Creatinine generation is reduced in patients requiring continuous venovenous hemodialysis and independently predicts mortality

Wilson, F. Perry; Sheehan, Jessica M.; Mariani, Laura; Berns, Jeffrey S.

doi:10.1093/ndt/gfr809

Cited by 45 publications

(36 citation statements)

References 28 publications

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“…Critically ill patients who have suffered AKI, experienced a significant decrease in creatinine generation [10,11] not only during their illness but also at the time of hospital discharge, and then weeks into their recovery. This means it is likely that estimates of creatinine generation, implicit in eGFR equations, are poorly calibrated to this group; eGFR could therefore significantly overestimate true GFR in many survivors of critical illness for a significant period after the acute illness [5].…”

Section: Discussionmentioning

confidence: 99%

Critically Ill Patients Requiring Acute Renal Replacement Therapy Are at an Increased Risk of Long-Term Renal Dysfunction, but Rarely Receive Specialist Nephrology Follow-Up

Kirwan¹,

Blunden

Dobbie

et al. 2015

Nephron

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Background: Episodes of acute kidney injury (AKI) have been associated with the development of chronic kidney disease (CKD). However, follow-up pathways for patients who have survived AKI complicating critical illness are not well established. We hypothesised that patients who had AKI requiring renal replacement therapy (RRT) in intensive care are at risk of CKD, but are rarely referred for nephrology follow-up at hospital discharge. Methods: We performed a retrospective analysis of all patients who survived AKI requiring renal replacement therapy in intensive care units (ICUs) in the East London region, examining renal function at baseline, hospital discharge and 3-6 months follow-up. We excluded patients who were known to renal services prior to index admission. Results: From 5,544 critical care admissions, we identified 219 patients who survived to be discharged, having undergone RRT for AKI, that were not previously known to renal services. Of these, 124 (57%) had creatinine measured within 3-6 months after discharge, 104 having a pre-morbid baseline for comparison. Only 26 patients (12%) received specialist nephrology follow-up. At 3-6 months follow-up, the estimated glomerular filtration rate was significantly lower than baseline (48 vs. 60 ml/min/1.73 m²; p < 0.001), with the prevalence of CKD stage III-V rising from 49 to 70% (p < 0.001). Conclusions: Follow-up of patients who required RRT for AKI in ICU is inconsistent despite evidence of a significant increase in the prevalence of CKD. There is strong justification for the development of robust pathways to identify survivors of AKI in order to detect and manage CKD and its complications.

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Section: Discussionmentioning

confidence: 99%

Critically Ill Patients Requiring Acute Renal Replacement Therapy Are at an Increased Risk of Long-Term Renal Dysfunction, but Rarely Receive Specialist Nephrology Follow-Up

Kirwan¹,

Blunden

Dobbie

et al. 2015

Nephron

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“…At higher creatinine generation rate, the rate of creatinine rise in AKI is greater. Creatinine generation rate is a proxy for muscle mass, and higher levels may identify a healthier subset of patients with AKI (31). It has been suggested that creatinine generation rate may be increased by catabolic states, although this has not been measured in AKI populations to our knowledge (32).…”

Section: Creatinine Kinetics and Dialysis In Akimentioning

confidence: 99%

Dialysis versus Nondialysis in Patients with AKI

Wilson

Yang

Machado

et al. 2014

Clinical Journal of the American Society of Nephrology

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Background and objectives The benefit of the initiation of dialysis for AKI may differ depending on patient factors, but, because of a lack of robust evidence, the decision to initiate dialysis for AKI remains subjective in many cases. Prior studies examining dialysis initiation for AKI have examined outcomes of dialyzed patients compared with other dialyzed patients with different characteristics. Without an adequate nondialyzed control group, these studies cannot provide information on the benefit of dialysis initiation. To determine which patients would benefit from initiation of dialysis for AKI, a propensity-matched cohort study was performed among a large population of patients with severe AKI.Design, setting, participants, & measurements Adults admitted to one of three acute care hospitals within the University of Pennsylvania Health System from January 1, 2004, to August 31, 2010, who subsequently developed severe AKI were included (n=6119). Of these, 602 received dialysis. Demographic, clinical, and laboratory variables were used to generate a time-varying propensity score representing the daily probability of initiation of dialysis for AKI. Not-yet-dialyzed patients were matched to each dialyzed patient according to day of AKI and propensity score. Proportional hazards analysis was used to compare time to all-cause mortality among dialyzed versus nondialyzed patients across a spectrum of prespecified variables.Results After propensity score matching, covariates were well balanced between the groups, and the overall hazard ratio for death in dialyzed versus nondialyzed patients was 1.01 (95% confidence interval, 0.85 to 1.21; P=0.89). Serum creatinine concentration modified the association between dialysis and survival, with a 20% (95% confidence interval, 9% to 30%) greater survival benefit from dialysis for each 1-mg/dl increase in serum creatinine concentration (P=0.001). This finding persisted after adjustment for markers of disease severity. Dialysis initiation was associated with more benefit than harm at a creatinine concentration$3.8 mg/dl.Conclusions Dialysis was associated with increased survival when initiated in patients with AKI who have a more elevated creatinine level but was associated with increased mortality when initiated in patients with lower creatinine concentrations.

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“…However, large improvements in GFR from baseline after critical illness would seem implausible, whereas large and sustained falls in creatinine generation have been shown in animal models of sepsis (14), patients with advanced CKD (15), and critically ill humans (16)(17)(18), with greatest decrease occurring in the sickest patients (16). Skeletal muscle is the major source of creatinine production, and critical illness is associated with profound loss of skeletal muscle protein (10,19,20), with muscle thickness steadily decreasing over time after ICU admission (10,21,22).…”

Section: Study Findingsmentioning

confidence: 99%

Serum Creatinine Changes Associated with Critical Illness and Detection of Persistent Renal Dysfunction after AKI

Prowle

Kolic²,

Purdell-Lewis³

et al. 2014

Clinical Journal of the American Society of Nephrology

137

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Background and objectives AKI is a risk factor for development or worsening of CKD. However, diagnosis of renal dysfunction by serum creatinine could be confounded by loss of muscle mass and creatinine generation after critical illness.Design, setting, participants, & measurements A retrospective, single center analysis of serum in patients surviving to hospital discharge with an intensive care unit admission of 5 or more days between 2009 and 2011 was performed.Results In total, 700 cases were identified, with a 66% incidence of AKI. In 241 patients without AKI, creatinine was significantly lower (P,0.001) at hospital discharge than admission (median, 0.61 versus 0.88 mg/dl; median decrease, 33%). In 160 patients with known baseline, discharge creatinine was significantly lower than baseline in all patients except those patients with severe AKI (Kidney Disease Improving Global Outcomes category 3), who had no significant difference. In a multivariable regression model, median duration of hospitalization was associated with a predicted 30% decrease (95% confidence interval, 8% to 45%) in creatinine from baseline in the absence of AKI; after allowing for this effect, AKI was associated with a 29% (95% confidence interval, 10% to 51%) increase in predicted hospital discharge creatinine. Using a similar model to exclude the confounding effect of prolonged major illness on creatinine, 148 of 700 patients (95% confidence interval, 143 to 161) would have eGFR,60 ml/min per 1.73 m 2 at hospital discharge compared with only 63 of 700 patients using eGFR based on unadjusted hospital creatinine (a 135% increase in potential CKD diagnoses; P,0.001).Conclusion Critical illness is associated with significant falls in serum creatinine that persist to hospital discharge, potentially causing inaccurate assessment of renal function at discharge, particularly in survivors of AKI. Prospective measurements of GFR and creatinine generation are required to confirm the significance of these findings.

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Creatinine generation is reduced in patients requiring continuous venovenous hemodialysis and independently predicts mortality

Abstract: Grading systems for severity of AKI fail to account for variation in CGR, limiting their ability to predict relevant outcomes. Calculation of CGR is superior to other risk metrics in predicting hospital mortality in this population.

Cited by 45 publications

References 28 publications

Critically Ill Patients Requiring Acute Renal Replacement Therapy Are at an Increased Risk of Long-Term Renal Dysfunction, but Rarely Receive Specialist Nephrology Follow-Up

Critically Ill Patients Requiring Acute Renal Replacement Therapy Are at an Increased Risk of Long-Term Renal Dysfunction, but Rarely Receive Specialist Nephrology Follow-Up

Dialysis versus Nondialysis in Patients with AKI

Serum Creatinine Changes Associated with Critical Illness and Detection of Persistent Renal Dysfunction after AKI

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