The aftermath of acute kidney injury: a narrative review of long-term mortality and renal function.

Acute kidney injury (AKI) is a frequent complication of hospitalization and is associated with an increased risk of chronic kidney disease (CKD), end-stage renal disease (ESRD), and mortality. While AKI is a known risk factor for short-term adverse outcomes, more recent data suggest that the risk of mortality and renal dysfunction extends far beyond hospital discharge. However, determining whether this risk applies to all patients who experience an episode of AKI is difficult. The magnitude of this risk seems highly dependent on the presence of comorbid conditions, including cardiovascular disease, hypertension, diabetes mellitus, preexisting CKD, and renal recovery. Furthermore, these comorbidities themselves lead to structural renal damage due to multiple pathophysiological changes, including glomeruloscleroses and tubulointerstitial fibrosis, which can lead to the loss of residual capacity, glomerular hyperfiltration, and continued deterioration of renal function. AKI seems to accelerate this deterioration and increase the risk of death, CDK, and ESRD in most vulnerable patients. Therefore, we strongly advocate adequate hemodynamic monitoring and follow-up in patients susceptible to renal dysfunction. Additionally, other potential renal stressors, including nephrotoxic medications and iodine-containing contrast fluids, should be avoided. Unfortunately, therapeutic interventions are not yet available. Additional research is warranted and should focus on the prevention of AKI, identification of therapeutic targets, and provision of adequate follow-up to those who survive an episode of AKI.

Renal function at 1 year after cardiac transplantation rather than acute kidney injury is highly associated with long-term patient survival and loss of renal function - a retrospective cohort study.

This study aimed to assess the association between acute kidney injury (AKI), renal function 1 year after transplantation, and long-term adverse outcomes after cardiac transplantation. A retrospective cohort study was performed including 471 adult cardiac transplantation recipients that survived the first postoperative year between 1984 and 2012. Primary outcome variables were long-term overall and renal survival. During the first postoperative week, 40% (n = 188) of the recipients developed AKI stage I, 22% (n = 104) stage II, and 13% (n = 63) stage III, and 4% (n = 17) required temporary renal replacement therapy (RRT). No crude association was found between the development of AKI and long-term mortality (P = 0.50) or chronic RRT dependence (P = 0.27). In multivariable analysis, only AKI requiring RRT was associated with an increased risk for mortality (HR = 2.59, 95% CI = 1.17-5.73) and chronic RRT dependence (HR = 13.14, 95% CI = 3.26-52.92). While less severe episodes of AKI did not affect the recipient's long-term prognosis, renal function 1 year after transplantation had a strong association with long-term outcome. An eGFR <30 ml/min/1.73 was independently associated with mortality (HR = 2.69, 95% CI = 1.68-4.32) and an eGFR <60 ml/min/1.73 with chronic RRT dependence (eGFR 30-59: HR = 3.57, 95% CI = 1.41-9.01; eGFR <30: HR = 16.53, 95% CI = 5.72-47.78). In conslusion, besides AKI requiring RRT, less severe episodes of AKI have limited implications for the recipient's prognosis and long-term outcome after cardiac transplantation is strongly determined by the degree of renal impairment 1 year after transplantation.

Acute Kidney Injury as a Complication of Cardiac Transplantation: Incidence, Risk Factors, and Impact on 1-year Mortality and Renal Function.

BACKGROUND: Although chronic deterioration in renal function is frequently seen after cardiac transplantation, which is partly explained by the use of calcineurin inhibitors, data on the consequences of acute kidney injury (AKI) after cardiac transplantation are scarce. In the current study, the incidence of AKI and its impact on mortality and renal function was evaluated. METHODS: Five hundred thirty-one cardiac transplant recipients (age ≥18 years) were evaluated for the postoperative incidence of AKI defined by the Kidney Disease Improving Global Outcome criteria. Secondary outcomes were renal function and mortality during the first postoperative year. RESULTS: Overall, 405 (76%) recipients met the AKI criteria of which 211 (40%) had AKI stage I, 119 (22%) stage II, 75 (14%) stage III, and 25 patients (5%) required renal replacement therapy (RRT). One-year mortality rates in patients without AKI, stages I, II, and III were 4.8%, 7.6%, 11.8%, and 14.7%, respectively (log-rank test for trend, P = 0.008). In patients that required RRT 1-year mortality was 28.2% (log-rank test P = 0.001). In multivariable analysis only AKI requiring RRT was an independent predictor of 1-year mortality (hazard ratio, 2.75; P = 0.03). Improvement in renal function, compared with baseline values, occurred in 27% of recipients 1 month after transplantation. This was less likely to occur after previous AKI (P ≤ 0.04). The AKI stages I to III were independently proportionally associated with a worse renal function 1 year after transplantation (P ≤ 0.01). CONCLUSIONS: Acute kidney injury is highly frequent after cardiac transplantation, and the stage of AKI is associated with increased mortality and impaired renal function in the first postoperative year.

Long-term sequelae of severe acute kidney injury in the critically ill patient without comorbidity: a retrospective cohort study.

BACKGROUND AND OBJECTIVES: Acute kidney injury (AKI) necessitating renal replacement therapy (RRT) is associated with high mortality and increased risk for end stage renal disease. However, it is unknown if this applies to patients with a preliminary unremarkable medical history. The purpose of this study was to describe overall and renal survival in critically ill patients with AKI necessitating RRT stratified by the presence of comorbidity. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: A retrospective cohort study was performed, between 1994 and 2010, including all adult critically ill patients with AKI necessitating RRT, stratified by the presence of comorbidity. Logistic regression, survival curve and cox proportional hazards analyses were used to evaluate overall and renal survival. Standardized mortality rate (SMR) analysis was performed to compare long-term survival to the predicted survival in the Dutch population. RESULTS: Of the 1067 patients included only 96(9.0%) had no comorbidity. Hospital mortality was 56.6% versus 43.8% in patients with and without comorbidity, respectively. In those who survived hospitalization 10-year survival was 45.0% and 86.0%, respectively. Adjusted for age, sex and year of treatment, absence of comorbidity was not associated with hospital mortality (OR=0.74, 95%-CI=0.47-1.15), while absence of comorbidity was associated with better long-term survival (adjusted HR=0.28, 95%-CI = 0.14-0.58). Compared to the Dutch population, patients without comorbidity had a similar mortality risk (SMR=1.6, 95%-CI=0.7-3.2), while this was increased in patients with comorbidity (SMR=4.8, 95%-CI=4.1-5.5). Regarding chronic dialysis dependency, 10-year renal survival rates were 76.0% and 92.9% in patients with and without comorbidity, respectively. Absence of comorbidity was associated with better renal survival (adjusted HR=0.24, 95%-CI=0.07-0.76). CONCLUSIONS: While hospital mortality remains excessively high, the absence of comorbidity in critically ill patients with RRT-requiring AKI is associated with a relative good long-term prognosis in those who survive hospitalization.

Time of injury affects urinary biomarker predictive values for acute kidney injury in critically ill, non-septic patients.

BACKGROUND: The predictive value of acute kidney injury (AKI) urinary biomarkers may depend on the time interval following tubular injury, thereby explaining in part the heterogeneous performance of these markers that has been reported in the literature. We studied the influence of timing on the predictive values of tubular proteins, measured before the rise of serum creatinine (SCr) in critically ill, non-septic patients. METHODS: Seven hundred adult critically ill patients were prospectively included for urine measurements at four time-points prior to the rise in serum creatinine (T = 0, -16, -20 and -24 h). Patients with sepsis and or AKI at ICU entry were excluded. The urinary excretion of the proteins, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1), which are up-regulated in the distal and proximal tubules, respectively, were measured as well as the constitutive cytoplasmatic enzymes, π- and α-glutathione-S-transferase (GST), which are released by the distal and proximal tubules, respectively. RESULTS: Five hundred and forty-three subjects were eligible for further analyses; however, 49 developed AKI in the first 48 h. Both NGAL (P = 0.001 at T = -24 vs. non-AKI patients) and KIM-1 (P < 0.0001 at T = 0 vs. non-AKI patients) concentrations gradually increased until AKI diagnosis, whereas π- and α-GST peaked at T = -24 before AKI (P = 0.006 and P = 0.002, respectively vs. non-AKI patients) and showed a rapid decline afterwards. The predictive values at T = -24 prior to AKI were modest for π- and α-GST, whereas NGAL sufficiently predicted AKI at T = -24 and its predictive power improved as the time interval to AKI presentation decreased (area under the receiver operating characteristic curve; AUC = 0.79, P < 0.0001). KIM-1 was a good discriminator at T = 0 only (AUC = 0.73, P < 0.0001). CONCLUSIONS: NGAL, KIM-1, pi- and alpha-GST displayed unique and mutually incomparable time dependent characteristics during the development of non-sepsis related AKI. Therefore, the time-relationship between the biomarker measurements and the injurious event influences the individual test results.

Novel biomarkers for the prediction of acute kidney injury in patients undergoing liver transplantation.

AIM: Because of the delayed rise of serum creatinine concentrations, novel biomarkers such as NGAL, GST and KIM-1 are proposed to detect acute kidney injury (AKI). In this study we evaluated these biomarkers. MATERIALS & METHODS: Twenty-six consecutive adult liver transplantations were evaluated. Markers were measured at four different time points during an intensive care unit admission. RESULTS: Plasma NGAL detected AKI with an optimal area under the curve at 8 h after admission (0.86; p = 0.004) and at 4 h after admission for urinary NGAL (0.80; p = 0.012). The other markers failed to detect AKI. CONCLUSION: NGAL is a promising biomarker for detecting AKI in patients after liver transplantation.

Impaired kidney function at hospital discharge and long-term renal and overall survival in patients who received CRRT.

BACKGROUND AND OBJECTIVES: Critically ill patients with AKI necessitating renal replacement therapy (RRT) have high in-hospital mortality, and survivors are at risk for kidney dysfunction at hospital discharge. The objective was to evaluate the association between impaired kidney function at hospital discharge with long-term renal and overall survival. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Degree of kidney dysfunction in relation to long-term effects on renal survival and patient mortality was investigated in a retrospective cohort study of 1220 adults admitted to an intensive care unit who received continuous RRT between 1994 and 2010. RESULTS: After hospital discharge, median follow-up of survivors (n=475) was 8.5 years (range, 1-17 years); overall mortality rate was 75%. Only 170 (35%) patients were discharged with an estimated GFR (eGFR) >60 ml/min per 1.73 m(2). Multivariate proportional hazards regression analysis demonstrated that age, nonsurgical type of admission, preexisting kidney disease, malignancy, and eGFR of 29-15 ml/min per 1.73 m(2) (hazard ratio [HR], 1.62; 95% confidence interval [CI], 1.01 to 2.58) and eGFR <15 ml/min per 1.73 m(2) (HR, 1.93; 95% CI, 1.23 to 3.02) at discharge were independent predictors of increased mortality. Renal survival was significantly associated with degree of kidney dysfunction at discharge. An eGFR of 29-15 ml/min per 1.73 m(2) (HR, 26.26; 95% CI, 5.59 to 123.40) and <15 ml/min per 1.73 m(2) (HR, 172.28; 95% CI, 37.72 to 786.75) were independent risk factors for initiation of long-term RRT. CONCLUSIONS: Most critically ill patients surviving AKI necessitating RRT have impaired kidney function at hospital discharge. An eGFR <30 ml/min per 1.73 m(2) is a strong risk factor for decreased long-term survival and poor renal survival.

Determinants of renal function at hospital discharge of patients treated with renal replacement therapy in the intensive care unit.

PURPOSE: Identification of risk factors for impaired renal function at hospital discharge in critically ill patients with acute kidney injury (AKI) requiring renal replacement therapy (RRT). METHODS: A single-center retrospective cohort study was performed evaluating demographic and clinical parameters as potential risk factors for a modest to severely impaired renal function at hospital discharge in patients with AKI requiring RRT in the intensive care unit. RESULTS: Of the 353 patients in our cohort, 90 (25.5%) patients had pre-existing chronic kidney disease (CKD). An estimated glomerular filtration rate (eGFR) ≤60 mL min(-1) 1.73 m(-2) at hospital discharge occurred in 64.0% of which 63.7% without known renal impairment before hospital admission and 8.2% of all cases left the hospital dialysis-dependent. Multivariable logistic regression showed that age (OR = 1.051, P < .001), serum creatinine concentration at start of RRT (OR = 1.004, P < .001) and administration of iodine-containing contrast fluid (OR = 0.830, P = .045) were associated with an eGFR ≤60 mL min(-1) 1.73 m(-2). Furthermore, a medical history of CKD (OR = 5.865, P < .001) was associated with dialysis dependence. CONCLUSIONS: Elderly and patients with pre-existing CKD are at a high risk for modest to severely impaired renal function at hospital discharge after AKI requiring RRT.