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Diabetic Nephropathy

Original Editor - Oluwafikunayomi Wole-Bankole and Kadeba Bisola|Kadeba Bisola

Top Contributors - Oluwafikunayomi Wole-Bankole, Rishika Babburu, Tolulope Adeniji, Vidya Acharya and Alexandra Stead  

ORIGINAL EDITORS: Oluwafikunayomi Wole-Bankole and Kadeba Bisola as part of the Redeemer's University Physioculture Journal Project

Diabetic Nephropathy

Definition

Diabetic nephropathy, also known as chronic kidney disease, is a condition characterized by excessive urine albumin, diabetic glomerular lesions, and a decline in glomerular filtration rate in diabetics.[1]   In most developed countries, diabetic nephropathy is the most common cause of end-stage renal disease and it affects about 40% of people with diabetes. [2]. Diabetic nephropathy is linked with a high cardiovascular death rate.[3] 

Classification

Diabetic nephropathy has been classified into various phases: microalbuminuria (UAE >20 μg/min and ≤199 μg/min) and macroalbuminuria (UAE ≥200 μg/min).Depending on the type of diabetes and whether microalbuminuria (defined as >30 mg but <300 mg albumin in the urine per day) or macroalbuminuria (defined as >300 mg albumin in the urine per day) is present, the natural course of diabetic nephropathy varies.

Approximately 80% of individuals with type 1 diabetes and microalbuminuria who are neglected will eventually develop overt nephropathy, whereas about 20-40% of people with type 2 diabetes will progress into the nephropathic stage. Diabetic nephropathy is one of the causes of chronic kidney disease.[4].

Epidemiology

Between 10 and 15 years following the commencement of the disease, type 1 diabetes patients have their peak nephropathy development. According to previous reports, type 2 diabetic patients have a reduced prevalence of progressive renal disease. The prevalence of diabetic nephropathy is increasing worldwide.

Globally, the prevalence of diabetes was about 171 million in 2000, increasing to 382 million in 2013, and is projected to reach 592 million by 2035.[5] Diabetic nephropathy is now the most common cause of end-stage renal disease (ESRD) in most countries because of the diabetes epidemic. In Malaysia, Mexico, and Singapore, diabetes accounted for 60% of cases of ESRD between 2009 and 2011.[5] In 2015, it was predicted that 415 million individuals globally had diabetes; by 2040, it is expected to rise to 642 million, with a significant rise in low- and middle-income nations.

Pathophysiology

In both Type I and Type II diabetes, similar effects on the kidney occur. An increase in glucose levels in the blood damages blood vessels, including the arteries that supply the kidney. The nephrons of the kidneys are also affected as they begin to thicken and become scarred. They also begin to leak protein contents that are supposed to be retained rather than passed out with urine. Over time, this leads to diabetic nephropathy[6].

Clinical Manifestations

Due to diabetes, there is an onset of kidney failure; however, the symptoms do not manifest until the end stages (between five to ten years[7]. The symptoms of end stage kidney damage include:

Swelling - Fluid accumulation in the tissues due to impaired kidney function.

Itching - A common symptom related to waste product accumulation in the blood.

Nausea and Vomiting - Results from the buildup of toxins that the kidneys can no longer filter effectively.

Shortness of Breath - Due to the accumulation of fluid in the lungs as a result of kidney failure.

Hypertension - High blood pressure is both a cause and consequence of diabetic nephropathy.

Weight Loss - Due to loss of appetite associated with kidney dysfunction.

Bone Pain (Renal Osteodystrophy) - This occurs in diabetic nephropathy due to reduction in minerals and hormones in the blood required for bone growth. Bone growth is thus hindered, causing pain in the bones and leading to fractures[8].

Chest Pain - Due to the reduction in mineral contents, the heart does more work to pump blood through the body. This also increases stress on arteries and the cardiovascular system at large. Additionally, the lining of the heart can become inflamed, which causes chest pain.[9]

Cardiovascular Diseases - These are common in diabetic patients with chronic kidney disease due to the decreased estimated glomerular filtration rate and decreased levels of albuminuria. Low-grade albuminuria levels or reduced albuminuria is said to be an indicator for cardiovascular diseases, as it represents vascular disorders of the kidney and vascular beds.[10]

Diagnosis

Diagnosis of chronic kidney disease in individuals with type 2 diabetes is done with a simple, cost-effective kidney test, which is represented by eGFR determination in the serum and urine albumin measurement.[11]

Medical Management

The major management of the condition is the prevention of various cardiovascular diseases such as hypertension, as reduced albuminuria causes disturbances to cardiovascular health[12]. The use of precision medicine, which puts into consideration the individuality of diseases and various treatment strategies required, characterizes diseases based on underlying molecular pathology[11].

Management strategies include:

  • Reduction of dietary proteins and achieving close to normal or normal blood glucose levels[13].
  • Oral hypoglycemic agents such as SGLT2 inhibitors, which reduce reabsorption in the kidney, causing excretion of glucose and reducing hyperglycemia
  • Angiotensin-converting enzyme (ACE) inhibitors, which are used to control blood pressure[14]

Physiotherapy Management

Physiotherapy management involves the control of blood pressure, obesity, and diabetes. This is achieved by enhancing cardiovascular health, improving circulation, and reducing blood sugar and body fat levels. Recommended interventions include aerobic exercises (low to moderate intensity) such as swimming and cycling, as well as stretching exercises.[15]

Exercise interventions slow the progression of kidney disease and improve vascular endothelial function. However, high-intensity exercises should be avoided as they can lead to hypoperfusion and proteinuria in renal disease due to arteriolar vasoconstrictor actions.[16].

Precautions

Cautions during management include:

  • Ensure proper foot care
  • Do not engage in exercise when blood sugar levels are higher than 250 mg/dL or less than 100 mg/dL[17]
  • Also, patients are advised not to participate in exercise with a blood pressure 180/110mmHg[18]

References

  1. ↑ Pálsson R, Patel UD. Cardiovascular complications of diabetic kidney disease. Advances in chronic kidney disease. 2014 May 1;21(3):273-80.
  2. ↑ Wang G, Ouyang J, Li S, Wang H, Lian B, Liu Z, Xie L. The analysis of risk factors for diabetic nephropathy progression and the construction of a prognostic database for chronic kidney diseases. J Transl Med. 2019 Aug 13;17(1):264. doi: 10.1186/s12967-019-2016-y. PMID: 31409386; PMCID: PMC6693179.
  3. ↑ Valmadrid CT, Klein R, Moss SE, Klein BE. The risk of cardiovascular disease mortality associated with microalbuminuria and gross proteinuria in persons with older-onset diabetes mellitus. Arch Intern Med. 2000 Apr 24;160(8):1093-100. doi: 10.1001/archinte.160.8.1093. PMID: 10789601.
  4. ↑ Dronavalli S, Duka I, Bakris GL. The pathogenesis of diabetic nephropathy. Nat Clin Pract Endocrinol Metab. 2008 Aug;4(8):444-52. doi: 10.1038/ncpendmet0894. Epub 2008 Jul 8. PMID: 18607402.
  5. ↑ 5.0 5.1 Lim AKh. Diabetic nephropathy - complications and treatment. Int J Nephrol Renovasc Dis. 2014 Oct 15;7:361-81. doi: 10.2147/IJNRD.S40172. PMID: 25342915; PMCID: PMC4206379.
  6. ↑ American Diabetes Association Professional Practice Committee. 12. Retinopathy, Neuropathy, and Foot Care: Standards of Medical Care in Diabetes-2022. Diabetes Care. 2022 Jan 1;45(Suppl 1):S185-S194. doi: 10.2337/dc22-S012. PMID: 34964887.
  7. ↑ Retinopathy, Neuropathy, and Foot Care: Standards of Medical Care in Diabetes-2022.American Diabetes Association Professional Practice Committee Diabetes care, 45, Suppl 1, 1 2022
  8. ↑ Shah A, Hashmi MF, Aeddula NR. Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD) [Updated 2024 Apr 3]. In: StatPearls
  9. ↑ Negi S, Koreeda D, Kobayashi S, Yano T, Tatsuta K, Mima T, Shigematsu T, Ohya M. Acute kidney injury: Epidemiology, outcomes, complications, and therapeutic strategies. Semin Dial. 2018 Sep;31(5):519-527. doi: 10.1111/sdi.12705. Epub 2018 May 8. PMID: 29738093.
  10. ↑ Weir MR. Microalbuminuria and cardiovascular disease. Clin J Am Soc Nephrol. 2007 May;2(3):581-90. doi: 10.2215/CJN.03190906. Epub 2007 Feb 14. PMID: 17699466.
  11. ↑ 11.0 11.1 Fliser D, Wanner C. Precision medicine in diabetic nephropathy and chronic kidney disease. Nephrol Dial Transplant. 2021 Jun 22;36(Suppl 2):10-13. doi: 10.1093/ndt/gfaa380. PMID: 34153982.
  12. ↑ Foggensteiner L, Mulroy S, Firth J. Management of diabetic nephropathy. J R Soc Med. 2001 May;94(5):210-7. doi: 10.1177/014107680109400504. PMID: 11385086; PMCID: PMC1281451.
  13. ↑ de Boer IH, Caramori ML, Chan JCN, Heerspink HJL, Hurst C, Khunti K, Liew A, Michos ED, Navaneethan SD, Olowu WA, Sadusky T, Tandon N, Tuttle KR, Wanner C, Wilkens KG, Zoungas S, Lytvyn L, Craig JC, Tunnicliffe DJ, Howell M, Tonelli M, Cheung M, Earley A, Rossing P. Executive summary of the 2020 KDIGO Diabetes Management in CKD Guideline: evidence-based advances in monitoring and treatment. Kidney Int. 2020 Oct;98(4):839-848. doi: 10.1016/j.kint.2020.06.024. Epub 2020 Jul 10. PMID: 32653403.F
  14. ↑ Kim MK. Treatment of diabetic kidney disease: current and future targets. Korean J Intern Med. 2017 Jul;32(4):622-630. doi: 10.3904/kjim.2016.219. Epub 2017 Jun 30. PMID: 28704915; PMCID: PMC5511942.
  15. ↑ Billinger SA, Sisante JV, Alqahtani AS, Pasnoor M, Kluding PM. Aerobic exercise improves measures of vascular health in diabetic peripheral neuropathy. Int J Neurosci. 2017 Jan;127(1):80-85. doi: 10.3109/00207454.2016.1144056. Epub 2016 Feb 16. PMID: 26785723; PMCID: PMC4987267
  16. ↑ Amaral LSB, Souza CS, Lima HN, Soares TJ. Influence of exercise training on diabetic kidney disease: A brief physiological approach. Exp Biol Med (Maywood). 2020 Jul;245(13):1142-1154. doi: 10.1177/1535370220928986. Epub 2020 Jun 2. PMID: 32486850; PMCID: PMC7400720.
  17. ↑ Diabetes - Physiopedia [Internet]. [cited 2023 Jan 29]. Available from: https://www.physio-pedia.com/Diabetes
  18. ↑ Ghadieh AS, Saab B. Evidence for exercise training in the management of hypertension in adults. Can Fam Physician. 2015 Mar;61(3):233-9. PMID: 25927108; PMCID: PMC4369613.
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