Part of your role as a pharmacist, is to understand the pathophysiology of CKD and what role it plays in CVRM disorder. You will then be able to understand your role is in the management of these patients. 

WHAT IS CHRONIC KIDNEY DISEASE? 

CKD, also known as chronic renal disease, is a condition characterised by a gradual loss of kidney function (elimination of drugs/metabolites) over time. 

CKD includes disease conditions that adversely affect the kidneys and decreases their filtering ability. This leads to waste products that accumulate in the blood circulation, which can then lead to worsening of CKD. Complications that may develop include: 

• Hypertension 
• Anaemia 
• Bone loss 
• Poor nutritional status 
• Neuronal damage. 

CAUSES 

Conditions most likely to lead to CKD include: 

• Diabetes – hyperglycaemia can lead to damage of the kidney, heart, blood vessels, and the eyes 
• Hypertension – can lead to damage of blood vessels in the kidney, but also be a leading cause for heart attack 
• CVDs 
• Genetic predisposition 
• Age – the longer a person suffers from diabetes, hypertension, or CVD, the more likely they will develop CKD. 

Other conditions that can also affect kidney function, include: 

• Glomerulonephritis 
• Polycystic kidney disease 
• Autoimmune diseases 
• An enlarged prostate gland or repeated UTIs. 

 SIGNS AND SYMPTOMS* 

Most people may not have any severe symptoms until their kidney disease is advanced. However, some of the following symptoms may be indicative of kidney disease: 

• Fatigue* 
• Trouble concentrating* 
• Poor appetite* 
• Oedema* of the feet and ankles 
• Dry, itchy skin* 
• Increased or decreased urination* 
• Numbness* 
• Headaches* 
• Muscle cramping* at night 
• Nausea* 
• Sleeping difficulties 
• Chest pain 
• Apnoea/shortness of breath 
• Unintended weight loss. 

Note: *symptoms that are shared with the different stages of CKD. 

DIAGNOSIS OF CKD 

CKD can be diagnosed with blood and urine tests. Creatinine is a waste product that originates from muscle activity and is a key indicator of kidney function. When the kidney function is normal, it means that creatinine is removed from the blood; but as kidney function decreases, blood levels of creatinine rise. 

Laboratory investigation studies to determine the extent of kidney disease include the following: 

• Firstly, an albumin: creatinine ratio is determined (this notes the presence of albumin in the urine) 
• Secondly: calculation of the creatinine level and the eGFR (estimated glomerular filtration rate [ml/min/1.73 m2]) is done. 

By combining the albumin:creatinine ratio and the eGFR (estimated glomerular filtration rate [ml/min/1.73 m2]) values, a CV and progressive renal risk is calculated. The higher the levels of albuminuria, the lower the eGFR and the higher the risk. 

Stages of CKD 

Stage 1: Normal or high eGFR (eGFR ≥ 90 ml/min/1.73 m2) 

• Patients only find out that they have stage 1 CKD when they are tested for diabetes or hypertension 
• Diagnosis may be made by: 
  • Having higher than normal creatinine/urea in their blood 
  • Blood/protein in the urine. 

Stage 2: Mild CKD (eGFR = 60-89 ml/min/1.73 m2) 

• Has the same criteria as Stage 1. 

Stage 3A: Mild to moderate (45-59 ml/min/1.73 m2), Stage 3B: Moderate to severe (30-44 ml/min/1.73 m2) 

• Diagnosis is made by: 
  • Testing the kidney function – a decrease in the function can result in uraemia 
• Symptoms^# that may appear are: 
  • Fatigue¹ 
  • Oedema^#2 of extremities and shortness of breath 
  • Urine changes^#2 e.g., dark orange, tea-coloured or red (indicative of the presence of blood), a change in urination pattern 
  • Kidney pain^#4 
  • Muscle cramps/restless leg syndrome^#5. 

Stage 4: Severe CKD (eGFR = 15-30 ml/min/1.73 m2) 

• Diagnosis is made by: 
  • A decrease in the eGFR – which may lead to future dialysis or a kidney transplant 
  • Testing of the kidney function reveals a state of uraemia 
  • Increased development of complications e.g., hypertension, anaemia, bone disease, and CVDs 
• Symptoms1-5 that may appear include: 
  • Nausea and/or vomiting^#6 
  • Loss of appetite^#7 
  • Difficulty in concentrating^#8 
  • Nerve problems^#9 e.g., numbness or tingling in the fingers and toes 
  • Metallic taste in the mouth 
  • Bad breath due to increased urea in the blood. 

Stage 5: End Stage CKD (renal failure) (eGFR < 15 ml/min/1.73 m2) 

• Diagnosis is made for advanced kidney disease which leads to the need for dialysis or a kidney transplant for survival 
• The inability of the body to regulate blood pressure 
• Symptoms^#1,2,5-9 that may appear: 
  • Headaches 
  • Itching 
  • Changes in skin colour 
  • Increased skin pigmentation. 

Note: Symptoms = #Superscripts ‘1-9’ are symptoms that are shared among the different stages. 

The role of the pharmacist within the healthcare working environment is valuable when a patient has CKD. This creates new opportunities to understand the treatment of CKD within the CVRM diseases. 

REFERENCES:  

This article was based on: 

• ^1aMedTalk presented by Prof. Brian Rayner. Cardiorenal series. Module 2. Type 2 diabetes and the kidney. 2021. Available at: https://vimeo.com/560385392/66776b80b6 - accessed: 05 June 2023.
• ^1bAalbers, J. Type 2 diabetes and the kidneys. deNovo Medica, 2021, July, 1-6
• ^2aA MEDTalk presented by: Dr. Julian Trokis. MedTalk ZA. Diabetic Kidney Disease. Early detection and treatment. 2022. Available at: https://player.vimeo.com/video/711152088 as well as denovomedica.com - accessed: 05 June 2023

• ^2bAalbers, J. Early intervention in type 2 diabetes to reduce kidney and cardiovascular complications. deNovo Medica, 2022, August, 1-12

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7. De Boer IH, Caramori ML, Chan JCN, et al. Executive summary of the 2020 KDIGO Diabetes Management in CKD Guidelines: evidence-based advances in monitoring and treatment. Kidney International 2020; 98: 839-848. 
8. National Institute of Diabetes and Digestive and Kidney Diseases (NIH). Health information. Chronic Kidney Disease. Available at: https://www.niddk.nih.gov/health-information/kidney-disease/chronic-kidney-disease-ckd/all-content . – accessed: 06 June 2023 
9. National Kidney Foundation. Chronic Kidney Disease (CKD). Available at: https://www.kidney.org/atoz/content/about-chronic-kidney-disease#kidney-disease-facts – accessed: 06 June 2023 
10. Rossiter, Dawn. South African Medicines Formulary. Ed. Dawn Rossiter. 12th ed. Rondebosch, South Africa: Health and Medical Pub. Group of the South African Medical Association, 2016. Print