scholarly journals Common Drug Pipelines for the Treatment of Diabetic Nephropathy and Hepatopathy: Can We Kill Two Birds with One Stone?

2020 ◽  
Vol 21 (14) ◽  
pp. 4939
Author(s):  
Yoshio Sumida ◽  
Masashi Yoneda ◽  
Hidenori Toyoda ◽  
Satoshi Yasuda ◽  
Toshifumi Tada ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
The United States ◽  
Severe Form ◽  
Peroxisome Proliferator ◽  
Related Factor ◽  
Cross Sectional ◽  
Common Drug ◽  
Glucagon Like Peptide 1 ◽  
Peroxisome Proliferator Activated Receptors ◽  
Stage Renal Disease

Type 2 diabetes (T2D) is associated with diabetic nephropathy as well as nonalcoholic steatohepatitis (NASH), which can be called “diabetic hepatopathy or diabetic liver disease”. NASH, a severe form of nonalcoholic fatty disease (NAFLD), can sometimes progress to cirrhosis, hepatocellular carcinoma and hepatic failure. T2D patients are at higher risk for liver-related mortality compared with the nondiabetic population. NAFLD is closely associated with chronic kidney disease (CKD) or diabetic nephropathy according to cross-sectional and longitudinal studies. Simultaneous kidney liver transplantation (SKLT) is dramatically increasing in the United States, because NASH-related cirrhosis often complicates end-stage renal disease. Growing evidence suggests that NAFLD and CKD share common pathogenetic mechanisms and potential therapeutic targets. Glucagon-like peptide 1 (GLP-1) receptor agonists and sodium–glucose cotransporter 2 (SGLT2) inhibitors are expected to ameliorate NASH and diabetic nephropathy/CKD. There are no approved therapies for NASH, but a variety of drug pipelines are now under development. Several agents of them can also ameliorate diabetic nephropathy/CKD, including peroxisome proliferator-activated receptors agonists, apoptosis signaling kinase 1 inhibitor, nuclear factor-erythroid-2-related factor 2 activator, C-C chemokine receptor types 2/5 antagonist and nonsteroidal mineral corticoid receptor antagonist. This review focuses on common drug pipelines in the treatment of diabetic nephropathy and hepatopathy.

scholarly journals Peroxisome Proliferator-Activated Receptors in Diabetic Nephropathy

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-11 ◽  
Author(s):  
Shinji Kume ◽  
Takashi Uzu ◽  
Keiji Isshiki ◽  
Daisuke Koya
Keyword(s):  
Diabetic Nephropathy ◽  
Therapeutic Potential ◽  
Experimental Studies ◽  
Renin Angiotensin System ◽  
Pressure Control ◽  
Peroxisome Proliferator ◽  
Patients With Diabetes ◽  
Ppar Agonists ◽  
Peroxisome Proliferator Activated Receptors ◽  
Stage Renal Disease

Diabetic nephropathy is a leading cause of end-stage renal disease, which is increasing in incidence worldwide, despite intensive treatment approaches such as glycemic and blood pressure control in patients with diabetes mellitus. New therapeutic strategies are needed to prevent the onset of diabetic nephropathy. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear transcription factors that play important roles in lipid and glucose homeostases. These agents might prevent the progression of diabetic nephropathy, since PPAR agonists improve dyslipidemia and insulin resistance. Furthermore, data from murine models suggest that PPAR agonists also have independent renoprotective effects by suppressing inflammation, oxidative stress, lipotoxicity, and activation of the renin-angiotensin system. This review summarizes data from clinical and experimental studies regarding the relationship between PPARs and diabetic nephropathy. The therapeutic potential of PPAR agonists in the treatment of diabetic nephropathy is also discussed.

scholarly journals Diabetic nephropathy as a cause of end-stage renal disease in Egypt: a six-year study

2004 ◽  
Vol 10 (4-5) ◽  
pp. 620-626 ◽  
Author(s):  
A. Afifi ◽  
M. El Setouhy ◽  
M. El Sharkawy ◽  
M. Ali ◽  
H. Ahmed ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Large Scale ◽  
Cross Sectional Study ◽  
Diabetic Patients ◽  
Cross Sectional ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients

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

scholarly journals PPARα and PPARβ/δ are negatively correlated with proinflammatory markers in leukocytes of an obese pediatric population

2020 ◽  
Author(s):  
Karina Vargas-Sánchez ◽  
Laura Vargas ◽  
Yenny Urrutia ◽  
Iván Beltrán ◽  
Ana Beatriz Rossi ◽  
...  
Keyword(s):  
Pediatric Obesity ◽  
Pediatric Population ◽  
Fat Distribution ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Tnf Α ◽  
Android Fat ◽  
Glucagon Like Peptide 1 ◽  
Peroxisome Proliferator Activated Receptors ◽  
Inflammatory Profile

Abstract Background: Obesity configures a pathophysiological profile that predisposes the development of metabolic and cardiovascular diseases, critically impacting public health. The chronic dysregulation of immuno-metabolic components triggered by pediatric obesity is a common but scarcely understood aspect of the disease. Peroxisome proliferator-activated receptors (PPARs) are a group of transcription factors essential for energy and immune homeostasis of different tissues. Besides, the glucagon-like peptide-1 receptor (GLP-1R) activation influences insulin secretion, but also regulates the cytokine profile possibly mediated through a PPAR isotype. However, the role of PPARs and GLP-1R in leukocytes from obese pediatric patients remains unclear. Therefore, we examined the expression of PPARs isotypes and GLP-1R in leukocytes, and its correlation with metabolic, hormonal, inflammatory, and anthropometric markers in an obese pediatric population.Results: Obese children and adolescents presented a significant increase in anthropometric and body composition parameters, TG, VLDL, TG/HDL, android fat (%)/gynoid fat (%) (A/G%) index, and HOMA score when compared with the control group. Obese participants exhibited a pro-inflammatory profile with an augment of IL-8 (p=0,0081), IL-6 (p=0,0005), TNF-α (p=0,0004), IFN-γ (p=0,0110), MCP-1 (p=0,0452), and adipsin (p=0,0397), whereas displayed a reduction of adiponectin (p=0,0452). The expression of PPARα and GLP-1R was lower in the leukocytes from obese participants than in lean subjects. Furthermore, PPARα correlates negatively with TNF-α (p=0,0383), while GLP-1R did not show correlation with any inflammatory variable. However, both receptors correlate negatively with the abdominal skinfold. Although PPARβ/δ expression was similar between groups, it was negatively associated with IL-8 levels (p=0,0085).Conclusions: PPARα and PPARβ/δ expression are negatively correlated with the proinflammatory markers TNF-α and IL-8, respectively, suggesting participation in the regulation of inflammation which was observed to be altered in pediatric obesity. Furthermore, PPARα and GLP-1R are downregulated in leukocytes from obese participants. The low expression of both receptors is correlated with an increase in abdominal skinfold, suggesting a role in fat distribution that could indirectly affect cytokine secretion from different immune and adipose cells, likely triggering an inflammatory profile as a consequence of obesity. Altogether, these findings may impact the understanding and implementation of PPARα or GLP-1R agonists in the clinic.

scholarly journals Rate of change of end-stage renal disease treatment incidence 1978-1987--has there been selection?

1992 ◽  
Vol 2 (10) ◽  
pp. 1502-1506
Author(s):  
S J Rosansky ◽  
K Jackson
Keyword(s):  
Diabetic Nephropathy ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
The United States ◽  
Rate Of Change ◽  
Analysis Of Covariance ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Stage Renal Disease ◽  
End Stage

End-stage renal disease (ESRD) treatment rates in the United States have increased steadily since 1973. Decreasing selection against elderly patients with a poor prognostic primary cause of ESRD (i.e., diabetic nephropathy) may partly account for this increase in rates. To test this hypothesis, we calculated log ESRD treatment incidence (ESRDI) rates by four major primary causes of ESRD (diabetic nephropathy (DN), hypertensive nephropathy (HN), glomerulonephritis (GN), and cystic kidney disease (PC); two age groups (old (O), greater than 65 and young (Y), 15 to 44 yr of age) for black and white, male and female, new ESRD patients from 1978 to 1987. As predicted, summary log ESRDI slopes (produced by analysis of covariance) occurred in the following decreasing order, ODN (0.19), OGN = OHN = YDN (0.134). YHN = YPC = YGN (in white patients) = slope not significantly different from 0. Log ESRDI slopes for young black males and females with GN increased significantly between 1978 and 1987, possibly as a result of an increased incidence of GN. In conclusion, decreasing selection may be a factor in the continuing increase in the U.S. ESRD population.

scholarly journals Etiology of End-Stage Renal Disease and Arterial Stiffness among Hemodialysis Patients

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Balsam El Ghoul ◽  
Yazan Daaboul ◽  
Serge Korjian ◽  
Andrew El Alam ◽  
Anthony Mansour ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Arterial Stiffness ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Hemodialysis Patients ◽  
Cross Sectional ◽  
History Of ◽  
Stage Renal Disease ◽  
End Stage

Background. Prior studies have demonstrated that conventional and emerging CV risk factors are associated with worsening arterial stiffness among end-stage renal disease (ESRD) patients on hemodialysis. The present cross-sectional study evaluates the association between the etiology of ESRD and arterial stiffness among a cohort of hemodialysis patients.Methods. Etiology of ESRD was identified from patients’ medical records and classified as either vascular renal disease, diabetic nephropathy, nondiabetic glomerulopathy, tubular interstitial nephropathy, hereditary nephropathy, or ESRD of unconfirmed etiology.Results. A total of 82 subjects were enrolled. cfPWV was independently associated with the composite of either diabetic nephropathy or vascular renal disease (p=0.022), pulse pressure (p=0.001), and a history of CV events (p=0.025), but not history of hypertension or diabetes mellitus alone. The median cfPWVs in diabetic nephropathy and vascular renal disease were comparable and significantly higher than median cfPWVs in other etiologies of ESRD.Conclusion. The study suggests that the etiology of ESRD is independently associated with arterial stiffness among hemodialysis patients. Furthermore, arterial stiffness was higher among patients who developed renal sequelae of either diabetes mellitus or hypertension as compared with those who have a history of either diabetes mellitus or hypertension alone.

scholarly journals Peroxisome proliferator-activated receptors and thiazolidinediones in diabetic nephropathy

2019 ◽  
Vol 8 (10) ◽  
pp. 2344
Author(s):  
Navneet O. Soni ◽  
Saroja V. Pawar ◽  
Sheetal Kale ◽  
Uday A. Mane ◽  
Pravin U. Bhosale ◽  
...  
Keyword(s):  
Heart Failure ◽  
Diabetic Nephropathy ◽  
Volume Expansion ◽  
Peroxisome Proliferator ◽  
Ppar Γ ◽  
Intracellular Mechanism ◽  
Current Article ◽  
Peroxisome Proliferator Activated Receptors ◽  
Expansion Effect

Diabetic nephropathy is global problem with several drugs into trial without much success the current article highlights the role of thiazolidinedione’s in diabetic nephropathy by scrutinizing and reconnoitring the cellular and intracellular mechanism and shielding action and the role of peroxisome proliferator-activated gamma receptors (PPARγ) receptors. Not only anti-diabetic action but renal protective effect with evidence based study has been highlighted. PPAR γ-is versatile target having numerous benefits and mainly preventing fibrosis in diabetic experimental model and some clinical case report yet, the benefits are not up to mark, since renal failure itself causes volume expansion and the thiazolidinedione’s (TZDs) also preserve salt and water and lead to congestive heart failure which constraints its clinical application. Dual activators and balaglitazone selective PPAR modulator are having upcoming potential for treatment of diabetic nephropathy. Further detail investigation on such drug is needed to explore. However adverse effect like heart failure, osteoporosis and volume expansion effect over-rides the beneficial effect thus limiting its clinical use of currently available TZDs.

scholarly journals Urinary nephrin is earlier, more sensitive and specific marker of diabetic nephropathy than microalbuminuria

2019 ◽  
Vol 0 (0) ◽  
Author(s):  
Irena Kostovska ◽  
Tosheska Trajkovska ◽  
Sonja Topuzovska ◽  
Svetlana Cekovska ◽  
Goce Spasovski ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Early Detection ◽  
Cross Sectional Study ◽  
Specific Protein ◽  
Control Group ◽  
Photometric Method ◽  
Specific Marker ◽  
Cross Sectional ◽  
Potential Biomarker ◽  
Stage Renal Disease

Summary Background Diabetic nephropathy (DN) is a leading cause of end-stage renal disease. Progressive damage and decline in the number of podocytes often occur in the early stages of DN. Thus, nephrin as a podocyte-specific protein may be regarded as a potential biomarker of early detection of DN. The aim of this study is to determine whether urinary nephrin is an earlier marker in DN than microalbuminuria and to test the significance of urinary nephrin as a marker for early detection of DN. Methods Our cross-sectional study included 90 patients with type 2 diabetes mellitus (T2DM), 30 patients with diagnosed DN and 60 patients without diagnosed DN. As a control group, we used 30 healthy subjects. All patients with T2DM were classified into three subgroups according to urinary microalbumin/creatinine ratio (UMCR): normoalbuminuric, microalbuminuric and macroalbuminuric patients. Nephrin in urine was measured by immunoenzyme assay, microalbumin with turbidimetric and creatinine with the photometric method. In blood sera, we measured a few standard biochemical parameters. Results Nephrinuria was found to be present in 100% of patients with T2DM and macroalbuminuria, in 88% with microalbuminuria, as well as 82% of patients with T2DM and normoalbuminuria. A concentration of urinary nephrin was significantly increased in all groups of subjects with T2DM compared to the control group (p<0.05). Nephrinuria correlated statistically negative with eGFR (r=-0.54). ROC analysis showed that nephrin has a total predicted probability of 96% in patients with DN. Conclusions Urinary nephrin is earlier, more specific and sensitive marker than microalbumin in early detection of DN.

scholarly journals Plasma Cyclophilin A as a Novel Biomarker in Chronic Nephropathy

2020 ◽  
pp. 63-72
Author(s):  
Mohy Eldin Abd EL-Fattah ◽  
Taghrid B. El-abaseri ◽  
Hegazy Mohamed Abd Elaziz Mohamed
Keyword(s):  
Diabetic Nephropathy ◽  
Cyclophilin A ◽  
Cross Sectional Study ◽  
Control Group ◽  
Diabetic Patients ◽  
Cross Sectional ◽  
Stage Renal Disease ◽  
End Stage ◽  
G Ratio

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.

scholarly journals Validity of Serum Uromodulin as Early Diagnosis Marker of Diabetic Nephropathy in T2DM

2021 ◽  
Vol 53 (2) ◽  
Author(s):  
Rizki Dumpatna ◽  
Nina Tristina ◽  
Dewi Kartika Turbawaty ◽  
Anna Tjandrawati
Keyword(s):  
Diabetic Nephropathy ◽  
Predictive Value ◽  
Gold Standard ◽  
Early Stage ◽  
Distal Tubule ◽  
Thick Ascending Limb ◽  
Tubular Atrophy ◽  
Cross Sectional ◽  
Stage Renal Disease ◽  
Early Diagnose

Increased prevalence of DM is accompanied by increased in its various complications include diabetic nephropathy, which can lead to end stage renal disease (ESRD). Urinary albumin-creatinine ratio (uACR) is the gold standard for diabetic nephropathy; however, it has several limitations, including the inability to early diagnose due to the absence of increased level in uACR. Uromodulin is produced by thick ascending limb (TAL) at Henle’s loop and early distal tubule of nephron. Uromodulin will decrease when tubular atrophy occurs in early stage of renal impairment with normoalbuminuria. The aim of this study was to determine the validity of serum uromodulin in type 2 diabetes mellitus (T2DM) in identifying diabetic nephropathy by comparing it with uACR as gold standard. This study was a cross-sectional analytical observational study at Dr. Hasan Sadikin (RSHS) Bandung from June to August 2020. Subjects consisted of 62 patiens with T2DM. Results showed that the serum uromodulin level had a sensitivity of 93.3%, a specificity of 88.2%, a positive predictive value of 95.5%, a negative predictive value of 83.3%, and an accuracy of 91,9% and an AUC value of 0.975. The cut-off point of serum uromodulin in this study was 47.195 ng/mL. In conclusion, serum uromodulin, when compared to the uACR as the gold standard, has good sensitivity and specificity for identifying diabetic nephropathy.

scholarly journals MIKROALBUMIN AIR KEMIH (URIN) PASIEN DM TIPE 2

2018 ◽  
Vol 15 (3) ◽  
pp. 98
Author(s):  
Emmy Wahyuni ◽  
Imam Budiwiyono
Keyword(s):  
Diabetic Nephropathy ◽  
Diastolic Pressure ◽  
The Body ◽  
P Value ◽  
Cross Sectional ◽  
Type 2 Dm ◽  
Stage Renal Disease ◽  
End Stage ◽  
Distribution Frequency

Diabetic Nephropathy is one of several chronic complication of type 2 DM that could lead to end stage renal disease (ESRD). In type2 DM patients, about 85% of ESRD caused by diabetic nephropathy. Persistent microalbuminuria can be predictor for nephropathy. Earlydetection of microalbuminuria could be useful in improving an aggressive treatment to avoid ESRD and other macrovasculer disorder intype 2 DM patients. The purpose of this study was to describe the microalbuminuria profile in type 2 DM patients. A cross sectional studywas taken on 21 type 2 DM patients. Data were analyzed by descriptive analyzed (distribution, frequency, mean, standard deviation, ttest). P value < 0.05 was considered significant. This study reveals that frequency microalbuminuria was 78.9%. There was no differentage between microalbuminuria and normoalbuminuria. Duration of diabetes in microalbuminuria patients were more longer. Themean time is 45.3 (41) months and normoalbuminuria 36(16) months. The systolic and diastolic pressure in microlabuminuria washigher than normoalbuminuria. The body mass index between microalbuminurian and normoalbuminuria (P < 0.05) was significantlydifferent. In patient with microalbuminuria the mean of HbA1c value was 7.9(2.5) and in normoalbuminuria patient it was 9(1.8).There were no significant different of lipid profile between both samples. In this study was only found significantly different of body massindex between microalbuminuria and normoalbuminuria patients.

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