Racial/Ethnic Trends in Prevalence of Diabetic Kidney Disease in the United States

Youth-onset Type 2 Diabetes Mellitus (T2DM) represents a major burden worldwide. In the last decades, the prevalence of T2DM became higher than that of Type 1 Diabetes Mellitus (T1DM), helped by the increasing rate of childhood obesity. The highest prevalence rates of youth-onset T2DM are recorded in China (520 cases/100,000) and in the United States (212 cases/100,000), and the numbers are still increasing. T2DM young people present a strong hereditary component, often unmasked by social and environmental risk factors. These patients are affected by multiple coexisting risk factors, including obesity, hyperglycemia, dyslipidemia, insulin resistance, hypertension, and inflammation. Juvenile T2DM nephropathy occurs earlier in life compared to T1DM-related nephropathy in children or T2DM-related nephropathy in adult. Diabetic kidney disease (DKD) is T2DM major long term microvascular complication. This review summarizes the main mechanisms involved in the pathogenesis of the DKD in young population and the recent evolution of treatment, in order to reduce the risk of DKD progression.

Download Full-text

Targeting Inflammation in Diabetic Kidney Disease: Is There a Role for Pentoxifylline?

Kidney360 ◽

10.34067/kid.0001252019 ◽

2020 ◽

Vol 1 (4) ◽

pp. 292-299

Author(s):

David J. Leehey

Keyword(s):

Clinical Trials ◽

Kidney Disease ◽

Diabetic Kidney Disease ◽

Standard Of Care ◽

The United States ◽

Sglt2 Inhibitors ◽

Low Grade ◽

Diabetic Kidney ◽

Raas Blockade ◽

Patients With Diabetes

Diabetic kidney disease (DKD) is the most common cause of ESKD in the United States and worldwide. Current treatment for DKD includes strict glycemic control and normalization of BP with renin-angiotensin-aldosterone system (RAAS) blockade. Although RAAS blockers slow progression of disease, they do not generally prevent ESKD and none of the studies with these agents in DKD included patients who were nonproteinuric, which make up an increasingly large percentage of patients with diabetes now seen in clinical practice. Recent studies with glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 (SGLT2) inhibitors have shown beneficial renal effects, and the benefits of SGLT2 inhibitors likely extend to patients who are nonproteinuric. However, there remains a need to develop new therapies for DKD, particularly in those patients with advanced disease. A role of chronic low-grade inflammation in microvascular complications in patients with diabetes has now been widely accepted. Large clinical trials are being carried out with experimental agents such as bardoxolone and selonsertib that target inflammation and oxidative stress. The Food and Drug Administration–approved, nonspecific phosphodiesterase inhibitor pentoxifylline (PTX) has been shown to have anti-inflammatory effects in both animal and human studies by inhibiting the production of proinflammatory cytokines. Small randomized clinical trials and meta-analyses indicate that PTX may have therapeutic benefits in DKD, raising the possibility that a clinically available drug may be able to be repurposed to treat this disease. A large, multicenter, randomized clinical trial to determine whether this agent can decrease time to ESKD or death is currently being conducted, but results will not be available for several years. At this time, the combination of RAAS blockade plus SGLT2 inhibition is considered standard of care for DKD, but it may be reasonable for clinicians to consider addition of PTX in patients whose disease continues to progress despite optimization of current standard-of-care therapies.

Download Full-text

Racial/Ethnic Differences in the Prevalence of Proteinuric and Nonproteinuric Diabetic Kidney Disease

Diabetes Care ◽

10.2337/dc12-0951 ◽

2012 ◽

Vol 36 (5) ◽

pp. 1215-1221 ◽

Cited By ~ 33

Author(s):

V. Bhalla ◽

B. Zhao ◽

K. M. J. Azar ◽

E. J. Wang ◽

S. Choi ◽

...

Keyword(s):

Kidney Disease ◽

Ethnic Differences ◽

Diabetic Kidney Disease ◽

Diabetic Kidney ◽

Racial Ethnic

Download Full-text

Diabetic Kidney Disease: A Renin-Angiotensin-Aldosterone System Focused Review

Journal of Pharmacy Practice ◽

10.1177/0897190009333163 ◽

2009 ◽

Vol 22 (6) ◽

pp. 560-570 ◽

Cited By ~ 1

Author(s):

Pamela F. Hite ◽

Heather F. DeBellis

Keyword(s):

Kidney Disease ◽

Diabetic Kidney Disease ◽

Angiotensin Receptor Blockers ◽

The United States ◽

Diabetic Patients ◽

Converting Enzyme Inhibitors ◽

Renin Angiotensin Aldosterone System ◽

Diabetic Kidney ◽

Renin Angiotensin ◽

Renin Inhibitors

Diabetic nephropathy, also referred to as diabetic kidney disease, is a multifaceted complication of one of the largest epidemics in the United States. Diabetic patients currently represent approximately 8% of the US population. Aggressive screening and control of diabetes, hypertension, and dyslipidemia as well as dietary protein restriction are vital to the prevention and management of diabetic kidney disease. Because there are no direct pharmacologic options for diabetic kidney disease, treatment is focused on controlling comorbidities that exacerbate the development and progression of diabetic kidney disease. This article will provide an overview of structural renal alterations during the progression of diabetic kidney disease as well as a concise review of current diabetic kidney disease management guidelines with a focus on agents that affect the renin-angiotensin-aldosterone system. At this point in time, the mainstays of therapy are angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. More research is currently needed to determine if renin inhibitors will have an active role in the management of diabetic kidney disease.

Download Full-text

Immunity and inflammation in diabetic kidney disease: translating mechanisms to biomarkers and treatment targets

AJP Renal Physiology ◽

10.1152/ajprenal.00314.2016 ◽

2017 ◽

Vol 312 (4) ◽

pp. F716-F731 ◽

Cited By ~ 55

Author(s):

Raimund Pichler ◽

Maryam Afkarian ◽

Brad P. Dieter ◽

Katherine R. Tuttle

Keyword(s):

Kidney Disease ◽

Renal Disease ◽

End Stage Renal Disease ◽

Diabetic Kidney Disease ◽

The United States ◽

Diabetic Kidney ◽

Amyloid A ◽

Obesity And Diabetes ◽

Stage Renal Disease ◽

End Stage

Increasing incidences of obesity and diabetes have made diabetic kidney disease (DKD) the leading cause of chronic kidney disease and end-stage renal disease worldwide. Despite current pharmacological treatments, including strategies for optimizing glycemic control and inhibitors of the renin-angiotensin system, DKD still makes up almost one-half of all cases of end-stage renal disease in the United States. Compelling and mounting evidence has clearly demonstrated that immunity and inflammation play a paramount role in the pathogenesis of DKD. This article reviews the involvement of the immune system in DKD and identifies important roles of key immune and inflammatory mediators. One of the most recently identified biomarkers is serum amyloid A, which appears to be relatively specific for DKD. Novel and evolving treatment approaches target protein kinases, transcription factors, chemokines, adhesion molecules, growth factors, advanced glycation end-products, and other inflammatory molecules. This is the beginning of a new era in the understanding and treatment of DKD, and we may have finally reached a tipping point in our fight against the growing burden of DKD.

Download Full-text

Therapeutic Advances in Diabetic Nephropathy

Journal of Clinical Medicine ◽

10.3390/jcm11020378 ◽

2022 ◽

Vol 11 (2) ◽

pp. 378

Author(s):

Hanny Sawaf ◽

George Thomas ◽

Jonathan J. Taliercio ◽

Georges Nakhoul ◽

Tushar J. Vachharajani ◽

...

Keyword(s):

Kidney Disease ◽

Diabetic Kidney Disease ◽

Treatment Options ◽

The United States ◽

Additional Treatment ◽

Diabetic Kidney ◽

Raas Blockade ◽

Risk Factor Modification ◽

Glucagon Like Peptide 1 ◽

End Stage

Diabetic kidney disease (DKD) is the most common cause of end-stage kidney disease (ESKD) in the United States. Risk factor modification, such as tight control of blood glucose, management of hypertension and hyperlipidemia, and the use of renin–angiotensin–aldosterone system (RAAS) blockade have been proven to help delay the progression of DKD. In recent years, new therapeutics including sodium-glucose transport protein 2 (SGLT2) inhibitors, endothelin antagonists, glucagon like peptide-1 (GLP-1) agonists, and mineralocorticoid receptor antagonists (MRA), have provided additional treatment options for patients with DKD. This review discusses the various treatment options available to treat patients with diabetic kidney disease.

Download Full-text

NAD metabolism modulates mitochondrial function and inflammation and prevents progression of diabetic kidney disease

10.1101/2021.12.05.471273 ◽

2021 ◽

Author(s):

Komuraiah Myakala ◽

Xiaoxin X Wang ◽

Bryce A. Jones ◽

Matthew D Hirschey ◽

Xiaoping Yang ◽

...

Keyword(s):

Kidney Disease ◽

Mitochondrial Function ◽

Diabetic Kidney Disease ◽

The United States ◽

Diabetic Kidney ◽

Nad Metabolism ◽

Nicotinamide Riboside ◽

Mitochondrial Dna Damage ◽

Patients With Diabetes

ABSTRACTBackgroundDiabetes mellitus is the leading cause of cardiovascular and renal disease in the United States. In spite of all of the beneficial interventions implemented in patients with diabetes, there remains a need for additional therapeutic targets in diabetic kidney disease (DKD). Mitochondrial dysfunction and inflammation are increasingly recognized as important causes of the development and progression of DKD. However, the molecular connection between mitochondrial function, inflammation, and fibrosis remains to be elucidated.MethodsIn the present studies we tested the hypothesis that enhancing NAD metabolism could increase mitochondrial sirtuin 3 (SIRT3) activity, improve mitochondrial function, decrease mitochondrial DNA damage, and prevent inflammation and progression of DKD.ResultsWe found that treatment of db-db mice with type 2 diabetes with nicotinamide riboside (NR) prevented albuminuria, increased urinary KIM1 excretion, and several parameters of DKD. These effects were associated with increased SIRT3 activity, improved mitochondrial function, and decreased inflammation at least in part via inhibiting the activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway.ConclusionsNR supplementation boosted the NAD metabolism to modulate mitochondrial function and inflammation and prevent progression of diabetic kidney disease.

Download Full-text