Treatment of dabigatran intoxication in critically ill patients with Acute Kidney Injury: The role of Sustained Low-Efficiency Dialysis.

The use of dabigatran in patients with non-valvular atrial fibrillation (AF) has widely increased in the last decades, due to its positive effects in terms of safety/efficacy. However, because of the risk of major bleeding, a great degree of attention has been suggested in elderly patients with multiple comorbidities. Notably, dabigatran mainly undergoes renal elimination and dose adjustment is recommended in patients with Chronic Kidney Disease (CKD). In this regard, the onset of an abrupt decrease of kidney function may further affect dabigatran pharmacokinetic profile, increasing the risk of acute intoxication. Idarucizumab is the approved antagonist in the case of dabigatran-associated major bleeding or concomitant need of urgent surgery, but its clinical use is limited by the lack of data in patients with Acute Kidney Injury (AKI). Thus, the early start of Extracorporeal Kidney Replacement Therapy (EKRT) could be indicated to remove the drug and to reverse the associated excess anticoagulation. Sustained Low-Efficiency Dialysis (SLED) could represent an effective therapeutic option to reduce the dabigatran plasma levels rapidly while avoiding post-treatment rebound. We present here a case series of three AKI patients with acute dabigatran intoxication, effectively and safely resolved with a single SLED session.

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).

Muscle mass assessment in renal disease: the role of imaging techniques.

Muscle wasting is a frequent finding in patients with chronic kidney disease (CKD), especially in those with end-stage kidney disease (ESKD) on chronic dialysis. Muscle wasting in CKD is a main feature of malnutrition, and results principally from a vast array of metabolic derangements typical of the syndrome, that converge in determining reduced protein synthesis and accelerated protein catabolism. In this clinical setting, muscle wasting is also frequently associated with disability, frailty, infections, depression, worsened quality of life and increased mortality. On these grounds, the evaluation of nutritional status is crucial for an adequate management of renal patients, and consists of a comprehensive assessment allowing for the identification of malnourished patients and patients at nutritional risk. It is based essentially on the assessment of the extent and trend of body weight loss, as well as of spontaneous dietary intake. Another key component of this evaluation is the determination of body composition, which, depending on the selected method among several ones available, can identify accurately patients with decreased muscle mass. The choice will depend on the availability and ease of application of a specific technique in clinical practice based on local experience, staff resources and good repeatability over time. Surrogate methods, such as anthropometry and bioimpedance analysis (BIA), represent the most readily available techniques. Other methods based on imaging modalities [dual-energy X-ray absorptiometry (DXA), magnetic resonance imaging (MRI), and whole body computed tomography (CT)] are considered to be the "gold standard" reference methods for muscle mass evaluation, but their use is mainly confined to research purposes. New imaging modalities, such as segmental CT scan and muscle ultrasound have been proposed in recent years. Particularly, ultrasound is a promising technique in this field, as it is commonly available for bedside evaluation of renal patients in nephrology wards. However, more data are needed before a routine use of ultrasound for muscle mass evaluation can be recommended in clinical practice.

BMI, nephroangiosclerosis and glomerulonephritis: Is there any meeting point?

AIM: Overweight has been related to renal arteriolosclerosis and is able to modify intrarenal haemodynamics. Increasing evidence suggests an association between weight in excess and primary glomerulonephritis (GN). The aim of this study was to evaluate the relationship between nutritional status and intrarenal arterial stiffness in primary GN associated to arteriolosclerosis. We have considered the glomerular diameter (GD) as morphological parameter in overweight and obese patients. METHODS: Clinical, laboratory, anthropometric data and renal Doppler ultrasound were performed immediately before kidney biopsy. RESULTS: Primary GN was diagnosed in 92 patients. Mild arteriolosclerosis was found in 19.6% of patients, moderate in the 20.6%, severe in the 10.9% while nephroangiosclerosis was diagnosed in 8.7% of patients. A positive correlation was found between body mass index (BMI) and renal resistive index (RRI) (P < 0.01, r = 0.34). RRI were significantly higher in patients with severe arteriolosclerosis at kidney biopsy (P < 0.05). Furthermore, higher BMI (P < 0.01) was found in patients with renal arteriolosclerosis than patients without renal arteriolosclerosis (26.1 ± 4.4 kg/m2 vs. 24.4 ± 4.5 kg/m2 ). Finally, in overweight and obesity patients we found a positive correlation between maximal GD and BMI (P < 0.01) and maximal GD and RRI (P < 0.01). CONCLUSION: In overweight and obese patients affected by primary GN, it might be found not only glomerular but also renal vascular lesions. Finally, we believe that nephroangiosclerosis, in combination with weight in excess, is able to modify intrarenal haemodynamic parameters. Moreover, in response to these changes, the renal tissue morphologically promotes a GD increase regardless of the underlying GN.

Renal parenchymal resistance in patients with biopsy proven glomerulonephritis: Correlation with histological findings.

Renal Doppler ultrasound is increasingly used in nephrology for the evaluation of renovascular disease, allograft dysfunction, and chronic nephropathies. We compared intrarenal hemodynamic parameters to biopsy findings of glomerular sclerosis, tubular atrophy, interstitial fibrosis, crescents, arteriolosclerosis, and clinical variables in 100 patients. A positive correlation exists between renal function and percentage of glomerular sclerosis (P <0.01, r = 0.26), conversely a negative correlation exists between glomerular filtrate rate and percentage of glomerular sclerosis(P <0.0001, r = -0.35). The percentage of glomerular sclerosis correlate positively with pulsatile index (PI) (P <0.05, r = 0.21) and renal resistive index (RI) (P <0.05, r = 0.20). The percentage of crescents correlates positively with PI(P <0.05, r = 0.21) and RI (P <0.05, r = 0.20). Classifying arteriolosclerosis in four groups according to a severity scale, from absence to severe, PI (P <0.05) and RI (P <0.01) were significantly different. In the post hoc analysis, the median values of PI and RI are significantly different in patients with severe arteriolosclerosis than others. Ultrasound examination is a non-invasive diagnostic technique used on patients with suspected or established renal disease. Our study shows a close correlation between kidney function, ultrasound parameters, and histological findings. Measurement of renal parenchymal resistance by ultrasound could be used in association with biopsy and glomerular function for the evaluation of renal damage in patients with glomerulonephritis.