title: Accurate assessment of long-term nephrotoxicity after peptide receptor radionuclide therapy with (177)Lu-octreotate.
abstract: OBJECTIVE
  Renal radiation during peptide receptor radionuclide therapy (PRRT) may result in glomerular damage, a potential reduction of glomerular filtration rate (GFR) and ultimately lead to renal failure. While reported PRRT nephrotoxicity is limited to data derived from serum creatinine-allowing only approximate estimates of GFR-the aim of this study is to accurately determine PRRT-induced long-term changes of renal function and associated risk factors according to state-of-the-art GFR measurement.
  
  
  METHODS
  Nephrotoxicity was analysed using (99m)Tc-diethylenetriaminepentaacetic acid (DTPA) clearance data of 74 consecutive patients with gastroenteropancreatic neuroendocrine tumours (GEP NET) undergoing PRRT with (177)Lu-octreotate. The mean follow-up period was 21 months (range 12-50) with a median of five GFR measurements per patient. The change of GFR was analysed by linear curve fit. Potential risk factors including diabetes mellitus, arterial hypertension, previous chemotherapy, renal impairment at baseline and cumulative administered activity were analysed regarding potential impact on renal function loss. In addition, Common Terminology Criteria for Adverse Events (CTCAE) v3.0 were used to compare nephrotoxicity determined by (99m)Tc-DTPA clearance versus serum creatinine.
  
  
  RESULTS
  The alteration in GFR differed widely among the patients (mean -2.1 ± 13.1 ml/min/m(2) per year, relative yearly reduction -1.8 ± 18.9%). Fifteen patients (21%) experienced a mild (2-10 ml/min/m(2) per year) and 16 patients (22%) a significant (>10 ml/min/m(2) per year) decline of GFR following PRRT. However, 11 patients (15%) showed an increase of >10 ml/min/m(2) per year. Relevant nephrotoxicity according to CTCAE (grade ≥3) was observed in one patient (1.3%) with arterial hypertension and history of chemotherapy. Nephrotoxicity according to serum creatinine was discordant to that defined by GFR in 15% of the assessments and led to underestimation in 12% of patients. None of the investigated factors including cumulative administered activity contributed to the decline of renal function.
  
  
  CONCLUSIONS
  Serious nephrotoxicity after PRRT with (177)Lu-octreotate is rare (1.3%). However, slight renal impairment (GFR loss >2 ml/min/m(2) per year) can frequently (43%) be detected by (99m)Tc-DTPA clearance assessments. Cumulative administered activity of (177)Lu-octreotate is not a major determinant of renal impairment in our study.
authors.affiliation: Department of Nuclear Medicine, University Hospital Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany.
authors.forename: Amir
authors.initials: A
authors.lastname: Sabet
authors.forename: Khaled
authors.initials: K
authors.lastname: Ezziddin
authors.forename: Ulrich-Frank
authors.initials: UF
authors.lastname: Pape
authors.forename: Karl
authors.initials: K
authors.lastname: Reichman
authors.forename: Torjan
authors.initials: T
authors.lastname: Haslerud
authors.forename: Hojjat
authors.initials: H
authors.lastname: Ahmadzadehfar
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Biersack
authors.forename: James
authors.initials: J
authors.lastname: Nagarajah
authors.forename: Samer
authors.initials: S
authors.lastname: Ezziddin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003920:Diabetes Mellitus / Q000209:etiology; D005260:Female; D005919:Glomerular Filtration Rate / Q000528:radiation effects; D006801:Humans; D006973:Hypertension / Q000209:etiology; D007668:Kidney / Q000528:radiation effects*; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000532:radiotherapy*; D015282:Octreotide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019275:Radiopharmaceuticals / Q000009:adverse effects* / Q000627:therapeutic use; D051437:Renal Insufficiency / Q000209:etiology; D016284:Technetium Tc 99m Pentetate
chemical_list: C554548:177Lu-octreotate; D019275:Radiopharmaceuticals; D015282:Octreotide; D016284:Technetium Tc 99m Pentetate