Association Between Phthalates Exposure and Renal Function Impairment in TYpe 2 Diabetes

Diabetes Mellitus, Type 2 Clinical Trial

— PURITY-2  

Official title:

Exploring the Association Between Phthalates Exposure, Measured Through Their Urinary Metabolites, and Renal Function Impairment in Individuals With TYpe 2 Diabetes - Protocol 2

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03622957
• Other study ID #: PURITY - Protocol 2
• Status: Not yet recruiting
• Start date: August 10, 2018
• Est. completion date: September 3, 2018

Study information

• Verified date: August 2018
• Source: University of Pisa
• Contact: Anna Solini, Associate Professor, MD, PhD
• Phone: +39 050993482
• Email: anna.solini[@]med.unipi
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The global incidence of diabetic nephropathy (DN) is increasing, with no appreciable reduction in the percent of patients progressing toward end stage renal disease (ESRD) and dialysis (Tuttle et al, 2014, Winocour et al, 2018). Therefore, identification of modifiable risk factors and early biomarkers of progressive decline in kidney function is an urgent clinical need. Phthalates are environmental and dietary contaminants with a various array of use that are identified in many consumer and industrial products; among them, di-(2-ethylhexyl) phthalate (DEHP) and its metabolites (mono 2-ethylhexyl phthalate (MEHP), 5OH-MEHP (MEHHP) and 5oxo-MEHP (MEOHP)) are widely used (Kato et al 2004, Braun et al, 2013). They partially distribute to the human tissues and their urinary and serum levels are directly related; therefore, urinary concentration of phthalates is commonly used as proxy of their exposure in humans (Kato et al 2004).

While the association between phthalates exposure and development of T2D is currently being explored (Dong et al 2017, Dales et al, 2018), little is known about their role in DN. Recent observations show that DEHP and its metabolites are associated with a higher prevalence of low-grade albuminuria and in children exposed to higher phthalates concentrations (Trasande et al, 2014, Wu et al, 2018), however such association has yet to be verified in adults. The environmental ubiquity of the phthalates enhances the importance of investigating the potential relation between their exposure and different degrees of renal function. (Kato et al 2004, Kataria et al, 2015).

Given this premise, the investigators will explore this potential association in a population of subjects with T2D consecutively referring to the outpatient diabetes clinic in Santa Chiara Hospital, Pisa, enrolled on a volunteer basis. During their routine visit at Santa Chiara Hospital outpatient diabetes clinic participants will provide the results of blood tests prescribed as per standard clinical practice along with a first morning, overnight fasting, urine sample collected in a phthalates-free container.

The investigators will record the participants' clinical history, physical examination and anthropometric measurements, will measure their renal function, evaluated by eGFR (calculated with the CDK-EPI formula), albumin excretion, fasting glucose, HbA1c%, and the exposure to phthalates, assessed by total concentrations of MEHP, MEOHP, MEHHP and adjusted for urinary creatinine. In this way, the investigators aim to point out the relationship of urinary phthalates with higher degrees of albuminuria and/or lower eGFR after adjustment for all potential confounders, including therapies.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 200
• Est. completion date: September 3, 2018
• Est. primary completion date: September 3, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

Age 18-85 years, T2D diagnosis, T2D duration >6 months,

Exclusion Criteria:

occurring acute clinical conditions, eGFR <15 ml/min/1.73m2, BMI > 40 Kg/m2.

Related Conditions & MeSH terms

• Albuminuria
• Cardiovascular Risk Factor
• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Locations

Country	Name	City	State
Italy	University of Pisa	Pisa

Sponsors (2)

Lead Sponsor	Collaborator
University of Pisa	Istituto di Fisiologia Clinica CNR

Country where clinical trial is conducted

Italy, 

References & Publications (9)

Braun JM, Sathyanarayana S, Hauser R. Phthalate exposure and children's health. Curr Opin Pediatr. 2013 Apr;25(2):247-54. doi: 10.1097/MOP.0b013e32835e1eb6. Review. — View Citation

Dales RE, Kauri LM, Cakmak S. The associations between phthalate exposure and insulin resistance, ß-cell function and blood glucose control in a population-based sample. Sci Total Environ. 2018 Jan 15;612:1287-1292. doi: 10.1016/j.scitotenv.2017.09.009. Epub 2017 Sep 8. — View Citation

Dong R, Zhao S, Zhang H, Chen J, Zhang M, Wang M, Wu M, Li S, Chen B. Sex Differences in the Association of Urinary Concentrations of Phthalates Metabolites with Self-Reported Diabetes and Cardiovascular Diseases in Shanghai Adults. Int J Environ Res Public Health. 2017 Jun 5;14(6). pii: E598. doi: 10.3390/ijerph14060598. — View Citation

Kataria A, Trasande L, Trachtman H. The effects of environmental chemicals on renal function. Nat Rev Nephrol. 2015 Oct;11(10):610-25. doi: 10.1038/nrneph.2015.94. Epub 2015 Jun 23. Review. — View Citation

Kato K, Silva MJ, Reidy JA, Hurtz D 3rd, Malek NA, Needham LL, Nakazawa H, Barr DB, Calafat AM. Mono(2-ethyl-5-hydroxyhexyl) phthalate and mono-(2-ethyl-5-oxohexyl) phthalate as biomarkers for human exposure assessment to di-(2-ethylhexyl) phthalate. Environ Health Perspect. 2004 Mar;112(3):327-30. — View Citation

Trasande L, Sathyanarayana S, Trachtman H. Dietary phthalates and low-grade albuminuria in US children and adolescents. Clin J Am Soc Nephrol. 2014 Jan;9(1):100-9. doi: 10.2215/CJN.04570413. Epub 2013 Oct 31. — View Citation

Tuttle KR, Bakris GL, Bilous RW, Chiang JL, de Boer IH, Goldstein-Fuchs J, Hirsch IB, Kalantar-Zadeh K, Narva AS, Navaneethan SD, Neumiller JJ, Patel UD, Ratner RE, Whaley-Connell AT, Molitch ME. Diabetic kidney disease: a report from an ADA Consensus Conference. Diabetes Care. 2014 Oct;37(10):2864-83. doi: 10.2337/dc14-1296. — View Citation

Winocour PH. Diabetes and chronic kidney disease: an increasingly common multi-morbid disease in need of a paradigm shift in care. Diabet Med. 2018 Mar;35(3):300-305. doi: 10.1111/dme.13564. Epub 2018 Jan 8. Review. — View Citation

Wu CF, Hsiung CA, Tsai HJ, Tsai YC, Hsieh HM, Chen BH, Wu MT. Interaction of melamine and di-(2-ethylhexyl) phthalate exposure on markers of early renal damage in children: The 2011 Taiwan food scandal. Environ Pollut. 2018 Apr;235:453-461. doi: 10.1016/j.envpol.2017.12.107. Epub 2018 Jan 6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phthalates exposure [ug/g]	Concentrations of metabolites of DEHP [ug/ml] in a first morning spot urine sample (obtained during clinical visit) measured by ultra-HPLC coupled with electrospray ionization/quadrupole time-of-flight MS and then normalized for urinary creatinine [g/ml].	Single routine clinical visit
Primary	Albuminuria [mg/g]	Grade of albuminuria measured by albuminuria/creatininuria ratio [mg/g] in a first morning spot urine sample (obtained during clinical visit).	Single routine clinical visit
Primary	Glomerular Filtration Rate [ml/min/1.73m2]	GFR measured by eGFR (calculated with CDK-EPI formula). Creatinine [mg/dL] is measured in a serum sample (obtained during clinical visit). Physiological parameters (age, sex, race) are obtained during clinical visit.	Single routine clinical visit
Secondary	CV Events (Yes/No)	History of cardiovascular events (Non fatal: Acute Myocardial infarction, Unstable Angina, Stroke), evaluated by clinical interview during routine clinical visit.	Single routine clinical visit