Beneficial effects of ketoanalogues on the evolution of renal function and bone mineral disorders in patients with advanced chronic kidney disease :A pilot study.

Introduction The supplementation with Ketoanalogues in patients on very low protein diets has shown an favorable effect in the evolution of renal function . The aim of the present study is to evaluate the progression of renal function in advanced CKD patients on a low protein diet (<0.8 g/kg/d) with or without additional Ketoanalogues. Methods The primary criterion is the evolution of the renal function at 6, 12 and 24 months for the two groups. The secondary criteria comprise the evolution of the body weight, mean blood pressure, 24h proteinuria, salt and protein consumption, energy consumption, hemoglobin levels, serum albumin, prealbumin, C-reactive protein, liver function tests,serum electrolyte levels and phosphate, parathormone as well as calcium levels at the same time periods. Results There was a significant nephroprotective effect of the Ketoanalogues after 12 and 24 months with no differences in the protein consumption between the two groups. Mean blood pressure, hemoglobin levels, 24-four hour proteinuria, serum electrolyte , liver function tests, salt and protein consumption, serum albumin and prealbumin did not present any significant differences. Serum bicarbonate and calcium levels were higher while serum phosphate and parathormone levels were lower in the Ketoanalogue group at all follow-up time points. During the 24 months follow-up period, 4 patients from the Ketoanalogue group and 8 patients from the control group quitted the study. Conclusion A low protein diet supplemented with Ketoanalogues exerts significant nephroprotective effects and better bone mineral metabolism parameters compared to a low protein diet only.

Deleterious effects of intradialytic meals' suppression during the COVID pandemic.

BACKGROUND&AIMS: Patients with end-stage renal failure on chronic hemodialysis present an important risk of malnutrition, which is associated with a significant risk of morbidity and mortality. Meals during the dialysis session are important for maintaining the nutritional status of dialysis patients but represent a risk for intradialytic hypotension. During the COVID-19 pandemic, several dialysis centers stopped providing meals during the dialysis session as a protective measure. The aim of this retrospective, multicentric cross-over study was to study the evolution of the nutritional parameters of a cohort of hemodialysis patients for 12 months before, during and after the suspension of meals during dialysis due to the COVID-19 pandemics. METHODS: We registered the evolution of dry weight, C Reactive Protein (CRP), serum Potassium and Phosphate before the dialysis session, serum albumin and prealbumin levels as well as normalized Protein Catabolic Ratio (nPCR). RESULTS: We studied 168 hemodialysis patients (113M, 55F, mean age at inclusion:68.45 ± 0.45 years). The results ares shown as mean values (±SEM). The supression of the intradialytic meals led to significant reduction of the patients' dry weight (in Kg) from 78.66 ± 0.72 to 76.50 ± 0.49, p = 0.013, serum albumin (in g/l) (from 40.72 ± 0.16 to 39.25 ± 0.12, p < 0.001) and prealbumin levels (in g/l) (from 33.82 ± 0.31 to 32.73 ± 0.22, p = 0.004) as well as the nPCR values (from 1.08 ± 0.08 to 1.05 ± 0.11, p = 0.021). Serum CRP as well as predialytic Potassium and Phosphate levels did not change significantly. The reinstitution of the intradialytic meals led to a complete correction of the studied nutritional parameters with Body weight values evolving from 76.50 ± 0.49 to 78.28 ± 1.01, p = 0.025, serum albumin from 39.25 ± 0.12 to 40.53 ± 1.04, p < 0.001, serum prealbumin levels from 32.73 ± 0.22 to 33.95 ± 0.64, p = 0.001 an nPCR from 1.05 ± 0.11 to 1.08 ± 0.08, p = 0.021. CONCLUSION: In conclusion, the suppression of intradialytic meals during the COVID-19 pandemic had deleterious effects on the nutritional parameters of patients on chronic hemodialysis.

Hemodialysis access flow measurement: Comparison of ultrasound dilution and ultrafiltration method on NIKKISO DBB-EXA™ dialysis machine.

BACKGROUND: The methods of estimating vascular access (VA) flow rates are usually based on the indicator dilution theory by measuring recirculation during dialysis sessions. METHODS: This is an observational study comparing the VA flow rates measured by NIKKISO DBB-EXA™ and Transonic®. Sixty-five patients (38 M/27 F, mean age 72 ± 10 years) participated in the study. We measured the VA flow rates during dialysis twice with each method and repeated the procedure 7 days later. RESULTS: In 130 double measurements for each method on the same day, mean flow with Transonic® was 1413±715 ml/min and with DBB-EXA™ 1297 ± 664 ml/min. In Bland-Altman analysis, the mean difference between the two methods was 159 ± 211 ml/min (limits of agreement: -274 and 572 ml/min). Eighty-one out of the 130 DBB-EXA™ measurements were within 25% of the Transonic® measurements (62% accuracy). Regarding reproducibility of each method on different days, mean difference in the Bland-Altman analysis was 29 ± 620 ml/min (limits of agreement: -1186 and 1244 ml/min) for the Transonic® measurements and 132 ± 625 ml/min (limits of agreement: -1092 and 1356 ml/min) for the DBB-EXA™ measurements. The measurements on two different days were within 25% of each other for 52 of the 65 patients (80%) with the Transonic® method, and for 35 of the 65 patients (54%) with the DBB-EXA™ method. CONCLUSIONS: In conclusion, the DBB-EXA™ method underestimates VA flow rates compared to the Transonic® technique, resulting in a limited accuracy of 62%. There was poor reproducibility for both methods in different day measurements with better performance of the Transonic® technique. The DBB-EXA™ method could be used as a simple tool for a rough estimate of VA flow rates but cannot replace the Transonic® reference method.

Day and night changes in energy expenditure of patients on automated peritoneal dialysis.

RATIONALE: Automated peritoneal dialysis (APD) treatment for end-stage kidney disease affords patients a degree of autonomy in everyday life. Clinical investigations of their energy expenditure (EE) are usually based on resting EE, which could mask day and night variations in EE. The aim of this study, therefore, was to compare the components of EE in APD patients and healthy control (C) subjects. MATERIAL AND METHOD: Patients treated with APD for more than 3 months were compared with C volunteers matched for age and lean body mass (LBM). Biochemical analyses were performed and body composition was determined by DEXA to adjust EE to LBM. Total EE, its different components and respiratory quotients (RQ) were measured by a gas exchange method in calorimetric chambers. Spontaneous total and activity-related EE (AEE) were also measured in free-living conditions over 4 days by a calibrated accelerometer and a heart rate monitor. RESULTS: APD (n = 7) and C (n = 7) patients did not differ in age and body composition. REE did not differ between the two groups. However, prandial increase in EE adjusted for dietary energy intake was higher in APD patients (+57.5 ± 12.71 kcal/h) than in C subjects (+33.8 ± 10.5 kcal/h, p = 0.003) and nocturnal decrease in EE tended to be lower in APD patients undergoing dialysis sessions (- 4.53 ± 8.37 kcal/h) than in subjects (- 11.8 ± 7.69 kcal/h, p = 0.059). Resting RQ (0.91 ± 0.09 vs 0.81 ± 0.04, p = 0.032) and nocturnal RQ (0.91 ± 0.09 vs 0.81 ± 0.04, p = 0.032) were significantly higher in APD patients, indicating a preferential use of glucose substrate potentially absorbed across the peritoneum. AEE was lower in APD patients (595.9 ± 383.2 kcal/d) than in C subjects (1205.2 ± 370.5 kcal/d, p = 0.011). In contrast, energy intakes were not significantly different (1986 ± 465 vs 2083 ± 377 kcal/d, p = 0.677). CONCLUSION: Although the two groups had identical resting EE, APD patients had a higher prandial increase in EE, a lower activity-related EE and higher resting and nocturnal RQ than healthy subjects.

Repurposing Zileuton as a Depression Drug Using an AI and In Vitro Approach.

Repurposing drugs to target M1 macrophages inflammatory response in depression constitutes a bright alternative for commonly used antidepressants. Depression is a significant type of mood disorder, where patients suffer from pathological disturbances associated with a proinflammatory M1 macrophage phenotype. Presently, the most commonly used antidepressants such as Zoloft and Citalopram can reduce inflammation, but suffer from dangerous side effects without offering specificity toward macrophages. We employed a new strategy for drug repurposing based on the integration of RNA-seq analysis and text mining using deep neural networks. Our system employs a Google semantic AI universal encoder to compute sentences embedding. Sentences similarity is calculated using a sorting function to identify drug compounds. Then sentence relevance is computed using a custom-built convolution differential network. Our system highlighted the NRF2 pathway as a critical drug target to reprogram M1 macrophage response toward an anti-inflammatory profile (M2). Using our approach, we were also able to predict that lipoxygenase inhibitor drug zileuton could modulate NRF2 pathway in vitro. Taken together, our results indicate that reorienting zileuton usage to modulate M1 macrophages could be a novel and safer therapeutic option for treating depression.

[Acute interstitial nephritis of fluindione: about three cases]. / Néphropathie interstitielle aiguë à la fluindione: à propos de trois cas.

Acute interstitial nephritis is a frequent cause of acute renal failure, representing about 10% of all biopsied cases. Early recognition of drug-induced acute immunoallergic interstitial nephritis prevents the development of severe chronic renal injury. The list of imputable drugs includes phenindione, a vitamin K antagonist. Fluindione which is also an indanedione derivative is another vitamin K antagonist. We report three biopsy-proved cases of fluindione related acute interstitial nephritis with recovery of renal function after drug withdrawal and prednisone therapy.

[A case of renal paradoxical embolism]. / Un cas d'embolies rénales paradoxales.

Acute renal failure due to paradoxical embolism is exceptionally reported. A new case gives the opportunity to review mechanisms, diagnosis and therapeutic issues. A 49-year-old woman without medical history is admitted for crural venous thrombosis and acute pulmonary embolism. At day 2, a left flank acute pain with fever, doubling of plasma creatinine, and controlateral recurrence at day 12, leads to diagnosis of acute bilateral renal infarction only at day 20. Paradoxical embolism is then suspected and confirmed by transoesophageal contrast echocardiography, disclosing patent foramen ovale with right-to-left shunt. Nine months later, successful percutaneous closure of patent foramen ovale with Amplatzer PFO occluder 25 mm allows subsequent discontinuation of oral anticoagulation. Diagnostic criteria for paradoxical embolism are present in our case. If this mechanism is often discussed in cryptogenic cerebrovascular stroke of young patients, it is exceptionally reported as responsible for clinical renal disease, particularly acute renal failure (whereas anatomical renal involvement is not unfrequent). The clue is the difficulty to suspect and confirm renal infarction, especially when classical causes of cardiac embolism are lacking. The relevance is the opportunity to save renal tissue in the acute phase, and to close patent foramen ovale (currently most often percutaneously) weeks or months after the acute bout.

[Metastatic renal failure]. / Insuffisance rénale aiguë métastatique.

A 52-year-old man, treated 15 months earlier for a poorly differentiated bronchial adenosquamous carcinoma, was admitted for oligoanuric renal failure preceded by macroscopic hematuria. Clinical and paraclinical investigations were unremarkable except ++proteinuria and mild echographic enlargement of both kidneys. Bilateral renal biopsy disclosed replacement of normal renal tissue by an adenocarcinomatous proliferation. Despite transient improvement and cessation of hemodialysis, the patient died one month later. Analysis of literature reveals that secondary kidney tumours -especially of bronchial origin- are more frequent than primary ones, but that cases of renal failure are uncommonly reported, probably because of underdiagnosis, poor prognosis and limited therapeutic issues. Features of previously published cases are listed in a synthetic table.