It is important to note that a significant proportion of people are asymptomatic, and the diagnosis relies on pathologic evidence of kidney damage such as hematuria and/or proteinuria, or laboratory evidence of a reduction in the glomerular filtration rate (GFR) with an elevated serum creatinine.
History
Signs and symptoms are often vague, including fatigue (which may be related to uremia or the anemia associated with CKD), nausea, and possibly the development of edema. Uremic illness is due largely to the accumulation of organic waste products that are normally cleared by the kidneys, and symptoms may be present to some degree in the early stages of kidney failure.[44]Meyer TW, Hostetter TH. Uremia. N Engl J Med. 2007 Sep 27;357(13):1316-25.
http://www.ncbi.nlm.nih.gov/pubmed/17898101?tool=bestpractice.com
As kidney failure progresses to the more advanced stages of uremia, patients will often describe anorexia, nausea, vomiting, restless legs, pruritus, and overall not feeling well.[45]National Kidney Foundation. KDOQI clinical practice guideline for hemodialysis adequacy: 2015 update. Am J Kidney Dis. 2015 Nov;66(5):884-930.
https://www.ajkd.org/article/S0272-6386(15)01019-7/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/26498416?tool=bestpractice.com
If patients begin to have a lack of urine production, then the resulting fluid overload may be present with dyspnea and orthopnea due to pulmonary edema. Cognition may be affected in all stages of CKD.[3]Webster AC, Nagler EV, Morton RL, et al. Chronic kidney disease. Lancet. 2017 Mar 25;389(10075):1238-52.
http://www.ncbi.nlm.nih.gov/pubmed/27887750?tool=bestpractice.com
In the most advanced stages of uremia, patients may present with seizures or coma.[46]Arnold R, Issar T, Krishnan AV, et al. Neurological complications in chronic kidney disease. JRSM Cardiovasc Dis. 2016 Jan-Dec;5:2048004016677687.
https://journals.sagepub.com/doi/10.1177/2048004016677687
http://www.ncbi.nlm.nih.gov/pubmed/27867500?tool=bestpractice.com
Examination
Signs as a consequence of CKD are hypertension, peripheral edema (due to sodium retention and exacerbated by hypoalbuminemia), and pallor due to anemia.[3]Webster AC, Nagler EV, Morton RL, et al. Chronic kidney disease. Lancet. 2017 Mar 25;389(10075):1238-52.
http://www.ncbi.nlm.nih.gov/pubmed/27887750?tool=bestpractice.com
Physical exam findings are also directed toward the discovery of end-organ damage associated with causative disease states such as diabetes or hypertension, which cause CKD. A fundoscopic eye exam is critical for the diagnosis of diabetic or hypertensive retinopathy as evidence of microvascular damage that has likely occurred in the kidney, resulting in CKD. In men, a rectal exam for prostatic enlargement or for the diagnosis of prostate nodules can be helpful in determining a diagnosis of obstructive uropathy. In glomerular nephrotic and nephritic syndromes, the signs and symptoms of CKD may present more acutely with accelerated hypertension, periorbital and peripheral edema, rashes, or arthritis on musculoskeletal exam for patients with autoimmune disorders.[47]Khanna R. Clinical presentation & management of glomerular diseases: hematuria, nephritic & nephrotic syndrome. Mo Med. 2011 Jan-Feb;108(1):33-6.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6188440
http://www.ncbi.nlm.nih.gov/pubmed/21462608?tool=bestpractice.com
Patients may describe their urine as foamy if significant proteinuria is present, or tea- or cola-colored in the setting of hematuria.
Initial investigations
Most people are unaware that they have CKD and are informed only after abnormalities are discovered by blood and/or urine tests.[3]Webster AC, Nagler EV, Morton RL, et al. Chronic kidney disease. Lancet. 2017 Mar 25;389(10075):1238-52.
http://www.ncbi.nlm.nih.gov/pubmed/27887750?tool=bestpractice.com
The first diagnostic tests to order are a serum creatinine (as part of renal chemistry), estimated GFR (with consideration of serum cystatin-C in people with extremes of muscle mass), and urinalysis to assess for hematuria and proteinuria.[1]Kidney Disease: Improving Global Outcomes (KDIGO). KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013 Jan;3(1):1-150.
https://kdigo.org/wp-content/uploads/2017/02/KDIGO_2012_CKD_GL.pdf
[3]Webster AC, Nagler EV, Morton RL, et al. Chronic kidney disease. Lancet. 2017 Mar 25;389(10075):1238-52.
http://www.ncbi.nlm.nih.gov/pubmed/27887750?tool=bestpractice.com
Do not order serum creatinine alone to test patients with risk factors such as diabetes or hypertension for CKD.[48]American Society for Clinical Pathology. Thirty five things physicians and patients should question. Choosing Wisely, an initiative of the ABIM Foundation. 2021 [internet publication].
https://web.archive.org/web/20230316185857/https://www.choosingwisely.org/societies/american-society-for-clinical-pathology
[49]National Institute for Health and Care Excellence. Chronic kidney disease: assessment and management. 2021 [internet publication].
https://www.nice.org.uk/guidance/ng203
[50]Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 Clinical practice guideline for the evaluation and management of chronic kidney disease (CKD). Kidney Int. 2024 Apr;105(4S):S117-314.
https://www.kidney-international.org/article/S0085-2538(23)00766-4/fulltext
Laboratories should estimate GFR using an equation without a race variable.[51]Delgado C, Baweja M, Crews DC, et al. A unifying approach for GFR estimation: recommendations of the NKF-ASN task force on reassessing the inclusion of race in diagnosing kidney disease. Am J Kidney Dis. 2022 Feb;79(2):268-88.e1.
https://www.ajkd.org/article/S0272-6386(21)00828-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/34563581?tool=bestpractice.com
[52]Kramer HJ, Jaar BG, Choi MJ, et al. An endorsement of the removal of race from GFR estimation equations: a position statement from the National Kidney Foundation Kidney Disease Outcomes Quality Initiative. Am J Kidney Dis. 2022 Dec;80(6):691-6.
https://www.ajkd.org/article/S0272-6386(22)00859-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/36058427?tool=bestpractice.com
[49]National Institute for Health and Care Excellence. Chronic kidney disease: assessment and management. 2021 [internet publication].
https://www.nice.org.uk/guidance/ng203
National Kidney Foundation: eGFR calculator
Opens in new window
[
Glomerular Filtration Rate Estimation (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Equation with Creatinine, without Race (2021)
]
For the diagnosis of CKD, urinary albumin assessment is usually preferred to that of total urine protein with calculation of the albumin excretion rate or the albumin to creatinine ratio.[1]Kidney Disease: Improving Global Outcomes (KDIGO). KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013 Jan;3(1):1-150.
https://kdigo.org/wp-content/uploads/2017/02/KDIGO_2012_CKD_GL.pdf
[49]National Institute for Health and Care Excellence. Chronic kidney disease: assessment and management. 2021 [internet publication].
https://www.nice.org.uk/guidance/ng203
However, nephrotic level proteinuria is conventionally defined as >3.5 g proteinuria per 24 hours.[2]Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 clinical practice guideline for the management of glomerular diseases. Kidney Int. 2021 Oct;100(4s):S1-276.
https://kdigo.org/guidelines/gd
http://www.ncbi.nlm.nih.gov/pubmed/34556256?tool=bestpractice.com
Proteinuria is both a diagnostic and a prognostic variable in the evaluation of patients with CKD.[3]Webster AC, Nagler EV, Morton RL, et al. Chronic kidney disease. Lancet. 2017 Mar 25;389(10075):1238-52.
http://www.ncbi.nlm.nih.gov/pubmed/27887750?tool=bestpractice.com
[53]Levey AS, Gansevoort RT, Coresh J, et al. Change in albuminuria and GFR as end points for clinical trials in early stages of CKD: a scientific workshop sponsored by the National Kidney Foundation in Collaboration with the US Food and Drug Administration and European Medicines Agency. Am J Kidney Dis. 2020 Jan;75(1):84-104.
https://www.ajkd.org/article/S0272-6386(19)30883-2/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/31473020?tool=bestpractice.com
Renal ultrasound is required to evaluate kidney size, mass lesions, urinary tract obstruction, and, with a duplex examination, renal arterial flow.[3]Webster AC, Nagler EV, Morton RL, et al. Chronic kidney disease. Lancet. 2017 Mar 25;389(10075):1238-52.
http://www.ncbi.nlm.nih.gov/pubmed/27887750?tool=bestpractice.com
[54]Expert Panel on Urologic Imaging., Wong-You-Cheong JJ, Nikolaidis P, et al. ACR Appropriateness Criteria® Renal Failure. J Am Coll Radiol. 2021 May;18(5s):S174-S188.
https://www.doi.org/10.1016/j.jacr.2021.02.019
http://www.ncbi.nlm.nih.gov/pubmed/33958111?tool=bestpractice.com
Additional investigations
Kidney biopsies are performed in a minority of patients with CKD.[1]Kidney Disease: Improving Global Outcomes (KDIGO). KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013 Jan;3(1):1-150.
https://kdigo.org/wp-content/uploads/2017/02/KDIGO_2012_CKD_GL.pdf
A kidney biopsy to determine a pathologic diagnosis is indicated if a glomerular nephrotic or nephritic syndrome is suspected, or in people with diabetes with atypical presentations such as rapidly progressive kidney failure. Nephrotic syndrome may be suggested by proteinuria, and both nephritic and nephrotic syndromes may be suggested by severe presenting symptoms (accelerated hypertension, periorbital and peripheral edema) or with symptoms of underlying autoimmune diseases (rashes or arthritis). Certain infections, such as hepatitis B and C, syphilis, and streptococcal pharyngitis are associated with glomerular disorders. A kidney biopsy is critical in these cases to determine the correct diagnosis.[2]Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 clinical practice guideline for the management of glomerular diseases. Kidney Int. 2021 Oct;100(4s):S1-276.
https://kdigo.org/guidelines/gd
http://www.ncbi.nlm.nih.gov/pubmed/34556256?tool=bestpractice.com
Imaging of the genitourinary tract may be helpful in the evaluation of a patient with CKD. A plain abdominal x-ray is a nonspecific test that may aid in the detection of calcium-containing kidney stones. Other radiologic tests, such as an abdominal computed tomography, are reserved for evaluation of stone disease and further characterization of renal cystic or mass lesions. Magnetic resonance imaging is reserved for renal mass lesions such as renal cell carcinoma.