Effect of bromhexine in hospitalized patients with COVID-19.

BACKGROUND: Bromhexine is a potent inhibitor of transmembrane serine protease 2 and appears to have an antiviral effect in controlling influenza and parainfluenza infection; however, its efficacy in COVID-19 is controversial. METHODS: A group of hospitalized patients with confirmed COVID-19 pneumonia were randomized using 1:1 allocation to either standard treatment lopinavir/ritonavir and interferon beta-1a or bromhexine 8 mg four times a day in addition to standard therapy. The primary outcome was clinical improvement within 28 days, and the secondary outcome measures were time to hospital discharge, all-cause mortality, duration of mechanical ventilation, the temporal trend in 2019-nCoV reverse transcription-polymerase chain reaction positivity and the frequency of adverse drug events within 28 days from the start of medication. RESULTS: A total of 111 patients were enrolled in this randomized clinical trial and data from 100 patients (48 patients in the treatment arm and 52 patients in the control arm) were analyzed. There was no significant difference in the primary outcome of this study, which was clinical improvement. There was no significant difference in the average time to hospital discharge between the two arms. There were also no differences observed in the mean intensive care unit stay, frequency of intermittent mandatory ventilation, duration of supplemental oxygenation or risk of death by day 28 noted between the two arms. CONCLUSION: Bromhexine is not an effective treatment for hospitalized patients with COVID-19. The potential prevention benefits of bromhexine in asymptomatic postexposure or with mild infection managed in the community remain to be determined.

Hypophosphatemia after hemodialysis and its association with some clinical complications in patients with chronic kidney disease.

Background: Beyond the adverse effects of hyperphosphatemia in patients with chronic kidney disease (CKD(, hypophosphatemia has also been proposed as a common challenge after dialysis. Therefore, the present study aimed to evaluate the serum phosphate level immediately after hemodialysis (HD) and its association with some clinical complications in CKD patients. Methods: The present cross-sectional study was conducted on 54 eligible CKD patients undergoing regular hemodialysis. Blood samples were taken, prior to the start and immediately after the end of hemodialysis to determine the serum levels of urea, creatinine, sodium, potassium, phosphorus, PTH, blood sugar and albumin. Moreover, the clinical complications of patients including muscle cramps, nausea, vomiting, headache, confusion, weakness and inability to speak are assessed by a questionnaire, before and after HD. Results: As we expected, the mean of serum creatinine, urea and phosphate levels significantly decreased after dialysis. Post-dialysis hypophosphatemia was graded as mild (3.5 > P ≥ 2.5 mg/dl), moderate (2.5 > P ≥ 1 mg/dl), and severe (<1 mg/dl) based on serum phosphate levels. The frequency of mild and moderate hypophosphatemia was 39.2% and 45.1 %, respectively. None of the participants had severe hypophosphatemia and 13.7% had normal phosphate levels. There was a significant correlation between post-dialysis hypophosphatemia and incidence of nausea and confusion after adjusting for confounding factors. Conclusion: To our knowledge, this is the first time that the possible association of some of the post-dialysis clinical complications with hypophosphatemia was investigated. Future large-scale studies are required to confirm the association of post-dialysis hypophosphatemia with clinical complications.

Using Two Predictor Scoring Systems Together to Increase the Chance of Identifying the Augmented Renal Clearance Phenomenon: A Cross-sectional Study.

INTRODUCTION: Augmented Renal Clearance (ARC) reflects a measured creatinine clearance (CrCl) of more than 130 ml/min. Also, there are two scoring systems for the prediction of the ARC phenomenon i.e., the ARC score (ARCS) and the Augmented Renal Clearance in Trauma Intensive Care score (ARCTICs). The objectives of the current study were the evaluation the effect of using both scoring systems, on the chance of identifying this phenomenon and evaluating the accuracy of the three commonly used formulas for estimating glomerular filtration rate (eGFR) in ICU patients. METHODS: In this prospective cross-sectional study, the CrCls of all patients admitted to the ICU were evaluated by using ARCS and ARCTICS, and for high-risk subjects based on scoring systems, a 12-hour urine sample was collected to measure CrCl. Besides, daily serum creatinine was recorded to estimate the daily eGFR. RESULTS: During the study period, 810 subjects were evaluated and 145 were categorized as high-risk using scoring systems. The ARC phenomenon was confirmed in 79 patients on the recruitment day and 81.01 and 18.98% of them were recruited by ARCS and ARCTICS, respectively. The ROC curves showed AUCs > 0.5 for CockcroftGault (C-G) and CKD-EPI with the cut-off of 100.48 and 107.05 mL/min/ 1.73m2, respectively; to detect the ARC phenomenon. CONCLUSION: We recommend using ARCS and ARCTICS simultaneously to assess critically ill patients regarding the possibility of the ARC phenomenon which should be confirmed by using urinary CrCl, as none of the formulas could accurately detect the ARC phenomenon, neither the 12-hour CrCl.  DOI: 10.52547/ijkd.6695.

COVID-19 and renal infarct: To be or not to be on anticoagulation.

We present a unique case of a male veteran with a history of Castleman disease, presenting with multiple arterial and venous vascular thromboses in the setting of recent Coronavirus (COVID-19)-disease diagnosis. We explore this patient's morbidity related to thrombotic complications of his COVID-19 diagnosis that were potentially avoidable with a comprehensive outpatient evaluation of his risk for thrombosis, as well as the initiation of anticoagulation and/or antiplatelet therapy given his high risk. Our case highlights the need for a standardized clinical workup of patients in the outpatient setting for risk assessment of vascular thrombosis associated with COVID-19 infection to direct medical management, in order to minimize adverse outcomes, complications requiring inpatient admission, and the need for additional yet limited medical resources and interventions. We propose a minimum of low-dose aspirin 81 mg daily as a reasonable approach for outpatient clinicians to consider, based on their best clinical judgement, when managing mild COVID-19, while other options, such as novel oral anticoagulants, are undergoing further investigation.

Effect of bromhexine on clinical outcomes and mortality in COVID-19 patients: A randomized clinical trial.

Introduction: Bromhexine is a potential therapeutic option in COVID-19, but no data from a randomized clinical trial has been available. The present study aimed to evaluate the efficacy of bromhexine in intensive care unit (ICU) admission, mechanical ventilation, and mortality in patients with COVID-19. Methods: An open-label randomized clinical trial study was performed in Tabriz, North-West of Iran. They were randomized to either the treatment with the bromhexine group or the control group, in a 1:1 ratio with 39 patients in each arm. Standard therapy was used in both groups and those patients in the treatment group received oral bromhexine 8 mg three times a day additionally. The primary outcome was a decrease in the rate of ICU admissions, intubation/mechanical ventilation, and mortality. Results: A total of 78 patients with similar demographic and disease characteristics were enrolled. There was a significant reduction in ICU admissions (2 out of 39 vs. 11 out of 39, P = 0.006), intubation (1 out of 39 vs. 9 out of 39, P = 0.007) and death (0 vs. 5, P = 0.027) in the bromhexine treated group compared to the standard group. No patients were withdrawn from the study because of adverse effects. Conclusion: The early administration of oral bromhexine reduces the ICU transfer, intubation, and the mortality rate in patients with COVID-19. This affordable medication can easily be administered everywhere with a huge positive impact(s) on public health and the world economy. Altogether, the verification of our results on a larger scale and different medical centers is strongly recommended. Trial Registration: IRCT202003117046797N4; https://irct.ir/trial/46969.

Liver and Cardiac Iron Deposition in Patients on Maintenance Hemodialysis by Magnetic Resonance Imaging T2.

INTRODUCTION: Magnetic resonance imaging (MRI) sequence acquisition techniques for iron assessment have revolutionized the study of iron overload in different organs. We hypothesized that MRI can accurately and reliably assess possible iron deposition in the myocardium and liver by measurement of T2* value. MATERIALS AND METHODS: Seventeen patients with end-stage renal disease on hemodialysis were enrolled. An electrocardiography-gated single breath hold fast multiecho T2* sequence was acquired in the short axis at basal and mid-ventricular levels. The same technique was utilized to estimate liver parenchyma iron content. RESULTS: Iron deposition in the liver was present in 50% of the hemodialysis patients. No iron deposition was found in the myocardium. A strong univariable inverse linear association was detected between serum albumin and T2* in the liver (r = -0.84, P < .001). Patients who had been on dialysis for 10 years and longer had a 91% reduction in their odds of developing iron overload in the liver compared to the referent group (exact odds ratio, 0.09; P = .048). CONCLUSIONS: Even though using intravenous iron infusion is a common practice in chronic dialysis patients, it seems the myocardium as opposed to the liver is resistant to or protected against iron deposition. There were no meaningful differences in the relationship between iron overload in the liver and the dialysis time vintage. A more aggressive trend of iron therapy and different formulations of iron infusion could be an explanation of iron deposition in the liver.

Lessons from the profile of kidney diseases among Afghan refugees.

BACKGROUND: Due to a paucity of research on the profile of kidney diseases among refugee populations, specifically Afghan refugees in Iran, this study aimed to illustrate the pattern of kidney disease among Afghan refugees in Iran and create a database for evaluating the performance of future health services. MATERIAL AND METHODS: This was a retrospective cross sectional study, in which we collected the demographics and profile of kidney diseases among Afghan refugees between 2005 and 2010 from referrals to the United Nations High Commissioner for Refugees (UNHCR) offices in Iran. RESULTS: The total number of referrals in this group of diseases was 3193 out of 23 152 with 41.5% female and 58.5% male. Regarding age distribution, 10.5% were 0-14 years of age, 78% were 15-59, and 11.5% were ≥60. The most common health referral for females and males (0-14) was end-stage renal disease (ESRD), accounting for 34.6%. This was also the main reason of referrals for females and males aged 15-59, accounting for 73.5% and 66.6%, respectively, and in both sexes in the ≥60 age range it was 63.1%. CONCLUSIONS: The pattern of our renal clinic referrals may gradually change to ESRD, which is associated with a huge economic burden. The need to provide health insurance to everyone or reform the health care system to provide coverage for more of the population can be justified and would improve cost effectiveness.

Obesity and kidney protection.

CONTEXT: Obesity, both directly and indirectly, increases the risk for a variety of disease conditions including diabetes, hypertension, liver disease, and certain cancers, which in turn, decreases the overall lifespan in both men and women. Though the cardiovascular risks of obesity are widely acknowledged, less often identified is the relationship between obesity and renal function. EVIDENCE ACQUISITIONS: Directory of Open Access Journals (DOAJ), Google Scholar, PubMed, EBSCO and Web of Science has been searched. RESULTS: The concept of the "Metabolic Syndrome" helps us to understand this close link between obesity, diabetes, hypertension, and renal dysfunction. An elevated body mass index has shown to be one of the major determinants of glomerular hyperfiltration that lead to the development of chronic kidney disease. Interestingly, weight loss can lead to attenuation of hyperfiltration in severely obese patients suggesting a possible therapeutic option to combat obesity-related hyperfiltration. CONCLUSIONS: Various treatment strategies had been suggested to decrease impact of obesity on kidneys. These are blood pressure controling, inhibition of the renin-angiotensinaldosterone axis, improving glycemic control, improving dyslipidemia, improving protein uriaand lifestyle modifications. Regardless of the numerous pharmacotherapies, the focus should be on the root cause: obesity.

A comparative effectiveness research study of the change in blood pressure during hemodialysis treatment and survival.

It is not clear to what extent changes in blood pressure (BP) during hemodialysis affect or predict survival. Studying comparative outcomes of BP changes during hemodialysis can have major clinical implications including the impact on management strategies in hemodialysis patients. Here we undertook a retrospective cohort study of 113,255 hemodialysis patients over a 5-year period to evaluate an association between change in BP during hemodialysis and mortality. The change in BP was defined as post-hemodialysis minus pre-hemodialysis BP, and mean of BP change values during the hemodialysis session was used as a mortality predictor. The patients' average age was 61 years old and consisted of 45% women, 32% African-Americans and 58% diabetics. Over a median follow-up of 2.2 years, a total of 53,461 (47.2%) all-cause and 21,548 (25.7%) cardiovascular deaths occurred. In a fully adjusted Cox regression model with restricted cubic splines, there was a U-shaped association between change in systolic BP and all-cause mortality. Post-dialytic drops in systolic BP between -30 and 0 mm Hg were associated with greater survival, but large decreases of systolic BP (more than -30 mm Hg) and any increase in systolic BP (over 0 mm Hg) were related to increased mortality. Peak survival was found at a change in systolic BP of -14 mm Hg. The U-shaped association was also found for cardiovascular mortality. Thus, modest declines in BP after hemodialysis are associated with the greatest survival, whereas any rise or large decline in BP is associated with worsened survival.

Iron infusion and deposition in the kidney.

BACKGROUND: Parenteral iron therapy is the mainstay of treating iron deficiency anemia in chronic kidney disease (CKD) patients. METHODS: Retrospective case study of iron staining of renal tissues in 2 CKD patients who had received intravenous iron prior to the renal biopsy. RESULTS: Following the infusion of ferumoxytol, iron staining of renal biopsy demonstrated blue curvilinear deposition of iron in the tissue macrophages (histocytes) and interstitium of the kidney. Renal iron deposition was not observed in a patient administered intravenous iron dextran. CONCLUSION: We postulate that the higher molecular weight of ferumoxytol and different carbohydrate components may lead to deposition and trapping of the ironcarbohydrate complexes in the reticuloendothelial system of the kidney. Potential renal toxicity from iron induced oxidant stress, especially in patients with underlying chronic kidney disease, merits further investigation.

Dietary sodium and clinical outcome in hemodialysis: where do we stand and what is next?

The association of dietary sodium and outcome is widely studied in the general population, but less is known in hemodialysis patients. The evidence supporting daily dietary sodium intake of 2 g on hemodialysis is not strong. Mc Causland et al. found that higher dietary sodium intake was marginally associated with a higher ultrafiltration requirement and mortality, but not with blood pressure. Well-designed clinical trials are needed to examine the association of dietary sodium modification and outcomes in hemodialysis patients.

The inception and formation of the theory of hyperfiltration through the ages.

With the rising incidence of metabolic syndrome and progressive kidney disease, efforts to halt this progression have become the mainstay of therapies in the era of modern nephrology. The necessity of one versus two kidneys has occupied the minds of leading scientists and philosophers throughout the ages and has laid the foundation for our understanding of progressive kidney disease. This review focuses on the major discoveries of the leading thinkers who with their paradigm shifting ideas and skepticism pushed the boundaries of our knowledge and shaped the theory of hyperfiltration.

Using a filtration technique to isolate platelet free plasma for assaying pyrophosphate.

BACKGROUND: Vascular calcification (VC) is a strong prognostic marker of mortality from cardiovascular disease. Extracellular inorganic pyrophosphate (PPi) is a critical inhibitor of vascular calcification and it has been reported that hemodialysis patients have reduced plasma PPi levels, suggesting that altered PPi metabolism could contribute to VC in hemodialysis patients. Platelets are rich in PPi and release of PPi from platelets during storage or processing of plasma can lead to falsely elevated plasma PPi levels. To prepare plasma samples that are suitable for measuring PPi levels, ultracentrifugation has been used to remove platelets. Consequently, plasma PPi measurements have been limited to research laboratories since the majority of clinical laboratories do not have access to an ultracentrifuge. The purpose of the present study was to test the validity of an improved method of preparing platelet free plasma that uses filtration with a 300,000 Dalton molecular weight cut-off filter to exclude platelets, while minimizing their release of PPi. METHODS: In 20 maintenance hemodialysis patients, PPi levels were measured in plasma samples prepared by the conventional technique of low-speed centrifugation to remove red and white blood cells versus a novel filtration technique. RESULTS: Plasma prepared by filtration had significantly lower platelet counts (0 vs. 3 - 7 10(3)/microL) and PPi levels (1.39 +/- 0.30 microM vs. 2.74 +/- 1.19 microM; mean +/- SD, p < 0.01). CONCLUSIONS: The filtration method appears effective in excluding platelets without causing trauma to platelets and can be used by clinical laboratories to prepare platelet-depleted plasma for PPi measurement.

The correlation of hip fracture and hyponatremia in the elderly.

BACKGROUND: Increasing age is considered one of the risk factors for hyponatremia. The concept of asymptomatic hyponatremia is not correct anymore as these patients have a greater risk for falls, bone fractures and attention impairment. The combination of old age and a fall is a common recipe for admission to a nursing home. METHODS: We identified 249 patients 65 years of age or older who were admitted to hospital with the diagnosis of hip fracture secondary to fall, during a 3-year period. We compared their serum Na level on admission with that of controls: 44 ambulatory patients admitted for elective hip or knee replacement surgery during the same time frame. Odds ratios (ORs) were calculated using logistic regression. RESULTS: The prevalence of hyponatremia in cases was 16.9%, versus 4.6% in controls (p=0.03). Age and hyponatremia were strongly correlated with hip fracture secondary to fall. The univariate OR for hip fracture associated with each 10-year increase in age was 5.57 (p<0.0001). After controlling for age, cases were almost 5 times as likely as controls to be hyponatremic (OR=4.80, p=0.04). CONCLUSIONS: Even mild hyponatremia in the elderly should be considered a risk factor for falls. Correction of hyponatremia in the elderly may reduce morbidity and mortality, and at the same time, it has a huge impact on socioeconomic status.

A new approach for evaluating bone turnover in chronic kidney disease.

BACKGROUND: The validity of serum parathyroid hormone (PTH) as a surrogate marker of bone turnover in chronic kidney disease (CKD) is limited by several factors such as relative resistance of bone to PTH, hyperphosphatemia, diabetes, gender, age, race and vitamin D analog action on the PTH-bone axis. Urinary collagen N-terminal telopeptide X (NTx), a bone collagen degradation product, expressed as bone collagen equivalents (BCE) per mM of creatinine (NTx/Cr ratio), is routinely used to estimate bone turnover in osteoporosis. The purpose of this study is to evaluate NTx as a marker of bone turnover in CKD. METHODS: We studied the relationship between bone-specific alkaline phosphatase (BSAP), PTH and urine NTx/Cr in 37 CKD out-patients. RESULTS: In a multivariate model, PTH had a positive correlation with BSAP (r=0.44, P<0.19) and U-NTx/Cr (r=0.55, P<0.30), after adjusting for age, gender, estimated glomerular filtration rate (GFR), serum phosphorus, corrected calcium, and race. However, the strongest correlation was found between the two direct markers of bone resorption and formation (U-NTx vs. BSAP; r=0.80; P<0.0001), suggesting a tight coupling of bone resorption and formation in CKD. The effect of gender on U-NTx/Cr was studied in a multivariate model after adjusting for age, race, GFR, serum calcium, phosphorus and PTH. Females had a higher U-NTx/Cr than males. CONCLUSION: Our findings indicate that urinary NTx, a promising marker of bone resorption in CKD patients, exhibits a strong positive correlation with other markers used to assess renal osteodystrophy i.e. PTH and BSAP. Unlike PTH and BSAP, urine NTx also measures bone loss secondary to osteoporosis.

Oral alkalinizing solution as a potential prophylaxis against myoglobinuric acute renal failure: preliminary data from healthy volunteers.

BACKGROUND: Acute renal failure (ARF) secondary to crush injury is one of the leading causes of hospitalization and death in survivors of massive disasters. The standard therapy for crush injury, intravenous (i.v.) hydration and alkalinization of urine, is often not feasible after a mass disaster; therefore, oral rehydration and urinary alkalinization may be a useful substitute. METHODS: We developed and evaluated an oral alkalinizing solution (OAS) to induce alkaline diuresis. We enrolled 12 volunteer Iranian Army recruits (mean age 19.4+/-0.8 years) who drank an average of 650 ml of OAS for 12 h. We checked the volume and pH of their urine every hour, and measured venous blood gas and electrolytes at 6, 12 and 15 h. RESULTS: All subjects tolerated the OAS without adverse events, and had active diuresis (>200 ml/h) after an average of 3.0+/-0.7 h. Their urine became alkaline (pH>7.0) within an average of 3.25+/-0.8 h. There were no significant electrolyte abnormalities. CONCLUSIONS: OAS seems to be a safe and promising means of inducing alkaline diuresis. It may be a feasible alternative to i.v. hydration to prevent ARF secondary to crush injuries in the context of mass disasters where i.v. hydration is not possible. A dose of 10 ml/kg/h may be the correct amount to induce alkaline diuresis within the first 12 h after crush injuries. The use of OAS for this purpose should be evaluated further.