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1.
Phosphate clearance in peritoneal dialysis.
Debowska, M, Gomez, R, Pinto, J, Waniewski, J, Lindholm, B
Scientific reports. 2020;(1):17504
Abstract
In renal failure, hyperphosphatemia is common and correlates with increased mortality making phosphate removal a key priority for dialysis therapy. We investigated phosphate clearance, removal and serum level, and factors associated with phosphate control in patients undergoing continuous ambulatory (CAPD), continuous cyclic (CCPD) and automated (APD) peritoneal dialysis (PD). In 154 prevalent PD patients (mean age 53.2 ± 17.6 year, 59% men, 47% anuric), 196 daily collections of urine and 368 collections of dialysate were evaluated in terms of renal, peritoneal and total (renal plus peritoneal) phosphorus removal (g/week), phosphate and creatinine clearances (L/week) and urea KT/V. Dialytic removal of phosphorus was lower in APD (1.34 ± 0.62 g/week) than in CAPD (1.89 ± 0.73 g/week) and CCPD (1.91 ± 0.63 g/week) patients; concomitantly, serum phosphorus was higher in APD than in CAPD (5.55 ± 1.61 vs. 4.84 ± 1.23 mg/dL; p < 0.05). Peritoneal and total phosphate clearances correlated with peritoneal (rho = 0.93) and total (rho = 0.85) creatinine clearances (p < 0.001) but less with peritoneal and total urea KT/V (rho = 0.60 and rho = 0.65, respectively, p < 0.001). Phosphate removal, clearance and serum levels differed between PD modalities. CAPD was associated with higher peritoneal removal and lower serum level of phosphate than APD.
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2.
Efficacy and safety of trelagliptin in Japanese patients with type 2 diabetes with severe renal impairment or end-stage renal disease: Results from a randomized, phase 3 study.
Kaku, K, Ishida, K, Shimizu, K, Achira, M, Umeda, Y
Journal of diabetes investigation. 2020;(2):373-381
Abstract
INTRODUCTION To investigate the efficacy and safety of trelagliptin 25 mg in patients with type 2 diabetes mellitus with severe renal impairment or end-stage renal disease. MATERIALS AND METHODS This multicenter, randomized, phase 3 study comprised a 12-week double-blind phase followed by a 40-week open-label phase. Patients had type 2 diabetes mellitus with severe renal impairment (creatinine clearance <30 mL/min) or end-stage renal disease (undergoing hemodialysis), and were receiving diet and/or exercise therapy with/without one antidiabetic drug. RESULTS Patients were randomized to trelagliptin (A/A, n = 55) or placebo (P/A, n = 52; double-blind phase). Both groups received trelagliptin in the open-label phase. The least square mean change (95% confidence interval [CI]) from baseline in hemoglobin A1c at the end of the double-blind phase was -0.71% (95% CI -0.885, -0.542) and 0.01% (95% CI -0.170, 0.183) in the A/A and P/A groups, respectively (intergroup least square means difference -0.72%, 95% CI -0.966, -0.473; P < 0.0001). Mean hemoglobin A1c decreased after trelagliptin treatment in the P/A group to similar levels observed in the A/A group and remained comparable in both groups versus baseline up to week 52. In the double-blind phase, the incidence of treatment-emergent adverse events (TEAEs) was 72.7% and 61.5% in the A/A and P/A group, respectively; most TEAEs were mild-to-moderate, except in one patient (P/A group), who experienced two severe TEAEs. The incidence of serious TEAEs was 7.3% and 3.8% in the A/A and P/A group, respectively. CONCLUSIONS Once-weekly trelagliptin 25 mg was efficacious, with no major safety concerns, and represents a meaningful treatment option in this patient population.
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3.
Preventive Effects of Nicorandil Against Contrast-Induced Nephropathy in Patients With Moderate Renal Insufficiency Undergoing Percutaneous Coronary Intervention.
Zhang, P, Li, WY, Yang, SC, Fu, NK, Liu, XG, Zhang, X, Cong, HL, Lin, WH, Tian, FS, Lu, CZ, et al
Angiology. 2020;(2):183-188
Abstract
We investigated the preventive effect of nicorandil on contrast-induced nephropathy (CIN) in patients with moderate renal insufficiency undergoing percutaneous coronary intervention (PCI). A total of 250 patients with a creatinine clearance (crCl) ≤60 mL/min undergoing PCI were randomly assigned to either a nicorandil group (nicorandil 10 mg 3 times/d and hydration; n = 125) or a control group (hydration only; n = 125). The first end point was the incidence of CIN defined as an increase in serum creatinine (Scr) levels by ≥0.5 mg/dL or ≥25% within 72 hours after exposure to the contrast medium. The secondary end points were (1) changes in Scr, blood urea nitrogen, and crCl and (2) the incidence of major adverse events during hospitalization. The incidence of CIN was 1.6% (2/125) in the nicorandil group and 9.6% (12/125) in the control group (P = .011). There was no obvious difference in the incidence of major adverse events during hospitalization between the nicorandil and the control group (4.0% vs 4.8%, P = 1.000). Multivariate logistic regression analysis showed that nicorandil was a protective factor for CIN (odds ratios = 0.126, 95% confidence interval: -19.996 to -0.932, P = .012). Prophylactic administration of nicorandil may prevent against CIN in patients with moderate renal insufficiency undergoing PCI.
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4.
[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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5.
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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6.
Post-mortem diagnosis of kidney impairment: An experimental study.
Maskell, PD, Penney, E, Smith, PR, Hikin, LJ, Morley, SR
Forensic science international. 2019;:271-277
Abstract
The determination of the role that drugs may have played in a death is an important part of the investigation into unexplained deaths. Renal impairment may lead to a reduction in drug excretion rate and therefore an accumulation of drugs or metabolites, leading to possible toxic or lethal effects. Creatinine levels are known to be stable in the post mortem period and in life can give an indication of kidney function. There are however widely reported limitations when using creatinine in isolation and so we investigated the usefulness of using estimated glomerular filtration rate (eGFR) for scoring an individual as having renal impairment using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. We analysed unpreserved vitreous for creatinine in 812 individuals using an isotope dilution mass spectrometry (ID-MS) traceable enzymatic. We found that the biochemical analysis of post mortem vitreous creatinine and subsequent calculation of eGFR is a useful adjunct to the standard testing that takes place during a post-mortem examination and can assist in death investigation. Using an eGFR of <60 mL/min/1.73 m2 gave a sensitivity of 94.3% and specificity of 97.3% when scoring an individual as having renal impairment. We therefore recommend the calculation of eGFR for the determination of possible renal impairment in post mortem investigations. It is, of course, always pertinent to interpret any results using a wealth of case information. Extreme caution should be exercised in cases where insufficient clinical information/history is available, particularly in cases in which there is suspected diabetic ketoacidosis, dehydration or hospitalisation prior to death.
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7.
Effectiveness of Intradialytic Parenteral Nutrition in Treating Protein-Energy Wasting in Hemodialysis: A Rapid Systematic Review.
Anderson, J, Peterson, K, Bourne, D, Boundy, E
Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. 2019;(5):361-369
Abstract
Intradialytic parenteral nutrition (IDPN) is commonly requested before recommended therapies in malnourished patients on hemodialysis. This review provides updated critical synthesis of the evidence on the use of IDPN in patients on hemodialysis. We searched MEDLINE, CINAHL, and other sources to identify evidence. Two reviewers sequentially selected studies, abstracted data, rated study quality, and synthesized evidence using predefined criteria. IDPN did not improve clinically relevant outcomes compared with dietary counseling or oral supplementation and had varied results compared with usual care in 12 studies. Data are limited on adverse events or cost-effectiveness of IDPN. Important limitations of the evidence, including limited measurement of clinically important outcomes, methodological concerns, and heterogeneity between studies, weaken our confidence in these findings. IDPN may be a reasonable treatment option for patients who fail to respond or cannot receive recommended treatments, but the broad usage of IDPN before recommended treatment options does not appear warranted.
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8.
Effects of dapagliflozin on development and progression of kidney disease in patients with type 2 diabetes: an analysis from the DECLARE-TIMI 58 randomised trial.
Mosenzon, O, Wiviott, SD, Cahn, A, Rozenberg, A, Yanuv, I, Goodrich, EL, Murphy, SA, Heerspink, HJL, Zelniker, TA, Dwyer, JP, et al
The lancet. Diabetes & endocrinology. 2019;(8):606-617
Abstract
BACKGROUND Sodium-glucose co-transporter-2 (SGLT2) inhibitors have shown beneficial effects on renal outcomes mainly in patients with established atherosclerotic cardiovascular disease. Here we report analyses of renal outcomes with the SGLT2 inhibitor dapagliflozin in the DECLARE-TIMI 58 cardiovascular outcomes trial, which included patients with type 2 diabetes both with and without established atherosclerotic cardiovascular disease and mostly with preserved renal function. METHODS In DECLARE-TIMI 58, patients with type 2 diabetes, HbA1c 6·5-12·0% (47·5-113·1 mmol/mol), with either established atherosclerotic cardiovascular disease or multiple risk factors, and creatinine clearance of at least 60 mL/min were randomly assigned (1:1) to 10 mg dapagliflozin or placebo once daily. A prespecified secondary cardiorenal composite outcome was defined as a sustained decline of at least 40% in estimated glomerular filtration rate [eGFR] to less than 60 mL/min per 1·73m2, end-stage renal disease (defined as dialysis for at least 90 days, kidney transplantation, or confirmed sustained eGFR <15mL/min per 1·73 m2), or death from renal or cardiovascular causes; a prespecified renal-specific composite outcome was the same but excluding death from cardiovascular causes. In this renal analysis, we report findings for the components of these composite outcomes, subgroup analysis of these composite outcomes, and changes in eGFR at different timepoints. DECLARE-TIMI 58 is registered with ClinicalTrials.gov, number NCT01730534. FINDINGS The trial took place between April 25, 2013, and Sept 18, 2018; median follow-up was 4·2 years (IQR 3·9-4·4). Of the 17 160 participants who were randomly assigned, 8162 (47·6%) had an eGFR of at least 90 mL/min per 1·73 m2, 7732 (45·1%) had an eGFR of 60 to less than 90 mL/min per 1·73 m2, and 1265 (7·4%) had an eGFR of less than 60 mL/min per 1·73 m2 at baseline (one participant had missing data for eGFR); 6974 (40·6%) had established atherosclerotic cardiovascular disease and 10 186 (59·4%) had multiple risk factors. As previously reported, the cardiorenal secondary composite outcome was significantly reduced with dapagliflozin versus placebo (hazard ratio [HR] 0·76, 95% CI 0·67-0.87; p<0·0001); excluding death from cardiovascular causes, the HR for the renal-specific outcome was 0·53 (0·43-0·66; p<0·0001). We identified a 46% reduction in sustained decline in eGFR by at least 40% to less than 60 mL/min per 1·73 m2 (120 [1·4% vs 221 [2·6%]; HR 0·54 [95% CI 0·43-0·67]; p<0·0001). The risk of end-stage renal disease or renal death was lower in the dapagliflozin group than in the placebo group (11 [0·1%] vs 27 [0·3%]; HR 0·41 [95% CI 0·20-0·82]; p=0·012). Both the cardiorenal and renal-specific composite outcomes were improved with dapagliflozin versus placebo across various prespecified subgroups, including those defined by baseline eGFR (cardiorenal outcome pinteraction=0·97; renal-specific outcome pinteraction=0·87) and the presence or absence of established atherosclerotic cardiovascular disease (cardiorenal outcome pinteraction=0·67; renal-specific outcome pinteraction=0·72). 6 months after randomisation, the mean decrease in eGFR was larger in the dapagliflozin group than in the placebo group. The mean change equalised by 2 years, and at 3 and 4 years the mean decrease in eGFR was less with dapagliflozin than with placebo. INTERPRETATION Dapagliflozin seemed to prevent and reduce progression of kidney disease compared with placebo in this large and diverse population of patients with type 2 diabetes with and without established atherosclerotic cardiovascular disease, most of whom had preserved renal function. FUNDING AstraZeneca.
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9.
[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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10.
Effects of tolvaptan add-on therapy in patients with acute heart failure: meta-analysis on randomised controlled trials.
Ma, G, Ma, X, Wang, G, Teng, W, Hui, X
BMJ open. 2019;(4):e025537
Abstract
OBJECTIVES Treating acute decompensated heartfailure (ADHF) for improving congestion with diuretics may cause worsening renal function (WRF), but the clinical efficacy of tolvaptan add-on therapy on reducing WRF in ADHF patients is inconsistent. This analysis is to evaluate the effects of tolvaptan add-on therapy on reducing WRF in ADHF patients. METHODS Meta-analysis of randomised trials of tolvaptan add-on therapy on reducing WRF in ADHF patients. The MEDLINE, Embase and Cochrane Central Register of Controlled Trials databases were searched for relevant articles from their inception to 31 October, 2017. Two reviewers filtrated the documents on WRF, short-term all-cause mortality, body weight decreased, elevated sodium level for calculating pooled relatives risks, weighted mean difference and associated 95% CIs. We used fixed-effects or random-effects models according to I2 statistics. ACHIEVEMENTS Seven random controlled trials with 937 patients were included for analysis. Compared with the control, tolvaptan add-on therapy did not improve incidence of worsening renal function (RR 0.78, 95% CI 0.48 to 1.26, p=0.31, I2=66%) and short-term all-cause mortality (RR 0.85, 95% CI 0.47 to 1.56, p=0.61, I2=0%). On subgroup analyses, there was a suggestion of possible effect modification by dose of tolvaptan, in which benefit was observed in low-dose (≤15 mg/day) group (RR 0.48, 95% CI 0.23 to 1.02, p=0.05, I2=54%), but not with high-dose (30 mg) group (RR 1.33, 95% CI 0.99 to 1.78, p=0.05, I2=0%). However, tolvaptan add-on therapy reduced body weight in 2 days (standardised mean difference -0.49, 95% CI -0.64 to -0.34, p<0.00001, I2=0%), increased sodium level (mean difference 1.56, 95% CI 0.04 to 3.07, p=0.04, I2=0%). CONCLUSION The result suggests that comparing with the standard diuretic therapy, tolvaptan add-on therapy did not reduce the incidence of WRF and short-term mortality, however, it can decrease body weight and increase the sodium level in patients who are with ADHF. Further researches are still required for confirmation.