Progression of albuminuria in patients with sickle cell anemia: a multicenter, longitudinal study

Abstract

Sickle cell nephropathy results in chronic kidney disease (CKD), which is associated with significant morbidity and mortality in sickle cell anemia (SCA). Albuminuria is an early manifestation of sickle nephropathy; however, little is known about progression of albuminuria or its correlation with glomerular filtration rate (GFR) decline or CKD. We studied nephropathy progression in 303 SCA participants in a prospective, multicenter, longitudinal study. We collected steady-state urine and serum samples yearly and assessed albumin/creatinine ratio (ACR), estimated GFR (eGFR), and SCA and nephropathy biomarkers. Participants with albuminuria (ACR ≥30 mg/g) for ≥2 annual measurements were classified as having persistent albuminuria (PA). At baseline (mean age, 21 years; range, 2-64 years), 32% had albuminuria. In longitudinal multivariate analysis, ACR was associated with sex, anemia, older age, and higher bilirubin and kidney injury molecule-1 levels. Albuminuria increased with age by 3.5 mg/g per year (P < .0001). Of 175 participants with ≥3 annual samples, 81% with baseline albuminuria ≥100 mg/g developed PA. Decreased eGFR and adult CKD were associated with PA (P = .002 and P = .02, respectively), but not with baseline albuminuria. Rate of eGFR decline was steeper among adults (but not children) with albuminuria, compared with those without (P = .02). Participants with PA were more likely to have rapid eGFR decline compared with those without (P = .03). In this longitudinal study, albuminuria progressed with age, and adults with albuminuria had worse eGFR decline than those without. Albuminuria ≥100 mg/g predicted PA, which was associated with rapid eGFR decline and CKD development in adults with SCA. This trial was registered at www.clinicaltrials.gov as #NCT02239016.

Investigations of Kidney Dysfunction-Related Gene Variants in Sickle Cell Disease Patients in Cameroon (Sub-Saharan Africa)

“…Some haematological variables, such as MCV and Hb level ( Table 3 ), influence crude albuminuria among SCD patients from Cameroon, Hb level observed to be protective against micro- albuminuria. This is in accordance with studies in Jamaica and the United States ( Aban et al, 2017 ; Niss et al, 2020 ) which revealed that lower concentration of Hb is associated with development of micro-albuminuria, leading to relative renal ischemia, ischemia-reperfusion injury, and increased medullary sickling ( Aban et al, 2017 ). BMI provides the highest mean variation explained for crude-albuminuria and may be a major anthropometric factor leading to renal dysfunction.…”

“…The eGFR was highly associated with haemoglobin, HbF and SBP, as previously observed in patients from the United Kingdom ( Wu et al, 2009 ). The strong association between SBP and eGFR is also consistent with data reported in the study by Niss et al (2020) in Jamaica confirming the highly protective role of stable SBP against glomerular hyperfiltration ( Table 3 ). VOC frequencies are also highly correlated to eGFR, explaining the morbidity due to renal dysfunction among SCD patients in Cameroon.…”

Impact of pre‐eclampsia on renal outcome in sickle cell disease patients

“…In this setting, Niss et al . recently demonstrated a close relationship between albuminuria and the deterioration of renal function in a population of adults with SCD 17 . Albuminuria was negative in both groups before pregnancy but was greater in the PrE‐SCD group after pregnancy.…”

“…In this setting, Niss et al recently demonstrated a close relationship between albuminuria and the deterioration of renal function in a population of adults with SCD. 17 Albuminuria was negative in both groups before pregnancy but was greater in the PrE-SCD group after pregnancy. However, because of the retrospective design of our study, we did not manage to establish precisely which renal protective treatments were given to the patients after pregnancy.…”

“…UPCR was recorded at the same time points. We estimated GFR (eGFR) with the creatinine‐based CKD Epidemiology Collaboration (CKD‐EPI) equation 7,8,16,17 . Acute kidney injury (AKI) was defined according to the Kidney Disease Improving Global Outcome (KDIGO) criteria 18 and AKI events were assessed within 48 h of delivery.…”