Carlos E. Palant

Outcomes following diagnosis of acute renal failure in U.S. veterans: focus on acute tubular necrosis

When patients develop acute kidney injury, a small fraction of them will develop end-stage renal disease later. The severity of renal impairment in the remaining patients is uncertain because studies have not carefully examined renal function over time or the precise timing of entry into a late stage of chronic kidney disease. To determine these factors, we used a United States Department of Veterans Affairs database to ascertain long-term renal function in 113,272 patients. Of these, 44,377 had established chronic kidney disease and were analyzed separately. A cohort of 63,491 patients was hospitalized for acute myocardial infarction or pneumonia and designated as controls. The remaining 5,404 patients had diagnostic codes indicating acute renal failure or acute tubular necrosis. Serum creatinine, estimated glomerular filtration rates, and dates of death over a 75-month period were followed. Renal function deteriorated over time in all groups, but with significantly greater severity in those who had acute renal failure and acute tubular necrosis compared to controls. Patients with acute kidney injury, especially those with acute tubular necrosis, were more likely than controls to enter stage 4 chronic kidney disease, but this entry time was similar to that of patients who initially had chronic kidney disease. The risk of death was elevated in those with acute kidney injury and chronic kidney disease compared to controls after accounting for covariates. We found that patients who had an episode of acute tubular necrosis were at high risk for the development of stage 4 disease and had a reduced survival time when compared to control patients.

Association between AKI and Long-Term Renal and Cardiovascular Outcomes in United States Veterans

BACKGROUND AND OBJECTIVES AKI is associated with major adverse kidney events (MAKE): death, new dialysis, and worsened renal function. CKD (arising from worsened renal function) is associated with a higher risk of major adverse cardiac events (MACE): myocardial infarction (MI), stroke, and heart failure. Therefore, the study hypothesis was that veterans who develop AKI during hospitalization for an MI would be at higher risk of subsequent MACE and MAKE. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Patients in the Veterans Affairs (VA) database who had a discharge diagnosis with International Classification of Diseases, Ninth Revision, code of 584.xx (AKI) or 410.xx (MI) and were admitted to a VA facility from October 1999 through December 2005 were selected for analysis. Three groups of patients were created on the basis of the index admission diagnosis and serum creatinine values: AKI, MI, or MI with AKI. Patients with mean baseline estimated GFR<45 ml/min per 1.73 m(2) were excluded. The primary outcomes assessed were mortality, MAKE, and MACE during the study period (maximum of 6 years). The combination of MAKE and MACE-major adverse renocardiovascular events (MARCE)-was also assessed. RESULTS A total of 36,980 patients were available for analysis. Mean age±SD was 66.8±11.4 years. The most deaths occurred in the MI+AKI group (57.5%), and the fewest (32.3%) occurred in patients with an uncomplicated MI admission. In both the unadjusted and adjusted time-to-event analyses, patients with AKI and AKI+MI had worse MARCE outcomes than those who had MI alone (adjusted hazard ratios, 1.37 [95% confidence interval, 1.32 to 1.42] and 1.92 [1.86 to 1.99], respectively). CONCLUSIONS Veterans who develop AKI in the setting of MI have worse long-term outcomes than those with AKI or MI alone. Veterans with AKI alone have worse outcomes than those diagnosed with an MI in the absence of AKI.

The Acute Kidney Injury to Chronic Kidney Disease Transition: A Potential Opportunity to Improve Care in Acute Kidney Injury

Recent controlled trials, epidemiological analyses and basic research studies offer a comprehensive view of the short and long-term clinical repercussion of de novo acute kidney injury or AKI. While most post-AKI patients recover their baseline renal function, a significant number, approximately ~20% of those affected, will go on to develop long term illness characterized by an increase in late stage CKD, cardiovascular complications, and increased death rates. When AKI occurs in hospitalized patients, selected demographic and laboratory results can be incorporated into risk calculators that identify those at higher risk for long-term complications. This review touches on some of the salient epidemiological studies of the AKI to CKD transition. It also focuses on certain recent advancements in our understanding of the biological and functional impact of AKI on the renal tubule repair mechanism, as well as the important role that genetic, epigenetic, biochemical and inflammatory events, seemingly beneficial to the re-establishment of normal renal function, can be offset by mediators of progressive fibrosis and irreversible structural changes. Characterization of basic processes that mediate the AKI to CKD transition reveals promising pharmacological and biological agents that hopefully will one day be used in the early stages of AKI to prevent its deadly consequences.

Long-term consequences of acute kidney injury in the perioperative setting.

Purpose of review Recent studies indicate that acute kidney injury (AKI) and chronic kidney disease (CKD) are interconnected syndromes. Although the majority of patients who suffer an episode of AKI will recover laboratory indices suggesting complete or near complete recovery of renal function, a significant portion of post-AKI survivors will develop major kidney events, including development of late-stage CKD, need for renal replacement therapies, and death. Recent findings Our review highlights epidemiology of adverse post-AKI events, association of AKI with late development of nonrenal adverse outcomes, use of bedside equations that facilitate prognostication of adverse renal outcomes of AKI, and how variability in serum creatinine values in individual patients, even among those with normal baseline renal function may indicate risk for the development of CKD. Use of common laboratory parameters such as serum creatinine and albumin, along with certain clinical and demographic markers, individualize patients at high risk of complications and in need of close postdischarge follow-up. Evidence that ‘organ crosstalk’ following a major AKI episode may increase the risk of heart failure, stroke, and hypertension, places its survivors in a special patient category deserving active efforts to minimize risk for cardiovascular events. Summary AKI is a major cause for acute in-hospital mortality and development of both late-stage CKD and cardiovascular events. Perioperative care to prevent AKI must challenge the notion that a single normal point of contact serum creatinine value substantially reduces the likelihood of its occurrence.

Impact of Acute Kidney Injury in Patients Hospitalized With Pneumonia.

Objectives: Pneumonia is a common cause of hospitalization and can be complicated by the development of acute kidney injury. Acute kidney injury is associated with major adverse kidney events (death, dialysis, and durable loss of renal function [chronic kidney disease]). Because pneumonia and acute kidney injury are in part mediated by inflammation, we hypothesized that when acute kidney injury complicates pneumonia, major adverse kidney events outcomes would be exacerbated. We sought to assess the frequency of major adverse kidney events after a hospitalization for either pneumonia, acute kidney injury, or the combination of both. Design and Setting: We conducted a retrospective database analysis of the national Veterans Affairs database for patients with a admission diagnosis of International Classification of Diseases-9 code 584.xx (acute kidney injury) or 486.xx (pneumonia) between October 1, 1999, and December 31, 2005. Three groups of patients were created, based on the diagnosis of the index admission and serum creatinine values: 1) acute kidney injury, 2) pneumonia, and 3) pneumonia with acute kidney injury. Patients with mean baseline estimated glomerular filtration rate less than 45 mL/min/1.73 m2 were excluded. Measurements and Main Results: The primary endpoint was major adverse kidney events defined as the composite of death, chronic dialysis, or a permanent loss of renal function after the primary discharge. The observations of 54,894 subjects were analyzed. Mean age was 68.7 ± 12.3 years. The percentage of female was 2.4, 73.3% were Caucasian, and 19.7% were African-American. Differences across the three diagnostic groups were significant for death, 25% decrease in estimated glomerular filtration rate from baseline, major adverse kidney events following admission, and major adverse kidney events during admission (all p < 0.0001). Death alone and major adverse kidney events after discharge were most common in the pneumonia + acute kidney injury group (51% died and 62% reached major adverse kidney events). In both unadjusted and adjusted time to event analyses, patients with pneumonia + acute kidney injury were most likely to die or reach major adverse kidney events. Conclusions: When acute kidney injury accompanies pneumonia, postdischarge outcomes are worse than either diagnosis alone. Patients who survive a pneumonia hospitalization and develop acute kidney injury are at high risk for major adverse kidney events including death and should receive careful follow-up.

High serum creatinine nonlinearity: a renal vital sign?

Patients with chronic kidney disease (CKD) may have nonlinear serum creatinine concentration (SC) trajectories, especially as CKD progresses. Variability in SC is associated with renal failure and death. However, present methods for measuring SC variability are unsatisfactory because they blend information about SC slope and variance. We propose an improved method for defining and calculating a patients SC slope and variance so that they are mathematically distinct, and we test these methods in a large sample of US veterans, examining the correlation of SC slope and SC nonlinearity (SCNL) and the association of SCNL with time to stage 4 CKD (CKD4) and death. We found a strong correlation between SCNL and rate of CKD progression, time to CKD4, and time to death, even in patients with normal renal function. We therefore argue that SCNL may be a measure of renal autoregulatory dysfunction that provides an early warning sign for CKD progression.

Acute Kidney Injury and CKD: No Respite for a Weary Kidney

In the Department of Veterans Affairs system, the largest health care organization in the United States, acute kidney injury (AKI) was the seventh most frequent cause for medical hospitalization from 2001 through 2003. Current data suggest that up to 20% of patients who have AKI will develop late-stage chronic kidney disease (CKD), and notable risk factors for kidney failure subsequent to AKI include preexisting CKD, older age, and diabetes mellitus. When these and other traditional AKI risk indicators are considered, especially in a larger, more demographically mixed population, which risk factors emerge as critically important? In this issue of AJKD, 2 meta-analyses that together include almost 1.3 million patients, provide important insights into this question. These metaanalyses examined the incidence and risk factors for developing AKI in relation to pre-existing decreased estimated glomerular filtration rate (eGFR); the presence of albuminuria; age, race, and sex; and diabetes and hypertension. Among the risk factors examined, albuminuria and decreased eGFR emerged as the strongest predictors of AKI. Over a mean follow-up period of 4 years, a urinary albumin-creatinine ratio (ACR) of 300 mg/g was associated with a hazard ratio (HR) for AKI of 2.73 (95% confidence interval [CI], 2.18-3.43) as compared with an ACR of 5 mg/g. With respect to level of kidney function, patients with an eGFR of 45 mL/min/1.73 m had an adjusted HR for AKI of 3.35 (95% CI, 2.75-4.07) compared with patients having an eGFR of 80 mL/min/1.73 m. Other risk factors were weaker in comparison to albuminuria and decreased eGFR. The remainder of this editorial considers these findings from a physiological vantage point, their significance to clinicians dealing with everyday clinical care decision making, and finally their implications regarding public health. Nephrologists recognize that regardless of the underlying cause of kidney disease, proteinuria is a significant risk factor for its progression. However, the link between proteinuria and AKI risk requires further study and an understanding of putative mechanisms. Multiple lines of experimental evidence show that

Acute Kidney Injury Recovery

BACKGROUND Acute kidney injury (AKI) is associated with both short- and long-term clinical consequences including progression to chronic kidney disease. Recovery of renal function has gained importance, as interventions to prevent or treat AKI are limited. Basing recovery on a return of serum creatinine values excludes mounting evidence that AKI, even when reversible, is a very serious clinical event that will result in a significant number of both renal and extra-renal complications such as late stage kidney disease, major cardiovascular events, and death. SUMMARY Development of a definition for renal recovery is critical to organizing research in AKI treatment. Assessment of serum creatinine remains the primary measure of renal recovery despite known limitations. Patterns of renal recovery are highly associated with clinical outcomes including survival. Additional research in basic mechanisms of renal injury and repair is needed to help formulate a more comprehensive assessment of renal recovery. Novel biomarkers for assessment of AKI may also aid in the determination of renal recovery. Key Messages: (1) The concept of acute kidney disease (7-90 days post AKI) should direct clinicians as well as researchers to pay attention to a critical time period for renal recovery in which interventions may alter long-term outcomes. (2) Recent studies have evaluated AKI recovery patterns, or trajectories, and is an important step towards defining long-term prognosis. (3) Serum creatinine alone is not a reliable marker of recovery after AKI and is associated with poor clinical outcomes despite a return to baseline levels. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply. Published by S. Karger AG, Basel.

Sequelae of AKI

Large epidemiologic studies in a variety of patient populations reveal increased morbidity and mortality that occur months to years after an episode of acute kidney injury (AKI). Even milder forms of AKI have increased associated morbidity and mortality. Residual confounding may account for these findings, but considering the huge number of individuals afflicted with AKI, the sequelae of AKI may be a very large public health burden. AKI may simply be a marker for increased risk, but there is increasing evidence that it is part of the causal pathway to chronic kidney disease. These studies have upended the traditional view that AKI survivors who returned to baseline, or near baseline renal function, do not suffer additional long-term consequences. Recovery of renal function after AKI, short of independence from renal replacement therapy, is yet to be clearly defined but may be of significant importance in the management of AKI survivors. The association between AKI in patients who undergo cardiac surgery and clinical outcomes is of considerable importance to clinicians, surgeons, and anesthesiologists alike and is a major focus of this review.