Sickle Cell Information Center Guidelines

Edited by James Eckman, M.D. and Allan Platt, PA-C

Proteinuria is becoming a common finding in patients with sickle cell anemia, and results from damage to the glomerulus (sickle cell glomerulopathy). It may occur in up to 27% of adults with hemoglobin SS and in 5-8% of adults with other sickle hemoglobinopathies. Despite the paucity of associated clinical findings, it may herald the development of progressive renal insufficiency, and lead to end-stage renal disease and, therefore, should be thoroughly investigated

Present Illness. Proteinuria is usually asymptomatic, and detected at the time of a routine urinalysis. When severe (> 3.5 grams/day) it may be associated with peripheral edema, pleural effusions, and anasarca.

Past Medical History. Define history of hematuria, UTIs, use of potential nephrotoxic medications, past infections (hepatitis, HIV, etc.), comorbid conditions (hypertension, diabetes, congestive heart failure) and family history of renal disease

Review of symptoms. Note change in weight and general ROS to suggest systemic disease

• General. Degree of distress, weight change, hydration. periorbital swelling,
• Vital Signs. Temperature, Blood pressure, Pulse.

• Lungs - dullness and decreased breath sounds from effusions
• Abdomen. Costovertebral angle tenderness, masses, palpable kidneys, supra-pubic tenderness.
• Genitourinary. Vaginal bleeding, urethral irritation, bladder or pelvic masses, prostate enlargement or tenderness, rectal masses.
• Extremites - Pedal edema

- Minimum Evaluation. Proteinuria is detected on a urinalysis. If present a complete urinalysis with microscopic examination should be performed, and followed with a 24-hour urine collection to quantitate the degree of proteinuria and to measure renal function (creatinine clearance), along with a CBC and a Chem profile with electrolytes, BUN, Creat, uric acid, calcium, phos. AST, bilirubin, alk ptase, LDH. The extent of further evaluation is determined by the magnitude of the proteinuria and the presence of renal insufficiency.

Additional Studies: Serological test are performed to detect infections (hepatitis, HIV, etc.) autoimmune diseases, paraproteinemias, etc., which could cause glomerular involvement. A kidney ultrasound should be performed. Early nephrology referral for further evaluation and possible kidney biopsy should also be done

- Sickle cell glomerulopathy: It presents after > 10 years of disease (thus in the teenage years and in adults). It is asymptomatic in most cases and only detected at the time of a routine urinalysis. Typically, sickle cell glomerulopathy presents with non-nephrotic range proteinuria (usually 1-2 grams/day), but nephrotic syndrome (proteinuria >3.5 grams/day) may also occur. Urinalysis reveals proteinuria, but no hematuria or glucosuria, and the sediment is "bland" (no formed cells or cellular casts). Hypertension is not a common finding. Serological evaluation for autoimmune disease is normal or negative. Proteinuria is the earliest manifestation of sickle glomerulopathy and occurs before renal insufficiency (elevated serum creatinine or reduced creatinine clearance) is present. Serum creatinine is very insensitive in detecting renal insufficiency in patients with sickle cell anemia and should not be used to screen for renal involvement. Proteinuria is much more sensistive than abnormal serum creatinine levels to detect glomerular disease. When serum creatinine is elevated, the disease has reached an advanced stage and will lead to renal failure. In the early stages, proteinuria is associated with a normal serum creatinine and creatinine clearance, but after a period of time, renal insufficiency ensues, and may lead to renal failure, requiring dialysis. A kidney biopsy usually reveals focal, segmental glomerulosclerosis.

- Other glomerular diseases. Proteinuria is a non-specific manifestation of glomerular damage that occurs in a variety of kidney diseases. A nephrology evaluation is necessary to rule out these conditions such as diabetes mellitus, hypertensive nephrosclerosis, membranous nephropathy, and amyloidosis that cause a clinical presentation almost indistinguishable from sickle cell glomerulopathy. Glomerulonephritis may present with proteinuria. It is usually associated with hematuria and a cellular sediment. Chronic tubulointerstitial disease may also present with non-nephrotic proteinuria, and variable pyuria and microscopic hematuria.

Treatment

Once the diagnosis has been established, the treatment of sickle cell glomerulopathy should be aimed at preserving renal function and slowing down progression of renal disease. Short-term treatment with angiotensin converting enzyme inhibitors reduce proteinuria without worsening renal function, and may improve the long-term outcome. There are no long-term studies that establish the effectiveness of ACE inhibition in slowing progression of sickle cell glomerulopathy. ACE inhibitors should be used cautiously because they may cause hypotension, hyperkalemia and increased renal tubular acidosis. Hypertension should be aggressively treated. A low protein diet may reduce proteinuria and slow down progression. End-stage renal failure is treated with dialysis (hemodialysis or peritoneal dialysis). Sickle cell patients requiring dialysis should be considered for renal transplant.

The mainstem of prevention is to maintain an adequate hydration and urine output, specially those instances that seems to be induced by physical activity. Prompt treatment of urinary tract infection with adequate bacteriologic follow-up of cure is advocated. Early detection with 24 hour urine protein is important. Chronic transfusion or hydroxyurea therapy may also slow the progression of glomerular disease.

Patients should be taught the importance of regular check-ups for protein in the urine, the first sign of kidney involvement.

Allon M: Renal Abnormalities In Sickle Cell Disease. Arch Intern Med 150:501-504, 1990

Buckalew Vm, Jr., Someren A: Renal Manifestations Of Sickle Cell Disease. Arch Intern Med 133:660-669, 1974

Guasch A, Cua M, Mitch We: Extent And The Course Of Glomerular Injury In Patients With Sickle Cell Anemia. Kidney Int 49:786-791, 1996

Black Wd, Hatch Fe, Acchiardo S: Aminocaproic Acid In Prolonged Hematuria Of Patients With Sicklemia. Arch Intern Med 136:678-681, 1976

Zayas Cf, Platt J, Eckman Jr, Elsas L, Clark Ws, Mitch We, Guasch A: Prevalence And Predictors Of Glomerular Involvement In Sickle Cell Anemia. J Am Soc Nephrol 7:1401, 1996 (Abstract).

Falk Rj, Scheinman J, Phillips G, Orringer E, Johnson A, Jennette Jc: Prevalence And Pathologic Features Of Sickle Cell Nephropathy And Response To Inhibition Of Angiotensin-Converting Enzyme. N Engl J Med 326:910-915, 1992

Powars Dr, Elliott-Mills Dd, Chan L, Niland J, Hiti Al, Opas Lm, Johnson C: Chronic Renal Failure In Sickle Cell Disease: Risk Factors, Clinical Course, And Mortality. Ann Intern Med 115:614-620, 1991

Bakir Aa, Hathiwala Sc, Ainis H, Hryhorczuk Do, Rhee Hl, Levy Ps, Dunea G: Prognosis Of The Nephrotic Syndrome In Sickle Glomerulopathy. A Retrospective Study. Am J Nephrol 7:110-115, 1987

Send mail to aplatt@emory.edu with questions or comments about this web site.
Copyright © 1997 Sickle Cell Information Center
Last modified: October 08, 2000