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1.
Dose discordance of direct acting oral anticoagulants using different equations for estimating GFR: a literature review.
Nabiee, M, Dashti-Khavidaki, S, Khajeh, B
Expert review of clinical pharmacology. 2020;(8):857-863
Abstract
INTRODUCTION Direct oral anticoagulants (DOACs) are widely prescribed nowadays. Available DOACs are renally eliminated to some extent and need dose adjustment in patients with kidney dysfunction. Cockcroft-Gault (CG) formula has been used to estimate creatinine clearance in DOACs trials. Nowadays, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) are preferred equations for estimating glomerular filtration rate (GFR). We reviewed studies that simulated DOACs dosing in patients with atrial fibrillation by MDRD, CKD-EPI, and CG. AREAS COVERED DOACs dose discordance varies from 28.8% underdosing to 59.2% overdosing when MDRD or CKD-EPI equations are substituted for CG. MDRD and CKD-EPI overestimate the GFR in lower thresholds of kidney function especially in elderly and females and result in overestimation of DOACs dosing or misclassifying the patients to be eligible for receiving DOACs when they are contraindicated. Compared with CG, MDRD and CKD-EPI underestimate the level of kidney function in higher GFR extremes and in these patients suggest DOACs when they are not recommended or suggest lower doses. EXPERT OPINION Until running large clinical studies on efficacy/safety of DOACs dosing using MDRD or CKD-EPI equations, use of CG method for DOACs dosing is recommended in real practice.
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2.
Comparison of the Effects of Glucagon-Like Peptide Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors for Prevention of Major Adverse Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus.
Zelniker, TA, Wiviott, SD, Raz, I, Im, K, Goodrich, EL, Furtado, RHM, Bonaca, MP, Mosenzon, O, Kato, ET, Cahn, A, et al
Circulation. 2019;(17):2022-2031
Abstract
BACKGROUND Glucagon-like peptide 1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) have emerged as 2 new classes of antihyperglycemic agents that also reduce cardiovascular risk. The relative benefits in patients with and without established atherosclerotic cardiovascular disease for different outcomes with these classes of drugs remain undefined. METHODS We performed a systematic review and trial-level meta-analysis of GLP1-RA and SGLT2i cardiovascular outcomes trials using the PubMed and EMBASE databases (Excerpta Medica Database). The primary outcomes were the composite of myocardial infarction, stroke, and cardiovascular death (MACE); hospitalization for heart failure; and progression of kidney disease. RESULTS In total, data from 8 trials and 77 242 patients, 42 920 (55.6%) in GLP1-RA trials, and 34 322 (44.4%) in SGLT2i trials, were included. Both drug classes reduced MACE in a similar magnitude with GLP1-RA reducing the risk by 12% (hazard ratio [HR], 0.88; 95% CI, 0.84-0.94; P<0.001) and SGLT2i by 11% (HR, 0.89; 95% CI, 0.83-0.96; P=0.001). For both drug classes, this treatment effect was restricted to a 14% reduction in those with established atherosclerotic cardiovascular disease (HR, 0.86; 95% CI, 0.80-0.93; P=0.002), whereas no effect was seen in patients without established atherosclerotic cardiovascular disease (HR, 1.01; 95% CI, 0.87-1.19; P=0.81; P interaction, 0.028). SGLT2i reduced hospitalization for heart failure by 31% (HR, 0.69; 95% CI, 0.61-0.79; P<0.001), whereas GLP1-RA did not have a significant effect (HR, 0.93; 95% CI, 0.83-1.04; P=0.20). Both GLP1-RA (HR, 0.82; 95% CI, 0.75-0.89; P<0.001) and SGLT2i (HR, 0.62; 95% CI, 0.58-0.67; P<0.001) reduced the risk of progression of kidney disease including macroalbuminuria, but only SGLT2i reduced the risk of worsening estimated glomerular filtration rate, end-stage kidney disease, or renal death (HR, 0.55; 95% CI, 0.48-0.64; P<0.001). CONCLUSIONS In trials reported to date, GLP1-RA and SGLT2i reduce atherosclerotic MACE to a similar degree in patients with established atherosclerotic cardiovascular disease, whereas SGLT2i have a more marked effect on preventing hospitalization for heart failure and progression of kidney disease. Their distinct clinical benefit profiles should be considered in the decision-making process when treating patients with type 2 diabetes mellitus.
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3.
Low-Iodine-Load and Low-Tube-Voltage CT Angiographic Imaging of the Kidney by Using Bolus Tracking with Saline Flushing.
Kanematsu, M, Goshima, S, Kawai, N, Kondo, H, Miyoshi, T, Watanabe, H, Noda, Y, Tanahashi, Y, Bae, KT
Radiology. 2015;(3):832-40
Abstract
PURPOSE To prospectively determine the feasibility of low-iodine-load and low-tube-voltage computed tomographic (CT) angiographic imaging of the kidney and to evaluate the opacification and image quality compared with moderate-iodine-load and high-iodine-load techniques. MATERIALS AND METHODS Institutional review board approval and written informed consent was obtained. One hundred thirteen consecutive patients randomly underwent three protocols for dual-phase renal CT angiographic imaging: high-iodine-load (600 mg iodine per kilogram of body weight at 120 kVp); moderate-iodine-load (400 mg iodine per kilogram of body weight at 80 kVp); and low-iodine-load (contrast agent injection initially prepared at 400 mg iodine per kilogram of body weight but stopped immediately after bolus-tracking trigger at 80 kVp) scanning. CT numbers of vessels and kidneys were measured. CT numbers and signal-to-noise ratio (SNR) were compared with one-way analysis of variance and posthoc Tukey-Kramer test and depiction of vessels and image noise, with Kruskal-Wallis test and pair-wise Mann-Whitney test with Bonferroni correction. RESULTS Mean iodine weight administered was significantly reduced in order of low- (16.4 g), moderate- (23.5 g), and high-iodine-load (33.7 g) protocols (P < .001). Mean CT numbers of abdominal aorta, renal artery, and renal cortex in first phase were significantly lower with high-iodine-load protocol (308, 274, and 132 HU, respectively) than with moderate- (347, 334, and 156 HU, respectively; P = .001-.006) or low-iodine-load (362, 316, and 161 HU, respectively; P = .001-.003) protocol. Mean CT number of renal vein in second phase was significantly lower with low-iodine-load protocol (223 HU) than with moderate- (299 HU; P < .001) or high-iodine-load (258 HU; P = .020). Mean SNR of renal medulla in second phase was significantly lower (P = .019) with moderate-iodine-load protocol (mean SNR, 7.2) than with high-iodine-load protocol (mean SNR, 10.0). No significant difference in image quality grades was found between high-iodine-load (mean grade, 2.6-2.9), moderate-iodine-load (mean grade, 2.6-3.0), and low-iodine-load (mean grade, 2.6-2.9) protocols (P = .018-.31). CONCLUSION Combined application of low-iodine-load, bolus tracking with saline flushing, and low-tube-voltage scanning is feasible and resulted in substantial reduction of iodine dose for renal CT angiographic imaging without compromising image quality.
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Efficacy of IV iron compared to oral iron for increment of haemoglobin level in anemic chronic kidney disease patients on erythropoietin therapy.
Adhikary, L, Acharya, S
JNMA; journal of the Nepal Medical Association. 2011;(183):133-6
Abstract
INTRODUCTION Anemia is the most common finding in chronic kidney disease patients. Iron supplements are commonly prescribed for these patients with or without erythropoietin therapy by means of oral and intravenous iron. Both oral and intravenous irons have their own advantage and disadvantage, and the efficacy is also different. The objective of the study is to analyze the efficacy of oral and intravenous iron in chronic kidney disease patients on erythropoietin therapy, an erythropoiesis stimulating agents for increment of haemoglobin. METHODS This is a prospective study comparing intravenous iron to oral iron in chronic kidney disease patients who underwent maintenance hemodialysis at different centers and visited Kathmandu Medical College Teaching Hospital from April 2010 to April 2011. Patients having a haemoglobin level of < 11 g/dl, transferrin saturation (TSAT) < 25%, ferritin < 300ng/ml and who were on erythropoietin therapy were allocated alternately into two groups to receive oral iron (iron fumarate) or IV iron (iv sucrose). Haemoglobin was measured after 30 days of therapy. RESULTS A significant increase in haemoglobin levels was observed in both groups. But the mean haemoglobin increment was more in the IV iron group than in the oral iron group. Sixty percent 60% of patients in the IV iron group had an increase in the haemoglobin level of more than 1gm/dl while only 20% of the oral iron group had this increase. CONCLUSIONS Intravenous iron therapy is more effective in raising the hemoglobin level in hemodialysis dependent chronic kidney disease patients.
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5.
Effects of lipid-lowering therapy with rosuvastatin on kidney function and oxidative stress in patients with diabetic nephropathy.
Abe, M, Maruyama, N, Okada, K, Matsumoto, S, Matsumoto, K, Soma, M
Journal of atherosclerosis and thrombosis. 2011;(11):1018-28
Abstract
AIM: We aimed to assess the effects of rosuvastatin treatment on lipid levels, a biomarker of oxidative stress, albuminuria, and kidney function in patients with diabetic nephropathy. METHODS We conducted a prospective, open-label, parallel group, controlled study of 104 patients with diabetic nephropathy, low-density lipoprotein cholesterol (LDL-C) levels of > 120 mg/dL, and well-controlled blood pressure who were undergoing treatment with renin angiotensin system inhibitors. Patients were randomly assigned to two groups: the rosuvastatin group (n = 52; 2.5 mg/day rosuvastatin, increased to 10 mg/day) and the control group (n = 52; no rosuvastatin administered). We determined the efficacy of rosuvastatin by monitoring serum lipid profiles, high sensitivity C-reactive protein (hs-CRP), malondialdehyde-modified LDL (MDA-LDL), and cystatin C levels. In addition, urinary albumin, 8-hydroxydeoxyguanosine (8-OHdG) and liver-type fatty acid-binding protein (L-FABP) levels were measured before and 6 months after rosuvastatin was added to the treatment. RESULTS Rosuvastatin effectively reduced total cholesterol, LDL-C, triglycerides, non-high-density lipoprotein cholesterol (non-HDL-C) levels, and the LDL-C/ HDL-C ratio in the rosuvastatin group. These parameters remained unchanged in patients who were not treated with rosuvastatin. Although there was no significant change in the estimated glomerular filtration rate level, serum cystatin C levels and urinary albumin excretion rates were significantly decreased in the rosuvastatin group. In addition, rosuvastatin significantly reduced hs-CRP and MDA-LDL levels. Moreover, urinary 8-OHdG and L-FABP levels at baseline (13.5±5.1 and 41.7±26.1 ng/mgCr, respectively) decreased significantly at 6 months (11.5±4.0 and 26.9±13.4 ng/mgCr, respectively), and there was a significant correlation (r = 0.48, p < 0.01). Multivariate analysis revealed that albuminuria was significantly correlated with only rosuvastatin use (p = 0.0006, R(2)= 0.53). CONCLUSION Rosuvastatin administration reduced albuminuria, oxidative stress, and serum cystatin C levels, independent of blood pressure and lipid levels.
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6.
Short-term efficacy of sevelamer versus calcium acetate in patients with chronic kidney disease stage 3-4.
Gulati, A, Sridhar, V, Bose, T, Hari, P, Bagga, A
International urology and nephrology. 2010;(4):1055-62
Abstract
BACKGROUND The relative effectiveness and safety of sevelamer, a mineral-free phosphate binder, for treatment of hyperphosphatemia in children with chronic kidney disease is uncertain. AIM: This study was designed to compare the efficacy and acceptability of sevelamer hydrochloride to calcium acetate as a phosphate binder in pediatric patients with chronic kidney disease. METHODS A 12-week open-label trial of sevelamer hydrochloride vs calcium acetate was initiated in 22 patients, aged 2-18, with CKD stages 3 and 4. After a 2-week washout of phosphate binders and vitamin D, patients were randomized to receive sevelamer hydrochloride or calcium acetate. The effect of therapy was adjusted for baseline blood levels of calcium, phosphorus, calcium-phosphate product, alkaline phosphatase, PTH and GFR using ANOVA. The primary end point was the decrease in serum phosphorus levels after 12 weeks of treatment. RESULTS Of the 22 patients enrolled, data of 19 patients were used for analysis. The adjusted mean serum phosphate levels at 12 weeks did not differ significantly between calcium acetate- (5.3 mg/dl) and sevelamer-treated subjects (6.1 mg/dl) (P adjusted means = 0.6). The adjusted blood level of calcium at 12 weeks was significantly lower in the sevelamer-treated patients (8.2 mg/dl) compared to those treated with calcium acetate (9.1 mg/dl) (P adjusted means = 0.01). In the sevelamer group, there was a non-significant decrease in serum bicarbonate, whereas the total and LDL cholesterol significantly decreased at 12 weeks (P = 0.04). Sevelamer hydrochloride was well tolerated and without adverse effects related to the drug. CONCLUSIONS Compared to calcium acetate, use of sevelamer in children with chronic kidney disease is associated with similar reduction in serum phosphate levels, lower risk of hypercalcemia, and marked decrease in serum lipid levels.
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A pharmacokinetics evaluation of a new, low-volume, oral sulfate colon cleansing preparation in patients with renal or hepatic impairment and healthy volunteers.
Pelham, RW, Alcorn, H, Cleveland, Mv
Journal of clinical pharmacology. 2010;(3):350-4
Abstract
The pharmacokinetics (PK) of an oral sulfate solution (OSS) for bowel cleansing preparation was studied. OSS (30 g of sulfate) was split between 2 doses, 12 hours apart. Safety measures included electrocardiography, vital signs, adverse events, hematology, blood chemistry, and urinalysis. Six adult patients with moderate renal disease (MRD), 6 with mild-moderate hepatic disease (M/MHD), and 6 normal healthy volunteers (NHVs) completed the study. Adverse events were mild to moderate in severity and were mainly limited to headache and expected gastrointestinal symptoms. Serum sulfate levels were highly variable at all times, even after adjusting for baseline. Sulfate was higher in MRD in comparison to the other groups. The C(max) and AUC were higher in the patients, but no statistically significant differences emerged. Sulfate levels returned to predose values within 54 hours after dosing. No electrolyte disturbances occurred. Urinary sulfate excretion was approximately 20% of the dose. OSS was well tolerated. The types and severity of adverse events were similar to those seen in large phase III trials. While patients with MRD had elevated sulfate, the levels were less than those in renal failure and did not alter biochemical parameters that are associated with hypersulfatemia.
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8.
A randomized, crossover design study of sevelamer carbonate powder and sevelamer hydrochloride tablets in chronic kidney disease patients on haemodialysis.
Fan, S, Ross, C, Mitra, S, Kalra, P, Heaton, J, Hunter, J, Plone, M, Pritchard, N
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2009;(12):3794-9
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Abstract
BACKGROUND Sevelamer carbonate is an improved, buffered form of sevelamer hydrochloride developed for the treatment of hyperphosphataemia in CKD patients. Sevelamer carbonate formulated as a powder for oral suspension presents a novel, patient-friendly alternative to tablet phosphate binders. This study compared the safety and efficacy of sevelamer carbonate powder with sevelamer hydrochloride tablets in CKD patients on haemodialysis. METHODS This was a multi-centre, open-label, randomized, crossover design study. Thirty-one haemodialysis patients were randomly assigned to either sevelamer carbonate powder or sevelamer hydrochloride tablets for 4 weeks followed by a crossover to the other regimen for an additional 4 weeks. RESULTS The mean serum phosphorus was 1.6 +/- 0.5 mmol/L (5.0 +/- 1.5 mg/dL) during sevelamer carbonate powder treatment and 1.7 +/- 0.4 mmol/L (5.2 +/- 1.1 mg/dL) during sevelamer hydrochloride tablet treatment. Sevelamer carbonate powder and sevelamer hydrochloride tablets are equivalent in controlling serum phosphorus; the geometric least square mean ratio was 0.95 (90% CI 0.87-1.03). No statistically significant or clinically meaningful differences were observed in calcium x phosphorus product and lipid levels between sevelamer carbonate powder and sevelamer hydrochloride tablets. Serum bicarbonate levels increased 2.7 +/- 3.7 mmol/L (2.7 +/- 3.7 mEq/L) during sevelamer carbonate treatment. No statistically significant change in bicarbonate was observed during sevelamer hydrochloride treatment. Sevelamer carbonate powder and sevelamer hydrochloride were well tolerated during this study. CONCLUSIONS Sevelamer carbonate powder and sevelamer hydrochloride tablets are equivalent in controlling serum phosphorus and well tolerated in CKD patients on haemodialysis. Bicarbonate levels improved only during sevelamer carbonate treatment. Sevelamer carbonate powder should provide a welcomed new option for the treatment of hyperphosphataemia for CKD patients on dialysis.
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The effects of calcium-based versus non-calcium-based phosphate binders on mortality among patients with chronic kidney disease: a meta-analysis.
Jamal, SA, Fitchett, D, Lok, CE, Mendelssohn, DC, Tsuyuki, RT
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2009;(10):3168-74
Abstract
BACKGROUND The effects of calcium compared with non-calcium-based phosphate binders on mortality, cardiovascular events and vascular calcification in patients with chronic kidney disease (CKD) are unknown. METHODS To address this question, we conducted a systematic review. We electronically searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and CINAHL. We identified 160 potential studies and included 8 randomized trials. Eligible studies, determined by consensus using predefined criteria, were reviewed, and data were extracted onto a standard from. RESULTS There was a trend towards a decrease in all-cause mortality among non-calcium-based versus calcium-based phosphate binders [relative risk (RR) 0.68; 95% CI 0.41-1.11] based upon eight randomized controlled trials and 2873 subjects. Two trials reported on cardiovascular events with a RR of 0.85 (95% CI 0.35-2.03) in patients receiving calcium-based versus non-calcium-based binders. Coronary artery calcification was reported in five trials involving 469 patients; the difference in the change in the calcium score from baseline to follow-up among subjects taking non-calcium-based binders versus calcium-based binders was -76.35 (95% CI -158.25-5.55). CONCLUSION Despite the trends observed, we did not find a statistically significant difference in cardiovascular mortality and coronary artery calcification in patients receiving calcium-based phosphate binders compared to non-calcium-based phosphate binders. However, the data are limited by the small number of studies and the confidence intervals do not exclude a potentially important beneficial effect. Therefore, further randomized trials are required.
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A comparison of sodium bicarbonate infusion versus normal saline infusion and its combination with oral acetazolamide for prevention of contrast-induced nephropathy: a randomized, double-blind trial.
Pakfetrat, M, Nikoo, MH, Malekmakan, L, Tabandeh, M, Roozbeh, J, Nasab, MH, Ostovan, MA, Salari, S, Kafi, M, Vaziri, NM, et al
International urology and nephrology. 2009;(3):629-34
Abstract
BACKGROUND Contrast-induced nephropathy (CIN) is commonly encountered. Because the therapy of choice for prevention of CIN is controversial, in this study we compared the preventive efficacy of bicarbonate (Bi) infusion in dextrose water versus normal saline (NLS) infusion alone or in combination with oral acetazolamide (AZ). METHODS In a double-blind and randomized clinical trial, all patients undergoing coronary angiography or percutaneous coronary intervention received NLS (NLS group), its combination with AZ (AZ group) or infusion of Bi (Bi group) before the procedures. RIFLE (risk of renal failure, injury to the kidney, failure of kidney function, loss of kidney function, and end-stage renal disease) criteria were used to define CIN-associated acute kidney injury (AKI). RESULTS The risk of AKI in CIN was significantly lower in the Bi and AZ groups than in the NLS group (P 0.05). CONCLUSIONS It seems that both Bi and AZ reduce the risk of CIN-related AKI, and close monitoring of serum potassium is needed during bicarbonate infusion.