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Background: Due to the excess demand for deceased donor kidneys, risk quantification scores were developed to help with kidney allocation. The kidney donor risk index (KDRI) is used in the US kidney allocation system. We currently use expanded criteria (UNOS) and Remuzzi scoring for allocation of deceased donor kidneys and the utility of KDRI in our cohort is unknown. We aim to evaluate the association of KDRI with relation to 5 year graft and patient survival., Methods: Retrospective cohort study of 225 adults who received a deceased donor kidney transplant between 1 Nov 2005 and 30 June 2014. Patients were followed up for 5 years or until graft-loss or death. Implant biopsies of donor kidneys were done and the Remuzzi score was calculated., Results: The median age was 48 (IQR 42, 52.5) years and 50.7% were male. KDRI-USA, KDRI-THAI, and KDRI-AUST were found to have no correlation with 5 year graft survival. Donor characteristics which define an expanded criteria donor kidney, not associated with 5 year graft survival are age (p = 0.58), terminal creatinine (p = 0.71) and history of hypertension (p = 0.35). Donor cerebrovascular accident (CVA) as a cause of death (p = 0.02) and Remuzzi score were associated with graft survival at 5 years, with 75.8% with Remuzzi score ≤ 3 vs 24.2% with Remuzzi score of > 3 achieving 5 year graft survival (p = 0.001)., Conclusion: The association of KDRI with graft and patient survival was not demonstrated in our cohort. Histological assessment of the transplant kidney remains the best method of predicting long-term survival during donor selection., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction: The anion gap (AG) is commonly used to screen for acid-base disorders. It was proposed that the cut-off for high anion gap metabolic acidosis (HAGMA) may be lower with current laboratory techniques, although modern laboratory equipment are still calibrated to familiar reference ranges established with earlier techniques. The appropriate cut-off for HAGMA is unclear. This study aimed to assess the performance of AG as a screening test for HAGMA and to determine the optimal diagnostic threshold of AG for HAGMA., Methods: This was a retrospective analysis of a large, anonymised dataset extracted by computerised protocol from 2017 to 2019. All inpatients with blood samples taken for organic acids (lactate, ketone or salicylate) paired with a metabolic panel were included. The target condition was HAGMA secondary to elevated blood lactate, ketone and/or salicylate. Sensitivity for HAGMA was explored at various AG cut-off levels., Results: Of 16,475 patients, 2,621 had organic acidosis. Median age was 65 years, and median estimated glomerular filtration rate was 70 mL/min/1.73 m2. With organic acidosis, the median AG was 23 (interquartile range [IQR] 20-29) mEq/L, while without organic acidosis, the median AG was 16 (IQR 14-19) mEq/L. The area under the curve-receiver operating characteristic of AG for HAGMA was 0.873. Desired sensitivity for HAGMA was set at ≥95%, and this was found with an AG threshold of ≥15 mEq/L (sensitivity 98.1%, specificity 34.0%)., Conclusion: The recommended AG threshold value is ≥15 mEq/L with a high sensitivity for HAGMA. The AG should always be interpreted with the clinical context, and it should be repeated as the clinical picture evolves., (Copyright © 2024 Copyright: © 2024 Singapore Medical Journal.)

Background: Bleeding is a potential complication following haemodialysis catheter-related procedures. Besides uraemia, bleeding risk is perceived to be even higher in patients receiving antiplatelets. This study aims to evaluate the risk factors for bleeding following dialysis catheter-related procedures., Methods: This is a secondary analysis of a single-centre, prospective cohort study between March 2019 and June 2020. Potential risk factors for bleeding were collected, including use of antiplatelets and anticoagulants, serum urea and haematological results. Patients were observed closely for external bleeding following haemodialysis catheter-related procedures., Results: From 413 patients screened, 250 were recruited. Of these, 177 underwent dialysis catheter insertion (157 tunnelled and 20 non-tunnelled) while 73 had dialysis catheter removed (35 tunnelled and 38 non-tunnelled). One hundred and four patients (41.6%) were on a single anti-platelet agent, of whom 75 (30.0%) were on aspirin and 29 (11.6%) had clopidogrel alone. Twenty-nine patients (11.6%) were on both aspirin and clopidogrel.There were 36 episodes (14.4%) of bleeding. The risk of bleeding was not significantly higher with the use of aspirin alone (odds ratio = 0.85, 95% CI: 0.36-2.02, p  = 0.709), clopidogrel alone (odds ratio = 1.04, 95% CI: 0.31-3.49, p  = 0.953) and both aspirin and clopidogrel (odds ratio = 0.95, 95% CI: 0.28-3.25, p  = 0.938). In a multivariate analysis, none of the known bleeding risk factors had a statistically significant association with bleeding., Conclusions: Overall, the use of antiplatelet agents was not associated with an increased risk of bleeding.

Introduction: Vitamin D deficiency is common in chronic kidney disease (CKD) and is associated with lower bone mineral density (BMD), decreased muscle strength, and increased hip fracture risk. Guidelines have suggested targeting 25-OH vitamin D (25(OH)D) levels between 20 and 30 ng/ml. However, vitamin D metabolism is altered in CKD, and threshold levels for optimal BMD are unknown. Methods: We included 1097 patients with hip fractures. CKD was defined as estimated glomerular filtration rate <60 ml/min/1.73 m (Mucsi et al., Clin. Nephrol., 2005, 64(4), 288-294) and low BMD defined as T score ≤ -2.5 at femoral neck. We assessed the association of 25(OH)D with low BMD in patients with and without CKD: using the conventional threshold 25(OH)D < 30 ng/dl, as well as a new threshold. Results: CKD was present in 479 (44%) patients. Using a threshold of 25(OH)D < 30 ng/ml, there were no significant differences in patients with CKD and low BMD when compared to the other groups. We identified 27 ng/ml as a better threshold with the Youden index. Using 25(OH)D < 27 ng/ml as a threshold, 360 of 482 patients (74.7%) with low 25(OH)D had low BMD, compared to only 185/276 (67%) of patients with adequate vitamin D, p = 0.02, which was irrespective of the presence or absence of CKD. Furthermore, patients with CKD and 25(OH)D < 27 ng/ml had a higher odds ratio of mortality upon follow-up, 1.61, 95% CI: 1.08-2.39, compared to those with CKD and 25(OH)D ≥ 27 ng/ml. Conclusion: We find that 25(OH)D < 27 ng/ml is associated with low BMD in patients with and without CKD. Further prospective studies targeting vitamin D repletion to at least 27 ng/ml and the outcome of hip fractures will be useful to validate these findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Roy, Ng, Kog, Yeon, Poh, Koduri, Chionh, Sultana and Hai Kiat Puar.)

Background: The anion gap (AG) is often used to evaluate acid-base disorders. The reference interval for normal AG is used to differentiate between raised (gap) or normal AG (non-gap) acidosis. Historically accepted AG values may not be valid with the evolution of modern analytical techniques and the reference interval requires revalidation., Aims: To determine the reference interval for AG based on current laboratory techniques., Methods: During a health-screening exercise, 284 participants with no major illnesses volunteered surplus blood for analysis. The samples were tested in an internationally accredited clinical laboratory. AG was calculated by [Na + ] - [Cl - ] - [HCO 3 - ] and AG K by [Na + ] + [K + ] - [Cl - ] - [HCO 3 - ]. The reference interval was determined at 2.5th-97.5th percentiles. Analysis was further undertaken for a subcohort of 156 individuals with no suboptimal health indicators., Results: Median age was 35 years, body mass index 23.4 kg/m 2 and the glomerular filtration rate was 106 mL/min/1.73 m 2 . Median AG was 13 mmol/L and the reference interval for normal AG is 10-18 mmol/L with a 99% level of confidence. Statistically significant differences in AG were detected for sex, race, obesity and serum albumin, but the difference was 1 mmol/L between subgroups. The reference interval was the same for the sub-cohort of 156 individuals. Median AG K was 17.7 mmol/L and reference interval was 14.6-22.5 mmol/L., Conclusions: The AG reference interval of 10-18 mmol/L is valid for laboratories with similar reference intervals for electrolytes. Lower values expected with current laboratory techniques were not observed. The median AG of 13 mmol/L may be used to differentiate gap acidosis, non-gap acidosis or mixed acid-base disorders., (© 2021 Royal Australasian College of Physicians.)

Introduction: In patients with end-stage kidney disease (ESKD) suitable for peritoneal dialysis (PD), PD should ideally be planned and initiated electively (planned-start PD). If patients present late, some centres initiate PD immediately with an urgent-start PD strategy. However, as urgent-start PD is resource intensive, we evaluated another strategy where patients first undergo emergent haemodialysis (HD), followed by early PD catheter insertion, and switch to PD 48-72 hours after PD catheter insertion (early-start PD). Conventionally, late-presenting patients are often started on HD, followed by deferred PD catheter insertion before switching to PD≥14 days after catheter insertion (deferred start PD)., Methods: This is a retrospective study of new ESKD patients, comparing the planned-start, early-start and deferred-start PD strategies. Outcomes within 1 year of dialysis initiation were studied., Results: Of 148 patients, 57 (38.5%) patients had planned-start, 23 (15.5%) early-start and 68 (45.9%) deferred-start PD. Baseline biochemical parameters were similar except for a lower serum urea with planned-start PD. No significant differences were seen in the primary outcomes of technique and patient survival across all 3 subgroups. Compared to planned-start PD, early-start PD had a shorter time to catheter migration (hazard ratio [HR] 14.13, 95% confidence interval [CI] 1.65-121.04, P =0.016) while deferred-start PD has a shorter time to first peritonitis (HR 2.49, 95% CI 1.03-6.01, P =0.043) and first hospital admission (HR 2.03, 95% CI 1.35-3.07, P =0.001)., Conclusion: Planned-start PD is the best PD initiation strategy. However, if this is not possible, early-start PD is a viable alternative. Catheter migration may be more frequent with early-start PD but does not appear to impact technique survival.

Background: Regional citrate anti-coagulation (RCA) is the recommended anti-coagulation for continuous renal replacement therapy (CRRT). Citrated replacement fluids provide convenience but may compromise effluent delivery when adjusted to maintain circuit ionised calcium levels (circuit-iCa). This study aims to evaluate the effect of RCA titration on the delivered CRRT effluent dose., Methods: This prospective observational study evaluated patients on RCA-CRRT in continuous veno-venous hemodiafiltration mode. Citrated replacement fluid was titrated to target circuit-iCa 0.26-0.40 mmol/L. Patients were then stratified into 'reduced-dose' who required citrate down-titration and 'stable-dose' who did not., Results: Data from 200 RCA-CRRT sessions were collected. The reduced-dose RCA group (n = 114) had higher median initial citrate dose (3.00 vs 2.50; P < 0.001) but lower time-averaged dose (2.49 vs 2.60; P < 0.001). In addition, median prescribed effluent dose was 33.3 mL/kg/h (28.6-39.2) but median delivered effluent dose was significantly lower at 29.9 mL/kg/h (25.4-36.9; P < 0.001). Mortality was higher in the reduced-dose RCA group (39.5% vs 25.6%; P = 0.022) and in patients with delivered-to-prescribed effluent dose ratio of < 0.9 vs ≥ 0.9 (51.3% vs 29.2%; P = 0.014)., Conclusion: RCA titration can significantly impact delivered CRRT effluent dose. Measures should be taken to address the CRRT dose deficit and prevent poor outcomes due to inadequate dialysis., (© 2021. Japanese Society of Nephrology.)

Background: Peritoneal dialysis (PD) is a viable option for renal replacement therapy in acute kidney injury (AKI), especially in challenging times during disasters and pandemics when resources are limited. While PD techniques are well described, there is uncertainty about how to determine the amount of PD to be prescribed toward a target dose. The aim of this study is to derive practical equations to assist with the prescription of PD for AKI., Methods: Using established physiological principles behind PD clearance and membrane transport, a primary determinant of dose delivery, equations were mathematically derived to estimate dialysate volume required to achieve a target dose of PD., Results: The main derivative equation is V D = (1.2 × std- Kt / V × TBW)/( t dwell + 4), where V D is the total dialysate volume per day, std- Kt / V is the desired weekly dose, TBW is the total body water, and t dwell is the dwell time. V D can be expressed in terms of dwell volume, v dwell , by V D = (0.3 × std- Kt / V × TBW) - (6 × v dwell ). Two further equations were derived which directly describe the mathematical relationship between t dwell and v dwell . A calculator is included as an Online Supplementary Material., Conclusions: The equations are intended as a practical tool to estimate solute clearances and guide prescription of continuous PD. The estimated dialysate volume required for any dose target can be calculated from cycle duration or dwell volume. However, the exact target dose of PD is uncertain and should be adjusted according to the clinical circumstances and response to treatment. The equations presented in this article facilitate the adjustment of PD prescription toward the targeted solute clearance.

Aim: Compared to Standard Criteria Donors (SCD), Expanded Criteria Donor (ECD) kidneys are associated with poorer outcomes, although pre-transplant biopsy may mitigate risks. This study assessed 5-year outcomes of deceased-donor kidney transplant recipients, comparing recipients of ECD allografts evaluated histologically to recipients of SCD and ECD kidneys assessed clinically., Methods: This is a single-centre retrospective study. From November 2005 to December 2009 (Era 1), donors were assessed clinically for suitability for kidney donation. From December 2009 to October 2017 (Era 2), kidneys from ECDs and diabetics underwent pre-transplant biopsy and were allocated based on Remuzzi score. Outcomes of Era 1 and 2 recipients were compared., Results: ECD kidney transplantation increased from 30.4% to 40.0% from Era 1 to 2. Univariable Cox regression, stratified by transplant era, found that 5-year graft loss was highest with Era 1 ECD (HR 2.5, 95% CI 1.1-5.5, P = .027) while graft loss for Era 2 ECD recipients was similar to SCD recipients. There was no difference in 5-year recipient survival. Amongst Era 1 ECD recipients, 51.2% experienced rejection compared to 30.8-41.5% for other subgroups. Five-year eGFR was higher with Era 2 ECD at 48.4 (33.3-60.7) ml/min/1.73 m 2 compared to 42.2 (35.8-57.3) ml/min/1.73 m 2 for Era 1 ECD. However, these differences were not statistically significant., Conclusion: Introduction of pre-transplant biopsy assessment may be associated with improved outcomes of ECD kidney recipients such that they are now comparable to SCD kidney recipients, with benefits persisting over 5 years., (© 2020 Asian Pacific Society of Nephrology.)

Heart failure (HF) is a major cause of morbidity and mortality. Extracorporeal (EC) therapy, including ultrafiltration (UF) and haemodialysis (HD), peritoneal dialysis (PD) and peritoneal ultrafiltration (PUF) are potential therapeutic options in diuretic-resistant states. This systematic review assessed outcomes of PD and compared the effects of PD to EC. A comprehensive search of major databases from 1966 to 2017 for studies utilising PD (or PUF) in diuretic-resistant HF was conducted, excluding studies involving patients with end-stage kidney disease. Data were extracted and combined using a random-effects model, expressed as odds ratio (OR). Thirty-one studies ( n = 902) were identified from 3195 citations. None were randomised trials. Survival was variable (0-100%) with a wide follow-up duration (36 h-10 years). With follow-up > 1 year, the overall mortality was 48.3%. Only four studies compared PD with EC. Survival was 42.1% with PD and 45.0% with EC; the pooled effect did not favour either (OR 0.80; 95% confidence interval (CI): 0.24-2.69; p = 0.710). Studies on PD in patients with HF reported several benefits. Left ventricular ejection fraction (LVEF) improved after PD (OR 3.76, 95%CI: 2.24-5.27; p < 0.001). Seven of nine studies saw LVEF increase by > 10%. Twenty-one studies reported the New York Heart Association status and 40-100% of the patients improved by ≥ 1 grade. Nine of 10 studies reported reductions in hospitalisation frequency and/or duration. When treated with PD, HF patients had fewer symptoms, lower hospital admissions and duration compared to diuretic therapy. However, there is inadequate evidence comparing PD versus UF or HD. Further studies comparing these modalities in diuretic-resistant HF should be conducted.

Post-procedural wound haemorrhage is a potentially life-threatening complication. For haemodialysis patients, bleeding is often encountered after vascular access procedures and fatal episodes have been reported. Visual monitoring for bleeding is manpower intensive and bleeding episodes may still be missed between inspections. A device, Blood WArning Technology with Continuous Haemoglobin sensor (BWATCH), was developed to detect bleeding from wounds. This a prospective, observational clinical trial on patients who have had a dialysis catheter inserted or removed. The battery-powered, disc-shaped device (43 mm diameter, 12 mm height) was placed over the dressing for at least six hours. The device detects reflected light with characteristics specific for haemoglobin and an alarm would be triggered if bleeding occurs. There were 250 participants (177 post-insertion, 73 post-removal) and 36 episodes of bleeding occurred. The device alarm was triggered in all instances but there were also 9 false alarms. Specificity was 95.8%, false positive rate was 4.2% and positive predictive value was 80.0%. Sensitivity and negative predictive value were 100% but detection failure may still occur due to improper application or device maintenance. The use of technological aids for monitoring improves patient safety and may reduce demand on manpower.

With the exponential surge in patients with coronavirus disease 2019 (COVID-19) worldwide, the resources needed to provide continuous kidney replacement therapy (CKRT) for patients with acute kidney injury or kidney failure may be threatened. This article summarizes subsisting strategies that can be implemented immediately. Pre-emptive weekly multicenter projections of CKRT demand based on evolving COVID-19 epidemiology and routine workload should be made. Corresponding consumables should be quantified and acquired, with diversification of sources from multiple vendors. Supply procurement should be stepped up accordingly so that a several-week stock is amassed, with administrative oversight to prevent disproportionate hoarding by institutions. Consumption of CKRT resources can be made more efficient by optimizing circuit anticoagulation to preserve filters, extending use of each vascular access, lowering blood flows to reduce citrate consumption, moderating the CKRT intensity to conserve fluids, or running accelerated KRT at higher clearance to treat more patients per machine. If logistically feasible, earlier transition to intermittent hemodialysis with online-generated dialysate, or urgent peritoneal dialysis in selected patients, may help reduce CKRT dependency. These measures, coupled to multicenter collaboration and a corresponding increase in trained medical and nursing staffing levels, may avoid downstream rationing of care and save lives during the peak of the pandemic., (Copyright © 2020 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Aims: Regional citrate anticoagulation (RCA) is the preferred mode of anticoagulation for continuous renal replacement therapy (CRRT). Conventional RCA-CRRT citrate dose ranges from 3 to 5 mmol/L of blood. This study explored the effectiveness of an RCA protocol with lower citrate dose and its impact on citrate-related complications., Methods: This prospective observational study compared two RCA-CRRT protocols in the intensive care unit. RCA Protocol 1 used an initial citrate dose of 3.0 mmol/L while Protocol 2 started with 2.5 mmol/L. The citrate dose was titrated by sliding scale to target circuit-iCa 0.26-0.40 mmol/L. Calcium was re-infused post-dialyzer and titrated by protocol to target systemic-iCa 1.01-1.20 mmol/L., Results: Two hundred RCA-CRRT sessions were performed (81 Protocol 1; 119 Protocol 2). The median age was 65.4 years and median APACHE-II score was 23. Citrate dose for Protocol 1 was significantly higher than Protocol 2 in the first 12 h. The circuit clotting rate was similar in both arms (Protocol 1: 9.9%; Protocol 2: 9.2%; P = 0.881). With Protocol 2, circuit-iCa levels were 2.42 times more likely to be on target (P = 0.003) while the odds of hypocalcaemia was 4.67 times higher with Protocol 1 (P < 0.001). There was a wider anion gap was noted with Protocol 1, which suggests a propensity for citrate accumulation with higher citrate exposure., Conclusion: The RCA protocol with a lower initial citrate dose of 2.5 mmol/L blood had less citrate-related complications with no loss of efficacy. A more precise RCA prescription at the start of treatment avoids unnecessary citrate exposure and improves safety., (© 2019 Asian Pacific Society of Nephrology.)

Introduction: Acute kidney injury (AKI) with fluid overload is associated with poor outcomes. While percentage fluid overload (PFO) using intake/output charts (PFOi/o) has been validated as a marker of overload, accurate PFOi/o measurements may not be possible in a general ward. We propose an alternative weight-based PFO calculation: PFOw = [(maximum weight - baseline weight) ÷ baseline weight] × 100%., Methods: This is a prospective, observational pilot study on general ward inpatients with AKI who were referred for nephrology consult. PFOw was compared with PFOi/o, and both were evaluated for associations with dialysis requirement, AKI stage 2 or 3, and 90-day mortality., Results: Fifty-eight patients with a median age of 67.5 years (interquartile range 18.0) were recruited. Of which, 33 (56.9%) were males and 41 (70.7%) had preexisting CKD 3 or higher. We found no correlation between PFOi/o and PFOw (R2 = 0.015, p = 0.531). A higher PFOw was observed in AKI stage 2 or 3 (p = 0.005) and in patients requiring dialysis (p = 0.001). On multivariate analysis, each percentage increase in PFOw was associated with increased odds of AKI stage 2 or 3 (odds ratio 1.37 [95% CI 1.05-1.78], p = 0.020) and dialysis need (odds ratio 1.69 [95% CI 1.20-2.39], p = 0.003). Twenty-nine patients had complete quantitative data to calculate PFOi/o. Multivariate analysis of these 29 patients showed that PFOw correlated with AKI stage 2 or 3 and dialysis requirement, while PFOi/o had no correlation with these events. The area under the curve receiver operating characteristics of PFOw was 0.706 for AKI stage 2 or 3 and 0.819 for AKI requiring dialysis. The optimal PFOw cutoff was determined at ≥1%. Three deaths occurred within 90 days, and all had PFOw ≥ 1%, although the log-rank test did not achieve statistical significance (p = 0.050)., Conclusion: The proposed PFOw is a potential prognostic indicator for general ward patients with AKI. PFOw ≥ 1% is associated with poor renal outcomes., (© 2020 S. Karger AG, Basel.)

Background and Objectives: The role of peritoneal dialysis in the management of AKI is not well defined, although it remains frequently used, especially in low-resource settings. A systematic review was performed to describe outcomes in AKI treated with peritoneal dialysis and compare peritoneal dialysis with extracorporeal blood purification, such as continuous or intermittent hemodialysis., Design, Setting, Participants, & Measurements: MEDLINE, CINAHL, and Central Register of Controlled Trials were searched in July of 2012. Eligible studies selected were observational cohort or randomized adult population studies on peritoneal dialysis in the setting of AKI. The primary outcome of interest was all-cause mortality. Summary estimates of odds ratio were obtained using a random effects model., Results: Of 982 citations, 24 studies (n=1556 patients) were identified. The overall methodological quality was low. Thirteen studies described patients (n=597) treated with peritoneal dialysis only; pooled mortality was 39.3%. In 11 studies (7 cohort studies and 4 randomized trials), patients received peritoneal dialysis (n=392, pooled mortality=58.0%) or extracorporeal blood purification (n=567, pooled mortality=56.1%). In the cohort studies, there was no difference in mortality between peritoneal dialysis and extracorporeal blood purification (odds ratio, 0.96; 95% confidence interval, 0.53 to 1.71). In four randomized trials, there was also no difference in mortality (odds ratio, 1.50; 95% confidence interval, 0.46 to 4.86); however, heterogeneity was significant (I(2)=73%, P=0.03)., Conclusions: There is currently no evidence to suggest significant differences in mortality between peritoneal dialysis and extracorporeal blood purification in AKI. There is a need for good-quality evidence in this important area.

BACKGROUND: Cardiorenal syndrome (CRS) type 1 is characterized by a rapid worsening of cardiac function leading to acute kidney injury (AKI). An immune-mediated damage and alteration of immune response have been postulated as potential mechanisms involved in CRS type 1. In this pilot study, we examined the possible role of the immune-mediated mechanisms in the pathogenesis of this syndrome. The main objective was to analyze in vitro that plasma of CRS type 1 patients was able to trigger a response in monocytes resulting in apoptosis. The secondary aim was to evaluate TNF-α and IL-6 plasma levels of CRS type 1 patients. METHODS: Fifteen patients with acute heart failure (AHF) and CRS type 1 were enrolled and 20 healthy volunteers without AHF or AKI were recruited as control group. Plasma from these two groups was incubated with monocytes and, subsequently, cell apoptosis was evaluated. In addition, the activity of caspase-8 was assessed after 24 h incubation. Quantitative determination of TNF-α and IL-6 levels was performed. RESULTS: Plasma-induced apoptosis was significantly higher in CRS type 1 patients compared with healthy controls at 72 h (78 vs. 11%) and 96 h (81 vs. 11%). At 24 h, the activity of caspase-8 was significantly higher in monocytes incubated with plasma from the CRS type 1 group. TNF-α (2.39 vs. 28.49 pg/ml) and IL-6 (4.8 vs. 16.5 pg/ml) levels were significantly elevated in the CRS type 1 group (p < 0.01). CONCLUSIONS: In conclusion, there is a defective regulation of monocyte apoptosis in CRS type 1 patients, and inflammatory pathways may have a central role in the pathogenesis of CRS type 1 and may be fundamental in damage to distant organs.

Neutrophil gelatinase-associated lipocalin (NGAL) protein is an early biomarker for acute kidney injury (AKI). It is unknown if extracorporeal therapies (EC) have an effect on circulating NGAL levels. This study was designed to describe the kinetics of NGAL molecule in different EC techniques and to evaluate NGAL clearance in different operational conditions. A mock hemofiltration (HF) and hemoperfusion (HP) setup was used. NGAL was added to the blood reservoir and then measured at 30-minute intervals from arterial, venous, and ultrafiltrate (UF) lines. Removal kinetics and NGAL sieving coefficient were calculated. In our experiments, baseline NGAL concentration averaged 452 microg/L. There was a consistent downward trend throughout the experiment. NGAL concentration in the UF was between 80 and 90 microg/L, though it showed a slight increase in the second hour. The sieving coefficient of NGAL ranged from 0.2 to 0.4 during HF and it appeared to increase with time, suggesting an initial effect of membrane adsorption. HP proved clearly that there was adsorption of NGAL by the membrane and the point of saturation occured at approximately 60 minutes from the start of circulation. Our evaluation demonstrates that NGAL can be adsorbed and ultrafiltrated with polysulfone membranes. This should be taken into consideration when using NGAL as an AKI biomarker in patients undergoing EC circulation.

Neutrophil gelatinase-associated lipocalin (NGAL) is a 25 kDa protein belonging to the lipocalin superfamily. It was initially found in activated neutrophils, however, many other cells, like kidney tubular cells, may produce NGAL in response to various insults. Recently, it has been found to have a role in iron metabolism by virtue of its binding with siderophores. It has also been found to have a role in kidney development and tubular regeneration after injury. In experimental studies, it was found to be highly expressed in response to tubular injury. In subsequent clinical studies, urine NGAL has been found to be an early predictor for acute kidney injury (AKI). Newer devices for early bedside detection of NGAL are now available. Since serum creatinine is known to be an inadequate and late marker of AKI, NGAL might soon emerge as a troponin-like early marker for AKI. Recent evidence also suggests its role as a biomarker in a variety of other renal and non-renal conditions.

Aims/hypothesis: Evolving research suggests that common and rare alleles jointly constitute the genetic landscape of complex disease. We studied the association between 43 pathway-related candidate genes with 'intermediate phenotype' (i.e. corresponding plasma protein) and diabetic nephropathy in a customised microarray of 1,536 SNPs., Methods: In this case-control study of type 2 diabetic Chinese individuals with and without diabetic nephropathy, cases (n = 545) were defined on the basis of a spot urinary albumin/creatinine ratio (ACR) > 113 mg/mmol; the value for controls (n = 503) was ACR < 3.3 mg/mmol. Genotyping was performed using Illumina GoldenGate assay., Results: No single nucleotide polymorphism (SNP) remained significant in single locus analysis after correction for multiple testing. Therefore, we explored the best approximately 1% SNPs. Of these 13 SNPs, four clustered to a 5' end NADPH oxidase homologue 4 (NOX4) haplotype (GGCC frequency = 0.776) with estimated OR for diabetic nephropathy of 2.05 (95% CI 1.04-4.06) (heterozygous) and 2.48 (1.27-4.83) (homozygous) (p = 0.0055). The haplotype was correlated with plasma Cu/Zn superoxide dismutase (SOD) concentration, suggesting increased oxidative burden. Endothelin-1 SNP (rs1476046G>A, frequency = 0.252) was correlated with plasma C-terminal pro-endothelin-1 concentrations with an estimated OR for diabetic nephropathy of (heterozygous) 1.26 (0.96-1.66) and (homozygous) 1.87 (1.13-3.12) (p = 0.0072). Nitric oxide synthase 1 (NOS1) 5' haplotype (TGTC frequency = 0.38) also revealed a suggestive association with diabetic nephropathy: heterozygous 1.26 (0.95-1.67), homozygous 1.57 (1.04-2.35) (p = 0.0073). A rare NADPH oxidase homologue 1 (NOX1)-coding non-synonymous SNP (Arg315His, frequency = 0.006) was found exclusively among cases., Conclusions/interpretation: Our preliminary observations suggest that common haplotypes from NOX4 and endothelin-1 SNP correlated with plasma Cu/Zn SOD and C-terminal pro-endothelin-1 concentrations, respectively, and might have conferred diabetic nephropathy susceptibility. Common NOS1 and rare NOX1 variants also revealed a suggestive association with diabetic nephropathy. Future studies to validate our observation are needed.

A significant number of advancements have taken place since the beginning of continuous renal replacement therapy (CRRT). In particular, high volume hemofiltration and high permeability hemofiltration have been successful extensions of the technique. The additional and combined use of sorbent has also been tested successfully. Specific machines have now been designed to permit safe and reliable performance of the therapy. These new devices are equipped with a friendly user interface that allows for easy performance and monitoring. The apparent complexity of the circuit is made simple by a self-loading circuit or a cartridge which includes the filter and the blood and dialysate lines. Priming is performed automatically by the machine and pre- or postdilution (reinfusion of substitution fluid before or after the filter) can easily be performed by changing the position of the reinfusion line. These new machines permit all CRRT methodologies to be performed by programming the flows and the total amounts of fluid to be exchanged or circulated as a countercurrent dialysate at the beginning of the session. Progress has been made not only in technology in this area but also on our understanding of the pathophysiology of acute renal failure. New biomaterials and new devices are now available with new frontiers are on the horizon. We might, however, speculate that although improvements have been made, a lot remains to be done. There is no doubt that technology has progressed enormously in critical care nephrology and that more progress will come in the near future. The goal, and likely outcome, is an improvement in the morbidity and mortality of the most severely ill patients.

Assessment of body fluids in peritoneal dialysis is an important issue in the treatment of renal failure. Overhydration is related with hypertension and left ventricular hypertrophy and dehydration leads to hypotension and reduction of residual renal function. Bioimpedance analysis (BIA) provides objective information in assessment of hydration status of the patients. In the past BIA was not widely used in patients undergoing peritoneal dialysis. Our aim was to estimate the status of hydration in our peritoneal dialysis population by body composition monitoring (BCM) device to modify our pharmacological and dialysis policy. We used a Fresenius Body Composition Monitor, a whole-body bioimpedance spectroscopy (50 frequencies, 5-1,000 kHz ), to assess the body composition of 97 patients on peritoneal dialysis in our center. The patients were subjected to a physical examination every three months: We measured body weight, 24 h diuresis and performed a BIA session. BIA measurements were repeated according to different clinical situations. Every patient underwent BIA at least on two different occasions. Our preliminary results have found a strict correlation between weight increase or decrease and the results (total body water, extracellular water, lean mass index) shown by BCM. Modifications of therapy in patients dehydrated restored a satisfying amount of diuresis. Hypertensive overhydrated patients changed their scheduled treatment improving their blood pressure and achieving a lower body weight. Bio impedance analysis is the most reliable, repetitive, not invasive, simple, portable and relatively inexpensive technique to assess the fluid status of a dialysis patient is bioimpedance.

It has not been clearly shown which modality of dialysis is superior in the management of acute kidney injury (AKI). Most centers in developed countries have adopted extracorporeal blood purification (EBP) strategies, such as continuous or intermittent forms of hemodialysis or hemofiltration, for the supportive management of AKI. On the other hand, the use of peritoneal dialysis (PD) is widespread in developing countries in view of its ease of use, low cost and minimal requirements on infrastructure. The dose of dialysis required for AKI remains controversial, although an augmented dose with a high small solute clearance is advocated until further definitive evidence becomes available. No studies have directly examined the effects of the dose of PD on outcomes in AKI. The targets of dose for PD are inferred from studies conducted with EBP. There are concerns that PD is unable to achieve high clearances required to support a patient with renal failure. However, various techniques have been described which are able to achieve the targets of small solute clearance. These include high volume PD and continuous flow PD. The selection of flexible peritoneal catheters with better catheter function and dialysate flow rates can improve the efficiency of PD. Other aspects of dose should also be examined, including clearance of middle molecular weight toxins as well as adequate fluid removal. With careful selection of techniques to meet the individual demands of the patient, PD is an appropriate modality of dialysis for patients with AKI.

The term 'cardiorenal syndrome' (CRS) has increasingly been used in recent years without a constant meaning and a well-accepted definition. To include the vast array of interrelated derangements, and to stress the bidirectional nature of the heart-kidney interactions, the classification of the CRS today includes 5 subtypes whose etymology reflects the primary and secondary pathology, the time frame and simultaneous cardiac and renal codysfunction secondary to systemic disease. The CRS can generally be defined as a pathophysiological disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other organ. Type I CRS reflects an abrupt worsening of cardiac function (e.g. acute cardiogenic shock or decompensated congestive heart failure) leading to acute kidney injury. Type II CRS describes chronic abnormalities in cardiac function (e.g. chronic congestive heart failure) causing progressive and permanent chronic kidney disease. Type III CRS consists in an abrupt worsening of renal function (e.g. acute kidney ischemia or glomerulonephritis) causing acute cardiac disorder (e.g. heart failure, arrhythmia, ischemia). Type IV CRS describes a state of chronic kidney disease (e.g. chronic glomerular disease) contributing to decreased cardiac function, cardiac hypertrophy and/or increased risk of adverse cardiovascular events. Type V CRS reflects a systemic condition (e.g. diabetes mellitus, sepsis) causing both cardiac and renal dysfunction. Biomarkers can help to characterize the subtypes of the CRS and to indicate treatment initiation and effectiveness. The identification of patients and the pathophysiological mechanisms underlying each syndrome subtype will help to understand clinical derangements, to make the rationale for management strategies and to design future clinical trials with accurate selection and stratification of the studied population.