Improvement of renal function in type 2 diabetic nephropathy

BACKGROUND: Therapeutic failure in preventing renal disease progression in type 2 diabetic nephropathy (DN) is due to a failure in the early detection of DN by microalbuminuria and the inappropriate correction of renal hemodynamic maladjustment secondary to glomerular endothelial dysfunction. METHODS: Thirty patients associated with normoalbuminuric type 2 DN were subject to the following studies: tubular function by means of fractional excretion of magnesium (FE Mg), vascular function by means of determining the circulating endothelial cell, VEGF, VEGF/TGF B ratio, and intrarenal hemodynamic studies. RESULTS: FE Mg, circulating endothelial cells, and TGF B were abnormally elevated, and VEGF/TGF B ratio was decreased in these normoalbuminuric patients. The intrarenal hemodynamic study revealed a hemodynamic maladjustment characterized by a preferential constriction at the efferent arteriole and a reduction in peritubular capillary flow. Following treatment with vasodilators, a decrease in efferent arteriolar resistance and increase in peritubular capillary flow as well as glomerular clearance were observed. CONCLUSION: FE Mg appears to be a more sensitive marker than microalbuminuria for the early detection of DN. Increased endothelial cell injury is reflected by enhanced circulating endothelial cell loss in conjunction with the increased TGF B and the decreased ratio between VEGF and TGF B. This is further supported by the dysfunctioning glomerular endothelium, which is characterized by hemodynamic maladjustment and a reduction in the peritubular capillary flow. A correction of such hemodynamic maladjustment by multidrug vasodilators effectively improves renal perfusion and restores renal function in type 2 DN.     

Renal function in diabetic nephropathy

Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. Cardiovascular and renal complications share common risk factors such as blood pressure, blood lipids, and glycemic control. Thus, chronic kidney disease may predict cardiovascular disease in the general population. The impact of diabetes on renal impairment changes with increasing age. Serum markers of glomerular filtration rate and microalbuminuria identify renal impairment in different segments of the diabetic population, indicating that serum markers as well as microalbuminuria tests should be used in screening for nephropathy in diabetic older people. The American Diabetes Association and the National Institutes of Health recommend Estimated glomerular filtration rate (eGFR) calculated from serum creatinine at least once a year in all people with diabetes for detection of kidney dysfunction. eGFR remains an independent and significant predictor after adjustment for conventional risk factors including age, sex, duration of diabetes, smoking, obesity, blood pressure, and glycemic and lipid control, as well as presence of diabetic retinopathy. Cystatin-C (Cys C) may in future be the preferred marker of diabetic nephropathy due differences in measurements of serum creatinine by various methods. The appropriate reference limit for Cys C in geriatric clinical practice must be defined by further research. Various studies have shown the importance of measurement of albuminuria, eGFR, serum creatinine and hemoglobin level to further enhance the prediction of end stage renal disease.     

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。     

Influence of pregnancy on progression of diabetic nephropathy and subsequent requirement of renal replacement therapy in female type I diabetic patients with impaired renal function.

The influence of pregnancy on the progression of diabetic nephropathy in diabetic women with pre-existing moderate renal insufficiency is a subject of considerable controversy in the literature. In four of five female patients with type I diabetes mellitus with pre-existing impaired renal function (creatinine clearance less than 80 ml/min), significant proteinuria (greater than 2 g/24 h urine) and hypertension we have found a further decline in renal function during pregnancy, with an increased deterioration rate of creatinine clearance in comparison to the time before and after pregnancy. The mean decline of the glomerular filtration rate was 1.8 ml/min per month during pregnancy and 1.4 ml/min per month postpartum until the start of dialysis treatment. The difference in the progression of diabetic nephropathy during and after pregnancy can be explained by increased hypertension during pregnancy, especially in the third trimester, despite an intensified antihypertensive therapy. The long-term effect of pregnancy on renal function in our patients was therefore an earlier requirement for renal replacement therapy than would have been expected without pregnancy.     

Comparison of methods for preservation of renal function during ischemic renal surgery

Three methods of providing in situ protection to an ischemic kidney were compared in dogs. These were surface cooling using external coils, transvenous hypothermic perfusion and intravenous inosine. The dogs were divided into 3 groups with 20 dogs in each group. Group 1 had the artery occluded for 45 minutes, group 2 for 60 minutes and group 3 for 90 minutes. A further control group of 5 dogs underwent mobilization of the left kidney without ischemia. Contralateral nephrectomy was performed on all animals. The 20 dogs in each group were randomized; 5 undergoing surface cooling, 5 cooling by renal vein perfusion, 5 receiving intravenous inosine and 5 receiving no protection. Function of the solitary kidney was monitored by serum creatinine levels. All 3 methods provided significant protection. Protection provided by surface cooling and inosine was greater than by venous cooling. The protection provided by intravenous inosine was similar to surface cooling for up to 60 minutes but was less at 90 minutes.     

Renal size and function in diabetic nephropathy

The purpose of this investigation was to study in a group of diabetics with varying degrees of renal failure, the relationship of renal size to the degree of renal function. A literature search of the past 25 years has failed to document a precise relationship between structure and function in this setting. Patients were admitted, and sex, age, race, serum creatinine levels, renal size and mean blood pressure were ascertained. Patients with polycystic kidney disease were, obviously, excluded. The group consisted of 26 diabetics, divided into two groups based on previous (prior to onset of uremia) insulin and ketone status. Interestingly, there was no significant difference between groups with insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) as regards mean blood pressure (106.5 +/- 15.3 mm Hg vs. 108.9 +/- 17.64 mm Hg; t = 0.3607892, p = 0.9). Mean kidney length was inversely related to serum creatinine level (r = 0.3980, n = 26, p less than 0.05). There was no correlation between mean renal length and mean blood pressure (r = 0.189, p greater than 0.05). However, there was a significantly higher proportion of larger kidneys (11 cm or more) in the IDDM group than in the NIDDM group (Fischer's exact test; p less than 0.0001) which was related neither to age nor blood pressure. In this paper, we show an inverse correlation between kidney length and serum creatinine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Glomerular function in advanced human diabetic nephropathy

Intrinsic membrane properties of the glomerular capillary wall were evaluated in 20 diabetic patients, who had heavy proteinuria and reduced GFR, and in 15 healthy control subjects. The glomerular sieving coefficients were determined for narrow dextran fractions with molecular radii between 20 and 64 A. GFR determinants were directly measured or indirectly estimated. These quantities were then subjected to a theoretical analysis based upon (1) a mathematical model of glomerular ultrafiltration and (2) a pore model of transmembrane solute transport. The results indicated that in patients with diabetic nephropathy and glomerular ultrafiltration coefficient (0.02 vs. 0.16 ml . sec-1 . mm Hg-1 . 1.73m-2), effective pore area-to-pore length (2.6 x 10(6) vs. 20.0 x 10(6) cm), and mean pore radius (56.8 vs. 58.0 A) are all reduced relative to normal control subjects. It is suggested that (1) hypofiltration in advanced diabetic nephropathy results, in part, from reduction of the surface area available for filtration, while (2) proteinuria is a consequence of either loss of electrostatic barrier function, of isolated focal disruptions within the glomerular filtration barrier, or a combination thereof.     

Macrophages in streptozotocin-induced diabetic nephropathy: potential role in renal fibrosis.

BACKGROUND: Renal fibrosis is central to the progression of diabetic nephropathy; however, the mechanisms responsible for fibroblast and matrix accumulation in this disease are only partially understood. Macrophages accumulate in diabetic kidneys, but it is unknown whether macrophages contribute to renal fibrosis. Therefore, we examined whether macrophage accumulation is associated with the progression of renal injury and fibrosis in type 1 diabetic nephropathy and whether macrophages exposed to the diabetic milieu could promote fibroblast proliferation. METHODS: Kidney macrophages, renal injury and fibrosis were analysed in diabetic C57BL/6J mice at 2, 8, 12 and 18 weeks after streptozotocin injection. Isolated rat bone marrow macrophages were stimulated with diabetic rat serum or carboxymethyllysine (CML)-bovine serum albumin (BSA) to determine whether macrophage-conditioned medium could promote the proliferation of rat renal (NRK-49F) fibroblasts. RESULTS: Progressive injury and fibrosis in diabetic nephropathy was associated with increased numbers of kidney macrophages. Macrophage accumulation in diabetic mice correlated with hyperglycaemia (blood glucose, HbA1c levels), renal injury (albuminuria, plasma creatinine), histological damage and renal fibrosis (myofibroblasts, collagen IV). Culture supernatant derived from bone marrow macrophages incubated with diabetic rat serum or CML-BSA induced proliferation of fibroblasts, which was inhibited by pre-treating fibroblasts with interleukin-1 (IL-1) receptor antagonist or the platelet-derived growth factor (PDGF) receptor kinase inhibitor, STI-571. CONCLUSION: Kidney macrophage accumulation is associated with the progression of renal injury and fibrosis in streptozotocin-induced mouse diabetic nephropathy. Elements of the diabetic milieu can stimulate macrophages to promote fibroblast proliferation via IL-1- and PDGF-dependent pathways which may enhance renal fibrosis.     

De novo diabetic nephropathy on renal allografts

BACKGROUND: Posttransplant diabetes mellitus (PTDM) is a well-recognized clinical problem following renal transplantation. Long-term risks of PTDM are similar to those of diabetes mellitus in general population. The aim of our study was to identify de novo diabetic nephropathy (DN) in our group of patients with PTDM. METHODS: Thirty-four patients with PTDM were reviewed retrospectively. Light microscopy, immunofluorescence, and electron microscopy techniques were performed in 10 of 21 patients with graft biopsy. RESULTS: Five patients (four women, one man), aged 47.4 years (range, 29 to 58), four of whom received cadaveric grafts, were found to have de novo DN. Their serum creatinine was 211.4 micromol/L (range, 140 to 294). Three patients were slightly proteinuric (0.3 to 0.5 g/L). PTDM was diagnosed 2.4 months after transplantation (range, 1 to 6). Histologic diagnosis of de novo DN was made, on average, 52.6 months after transplantation (range, 8 to 115), and 50.2 months (range, 2 to 114) after PTDM. De novo DN presented as diffuse diabetic glomerulosclerosis in four patients and nodular diabetic sclerosis in one patient, and combined with transplant glomerulopathy in all five patients. The mean graft survival time for this group of patients was equivalent with a control group. Although the difference in slopes of serum creatinine between the studied groups was clinically relevant, it was not statistically significant. CONCLUSION: In view of our findings, when histologic de novo DN was found in 5 out of 10 patients, one could conclude that de novo DN could be a frequent complication of PTDM.     

Role of nephrin in renal disease including diabetic nephropathy

Nephrin, a newly described protein, has been localized to the slit membrane between adjacent podocytes of the glomerulus. Its discovery followed the demonstration of the gene NPHS1 and its mutation, resulting in the absence of the protein product, nephrin, in the congenital nephrotic syndrome of the Finnish type. The link between permutations in nephrin expression and proteinuria has been shown in animal models by using neutralizing antibodies or studying mice with inactivation of the nephrin gene. Moreover, the expression of nephrin has been shown to be reduced in various animal models of proteinuric renal disease. The relationship between changes in nephrin expression and proteinuric renal disease in humans is not fully elucidated, with a reduction in expression of this protein reported in a range of renal diseases. Diabetic nephropathy, one of the major causes of end-stage renal disease, is associated with substantial proteinuria and in experimental models with a reduction in slit pore density. In experimental models of diabetes, nephrin expression has been described as being transiently increased in the first 8 weeks of diabetes, followed in longer-term studies with reduced nephrin expression in association with increasing proteinuria. An angiotensin II-receptor blocker has been shown to prevent depletion in glomerular nephrin expression in the diabetic kidney. Human studies in both type 1 and type 2 diabetes suggest down-regulation of nephrin expression in the diabetic kidney and it has been postulated that these changes may play a role in the pathogenesis of diabetic nephropathy, specifically the development of proteinuria in this condition. Although there are other proteins involved in the structure of the epithelial podocyte and specifically the slit pore, nephrin seems to play a pivotal role in preventing passage of protein through the glomerular barrier. Furthermore, it is suggested that the antiproteinuric effects of inhibition of the renin-angiotensin system may partly relate to the effects of these agents on nephrin expression.     

Histopathological atlas of renal diseases: diabetic nephropathy

Renal involvement in type 2 diabetes is a well known clinical occurrence. According to data from the literature, besides diabetic glomerulosclerosis, type 2 diabetic nephropathy may occur as a non specific chronic damage mostly related to vascular changes, or as a glomerular disease superimposed on or even unrelated to diabetic glomerulosclerosis. The most common picture remains in any case diabetic glomerulosclerosis (diabetic GS), that is characterized by variable degrees of mesangial sclerosis.     

Recurrent and de novo diabetic nephropathy in renal allografts

BACKGROUND: Histologic findings of diabetic nephropathy (DN) are observed in allografts of patients with pretransplant (PreTx) diabetes mellitus (DM) and in patients who develop DM posttransplant (PostTx). Patients with allograft biopsies (Bx) were retrospectively studied to determine the incidence of recurrent and de novo DN and to ascertain what, if any, risk factors predispose to histologic DN in either patient population. METHODS: From the renal transplant services at four hospitals from 1992 to 2000, the authors identified all patients with PreTxDM and PostTxDM (n=81). Those with renal biopsies performed >/=18 months PostTx were classified according to the presence or absence of histologic DN (Bx-positive, n=23; Bx-negative, n=35). Patients were then subdivided into four categories-recurrent DN (n=16), de novo DN (n=7), no recurrent DN (n=27), and no de novo DN (n=8)-for analyses. RESULTS: Among these 58 patients, 74.1% had PreTx and 25.9% had PostTx diabetes. Of those with histologic DN, 69.6% were recurrent DN and 30.4% were de novo DN, making de novo DN at least as likely to develop as recurrent DN. After the onset of diabetes in the de novo population, the time to development of histologic DN was similar in the recurrent and the de novo patients (6.68+/-3.86 years vs. 5.90+/-3.13 years, P=0.66) and more rapid than previously reported. Apart from a more frequent family history of hypertension in patients with allograft DN compared with those without allograft DN, known risk factors for the development of native DN did not significantly differ among patients in the four cohorts. Proposed risk factors related to transplantation did not correlate with the development of recurrent or de novo DN. CONCLUSION: Among patients with histologic DN, de novo DN occurred at least as frequently as recurrent DN, and the time to onset of histologically apparent DN was more rapid than previously reported. Neither the usual clinical predictors of DN nor clinical variables related to transplantation clearly distinguished the group with DN from the group without it, potentially implicating novel mechanisms in its pathogenesis.     

Aminoglycoside dosing in renal transplant patients. Comparison of nomogram and individualized pharmacokinetic methods in patients with shifting renal function.

Serum amikacin concentrations were compared in infected renal transplant recipients that were compared in infected renal transplant recipients that were dosed using a creatinine-based nomogram (group I) or an individual computer-assisted pharmacokinetic dosing method (group II). A total of 30 treatment courses were administered. Mean postinfusion peak levels were 22 microgram/ml in group I and 23.4 microgram/ml in group II. Mean serum trough levels were 8.8 microgram/ml and 5.5 microgram/ml in groups I and II, respectively. Both peak and trough serum levels were significantly more often in the acceptable therapeutic (peak 20-32 microgram/ml) and nontoxic (through less than 10 microgram/ml) ranges in group 11 patients. Seventy-seven per cent of group II and 38% of group I peak levels were in the therapeutic range, while 87% of group II and 70% of group I trough levels were less than 10 microgram/ml. Ototoxicity developed with similar frequency in both groups and occurred significantly more often with a peak level greater than 32 microgram/ml. Declining renal function, usually as a result of allograft rejection, occurred in seven (44%) group I and only three (25%) group II patients but could not be exclusively related to amikacin in any patient. A serum trough level of greater than 10 microgram/ml was associated with an increased risk of declining renal function independent of other risk factors. Failures of aminoglycoside therapy are frequently associated with inadequate serum levels. Conversely, ototoxicity and nephrotoxicity may be related to elevated serum aminoglycoside concentrations. For these reasons, the computer-assisted pharmacokinetic dosing method should be used in septic surgical patients whose renal function is subject to sudden and unexpected changes.     

Inhibiting microRNA-192 ameliorates renal fibrosis in diabetic nephropathy

TGF-β1 upregulates microRNA-192 (miR-192) in cultured glomerular mesangial cells and in glomeruli from diabetic mice. miR-192 not only increases collagen expression by targeting the E-box repressors Zeb1/2 but also modulates other renal miRNAs, suggesting that it may be a therapeutic target for diabetic nephropathy. We evaluated the efficacy of a locked nucleic acid (LNA)-modified inhibitor of miR-192, designated LNA-anti-miR-192, in mouse models of diabetic nephropathy. LNA-anti-miR-192 significantly reduced levels of miR-192, but not miR-194, in kidneys of both normal and streptozotocin-induced diabetic mice. In the kidneys of diabetic mice, inhibition of miR-192 significantly increased Zeb1/2 and decreased gene expression of collagen, TGF-β, and fibronectin; immunostaining confirmed the downregulation of these mediators of renal fibrosis. Furthermore, LNA-anti-miR-192 attenuated proteinuria in these diabetic mice. In summary, the specific reduction of renal miR-192 decreases renal fibrosis and improves proteinuria, lending support for the possibility of an anti-miRNA-based translational approach to the treatment of diabetic nephropathy.     

Comparison of methods of assessment of renal function in cystic fibrosis (CF) patients.

Renal failure is increasingly being recognised in CF patients, usually as a consequence of long-term nephrotoxic therapy. There is a need for a simple method of assessment of renal function in this patient group. We compared measured creatinine clearance from validated timed urine collections (the generally accepted practical test of glomerular filtration) with 10 formulae used to estimate creatinine clearance in a group of 74 CF adult patients and 29 matched normal controls. Compared to direct measurement, formulae gave a range of values (95% CI for mean bias -13 to +27.9 ml/min). Even those with the best correlation (r=0.7) gave wide error ranges (limits of agreement: -42.3 to 45.9 ml/min). The most commonly used formulae (Cockroft-Gault [CGF] and abbreviated Modification of Diet in Renal Disease [aMDRD]) were not superior to most other formulae tested. Both CGF and aMDRD-derived estimates compared less favourably in CF patients than controls (mean bias: 9.7 vs 3.4 ml/min (p<0.05) and 4.9 vs 1.4 (p<0.05) respectively; 78% vs 95% (p<0.01) and 77% vs 97% (p<0.01) of estimates within 33% of measurement respectively). In particular, both CGF and aMDRD grossly overestimated renal function (mean bias 18.3 and 15.8 ml/min respectively, p<0.001) in CF patients with reduced creatinine clearance (<80 ml/min). CGF, aMDRD and other formulae cannot be used to reliably assess renal function in CF patients, since they will fail to detect those with renal impairment. Some form of carefully supervised direct measurement is still required.     

Glomerular structure and function in diabetic nephropathy. Early to advanced stages

Kidney biopsies from 14 insulin-dependent diabetes mellitus patients with persistent albuminuria were studied by light and electron microscopy. In terms of kidney function, the patients spanned stages from early to advanced nephropathy. The clinical parameters were (ranges, with medians in parentheses) urinary albumin excretion (UAE) 158-5494 micrograms/min (1153 micrograms/min), glomerular filtration rate (GFR) 30-128 ml.min-1 x 1.73 m-2 (90 ml.min-1 x 1.73 m-2) and mean arterial blood pressure (BP) 87-122 mmHg (109 mmHg). The severity of clinical nephropathy (UAE, GFR, and BP together) correlated with an index of the structural lesions (basement membrane [BM] thickness, mesangial expansion, and glomerular occlusion together; r = 0.62, 2P less than 0.05). GFR compared with remnant surface of glomerular capillaries (filtration surface; FS) gave values of r = 0.72 and 2P = 0.004, and UAE compared with the percentage of the peripheral BM surface carrying fluffy loose intrinsic fine structure gave r = 0.62 and 2P = 0.02. BP per se did not correlate with structural parameters. The area of FS per open glomerulus did not decrease with increasing mesangial volume fraction, which indicates compensatory changes of the capillaries in early and advanced stages of glomerulopathy. In 7 patients with less than 10% occluded glomeruli, correlations between glomerular volume and the parameters of diabetic glomerulopathy (i.e., BM thickness and volume fractions of mesangium and mesangial matrix) failed to reach statistical significance. The actual glomerular volume, however, is a product of the individual's original glomerular volume, probably the early diabetic hypertrophy and modifying changes consequent to the development of glomerulopathy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pravastatin modulates early diabetic nephropathy in an experimental model of diabetic renal disease

BACKGROUND: Development of diabetes causes early functional (endothelial dysfunction) and morphological abnormalities in the kidney. If left untreated, these will ultimately progress to renal failure. Apart from strategies aimed at maintaining very tight glycemic control, attention has turned to the development of adjuvant therapy to maintain endothelial function in these patients. The agents receiving the most critical appraisal due to their endothelial protective effects are the 3-hydrox 3-methylglutaryl (HMG)-Co-enzyme A (CoA) reductase inhibitors. The aim of the study was to investigate: (1) the early alterations in the renal diabetic injury; and (2) to examine the protective role of Pravastatin in this end-organ diabetic model. MATERIALS AND METHODS: Sprague Dawley rats (n = 21) were randomized into three groups: (1) control; (2) diabetic; and (3) diabetic treated with Pravastatin. Diabetic nephropathy was investigated with serum biochemical parameters (urea, creatinine), functional parameters (total urinary protein loss, glomerular filtration rate, renal cortical blood flow), and structural assessment (hemotoxylin and eosin staining). RESULTS: We demonstrated impairment in functional, biochemical, and structural parameters in the diabetic nephropathy group, which was diminished by treatment with Pravastatin. This was attributed to an up-regulation in endothelial constitutive nitric oxide synthase (ecNOS) expression in the treated diabetic group. CONCLUSIONS: We have shown that Pravastatin, in an experimental model of early diabetes nephropathy preserves microvascular endothelial function in the presence of hyperglycemia, thus inhibiting the early stage of diabetic microangiopathy.     

A differential diagnostic model of diabetic nephropathy and non-diabetic renal diseases.

BACKGROUND: Renal diseases in diabetes include diabetic nephropathies (DN) and non-diabetic renal diseases (NDRD). The clinical differentiation between these two categories is usually not so clear and effective. This study aims to develop a quantified differential diagnostic model. METHODS: We consecutively screened the diabetic patients with overt proteinuria but no severe renal failure for kidney biopsy from 1993 to 2003. The finally enrolled 110 patients were divided into two groups according to pathological features (60 in DN group and 50 in NDRD group). Clinical and laboratory data were compared between two groups. Then a diagnostic model was developed based on the logistic regression analysis. RESULTS: Forty-six percent of patients were NDRD including a variety of pathological types. Many differences between DN and NDRD were found by comparison of the clinical indices. In the final logistic regression analysis, only diabetes duration (Dm), systolic blood pressure (Bp), HbA1c (Gh), haematuria (Hu) and diabetic retinopathy (Dr) showed statistical significance. Based on the logistic regression model: pi = e(z)/(1 + e(z)), a diagnostic model was constructed as follows: P(DN) = exp(-13.5922 + 0.0371Dm + 0.0395Bp + 0.3224Gh - 4.4552Hu + 2.9613Dr)/ [1 + exp(-13.5922 + 0.0371Dm + 0.0395Bp + 0.3224Gh - 4.4552Hu + 2.9613Dr)]. P(DN) was the probability of DN diagnosis (P(DN) >or= 0.5 as DN, P(DN) < 0.5 as NDRD). Validation tests showed that this model had good sensitivity (90%) and specificity (92%). CONCLUSIONS: This diagnostic model may be helpful to clinical differentiation of DN and NDRD in type 2 diabetic patients with overt proteinuria.