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1.
[Peculiarities of the treatment of venous thromboembolism with direct oral anticoagulants in challenging patients: senile age, renal failure, fragility].
Schastlivtsev, IV, Lobastov, KV
Khirurgiia. 2020;(7):68-75
Abstract
The paper is a narrative review of the literature on the use of direct oral anticoagulants (DOACs) for the VTE treatment in challenging patients: senile age (≥75 years), impaired renal function (estimated glomerular filtration rate ≤50 ml/min), fragility (one of the previous characteristics and/or bodyweight ≤50 kg). The paper discusses the studies of EINSTEIN DVT and PE (rivaroxaban), AMPLIFY (apixaban), HOKUSAI-VTE (edoxaban), RE-COVER I and II (dabigatran) in the focus of the secondary analysis in the pre-specified patient's subgroups, as well as their pooled analyzes and meta-analyzes. Based on the results of this review, it was concluded that in a subgroup of senile age patients, dabigatran increases the risk of major bleeding by 4.8 times and has no advantages over vitamin K antagonists (VKA); rivaroxaban and apixaban retain superiority over VKA on the safety outcomes and reduce the risk of major bleeding by 73% and 77%. In the subgroup of patients with impaired renal function, the use of apixaban and dabigatran is associated with an increase in the risk of major bleeding by 6.5 and 7.3 times, and these DOACs do not have advantages over VKA; rivaroxaban retains its superiority over VKA and reduces the risk of major bleeding by 78%. For fragile patients, a secondary analysis is available only for rivaroxaban, which remains superior to VKA on safety endpoints and reduces the risk of major bleeding by 73%. In the absence of direct comparisons between the available DOACs, the presented data can be used as a rational approach for the choice of appropriate treatment for VTE in challenging patients.
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2.
Dietary Protein, Kidney Function and Mortality: Review of the Evidence from Epidemiological Studies.
Bilancio, G, Cavallo, P, Ciacci, C, Cirillo, M
Nutrients. 2019;(1)
Abstract
The World Health Organization recommends a minimum requirement of 0.8 g/day protein/kg ideal weight. Low protein diets are used against kidney failure progression. Efficacy and safety of these diets are uncertain. This paper reviews epidemiological studies about associations of protein intake with kidney function decline and mortality. Three studies investigated these associations; two reported data on mortality. Protein intake averaged >60 g/day and 1.2 g/day/kg ideal weight. An association of baseline protein intake with long-term kidney function decline was absent in the general population and/or persons with normal kidney function but was significantly positive in persons with below-normal kidney function. Independent of kidney function and other confounders, a J-curve relationship was found between baseline protein intake and mortality due to ≈35% mortality excess for non-cardiovascular disease in the lowest quintile of protein intake, a quintile where protein intake averaged <0.8 g/day/kg ideal weight. Altogether, epidemiological evidence suggests that, in patients with reduced kidney function, protein intakes of ≈0.8 g/d/kg ideal weight could limit kidney function decline without adding non-renal risks. Long-term lower protein intake could increase mortality. In most patients, an intake of ≈0.8 g/day/kg would represent a substantial reduction of habitual intake considering that average intake is largely higher.
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3.
[Glomerulopathy associated with lecithin-cholesterol-acyltransferase deficiency: A case report and literature review].
Delteil, C, Macagno, N, Appay, R, Uzan, M, Jourde-Chiche, N, Daniel, L
Annales de pathologie. 2019;(2):172-176
Abstract
Glomerulopathy associated with lecithin-cholesterol-acyltransferase deficiency (LCAT) is a rare automosal recessive disease. Acquired LCAT deficiency due to inhibitory autoantibodies against LCAT are also described. This disease is induced by systemic deposits related to a lipid metabolism disorder and lead to multi-organ involvement including renal involvement. Lipid profile usually shows variable cholesterol levels but very low HDL levels. Here we describe the case of a 33-year-old man presenting a nephrotic syndrome associated with moderate renal insufficiency for which the pathological analysis allowed to guide towards the diagnosis of LCAT deficiency. Laboratory and genetic data confirmed this diagnosis. Familial history and lipid profile abnormalities are important in the identification of this disease.
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4.
Review of Biguanide (Metformin) Toxicity.
Wang, GS, Hoyte, C
Journal of intensive care medicine. 2019;(11-12):863-876
Abstract
In the 1920s, guanidine, the active component of Galega officinalis, was shown to lower glucose levels and used to synthesize several antidiabetic compounds. Metformin (1,1 dimethylbiguanide) is the most well-known and currently the only marketed biguanide in the United States, United Kingdom, Canada, and Australia for the treatment of non-insulin-dependent diabetes mellitus. Although phenformin was removed from the US market in the 1970s, it is still available around the world and can be found in unregulated herbal supplements. Adverse events associated with therapeutic use of biguanides include gastrointestinal upset, vitamin B12 deficiency, and hemolytic anemia. Although the incidence is low, metformin toxicity can lead to hyperlactatemia and metabolic acidosis. Since metformin is predominantly eliminated from the body by the kidneys, toxicity can occur when metformin accumulates due to poor clearance from renal insufficiency or in the overdose setting. The dominant source of metabolic acidosis associated with hyperlactatemia in metformin toxicity is the rapid cytosolic adenosine triphosphate (ATP) turnover when complex I is inhibited and oxidative phosphorylation cannot adequately recycle the vast quantity of H+ from ATP hydrolysis. Although metabolic acidosis and hyperlactatemia are markers of metformin toxicity, the degree of hyperlactatemia and severity of acidemia have not been shown to be of prognostic value. Regardless of the etiology of toxicity, treatment should include supportive care and consideration for adjunct therapies such as gastrointestinal decontamination, glucose and insulin, alkalinization, extracorporeal techniques to reduce metformin body burden, and metabolic rescue.
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5.
[Novel hormones related to the calcium and phosphate homeostasis in kidney disease].
Mace, ML, Ølgaard, K, Lewin, E
Ugeskrift for laeger. 2018;(21)
Abstract
Calcium and phosphate levels are regulated by a complex interplay between parathyroid hormone (PTH), calcitriol, fibroblast growth factor 23 (FGF23) and its co-receptor αKlotho. Kidney failure causes severe disturbances in the mineral and bone homeostasis resulting in phosphate retention, hypocalcaemia and high plasma levels of FGF23 and PTH, and the patients develop fragile bones and vascular calcifications. Today's treatments aim to lower the levels of phosphate and PTH. Future studies need to clarify, if lowering the FGF23 level or supplementation with αKlotho will improve survival for patients with chronic kidney disease.
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6.
Cell Sheet Engineering and Kidney Diseases.
Oka, M, Miyabe, Y, Sugiura, N, Nitta, K
Contributions to nephrology. 2018;:74-80
Abstract
Treatment using the cell sheet technology has been applied to various organs, including the cornea, heart, esophagus, periodontium, cartilage, middle ear, and lungs. It has been shown that the therapeutic efficacy of cell sheet transplantation involves 2 aspects, supplementation of cells and provision of cytokines to the affected organ. In addition, cell sheet transplantation also promotes repair of damage through the paracrine effects of cytokines derived from the transplanted cells. It is known that in cases of cell transplantation by injection, the transplanted cells are less likely to differentiate into renal tissue to supply cells, but repair is promoted by the actions of the transplanted cell-derived renotropic factors. Renal function requires functional conjugation of various tissues, including blood vessels, glomeruli, renal tubules, and collecting ducts. It is difficult to supply the necessary cells directly to the affected site of the renal tissue composed of complex structures. On the contrary, the 2-dimensional cell sheet can produce proteins such as erythropoietin, and is thus suitable for transplantation into the living body. It would be desirable to develop cell sheet therapy for the suppression of kidney damage in the future, taking advantage of the beneficial characteristics of cell sheets.
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7.
Potential Adverse Effects of Creatine Supplement on the Kidney in Athletes and Bodybuilders.
Davani-Davari, D, Karimzadeh, I, Ezzatzadegan-Jahromi, S, Sagheb, MM
Iranian journal of kidney diseases. 2018;(5):253-260
Abstract
INTRODUCTION Nowadays, creatine is one of the most common oral supplements used by professional athletes for boosting their strength and muscle mass. In this review, we collect available experimental and clinical data about renal safety of both short-term and long-term use of creatine. MATERIALS AND METHODS Scientific literature was critically searched by keywords "creatine," "renal insufficiency," and "renal dysfunction" and their synonyms in medical databases (Scopus, MEDLINE, EMBase, and ISI Web of Knowledge). Overall, 19 relevant clinical and experimental articles were selected for this review. RESULTS Short- and long-term creatine supplementations (range, 5 days to 5 years) with different doses (range, 5 g/d to 30 g/d) had no known significant effects on different studied indexes of kidney function such as glomerular filtration rate at least in healthy athletes and bodybuilders with no underlying kidney diseases. In addition, although short-term (range, 5 days to 2 weeks) high-dose oral creatine supplementation (range, 20 g/d to 0.3 g/kg/d) stimulated the production of methylamine and formaldehyde (as potential cytotoxic metabolites of creatine) in the urine of healthy humans, there was currently no definite clinical evidence about their adverse effects on the kidney function. CONCLUSIONS Although creatine supplementation appears to have no detrimental effects on kidney function of individuals without underlying kidney diseases, it seems more advisable to suggest that creatine supplementation not to be used by sportsmen or women with pre-existing kidney disease or those with a potential risk for kidney dysfunction.
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8.
Lithium Poisoning.
Baird-Gunning, J, Lea-Henry, T, Hoegberg, LCG, Gosselin, S, Roberts, DM
Journal of intensive care medicine. 2017;(4):249-263
Abstract
Lithium is a commonly prescribed treatment for bipolar affective disorder. However, treatment is complicated by lithium's narrow therapeutic index and the influence of kidney function, both of which increase the risk of toxicity. Therefore, careful attention to dosing, monitoring, and titration is required. The cause of lithium poisoning influences treatment and 3 patterns are described: acute, acute-on-chronic, and chronic. Chronic poisoning is the most common etiology, is usually unintentional, and results from lithium intake exceeding elimination. This is most commonly due to impaired kidney function caused by volume depletion from lithium-induced nephrogenic diabetes insipidus or intercurrent illnesses and is also drug-induced. Lithium poisoning can affect multiple organs; however, the primary site of toxicity is the central nervous system and clinical manifestations vary from asymptomatic supratherapeutic drug concentrations to clinical toxicity such as confusion, ataxia, or seizures. Lithium poisoning has a low mortality rate; however, chronic lithium poisoning can require a prolonged hospital length of stay from impaired mobility and cognition and associated nosocomial complications. Persistent neurological deficits, in particular cerebellar, are described and the incidence and risk factors for its development are poorly understood, but it appears to be uncommon in uncomplicated acute poisoning. Lithium is readily dialyzable, and rationale support extracorporeal treatments to reduce the risk or the duration of toxicity in high-risk exposures. There is disagreement in the literature regarding factors that define patients most likely to benefit from treatments that enhance lithium elimination, including specific plasma lithium concentration thresholds. In the case of extracorporeal treatments, there are observational data in its favor, without evidence from randomized controlled trials (none have been performed), which may lead to conservative practices and potentially unnecessary interventions in some circumstances. More data are required to define the risk-benefit of extracorporeal treatments and their use (modality, duration) in the management of lithium poisoning.
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9.
[Hypervitaminosis D due to a dietary supplement].
Zigenhorn, M, Westerman, EM, Rietveld, AP
Nederlands tijdschrift voor geneeskunde. 2016;:A9360
Abstract
In the Netherlands, over-the-counter dietary supplements are controlled by the NVWA (Netherlands Food and Consumer Product Safety Authority). Nevertheless, health problems may ensue from the use of these freely available supplements. We describe the case of a 39-year-old woman with a four-week history of headaches, nausea, reduced appetite and weight loss. Laboratory results showed severe hypercalcemia and impaired kidney function. An isolated increased vitamin D level was shown to be the cause. Although initial drug-taking history was negative, it appeared our patient had consumed a concentrated vitamin D supplement, supplied by a naturopath. The vitamin D concentration of the contents of this specific flacon proved to be 78 times higher than stated on the label. Consumers must be aware of the potential health risks posed by over-the-counter dietary supplements. We appeal to GPs, medical specialists and pharmacists to report these kinds of intoxications, allowing relevant authorities to subject the associated companies to adequate control measures.
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10.
Major Bleeding and Hemorrhagic Stroke With Direct Oral Anticoagulants in Patients With Renal Failure: Systematic Review and Meta-Analysis of Randomized Trials.
Raccah, BH, Perlman, A, Danenberg, HD, Pollak, A, Muszkat, M, Matok, I
Chest. 2016;(6):1516-24
Abstract
BACKGROUND Direct oral anticoagulants (DOACs) are used as an alternative for traditional antithrombotic therapy. However, the safety profile of DOACs in patients with renal failure (RF) has not been determined. METHODS A systematic review was performed assessing the reported safety of DOACs compared with vitamin K antagonists (VKAs) in patients with RF and estimated creatinine clearance (eCrCL) < 50 mL/min and eCrCL 50 to 80 mL/min. MEDLINE, EMBASE, Cochrane, and the Clinical Trials Registry (ClinicalTrials.gov) were searched for randomized clinical trials up to November 2015. The data were pooled by using both traditional frequentist and Bayesian random effects models. RESULTS Nine trials met the inclusion criteria. Among 94,897 participants, 54,667 (58%) had RF. Compared with VKAs, DOACs were associated with a significantly decreased risk for major bleeding in patients with eCrCL 50 to 80 mL/min (risk ratio, 0.87 [95% CI, 0.81-0.93]) and a nonsignificant decrease in the risk for major bleeding in patients with eCrCL < 50 mL/min (risk ratio, 0.83 [95% CI, 0.68-1.02]); there was evidence of significant heterogeneity. Indirect comparisons, using Bayesian network analysis, indicated that apixaban was associated with a decreased rate of major bleeding compared with other DOACs in patients with eCrCL < 50 mL/min. DOACs were associated with a significant decrease in the risk for hemorrhagic stroke compared with VKAs in patients with eCrCL < 50 mL/min and 50 to 80 mL/min. CONCLUSIONS As a class, DOACs are associated with a reduced risk for hemorrhagic stroke compared with VKAs in patients with RF. However, DOACs may differ from each other in their relative risk for major bleeding in patients with eCrCL < 50 mL/min. TRIAL REGISTRY PROSPERO registry; No.: CRD42014013730; URL: http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42014013730.