Technique Failure in Peritoneal Dialysis: Etiologies and Risk Assessment.

Technique failure (TF) is a well-recognized challenge encountered in patients undergoing peritoneal dialysis (PD). Identification of patients at risk for this complication is of utmost importance. Early detection of patients at risk and development of preventative strategies can improve technique survival that may lead to an increased utilization of PD. It will also promote a safe and planned transfer to hemodialysis once a patient identified with TF. The aim of this review is to summarize risk factors and scenarios associated with TF focusing on prevention of remediable factors at their earliest stage. Furthermore, integration of this knowledge into quality improvement initiatives should be entertained in an effort to improve outcomes.

Mitochondria in Sepsis-Induced AKI.

AKI is a common clinical condition associated with the risk of developing CKD and ESKD. Sepsis is the leading cause of AKI in the intensive care unit (ICU) and accounts for nearly half of all AKI events. Patients with AKI who require dialysis have an unacceptably high mortality rate of 60%-80%. During sepsis, endothelial activation, increased microvascular permeability, changes in regional blood flow distribution with resulting areas of hypoperfusion, and hypoxemia can lead to AKI. No effective drugs to prevent or treat human sepsis-induced AKI are currently available. Recent research has identified dysfunction in energy metabolism as a critical contributor to the pathogenesis of AKI. Mitochondria, the center of energy metabolism, are increasingly recognized to be involved in the pathophysiology of sepsis-induced AKI and mitochondria could serve as a potential therapeutic target. In this review, we summarize the potential role of mitochondria in sepsis-induced AKI and identify future therapeutic approaches that target mitochondrial function in an effort to treat sepsis-induced AKI.

Tissue inhibitor metalloproteinase-2 (TIMP-2) • IGF-binding protein-7 (IGFBP7) levels are associated with adverse outcomes in patients in the intensive care unit with acute kidney injury.

The G1 cell cycle inhibitors tissue inhibitor metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) have been identified as novel biomarkers for the prediction of moderate to severe acute kidney injury (AKI) risk. However, the prognostic value of [TIMP-2]•[IGFBP7] in predicting adverse outcomes in intensive care unit (ICU) patients with AKI was not previously described. To evaluate this, we conducted a cohort study, measuring [TIMP2]•[IGFBP7] levels in critically ill patients admitted to the ICU and classified the patients as NephroCheck (NC) (+) or NC (-) according to [TIMP-2]•[IGFBP7] values and AKI (+) or AKI (-) according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We then evaluated the incidence of continuous renal replacement therapy initiation, all-cause mortality and a composite endpoint of both in the four groups. Baseline [TIMP-2]•[IGFBP7] values were available for 719 patients, of whom 239 developed AKI and 151 met the composite endpoint. Compared to NC (-)/AKI (+) patients, NC (+)/AKI (+) patients had a significant risk of ICU mortality and the composite endpoint. Kaplan-Meier curves showed that the survival estimate for the composite endpoint of NC (+)/AKI (+) patients was 34.4%; significantly worse than NC (-)/AKI (+) patients (67.4%). Multivariate analyses showed strong association between NC positivity and the composite endpoint. The inflammatory marker, procalcitonin, was an additional prognostic biomarker to compare and confirm the incremental value of NephroCheck. No association between procalcitonin and the composite endpoint was found, especially in patients with AKI, suggesting that NephroCheck may be more kidney specific. Thus, the [TIMP-2]•[IGFBP7] values can serve to identify patients with AKI at increased risk for adverse outcomes in the ICU.

Current understanding and future directions in the application of TIMP-2 and IGFBP7 in AKI clinical practice.

NephroCheck® is the commercial name of a combined product of two urinary biomarkers, tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7), expressed as [TIMP-2]·[IGFBP7], used to identify patients at high risk of acute kidney injury (AKI). AKI is a common and harmful complication especially in critically-ill patients, which can induce devastating short- and long-term outcomes. Over the past decade, numerous clinical studies have evaluated the utility of several biomarkers (e.g. neutrophil gelatinase-associated lipocalin, interleukin-18, liver-type fatty acid binding protein and kidney injury molecule-1, cystatin C) in the early diagnosis and risk stratification of AKI. Among all these biomarkers, [TIMP-2]·[IGFBP7] was confirmed to be superior in early detection of AKI, before the decrease of renal function is evident. In 2014, the US Food and Drug Administration permitted marketing of NephroCheck® (Astute Medical) (measuring urinary [TIMP-2]·[IGFBP7]) to determine if certain critically-ill patients are at risk of developing moderate to severe AKI. It has since been applied to clinical work in many hospitals of the United States and Europe to improve the diagnostic accuracy and outcomes of AKI patients. Now, more and more research is devoted to the evaluation of its application value, meaning and method in different clinical settings. In this review, we summarize the current research status of [TIMP-2]·[IGFBP7] and point out its future directions.

International Survey on the Management of Acute Kidney Injury and Continuous Renal Replacement Therapies: Year 2018.

INTRODUCTION: Definition, prevention, and management of acute kidney injury (AKI) and the optimal prescription and delivery of renal replacement therapy (RRT) are currently matters of ongoing discussion. Due to the lack of definitive published literature, a wide gap might exist between routine clinical practice and available recommendations. The aim of this survey was to explore the clinical approach to AKI and RRT in a broad population of nephrologists and intensivists participating in the 36th International course on AKI and Continuous RRT (CRRT), held in Vicenza in June 2018. The responses of the 369 participants to a questionnaire on several aspects of critical care nephrology were analyzed and detailed. RESULTS: Approximately 450 participants attended the course; of these, 369 (82%) correctly filled the survey forms. According to the reported answers, the average incidence of AKI in respondents' intensive care units (ICU) was 26.8% (SD ±15.99) and AKI requiring dialysis was 13% (SD ±29.7). Sixty-four percent of participants defined AKI as an increase in serum creatinine (SCr) up to 0.99 mg/dL (SD ±0.88 mg/dL); 2.4% defined AKI as an increase in urea nitrogen up to 83.6 mg/dL (SD ±36.6 mg/dL); 33.6% defined AKI as decreased urine output to less than 1 mL/kg/h (SD ±0.6 mL/kg/h). The most common answer to classify AKI was Kidney Disease: Improving Global Outcomes (KDIGO; 41%) criteria. Most of the participants (25%) think novel biomarkers should replace SCr on daily routine laboratory screening, and Cystatin C was the most commonly used biomarker (19%). The use of diuretics in AKI patients was high (62%). Continuous RRT (59%) and heparin anticoagulation (42%) appeared to be the most common approaches in ICU. CONCLUSIONS: KDIGO appeared to be widely applied. The use of novel biomarkers has also emerged in recent years even if some consistent cost-benefit evidence is still lacking. There is a trend of increased awareness about AKI and extracorporeal treatments seem to be increasingly applied, when compared to previous surveys. Educational efforts and AKI management standardization still appear to be a fundamental aspect to harmonize therapeutic approaches and improve patients' outcomes.

Gut-kidney crosstalk in septic acute kidney injury.

Sepsis is the leading cause of acute kidney injury (AKI) in the intensive care unit (ICU). Septic AKI is a complex and multifactorial process that is incompletely understood. During sepsis, the disruption of the mucus membrane barrier, a shift in intestinal microbial flora, and microbial translocation may lead to systemic inflammation, which further alters host immune and metabolic homeostasis. This altered homeostasis may promote and potentiate the development of AKI. As part of this vicious cycle, when AKI develops, the clearance of inflammatory mediators and metabolic products is decreased. This will lead to further gut injury and breakdown in mucous membrane barriers. Thus, changes in the gut during sepsis can initiate and propagate septic AKI. This deleterious gut-kidney crosstalk may be a potential target for therapeutic maneuvers. This review analyses the underlying mechanisms in gut-kidney crosstalk in septic AKI.

How Does Continuous Renal Replacement Therapy Affect Septic Acute Kidney Injury?

Sepsis is the leading cause of acute kidney injury (AKI) in the intensive care unit. As the most common treatment of septic AKI, it is believed that continuous renal replacement therapy (CRRT) can not only maintain the water balance and excrete the metabolic products but also regulate the inflammation and promote kidney recovery. CRRT can remove the inflammatory cytokines to regulate the metabolic adaption in kidney and restore the kidney recovery to protect the kidney in septic AKI. Second, CRRT can provide extra energy supply in septic AKI to improve the kidney energy balance in septic AKI. Third, the anticoagulant used in CRRT also regulates the inflammation in septic AKI. CRRT is not only a treatment to deal with the water balance and metabolic products, but also a method to regulate the inflammation in septic AKI.

Ultraviolet Radiations: Skin Defense-Damage Mechanism.

UV-radiations are the invisible part of light spectra having a wavelength between visible rays and X-rays. Based on wavelength, UV rays are subdivided into UV-A (320-400 nm), UV-B (280-320 nm) and UV-C (200-280 nm). Ultraviolet rays can have both harmful and beneficial effects. UV-C has the property of ionization thus acting as a strong mutagen, which can cause immune-mediated disease and cancer in adverse cases. Numbers of genetic factors have been identified in human involved in inducing skin cancer from UV-radiations. Certain heredity diseases have been found susceptible to UV-induced skin cancer. UV radiations activate the cutaneous immune system, which led to an inflammatory response by different mechanisms. The first line of defense mechanism against UV radiation is melanin (an epidermal pigment), and UV absorbing pigment of skin, which dissipate UV radiation as heat. Cell surface death receptor (e.g. Fas) of keratinocytes responds to UV-induced injury and elicits apoptosis to avoid malignant transformation. In addition to the formation of photo-dimers in the genome, UV also can induce mutation by generating ROS and nucleotides are highly susceptible to these free radical injuries. Melanocortin 1 receptor (MC1R) has been known to be implicated in different UV-induced damages such as pigmentation, adaptive tanning, and skin cancer. UV-B induces the formation of pre-vitamin D3 in the epidermal layer of skin. UV-induced tans act as a photoprotection by providing a sun protection factor (SPF) of 3-4 and epidermal hyperplasia. There is a need to prevent the harmful effects and harness the useful effects of UV radiations.