Study Identifies Risk Factors for CKD in Patients with Sickle Cell Anemia

Findings from a new study identified various risk factors for chronic kidney disease (CKD) stage II in patients with sickle cell anemia.

Currently, there is a dearth of data on the natural history of sickle cell anemia-related nephropathy as well as the onset of CKD.

To help elucidate the prevalence of CKD in sickle cell patients, a team led by Camille Roger, of the University of Lille, conducted a prospective observational study in Tenon Hospital sickle cell centre between October 2006 – September 2017.

The Study

All patients had sickle cell anemia and were seen roughly every 6 months as part of routine medical routines (or more if determined by a physician).

Medical visits included a clinical examination, which consisted of cardiovascular evaluations, as well as routine blood and urine tests. Roger and colleagues excluded any patients with impaired kidney function.

Patients were thus screened for chronic kidney disease at each subsequent medical evaluation. As such, the primary outcome of the study was the time of first occurrence of CKD stage II, as defined by eGFR< 90mL/min/1.73m2.

Pediatric of first CKD occurrence was determined using univariate and multivariate Cox’s regressions models, and hazard ratios (HRs) were calculated.

The Results

Overall, 535 patients were included in the analysis. They were followed up for a median of 5.33 years, whereby a majority (71.6%) were followed longer than 2.5 years. Up to 30.1% were followed for more than 7.5 years.

The median age of the population was 22 years older, and 58.7% were women.

"Among patients with baseline glomerular hyperfiltration (eGFR> 130mL/min/1.73m²), 4 patients experienced CKD stage II during follow up with a mean eGFR decrease of 8.4 ml/min/year whereas mean eGFR decrease was 1.73 mL/min/year in the rest of the subgroup," the investigators reported.

"Among the 15 patients with a baseline eGFR between 90 and 95 ml/min/1.73 m², 7 patients experienced CKD stage II whereas eGFR remained stable in the 8 other cases."

The investigators noted that a history of skin ulcer (HR: 2.26; 95% CI, 1.12-4.54) and higher BMI were both associated with a greater risk for CKD stage II (HR, 1.15; 1.06-1.25).

Being born in France was associated with a decreased risk for CKD (HR, 0.21; (0.09-0.48). However, these associations were not statistically significant following adjustment of age and baseline eGFR.

“Age appeared as a strong factor associated with an increased risk of kidney function impairment with a HR of 1.13 [95% CI, 1.09-1.16] per year increase,” they observed.

“CKD stage II risk increased by 13.3 and 43.6 fold in patients above 30 and 40 years of age respectively compared to patients below 20 years of age.”

Other notable risks for CKD onset were baseline eGFR (HR, 0.91; 95% CI, 0.90-0.93), LDH (for 100 UI/L) (HR, 1.15; 95% CI, 1.00-1.32), proteinuria (for 100 mg/mmol) (HR, 1.32; 95% CI, 1.18-1.48), and macroalbuminaria (HR, 4.20; 95% CI, 1.88-9.38).

Additionally, a 10 mmHg increase from baseline diastolic blood pressure was strongly associated with CKD impairment (HR, 1.51; 95% CI, 1.22-1.86). Baseline DBP >70 mmHg was linked to an HR of 3.76 (95% CI, 1.97-7.17l P<.001).

Baseline LDH, macroalbuminaria, proteinuria, and diastolic blood pressure above 70 mmHg were significant risk factors for CKD following adjustment of age and eGFR at baseline.

“To our knowledge this study is the largest clinical cohort looking at eGFR decline and its related risk factors in an SCA population,” the investigators wrote. “This study provides an insight of SCA nephropathy natural course and pinpoints different risk factors for CKD stage II onset”

They indicated that future studies of patients with sickle cell anemia at risk for CKD should assess the effectiveness of targeting optimal blood pressure, adequate monitoring, and preemptive treatments.

The study, “Risk factors for CKD stage II onset in a prospective cohort of homozygous sickle cell adults,” was published online in American Journal of Hematology.