Podocalyxin as an early marker predicting diabetic nephropathy and its correlation with stages of diabetic nephropathy in type two diabetic patients

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Salah El-Din A Shelbaya ◽  
Hanan M Ali ◽  
Rana H Ibrahim ◽  
Nourhan Safwat Sawirs

Abstract Background Nephropathy, a major complication of diabetes, is the leading cause of end-stage renal disease. Early identification of nephropathy in diabetes patients is crucial because it creates opportunity for preventing the incidence of DN and/or even slows down the process of end-stage renal disease attributed to diabetes. Human podocytes (Pods) have been demonstrated to be functionally and structurally injured in the natural history of diabetic nephropathy. Aim of the Work To evaluate the possible association between the urinary podocalyxin levels and severity and grade of diabetic nephropathy and to use urinary podocalyxin as a non-invasive marker for early stage of diabetic nephropathy in type 2 DM. Patients and Methods We collected 60 known clinically and biochemically type 2 diabetic patients.20 diabetic patients with no evidence of diabetic nephropathy, 20 patients diagnosed as diabetic nephropathy in microalbuminuria stages and 20 patients diagnosed as diabetic nephropathy in macroalbuminuria stages from Ain Shams University hospitals between April and December 2018 and 20 apparently healthy volunteers will included as a control group. Results Urinary PCX was significantly higher in patients group compared to control group. Urinary PCX was significantly higher in microalbuminuric group than in normoalbuminuric group and higher in macroalbuminuric group than in microalbuminuric group. There was a positive significant correlation between FBS, 2HrPP, HBA1C and urinary PCX. There was a positive significant correlation between s.create and urinary PCX. There was a positive significant correlation between ACR and urinary PCX. Conclusion Urinary podocalyxin seems to be beneficial as an early marker for early stages of diabetic nephropathy in type 2 DM patients.

2020 ◽  
Vol 9 (9) ◽  
pp. 912-921
Author(s):  
Yu Ah Hong ◽  
Kyung-Do Han ◽  
Jae-Seung Yun ◽  
Eun Sil Sil ◽  
Seung-Hyun Ko ◽  
...  

Objective: Although short adult height has been associated with an increasing variety of diseases and all-cause death, no reliable data exist on the association between adult height and end-stage renal disease (ESRD) in diabetic patients. We investigated the relationship between short adult height, development of ESRD, and mortality in type 2 diabetes mellitus (DM). Methods: This nationwide population-based cohort study analyzed clinical data from a total of 2,621,907 subjects aged ≥30 years with type 2 DM between January 1, 2009 and December 31, 2012, using the National Health Insurance Database in Korea. Results: During a 6.9-year follow-up period, 220,457 subjects (8.4%) died, and 28,704 subjects (1.1%) started dialysis. Short adult height significantly increased the incidence of ESRD and all-cause mortality in the overall cohort analysis. In multivariable Cox models, hazard ratios (HR) for the development of ESRD comparing the highest and lowest quartiles of adult height were 0.86 (95% CI 0.83–0.89). All-cause mortality also decreased with the highest height compared to patients with the lowest height, after fully adjusting for confounding variables (HR 0.79, 95% CI 0.78–0.81). Adult height had an inverse relationship to newly diagnosed ESRD (male: HR 0.86, 95% CI 0.83–0.90, female: HR 0.84, 95% CI 0.79–0.90) and all-cause mortality (male: HR 0.81, 95% CI 0.79–0.82, female: HR 0.80, 95% CI 0.78–0.82). Conclusions: Short adult height is strongly associated with the increased risk of ESRD development and all-cause mortality in type 2 DM.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Oleksandr Susla ◽  
Mykola Shved ◽  
Zoriana Litovkina ◽  
Svitlana Danyliv ◽  
Anatoliy Gozhenko

Abstract Background and Aims Systematic analysis of cardiac remodeling features in type 2 diabetic patients with end-stage renal disease (ESRD) is important both in stratification of cardiovascular risk and in choice of adequate treatment strategies. The lack of number and fragmentation of studies, the ambiguity of their data regarding the problem of myocardial reconstruction and cardiac valve calcification (CVC) under these conditions have substantiated the need for this study, its relevance and purpose. Method 136 ESRD patients on chronic hemodialysis (HD) were included in this observational cross-sectional study (men, 78; age, 53.9±1.0 years; HD duration, 47.6±4.2 months). The study was performed in accordance with the provisions of the Declaration of Helsinki last revision. Depending on the presence/absence of diabetic nephropathy (DN) all patients were divided into two groups: the 1st one – without DN (n=88); the 2nd one – with DN (n=48). A complete ultrasound examination of the cardiac structure and function including CVC analysis was performed. Data are presented as means±SEM. Mann-Whitney U-test was used for comparison of the quantitative variables, χ2-test – qualitative ones. Results Left ventricular (LV) hypertrophy (93.8 vs. 78.4%, р=0.020) and eccentric hypertrophy (47.9 vs. 28.4%, р=0.023) were diagnosed more often in patients with DN than those without diabetes. Prevalence of pseudonormal and restrictive types of LV diastolic dysfunction (62.5 vs. 28.4%, p<0.001), systolic dysfunction (27.1 vs. 9.1%, p=0.006) and pulmonary hypertension (PH) (64.6 vs. 35.2%, p=0.001) were significant in the 2nd group. CVC (66.6 vs. 38.6%, р=0.002), combined calcification of mitral (MV) and aortal (AV) valves (35.4 vs. 13.6%, p=0.003), stenoses of MV (16.7 vs. 3.4%, p=0.007) and AV (39.6 vs. 15.9%, p=0.004), and insufficiency of MV (66.7 vs. 44.3%, p=0.013) and AV (35.4 vs. 14.8%, p=0.006) were recorded more often in HD patients with DN. LV myocardial mass index (181.0±7.2 vs. 155.0±5.3 g/m2, p=0.001) as well as right ventricle (RV) diameter (2.80±0.09 vs. 2.47±0.04 cm, p=0.003) were also greater in the 2nd group. Conclusion In type 2 diabetic patients with ESRD occurs maladaptive cardiac remodeling with predominance of unfavourable (especially eccentric) types of LV hypertrophy, RV dilatation, PH, severe LV diastolic and systolic dysfunction, and widespread combined calcification of MV and AV with the valve defects. The identification of risk factors for the progression of the pathological reconstruction of myocardium and CVC in HD patients with DN will be the subject of our further research.


2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Eduardo De la Cruz-Cano ◽  
Cristina del C. Jiménez-González ◽  
Vicente Morales-García ◽  
Conny Pineda-Pérez ◽  
Juan G. Tejas-Juárez ◽  
...  

Abstract Background Diabetic nephropathy is a global common cause of chronic kidney disease and end-stage renal disease. A lot of research has been conducted in biomedical sciences, which has enhanced understanding of the pathophysiology of diabetic nephropathy and has expanded the potential available therapies. An increasing number of evidence suggests that genetic alterations play a major role in development and progression of diabetic nephropathy. This systematic review was focused on searching an association between Arg913Gln variation in SLC12A3 gene with diabetic nephropathy in individuals with Type 2 Diabetes and Gitelman Syndrome. Methods An extensive systematic review of the literature was completed using PubMed, EBSCO and Cochrane Library, from their inception to January 2018. The PRISMA guidelines were followed and the search strategy ensured that all possible studies were identified to compile the review. Inclusion criteria for this review were: 1) Studies that analyzed the SLC12A3 gene in individuals with Type 2 Diabetes and Gitelman Syndrome. 2) Use of at least one analysis investigating the association between the Arg913Gln variation of SLC12A3 gene with diabetic nephropathy. 3) Use of a case–control or follow-up design. 4) Investigation of type 2 diabetes mellitus in individuals with Gitelman’s syndrome, with a history of diabetic nephropathy. Results The included studies comprised 2106 individuals with diabetic nephropathy. This review shows a significant genetic association in most studies in the Arg913Gln variation of SLC12A3 gene with the diabetic nephropathy, pointing out that the mutations of this gene could be a key predictor of end-stage renal disease. Conclusions The results showed in this systematic review contribute to better understanding of the association between the Arg913Gln variation of SLC12A3 gene with the pathogenesis of diabetic nephropathy in individuals with T2DM and GS.


2004 ◽  
Vol 10 (4-5) ◽  
pp. 620-626 ◽  
Author(s):  
A. Afifi ◽  
M. El Setouhy ◽  
M. El Sharkawy ◽  
M. Ali ◽  
H. Ahmed ◽  
...  

The prevalence of diabetic nephropathy as a cause of end-stage renal disease [ESRD] in Egypt has been examined in small cross-sectional studies, with conflicting results. The need for a large-scale study prompted us to perform this 6-year multiple cross-sectional study. A sample of ESRD patients enrolled in the Egyptian renal data system was evaluated during the period 1996-2001 for the prevalence of diabetic nephropathy. Prevalence gradually increased from 8.9% in 1996, to 14.5% in 2001. The mean age of patients with diabetic nephropathy was significantly higher than that of patients with ESRD from other causes. Mortality was also significantly higher in diabetic patients with ESRD


Author(s):  
L. Zhao ◽  
Y. Zhang ◽  
F. Liu ◽  
H. Yang ◽  
Y. Zhong ◽  
...  

Abstract Purpose To investigate the association between urinary complement proteins and renal outcome in biopsy-proven diabetic nephropathy (DN). Methods Untargeted proteomic and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analyses and targeted proteomic analysis using parallel reaction-monitoring (PRM)-mass spectrometry was performed to determine the abundance of urinary complement proteins in healthy controls, type 2 diabetes mellitus (T2DM) patients, and patients with T2DM and biopsy-proven DN. The abundance of each urinary complement protein was individually included in Cox proportional hazards models for predicting progression to end-stage renal disease (ESRD). Results Untargeted proteomic and functional analysis using the KEGG showed that differentially expressed urinary proteins were primarily associated with the complement and coagulation cascades. Subsequent urinary complement proteins quantification using PRM showed that urinary abundances of C3, C9, and complement factor H (CFAH) correlated negatively with annual estimated glomerular filtration rate (eGFR) decline, while urinary abundances of C5, decay-accelerating factor (DAF), and CD59 correlated positively with annual rate of eGFR decline. Furthermore, higher urinary abundance of CFAH and lower urinary abundance of DAF were independently associated with greater risk of progression to ESRD. Urinary abundance of CFAH and DAF had a larger area under the curve (AUC) than that of eGFR, proteinuria, or any pathological parameter. Moreover, the model that included CFAH or DAF had a larger AUC than that with only clinical or pathological parameters. Conclusion Urinary abundance of complement proteins was significantly associated with ESRD in patients with T2DM and biopsy-proven DN, indicating that therapeutically targeting the complement pathway may alleviate progression of DN.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lijun Zhao ◽  
Fang Liu ◽  
Lin Li ◽  
Junlin Zhang ◽  
Tingli Wang ◽  
...  

AbstractFew 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.


Author(s):  
Mohy Eldin Abd EL-Fattah ◽  
Taghrid B. El-abaseri ◽  
Hegazy Mohamed Abd Elaziz Mohamed

Background: Type 2 diabetes mellitus (DM) is the most common cause of end- stage renal disease. Albuminuria is the foremost commonly utilized marker to anticipate onset of diabetic nephropathy (DN) without sufficient affectability and specificity to identify early DN. Aim: This study aimed to evaluate Plasma cyclophilin A (CypA) as a new biomarker for early DN. Methods: This cross sectional study included 125 Egyptian subjects attending the out Patients Clinic of the Department of Internal Medicine, 10Th of Ramadan city Health Insurance Hospital and divided into-:control group, patient with diabetic mellitus, patients with Diabetic nephropathy and patient with diabetic nephropathy and other complications. Patients were subjected to measurement of plasma cyclophyline A, FBS, HbAIC, serum creatinine, serum urea, serum uric acid, k, Na, serum phosphorus, Albumin:Creatinine Ratio, GFR, Chol, TG, LDL HDL, AST, ALT, T.BIL, D.BIL ALB, TP, GLB and A/G ratio. Results: Results showed that Cyclophilin A was significantly correlated with duration of DM, CR, Urea, UR.A, Na, phosphorus, ACR, Chol, TG, LDL, AST, ALT, T.BIL, D.BIL. Meanwhile, Cyclophilin A was negatively correlated with HA1C, K, GFR, HDL, ALB, TP, GLB and A/G ratio. At cut-off level ≥84.14, cyclophilin A had 91% sensitivity and 62% specificity for diagnosing diabetic nephropathy. Conclusion: CypA can be used as an early marker for DN as we found early significant high levels of urinary CypA in diabetic patients with stage 2 DN even before the appearance of albuminuria.


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