Tubular dysfunction in stable adult sickle cell patients in Kinshasa: prevalence and associated factors - a cross-sectional study.
One in five stable adult sickle cell patients in Kinshasa has tubular dysfunction, which is associated with hemolysis and lower kidney function.
Where it sits
this study against the rest of the epitalon (epithalon) corpusSummary and findings
This study measured the prevalence of tubular dysfunction in stable adult sickle cell disease patients in Kinshasa. A total of 279 patients were enrolled, and 20.8% were identified with tubulopathy. The study found significant differences in various renal function markers between those with and without tubulopathy.
Abstract
Renal complications of sickle cell disease (SCD) often begin with tubular dysfunction (TD), yet this entity remains insufficiently recognized in African populations. Data from adults in Kinshasa are particularly scarce. We conducted a cross-sectional study between March 2023 and April 2024, enrolling 279 clinically stable adult SCD patients from 14 centers in Kinshasa. Tubulopathy was defined by the concomitant presence of three abnormalities: urinary α1-microglobulin-to-creatinine ratio (A1M/Cr) ≥20 mg/g, dipstick glucosuria ≥1+ with plasma glucose <126 mg/dL, and urine pH ≥5.5. Glomerular involvement was assessed by urinary albumin to creatinine ratio (UACR ≥30 mg/g). Measured GFR (mGFR) was obtained by iohexol clearance. Multivariable logistic regression was used to identify independent factors associated with tubulopathy. Tubulopathy was identified in 58 patients (20.8%). Compared with those without tubulopathy, affected patients had significantly higher median A1M/Cr (44.7 vs. 14.2 mg/g; <i>p</i> < 0.001) and UACR (22.1 vs. 10.7 mg/g; <i>p</i> = 0.007). They also displayed lower mean eGFR by CKD-EPI<sub>crea+cys2021</sub> (107.4 vs. 115.9 mL/min/1.73 m²; <i>p</i> = 0.031) and higher LDH levels (217.0 vs. 209.1 IU/L; <i>p</i> = 0.016). In multivariable analysis, independent predictors of tubulopathy included higher LDH (per 100 IU/L increase) (aOR 2.53, 95% CI 1.14-5.61), UACR ≥30 mg/g (aOR 1.94, 95% CI 1.18-5.18), while hydroxyurea use was independently associated with lower odds of tubulopathy (aOR 0.37, 95% CI 0.16-0.87). One in five stable adult SCD patients in Kinshasa presented with tubulopathy. This phenotype was associated with hemolysis, albuminuria, and lower eGFR, whereas hydroxyurea use was inversely associated with tubulopathy.
Background
This paper addresses the prevalence of tubular dysfunction in sickle cell disease (SCD), particularly in African populations where data is scarce. Previous studies have noted renal complications in SCD, but the recognition of tubular dysfunction remains limited. Understanding the prevalence and associated factors of tubulopathy in this population is crucial for improving patient management.
Methods
The study employed a cross-sectional design, enrolling 279 clinically stable adult SCD patients from 14 centers in Kinshasa between March 2023 and April 2024. Tubulopathy was defined by specific urinary abnormalities, and glomerular involvement was assessed using urinary albumin to creatinine ratio. Measured GFR was obtained through iohexol clearance, and multivariable logistic regression was used to identify predictors of tubulopathy.
Results
Tubulopathy was identified in 58 patients (20.8%). The median A1M/Cr was significantly higher in tubulopathy patients at 44.7 mg/g compared to 14.2 mg/g in non-tubulopathy patients (p < 0.001). Additionally, UACR was higher in tubulopathy patients (22.1 mg/g) than in non-tubulopathy patients (10.7 mg/g, p = 0.007). The mean eGFR was lower in tubulopathy patients (107.4 mL/min/1.73 m²) compared to non-tubulopathy patients (115.9 mL/min/1.73 m², p = 0.031). Higher LDH levels were also noted in tubulopathy patients (217.0 IU/L) versus non-tubulopathy patients (209.1 IU/L, p = 0.016).
Interpretation
The findings indicate a significant prevalence of tubular dysfunction in stable adult SCD patients in Kinshasa, aligning with previous literature that highlights renal complications in SCD. While the statistical significance of the findings is clear, the clinical significance may vary, particularly given the small effect sizes in some comparisons. Limitations such as the cross-sectional design and single-site data collection may confound the results and limit broader applicability.
Key findings
- 20.8% of patients had tubulopathy.
- Median A1M/Cr was 44.7 mg/g in tubulopathy patients vs 14.2 mg/g in non-tubulopathy patients, p < 0.001.
- UACR was 22.1 mg/g in tubulopathy patients vs 10.7 mg/g in non-tubulopathy patients, p = 0.007.
- Mean eGFR was 107.4 mL/min/1.73 m² in tubulopathy patients vs 115.9 mL/min/1.73 m² in non-tubulopathy patients, p = 0.031.
- Higher LDH levels were observed in tubulopathy patients (217.0 IU/L) vs non-tubulopathy patients (209.1 IU/L), p = 0.016.
- Hydroxyurea use was associated with lower odds of tubulopathy (aOR 0.37, 95% CI 0.16-0.87).
Limitations
- cross-sectional design limits causal inference
- single-site study may affect generalizability
- limited demographic diversity in sample