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1.
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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2.
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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3.
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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4.
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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5.
[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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6.
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.
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7.
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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8.
Serum Uromodulin: A Biomarker of Long-Term Kidney Allograft Failure.
Bostom, A, Steubl, D, Garimella, PS, Franceschini, N, Roberts, MB, Pasch, A, Ix, JH, Tuttle, KR, Ivanova, A, Shireman, T, et al
American journal of nephrology. 2018;(4):275-282
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Abstract
BACKGROUND Uromodulin is a kidney-derived glycoprotein and putative tubular function index. Lower serum uromodulin was recently associated with increased risk for kidney allograft failure in a preliminary, longitudinal single-center -European study involving 91 kidney transplant recipients (KTRs). METHODS The Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial is a completed, large, multiethnic controlled clinical trial cohort, which studied chronic, stable KTRs. We conducted a case cohort analysis using a randomly selected subset of patients (random subcohort, n = 433), and all individuals who developed kidney allograft failure (cases, n = 226) during follow-up. Serum uromodulin was determined in this total of n = 613 FAVORIT trial participants at randomization. Death-censored kidney allograft failure was the study outcome. RESULTS The 226 kidney allograft failures occurred during a median surveillance of 3.2 years. Unadjusted, weighted Cox proportional hazards modeling revealed that lower serum uromodulin, tertile 1 vs. tertile 3, was associated with a threefold greater risk for kidney allograft failure (hazards ratio [HR], 95% CI 3.20 [2.05-5.01]). This association was attenuated but persisted at twofold greater risk for allograft failure, after adjustment for age, sex, smoking, allograft type and vintage, prevalent diabetes mellitus and cardiovascular disease (CVD), total/high-density lipoprotein cholesterol ratio, systolic blood pressure, estimated glomerular filtration rate, and natural log urinary albumin/creatinine: HR 2.00, 95% CI (1.06-3.77). CONCLUSIONS Lower serum uromodulin, a possible indicator of less well-preserved renal tubular function, remained associated with greater risk for kidney allograft failure, after adjustment for major, established clinical kidney allograft failure and CVD risk factors, in a large, multiethnic cohort of long-term, stable KTRs.
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9.
[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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10.
SGLT2 inhibitors and renal outcomes in type 2 diabetes with or without renal impairment: A systematic review and meta-analysis.
Seidu, S, Kunutsor, SK, Cos, X, Gillani, S, Khunti, K, ,
Primary care diabetes. 2018;(3):265-283
Abstract
BACKGROUND Sodium-glucose co-transporter 2 (SGLT2) inhibitors may have renal protective effects in people with impaired kidney function. We assessed the use of SGLT2 inhibitors in people with type 2 diabetes with or without renal impairment [defined as estimated glomerular filtration rate (eGFR) of ≥30 and <60ml/min/1.73m2 and/or UACR>300 and ≤5000mg/g] by conducting a systematic review and meta-analysis of available studies. METHODS Randomised controlled trials (RCTs) were identified from MEDLINE, EMABASE, Web of Science, the Cochrane Library, and search of bibliographies to March 2017. No relevant observational study was identified. Summary measures were presented as mean differences and narrative synthesis performed for studies that could not be pooled. RESULTS 42 articles which included 40 RCTs comprising 29,954 patients were included. In populations with renal impairment, SGLT2 inhibition compared with placebo was consistently associated with an initial decrease in eGFR followed by an increase and return to baseline levels. In pooled analysis of 17 studies in populations without renal impairment, there was no significant change in eGFR comparing SGLT2 inhibitors with placebo (mean difference, 0.51ml/min/1.73m2; 95% CI: -0.69, 1.72; p=403). SGLT2 inhibition relative to placebo was associated with preservation in serum creatinine levels or initial increases followed by return to baseline levels in patients with renal impairment, but levels were preserved in patients without renal impairment. In populations with or without renal impairment, SGLT2 inhibitors (particularly canagliflozin and empagliflozin) compared with placebo were associated with decreased urine albumin, improved albuminiuria, slowed progression to macroalbuminuria, and reduced the risk of worsening renal impairment, the initiation of kidney transplant, and death from renal disease. CONCLUSIONS Emerging data suggests that with SGLT2 inhibition, renal function seems to be preserved in people with diabetes with or without renal impairment. Furthermore, SGLT2 inhibition prevents further renal function deterioration and death from kidney disease in these patients.