Renal abnormalities in sickle cell disease

Abstract

Sickle cell anemia and the related hemoglobinopathies are associated with a large spectrum of renal abnormalities. The patients have impaired urinary concentrating ability, defects in urinary acidification and potassium excretion, and supranormal proximal tubular function. The latter is manifest by increased secretion of creatinine and by reabsorption of phosphorus and β2‐microglobulin. Young patients with sickle cell disease (SCD) have supranormal renal hemodynamics with elevations in both effective renal plasma flow (ERPF) and glomerular filtration rate (GFR). These parameters decrease with age as well as following the administration of prostaglandin inhibitors. Proteinuria, a common finding in adults with sickle cell disease, may progress to the nephrotic syndrome. Proteinuria, hypertension, and increasing anemia predict end‐stage renal disease (ESRD). While ESRD can be managed by dialysis and/or renal transplantation, there may be an increased rate of complications in renal transplant recipients with SCD. Hematuria is seen in individuals with all of the SCDs as well as with sickle cell trait. In most cases the etiology of the hematuria turns out to be benign. However, there does appear to be an increased association between SCD and renal medullary carcinoma. Therefore, those SCD patients who present with hematuria should initially undergo a thorough evaluation in order to exclude this aggressive neoplasm. Papillary necrosis may occur due to medullary ischemia and infarction. Erythropoietin levels are usually lower than expected for their degree of anemia and decrease further as renal function deteriorates. An abnormal balance of renal prostaglandins may be responsible for some of the changes in sickle cell nephropathy. Acute renal failure is a component of the acute multiorgan failure syndrome (MOFS). Finally, progression of sickle cell nephropathy to ESRD may be slowed by adequate control of hypertension and proteinuria. However, the prevention of the renal complications of SCD will require a cure for this genetic disorder. Am. J. Hematol. 63:205–211, 2000. © 2000 Wiley‐Liss, Inc.

Comparison of renal function markers in Kuwaiti patients with sickle cell disease

“…1-3 Abnormal proximal tubular function, partly related to chronic use of analgesics, results in increased clearance of creatinine and possibly other markers of GFR. [1][2][3] Young patients present with hyperfiltration, which declines towards adolescence and then declines with age. [1][2][3] Monitoring renal function in these patients with the ubiquitously used plasma creatinine and creatinine clearance may lead to late detection of deteriorating renal function.…”

“…[1][2][3] The main renal functional abnormalities in patients with SCD are alterations in the glomerular filtration rate (GFR) and proteinuria. [1][2][3] However, accurate and convenient assessment of GFR in patients with SCD has always been elusive.…”

“…Furthermore, as tubular secretion is the predominant mode of creatinine excretion when the GFR is less than 40 ml/min/1.73 m 2 , plasma creatinine results would not give an assessment of GFR in older patients with SCD who may have disordered metabolism and tubular dysfunction. [1][2][3][4][5] Although b 2 -microglobulin has been shown to be better than plasma creatinine estimation in patients with SCD, 4 the plasma concentration is affected by cellular proliferation. 6 7 Several low molecular weight proteins (ribonuclease, b 2microglobulin, retinol binding protein, free protein HC (a1microglobulin), and cystatin C) have been investigated for their value in detecting reduced GFR.…”

Sickle Cell Disease Complications

“…16 Microalbuminuria is most often the first manifestation of chronic kidney disease in SCD. Proteinuria due to glomerular injury is also common, but both microalbuminuria and macroalbuminuria are typically asymptomatic.…”

Managing sickle cell disease

“…Genitourinary problems are common in patients with sickle cell disease 18. The earliest lesion is hyposthenuria, which may become evident in childhood as enuresis and dehydration.…”