Otto Mehls1, Anders Lindberg2, Dieter Haffner3, Franz Schaefer4, Elke Wühl4. 1. Pediatric Nephrology Division, Center for Pediatrics and Adolescent Medicine, Heidelberg University Hospital, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany. Otto-Mehls@gmx.de. 2. Pfizer Health AB, Pfizer Endocrine Care, Sollentuna, Sweden. 3. Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany. 4. Pediatric Nephrology Division, Center for Pediatrics and Adolescent Medicine, Heidelberg University Hospital, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany.
Abstract
BACKGROUND: Recombinant human (rh) growth hormone (GH) raises the glomerular filtration rate (GFR) in healthy individuals. Concern has been raised that long-term rhGH treatment in short children with chronic kidney disease (CKD) may accelerate the progression of CKD via induction of glomerular hyperfiltration. PATIENTS AND METHODS: We compared the decline in GFR in children with CKD enrolled in two large clinical studies with (KIGS registry) and without (ESCAPE trial) concomitant rhGH treatment and followed for up to 10 years. Estimated GFR (eGFR) was determined at yearly intervals. The annual decline in eGFR was analyzed cross-sectionally for up to 10 years and longitudinally for 5 years. RESULTS: In the KIGS registry 367 patients with CKD stages II-IV (mean age 8.0 years; 72% boys; mean eGFR 38.4 ml/min/1.73 m(2)) were treated with 0.33 mg rhGH/kg per week for at least 1 year. In the ESCAPE trial 274 non-rhGH-treated patients with CKD stages II-IV (mean age 11.6 years; 61% boys; mean GFR 47.3 ml/min/1.73 m(2)) were followed for at least 1 year. At the 5-year follow-up, the mean loss of eGFR in the KIGS children receiving continuous rhGH treatment (n = 97) did not differ significantly from that in the controls (n = 113) in the ESCAPE trial (-5.8 vs. -8.6 ml/5 years, respectively; p = 0.17). Absolute height and eGFR at baseline were significant correlates of the annual eGFR loss (model R (2) =0.121). CONCLUSIONS: Long-term rhGH-treatment does not accelerate the decline in GFR in short children with CKD. Height and baseline eGFR are significant predictors of the loss of GFR in CKD patients.
BACKGROUND: Recombinant human (rh) growth hormone (GH) raises the glomerular filtration rate (GFR) in healthy individuals. Concern has been raised that long-term rhGH treatment in short children with chronic kidney disease (CKD) may accelerate the progression of CKD via induction of glomerular hyperfiltration. PATIENTS AND METHODS: We compared the decline in GFR in children with CKD enrolled in two large clinical studies with (KIGS registry) and without (ESCAPE trial) concomitant rhGH treatment and followed for up to 10 years. Estimated GFR (eGFR) was determined at yearly intervals. The annual decline in eGFR was analyzed cross-sectionally for up to 10 years and longitudinally for 5 years. RESULTS: In the KIGS registry 367 patients with CKD stages II-IV (mean age 8.0 years; 72% boys; mean eGFR 38.4 ml/min/1.73 m(2)) were treated with 0.33 mg rhGH/kg per week for at least 1 year. In the ESCAPE trial 274 non-rhGH-treated patients with CKD stages II-IV (mean age 11.6 years; 61% boys; mean GFR 47.3 ml/min/1.73 m(2)) were followed for at least 1 year. At the 5-year follow-up, the mean loss of eGFR in the KIGS children receiving continuous rhGH treatment (n = 97) did not differ significantly from that in the controls (n = 113) in the ESCAPE trial (-5.8 vs. -8.6 ml/5 years, respectively; p = 0.17). Absolute height and eGFR at baseline were significant correlates of the annual eGFR loss (model R (2) =0.121). CONCLUSIONS: Long-term rhGH-treatment does not accelerate the decline in GFR in short children with CKD. Height and baseline eGFR are significant predictors of the loss of GFR in CKD patients.
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