Sevag Demirjian

Parenchymal Volume Preservation and Ischemia During Partial Nephrectomy: Functional and Volumetric Analysis

OBJECTIVE To determine the relative effect of type and duration of ischemia and parenchymal volume preservation on renal function after partial nephrectomy (PN). MATERIALS AND METHODS Ninety-two patients with localized renal tumors (2007-2012) managed with PN at our center with necessary studies for analysis were included. This comprised 37 patients with a solitary kidney and 55 with a contralateral kidney. Thirty-five patients were managed with hypothermia and 57 with limited warm ischemia. Volumetric computed tomography was used to measure the volume of functional parenchyma before and after PN in the operated and contralateral kidneys. Glomerular filtration rate (GFR) was determined by the modification of diet in renal disease 2 equation, along with renal scan data for patients with a contralateral kidney. Regression analysis assessed the relationships between %GFR preserved in the operated kidney and potential predictive factors. All postoperative analyses were performed 4-12 months after surgery. RESULTS Median age was 61 years, median tumor size 3.5 cm, and median RENAL nephrometry score 8. Median cold ischemia time was 28 minutes and median warm ischemia time 21 minutes. Median %GFR preserved in the operated kidney was 79%. Median %parenchymal volume saved was 83%. Function in the contralateral kidney only increased marginally (median increase 6%). On regression analysis, %GFR preserved associated most strongly with %parenchymal volume saved (P <.0001), but also with lower RENAL scores (P = .0457) and the use of hypothermia (P = .0209). In contrast, ischemia time did not correlate with %GFR preserved (P = .5051). CONCLUSION Ultimate function after PN primarily correlated with parenchymal volume preservation, whereas ischemia played a secondary role. Thus, maximal parenchymal preservation with a precise PN should be a priority during PN.

Surgically Induced Chronic Kidney Disease May be Associated with a Lower Risk of Progression and Mortality than Medical Chronic Kidney Disease

PURPOSE Chronic kidney disease from medical causes is present in 25% to 30% of patients before surgery for renal cancer. Although chronic kidney disease due to medical causes is typically associated with a 2% to 5% annual renal functional decline and decreased overall survival, reduced glomerular filtration rate occurring only after surgery may not have the same negative consequences. MATERIALS AND METHODS All patients undergoing surgery for suspected renal malignancy were identified in an institutional registry. Median clinical followup was 6.6 years. RESULTS Of 4,180 patients 28% had a preoperative glomerular filtration rate of less than 60 ml/minute/1.73 m(2) (chronic kidney disease due to medical causes) and in 22% the glomerular filtration rate decreased to less than 60 ml/minute/1.73 m(2) only after surgery (surgically induced chronic kidney disease). Preoperative glomerular filtration rate was a strong predictor of overall survival on univariable and multivariable analysis. The risk of death after renal surgery was 1.8, 3.5 and 4.4-fold higher in patients with preoperative chronic kidney disease stages 3, 4 and 5, respectively, vs normal preoperative glomerular filtration rate. Average overall loss of renal function was 23%, including 13% within 90 days after surgery and 3.5% annually thereafter. Postoperative glomerular filtration rate only predicted survival for patients with preexisting chronic kidney disease due to medical causes. Neither surgically induced chronic kidney disease nor postoperative glomerular filtration rate was a significant predictor of survival in patients without preexisting chronic kidney disease due to medical causes. Annual renal functional decline was 4.7% and 0.7% for patients with chronic kidney disease due to medical causes and surgically induced chronic kidney disease, respectively, with a greater than 50% reduction in glomerular filtration rate in 7.3% and 2.2%, respectively (p <0.0001). Annual renal functional decline greater than 4.0% was associated with a 43% increase in mortality (p <0.0001). CONCLUSIONS Surgically induced chronic kidney disease is associated with a relatively low risk of progressive renal functional decline and impact on survival does not appear to be substantial during intermediate term followup. In contrast, preoperative chronic kidney disease due to medical causes places patients at increased risk, indicating nephron sparing surgery for such patients.

Decline in Renal Function after Partial Nephrectomy: Etiology and Prevention

PURPOSE Partial nephrectomy is the reference standard for the management of small renal tumors and is commonly used for localized kidney cancer. A primary goal of partial nephrectomy is to preserve as much renal function as possible. New baseline glomerular filtration rate after partial nephrectomy can have prognostic significance with respect to long-term outcomes. Recent studies provide an increased understanding of the factors that determine functional outcomes after partial nephrectomy as well as preventive measures to minimize functional decline. We review these advances, highlight ongoing controversies and stimulate further research. MATERIALS AND METHODS A comprehensive literature review consistent with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria was performed from January 2006 to April 2014 using PubMed®, Cochrane and Ovid Medline. Key words included partial nephrectomy, renal function, warm ischemia, hypothermia, nephron mass, parenchymal volume, surgical approaches to partial nephrectomy, preoperative and intraoperative imaging, enucleation, hemostatic agents and energy based resection. Relevant reviews were also examined as well as their cited references. An additional Google Scholar search was conducted to broaden the scope of the review. Only English language articles were included in the analysis. The primary outcomes of interest were the new baseline level of function after early postoperative recovery, percent decline in function, potential etiologies and preventive measures. RESULTS Decline in function after partial nephrectomy averages approximately 20% in the operated kidney, and can be due to incomplete recovery from the ischemic insult or loss of nephron mass related to parenchymal excision or collateral damage during reconstruction. Compensatory hypertrophy in the contralateral kidney after partial nephrectomy in adults is marginal and decline in global renal function for patients with 2 kidneys averages about 10%, although there is some variance based on tumor size and location. Irreversible ischemic injury can be minimized by pharmacological intervention or surgical approaches such as hypothermia, limited warm ischemia, or zero or segmental ischemia. Excessive loss of nephron mass can be minimized by improved preoperative or intraoperative imaging, use of a bloodless field, enucleation and vascular microdissection. Hemostatic agents or energy based resection that minimizes the need for parenchymal and capsular suturing can also optimize preservation of the vascularized nephron mass. CONCLUSIONS Our understanding of the decline in renal function after partial nephrectomy has advanced considerably, including better appreciation of its magnitude and impact in various settings, possible etiologies and potential preventive measures. Many controversies persist and this remains an important area of investigation.

Survival and Functional Stability in Chronic Kidney Disease Due to Surgical Removal of Nephrons: Importance of the New Baseline Glomerular Filtration Rate.

BACKGROUND Chronic kidney disease (CKD) can be associated with a higher risk of progression to end-stage renal disease and mortality, but the etiology of nephron loss may modify this. Previous studies suggested that CKD primarily due to surgical removal of nephrons (CKD-S) may be more stable and associated with better survival than CKD due to medical causes (CKD-M). OBJECTIVE We addressed limitations of our previous work with comprehensive control for confounding factors, differentiation of non-renal cancer-related mortality, and longer follow-up for more discriminatory assessment of the impact of CKD-S. DESIGN, SETTING, AND PARTICIPANTS From 1999 to 2008, 4299 patients underwent surgery for renal cancer at a single institution. The median follow-up was 9.4 yr (7.3-11.0). The new baseline glomerular filtration rate (GFR) was defined as the highest GFR between the nadir and 42 d after surgery. Three cohorts were retrospectively evaluated: no CKD (new baseline GFR >60 ml/min/1.73 m(2)); CKD-S (new baseline GFR<60 but preoperative >60 ml/min/1.73 m(2)); and CKD-M/S (new baseline and preoperative GFR both <60 ml/min/1.73 m(2)). Cohort status was permanently set at 42 d after surgery. INTERVENTION Renal surgery. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Decline in renal function (50% reduction in GFR or dialysis), all-cause mortality, and non-renal cancer mortality were examined using a multivariable Cox proportional hazards model. RESULTS AND LIMITATIONS CKD-M/S had a higher incidence of relevant comorbidities and the new baseline GFR was lower. On multivariable analysis (controlling for age, gender, race, diabetes, hypertension, and cardiac disease), CKD-M/S had higher rates of progressive decline in renal function, all-cause mortality, and non-renal cancer mortality when compared to CKD-S and no CKD (hazard ratio [HR] 1.69-2.33, all p<0.05). All-cause mortality was modestly higher for CKD-S than for no CKD (HR 1.19, p=0.030), but renal stability and non-renal cancer mortality were similar for these groups. New baseline GFR of <45 ml/min/1.73 m(2) significantly predicted adverse outcomes. The main limitation is the retrospective design. CONCLUSIONS CKD-S is more stable than CKD-M/S and has better survival, approximating that for no CKD. However, if the new baseline GFR is <45 ml/min/1.73 m(2), the risks of functional decline and mortality increase. These findings may influence counseling for patients with localized renal cell carcinoma and higher oncologic potential when a normal contralateral kidney is present. PATIENT SUMMARY Survival is better for surgically induced chronic kidney disease (CKD) than for medically induced CKD, particularly if the postoperative glomerular filtration rate is ≥45 ml/min/1.73 m(2). Patients with preexisting CKD are at risk of a significant decline in kidney function after surgery, and kidney-preserving treatment should be strongly considered in such cases.

Hypophosphatemia during continuous hemodialysis is associated with prolonged respiratory failure in patients with acute kidney injury

BACKGROUND Hypophosphatemia is common in critically ill patients and has been associated with generalized muscle weakness, ventilatory failure and myocardial dysfunction. Continuous renal replacement therapy causes phosphate depletion, particularly with prolonged and intensive therapy. In a prospective observational cohort of critically ill patients with acute kidney injury (AKI), we examined the incidence of hypophosphatemia during dialysis, associated risk factors and its relationship with prolonged respiratory failure and 28-day mortality. METHODS This is a single-center prospective observational study. Included in the study were 321 patients with AKI on continuous dialysis as initial treatment modality. RESULTS Four per cent of the patients had a phosphate level <2 mg/dL at initiation and 27% during dialysis. Low baseline phosphate was associated with older age, female gender, parenteral nutrition, vasopressor support, low calcium, and high urea, bilirubin and creatinine, whereas hypophosphatemia during dialysis correlated with the ischemic acute tubular necrosis etiology of renal failure, intensive dose and longer therapy. Serum phosphate decline during dialysis was associated with higher incidence of prolonged respiratory failure requiring tracheostomy [odds ratio (OR) = 1.81; 95% confidence interval (CI) = 1.07-3.08], but not 28-day mortality (OR = 1.16; 95% CI = 0.76-1.77) in multivariable analysis. CONCLUSIONS Hypophosphatemia occurs frequently during dialysis, particularly with long and intensive treatment. Decline in serum phosphate levels during dialysis is associated with higher incidence of prolonged respiratory failure requiring tracheostomy, but not 28-day mortality.

Cardiorenal outcomes after slow continuous ultrafiltration therapy in refractory patients with advanced decompensated heart failure

OBJECTIVES The purpose of this study was to examine the clinical outcomes of using slow continuous ultrafiltration (SCUF) in patients with acute decompensated heart failure (HF) refractory to intensive medical therapy. BACKGROUND Several studies have demonstrated the clinical usefulness of early SCUF in patients with acute decompensated HF to improve fluid overload and hemodynamics. METHODS We reviewed clinical data from 63 consecutive adult patients with acute decompensated HF admitted to the Heart Failure Intensive Care Unit from 2004 through 2009 who required SCUF because of congestion refractory to hemodynamically guided intensive medical therapy. RESULTS The mean creatinine level was 1.9 ± 0.8 mg/dl on admission and 2.2 ± 0.9 mg/dl at SCUF initiation. After 48 hours of SCUF, there were significant improvements in hemodynamic variables (mean pulmonary arterial pressure: 40 ± 12 mm Hg vs. 33 ± 8 mm Hg, p = 0.002, central venous pressure: 20 ± 6 mm Hg vs. 16 ± 8 mm Hg, p = 0.007, mean pulmonary wedge pressure: 27 ± 8 mm Hg vs. 20 ± 7 mm Hg, p = 0.02, Fick cardiac index: 2.2 l/min/m(2) [interquartile range: 1.87 to 2.77 l/min/m(2)] vs. 2.6 l/min/m(2) [interquartile range: 2.2 to 2.9 l/min/m(2)], p = 0.0008), and weight loss (102 ± 25 kg vs. 99 ± 23 kg, p < 0.0001). However, there were no significant improvements in serum creatinine levels (2.2 ± 0.9 mg/dl vs. 2.4 ± 1 mg/dl, p = 0.12) and blood urea nitrogen (60 ± 30 mg/dl vs. 60 ± 28 mg/dl, p = 0.97). Fifty-nine percent required conversion to continuous hemodialysis during their hospital course, and 14% were dependent on dialysis at hospital discharge. Thirty percent died during hospitalization, and 6 patients were discharged to hospice care. CONCLUSIONS In our single-center experience, SCUF after admission for acute decompensated HF refractory to standard medical therapy was associated with high incidence of subsequent transition to renal replacement therapy and high in-hospital mortality, despite significant improvement in hemodynamics.

Urine neutrophil gelatinase–associated lipocalin levels do not improve risk prediction of progressive chronic kidney disease

Novel biomarkers may improve our ability to predict which patients with chronic kidney disease (CKD) are at higher risk for progressive loss of renal function. Here we assessed the performance of urine neutrophil gelatinase-associated lipocalin (NGAL) for outcome prediction in a diverse cohort of 3386 patients with CKD in the CRIC study. In this cohort, the baseline mean estimated glomerular filtration rate (eGFR) was 42.4 ml/min/1.73m2; the median 24-hour urine protein was 0.2 gm/day; and the median urine NGAL concentration was 17.2 ng/mL. Over an average follow-up of 3.2 years, there were 689 cases in which the eGFR was decreased by half or incident end-stage renal disease developed. Even after accounting for eGFR, proteinuria and other known CKD progression risk factors, urine NGAL remained a significant independent risk factor (Cox model hazard ratio 1.70 highest to lowest quartile). The association between baseline urine NGAL levels and risk of CKD progression was strongest in the first two years of biomarker measurement. Within this time frame, adding urine NGAL to a model which included eGFR, proteinuria and other CKD progression risk factors led to net reclassification improvement of 24.7%; but the C-statistic remained nearly identical. Thus, while urine NGAL was an independent risk factor of progression among patients with established CKD of diverse etiology, it did not substantially improve prediction of outcome events.

Combined Effect of Chronic Kidney Disease and Peripheral Arterial Disease on All-Cause Mortality in a High-Risk Population

BACKGROUND AND OBJECTIVES Chronic kidney disease (estimated glomerular filtration rate <60 ml/min per 1.73 m(2)) and peripheral arterial disease (ankle-brachial index <0.9) independently predict mortality. It was hypothesized that the risk for death is higher in patients with both chronic kidney disease and peripheral arterial disease compared with those with chronic kidney disease or peripheral arterial disease alone. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A total of 1079 patients who had an ankle-brachial index and serum creatinine recorded within 90 d of each other in 1999 were studied retrospectively. Glomerular filtration rate was estimated using the Modification of Diet in Renal Disease equation. Patients were categorized into four groups: Chronic kidney disease and peripheral arterial disease, chronic kidney disease alone, peripheral arterial disease alone, or no chronic kidney disease or peripheral arterial disease. RESULTS The overall 6-yr mortality rate was 28% (n = 284). Patients with both chronic kidney disease and peripheral arterial disease had the highest mortality rate (45%) compared with patients with chronic kidney disease alone (28%), peripheral arterial disease alone (26%), and neither condition (18%). After adjustment for clinical and demographic variables, the chronic kidney disease and peripheral arterial disease group had an increased odds for death when compared with the no chronic kidney disease or peripheral arterial disease group or the single disease groups. CONCLUSIONS These findings indicate that patients with both chronic kidney disease and peripheral arterial disease have a significantly higher risk for death than patients with either disease alone.

Model to Predict Mortality in Critically Ill Adults with Acute Kidney Injury

BACKGROUND AND OBJECTIVES Acute kidney injury (AKI) requiring dialysis is associated with high mortality. Most prognostic tools used to describe case complexity and to project patient outcome lack predictive accuracy when applied in patients with AKI. In this study, we developed an AKI-specific predictive model for 60-day mortality and compared the model to the performance of two generic (Sequential Organ Failure Assessment [SOFA] and Acute Physiology and Chronic Health Evaluation II [APACHE II]) scores, and a disease specific (Cleveland Clinic [CCF]) score. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Data from 1122 subjects enrolled in the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network study; a multicenter randomized trial of intensive versus less intensive renal support in critically ill patients with AKI conducted between November 2003 and July 2007 at 27 VA- and university-affiliated centers. RESULTS The 60-day mortality was 53%. Twenty-one independent predictors of 60-day mortality were identified. The logistic regression model exhibited good discrimination, with an area under the receiver operating characteristic (ROC) curve of 0.85 (0.83 to 0.88), and a derived integer risk score yielded a value of 0.80 (0.77 to 0.83). Existing scoring systems, including APACHE II, SOFA, and CCF, when applied to our cohort, showed relatively poor discrimination, reflected by areas under the ROC curve of 0.68 (0.64 to 0.71), 0.69 (0.66 to 0.73), and 0.65 (0.62 to 0.69), respectively. CONCLUSIONS Our new risk model outperformed existing generic and disease-specific scoring systems in predicting 60-day mortality in critically ill patients with AKI. The current model requires external validation before it can be applied to other patient populations.

Performance of the Chronic Kidney Disease-Epidemiology Study Equations for Estimating Glomerular Filtration Rate Before and After Nephrectomy

PURPOSE Accurate renal function determination before and after nephrectomy is essential for proper prevention and management of chronic kidney disease due to nephron loss and ischemic injury. We compared the estimated glomerular filtration rate using several serum creatinine based formulas against the measured rate based on (125)I-iothalamate clearance to determine which most accurately reflects the rate in this setting. MATERIALS AND METHODS Of 7,611 patients treated at our institution since 1975 the measured glomerular filtration rate was selectively determined before and after nephrectomy in 268 and 157, respectively. Performance of the Cockcroft-Gault, Modification of Diet in Renal Disease Study, re-expressed Modification of Diet in Renal Disease Study and Chronic Kidney Disease-Epidemiology Study equations, each of which estimates the glomerular filtration rate, were determined using serum creatinine, age, gender, weight and body surface area. The performance of serum creatinine, reciprocal serum creatinine and the 4 formulas was compared with the measured rate using Pearsons correlation, Lins concordance coefficient and residual plots. RESULTS Median serum creatinine was 1.4 mg/dl and the median measured glomerular filtration rate was 50 ml per minute per 1.73 m(2). The correlation between serum creatinine and the measured rate was poor (-0.66) compared with that of reciprocal serum creatinine (0.78) and the 4 equations (0.82 to 0.86). The Chronic Kidney Disease-Epidemiology Study equation performed with greatest precision and accuracy, and least bias of all equations. Stage 3 or greater chronic kidney disease ((125)I-iothalamate glomerular filtration rate 60 ml per minute per 1.73 m(2) or less) was present in 44% of patients with normal serum creatinine (1.4 mg/dl or less) postoperatively. Such missed diagnoses of chronic kidney disease decreased 42% using the Chronic Kidney Disease-Epidemiology Study equation. CONCLUSIONS Glomerular filtration rate estimation equations outperform serum creatinine and better identify patients with perinephrectomy compromised renal function. The newly developed, serum creatinine based, Chronic Kidney Disease-Epidemiology Study equation has sufficient accuracy to render direct glomerular filtration rate measurement unnecessary before and after nephrectomy for cause in most circumstances.