Diabetic Kidney Disease

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Introduction   

Diabetes is an epidemic in the United States, with 1.2 million Americans diagnosed with diabetes each year, and in 2023, 11.6% of Americans had diabetes. People with diabetes are at a greater risk of developing many different chronic health problems including diabetic retinopathy, cardiovascular disease and chronic kidney disease. In the United States, diabetes is the leading cause of diabetic nephropathy or chronic kidney disease [1]. 

Due to the increased prevalence of diabetes and diabetic kidney disease, nurses and other healthcare professionals need to have a strong understanding of diabetes and the impact it can have on their patient’s well-being. And, with diabetes being the leading cause of chronic kidney disease, it is essential that health professionals can define diabetic kidney disease, explain assessment findings that support a diagnosis, and educate patients and family members on how to manage the chronic condition.   

Definition 

What is Diabetes? 

Before we can discuss diabetic kidney disease, you must understand diabetes and how it impacts the body. Most of our food breaks down into sugar, also known as glucose, and is released into our bloodstream for energy. Insulin is a hormone produced by the pancreas that helps manage your blood sugar (the amount of sugar in your blood). As your blood sugar increases, your pancreas will release insulin, which helps regulate the amount of glucose released into the bloodstream.  

With diabetes, your body does not make enough insulin or use the insulin properly, leading to increased glucose in the bloodstream. This process differentiates people with type 1 diabetes from Type 2 diabetes (National Kidney Foundation).  

What is Diabetic Kidney Disease? 

Diabetic kidney disease can occur when blood sugars are elevated and uncontrolled. Hyperglycemia can cause the vessels in the kidney to become narrow and clogged, reducing blood flow. Over time, this decrease in blood flow can damage the kidneys (National Kidney Foundation). 

Diabetic kidney disease is a form of chronic kidney disease. It is broken down into five stages, indicating the degree of damage to the kidney based on the glomerular filtration rate (GFR) [4].    

• Stage 1 (GFR 90 or greater): Kidney work as well as normal 

• Stage 2 (GFR 60-89): Mild kidney disease and kidneys still work well 

• Stage 3a (GFR 45-59): Mild to moderate kidney disease. Kidneys are not working as well as they should 

• Stage 3b (GFR 30-44): Moderate to severe kidney disease. Kidneys are not working as well as they should 

• Stage 4 (GFR 15-29): Severe kidney disease. Kidneys are barely working 

• Stage 5 (GFR less than 15): The most severe type of kidney disease, often referred to as end-stage kidney disease. Kidneys are very close to not working or have failed.  

Epidemiology  

Diabetes is the leading cause of chronic kidney disease and end-stage kidney disease both in the United States and worldwide. The number of people diagnosed with diabetes in the United States has increased over the last 20 years from six to eleven percent. Of those with diabetes, it is estimated that 25 to 30 percent have chronic kidney disease. While over a fourth of people with diabetes have chronic kidney disease, less than 60% of these people are aware of their chronic kidney disease.  Even more concerning, the prevalence of end-stage kidney disease more than doubled from 2000 to 2019 to nearly 800,000—and as of 2019, almost 40% or more than 307,000 people in the United States had end-stage kidney disease primarily caused by diabetes [13]. 

Risk Factors 

Being able to identify patients at risk and providing education early on regarding diabetic kidney disease and steps to help prevent or slow down the progression is essential. Below is a list of modifiable and non-modifiable risk factors associated with diabetes and the development of diabetic kidney disease [13].  

Age 

Advancing age is directly related to the development of diabetic kidney disease. This is most likely since the older you are, the more likely you have had a greater exposure to diabetes, which is associated with progressive kidney disease. This may be due to the natural age-related changes in the kidney, which can lead to chronic kidney disease for many reasons [13].  

Ancestry/Ethnicity 

African Americans, Hispanic Americans, and American Indian populations have higher rates of albuminuria, decreased eGFR, and end-stage kidney disease when compared with white populations. The incidence of diabetic end-stage kidney disease is estimated at  

• African Americans: 409 cases per 100,000 diabetic persons 

• Hispanic Americans: 307 cases per 100,000 diabetic persons 

• White Americans: 266 cases per 100,000 diabetic persons 

These rates may be declining among white patients, but there may be a rise among the Mexican American population [13].  

Sex 

Diabetic kidney disease is more common in men than women [13].  

Low Socio-Economic Status 

Diabetic kidney disease is more common in people with lower education levels and those who live below the poverty level—and social determinants of health play a factor in this [13].  

Obesity 

You are six times more likely to develop type II diabetes if you are obese compared to those who are at a normal weight [2][13][18]. 

Smoking 

There is a higher risk of developing kidney disease in those who smoke compared to those who do not smoke [13].  

Hypertension 

Hypertension increases the risk of kidney damage. Consistent systolic blood pressure of greater than 140mmHg increases the risk of developing albuminuria and chronic kidney disease [13] [3]. 

Pathophysiology 

The pathophysiology of diabetic kidney disease is complex and multifactorial. It occurs due to a critical metabolic impairment involving the upstream influence of hyperglycemia, which leads to a dysregulated intracellular metabolism, inflammatory lesions, increased apoptosis processes, and tissue fibrosis. Three steps occur at the foundational level leading to diabetic kidney disease, which include: 

• Glomerular hypertrophy leading to hyperfiltration 

• Glomerular and tubulointerstitial inflammation related to chemokines, cytokines, and profibrotic factors activation 

• Dysregulated cellular apoptosis and changes in the extracellular matrix  

These three steps lead to the thickening of the glomerular basement, podocyte depletion, mesangial matrix expansion, and tubular damage. These factors contribute to the progression of diabetic kidney disease through vascular remodeling, endothelial dysfunction, glomerulosclerosis, and tubulointerstitial fibrosis [10].  

When looking at diabetic kidney disease specifically, it begins with glomerular hyperinflation, which is in the early stages of renal injury and mild hypertension. The glomerular filtration rate (GFR) is normal but will worsen over time, decreasing GFR. Next, microalbuminuria is typically seen in a range of 30-300 mg albumin/day—the term microalbuminuria is used because detecting protein in the urine is difficult unless the albumin level is greater than 300 mg/day. Nephrotic syndrome occurs when albumin level, or proteinuria, exceeds 3 grams/day, and this often occurs approximately 3-5 years before end-stage kidney disease [10]. 

Urinary tract abnormalities such as papillary necrosis, type IV renal tubular acidosis, and urinary tract infections may also occur with diabetic kidney disease, leading to a faster decline of kidney function [10].  

Clinical Signs and Symptoms 

Often, people in the early stages of chronic kidney disease or diabetic kidney disease do not experience any symptoms. It is not until a person is in stage IV kidney disease that symptoms typically start to develop. Below are a few signs and symptoms people with diabetic kidney disease may experience.  

• High blood pressure that gets harder to control  

• Swelling of feet, ankles, hands or eyes 

• Foamy urine 

• Confusion or difficulty thinking 

• Shortness of breath. 

• Loss of appetite 

• Nausea and vomiting 

• Itching 

• Tiredness and weakness 

• Increased or decreased urine output 

Because these symptoms are nonspecific and may be associated with many other problems, it is important to have your kidney function routinely assessed if you have diabetes [5].  

Assessment Findings 

Patients with diabetes should be tested for diabetic kidney disease routinely because too many do not experience any symptoms until the disease is advanced. Type 2 diabetics should be tested for diabetic kidney disease yearly, and once type 1 diabetics who have had diabetes for more than five years should be tested annually [13].  

Hemoglobin A1C (Hgb A1C) 

Hemoglobin (Hgb) A1C is a blood test used to diagnose diabetes. A Hgb A1C of 6.5% or greater is considered a positive test for diabetes, and a Hgb A1C between 5.7% and 6.4% indicates prediabetes. Once diagnosed with diabetes, you should have your Hgb A1C checked every three months or 91 days, as this test is used to monitor how well a person’s diabetes is managed [8] [13].  

Decrease Glomerular Filtration Rate (GFR) 

The GFR is a lab test that shows how quickly and efficiently the kidneys can filter the blood. A GFR of 60 or greater is considered normal, a GFR between 15 and 60 indicates kidney disease, and a GFR of 15 or less indicates kidney failure. These levels are monitored closely in people with diabetes as it is a strong indicator of how well a person’s kidneys are functioning and if their diabetic kidney disease is progressing [13][16].  

Persistent Albuminuria 

Albumin is a protein found in the blood, and albuminuria is the presence of albumin in the urine. A healthy kidney does not allow albumin to pass from the blood to the urine, so when albumin is seen in the urine, it is often a marker of either an injury or damage to the kidney. A normal albumin level in your urine is less than 30mg/g—so anything more than this may suggest kidney disease even if your GFR is normal.  

Albuminuria is not a requirement to diagnose a person with diabetic kidney disease, but it is often seen in those with diabetic kidney disease [13][15].  

Albumin/Creatinine Ratio 

If the albumin level is abnormal or elevated on your microalbumin creatinine ratio urine test, it could mean that you have kidney disease. Your family practice provider or endocrinologist can trend this level yearly to determine if your kidney disease is worsening. Higher levels of albumin in your urine can also indicate that you are at a greater risk of developing heart and vascular problems [12].  

However, this test is not diagnostic as you can have an abnormal microalbumin creatinine ratio test for other problems such as a urinary tract infection or hepatitis [12].  

Treatment and Self-Management 

There is no cure for diabetic kidney disease, but there are ways to help prevent further damage to the kidney or slow down the progression [17].  

Control Your Blood Sugar 

Management of blood sugar is one of the best ways to prevent or slow down kidney damage. This includes monitoring your hemoglobin A1C every three months and keeping a blood sugar log per the direction of your healthcare provider. Diabetes management is achieved through diet, exercise, and medications such as insulin or pills that help lower and stabilize blood sugar levels [17].  

Control Your Blood Pressure 

Blood pressure management is important in preventing and slowing down kidney disease. Hypertension, or uncontrolled high blood pressure, can lead to scarring of the kidneys, which impairs how the kidneys filter the blood and regulate fluid and electrolytes. Subsequently, the more damage done to the kidneys, the more difficult it may be to manage high blood pressure. Therefore, discussing your target blood pressure goal with your healthcare provider and how to achieve it best (AHA, American kidney specialists) is important [3][17].  

Monitoring Cholesterol Levels  

Managing cholesterol levels, including total cholesterol, LDL, and HDL, is important to minimize damage to larger blood vessels such as the brain or heart [17].  

Take an ACE or ARB to Protect Kidney Function 

Research has shown that certain blood pressure medications, specifically an ACE inhibitor (e.g., lisinopril) or an ARB (e.g., losartan), can slow down the loss of kidney function in those with diabetes. Diabetics can take these medications at a low dose for their kidney-protectant properties, even if they do not have hypertension [17]. 

Monitor Protein Intake 

Consumption of protein is okay for those with diabetic kidney disease; it’s just important not to overeat it. Research has shown that eating less protein can slow down the damage to the kidney; however, protein is still needed for one’s overall health. Therefore, if you decide to start a low-protein diet, it is recommended to discuss this plan with a dietician, specifically one who specializes in diabetes and kidney disease, to ensure the right approach is taken [17]. 

Limit Salt in Your Diet 

Diets high in salt can lead to elevated pressure, which in turn can lead to kidney damage. Therefore, it is important to limit the salt in your diet [17].  

Avoid Medications that May Damage Your Kidneys 

Do not take medications that may damage your kidneys, such as nonsteroidal anti-inflammatory drugs (NSAIDs), which include ibuprofen and naproxen. Also, be sure to discuss any supplements you are taking, as these may also lead to kidney damage [17].  

Use Medications to Manage Diabetes that Also Are Renal Protectants 

There are medications used to help manage diabetes, but they are also known to be kidney protectants. Two classes of medications that have been demonstrated to be kidney protectants include SGLT2 inhibitors, such as empagliflozin and canagliflozin, and GLP-1, such as semaglutide. Finerenone is another medication that people with diabetes can use to treat diabetes, but it also provides kidney protection. [6][11][17]   

Dialysis 

End-stage renal disease occurs when significant damage is done to the kidneys, and it is irreversible. Once you have end-stage renal disease, dialysis is used to treat it and is typically completed three times a week, with each session lasting 3-5 hours. The purpose of dialysis is to remove waste products and extra fluid from the blood and body since the kidneys are no longer able to do this on their own [4].  

Research  

A lot of research is emerging around managing diabetes, specifically how to preserve kidney function by slowing down the progression of kidney disease. A lot of the study is being tailored around medication management, specifically using medications initially approved to treat one chronic condition, such as hypertension or diabetes. Still, it can now be prescribed for patients starting to show a decline in kidney function. For example, blood pressure medications such as an ACE or ARB have an impact on the renin-angiotensin-aldosterone system (RAAS), and research is finding that if these medications are initiated after being diagnosed with type 2 diabetes, they can delay the onset or progression of diabetic kidney disease.  

Another example is sodium-glucose cotransporter 2 (SGLT2) inhibitors, which initially were prescribed to treat type 2 diabetes and have been shown to decrease the risk of kidney disease in those with diabetes and cardiovascular disease [9].  

Research also supports the idea that lifestyle modifications, such as blood sugar management, diet, exercise, and weight loss, can prevent or slow down the progression of diabetic kidney disease [8].  

Ongoing research is continuing to find new therapies to treat and slow down the progression of diabetic kidney disease, which include stem cell therapy, gene therapy, and immunotherapy [9].  

Conclusion

Diabetic kidney disease is becoming increasingly prevalent in the United States. As healthcare professionals, it is our responsibility to be competent in identifying those at risk of developing diabetic kidney disease, understand the appropriate diagnostic tests, and be prepared to educate our patients on the importance of managing their diabetes and the consequences of uncontrolled diabetes, such as diabetic kidney disease. 

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