Clinical Applications of Biomarkers for Acute Kidney Injury.
Am J Kidney Dis. 2011 Mar 14;
Authors: Belcher JM, Edelstein CL, Parikh CR
Research into novel therapies for acute kidney injury (AKI) has been hampered by r…

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Management of Gram-Positive Coccal Bacteremia and Hemodialysis.

Am J Kidney Dis. 2011 Feb 16;

Authors: Fitzgibbons LN, Puls DL, Mackay K, Forrest GN

Gram-positive cocci are the most common cause of bloodstream infections in hemodialysis patients, with Staphylococcus aureus and coagulase-negative staphylococci causing most infections. Management of these infections often is complicated by limited vascular access options, as well as an increasing prevalence of drug-resistant bacteria in hemodialysis centers, including the emergence of strains of methicillin-resistant S aureus with vancomycin heteroresistance and increasing rates of vancomycin-resistant enterococci, both of which have limited antibiotic treatment options. This article describes the management of these infections based on the organism and its susceptibility profile, including catheter management, antibiotic lock therapies, and systemic antibiotic choices. Although coagulase-negative staphylococci bacteremia often may be managed with preservation of the catheter, antibiotic lock therapy, and intravenous antibiotics, this is rarely the case with S aureus bacteremia because of frequent relapse and the risk of complications, including endocarditis. Enterococcal bacteremia requires more individualization of care, but catheters are less likely to be salvaged, especially when vancomycin-resistant Enterococcus is the causative organism. Finally, strong infection control policies in the hemodialysis unit, conversion from catheter to arteriovenous access when possible, and appropriate use of antibiotics are essential factors in the prevention of these bloodstream infections.

PMID: 21333430 [PubMed - as supplied by publisher]

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Early Nephrologist Involvement in Hospital-Acquired Acute Kidney Injury: A Pilot Study.

Am J Kidney Dis. 2010 Dec 30;

Authors: Balasubramanian G, Al-Aly Z, Moiz A, Rauchman M, Zhang Z, Gopalakrishnan R, Balasubramanian S, El-Achkar TM

BACKGROUND:: The optimal timing of nephrology consultation in patients with hospital-acquired acute kidney injury (AKI) is unknown. STUDY DESIGN:: Prospective controlled nonrandomized intervention study. SETTING & PARTICIPANTS:: We screened daily serum creatinine (SCr) levels of 4,296 patients admitted to the St. Louis Veterans Affairs Medical Center between September and November 2008 (control group) and January to May 2009 (intervention group). 354 patients (8.2%) met the definition of in-hospital AKI (SCr level increase of 0.3 mg/dL over 48 hours); 176 of whom met all inclusion criteria; 85 and 91 patients were enrolled in the control (standard care) and intervention groups, respectively. INTERVENTION:: Early renal service involvement (EARLI), defined as a 1-time nephrology consultation within 18 hours of the onset of AKI. OUTCOME:: Primary outcome defined as 2.5-fold increase in SCr level from admission. MEASUREMENT:: Daily SCr until discharge. RESULTS:: The 2 groups had similar characteristics at baseline and at the time of AKI. The intervention was completed at a mean of 13.1 ± 0.8 hours from the onset of AKI. Nephrology recommendations in the EARLI group included specific diagnostic, therapeutic, and preventative components. The primary outcome occurred in 12.9% of patients in the control group compared with 3.3% of patients in the EARLI group (P = 0.02). Patients in the EARLI group had a lower peak SCr level of 1.8 ± 0.1 versus 2.1 ± 0.2 mg/dL in controls (P = 0.01). LIMITATIONS:: Single-center nonrandomized study of mostly US male veterans. CONCLUSIONS:: Early nephrologist involvement in patients with AKI may reduce the risk of a further decrease in kidney function. A larger randomized trial is needed to confirm the findings.

PMID: 21195518 [PubMed - as supplied by publisher]

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A computerized provider order entry intervention for medication safety during acute kidney injury: a quality improvement report.

Am J Kidney Dis. 2010 Nov;56(5):832-41

Authors: McCoy AB, Waitman LR, Gadd CS, Danciu I, Smith JP, Lewis JB, Schildcrout JS, Peterson JF

BACKGROUND: Frequently, prescribers fail to account for changing kidney function when prescribing medications. We evaluated the use of a computerized provider order entry intervention to improve medication management during acute kidney injury. STUDY DESIGN: Quality improvement report with time series analyses. SETTING & PARTICIPANTS: 1,598 adult inpatients with a minimum 0.5-mg/dL increase in serum creatinine level over 48 hours after an order for at least one of 122 nephrotoxic or renally cleared medications. QUALITY IMPROVEMENT PLAN: Passive noninteractive warnings about increasing serum creatinine level appeared within the computerized provider order entry interface and on printed rounding reports. For contraindicated or high-toxicity medications that should be avoided or adjusted, an interruptive alert within the system asked providers to modify or discontinue the targeted orders, mark the current dosing as correct and to remain unchanged, or defer the alert to reappear in the next session. OUTCOMES & MEASUREMENTS: Intervention effect on drug modification or discontinuation, time to modification or discontinuation, and provider interactions with alerts. RESULTS: The modification or discontinuation rate per 100 events for medications included in the interruptive alert within 24 hours of increasing creatinine level improved from 35.2 preintervention to 52.6 postintervention (P < 0.001); orders were modified or discontinued more quickly (P < 0.001). During the postintervention period, providers initially deferred 78.1% of interruptive alerts, although 54% of these eventually were modified or discontinued before patient death, discharge, or transfer. The response to passive alerts about medications requiring review did not significantly change compared with baseline. LIMITATIONS: Single tertiary-care academic medical center; provider actions were not independently adjudicated for appropriateness. CONCLUSIONS: A computerized provider order entry-based alerting system to support medication management after acute kidney injury significantly increased the rate and timeliness of modification or discontinuation of targeted medications.

PMID: 20709437 [PubMed - indexed for MEDLINE]

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Sodium bicarbonate therapy for prevention of contrast-induced nephropathy: a systematic review and meta-analysis.

Am J Kidney Dis. 2009 Apr;53(4):617-27

Authors: Navaneethan SD, Singh S, Appasamy S, Wing RE, Sehgal AR

BACKGROUND: Optimal hydration measures to prevent contrast-induced nephropathy are controversial. STUDY DESIGN: We conducted a systematic review and meta-analysis using the MEDLINE database (1966 to January 2008), EMBASE (January 2008), and abstracts from conference proceedings. SETTING & POPULATION: Adult patients undergoing contrast procedures. SELECTION CRITERIA FOR STUDIES: Randomized controlled trials comparing intravenous hydration with sodium bicarbonate with hydration with intravenous normal saline for prevention of contrast-induced nephropathy. INTERVENTION: Hydration with intravenous sodium bicarbonate with or without N-acetylcysteine versus hydration with normal saline with or without N-acetylcysteine. OUTCOMES: Contrast-induced nephropathy, need for renal replacement therapy, and worsening of heart failure. RESULTS: Twelve trials (1,854 participants) were included. Sodium bicarbonate significantly decreased the risk of contrast-induced nephropathy (12 trials, 1,652 patients; odds ratio [OR], 0.46; 95% confidence interval [CI], 0.26 to 0.82; I2 = 55.9%) without a significant difference in need for renal replacement therapy (9 trials, 1,215 patients; OR, 0.50; 95% CI, 0.16 to 1.53; I2 = 0%), in-hospital mortality (11 trials, 1,640 patients; OR, 0.51; 95% CI, 0.15 to 1.69), or congestive heart failure compared with controls. Similar results were seen for the risk of contrast-induced nephropathy when sodium bicarbonate was compared with normal saline alone (OR, 0.39; 95% CI, 0.20 to 0.77), but not when sodium bicarbonate/N-acetylcysteine combination was compared with N-acetylcysteine/normal saline combination (OR, 0.68; 95% CI, 0.34 to 1.37). A subgroup analysis limited to published trials showed similar results (OR, 0.26; 95% CI, 0.10 to 0.64; I2 = 63.3%), whereas unpublished studies showed a nonsignificant decrease (OR, 0.85; 95% CI, 0.46 to 1.57; I2 = 25.9%) in risk of contrast-induced nephropathy. LIMITATION: Publication bias and heterogeneity. CONCLUSION: Hydration with sodium bicarbonate decreases the incidence of contrast-induced nephropathy in comparison to hydration with normal saline without a significant difference in need for renal replacement therapy and in-hospital mortality. Larger studies analyzing patient-centered outcomes are needed.

PMID: 19027212 [PubMed - indexed for MEDLINE]

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CKD as an underrecognized threat to patient safety.

Am J Kidney Dis. 2009 Apr;53(4):681-8

Authors: Fink JC, Brown J, Hsu VD, Seliger SL, Walker L, Zhan M

Chronic kidney disease (CKD) is common, but underrecognized, in patients in the health care system, where improving patient safety is a high priority. Poor disease recognition and several other features of CKD make it a high-risk condition for adverse safety events. In this review, we discuss the unique attributes of CKD that make it a high-risk condition for patient safety mishaps. We point out that adverse safety events in this disease have the potential to contribute to disease progression; namely, accelerated loss of kidney function and increased incidence of end-stage renal disease. We also propose a framework in which to consider patient safety in CKD, highlighting the need for disease-specific safety indicators that reflect unsafe practices in the treatment of this disease. Finally, we discuss the hypothesis that increased recognition of CKD will reduce disease-specific safety events and in this way decrease the likelihood of adverse outcomes, including an accelerated rate of kidney function loss and increased incidence of end-stage renal disease.

PMID: 19246142 [PubMed - indexed for MEDLINE]

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Interventions for hemolytic uremic syndrome and thrombotic thrombocytopenic purpura: a systematic review of randomized controlled trials.

Am J Kidney Dis. 2009 Feb;53(2):259-72

Authors: Michael M, Elliott EJ, Craig JC, Ridley G, Hodson EM

BACKGROUND: Hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are related conditions with similar clinical features of variable severity. The objective of this systematic review is to evaluate the benefits and harms of available interventions for HUS and TTP. SELECTION CRITERIA FOR STUDIES: MEDLINE (1966 to June 2006), EMBASE (1980 to June 2006), the Cochrane Central Register, conference proceedings, and reference lists were searched to find randomized controlled trials (RCTs) of any intervention for HUS or TTP in patients of all ages selected for inclusion for this systematic review. INTERVENTIONS: Trials that compared an intervention with placebo, an intervention with supportive therapy, or one or more different interventions for HUS or TTP. OUTCOMES: For TTP trials, failure of remission at 2 weeks or less and at 1 month or longer, all-cause mortality rate, and relapse rate. For HUS trials, all-cause mortality, chronic reduced kidney function, and persistent proteinuria or hypertension at last follow-up. RESULTS: For TTP in adults, we found 6 RCTs of 331 patients. Two trials compared plasma infusion with plasma exchange using fresh frozen plasma and showed failure of remission at 2 weeks (2 trials, 140 patients; relative risk, 2.87; 95% confidence interval, 1.41 to 5.84), and all-cause mortality (relative risk, 1.91; 95% confidence interval, 1.09 to 3.33) occurred more frequently in the plasma infusion group. Three trials compared plasma exchange using cryosupernatant plasma with plasma exchange using fresh frozen plasma, and a meta-analysis of these trials showed no difference. Seven RCTs in 476 young children with postdiarrheal HUS have been conducted. None of the evaluated interventions (fresh frozen plasma transfusion, heparin with or without urokinase or dipyridamole, Shiga toxin-binding protein, and steroid) were superior to supportive therapy alone for any outcomes. LIMITATIONS: Limitations of this review include the small number and suboptimal quality of reporting of included trials, possibility of publication bias, small number of participants with atypical HUS, and failure to report results for patients with atypical and typical HUS separately. CONCLUSIONS: No additional therapy has been shown to increase efficacy over plasma exchange for TTP. No intervention has been shown to be superior to supportive therapy in patients with postdiarrheal HUS.

PMID: 18950913 [PubMed - indexed for MEDLINE]

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Intravenous versus oral iron supplementation for the treatment of anemia in CKD: systematic review and meta-analysis.

Am J Kidney Dis. 2008 Nov;52(5):897-906

Authors: Rozen-Zvi B, Gafter-Gvili A, Paul M, Leibovici L, Shpilberg O, Gafter U

BACKGROUND: Iron supplementation is essential for the treatment of patients with anemia of chronic kidney disease (CKD). It is not clear which is the best method of iron administration. STUDY DESIGN: Systematic review and meta-analysis. A search was performed until January 2008 of MEDLINE, Cochrane Central Register of Controlled Trials, conference proceedings in nephrology, and reference lists of included trials. SETTING & POPULATION: Patients with CKD (stages III to V). We included dialysis patients and patients with CKD not on dialysis therapy (hereafter referred to as patients with CKD). SELECTION CRITERIA FOR STUDIES: We included all randomized controlled trials regardless of publication status or language. INTERVENTION: Intravenous (IV) versus oral iron supplementation. OUTCOMES MEASURES: Primary outcomes assessed: absolute hemoglobin (Hb) level or change in Hb level from baseline. We also assessed all-cause mortality, erythropoiesis-stimulating agent requirement, adverse events, ferritin level, and need for renal replacement therapy in patients with CKD. RESULTS: 13 trials were identified, 6 including patients with CKD and 7 including dialysis patients. Compared with oral iron, there was a significantly greater Hb level in dialysis patients treated with IV iron (weighted mean difference, 0.83 g/dL; 95% confidence interval, 0.09 to 1.57). Meta-regression showed a positive association between Hb level increase and IV iron dose administered and a negative association with baseline Hb level. For patients with CKD, there was a small but significant difference in Hb level favoring the IV iron group (weighted mean difference, 0. 31 g/dL; 95% confidence interval, 0.09 to 0. 53). Data for all-cause mortality were sparse, and there was no difference in adverse events between the IV- and oral-treated patients. LIMITATIONS: There was significant heterogeneity between trials. Follow-up was limited to 2 to 3 months. CONCLUSIONS: Our review shows that patients on hemodialysis therapy have better Hb level response when treated with IV iron. For patients with CKD, this effect is small.

PMID: 18845368 [PubMed - indexed for MEDLINE]

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Management of hyperuricemia and gout in CKD.

Am J Kidney Dis. 2008 Nov;52(5):994-1009

Authors: Gaffo AL, Saag KG

PMID: 18971014 [PubMed - indexed for MEDLINE]

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Neutrophil gelatinase-associated lipocalin (NGAL) as a marker of kidney damage.

Am J Kidney Dis. 2008 Sep;52(3):595-605

Authors: Bolignano D, Donato V, Coppolino G, Campo S, Buemi A, Lacquaniti A, Buemi M

Neutrophil gelatinase-associated lipocalin (NGAL) is a protein belonging to the lipocalin superfamily initially found in activated neutrophils, in accordance with its role as an innate antibacterial factor. However, it subsequently was shown that many other types of cells, including in the kidney tubule, may produce NGAL in response to various injuries. The increase in NGAL production and release from tubular cells after harmful stimuli of various kinds may have self-defensive intent based on the activation of specific iron-dependent pathways, which in all probability also represent the mechanism through which NGAL promotes kidney growth and differentiation. NGAL levels predict the future appearance of acute kidney injury after treatments potentially detrimental to the kidney and even the acute worsening of unstable nephropathies. Furthermore, recent evidence also suggests that NGAL somehow may be involved in the pathophysiological process of chronic renal diseases, such as polycystic kidney disease and glomerulonephritis. NGAL levels clearly correlate with severity of renal impairment, probably expressing the degree of active damage underlying the chronic condition. For all these reasons, NGAL may become one of the most promising next-generation biomarkers in clinical nephrology and beyond.

PMID: 18725016 [PubMed - indexed for MEDLINE]

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Timing of renal replacement therapy initiation in acute renal failure: a meta-analysis.

Am J Kidney Dis. 2008 Aug;52(2):272-84

Authors: Seabra VF, Balk EM, Liangos O, Sosa MA, Cendoroglo M, Jaber BL

BACKGROUND: Some studies have suggested that early institution of renal replacement therapy (RRT) might be associated with improved outcomes in patients with acute renal failure (ARF). STUDY DESIGN: A systematic review and meta-analysis of randomized controlled trials and cohort comparative studies to assess the effect of early RRT on mortality in patients with ARF. SETTING & POPULATION: Hospitalized adult patients with ARF. SELECTION CRITERIA FOR STUDIES: We searched several databases for studies that compared the effect of "early" and "late" RRT initiation on mortality in patients with ARF. We included studies of various designs. INTERVENTION: Early RRT as defined in the individual studies. OUTCOMES: The primary outcome measure was the effect of early RRT on mortality stratified by study design. The pooled risk ratio (RR) for mortality was compiled using a random-effects model. Heterogeneity was evaluated by means of subgroup analysis and meta-regression. RESULTS: We identified 23 studies (5 randomized or quasi-randomized controlled trials, 1 prospective and 16 retrospective comparative cohort studies, and 1 single-arm study with a historic control group). By using meta-analysis of randomized trials, early RRT was associated with a nonsignificant 36% mortality risk reduction (RR, 0.64; 95% confidence interval, 0.40 to 1.05; P = 0.08). Conversely, in cohort studies, early RRT was associated with a statistically significant 28% mortality risk reduction (RR, 0.72; 95% confidence interval, 0.64 to 0.82; P < 0.001). The overall test for heterogeneity among cohort studies was significant (P = 0.005). Meta-regression yielded no significant associations; however, early dialysis therapy was associated more strongly with lower mortality in smaller studies (n < 100) by means of subgroup analysis. LIMITATIONS: Paucity of randomized controlled trials, use of variable definitions of early RRT, and publication bias preclude definitive conclusions. CONCLUSION: This hypothesis-generating meta-analysis suggests that early initiation of RRT in patients with ARF might be associated with improved survival, calling for an adequately powered randomized controlled trial to address this question.

PMID: 18562058 [PubMed - indexed for MEDLINE]

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A review of drug-induced hyponatremia.

Am J Kidney Dis. 2008 Jul;52(1):144-53

Authors: Liamis G, Milionis H, Elisaf M

Hyponatremia (defined as a serum sodium level < 134 mmol/L) is the most common electrolyte abnormality in hospitalized patients. Certain drugs (eg, diuretics, antidepressants, and antiepileptics) have been implicated as established causes of either asymptomatic or symptomatic hyponatremia. However, hyponatremia occasionally may develop in the course of treatment with drugs used in everyday clinical practice (eg, newer antihypertensive agents, antibiotics, and proton pump inhibitors). Physicians may not always give proper attention in time to undesirable drug-induced hyponatremia. Effective clinical management can be handled through awareness of the adverse effect of certain pharmaceutical compounds on serum sodium levels. Here, we review clinical information about the incidence of hyponatremia associated with specific drug treatment and discuss the underlying pathophysiologic mechanisms.

PMID: 18468754 [PubMed - indexed for MEDLINE]

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