Glomerular Involvement in Adults with Sickle Cell Hemoglobinopathies

Abstract

Patients with sickle cell anemia (SCA) may develop a glomerulopathy with proteinuria and progressive renal insufficiency, leading to ESRD. Albuminuria is a sensitive marker of glomerular damage in this population and precedes the development of renal insufficiency. For determination of the prevalence of glomerular damage in SCA and the clinical correlates of renal insufficiency, 300 adult patients with SCA were studied (hemoglobin SS ‫؍‬ 184; and 116 with other sickling hemoglobinopathies: SC, SD, and S-␤ thalassemia); albumin excretion rates (AER) and renal function (Cockroft-Gault formula) were determined, and clinical and hematologic evaluations were conducted. In hemoglobin SS disease, increased AER (micro-and macroalbuminuria) occurred in 68% of adult patients, and macroalbuminuria occurred in 26%. In other sickling disorders, increased AER occurs in 32% of adults, and macroalbuminuria occurs in 10%. The development of graded albuminuria was age dependent, so at 40 yr, 40% of patients with SS disease had macroalbuminuria. There were no differences in hematologic parameters (hemoglobin levels, white blood cell count, percentage of reticulocytes, platelet counts, or lactate dehydrogenase levels) between patients with normoalbuminuria and those with micro-or macroalbuminuria. By multivariate analysis, albuminuria correlated with age and serum creatinine in SS disease but not with BP or hemoglobin levels. In other sickling disorders, albuminuria tended to be associated with age but not with hemoglobin or BP levels. The diastolic BP was lower in patients with SCA than in African American control subjects, and the development of renal insufficiency, which was present in 21% of adults with SS disease, was not accompanied by significant hypertension. It is concluded that glomerular damage in adults with SCA is very common, and a majority of patients with SS disease are at risk for the development of progressive renal failure. The development of micro-and macroalbuminuria is not related to the degree of anemia, suggesting that sickle cell glomerulopathy is not solely related to hemodynamic adaptations to chronic anemia. In contrast to other glomerulopathies, the development of systemic hypertension is uncommon in SS disease with renal insufficiency.

Acute kidney injury in children with sickle cell disease—compounding a chronic problem

“…The endpoint of this hyperfiltration is glomerular scarring with progressive loss of renal function. Glomerular injury is evident in adults with SCD, with up to 50% of this patient group showing evidence of hyperfiltration and 21-27% having CKD, defined as an estimated glomerular filtration rate (eGFR) of <90 mL/min/ 1.73 m 2 [9][10][11][12]. The prevalence of end-stage renal disease (ESRD) in the adult SCD population has been estimated to be between 4 and 12%, with a mean time to ESRD of 37 years [12,13].…”

Estimated glomerular filtration rate in sickle cell anemia is associated with polymorphisms of bone morphogenetic protein receptor 1B

“…For patients under 12 years of age, we used the Schwartz formula [23], which does not take weight into account in its estimation. These formulae for GFR were used because excessive and wide-ranging results were obtained in children and adults using the Modification of Diet in Renal Disease study formula, which lacks a weight term, was designed for creatinines from 1.2 to 7.0 mg/dl, and has never been validated in a sickle cell population [24,25].…”

Genetic variants and cell-free hemoglobin processing in sickle cell nephropathy

“…19 Markers of hemolysis have been associated with kidney disease in some [26][27][28][29][30] but not all [31][32][33] SCD cohorts. Hemoglobinuria, determined by urine dipstick analysis, has been observed in 15-42% of adults with SCD, [34][35][36] and is associated with elevated markers of hemolysis and risk of CKD progression.…”