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.     

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.     

Biomarkers upon discontinuation of renal replacement therapy predict 60‐day survival and renal recovery in critically ill patients with acute kidney injury

Introduction: There is no consensus on the specific indications for weaning critically ill patients with acute kidney injury (AKI) off renal replacement therapy (RRT). This study aimed to explore the prognostic value of several biomarkers measured upon discontinuation of RRT for their value in predicting 60‐day survival and renal recovery in an effort to add knowledge to the decision‐making process regarding RRT withdrawal. Methods: We prospectively enrolled 102 patients with AKI who required RRT from the intensive care unit. Serum osteopontin (sOPN), serum interleukin 6 (sIL‐6), serum cystatin C (sCysC), sIL‐18, serum neutrophil gelatinase‐associated lipocalin and urinary IL‐18 and urinary neutrophil gelatinase‐associated lipocalin were measured upon discontinuation of RRT. Patients were followed up at 60 days for survival and renal recovery. Findings: Patients who survived showed lower levels of all serum and urinary biomarkers. Serum OPN (OR 1.029, 95% CI 1.013–1.047, P = 0.001), diabetes (OR 23.157, 95% CI 4.507–118.981, P < 0.001) and APACHE II score (OR 1.308, 95% CI 1.121–1.527, P = 0.001) were independent predictors of 60‐day mortality. Patients whose sOPN values fell within the highest and middle tertiles showed 5.25‐ and 2.31‐fold increased risks of mortality, respectively, compared with that of patients in the lowest tertile. The addition of sOPN to the clinical model resulted in significant net reclassification improvement of 0.453 (P = 0.026) and an integrated discriminative index of 0.155 (P = 0.032). Lower levels of sOPN and sIL‐6 were associated with greater odds of 60‐day survival (AUC 0.812 and 0.741). The AUC value for predicting survival reached its highest level when all biomarkers were combined with urine output (UO) and urinary and serum creatinine upon discontinuation of RRT (0.882). Lower sCysC performed as well as higher UO in predicting 60‐day renal recovery with the greatest AUC of 0.743. Discussion: Upon discontinuation of RRT, serum and urinary biomarkers, particularly sOPN, may predict 60‐day survival and renal recovery in critically ill patients with AKI. The serum levels of OPN, IL‐6 and CysC may be useful when considering withdrawal of RRT on the basis of conventional indicators.     

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.     

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.     

Evaluating safety of tunneled small bore central venous catheters in chronic kidney disease population: A quality improvement initiative

Introduction: Peripherally inserted central venous catheters (PICCs) may adversely impact future successful arteriovenous fistulae (AVF). As part of a quality improvement project, the performance of tunneled small bore tunneled central venous catheters (TSB‐CVCs), as alternatives to PICCs, was evaluated. Methods: A retrospective observational study, involving individuals ≥18 years of age who underwent TSB‐CVC placement by Interventional Radiology at Mayo Clinic, Rochester, MN between 1/1/2010 and 8/30/2013. Findings: The study cohort included 92 patients with a median age of 55 (46–67) years, who underwent 108 TSB‐CVC placements. Baseline renal disease was present in 71% (77/108). Most TSB‐CVCs were placed in hospitalized patients (94%; 102/108); five French in diameter (61%; 66/108) and located in an internal jugular vein (84%; 91/108). Median catheter indwelling time was 20 (11–43) days (n = 84). TSB‐CVC‐related bloodstream infection, deep venous thrombosis (DVT), and superficial venous thrombosis (SpVT) rates per line were 0.009 (1/108), 0.018 (2/108), and 0.009 (1/108), respectively. Venous outcomes in a subgroup of 54 patients, who had documented PICC placements (n = 161) in addition to TSB‐CVC (n = 58) were compared. TSB‐CVC‐DVT rate was lower than the PICC‐DVT rate (0.017 [1/58] vs. 0.106 per line [17/161]; P = 0.04). The TSB‐CVC‐SpVT rate was not different from the PICC‐SpVT rate (0 [0/58] vs. 0.037 [6/161] per line; P = 0.14). Discussion: TSB‐CVCs demonstrated an excellent safety profile in our study. These catheters should be preferentially utilized for arm vein preservation in advanced kidney disease. Their impact on future AVF success needs further evaluation.     

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.