Urine IgM-excretion as a prognostic marker for progression of type 2 diabetic nephropathy

Although the clinical manifestations of type 2 diabetic nephropathy and decline in kidney function are similar to those in type 1, the clinical course and the renal structural changes are more heterogeneous in type 2 diabetic patients. Previous studies have shown that an increased urine IgM excretion in patients with type 1 diabetic nephropathy was associated with poor outcome. In the present follow-up study we examine the prognostic value of baseline urine IgM excretion in patients with type 2 diabetes mellitus.

Methods

A cohort of 106 (74 male and 32 female) patients with type 2 diabetes regularly attending our diabetes out-patient clinic at Skane University Hospital in Lund. They were recruited prospectively under the period between 1992 and 2004. Patients were followed-up until January 2009. The end point was cardiovascular (CV) death or end-stage renal disease (ESRD). The median follow-up time was 5 years (0.5-13 years). Participants were divided according to degree of albuminuria and IgM-uria.

Results

During follow-up time, 28 (19 male and 9 female) patients died of CV events and 41 (26 male and 15 female) developed ESRD. The risk of CV mortality was 2.4 fold, and the risk of renal failure 4.9 fold higher in patients with increased urine IgM excretion compared to patients with low urine IgM excretion. Stratified analysis showed that an increased urine IgM excretion was an independent predictor of renal and cardiovascular death irrespective of the degree of albuminuria (HR = 3.6, 95% CI: 2.1-6.0, P < 0.001).In conclusion, type 2 diabetic nephropathy patients with high urine IgM excretion rates carry an increased risk of renal and cardiovascular death.     

Urinary neutrophil gelatinase associated lipocalin (NGAL), a marker of tubular damage, is increased in patients with chronic heart failure

Renal impairment, as measured by reduced glomerular filtration rate (GFR) and increased urinary albumin excretion (UAE), is prevalent in patients with chronic heart failure (CHF) and is associated with reduced survival. The prevalence of structural tubular damage in CHF is unknown. We investigated 90 CHF patients and 20 age and sex matched healthy controls, and determined estimated GFR, UAE, N terminal-pro brain natriuretic peptide (NT-proBNP) and urinary neutrophil gelatinase associated lipocalin (NGAL) as a marker for tubular damage. CHF patients had significantly lower averaged estimated GFR (64+/-17 vs 90+/-12 mL/min/1.73 m(2), P<0.0001), but higher NT-proBNP and UAE levels (both P<0.0001). Median urinary NGAL levels were markedly increased in CHF patients compared to controls (175 (70-346) vs 37 (6-58) microg/gCr, P<0.0001). Both serum creatinine (r=0.26, P=0.006) and eGFR (r=-0.29, P=0.002) were significantly associated with urinary NGAL levels as were NT-proBNP and UAE but to a lesser extent. In conclusion, renal impairment in CHF patients is not only characterised by decreased eGFR and increased UAE, but also by the presence of tubular damage, as measured by increased urinary NGAL concentrations.     

Epidemiological investigation on chronic kidney disease in hypertension and diabetes mellitus patients in Kunming urban community

Objective To investigate the epidemiology of chronic kidney disease (CKD) in patients with hypertension and diabetes mellitus in Kunming urban area. Methods A multistage cluster randomized sampling method was used to collect 400 randomly selected patients (community managed hypertension and diabetes mellitus) in community service centers in the 4 main urban districts of Kunming, Yunnan province. The subjects were screened for CKD by questionnaires, physical examinations, and microalbuminuria tests. Results A total of 343 people were surveyed. The prevalence of albuminuria, proteinuria by routine urinalysis, decreased glomerular filtration rate, and CKD prevalence were respectively 37.3%, 12.2%, 5.0% and 39.1%.A total of 134 patients with CKD (134/343) were screened. Logistic regression analysis showed male (OR=2.312, 95%CI 1.325-4.037, P=0.003), hyperuricemia (OR=1.751, 95%CI 1.109-2.765, P=0.016) and obesity (OR=2.150, 95%CI 1.115-4.146, P=0.022) were related to CKD. Conclusions The prevalences of CKD and albuminuria are 39.1% and 37.3% in patients with chronic diseases (hypertension and diabetes) in the main urban community of Kunming, Yunnan. Hyperuricemia, male and obesity are independent risk factors for CKD.     

Dapagliflozin: potential beneficial effects in the prevention and treatment of renal and cardiovascular complications in patients with type 2 diabetes

Introduction: Diabetic kidney disease is the leading cause of end-stage renal disease, a significant contributor to cardiovascular (CV) disease, responsible for much of the morbidity and mortality in patients with type 2 diabetes (T2DM). Strategies to slow or prevent the onset and progression of diabetic kidney disease are critical for effectively managing T2DM and reducing CV risk. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are effective antidiabetic agents, which may provide nephroprotective and CV protective effects.

Areas covered: This review examines the role of the kidney in glucose homeostasis, discusses renal hemodynamic changes in diabetes, and outlines the major hypotheses regarding the mechanisms underlying renal injury in diabetes. The potential benefits of SGLT2 inhibitors in the prevention and treatment of CV complications in patients with T2DM are reviewed, with particular focus on dapagliflozin.

Expert opinion: Dapagliflozin and other SGLT2 inhibitors have the capacity to decrease hyperglycemia and visceral fat, components of the metabolic syndrome particularly associated with the progression of CV disease. However, the mechanisms of action of SGLT2 inhibitors resulting in their positive CV effects remain unclear. Furthermore, the mechanism of action of SGLT2 inhibitors on heart function in non-diabetic patients with decompensated heart failure remains to be explored.     

Pioglitazone delays proximal tubule dysfunction and improves cerebral vessel endothelial dysfunction in normoalbuminuric people with type 2 diabetes mellitus

Aim

The renal and cerebral protective effects of pioglitazone were assessed in normoalbuminuric patients with type 2 diabetes mellitus (DM).

Methods

A total of 68 normoalbuminuric type 2 DM patients were enrolled in a one-year open-label randomized controlled trial: 34 patients (pioglitazone-metformin) vs. 34 patients (glimepiride-metformin). All patients were assessed concerning urinary albumin: creatinine ratio (UACR), urinary alpha1-microglobulin, urinary beta2-microglobulin, plasma asymmetric dymethyl-arginine (ADMA), GFR, hsC-reactive protein, fibrinogen, HbA1c; pulsatility index, resistance index in the internal carotid artery and middle cerebral artery, intima-media thickness in the common carotid artery; cerebrovascular reactivity was evaluated through the breath-holding test.

Results

At 1 year there were differences between groups regarding ADMA, urinary beta2-microglobulin, urinary alpha1-microglobulin, parameters of inflammation, serum creatinine, GFR, UACR, the cerebral haemodynamic indices. Significant correlations were found between alpha 1-microglobulin-UACR (R² = 0.143; P = 0.001) and GFR (R² = 0.081; P = 0.01); beta2-microglobulin-UACR (R² = 0.241; P = 0.0001) and GFR (R² = 0.064; P = 0.036); ADMA-GFR (R² = 0.338; P = 0.0001), parameters of inflammation, HbA1c, duration of DM, cerebral indices. There were no correlations between ADMA-UACR, urinary alpha1-microglobulin and beta2-microglobulin.

Conclusion

Proximal tubule (PT) dysfunction precedes albuminuria and is dissociated from endothelial dysfunction in patients with type 2 DM. Pioglitazone delays PT dysfunction and improves cerebral vessels endothelial dysfunction in normoalbuminuric patients with type 2 DM. Key words: proximal tubule; endothelial dysfunction, albuminuria; pioglitazone.     

Beneficial Effects of L‐ and N‐type Calcium Channel Blocker on Glucose and Lipid Metabolism and Renal Function in Patients with Hypertension and Type II Diabetes Mellitus

It has been proved that cilnidipine has N‐type calcium channels inhibitory activity as well as L‐type calcium channels and inhibits excessive release of norepinephrine from the sympathetic nerve ending. This study was undertaken to compare the efficacy of amlodipine (an inhibitor of L‐type calcium channels) and cilnidipine (an inhibitor of both L‐type and N‐type calcium channels) in patients with hypertension and type II diabetes mellitus. Seventy‐seven hypertensive patients were divided into two groups according to presence/absence of type II diabetes mellitus. In these two groups of patients, the effects of amlodipine and cilnidipine on glucose and lipid metabolism and renal function were compared. As for glucose and lipid metabolism, homeostasis model assessment insulin resistance (HOMA‐R) level in the non‐diabetic group and triglyceride in the diabetes group were significantly lower with cilnidipine than with amlodipine. As regards renal function in the diabetic group, estimated glomerular filtration rate (eGFR) was significantly higher and urinary albumin/creatinine ratio was significantly lower with cilnidipine than with amlodipine. Cilnidipine which inhibits N‐type calcium channels is more useful for patients with hypertension and diabetes mellitus from its effects on glucose and lipid metabolism and renal function.     

糖尿病患者尿液中期因子与糖尿病肾病的关系

目的探讨尿液中期因子（MK）与糖尿病肾病的关系。方法96例糖尿病患者,根据尿白蛋白排泄率分为正常白蛋白尿组（NUAlb组）,微量白蛋白尿组（MUAlb组）,大量白蛋白尿组（CUAlb组）,设对照组（NC组）。用酶联免疫吸附法测定尿液MK水平。结果CUAlb组尿液MK水平高于NC组、NUAlb组及MuAlb组（P〈0．01）,MUAlb组高于NC组及NUAlb组（P〈0．05）,NUAlb组与NC组差异无统计学意义（P〉O．05）。相关分析显示,尿液MK与尿白蛋白排泄率（r=0．40,P〈O．05）及病程（r=0．23,P〈0．05）呈正相关,与内生肌酐清除率（CCr）呈负相关（r=-0．20,P=〈0．05）。结论尿液MK可能参与临床糖尿病肾病的发生。     

2型糖尿病患者脂联素及脂联素基因启动子区多态性与白蛋白尿的相关性

目的 研究2型糖尿病患者血浆脂联素水平及脂联素基因启动子区-11377位点单核苷酸多态性(SNP)与尿白蛋白排泄率(UAER)之间的关系.方法 按1999年世界卫生组织制定的糖尿病诊断标准,自2006年4月至2009年4月选取福建医科大学附属第二医院内分泌科2型糖尿病患者403例,根据24 h UAER分为正常组(UAER<30 mg/24 h,NAU组)201例、微量白蛋白尿组(30 mg/24 h≤UAER<300 mg/24 h,MiAU组)134例和大量白蛋白尿组(UAER≥300 mg/24 h,MaAU组)68例.采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术,检测脂联素基因启动子区SNP-11377C→G多态性.同时检测血浆脂联素、血脂、血糖、空腹胰岛素、血肌酐和内生肌酐清除率.脂联素水平与临床指标的相关性采用简单相关分析和偏相关分析.结果 脂联素水平随UAER增高呈递增趋势[NAU、MiAU、MaAU组分别为6.33(0.10～24.32)mg/L,6.97(0.25～20.12)mg/L,9.38(1.88～26.99)mg/L],MaAU组显著高于NAU和MiAU组(P<0.01).脂联素水平与血浆肌酐呈正相关(r=0.212,P<0.01),与肌酐清除率呈负相关(r=-0.157,P<0.05),与稳态模型胰岛素抵抗指数(HOMA-IR)呈负相关(r=-0.215,P<0.01).脂联素基因启动子SNP-11377C→G的基因型(CC型、CG型和GG型)和等位基因频率分布在NAU组、AU组间的差异无统计学意义(P>0.05).未发现启动子区SNP-11377C→G与脂联素水平有关.结论 2型糖尿病患者血脂联素随糖尿病肾病进展白蛋白尿加重而增高.未发现福建地区2型糖尿病患者脂联素基因启动子区-11377C→G多态性与UAER明显相关.