Biomarkers of sickle cell nephropathy in Senegal

Abstract

Sickle cell anemia (SCA) is caused by a single point variation in the β-globin gene (HBB): c.20A> T (p.Glu7Val), in homozygous state. SCA is characterized by sickling of red blood cells in small blood vessels which leads to a range of multiorgan complications, including kidney dysfunction. This case-control study aims at identifying sickle cell nephropathy biomarkers in a group of patients living with SCA from Senegal. A total of 163 patients living with SCA and 177 ethnic matched controls were investigated. Biological phenotyping included evaluation of glycemia, glucosuria, albuminuria, proteinuria, tubular proteinuria, serum creatinine, urine creatinine, urine specific gravity and glomerular filtration rate. Descriptive statistics of biomarkers were performed using the χ2 –test, with the significance level set at p<0.05. Patients living with SCA had a median age of 20 years (range 4 to 57) with a female sex frequency of 53.21%. The median age of the control participants was 29 years (range: 4–77) with a female sex frequency of 66.09%. The following proportions of abnormal biological indices were observed in SCA patients versus (vs.) controls, as follows: hyposthenuria: 35.3%vs.5.2% (p<0.001); glomerular hyperfiltration: 47.66%vs.19.75% (p<0.001), renal insufficiency: 5.47%vs.3.82% (p = 0.182); microalbuminuria: 42.38%vs.5.78% (p<0.001); proteinuria: 39.33%vs.4.62% (p<0.001); tubular proteinuria: 40.97%vs.4.73% (p<0.001) and microglucosuria: 22.5%vs.5.1% (p<0.001). This study shows a relatively high proportion of SCA nephropathy among patients living with SCA in Senegal. Microglucosuria, proteinuria, tubular proteinuria, microalbuminuria, hyposthenuria and glomerular hyperfiltration are the most prevalent biomarkers of nephropathy in this group of Senegalese patients with SCA.

Performances of Proteinuria as Compared with Albuminuria in Screening for Microalbuminuria During Sickle Cell Anaemia

“…The prevalence of the pathological albuminuria found was 42.67% (Figure 1). Such non negligible prevalence was superimposable to the one described and already discussed in the Article [27]. Proteinuria, for its part, was determined by the pyrogallol redmolybdate method, a non-specific colorimetric method that measures all proteins present in urine, including albumin.…”

“…In view of these observations these two cut-offs which lead to exactly identical results would be more appropriate in sickle cell populations than the 150 mg/g cut-off proposed by KDIGO (Figure 3, Table 2) [12]. This reduction of the cut-off from 150 mg/g to 135 mg/g in the Senegalese sickle cell population could be explained by the fact that loss of urine concentration ability is very common in this group of patients [27]. This loss of urine concentration ability would result in the emission of diluted urine reducing the concentration of proteins in the urine leading in turn to a reduction in the UPCR cut-off.…”

“…By expressing this proteinuria in the form of UPCR, a pathological albuminuria prevalence of 43.33% superimposed on that determined by UACR was obtained with a UPCR threshold not of 150 mg/g as proposed by KDIGO, but rather with a threshold of 180 mg/g (Figure 1). This could be explained by the results of the study by Ndour and coworkers who found that the upper limit of the reference interval for proteinuria in a supposedly healthy Senegalese population should be 180 mg/g [27]. This threshold of 180 mg/g also appears to be the one adopted by Bökenkamp in his review of the literature [15].…”

“…This could be explained by a higher number of false positives if the UPCR threshold was set at these cut-offs values. The increase in the number of false positives could be explained not only by the low threshold values, but also probably by the high prevalence of proteinuria of tubular origin in the Senegalese sickle cell population described in the study by Ndour and coworkers [27]. Indeed, the tubular proteinuria is a proteinuria where albumin is in the minority as compared with proteins of low-molecular weight [15,28].…”

Looking ahead: ethical and social challenges of somatic gene therapy for sickle cell disease in Africa

“…While gene therapy has been presented as a potential one-time cure for SCD, there are risks related to gene silencing, gene toxicity, phototoxicity, uncertainties (even if transient) around germline transmission of DNA, and viral shedding. It is important to acknowledge the current lack of comprehensive information on long-term benefits, including clarity on whether gene therapy will prevent occurrences of chronic organ dysfunction and failure in SCD [ 47 ]. It is important to ensure that the optimism of scientists and clinicians do not influence the final decision of patients and that potential trial participants are clear about the potential benefits, risks and uncertainties of gene therapy.…”