Although chronic kidney disease is a progressive disease the good news is that not everyone will go on to develop kidney failure. Dr Louise Johnson explains the stages and why screening is imperative for people with diabetes.

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World Kidney Day is 14 March 2024. Visit worldkidneyday.org

Chronic kidney disease (CKD) is a term that includes all degrees of decreased kidney function from at risk to mild, moderate and severe kidney failure.

Almost half of patients with CKD are older than 70 years of age. The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines established the diagnosis of CKD as:

Either kidney damage or a decreased glomerular filtration rate (GFR) of less than 60ml/min/1.73m2 for at least three months.

The different stages form a continuum and are classified as:

• Stage 1 – Kidney damage with normal or increased estimated GFR (>90ml/min).
• Stage 2 – Mild reduction in GFR (60 – 89ml/min).
• Stage 3a – Moderate reduction in GFR (45 – 59ml/min).
• Stage 3b – Moderate reduction in GFR (30 – 44ml/min).
• Stage 4 – Severe reduction in GFR (15 – 29ml/min).
• Stage 5 – Kidney failure GFR < 15ml/min.

Markers

By itself measurement of estimated GFR may not be sufficient to identify Stage 1 and Stage 2 CKD. In these patients, the estimated GFR may be normal or near normal. In such cases, the presence of one or more of the following markers of kidney damage can establish the diagnosis:

• Albuminuria (albumin excretion in the kidneys >30mg/24 or Albumin: creatinine ratio > 30mg/g)
• Urine sediment abnormalities
• Electrolyte disorders
• Structural kidney abnormalities as seen by imaging
• History of kidney transplant

Two important tests

1. Urine Albumin-to- Creatinine ratio (UACR)

This is a test of the urine to assess the relationship between albumin (which is a protein that shouldn’t be in urine) and creatinine. If protein leaks into the urine, it’s a sign of kidney damage.

UACR levels are staged as:

• A1 – lower than 3mg/mmol
• A2 – 3 to 30mg/mmol – moderate increase
• A3 – higher than 30mg/mmol – severe increase

2. Estimated Glomerular Filtration Rate (eGFR)

This is a blood test that shows how well your kidneys filter your blood per minute. A GFR of 100 is normal.

Stage 1 kidney disease

In Stage 1, there is mild damage to the kidneys. They are quite adaptable for this, allowing them to keep performing at 90% or better. At this stage, CKD is likely to be discovered by chance during routine blood analysis. Usually in people with diabetes or hypertension (these are the two main causes of CKD).

Symptoms

None

Treatment

Manage all risk factors:

• Keep blood glucose in normal range or HbA1c below 7%.
• Keep blood pressure below 130/80 mmHg.
• Don’t smoke.
• Sleep seven to eight hours per day.
• Exercise 30 minutes five times a week
• Reduce stress and anxiety.
• Maintain a healthy weight.

Stage 2 kidney disease

In Stage 2, the kidney function is between 60 and 89%.

Symptoms

Usually, asymptomatic

Treatment

Manage risk factors as in Stage 1.

Stage 3 kidney disease

Stage 3a is when your kidney function is 45 to 59%.

Stage 3b is when your kidney function is 30 to 44%

The kidneys aren’t filtering waste, toxins and fluids as well as it should, and toxin and fluid build-up begin to manifest.

This is usually the first time when people with CKD are diagnosed.

Symptoms

Not all people are symptomatic yet, but you can have these symptoms:

• Back pain
• Fatigue
• Loss of appetite
• Persistent itching
• Sleep problems
• Swelling of hand and feet
• Urinating more or less
• Weakness

Treatment

Dietitians may help to prescribe a diet that is low in sodium, phosphate, potassium and protein to protect the kidneys.

Medication that reduce symptoms and preserve kidney function:

1. Angiotensin-converting enzyme (ACE) inhibitor.
2. Sodium glucose cotransport 2 (SGLT2) inhibitors. In SA, there are two drugs in this class dapagliflozin and empagliflozin. This class showed in specific studies with patients with and without diabetes an improvement in kidney function on this drug.
3. Diuretic for fluid retention.
4. Cholesterol lowering drug. This is important since the risk of ischemic heart disease and stroke increases in this stage. Important to stop taking certain pain killers called non-steroidal anti-inflammatory drugs (NSAIDS).

Stage 4 kidney disease

This stage has moderate to severe kidney damage. The kidneys function between 15 and 29%. According to the Centre for Disease Control and Prevention (CDC), 40% of people with severe reduced kidney function aren’t aware they have it.

Symptoms

• Back pain
• Decreased mental sharpness.
• Fatigue
• Loss of appetite
• Muscle cramps and twitches
• Nausea and vomiting
• Persistent itching
• Shortness of breath
• Sleep problems
• Swelling of hand and feet
• Weakness
• Weight loss

This stage is also at high risk for heart disease and stroke.

Treatment

The same as Stage 3. In Stage 4, it’s important to be part of a health team to monitor you closely regarding electrolytes, medication, diet as well as possible complications, such as anaemia, bone loss and hypertension.

In Stage 4, erythropoietin supplement for anaemia is important.

Stage 5 kidney disease

This stage means your kidney function is less than15% or you have kidney failure.

Symptoms

The symptoms are the same as Stage 4, but the intensity is worse. A significant drop in kidney function puts more stress on the heart, increasing the risk of heart disease and stroke.

Once you have Stage 5 kidney failure, life expectancy is a lot shorter without dialysis or a kidney transplant.

Dialysis isn’t a cure for CKD but a process to remove fluid and toxins.

Although CKD is a progressive disease, not everyone will go on to develop kidney failure. Symptoms of early kidney disease are mild or even absent. It’s important to screen for kidney disease if you have risk factors such as diabetes and hypertension. Always join a healthcare team to help you along this journey.

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Time in range 101

Let’s start off by discussing time in range (TIR) and the importance of this concept.

• Time in range is the amount of time spent in a specific target blood glucose range and is measured in %.
• Target range is set at 3.9mmol/L – 10.0mmol/L for most people with diabetes.
• Guidelines recommend that at least 70% of a day should be spent in range, which equates to just shy of 17 of 24 hours.
• Less than 4% should be lower than 3.8mmol/L and less than 1% lower than 3mmol/L.
• Time above range, higher than 10.1mmol/L should be kept to below 25%.
• Pregnancy has a much narrower range of 3.5mmol/L – 7.8mmol/L. This is to mitigate the risks of pregnancy and birth complications including premature birth, high birth weight babies, miscarriage, or a stillborn baby.

Important to note: The guideline ranges may be too low for certain people. Factors that need to be considered for setting different target ranges in these certain populations would include age, duration of diabetes, life expectancy, physical or mental disabilities and work environment. These targets should be discussed with your health care provider for best long-term outcomes.

How is TIR calculated?

It’s calculated by taking a certain number of readings over a 24-hour period and dividing the number of readings in range by the total number of readings taken and multiplying by 100. This will give a percentage.

The easiest way to determine TIR is by wearing a continuous or flash glucose monitor. These systems measure glucose every five minutes, 288 times a day. An individual using these sensors can see TIR for a rolling 24hours. To get a true reflection of overall glucose control, a period of at least 14 days should be used.

TIR and Hba1c

Hba1c used to be the gold standard for measuring long-term glucose control. Unfortunately, there are shortfalls to using this method; it’s unable to expose glucose excursions and misses hypoglycaemia.

In the below image, all three patients have an Hba1c of 7%. The glucose readings of these patients are vastly different. Patient 3 has a TIR of 100% whereas patient 1 has huge variability. Glucose variability is considered an independent risk factor for developing long-term diabetes complications. TIR and Hba1c are closely correlated. Depending on baseline Hba1c, for every 10% change in TIR there is a 0.4 -1.0% change in Hba1c.

Ticking the TIR boxes

Maintaining a good TIR is possible and made easier by following some of these 10 simple tips:

1. Medication

Take your diabetes medication as prescribed. Timing and dosage are imperative. Missing doses, taking too much or too little medication or insulin will reduce TIR. If necessary, set a reminder alarm on your phone to take medication timeously.

2. Eating

Eating low-carb and low-GI foods prevent huge swings in glucose levels. Adding a protein to a meal assists in stabilising glucose levels. Eating vegetables with meals adds fibre, once again preventing spikes. If you are snacking, aim for less than 15g of carbs per snack. Be aware of portion sizes of meals, as the larger the meal, the greater the glucose fluctuation.

3. Exercise

Regular exercise improves insulin sensitivity. It allows your body to better use the ingested glucose. Exercise can lower glucose levels for up to 24 hours post exercise. To remain in range, it’s important to make sure your glucose levels are not above 14mmol/L when starting exercise or below 5,5mmol/L. Exercise can assist in weight loss.

4. Stress management

Stress releases hormones such as glucagon, adrenaline and cortisol. These increase insulin resistance causing an increase in blood glucose levels. Illness is a form of stress. Seek medical attention if you are ill.

To manage daily stress, meditation, breathing exercises and general exercise are excellent. If the stress is too great to manage alone, make an appointment to see a doctor or psychologist. During times of stress, try to increase glucose testing frequency.

5. Monitor blood glucose levels

If you are fortunate enough to have access to sensor technology, use it. But, most importantly is to react to any alerts, high or low. It doesn’t help to know what your glucose level is if you’re not going to do anything about it.

Finger stick monitoring is most common in SA. The general rule is for every insulin injection given; you should be testing. Testing two hours post meal can assist you to increase your TIR by adjusting future meals or insulin doses. If a reading is out of range, think why that would be and see what changes you can make for next time. Advocacy is being done to enable more people with diabetes in SA have access to continuous glucose monitoring sensors.

6. Sleep

Insufficient sleep can cause insulin resistance giving rise to elevated blood glucose levels in people with diabetes and increasing the risk of developing diabetes for those without.

Hormones released overnight also cause insulin resistance which result in elevated glucose readings in the hours before rising.

This overnight rise can be managed with diabetes medication. Sleep apnoea is another cause of insulin resistance, worsening TIR. If you snore or stop breathing overnight (often mentioned by your partner), it may be worth testing for sleep apnoea.

7. Weight

Maintaining a healthy stable weight aids in keeping glucose levels stable. If you are overweight, losing just 5% of your body weight will improve insulin sensitivity and therefore glucose levels. If more weight is lost, medication doses may need to be reduced to prevent hypoglycaemia. Imagine having greater TIR with less medication.

8. Sensor augmented insulin pump therapy

Having the privilege of wearing an insulin pump with a connected sensor is one of the easiest ways to maintain a high TIR. The insulin pump adjusts the insulin doses according to the sensor blood glucose levels. These systems enable you to reach a high TIR with a very low time below range.

Unfortunately, these systems are very expensive and not available to most people with diabetes. As mentioned earlier, there are wonderful advocacy groups putting pressure on the necessary bodies to get these pump systems to more individuals.

9. Sick day/back up

When you are sick, glucose levels usually spike. It’s important to have a sick day protocol especially when using insulin. This will aid in keeping you in range. Your healthcare provider will be able to assist you with this.

Having backup stock for hypos is important, be prepared. Carry sugar or honey sachets, Super C’s or Jelly Babies. To remain within range don’t over correct a low blood glucose. Have 1 to 2 Super C sweets and wait twenty minutes, then retest your glucose level. If still below 3.9mmol/L, then have 1 more Super C.

10. Consistency

Try to remain consistent with all the above. Routine makes staying in range easier. There will be days that regardless of what you do your blood glucose will appear to have its own agenda. That happens. Accept it and move on. It’s the bigger picture that counts, long term, a less than good day here and there is not the end of the world.

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We learn about the science behind the fat-burning heart rate zone as well as practical tips to help reach your weight loss goals.

The science of fat-burning heart rate

When you exercise, your body uses different energy sources, primarily carbohydrates and fats. The fat-burning zone represents the range of heart rates at which your body burns more fat for fuel.

Typically, this zone falls within 60 to 70% of your maximum heart rate (MHR). Your MHR is a rough estimate of the maximum number of beats your heart can handle in one minute, and it’s often calculated using the formula 220 minus your age. 

For example, if you’re over 30, your estimated MHR would be 190 beats per minute (220 minus 30). So, in this case, your fat-burning heart rate zone would be 114 to 133 beats per minute (60 to 70% of 190).

Myth busting: the fat-burning zone isn’t a magic bullet

It’s important to understand that the fat-burning zone doesn’t magically help you shed unwanted kilograms without you having to work. Here’s why:

• Calories still matter:While you burn more fat calories in the fat-burning zone, the overall number of calories burned might be lower than in higher-intensity workouts. Weight loss ultimately boils down to burning more calories than you consume.
• Total fat burn:Working out at a higher intensity may lead to higher complete fat burn, even though the percentage of calories burned from fat is lower. It’s like the difference between a gentle, steady stream eroding a rock over time and a powerful waterfall breaking it down faster.
• Time and consistency:Staying in the fat-burning zone for extended periods can be time-consuming. It’s vital to consider your lifestyle and how much time you can devote to exercise.
• Individual variations matter: It’s essential to recognise that individual variations play a significant role in the effectiveness of the fat-burning zone. Genetics, fitness level, andmetabolism can influence how your body responds to exercise. What works for one person might work differently for another.

Finding your fat-burning zone

You might wonder, “Is the fat-burning zone still relevant?” In short, the answer is yes, especially for beginners, those with medical conditions, or if you are looking for a low-impact workout. 

While calculating your fat-burning zone, as mentioned earlier, the easiest way to ensure you’re exercising within your target heart rate range is to wear a heart rate monitor during your workouts. Many fitness trackers and smartwatches have this feature built-in.

Some exercises can burn more calories per hour than others. To burn the maximum calories, you should consider running. Running is the biggest calorie-burning activity per hour. If running isn’t your thing, other calorie-burning activities include HIIT workouts, jumping rope, and swimming. You can perform any combination of these exercises depending on your interests and fitness level.

Practical tips for effective fat burning

Start with a light warm-up to elevate your heart rate gradually. This prepares your body for more intense exercise. While the fat-burning zone can be effective, keep yourself open to workouts outside this range. Incorporate a variety of workout intensities to keep your routine exciting and maximise overall calorie burn.

Remember that muscle burns more calories at rest than fat (about 50 times more), so incorporate strength training into your fitness regimen to boost your metabolism. Give your body adequate time to recover between workouts. Overtraining can lead to burnout and hinder your progress.

Tracking your progress

To gauge the effectiveness of your workouts within the fat-burning zone and assess your weight loss journey, keep an eye on changes in your body measurements, such as waist circumference and body fat percentage. 

Notice how you feel during and after your workouts. Increased energy levels and improved stamina can be indicators of progress. 

Lastly, while not the sole measure of success, tracking your weight on a scale over time can help you see trends and make necessary adjustments to your routine.

*This article is attributed to Affinity Health.

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In 1855, English physician, Thomas Addison, described bronze skin disease as being caused by the destruction of the adrenal glands. This resulted in a deficiency of the hormones produced by the adrenals.

The adrenal gland

Image by hopkinsmedicine.org

Addison’s work showed that the adrenal gland is essential for life. The gland is divided into two sections (cortex and medulla) and produces three main hormones:

• Glucocorticoid – cortisol
• Mineralcorticoid – aldosterone
• Adrenalin

These hormones are critical for, among other things, the regulation of blood pressure, fluid balance, immune function, and carbohydrate metabolism. Any damage to the glands will result in a decrease in the hormones produced and thus, cause a range of clinical problems.

Decreased function of the adrenal glands may be described as primary or secondary.

Primary – Direct damage to the adrenal glands.

Secondary – Damage is to the pituitary gland and affects the secretion of ACTH, the hormone that control glucocorticoid release. The most common cause of this is the use of cortisone-based medications (e.g. prednisone).

Primary Addison’s disease (adrenocorticoid deficiency)

Causes

1. Autoimmune – This is the most common cause and can occur in combination with other autoimmune conditions and this is known as polyglandular endocrinopathies:
   1. Type 1 Autoimmune polyglandular syndrome – This has a classic triad of Addison’s disease, hypoparathyroidism and mucocutaneous candidiasis (a skin disorder).
   2. Type 2 Autoimmune polyglandular syndrome – Combines several conditions such as Addison’s disease, Type 1 diabetes, thyroiditis, pernicious anaemia (vitamin B12 deficiency), vitiligo or alopecia.
2. Infections – In South Africa HIV and tuberculosis are more common ones.
3. Adrenal haemorrhage – This can be caused by trauma or severe illness.
4. Infiltrations – Unusual conditions such as haemochromatosis (iron overload) and, rarely, cancer that has spread.
5. Congenital disorders occur rarely.
6. Medications – Ketoconazole (an antifungal) and etomidate (a sedative).

Clinical presentation

Addison’s disease can develop insidiously and be missed for a long time. Patients may complain of general feelings of fatigue, general body weakness, loss of weight, nausea and vomiting with abdominal pain, and dizziness.

On examining the patient, it’s important to test blood pressure lying and standing as a drop in blood pressure on standing confirms postural hypotension which is a feature of Addison’s disease.

Almost all patients will have areas of their skin that are dark in colour (hyperpigmented), especially in sun-exposed skin. This is due to the high levels of ACTH binding to melanocyte receptors which are responsible for pigmentation.

There really does need to be a high level of suspicion to diagnose Addison’s disease early due to non-specific presentation. Patients at increased risk of Addison’s disease are those with other autoimmune diseases as listed above.

Addison’s crisis

Some patients develop adrenal insufficiency rapidly, often after trauma or severe infection. They present critically ill with dehydration, severely low blood pressure, confusion and can go into shock. Areas of skin hyperpigmentation may be present.

Diagnosis

Adrenal hormone secretion is controlled by the hypothalamus and pituitary gland. The hypothalamus secretes corticotropin releasing hormone (CRH) which stimulates the release of adrenocorticotrophic hormone (ACTH) in the pituitary gland. ACTH then stimulates the release of cortisol from the adrenal gland. This is all controlled by a precise feedback loop.

Image by courses.washington.edu

If an Addison’s crisis is suspected, the blood tests should be taken immediately in casualty, so that empirical treatment can be started, and the diagnosis reviewed later.

Imaging studies may help with the cause of Addison’s disease, e.g. an ultrasound or CT scan of the adrenals can show haemorrhage or infiltration. Autoimmune destruction of the adrenals will reveal small glands.

Treatment

The mainstay of treatment is to replace the hormones that aren’t being produced:

• Glucocorticoid (cortisol) – hydrocortisone or prednisone given in divided doses.
• Mineralocorticoid (aldosterone)– fludrocortisone usually daily.

In Addison’s crisis fluid replacement is critical and large doses of glucocorticoids will be given intravenously.

Maintenance

It’s important for patients with Addison’s to be aware of the impact any stress to their body will have on their chronic management of their condition. When the human body is stressed (due to illness, trauma), the adrenal glands produce more hormones to compensate.

A person with Addison’s disease must increase their medication dose during these periods to provide the same protection and avoid a crisis. They should also wear a medical alert bracelet so that if in an accident the emergency personnel will know to give life-saving cortisone.

The person living with Addison’s disease and Type 1 diabetes

Although the risk is there, this is an unusual combination. It’s not recommended to routinely screen people living with Type 1 diabetes for Addison’s disease. There are some factors that would increase the risk of the combination and indicate to the doctor that tests should be done. These risks factors are:

1. Recurrent, unexplained hypoglycaemia – This would naturally mean the person is constantly decreasing their insulin dose.
2. Repeat requests for a glucagon hypo kit prescription – Again the increased use of glucagon would indicate frequent and significant hypoglycaemia.
3. Presence of diabetic retinopathy.
4. Concomitant diagnosis of autoimmune thyroid disease.

The daily burden of care will still be directed at Type 1 diabetes. Studies have shown that overall people living with both Type 1 diabetes and Addison’s disease have a lower basal insulin requirement and increased mealtime insulin needs. This is related to the change in the insulin sensitivity due to cortisone replacement. There are further challenges when there is an intercurrent illness or other stress as this will affect both the corticosteroid requirement and the glucose levels. Similarly, if diabetes control is not good this will cause ongoing stress to the body and higher doses of glucocorticoid replacement may be required.

A specialist and latest technology are a must

For this reason, people living with both conditions should be given access to flash or continuous glucose monitoring, and the option of insulin pump therapy. Access to this technology will allow more regular and accurate adjustments to the insulin regimen.

A patient with the combination of Addison’s disease and Type 1 diabetes must be looked after by a specialist. They must have access to 24/7 advice and have a home protocol of what to do if unwell. In this way the complications of hypoglycaemia, diabetic ketoacidosis and adrenal crisis can be avoided.

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