An unorthodox pathophysiology of severe cases of COVID-19 the weak heme hypothesis.

Important amount of severe cases is the main concern in COVID-19 pandemic. It could be the running cause of the burn out of the health system in many countries. The aim of this paper is to suggest a pathophysiologic hypothesis to explain the main characteristics of severe cases of COVID-19 and its underlying conditions. In fact, the clinical and biological picture of severe cases of COVID-19 can easily be explained by free heme toxicity exceeding the endogenous antioxidant systems. Severe cases of COVID-19 are comparable to acute porphyria. On the other hand, the geographical distribution of severe cases of COVID-19 is directly associated to how fresh or polluted the air is. Finally, the relatively low rate of severe cases of COVID-19 could be explained by the presence of an unstable hemoglobin variant highly sensitive to the intrinsic conditions resulting from the acute pneumonia secondary to SARS-CoV2 infection. The combination of air pollution and free heme toxicity, resulting from the interaction between an unstable hemoglobin variant and SARS-CoV2 infection, seems to be the best scheme to explain clinical and biological manifestations in severe COVID-19. The arguments to support this hypothesis are detailed. We also propose some strategies to verify the concordance of our hypothesis with the reality and the implications it could have, if verified, either for scientists and decision makers.

Utility of a blood volume monitor in the management of anemia in dialysis by computing the total hemoglobin mass.

INTRODUCTION: The degree of interdialytic weight gain and ultrafiltration may influence anemia results in dialysis. The purpose of this study is to evaluate the utility of a blood volume monitor (BVM) in the management of renal anemia and its ability to avoid the variability of hematocrit (Hct) and hemoglobin values (Hb) depending on plasma volume through a simple method of monitoring the total hemoglobin mass (MtHb ). METHODS: Predialysis blood samples for measurement were drawn at both the midweek treatment and the beginning-of-the-dialysis-week treatment in 30 patients. The MtHb was calculated as MtHb = Vb × Hb, where Vb is the absolute blood volume determined by online dialysate dilution using an online hemodiafiltration machine incorporating a relative BVM. FINDINGS: The MtHb and the total red cell volume (VRBC ) as measured with the bolus method at the starting of the treatment were 540 ± 148 grams and 1544 ± 339 mL, respectively. There were significant differences between the Hb levels and between the hematocrit levels according to the time of dialysis. However, the MtHb remained constant. There was also an excellent correlation between the Hb measurements by the BVM and the blood sampling method (R = 0.89, P value <0.001). CONCLUSION: Our study suggests that BVM could be very useful in the management of anemia in dialysis by computing the total Hb mass in clinical practice and may support better and more appropriate assessments of the factors influencing circulating Hb.

Usefulness of ambulatory blood pressure monitoring in chronic kidney disease: The moroccan experience.

Among patients with chronic kidney disease (CKD), hypertension (HTN) is very common and widely recognized to accelerate the progression of CKD and increase the risk for cardiovascular events. Accumulated data indicate that ambulatory blood pressure monitoring (ABPM) is better in detecting HTN than office blood pressure (BP) measurement. The goal of this study is to describe the ABPM characteristics in a group of CKD and hypertensive patients. A transversal study was conducted over a period of six months, to evaluate the ABPM patterns among a group of hypertensive patients with CKD (Group 1) and compared the data with a control group (Group 2). ABPM was performed with measurement rate every 15 min during daytime and 30 min at night. Nondipping BP patterns were defined as the absence of fall in nocturnal systolic and diastolic BP >10% of daytime values. Masked HTN was defined as controlled office BP (<140/90 mm Hg) with an elevated overall average BP by 24-h ABPM (>125/75 mm Hg), and white-coat HTN was defined as association of elevated BP readings (>140/90 mm Hg) in a clinical setting and normal 24-h average BP levels (<130/80 mm Hg). Fifty patients were included in each group. HTN was much longer in duration among hypertensive patients with CKD and frequently associated with obesity, dyslipidemia, and diabetes (64% vs. 39.60%). Positive proteinuria was present in 82% of CKD patients with HTN. CKD patients with HTN received more antihypertensive drugs than Group 2 patients. HTN was much more uncontrolled among CKD patients (60% vs. 24%), more serious with higher daytime and nighttime SBP, and loss of physiologic dipping during nighttime BP measurement (80%). Out-of-office BP monitoring by ABPM may improve the assessment and the successful management of HTN in patients with CKD. Standardized definitions for the diagnosis of masked and white-coat HTN would facilitate research.

The cost-utility of treating anemia with continuous erythropoietin receptor activator or Epoetin versus routine blood transfusions among chronic hemodialysis patients.

OBJECTIVE: The purpose of this study was to determine the cost-utility of treating anemic dialysis patients with continuous erythropoietin receptor activator (CERA) once monthly or Epoetin Beta (EpoB) thrice weekly compared with a reference strategy of managing anemia with red blood cell transfusion (RBCT). METHODS: Cost-utility analysis study design. Decision analysis model, National health care payer, over 1 year with the publicly funded health care system. Chronic hemodialysis patients with renal anemia were included. The outcome marker of this study was the incremental cost per quality-adjusted life-year (QALY) gained (incremental cost-utility ratio [ICUR]) of CERA or EpoB relative to RBCT. RESULTS: The total cost per patient (in US$) was estimated at $2,176.37, $4,107.01, and $4,356.69 for RBCT, CERA, and EpoB, respectively. The cost-utility ratio was calculated at 4,423.52, 6,955.50, and 7,406.38 $/QALY for RBCT, CERA, and EpoB, with an ICUR of CERA and EpoB in relation to RBCT at 19,606.40 and 22,466.09 $/QALY, respectively. In sensitivity analysis, the model was most sensitive to hospitalization costs, hospital stay, and annual number of RBCT units. Also, assuming utility and survival improvement with erythropoiesis stimulating agents use resulted in a decrease in ICUR at 13,429 $/QALY for CERA and 15,331 $/QALY for EpoB. In probabilistic sensitivity analysis, the main results of our model were unchanged; CERA and EpoB were more costly and more effective than RBCT below a threshold of 19,500 $/QALY. CERA was the best option for a willingness to pay over 19,500 $/QALY. LIMITATIONS: Some model parameters were obtained from observational data, the comparator RBCT is not the standard of care. CONCLUSION: Our study suggests that managing anemia in dialysis patients with CERA or EpoB may result in better outcomes with higher overall costs. Considering different assumptions, we found substantial variability in the estimates of the cost-utility and incremental of using CERA or EpoB.

The Cost-Effectiveness of Continuous Erythropoiesis Receptor Activator Once Monthly versus Epoetin Thrice Weekly for Anaemia Management in Chronic Haemodialysis Patients.

Introduction. The aim of this study was to compare the cost-effectiveness of continuous erythropoietin receptor activator (CERA) once monthly to epoetin beta (EpoB) thrice weekly to maintain haemoglobin (Hb) within the range 10.5-12 g/dL. Methods. Prospective cohort study and cost-effectiveness analysis. Chronic haemodialysis patients (CHP), being treated with EpoB, were selected for two periods of follow-up: period 1, maintaining prior treatment with EpoB, and period 2, conversion to CERA once monthly. Hb concentrations and costs were measured monthly. Health care payer perspective for one year was adopted. Results. 75 CHP completed the study, with a mean age of 52.9 ± 14.3 years. Baseline Hb was 11.14 ± 1.18 g/dL in EpoB phase and 11.46 ± 0.79 g/dL in CERA phase; we observed a significant increase in the proportion of patients successfully treated (Hb within the recommended range), 65.3% versus 70.7%, p: 0.008, and in the average effectiveness by 4% (0.55 versus 0.59). Average cost-effectiveness ratios were 6013.86 and 5173.64$, with an ICER CERA to EpoB at -6457.5$. Conclusion. Our health economic evaluation of ESA use in haemodialysis patients suggests that the use of CERA is cost-effective compared with EpoB.

Commentary: the practice of dialysis in the intensive care unit in a developing country.

INTRODUCTION AND AIMS: In developing countries, little is known about renal replacement therapy (RRT) for acute kidney injury (AKI) in critically ill patients. The aim of this study is to describe characteristics of patients, clinical practice of renal support and outcomes in intensive care units (ICU) in a developing country. METHODS: Patients who underwent RRT for AKI from May 2003 to July 2008, in four ICUs in our institution were included in this retrospective study. Patients with end stage renal disease or younger than aged 18 years were exclueded. We have considered: patient demographics, indications of RRT, number of dialysis session, comorbidities, APACH II score for illness severity, mechanical ventilation, use of vasoactive drugs, and mortality rate. RESULTS: 105 critically ill patients admitted during the study period were treated with RRT, with a mean age of 56.13 +/- 16.8 (19-85) years. Sixty five were male and 40 female; all received intermittent hemodialysis. The total number of dialysis sessions was 284, and the mean number was 3.7 +/- 2.9; mean length of session was 225.22 +/- 75.16 (60-290) min. The majority of the cases (67%) were from medical ICU, followed by 30.2% from surgical ICUs (including cardiothoracic surgery ICU) and 2.8% were from burn ICU. The most common comorbidities were type 2 diabetes mellitus in 46 (44%) and hypertension in 35 (33.4%). Sepsis was a contributing factor to AKI in 60 patients (57.14%), hypovolemia in 30 (28.5%), and cardiogenic shock in 9 (8.5%). The APACHE II score was 25.86 +/- 11.8; the majority of patients (66.7%) were ventilated; 63 (60%) were under vasoactive drugs and 88 (83.8%) were oliguric. The most common indication for initiation of dialysis was hyperkalemia in 51 (48.5%) of the cases, followed by severe acidosis in 35 (33.3%) and acute pulmonary edema for 20 (19%). ICU mortality was 68.5% and increased to 95.2% when more than two organs were involved. CONCLUSIONS: Our experience suggests that indications for initiation of RRT in ICU are not greatly different from that in industrialized countries; yet, the big difference is in a high mortality rate among our patients.

Quantification of hemodialysis dose: what Kt/V to choose?

BACKGROUND: Quantification of hemodialysis became more accurate and easier after the advent of ionic dialysance and the use of methods for estimating urea distribution volume (V). The aim of this study was to compare different methods of hemodialysis dose assessment: Kt/VDau (Daugirdas 2nd generation), Kt/VOCM (Kt by OCM (Online Clearance Monitor) and V by Watson), and Kt/VBCM (Kt by OCM and V by bio-impedance); and to assess the dialysis adequacy, defined by a Kt/V>1.4. DESIGN: Prospective, observational study. METHODS: 35 hemodialysis sessions were evaluated in 35 chronic hemodialysis patients. During each session, we measured simultaneously, Kt/VOCM, Kt/VBCM and calculated Kt/VDau by performing blood samples before and after each session. RESULTS: 35 patients, gender (M/F: 19/16), mean age of 50.49 years, were evaluated. We noted a difference between the three methods of evaluating Kt/V index: Kt/VDau, Kt/VOCM and Kt/VBCM (1.82 ± 0.29; 1.45 ± 0.23; 1.8 ± 0.33, p<0.001). Comparison of Kt/VOCM with Kt/VDau and Kt/VBCM leads to a significant systematic underestimate of Kt/V by 22% and 20.5% respectively. Better agreement between Kt/VDau and Kt/VBCM was observed. The adequate hemodialysis was achieved, according to three methods: Kt/VDau, Kt/VOCM and Kt/VBCM respectively in 100%, 57,1% and 88.6% of the cases. CONCLUSIONS: The Kt/V index is different depending on the method used for its evaluation. The three methods can be used for quantification of hemodialysis with a better agreement between Kt/VDau and Kt/VBCM. In this study, Kt/VOCM results underestimate hemodialysis efficiency. This difference has to be considered when applying quantification of hemodialysis to clinical practice.

Serum tumor markers in hemodialysis patients.

AIMS: The main objective of this work was to evaluate the influence of end-stage renal disease (ESRD) on concentrations of five tumor markers (TMs): carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9 (CA19-9), CA15-3, CA125, and prostate specific antigen (PSA) in a group of chronic hemodialysis patients (CHPs); and to study the influence of hemodialysis (HD) sessions on concentrations of the same TMs. METHODS: We compared TMs levels in CHP before HD sessions to a control group of 50 healthy volunteers, the dosages were determined before and immediately after the HD session Comparisons were made before and after correction for dialysis-induced hemoconcentrations. RESULTS: We enrolled 74 CHPs, all TM concentrations were higher in this group compared to control group, but this increase was significant for CEA (4.25 ± 2.89 vs 2.41 ± 1.81ng/ml; p<0.0001), CA125 (27.84 ± 92.27 vs 13.30 ± 9.85 ng/ml; p = 0.048) and CA19-9 (19.65 ± 25.02 vs 10.23 ± 11.00 U/ml; p = 0.011). Post-dialysis levels were significantly higher than those in pre-dialysis. CEA (3.35 [2,46-5.51] vs 4,06 [2.60-6.78] ng/ml; p<0.0001), CA125 (13.24 [9.66-18.63] vs 16.01 [11.33-22.53] ng/ml; p<0.0001), CA19-9 (12.29 [5.59-21.97] vs 16.29 [7.18-24.7] U/ml; p<0.0001), CA15-3 (13.06 [10.05-17.48] vs 14.58 [11.72-19.35] ng/ml; p<0.0001 and PSA (0.83 [0.5-1.24] vs 1.06 [0.62-1.43] ng/ml; p<0.0001). CONCLUSIONS: Our work confirms that HD increases concentrations of the five TMs evaluated and suggests that the use of CA15-3 and PSA remains valid in CHPs since their concentrations were not altered by ESRD, unlike CEA, CA125, and CA19-9.

Late care in marathon runs leading to exertional heat stroke with multiple organ failure.

BACKGROUND: Exertional heat stroke (EHS) is still a main cause of death in sport. Many of EHS complications could have been prevented if EHS had been recognized and treated early and properly. CASE PRESENTATION: We report an unusual case of multiple organ failure caused by EHS due to intensive sportive activities in a hot environment with lack of primary care. A 35-year-old healthy sportive man was admitted in our hospital because of muscle aches and weakness as well as dark urine three days after a six hour marathon run (Agadir Semi-Marathon) in a very sunny day. Patient developed rhabdomyolysis, acute renal failure (ARF) requiring hemodialysis because of hyperkaliémia, azotémia and severe metabolic acidosis, disseminated intravascular coagulation and acute liver failure. Unfortunately, after eight days of intensive care, the patient died from septic shock and multiple organ failure. CONCLUSION: This case reminds us that, despite the advancements of knowledge in the area of EHS prevention, recognition, and treatment, knowledge has not been translated into practice.

Parameters to assess nutritional status in a Moroccan hemodialysis cohort.

INTRODUCTION: Malnutrition is common in maintenance hemodialysis (HD) and is associated with increased mortality and morbidity in affected patients. The aim of this study was to determine the prevalence of malnutrition and correlate the methods of nutritional assessment. METHODS: We evaluated the nutritional status of 40 prevalent HD patients by subjective global assessment (SGA) score, anthropometrics [body mass index (BMI), arm circumference (AC), triceps skin-fold thicknesses (TSF), arm muscle circumference (AMC)], biochemical tests [normalized protein equivalent to total nitrogen appearance (nPNA), and pre-dialysis serum albumin and serum prealbumin levels] and bio-electrical impedance (BEI) analysis to estimate body composition [lean tissue index (LTI) and fat tissue index (FTI)]. RESULTS: The study assessed 40 patients (20 males and 20 females) with a mean age of 50.7±16.5 years. The prevalence of malnutrition according to the different methods ranged from 5 % to 65%. There were highly significant gender-specific differences in AMC (p<0.001) and TSF (p<0.001). The BEI revealed a highly significant difference in LTI (p<0.001) but no difference in FTI (p=0.14) according to gender. There was a positive correlation between LTI and both serum albumin (r=0.37; p=0.018) and serum prealbumin (r=0.53; p<0.001). Also, there was a significant positive correlation between FTI and BMI (r=0.59; p<0.001), AC (r=0.44; p=0.004) and TSF (r=0.61; p<0.001). CONCLUSION: Our data suggest that BEI analysis provides a useful means of assessing nutritional status and was correlated with anthropometrics and biochemical findings.