The Influence of Indomethacin on Renal Haemodynamics in Sickle Cell Anaemia

Abstract

1. Glomerular filtration rate and effective renal blood-flow were normal in a series of patients with sickle cell anaemia. Fractional creatinine excretion and fractional urea excretion were increased.2. During indomethacin administration there were significant falls in glomerular filtration rate, effective renal blood-flow, creatinine clearance and urea clearance in the patients with sickle cell anaemia; fractional urea excretion also fell markedly. In control subjects none of these variables changed after indomethacin.3. Serum concentration of urea rose markedly during indomethacin administration in sickle cell anaemia, owing to both the decrease in glomerular filtration rate and the increase in fractional urea reabsorption. 4. We conclude that prostaglandins have an important role in maintaining a normal glomerular filtration rate and effective renal blood-flow in sickle cell anaemia. The abnormal urea handling in patients with this disease remains to be elucidated.

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

“…In addition, serum creatinine may be an inaccurate marker of GFR in SCD due to the relatively high proximal tubular secretion of creatinine found in this population [26]. Interestingly, a recent adult study showed that even in patients with a normal creatinine level during a pain crisis, acute tubular injury likely occurs, as evidenced by a more than twofold rise in urinary neutrophil gelatinase-associated lipoprotein excretion [27].…”

“…These effects are mediated in part through the local production of prostaglandins, which are increased due to medullary ischemia [28]. Studies in adult patients with SCD support a role for prostaglandins in maintaining a normal GFR, as treatment with indomethacin results in a significant decrease in GFR [26,29]. In addition, NSAID use is common in children with SCD [30], without evidence to support its benefit compared to other less nephrotoxic options [31].…”

Beta-2-Microglobulin in Sickle Cell Anaemia

“…Etteldorfet al [4] demonstrated an increased Tm for/t-aminohippurate in infants with SCA and recently we found an elevated fractional creatinine excretion [14]. In addition, Diamond et al [3] established an increased tubular secretion o f urate.…”

“…In contrast to the severe abnormalities in renal medul lary function, glomerular filtration rate (GFR) and efifective renal blood flow (ERBF) are normal or even super normal in sickle cell anaemia (SCA), especially in young children [4,10,14], Proximal tubular functions have also been found supernormal. Etteldorfet al [4] demonstrated an increased Tm for/t-aminohippurate in infants with SCA and recently we found an elevated fractional creatinine excretion [14].…”

Early and prominent alterations in hemodynamics, signaling, and gene expression following renal ischemia in sickle cell disease

“…Renal tubules showed no injury in WT and SCD mice. function, as creatinine is secreted in the urine in increased amounts in SCD (12). Since the present study was undertaken to address whether the vulnerability of the kidney in SCD appears promptly after ischemia, the study of renal hemodynamics affords an approach that is sufficiently sensitive to reliably detect differences in renal responses in wild-type and sickle mice.…”