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1.
Association of vitamin D receptor TaqI and ApaI genetic polymorphisms with nephrolithiasis and end stage renal disease: a meta-analysis.
Hussain, T, Naushad, SM, Ahmed, A, Alamery, S, Mohammed, AA, Abdelkader, MO, Alkhrm, NAN
BMC medical genetics. 2019;(1):193
Abstract
BACKGROUND The deficiency of vitamin D receptor (VDR) or its ligand, vitamin D3, is linked to the development of renal diseases. The TaqI (rs731236) and ApaI (rs7975232) polymorphisms of VDR gene are widely studied for their association with renal disease risk. However, studies have largely been ambiguous. METHODS Meta-analysis was carried out to clarify the association of TaqI (2777 cases and 3522 controls) and ApaI (2440 cases and 3279 controls) polymorphisms with nephrolithiasis (NL), diabetic nephropathy (DN) and end stage renal disease (ESRD). RESULTS The VDR TaqI C-allele under allele contrast was significantly associated with ESRD in both fixed effect and random effect models, and ApaI C-allele with ESRD only under fixed effect model. Cochrane Q-test showed no evidence of heterogeneity for TaqI polymorphism and a significant heterogeneity for Apa I polymorphism. No publication bias was observed for both the polymorphisms. CONCLUSIONS The present meta-analysis identifies TaqI and ApaI polymorphisms of VDR gene as risk factors for renal diseases.
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2.
How Low Do We Go (in the Post-SPRINT Era)?
Burgner, A, Lewis, JB
Advances in chronic kidney disease. 2019;(2):110-116
Abstract
Hypertension is frequently both a cause and complication of CKD. The optimal blood pressure target in CKD has been of hot debate over the decades with little data to inform the goals. Here, we review the data from the Systolic Blood Pressure Intervention Trial (SPRINT), Modification of Diet in Renal Disease (MDRD), African American Study of Kidney Disease and Hypertension (AASK), Ramipril Efficacy in Nephropathy-2 (REIN-2), and Action to Control Cardiovascular Risk in Diabetes (ACCORD) trials to use the available evidence to better inform what blood pressure goal should be recommended in patients with CKD and to answer the question "How low should we go?".
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3.
Arg913Gln variation of SLC12A3 gene is associated with diabetic nephropathy in type 2 diabetes and Gitelman syndrome: a systematic review.
De la Cruz-Cano, E, Jiménez-González, CDC, Morales-García, V, Pineda-Pérez, C, Tejas-Juárez, JG, Rendón-Gandarilla, FJ, Jiménez-Morales, S, Díaz-Gandarilla, JA
BMC nephrology. 2019;(1):393
Abstract
BACKGROUND Diabetic nephropathy is a global common cause of chronic kidney disease and end-stage renal disease. A lot of research has been conducted in biomedical sciences, which has enhanced understanding of the pathophysiology of diabetic nephropathy and has expanded the potential available therapies. An increasing number of evidence suggests that genetic alterations play a major role in development and progression of diabetic nephropathy. This systematic review was focused on searching an association between Arg913Gln variation in SLC12A3 gene with diabetic nephropathy in individuals with Type 2 Diabetes and Gitelman Syndrome. METHODS An extensive systematic review of the literature was completed using PubMed, EBSCO and Cochrane Library, from their inception to January 2018. The PRISMA guidelines were followed and the search strategy ensured that all possible studies were identified to compile the review. Inclusion criteria for this review were: 1) Studies that analyzed the SLC12A3 gene in individuals with Type 2 Diabetes and Gitelman Syndrome. 2) Use of at least one analysis investigating the association between the Arg913Gln variation of SLC12A3 gene with diabetic nephropathy. 3) Use of a case-control or follow-up design. 4) Investigation of type 2 diabetes mellitus in individuals with Gitelman's syndrome, with a history of diabetic nephropathy. RESULTS The included studies comprised 2106 individuals with diabetic nephropathy. This review shows a significant genetic association in most studies in the Arg913Gln variation of SLC12A3 gene with the diabetic nephropathy, pointing out that the mutations of this gene could be a key predictor of end-stage renal disease. CONCLUSIONS The results showed in this systematic review contribute to better understanding of the association between the Arg913Gln variation of SLC12A3 gene with the pathogenesis of diabetic nephropathy in individuals with T2DM and GS.
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4.
Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Renal Outcomes in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Bae, JH, Park, EG, Kim, S, Kim, SG, Hahn, S, Kim, NH
Scientific reports. 2019;(1):13009
Abstract
This study was conducted to investigate the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on individual renal outcomes in patients with type 2 diabetes. We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception to September 2017 to identify randomized controlled trials comparing SGLT2 inhibitors with placebo or antidiabetic drugs and reporting any renal outcomes in patients with type 2 diabetes. Additionally, we identified 4 articles which were published after the predefined period to include relevant data. A meta-analysis was performed to calculate weighted mean differences (WMDs) and relative risks (RRs) with 95% confidence intervals (CIs) for each renal outcome. We included 48 studies involving 58,165 patients in the analysis. SGLT2 inhibitors significantly lowered urine albumin-to-creatinine ratio (UACR) (WMD, -14.64 mg/g; 95% CI, -25.15 to -4.12; P = 0.006) compared with controls. The UACR-lowering effects of SGLT2 inhibitors were greater with a higher baseline UACR. Overall changes in estimated glomerular filtration rate (eGFR) were comparable between two groups (WMD, 0.19 mL/min/1.73 m2; 95% CI, -0.44 to 0.82; P = 0.552). However, SGLT2 inhibitors significantly slowed eGFR decline in patients with a higher baseline eGFR and a longer duration of treatment. Compared with controls, SGLT2 inhibitors significantly reduced the risk of microalbuminuria (RR, 0.69; 95% CI, 0.49 to 0.97; P = 0.032), macroalbuminuria (RR, 0.49; 95% CI, 0.33 to 0.73; P < 0.001), and worsening nephropathy (RR, 0.73; 95% CI, 0.58 to 0.93; P = 0.012). In addition, the risk of end-stage renal disease was significantly lower in SGLT2 inhibitors than in controls (RR, 0.70; 95% CI, 0.57 to 0.87; P = 0.001). In conclusion, SGLT2 inhibitors had beneficial renal effects by lowering the risk of albuminuria development or progression and reducing the risk of end-stage renal disease compared with placebo or other antidiabetic drugs.
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5.
How Does CREDENCE Inform Best Use of SGLT2 Inhibitors in CKD?
Neumiller, JJ, Kalyani, RR
Clinical journal of the American Society of Nephrology : CJASN. 2019;(11):1667-1669
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6.
Association of non-alcoholic fatty liver disease with microvascular complications of type 2 diabetes.
Afarideh, M, Aryan, Z, Ghajar, A, Ganji, M, Ghaemi, F, Saadat, M, Heidari, B, Mechanick, JI, Esteghamati, A
Primary care diabetes. 2019;(6):505-514
Abstract
INTRODUCTION Non-alcoholic fatty liver disease (NAFLD) affects risks of type 2 diabetes (T2D), diabetes-related complications, and cardiovascular disease in a complex manner. This study is designed to clarify associations of sonographically-detected NAFLD and serum liver enzymes with diabetes-related microvascular complications. METHODS A matched case-contorl study was designed for 440 patients with T2D and at least one of the chronic diabetes-related microvascular complications and 495 age- and gender-matched control patients with T2D. RESULTS Considering pre-existing and newly developed chronic microvascular complications, diabetic peripheral neuropathy was found in 347 out of 935 (37.1%) study patients, diabetic retinopathy in 141/935 (15.1%), and diabetic nephropathy in 103/935 (11.0%). Diagnosis of diabetic retinopathy and diabetic nephropathy were inversely associated with the presence of NAFLD in the crude logistic regressions (OR [95% CI] = 0.18 [0.05-0.63], p value = 0.007; OR [95% CI] = 0.17 [0.04-0.59], p value = 0.011, respectively). The subgroup of NAFLD with elevated liver enzymes had lower odds of having diabetic peripheral neuropathy in the fully adjusted model (OR [95% CI] = 0.34 [0.12-0.98], p value = 0.048). CONCLUSION Diagnosis of NAFLD with or without elevated serum liver enzymes was inversely correlated with certain chronic diabetes microvascular complications. Possible explanations for this counter-intuitive and unexpected finding are discussed and center on reverse-causality, wherein sicker patients may develop beneficial compensatory physiological and behavioral adaptations. Diversity of studied patients, in particular with regards to the ethnic and racial differences among the Western and Asian populations may also partly account for contrasting findings of the relationship between NAFLD and microvascular complications of diabetes.
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7.
Research digest: SGLT2 inhibition in kidney and liver disease.
Preiss, D, Sattar, N
The lancet. Diabetes & endocrinology. 2019;(6):427
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8.
The effect of SGLT-2 inhibitors on albuminuria and proteinuria in diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.
Piperidou, A, Sarafidis, P, Boutou, A, Thomopoulos, C, Loutradis, C, Alexandrou, ME, Tsapas, A, Karagiannis, A
Journal of hypertension. 2019;(7):1334-1343
Abstract
: Diabetic kidney disease is a serious microvascular complication of diabetes mellitus and the leading cause of end-stage renal disease in western countries. New therapeutic agents are needed to delay its onset and progression. Recent literature suggests that sodium-glucose cotransporter 2 (SGLT-2) inhibitors may have renoprotective effects. Our aim was to systematically review the effect of SGLT-2 inhibitors on albuminuria and proteinuria in patients with diabetes mellitus. Studies were identified by search in major electronic databases, clinical trial registers, and sources of gray literature. We included randomized controlled trials of currently approved SGLT-2 inhibitors with a duration of at least 12 weeks. The primary outcome was the between-groups difference in the proportional (%) change of albuminuria or proteinuria between baseline and end of treatment. SGLT-2 inhibitors were associated with statistically significant reduction in albuminuria compared to placebo or active control [weighted mean difference (WMD) -25.39%, 95% confidence interval (CI) -34.17 to -16.62] (15 studies, N = 17 540 patients). When trials were stratified according to the level of baseline albuminuria, reduction in urine albumin-to-creatinine ratio was more prominent in randomized controlled trials in patients with moderately (WMD -40.78%, 95% CI -63.21 to -18.34) or severely increased albuminuria (WMD -36.40%, 95% CI -51.53 to -21.26). Only one study reported data for urine protein-to-creatinine ratio. Finally, SGLT-2 inhibitors reduced systolic and diastolic blood pressure by 4.43 mmHg (95% CI -5.24 to -3.63) and 1.81 mmHg (95% CI -2.38 to -1.23), respectively.
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9.
High-Resistant Starch, Low-Protein Flour Intervention on Patients With Early Type 2 Diabetic Nephropathy: A Randomized Trial.
Meng, Y, Bai, H, Yu, Q, Yan, J, Zhao, L, Wang, S, Li, Z, Wang, Q, Chen, L
Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. 2019;(5):386-393
Abstract
OBJECTIVE The objective of this study is to explore the effect of high-resistant starch (RS), low-protein flour as a source of RS on patients with early type 2 diabetic nephropathy (DN) through the clinical intervention trial. DESIGN This was a single center, randomized, comparative, open-label trial. Seventy-five patients with early DN, aged 18 to 80 y, were recruited and randomly assigned to two groups. During the 12-week intervention, the control group patients (38 cases) followed protein-restriction diet daily with a common staple. The intervention group (37 cases) received 50 g of high-RS, low-protein flour instead of a common staple of equal quality at lunch and dinner each day. The blood glucose, blood lipids, nutritional parameters, indicators of renal function, oxidative stress, and inflammatory markers were measured. RESULTS Compared with the control group, high-RS, low-protein flour intake led to a significant reduction in fasting blood glucose, HbA1c, total cholesterol, and triglycerides levels (P < .05 for all). The changes in serum uric acid (UA) and β2-microglobulin (β2-MG) level were observed after high-RS, low-protein flour intervention (uric acid [mean ± standard deviation]: -24.7 ± 38.5 μmol/L, P = .001; β2-MG: 0.5 ± 0.9 mg/L, P = 0.018). In addition, high-RS, low-protein flour intake increased serum superoxide dismutase level by 10.1 ± 27.7 U/mL (P < .05); however, it did not change the interleukin-6 and Tumor Necrosis Factor α (TNF-α) concentration. CONCLUSIONS Twelve-week intervention with high-RS, low-protein flour improved the blood glucose and blood lipid levels, decreased the serum uric acid (UA) and urine β2-MG, and enhanced the ability to prevent antioxidative stress in patients with early DN.
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10.
Nonproteinuric progressive diabetic kidney disease.
Zoccali, C, Mallamaci, F
Current opinion in nephrology and hypertension. 2019;(3):227-232
Abstract
PURPOSE OF REVIEW We will summarize recent epidemiological observations on the risk for overt diabetic kidney disease (DKD) in nonproteinuric patients, will focus on novel studies based on a proteomic biomarker of DKD and will discuss the possibility of preventing the progression of DKD in nonproteinuric patients by sodium glucose transporter 2 (SGLT2) inhibitors. RECENT FINDINGS Although less frequently than in type 2 diabetes, DKD may develop also in nonproteinuric type 1 diabetes. However, the progression rate to kidney failure in nonproteinuric diabetic people is much lower than in proteinuric ones. A new proteomic biomarker, the chronic kidney disease (CKD)273, reliably predicts the risk of incident micro and macroalbuminuria and of CKD in nonalbuminuric diabetic people. SGLT2 inhibition markedly reduces albuminuria in macro and microalbuminuric patients and discernibly mitigates albumin excretion also in those with albuminuria in the normal range. SUMMARY Studies focusing on risk factors for DKD in nonproteinuric patients are a clinical research priority. The CKD273 classifier is a promising biomarker for the early identification of nonproteinuric patients at high risk for progressive DKD. Empagliflozin and SGLT2 inhibitors may have a favorable impact on the progression of DKD in nonalbuminuric diabetic people, a hypothesis to be tested in specific clinical trials.