title: Antiproteinuric effect of add-on paricalcitol in CKD patients under maximal tolerated inhibition of renin-angiotensin system: a prospective observational study.
abstract: BACKGROUND
  Whether paricalcitol (PCT) reduces proteinuria in the presence of intensified inhibition of Renin-Angiotensin-System (RAS) is poorly studied. We evaluated the antiproteinuric effect of PCT in non-dialysis chronic kidney disease (CKD) patients with proteinuria greater than 0.5 g/24 h persisting despite anti-RAS therapy titrated to minimize proteinuria in the absence of adverse effects.
  
  
  METHODS
  Forty-eight CKD patients were studied in the first six months of add-on oral PCT (1 mcg/day) and three months after drug withdrawal.
  
  
  RESULTS
  Males were 87.5%, age 63 ± 14 yrs, systolic/diastolic blood pressure (BP) 143 ± 22/78 ± 11 mmHg, eGFR 29.7 ± 14.5 mL/min/1.73 m(2), diabetes 40%, and cardiovascular disease 38%. At referral in the center (28 months prior to study baseline), proteinuria was 2.44 (95% CI 1.80-3.04) g/24 h with 6 patients not receiving any anti-RAS and 42 treated with a single agent, at low dosage in most cases. At study baseline, twenty patients were under 2-3 anti-RAS drugs while twenty-eight received 1 agent at full dose and proteinuria resulted to be reduced versus referral to 1.23 g/24 h (95%CI 1.00-1.51). Six months of add-on PCT significantly decreased proteinuria to 0.61 g/24 h (95%CI 0.40-0.93), with levels less than 0.5 g/24 h achieved in 37.5% patients, in the absence of changes of BP and GFR. Proteinuria recovered to basal value after drug withdrawal. The extent of antiproteinuric response to PCT was positively associated with diabetes, eGFR and daily Na excretion (R(2) = 0.459, P < 0.0001). PTH decreased from 201 (IQR 92-273) to 83 (IQR 50-189) pg/mL.
  
  
  CONCLUSIONS
  In CKD patients, add-on PCT induces a significant reduction of proteinuria that is evident despite intensified anti-RAS therapy and larger in the presence of diabetes, higher GFR and unrestricted salt intake.
authors.affiliation: Nephrology Departments at Second University, Napoli, Italia. luca.denicola@unina2.it
authors.forename: Luca
authors.initials: L
authors.lastname: De Nicola
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Conte
authors.forename: Domenico
authors.initials: D
authors.lastname: Russo
authors.forename: Antonio
authors.initials: A
authors.lastname: Gorini
authors.forename: Roberto
authors.initials: R
authors.lastname: Minutolo
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D004872:Ergocalciferols / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011507:Proteinuria / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D012083:Renin / Q000502:physiology; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology; D000092502:Renin Inhibitors
chemical_list: D000959:Antihypertensive Agents; D004872:Ergocalciferols; D012083:Renin; D000092502:Renin Inhibitors; C084656:paricalcitol