History

Uremia can occur once the creatinine clearance is below 10-20 mL/min. Clinically, it is heralded by the onset of the following signs and symptoms:

Nausea
Vomiting
Fatigue
Anorexia
Weight loss
Muscle cramps
Pruritus
Mental status changes
Visual disturbances
Increased thirst

Patients may report nonspecific symptoms, which become chronic and progressive over time because of the gradual onset of the disease. Making the diagnosis of uremia may be difficult in young children because of the nonspecificity of clinical symptoms.

Metabolic abnormalities such as anemia, acidemia, and electrolyte abnormalities are prominent.

Patients with diabetes may appear to be in better glycemic control but may tend to have more hypoglycemic episodes as renal function declines. This paradoxical improvement in glycemic control results from increased insulin secretion and insulin half-life, both of which occur as renal function declines.

Cardiovascular system

Cardiovascular abnormalities such as hypertension, atherosclerosis, valvular stenosis and insufficiency, chronic heart failure, and angina accelerate as renal function declines. These abnormalities may contribute to clinical manifestations of uremia if not treated appropriately.

Gastrointestinal system

Occult GI bleeding may occur. Nausea and vomiting are common in patients with severe uremia. Uremic fetor (ammonia or urinelike odor to the breath) also may be present.

Neurologic system

Clinical manifestations of uremic encephalopathy include fatigue, muscle weakness, malaise, headache, restless legs, asterixis, polyneuritis, mental status changes, muscle cramps, seizures, stupor, and coma.^[25]Amyloid deposits may result in medial nerve neuropathy, carpal tunnel syndrome, or other nerve entrapment syndromes.

Cutaneous

Fluid retention, pruritus associated with calcium phosphate deposition, and nail atrophy are common in persons with uremia.

Physical Examination

Typical physical findings in persons with uremia are those associated with fluid retention, anemia, and acidemia. Severe malnutrition can contribute to muscle wasting, while electrolyte abnormalities may cause muscle cramping, cardiac arrhythmias, and mental status changes.

Skin

The classic skin finding in persons with uremia is uremic frost, which is a fine residue thought to consist of excreted urea left on the skin after evaporation of water. The skin may have a velvety appearance and feel, particularly in patients who are pigmented. Patients who are uremic also may have a sallow coloration of the skin due to urochrome, the pigment that gives urine its color. Patients may become hyperpigmented as uremia worsens (melanosis).

Eyes and mouth.

The sclera may become slightly icteric. Calcium deposition in the sclera can cause "red eye." In patients with chronic uremia, a broad range of oral lesions may be present, such as gingival hyperplasia, enamel hypoplasia, petechiae, or gingival bleeding.^[26]

Cardiovascular system

Uremic pericarditis can be associated with a pericardial rub or a pericardial effusion. Increased fluid retention may result in pulmonary edema, peripheral edema, and severe hypertension. Valvular calcification may cause aortic stenosis or accelerate underlying disease.

Lungs

Fluid retention may result in pulmonary edema and corresponding crackles in the lungs. Pleural rubs occur in the setting of uremic lungs.

Differential Diagnoses

Zemaitis MR, Foris LA, Katta S, Bashir K. Uremia. 2021 Jan. [QxMD MEDLINE Link]. [Full Text].
Raghavan R, Eknoyan G. Uremia: A historical reappraisal of what happened . Clin Nephrol. 2018 May. 89 (5):305-313. [QxMD MEDLINE Link].
Piorry PA, l'Heritier D. Traite des Alterations du Sang. Paris, France: Bury & JB Bailliere; 1840.
Lau WL, Vaziri ND. Urea, a true uremic toxin: the empire strikes back. Clin Sci (Lond). 2017 Jan 1. 131 (1):3-12. [QxMD MEDLINE Link]. [Full Text].
Yavuz A, Tetta C, Ersoy FF, D'intini V, Ratanarat R, De Cal M, et al. Uremic toxins: a new focus on an old subject. Semin Dial. 2005 May-Jun. 18(3):203-11. [QxMD MEDLINE Link].
Cohen G, Vanholder R. Special Issue: Immune Dysfunction in Uremia. Toxins (Basel). 2021 Jan 19. 13 (1):[QxMD MEDLINE Link]. [Full Text].
Meyer TW, Hostetter TH. The Pathophysiology of Uremia. Brenner BM, ed. Brenner & Rector's The Kidney. 10th ed. Philadelphia, PA: Elsevier; 2016. Vol 2: 1807-21.
Carrero JJ, Witasp A, Stenvinkel P, et al. Visfatin is increased in chronic kidney disease patients with poor appetite and correlates negatively with fasting serum amino acids and triglyceride levels. Nephrol Dial Transplant. 2010 Mar. 25(3):901-6. [QxMD MEDLINE Link].
Almoznino-Sarafian D, Shteinshnaider M, Tzur I, et al. Anemia in diabetic patients at an internal medicine ward: Clinical correlates and prognostic significance. Eur J Intern Med. 2010 Apr. 21(2):91-96. [QxMD MEDLINE Link].
Camaschella C. Iron and hepcidin: a story of recycling and balance. Hematology Am Soc Hematol Educ Program. 2013. 2013:1-8. [QxMD MEDLINE Link]. [Full Text].
Ganz T. Hepcidin and iron regulation, 10 years later. Blood. 2011 Apr 28. 117(17):4425-33. [QxMD MEDLINE Link]. [Full Text].
Schlieper G, Aretz A, Verberckmoes SC, et al. Ultrastructural Analysis of Vascular Calcifications in Uremia. J Am Soc Nephrol. 2010 Mar 4. [QxMD MEDLINE Link]. [Full Text].
Teng M, Wolf M, Lowrie E, Ofsthun N, Lazarus JM, Thadhani R. Survival of patients undergoing hemodialysis with paricalcitol or calcitriol therapy. N Engl J Med. 2003 Jul 31. 349(5):446-56. [QxMD MEDLINE Link].
Sprague SM, Llach F, Amdahl M, Taccetta C, Batlle D. Paricalcitol versus calcitriol in the treatment of secondary hyperparathyroidism. Kidney Int. 2003 Apr. 63(4):1483-90. [QxMD MEDLINE Link].
Fishbane S, Shapiro WB, Corry DB, Vicks SL, Roppolo M, Rappaport K, et al. Cinacalcet HCl and concurrent low-dose vitamin D improves treatment of secondary hyperparathyroidism in dialysis patients compared with vitamin D alone: the ACHIEVE study results. Clin J Am Soc Nephrol. 2008 Nov. 3(6):1718-25. [QxMD MEDLINE Link]. [Full Text].
Cunningham J, Danese M, Olson K, Klassen P, Chertow GM. Effects of the calcimimetic cinacalcet HCl on cardiovascular disease, fracture, and health-related quality of life in secondary hyperparathyroidism. Kidney Int. 2005 Oct. 68(4):1793-800. [QxMD MEDLINE Link].
Restrepo D, Vaduganathan M, Fenves AZ. Uremic Pericarditis: Distinguishing Features in a Now-Uncommon Clinical Syndrome. South Med J. 2018 Dec. 111 (12):754-757. [QxMD MEDLINE Link].
El-Agroudy AE, El-Baz A. Soluble Fas: a useful marker of inflammation and cardiovascular diseases in uremic patients. Clin Exp Nephrol. 2010 Jan 26. [QxMD MEDLINE Link].
Fort J. Chronic renal failure: a cardiovascular risk factor. Kidney Int Suppl. 2005 Dec. 99:S25-9. [QxMD MEDLINE Link].
Chang CT, Shen MY, Hsieh JY, Chang CM, Liao HY, Chen FY, et al. Increased electronegativity of high-density lipoprotein in uremia patients impairs its functional properties and is associated with the risk of coronary artery disease. Atherosclerosis. 2018 Nov. 278:147-155. [QxMD MEDLINE Link].
Muscaritoli M, Molfino A, Bollea MR, et al. Malnutrition and wasting in renal disease. Curr Opin Clin Nutr Metab Care. 2009 Jul. 12(4):378-83. [QxMD MEDLINE Link].
Scherer A, Günther OP, Balshaw RF, Hollander Z, Wilson-McManus J, Ng R, et al. Alteration of human blood cell transcriptome in uremia. BMC Med Genomics. 2013 Jun 28. 6:23. [QxMD MEDLINE Link]. [Full Text].
Santos AH Jr, Casey MJ, Wen X, Zendejas I, Faldu C, Rehman S, et al. Outcome of kidney transplants for adults with hemolytic uremic syndrome in the U.S.: a ten-year database analysis. Ann Transplant. 2014 Jul 21. 19:353-61. [QxMD MEDLINE Link].
Tonelli M, Karumanchi SA, Thadhani R. Epidemiology and Mechanisms of Uremia-Related Cardiovascular Disease. Circulation. 2016 Feb 2. 133 (5):518-36. [QxMD MEDLINE Link].
Rosner MH, Husain-Syed F, Reis T, Ronco C, Vanholder R. Uremic encephalopathy. Kidney Int. 2021 Nov 1. [QxMD MEDLINE Link].
Dioguardi M, Caloro GA, Troiano G, Giannatempo G, Laino L, Petruzzi M, et al. Oral manifestations in chronic uremia patients. Ren Fail. 2016 Feb. 38 (1):1-6. [QxMD MEDLINE Link].
GFR Calculator. National Kidney Foundation. Available at https://www.kidney.org/professionals/kdoqi/gfr_calculator. Accessed: May 27, 2020.
Dobre M, Meyer TW, Hostetter TH. Searching for uremic toxins. Clin J Am Soc Nephrol. 2013 Feb. 8 (2):322-7. [QxMD MEDLINE Link]. [Full Text].
Shirazian S, Aina O, Park Y, Chowdhury N, Leger K, Hou L, et al. Chronic kidney disease-associated pruritus: impact on quality of life and current management challenges. Int J Nephrol Renovasc Dis. 2017. 10:11-26. [QxMD MEDLINE Link]. [Full Text].
Mettang T, Kremer AE. Uremic pruritus. Kidney Int. 2015 Apr. 87 (4):685-91. [QxMD MEDLINE Link].
Chuang YW, Shu KH, Yu TM, et al. Hypokalaemia: an independent risk factor of Enterobacteriaceae peritonitis in CAPD patients. Nephrol Dial Transplant. 2009 May. 24(5):1603-8. [QxMD MEDLINE Link].
Seyffart G, Schulz T, Stiller S. Use of two calcium concentrations in hemodialysis--report of a 20-year clinical experience. Clin Nephrol. 2009 Mar. 71(3):296-305. [QxMD MEDLINE Link].
Cozzolino M, Ronco C. Medium Cut-Off Membranes: Incremental or Quantum Leap Innovation in Haemodialysis?. Blood Purif. 2021. 50 (4-5):449-452. [QxMD MEDLINE Link]. [Full Text].
Catar R, Moll G, Kamhieh-Milz J, Luecht C, Chen L, Zhao H, et al. Expanded Hemodialysis Therapy Ameliorates Uremia-Induced Systemic Microinflammation and Endothelial Dysfunction by Modulating VEGF, TNF-α and AP-1 Signaling. Front Immunol. 2021. 12:774052. [QxMD MEDLINE Link]. [Full Text].
FDA Drug Safety Communication: Modified dosing recommendations to improve the safe use of Erythropoiesis-Stimulating Agents (ESAs) in chronic kidney disease. Available at http://www.fda.gov/Drugs/DrugSafety/ucm259639.htm. June 24, 2011; Accessed: December 6, 2018.
[Guideline] K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis. 2003 Oct. 42(4 Suppl 3):S1-201. [QxMD MEDLINE Link]. [Full Text].
KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl. 2009 Aug. S1-130. [QxMD MEDLINE Link].
Sumida K, Lau WL, Kovesdy CP, Kalantar-Zadeh K, Kalantar-Zadeh K. Microbiome modulation as a novel therapeutic approach in chronic kidney disease. Curr Opin Nephrol Hypertens. 2021 Jan. 30 (1):75-84. [QxMD MEDLINE Link].
Fouque D, Laville M. Low protein diets for chronic kidney disease in non diabetic adults. Cochrane Database Syst Rev. 2009 Jul 8. CD001892. [QxMD MEDLINE Link].
Peterson JC, Adler S, Burkart JM, Greene T, Hebert LA, Hunsicker LG, et al. Blood pressure control, proteinuria, and the progression of renal disease. The Modification of Diet in Renal Disease Study. Ann Intern Med. 1995 Nov 15. 123 (10):754-62. [QxMD MEDLINE Link].
Fakhouri F, Roumenina L, Provot F, et al. Pregnancy-Associated Hemolytic Uremic Syndrome Revisited in the Era of Complement Gene Mutations. J Am Soc Nephrol. 2010 Mar 4. [QxMD MEDLINE Link].

Media Gallery

of 0

Author

A Brent Alper, Jr, MD, MPH Associate Professor of Medicine, Section of Nephrology and Hypertension, Department of Medicine, Tulane University School of Medicine

A Brent Alper, Jr, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society of Hypertension, American Society of Nephrology, National Kidney Foundation, Phi Beta Kappa

Disclosure: Nothing to disclose.

Coauthor(s)

Rajesh G Shenava, MD, FASN Former Assistant Professor of Medicine, Section of Nephrology and Hypertension, Department of Internal Medicine, Louisiana State University School of Medicine in New Orleans

Rajesh G Shenava, MD, FASN is a member of the following medical societies: American College of Physicians, American Society of Nephrology, National Kidney Foundation, Renal Physicians Association

Disclosure: Nothing to disclose.

Bessie A Young, MD, MPH Associate Professor of Medicine, Division of Nephrology, University of Washington School of Medicine; Core Investigator, Seattle Epidemiologic Research and Information Center

Bessie A Young, MD, MPH is a member of the following medical societies: American College of Physicians, American Diabetes Association, International Society of Nephrology, National Kidney Foundation, American Society of Nephrology

Disclosure: Nothing to disclose.

Chief Editor

Vecihi Batuman, MD, FASN Professor of Medicine, Section of Nephrology-Hypertension, Deming Department of Medicine, Tulane University School of Medicine

Vecihi Batuman, MD, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Acknowledgements

Eleanor Lederer, MD Professor of Medicine, Chief, Nephrology Division, Director, Nephrology Training Program, Director, Metabolic Stone Clinic, Kidney Disease Program, University of Louisville School of Medicine; Consulting Staff, Louisville Veterans Affairs Hospital

Eleanor Lederer, MD is a member of the following medical societies: American Association for the Advancement of Science, American Federation for Medical Research, American Society for Biochemistry and Molecular Biology, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, International Society of Nephrology, Kentucky Medical Association, National Kidney Foundation, and Phi Beta Kappa

Disclosure: Dept of Veterans Affairs Grant/research funds Research

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment