scholarly journals Antiinflammatory Actions of Klotho: Implications for Therapy of Diabetic Nephropathy

2021 ◽  
Vol 22 (2) ◽  
pp. 956
Author(s):  
Marlena Typiak ◽  
Agnieszka Piwkowska
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Calcium Metabolism ◽  
Renal Involvement ◽  
Therapeutic Effects ◽  
Beneficial Effects ◽  
Early Biomarker ◽  
Klotho Protein ◽  
Urine Levels ◽  
Proinflammatory Factors

Klotho was initially introduced as an antiaging molecule. Klotho deficiency significantly reduces lifespan, and its overexpression extends it and protects against various pathological phenotypes, especially renal disease. It was shown to regulate phosphate and calcium metabolism, protect against oxidative stress, downregulate apoptosis, and have antiinflammatory and antifibrotic properties. The course of diabetes mellitus and diabetic nephropathy resembles premature cellular senescence and causes the activation of various proinflammatory and profibrotic processes. Klotho was shown to exert many beneficial effects in these disorders. The expression of Klotho protein is downregulated in early stages of inflammation and diabetic nephropathy by proinflammatory factors. Therefore, its therapeutic effects are diminished in this disorder. Significantly lower urine levels of Klotho may serve as an early biomarker of renal involvement in diabetes mellitus. Recombinant Klotho administration and Klotho overexpression may have immunotherapeutic potential for the treatment of both diabetes and diabetic nephropathy. Therefore, the current manuscript aims to characterize immunopathologies occurring in diabetes and diabetic nephropathy, and tries to match them with antiinflammatory actions of Klotho. It also gives reasons for Klotho to be used in diagnostics and immunotherapy of these disorders.

scholarly journals PGNMID in a patient with diabetes mellitus

2021 ◽  
pp. 239936932098478
Author(s):  
Joana Marques ◽  
Patrícia Cotovio ◽  
Mário Góis ◽  
Helena Sousa ◽  
Fernando Nolasco
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Renal Disease ◽  
Renal Involvement ◽  
Organ Damage ◽  
Therapeutic Implications ◽  
Stage Renal Disease

Diabetic nephropathy is a well known complication of diabetes mellitus and the leader cause of end -stage renal disease worldwide. Nonetheless, other forms of renal involvement can occur in diabetic population. Since it has prognostic and therapeutic implications, differentiating non-diabetic renal disease from diabetic nephropathy is of great importance. We report an 80-year-old man with well-controlled type 2 diabetes mellitus and hypertension, who presented with rapid deterioration of renal function, nephrotic proteinuria, microscopic hematuria and leukocyturia. The atypical clinical presentation prompted us to perform a kidney biopsy. A diagnosis of proliferative glomerulonephritis with monoclonal immunoglobulin deposits (light chain only variant) was made, with however some chronic histological aspects which made us took a conservative therapeutic attitude. We emphasize that other causes of chronic proteinuric kidney disease should be considered in patients with type 2 diabetes mellitus, based on clinical suspicion, absence of other organ damage and mostly if an atypical presentation is seen. We review the spectrum of monoclonal gammopathies of renal significance, focusing on this rare and newly describe entity.

scholarly journals Application of Liquid Chromatography with Fluorimetric Detection for the Determination of Urinary Pentosidine in Type 2 Diabetes Mellitus Patients: Effect of Telmisartan Administration on Podocyturia and Relationship with Metabolic Control

2018 ◽  
Vol 62 (2) ◽  
Author(s):  
Carlos Kornhauser ◽  
Gloria Barbosa-Sabanero ◽  
Noemí Gutierrez-Romero ◽  
Myrna Sabanero ◽  
Elva L. Perez-Luque ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Metabolic Control ◽  
Fluorimetric Detection ◽  
Beneficial Effects ◽  
Short Period ◽  
The Face

The beneficial effects of a short period of Telmisartan administration were successfully assessed trough pentosidine urinary levels (uPen) and urinary podocyte excretion (UPE), in type 2 diabetes mellitus (DM2) patients. Patients with podocyturia received Telmisartan treatment (80 mg/day) for two months.  uPen were quantified pre and post treatment using HPLC with fluorimetric detection and in-lab synthesized standard. Immunofluorescence method for podocalyxin was used to evaluate urinary excretion of podocytes. uPen and UPE significantly decrease after treatment (p<0.01255 and p<0.005 respectively), as well as serum total cholesterol and LDL levels (p<0.001). These results suggest that podocyte protection by Telmisartan even in the face of deficient metabolic control could be an important matter in the prevention and progression of diabetic nephropathy. This study also strengthens evidence of the promising role of pentosidine as prognostic and diagnostic markers in diabetic nephropathy

scholarly journals Hyperlipidemia: a factor contributing to diabetic nephropathy development and progress

1993 ◽  
Vol 39 (5) ◽  
pp. 7-9 ◽  
Author(s):  
M. V. Shestakova ◽  
I. I. Dedov ◽  
I. I. Neverov ◽  
E. S. Severghina ◽  
T. G. Dyuzheva ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Low Density Lipoprotein ◽  
Renal Involvement ◽  
Density Lipoprotein ◽  
Insulin Dependent Diabetes Mellitus ◽  
Serum Levels ◽  
Renal Tissue ◽  
Dependent Diabetes Mellitus ◽  
Insulin Dependent

Twenty-nine patients with insulin-dependent diabetes mellitus with similarly manifest renal involvement were examined to elucidate the role of dyslipidemia in diabetic nephropathy progress. Clinicolaboratory parameters (urinary albumin excretion, blood serum levels of total cholesterol, triglycerides, low, very low, and high density lipoprotein cholesterol) and morphologic changes in renal tissue biopsy specimens were analyzed. An increment of the number of large lipid incorporations was observed in various cells of renal glomeruli and interstitium, as well as a high prevalence of low density lipoprotein deposition in glomerular basal membranes and canaliculi as the renal process augmented in severity. Since lipids accumulating in glomerular structures may stimulate mesangial cell proliferation and mesangial matrix hyperproduction, the authors believe that dyslipidemia in diabetes mellitus may be conducive to a more rapid progress of renal disease.

scholarly journals Mir-138 plays an important role in diabetic nephropathy through SIRT1-p38-TTP regulatory axis

2020 ◽  
Author(s):  
Fengxun Liu ◽  
Jia Guo ◽  
Yingjin Qiao ◽  
Shaokang Pan ◽  
Jiayu Duan ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Experimental Methods ◽  
Therapeutic Effects ◽  
Key Factors ◽  
Regulatory Relationship ◽  
Podocyte Injury ◽  
P38 Pathway

Abstract Background : Diabetic nephropathy (DN) is the main cause of chronic kidney disease (CKD) and is one of the most common and serious complications of diabetes mellitus (DM). SIRT1 and TTP are two important protective factors in DN, however, the regulatory relationship between SIRT1 and TTP and the underneath mechanism are interesting but still unclear. Identifying the key factors that regulate SIRT1 or TTP may be of great value to the understanding and treatment of the DN. Methods : in this study, through systematic experimental methods, we found that the expression of miR-138 was significantly up-regulated in DN clinical patients samples, and our experimental results suggested that miR-138 could bind the 3’UTR of SIRT1 and inhibit its expression in both cultured podocytes and db/db mice kidney tissues. Results : furthermore, our in vitro and in vivo date also indicated miR-138 could target SIRT1 and affect TTP through p38 pathway. And down-regulation of miR-138 attenuated podocyte injury and showed some extend of therapeutic effects in DN mice models. Conclusion : our findings reveal that the regulatory axis of miR-138-SIRT1-p38-TTP might play a key role in DN. We believe these findings may be of some value for deepening the understanding of DN and may serve as a reference for future treatment of this disease.

Abstract 158: Role of Prorenin Receptor in the Enhancement of Renin Activity in the Urine of Diabetic Patients

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Danielle Y Arita ◽  
Christina Luffman ◽  
Camille T Bourgeois ◽  
Tina Thethi ◽  
Gabrielle Dawkins ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Low Ph ◽  
Renin Activity ◽  
Soluble Form ◽  
Urine Ph ◽  
Prorenin Receptor ◽  
Membrane Bound ◽  
Urine Levels

High prorenin levels in the circulation are associated with the progression of diabetic nephropathy and microvascular changes in diabetes. In spite of high plasma prorenin, the urine of diabetes mellitus patients exhibits very low pH and contains high levels of “active” renin, but low levels of prorenin. Prorenin binding to the prorenin receptor (PRR) results in non-proteolytic activation of prorenin and stimulation of intracellular synthesis of transforming growth factor-beta (TGF-β). Furthermore, the PRR cytosolic domain is associated with the vacuolar H+-ATPase, which is involved in acid-base homeostasis by renal intercalated cells. In diabetes, the collecting duct is the major source of prorenin and PRR is upregulated in the kidneys of diabetic rats. We examined the relationships among urine levels of renin (uRen), prorenin (uPro), soluble PRR (sPRR) and TGF-β (uTGF-β) in 93 subjects, including non-diabetes mellitus (Non-DM: n=64); and type-2 diabetes mellitus (DM; n=29) patients. Urine albumin (uAlb), creatinine (uCr) and pH were also assessed. DM patients showed higher uRen levels (DM: 81±21 vs Non-DM: 29±4.5 ng AngI/mL/hr; p<0.001), which were positively associated with uAlb/uCr (p<0.05, r=0.21) and inversely correlated with urine pH (p<0.01, r=-0.38). These values contrasted with uPro levels, which were no different between groups. DM patients showed increased uTGF-β compared to Non-DM (DM: 22±5.3 vs Non-DM: 5.6±1.5 pg/mg uCr; p<0.0001). Urine sPRR levels were positively correlated with urine pH (p<0.0001, r=0.56). No differences were observed in sPRR plasma and urine levels between non-DM and DM patients. However, the plasma levels of sPRR were 12.5 and 18.5-fold higher than in urine of Non-DM and DM, respectively. Treatment with RAS blockers increased sPRR in plasma (DM with RAS blockade: 24,455±2,151 vs DM without RAS blockade: 17,726±1,255 pg/mL, p<0.001) but not in urine. These data suggest that the cell membrane-bound PRR, not the soluble form, might be responsible for the increases in renin activity and TGF-β, as well as in the low pH in the urine of type-2 DM patients. It is likely that prorenin-mediated activation of membrane bound PRR promotes diabetic nephropathy by increasing urinary formation of TGF-β.

Diabetic nephropathy and arterial stiffness in patients with type 1 diabetes mellitus

2019 ◽  
Author(s):  
Karina Sarkisova ◽  
Iwona-Renata Jarek-Martynowa ◽  
Marina Shestakova ◽  
Minara Shamkhalova ◽  
Alexander Parfenov
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Diabetic Nephropathy ◽  
Arterial Stiffness ◽  
Type 1 Diabetes Mellitus
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