Homozygous sickle cell disease (HSCD) is a life-threatening and debilitating condition, with high mortality rates recorded even in affluent countries such as the USA, where the median survival of HSCD patients is 40–50 years [1]. In recent decades, a myriad of interventions such as a chronic transfusion programme, vaccination, antibiotic prophylaxis and early recognition of crises have played a key role in achieving these improved survival figures. Such interventions, often very costly, are mostly confined to richer nations with sophisticated healthcare systems. In Equatorial Africa, the bedrock of sickle cell disease in the world (Figure 1), the median survival is still very low. Accurate data are lacking but the majority of children born with HSCD in Sub-Saharan Africa are probably unlikely to see the end of the first decade of life [2]. Such abysmal mortality figures, completely in discord with improvements seen elsewhere, need to be brought to the public domain, backed by data from local studies in areas where the disease is endemic. Such studies will not only provide accurate data regarding the urgency to tackle this issue, but also guide locally relevant and adapted disease combat strategies, and may uncover local disease idiosyncrasies which may render ‘imported’ strategies relatively ineffective [3]. For instance, a well-conducted, bacteriological study in Uganda found Staphylococcus aureus (60%) to be the leading cause of bacterial infections in febrile children with sickle cell disease, not Streptococcus pneumoniae (19%), raising questions about the justification of routine pneumococcal vaccination in African sufferers [4]. In a large cohort followed up by Platt et al. [1], renal failure was the predominant organ failure, found in 40% of HSCD patients who died (7.6% of the overall study population). This suggests that interventions to identify, prevent and promptly treat renal involvement in HSCD will save many lives and help improve the dismal mortality figures seen with this condition. Renal abnormalities in HSCD have been previously well characterized, the primum movens being microvascular obstruction causing an ischaemic glomerular and/or tubular injury resulting in cortical infarction, papillary necrosis, focal segmental glomerulosclerosis, tubular atrophy and interstitial fibrosis in the main [5]. The main clinical syndromes associated with these include proteinuria (in approximately 20–30% of cases), haematuria, glomerular hyperfiltration, impaired concentration ability, renal tubular acidosis and chronic renal insufficiency [5]. Proteinuria, haematuria and severe anaemia have been shown to be the independent predictors of progression to chronic renal insufficiency [6]. As such, interventions to address these, such as the use of hydroxyurea, a proactive transfusion programme, and the routine use of ace inhibitors and angiotensin receptor blockers, are now standard practice in HSCD patients [7]. Such evidencebased interventions, however, do not seem to have achieved universal adoption, particularly in high prevalence areas such as Sub-Saharan African countries; if they have, the extent is unclear due to the paucity of studies. In this issue of CKJ, Kaze et al. [8] report the renal abnormalities found in a reasonably large cohort of Cameroonian children and adults homozygous for sickle cell disease. Various American and Caribbean studies have previously reported the predominant renal clinical findings in sickle cell disease to be albuminuria, proteinuria, glomerular hyperfiltration and reduced glomerular filtration rate (GFR), with the majority of such studies looking at a paediatric population [7, 9–11]. In Yaounde, Cameroon, an equatorial city where sickle cell disease is endemic, Kaze et al. recruited 72 treatment (ACE-I and hydroxyurea) naive HSCD adults and children and measured their renal function, blood pressure, urine protein, albumin and levels of red and white blood cells in the urine. It was staggering to find a 9 in 10 prevalence of overt proteinuria (protein–creatinine ratio >200 mg/g) in this cohort [8]. This indicates that almost all of these patients had some degree of renal damage requiring urgent intervention to prevent further nephron loss. Recently, Bolarinwa et al. reported a much lower prevalence of proteinuria (microalbuminuria and albuminuria) in a somewhat similar population from Western Nigeria [12]. This Cameroonian cohort clearly presents a much higher frequency of proteinuria than seen in other parts of the world. It will seem from this data that proactive routine ace inhibition is not yet the rule in the setting of this study, but whether this fully explains the finding remains to be seen. We look forward to data following therapeutic interventions, from the authors and other research groups in similar settings. Disease duration was found to be a key factor associated with proteinuria, as mean and median protein–creatinine ratios increased with increasing age quartile, and hence increasing the disease duration. Almost all of the patients had serum creatinine values within the normal range, translating into ‘normal’ GFRs
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Dec 9, 2015
Sarah Deyo + 2
Open Access
