Clearance of NT-proBNP and Procalcitonin during Continuous Venovenous Hemodialysis with the Medium Cutoff Filter in Patients with Rhabdomyolysis-Associated Early Acute Kidney Injury.

INTRODUCTION: In polytrauma patients with AKI continuous venovenous hemodialysis (CVVHD) with medium cutoff membrane filters is commonly adopted to increase the removal of both myoglobin and inflammatory mediators, but its impact on increasing molecular weight markers of inflammation and cardiac damage is debated. METHODS: Twelve critically ill patients with rhabdomyolysis (4 burns and 8 polytrauma patients) and early AKI requiring CVVHD with EMIc2 filter were tested for 72 h on serum and effluent levels for NT-proBNP, procalcitonin (PCT), myoglobin, C-reactive protein (CRP), alpha1-glycoprotein, albumin, and total protein. RESULTS: The sieving coefficients (SCs) for proBNP and myoglobin were as higher as 0.5 at the start, decreased to 0.3 at the 2nd h, and then slowly declined to the final value of 0.25 and 0.20 at the 72nd h, respectively. PCT showed a negligible SC at the 1st h, a peak of 0.4 at the 12th h, and a final value of 0.3. SCs for albumin, alpha1-glycoprotein, and total protein were negligible. A similar trend was observed for the clearances (17-25 mL/min for proBNP and myoglobin; 12 mL/for PCT; <2 mL/min for albumin, alpha1-glycoprotein, and total protein). No correlation was found between systemic determinations and filter clearances of proBNP, PCT, and myoglobin. Net fluid loss/hour during CVVHD positively correlated with systemic myoglobin for all patients and NT-proBNP in the burn patients. CONCLUSION: CVVHD with EMiC2 filter showed low clearances for NT-proBNP and procalcitonin. CVVHD did not significantly affect the serum levels of these biomarkers, which could be adopted in the clinical management of early CVVHD patients.

Long-Term Preservation of Renal Function in Septic Shock Burn Patients Requiring Renal Replacement Therapy for Acute Kidney Injury.

BACKGROUND: The real impact of septic shock-associated acute kidney injury (AKI) on the long-term renal outcome is still debated, and little is known about AKI-burn patients. In a cohort of burn survivors treated by continuous renal replacement therapy (CRRT) and sorbent technology (CPFA-CRRT), we investigated the long-term outcome of glomerular and tubular function. METHODS: Out of 211 burn patients undergoing CRRT from 2001 to 2017, 45 survived, 40 completed the clinical follow-up (cumulative observation period 4067 months, median 84 months, IR 44-173), and 30 were alive on 31 December 2020. Besides creatinine and urine albumin, in the 19 patients treated with CPFA-CRRT, we determined the normalized GFR by 99mTc-DTPA (NRI-GFR) and studied glomerular and tubular urine protein markers. RESULTS: At the follow-up endpoint, the median plasma creatinine and urine albumin were 0.99 (0.72-1.19) and 0.0 mg/dL (0.0-0.0), respectively. NRI-GFR was 103.0 mL/min (93.4-115). Four patients were diabetic, and 22/30 presented at least one risk factor for chronic disease (hypertension, dyslipidemia, and overweight). Proteinuria decreased over time, from 0.47 g/day (0.42-0.52) at 6 months to 0.134 g/day (0.09-0.17) at follow-up endpoint. Proteinuria positively correlated with the peak of plasma creatinine (r 0.6953, p 0.006) and the number of CRRT days (r 0.5650, p 0.035) during AKI course, and negatively with NRI-GFR (r -0.5545, p 0.049). In seven patients, urine protein profile showed a significant increase of glomerular marker albumin and glomerular/tubular index. CONCLUSIONS: Burn patients who experienced septic shock and AKI treated with CRRT had a long-term expectation of preserved renal function. However, these patients were more predisposed to microalbuminuria, diabetes, and the presence of risk factors for intercurrent comorbidities and chronic renal disease.

Coupled-plasma filtration and adsorption for severe burn patients with septic shock and acute kidney injury treated with renal replacement therapy.

BACKGROUND: Coupled-plasma filtration adsorption (CPFA) is a sorbent-based technology aimed at removing soluble mediators of septic shock. We present our experience on the use of CPFA in septic shock severe burn patients with acute kidney injury (AKI) needing renal replacement therapy (RRT) with the main goal to evaluate efficacy and safety of CPFA in this specific subset of septic shock patients. METHODS: In this observational study, we retrospectively reviewed the medical notes of all burn patients admitted to our adult Burn Center who received CPFA, as part of the septic shock treatment requiring RRT, between January 2001 and December 2017 (CPFA group). We compared CPFA group with all the burn patients admitted to our Center in the same period of time, with the same range of relevant clinical characteristics, who developed AKI and were treated with RRT, but not CPFA (control group). We collected demographic characteristics, burn size, Sequential Organ Assessment Failure (SOFA) score, microbiological data, and patient outcome, in terms of in-hospital mortality rate and the probability of survival calculated using the revised Baux score. We also collected data regarding CPFA safety (hemorrhagic episodes, catheter associated-complications, hypersensitivity reactions) and efficiency (number and duration of CPFA sessions, plasma treated amount, plasma processed dose). RESULTS: 39 severe burn patients were treated with CPFA (CPFA group) (mean age 46.0 years, range 40.0-56.0 years; mean burn size 48.0% TBSA, range 35.0-60.0% TBSA), and 87 patients treated with RRT, but not CPFA, who had similar clinical characteristics (control group). Observed mortality rate was 51.3% in the CPFA group and 77.1% in the control group (p 0.004). Regarding factors affecting survival in the CPFA group, SOFA score on the 1st day of CPFA resulted significant (OR 2.016, 95% CI, 1.221-3.326; p < 0.004) in the multivariate analysis logistic model. CONCLUSIONS: CPFA treatment for burn patients with AKI-RRT and septic shock, sustained by bacterial strains non or poorly responsive to therapy, was associated with a lower mortality rate, compared to RRT alone. However, further research, such as large prospective studies, is required to clarify the role of CPFA in the treatment of burns with septic shock and AKI-RRT.

Citrate pharmacokinetics at high levels of circuit citratemia during coupled plasma filtration adsorption.

BACKGROUND: The heparin requirement for coupled plasma filtration adsorption (CPFA) is usually high. Heparin administration often cannot be adherent to prescription, leading to a premature clotting of circuit and an insufficient volume of treated plasma. Regional citrate anticoagulation (RCA) could be an attractive alternative; however, no data are available on citrate pharmacokinetics at high levels of circuit citratemia. METHODS: Fifteen septic shock patients with acute kidney injury undergoing CPFA with RCA at target circuit citratemia of 6 mmol/L were treated with CPFA-haemofiltration in pure predilution (CPFA-HF predilution group, n = 5 patients), or predilution haemodiafiltration (CPFA-HDF predilution group, n = 5 patients) or pre- and postdilution haemofiltration (CPFA-HF pre/postdilution group, n = 5 patients). Citrate pharmacokinetics was carried out through its determination in systemic and circuit blood, and effluent at time 0, 0.2, 1, 3, 6 and 9 h. RESULTS: The systemic concentrations of citrate in the CPFA-HF predilution group significantly increased over the sessions (from basal level of 0.21 to 0.76 mmol/L at 3 h), whereas they did not change in CPFA-HDF predilution and CPFA-HF pre/postdilution groups. Circuit plasma citrate concentrations (from 3 to 8 mmol/L) correlated strongly with circuit iCa++ levels (Spearman R = -0.7022, P < 0.01). Sieving coefficients of citrate were near the unit in all three groups and unrelated to blood and infusion flow rates in predilution. However, the amount of citrate removed by effluent was ∼40% for the CPFA-HF predilution group and reached 60% for both the CPFA-HDF predilution and CPFA-HF pre/postdilution groups (P < 0.05). As for the efficiency of plasmafiltration, the plasmafiltrate volume (from 17 to 20 mL/kg/day) was not significantly different among the groups. CONCLUSIONS: These results demonstrated that in refractory septic shock patients on CPFA at circuit citratemia of 6 mmol/L both HDF predilution and HF pre/postdilution were the best dialysis modalities to maintain a normal systemic citratemia through a high rate of citrate loss in the effluent.

Citrate anticoagulation for continuous renal replacement therapy in critically ill patients: success and limits.

Citrate anticoagulation has risen in interest so it is now a real alternative to heparin in the ICUs practice. Citrate provides a regional anticoagulation virtually restricted to extracorporeal circuit, where it acts by chelating ionized calcium. This issue is particularly true in patients ongoing CRRT, when the "continuous" systemic anticoagulation treatment is per se a relevant risk of bleeding. When compared with heparin most of studies with citrate reported a longer circuit survival, a lower rate of bleeding complications, and transfused packed red cell requirements. As anticoagulant for CRRT, the infusion of citrate is prolonged and it could potentially have some adverse effects. When citrate is metabolized to bicarbonate, metabolic alkalosis may occur, or for impaired metabolism citrate accumulation leads to acidosis. However, large studies with dedicated machines have indeed demonstrated that citrate anticoagulation is well tolerated, safe, and an easy to handle even in septic shock critically ill patients.

Blood and ultrafiltrate dosage of citrate as a useful and routine tool during continuous venovenous haemodiafiltration in septic shock patients.

BACKGROUND: Citrate anticoagulation is gaining popularity in renal replacement therapies (RRT) for critically ill patients. In order to study whether citrate accumulates in septic shock patients, we determined citrate in plasma and dialysate during continuous venovenous haemodiafiltration (CVVHDF). METHODS: An automated routine determination of citrate was set up using a commercial kit (citrate lyase method). Twelve patients with septic shock on CVVHDF and citrate anticoagulation were studied ex vivo for citrate levels in systemic and circuit blood and in the ultrafiltrate (at 0, 0.5, 1, 3, 6, 9, 12, 24, 48 and 72 h). RESULTS: In vitro blood studies showed a near unit correlation between the plasma measured and predicted citrate concentrations for an exclusive extracellular distribution of citrate. Median systemic arterial citratemias were 0.09 (0.06-0.12) mmol/L (Time 0) and 0.23 (0.18-0.31) mmol/L during treatment; median sieving coefficient for citrate was 0.95 (0.88-1.02) and did not change with different volumes of CVVHDF effluent (from 1350 to 5100 mL/h). Net citrate and calcium removal by filter significantly correlated with effluent volume (r = 0.85 and 0.78, respectively). Median citrate load entering in the patients' bloodstream was 13.60 (9.1-19.6, n = 68) mmol/h. Although cost analysis of the citrate test demonstrated a minimally increased daily cost (from 2.96 to 3.51€), saving costs could be potentially relevant with more extended use of citrate anticoagulation. CONCLUSIONS: In septic shock patients with liver dysfunction citratemia is useful in guiding clinical application of RRT, where the citrate losses in the ultrafiltrate can be efficiently modulated by increasing the effluent volume.

Guidelines audit may overcome disparities in health care: experience of an Italian region.

BACKGROUND: A clinical audit is used to verify the application of evidence-based clinical guidelines. Our regional section of the Italian Society of Nephrology was the first to establish a region-based program of clinical audits of compliance with guidelines for treating osteodystrophy and anemia of patients on chronic dialysis. This study summarizes the main results of the 2 audits of the Piemonte region. METHODS: Structured questionnaires were sent twice to all of the 22 dialysis centers of Piemonte and to the Center of Valle D'Aosta for an Audit on Osteodystrophy (in 2000 and 2004) and for the Audit on Anemia (2003). The questionnaires were meant to evaluate the clinical schedule of treatment relative to calcium-phosphate balance and anemia in dialysis patients. RESULTS: All centers responded, showing low levels of agreement with the targets of Italian guidelines. In sum, in 2000 only 27% of centers had more than 70% of patients with serum phosphate <5.5 mg/dL, but that rate had increased to 33% in 2004. Only 35% (in 2000) and 40% (in 2004) of the centers had more than 90% of patients with Kt/V >1.2. The Audit on Anemia showed a median of 42% of patients with hemoglobin between 11 and 12 g/dL, and only 2 centers had more than 70% of patients above this target. CONCLUSIONS: The first result of our pioneering experience was that we found that compliance with minimal levels of care was still inadequate, with regard to hyperphosphatemia, dialysis adequacy and anemia. Nevertheless, the 2nd Audit on Osteodystrophy showed a relative improvement in the results. But, most importantly, this open regional report has encouraged comparisons, and motivated centers to adopt a strategy of understanding, addressing and correcting inadequate levels of care, and furthermore increased satisfaction with the care being offered.