Resveratrol reduces albuminuria in diabetic nephropathy: A randomized double-blind placebo-controlled clinical trial

Aim

Albuminuria is the most important indicator of diabetic nephropathy (DN). Resveratrol, a natural compound found in grape skins and red wine, has antioxidant effects. This study aimed to evaluate the effects of resveratrol on DN.

Assessment of kidney function and associated risk factors among type 2 diabetic patients

Aimdiabetic patients are required for continuous monitoring programs hence continuous assessment of kidney function parameters is crucial. So, we aimed to determine the prevalence of Chronic Kidney Disease (CKD) and abnormal renal parameters, with poorly controlled type 2 diabetes mellitus pateintsMaterials and methodsA cross-sectional study was carried out at private health care centre. A total of 300 diabetic patients aged 18 years and above attended the clinic from February 2018 to Dec 2018 were included. Socio-demographic, clinical, and laboratory data were obtained from the medical records of patients. Statistical analysis was carried out using (SPSS, version 23).Resultsout of the 300 diabetes patients recruited 42% of patients with type 2 diabetes had abnormal Creatinine Serum levels and 22.3% had abnormal glomerular filtration rate (GFR). Abnormal albumin urine levels were found in 28.3% and 11.3% had abnormal creatinine in urine. Abnormal Albumin: Creatinine Ratios (Alb/Cr), were found in 23%. Of the total, 77% (n = 231) had normal Alb: Cr Ratio, 20% had risk of nephropathy and 9% had nephropathy.ConclusionCurrent study revealed a high prevalence of abnormal renal parameters in patients with type 2 diabetes Mellitus. This necessitates the need for early and universal screening of renal functions. There is also an urgent demand for measures that target tight glycaemic, Vitamin D level and life style modifications is also required to all diabetic patients to achieve target value of HbA1C ≤ 7.     

Microalbustix试纸检测2型糖尿病患者微量白蛋白尿的临床评价

用Microalbustix试纸测定95例2型糖尿病患者尿微量白蛋白的敏感性，准确性和特异性。结果分别为89％，96％和100％。这与化学发光法测定结果无明显差异。     

Microalbuminuria is an early response following acute myocardial infarction

Ninety-six patients admitted to two coronary care units withsuspected acute myocardial infarction were studied. The diagnosiswas confirmed in 44, the remaining 52 were used as a controlgroup. The first urine passed after admission, together withearly morning urines on the following 3 days, were saved inall patients. Urinary albumin and IgG were measured by automatedimmunoturbidimetry and expressed as the protein creatinine ratioin mg.mmol^–1. The log mean (SD) albumin creatinine ratiosfor the first urine passed in the myocardial infarction andnon-myocardial infarction patient groups were 6.2(4.2) and 1.3(3.4)respectively. The difference in log mean albumin creatinineratio was 4–9 mg.mmol^–1, 95% CI3.4 to 6.2 mg.mmol^–1t=6.127 df=94, P<0.0001. The median IgG creatinine ratiofor the first urine passed after admission in myocardial infarctionpatients was 1.0 mg.mmol^–1 (95% Cl 0.5 to 1.2) and fornon-myocardial infarction patients 0.3 (95% Cl 0.2 to 0.4).Increased urinary protein excretion appears to be an early andproportional response to acute myocardial infarction.     

Reversible tubular proteinuria precedes microalbuminuria and correlates with the metabolic status in diabetic children

Early tubular alterations were studied in 53 children with insulin-dependent diabetes mellitus (IDDM), 32 of whom were followed at regular 6-monthly intervals for 3 years. The urinary levels of retinol-binding protein (RBP), ₂-microglobulin and brush border antigens and brush border antigens (BBA) (determined by monoclonal enzyme immunoassay) were taken as indices of functional and cellular tubular alterations; urinary albumin was considered an early marker of glomerular alterations. All indices of tubular alterations were higher in IDDM children than in 368 normal children, while albuminuria was unchanged. Urinary levels of BBA, however, varied widely during follow-up, with 25 of the 32 IDDM patients who were followed at regular intervals having pathological values for BBA on at least one occasion, folowed by normalization. Metabolic alteration was found to be the main cause of this variability, since a high statistical correlation was found between urinary BBA and fructosamine (P<0.001) and between RBP and the stable fraction of glycosylated haemoglobin (P<0.001). The data confirm that transient tubular proteinuria occurs in diabetic children before any other marker of renal involvement such as microalbuminuria. The maintenance of good metabolic control is essential to normalize this early abnormality that can be considered a reversible sign of functional renal involvement.     

人参固本口服液联合泼尼松治疗成人肾病综合征的疗效观察

目的:探讨人参固本口服液联合泼尼松治疗成人肾病综合征的疗效,为临床治疗提供参考。方法:选取2017年3月至2018年2月西南医科大学附属医院肾病内科收治的肾病综合征患者108例作为研究对象,随机分为对照组、观察组A(低剂量组)和观察组B(高剂量组),每组36例。对照组患者给予泼尼松治疗,初始剂量1. 0 mg/(kg·d),最大剂量60 mg/d,尿蛋白转阴或每日最大剂量服用4周后减量,每周减少10%剂量,直至调至20 mg/d,并在2个月后减量至10 mg/d,以10 mg/d维持至疗程结束。观察组A在对照组基础上,给予口服人参固本口服液治疗,每次餐前口服10 mL,2次/d,1周后减量至1次/d,继续服用1周后减量,口服5 mL/次,隔日顿服,并以此剂量维持至疗程结束。观察组B在对照组基础上,给予口服人参固本口服液治疗,每次餐前口服10 mL,2次/d,1周后减量至1次/d,并以此剂量维持至疗程结束。观察组A和观察组B的疗程均为1个月。比较3组的治疗效果。结果:3组患者在疗程结束后总治愈率有明显差别,观察组A和观察组B的总有效率分别为94. 44%、97. 22%,均优于对照组的总有效率77. 22%,差异有统计学意义(P 0. 05)。但观察组A和观察组B总有效率比较,差异无统计学意义(P 0. 05)。观察组A和观察组B患者的尿液蛋白指标和血脂水平均低于对照组,差异有统计学意义(P 0. 05)。但观察组A、观察组B的尿液蛋白指标和血脂水平比较,差异无统计学意义(P 0. 05)。观察组A不良反应发生率比观察组B低,差异无统计学意义(P 0. 05)。结论:人参固本口服液联合泼尼松治疗肾病综合征的疗效显著,明显优于泼尼松单独治疗。但临床建议使用低剂量的人参固本口服液联合泼尼松治疗肾病综合征。     

Diabetes and kidney disease: the role of sodium–glucose cotransporter-2 (SGLT-2) and SGLT-2 inhibitors in modifying disease outcomes

Patients with type 2 diabetes (T2D) often have coexisting chronic kidney disease (CKD). However, healthy renal function is crucial in maintaining glucose homeostasis, assuring that almost all of the filtered glucose is reabsorbed by the sodium glucose cotransporters (SGLTs) SGLT-1 and SGLT-2. In diabetes, an increased amount of glucose is filtered by the kidneys and SGLT-2 is upregulated, leading to increased glucose absorption and worsening hyperglycemia. Prolonged hyperglycemia contributes to the development of CKD by inducing metabolic and hemodynamic changes in the kidneys. Due to the importance of SGLT-2 in regulating glucose levels, investigation into SGLT-2 inhibitors was initiated as a glucose-dependent mechanism to control hyperglycemia, and there are three agents currently approved for use in the United States: dapagliflozin, canagliflozin, and empagliflozin. SGLT-2 inhibitors have been shown to reduce glycated hemoglobin (A1C), weight, and blood pressure, which not only affects glycemic control, but may also help slow the progression of renal disease by impacting the underlying mechanisms of kidney injury. In addition, SGLT-2 inhibitors have shown reductions in albuminuria, uric acid, and an increase in magnesium. Caution is advised when prescribing SGLT-2 inhibitors to patients with moderately impaired renal function and those at risk for volume depletion and hypotension. Published data on slowing of the development, as well as progression of CKD, is a hopeful indicator for the possible renal protection potential of this drug class. This narrative review provides an in-depth discussion of the interplay between diabetes, SGLT-2 inhibitors, and factors that affect kidney function.     

The safety of isotretinoin in patients with lupus nephritis: a comprehensive review

Oral isotretinoin (13-cis-retinoinc acid) is a derivative of vitamin A and belongs to the first generation of retinoids, which act as synthetic isomers of retinoic acid (RA). It is a very effective agent in a treatment of acne vulgaris; however, multiple side effects related to therapy with retinoids preclude the use of isotretinoin in less severe acne vulgaris. A significant limitation for the administration of isotretinoin appears in case of concomitant kidney disease with a special attention regarding the safety of the agent in patients with lupus nephritis (LN). The aim of this review is an assessment of the safety of isotretinoin for the treatment of acne vulgaris in patients with LN. We searched both MEDLINE and SCOPUS databases, as well as several dermatological textbooks, to present all limitations and benefits of therapy with isotretinoin or its isomer (ATRA) for patients with kidney diseases. Several mouse models of SLE revealed a significant modulatory influence of retinoids on autoimmune injury of the glomerular unit. Retinoids were demonstrated to affect mononuclear cell infiltrations of renal tissue allowing for a reduction in the overall glomerular damage. Presumptively, they can affect a synthesis of autoantibodies significantly limiting their deposition in the glomerular unit. Moreover, retinoids were also shown to affect the synthesis of different cytokines specific both for lymphocytes Th1 (IL-2, IL-12, INFγ) ant Th2 (IL-4, IL-10). The influence of retinoids on the course of LN seems to be more multidimensional than only restricted to immune aspects and these synthetic RA isomers manifest also antiproteinuric activity in comparable extent to steroidal agents. The agents were demonstrated to counteract a loss of podocytes after the injury of the glomerular unit. They can promote a differentiation of renal progenitor cells (RPCs) within the Bowman capsule into mature podocytes leading to regeneration of podocyte number. Additionally, retinoids can probably protect podocytes from injury limiting their apoptosis, as well as reducing foot process effacement. Although, an endogenous production of RA isomers increases after the injury of the glomerular unit aiming to the restoration of podocyte number, it can be significantly impaired by a loss of albumins into urine. RA isomers are progressively sequestered by albumin within the Bowman’s space and therefore, they are quickly eliminated with urine. It was demonstrated that the administration of exogenous RA isomers (retinoids) can bypass the activity of albumins enhancing the regeneration of podocytes. Finally, retinoids can regulate the production of vasoactive substances influencing on different vascular functions in the kidney. They can beneficially change a balance of angiotensin metabolites through by down-regulation of angiotensin-converting enzyme type 1 and the enhancement of an expression of angiotensin-converting enzyme type 2. Another studies revealed that retinoids could also alter the activity of renal endothelin pathway; however, the significance of this effect requires further elucidation. Taken all these presented effects of retinoids in the kidney into consideration, we can conclude that isotretinoin can be the safe treatment option of acne vulgaris in patients with LN.     

The influence of the ACE inhibitor lisinopril on the glomerular metabolism of proteolytic enzymes in diabetic rats

Clinical studies indicate a nephro-protective effect in conjunction with the use of ACE inhibitors. This study's aim was to determine whether ACE inhibitors influence the metabolism of glomerular cells in addition to their known hemodynamic effects. Streptozotocin diabetic rats were treated with lisinopril (DLis 1.5 mg/l water), or hydralazine (Dhyd, 50 mg/l water) over 4 weeks. Untreated diabetic rats (DC) and non-diabetic rats (C) served as controls. After four weeks of treatment, urinary excretion of albumin, blood pressure and metabolic control (Glyc-Hb) were measured. After treatment glomeruli were isolated and homogenized, and β-NAG and total proteolytic activity against azocasein were measured. Glycated hemoglobin levels were similar in all diabetic groups (DC, 12%, Dhyd, 10%; DLis 11%). Blood pressure of DLis rats (79 ± 3 mmHg) and DHyd rats (46 ± 2 mmHg) was lower than that of DC rats (111 ± 3 mmHg). Urinary albumin excretion of diabetic groups was lowest in DLis. Diabetic rats showed a decrease in glomerular β-NAG (10 vs. 60.5 U/g protein) and total proteolytic activity against azocasein (148 vs. 170 U/mg protein hour) compared to non-diabetic rats. Lisinopril increased β-NAG (30 vs. 14 U/g protein) and total proteolytic activity (160.5 vs. 141.5 U/mg protein hour) compared with hydralazine. Our study confirms that the nephro-protective effect of ACE inhibitors is partially due to modulatory effects on the metabolism of basement membrane proteins. Received: 2 February 2000 / Accepted in revised form: 2 March 2001