Simplified regional citrate anticoagulation protocol for CVVH, CVVHDF and SLED focused on the prevention of KRT-related hypophosphatemia while optimizing acid-base balance.

BACKGROUND: Hypophosphatemia is a common electrolyte disorder in critically ill patients undergoing prolonged kidney replacement therapy (KRT). We evaluated the efficacy and safety of a simplified regional citrate anticoagulation (RCA) protocol for continuous venovenous hemofiltration (CVVH), continuous venovenous hemodiafiltration (CVVHDF) and sustained low-efficiency dialysis filtration (SLED-f). We aimed at preventing KRT-related hypophosphatemia while optimizing acid-base equilibrium. METHODS: KRT was performed by the Prismax system (Baxter) and polyacrylonitrile AN69 filters (ST 150, 1.5 m2, Baxter), combining a 18 mmol/L pre-dilution citrate solution (Regiocit 18/0, Baxter) with a phosphate-containing solution (HPO42- 1.0 mmol/L, HCO3- 22.0 mmol/L; Biphozyl, Baxter). When needed, phosphate loss was replaced with sodium glycerophosphate pentahydrate (Glycophos™ 20 mmol/20 mL, Fresenius Kabi Norge AS, Halden, Norway). Serum citrate measurements were scheduled during each treatment. We analyzed data from three consecutive daily 8-h SLED-f sessions, as well as single 72-h CVVH or 72-h CVVHDF sessions. We used analysis of variance (ANOVA) for repeated measures to evaluate differences in variables means (i.e. serum phosphate, citrate). Because some patients received phosphate supplementation, we performed analysis of covariance (ANCOVA) for repeated measures modelling phosphate supplementation as a covariate. RESULTS: Forty-seven patients with acute kidney injury (AKI) or end stage kidney disease (ESKD) requiring KRT were included [11 CVVH, 11 CVVHDF and 25 SLED-f sessions; mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score 25 ± 7.0]. Interruptions for irreversible filter clotting were negligible. The overall incidence of hypophosphatemia (s-P levels <2.5 mg/dL) was 6.6%, and s-P levels were kept in the normality range irrespective of baseline values and the KRT modality. The acid-base balance was preserved, with no episode of citrate accumulation. CONCLUSIONS: Our data obtained with a new simplified RCA protocol suggest that it is effective and safe for CVVH, CVVHDF and SLED, allowing to prevent KRT-related hypophosphatemia and maintain the acid-base balance without citrate accumulation. TRIAL REGISTRATION: NCT03976440 (registered 6 June 2019).

SARS-CoV-2 Infection in Patients on Dialysis: Incidence and Outcomes in the Lazio Region, Italy.

Patients with end-stage kidney disease represent a frail population and might be at higher risk of SARS-CoV-2 infection. The Lazio Regional Dialysis and Transplant Registry collected information on dialysis patients with a positive swab. The study investigated incidence of SARS-CoV-2 infection, mortality and their potential associated factors in patients undergoing maintenance hemodialysis (MHD) in the Lazio region. Method: The occurrence of infection was assessed among MHD patients included in the RRDTL from 1 March to 30 November 2020. The adjusted cumulative incidence of infection and mortality risk within 30 days of infection onset were estimated. Logistic and Cox regression models were applied to identify factors associated with infection and mortality, respectively. Results: The MHD cohort counted 4942 patients; 256 (5.2%) had COVID-19. The adjusted cumulative incidence was 5.1%. Factors associated with infection included: being born abroad, educational level, cystic renal disease/familial nephropathy, vascular disease and being treated in a dialysis center located in Local Health Authority (LHA) Rome 2. Among infected patients, 59 (23.0%) died within 30 days; the adjusted mortality risk was 21.0%. Factors associated with 30-day mortality included: age, malnutrition and fever at the time of swab. Conclusions: Factors associated with infection seem to reflect socioeconomic conditions. Factors associated with mortality, in addition to age, are related to clinical characteristics and symptoms at the time of swab.

Preventing Continuous Renal Replacement Therapy-Induced Hypophosphatemia: An Extended Clinical Experience with a Phosphate-Containing Solution in the Setting of Regional Citrate Anticoagulation.

AIMS: To evaluate the efficacy and safety of a commercially available phosphate-containing solution for continuous renal replacement therapy (CRRT) in preventing CRRT-related hypophosphatemia. METHODS: In heart surgery patients undergoing continuous veno-venous haemodiafiltration (CVVHDF) with regional citrate anticoagulation (RCA), we combined an 18 mmol/l citrate solution with a phosphate-containing (1.2 mmol/l) dialysate/replacement fluid evaluating the incidence of hypophosphatemia and the need for parenteral phosphorus supplementation. RESULTS: In 75 patients on RCA-CVVHDF, the mean filter life was 53.9 ± 33.6 h. Regardless of baseline levels, phosphoremia was progressively corrected and maintained in a narrow normality range throughout RCA-CRRT days (after 72 h: 1.14 ± 0.25 mmol/l). Considering the whole CRRT period, 45 out of 975 (4.6%) serum phosphorus determinations met the criteria for mild (<0.81 mmol/l) or moderate (<0.61 mmol/l) hypophosphatemia; severe hypophosphatemia (<0.32 mmol/l) never occurred. After 72 h 88% of the patients were normophosphatemic, 9% hyperphosphatemic and 3% hypophosphatemic. CONCLUSIONS: RCA-CVVHDF with a phosphate-containing solution enabled the maintenance of phosphorus levels within normophosphatemic range in most of the patients, minimizing the occurrence of CRRT-related hypophosphatemia.

Renal resistive index by transesophageal and transparietal echo-doppler imaging for the prediction of acute kidney injury in patients undergoing major heart surgery.

BACKGROUND: Acute kidney injury (AKI) following major heart surgery (MHS) is associated with early decrease in renal blood flow and worsened prognosis. Doppler-derived renal resistive index (RRI), which reflects renal vascular resistance, may predict the development of AKI in patients undergoing MHS. METHODS: We studied 60 consecutive patients (mean age 69.5 years, range 30-88, 41 males) undergoing MHS. We measured RRI, both at the renal sinus and intraparenchymally, by transesophageal echo-Doppler ultrasound (TE-EDus) at anesthesia induction and at the end of surgery in all patients. Additionally, we measured RRI by external transparietal echo-Doppler ultrasound (TP-EDus) at the following time points: anesthesia induction, end of surgery, 4 and 24 h from cardiopulmonary bypass (CPB) start. We also measured serum neutrophil gelatinase associated lipocalin (NGAL) at the same time points. RESULTS: AKI [serum creatinine (sCr) increase ≥0.3 mg/dl vs. baseline within 72 h] developed in 23/60 (38.3 %) patients, with two requiring dialysis. Systemic hemodynamic parameters were similar in the patients who developed AKI (AKI+) and in those who did not (AKI-). Intraparenchymal RRI at end-surgery was significantly higher in AKI+ compared to AKI- patients, both at TE-EDus and TP-EDus (TE-EDus mean difference, p = 0.004; TP-EDus mean difference, p = 0.013; difference between TE-EDus and TP-EDus results, p = 0.066), although the predictive performance was limited with both methods (area under the curve [AUC] of the receiver-operator characteristics: 0.71 and 0.70 for TE-EDus and TP-EDus, respectively). Serum NGAL values were higher in AKI + than in AKI- patients (anesthesia induction, p = 0.037; end-surgery, p = 0.007; 4 h from CPB start, p = 0.093; 24 h from CPB start, p = 0.024. However, combining RRI with serum NGAL at end-surgery did not provide a clear-cut advantage in predicting AKI. CONCLUSIONS: In patients undergoing MHS, increased echo-Doppler ultrasound-derived RRI at end-surgery is significantly associated with the risk of AKI, but has limited practical utility for identifying the patients who will develop AKI.

Severe acute kidney injury following cardiac surgery: short-term outcomes in patients undergoing continuous renal replacement therapy (CRRT).

BACKGROUND: Acute kidney injury (AKI) represents a major complication of cardiac surgery. Our aim was to evaluate, in patients undergoing continuous renal replacement therapy (CRRT) for cardiac surgery-associated AKI (CS-AKI), prognostic factors related to in-hospital survival and renal function recovery to independence from RRT. METHODS: We conducted a retrospective analysis in patients with severe CS-AKI who underwent CRRT for at least 48 h. The sequential organ failure assessment (SOFA) score was calculated on a daily basis to evaluate illness severity throughout the intensive care unit (ICU) stay. RESULTS: In 264 patients (age 66.4 ± 11.7 years, 192 males), 30-day survival was 57.6 % while survival to discharge from the hospital was 40.5 %. Renal function recovery occurred in 96.3 % of survivors and in 13.4 % of non-survivors (p < 0.001). Multivariate analysis selected advancing age, oliguria, sepsis and the highest level of SOFA score within the first week of CRRT (SOFA-max) as independent prognostic factors for failure to recover renal function. Female gender was associated with a higher probability of survival, while higher serum creatinine at the start of CRRT, oliguria, sepsis and SOFA-max were independently associated with mortality. The subgroup of patients with a day-1 SOFA score above the median (≥10) showed a lower probability of survival and a lower cumulative incidence of renal function recovery. CONCLUSIONS: In a selected population of patients with severe CS-AKI requiring RRT, short-term outcomes appear strongly associated with the worst grade of illness severity during the first week of CRRT, thus reflecting the sequential occurrence of additional major complications during ICU stay. Renal function recovery and in-hospital survival appear mutually linked, sharing oliguria, sepsis and SOFA score as the main determinants of both outcomes.

Continuous veno-venous hemofiltration using a phosphate-containing replacement fluid in the setting of regional citrate anticoagulation.

PURPOSE: The need for prolonged anticoagulation and the occurrence of hypophosphatemia are well known drawbacks of continuous renal replacement therapies (CRRT). The aim was to evaluate the effects on acid-base status and serum phosphate of a regional citrate anticoagulation (RCA) protocol for continuous veno-venous hemofiltration (CVVH) combining the use of citrate with a phosphate-containing replacement fluid. METHODS: In a small cohort of heart surgery patients undergoing CRRT for acute kidney injury, we adopted an RCA-CVVH protocol based on a commercially available citrate solution (18 mmol/l) combined with a recently introduced phosphate-containing replacement fluid (HCO3 -30 mmol/l, phosphate 1.2), aimed at preventing phosphate depletion. RESULTS: In 10 high bleeding-risk patients, the RCA-CVVH protocol provided an adequate circuit lifetime (46.8 ± 30.3 h) despite the adoption of a low citrate dose and a higher than usual target circuit Ca2+ (≤0.5 mmol/l). Acid-base status was adequately maintained without the need for additional interventions on RCA-CVVH parameters and without indirect sign of citrate accumulation [(pH 7.43 (7.41-7.47), bicarbonate 24.4 mmol/l (23.2-25.6), BE 0 (-1.5 to 1.1), calcium ratio 1.97 (1.82-2.01); median (IQR)]. Serum phosphate was steadily maintained in a narrow range throughout RCA-CVVH days [1.1 mmol/l (0.9-1.4)]. A low amount of phosphorus supplementation (0.9 ± 2 g/day) was required in only 30% of patients. CONCLUSIONS: Although needing further evaluation, the proposed RCA-CVVH protocol ensured a safe and effective RCA without electrolyte and/or acid-base derangements. CRRT-induced hypophosphatemia was prevented in most of the patients by the adoption of a phosphate-containing replacement solution, minimizing phosphate supplementation needs.

Continuous venovenous hemodiafiltration with a low citrate dose regional anticoagulation protocol and a phosphate-containing solution: effects on acid-base status and phosphate supplementation needs.

BACKGROUND: Recent guidelines suggest the adoption of regional citrate anticoagulation (RCA) as first choice CRRT anticoagulation modality in patients without contraindications for citrate. Regardless of the anticoagulation protocol, hypophosphatemia represents a potential drawback of CRRT which could be prevented by the adoption of phosphate-containing CRRT solutions. The aim was to evaluate the effects on acid-base status and phosphate supplementation needs of a new RCA protocol for Continuous Venovenous Hemodiafiltration (CVVHDF) combining the use of citrate with a phosphate-containing CRRT solution. METHODS: To refine our routine RCA-CVVH protocol (12 mmol/l citrate, HCO3- 32 mmol/l replacement fluid) (protocol A) and to prevent CRRT-related hypophosphatemia, we introduced a new RCA-CVVHDF protocol (protocol B) combining an 18 mmol/l citrate solution with a phosphate-containing dialysate/replacement fluid (HCO3- 30 mmol/l, Phosphate 1.2). A low citrate dose (2.5-3 mmol/l) and a higher than usual target circuit-Ca(2+) (≤ 0.5 mmol/l) have been adopted. RESULTS: Two historical groups of heart surgery patients (n = 40) underwent RCA-CRRT with protocol A (n = 20, 102 circuits, total running time 5283 hours) or protocol B (n = 20, 138 circuits, total running time 7308 hours). Despite higher circuit-Ca(2+) in protocol B (0.37 vs 0.42 mmol/l, p < 0.001), circuit life was comparable (51.8 ± 36.5 vs 53 ± 32.6 hours). Protocol A required additional bicarbonate supplementation (6 ± 6.4 mmol/h) in 90% of patients while protocol B ensured appropriate acid-base balance without additional interventions: pH 7.43 (7.40-7.46), Bicarbonate 25.3 (23.8-26.6) mmol/l, BE 0.9 (-0.8 to +2.4); median (IQR). No episodes of clinically relevant metabolic alkalosis, requiring modifications of RCA-CRRT settings, were observed. Phosphate supplementation was needed in all group A patients (3.4 ± 2.4 g/day) and in only 30% of group B patients (0.5 ± 1.5 g/day). Hypophosphatemia developed in 75% and 30% of group A and group B patients, respectively. Serum phosphate was significantly higher in protocol B patients (P < 0.001) and, differently to protocol A, appeared to be steadily maintained in near normal range (0.97-1.45 mmol/l, IQR). CONCLUSIONS: The proposed RCA-CVVHDF protocol ensured appropriate acid-base balance without additional interventions, providing prolonged filter life despite adoption of a higher target circuit-Ca(2+). The introduction of a phosphate-containing solution, in the setting of RCA, significantly reduced CRRT-related phosphate depletion.

Regional citrate anticoagulation in CVVH: a new protocol combining citrate solution with a phosphate-containing replacement fluid.

Regional citrate anticoagulation (RCA) is a valid anticoagulation method in continuous renal replacement therapies (CRRT) and different combination of citrate and CRRT solutions can affect acid-base balance. Regardless of the anticoagulation protocol, hypophosphatemia occurs frequently in CRRT. In this case report, we evaluated safety and effects on acid-base balance of a new RCA- continuous veno-venous hemofiltration (CVVH) protocol using an 18 mmol/L citrate solution combined with a phosphate-containing replacement fluid. In our center, RCA-CVVH is routinely performed with a 12 mmol/L citrate solution and a postdilution replacement fluid with bicarbonate (protocol A). In case of persistent acidosis, not related to citrate accumulation, bicarbonate infusion is scheduled. In order to optimize buffers balance, a new protocol has been designed using recently introduced solutions: 18 mmol/L citrate solution, phosphate-containing postdilution replacement fluid with bicarbonate (protocol B). In a cardiac surgery patient with acute kidney injury, acid-base status and electrolytes have been evaluated comparing protocol A (five circuits, 301 hours) vs. protocol B (two circuits, 97 hours): pH 7.39 ± 0.03 vs. 7.44 ± 0.03 (P < 0.0001), bicarbonate 22.3 ± 1.8 vs. 22.6 ± 1.4 mmol/L (NS), Base excess -2.8 ± 2.1 vs. -1.6 ± 1.2 (P = 0.007), phosphate 0.85 ± 0.2 vs. 1.3 ± 0.5 mmol/L (P = 0.027). Protocol A required bicarbonate and sodium phosphate infusion (8.9 ± 2.8 mmol/h and 5 g/day, respectively) while protocol B allowed to stop both supplementations. In comparison to protocol A, protocol B allowed to adequately control acid-base status without additional bicarbonate infusion and in absence of alkalosis, despite the use of a standard bicarbonate concentration replacement solution. Furthermore, the combination of a phosphate-containing replacement fluid appeared effective to prevent hypophosphatemia.

Regional citrate anticoagulation in cardiac surgery patients at high risk of bleeding: a continuous veno-venous hemofiltration protocol with a low concentration citrate solution.

INTRODUCTION: Regional citrate anticoagulation (RCA) is a valid option in patients at high risk of bleeding who are undergoing continuous renal replacement therapy (CRRT). The aim of this study was to evaluate, in critically ill patients with severe acute kidney injury following cardiac surgery, the efficacy and safety of RCA-continuous veno-venous hemofiltration (CVVH) using a low concentration citrate solution. METHODS: In high bleeding-risk cardiac surgery patients, we adopted, as an alternative to heparin or no anticoagulation, RCA-CVVH using a 12 mmol/l citrate solution. For RCA-CVVH settings, we developed a mathematical model to roughly estimate citrate load and calcium loss. In order to minimize calcium chloride supplementation, a calcium-containing solution was used as post-dilution replacement fluid. RESULTS: Thirty-three patients (age 70.8 ± 9.5, Sequential Organ Failure Assessment (SOFA) score 13.9 ± 2.5) were switched to RCA-CVVH from no anticoagulation CRRT. Among them, 16 patients had been previously switched from heparin to no anticoagulation because of bleeding or heparin-related complications. RCA-CVVH filter life (49.8 ± 35.4 hours, median 41, 152 circuits) was significantly longer (P < 0.0001) when compared with heparin (30.6 ± 24.3 hours, median 22, 73 circuits) or no anticoagulation (25.7 ± 21.2 hours, median 20, 77 circuits). Target circuit and systemic Ca(++) were easily maintained (0.37 ± 0.09 and 1.18 ± 0.13 mmol/l), while the persistence of a mild metabolic acidosis required bicarbonate supplementation (5.8 ± 5.9 mmol/hours) in 27 patients. The probability of circuit running at 24, 48, 72 hours was higher during RCA-CVVH (P < 0.0001), with a lower discrepancy between delivered and prescribed CRRT dose (P < 0.0001). RCA was associated with a lower transfusion rate (P < 0.02). Platelet count (P = 0.012) and antithrombin III activity (P = 0.004) increased throughout RCA-CVVH, reducing the need for supplementation. CONCLUSIONS: RCA safely prolonged filter life while decreasing CRRT downtime, transfusion rates and supplementation needs for antithrombin III and platelets. In cardiac surgery patients with severe multiple organ dysfunction syndrome, the adoption of a 12 mmol/l citrate solution may provide a suboptimal buffers supply, easily overwhelmed by bicarbonate supplementation.

Choroidopathy in patients with systemic lupus erythematosus with or without nephropathy.

BACKGROUND: The aim of this study was to evaluate indocyanine green angiographic findings in patients with systemic lupus erythematosus (SLE) with or without lupus nephritis. In particular, the presence of choroidal abnormalities at indocyanine green angiography (ICG-A) that could not be detected by fluorescein angiography (FAG) was investigated. METHODS: Sixteen patients with SLE underwent simultaneous ICG-A and FAG. Patients were divided into 2 groups based on whether renal disease was present (group A, n=9) or not (group B, n=7). RESULTS: Drusen-like deposits were ophthalmoscopically evident in only 1 out of 9 group A patients (11.1%). While FAG disclosed the deposits in 4 out of 9 group A patients (44.4%), drusen-like deposits were otherwise found in all group A patients (100%) by ICG-A. FAG and ICG-A did not show choroidal alterations in group B patients. CONCLUSIONS: ICG-A can provide information that is not detectable by clinical or FAG examination in patients with lupus nephritis (group A). The findings of choroidopathy by ICG-A represent an indicator of ocular involvement and could be an indirect sign of renal involvement. Given that histological lesions may be present where there are no anomalies in urinary sediment and/or proteinuria, the positivity of ICG-A could help in deciding whether or not to carry out a renal biopsy. Therefore, ICG-A could be useful in the screening of patients with SLE, especially where there are no evident signs of renal involvement.

Is Cronkhite-Canada Syndrome necessarily a late-onset disease?

Cronkhite-Canada Syndrome is a non-inherited, non-congenital disease characterized by juvenile hamartomatous gastrointestinal polyps with a typically late onset. In the case described herein the disease was diagnosed in a 17-year-old male with type I diabetes and thalassaemia minor, in coincidence with severe symptomatic intestinal candidiasis. Following the disappearance of the mycosis and correction of the protein and electrolyte imbalance, the ectodermal abnormalities returned to normal and the patient remained asymptomatic during a 7-year follow-up period, despite proteinuria resulting from membranous glomerulopathy. The concept that Cronkhite-Canada Syndrome is a late-onset disease should probably be reconsidered as it may remain asymptomatic, and thus not diagnosed, for a long a time.

Continuous renal replacement therapies: anticoagulation in the critically ill at high risk of bleeding.

BACKGROUND: The ongoing necessity for systemic heparinization is a well-known disadvantage of continuous renal replacement therapies (CRRT), and alternative methods of anticoagulation may be required. Our aim was to evaluate, in patients with a high risk of bleeding, the possibility of an acceptable filter life with non-anticoagulation CRRT and, in case of early filter failure, the efficacy and safety of bedside monitored regional anticoagulation with heparin and protamine. METHODS: Fifty-nine patients underwent CRRT for acute renal failure (ARF) following cardiac surgery. Patients who fulfilled one of the following criteria were selected for non-anticoagulation CRRT: spontaneous bleeding, aPTT > 45 sec, thrombocytopenia and recent surgery (< 48 hr). Filter life < 24 hr without anticoagulation was the cut-off point for starting the regional anticoagulation CRRT. Heparin was infused pre-filter and protamine post-filter at an initial ratio of 1 mg protamine:100 IU heparin. The ratio was adjusted to achieve a patient aPTT < 45 sec and a circuit > 55 sec. RESULTS: Twenty-two (37.3%) patients had been selected for non-anticoagulation. Of them, 12 patients continued to receive non-anticoagulation (filter life: 38.3 +/- 30.5 hr) while 10 switched to regional anticoagulation (filter life: 38.6 +/- 25 hr). During regional anticoagulation no statistical difference was found between baseline aPTT (36.7 +/- 6.4 sec) and patient aPTT (41.5 +/- 12.6 sec) while circuit aPTT (77.7 +/- 43.3 sec) was significantly higher than patient aPTT (p < 0.0001). The probabilities of the circuits remaining free from clotting after 24, 48 and 72 hr were: a) non-anticoagulation: 55.5%, 30.1% and 16.6%, b) regional anticoagulation: 76.2%, 39.6% and 19.8%. There was no rebound anticoagulation observed after regional anticoagulation CRRT ended. CONCLUSIONS: Non-anticoagulation CRRT allowed an adequate filter life in most patients with a high risk of bleeding for prolonged aPTT and/or thrombocytopenia. Despite concerns regarding the need for careful monitoring, regional anticoagulation with heparin and protamine can be considered as a safe and valid alternative when non-anticoagulation is unsuitable because of early filter failure.