Renal replacement therapy in the critically ill patient with acute kidney injury

The mortality of patients with acute renal failure (ARF) has remained unacceptably high for many years, with renal replacement therapy (RRT) remaining the mainstay of treatment. Clinical research has hitherto been hindered by a lack of a universal definition. However, changes are upon us in the shape of a new term, acute kidney injury (AKI), proposed to encompass the spectrum of ARF, along with a new definition and staging system. There is a renewed optimism that the establishment of clinical databases and the utilization of new clinical biomarkers will catalyze the development of new therapeutic strategies. In the interim, we must optimize the delivery of RRT to patients with AKI. It is remarkable how few studies are currently available in the literature to guide medical practitioners on the key issues of initiation, modality, type of buffer, dose of RRT, vascular access, and anticoagulation. On the horizon, the outcomes of two major clinical trials comparing doses and modalities of RRT in AKI are eagerly awaited.     

Continuous renal replacement therapy is associated with acute cardiac stunning in critically ill patients

Introduction: Intermittent renal replacement therapy induces cardiac stunning in chronic hemodialysis and acute kidney injury (AKI) patients. In chronic hemodialysis, recurrent stunning contributes to heart failure and cardiac death, with ultrafiltration and intradialytic hypotension being the principal determinants of this injury. Continuous renal replacement therapy (CRRT), with its lower ultrafiltration rates and improved hemodynamic profile, should protect against cardiac stunning in AKI. The objective of this study was to assess whether CRRT is associated with cardiac stunning in critically ill patients with AKI. Methods: We prospectively measured cardiac function using global and segmental longitudinal left ventricular strain using transthoracic echocardiography in 11 critically ill patients who were started on CRRT for AKI. We compared measurements at 4, 8, and 24 hours to baseline immediately prior to initiation of CRRT, with each patient serving as their own control. We also recorded blood pressure, heart rate, dose of vasoactive medications and intensive care unit mortality. Findings: Ten of 11 patients developed new regional cardiac stunning, with 8/11 within 4 hours of starting CRRT, despite stable hemodynamics. The number of affected left ventricular segments varied from 1 to 11 (out of 12). The stunning occurred both in patients with preserved and impaired baseline cardiac function, and 7/11 patients died in the intensive care unit. Discussion: Initiation of CRRT in critically ill patients with AKI is associated with cardiac stunning despite stable hemodynamics. This mechanism may explain lack of clinical benefit of CRRT over intermittent modalities and warrants further investigation to improve cardiovascular outcomes in critically ill patients with AKI.     

Predictors of post‐hospitalization recovery of renal function among patients with acute kidney injury requiring dialysis

Introduction: Acute kidney injury (AKI) requiring dialysis complicates 1% of all hospital admissions, and up to 30% of survivors will still require dialysis at hospital discharge. There is a paucity of data to describe the postdischarge outcomes or to guide evidence‐based dialysis management of this vulnerable population. Methods: Single‐center, retrospective analysis of 100 consecutive patients with AKI who survived to hospital discharge and required outpatient dialysis. Data collection included baseline characteristics, hospitalization characteristics, and outpatient dialysis treatment variables. Primary outcome was dialysis independence 90 days after discharge. Findings: Overall, 43% of patients recovered adequate renal function to discontinue dialysis, with the majority recovering within 30 days post discharge. Worse baseline renal function was associated with lower likelihood of renal recovery. In the first week postdischarge, patients with subsequent nonrecovery of renal function had greater net fluid removal (5.3 vs. 4.1 L, P = 0.037), higher ultrafiltration rates (6.0 vs. 4.7 mL/kg/h, P = 0.041) and more frequent intradialytic hypotension (24.6% vs. 9.3% with 3 or more episodes, P = 0.049) compared to patients that later recovered. Discussion: A significant proportion of AKI survivors will recover renal function following discharge. Outpatient intradialytic factors may influence subsequent renal function recovery.     

Outcomes of patients with end‐stage renal disease (ESRD) under chronic hemodialysis requiring continuous renal replacement therapy (CRRT) and patients without ESRD in acute kidney injury requiring CRRT: A single‐center study

In most continuous renal replacement therapy (CRRT) studies, end‐stage renal disease (ESRD) patients were excluded and the outcomes of patients with ESRD treated with chronic hemodialysis (HD) were unknown. The purposes of this study were to (1) evaluate short‐term patient survival and (2) compare the survival of conventional HD patients needing CRRT with the survival of non‐ ESRD patients in acute kidney injury (AKI) requiring CRRT. We evaluated adults (>18 years) requiring CRRT who were treated in the intensive care unit (ICU) at Kosin University Gospel Hospital from January 1, 2009 to December 31, 2010. A total of 100 (24 ESRD, 76 non‐ESRD) patients underwent CRRT during the study period. Patients were divided into two major groups: patients with ESRD requiring chronic dialysis and patients without ESRD (non‐ESRD) with AKI. We compared the survival of conventional HD patients requiring CRRT with the survival of non‐ ESRD patients in AKI requiring CRRT. For non‐ESRD patients, the 90‐day survival rate was 41.6%. For ESRD patients, the 90‐day survival rate was 55.3%. Multivariate Cox proportional hazards analyses demonstrated that conventional HD was not a significant predictor of mortality (hazard ratio [HR]: 0.334, 95% confidence interval [CI]: 0.063–1.763, P = 0.196), after adjustment for age, gender, presence of sepsis, APACHE score, use of vasoactive drugs, number of organ failures, ultrafiltration rate, and arterial pH. The survival rates of non‐ESRD and ESRD patients requiring CRRT did not differ; ESRD with conventional HD patients may be not a significant predictor of mortality.     

Fluid overload and acute kidney injury

Acute kidney injury is commonly encountered in critically ill patients, and is associated with worse outcomes. Fluid therapy is a key component in the management of these patients, often leading to fluid overload, especially in the setting of septic acute kidney injury. Emerging data overwhelmingly suggest that fluid overload in these patients may be associated with adverse outcomes. Management of such patients should include a strategy of early guided resuscitation, followed by careful assessment of fluid status, and early initiation of renal replacement therapy as soon as it is deemed safe, aiming for a neutral or negative fluid balance. This review will focus on the pathophysiological link between fluid overload and acute kidney injury, mechanisms of organ dysfunction in fluid overload, and strategies for management.     

Effect of timing of dialysis on mortality in critically ill, septic patients with acute renal failure

Acute renal failure with concomitant sepsis in the intensive care unit is associated with significant mortality. The purpose of this study was to determine if the timing of initiation of renal replacement therapy (RRT) in septic patients had an effect on the 28-day mortality. Retrospective data on medical intensive care unit patients with sepsis and acute renal failure requiring RRT were included. Renal replacement therapy started with a blood urea nitrogen (BUN) of <100 mg/dL was defined as early initiation, and initiation with a BUN ≥100 mg/dL was defined as late. Multivariate logistic regression analysis with the primary outcome of death at 14, 28, and 365 days following the initiation of RRT was performed. One hundred thirty patients were studied. The early dialysis (mean BUN 66 mg/dL) group had 85 patients; the late group (mean BUN 137 mg/dL) had 62 patients. The mean acute physiology and chronic health evaluation II score was 24.5 in both groups. The overall 14, 28, and 365-day survival rates were 58.1%, 41.9%, and 23.6%. Survival rates for the early group were 67%, 47.7%, and 30.7% at 14, 28, and 365 days. Survival rates for the late group were 46.7%, 31.7%, and 13.3% at 14, 28, and 365 days. Upon logistic regression analysis, initiating dialysis with a BUN >100 mg/dL predicted death at 14 days (odds ratio [OR] 3.6, 95% confidence interval [CI] 1.7–7.6, P=0.001), 28 days (OR 2.6, 95% CI 1.2–5.7, P=0.01), and 365 days (OR 3.5, 95% CI 1.2–10, P=0.02). Septic patients who started dialysis with a BUN <100 mg/dL had improved mortality rates up to 1 year after initiation of dialysis in this single-center, retrospective analysis.     

Early start on continuous hemodialysis therapy improves survival rate in patients with acute renal failure following coronary bypass surgery

Acute renal failure requiring dialysis therapy after cardiac surgery occurs in 1% to 5% of patients; however, the optimal timing for initiation of dialysis therapy still remains undetermined. To assess the validity of early start of dialysis therapy, we studied the comparative survival between 14 patients who started to receive dialysis therapy when urine volume decreased to less than 30 mL/hr and another group of 14 patients who waited to begin dialysis therapy until the level of urine volume was less than 20 mL/hr for 14 days following coronary bypass graft surgery. Twelve of 14 patients who received early intervention survived. In contrast, only 2 of 14 patients in the late‐dialysis group survived. There was a significant difference in survival between the two groups (p < 0.01). There were no significant differences between the two groups with respect to age, sex ratio, the APACHE (Acute Physiologic and Chronic Health Evaluation) II score, and the levels of serum creatinine at the start of dialysis therapy (2.9 ± 0.2 mg/dL vs. 3.1 ± 0.2 mg/dL), as well as the levels of serum creatinine at admission. We propose that the timing of the start for treatment of acute renal failure following cardiac surgery should be determined by the decrease of urine volume and not the levels of serum creatinine. Early start of dialysis therapy may help improve the survival of patients with acute renal failure following cardiac surgery.     

Comparison of risk factors for contrast‐induced acute kidney injury between patients with and without diabetes

Although it is well known that diabetics are at a higher risk of contrast‐induced acute kidney injury (CI‐AKI) than nondiabetic patients, the reason for this discrepancy is not well known. Thus, in this study, we compared the predisposing factors for CI‐AKI between patients with and without diabetes. We prospectively studied 290 consecutive in‐hospital patients including 88 diabetics undergoing coronary angiography or a percutaneous coronary intervention in Kowsar hospital, and we compared risk factors for CI‐AKI between diabetic and nondiabetic patients. CI‐AKI was defined as RIFLE criteria within 48 hours after contrast exposure. The incidence of CR‐AKI was significantly higher in diabetic patients compared with nondiabetics (P<0.05). The incidence of CI‐AKI was significantly higher in patients with diabetes and left‐ventricular ejection fraction ≤40%, hypercholesterolemia, serum creatinine ≥1.1 mg/dL, estimated glomerular filtration rate (eGFR) <90 mL/min, Contrast volume ≥80 (mL), maximum safe contrast volume factor of 1.5, and dehydration, while in nondiabetics, a significantly higher incidence of CR‐AKI was observed in those with serum creatinine ≥1.1 mg/dL (P=0.02) and/or eGFR<60 mL/min (P=0.01). Multiple logistic regression analysis showed hyperchlosteremia to be the strongest predictor of AKI (P=0.01, B:14.5) in diabetics, followed by eGFR<90 (P=0.05, B:12.4) but, in nondiabetics, only eGFR<60 predicted the occurrence of CI‐AKI (P=0.04, B:2.3). It seems that the predisposing factors to CI‐AKI differ in diabetics and nondiabetics. In patients with diabetes, hypercholesterolemia is the strongest predictor of CI‐AKI, followed by eGFR and diabetics are at risk for CI‐AKI in the early stage of chronic kidney disease (stage 2), accounting for the higher incidence of CI‐AKI in them.     

Hemolysis‐induced acute kidney injury following cardiac surgery: A case report and review of the literature

Acute kidney injury is a common complication following cardiac surgery. Even small increases in creatinine levels are associated with increases in morbidity and mortality. Numerous factors such as hemolysis can contribute to the development of acute kidney injury after cardiac surgery. We present a rare case of severe hemolysis related to cardiopulmonary bypass resulting in kidney injury and requiring dialysis. The patient's renal function gradually recovered when hemolysis was improved. After follow‐up for 3 months, his creatinine levels returned to normal. We discussed the pathogenesis of this hemolysis‐related kidney dysfunction, the causes of hemolysis during cardiac surgery, and a new treatment option.     

Association between depression and inflammatory/anti‐inflammatory cytokines in chronic kidney disease and end‐stage renal disease patients: A review of literature

Depression is a common psychiatric disorder in patients with advanced chronic kidney diseases (CKDs). Strong correlation has been reported between depression and patients' morbidity and mortality among dialysis patients. On the contrary, chronic inflammation may be a major contributor to morbidity and mortality in these patients. Elevated plasma levels of proinflammatory cytokines, especially C‐reactive protein and interleukin (IL)‐6, have been correlated with cardiovascular events, hospitalization, and all‐cause and cardiovascular‐associated mortality in dialysis patients. Studies suggested that inflammation‐mediated atherosclerotic cardiovascular diseases are the possible reasons for depression‐induced mortality among patients without renal diseases. Several studies found significant elevations in circulating levels of proinflammatory cytokines, particularly IL‐6 and tumor necrosis factor‐α, in patients with major depression. Furthermore, depressive mood and behaviors, including sadness and suicidal ideation, were observed in patients who received repeated injections of recombinant cytokines. A thorough literature review indicates that while depressive symptoms and elevated inflammatory cytokine levels coexist in CKD and dialysis patients, their association is uncertain. Depression seems to be more associated with elevated serum levels of IL‐6 than other cytokines in these patients. Further studies are needed to clarify the possibility of a causal relationship between inflammation and depressive symptoms in CKD and dialysis patients.     

Use of mammalian target of rapamycin inhibitors after failure of tyrosine kinase inhibitors in patients with metastatic renal cell carcinoma undergoing hemodialysis: A single‐center experience with four cases

We retrospectively identified patients with end‐stage renal disease undergoing hemodialysis treated with the mammalian target of rapamycin inhibitors as a second‐ and/or third‐line targeted therapy after treatment failure with the tyrosine kinase inhibitors for metastatic renal cell carcinoma. Patient medical records were reviewed to evaluate the response to therapies and treatment‐related toxicities. Four patients were identified. All patients had undergone nephrectomy, and one had received immunotherapy before targeted therapy. Two patients had clear cell histology, and the other two had papillary histology. All patients were classified into the intermediate risk group according to the Memorial Sloan‐Kettering Cancer Center risk model. All patients were treated with everolimus as a second‐ or third‐line therapy, and two patients were treated with temsirolimus as a second‐ or third‐line therapy after treatment failure with sorafenib or sunitinib. The median duration of everolimus therapy was 6.7 months, whereas that of temsirolimus was 9.5 months. All patients had stable disease as the best response during each period of therapy. There were no severe adverse events. The use of mammalian target of rapamycin inhibitors in patients who previously failed to respond to tyrosine kinase inhibitors appears to be feasible in patients with end‐stage renal disease requiring hemodialysis.     

Risk of major depression in patients with chronic renal failure on different treatment modalities: A matched‐cohort and population‐based study in Taiwan

The influence of different treatment modalities on the risk of developing major depression in patients with chronic renal failure (CRF) is not well understood. We aimed to explore the incidence of major depression among patients with CRF who were on different dialysis modalities, who had received renal transplantation (RT), and those who had not yet received any of the aforementioned renal replacement therapies. We conducted a population‐based retrospective cohort study using a national health insurance research database. This study investigated 89,336 study controls, 17,889 patients with chronic kidney disease on conservative treatment, 3823 patients on hemodialysis (HD), 351 patients on peritoneal dialysis (PD), and 322 patients who had RT. We followed all individuals until the occurrence of major depression or the date of loss to follow‐up. The PD group had the highest risk (hazard ratio [HR] 2.43; 95% confidence interval [CI] 1.26–4.69), whereas the RT group had the lowest risk (HR 0.18; 95% CI 0.03–1.29) of developing major depression compared with the control group. Patients initiated on PD had a higher risk of developing major depression than patients initiated on HD (pairwise comparison: HR 2.20; 95% CI 1.09–4.46). Different treatment modalities are associated with different risks of developing major depression in patients with CRF. Among renal replacement therapies, patients who have had RT have the lowest risk of developing major depression. Patients who initiate renal therapy on PD may have a higher risk of major depression compared with patients who initiate renal therapy on HD.