Impaired creatinine secretion after an intravenous creatinine load is an early characteristic of the nephropathy of sickle cell anaemia

Abstract

Patients with SCA have impaired response to the TST before there are reductions in glomerular filtration. Therefore, a reduction in the tubular secretory reserve capacity represents an early event in the nephropathy of this condition.

Glomerular Hyperfiltration in Adult Sickle Cell Anemia

“…The prevalence of true glomerular hyperfiltration in patients with SS disease assessed by mGFR, using urinary 51 Cr EDTA renal clearance, has not been investigated to our knowledge, although a previous study performed in young men and women with SS disease (including some patients with CKD) has reported high mean mGFR values of 136 and 117 ml/min per 1.73 m 2 , respectively (13). Other studies support this finding using other mGFR methods, such as inulin (9) or iothalamate clearance (14). Our mGFR data from the subgroup of 48 patients validate the MDRD eGFR approach for the unbiased whole population (sensitivity 94%, specificity 63%, and predictive positive value 82%) because it gives a better estimate than Cockroft-Gault formula to assess hyperfiltration status, despite a systematic overestimation of GFR (see Table 3).…”

Acute kidney disease and renal recovery: consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup

“…Methods to assess glomerular functional reserve (for example, by assessing the effect of a protein load on GFR) or tubular functional reserve (for example, through furosemide stress testing or the administration of intravenous creatinine) have also been developed in the CKD setting but have yet to be applied to patients with AKD 67,68 . Interestingly, serum creatinine level has been the standard approach to the assessment of renal function for decades, but intravenously administered creatinine fails to increase GFR in humans, regardless of renal function 68 . Intravenous creatinine does, however, significantly increase creatinine clearance 68 , demonstrating that glomerular and tubular reserve do not necessarily correlate and suggesting that patients with CKD can maintain some preservation of glomerular renal reserve but fail to show any measurable tubular reserve [68][69][70][71] .…”

“…Interestingly, serum creatinine level has been the standard approach to the assessment of renal function for decades, but intravenously administered creatinine fails to increase GFR in humans, regardless of renal function 68 . Intravenous creatinine does, however, significantly increase creatinine clearance 68 , demonstrating that glomerular and tubular reserve do not necessarily correlate and suggesting that patients with CKD can maintain some preservation of glomerular renal reserve but fail to show any measurable tubular reserve [68][69][70][71] . On the basis of these findings, assessments of glomerular and tubular reserve are likely to assess different facets of kidney disease.…”

The five key things you need to know to manage adult patients with sickle cell disease

“…In addition to hyposthenuria increased renal tubular secretion of creatinine also starts in childhood. 24 Due to this, serum creatinine values in SCD do not rise until significant renal impairment occurs (GFR of 30 mL/min or less). 10 Relying on serum creatinine levels will lead providers to miss significant renal disease.…”

“…Along with the increased secretion of creatinine, patients with SCD will also hypersecrete uric acid. 24 The development of gout should therefore lead to a thorough investigation of renal function as it suggests that renal impairment is preventing the hypersecretion of uric acid and causing the increase in serum levels. In addition, this patient may be at greater risk for renal disease and gout because of his high red cell turnover as reflected by his high reticulocyte count.…”