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Nephrin as a biomarker of sickle cell glomerulopathy in Malawi
J Brett Heimlich1,2, Godwin Chipoka1, Laila Elsherif3
1UNC Project-Malawi, Lilongwe, Malawi.
Insights
Urinary nephrin shows promise as an early biomarker for kidney disease in children with sickle cell disease (SCD). This novel marker, the nephrin-creatinine ratio (NCR), can help identify at-risk individuals for early intervention.
Area of Science:
- Nephrology
- Pediatrics
- Hematology
Background:
- Glomerulopathy is a growing concern in pediatric sickle cell disease (SCD).
- The progression of kidney disease in SCD typically involves hyperfiltration, albuminuria, declining glomerular filtration rates, and end-stage renal disease (ESRD).
- Limited biomarkers exist for early detection of renal disease in SCD patients.
Purpose of the Study:
- To assess the renal profile of children with SCD in Malawi.
- To identify a novel urinary biomarker for early detection of renal disease in this population.
Main Methods:
- A cohort of 101 children with SCD in Malawi was studied.
- Urinary albumin-creatinine ratio (ACR) and urinary nephrin levels were measured.
- Statistical analyses, including univariate and multivariable analyses, were performed to identify associations between biomarkers and albuminuria.
Main Results:
- 24.8% of children with sickle cell anemia exhibited albuminuria (ACR ≥ 30 mg/g).
- Higher urinary nephrin levels were significantly associated with albuminuria in both univariate and multivariable analyses.
- A nephrin-creatinine ratio (NCR) cut-point of 622 ng/mg demonstrated high sensitivity (96%) and negative predictive value (98%) for detecting albuminuria.
Conclusions:
- A significant proportion of children with SCD in Malawi have renal disease, posing a risk for progressive nephropathy and ESRD.
- Urinary nephrin, as indicated by the NCR, is a potential early diagnostic marker for glomerular disease in pediatric SCD.
Background:
Glomerulopathy is an increasingly identified complication in young patients with sickle cell disease (SCD). Hyperfiltration and albuminuria followed by declining glomerular filtration rates and eventual end-stage renal disease (ESRD) is assumed to be the typical progression of glomerular disease. There are only a few reported biomarkers to identify early-stage renal disease in SCD.
Procedures:
We detail the renal profile of 101 children with SCD in Malawi and propose a novel urinary biomarker for the identification of early renal disease.
Results:
Among children with sickle cell anemia, 24.8% had a urine albumin-creatinine ratio of 30 mg/g or above. In univariate analysis, only patients with higher urinary nephrin, a urinary marker of glomerular injury, had significantly greater odds of having albuminuria. In multivariable analysis, nephrin remained significantly associated with albuminuria. A nephrin-creatinine ratio (NCR) cut-point of 622 ng/mg, the 50th percentile, was associated with a 45.8 times greater odds of having albuminuria in children with nephrinuria above this value. Further analysis revealed this urinary NCR cut-point to have 96% sensitivity, 64% specificity, 47% positive predictive value, and 98% negative predictive value for the presence of albuminuria.
Conclusions:
These data suggest that a substantial number of children with SCD in Malawi have renal disease and could be at risk for worsening nephropathy and ESRD as they age. Our data suggest that urinary nephrin could be utilized as an early marker of glomerular disease in SCD.
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