Renal Dysfunction in Thalassemia.
Authors: Quinn Charles T , Johnson Valerie L , Kim Hae-Young , Trachtenberg Felicia , Vogiatzi Maria G , Kwiatkowski Janet L , Neufeld Ellis J , Fung Ellen , Olivieri Nancy F , Kirby-Allen Melanie , Giardina Patricia J 
Published: October 2019

Abstract
Abstract 2008
Poster Board I-1030

BACKGROUND:
Renal function is generally thought to be normal in patients with thalassemia, but it has not been studied in detail. There are recent reports of renal tubular defects in both thalassemia intermedia and major. The cause is unclear, but both iron toxicity and iron chelation therapy have been suggested. The study of renal function in thalassemia is timely, because the new oral iron chelator, deferasirox, may increase creatinine concentration and cause proteinuria. Pre-existing, thalassemia-related renal function abnormalities could be a risk factor for deferasirox-related nephropathy. Therefore, it is critical to know how thalassemia affects the kidney. We aimed to determine the prevalence of renal function abnormalities in patients with thalassemia before deferasirox was widely clinically available and to evaluate associations between renal abnormalities and genetic factors, environmental factors, and transfusion regimens.

METHODS:
We studied patients who participated in the Low Bone Mass Cross-sectional Observational Study (LBMCOS) of the NIH Thalassemia Clinical Research Network. We included all LBMCOS patients (≥6 years of age) with a creatinine clearance (CCr) and calcium to creatinine ratio (Ca:Cr) measured by 24-hour urine collection. We only included patients whose urinary creatinine excretion rate was appropriate for age and gender, indicating a complete urine collection. Notably, none of these patients was treated with deferasirox; nearly all were treated with deferoxamine. We used multivariable models to determine significant predictors of CCr and Ca:Cr. Potential predictors included age, gender, diagnosis, transfusion status, serum transferrin receptor concentration, serum ferritin, and the presence of a variety of clinical complications.

RESULTS:
This cohort included 216 patients [51.4% female, mean age 12.6 years (range 6.1 – 75.4)]. 188 had beta thalassemia, 14 had Hb H disease or Hb H-Constant Spring, 13 had Hb E-beta-thalassemia, and 1 had homozygous alpha thalassemia major. 180 subjects were regularly transfused (≥8/yr) and 36 were not. Among all patients, 7.8% had a low CCr, 71.3% had a normal CCr, and 20.8% had a high CCr (adjusted for age, gender and body surface area). Regularly transfused patients had significantly lower mean CCr than those not regularly transfused [143.8 ± 54.3 (mean ± SD) mL/min/1.73 m2 vs. 173.4 ± 65; P=0.004]. Among all patients, 71.3% had a normal Ca:Cr, whereas 28.7% had a high Ca:Cr. Regularly transfused patients had significantly higher mean Ca:Cr than those not regularly transfused (0.18 ± 0.10 vs. 0.10 ± 0.08; P<0.0001). Multivariable models showed that the only significant predictors of CCr were regular transfusion status [Odds Ratio (OR) 0.39, 0.17-0.88] and serum transferrin receptor concentration (OR 1.03, 1.01-1.05). Likewise, the only significant predictors of Ca:Cr were regular transfusion status (OR 3.72, 1.24-11.2) and serum transferrin receptor concentration (OR 0.98, 0.95-0.99).

CONCLUSIONS:
Renal hyperfiltration is common in thalassemia patients, especially those who are not regularly transfused. Hyperfiltration could be the consequence of chronic anemia. Regularly transfused thalassemia patients have a lower CCr and are more likely to have hypercalciuria than patients who are not regularly transfused. This transfusion-related effect could represent iron-mediated tubular and glomerular injury. Awareness of underlying renal dysfunction in thalassemia patients could inform decisions about the use and monitoring of potentially nephrotoxic agents, such as deferasirox. Further studies are needed to better understand renal function in patients with thalassemia.

Disclosures:
No relevant conflicts of interest to declare.