Kidney Disease among Patients with Sickle Cell Disease, Hemoglobin SS and SC

Abstract

Background and objectives Sickle cell disease (SCD) is an inherited anemia that afflicts millions worldwide. Kidney disease is a major contributor to its morbidity and mortality. We examined contemporary and historical SCD populations to understand how renal disease behaved in hemoglobin SS (HbSS) compared with HbSC. . Macroalbuminuria was seen in 20% of participants with SCD (HbSS or HbSC; P=0.45; Walk-PHaSST Trial), but microalbuminuria was more prevalent in HbSS (44% versus 23% in HbSC; P,0.002). In the Walk-PHaSST Trial, albuminuria was associated with hemolysis (higher lactate dehydrogenase, P,0.001; higher absolute reticulocyte count, P,0.02; and lower Hb, P=0.07) and elevated systolic BP (P,0.001) in HbSS. One half of all participants with HbSS (20 of 39) versus one fifth without (41 of 228) elevated tricuspid regurgitant jet velocity ($3 m/s; adverse prognostic indicator in SCD) had macroalbuminuria (P,0.001). In the CSSCD, overt proteinuria, detected (less sensitively) by urine dipstick, associated with higher 3-year mortality (odds ratio, 2.48; 95% CI, 1.07 to 5.77). Serum bicarbonate was lower in HbSS (23.8 versus 24.8 mEq/dl in HbSC; P,0.05) and associated with reticulocytopenic anemia and decreased renal function.Conclusions In SCD, albuminuria or proteinuria was highly prevalent, in HbSS more than in HbSC. Proteinuria associated with mortality in HbSS. Older individuals had a lower than expected eGFR, and this was more prominent in HbSS. Current management does not routinely address renal complications in SCD, which could plausibly reduce morbidity and mortality.

The spectrum of sickle hemoglobin-related nephropathy: from sickle cell disease to sickle trait

“…The phenotypic variation observed with sickling genotypes relates to differences in degree of hemolysis, endothelial dysfunction, and viscosity, with hemolytic complications such as pulmonary hypertension and leg ulcers being more common in SCA genotypes and viscosity-related manifestations such as retinopathy and possibly avascular necrosis being more common in sickle variant syndromes [54]. Renal medullary vasculopathy appears to fit into the former category; albuminuria and advanced renal insufficiency have consistently been found to be more prevalent among individuals with SCA compared to those with SC or Sβ + thalassemia [36,55]. …”

Knowledge insufficient: the management of haemoglobin SC disease

“…The sickle nephropathy of HbSC is distinct from HbSS in that it occurs later in life and rarely leads to end-stage-renal-disease (ESRD) (Aygun et al, 2011;Lionnet et al, 2012). Microalbuminuria occurs in 30% of patients with HbSC, and ESRD develops in 2-3% by their 5th decade (Powars et al, 1991(Powars et al, , 2002Lionnet et al, 2012;Drawz et al, 2016). Children with HbSC typically develop irreversible hyposthenuria at 10-15 years of age and have evidence of glomerular damage and medullary injury (Iyer et al, 2000;Drawz et al, 2016).…”

Diffusion tensor imaging MRI of sickle cell kidney disease: initial results and comparison with iron deposition

“…Although these abnormalities are present in almost all pediatric patients with SCD, only a subset of patients progress to overt CKD (decreased eGFR and/or proteinuria indicative of underlying glomerulosclerosis and tubulointerstitial scarring). Recent data from our group examining cross‐sectional data from multiple databases, as well as the longitudinal Jamaica Sickle Cell Study, indicate that the mean decline in eGFR for adult patients with SCD with homozygous sickle cell genes ranges between 1.78 and 3 mL/min/1.73 m 2 /year, which is more than twice the rate of decline seen in the general population . However, analogous kidney disease progression data are not available in pediatric patients with SCD.…”

“…This is particularly problematic in SCD, given the hyperfiltration/‘supranormal’ GFRs observed in many patients with SCD. Albuminuria (microalbuminuria and/or overt proteinuria) is another marker of CKD progression that occurs commonly in adults with SCD . Microalbuminuria has been reported to occur in approximately 15% of children, especially those who demonstrate hyperfiltration.…”