CCL14 Predicts Oliguria and Dialysis Requirement in Patients with Moderate to Severe Acute Kidney Injury.

INTRUDUCTION: AKI is a frequent complication in critical illness and portends poor outcome. CCL14 has been validated to predict persistent severe AKI in critically ill patients. We examined the association of CCL14 with urine output within 48 hours. METHODS: In pooled data from 2 studies of critically ill patients with KDIGO stage 2-3 AKI, CCL14 was measured by NEPHROCLEAR™CCL14 Test on the Astute 140® Meter, and divided to low, intermediate and high categories (1.3 and 13 ng/mL). Average hourly urine output over 48 hours, stage 3 AKI per urine output criterion on day 2, and composite of dialysis or death within 7 days were examined using multivariable mixed, and logistic regression models. RESULTS: Of the 497 subjects with median age of 65 [56-74] years, 49% (242/497) were on diuretics. CCL14 concentration was low in 219 (44%), intermediate in 217 (44%), and high in 61 (12%) patients. In mixed regression analysis, urine output trajectory over time was different within each CCL14 risk category based on diuretic use due to significant three-way interaction (p < 0.001). In logistic regression analysis CCL14 risk category was independently associated with low urine output on day 2 (KDIGO stage 3) adjusted for diuretic use and baseline clinical variables and composite of dialysis or death within 7 days (adjusted for urine output within 48 hours of CCL14 measurement). CONCLUSIONS: CCL14 measured in patients with moderate to severe AKI is associated with urine output trajectory within 48 hours, oliguria on day 2, and dialysis within 7 days.

Sex Bias in Prediction and Diagnosis of Cardiac Surgery Associated Acute Kidney Injury.

Background: Female sex has been recognized as a risk factor for cardiac surgery associated acute kidney injury (CS-AKI). The current study sought to evaluate whether female sex is a risk factor for CS-AKI, or modifies the association of peri-operative change in serum creatinine with CS-AKI. Methods: Observational study of adult patients undergoing cardiac surgery between 2000 and 2019 in a single U.S. center. The main variable of interest was registered patient sex, identified from electronic medical records. The main outcome was CS-AKI within 2 weeks of surgery. Results: Of 58526 patients, 19353 (33%) were female; 12934 (22%) incurred AKI based on ≥ 0.3 mg/dL or ≥ 50% rise in serum creatinine (any AKI), 3320 (5.7%) had moderate to severe AKI, and 1018 (1.7%) required dialysis within 2 weeks of surgery. Female sex was associated with higher risk for AKI in models that were based on preoperative serum creatinine (OR, 1.35; 95% CI, 1.29-1.42), and lower risk with the use of estimated glomerular filtration, (OR, 0.90; 95% CI, 0.86-0.95). The risk for moderate to severe CS-AKI for a given immediate peri-operative change in serum creatinine was higher in female compared to male patients (p < .0001 and p < .0001 for non-linearity), and the association was modified by pre-operative kidney function (p < .0001 for interaction). Conclusions: The association of patient sex with CS-AKI and its direction was dependent on the operational definition of pre-operative kidney function, and differential outcome misclassification due to AKI defined by absolute change in serum creatinine.

Hemodynamic Determinants of Cardiac Surgery-Associated Acute Kidney Injury.

OBJECTIVES: Examine the: 1) relative role of hemodynamic determinants of acute kidney injury (AKI) obtained in the immediate postcardiac surgery setting compared with established risk factors, 2) their predictive value, and 3) extent mediation via central venous pressure (CVP) and mean arterial pressure (MAP). DESIGN: Retrospective observational study. The main outcome of the study was moderate to severe AKI, per kidney disease: improving global outcomes, within 14 days of surgery. SETTING: U.S. academic medical center. PATIENTS: Adult patients undergoing cardiac surgery between January 2000 and December 2019 (n = 40,426) in a single U.S.-based medical center. Pulmonary artery catheter measurements were performed at a median of 102 minutes (11, 132) following cardiopulmonary bypass discontinuation. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The median age of the cohort was 67 years (58, 75), and 33% were female; 70% had chronic hypertension, 29% had congestive heart failure, and 3% had chronic kidney disease. In a multivariable model, which included comorbidities and traditional intraoperative risk factors, CVP (p < 0.0001), heart rate (p < 0.0001), cardiac index (p < 0.0001), and MAP (p < 0.0001), were strong predictors of AKI, and superseded factors such as surgery type and cardiopulmonary bypass duration. The cardiac index had a significant interaction with heart rate (p = 0.026); a faster heart rate had a differentiating effect on the relationship of cardiac index with AKI, where a higher heart rate heightened the risk of AKI primarily in patients with low cardiac output. There was also significant interaction observed between CVP and MAP (p = 0.009); where the combination of elevated CVP and low MAP had a synergistic effect on AKI incidence. CONCLUSIONS: Hemodynamic factors measured within a few hours of surgery showed a strong association with AKI. Furthermore, determinants of kidney perfusion, namely CVP and arterial pressure are interdependent; as are constituents of stroke volume, that is, cardiac output and heart rate.

Prognostic Value of Natriuretic Peptide Levels for Adverse Renal Outcomes in Patients With Moderate to Severe Acute Kidney Injury With or Without Heart Failure.

Background Natriuretic peptides have been recommended as biomarkers for the diagnosis and prognosis of patients with heart failure and are often elevated in the setting of acute kidney injury. We sought to demonstrate the associations between increased baseline NT-proBNP (N-terminal pro-B-type natriuretic peptide) and adverse renal outcomes in patients with moderate-to-severe acute kidney injury. Methods and Results We reviewed electronic medical records of consecutive patients with acute kidney injury stage 2 and 3 admitted to the Cleveland Clinic between September 2011 and December 2021. Patients with NT-proBNP levels collected before renal consultation or dialysis initiation were included. Adverse renal outcomes included dialysis requirement and dialysis dependence defined as patients undergoing dialysis within 72 hours before hospital discharge or in-hospital mortality. In our study cohort (n=3811), 2521 (66%) patients underwent dialysis, 1619 (42%) patients became dialysis dependent, and 1325 (35%) patients had in-hospital mortality. After adjusting for cardiorenal risk factors, compared with the lowest quartile, the highest quartile of NT-proBNP (≥18 215 pg/mL) was associated with increased likelihood of dialysis requirement (adjusted odds ratio [OR], 2.36 [95% CI, 1.87-2.99]), dialysis dependence (adjusted OR, 1.89 [95% CI, 2.53-1.34]), and in-hospital mortality (adjusted OR, 1.34 [95% CI, 1.01-1.34]). Conclusions Increased NT-proBNP was associated with an increased risk of dialysis requirement, becoming dialysis dependent, and in-hospital mortality in patients with moderate-to-severe acute kidney injury.

Rapid implementation of an emergency on-site CKRT dialysate production system during the COVID-19 pandemic.

BACKGROUND: On December 29, 2021, during the delta wave of the Coronavirus Disease 2019 (COVID-19) pandemic, the stock of premanufactured solutions used for continuous kidney replacement therapy (CKRT) at the University of New Mexico Hospital (UNMH) was nearly exhausted with no resupply anticipated due to supply chain disruptions. Within hours, a backup plan, devised and tested 18 months prior, to locally produce CKRT dialysate was implemented. This report describes the emergency implementation and outcomes of this on-site CKRT dialysate production system. METHODS: This is a single-center retrospective case series and narrative report describing and reporting the outcomes of the implementation of an on-site CKRT dialysate production system. All adults treated with locally produced CKRT dialysate in December 2021 and January 2022 at UNMH were included. CKRT dialysate was produced locally using intermittent hemodialysis machines, hemodialysis concentrate, sterile parenteral nutrition bags, and connectors made of 3-D printed biocompatible rigid material. Outcomes analyzed included dialysate testing for composition and microbiologic contamination, CKRT prescription components, patient mortality, sequential organ failure assessment (SOFA) scores, and catheter-associated bloodstream infections (CLABSIs). RESULTS: Over 13 days, 22 patients were treated with 3,645 L of locally produced dialysate with a mean dose of 20.0 mL/kg/h. Fluid sample testing at 48 h revealed appropriate electrolyte composition and endotoxin levels and bacterial colony counts at or below the lower limit of detection. No CLABSIs occurred within 7 days of exposure to locally produced dialysate. In-hospital mortality was 81.8% and 28-day mortality was 68.2%, though illness severity was high, with a mean SOFA score of 14.5. CONCLUSIONS: Though producing CKRT fluid with IHD machines is not novel, this report represents the first description of the rapid and successful implementation of a backup plan for local CKRT dialysate production at a large academic medical center in the U.S. during the COVID-19 pandemic. Though conclusions are limited by the retrospective design and limited sample size of our analysis, our experience could serve as a guide for other centers navigating similar severe supply constraints in the future.

Performance of a Standardized Clinical Assay for Urinary C-C Motif Chemokine Ligand 14 (CCL14) for Persistent Severe Acute Kidney Injury.

Background: Clinical use of biomarkers requires the development of standardized assays and establishment of cutoffs. Urinary C-C motif chemokine ligand 14 (CCL14) has been validated to predict persistent severe AKI in critically ill patients with established AKI. We now report on the performance of standardized cutoffs using a clinical assay. Methods: A second aim of the multicenter RUBY Study was to establish two cutoffs for the prediction of persistent severe AKI (defined as KDIGO stage 3 AKI for at least 72 consecutive hours). Patients who received renal replacement therapy (RRT) or died before achieving 72 hours in stage 3 AKI were also considered to have reached the end point. Results: A cutoff value for urinary CCL14 of 1.3 ng/ml was determined to achieve high sensitivity (91%; 95% CI, 84% to 96%), and 13 ng/ml achieved high specificity (93%; 95% CI, 89% to 96%). The cutoff of 1.3 ng/ml identifies the majority (91%) of patients who developed persistent severe AKI with a negative predictive value of 92%. The cutoff at 13 ng/ml had a positive predictive value of 72% (with a negative predictive value of 75%). In multivariable adjusted analyses, a CCL14 concentration between 1.3 and 13 ng/ml had an adjusted odds ratio (aOR) of 3.82 (95% CI, 1.73 to 9.12; P=0.001) for the development of persistent severe AKI compared with those with a CCL14 ≤1.3 ng/ml, whereas a CCL14 >13 ng/ml had an aOR of 10.4 (95% CI, 3.89 to 29.9; P<0.001). Conclusions: Using a clinical assay, these standardized cutoffs (1.3 and 13 ng/ml) allow for the identification of patients at high risk for the development of persistent severe AKI. These results have immediate utility in helping to guide AKI patient care and may facilitate future clinical trials.Clinical Trial registry name and registration number: Identification and Validation of Biomarkers of Acute Kidney Injury Recovery, NCT01868724.

Predictive Accuracy of a Perioperative Laboratory Test-Based Prediction Model for Moderate to Severe Acute Kidney Injury After Cardiac Surgery.

Importance: Effective treatment of acute kidney injury (AKI) is predicated on timely diagnosis; however, the lag in the increase in serum creatinine levels after kidney injury may delay therapy initiation. Objective: To determine the derivation and validation of predictive models for AKI after cardiac surgery. Design, Setting, and Participants: Multivariable prediction models were derived based on a retrospective observational cohort of adult patients undergoing cardiac surgery between January 2000 and December 2019 from a US academic medical center (n = 58 526) and subsequently validated on an external cohort from 3 US community hospitals (n = 4734). The date of final follow-up was January 15, 2020. Exposures: Perioperative change in serum creatinine and postoperative blood urea nitrogen, serum sodium, potassium, bicarbonate, and albumin from the first metabolic panel after cardiac surgery. Main Outcomes and Measures: Area under the receiver-operating characteristic curve (AUC) and calibration measures for moderate to severe AKI, per Kidney Disease: Improving Global Outcomes (KDIGO), and AKI requiring dialysis prediction models within 72 hours and 14 days following surgery. Results: In a derivation cohort of 58 526 patients (median [IQR] age, 66 [56-74] years; 39 173 [67%] men; 51 503 [91%] White participants), the rates of moderate to severe AKI and AKIrequiring dialysis were 2674 (4.6%) and 868 (1.48%) within 72 hours and 3156 (5.4%) and 1018 (1.74%) within 14 days after surgery. The median (IQR) interval to first metabolic panel from conclusion of the surgical procedure was 10 (7-12) hours. In the derivation cohort, the metabolic panel-based models had excellent predictive discrimination for moderate to severe AKI within 72 hours (AUC, 0.876 [95% CI, 0.869-0.883]) and 14 days (AUC, 0.854 [95% CI, 0.850-0.861]) after the surgical procedure and for AKI requiring dialysis within 72 hours (AUC, 0.916 [95% CI, 0.907-0.926]) and 14 days (AUC, 0.900 [95% CI, 0.889-0.909]) after the surgical procedure. In the validation cohort of 4734 patients (median [IQR] age, 67 (60-74) years; 3361 [71%] men; 3977 [87%] White participants), the models for moderate to severe AKI after the surgical procedure showed AUCs of 0.860 (95% CI, 0.838-0.882) within 72 hours and 0.842 (95% CI, 0.820-0.865) within 14 days and the models for AKI requiring dialysis and 14 days had an AUC of 0.879 (95% CI, 0.840-0.918) within 72 hours and 0.873 (95% CI, 0.836-0.910) within 14 days after the surgical procedure. Calibration assessed by Spiegelhalter z test showed P >.05 indicating adequate calibration for both validation and derivation models. Conclusions and Relevance: Among patients undergoing cardiac surgery, a prediction model based on perioperative basic metabolic panel laboratory values demonstrated good predictive accuracy for moderate to severe acute kidney injury within 72 hours and 14 days after the surgical procedure. Further research is needed to determine whether use of the risk prediction tool improves clinical outcomes.

The Production, Efficacy, and Safety of Machine-Generated Bicarbonate Solution for Continuous Venovenous Hemodialysis (CVVHD): The Cleveland Clinic Method.

RATIONALE & OBJECTIVE: Since 1994, the Nephrology and Hypertension Department at the Cleveland Clinic has prepared and used bicarbonate-based solution for continuous venovenous hemodialysis (CVVHD) using a standard volumetric hemodialysis machine rather than purchasing from a commercial vendor. This report describes the process of producing Cleveland Clinic UltraPure Solution (CCUPS), quality and safety monitoring, economic costs, and clinical outcomes. STUDY DESIGN: Retrospective study. SETTING & PARTICIPANTS: CVVHD experience at Cleveland Clinic, focusing on dialysate production, institutional factors, and patients requiring continuous kidney replacement therapy. Production is shown at www.youtube.com/watch?v=WGQgephMEwA. OUTCOMES: Feasibility, safety , and cost. RESULTS: Of 6,426 patients treated between 2011 and 2019 with continuous kidney replacement therapy, 59% were men, 71% were White, 40% had diabetes mellitus, and 74% presented with acute kidney injury. 98% of patients were treated with CVVHD using CCUPS, while the remaining 2% were treated with either continuous venovenous hemofiltration or continuous venovenous hemodiafiltration using commercial solution. The prescribed and delivered effluent doses were 24.8 (IQR) versus 20.7 mL/kg/h (IQR), respectively. CCUPS was as effective in restoring electrolyte and serum bicarbonate levels and reducing phosphate, creatinine, and serum urea nitrogen levels as compared with packaged commercial solution over a 3-day period following initiation of dialysis, with a comparable effluent dose. Among those with acute kidney injury, mortality was similar to that predicted with the 60-day acute kidney injury predicted mortality score (r = 0.997; CI: 0.989-0.999). At our institution, the cost of production for 1 L of CCUPS is $0.67, which is considerably less than the cost of commercially purchased fluid. LIMITATIONS: Observational design without a rigorous control group. CONCLUSIONS: CVVHD using locally generated dialysate is safe and cost-effective.

COVID-19 and the kidney.

COVID-19 is primarily considered a respiratory illness, but the kidney may be one of the targets of SARS-CoV-2 infection, since the virus enters cells through the angiotensin-converting enzyme 2 receptor, which is found in abundance in the kidney. Information on kidney involvement in COVID-19 is limited but is evolving rapidly. This article discusses the pathogenesis of acute kidney injury (AKI) in COVID-19, its optimal management, and the impact of COVID-19 on patients with chronic kidney disease, patients with end-stage kidney disease on dialysis, and kidney transplant recipients.

Partial Nephrectomy for Patients with Severe Chronic Kidney Disease-Is It Worthwhile?

PURPOSE: Partial nephrectomy is prioritized over radical nephrectomy in patients with chronic kidney disease whenever feasible. However, we hypothesized that some patients with severe chronic kidney disease might rapidly progress to end stage renal disease, in which case the morbidity that can be associated with partial nephrectomy would not be justified. MATERIALS AND METHODS: A retrospective review of all 62 patients with stage IV chronic kidney disease undergoing partial nephrectomy at our institution (1999-2015) was performed. We analyzed preoperative/intraoperative factors and postoperative outcomes. Survival-analyses evaluated factors associated with time-to-progression to end stage renal disease the primary end point. RESULTS: Median age was 67 years, 71% of patients were male, and 84% Caucasian. Comorbidities included hypertension (94%), cardiovascular disease (53%) and diabetes (32%). Median preoperative estimated glomerular filtration rate was 23 ml/minute/1.73 m2 and 73% had an open approach. Benign pathology was found in 10 (16%) patients; only 23 (37%) and 7 (11%) patients had tumor grade 3/4 or pT3a disease, respectively. Unfavorable outcomes occurred in 15 patients (24%) defined as either 90-day mortality (3%), postoperative complication Clavien IIIb or greater (14%), or positive surgical margin (12%). Median time to progression to end stage renal disease was only 27 months (58 months for preoperative glomerular filtration rate greater than 25 ml/minute/1.73 m2 versus only 14 months when preoperative glomerular filtration rate was less than 20 ml/minute/1.73 m2). On multivariable analysis African American race (HR 2.55 [1.10-5.95]), preoperative estimated glomerular filtration rate 20 to 25 ml/minute/1.73 m2 or less than 20 ml/minute/1.73 m2 (HR 2.59 [1.16-5.84] and 5.03 [2.03-12.4], respectively) and minimally invasive approach (HR 2.05 [1.01-4.19]) were independently associated with progression to end stage renal disease. CONCLUSIONS: Our data suggest that some patients with stage IV chronic kidney disease undergoing partial nephrectomy have substantial comorbidities and nonaggressive pathology, and are at risk for unfavorable perioperative outcomes and rapid-progression to end stage renal disease. Renal mass biopsy should be strongly considered to improve patient-selection. Alternate strategies (active surveillance or radical nephrectomy) may be more appropriate, particularly when partial nephrectomy is high complexity or when the patient is African American, or preoperative glomerular filtration rate is less than 25 ml/minute/1.73 m2.

Correction to: Clinical predictors of renal non-recovery in acute respiratory distress syndrome.

Following publication of the original article.

Correction to: Factors associated with acute kidney injury in acute respiratory distress syndrome.

After publication of the original article [1], we were notified that an author's name has been incorrectly spelled. Andrei Hasting should be replaced with Andrei Hastings.

Factors associated with acute kidney injury in acute respiratory distress syndrome.

BACKGROUND: Acute kidney injury (AKI) is the most frequent extra-pulmonary organ failure in acute respiratory distress syndrome (ARDS). The objective of this study was to assess the factors associated with the development and severity of AKI in patients with ARDS. METHODS: This is a retrospective cohort study of ARDS patients without acute or chronic kidney disease prior to the onset of ARDS over a 7-year period (2010-2017). AKI and severity of AKI were defined according to the Kidney Disease Improving Global Outcomes 2012 guidelines. RESULTS: Of the 634 ARDS patients, 357 patients met study criteria. A total of 244 (68.3%) patients developed AKI after ARDS onset: 60 (24.6%) had stage I AKI, 66 (27%) had stage II AKI, and 118 (48.4%) had stage III AKI. The median time of AKI onset for stage I AKI was 2 days (interquartile range, 1.5-5.5) while stage II and III AKI was 4 days. On multivariable analysis, factors associated with development of AKI were age [subdistribution hazard ratio (SHR) 1.01, 95% confidence interval (CI) 1.00-1.02], SOFA score (SHR 1.16, 95%CI 1.12-1.21), a history of diabetes mellitus (DM) (SHR 1.42, 95%CI 1.07-1.89), and arterial pH on day 1 of ARDS (SHR per 0.1 units decrease was 1.18, 95%CI 1.05-1.32). In severity of AKI, stage I AKI was associated with age (SHR 1.03, 95%CI 1.01-1.05) and serum bicarbonate on day 1 of ARDS (SHR 1.07, 95%CI 1.02-1.13). Stage II AKI was associated with age (SHR 1.03, 95%CI 1.01-1.05), serum bicarbonate on day 1 (SHR 1.12, 95%CI 1.06-1.18), SOFA score (SHR 1.19, 95%CI 1.10-1.30), history of heart failure (SHR 3.71, 95%CI 1.63-8.46), and peak airway pressure (SHR 1.04, 95%CI 1.00-1.07). Stage III AKI was associated with a higher BMI (SHR 1.02, 95%CI 1.00-1.03), a history of DM (SHR 1.79, 95%CI 1.18-2.72), SOFA score (SHR 1.29, 95%CI 1.22-1.36), and arterial pH on day 1 (SHR per 0.1 units decrease was 1.25, 95%CI 1.05-1.49). CONCLUSIONS: Age, a higher severity of illness, a history of diabetes, and acidosis were associated with development of AKI in ARDS patients. Severity of AKI was further associated with BMI, history of heart failure, and peak airway pressure.

Clinical predictors of renal non-recovery in acute respiratory distress syndrome.

BACKGROUND: Acute kidney injury (AKI) is the most common extra-pulmonary organ failure in acute respiratory distress syndrome (ARDS). Renal recovery after AKI is determined by several factors. The objective of this study was to determine the predictors of renal non-recovery in ARDS patients. METHODS: A single center retrospective cohort study of patients with AKI after onset of ARDS. Patients with preexisting chronic kidney disease or intensive care unit stay < 24 h were excluded. AKI staging was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) 2012 guidelines. Renal non-recovery was defined as death, dialysis dependence, serum creatinine ≥1.5 times the baseline, or urine output < 0.5 mL/kg/h more than 6 h. RESULTS: Of the 244 patients that met study criteria, 60 (24.6%) had stage I AKI, 66 (27%) had stage II AKI, and 118 (48.4%) had stage III AKI. Of those, 148 (60.7%) patients had renal non-recovery. On multivariable analysis, factors associated with renal non-recovery were a higher stage of AKI (odds ratio [OR] stage II 5.71, 95% confidence interval [CI] 2.17-14.98; OR stage III 45.85, 95% CI 16.27-129.2), delay in the onset of AKI (OR 1.12, 95% CI 1.03-1.21), history of malignancy (OR 4.02, 95% CI 1.59-10.15), septic shock (OR 3.2, 95% CI 1.52-6.76), and a higher tidal volume on day 1-3 of ARDS (OR 1.41, 95% CI 1.05-1.90). Subgroup analysis of survival at day 28 of ARDS also found that higher severity of AKI (OR stage II 8.17, 95% CI 0.84-79.91; OR stage III 111.67, 95% CI 12.69-982.91), delayed onset of AKI (OR 1.12, 95% CI 1.02-1.23), and active malignancy (OR 6.55, 95% CI 1.34-32.04) were significant predictors of renal non-recovery. CONCLUSIONS: A higher stage of AKI, delayed onset of AKI, a history of malignancy, septic shock, and a higher tidal volume on day 1-3 of ARDS predicted renal non-recovery in ARDS patients. Among survivors, a higher stage of AKI, delayed onset of AKI, and a history of malignancy were associated with renal non-recovery.

Renal Cancer Surgery in Patients without Preexisting Chronic Kidney Disease-Is There a Survival Benefit for Partial Nephrectomy?

PURPOSE: Retrospective studies suggest that partial nephrectomy provides improved survival compared to radical nephrectomy even when performed electively. However, selection bias may contribute. We evaluated factors associated with nonrenal cancer related mortality after partial and radical nephrectomy in patients with a preoperative glomerular filtration rate of 60 ml/minute/1.73 m2 or greater. MATERIALS AND METHODS: We retrospectively evaluated the records of 3,133 patients with a preoperative glomerular filtration rate of 60 ml/minute/1.73 m2 or greater who underwent partial or radical nephrectomy. Nonrenal cancer related mortality was analyzed by the Kaplan-Meier test based on procedure and functional parameters, including the new baseline glomerular filtration rate. We used the Cox proportional hazards model to assess factors associated with nonrenal cancer related mortality among patients with a new baseline rate of 45 ml/minute/1.73 m2 or greater. RESULTS: Overall median age was 59 years and the median preoperative glomerular filtration rate was 85 ml/minute/1.73 m2. The new baseline glomerular filtration rate was 80 and 63 ml/minute/1.73 m2 and 10-year nonrenal cancer related mortality was 11.3% and 17.7% after partial and radical nephrectomy, respectively (each p <0.001). Median followup was 9.3 years. Nonrenal cancer related mortality was similar in all patients with a new baseline glomerular filtration rate of 45 ml/minute/1.73 m2 or greater (p = 0.26). However, it increased 50% or more in the 290 patients with a new baseline below this level (p = 0.001). In patients with a new baseline greater than 45 ml/minute/1.73 m2 10-year nonrenal cancer related mortality was still substantially improved after partial nephrectomy (10.6% vs 16.3%, p <0.001). In this population age, gender and partial vs radical nephrectomy were associated with nonrenal cancer related mortality on multivariable analysis (all p ≤0.001). In contrast, the increased new baseline glomerular filtration rate, as seen for partial nephrectomy, was not associated with reduced nonrenal cancer related mortality. CONCLUSIONS: In patients with a glomerular filtration rate of 60 ml/minute/1.73 m2 or greater who undergo partial or radical nephrectomy our data suggest that treatment should achieve a new baseline of 45 ml/minute/1.73 m2 or greater if feasible. Partial nephrectomy should be prioritized if needed to accomplish this. In patients with a new baseline rate of 45 ml/minute/1.73 m2 or greater partial nephrectomy was associated with improved survival. However, the functional dividend, namely the increased new baseline rate, failed to correlate, suggesting that selection bias may also impact outcomes.

Acute kidney injury in postoperative shock: is hyperoncotic albumin administration an unrecognized resuscitation risk factor?

BACKGROUND: The use of hyperoncotic albumin (HA) for shock resuscitation is controversial given concerns about its cost, effectiveness, and potential for nephrotoxicity. We evaluated the association between early exposure to hyperoncotic albumin (within the first 48 h of onset of shock) and acute organ dysfunction in post-surgical patients with shock. METHODS: This retrospective, cohort study included 11,512 perioperative patients with shock from 2009 to 2012. Shock was defined as requirement for vasopressors to maintain adequate mean arterial pressure and/or elevated lactate (> 2.2 mmol/L). Subsets of 3600 were selected after propensity score and exact matching on demographics, comorbidities, and treatment variables (> 30). There was a preponderance of cardiac surgery patients. Proportional odds logistic regression, multivariable logistic regression or Cox proportional hazard regression models measured association between hyperoncotic albumin and acute kidney injury (AKI), hepatic injury, ICU days, and mortality. RESULTS: Hyperoncotic albumin-exposed patients showed greater risk of acute kidney injury compared to controls (OR 1.10, 95% CI 1.04, 1.17. P = 0.002), after adjusting for imbalanced co-variables. Within matched patients, 20.3%, 2.9%, and 4.4% of HA patients experienced KDIGO stages 1-3 AKI, versus 19.6%, 2.5%, and 3.0% of controls. There was no difference in hepatic injury (OR 1.16; 98.3% CI 0.85, 1.58); ICU days, (HR 1.05; 98.3% CI 1.00, 1.11); or mortality, (OR 0.88; 98.3% CI 0.64, 1.20). CONCLUSIONS: Early exposure to hyperoncotic albumin in postoperative shock appeared to be associated with acute kidney injury. There did not appear to be any association with hepatic injury, mortality, or ICU days. The clinical and economic implications of this finding warrant further investigation.

Cytokine Clearances in Critically Ill Patients on Continuous Renal Replacement Therapy.

BACKGROUND/AIMS: We sought to quantify any differences in cytokine clearance between continuous venovenous hemofiltration (CVVH-convective) compared to continuous venovenous hemodialysis (CVVHD-diffusive). METHODS: We conducted a 20 patient, multicenter, prospective, open-label randomized trial (CVVH or CVVHD) at continuous renal -replacement therapy (CRRT) initiation. Blood, urine, and effluent were collected at 0, 4, 24, and 48 h after initiation of CRRT. Serum electrolytes, cytokines levels, and clearances were measured. Cytokines studies included IL-1ß, IL-1RA, IL-6, IL-10, and TNFα. RESULTS: We randomized 20 patients to receive CRRT. After 4 h of CRRT there was no difference in total cytokine levels or change in cytokine concentrations across the 2 groups. With the exception of IL-1 RA, all cytokines levels decreased across patient groups regardless of modality. There was no significant difference in cytokine concentration across CRRT modality for any time point. CONCLUSION: Within the first 4 h of CRRT initiation, there is no significant difference between cytokine or solute clearance between CVVH and CVVHD.

Predictors of Long-Term Survival after Renal Cancer Surgery.

PURPOSE: Renal cancer surgery can adversely impact long-term function and survival. We evaluated predictors of chronic kidney disease 5 years and nonrenal cancer mortality 10 years after renal cancer surgery. MATERIALS AND METHODS: We analyzed the records of 4,283 patients who underwent renal cancer surgery from 1997 to 2008. Radical and partial nephrectomy were performed in 46% and 54% of patients, respectively. Cumulative probability ordinal modeling was used to predict chronic kidney disease status 5 years after surgery and multivariable logistic regression was used to predict nonrenal cancer mortality at 10 years. Relevant patient, tumor and functional covariates were incorporated, including the preoperative glomerular filtration rate (A), the new baseline glomerular filtration rate after surgery (B) and the glomerular filtration rate loss related to surgery (C), that is C = A - B. In contrast, partial or radical nephrectomy was not used in the models due to concerns about strong selection bias associated with the choice of procedure. RESULTS: Multivariable modeling established the preoperative glomerular filtration rate and the glomerular filtration rate loss related to surgery as the most important predictors of the development of chronic kidney disease (Spearman ρ = 0.78). Age, gender and race had secondary roles. Significant predictors of 10-year nonrenal cancer mortality were the preoperative glomerular filtration rate, the new baseline glomerular filtration rate, age, diabetes and heart disease (all p <0.05). Multivariable modeling established age and the preoperative glomerular filtration rate as the most important predictors of 10-year nonrenal cancer mortality (c-index 0.71) while the glomerular filtration rate loss related to surgery only changed absolute mortality estimates 1% to 3%. CONCLUSIONS: Glomerular filtration rate loss related to renal cancer surgery, whether due to partial or radical nephrectomy, influences the risk of chronic kidney disease but it may have less impact on survival. In contrast, age and the preoperative glomerular filtration rate, which reflects general health status, are more robust predictors of nonrenal cancer mortality, at least in patients with good preoperative function or mild chronic kidney disease.

Analysis of survival for patients with chronic kidney disease primarily related to renal cancer surgery.

OBJECTIVES: To evaluate predictors of long-term survival for patients with chronic kidney disease primarily due to surgery (CKD-S). Patients with CKD-S have generally good survival that approximates patients who do not have CKD even after renal cancer surgery (RCS), yet there may be heterogeneity within this cohort. PATIENTS AND METHODS: From 1997 to 2008, 4 246 patients underwent RCS at our centre. The median (interquartile range [IQR]) follow-up was 9.4 (7.3-11.0) years. New baseline glomerular filtration rate (GFR) was defined as highest GFR between nadir and 6 weeks after RCS. We retrospectively evaluated three cohorts: no-CKD (new baseline GFR of ≥60 mL/min/1.73 m2 ); CKD-S (new baseline GFR of <60 mL/min/1.73 m2 but preoperative GFR of ≥60 mL/min/1.73 m2 ); and CKD due to medical aetiologies who then require RCS (CKD-M/S, preoperative and new baseline GFR both <60 mL/min/1.73 m2 ). Analysis focused primarily on non-renal cancer-related survival (NRCRS) for the CKD-S cohort. Kaplan-Meier analysis assessed the longitudinal impact of new baseline GFR (45-60 mL/min/1.73 m2 vs <45 mL/min/1.73 m2 ) and Cox regression evaluated relative impact of preoperative GFR, new baseline GFR, and relevant demographics/comorbidities. RESULTS: Of the 4 246 patients who underwent RCS, 931 had CKD-S and 1 113 had CKD-M/S, whilst 2 202 had no-CKD even after RCS. Partial/radical nephrectomy (PN/RN) was performed in 54%/46% of the patients, respectively. For CKD-S, 641 patients had a new baseline GFR of 45-60 mL/min/1.73 m2 and 290 had a new baseline GFR of <45 mL/min/1.73 m2 . Kaplan-Meier analysis showed significantly reduced NRCRS for patients with CKD-S with a GFR of <45 mL/min/1.73 m2 compared to those with no-CKD or CKD-S with a GFR of 45-60 mL/min/1.73 m2 (both P ≤ 0.004), and competing risk analysis confirmed this (P < 0.001). Age, gender, heart disease, and new baseline GFR were all associated independently with NRCRS for patients with CKD-S (all P ≤ 0.02). CONCLUSION: Our data suggest that CKD-S is heterogeneous, and patients with a reduced new baseline GFR have compromised survival, particularly if <45 mL/min/1.73 m2 . Our findings may have implications regarding choice of PN/RN in patients at risk of developing CKD-S.