Non-diabetic renal disease with or without diabetic nephropathy in type 2 diabetes: clinical predictors and outcome

Abstract

Background: Renal involvement in type 2 diabetes is mostly due to diabetic nephropathy (DN), but a subset of diabetic patients could present with pure non-diabetic renal disease (NDRD) or NDRD superimposed on DN. We conducted a prospective cohort study to identify the underline renal pathology in type 2 diabetic patients with defined clinical criteria for renal biopsy. Methods: A total of 46 patients (27 female, mean age of 48.9?±?11.9 years) with type 2 diabetes mellitus (DM) and atypical features of DN with unexpected proteinuria, hematuria, and/or renal impairment were enrolled in this study. Results: Of 46 patients with type 2 diabetes, 16 (34.8%) had DN, 20 (43.5%) had NDRD, and 10 (21.7%) had NDRD superimposed on DN. Membranous nephropathy (34%) was the most common NDRD. Patients with NDRD had a lower frequency of diabetic retinopathy (5%), shorter duration of diabetes, higher range of proteinuria, and better kidney survival. In multiple logistic regression analysis, only lack of diabetic retinopathy was independent predictor of NDRD. Positive and negative predictive value of diabetic retinopathy (DR) for diabetic nephropathy was 94 and 68%, respectively. Conclusion: Kidney biopsy is strongly recommended for patients with type 2 diabetes and atypical renal presentation for DN, particularly in the absence of DR. This approach could lead to diagnosis of NDRD with better renal survival.     

Renal pathological change in patients with type 2 diabetes is not always diabetic nephropathy: a report of 52 cases

AIMS: The present study examined the relationship between clinical features and renal histological changes in the Type 2-diabetic patients and evaluated the usefulness of renal biopsy in the diagnosis of diabetic versus non-diabetic kidney disease. METHODS: 52 patients with Type 2-diabetic mellitus were retrospectively analyzed for differential clinical, laboratory features and pathological characteristics including overt proteinuria (> 0.5 g/day), elevated serum creatinine and/or the development of hematuria. RESULTS: Of 52 patients, 20 cases (38.5%) showed no detectable diabetic lesions and, thus, were diagnosed as non-diabetic renal disease (NDRD), while 32 patients (61.5%) exhibited diabetic nephropathy. Interestingly, while 29 patients showed diabetic nephropathy (DN) alone, NDRD was also found in 3 patients with DN. Clinically, 24 out of 52 patients (46.16%) had a diagnosis consistent with the pathological findings, while 10 (19.23%) were diagnosed incorrectly. Compared to NDRD patients, patients with DN had prolonged diabetic history with or without retinopathy, while 25% of patients with NDRD exhibited mesangial proliferative glomerulonephritis. CONCLUSIONS: NDRD was a common feature in Type 2-diabetic patients with renal involvement. The absence of retinopathy and short periods of diabetic history may be useful indicators for diagnosis of NDRD clinically.     

Renal pathology and clinical features of patients with type 2 diabetes mellitus and chronic kidney disease

Objective To retrospectively investigate the pathological and clinical characteristics of diabetic nephropathy and non-diabetic nephropathy diagnosed with renal pathology. Methods Data of 110 patients diagnosed as type 2 diabetes mellitus combined with chronic kidney disease (CKD) and conducted renal biopsy from January 2004 to December 2013 in our hospital were retrospectively analyzed. According to pathological diagnosis, patients were categorized into three groups: DN group, NDRD group and DN with NDRD group (MIX group). Results Membranous nephropathy was the most prevalent pathological type in NDRD group while IgA nephropathy was the major pathological type in MIX group. Compared with NDRD, DN patients had a higher anemia and diabetic retinopathy(DR) rate (all P＜0.05). The prevalence of having both nephrotic range proteinuria and kidney function decrease was higher in DN than NDRD (P＜0.05). Conclusions Renal pathology is important for the differential diagnosis of DN and NDRD since there is a relatively high rate of NDRD in patients with type 2 diabetes mellitus and CKD.     

糖尿病肾病与非糖尿病性肾脏疾病的对比分析及其诊断概率回归方程的建立

目的 对比分析糖尿病肾病和糖尿病合并的非糖尿病性肾脏疾病的不同临床特征，探索两组疾病的临床鉴别诊断依据，建立糖尿病肾病诊断概率回归方程。方法肾活检前临床诊断为糖尿病肾病患者共110例，经肾活检后，按病理诊断分为两组：DN组(糖尿病肾病)60例，NDRD组(非糖尿病性肾脏疾病)50例。对两组资料进行统计分析。结果单因素及多因素回归分析显示，糖尿病患病时间、收缩压、糖化血红蛋白、有无血尿和视网膜病变与糖尿病肾病诊断相关。由所得参数建立糖尿病肾病诊断概率回归方程。经检验，方程判断糖尿病肾病灵敏度为90%，特异度为92％，阳性预测值为93％，阴性预测值为88％，准确率为91％。结论2型糖尿病伴肾脏损害并不一定是糖尿病肾病，相当部分是非糖尿病性肾脏疾病，回归方程的建立可为临床鉴别诊断提供帮助。     

Development and validation of a predictive model for the differential diagnosis of diabetic nephropathy and non-diabetic renal disease in patients with type 2 diabetes mellitus

Objective To develop and validate a predictive model for the differential diagnosis of diabetic nephropathy (DN) and non-diabetic renal disease (NDRD) in patients with type 2 diabetes mellitus. Methods A retrospective study with patients with type 2 diabetes who underwent renal biopsy in the First Affiliated Hospital of Zhengzhou University from February 2012 to January 2015 was conducted. The dataset was randomly split into development (70.0%) and validation (30.0%) cohorts. Baseline predictors for model development was selected by using univariable and multivariable logistic regression. The model's performance in the two cohorts, including discrimination and calibration, was evaluated by the C-statistic, calibration curve and the P value of the Hosmer-Lemeshow test. Results Among the 931 patients with type 2 diabetes, 478 cases (51.3%) diagnosed as DN alone, 214 cases (23.0%) as NDRD alone and 239 cases (25.7%) as DN plus superimposed NDRD (MIX). Among NDRD and MIX patients, membranous nephropathy was the most common pathological type, followed by IgA nephropathy. The variables selected in the final predictive model were age, duration of diabetes, diabetic retinopathy, systolic blood pressure, hemoglobin, fasting blood glucose, glycosylated hemoglobin, cystatin C. The model performed well with good discrimination and calibration. The C-statistics were 0.913(95%CI 0.892-0.935) in the derivation cohort and 0.897(95%CI 0.876-0.919) in the validation cohort. The model had the best P value of 0.934 of the Hosmer-Lemeshow test. Conclusions A simple predictive model with high accuracy is constructed for predicting the presence of NDRD and MIX for type 2 diabetic patients. The nomogram can be used as a decision support tool to provide a non-invasive method for differential diagnosis of DN and NDRD, which may help clinicians assess the risk-benefit ratio of kidney biopsy for type 2 diabetic patients with renal impairment.     

Clinical predictors of non-diabetic renal disease in patients with non-insulin dependent diabetes mellitus

Background: Several studies had suggested that non-diabetic renal disease (NDRD) was common among non-insulin dependent diabetes mellitus (NIDDM) patients with renal involvement. Methods: We prospectively studied the prevalence of NDRD among a Chinese NIDDM population. Renal biopsy specimens were evaluated with light-, immunohistological and electron-microscopy. The cohort consisted of 51 patients who had NIDDM and proteinuria >1 g/24 h. Results: Patients with both isolated diabetic nephropathy (DN, n=34) and NDRD (n=17) had comparable duration of DM, creatinine clearance, serum creatinine, albumin and glycosylated haemoglobin levels, as well as incidences of retinopathy, neuropathy and hypertension. Significantly more patients with NDRD had microscopic haematuria (P=0.043) or non-nephrotic proteinuria (P=0.004). IgA nephropathy accounted for 59% of the NDRD identified. Conclusions: In this study, microscopic haematuria and non-nephrotic proteinuria predicted the presence of NDRD among NIDDM patients presenting with renal disease.     

血红蛋白在鉴别糖尿病肾病与非糖尿病肾脏疾病中的作用

目的探讨血红蛋白在鉴别糖尿病肾病(DN)与非糖尿病肾脏疾病(NDRD)中的临床意义。 方法对2004年1月至2012年4月在解放军总医院肾脏病科行肾活检、病理诊断明确且病史资料完整的66例DN、78例NDRD患者进行回顾性分析,比较两组临床指标及合并症的差异,采用多因素Logistic回归分析方法明确DN的独立危险因素;比较DN及NDRD组不同CKD分期的血红蛋白水平差异,明确其贫血性质及贫血相关的独立危险因素。 结果DN组糖尿病罹病时间、肾病罹病时间、平均动脉压、血清肌酐、尿素氮、24 h尿蛋白定量水平及合并糖尿病视网膜病变、心血管病、贫血的比例均高于NDRD组,差异具有统计学意义(P<0.05);多因素分析显示糖尿病罹病时间长(OR＝1.012,95%CI 1.005～1.019)、合并糖尿病视网膜病变(OR＝ 4.265,95%CI 1.616～11.255)、血红蛋白水平低(OR＝ 0.952,95%CI 0.929～0.976)及合并心血管病(OR＝2.875,95%CI 1.089～7.593)是DN的独立危险因素;CKD1～3期DN组及NDRD组的血红蛋白水平均存在显著性差异(P<0.05),该差异在CKD 4～5期消失;DN及NDRD组共有60例诊断为贫血,均为正细胞正色素性贫血;多因素Logistic回归分析显示白蛋白降低(OR＝0.928,95%CI 0.879～0.980)、血清肌酐升高(OR＝1.011,95%CI 1.004～1.019)、病理诊断为DN(OR＝6.213,95%CI 2.690～14.347)是贫血的独立危险因素。 结论血红蛋白与DN显著独立相关,早期对血红蛋白水平的监测可能为临床鉴别DN与NDRD提供新线索。     

Relationship of p22phox C242T polymorphism with nephropathy in type 2 diabetic patients

BACKGROUND: In this case-control study, we investigated the possible involvement of the p22phox C242T polymorphism in the development and progression of diabetic nephropathy (DN) in 535 Caucasian Brazilians with type 2 diabetes. We also evaluated the effects of the interaction of the C242T polymorphism with smoking and hypercholesterolemia on the susceptibility to nephropathy. METHODS: Genotype analysis was performed using polymerase chain reaction (PCR) followed by digestion with restriction enzyme. Logistic regression analysis was used to control for independent risk factors associated with nephropathy. RESULTS: The genotype frequencies in patients with overt DN (CC/CT/TT: 0.36/0.47/0.17) were not significantly different from those of diabetic individuals with normoalbuminuria (0.47/0.41/0.12) or microalbuminuria (0.42/0.48/0.10) (p=0.214). Likewise, there were no differences in the T allele frequency among patients with normoalbuminuria, microalbuminuria or overt DN (0.33, 0.34 and 0.40, respectively; p=0.111). However, the T allele was found to be more frequent among smokers with overt nephropathy (macroalbuminuria and/or in dialysis) than those who had normoalbuminuria (43 vs. 32%, p=0.045). The multiple logistic regression analysis confirmed that the CT+TT genotypes were independently associated with a higher risk of having overt nephropathy among smokers [odds ratio (OR)=6.76, 95% confidence interval (95% CI) 1.83-25.02]. CONCLUSIONS: Our study shows a gene-environment interaction associated with the increased risk of DN progression in Caucasian Brazilian smokers with type 2 diabetes. Further studies should be performed to clarify whether it exists, and to what extent there is a relationship between the p22phox C242T polymorphism and DN.     

2型糖尿病合并肾脏损害的病理与临床分析

目的 分析2型糖尿病患者出现肾脏病变时病理诊断与临床表现的关系.探讨肾活检在2型糖尿病伴有肾脏病变诊断的意义.方法 分析52例尿检异常和（或）Scr升高的2型糖尿病患者的临床特征和病理改变特点.结果 52例2型糖尿病患者经肾活检,32例确诊为糖尿病肾病（DN）,占61.5%,其中3例为糖尿病肾病合并非糖尿病性肾脏疾病（NDRD）;余20例为非糖尿病性肾脏疾病,占38.5%.肾活检前后诊断符合率46.15%,误诊率19.23%.两组间除BUN、Scr、糖尿病病程和是否伴有糖尿病性视网膜病变有显著差异外,其他临床表现和实验室检查的差异均无统计学意义.结论 2型糖尿病伴肾脏病变时相当部分是非糖尿病性肾脏病变,单纯依靠临床资料常难以鉴别,肾活检对明确糖尿病伴肾病变的性质具有重要的意义.     

2型糖尿病并发慢性肾脏病临床病理特点分析

目的 研究2型糖尿病并发慢性肾脏病（CKD）患者的肾脏损害类型及临床特点。 方法 回顾性分析155例伴显性白蛋白尿的2型糖尿病患者的肾脏损害病理类型及临床特点。根据病理表现分为典型糖尿病肾小球病（DG）组、不典型糖尿病相关肾脏病（ADRD）组、非糖尿病肾病组（NDRD）和DG并发NDRD组。 结果 DG占18.7%,ADRD占12.9%,NDRD占60.0%,DG并发NDRD占8.4%。DG的糖尿病病程较长,空腹血糖较高,糖尿病视网膜病变（DR）发生率较高,收缩压和平均动脉压较高,尿蛋白量较多,GFR下降更明显。ADRD组年龄较小,体质量指数和肥胖比例较高。NDRD组多可见肉眼血尿和急性肾功能下降,对诊断NDRD有一定预测价值的因素有不伴DR、糖尿病病程小于5年、肉眼血尿、急性肾功能下降、自身免疫性疾病证据和尿蛋白量≥3.5 g/24 h且eGFR≥60 ml/min。 结论 2型糖尿病并发CKD的肾脏病理表现多样,NDRD常见,且与ADRD和DG有差异。如2型糖尿病并发慢性肾脏病患者出现以下任何1项：2型糖尿病病程少于5年、不伴DR、肉眼血尿史、急性肾功能下降、尿蛋白量≥3.5 g/24 h但eGFR≥60ml/min、有导致肾损害的系统性疾病证据,应考虑肾活检明确病理诊断。     

Non diabetic renal disease in type 2 diabetes mellitus

AIM: The aim of this analysis of renal biopsies in people with type 2 diabetes was to know the prevalence and nature of non-diabetic renal disease (NDRD) and to note its correlation with the duration of diabetes, extent of proteinuria and presence or absence of retinopathy. METHODS: From January 2000 to December 2004, 160 people with type 2 diabetes with clinically suspected NDRD underwent renal biopsy reported by a single pathologist. The case records of these patients were retrospectively analysed. Based on the biopsy findings, patients were grouped as Group I, isolated NDRD; Group II, NDRD with underlying diabetic glomerulosclerosis; and Group III, isolated diabetic glomerulosclerosis. The relation of histology with clinical profile in each group was noted and statistically analysed using strata 6 software. RESULTS: Of the 160 patients studied, 118 were males and 42 were females (2.8:1). The average age was 51.35 years (30-79). Indications for renal biopsy included: nephrotic syndrome in 55 (34.37%), acute renal failure (ARF) in 49 (30.62%), rapidly progressive renal failure (RPRF) in 24 (15%), absent retinopathy in 19 (11.87%), haematuria in 10 (6.25%) and acute on chronic renal failure (CRF) in three (1.87%) patients. Group I included 68 patients (42.50%), Group II included 48 patients (30%) and Group III included 44 patients (27.50%). The mean duration of diabetes was 5.37, 10.12 and 6.86 years in Groups I, II and III respectively. The duration of diabetes was significantly less in Group I compared with Group II and III combined (5.37 vs 8.53; P < 0.001). Diabetic retinopathy was absent in 61 (38.13%) patients, of whom 41 (67.21%) had isolated NDRD. The most common NDRD were acute interstitial nephritis (18.1%), post infectious glomerulonephritis (17.24%), membranous nephropathy (11.20%) and focal segmental glomerulosclerosis (7.75%). CONCLUSIONS: Prevalence of NDRD (either isolated or superimposed on underlying diabetic glomerulosclerosis) is very high in appropriate clinical settings. The shorter duration of diabetes and the absence of retinopathy, especially when associated with nephrotic proteinuria, strongly predict NDRD.     

Nondiabetic Renal Disease in Type 2 Diabetic Patients: A Review of our Experience in 220 Cases

Background: The purpose of this retrospective study was to evaluate the renal biopsies performed on type 2 diabetic patients for suspicion of nondiabetic renal disease (NDRD) and to correlate the pathological finding with the clinical and laboratory findings. Methods: From January 1999 to December 2009, 220 people with type 2 diabetes for clinically suspected NDRD underwent renal biopsy. The case records of these patients were retrospectively analyzed. Based on the biopsy findings, patients were divided into two groups: Group I, isolated diabetic glomerulosclerosis (DGS), and Group II, NDRD with underlying DGS. Clinical and laboratory data were analyzed in relation to the histopathological findings. Results: Of the 220 patients studied, 153 were males and 67 were females. The average age was 51.35 years (30–79). Renal biopsy showed that 100 patients (45.5%) had NDRD with underlying DGS. Group II had a significantly higher level of proteinuria and hematuria but less frequent diabetic retinopathy. There was no significant difference between the two groups in age, duration of diabetes, presence of hypertension, serum creatinine, and glomerular filtration rate. IgA nephropathy was the most common, accounting for 34% of Group II, membranous nephropathy ranked second accounting for 22.0%, followed by mesangial proliferative nephritis for 14%. Conclusion: This study showed that IgA nephropathy is the commonest NDRD among diabetics. The absence of retinopathy, especially when associated with nephritic proteinuria and hematuria, strongly predicts NDRD superimposed on DGS. Renal biopsy should be performed in diabetics when the clinical scenario is atypical.     

Diabetic nephropathy: Is it time yet for routine kidney biopsy?

Diabetic nephropathy (DN) is one of the most important long-term complications of diabetes. Patients with diabetes and chronic kidney disease have an increased risk of all-cause mortality, cardiovascular mortality, and kidney failure. The clinical diagnosis of DN depends on the detection of microalbuminuria. This usually occurs after the first five years from the onset of diabetes, and predictors of DN development and progression are being studied but are not yet implemented into clinical practice. Diagnostic tests are useful tools to recognize onset, progression and response to therapeutic interventions. Microalbuminuria is an indicator of DN, and it is considered the only noninvasive marker of early onset. However, up to now there is no diagnostic tool that can predict which patients will develop DN before any damage is present. Pathological renal injury is hard to predict only with clinical and laboratory findings. An accurate estimate of damage in DN can only be achieved by the histological analysis of tissue samples. At the present time, renal biopsy is indicated on patients with diabetes under the suspicion of the presence of nephropathies other than DN. Results from renal biopsies in patients with diabetes had made possible the classification of renal biopsies in three major groups associated with different prognostic features: diabetic nephropathy, non-diabetic renal disease (NDRD), and a superimposed non-diabetic condition on underlying diabetic nephropathy. In patients with type 2 diabetes with a higher degree of suspicion for NDRD, it is granted the need of a renal biopsy. It is important to identify and differentiate these pathologies at an early stage in order to prevent progression and potential complications. Therefore, a more extensive use of biopsy is advisable.     

Expression of human nephrin mRNA in diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is associated with functional changes in the filtration barrier, and microalbuminuria is a strong predictor of the development of overt DN. Nephrin is a novel podocyte-specific protein which localizes at the slit diaphragm. This study examines the expression of nephrin mRNA in the kidneys of type 2 diabetics with DN. METHODS: Renal tissues were obtained from 13 type 2 diabetics with DN. We also examined samples from five patients with minimal change nephrotic syndrome (MCNS) and five normal kidneys (normals) as control. The severity of DN was classified into two grades based on histopathological findings. DN grade 1 (DN1 = seven patients) presented mild mesangial expansion, and DN grade 2 (DN2 = six patients) moderate mesangial expansion. Nephrin mRNA was quantitated and localized by in situ hybridization. RESULTS: Cells positive for nephrin mRNA were detected exclusively in glomerular epithelial cells. The percentage of cells positive for nephrin mRNA in DN2 was significantly lower than in MCNS and normal kidneys. Furthermore, there was an inverse correlation between the percentage of cells positive for nephrin mRNA and extent of proteinuria. CONCLUSION: The low expression of nephrin mRNA may be closely linked to development and/or progression of proteinuria in human diabetic nephropathy.     

Diabetes mellitus as a cause or comorbidity of chronic kidney disease and its outcomes: the Gonryo study

Background

Diabetes mellitus (DM) is a major cause of end-stage kidney disease (ESKD). However, the difference in renal outcomes between DM patients with non-diabetic renal disease (DM and NDRD) and those with diabetic nephropathy (DN) is controversial. The aim of the present study was to evaluate the differences among patients with DN, DM, and NDRD, and non-DM chronic kidney disease (CKD) in a prospective observational study.

Methods

We extracted the data of 2484 patients from 11 nephrology care centers and categorized into three groups as described above. The primary outcome was ESKD requiring renal replacement therapy.

Results

During the median follow-up of 4.44 years, 281 patients (11.3%) developed ESKD. Renal outcomes of DM and NDRD patients were similar to those of non-DM patients (p ≥ 0.05). At CKD stage G3b, the hazard ratios (95% confidence intervals) of ESKD were 7.10 (2.46–20.49) in DN patients and 0.89 (0.19–4.24) in DM and NDRD. The annual change in the estimated glomerular filtration rate (eGFR) in DN patients was significantly larger than that in other groups at stage G3b (?9.7%/year).

Conclusions

We found that DN patients have a higher risk for ESKD than DM and NDRD or non-DM patients. In particular, GFR rapidly declined in DN at stage G3b. DM and NDRD patients can accomplish equally beneficial renal outcomes as non-DM CKD, regardless of their similar metabolic profiles as DN. In conclusion, we should prudentially consider the risk stratification of DM whether cause or comorbidity of CKD.

     

The need for early predictors of diabetic nephropathy risk: is albumin excretion rate sufficient?

Initial studies showing an approximately 80% rate of progression from microalbuminuria (MA) to proteinuria in type 1 diabetic patients led to the broad acceptance of MA as a useful clinical predictor of increased diabetic nephropathy (DN) risk. Some MA patients, however, have quite advanced renal structural changes, and MA may, in these cases, be a marker rather than a predictor of DN. More recent studies have observed only about a 30-45% risk of progression of MA to proteinuria over 10 years, while about 30% of type 1 diabetic patients with MA became normoalbuminuric and the rest remained microalbuminuric. The finding that some MA patients have only mild diabetic renal lesions is consistent with the lower than originally estimated risk of progression from MA to proteinuria and with the notion that some MA patients revert to normoalbuminuria. To increase the complexity of the scenario, some normoalbuminuric long-standing type 1 diabetic patients have well-established DN lesions and approximately 40% of all patients destined to progress to proteinuria are normoalbuminuric at initial screening, despite many years of diabetes. A similar picture is emerging in type 2 diabetic patients, although fewer studies have been conducted. Thus, the predictive precision for MA to progress to overt nephropathy over the subsequent decade or so is considerably less than originally described. It is unclear whether this is due to changes in the natural history of DN resulting from improved glycemia and blood pressure control, or whether there were overestimates of risk in the original studies due to the small sample sizes, post hoc analyses, and variable MA definitions. Albumin excretion rate (AER) remains the best available noninvasive predictor of DN risk and should be regularly measured according to established guidelines. However, AER may be unable to define patients who are safe from or at risk of DN with an accuracy that is adequate for optimal clinical decision making or for the design of certain clinical trials. Investigations into new risk markers or into the combined use of several currently available predictive parameters are needed.     

The effects of calcitriol on ameliorating podocytes impairment and its possible mechanism in DN rats

Objective To investigate the effects and underlying mechanism of calcitriol on ameliorating podocytes impairment in DN rats. Methods SD rats were randomly divided into four groups: normal control (NC) group, calcitriol treatment (VD) group: calcitriol 0.1μg•kg-1•d-1, diabetic nephropathy (DN) group: streptozocin (STZ) 58 mg/kg, DN treated with calcitriol (DN+VD) group：calcitriol 0.1 μg•kg-1•d-1 + STZ 58 mg/kg. Rats were sacrificed at the end of 18 weeks. Results Compared with the DN group, the DN+VD group exhibited significantly lower proteinuria by 36%, improved renal histology at the end of the experiment (P＜0.05), and similar levels of blood glucose,serum urea nitrogen as well as body weight (P＞0.05). There were no significant differences in the serum concentrations of creatinine, calcium and phosphorus among the four groups (P＞0.05). In DN group, the expressions of nephrin, podocin, VDR, PI3K-p85 and p-Akt were significantly decreased and the expression of desmin was increased compared to NC group. Calcitriol treatment could attenuate the above changes. Additionally, a positive correlation was observed between the expressions of nephrin and VDR (r=0.776, P＜0.05). Likewise, the expression of nephrin was positively correlated with either PI3K-p85 or p-Akt (r=0.736, r=0.855, all P＜0.05). Conclusion Calcitriol can ameliorate podocytes injury in DN rats, which might be related with the further up-regulation of PI3K/p-Akt signaling pathway.     

Evolving spectrum of diabetic nephropathy

Diabetes remains an important health issue as more patients with chronic and uncontrolled diabetes develop diabetic nephropathy(DN), which classically presents with proteinuria followed by a progressive decrease in renal function.However, an increasing proportion of DN patients have a decline in kidney function and vascular complications without proteinuria, known as nonproteinuric DN(NP-DN). Despite the increased incidence of NP-DN, few clinical or experimental studies have thoroughly investigated the pathophysiological mechanisms and targeted treatment for this form of DN. In this review, we will examine the differences between conventional DN and NP-DN and consider potential pathophysiological mechanisms, diagnostic markers, and treatment for both DN and NP-DN. The investigation of the pathophysiology of NP-DN should provide additional insight into the cardiovascular factors influencing renal function and disease and provide novel treatments for the vascular complications seen in diabetic patients.     

Effects of smoking on renal function in patients with type 1 and type 2 diabetes mellitus.

BACKGROUND: Smoking increases the risk of end-stage renal failure in patients with primary renal disease. Whether and to what extent smoking affects the kidneys in diabetic patients with normal renal function and variable degrees of proteinuria has not been fully studied. METHODS: We followed 185 patients with type 1 or 2 diabetes mellitus and with or without signs of overt renal disease for at least 3 years, median 5.1 (3-6.8) years. Each patient had a baseline visit and at least four follow-up visits (average 4.8+/-0.3). Cases were patients who were smoking (n = 44) at the time the survey was started. Controls were patients who had never smoked (n = 141). Glomerular filtration rate (GFR) was estimated using the MDRD formula. Multiple logistic regression was used to correct for confounding factors. RESULTS: At baseline, smokers were younger (47+/-14 vs 54+/-16 years, P < 0.01), and had a lower GFR (95+/-26 ml/min) than non-smokers (107+/-33 ml/min, P < 0.05). Mean GFR remained constant during follow-up in non-smokers (106+/-31 ml/min), but decreased significantly in smokers (83+/-22 ml/min, P < 0.0001), and this relationship persisted when adjusted for retinopathy, glycaemic control, age, body habitus, ACE-inhibitor treatment, blood pressure control or severity of proteinuria. The effect of smoking on GFR decline was stronger in patients with type 1 diabetes or male gender. CONCLUSIONS: Cigarette smoking causes a decrease in GFR in diabetic patients with normal or near-normal renal function, independent of confounding factors including severity of proteinuria. The latter finding suggests a mechanism independent of glomerular damage.