UNRAVELLING THE CONNECTION: HOW DIABETES IMPACTS RENAL HEALTH

By Masooma Hyder Baig

What is Diabetes?

Diabetes is a chronic condition affecting approximately 422 million people (World Health Organization, 2023). It is caused by uncontrolled concentrations of glucose in the blood (NHS, 2023) due to issues relating to the hormone insulin which modulates these glucose levels in normal bodily function. Type 1 diabetes is characterised by the body’s immune system attacking pancreatic beta cells that secrete insulin (American Diabetes Association, 2024). In contrast, type 2 diabetes results from the body’s cells not reacting to insulin effectively (Diabetes UK, 2023). 

Symptoms of type 2 diabetes include:

• Unintentional weight loss
•  Fatigue
• Blurred vision
• Needing to urinate more often
•  Feeling very thirsty 

 (World Health Organization, 2023)

The kidneys are responsible for many functions including filtering blood and excreting waste products through urine, regulating pH, electrolyte levels blood pressure and controlling the production of red blood cells. 

The kidney consists of two regions: the cortex (outer region) and the medulla (inner region). The medulla comprises cone-like structures called renal pyramids, which are made up of millions of functional units called nephrons. The kidneys are highly vascularised (Sequeira Lopez and Gomez, 2011). The hilum of the kidney acts as the entry and exit points for important structures linked to this vascularisation and function including the renal veins (exits the kidney after blood has been filtered), renal arteries (supply the kidneys with oxygenated blood and blood that is to be filtered), nerves and the ureter (where urine filters to via the minor, major calyces to the renal pelvis.) 

The nephrons are pivotal in allowing the kidney to maintain homeostasis through blood filtration and selective reabsorption. Filtration starts at the glomerulus of the nephron, which is a network of capillaries. Here, blood is received by the glomerulus at a high pressure which pushes small molecules (glucose, amino acids and electrolytes) past a fenestrated endothelial layer and to enter the nephron whilst large structures (red blood cells and proteins)  remain in the blood. The fluid within the nephron at this stage is called the filtrate. At the proximal convoluted tubule (PCT) glucose reabsorption occurs – the amount of glucose reabsorbed is dependent on the body’s need for glucose (NIDDK, 2019). The filtrate then travels through the loop of Henle and distal convoluted tubule (DCT) where electrolyte (primarily sodium) reabsorption and fluid balance by osmosis takes place. Depending on whether an individual is hydrated or dehydrated, the amount of electrolytes and water reabsorbed differs. Once past the DCT, the filtrate is funnelled through the minor and major calyces towards the ureter (Soriano and Leslie, 2023) to be excreted as urine via the bladder. Thus, by understanding the normal function of the kidneys we can begin to understand how disease impairs said functions over time. 

Diabetic Kidney Damage

Diabetic kidney damage is referred to as diabetic nephropathy (Varghese and Jialal, 2020). It is characterised by vascular damage leading to proteinuria (protein in the urine). This is due to high glucose levels in diabetic patients initiating the activation of various inflammatory signalling pathways resulting in the production of chemokines like TGF-beta (transforming growth factor-beta), and VEGF (vascular endothelial growth factor) which cause inflammation fibrosis and increased vascular permeability (Varghese and Jialal, 2020). Increased vascular permeability means that at the glomerulus, larger molecules like proteins can enter the filtrate (in turn in urine) when under normal conditions this would not be possible. Fibrosis is the thickening and scarring of tissue which renders the tissue incapable of performing its function. Over time increased scarring may result in patients needing a kidney transplant or dialysis (Panizo et al., 2021). 

Symptoms of diabetic nephropathy may include: 

• High blood pressure.
• 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 

(Mayo Clinic, 2021)

Lab tests can be done to inform a diagnosis of this condition. To detect proteinuria, experts can take a urine protein test using the patient’s urine sample. If protein levels are elevated above the normal range (31mg/g or more), this could indicate potential nephropathy (Phillips, 2017). Blood tests to detect the plasma concentration of creatinine (waste product) can be used to work out the estimated glomerular filtration rate (EGFR). This parameter measures the kidneys’ ability to filter blood at the glomerulus where a GFR of 60 and below could indicate kidney damage (Cornejo, 2023). Another way of measuring EGFR is by looking at the ratio between the amount of a protein called albumin to creatinine in a patient’s urine (UACR). Here, kidney damage would be considered if UCAR was greater than 3mg/mmol (Winocour et al., 2020). Diagnosing kidney damage (mild, moderate or severe) in diabetic patients will often include a combination of these tests in addition to medical and symptomatic history. 

General Management 

Encouraging patients to observe a healthy diet consisting of low-glycaemic index carbohydrates like fruits, green vegetables, whole grains and pulses in addition to regular exercise is considered to be an integral part of diabetes management, taking into consideration the patient’s weight and personal journey (NICE, 2022). Managing hypertension in diabetic patients is also heavily emphasised through diet and exercise whereby individuals should regularly get their blood pressure measured to regulate well-being (NICE, 2019). These factors alongside healthcare providers discussing what medications are best suited to individual patients empower patients to make informed decisions based on their circumstances.

Conclusion

To conclude, diabetes is a common chronic condition caused as a result of uncontrolled glucose levels. The reasons for these uncontrolled levels relate to the immune system attacking the cells that release the hormone insulin (type 1 diabetes) or the body not being able to respond to insulin properly (type 2 diabetes.) High glucose levels can lead to kidney damage referred to as diabetic nephropathy which can severely affect normal body function if not properly managed. Healthcare providers can conduct various lab tests to inform a diagnosis of diabetic nephropathy alongside other relevant symptoms. Lifestyle changes and education alongside taking medication are vital components in managing and mitigating the severe consequences of this condition.

Reference list

American Diabetes Association (2024). Type 1 Symptoms | ADA. [online] diabetes.org. Available at: https://diabetes.org/about-diabetes/type-1 [Accessed 1 Apr. 2024].

Cornejo, C. (2023). How to Screen for Diabetes-Related Nephropathy. [online] Healthline. Available at: https://www.healthline.com/health/diabetes/diabetic-nephropathy-screening#e-gfr-measurement [Accessed 5 Apr. 2024].

Diabetes UK (2023). Type 2 Diabetes. [online] Diabetes UK. Available at: https://www.diabetes.org.uk/diabetes-the-basics/types-of-diabetes/type-2 [Accessed 1 Apr. 2024].

El-Reshaid, K. and Al-Bader, S. (2020). Acute Renal Injury: Revisited. Journal of Drug Delivery and Therapeutics, 10(4), pp.221–224. doi:https://doi.org/10.22270/jddt.v10i4.4154.

Mayo Clinic (2021). Diabetic nephropathy – Symptoms and causes. [online] Mayo Clinic. Available at: https://www.mayoclinic.org/diseases-conditions/diabetic-nephropathy/symptoms-causes/syc-20354556 [Accessed 4 Apr. 2024].

NHS (2023). Diabetes. [online] NHS. Available at: https://www.nhs.uk/conditions/diabetes/ [Accessed 1 Apr. 2024].

NICE (2019). Recommendations | Hypertension in adults: diagnosis and management | Guidance | NICE. [online] Nice.org.uk. Available at: https://www.nice.org.uk/guidance/ng136/chapter/recommendations [Accessed 5 Apr. 2024].

NICE (2022). Recommendations | Type 2 diabetes in adults: management | Guidance | NICE. [online] http://www.nice.org.uk. Available at: https://www.nice.org.uk/guidance/ng28/chapter/Recommendations#individualised-care [Accessed 5 Apr. 2024].

NIDDK (2019). Your Kidneys & How They Work | . [online] National Institute of Diabetes and Digestive and Kidney Diseases. Available at: https://www.niddk.nih.gov/health-information/kidney-disease/kidneys-how-they-work#how [Accessed 1 Apr. 2024].

Panizo, S., Martínez-Arias, L., Alonso-Montes, C., Cannata, P., Martín-Carro, B., Fernández-Martín, J.L., Naves-Díaz, M., Carrillo-López, N. and Cannata-Andía, J.B. (2021). Fibrosis in Chronic Kidney Disease: Pathogenesis and Consequences. International Journal of Molecular Sciences, 22(1), p.408. doi:https://doi.org/10.3390/ijms22010408.

Phillips, N. (2017). Protein in Urine: A Chart of What Your Levels Should Be. [online] Healthline. Available at: https://www.healthline.com/health/protein-levels-in-urine-chart [Accessed 4 Apr. 2024].

Sequeira Lopez, M.L.S. and Gomez, R.A. (2011). Development of the Renal Arterioles. Journal of the American Society of Nephrology : JASN, [online] 22(12), pp.2156–2165. doi:https://doi.org/10.1681/ASN.2011080818.

Soriano, R.M. and Leslie, S.W. (2023). Anatomy, Abdomen and Pelvis, Kidneys. [online] Nih.gov. Available at: https://www.ncbi.nlm.nih.gov/books/NBK482385/ [Accessed 4 Apr. 2024].

Varghese, R.T. and Jialal, I. (2020). Diabetic Nephropathy. [online] PubMed. Available at: https://www.ncbi.nlm.nih.gov/books/NBK534200/ [Accessed 4 Apr. 2024].

Winocour, P., Diggle, J. and Davies, S. (2020). Testing for kidney disease in type 2 diabetes: consensus statement and recommendations – DiabetesontheNet. [online] Testing for kidney disease in type 2 diabetes: consensus statement and recommendations. Available at: https://diabetesonthenet.com/diabetes-primary-care/testing-for-kidney-disease-in-type-2-diabetes-consensus-statement-and-recommendations/ [Accessed 5 Apr. 2024].

World Health Organization (2023). Diabetes. [online] World Health Organisation. Available at: https://www.who.int/news-room/fact-sheets/detail/diabetes [Accessed 1 Apr. 2024].