Risk factors for cyclosporin A nephrotoxicity in children with steroid-dependant nephrotic syndrome.
OBJECTIVE
Cyclosporin A (CsA) is a well-established treatment for steroid-dependent nephrotic syndrome (SDNS) that may, however, cause chronic ischemic renal lesions. The objective of the study was to assess the prevalence of CsA nephrotoxicity (CsAN) in protocol biopsies of children with SDNS.


METHODS
From 1990 through 2008, we performed 71 renal biopsies in 53 patients with SDNS. The mean CsA C2 levels were 466 +/- 134 ng/ml, and the mean duration of treatment was 4.7 +/- 2.0 yr before biopsy (range 2.9 to 12.7 yr).


RESULTS
CsAN was observed in 22 (31%) of 71 renal biopsies. Of these, 11 corresponded to isolated vascular or tubular lesions, and 11 corresponded to combined vascular and tubular lesions. The majority of CsAN lesions were mild (17 of 22). In no cases were lesions graded as severe. By regression analysis, CsAN was positively associated with the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) and with hyperuricemia and negatively associated with minimal-change lesions. By multivariate analysis, only association with the use of ACEIs or ARBs retained significance. Stratification of the population according to CsA C2 levels showed increased risk for CsAN for C2 levels >600 ng/ml.


CONCLUSIONS
Mild to moderate CsAN occurs in approximately one third of patients who have SDNS and are treated with CsA for >3 yr. Our data suggest that patients who require high dosages of CsA or treatment for hypertension, in particular when ACEIs/ARBs are used, are at higher risk for CsAN.
Kengne-Wafo
Severin
S
Division of Nephrology, Bambino Gesù Children's Hospital and Research Institute, 00165 Rome, Italy.
Massella
Laura
L
Diomedi-Camassei
Francesca
F
Gianviti
Alessandra
A
Vivarelli
Marina
M
Greco
Marcella
M
Stringini
Gilda Rita
GR
Emma
Francesco
F
D000293:Adolescent; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects*; D018450:Disease Progression; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000209:etiology; D033461:Hyperuricemia / Q000209:etiology; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D007223:Infant; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology; D016015:Logistic Models; D008297:Male; D009404:Nephrotic Syndrome / Q000150:complications / Q000188:drug therapy*; D016017:Odds Ratio; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine