Tacrolimus therapy in adult-onset steroid-resistant nephrotic syndrome due to a focal segmental glomerulosclerosis single-center experience.
BACKGROUND
Management of adults with steroid-resistant (SR) nephrotic syndrome due to focal segmental glomerulosclerosis (FSGS) is a challenging task. Is tacrolimus (TAC) effective in this situation without serious adverse effects? This prospective study was done to answer this question.


METHODS
In patients with SR nephrotic syndrome due to FSGS, oral TAC (0.1 mg/kg/day) was started targeting a trough level of 5-10 ng/mL along with oral prednisolone (0.15 mg/kg/day) for 48 weeks. In patients with complete remission (CR), TAC dose was reduced to a target of 3-6 ng/mL whereas in partial responders, TAC trough levels were kept at 5-10 ng/mL. TAC was discontinued in those with no remission at 24 weeks and was deemed TAC resistant. Outcome, namely CR and partial remission (PR), was assessed at the end of 24 and 48 weeks. All patients were prospectively followed for 60 weeks. Relapses after CR or PR were recorded; adverse effects, namely nephrotoxicity (>25% rise in creatinine), cosmetic effects, infections and hyperglycemia, were recorded every month.


RESULTS
A total of 44 SR-FSGS [not otherwise specified 33 (75%), tip lesion 03 (6.8%) and cellular variant 8 (18.1%)] were analyzed. Mean age was 25.16 ± 8.26 (18-51) years. Of 44 patients, CR and PR were achieved in 17 (38.6%) and 06 (13.6%) patients, respectively. TAC resistance was seen in 21 (47.7%) patients. Time taken to achieve remission was 15.2 ± 6 weeks. Five (21.7%) patients with CR had relapse on tapering the dose and seven (30.4%) after stopping TAC. Reversible nephrotoxicity was seen in seven (15.9%) and irreversible in four patients (9%). TAC-related diarrhea was the problem in 10 (22.7%), and infections were seen in 19 patients (43.1%). Impaired fasting glucose and diabetes mellitus were seen in 10 patients (22.7%).


CONCLUSIONS
TAC is an effective agent in the management of SR-FSGS. However, strict renal function and blood sugar monitoring is required due to its potential nephrotoxicity and diabetogenic potential.
Department of Nephrology, PGIMER, Chandigarh, India.
Raja
R
Ramachandran
Department of Nephrology, PGIMER, Chandigarh, India.
Vivek
V
Kumar
Department of Nephrology, PGIMER, Chandigarh, India.
Manish
M
Rathi
Department of Histopathology, PGIMER, Chandigarh, India.
Ritambhra
R
Nada
Department of Nephrology, PGIMER, Chandigarh, India.
Vivekanand
V
Jha
Department of Nephrology, PGIMER, Chandigarh, India.
Krishan Lal
KL
Gupta
Department of Nephrology, PGIMER, Chandigarh, India.
Vinay
V
Sakhuja
Department of Nephrology, PGIMER, Chandigarh, India.
Harbir Singh
HS
Kohli
D000293:Adolescent; D000328:Adult; D003404:Creatinine / Q000097:blood; D004351:Drug Resistance / Q000187:drug effects*; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000150:complications*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000188:drug therapy* / Q000209:etiology; D011239:Prednisolone / Q000627:therapeutic use; D011446:Prospective Studies; D012008:Recurrence; D012074:Remission Induction; D013256:Steroids / Q000494:pharmacology*; D016559:Tacrolimus / Q000627:therapeutic use*; D055815:Young Adult
D007166:Immunosuppressive Agents; D013256:Steroids; D011239:Prednisolone; D003404:Creatinine; D016559:Tacrolimus
FSGS; TAC; eGFR