scholarly journals Kidney Disease in Diabetic Patients: From Pathophysiology to Pharmacological Aspects with a Focus on Therapeutic Inertia

2021 ◽  
Vol 22 (9) ◽  
pp. 4824
Author(s):  
Guido Gembillo ◽  
Ylenia Ingrasciotta ◽  
Salvatore Crisafulli ◽  
Nicoletta Luxi ◽  
Rossella Siligato ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Early Recognition ◽  
Microvascular Complications ◽  
Diabetic Patients ◽  
Therapeutic Inertia ◽  
Glycemic Target ◽  
The Right ◽  
Stage Renal Disease ◽  
Kidney Impairment ◽  
End Stage

Diabetes mellitus represents a growing concern, both for public economy and global health. In fact, it can lead to insidious macrovascular and microvascular complications, impacting negatively on patients’ quality of life. Diabetic patients often present diabetic kidney disease (DKD), a burdensome complication that can be silent for years. The average time of onset of kidney impairment in diabetic patients is about 7–10 years. The clinical impact of DKD is dangerous not only for the risk of progression to end-stage renal disease and therefore to renal replacement therapies, but also because of the associated increase in cardiovascular events. An early recognition of risk factors for DKD progression can be decisive in decreasing morbidity and mortality. DKD presents patient-related, clinician-related, and system-related issues. All these problems are translated into therapeutic inertia, which is defined as the failure to initiate or intensify therapy on time according to evidence-based clinical guidelines. Therapeutic inertia can be resolved by a multidisciplinary pool of healthcare experts. The timing of intensification of treatment, the transition to the best therapy, and dietetic strategies must be provided by a multidisciplinary team, driving the patients to the glycemic target and delaying or overcoming DKD-related complications. A timely nephrological evaluation can also guarantee adequate information to choose the right renal replacement therapy at the right time in case of renal impairment progression.

Management of acute kidney injury and chronic kidney disease

2017 ◽  
pp. 1087-1096
Author(s):  
Natalie Ebert ◽  
Elke Schaeffner
Keyword(s):  
Older Adults ◽  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Kidney Injury ◽  
Staging System ◽  
Kidney Damage ◽  
The Right ◽  
Stage Renal Disease ◽  
End Stage

Both acute and chronic states of kidney disease have considerable healthcare impact as they can produce enormous disease burden and costs. To classify chronic kidney disease into the CKD staging system, glomerular filtration rate as an index of kidney function, as well as albuminuria as a marker of kidney damage have to be assessed as correctly as possible. Misclassification is a serious concern due to the difficulties in precise GFR assessment and correct interpretation of results. Differentiating between pure senescence and true disease among older adults can be a delicate issue. To find the right renal replacement option for individuals that progress to end-stage renal disease can be challenging, and some older patients may even benefit from conservative care without dialysis. To prevent acute kidney injury as a frequent and potentially life-threatening complication, clinicians need to develop an understanding of the common vulnerability to kidney damage among older adults.

scholarly journals Kidney Disease in HIV Infection

2019 ◽  
Vol 8 (8) ◽  
pp. 1254 ◽  
Author(s):  
Gaetano Alfano ◽  
Gianni Cappelli ◽  
Francesco Fontana ◽  
Luca Di Lullo ◽  
Biagio Di Iorio ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Life Expectancy ◽  
Early Recognition ◽  
Renal Involvement ◽  
People Living With Hiv ◽  
Risk Of Death ◽  
Age Related ◽  
Stage Renal Disease ◽  
End Stage ◽  
Living With Hiv

Antiretroviral therapy (ART) has significantly improved life expectancy of infected subjects, generating a new epidemiological setting of people aging withHuman Immunodeficiency Virus (HIV). People living with HIV (PLWH), having longer life expectancy, now face several age-related conditions as well as side effects of long-term exposure of ART. Chronic kidney disease (CKD) is a common comorbidity in this population. CKD is a relentlessly progressive disease that may evolve toward end-stage renal disease (ESRD) and significantly affect quality of life and risk of death. Herein, we review current understanding of renal involvement in PLWH, mechanisms and risk factors for CKD as well as strategies for early recognition of renal dysfunction and best care of CKD.

scholarly journals Revisiting Experimental Models of Diabetic Nephropathy

2020 ◽  
Vol 21 (10) ◽  
pp. 3587
Author(s):  
Anna Giralt-López ◽  
Mireia Molina-Van den Bosch ◽  
Ander Vergara ◽  
Clara García-Carro ◽  
Daniel Seron ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Experimental Models ◽  
Diabetic Patients ◽  
Rodent Models ◽  
Basement Membrane Thickening ◽  
Matrix Expansion ◽  
Risk Biomarkers ◽  
Stage Renal Disease ◽  
End Stage

Diabetes prevalence is constantly increasing and, nowadays, it affects more than 350 million people worldwide. Therefore, the prevalence of diabetic nephropathy (DN) has also increased, becoming the main cause of end-stage renal disease (ESRD) in the developed world. DN is characterized by albuminuria, a decline in glomerular filtration rate (GFR), hypertension, mesangial matrix expansion, glomerular basement membrane thickening, and tubulointerstitial fibrosis. The therapeutic advances in the last years have been able to modify and delay the natural course of diabetic kidney disease (DKD). Nevertheless, there is still an urgent need to characterize the pathways that are involved in DN, identify risk biomarkers and prevent kidney failure in diabetic patients. Rodent models provide valuable information regarding how DN is set and its progression through time. Despite the utility of these models, kidney disease progression depends on the diabetes induction method and susceptibility to diabetes of each experimental strain. The classical DN murine models (Streptozotocin-induced, Akita, or obese type 2 models) do not develop all of the typical DN features. For this reason, many models have been crossed to a susceptible genetic background. Knockout and transgenic strains have also been created to generate more robust models. In this review, we will focus on the description of the new DN rodent models and, additionally, we will provide an overview of the available methods for renal phenotyping.

scholarly journals Association of HbA1C Variability and Renal Progression in Patients with Type 2 Diabetes with Chronic Kidney Disease Stages 3–4

2018 ◽  
Vol 19 (12) ◽  
pp. 4116 ◽  
Author(s):  
Mei-Yueh Lee ◽  
Jiun-Chi Huang ◽  
Szu-Chia Chen ◽  
Hsin-Ying Chiou ◽  
Pei-Yu Wu
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Lower Risk ◽  
Glycosylated Hemoglobin ◽  
Diabetic Patients ◽  
Patients With Diabetes ◽  
Cox Analysis ◽  
Stage Renal Disease ◽  
End Stage ◽  
Hba1c Variability

Little is known about the predictive value of glycosylated hemoglobin (HbA1C) variability in patients with advanced chronic kidney disease (CKD). The aim of this study was to investigate whether HbA1C variability is associated with progression to end-stage renal disease in diabetic patients with stages 3–5 CKD, and whether different stages of CKD affect these associations. Three hundred and eighty-eight patients with diabetes and stages 3–5 CKD were enrolled in this longitudinal study. Intra-individual HbA1C variability was defined as the standard deviation (SD) of HbA1C, and the renal endpoint was defined as commencing dialysis. The results indicated that, during a median follow-up period of 3.5 years, 108 patients started dialysis. Adjusted Cox analysis showed an association between the highest tertile of HbA1C SD (tertile 3 vs. tertile 1) and a lower risk of the renal endpoint (hazard ratio = 0.175; 95% confidence interval = 0.059–0.518; p = 0.002) in the patients with an HbA1C level ≥ 7% and stages 3–4 CKD, but not in stage 5 CKD. Further subgroup analysis showed that the highest two tertiles of HbA1C SD were associated with a lower risk of the renal endpoint in the group with a decreasing trend of HbA1C. Our results demonstrated that greater HbA1C variability and a decreasing trend of HbA1C, which may be related to intensive diabetes control, was associated with a lower risk of progression to dialysis in the patients with stages 3–4 CKD and poor glycemic control (HbA1c ≥ 7%).

scholarly journals The Role of MicroRNAs in the Pathogenesis of Diabetic Nephropathy

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Jian Tang ◽  
Deyi Yao ◽  
Haiying Yan ◽  
Xing Chen ◽  
Linjia Wang ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Molecular Mechanisms ◽  
Microvascular Complications ◽  
Diabetic Patients ◽  
Hemodynamic Changes ◽  
Clinical Value ◽  
New Ideas ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy (DN) is one of the most common microvascular complications in diabetic patients; it is also an important cause of renal dysfunction, renal fibrosis, and end-stage renal disease. Unfortunately, the pathogenesis of DN is complex and has not yet been fully elucidated; hence, the pathogenesis of DN to determine effective treatments of crucial importance is deeply explored. Early DN research focuses on hemodynamic changes and metabolic disorders, and recent studies have shown the regulatory role of microRNAs (miRNAs) in genes, which may be a new diagnostic marker and therapeutic target for diabetic nephropathy. In this review, we summarize the recent advances in the clinical value and molecular mechanisms of miRNAs in DN, providing new ideas for the diagnosis and treatment of DN.

scholarly journals The Multi-Therapeutic Role of MSCs in Diabetic Nephropathy

2021 ◽  
Vol 12 ◽  
Author(s):  
Yi Wang ◽  
Su-Kang Shan ◽  
Bei Guo ◽  
Fuxingzi Li ◽  
Ming-Hui Zheng ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Diabetic Kidney Disease ◽  
Microvascular Complications ◽  
Diabetic Patients ◽  
Differentiation Potential ◽  
Therapeutic Role ◽  
Promising Strategy ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy (DN) is one of the most common diabetes mellitus (DM) microvascular complications, which always ends with end-stage renal disease (ESRD). Up to now, as the treatment of DN in clinic is still complicated, ESRD has become the main cause of death in diabetic patients. Mesenchymal stem cells (MSCs), with multi-differentiation potential and paracrine function, have attracted considerable attention in cell therapy recently. Increasing studies concerning the mechanisms and therapeutic effect of MSCs in DN emerged. This review summarizes several mechanisms of MSCs, especially MSCs derived exosomes in DN therapy, including hyperglycemia regulation, anti-inflammatory, anti-fibrosis, pro-angiogenesis, and renal function protection. We also emphasize the limitation of MSCs application in the clinic and the enhanced therapeutic role of pre-treated MSCs in the DN therapy. This review provides balanced and impartial views for MSC therapy as a promising strategy in diabetic kidney disease amelioration.

scholarly journals Roles of mTOR in Diabetic Kidney Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 321
Author(s):  
Mako Yasuda-Yamahara ◽  
Shinji Kume ◽  
Hiroshi Maegawa
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Cell Injury ◽  
Nutrient Sensing ◽  
Diabetic Patients ◽  
Diabetic Kidney ◽  
Number Of Patients ◽  
New Treatment ◽  
Stage Renal Disease ◽  
End Stage

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease and the number of patients affected is increasing worldwide. Thus, there is a need to establish a new treatment for DKD to improve the renal prognosis of diabetic patients. Recently, it has shown that intracellular metabolic abnormalities are involved in the pathogenesis of DKD. In particular, the activity of mechanistic target of rapamycin complex 1 (mTORC1), a nutrient-sensing signaling molecule, is hyperactivated in various organs of diabetic patients, which suggests the involvement of excessive mTORC1 activation in the pathogenesis of diabetes. In DKD, hyperactivated mTORC1 may be involved in the pathogenesis of podocyte damage, which causes proteinuria, and tubular cell injury that decreases renal function. Therefore, elucidating the role of mTORC1 in DKD and developing new therapeutic agents that suppress mTORC1 hyperactivity may shed new light on DKD treatments in the future.

Molecular mechanisms of proteinuria in diabetes

2008 ◽  
Vol 36 (5) ◽  
pp. 946-949 ◽  
Author(s):  
Luigi Gnudi
Keyword(s):  
Kidney Disease ◽  
Renal Disease ◽  
Glucose Uptake ◽  
End Stage Renal Disease ◽  
Diabetic Patients ◽  
Diabetic Kidney ◽  
Glut 1 ◽  
Stage Renal Disease ◽  
End Stage ◽  
Tgf Β1

The epidemic of Type 2 diabetes, and the parallel rising incidence of end-stage renal disease, is progressively increasing worldwide. Kidney disease is one of the major chronic microvascular complications of diabetes, and both metabolic and haemodynamic perturbations participate in its development and progression towards end-stage renal disease. Hypertension and poor metabolic control seem to interact in causing the relentless decline in renal function seen in diabetic patients. Both high circulating glucose levels and increased glomerular capillary pressure act in conjunction in stimulating the different cellular pathways leading to kidney disease. It has been suggested that mechanical forces at the glomerular level may aggravate the metabolic insult by stimulating excessive cellular glucose uptake by up-regulating the facilitative GLUT-1 (glucose transporter-1). We propose the existence of a self-maintaining cellular mechanism whereby a haemodynamic stimulus on glomerular cells induces the up-regulation of GLUT-1, an event followed by greater glucose uptake and activation of intracellular metabolic pathways, resulting in excess TGF-β1 (transforming growth factor-β1) production. TGF-β1, one of the major prosclerotic cytokines in diabetic kidney disease, maintains the up-regulation of GLUT-1, perpetuating a series of cellular events that result, as their ultimate effect, in increased extracellular matrix synthesis and altered permeability of the glomerular filtration barrier. Mechanical and metabolic coupling could represent an important mechanism of injury in the diabetic kidney.

STUDY OF ANAEMIA & IRON PROFILE IN CHRONIC KIDNEY DISEASE (CKD) PATIENTS ON MAINTENANCE DIALYSIS AND ITS CORRELATION WITH DIABETES MELLITUS

2021 ◽  
pp. 37-39
Author(s):  
Sandeep Chavda ◽  
Shaila Shah ◽  
Jay Shah
Keyword(s):  
Diabetes Mellitus ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Diabetic Group ◽  
Diabetic Patients ◽  
Blood Indices ◽  
Poor Patient ◽  
Stage Renal Disease ◽  
End Stage ◽  
Iron Profile

Most patients with chronic kidney disease (CKD) have anaemia, the cause of which is erythropoietin and iron deciency. Anaemia in patients on haemodialysis is associated with poor patient outcomes. Diabetes remains one of the predominant aetiologies of CKD all over the world. The study was undertaken to study the iron prole in haemodialyzed patients and its corelation with diabetes mellitus. Sixty-six patients were enrolled in the study with the aim to study the prevalence of anaemia and diabetes in haemodialyzed patients as well as the iron prole in these patients. Patients were studied as a single group as well as divided into two groups, a non-diabetic group comprising of 36 patients and a diabetic group comprising of 30 patients. Anaemia was found to be prevalent in 56(84.84%) patients out of which 28(50%) were diabetics. Also, diabetics comprised of 45.45% of the study group. Various parameters like haemoglobin with blood indices and iron prole was studied and compared in both groups. There was no signicant difference in the various parameters in both groups except a signicantly low MCH and MCHC and signicantly high ferritin levels in the diabetic group. We concluded that the low MCH and MCHC might be suggestive of an increased cardiovascular risk in diabetic patients while higher levels of serum ferritin may suggest sub-clinical inammation rather than iron overload. In conclusion diabetes remains to be the single most important aetiology for the causation of end stage renal disease and appropriate management of anaemia in terms of EPO and iron therapy remains the mainstay of therapy in haemodialyzed patients.

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