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Filippo Mariano,1 Chiara Cogno,1 Fulvia Giaretta,2,3 Ilaria Deambrosis,2,3 Simona Pozza,4 Maurizio Berardino,5 Giuseppe Massazza,6 Luigi Biancone1,3 1Department of General and Specialist Medicine, Nephrology, Dialysis and Transplantation Unit, City of Health and Science, CTO Hospital, Turin, 2Department of General and Specialist Medicine, Laboratory of Nephrology and Immunopathology, City of Health and Science, Molinette Hospital, Turin, 3Department of Medical Sciences, University of Turin, Turin, 4Department of Radiology and Radiotherapy, CTO Radiology, City of Health and Science, CTO Hospital, Turin, 5Department of Anesthesiology and Intensive Care, Anesthesiology and Intensive Care 5, City of Health and Science, CTO Hospital, Turin, 6Department of Orthopedics and Traumatology, Week Hospital Unit, City of Health and Science, CTO Hospital, and University of Turin, Turin, Italy Background: Parenteral administration of ketorolac is very effective in controlling postoperative pain for orthopedic surgery. Ketorolac can induce clinically relevant renal alterations in elderly patients, whereas its short course is considered safe for young adults with normal preoperative renal function. In this study, of a cohort of young adults undergoing elective orthopedic day surgery, we sought cases complicated by readmission due to acute kidney injury (AKI).Patients and methods: Among 1397 young adults, aged 18–32 years who were admitted to undergo orthopedic day surgery from 2013 to 2015, four patients (0.29%, three males/one female) treated in postprocedure with ketorolac (from 60 to 90 mg/day for 1–2 days) were readmitted for suspected severe AKI. We evaluated functional outcome, urinary protein profiles and kidney biopsy (1 patient).Results: After day surgery discharge, they experienced gastrointestinal disturbances, flank pain and fever. Readmitted on post-surgery days 3–4, they presented with oliguric AKI (creatinine range 158.4–466.4 µmol/L) and frank proteinuria (albumin range 2.1–6.0 g/L). Urine protein profiles demonstrated a nonselective glomerular proteinuria, with a significant 9.4-fold increase in glomerular/tubular index on day 6. Kidney biopsy on day 19 showed normal glomeruli and minimal tubular alterations and negative immunofluorescence. All patients recovered their renal function, and after 20 days proteinuria disappeared.Conclusion: AKI can ensue even in young adults who have undergone a short course of ketorolac, when they suffered from relative dehydration, abdominal disturbances, flank pain and oliguria after discharge. Urine findings were characterized by a marked nonselective glomerular proteinuria disappearing in 2–3 weeks. Keywords: ketorolac, acute kidney injury, glomerular tubular index, orthopedic day surgery

Angiotensin converting enzyme inhibitors (ACEI) are the most effective antiproteinuric agents and should be used as first-line drugs in both diabetic and non-diabetic proteinuric nephropathies. The role of calcium channel blockers (CCB) is much more controversial. In diabetic patients verapamil and diltiazem seem more effective than dihydropyridines in reducing urinary protein excretion, and have additive effects with ACEI, but little is available on chronic treatment of non-diabetic nephropathies for non-dihydropyridine CCBs. To test whether the combination of verapamil 180 mg or amlodipine 5 mg with trandolapril 2 mg reduces urinary protein excretion more than trandolapril 2 mg alone, we planned a prospective, randomized, double-blind, multicenter trial. The secondary aims are to evaluate the effects of both treatments on the selectivity of proteinuria and check their safety. Consecutive patients aged between 18 and 70 years with non-diabetic proteinuria > or =2 g/24 h and plasma creatinine < 3 mg/dl or creatinine clearance > or = 20 ml/min are asked to participate. After a four-week run-in during which previous antihypertensive therapy is withdrawn, a single dose of trandolapril 2 mg is given once a day in open conditions for four weeks. At the end of this period patients are randomly assigned to receive once a day, in a double blind fashion, either trandolapril 2 mg and verapamil 180 mg [plus a placebo], or trandolapril 2 mg plus amlodipine 5 mg. They are monitored after one, two, five and eight months.