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Immunotactoid glomerulopathy (ITG), a condition characterised by highly organised microtubules on electron microscopy, and cryoglobulin glomerulopathy (CG) are rare forms of kidney injury that may be encountered in patients with cryoglobulinaemia. It has been proposed these two entities are part of the same disease process following observed clinical and histological similarities. [ABSTRACT FROM AUTHOR]

Background: Apoptosis and oxidative stress in kidneys are critical players in acute kidney injury (AKI). Rehmapicrogenin, a monomeric compound extracted from Rehmanniae radix, has been found to possess nitric oxide inhibitory and anti‐inflammatory activities. Thus, this study aimed to investigate the roles and mechanisms of rehmapicrogenin in AKI. Methods: Lipopolysaccharide (LPS) was used to induce AKI‐like conditions. Cell survival conditions were detected by cell counting kit‐8 assays and flow cytometry. Several renal function markers including blood urea nitrogen, proteinuria, creatinine, and albumin were measured. Apoptosis and reactive oxygen species (ROS) production were examined by TUNEL and dihydroethidium staining, respectively. Haematoxylin–eosin staining and periodic acid‐Schiff staining were conducted to assess histopathological changes. Gene expression was evaluated by western blotting, commercially available kits and immunofluorescence staining. Results: For in vitro analysis, rehmapicrogenin inhibited the LPS‐induced podocyte apoptosis by activating the Nrf2/ARE pathway. For in vivo analysis, rehmapicrogenin improved renal functions in LPS‐induced mice. Additionally, rehmapicrogenin suppressed LPS‐induced podocyte apoptosis and oxidative stress in kidney tissues. Mechanistically, rehmapicrogenin activated the Nrf2/ARE pathway in LPS‐induced mice. Conclusion: Rehmapicrogenin relieves the podocyte injury and renal dysfunctions through activating the Nrf2/ARE pathway to inhibit apoptosis and oxidative stress. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a common complication, affecting up to 37% of hospitalized patients with SARS‐CoV‐2 infection and is proportional to its severity and portends poor prognosis. Diverse mechanisms have been proposed and studies reported conflicting results. Moreover, renal tropism of SARS‐CoV‐2 does not equate to its renal pathogenicity. For a virus to be pathogenic, in addition to its affinity (tropism) for specific tissue(s), host cells must allow viral entry, and discuss the important role played by transmembrane protease, serine 2 (TMPRSS2) and coexpression of both ACE2 and TMPRSS2 in the same cells is important to cause damage. Lack of coexpression of ACE2 and TMPRSS2 in the same cells of the kidneys is the limiting factor of SARS‐CoV‐2 direct effects in the kidney. We present the rationale and cumulative evidence supporting that AKI is secondary to hemodynamic and immunologic effects of SARS‐CoV‐2 infection than the direct injury or infection. SUMMARY AT A GLANCE: The mechanisms of acute kidney injury (AKI) associated with COVID‐19 are diverse. The author carefully analyzed all the previously‐published studies and provided the rationale and cumulative evidence that AKI is secondary to hemodynamic and immunologic effects of SARS‐CoV‐2 infection rather than direct kidney injury. The use of immuno‐electron or in‐situ hybridization technique is warranted to confirm any direct viral infection in the kidney. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is a vital contributor to chronic kidney disease and limited therapeutic options are existed to preserve the renal injury. The research presented here investigated the protective effect of nodakenin against AKI and the underlying mechanism. Methods: The effect of nodakenin was investigated in ischaemia reperfusion‐induced renal injury (IRI) of AKI mice and hypoxia‐treated primary renal tubular cells. Briefly, renal functions including creatinine and urea nitrogen were determined and mechanisms associated inflammation were investigated by the advantage of immunohistochemistry, western blot, RT‐PCR and flow cytometry. Results: Deterioration of renal functions including and creatinine, urea nitrogen and tubular necrosis were observed in IRI‐AKI model. In contrast, nodakenin strikingly alleviated the deterioration of creatinine, urea nitrogen and tubular necrosis when compared with IRI model. Moreover, nodakenin could significantly inhibit the expression of pro‐inflammatory cytokines including interleukin (IL)‐1β, IL‐6 and tumour necrosis factor‐α both in hypoxia‐treated primary renal tubular cells and in AKI model. Mechanistic studies revealed that nodakenin dramatically suppressed the production of reactive oxygen species and subsequent NLPR3 inflammasome activation. Conclusion: In summary, these findings provided a solid evidence base and a new drug option for the treatment of AKI. SUMMARY AT A GLANCE: This study describes the use of a novel inhibitor, nodakenin to treat acute kidney injury from ischaemia‐reperfusion injury in a preclinical mouse model. Nodakenin targets reactive oxygen species and the NLPR3 inflammasome and significantly improved both renal functional and structural parameters. [ABSTRACT FROM AUTHOR]

Aim: The effects of methamphetamine intoxication on the kidney are not well reported. We aimed to investigate acute kidney injury (AKI) associated with methamphetamine intoxication, in particular its severity, duration and association with rhabdomyolysis. Methods: This is a prospective observational series of methamphetamine‐intoxicated patients presenting to an Emergency Department. Patients self‐reporting recent methamphetamine use, with a positive urine drug screen and an elevated creatinine, were eligible for the study. Urinary neutrophil gelatinase‐associated lipocalin (NGAL) was measured, and serum creatinine, creatine kinase and cystatin C concentrations were performed on arrival and at several time points until discharge from hospital. Demographic and clinical data were obtained from the medical records. Results: There were 634 presentations with methamphetamine intoxication over a 10‐month period, with 73/595(12%) cases having an elevated serum creatinine concentration on arrival. Fifty presentations in 48 patients were included in the study. Most patients (85%) were male with a median age of 32 years. The median serum creatinine concentration on presentation was 125 μmol/L (IQR:113‐135 μmol/L) with 45 (90%) presentations meeting diagnostic criteria for AKI. Concurrent rhabdomyolysis occurred in 22 (44%) presentations with a median CK of 2695 U/L (IQR:1598‐5060 U/L). Cystatin C was elevated (> 0.98 mg/L) in 18 cases. An elevated NGAL concentration (>150 μg/L) was present in five (10%) cases. No patients required dialysis. The median length of stay was 19 hours (IQR 14‐24 hours). Conclusion: AKI is common in methamphetamine intoxication. The kidney injury is relatively mild and short‐lived, resolving with crystalloid therapy. SUMMARY AT A GLANCE: One of the largest case series of metamphetamine associated AKI showing that AKI though commonly observed in metamphetamine abuse is often of low severity. [ABSTRACT FROM AUTHOR]

Aim: Helix B‐Surface peptide (HBSP) is the latest discovered erythropoietin (EPO) analogue that can retain the activity of EPO. EPO, which is widely used for treating renal anemia, has recently been proved to have protective effects on ischemia‐reperfusion injury of brain, heart and kidney. The protective effects of EPO and HBSP on cardiac function were found in rats with myocardial ischemia. However, the effect of HBSP on sepsis‐induced renal injury is still unclear. Methods: Establishment of rat kidney injury model and treated with HBSP and lipoposaccharide. Renal injury in rats was observed by hematoxylin‐eosin staining and injury index score. Levels of serum creatinine (SCr), blood urea nitrogen (BUN) and Cystatin C (Cys C) were detected using fully automatic biochemical analyzer, tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), and IL‐1β were detected by enzyme‐linked immunosorbent assay. Western blot analysis was performed to determine the role of HBSP in phosphatidylinositol 3‐kinase (PI3K)/Akt pathway. Results: Acute kidney injury (AKI) appeared after modeling, however, HBSP alleviated the pathological conditions of the kidney injury. In addition, HBSP lowered kidney injury index score in the rats, and decreased the levels of SCr, BUN, Cys C, TNF‐α, IL‐6 and IL‐1β, moreover, HBSP also showed the effect of activating PI3K/Akt pathway. Conclusion: HBSP alleviated lipoposaccharide‐induced AKI and improved kidney function of the rats with sepsis. More importantly, the effects of HBSP on lipoposaccharid‐induced AKI were realized via activating PI3K/Akt pathway. The findings in the current study provide new insights into the therapeutic mechanism for treating the disease. SUMMARY AT A GLANCE: Septic rats that were treated with helix B surface peptide (HBSP) had significantly lower kidney tissue injury score, serum creatinine and cytokines level such as IL‐6, IL‐1B in a model of sepsis associated acute kidney injury. The authors proposed that HBSP attenuates sepsis‐associated acute kidney injury via the PI3K/Akt pathway. [ABSTRACT FROM AUTHOR]

Background: Mortality in intensive care unit (ICU) patients with acute kidney injury (AKI) remains high. Previous studies have explored the role of HMG‐CoA reductase inhibitors (statins) with variable findings. Methods: The Randomized Evaluation of Normal versus Augmented Level Replacement Therapy (RENAL) Study recruited 1508 participants requiring dialysis in ICU between 2006 and 2009. Statin use was recorded at study baseline. Multivariate Cox modelling was used to assess associations of such statin use and all‐cause mortality. Propensity score analysis was performed for sensitivity analysis. The primary outcome was all‐cause mortality at 90 days. Results: Of the 1462 participants with the available data on statin usage, 187 (12.8%) received statin therapy at baseline. Participants who receiving statins were older (P < 0.001), less likely to have sepsis or require mechanical ventilation (P < 0.001). Multivariable analysis showed statin use did not have significant associations with mortality at both day 28 (hazard ratio (HR) = 1.053, 95% confidence interval (CI) = 0.784–1.415, P = 0.730) and day 90 (HR = 1.091, 95% CI = 0.836–1.424, P = 0.520). Propensity score analysis confirmed the lack of association between statin use and mortality at day 90 (HR = 1.042, 95% CI = 0.734–1.479, P = 0.819). However, in septic patients, multivariable analysis suggested statin therapy was associated with a trend to higher mortality at day 90 (HR = 1.688, 95% CI = 1.132–2.519, P = 0.010) and continuation of statins was associated with higher mortality (HR = 2.160, 95% CI = 1.296–3.599, P = 0.003), compared with statin withdrawal. Conclusion: In the RENAL study cohort, baseline statin use was not associated with mortality. Our findings do not support a protective role of statins in ICU patients with severe AKI. Clinical Trials registration number for the RENAL study: NCT00221013, the date of registration: September 14, 2005. SUMMARY AT A GLANCE: Among 1,462 patients requiring dialysis in the intensive care unit (ICU) between 2006 and 2009, there was no association between statin therapy and mortality. However, among patients with septic acute kidney injury (AKI) requiring dialysis, baseline statin use correlates with increased mortality. These findings do not support a protective role of statins in ICU patients with severe AKI, but raise caution about statin use among patients with septic AKI. [ABSTRACT FROM AUTHOR]

Aim: Studies have shown that cysteine‐rich protein 61 (Cyr61) increased in the post‐ischemic human kidney tissue. However, it is still unknown whether Cyr61 can be used as a biomarker in kidney ischemia/reperfusion (I/R) injury. Methods: Microarray data were collected from GSE58438 and GSE52004. The rat I/R model was established to evaluate the messenger RNA and protein expression of Cyr61, localization of Cyr61 by immunohistochemical and immunofluorescence staining, and changes in serum creatinine (Scr) at the same time. Results: Bioinformatics result showed that Cyr61 was significantly increased at 3 h after I/R in rat kidney, and involved in angiogene, positive regulation of locomotion and single organism cell adhesion. The rat I/R model results showed that Cyr61 was mainly expressed in renal tubular epithelial cells with I/R injury and the expression of Cyr61 was up‐regulated at I/R 1 h, peaked at 4–8 h and began to decay at 12 h. The area under curve of receiver operating characteristics of kidney tissue Cyr61 messenger RNA and urine Cyr61 were 90.2% and 86.1%, which all better than Scr 67.1% (P < 0.05). Conclusion: We made a preliminary investigation of the relationship between Cyr61 and AKI, which identifies that Cyr61 may replace Scr as an ultra‐early new biomarker in AKI. SUMMARY AT A GLANCE: Although Cystatin C (CysC) was recommended by some authors to be measured in addition to creatinine in glomerular filtration rate estimation, it has found its place in early detection of acute kidney injury after ischaemia/reperfusion injury in rat kidney. [ABSTRACT FROM AUTHOR]

Aim: Hyperuricemia is a risk factor for high morbidity and mortality in several diseases. However, the relationship between uric acid (UA) and the risk of acute kidney injury (AKI) and mortality remain unresolved in hospitalized patients. Methods: Data from 18 444 hospitalized patients were retrospectively reviewed. The odds ratio (OR) for AKI and the hazard ratio (HR) for all‐cause mortality were calculated based on the UA quartiles after adjustment for multiple variables. All analyses were performed after stratification by sex. Results: The fourth quartile group (male, UA > 6.7 mg/dL; female, UA > 5.4 mg/dL) showed a higher risk of AKI compared with the first quartile group (male, UA < 4.5 mg/dL; female, UA < 3.6 mg/dL), with the following OR: 3.2 (2.55–4.10) in males (P < 0.001); and 3.1 (2.40–4.19) in females (P < 0.001). There were more patients who did not recover from AKI in the fourth quartile compared with the first quartile, with the following OR: 2.0 (1.32–3.04) in males (P = 0.001) and 2.4 (1.43–3.96) in females (P = 0.001). The fourth quartile group had a higher risk of all‐cause mortality compared with the first quartile group, with the following HR: 1.4 (1.20–1.58) in males (P < 0.001) and 1.2 (1.03–1.46) in females (P = 0.019). The in‐hospital mortality risk was also higher in the fourth quartile compared with the first quartile, which was significant only in males (OR, 2.1 (1.33–3.31) (P = 0.002)). Conclusion: Hyperuricemia increases the risks of AKI and all‐cause mortality in hospitalized patients. Summary at a Glance: The present study revealed that patients with a high serum uric acid level had a higher risk of AKI compared with those with a low uric acid level. A high uric acid level was also associated with the risk of non‐recovery from AKI. These findings raise a possible further study about the dose‐response relationship (in particular, the non‐linear relationship) between serum uric acid and outcomes. [ABSTRACT FROM AUTHOR]

Background: Ischaemia‐reperfusion injury (IRI) is associated with programmed cell death that promotes inflammation and organ dysfunction. Necroptosis is mediated by members of receptor interacting protein kinases (RIPK1/3). Inhibition of RIPK1/3 provides a pro‐survival benefit in kidney IRI. Caspase‐8 initiates apoptosis and contributes to IRI. We studied whether inhibiting both RIPK3 and caspase‐8 would provide an additional benefit in kidney IRI. Methods: A clamp was applied to the left kidney pedicle for 45 min followed by right kidney nephrectomy. Kidney and serum from wild type, RIPK3−/−, and RIPK3−/− caspase‐8−/− double knockout (DKO) mice were collected post‐IRI for assessment of injury. Tubular epithelial cells (TEC) isolated from wild type, RIPK3−/−, and DKO mice were treated with interferons‐γ and interleukin‐1β to induce apoptotic death. Results: Kidney IRI of DKO mice did not show improvement over RIPK3−/− mice. We have found that DKO triggered 'intrinsic' apoptosis in TEC in response to interleukin‐1β and interferons‐γ. Up‐regulation of the B‐cell lymphoma 2 (Bcl‐2)‐associated death promoter, the Bcl‐2‐homologous antagonist killer and Bcl‐2‐associated X protein and enhanced activation of caspase‐3 and 9 were found in DKO TEC. TEC infected with Murine cytomegalovirus that encodes multiple cell death inhibitors resist to death. Conclusion: We show that the deletion of both RIPK3 and caspase‐8 does not provide additive benefit in IRI or TEC death and may enhance injury by up‐regulation of intrinsic apoptosis. This suggests blocking multiple death pathways may be required for the prevention of kidney IRI clinically. Summary at a Glance: Cell death is a feature of renal ischaemia/reperfusion injury and reducing necroptosis by targeting receptor interacting protein kinases (RIPK1/3) has been shown to exert a pro‐survival benefit. In this study, it was investigated whether loss of both RIPK1/3 and the apoptotic mediator caspase‐8 would provide an even greater survival advantage after ischaemia/reperfusion injury. Interestingly, additive benefits were not seen, instead renal injury appeared to be enhanced. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the prognostic value of baseline SOFA coagulation score (SOFA‐CS) and change in platelet counts in patients with severe acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT). Methods: We performed a secondary analysis from the Randomized Evaluation of Normal versus Augmented Level of RRT (RENAL) study. The primary endpoint was all‐cause mortality at 90 days after randomization. The association between baseline SOFA‐CS, changes in platelet counts, process of care, and clinical outcomes were analyzed using multivariate Cox model adjusted for baseline variables. Results: The complete SOFA‐CS data were available in 1454 out of 1508 patients from the RENAL study. Among them, 708 patients had an abnormal SOFA‐CS (defined as SOFA‐CS ≥ 1), while 746 patients had normal SOFA‐CS at baseline (SOFA‐CS = 0). An abnormal SOFA‐CS was independently associated with an increased risk of death at 90 days (HR = 1.27, 95% CI = 1.05–1.53, P = 0.015). An abnormal SOFA‐CS was associated with prolonged length of ICU stay and duration of mechanical ventilation as well. Furthermore, there was no significant association between changes in platelet counts in patients who survived beyond 4 days and 90 day mortality (HR = 1.26, 95% CI = 0.29–5.56, P = 0.76). However, on multivariable analysis a decline of ≥60% (HR = 1.93, 95% CI = 1.23–3.05, P = 0.004) was associated with 90 day mortality in patients who survived beyond the first 4 days. Conclusions: In the RENAL study, thrombocytopaenia is a common phenomenon in patients with severe AKI receiving CRRT. An abnormal baseline SOFA‐CS and reductions in platelet counts were associated with increased mortality at 90 days. Summary at a Glance: A secondary analysis of prospectively collected data from the RENAL study confirmed that an abnormal baseline SOFA CS (sequential organ failure assessment coagulation score), based on a reduced platelet count, was associated with increased 90‐day mortality in AKI patients on CRRT. [ABSTRACT FROM AUTHOR]

Aim: Acute kidney injury (AKI) is a frequent complication in cirrhotic patients. As serum creatinine is a poor marker of renal function in this population, we aimed to study the utility of several biomarkers in this context. Methods: A prospective study was conducted in hospitalized patients with decompensated cirrhosis. Serum creatinine (SCr), Cystatin C (CystC), NGAL and urinary NGAL, KIM‐1, protein, albumin and sodium were measured on three separate occasions. Renal resistive index (RRI) was obtained. We analyzed the value of these biomarkers to determine the presence of AKI, its aetiology [prerenal, acute tubular necrosis (ATN), or hepatorenal (HRS)], its severity and a composite clinical outcome at 30 days (death, dialysis and intensive care admission). Results: We included 105 patients, of which 55 had AKI. SCr, CystC, NGAL (plasma and urinary), urinary sodium and RRI at inclusion were independently associated with the presence of AKI. SCr, CystC and plasma NGAL were able to predict the subsequent development of AKI. Pre‐renal state showed lower levels of SCr, NGAL (plasma and urinary) and RRI. ATN patients had high levels of NGAL (plasma and urinary) as well as urinary protein and sodium. HRS patients presented an intermediate pattern. All biomarkers paralleled the severity of AKI. SCr, CystC and plasma NGAL predicted the development of the composite clinical outcome with the same performance as the MELD score. Conclusions: In patients with decompensated cirrhosis, early measurement of renal biomarkers provides valuable information on AKI aetiology. It could also improve AKI diagnosis and prognosis. Summary at a Glance: AKI is a frequent complication of patients with cirrhosis. Serum creatinine is unhelpful in differentiating potential etiologies. The role of renal biomarkers could bridge this gap and ultimately help diagnosis and prognosis. This well conducted study tests the performance of renal biomarkers in AKI. [ABSTRACT FROM AUTHOR]

Aim: Acute kidney injury (AKI) is an important clinical condition that is associated with increased mortality and morbidity. This study was performed to identify the factors that influence AKI stage, undergoing renal replacement therapy (RRT) and mortality. Methods: This study was retrospectively conducted on 219 children with AKI who had been referred to the paediatric nephrology division of Dr Sami Ulus Teaching Hospital during their inpatient treatment from 2008 to 2012. AKI was defined using pRIFLE criteria. Results: From the 219 enrolled patients, 131 were identified as having AKI at the time of hospital admission. Infant age group was the largest group. RRT was performed in 68 patients. Median RRT initiation time was 1.5 day (0–2) and the mortality increased significantly when RRT initiation time was >1 day. The likelihood of undergoing RRT was higher for patients who were younger, who were managed in PICU and who had intrinsic type of AKI. pRIFLE stage and AKI place did not influence the likelihood of undergoing RRT. Overall mortality was 26.9%. In log‐rank tests, factors influencing survival were younger age, being treated in PICU, developing AKI during inpatient treatment, having a comorbid condition and undergoing RRT. pRIFLE stage did not influence survival. In the logistic regression model, factors associated with mortality included younger age, undergoing RRT and having AKI during inpatient treatment. Having underlying disease and being managed in PICU did not influence the likelihood of death. Conclusion: Acute kidney injury is an important condition in all hospitalized patients. More studies and interventions are needed on this topic to identify, treat and prevent AKI. Summary at a Glance: AKI is a severe condition with high morbidity and mortality in hospitalized paediatric patients. From this study in AKI children, younger patients and those who had particular types of AKI were more likely to undergo RRT. It reinforces the need for research efforts in paediatric AKI and new strategies for early AKI detection and prevention. [ABSTRACT FROM AUTHOR]

With increasing longevity and the presence of multiple comorbidities, a significant proportion of hospitalized patients, and an even larger population in the community, is at increased risk of developing an episode of acute kidney injury (AKI). Because of improvements in short‐term outcomes following an episode of AKI, survivors of an episode of AKI are now predisposed to develop its long‐term sequel. The identification of risk for progression to chronic kidney disease (CKD) is complicated by the absence of good biomarkers that identify this risk and the variability of risk associated with clinical factors including, but not limited to, the number of AKI episodes, severity, duration of previous AKI and pre‐existing CKD that has made the prediction for long‐term outcomes in survivors of AKI more difficult. Being a significant contributor to the growing incidence of CKD, there is a need to implement measures to prevent AKI in both the community and hospital settings, target interventions to treat AKI that are also associated with better long‐term outcomes, accurately identify patients at risk of adverse consequences following an episode of AKI and institute therapeutic strategies to improve these long‐term outcomes. We discuss the lasting renal and non‐renal consequences following an episode of AKI, available biomarkers and non‐invasive testing to identify ongoing intra‐renal pathology and review the currently available and future treatment strategies to help reduce these adverse long‐term outcomes. Summary at a Glance: There is an imminent need to increase awareness among general physicians about the long term risk of an episode of AKI and the improved outcomes with early referral and follow up by a nephrologist. This review highlights the importance of recognising the renal and non‐renal consequences following an episode of AKI, and the available biomarkers for this condition. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) can increase the risk of developing incident chronic kidney disease (CKD). The severity, frequency and duration of AKI are crucial predictors of poor renal outcome. A repair process after AKI can be adaptive and kidney recovers completely after a mild injury. However, severe injury will lead to a maladaptive repair, which frequently progresses to nephron loss, vascular rarefaction, chronic inflammation and fibrosis. Although different mechanisms underlying AKI‐CKD transition have been extensively discussed, no definite intervention has been proved effective to block or to retard the transition until recently. In CKD, renin‐angiotensin system (RAS) inhibitor has been proved effective to slow down disease progression. Furthermore, RAS needs to be highlighted again in AKI‐CKD transition because recent animal studies have shown the activation of intra‐renal RAS after AKI, and RAS blockade can reduce the ensuing CKD and mortality. In patients with the complete renal recovery after AKI, administration of RAS inhibitor is associated with reduced risk of subsequent CKD as well. In this article, we will demonstrate the role of RAS in AKI‐CKD transition comprehensively. We will then emphasize the promising effect of RAS inhibitor on CKD prevention in patients recovering from AKI based on evidence from the bench to clinical research. All of these discussions will contribute to the establishment of reliable monitoring and therapeutic strategies for patients with functional recovery from AKI who can be most easily ignored. Summary at a Glance: Renin‐angiotensin system (RAS) is activated after AKI and leads to AKI‐CKD continuum. RAS blockade can reduce the ensuing CKD and mortality. Using RAS blockade could be considered for the monitoring and therapeutic strategies after AKI. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) has imposed a heavy disease burden in China, with substantial underdiagnosis and undertreatment. The incidence, cause and outcome of patients with AKI vary according to different geographic regions and economic development status; therefore, regional improvement strategies are needed. Defining the etiology of AKI is critical in making the proper therapeutic regimen, and a multidisciplinary cooperative AKI team is essential in order to establish the early diagnosis and proper management of patients with AKI. Summary at a Glance: This review considers the national health challenge posed by acute kidney disease, the importance of implementing regional improvement strategies and multidisciplinary cooperative AKI team in China. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy is one of the leading causes of end‐stage renal disease and creates heavy healthcare burdens globally. Dysfunction of mesangial cells and podocytes contributes to diabetic nephropathy. Dysregulation of signaling involved in renal development and regeneration may cause diabetic kidney damages. Growing evidences suggest the importance of dysregulated dickkopf‐1 (DKK1)/Wnt/ β‐catenin signaling pathways in the pathogenesis of diabetic glomerular injuries. The inhibition of Wnt signaling in injured mesangial cells is likely attributed to the high glucose‐induced Ras/Rac1 dependent superoxide formation. When DKK1, the cellular inhibitor of Wnt signaling, binds to the Kremen‐2 receptor, depositions of extracellular matrix increase in the mesangium of diabetic kidneys. Additionally, reactivation of Notch‐1 signaling has been implicated in podocytopathy during diabetic proteinuria development. Knocking down Notch‐1 alleviates vascular endothelial growth factor (VEGF) expression, nephrin repression and proteinuria in diabetic kidneys. It is also found that epigenetic modulations by histone deacetylase 4 (HDAC4) and miR‐29a could lead to diabetic nephropathy. High glucose increases the expression of HDAC4, which causes deacetylation with subsequent ubiquitination of nephrin. Overexpression of miR‐29a in diabetic transgenic mice would decrease the expression of HDAC4 and stabilize nephrin. Surprisingly, reprogramming or reactivation of signaling involved in renal development or regeneration often brings about diabetic glomerular sclerosis in mesangial cells and podocytes. Better knowledge about modifications of embryonic stem cell signaling will have a chance to implement strategically focused pharmacological research programs aiming to the development of new drugs for diabetic kidney injuries. Summary at a Glance: Dysregulation of signaling involved in renal development or regeneration often leads to diabetic nephropathy. Recent advances of these molecular mechanisms are discussed. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To assess the efficacy, safety and calcium balance of a membrane based regional citrate anticoagulation plasma exchange protocol. Methods: This was an observational, prospective, single centre study of membrane separation plasma exchange using regional citrate anticoagulation. It was performed using a fixed dose pre‐filter citrate infusion that was based on the plasma flow rate. Patients received a post filter calcium infusion that was modified during treatment based on systemic ionized calcium monitoring. Post filter ionized calcium was not assessed. Safety and efficacy were assessed by extraction of clinical events and laboratory data contemporaneously recorded in electronic health records. Results: Thirty‐six sessions in five patients were performed. No patients developed symptomatic hypocalcaemia, and no patient had a recorded ionized calcium below 0.81 mmol/L. Filter clotting occurred in two sessions. The mean net calcium gained was 9.6 ± 1.8 mmol per session. Conclusion: Regional citrate anticoagulated membrane separation plasma exchange can be performed safely and effectively without the need for post filter ionized calcium monitoring. The algorithm employed resulted in a net calcium gain. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To investigate the prognostic factors of acute kidney injury (AKI) in our daily practice. Methods: We analyzed the cohort of patients hospitalized for AKI in the period from January 2010 to December 2015 in the Department of Internal Medicine, University Hospital of Treichville. Kaplan–Meier curves were built for survival analysis. Cox regression analysis was used to identify independent predictors of mortality. Results: We collected 414 cases of AKI during the study period. The mean age was 48.3 ± 16.8 years. We observed a male predominance with a sex ratio (236/178) of 1.32. In multivariate analysis, the predictive factors of death were age ≥ 65 years (HR = 2.13; 95% CI = 1.28–3.55; P = 0.004), AKI stage 3 (HR = 1.69; 95%CI = 1.13–2.50; P = 0.009), haemoglobin <8 g/dL (HR = 2.91; 95% CI = 1.79–4.72; P = 0.0001), infection (HR = 1.85; 95% CI = 1.21–2.83; P = 0.004) and drug‐induced AKI (HR = 3.23; 95% CI = 1.65–6.29; P = 0.001). Factors associated with incomplete recovery or non‐recovery of renal function beyond 3 months were age ≥ 65 years (OR = 4.76; 95% CI = 1.85–12.50;P = 0.001), hypertension (OR = 2.17; 95% CI = 1.07–4.34; P = 0.03), haemoglobin <8 g/dL (OR = 6.66; 95% CI = 2.94–8.28; P < 0.001), AKI stage 3 (OR = 9.09; 95% CI = 4.54–16.66; P < 0.001) malignant hypertension (OR = 5; 95% CI = 1.67–7.27; P = 0.005) and cancer (OR = 4.69; 95% CI = 2.22–6.63; P = 0.001). Conclusion: The aetiologies are dominated by infections. The fatality rate is high and its risk factors are advanced age, low haemoglobin level, severe AKI, infection and drug intake. Prevention is essential. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to elucidatewhether urinary tubular markers during the chronic phase of acute kidney injury (AKI) are associated with chronic tubulointerstitial damage. Methods: Male human L-type fatty acid binding protein (L-FABP) chromosomal transgenic (Tg) mice underwent ischaemic reperfusion (I/R) injury via renal pedicle clamping for either 10 min or 20 min. Contralateral nephrectomy was performed at the time of tissue reperfusion. The kidneys were analyzed 20 days after the last I/R. Results: Serum creatinine levels 20 days post-I/R were significantly higher in the 20 min I/R than in the 10 min I/R and control groups and were similar between the 10min I/R and control groups. The degree of tubulointerstitial damage 20days post-I/Rwas significantly more severe in the 20 min I/R than in the 10 min I/R and control groups, as well as in the 10 min I/R than in the control group. Urinary levels of human L-FABP, albumin, and kidney injury molecule-1 (KIM-1) 20 days post-I/R were significantly higher in the 20 min I/R than in the control group, where as urinary L-FABP was significantly higher in the 10 min I/R than in the control group. Conversely, urinary neutrophil gelatinase-associated lipocalin levels did not significantly differ between the three groups. Finally, the urinary levels of human L-FABP, albumin, and KIM-1 levels 20 days post-I/R were significantly correlated with the degree of renal damage. Conclusions: Urinary levels of human L-FABP, albumin and,KIM-1may be useful for monitoring AKI-to-CKD transition in clinical practice. [ABSTRACT FROM AUTHOR]

Aim: To identify risk factors for acute kidney injury following major orthopaedic surgery. Methods: We included all patients undergoing major orthopaedic surgery at University Hospital Geelong between 2008 and 2014 in the study. Out of 2188 surgeries audited, we identified cases of acute kidney injury using the RIFLE criteria and matched those to controls 2:1 for age, sex, procedure and chronic kidney disease stage. We reviewed their records for risk factors of postoperative acute kidney injury, including medications such as gentamicin, diuretics, non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use. We reviewed the patients' history of cardiovascular disease, chronic liver disease, hypertension and diabetes mellitus along with presence of sepsis and obesity. Associations of hypothetical risk factors were estimated using conditional logistic regression. Results: We identified 164 cases of AKI in an elderly cohort (median age = 73 years). Controlling for baseline comorbidities, both diuretic and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use were found to be associated with a twofold risk of acute kidney injury (diuretic – OR 2.06 95% CI:1.30–3.26, P < 0.005, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use OR 2.09 95% CI:1.31–3.32, P < 0.005). A dose-effect model accounting for perioperative nonsteroidal anti-inflammatory drug administration demonstrated a linear relationship between the number of times these drugs were given and postoperative acute kidney injury risk (OR 1.35 95% CI:1.05–1.73, P = 0.02). Conclusions: We identified perioperative diuretics, non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to be significantly associated with postoperative AKI. Further prospective studies are required to confirm this. [ABSTRACT FROM AUTHOR]

Aim: The purpose of the study was to evaluate urinary renalase concentration before and after coronary angiography/percutaneous coronary interventions (CA/PCI) in patients with coronary artery disease (CAD) and preserved kidney function and verify its potential application as contrast-induced acute kidney injury (CI-AKI) diagnostic marker. Methods: This prospective study comprised 95 consecutive patients (69.5% men; median age 65 years) with CAD submitted to elective or urgent CA/PCI. Data regarding 128 clinical variables were obtained. Urine samples were collected on admission and 6 h after CA/PCI and tested for urinary renalase using ELISA method, which was expressed as renalase-to-creatinine ratio. The CI-AKI diagnosis was based on ≥50% relative or ≥0.3 mg/dl absolute increase of serum creatinine concentration 48 h following the procedure. Results: Nine patients developed CI-AKI (9.5%). In comparison to baseline values, urinary renalase-to-creatinine ratio significantly decreased 6 h following CA/PCI, (2843.6 vs.1540.7 ng/mg, P < 0.0001). Nine patients developed CI-AKI (9.5%).The reduction of renalase level was profound both in CI-AKI (2709.7 vs. 1585.7 ng/mg, P = 0.007) and non-CI-AKI group (2814.9 vs.1561.8 ng/mg, P < 0.0001). There was a trend towards a greater relative decrease of urinary renalase in CI-AKI group (−57.3 vs.–41.8%, P = 0.10). Univariate analysis revealed that both pre- and post-procedural urinary renalase did not predict CI-AKI onset; however, absolute decrease of renalase below 25 percentile was a predictor of CI-AKI (OR = 5.4, 95% CI:1.3–21.9, P = 0.027). Conclusion: Urinary renalase concentration is reduced in the aftermath of CA/PCI, which may be related to CI-AKI development. Further studies are warranted to elucidate the role of urinary renalase as a CI-AKI diagnostic marker. [ABSTRACT FROM AUTHOR]

Critically ill adults with acute kidney injury (AKI) experience considerable morbidity and mortality. Controversy remains regarding the optimal renal replacement intervention for these patients. Our systematic review aimed to determine the effect(s) of sustained low-efficiency dialysis (SLED) compared with continuous renal replacement (CRRT) therapy on relevant patient outcomes. A systematic search of Medline, Embase, CINAHL and the Cochrane Library was conducted. Identified citations were screened independently in duplicate for relevance, and the methodological quality of included studies was evaluated. Data were extracted on study, patient and intervention characteristics and relevant clinical outcomes. Results were pooled using inverse variance fixed and random effectsmeta-analysis. A total of 1564 patients from 18 studieswere included. Meta-analysis results indicated no statistically significant difference in our primary outcome, overall proportion of renal recovery (risk ratio (RR) 0.87, 95%confidence interval (CI) 0.63-1.20, I2 = 66%). No significant difference was observed for the secondary outcome of time to renal recovery (mean difference 1.33, 95% CI 0.23-2.88, I2=0%). Statistically, SLED was marginally favoured over CRRT for the secondary outcome of mortality (RR 1.21, 95% CI 1.02-1.43, I2= 47%); however, this diminished when sensitivity analysis of only randomized controlled trials was conducted (RR 1.25, 95%CI 1.00-1.57, I2=0%). There appears to be no clear for advantage continuous renal replacement in the hemodynamically unstable patient. Currently, both modalities are safe and effective means of treating AKI in the critically ill adult. [ABSTRACT FROM AUTHOR]

Aim This study aimed to determine the incidence and risk factors of acute kidney injury (AKI) following transcatheter aortic valve replacement (TAVR). Methods We included all adult patients undergoing TAVR for aortic stenosis from 1 January 2008 to 30 June 2014 at a tertiary referral hospital. AKI was defined based on Kidney Disease: Improving Global Outcomes criteria. We performed a multivariate logistic regression to identify factors associated with post-procedural AKI occurrence. Results Three hundred eighty-six patients met the inclusion criteria, of which 106 (28%) developed AKI. In multivariate analysis, AKI development was independently associated with a transapical approach (odds ratio (OR), 2.81; 95% confidence interval (CI), 1.72-4.65 compared with transfemoral approach) and the need for an intra-aortic balloon pump (OR, 9.11; 95% CI, 1.77-68.29). Higher baseline renal function (OR, 0.78 per 10 mL/min per 1.73 m2 increment in glomerular filtration rate; 95% CI, 0.68-0.87) was significantly associated with a decreased risk of AKI. After adjustment for the Society of Thoracic Surgeons' risk score, post-procedural AKI development remained significantly associated with an increased in-hospital (OR, 4.74; 95% CI, 1.39-18.48) and 6-month mortality (OR, 4.66; 95% CI, 2.32-9.63). Conclusion In a cohort of patients undergoing TAVR for aortic stenosis, AKI commonly occurred and was significantly associated with increased mortality. Baseline renal function, procedure approach and the need for circulatory support were important predictive factors for post-procedural AKI occurrence. [ABSTRACT FROM AUTHOR]

Aim Acute kidney injury (AKI) is a common complication of minimal change nephrotic syndrome (MCNS), particularly in adults. We evaluated the prevalence of AKI at the onset of adult MCNS and analyzed the influence of AKI on the duration of achieving complete remission (CR). Methods A retrospective, single-centre, dynamic cohort study was conducted with biopsy-proven, first-onset, adult MCNS patients treated with corticosteroids. Fifty-three consecutive patients diagnosed with MCNS from January 2000 to April 2014 were enrolled. Age, gender, daily urinary protein excretion, and serum creatinine levels were measured. To evaluate AKI during induction, we used the Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guidelines for AKI and judged AKI stage according to the fluctuations in serum creatinine levels during the first 4 weeks of starting corticosteroid therapy. Results Twenty patients (37.7%) met the AKI criteria and all 53 patients achieved CR within 1 year. Kaplan-Meier analysis showed that the median time to CR was significantly longer in patients with AKI than in patients without AKI. Cox proportional hazard analysis showed that the hazard ratio (HR) associated with the presence of AKI for achieving CR within 4 weeks was 0.36 after adjustment for age, gender, serum albumin, daily urinary protein excretion, hypertension, administration of 25% albumin, and methylprednisolone pulse therapy. A graded association was also observed between AKI stage and HR for achieving CR. Conclusions The prevalence of AKI is high in adult patients with MCNS during induction therapy. AKI is an independent factor that delays the time to CR. [ABSTRACT FROM AUTHOR]

A calendar of various programs at the Asian Pacific Congress of Nephrology (APCN) to be held on September 17-21 2016 is presented which includes seminars on topics such as cell metabolism in kidney disease, challenges in managing chronic kidney disease and acute kidney injury; and dialysis.

Aim Acute kidney injury (AKI) is a frequent complication of sepsis, a pro-inflammatory state that alters tubular handling of filtered albumin. We hypothesized that dipstick albuminuria (DA) is associated with a lower rate of AKI recovery in septic patients. Methods This was a single-centre, retrospective cohort study of adults with sepsis-associated AKI in an urban academic intensive care unit (ICU). Patients with unknown baseline serum creatinine (SCr), absent urinalysis, and those with estimated glomerular filtration rate (eGFR) <15 mL/min per 1.73m2 or receiving chronic renal replacement therapy (RRT) were excluded. The independent variable was DA (negative or trace, 30 mg/dL, and ≥100 mg/dL) within the first 72 h of ICU stay. The outcome variable was AKI recovery at 30 days following hospital discharge, defined as the last SCr returning to a level less than 1.5 times the baseline SCr level and independence of RRT. Results A total of 988 patients were included in the study. The median length of hospitalization was 11 days. The patients with higher degree of DA had worse critical illness scores. After adjustment for several confounders, DA ≥30 mg/dL was independently associated with 'no AKI recovery' at 30 days post-discharge (adjusted OR 1.40, 95% CI, 1.01-1.95 for DA =30 mg/dL and 1.67, 1.15-2.42 for DA ≥100 mg/dL, P = 0.02). Other independent predictors of 'no AKI recovery' were cumulative fluid balance, Sequential Organ Failure Assessment (SOFA) score, exposure to diuretics, and the need for mechanical ventilation. Conclusion Dipstick albuminuria ≥30 mg/dL is independently associated with lower rate of AKI recovery at 30 days post-discharge. Our findings emphasize the potential utility of a simple routine test of DA in the risk-stratification of AKI recovery in ICU septic patients. [ABSTRACT FROM AUTHOR]

Aim The use of cardiopulmonary bypass (CPB) can cause changes in serum creatinine and cystatin C independent of glomerular filtration rate. We aimed to quantify the temporal changes of these biomarkers and C-reactive protein (CRP) after CPB. Methods This was a prospective study at an academic medical centre between April and October 2013. We compared postoperative changes in serum creatinine and cystatin C in 38 patients with normal preoperative kidney function who underwent cardiac surgery using CPB and did not develop perioperative acute kidney injury (AKI). The effect of inflammation on intra-individual changes was examined in mixed effects regressions, using measurements of pre- and postoperative CRP. Results Both serum creatinine (79.9 ± 22.7 vs. 92.6 ± 21.4 µmol/L, P = 0.001) and cystatin C (1.16 ± 0.39 vs. 1.33 ± 0.37 mg/L, P = 0.012) decreased significantly in the first 8 h postoperatively compared to preoperatively, as a result of haemodilution. Thereafter serum creatinine returned to preoperative levels, whereas serum cystatin C continued to rise and was significantly elevated at 72 h post-CPB compared to preoperative levels (1.53 ± 0.48 vs. 1.33 ± 0.37 mg/L, P = 0.003). CRP levels increased significantly post-CPB and were significantly associated with increases in both serum creatinine and cystatin C. Conclusion Serum creatinine and cystatin C appear not to be interchangeable biomarkers during and immediately after CPB. Processes unrelated to kidney function such as acute inflammation have a significant effect on post-CPB changes in these biomarkers, and may result in significant increases in serum cystatin C that could erroneously be interpreted as AKI. [ABSTRACT FROM AUTHOR]

Aim Patients with chronic heart failure (CHF) are often characterized by the cardiorenal syndrome (CRS). The aim of the present study was to assess whether novel markers of kidney injury are able to predict progression of chronic kidney disease (CKD) in patients with CHF. Methods New renal biomarkers, N-acteyl-ß-D-glucosaminidase (NAG), kidney injury molecule-1 (KIM-1) and Neutrophil Gelatinase-Associated Lipocalin (NGAL), were assessed from urine samples of 149 patients with chronic heart failure. During a 5-year-follow-up, renal function was assessed by creatinine and estimated glomerular filtration rate (eGFR CKD EPI) and was available for 138 patients. Further, data regarding all-cause mortality was obtained. Results Twenty-six patients (18.8%) developed a progression of CKD during the follow-up period, as defined by decline in eGFR category accompanied by a ≥25% drop in eGFR form baseline. No difference regarding age, sex, body mass index, hypertension, diabetes or EF was present between patients with and without CKD progression (each P = n.s.). At baseline, creatinine concentrations and eGFR were significantly different between both groups (sCr: 1.50 ± 0.67 vs 1.04 ± 0.37, P = < 0.001; eGFR: 47.8 ± 12.3 vs. 77.3 ± 23.5 mL/min per 1.73m2, each P < 0.001). In a Kaplan-Meier-analysis, KIM-1 and NAG were significant predictors for CKD progression (both P < 0.05). In Cox regression analysis, NAG > median (OR 3.25, P = 0.013), initial eGFR (OR 0.94, P < 0.001) and diuretic use (OR 3.92, P = 0.001) were independent predictors of CKD progression. Further, KIM-1 and NAG were also independent predictors of a combined endpoint of CKD progression and all-cause mortality by Cox regression analysis (each P < 0.05). The combination of both markers showed additive value regarding both endpoints. NGAL showed no association with CKD progression. Conclusions During long-term follow-up chronic heart failure patients with CKD show a relevant disease progression. The current study emphasizes a strong association of the tubular biomarkers NAG and KIM-1 with CKD progression in chronic heart failure and suggests their usefulness as cardiorenal markers. [ABSTRACT FROM AUTHOR]

Histopathological findings can play an important role in the management of atypical haemolytic uraemic syndrome ( aHUS). We report a case of aHUS that did not recover from anuria, despite the administration of eculizumab, with impressive histopathological findings. A 3-month-old girl was admitted because of poor feeding, vomiting, and diarrhoea without haemorrhage. She had anuria and severe hypertension, and laboratory results showed haemolytic anaemia with schizocytes, thrombocytopenia, and renal impairment. Although no mutations in the complement system or diacylglycerol kinase epsilon were detected, she was diagnosed with a HUS owing to the clinical course and by the exclusion of E scherichia coli infection and thrombotic thrombocytopenic purpura. Plasma exchange was performed once at day 2 and eculizumab therapy was started from day 18, with a severe infusion reaction at the first administration. After the initiation of eculizumab, although the serum lactate dehydrogenase level improved gradually, she did not recover from anuria. Pathological findings of the kidney biopsy at day 37 included diffuse arteriolar and arterial luminal stenosis with remarkable thickness and sclerotic changes of the media and intima, which are suggestive of aHUS. In addition, most glomeruli had global sclerosis and were collapsed, and 80% of the tubulointerstitial compartment showed atrophic changes with infiltration of inflammatory cells. The present case is possibly a kidney-specific fulminant type of aHUS. Although showing efficacy against thrombotic microangiopathy, eculizumab did not improve kidney function. The pathological findings reflected the severe and irreversible kidney injury. [ABSTRACT FROM AUTHOR]

Aim This study aimed to investigate how varied methods of determining baseline serum creatinine ( SCr) would affect acute kidney injury ( AKI) diagnosis and prediction of 60 day mortality in critically ill patients following an episode of AKI. Methods This is a single-centre retrospective study conducted at a tertiary referral hospital. All adult intensive care unit ( ICU) patients between January and December 2011, who had at least one SCr values measured between 7 days and 180 days before hospital admission and during ICU stay, were analyzed. The baseline SCr was calculated using either the most recent ( SCrmost recent) or the minimum (SCrmin) value of SCr measurement over the specified assessment period before hospital admission. AKI was defined based on KDIGO SCr definition. The primary outcome was 60 day mortality after ICU admission. Results A total of 4020 patients were included in the analysis. AKI was detected in 1204 (30.0%) using the SCrmin and 945 (23.5%) using the SCrmost recent ( P < 0.001). Compared with patients without AKI regardless of baseline SCr methodology, the 60 day mortality risk of patients who developed AKI using the SCrmin and SCrmost recent was significantly increased (odds ratio ( OR) = 3.74; 95% confidence interval ( CI) 2.98-4.70). Similarly, the risk of 60 day mortality in patients who met AKI criteria using the SCrmin but not the SCrmost recent was significant higher than in patients without AKI ( OR = 2.04; 95% CI 1.36-3.00). Conclusion Using the minimum value of preadmission SCr as a baseline kidney function not only can detect more AKI cases, but also provides the better predictive ability for 60 day mortality. [ABSTRACT FROM AUTHOR]

Aim We report here, a case series of patients with acute kidney injury ( AKI) after ingestion of paraphenylene diamine ( PPD) a derivative of analine. It is used as a colouring agent to dye hair, fur and plastic and in photographic films. Methods Subjects for the study reported here comprised a cohort of 100 patients coming to this institution with AKI following PPD poisoning. AKI was defined according to RIFLE criteria and PPD poisoning on the basis of history and presenting features. All patients had normal sized kidneys on ultrasonography and no previous co- morbidity. Results One hundred patients with AKI after PPD exposure were brought to this institute between May 2010 and February 2015. Among these, 56 were females, with mean age of 23.11 ± 7.94 years. Cause of AKI was toxic rhabdomyolysis as indicated by marked rise in muscle enzymes with mean lactate dehydrogenase and creatinine phosphokinase levels of 6665.22 ± 6272.04 and 194 486.66 ± 301 905.80, respectively. Hepatotoxicity with raised aspartate aminotransferase and alanine aminotransferase was a main feature of the studied population. Renal replacement was required in 97% of patients. Complete renal recovery was observed in 77 patients, while 16 died during the acute phase of illness. Respiratory failure and recurrent hyperkalaemia were the main causes of mortality. Conclusion Easy availability and low cost of PPD has lead to a remarkable increase in the use of this substance, especially for suicidal purposes. Awareness of its effects among health professionals, as well as at a societal and government level, is needed at this time. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is characterized by both non‐inflammatory and inflammatory process, and accumulating evidence has demonstrated that inflammation plays a key role in the pathogenesis and progression of AKI. C‐reactive protein (CRP), an acute reactant produced by liver and many inflammatory cells, acts not only as an inflammation biomarker, but also as a pathogenic factor for AKI. Indeed, increased concentration of CRP is associated with poor outcome of varied etiologically related AKI patients. In recent years, the role of CRP is gradually recognized as an active participant in the pathogenesis and progression of AKI by exacerbating local inflammation, impairing the proliferation of damaged tubular epithelial cells and promoting fibrosis of injured renal tissue. Summary at a Glance: Accumulating evidence demonstrates that CRP is not only an inflammation biomarker, but also a mediator of AKI. Recent studies revealed that CRP may mediate AKI by promoting renal inflammation, autophagy, mitochondrial dysfunction, and importantly by impairing tubular epithelial cell regeneration. Thus, CRP can be used as a biomarker for AKI. It is also possible that targeting CRP may represent as a novel therapy for AKI. [ABSTRACT FROM AUTHOR]

Acute kidney injury is a common condition in hospitalized patients and a strong predictor of short‐term morbidity and mortality. In this article, local epidemiological data on the prevalence and outcome of acute kidney injury amongst hospitalized patient in a tertiary referral center were discussed. The latest practice guidelines endorsed by the Hong Kong College of Physicians will be discussed, with emphasis on local practical issues and problems of guideline implementation. Summary at a Glance: We review the upcoming Hong Kong College of Physicians guideline on acute kidney injury. The global epidemiology of AKI is also discussed.. [ABSTRACT FROM AUTHOR]

Epigenetic modifications have emerged as a new, important contributor to gene expression regulation in both normal and pathophysiological conditions. Epigenetics have been studied in many diseases and conditions such as acute kidney injury ( AKI), a syndrome with a high prevalence that carries a poor prognosis with increased morbidity and mortality. In addition, it has recently been shown that AKI increases the risk for the development of chronic kidney disease ( CKD). The specific molecular mechanisms by which AKI increases the risk of CKD and end stage renal disease ( ESRD) remain unknown, although there is new evidence supporting a role of epigenetic changes. The most studied epigenetic regulations in AKI are chromatin compaction, DNA methylation, and histone acetylation/deacetylation. These modifications predominantly increase the production of pro-inflammatory and profibrotic cytokines such as: monocyte chemoattractant protein-1 ( MCP-1), complement protein 3 ( C3), transforming growth factor β ( TGF-β) that have been shown for perpetuating inflammation, promoting epithelial-to-mesenchymal transition ( EMT) and ultimately causing renal fibrosis. A review of epigenetic mechanisms, the pathophysiology of AKI and recent studies that implicate epigenetic modifications in AKI and in the transition to CKD are discussed below. [ABSTRACT FROM AUTHOR]

Aim While patients with chronic kidney disease have reduced health-related quality of life ( HRQOL), long-term HRQOL of survivors of severe acute kidney injury ( AKI) remains unclear. Methods We analysed HRQOL from the Prolonged Outcomes Study of the Randomized Evaluation of Normal versus Augmented Level Replacement Therapy ( POST-RENAL) study and compared findings with those from a general Australian adult population enrolled in the Australian Diabetes, Obesity and Lifestyle ( Aus Diab) study. We used a multivariate analysis adjusted for baseline characteristics along with sensitivity analysis using age and sex-matched case controls. Results In the POST-RENAL study, 282 participants had HRQOL data collected using the SF-12 questionnaire. This was compared with 6330 participants from the Aus Diab study. Unadjusted analyses showed that POST-RENAL participants had lower physical component scores ( PCS, mean score 40.0 vs 49.8, P < 0.0001) and lower mental component scores ( MCS, mean score 49.8 vs 53.9, P < 0.0001) than the Aus Diab group. After age and sex matching, the difference in PCS and MCS remained statistically significant ( P < 0.0001). Advanced age, reduced renal function and albuminuria (all P ≤ 0.01) were all strongly associated with lower PCS values but not MCS values. After matching subsets of the cohorts on the basis of age, sex and renal function, PCS and MCS were lower in the POST-RENAL group ( P < 0.0001). Conclusion Survivors of severe AKI in the POST-RENAL study had lower physical and mental components of HRQOL compared with general population, even after adjustment for their reduced renal function. Increasing age and reduced renal function were associated with poorer physical QOL. [ABSTRACT FROM AUTHOR]

Aim The performance of plasma neutrophil gelatinase-associated lipocalin ( pNGAL) for prediction of acute kidney injury ( AKI) in non-cardiac surgical patients has not been well described. This study investigates the use of pNGAL for early detection of AKI in patients admitted to an intensive care unit ( ICU) after major or ultra-major non-cardiac surgery. Methods A total of 151 patients were recruited. Blood samples at 0 h and 6 h post- ICU admission were collected. Primary outcome was occurrence of AKI within 48 h of ICU admission defined using Acute Kidney Injury Network ( AKIN) classification. Results Forty-five (29.8%) patients developed AKI within 48 h of ICU admission. Among them, 22, 14, and nine were classified as AKIN Stage 1, 2, and 3 respectively. pNGAL levels at 0 h and 6 h were significantly related to AKI severity. The AUROC for pNGAL at 0 h and 6 h increased with AKI severity ( AKIN stage ≥1 0.671 ± 0.048 and 0.691 ± 0.047; stage ≥2 0.737 ± 0.055 and 0.796 ± 0.048; stage 3 0.829 ± 0.072 and 0.860 ± 0.065, respectively) and requirement of renal replacement therapy (0.880 ± 0.059 & 0.837 ± 0.088). Change of pNGAL from 0 h to 6 h showed no advantage in predictive power compared with pNGAL level at 0 h or 6 h alone. The addition of pNGAL into clinical AKI prediction model could only provide marginal benefit. Conclusion pNGAL correlated with severity of AKI and requirement of renal replacement therapy in ICU patients who received major or ultra-major non-cardiac surgery. However, the benefit of adding pNGAL into clinical AKI prediction model is marginal. [ABSTRACT FROM AUTHOR]

Aim Acute kidney injury ( AKI) is one of the main causes of morbidity and mortality in cases of envenomation by venomous snakes. The present study was carried out to investigate the clinical and laboratory manifestations in accidents with venomous snakes and the risk factors associated with AKI in these accidents. Methods A retrospective study was carried out with patients victims of snakebite admitted to a reference centre. AKI was defined according to the RIFLE and AKIN criteria. Results A total of 276 patients were included, of which 230 (83.7%) were males. AKI was observed in 42 cases (15.2%). The mean genus involved in the accidents was Bothrops (82.2%). Mean age of patients with AKI was higher than in patients without AKI (43 ± 20 vs. 34 ± 21 years, P = 0.015). The time elapsed between the accident and medical care was higher in the AKI group (25 ± 28 vs. 14 ± 16h, P = 0.034), as well as the time elapsed between the accident and the administration of antivenom (30.7 ± 27 vs. 15 ± 16 h, P = 0.01). Haemodialysis was required in 30% of cases and complete renal function recovery was observed in 54.8% of cases at hospital discharge. There were four deaths, none of which had AKI. Factors associated with AKI were haemorrhagic abnormalities ( P = 0.036, OR = 6.718, 95% CI: 1.067-25.661) and longer length of hospital stay ( P = 0.004, OR = 1.69, 95% CI 1.165-2.088). Conclusion Acute kidney injury is an important complication of snakebite accidents, showing low mortality, but high morbidity, which can lead to partial renal function recovery. [ABSTRACT FROM AUTHOR]

We aimed to examine the association between preoperative use of statins and postoperative acute kidney injury ( AKI) in patients undergoing major surgery by performing a systemic review and meta-analysis. MEDLINE and EMBASE, from inception to April 2013, and the reference lists of related articles were searched for relevant studies. Trials comparing preoperative statin therapy with no preoperative statin in patients undergoing major surgery were included. Outcome measures of interest were the risk of cumulative postoperative AKI and postoperative AKI requiring renal replacement therapy ( RRT). Fixed or random effect meta-analysis was performed to derive summary effect estimates. In five randomized controlled trials ( RCTs) and 19 observational studies, comprising a total of 989 173 patients undergoing major surgery, 112 840 patients (11.41%) received preoperative statin therapy. The specific type, dosage, and duration of statin therapy were not available in most studies. Preoperative statin therapy was associated with a significant risk reduction for cumulative postoperative AKI (weighted summary odds ratio ( OR) 0.87, 95% CI 0.79 to 0.95). The effect of risk reduction was also significant when considering postoperative AKI requiring RRT ( OR 0.80, 95% CI 0.72 to 0.90). When restricting the analysis to the five RCTs, preoperative statin therapy did not show significant protective effect on postoperative AKI ( OR 0.49, 95% CI 0.22 to 1.09). In patients undergoing major surgery, preoperative statin therapy could associate with a reduced risk for postoperative AKI. However, considerable heterogeneity existed among included studies. Future randomized trials were warranted for this critical clinical question. [ABSTRACT FROM AUTHOR]

Haemolytic uraemic syndrome is a rare condition with an overall incidence of one to two cases in a population of 100 000 and approximately 10% of these cases are classified as atypical. Atypical haemolytic uraemic syndrome (aHUS) is a thrombotic microangiopathy (TMA) characterized by microangiopathic haemolytic anaemia (MAHA), thrombocytopenia and acute kidney injury. aHUS can be genetic, acquired or idiopathic (negative genetic screening and no environmental triggers). We describe a case of aHUS triggered by monoclonal gammopathy of renal significance (MGRS) successfully treated with plasmapheresis and a bortezomib-based chemotherapy regimen, resulting in marked improvement in renal function and other markers of haemolysis. This patient has been in remission for more than 2 years currently. [ABSTRACT FROM AUTHOR]

Aim Cystatin- C ( CysC) has been demonstrated as a sensitive and reliable biomarker to predict the onset of acute kidney injury ( AKI). However, there are few studies concerned about the relationship between CysC and the outcomes of AKI. The aim of the present study was to determine whether CysC elevation prior to definite diagnosis of AKI is related to higher prevalence of death and dialysis need outcome. Methods A meta-analysis was conducted by searching PubMed, EMBASE and Cochrane Library database using the terms related to AKI combined with 'cystatin- C'. Bibliographies of relevant papers were reviewed manually. Eligible studies were those investigating death and dialysis need outcomes after AKI with CysC measurement, and were limited to English articles. Non-human studies were excluded. Random effect Mantel- Haenszel statistical method was used. Results Six studies were finally enrolled, consisting of 2332 patients. All of these studies were hospital-based prospective cohort studies. The follow-up duration varied from 5 days to 1 year. The odds ratio values for baseline CysC elevation and death as well as baseline CysC elevation and dialysis need were 2.34 (95% confidence interval [ CI] 1.46-3.75) and 4.40 (95% CI 1.58-12.22), respectively (both P < 0.05). Conclusion Patients with CysC elevated prior to AKI diagnosis have higher risk to develop death and need dialysis during short- and long-term follow-up after AKI, thus having worse outcomes. This population deserves more careful observation and might benefit from more frequent follow-up visits in the clinic. Future work is needed to get a consensus cut-off value defining CysC elevation. [ABSTRACT FROM AUTHOR]

Renal fibrosis results from an excess accumulation of connective tissue, primarily collagen, in response to tissue injury-associated aberrant wound healing, which is over-expressed in the renal vascular, glomerular and tubulointerstitial compartments. Despite being the final common pathway of end stage kidney disease, there is a lack of consensus on standardized approaches to measure fibrosis. In this article we therefore describe how a combination of immunohistochemical staining and biochemical measurement of hydroxyproline can be used to qualitatively and quantitatively examine the different forms of fibrosis. These techniques provide measures of both the composition of fibrosis, and a means of evaluating interventions in this significant process. [ABSTRACT FROM AUTHOR]

Aim Acute kidney injury ( AKI) is associated with increased mortality. While angiotensin-converting enzyme inhibitors ( ACEI) are known to slow progression of chronic kidney disease, their role in AKI remains unclear. Methods The Randomised Evaluation of Normal vs. Augmented Level Replacement Therapy ( RENAL) study data were analysed according to ACEI use over time. The primary outcome was all-cause mortality at 90 days following randomisation. Analyses used a multivariate Cox model adjusted for either baseline or for time-dependent covariates, and a sensitivity analysis of patients surviving to at least the median time to ACEI initiation. Results Of the 1463 participants with available data on ACE inhibitors usage, 142 (9.7%) received ACEI at least once during study data collection. Participants treated with ACEI were older ( P = 0.02) and had less sepsis at baseline ( P < 0.001). ACEI use was significantly associated with lower mortality at 90 days ( HR 0.46, 95% CI 0.30-0.71, P < 0.001), and an increase in renal replacement therapy-free days ( P < 0.001), intensive care unit-free days ( P < 0.001) and hospital free-days ( P < 0.001) after adjusting for baseline covariates. Using the time-dependent analysis, however, the effect of ACEI administration was not significant ( HR 0.78, 95% CI 0.51-1.21, P = 0.3). The sensitivity analysis in day 8 survivors produced similar results. Conclusion In the RENAL study cohort, the use of ACEI during the study was not common and, after adjustment for time-dependent covariates, was not significantly associated with reductions in mortality. Further assessment of the effect of ACEI use in AKI patients is needed. [ABSTRACT FROM AUTHOR]

Aim To evaluate the performance of urinary neutrophil gelatinase-associated lipocalin (uNGAL), kidney injury molecule, interleukin-18 and heat shock protein 72 for differential diagnosis between causes of acute kidney injury in kidney transplant recipients, especially immunological rejection. Patients and Methods We measured these biomarkers in 67 kidney transplant recipients with acute kidney injury according to the RIFLE criteria. Results There were no statistical differences in biomarkers between kidney transplant recipients with immunological rejection ( n = 20), pre-renal causes ( n = 20) and other AKI causes ( n = 27). Only the uNGAL level relative to urinary creatinine (uNGAL/uCr) for immunological rejection was different in comparison with others ( P < 0.001); a cut-off of 59 μg/g of uNGAL/uCr had a sensitivity and specificity of 60% and 58% respectively (area under the curve in receiver-operating characteristic curve, 0.65). The other biomarkers were not useful in differentiating the causes of acute kidney injury. Conclusion The biomarkers tested are not useful in identifying immunological rejection as cause of acute kidney injury in kidney transplant recipients. [ABSTRACT FROM AUTHOR]

Aim Sepsis has been shown to induce the expansion of CD4+ CD25+ regulatory T cells ( Tregs), and this paradoxical immune suppression has been suggested to be closely associated with the development of sepsis-induced organ dysfunction. In the present study, we aimed to investigate the possible link between immune suppression and the development of septic acute kidney injury ( AKI). Methods We prospectively enrolled patients with a diagnosis of sepsis, with or without AKI and as well as patients with AKI but without sepsis. Serum and urine samples at the time of the diagnosis were collected to measure neutrophil gelatinase-associated lipocalin ( NGAL), cytokines, and soluble CD25 ( sCD25). Results Of the 82 patients enrolled, 44, 18, and 20 patients were classified into septic- AKI, sepsis-non AKI and non-septic AKI groups. There were no differences in the baseline characteristics in all three groups and the severity of infection in the two sepsis groups. Serum levels of interleukin ( IL)-10 were significantly elevated in patients with septic- AKI compared to the other two groups. Serum and urine NGAL levels and the level of serum sCD25, a marker of regulatory T cells, were significantly elevated in patients with septic AKI group, indicating the potential association of paradoxical immune suppression and the development of septic- AKI. Conclusions These results suggest that immune suppression in sepsis may be closely linked to the development of AKI and that sCD25 or IL-10 may be useful as novel biomarkers for the development of septic AKI. [ABSTRACT FROM AUTHOR]

The present study therefore aimed to investigate the role of MT in protecting the kidney from high-glucose-induced oxidative stress under diabetic conditions, using MT deficient (MT-/-) and MT+/+ mice. We also used murine proximal tubular epithelial (mProx24) cells cultured under normal or high-glucose conditions to determine if knockdown of MT by small interfering RNA (siRNA) induced mitochondrial ROS, leading to inflammation. Diabetes was induced by streptozotocin injection in MT-/- and MT+/+ mice. Urinary albumin excretion, histological changes, markers for ROS and kidney inflammation were measured. mProx24 cells were used to further elucidate the role of MT under high-glucose conditions. Parameters of diabetic nephropathy and markers of ROS and inflammation were accelerated in diabetic MT-/- mice compared with diabetic MT+/+ mice, despite equivalent levels of hyperglycaemia. MT deficiency accelerated interstitial fibrosis and macrophage infiltration into the interstitium in diabetic kidney. Electron microscopy revealed abnormal mitochondrial morphology in proximal tubular epithelial cells in diabetic MT-/- mice. In vitro studies demonstrated that knockdown of MT by small interfering RNA enhanced mitochondrial ROS generation and inflammation-related gene expression in mProx24 cells cultured under high-glucose conditions. The results of this study suggest that MT may play a key role in protecting the kidney against high glucose-induced ROS and subsequent inflammation in diabetic nephropathy. Conclusion: The differentially expressed proteins and the target of miRNAs induced by high glucose involved in mitochondrial oxidative stress, autophagy and epithelial-mesenchymal transition. The over-expression of miR-503 and miR-181d in KKAy mice glomeruli may be responsible for the pathogenesis of DN by regulating the expression of the target proteins, such as heat shock protein 75, GRP75 and GRP78 et al. The differentially expression of serum miR-1179, miR- 148b and miR-150 may be responsible for the pathogenesis of diabetic nephropathy and are potential biomarkers for DN. Ursolic acid can regulate autophagy and EMT and ameliorate high glucose induced podocyte and mesangial cell injury by inhibiting PI3K/AKT/mTOR pathway, implying that ursolic acid could be a potential treatment for diabetic nephropathy. [ABSTRACT FROM AUTHOR]

The article presents an abstract of research paper offering guidelines for acute kidney injury in Australia and New Zealand.

Aims Very little data exist regarding community-acquired acute renal injury ( CA-AKI). We have identified and characterized a patient cohort with CA-AKI, and documented its impact on renal function and patient mortality. Methods Using the database of the Medical Biochemistry Department of the Cardiff and Vale University Health Board we identified all patients with CA-AKI over a 1 month period in 2009. Follow-up biochemical and clinical data were used to determine short-term (3 months) and long-term (3 years) outcomes. Comparisons were made to a random and an age/sex matched group. Results Patients with CA-AKI were older than a non- AKI cohort (70.3 vs 57.1 years; P < 0.0001), with a 61% male predominance. 38% had pre-existing chronic kidney disease ( CKD) compared with 25% in the age- and sex-matched non- CA-AKI cohort ( P = 0.007). 54% of CA-AKI were admitted for inpatient care. Admission was associated with a higher incidence of complete recovery of renal function. Mortality at 3 months was 16.5%, and was related to the severity of AKI. Over the 3 years of follow-up 71% of patients with CA-AKI developed progressive CKD which was more likely following incomplete/no recovery of renal function and in the context of pre-existing CKD. Three year mortality was 45%, which was higher than that of the age/sex matched control cohort (15.7%; P < 0.0001), but was not related to the development of progressive CKD. Conclusions CA-AKI carries significant implications in terms of both development of progressive renal disease and high long-term patient mortality. [ABSTRACT FROM AUTHOR]