The connection between kidney disease and diabetes

Diabetic kidney disease remains the most common cause of end-stage kidney disease in the world. It’s important to follow the five point treatment plan to decrease developemnt.

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The kidney is a vulnerable organ as well as the most important target of microvascular damage in both Type 1 and Type 2 diabetes.

The first description of the association between diabetes and kidney damage in humans was in 1552 BC.² As the disease spectrum has changed around the world, diabetic kidney disease (DKD) has become the single most frequent cause of end-stage kidney disease.

Kidney involvement both directly and indirectly increase involvement of other organs especially the heart and eye, and increase morbidity and mortality in diabetic patients.

The overall incidence 20 years after the diagnosis of diabetes is approximately 4 to 17% and after 30 years is about 16%. According to some studies the incidence of kidney disease in Type 1 diabetes is decreasing. The main reason for that is early diagnosis of Type 1 diabetes and good control of hyperglycemia.¹

In Type 2 diabetes. the kidney damage may be present at the time of diagnosis. This is why it’s so important to screen people susceptible to Type 2 diabetes regularly for abnormal glucose values.

Genetics

Many patients with long-term high glucose have no diabetic kidney disease while others with a short disease course have clinical diabetic kidney disease (nephropathy). This may be due to predisposing factors including genetics.

The risk of diabetic kidney disease increases in Type 1 and Type 2 diabetes if the patient has a history of diabetic kidney disease in one of their first-degree relatives.

Patients living with diabetes who have a family history of hypertension or heart disease are more likely to develop diabetic kidney disease.

Screening

The easiest screening method is to evaluate a urine sample. This can be done in a doctor’s office with a urine dipstick. If this is normal, the urine sample should be sent to a laboratory for a urine albumin-creatinine ratio test.

Natural course of diabetic kidney disease

First stage

The filtration through the kidney tubes, called glomeruli, increases and the kidney enlarge. The urine albumin-creatinine ratio is still normal and blood pressure is also normal.

Second stage: microalbuminuria

With the progression of kidney involvement, urine albumin-creatinine ratio will also increase. This stage is called hidden or subclinical kidney disease.

In this stage, the conventional urine test strip in the doctor’s rooms will be negative but the risk of heart disease starts to increase. With Type 1 diabetes, the prevalence of other microvascular (small vessel) diseases start to increase, such as the eye and the feet. With Type 2 diabetes, other factors, such as age, high cholesterol, high blood pressure and duration of disease, play a role to increase microalbuminuria (small proteins in urine).

Diagnosis at this stage is a very good opportunity to prevent progression to clinical kidney disease.

Third stage: macroalbuminuria

This stage is also called diabetic kidney disease or clinical nephropathy. It occurs about 10 to 20 years after onset of diabetes; about five to 10 years after the onset of microalbuminuria.

In this stage, heart disease and strokes also increases compared to the previous stage, and about 75% of patients have high blood pressure. Control of blood pressure in Type 2 diabetes with previous hypertension becomes more difficult.

The conventional dipstick test in the doctor’s rooms is positive for proteins. Due to the leaking of proteins in the urine, these patients can develop swelling of the legs. If the leaking of proteins increases more the swelling can also develop around the eyes.

Fourth stage: End stage kidney disease

The end stage of kidney disease is reached about 10 years after the onset of clinical kidney disease (stage 3). The risk of heart disease and stroke increases, and the incidence of foot ulcers are also increased.

The prevalence of Type 2 diabetes to develop end stage kidney disease is nine times higher than Type 1 diabetes.

Diagnosis

To prove the diagnosis of diabetic kidney disease, the following criteria is used:

• Enough time. At least 10 years past the onset of diabetes but this may be shorter in Type 2 diabetes.
• Persistent proteins in urine more than 300mg in 24 hours ( normal is less than 30mg per 24 hours).
• Diabetic retinopathy (eye disease) at the same time.

There are other causes in diabetes that can also lead to kidney disease:

• Uncontrolled blood pressure
• Recurrent bladder infections
• Increased cholesterol with renal artery stenosis (decreasing of blood flow to the kidney)

Five point treatment plan

Treatment is based on the following principles:

• Tight control of glucose

Keep the HbA1c (3 month average blood glucose) below 7% and in patient with glucose sensors; keep the time in range (time between 4 and 10 mmol\L in 24 hours) more than 70%.

• Control of blood pressure

Both high glucose and high blood pressure can progress to kidney disease. In the control of blood pressure, it’s important to use the correct drug that address the kidney function as well. The renin-angiotensin-aldosterone system inhibitors can reduce the progression of diabetic kidney disease. There are two groups in this class: ACE inhibitors (perindopril or enalapril) and ARB group. (valsartan or losartan).

• Restriction of protein intake

High protein intake increases the filtration of blood through the kidney. Protein restriction can decrease the progression of kidney disease

• Stop smoking

• Manage cholesterol

The aggressive treatment of abnormal lipids reduce both microvascular (small vessel disease such as eye, kidney and feet) and macrovascular disease (heart attack and stroke). The therapeutic target for LDL cholesterol (bad cholesterol) is below 1,8 mmol/L.

New drugs

The use of the ACE and ARB drugs was up to 2016 the only drugs, except cholesterol lowering medications, that could slow diabetic kidney disease.

There are now two new drugs available in SA that decrease the progression of diabetic kidney disease by 30%. These drugs are from the class sodium glucose transporter 2 inhibitor (SGLT2i) and work in the upper part (proximal tubuli) of the kidney. The reabsorption of glucose and salt are blocked. This leads to glucose in the urine and due to this: weight loss, decrease of blood pressure and improvement of kidney function are seen. The two available drugs in RSA are dapagliflozin and empagliflozin.

Final thought

Diabetic kidney disease remains the most common cause of end-stage kidney disease in the world. It’s important to follow the five-point treatment plan to decrease the chance to develop the disease, and should it already be present to use the correct drugs to decrease the progression of the disease.

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Reference:

1. Bojestig M et.al. “ Declining incidence of nephropathy in insulin dependent diabetes mellitus.” N Engl J Med 1994;330: 15-18
2. Cameron J.S. 2006 “The discovery of diabetic nephropathy: from small print to centre stage.” Journal of Nephrology 19 ( Suppl 10): S75-S87

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