Chronic renal failure natural history

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2]


Chronic renal failure can be complicated by the development of disorders such as hyperuricemia, myopathy, congestive heart failure, pallor, nausea, anorexia, and peptic ulcers amongst other disorders. The prognosis of the disease is poor if mismanaged. If untreated, patients will develop symptoms and signs of uremia (accumulation of uremic solutes), and chronic renal failure (CRF) will progress to end-stage renal disease, which has a high morbidity rate.

Natural History

If left untreated, patients progressively lose renal function and develop signs and symptoms associated with extracellular fluid overload, ion concentration derangements, and uremia. Patients with chronic kidney disease eventually reach end stage renal disease (ESRD) when GFR is below < 15 mL/min/1.73m2Usually and eventually necessitate renal replacement (either dialysis or transplantation) for survival. Usually, the time frame of progression to ESRD is very variable among individuals. Older age, male gender, and African American ethnicity are all associated with higher risk of progression. Tight blood pressure and glycemic control are essential to decrease the risk of development of ESRD in patients with pre-existing renal insufficiency.[1] A population-based study of a Swedish cohort of with pre-existing stage 4 or 5 CKD showed that 80% of patients would progress to require RRT within 5 years, with a mortality rate of up to 39%. Half of the cohort was on renal replacement by 18 months follow up.[2]


Cardiovascular Disease

Early stage CKD

The cardiovascular system is closely related to renal function. Studies have shown that even minor decreases in GFR (60-89 ml/min per 1.73 m2) can double the risk of myocardial infarction and stroke compared to patients with normal GFR.[3] The risk of adverse cardiovascular events also tends to increase with decreasing GFR. This underlines the impact of cardiovascular disease being the leading cause of mortality in patients with renal disease.

ESRD & Dialysis

Bone Disease



The prognosis of patients with chronic kidney disease is guarded as epidemiological data has shown that all cause mortality (the overall death rate) increases as kidney function decreases.[4] The leading cause of death in patients with chronic kidney disease is cardiovascular disease, regardless of whether there is progression to ESRD.[4][5][6]

Cystatin C adds to serum creatinine in predicting risk from chronic kidney disease.[7]

While renal replacement therapies can maintain patients indefinitely and prolong life, the quality of life of the patient is severely affected.[8][9] Renal transplantation increases the survival of patients with ESRD significantly when compared to other therapeutic options;[10][11] however, it is associated with an increased short-term mortality (due to complications of the surgery). Transplantation aside, high intensity home hemodialysis appears to be associated with improved survival and a greater quality of life when compared to the conventional thrice weekly hemodialysis and peritoneal dialysis.[12]


  1. Taal MW, Brenner BM (2006). "Predicting initiation and progression of chronic kidney disease: Developing renal risk scores". Kidney Int. 70 (10): 1694–705. doi:10.1038/ PMID 16969387.
  2. Evans M, Fryzek JP, Elinder CG, Cohen SS, McLaughlin JK, Nyrén O; et al. (2005). "The natural history of chronic renal failure: results from an unselected, population-based, inception cohort in Sweden". Am J Kidney Dis. 46 (5): 863–70. doi:10.1053/j.ajkd.2005.07.040. PMID 16253726.Review in: Evid Based Med. 2006 Aug;11(4):118
  3. Zhang L, Zuo L, Wang F, Wang M, Wang S, Lv J; et al. (2006). "Cardiovascular disease in early stages of chronic kidney disease in a Chinese population". J Am Soc Nephrol. 17 (9): 2617–21. doi:10.1681/ASN.2006040402. PMID 16885404.
  4. 4.0 4.1 Perazella MA, Khan S. Increased mortality in chronic kidney disease: a call to action. Am J Med Sci. 2006 Mar;331(3):150-3. PMID 16538076.
  5. Sarnak MJ, Levey AS, Schoolwerth AC, Coresh J, Culleton B, Hamm LL, McCullough PA, Kasiske BL, Kelepouris E, Klag MJ, Parfrey P, Pfeffer M, Raij L, Spinosa DJ, Wilson PW; American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation. 2003 Oct 28;108(17):2154-69. PMID 14581387. Free Full Text.
  6. Tonelli M, Wiebe N, Culleton B, House A, Rabbat C, Fok M, McAlister F, Garg AX. Chronic Kidney Disease and Mortality Risk: A Systematic Review. J Am Soc Nephrol. 2006 May 31; PMID 16738019.
  7. Shlipak MG, Matsushita K, Ärnlöv J, Inker LA, Katz R, Polkinghorne KR; et al. (2013). "Cystatin C versus creatinine in determining risk based on kidney function". N Engl J Med. 369 (10): 932–43. doi:10.1056/NEJMoa1214234. PMC 3993094. PMID 24004120.
  8. Heidenheim AP, Kooistra MP, Lindsay RM. Quality of life. Contrib Nephrol. 2004;145:99-105. PMID 15496796.
  9. de Francisco AL, Pinera C. Challenges and future of renal replacement therapy. Hemodial Int. 2006 Jan;10 Suppl 1:S19-23. PMID 16441862.
  10. Groothoff JW. Long-term outcomes of children with end-stage renal disease. Pediatr Nephrol. 2005 Jul;20(7):849-53. Epub 2005 Apr 15. PMID 15834618.
  11. Giri M. Choice of renal replacement therapy in patients with diabetic end stage renal disease. EDTNA ERCA J. 2004 Jul-Sep;30(3):138-42. PMID 15715116.
  12. Pierratos A, McFarlane P, Chan CT. Quotidian dialysis--update 2005. Curr Opin Nephrol Hypertens. 2005 Mar;14(2):119-24. PMID 15687837.

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