Sickle Cell Nephropathy and Associated Factors among Asymptomatic Children with Sickle Cell Anaemia

Abstract

Background. Sickle cell nephropathy (SCN) is a serious complication of sickle cell anaemia (SCA) with asymptomatic onset in childhood and possible progression to chronic kidney disease (CKD). In Southeast Nigeria, few studies have evaluated renal function in paediatric SCA patients for early detection of renal impairment and early intervention to reduce morbidity and mortality. Therefore, this study evaluated the renal function of paediatric SCA patients in a steady state based on glomerular filtration rate and urinalysis findings (proteinuria and haematuria). Methods. A cross-sectional study of consecutively recruited sixty haemoglobin SS (HbSS) children in a steady state and sixty age- and sex-matched haemoglobin AA (HbAA) controls aged 2–18 years was done. Renal function of HbSS subjects was evaluated using estimated glomerular filtration rate (eGFR) which was compared with healthy HbAA subjects. The prevalence of significant proteinuria and haematuria, its association with eGFR, and the effect of past sickle cell crisis (in the preceding 24 months) on renal function were also evaluated. Results. Mean eGFR was significantly higher in HbSS subjects than in the HbAA subjects (p=0.001) and decreased with age. Significant proteinuria and haematuria were more prevalent in the HbSS group (3.4% and 6.7%, respectively) compared to the HbAA subjects (0% and 0%, respectively) (p=0.496 and 0.119, respectively). No significant association was observed between eGFR and proteinuria (p=1.000) or haematuria (p=1.000). There was a positive correlation between eGFR and frequency of past painful crisis that required hospitalization (r=0.138, p=0.295) and between eGFR and frequency of blood transfusion (r=0.679, p≤0.001). Conclusions. Asymptomatic paediatric HbSS (SCA) patients had higher mean eGFR indicating an increased risk of nephropathy. There was no association between eGFR and proteinuria or haematuria. Frequent sickle cell crises especially one requiring transfusion were positively correlated with hyperfiltration.

From kidney injury to kidney cancer

“…153 Sickle cell disease-related kidney cancer is a paradigmatic example of how repetitive ischemic kidney injury can cause kidney cancer in the injured area of the kidney. [52][53][54] Epidemiologic and experimental studies now demonstrate the same for a wider r e v i e w AJ Peired et al: Kidney injury and cancer range of kidney cancers, and suggest a putative premalignant condition, just about the time new strategies for kidney cancer screening are debated. 154 But why do we observe a relatively low RCC prevalence despite the high prevalence of CKD/AKI patients?…”

“…The link between these 2 conditions is represented by the metabolic overload of the cells of proximal tubule in remnant nephrons experiencing a drastically increased single-nephron hyperfiltration (and tubular hyperreabsorption). 47 This drives chronic cortical damage and CKD in patients with obesity and diabetes, with possible subsequent development of ccRCC, which typically originates from cells of the cortical proximal tubule (S1/S2 segment) 47 (Figure 1 25,[44][45][46][48][49][50][51][52][53][54][55][56][57] ).…”

“…This affects collecting duct cells, driving the development of medullary carcinoma. [51][52][53][54] 81 even after adjustment for all potentially confounding factors. This supports the hypothesis that the typical renal cystic changes in patients with ADPKD, and particularly cluster-like papillary hyperplasia, may represent precancerous lesions that can evolve in RCC, usually of the papillary histotype.…”

“…Hypoxia and hyperosmolarity of the inner medulla, along with ischemia induced by red blood cell sickling, injure the vascular architecture. This affects collecting duct cells, driving the development of medullary carcinoma [51][52][53][54]. chRCC, chromophobe renal cell carcinoma; pRCC, papillary renal cell carcinoma; OSOM, outer stripe of outer medulla; SCA, sickle cell anemia.…”

Glomerular hyperfiltration in Yemeni children with sickle cell disease

“…Other few previous studies reported on the relationship between some SCD related complications and GFR, and found GFR did not relate with ACS and stroke [10]. One study reported a positive correlation between eGFR and frequency of blood transfusions [30], but other researchers found no difference between patients with and without hyper iltration [14]. Absence of such correlation was assumed to be resulted from the relatively small sample size or the factors contributing to the development of these complications may be different than those related to renal damage [10].…”