Uric Acid Nephropathy Treatment & Management

  • Author: Mark T Fahlen, MD; Chief Editor: Vecihi Batuman, MD, FACP, FASN   more...
 
Updated: Sep 21, 2011
 

Medical Care

  • Acute uric acid nephropathy
    • Prior to the dialysis era, treatment of acute uric acid nephropathy was not very successful, with mortality rates approaching 50%. As a result of the use of modern treatment, including prophylaxis and dialysis, uric acid nephropathy has become rare. Additionally, when it does occur, the prognosis for the acute renal failure is excellent. Management without dialysis involves attempts to lower the plasma urate level and the urate concentration within the renal tubules.
    • The xanthine oxidase inhibitor allopurinol has been a milestone in the prevention of acute uric acid nephropathy.[1] It blocks the conversion of hypoxanthine and xanthine to uric acid, resulting in a reduction in serum uric acid concentration and in urinary excretion of urates.[10] However, urinary excretion of hypoxanthine and xanthine increases. Hypoxanthine is highly soluble and does not cause clinical problems. Xanthine is less soluble than uric acid, and precipitated xanthine can be found in the urine of persons taking allopurinol. However, these precipitates do not correlate with renal failure, although well-documented cases of xanthine nephropathy do exist.
    • Allopurinol has been used extensively in the prevention of acute uric acid nephropathy in patients with malignancy who are undergoing chemotherapy, and considerable experience has been gained in patients with leukemia and lymphoma. The half-life of allopurinol is less than 2 hours, due to renal excretion and to the compound's rapid conversion to its chief metabolite, oxypurinol. Oxypurinol is an active metabolite, and it reduces serum uric acid concentration and urinary uric acid secretion half as much as does allopurinol. Oxypurinol is eliminated solely by the kidney, with a half-life of approximately 24 hours. Its clearance correlates directly with creatinine clearance. Because allopurinol has a short half-life, its clinical effects are probably mediated by oxypurinol.
    • For optimal prophylaxis of acute uric acid nephropathy, allopurinol should be administered at 48-72 hours or, preferably, 5 days before the initiation of cancer therapy. Uric acid nephropathy is relatively rare if this is accomplished.
    • The level of existing renal function must be considered when dosing the drug. In some instances, hyperuricemia and acute uric acid nephropathy cannot be avoided because of a large tumor burden, aggressive chemotherapy, and the inability to delay chemotherapy until allopurinol has lowered the serum uric acid concentration.
    • Allopurinol can lead to a life-threatening toxicity syndrome that is characterized by a diffuse desquamative skin rash, fever, hepatic dysfunction, eosinophilia, and worsening renal function of unknown etiology.[14] Eighty percent of patients reported to have this syndrome have preexisting renal insufficiency.
    • In patients with healthy renal function, a starting dose of 300-600 mg of allopurinol daily is safe and achieves a therapeutic level of oxypurinol (a serum concentration of 30-100 µmol/L).
    • Patients with end-stage renal disease achieve therapeutic levels after a single 300- to 600-mg dose and maintain this level until the next dialysis, at which time the serum level will be reduced by 40%. Therefore, the maintenance dose must be reduced in patients with renal insufficiency to avoid accumulation of oxypurinol.
    • If the creatinine clearance is approximately 50-90 mL/min, the dose should be 200 mg/d, and for a creatinine clearance of 10-50 mL/min, the dose should be 100 mg every 2 days. In patients with a creatinine clearance of less than 10 mL/min, the dose should be 100 mg every 3 days.
    • After hemodialysis, the patient should be supplemented with 50% of the allopurinol dose.
    • In pediatric patients older than 6 years, 300 mg of allopurinol daily is the usual dose. The dose is reduced to 150 mg/d in patients younger than 6 years.
    • No adequate or well-controlled studies have been performed on the drug's effect on fetuses.
    • In addition to the use of a xanthine oxidase inhibitor to prevent hyperuricemia, high tubular flow rates induced by large-volume fluid intake and solute and water diuresis also have a role in protecting the kidney from developing high, precipitate-generating concentrations of urate. Patients should be hydrated with 4-5 L of normal saline every 24 hours. If the patient is well hydrated and not maintaining the expected urine output, diuretics should be initiated. If the urine output remains low, adjust the fluid intake to match the output in order to avoid fluid overload.
    • Although evidence confirming its role is lacking, urinary alkalinization should, theoretically, increase uric acid solubility. In animal studies, high tubular flow rates were the most important factor in preventing uric acid and urate crystallization, with urinary alkalinization playing only a minor role. The agent used was acetazolamide, and its protection also may have resulted from its diuretic effect. Sodium bicarbonate administration carries the inherent risks of severe metabolic alkalosis, symptomatic hypocalcemia, and calcium phosphate precipitation, which, in itself, can cause acute renal failure. Therefore, bicarbonate therapy should be included in the prophylactic regimen only when an attempt is being made to correct hyperuricemia. If hyperuricemia is present prior to chemotherapy, bicarbonate should be added to intravenous fluids, with the goal of maintaining the urinary pH above 7.0. Once hyperuricemia has been corrected, bicarbonate therapy should be discontinued.
    • Occasionally, despite the use of allopurinol, diuretics, and urine alkalinization, patients progress to acute kidney failure. Dialysis assists in the management of acute uric acid nephropathy in 2 ways. First, it protects patients from the complications of kidney failure (eg, hyperkalemia, fluid overload, uremia). Cases of fatal hyperkalemia have been reported within hours of initiation of chemotherapy. Secondly, dialysis is an effective way to reduce the serum uric acid level. This is important, because patients with uric acid nephropathy do not recover until their serum uric acid level is reduced. In this regard, hemodialysis is superior to peritoneal dialysis, because hemodialysis has much higher uric acid clearance (approximately 90-150 mL/min, compared with 10-20 mL/min for peritoneal dialysis).
    • Once the serum uric acid level is reduced, usually after 1-4 dialysis sessions, recovery of kidney function is signaled by a brisk diuresis. As a rule, the plasma urate level is reduced by 50% for each 4- to 6-hour dialysis session.
    • Rasburicase (Elitek) is a drug that has been approved by the US Food and Drug Administration (FDA) for the treatment of tumor lysis syndrome in the pediatric population only,[10, 15, 16] although it is used in Europe for the adult and geriatric populations and is even considered the standard of care at some centers there. Rasburicase is a recombinant urate oxidase enzyme that converts uric acid into allantoin. In theory, this has the added benefit of converting existing uric acid into a nonnephrotoxic metabolite, in contrast with allopurinol, which prevents future formation of uric acid.
      • Rasburicase is a costly medication, and judicious use is recommended, because there is no evidence that it is superior to standard therapy with allopurinol and bicarbonate.
      • The FDA-recommended dosing guidelines for pediatric patients are 0.15 mg/kg or 0.2 mg/kg IV daily for a maximum of 5 days. Adverse effects include rash, hemolysis, and methehemoglobinemia; in various clinical trials, these occurred in less than 1% of patients.
  • Chronic urate nephropathy
    • Because of the lack of evidence that hyperuricemia in itself causes chronic nephropathy (except in cases of the above-mentioned rare enzyme deficiencies), the current trend is to not treat hyperuricemia for the prevention of chronic nephropathy alone, although this topic remains under active study and debate.
    • The significant toxicity of allopurinol and the lifelong expense of using it make this therapy unwarranted. The emphasis should be on controlling other risk factors for kidney failure, such as diabetes and hypertension.
  • Uric acid nephrolithiasis
    • The goals of uric acid nephrolithiasis therapy are to reduce the existing stone size and to prevent the formation of new stones. These objectives are achieved by decreasing the production of uric acid and increasing its solubility.
    • Curtailing dietary purine, chiefly in the form of animal protein, can substantially decrease uric acid production. Increasing fluid intake to maintain a urine output of 2-3 L/d can be achieved with minimal inconvenience. Ingestion of alkali in the form of bicarbonate or citrate at a dose of 0.5-1.5 mEq/kg/d, with the goal of a urinary pH of 6.0-6.5, can be effective. If the nocturnal urinary pH falls, a single dose of 250 mg oral acetazolamide at bedtime is usually effective in maintaining alkaline urine.
    • Allopurinol should be used if stones recur despite the above therapies, when the urinary uric acid excretion is greater than 1000 mg/d, or if the patient has gout. Allopurinol is also indicated for dissolving or reducing the size of existing stones and when large, nonobstructing renal pelvic stones are too large to pass.
    • Extracorporeal shock wave lithotripsy can be tried for problem calculi, but the procedure is less effective for uric acid stones than for other types of stones.
Proceed to Medication
 
 
Contributor Information and Disclosures
Author

Mark T Fahlen, MD  Inc

Mark T Fahlen, MD is a member of the following medical societies: American College of Physicians and Renal Physicians Association

Disclosure: Nothing to disclose.

Coauthor(s)

Mahendra Agraharkar, MD, MBBS, FACP, FASN  Clinical Associate Professor of Medicine, Baylor College of Medicine; President and CEO, Space City Associates of Nephrology

Mahendra Agraharkar, MD, MBBS, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Nephrology, and National Kidney Foundation

Disclosure: South Shore DaVita Dialysis Center Ownership interest Other

Specialty Editor Board

Frank C Brosius III, MD  Nephrology Program Director, Professor of Internal Medicine and Physiology, Department of Internal Medicine, Division of Nephrology, University of Michigan School of Medicine

Frank C Brosius III, MD is a member of the following medical societies: Alpha Omega Alpha, American Diabetes Association, American Society of Nephrology, and Phi Beta Kappa

Disclosure: Nothing to disclose.

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

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

Rebecca J Schmidt, DO, FACP, FASN  Professor of Medicine, Section Chief, Department of Medicine, Section of Nephrology, West Virginia University School of Medicine

Rebecca J Schmidt, DO, FACP, FASN is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Nephrology, International Society of Nephrology, National Kidney Foundation, Renal Physicians Association, and West Virginia State Medical Association

Disclosure: Renal Ventures Ownership interest Other

Chief Editor

Vecihi Batuman, MD, FACP, FASN  Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Medicine Service, Southeast Louisiana Veterans Health Care System

Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, and International Society of Nephrology

Disclosure: Nothing to disclose.

References

  1. Conger JD. Acute uric acid nephropathy. Med Clin North Am. Jul 1990;74(4):859-71. [Medline].

  2. Guest SS. Uric acid and the kidney. In: Nephrology Rounds 4. Snell Medical Communications; 2001:1-5.

  3. Dykman D, Simon EE. Hyperuricemia and uric acid nephropathy. Arch Intern Med. Jul 1987;147(7):1341-5. [Medline].

  4. Nickeleit V, Mihatsch MJ. Uric acid nephropathy and end-stage renal disease--review of a non-disease. Nephrol Dial Transplant. Sep 1997;12(9):1832-8. [Medline]. [Full Text].

  5. Mene P, Punzo G. Uric acid: bystander or culprit in hypertension and progressive renal disease?. J Hypertens. Nov 2008;26(11):2085-92. [Medline].

  6. Avram Z, Krishnan E. Hyperuricaemia--where nephrology meets rheumatology. Rheumatology (Oxford). Jul 2008;47(7):960-4. [Medline].

  7. Iseki K, Ikemiya Y, Inoue T, et al. Significance of hyperuricemia as a risk factor for developing ESRD in a screened cohort. Am J Kidney Dis. Oct 2004;44(4):642-50. [Medline].

  8. Edwards NL. The role of hyperuricemia and gout in kidney and cardiovascular disease. Cleve Clin J Med. Jul 2008;75 Suppl 5:S13-6. [Medline]. [Full Text].

  9. Johnson RJ, Segal MS, Srinivas T, et al. Essential hypertension, progressive renal disease, and uric acid: a pathogenetic link?. J Am Soc Nephrol. Jul 2005;16(7):1909-19. [Medline]. [Full Text].

  10. Pea F. Pharmacology of drugs for hyperuricemia. Mechanisms, kinetics and interactions. Contrib Nephrol. 2005;147:35-46. [Medline].

  11. Lin JL, Yu CC, Lin-Tan DT, et al. Lead chelation therapy and urate excretion in patients with chronic renal diseases and gout. Kidney Int. Jul 2001;60(1):266-71. [Medline]. [Full Text].

  12. Bainbridge SA, Deng JS, Roberts JM. Increased xanthine oxidase in the skin of preeclamptic women. Reprod Sci. Feb 5 2009;[Medline].

  13. Mukherjee E, Mukherji D, Jayawardene SA, et al. Tumor lysis syndrome and acute renal failure--an increasing spectrum of presentations. Clin Nephrol. Sep 2007;68(3):186-9. [Medline].

  14. Fagugli RM, Gentile G, Ferrara G, et al. Acute renal and hepatic failure associated with allopurinol treatment. Clin Nephrol. Dec 2008;70(6):523-6. [Medline].

  15. Ueng S. Rasburicase (Elitek): a novel agent for tumor lysis syndrome. Proc (Bayl Univ Med Cent). Jul 2005;18(3):275-9. [Medline]. [Full Text].

  16. Hochberg J, Cairo MS. Rasburicase: future directions in tumor lysis management. Expert Opin Biol Ther. Oct 2008;8(10):1595-604. [Medline].

  17. Feig DI, Kang DH, Johnson RJ. Uric acid and cardiovascular risk. N Engl J Med. Oct 23 2008;359(17):1811-21. [Medline].

 
Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.