Association between atherosclerotic cardiovascular diseases risk and renal outcome in patients with type 2 diabetes mellitus.

AIMS: Chronic kidney disease (CKD) and diabetes mellitus increase atherosclerotic cardiovascular diseases (ASCVD) risk. However, the association between renal outcome of diabetic kidney disease (DKD) and ASCVD risk is unclear. METHODS: This retrospective study enrolled 218 type 2 diabetic patients with biopsy-proven DKD, and without known cardiovascular diseases. Baseline characteristics were obtained and the 10-year ASCVD risk score was calculated using the Pooled Cohort Equation (PCE). Renal outcome was defined as progression to end-stage renal disease (ESRD). The association between ASCVD risk and renal function and outcome was analyzed with logistic regression and Cox analysis. RESULTS: Among all patients, the median 10-year ASCVD risk score was 14.1%. The median of ASCVD risk score in CKD stage 1, 2, 3, and 4 was 10.9%, 12.3%, 16.5%, and 14.8%, respectively (p = 0.268). Compared with patients with lower ASCVD risk (＜14.1%), those with higher ASCVD risk had lower eGFR, higher systolic blood pressure, and more severe renal interstitial inflammation. High ASCVD risk (>14.1%) was an independent indicator of renal dysfunction in multivariable-adjusted logistic analysis (OR, 3.997; 95%CI, 1.385-11.530; p = 0.010), though failed to be an independent risk factor for ESRD in patients with DKD in univariate and multivariate Cox analysis. CONCLUSIONS: DKD patients even in CKD stage 1 had comparable ASCVD risk score to patients in CKD stage 2, 3, and 4. Higher ASCVD risk indicated severe renal insufficiency, while no prognostic value of ASVCD risk for renal outcome was observed, which implied macroangiopathy and microangiopathy in patients with DKD were related, but relatively independent.

Solidified glomerulosclerosis, identified using single glomerular proteomics, predicts end-stage renal disease in Chinese patients with type 2 diabetes.

Few histological prognostic indicators for end-stage renal disease (ESRD) have been validated in diabetic patients. This biopsy-based study aimed to identify nephropathological risk factors for ESRD in Chinese patients with type 2 diabetes. Histological features of 322 Chinese type 2 diabetic patients with biopsy-confirmed diabetic nephropathy (DN) were retrospectively analysed. Cox proportional hazards analysis was used to estimate the hazard ratio (HR) for ESRD. Single glomerular proteomics and immunohistochemistry were used to identify differentially expressed proteins and enriched pathways in glomeruli. During the median follow-up period of 24 months, 144 (45%) patients progressed to ESRD. In multivariable models, the Renal Pathology Society classification failed to predict ESRD, although the solidified glomerulosclerosis (score 1: HR 1.65, 95% confidence interval [CI] 1.04-2.60; score 2: HR 2.48, 95% CI 1.40-4.37) and extracapillary hypercellularity (HR 2.68, 95% CI 1.55-4.62) were identified as independent risk factors. Additionally, single glomerular proteomics, combined with immunohistochemistry, revealed that complement C9 and apolipoprotein E were highly expressed in solidified glomerulosclerosis. Therefore, solidified glomerulosclerosis and extracapillary hypercellularity predict diabetic ESRD in Chinese patients. Single glomerular proteomics identified solidified glomerulosclerosis as a unique pathological change that may be associated with complement overactivation and abnormal lipid metabolism.

Serum transferrin predicts end-stage Renal Disease in Type 2 Diabetes Mellitus patients.

Background: To investigate the relationship between serum iron status and renal outcome in patients with type 2 diabetes mellitus (T2DM). Methods: Chinese patients (n=111) with T2DM and biopsy-proven diabetic nephropathy (DN) were surveyed in a longitudinal, retrospective study. Serum iron, total iron-binding capacity, ferritin, and transferrin were measured at the time of renal biopsy. Iron deposition and transferrin staining were performed with renal biopsy specimens of DN patients and potential kidney donors. End-stage renal disease (ESRD) was the end-point. ESRD was defined as an estimated glomerular filtration rate <15 mL/min/1.73 m2 or the need for chronic renal replacement therapy. Cox proportional hazard models were used to estimate the hazard ratios (HRs) for the influence of serum iron metabolism on ESRD. Results: During a median follow up of 30.9 months, 66 (59.5%) patients progressed to ESRD. After adjusting for age, sex, baseline systolic blood pressure, renal functions, hemoglobin, HbA1c, and pathological findings, lower serum transferrin concentrations were significantly associated with higher ESRD in multivariate models. Compared with patients in the highest transferrin quartile (≥1.65 g/L), patients in the lowest quartile (≤1.15 g/L) had multivariable-adjusted HR (95% confidence interval) of 7.36 (1.40-38.65) for ESRD. Moreover, tubular epithelial cells in DN exhibited a higher deposition of iron and transferrin expression compared with healthy controls. Conclusions: Low serum transferrin concentration was associated with diabetic ESRD in patients with T2DM. Free iron nephrotoxicity and poor nutritional status with accumulated iron or transferrin deposition might contribute to ESRD.

Corrigendum to "FcgRIII Deficiency and FcgRIIb Defeciency Promote Renal Injury in Diabetic Mice".

[This corrects the article DOI: 10.1155/2019/3514574.].

FcgRIII Deficiency and FcgRIIb Defeciency Promote Renal Injury in Diabetic Mice.

The immune system is involved in the development of diabetes complications and IgG Fc gamma receptors (FcgRs) are key immune receptors responsible for the effective control of both humoral and innate immunity. We investigated the effects of members of the FcgR superfamily into both the streptozotocin plus high fat-induced type 2 diabetes and high fat diet (HFD) models. FcgRIII-/- diabetic mice and FcgRIIb-/- diabetic mice had elevated levels of serum creatinine compared with wildtype (WT) diabetic mice. Renal histology of diabetic FcgRIII knockout and FcgRIIb knockout mice showed mesangial expansion and GBM thickening; the mechanistic study indicated a higher expression of TGF-ß1, TNF-α, and p-NFκB-p65 compared with wild type mouse. The HFD mouse with FcgRIII knockout or FcgRIIb knockout had increased biochemical and renal injury factors, but oxLDL deposition was higher than in FcgRIII-/- diabetic mice and FcgRIIb-/- diabetic mice. In vitro we further examined the mechanism by which the Fc gamma receptor promoted renal injury and transfected glomerular mesangial cells (GMCs) with FcgRI siRNA attenuated the level of TGF-ß1, TNF-α expression. In summary, FcgRI knockdown downregulated kidney inflammation and fibrosis and FcgRIIb knockout accelerated inflammation, fibrosis, and the anomalous deposition of oxLDL whereas FcgRIII deficiency failed to protect kidney from diabetic renal injury. These observations suggested that FcgRs might represent a novel target for the therapeutic intervention of diabetic nephropathy.

Serum levels of immunoglobulin G and complement 3 differentiate non-diabetic renal disease from diabetic nephropathy in patients with type 2 diabetes mellitus.

AIMS: Heavy proteinuria caused by non-diabetic renal disease (NDRD) is common in type 2 diabetes mellitus (T2DM). The aim of this study was to investigate specific predictors for NDRD in addition to traditional indicators in T2DM. METHODS: A total of 341 patients with T2DM who underwent renal biopsy were retrospectively included. Eligible patients were divided into a nephrotic-range group (n = 194) and a non-nephrotic-range group (n = 147) based on proteinuria level. Risk factors for NDRD were evaluated using logistic regression, and the diagnostic implications of these variables were assessed by subgroup. RESULTS: Multivariate logistic regression indicated that serum IgG level (OR, 0.762; 95% CI, 0.628-0.924; p = 0.006) was an independent predictor of NDRD in the nephrotic-range group. However, in the non-nephrotic-range group, increased C3 level was an independent risk factor for NDRD (OR, 1.313; 95% CI, 1.028-1.678; p = 0.029). In the nephrotic-range group, the optimal cutoff value of IgG for predicting NDRD was 734.0 mg/dl, with 67.8% sensitivity and 74.8% specificity, and IgG ≤ 734.0 mg/dl was the best predictor of NDRD. In the non-nephrotic-range group, the optimal cutoff value of C3 for predicting NDRD was 122.0 mg/dl with low sensitivity (30.9%) but high specificity (97.8%). CONCLUSIONS: At different levels of proteinuria, reduced IgG and increased C3 levels were independent indicators of NDRD in T2DM. Insights into these factors will help to advance the clinical management of NDRD.

Thyroid hormones and diabetic nephropathy: An essential relationship to recognize.

AIMS: Although abnormal thyroid hormone metabolism is common in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN), the relationship between thyroid hormones and DN is unclear and has been ignored during clinical practice. This study aimed to investigate the relationship between thyroid hormones and clinicopathologic changes in biopsy-proven DN patients. METHODS: Clinical and pathological data for 146 biopsy-proven DN patients were collected. The patients were divided into four groups: euthyroid group, high-thyroid stimulating hormone (TSH) group (SCH), low-free triiodothyronine (FT3) group (with normal levels of TSH and FT4), and high-TSH + low-FT3 group (with normal levels of FT4). The clinicopathologic features among the four groups were investigated. We evaluated the risks of abnormal thyroid hormone levels on DN by logistic regression with multivariable adjustments for other risk factors. We also performed quarterback and eight-point analyses of TSH and FT3 levels to determine their influences on DN. RESULTS: The overt proteinuria (>5 g/24 h) (P = 0.008) and severity of glomerular lesions (P = 0.011) differed between euthyroid group and high-TSH group significantly. Moreover, the levels of estimated glomerular filtration rate (P =0.019), serum creatinine (P =0.014), and severity of glomerular lesions (P =0.003) differed between the euthyroid group and low-FT3 group significantly. There were also significant differences between high-TSH, low-FT3 and high-TSH + low-FT3 patients, respectively. Respective correlations between high-TSH, low-FT3 and renal clinicopathologic changes were found to be significant according to logistic regression analyses. Quarterback and eight-point analyses indicated that patients with TSH levels of 4.54-5.67 mU/L had the most severe renal clinicopathologic changes, and the severity of renal changes decreased with increased FT3 levels. CONCLUSIONS: Diabetic nephropathy patients with high-TSH and/or low-FT3 had more severe proteinuria, renal insufficiency, and glomerular lesions, suggesting that regulating thyroid hormones might have a renoprotective effect.

Implications of a Family History of Diabetes and Rapid eGFR Decline in Patients With Type 2 Diabetes and Biopsy-Proven Diabetic Kidney Disease.

Objective: This study aimed to identify the risk factors for a rapid decline in the estimated glomerular filtration rate (eGFR) in Chinese patients with type 2 diabetes and biopsy-proven diabetic kidney disease (DKD). Method: This was a retrospective cohort study. Patients with biopsy-proven DKD who had been followed-up for at least 1 year were enrolled. Baseline clinicopathological data and serum creatinine levels that had been measured at least three times during follow-up in our hospital were collected. Patients were allocated to two groups of rapid decliners and slow decliners according to the median eGFR slope. The associations between potential risk factors and rapid eGFR decline were analyzed using logistic regression. Results: A total of 128 eligible patients were enrolled and they had a mean age of 51.5 ± 10.7 years. During a median follow-up of 2 years, the median eGFR slope was -8.1 ± 14.4 mL/min/1.73 m2/year. The eGFR decline was significantly faster in patients with a family history of diabetes in first-degree relatives, nephrotic-range proteinuria, higher grades of glomerular pathology, and interstitial inflammation. No differences in the rate of the eGFR decline were observed in subgroups created according to sex, age, hypertension, glycosylated hemoglobin, diabetic retinopathy, interstitial fibrosis, and tubular atrophy. Logistic regression indicated that a family history of diabetes was independently associated with a rapid decline in eGFR, even after adjustment for factors including baseline eGFR and proteinuria. Conclusion: A family history of diabetes in first-degree relatives is independently associated with a rapid decline in eGFR in the current relatively young studied patients. Our findings suggested that early diagnosis and treatment is important for these patients.

Effects of neutrophil-lymphocyte ratio on renal function and histologic lesions in patients with diabetic nephropathy.

AIM: Chronic low-grade inflammation related to diabetic nephropathy (DN) may affect the serum neutrophil-lymphocyte ratio (NLR). We aimed to examine the cross-sectional relationships of NLR with renal function and structural lesions of DN in patients with type 2 diabetes mellitus (T2DM). METHODS: The study retrospectively included 247 patients with T2DM and biopsy-proven DN. The severity of different pathological lesions was evaluated based on the criteria of Renal Pathology Society. The patients were divided into two groups based on the median (2.42) of NLR level, group 1: NLR < 2.42 (n = 122) and group 2: NLR ≥ 2.42 (n = 125). Renal dysfunction was defined by estimated glomerular filtration rate less than 60 mL/min per 1.73 m2 . The influence of NLR on renal dysfunction was evaluated using logistic regression analysis. RESULTS: The spearman's rank-correlation test indicted that NLR was positively correlated with interstitial fibrosis and tubular atrophy (r = 0.170, P = 0.007) and serum fibrinogen (r = 0.261, P < 0.001), whereas negatively related with estimated glomerular filtration rate (r = -0.233, P < 0.001). However, the NLR level demonstrated no association with glomerular lesions, interstitial inflammation and arteriolar hyalinosis. A multivariate logistic regression analysis showed that higher level of NLR (≥2.42) was significantly associated with renal dysfunction when adjusting for some important baseline clinical and pathological variables (odds ratio, 2.46; 95% confidence interval, 1.21-4.97; P = 0.012). CONCLUSION: Increased NLR affects renal function and histologic lesions in patients with T2DM and may be an important factor for the progression of DN.

The association between the red cell distribution width and diabetic nephropathy in patients with type-2 diabetes mellitus.

BACKGROUND: Red cell distribution width (RDW) has been reported to be involved in metabolic syndrome and cardiovascular events. Patients with diabetic nephropathy (DN) are often found to be with high level of RDW. The aim of this study was to explore whether RDW was associated with DN severity and progression in patients with type-2 diabetes mellitus (T2DM). METHODS: A total of 175 T2DM patients with biopsy-proven DN were enrolled. The baseline clinical and pathologic data of these patients was extracted from the medical records. The patients then were divided into two groups based on the median (13.6%) of RDW level; group 1: <13.6% and group 2: ≥13.6%. The effect of RDW level on the renal outcomes was evaluated by using cox regression analysis. RESULTS: Compared with the patients with lower RDW level, the patients with higher level of RDW had higher proportions of female, longer DM duration, lower levels of eGFR, albumin and hemoglobin, and more serious glomerular damage. Moreover, the RDW levels were negatively corrected with eGFR (r = -0.283, p < 0.001), but positively related with proteinuria (r = 0.227, p = 0.003). In the follow-up period, 81(46.3%) patients had reached ESRD from baseline. Importantly, the Cox regression analyses showed that the levels of RDM had a significant effect on the risk of progression to ESRD (HR = 1.92, p < 0.01), albeit not emerged as an independent predictor. CONCLUSIONS: These data indicated that the levels of RDW were significantly associated with increased risk of progression to ESRD in patients with DN, despite did not an independent predictor.

The association between cigarette smoking and diabetic nephropathy in Chinese male patients.

AIMS: To investigate the association between cigarette smoking and the clinicopathological features and renal prognosis of type 2 diabetic mellitus (T2DM) patients with diabetic nephropathy (DN). METHODS: A total of 223 T2DM male patients with biopsy-proven DN who received follow-up for at least 1 year were recruited. The patients were divided into two groups based on smoking status: smoking group and non-smoking group. Clinicopathologic differences were analyzed between the two groups. In addition, smokers were divided into two groups of binary analysis based on smoking amounts and two groups of former smokers and current smokers, and subgroups analysis based on age and DR, respectively. The influence of smoking on estimated glomerular filtration rate (eGFR) was estimated using logistic regression analysis and Cox regression on renal outcomes. Renal outcomes were defined by progression to end-stage renal disease (ESRD) or doubling of serum creatinine (D-SCr) level. RESULTS: Compared with nonsmokers, smoking patients had more moderate decline eGFR (p = 0.032) and tubular atrophy and interstitial fibrosis (p = 0.033). The adjusted logistic regression analysis suggested cigarette smoking was negatively associated with more severe decline eGFR (p = 0.015), especially for patients with DR (p = 0.010) and patients of age ≤ 50 years (p = 0.012) in the subgroup analysis. In the prognosis analysis, no obvious significant risk factor was shown about smoking. Interestingly, it was observed that former smokers had lower levels of plasma glucose and triglycerides than current smokers (both p < 0.05), while smokers with small smoking amounts had lower levels of triglycerides than those with large smoking amounts (p < 0.05). CONCLUSION: Cigarette smoking patients with T2DM and DN had more moderate decline eGFR, especially for DN patients with DR, and milder IFTA lesions, although an obviously significant risk factor was not shown about smoking for DN.

COL4A3 Gene Variants and Diabetic Kidney Disease in MODY.

BACKGROUND AND OBJECTIVES: Despite advances in identifying genetic factors of diabetic kidney disease (DKD), much of the heritability remains unexplained. Nine maturity-onset diabetes in young (MODY) probands with kidney biopsy-proven DKD were selected and included in this study. The probands had more severe DKD compared with their parents with MODY, with overt proteinuria or rapid progression to ESKD. We aimed to explore the contribution of the variants in susceptibility genes of DKD to the severity of kidney phenotype between the probands and their parents. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Whole-exome sequencing was performed to identify suspected MODY probands and their families. Known DKD susceptibility genes were reviewed. Variants reported to be associated with DKD, or those with minor allele frequency <0.05 and predicted to be pathogenic, were selected and analyzed. Immunofluorescence staining of COL4α3 was performed in kidney specimens of patients with DKD with or without R408H and M1209I of COL4A3 variants. RESULTS: HNF1B-MODY, CEL-MODY, PAX4-MODY, and WFS1-MODY were diagnosed among nine families. We identified 196 selected variants of 25 DKD susceptibility genes among the participants. Analysis of phenotype between probands and parents, gene function, and protein-protein interaction networks revealed that COL4A3 variants were involved in the progression of DKD. Weak granular staining of COL4α3 was observed in the glomerular basement membrane of patients with the R408H and M1209I variants, whereas strong consecutive staining was observed in patients without these variants. Moreover, more number of DKD variants were identified in probands than in their parents with MODY. CONCLUSIONS: The genetic effect of more pathogenic variants in various DKD susceptibility genes, especially variants in the COL4A3 gene, partially explained the more severe kidney phenotype in probands with kidney biopsy-proven DKD.

[Association of Serum Soluble CD36 with Clinical Variables in Diabetic Patients with Chronic Kidney Diseas].

OBJECTIVE: To investigate the levels of serum soluble CD36 (sCD36) in patients of diabetes mellitus (DM) with chronic kidney disease (CKD),and to analyze its correlation with clinical indicators. METHODS: A total of 161 patients with CKD were enrolled in this study. The patients were divided into two groups according to whether they had DM or not: DM+CKD group and non-DM CKD group. The levels of carotid intima-media thickness (IMT) and the combination of atherosclerotic plaques were measured by color Doppler ultrasonography. Serum fasting serum samples were collected and serum sCD36 level was measured by ELISA. the status of serum sCD36 was analyzed with the progress of renal disease,and the correlation of sCD36 level with clinical indicators were analyzed. RESULTS: Among the 161 patients,87 (54%) were DM+CKD and 74 (46%) were non-DM CKD. There was no significant difference in the levels of urea nitrogen (BUN),serum creatinine (sCr),estimated glomerular filtration rate (eGFR),cystatin C (Cys-C),triglyceride (TG),cholesterol (Chol),low density lipoprotein-chol (LDL-C),urinary albumin/creatinine and IMT in the two groups (P>0.05). Compared with non-DM CKD group,the serum sCD36 level (U/L) in DM+CKD group was lower (4.58±1.06 vs. 4.97±1.28,P<0.05). In DM+CKD group,serum sCD36 was negatively correlated with BUN,sCr and Cys-C (r=⁻0.355,⁻0.336,⁻0.323; P<0.01),and positively correlated with eGFR (r= 0.399; P<0.01),but not with TG,Chol,LDL-C or IMT (P>0.05). In non-DM CKD group,there was a positive correlation between sCD36 and TG,Chol and LDL-C (r= 0.251, 0.298, 0.292; P<0.05),and negatively correlated with Cys-C (r=⁻0.287; P<0.05),but not with eGFR,BUN,sCr or IMT (P>0.05). With the progress of CKD,serum sCD36 levels gradually decreased (P>0.05). CONCLUSION: Serum sCD36 level is associated with renal function in the patients with DM complicated with CKD,but not with lipid indicators.

Diabetic retinopathy may predict the renal outcomes of patients with diabetic nephropathy.

BACKGROUND: The patients with Type 2 diabetes mellitus (T2DM) and diabetic retinopathy (DR) are prone to develop diabetic nephropathy (DN). In this study, we aimed to clarify the relationship between DR and the progression of DN in patients with T2DM. METHODS: In the cross-section study, 250 patients with T2DM and biopsy-proven DN were divided into two groups: 130 in the DN without DR group (DN group) and 120 in the DN + DR group. Logistic regression analysis was performed to identify risk factors for DR. Of the above 250 patients, 141 were recruited in the cohort study who received follow-up for at least 1 year and the influence of DR on renal outcome was assessed using Cox regression. Renal outcome was defined as the progression to end-stage renal disease (ESRD). RESULTS: In the cross-section study, the severity of glomerular lesions (class IIb + III) and DM history >10 years were significantly associated with the odds of DR when adjusting for baseline proteinuria, hematuria, e-GFR, and interstitial inflammation. In the cohort study, a multivariate COX analysis demonstrated that the DR remained an independent risk factor for progression to ESRD when adjusting for important clinical variables and pathological findings (p < .05). CONCLUSIONS: These findings indicated that the severity of glomerular lesions was significantly associated with DR and DR was an independent risk factor for the renal outcomes in patients with DN, which suggested that DR may predict the renal prognosis of patients with T2DM and DN.

Serum fibrinogen predicts diabetic ESRD in patients with type 2 diabetes mellitus.

AIMS: Although increased serum fibrinogen level was often observed in patients with diabetic nephropathy (DN), its association with DN severity and progression remains unclear. The aim of this study was to investigate the relationship between the serum fibrinogen levels and clinicopathological features and renal prognosis in Chinese patients with type 2 diabetes mellitus (T2DM) and DN. METHODS: A total of 174 patients with T2DM and biopsy-proven DN were enrolled. Patients were stratified by the quartiles of serum fibrinogen levels; Q1: <3.30 g/L; Q2: between 3.30 and 4.00 g/L; Q3: between 4.00 and 4.74 g/L; Q4:≥4.74 g/L. The renal outcomes were defined by reaching end stage renal disease (ESRD). The influence of serum fibrinogen levels on renal outcomes was evaluated using Cox regression analysis. RESULTS: The factors associated with higher level of fibrinogen (Q3 and Q4) were diabetic retinopathy, low e-GFR, high proteinuria and severe glomerular and tubulointerstitial lesions. Importantly, in adjusted analysis, higher levels of fibrinogen were independently related with a greater risk of reaching ESRD with a hazard ratio (HR) of 1.64 per standard deviation (SD) of the natural log-transformed fibrinogen concentration (95%CI, 1.22-2.20; p = 0.001). In reference to the Q1, the risk of renal failure increased by quartiles of the serum fibrinogen level: the HRs were 7.12 for the Q2 (95%CI, 2.29-22.16; p = 0.001), 5.77 for Q3 (95%CI, 1.99-16.75; p = 0.001), and 8.81 for Q4 (95%CI, 2.79-27.80; p < 0.001). CONCLUSIONS: These findings suggested that the elevated serum levels of fibrinogen were associated with diabetic ESRD in patients with T2DM.

The relationship between the thickness of glomerular basement membrane and renal outcomes in patients with diabetic nephropathy.

AIMS: Glomerular basement membrane (GBM) thickening is considered as one of the earliest detectable pathological features of diabetic nephropathy (DN). However, whether the thickness of GBM will impact the prognosis of DN remains largely unknown. Our aim was to explore the relationship between thickness of GBM and DN progression in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 118 patients with T2DM and biopsy-proven DN who received follow-up for at least 1 year were recruited. The patients were divided into two groups according to the median (787 nm) of the GBM thickness: Group 1: GBM thickness < 787 nm (n = 59), and Group 2: GBM thickness ≥ 787 nm (n = 59). The GBM width was estimated by the direct GBM measurements as recently modified by Haas. Renal outcomes were defined by progression to ESRD and/or doubling of serum creatinine (D-Cr). The influence of GBM thickness on renal outcomes was assessed using Cox regression. RESULTS: Compared with the Group 1, patients in Group 2 had more serious renal insufficiency and glomerular lesions. During the follow-up, ESRD occurred in 39.8% of patients, and 8.5% of patients progressed to D-Cr. The univariate analysis indicated the greater width of GBM the higher risk of renal outcomes in T2DM patients with DN (HR [95% CI] = 2.180 [1.246-3.814], p = 0.006). However, the multivariate COX analysis demonstrated that the GBM thickness was not an independent risk factor for progression to ESRD or D-Cr (HR [95% CI] = 0.825 [0.404-1.685], p = 0.597) when adjusting for important clinical variables and pathological findings. CONCLUSIONS: In conclusion, the DN patients with greater width of GBM had relatively poorer renal prognosis, although it did not emerge as an independent indicator of disease progression.

Implication of decreased serum complement 3 in patients with diabetic nephropathy.

AIMS: The serum complement 3 (C3) level was reduced in many patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN). However, the clinical implications of such change are still less understood. This study was aimed to explore the association between C3 level and the baseline clinicopathological characteristics and the prognosis of T2DM patients with DN. METHODS: A total of 171 T2DM patients with biopsy-proven DN who received follow-up for at least 1 year were recruited. The patients were divided into two groups based on the C3 level: decreased C3 group: < 90 mg/dl (n = 75) and normal C3 group: ≥ 90 mg/dl (n = 96). Renal outcomes were defined by progression to end-stage renal disease (ESRD) or doubling of serum creatinine (D-SCr) level. The influence of serum C3 level on renal outcomes was estimated using Cox regression. RESULTS: The patients with decreased C3 level had more severe renal insufficiency and glomerular lesions than those in the normal C3 group. During a follow-up period (12-78 months), 51 patients with decreased C3 levels (68.0%) and 36 individuals with normal C3 levels (37.5%) reached the endpoint. The univariate Cox regression indicated that patients in the decreased C3 group had a higher rate of the renal outcomes than patients in the normal C3 group (HR 1.897, 95% CI 1.235-2.913, p = 0.003). But the multivariate COX analysis indicated that the C3 level was not an independent risk factor for progression to ESRD and/or D-SCr (HR 1.389, 95% CI 0.847-2.278, p = 0.193) when adjusting for important clinical variables and pathological findings. CONCLUSIONS: Decreased serum C3 level was significantly associated with more severe renal insufficiency, higher glomerular grading and poor renal outcomes, though it failed to be an independent risk factor in T2DM patients with DN.

Renal pathological implications in type 2 diabetes mellitus patients with renal involvement.

AIMS: To investigate the renal pathological implications in type 2 diabetes mellitus patients with renal involvement. METHODS: A total of 328 type 2 diabetes mellitus (T2DM) patients with renal involvement who underwent a renal biopsy and received follow-up for at least one year were recruited in our study. The patients were divided into the diabetic nephropathy (DN), non-diabetic renal disease (NDRD), and NDRD superimposed on DN groups based on the pathological diagnosis. Renal outcomes were defined by the initiation of renal replacement therapy or doubling of the serum creatinine. Kaplan-Meier analysis was used to compare renal survival, and Cox proportional hazard analysis was used to determine the predictors of renal outcomes in the DN group. RESULTS: Renal biopsy findings revealed that 188 patients (57.32%) had pure DN, 121 patients (36.89%) had NDRD alone, and 19 patients (5.79%) had NDRD superimposed on DN. The most frequent subclassification of NDRD was membranous nephropathy (MN). Compared with the NDRD and NDRD superimposed on DN groups, patients with pure DN had poorer renal function and lower renal survival rates. In the DN group, the five-year renal survival rates of glomerular classes of I, IIa, IIb, III and IV were 100%, 84.62%, 60%, 47.5% and 33.33%, respectively. Multivariate Cox proportional hazard analysis showed that the glomerular lesions, proteinuria and serum creatinine were independent risk factors for renal outcomes, while interstitial fibrosis/inflammation and arteriolar hyalinosis were not independently associated with renal outcomes in the DN group. CONCLUSIONS: Making an accurate pathologic diagnosis by renal biopsy is crucial for diabetes mellitus (DM) patients with renal involvement. The findings of our present study indicated that patients with pure DN had poorer renal outcomes than patients with NDRD or NDRD superimposed on DN. The classification of glomerular lesions, proteinuria and serum creatinine were independent risk factors for renal outcomes in the DN group. More studies with large samples and longer time follow-up are needed to evaluate the relationship between pathological changes and clinical characteristics in T2DM patients who have renal involvement.