Correcting hyponatremia by fluid sodium modulation in continuous renal replacement therapy with regional citrate anticoagulation.

A 40-year-old man presented with severe hyponatremia with a serum sodium of 102 mmol/L and concomitant acute kidney injury complicated by severe acidosis. He was started on continuous renal replacement therapy (CRRT) with regional citrate anticoagulation. We present the equations and strategy used to calculate and adjust the sodium concentration of the dialysate and replacement fluids to increase serum sodium levels by ≤8 mmol/L/day. The equations were based on fundamental chemistry principles and applicable to common CRRT solutions with 140 mmol/L of sodium. This simple strategy for CRRT fluid sodium titration required only one adjustment per day, and the serum sodium levels increased safely within the daily targets set. Although the citrated-replacement fluid was diluted for sodium adjustment, the citrate anticoagulation protocol was still able to achieve the targeted circuit ionized-calcium levels and provided adequate anticoagulation without issues related to frequent clotting and other electrolyte abnormalities.

Serum anion gap revisited: a verified reference interval for contemporary use.

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- ] - [HCO3 - ] and AGK by [Na+ ] + [K+ ] - [Cl- ] - [HCO3 - ]. 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/m2 and the glomerular filtration rate was 106 mL/min/1.73 m2 . 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 AGK 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.

Regional citrate anti-coagulation dose titration: impact on dose of continuous renal replacement therapy.

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.

Impact of pre-transplant biopsy on 5-year outcomes of expanded criteria donor kidney transplantation.

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 m2 compared to 42.2 (35.8-57.3) ml/min/1.73 m2 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.

Ensuring Sustainability of Continuous Kidney Replacement Therapy in the Face of Extraordinary Demand: Lessons From the COVID-19 Pandemic.

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.

Regional Citrate Anticoagulation for Continuous Renal Replacement Therapy - A Safe and Effective Low-Dose Protocol.

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.

Diagnostic threshold and performance of anion gap in screening for high anion gap metabolic acidosis.

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.

Predictive value of donor kidney quality assessment and risk quantification scores on 5-year outcomes of deceased donor kidney transplantation.

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.

Evaluation of factors associated with bleeding following haemodialysis catheter-related procedures and the risk with anti-platelet agents.

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.

Comparison of planned-start, early-start and deferred-start strategies for peritoneal dialysis initiation in end-stage kidney disease.

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.

25-OH vitamin D threshold for optimal bone mineral density in elderly patients with chronic kidney disease.

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.

Peritoneal dialysis for acute kidney injury: Equations for dosing in pandemics, disasters, and beyond.

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 VD = (1.2 × std-Kt/V × TBW)/(tdwell + 4), where VD is the total dialysate volume per day, std-Kt/V is the desired weekly dose, TBW is the total body water, and tdwell is the dwell time. VD can be expressed in terms of dwell volume, vdwell, by VD = (0.3 × std-Kt/V × TBW) - (6 × vdwell). Two further equations were derived which directly describe the mathematical relationship between tdwell and vdwell. 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.

Weight-Based Assessment of Fluid Overload in Patients with Acute Kidney Injury.

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.

The use of peritoneal dialysis in heart failure: A systematic review.

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.

A device for surveillance of vascular access sites for bleeding: results from a clinical evaluation trial.

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.

Machines for continuous renal replacement therapy.

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.

The cardiorenal syndrome.

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.