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Pentoxifylline improves haemoglobin and interleukin-6 levels in chronic kidney disease.
Nephrology (Carlton). 2010 Apr; 15(3):344-9.N

Abstract

AIM

To assess whether pentoxifylline improves anaemia of chronic kidney disease (CKD) via suppression of interleukin-6 (IL-6) and improved iron mobilization.

BACKGROUND

CKD patients may have elevated IL-6 and tumour necrosis factor alpha levels. These cytokines can increase hepcidin production, which in turn reduces iron release from macrophages resulting in reduced availability of iron for erythropoiesis. In experimental models, pentoxifylline was shown to reduce IL-6 expression.

METHODS

We studied 14 patients with stages 4-5 CKD (glomerular filtration rate <30mL/min per 1.73 m(2)) due to non-inflammatory renal diseases. None of the patients had received immunosuppressive or erythropoietin-stimulating agents or parenteral iron. Patients had weekly blood tests for iron studies and cytokines during a control run-in period of 3 weeks and during 4 weeks of pentoxifylline treatment.

RESULTS

Ten patients (eGFR 23 + or - 6 mL/min) completed the study. At the end of the run-in period average haemoglobin was 111 + or - 5 g/L, ferritin 92 + or - 26 microg/L, transferrin saturation 15 + or - 3% and circulating IL-6 10.6 + or - 3.8 pg/mL. Tumour necrosis factor alpha values were below threshold for detection. Treatment with pentoxifylline reduced circulating IL-6 (6.6 + or - 1.6 pg/mL, P < 0.01), increased transferrin saturation (20 + or - 5%, P < 0.003) and decreased serum ferritin (81 + or - 25 microg/L, P = NS). Haemoglobin increased after the second week of pentoxifylline, reaching 123 + or - 6 g/L by week 4 (P < 0.001).

CONCLUSIONS

Pentoxifylline reduces circulating IL-6 and improves haemoglobin in non-inflammatory moderate to severe CKD. These changes are associated with changes in circulating transferrin saturation and ferritin, suggesting improved iron release. It is hypothesized that pentoxifylline improves iron disposition possibly through modulation of hepcidin.

Authors+Show Affiliations

Department of Nephrology, Fremantle Hospital, Alma Street, Perth, WA 6160, Australia. paolo.ferrari@health.wa.gov.auNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20470305

Citation

Ferrari, Paolo, et al. "Pentoxifylline Improves Haemoglobin and Interleukin-6 Levels in Chronic Kidney Disease." Nephrology (Carlton, Vic.), vol. 15, no. 3, 2010, pp. 344-9.
Ferrari P, Mallon D, Trinder D, et al. Pentoxifylline improves haemoglobin and interleukin-6 levels in chronic kidney disease. Nephrology (Carlton). 2010;15(3):344-9.
Ferrari, P., Mallon, D., Trinder, D., & Olynyk, J. K. (2010). Pentoxifylline improves haemoglobin and interleukin-6 levels in chronic kidney disease. Nephrology (Carlton, Vic.), 15(3), 344-9. https://doi.org/10.1111/j.1440-1797.2009.01203.x
Ferrari P, et al. Pentoxifylline Improves Haemoglobin and Interleukin-6 Levels in Chronic Kidney Disease. Nephrology (Carlton). 2010;15(3):344-9. PubMed PMID: 20470305.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pentoxifylline improves haemoglobin and interleukin-6 levels in chronic kidney disease. AU - Ferrari,Paolo, AU - Mallon,Dominic, AU - Trinder,Deborah, AU - Olynyk,John K, PY - 2010/5/18/entrez PY - 2010/5/18/pubmed PY - 2010/8/25/medline SP - 344 EP - 9 JF - Nephrology (Carlton, Vic.) JO - Nephrology (Carlton) VL - 15 IS - 3 N2 - AIM: To assess whether pentoxifylline improves anaemia of chronic kidney disease (CKD) via suppression of interleukin-6 (IL-6) and improved iron mobilization. BACKGROUND: CKD patients may have elevated IL-6 and tumour necrosis factor alpha levels. These cytokines can increase hepcidin production, which in turn reduces iron release from macrophages resulting in reduced availability of iron for erythropoiesis. In experimental models, pentoxifylline was shown to reduce IL-6 expression. METHODS: We studied 14 patients with stages 4-5 CKD (glomerular filtration rate <30mL/min per 1.73 m(2)) due to non-inflammatory renal diseases. None of the patients had received immunosuppressive or erythropoietin-stimulating agents or parenteral iron. Patients had weekly blood tests for iron studies and cytokines during a control run-in period of 3 weeks and during 4 weeks of pentoxifylline treatment. RESULTS: Ten patients (eGFR 23 + or - 6 mL/min) completed the study. At the end of the run-in period average haemoglobin was 111 + or - 5 g/L, ferritin 92 + or - 26 microg/L, transferrin saturation 15 + or - 3% and circulating IL-6 10.6 + or - 3.8 pg/mL. Tumour necrosis factor alpha values were below threshold for detection. Treatment with pentoxifylline reduced circulating IL-6 (6.6 + or - 1.6 pg/mL, P < 0.01), increased transferrin saturation (20 + or - 5%, P < 0.003) and decreased serum ferritin (81 + or - 25 microg/L, P = NS). Haemoglobin increased after the second week of pentoxifylline, reaching 123 + or - 6 g/L by week 4 (P < 0.001). CONCLUSIONS: Pentoxifylline reduces circulating IL-6 and improves haemoglobin in non-inflammatory moderate to severe CKD. These changes are associated with changes in circulating transferrin saturation and ferritin, suggesting improved iron release. It is hypothesized that pentoxifylline improves iron disposition possibly through modulation of hepcidin. SN - 1440-1797 UR - https://www.unboundmedicine.com/medline/citation/20470305/Pentoxifylline_improves_haemoglobin_and_interleukin_6_levels_in_chronic_kidney_disease_ L2 - https://doi.org/10.1111/j.1440-1797.2009.01203.x DB - PRIME DP - Unbound Medicine ER -