Cyclosporine A causes maturation failure in embryonic-type glomeruli persisting after birth.
BACKGROUND
We analyzed renal histologic and immunohistologic findings in children with nephrotic syndrome (NS) who did (n=5) or did not (n=17) develop cyclosporine A (CyA) nephropathy despite appropriately low serum CyA concentrations being maintained over 2 years.


METHODS
To discriminate embryonic-type from mature glomeruli, we performed staining for type IV collagen a1, laminin ß1 and laminin ß2. Staining patterns were used to semiquantitatively assess glomerular immaturity (glomerular immaturity index, or GII).


RESULTS
In follow-up biopsy specimens, residual embryonic-type, collapsed embryonic-type and sclerotic glomeruli that had failed to differentiate were observed. Patients with early-onset CyA nephropathy had a high GII. In patients with a high GII, arteriopathy developed early in CyA treatment. Arteriopathy was observed mostly near embryonic-type glomeruli. Taken together, these glomeruli (surviving embryonic-type, collapsing embryonic-type, and sclerotic glomeruli) essentially equaled the total number of embryonic-type glomeruli in specimens obtained before CyA treatment.


CONCLUSIONS
Our findings indicate a need for caution in CyA therapy for patients with NS, even for a relatively short course of administration, because some patients may have embryonic-type glomeruli or immature arterioles that predispose them to CyA nephropathy.
Department of Pediatrics, Kinki University School of Medicine, Osaka-Sayama, Japan.
Shinsuke
S
Fujita
Keisuke
K
Sugimoto
Tomoki
T
Miyazawa
Kohei
K
Miyazaki
Yutaka
Y
Takemura
Hidehiko
H
Yanagida
Naoki
N
Sakata
Norihisa
N
Wada
Mitsuru
M
Okada
Tsukasa
T
Takemura
D002675:Child, Preschool; D024141:Collagen Type IV / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007223:Infant; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000254:growth & development* / Q000473:pathology; D007797:Laminin / Q000378:metabolism; D008297:Male; D009404:Nephrotic Syndrome / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric
D024141:Collagen Type IV; D007166:Immunosuppressive Agents; C478221:LAMB1 protein, human; D007797:Laminin; C058783:laminin beta2; D016572:Cyclosporine