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1.
Effect of different types of statins on kidney function decline and proteinuria: a network meta-analysis.
Esmeijer, K, Dekkers, OM, de Fijter, JW, Dekker, FW, Hoogeveen, EK
Scientific reports. 2019;(1):16632
Abstract
Previous studies showed that statins reduce the progression of kidney function decline and proteinuria, but whether specific types of statins are more beneficial than others remains unclear. We performed a network meta-analysis of randomized controlled trials (RCT) to investigate which statin most effectively reduces kidney function decline and proteinuria. We searched MEDLINE, Embase, Web of Science, and the Cochrane database until July 13, 2018, and included 43 RCTs (>110,000 patients). We performed a pairwise random-effects meta-analysis and a network meta-analysis according to a frequentist approach. We assessed network inconsistency, publication bias, and estimated for each statin the probability of being the best treatment. Considerable heterogeneity was present among the included studies. In pairwise meta-analyses, 1-year use of statins versus control reduced kidney function decline by 0.61 (95%-CI: 0.27; 0.95) mL/min/1.73 m2 and proteinuria with a standardized mean difference of -0.58 (95%-CI:-0.88; -0.29). The network meta-analysis for the separate endpoints showed broad confidence intervals due to the small number available RCTs for each individual comparison. In conclusion, 1-year statin use versus control attenuated the progression of kidney function decline and proteinuria. Due to the imprecision of individual comparisons, results were inconclusive as to which statin performs best with regard to renal outcome.
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2.
The impact of kidney function on colorectal cancer patients with localized and regional diseases: An observational study from Taiwan.
Chiang, SF, Chen, JS, Tang, R, Yeh, CY, Hsieh, PS, Tsai, WS, You, JF, Hung, HY, Lai, CC, Lin, JR, et al
Indian journal of cancer. 2019;(3):241-247
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Abstract
BACKGROUND Impaired kidney function is associated with different diseases. However, its impact on colorectal cancer has not been clarified. In order to understand the effect of preoperative kidney function on the outcome of patients with cancer, we analyzed colorectal cancer patients with localized or regional diseases. MATERIALS AND METHODS In total, 3731 stage I to III colorectal cancer (CRC) patients were analyzed in Chang Gung Memorial Hospital. Modification of Diet in Renal Disease (MDRD) formula was used for estimated glomerular filtration rate (eGFR). Receiver operating characteristic (ROC) analysis for kidney function cut-off value; Chi-square method, independent t test, or analysis of variance (ANOVA) method for clinicopathological factors; Kaplan-Meier method for disease-free survival (DFS); Cox proportional hazard model for multivariate analysis. RESULTS Among colon cancer patients, low eGFR (MDRD <70) was associated with more male patients, T2 stage, patients without adjuvant chemotherapy, and patients with elevated creatinine level. Low eGFR is a significant risk factor only for stage III colon cancer (hazard ratio 1.70, 95% CI: 1.28-2.26; P < 0.001). Furthermore, postoperative adjuvant chemotherapy did not significantly increase 5-year DFS for both high and low eGFR groups in stage II patients (5 yrs DFS, 94.8% vs. 84.1%, P = 0.098 for high eGFR subgroup; and 75.0% vs. 75.8%, P = 0.379 for low eGFR subgroup). However, significant improvement of 5-yrs DFS after chemotherapy was found in low eGFR stage III colon cancer patients (64.7% vs. 39.4%, P < 0.001 for low eGFR subgroup). In contrast, no significant DFS difference was caused by chemotherapy for high eGFR stage III subgroup (70.5% vs. 63.9%, P = 0.110). CONCLUSIONS Although low eGFR is an independent risk factor for stage III colon cancer. However, the adjuvant chemotherapy impacts on stage III colon cancer patients differently according to eGFR status.
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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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[Outcome studies on SGLT-2 inhibitors].
Seufert, J, Laubner, K
Der Internist. 2019;(9):903-911
Abstract
BACKGROUND Inhibitors of sodium-glucose cotransporters type 2 (SGLT-2) are a class of oral antidiabetic drugs with a novel specific mode of action in the kidneys. OBJECTIVE The effects of SGLT-2 inhibitors on cardiovascular (CV) and renal endpoints in outcome trials with type 2 diabetes patients. MATERIAL AND METHODS Differential analysis and interpretation of the results of outcome trials with the SGLT-2 inhibitors empagliflozin, canagliflozin and dapagliflozin in type 2 diabetes mellitus. RESULTS In the EMPA-REG OUTCOME trial, empagliflozin demonstrated a significant reduction in major cardiac adverse events (MACE), hospitalization for heart failure (HHI), renal endpoints, CV and total mortality vs. placebo in >7000 patients with type 2 diabetes and established CV disease over 3.1 years. In the CANVAS program, canagliflozin demonstrated a significant reduction of MACE, HHI and renal endpoints vs. placebo in >10,000 patients with type 2 diabetes and high CV risk over 2.4 years. In the CREDENCE trial, canagliflozin demonstrated a significant reduction of a combined renal endpoint and CV endpoints vs. placebo in >4000 patients with type 2 diabetes and established kidney disease with albuminuria over 2.6 years. In the DECLARE-TIMI 58 trial, dapagliflozin demonstrated a significant reduction in a combined endpoint of CV death and HHI vs. placebo in >17,000 patients with type 2 diabetes and established CV disease or with multiple CV risk factors over 3.1 years. CONCLUSION Outcome trials with SGLT-2 inhibitors have collectively demonstrated cardioprotective and nephroprotective effects in patients with type 2 diabetes and high CV risk. The use of SGLT-2 inhibitors is recommended in current guidelines and consensus statements as primary combination partners for metformin in patients with type 2 diabetes and established CV disease, high CV risk, heart failure or kidney disease.
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5.
Elagolix Pharmacokinetic Profiles in Women With Renal or Hepatic Impairment.
Ng, J, Duan, WR, Marbury, T, Schmidt, JM, Klein, CE
Clinical pharmacology in drug development. 2019;(8):1053-1061
Abstract
The aim of these studies was to assess the safety and pharmacokinetics of elagolix, an oral nonpeptide gonadotropin-releasing hormone antagonist following oral administration in women with renal or hepatic impairment. Two phase 1 studies were conducted in adult women with normal renal function versus renal impairment (reduced study), and normal hepatic function versus hepatic impairment (full study design). All women received a single dose of elagolix 200 mg (renal) or 150 mg (hepatic). Intensive pharmacokinetic blood samples were collected. Elagolix exposures were comparable in women with normal renal function and those with moderate/severe renal impairment or end-stage renal disease. Elagolix exposures also appeared to be similar in women with normal hepatic function and women with mild hepatic impairment. Elagolix area under the curve in women with moderate hepatic impairment and with severe hepatic impairment was approximately 3-fold and 7-fold higher than in women with normal hepatic function. The adverse event incidence was low, with the main events being mild nausea and headache. No dosage adjustment was needed in women with renal impairment or women with mild hepatic impairment. Although an elagolix dose of 150 mg once daily may be used in women with moderate hepatic impairment for up to 6 months, this elagolix dose should not be used in women with severe hepatic impairment.
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Sociodemographic and Kidney Disease Correlates of Nutrient Intakes Among Urban African Americans With Uncontrolled Hypertension.
Song, AY, Crews, DC, Ephraim, PL, Han, D, Greer, RC, Boyér, LL, Ameling, J, Gayles, DJ, Sneed, V, Carson, KA, et al
Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. 2019;(5):399-406
Abstract
OBJECTIVE The objective of this study was to determine the association between sociodemographic factors and intakes of 4 nutrients and associations between intakes and markers of kidney disease to identify opportunities to improve outcomes among clinically high-risk African Americans. DESIGN AND METHODS We conducted a cross-sectional study of baseline data from the Achieving Blood Pressure Control Together study, a randomized controlled trial of 159 African Americans (117 females) with uncontrolled hypertension in Baltimore MD. To determine the association between sociodemographic factors and nutrient intakes, we constructed linear and logistic regression models. Using logistic regression, we determined the association between below-median nutrient intakes and kidney disease. Our outcomes of interest were daily intakes of vitamin C, magnesium, dietary fiber, and potassium as estimated by the Block Fruit-Vegetable-Fiber Screener and kidney disease defined as estimated glomerular filtration rate <60 mL/min per 1.73 m2 or urinary albumin-to-creatinine ratio >=30 mg/g. SETTING AND SUBJECTS Baseline data from the Achieving Blood Pressure Control Together study, a randomized controlled trial of 159 African Americans (117 females) with uncontrolled hypertension, were obtained. METHODS To determine the association between sociodemographic factors and nutrient intakes, we constructed linear and logistic regression models. Using logistic regression, we determined the association between below-median nutrient intakes and kidney disease. MAIN OUTCOME MEASURES Our outcomes of interest were daily intakes of vitamin C, magnesium, dietary fiber, and potassium as estimated by the Block Fruit-Vegetable-Fiber Screener and kidney disease defined as estimated glomerular filtration rate <60 mL/min per 1.73 m2 or urinary albumin-to-creatinine ratio ≥30 mg/g. RESULTS Overall, compared to Institute of Medicine recommendations, participants had lower intakes of magnesium, fiber, and potassium but higher vitamin C intakes. For females, sociodemographic factors that significantly associated with lower intake of the 4 nutrients were older age, obesity, lower health numeracy, and lesser educational attainment. For males, none of the sociodemographic factors were significantly associated with nutrient intakes. Below-median intake was significantly associated with albumin-to-creatinine ratio ≥30 (adjusted odds ratio [95% confidence interval]: 3.4 [1.5, 7.8] for vitamin C; 3.6 [1.6, 8.4] for magnesium; 2.9 [1.3, 6.5] for fiber; 3.6 [1.6, 8.4] for potassium), but not with estimated glomerular filtration rate <60. CONCLUSION African Americans with uncontrolled hypertension may have low intakes of important nutrients, which could increase their risk of chronic kidney disease. Tailored dietary interventions for African Americans at high risk for chronic kidney disease may be warranted.
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The Renal Safety of L-Carnitine, L-Arginine, and Glutamine in Athletes and Bodybuilders.
Davani-Davari, D, Karimzadeh, I, Sagheb, MM, Khalili, H
Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. 2019;(3):221-234
Abstract
One of the major concerns about taking amino acid supplements is their potential adverse effects on the kidney as a major organ involved in the metabolism and excretion of exogenous substances. The aim of this study is to review available data about renal safety of the most prominent amino acid supplements including L-arginine, glutamine and also L-carnitine as well as creatine (as amino acid derivatives) in athletes and bodybuilders. The literature was searched by keywords such as "L-carnitine", "L-arginine", "glutamine", and "kidney injury" in databases such as Scopus, Medline, Embase, and ISI Web of Knowledge. Articles published from 1950 to December 2017 were included. Among 3171, 5740, and 1608 records after primary search in the relevant databases, 8, 7, and 5 studies have been finally included, respectively, for L-carnitine, L-arginine, and glutamine in this review. Arginine appears to have both beneficial and detrimental effects on kidney function. However, adverse effects are unlikely to occur with the routine doses (from 3 to >100 g/day). The risks and benefits of L-carnitine on the athletes' and bodybuilders' kidney have not been evaluated yet. However, L-carnitine up to 6000 mg/day is generally considered to be a safe supplement at least in healthy adults. Both short-term (20-30 g within a few hours) and long-term (0.1 g/kg four times daily for 2 weeks) glutamine supplementation in healthy athletes were associated with no significant adverse effects, but it can cause glomerulosclerosis and serum creatinine level elevation in the setting of diabetic nephropathy. Creatine supplementation (ranged from 5 to 30 g/day) also appears to have no detrimental effects on kidney function of individuals without underlying renal diseases. More clinical data are warranted to determine the optimal daily dose and intake duration of common supplemental amino acids associated with the lowest renal adverse effects in sportsmen and sports women.
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[Kidney disease in cobalamin C deficiency].
Lemoine, M, Grangé, S, Guerrot, D
Nephrologie & therapeutique. 2019;(4):201-214
Abstract
Cobalamin C deficiency (cblC) is the most common inborn error of vitamin B12 metabolism. This autosomal recessive disease is due to mutations in MMACHC gene, encoding a cyanocobalamin decyanase. It leads to hyperhomocysteinemia associated with hypomethioninemia and methylmalonic aciduria. Two distinct phenotypes have been described : early-onset forms occur before the age of one year and are characterized by a severe multisystem disease associating failure to thrive to neurological and ophthalmological manifestations. They are opposed to late-onset forms, less severe and heterogeneous. CblC deficiency-associated kidney lesions remain poorly defined. Thirty-eight cases have been described. Age at initial presentation varied from a few days to 28 years. Most of the patients presented renal thrombotic microangiopathy (TMA) associated with acute renal failure, and 21 patients presented typical lesions of renal thrombotic microangiopathy on kidney biopsy. Prognosis was poor, leading to death in the absence of treatment, and related to the severity of renal lesions in the early-onset forms. Late-onset disease had better prognosis and most of patients were weaned off dialysis after treatment initiation. We suggest that all the patients with renal TMA be screened for cobalamin metabolism disorder, regardless of age and even in the absence of neurological symptoms, to rapidly initiate the appropriate treatment.
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[18F-FDG positron emission tomography in non-oncological renal pathology: Current indications and perspectives].
Hanssen, O, Lovinfosse, P, Weekers, L, Hustinx, R, Jouret, F
Nephrologie & therapeutique. 2019;(6):430-438
Abstract
Positron emission tomography combined with computed tomography (PET/CT) is a nuclear imaging technique which provides anatomical and functional information. PET/CT is increasingly used in non-oncological nephrology since conventional radiological approaches after injection of contrast agents are relatively contra-indicated in patients with chronic kidney disease (CKD). PET/CT after i.v. injection of 18F-fluoro-deoxy-glucose (FDG) is not toxic and is characterized by a high sensitivity. The level of irradiation (∼5mSv) is acceptable. CKD does not significantly influence tissue uptake of 18F-FDG. The purpose of the present review aims at detailing the non-oncological indications of 18F-FDG PET/CT in general nephrology and after kidney transplantation. Particularly, 18F-FDG PET/CT appears useful in the diagnosis of cyst infection in patients with autosomal dominant polycystic kidney disease, as well as in the characterization of retroperitoneal fibrosis. In kidney transplant recipients, 18F-FDG PET/CT may help in the diagnostic work-up of suspected acute rejection, thereby eventually avoiding unnecessary kidney transplant biopsy. Perspectives in 18F-FDG PET/CT imaging are discussed, including innovative approaches of image analysis.
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Updates on Hypertension and New Guidelines.
Singer, PS
Advances in pediatrics. 2019;:177-187