Verônica Torres da Costa e Silva

Performance of the third generation models of severity scoring systems (APACHE IV, SAPS 3 and MPM-III) in acute kidney injury critically ill patients

BACKGROUND Severity scores are useful to guarantee similar disease severity among groups in clinical trials and to enable comparison between different studies. The aim of this study was to assess the performance of the third generation models of severity scoring systems [simplified acute physiology score (SAPS) 3, acute physiology and chronic health evaluation (APACHE) IV and mortality probability model (MPM)-III] in acute kidney injury (AKI) patients in the intensive care unit (ICU). METHODS Three hundred and sixty-six consecutive AKI critically ill patients were prospectively assessed in six ICUs of an academic tertiary care center. Scores were applied on AKI diagnosis day (DD) and on the day of nephrology consultation (NCD). Discrimination was assessed by area under the receiver operating characteristic curve (AUCROC) and calibration by Hosmer-Lemeshow (HL) goodness-of-fit test. RESULTS Hospital mortality rate was 67.8%. SAPS 3 general and Central and South America (CSA) customized equations presented identical good discrimination (AUCROC curve: 0.80 on NCD) and satisfactory HL tests on both analyzed days (P > 0.100). CSA SAPS 3 equation predicted mortality more accurately [standardized mortality ratio (SMR) on NCD = 1.00 (95% confidence interval (CI) 0.84-1.34)]. APACHE IV and MPM-III scores presented similar discrimination compared to SAPS 3 on both analyzed days (P > 0.05). APACHE IV presented satisfactory HL tests over time (P > 0.100) but underestimated mortality [SMR on DD = 1.92 (95% CI 1.61-2.23); SMR on NCD = 1.46 (95% CI 1.48-1.96)]. MPM-III showed unsatisfactory HL test results (P = 0.027 on DD; P = 0.045 on NCD) and underestimated mortality [SMR on NCD = 2.09 (95% CI 1.48-1.96)]. CONCLUSIONS SAPS 3, especially the geographical customized equation, presented good discrimination and calibration performances, accurately predicting mortality in this group of AKI critically ill patients.

Sequential evaluation of prognostic models in the early diagnosis of acute kidney injury in the intensive care unit

General and specific severity scores for patients with acute kidney injury have significant limitations due in part to the diversity of methods that have been used. Here we prospectively validated five general (APACHE II, SAPS II, SOFA, LODS, and OSF) and three specific (SHARF, Liaño, and Mehta) scoring systems in 366 critically ill patients who developed acute kidney injury in the intensive care unit. Sequential scores in each system were determined on the day that acute kidney injury was diagnosed, on the day when acute kidney injury-specific score criteria were achieved, and on the day of initial nephrology consultation. Acute kidney injury, defined as an increase of 50% or more in the baseline serum creatinine, was mainly due to sepsis, and had an incidence of 19% and an overall 68% mortality. A progressive improvement in score performance was found. On the day of initial nephrology consultation, most scores showed a good performance and two indices (SAPS II and SHARF) achieved an area under the receiver operating characteristic curve above 0.80. Calibration was good on all three defining days, except for OSF when score criteria were achieved, and Mehta at the time of nephrology consultation. Our study shows that early and sequential evaluation is a better approach for prognostic scoring in critically ill patients who develop acute kidney injury.

Risk factors for vancomycin nephrotoxicity: still a matter of debate*.

Vancomycin is considered the drug of choice to treat infections caused by methicillin-resistant Staphylococcus aureus (1). Nephrotoxicity is a dreaded adverse effect of vancomycin use, but its prevalence, risk factors, and prognostic importance are still a matter of debate. Current guidelines recommend higher target vancomycin through levels (15–20 μg/mL) (1, 2) to overcome bacterial resistance and to assure treatment response. Consequently, higher vancomycin doses have been used, potentially increasing nephrotoxicity risk (3, 4). In this issue of Critical Care Medicine, Hanrahan et al (5) retrospectively assessed several risk factors for vancomycin nephrotoxicity (VN) in a cohort of critically ill patients. The prevalence of vancomycin-associated acute kidney injury (AKI) was 21%. The independent risk factors identified for VN using logistic regression analysis (LR) were longer therapy, simultaneous use of vasoactive drugs, higher trough serum concentrations, and intermittent infusion (InI). A strength of this study was its number of patients (n = 1,430), which was greater than in most previous surveys (4, 6). There was a 35% loss of patients due to missing data. Age, weight, and estimated glomerular filtration rate (eGFR) of the excluded and included patients were similar, minimizing potential selection bias. This timely article raises important aspects for consideration by future studies, especially those related to methodological aspects. The authors used the Risk, Injury, Failure, Loss, End-stage kidney disease (RIFLE) definition for AKI diagnosis, which considers changes in serum creatinine (SCr) and/or eGFR (7). Although newer AKI definitions, such as Acute Kidney Disease Network (AKIN) (8) and Kidney Disease Improving Global Outcomes (KDIGO) (9), have been proposed, the RIFLE criteria have been validated in several surveys assessing AKI in a variety of situations, generally using the SCr criteria (10). However, the formulas for eGFR have not been validated for AKI diagnosis, and the decreases in eGFR do not correspond to the increases in SCr in the RIFLE definition (11). The use of the RIFLE eGFR criterion might have overestimated the AKI prevalence in the present study. Additionally, the 24-hour period for the SCr measurements used for AKI diagnosis might be insufficient to differentiate VN from other transitory unrecorded renal insults, confounding AKI prevalence. There is no universally accepted definition of acute VN; instead, 50% increases in SCr or absolute increases greater than 0.5 mg/dL are used most frequently (4, 6, 12). The heterogeneity of the AKI definitions reported to assess VN has been a drawback to the comparison of different studies. RIFLE and AKIN definitions have been infrequently used, and no study has included the KDIGO definition (13). The most important risk factor for VN identified in the current study was InI, which is still a controversial point in the assessment of VN. It has been reported that continuous vancomycin infusion (CoI) achieves faster and more consistent therapeutic serum concentrations, reducing the development of antibiotic resistance (14). Some observational and retrospective studies have found that CoI is associated with less nephrotoxicity (12), whereas others have shown inconclusive results (15). Two randomized controlled trials (RCTs) assessed a small number of patients (16, 17), and the current guidelines for vancomycin therapy do not recommend the use of a CoI regimen (1, 2), considering the insufficient evidence supporting a definitive conclusion. An important limitation of the present study is that the infusion strategy groups were dissimilar, with more severely ill patients in the CoI group. This group showed higher Sequential Organ Failure Assessment scores, greater use of vasoactive drugs, and higher mortality. Those patients received a higher vancomycin dose, had a longer treatment period, disclosed a higher serum concentration level, and had a higher AKI prevalence on the bivariate analysis. The authors justify the increased odds ratio for nephrotoxicity found by LR in the InI group by the intersections between *See also p. 2527.

Prostatic surgery associated acute kidney injury

Acute kidney injury (AKI) is associated with extended hospital stays, high risks of in-hospital and long-term mortality, and increased risk of incident and progressive chronic kidney disease. Patients with urological diseases are a high-risk group for AKI owing to the coexistence of obstructive uropathy, older age, and preexistent chronic kidney disease. Nonetheless, precise data on the incidence and outcomes of postoperative AKI in urological procedures are lacking. Benign prostatic hyperplasia and prostate cancer are common diagnoses in older men and are frequently treated with surgical procedures. Whereas severe AKI after prostate surgery in general appears to be unusual, AKI associated with transurethral resection of the prostate (TURP) syndrome and with rhabdomyolysis (RM) after radical prostatectomy have been frequently described. The purpose of this review is to discuss the current knowledge regarding the epidemiology, risk factors, outcomes, prevention, and treatment of AKI associated with prostatic surgery. The mechanisms of TURP syndrome and RM following prostatic surgeries will be emphasized.

Evaluation of Intermittent Hemodialysis in Critically Ill Cancer Patients with Acute Kidney Injury Using Single-Pass Batch Equipment

Background Data on renal replacement therapy (RRT) in cancer patients with acute kidney injury (AKI) in the intensive care unit (ICU) is scarce. The aim of this study was to assess the safety and the adequacy of intermittent hemodialysis (IHD) in critically ill cancer patients with AKI. Methods and Findings In this observational prospective cohort study, 149 ICU cancer patients with AKI were treated with 448 single-pass batch IHD procedures and evaluated from June 2010 to June 2012. Primary outcomes were IHD complications (hypotension and clotting) and adequacy. A multiple logistic regression was performed in order to identify factors associated with IHD complications (hypotension and clotting). Patients were 62.2 ± 14.3 years old, 86.6% had a solid cancer, sepsis was the main AKI cause (51%) and in-hospital mortality was 59.7%. RRT session time was 240 (180–300) min, blood/dialysate flow was 250 (200–300) mL/min and UF was 1000 (0–2000) ml. Hypotension occurred in 25% of the sessions. Independent risk factors (RF) for hypotension were dialysate conductivity (each ms/cm, OR 0.81, CI 0.69–0.95), initial mean arterial pressure (each 10 mmHg, OR 0.49, CI 0.40–0.61) and SOFA score (OR 1.16, CI 1.03–1.30). Clotting and malfunctioning catheters (MC) occurred in 23.8% and 29.2% of the procedures, respectively. Independent RF for clotting were heparin use (OR 0.57, CI 0.33–0.99), MC (OR 3.59, CI 2.24–5.77) and RRT system pressure increase over 25% (OR 2.15, CI 1.61–4.17). Post RRT blood tests were urea 71 (49–104) mg/dL, creatinine 2.71 (2.10–3.8) mg/dL, bicarbonate 24.1 (22.5–25.5) mEq/L and K 3.8 (3.5–4.1) mEq/L. Conclusion IHD for critically ill patients with cancer and AKI offered acceptable hemodynamic stability and provided adequate metabolic control.

Assessment of Kidney Function in Patients With Cancer

Cancer patients are living longer. The sequelae of cancer treatment and the role of comorbid conditions present before the diagnosis, such as CKD, have been increasingly recognized. The interface between CKD and cancer is multifaceted. CKD is frequently observed in patients with cancer, and cancer treatment contributes to CKD development and progression. In addition, CKD has been recognized as an important risk factor for cancer development and reduced specific cancer survival. In this context, an accurate evaluation of the glomerular filtration rate (GFR) during oncologic treatment is pivotal and is used to define surgery strategies, program prophylactic management of contrasted examinations, make decisions on cisplatin eligibility, and adjust drug prescriptions, particularly chemotherapy agents. Although the most commonly used equations to estimate GFR based on serum creatinine levels in clinical practice (Cockcroft-Gault, Modification of Diet in Renal Disease Study, and CKD Epidemiology Collaboration equations) have not been validated in patients with cancer in large prospective studies, there is increasingly evidence supporting the use of CKD Epidemiology Collaboration equation to assess the GFR in patients with cancer, including for the use of chemotherapy prescriptions. Many patients with cancer may have changes in nutrition status and clearance measurements such as exogenous filtration markers might be extremely useful when clinical decisions differ depending on the GFR level. Future perspectives include the advent of new serum GFR biomarkers such as cystatin C, beta-trace protein, and beta-2 microglobulin as well as the GFR assessment by measuring total kidney parenchymal volume through image examinations.

Drug-Induced Acute Kidney Injury

Abstract The epidemiology of acute kidney injury (AKI) has changed remarkably over the last few decades. Currently a majority of affected patients are critically ill older individuals hospitalized in an intensive care unit (ICU) with comorbidities and multiple organ failure. In the ICU, either nephrotoxicity alone or, most commonly, associated with ischemia, has been a relevant related factor in the pathogenesis of AKI in almost half of the cases. Virtually all mechanisms or processes potentially leading to renal injury have been associated with drug nephrotoxicity: acute tubular cell injury, changes in renal hemodynamics, intratubular obstruction, acute interstitial nephritis, hypersensitivity vasculitis, thrombotic microangiopathy, osmotic nephrosis, and rhabdomyolysis. Measurement of serum creatinine always should be performed before administration of potentially nephrotoxic drugs, and even small increments in creatinine are an independent risk factor for increased mortality in hospitalized patients. The use of a nonnephrotoxic drug must be considered for patients at higher risk for renal injury. Patients must be adequately hydrated and sodium repleted before receiving a nephrotoxic drug. The concomitant use of two or more different nephrotoxic drugs must be avoided. Drug dosage should be adjusted in accordance with organ functional status, distribution volume, and drug pharmacokinetics. It always should be checked if a nephrotoxic drug had specific measures to prevent or attenuate its potential for renal damage. Currently, numerous drugs have been related to development of AKI. Of the vast array of drugs with potential for nephrotoxicity, those more frequently prescribed for patients in the ICU are discussed in this chapter: antiinfective agents (aminoglycosides, vancomycin, amphotericin B, polymyxins, highly active antiretroviral therapy [HAART]), contrast agents, NSAIDs, and drugs blocking the renin-angiotensin-aldosterone system (ACEI, ARB, and renin inhibitors).

Use of regional citrate anticoagulation for continuous venovenous hemodialysis in critically ill cancer patients with acute kidney injury

Purpose: This study aimed to evaluate the safety and efficacy of a regional citrate anticoagulation (RCA) protocol for continuous venovenous hemodialysis (CVVHD) in cancer patients with acute kidney injury (AKI) in the intensive care unit (ICU) setting. Material and methods: One hundred twenty two consecutive ICU cancer patients with AKI treated with citrate‐based CVVHD were prospectively evaluated in this prospective observational study. Results: A total of 7198 h of CVVHD therapy (250 filters) were performed. Patients were 61.3 ± 15.7 years old, 78% had solid cancer and the main AKI cause was sepsis (50%). The in‐hospital mortality was 78.7%. Systemic ionized calcium (SCai) was 4.35 (4.10–4.60) mg/dL, severe hypocalcemia (SCai <3.6 mg/dL) was observed in 4.3% of procedures and post‐filter ionized calcium was 1.60 (1.40–1.80) mg/dL. Median filter patency was 24.8 (11–43) hours. Factors related to filter clotting were: no tumor evidence (OR 0.44, CI 0.18–0.99); genitourinary tumor (OR 1.83, CI 1.18–2.81); platelets number (each 10,000/mm3) (OR 1.02, CI 1.00–1.04); International Normatized Ratio (INR) (OR 0.59, CI 0.41–0.85) and citrate dose (each 10 mL/h) (OR 0.88, CI 0.82–0.95). Conclusion: Filter patency was relatively short and clotting was associated with active cancer disease, genitourinary tumor, lower citrate dose and lower INR. HighlightsRegional citrate anticoagulation was safe and associated with adequated metabolic control.The incidence of electrolytic and acid‐base disorders was similar to that observed in non cancer patients.Filter patency was relatively short 24.8 (11 – 43) hours.Factors related to filter clotting were, genitourinary tumor, platelets number and citrate dose.