neurohormonal axis and specifically the renin-angiotensin-aldosterone system, with drugs such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and beta-blockers, are utilized. Employment of these drugs markedly improves survival in patients with CHF. Recent animal and human data demonstrate that aldosterone is directly pathogenic in this disease process and is insufficiently suppressed by these agents. Furthermore, when aldosterone is directly antagonized, vascular and myocardial damage is greatly ameliorated in both experimental animals and humans. Significant mortality benefits of aldosterone antagonists in patients with CHF from systolic dysfunction have been subsequently witnessed. Herein, the pathophysiology of CHF, the beneficial role of aldosterone antagonists in this disease process, and potential adverse consequences of these agents are reviewed.

Aldosterone has recently been recognized as an important factor in the development and progression of cardiorenal disease. Animal and human data suggest that aldosterone contributes importantly to several disease states. These include congestive heart failure, coronary heart disease and progression of kidney disease. Recently, the discovery that aldosterone antagonists decrease pathologic injury in the kidneys and nonepithelial tissues, such as the myocardium and endothelium, has generated great controversy regarding the actual mechanisms of benefit of these agents. The available data is reviewed and conclusions drawn regarding the relative benefits of modulating aldosterone effects in the cardiovascular system and the kidney. In particular, the authors review their effects on reductions in cardiovascular events and progression of chronic kidney disease, as well as the safety and tolerability of these agents.

Background: Intravenous (i.v.) iron is employed to treat absolute and relative iron deficiency in end-stage renal disease patients. However, there exists the possibility that i.v. iron increases infection risk. This pilot study examines whether i.v. iron gluconate acutely increases tunnelled haemodialysis catheter colonization, microbial growth, or blood-borne infection., Methods: Nineteen patients with haemodialysis catheters who met criteria to receive an i.v. iron load entered the study. Six matched patients with catheters who did not receive iron were controls. Blood aspirated from the catheter prior to initiation of haemodialysis was sent for qualitative/quantitative cultures. The study consisted of three baseline cultures, five cultures during iron (125 mg of ferric gluconate per treatment), and three cultures following iron administration. Patients were monitored for infection for 30 days following iron., Results: Fifteen iron-treated patients and six controls completed the study. Thirty-three per cent of treated patients were colonized at baseline; 66% were colonized following iron. Thirty-three per cent of controls (2/6) were colonized at baseline; no new colonization developed during follow up. Neither treated patients nor controls had significant microbial growth within catheters; one patient in the iron-treated group developed candidaemia., Conclusion: Intravenous iron is not associated with acute microbial growth in catheters or clinical infection. However, a trend towards increased catheter colonization following iron administration exists.

The role of potassium in the progression of cardiovascular disease is complex and controversial. Animal and human data suggest that increases in dietary potassium, decreases in urinary potassium loss, or increases in serum potassium levels through other mechanisms have benefits in several disease states. These include the treatment of hypertension, stroke prevention, arrhythmia prevention, and treatment of congestive heart failure. Recently, the discovery that aldosterone antagonists not only decrease sodium reabsorption and decrease potassium secretion in the nephron, but also decrease pathological injury of such nonepithelial tissues as the myocardium and endothelium, has generated great controversy regarding the actual mechanisms of benefit of these agents. We review the available data and draw conclusions about the relative benefits of modulating potassium balance versus nonrenal effects of aldosterone blockade in patients with cardiovascular disease.