Nephrotic syndrome - Indian Studies

1. Nephrol Dial Transplant. 2008 Mar;23(3):910-3. Epub 2007 Nov 26.

Tacrolimus: a new therapy for steroid-resistant nephrotic syndrome in children.

Gulati S, Prasad N, Sharma RK, Kumar A, Gupta A, Baburaj VP.

Department of Nephrology, Sanjay Gandhi Post Graduate Institute of Medical
Sciences, Lucknow, India. sgulatipedneph@yahoo.com

This study was conducted to evaluate the safety and efficacy of tacrolimus (TAC) 
in children with SRNS. The study group comprised of 22 consecutive children with 
steroid-resistant nephrotic syndrome (SRNS) who were studied prospectively. TAC
was initiated with a dose of 0.10 mg/kg/day, and the dose was increased to attain
a trough level of 5.0-10.0 g/l. These patients were treated with concomitant
prednisone, which was subsequently tapered off and stopped. The primary outcome
variable was the number of patients who attained a complete remission (CR) or
partial remission (PR). The mean age of onset was 7.33 +/- 5.9 years, and there
were 20 boys and 2 girls. Of the 22 children, 9 had minimal change disease, 11
had focal segmental glomerulosclerosis and the other 2 had diffuse mesangial
hypercellularity on histopathology. TAC had to be withdrawn in 3 children because
of its side effects. Of the remaining 19 children who received adequate therapy
and were able to achieve target levels, CR was seen in 16 (84%) children, 2
(10.5%) attained PR and 1 was nonresponsive. The mean time to achieve remission
was 63.2 +/- 44 days and the mean dose of TAC was 0.18 +/- 0.07 mg/kg. The mean
urine spot protein/creatinine ratios were significantly lower (0.33 +/- 0.58 vs. 
13.5 +/- 21.9 mg/mg, p = 0.002) and the mean serum albumin levels were
significantly higher (3.92 +/- 0.35 g/dl vs. 2.39 +/- 0.56 g/dl, p = 0.00005), as
compared to those prior to starting TAC. The mean glomerular filtration rate
values at the end of the study were similar to those prior to starting TAC (97.9 
+/- 21.2 ml/min/1.73 m(2) vs. 96.4 +/- 18.4 ml/min/1.73 m(2), p = 0.30). The mean
duration of follow-up was 290 +/- 126 days. This is the largest study so far on
the safety and efficacy of TAC therapy in SRNS. Our results suggest that TAC is
an effective therapeutic modality for SRNS, including the subgroup of children
who are nonresponsive to the current therapeutic modalities like cyclophosphamide
and cyclosporine.


PMID: 18039644 [PubMed - indexed for MEDLINE]


2. Indian J Nephrol. 2008 Jan;18(1):31-9.

Revised guidelines for management of steroid-sensitive nephrotic syndrome.

Bagga A.

Department of Pediatrics, All India Institute of Medical Sciences, New Delhi,
India.

JUSTIFICATION: In 2001, the Indian Pediatric Nephrology Group formulated
guidelines for management of patients with steroid-sensitive nephrotic syndrome. 
In view of emerging scientific evidence, it was felt necessary to review the
existing recommendations.PROCESS: Following a preliminary meeting in March 2007, 
a draft statement was prepared and circulated among pediatric nephrologists in
the country to arrive at a consensus on the evaluation and management of these
patients.
OBJECTIVES: To revise and formulate recommendations for management of
steroid-sensitive nephrotic syndrome.
RECOMMENDATIONS: The need for adequate corticosteroid therapy at the initial
episode is emphasized. Guidelines regarding the initial evaluation, indications
for renal biopsy and referral to a pediatric nephrologist are updated. It is
proposed that patients with frequently relapsing nephrotic syndrome should, at
the first instance, be treated with longterm, alternate-day prednisolone. The
indications for use of alternative immunosuppressive agents, including
levamisole, cyclophosphamide, mycophenolate mofetil, and cyclosporin are
outlined. The principles of dietary therapy, management of edema, and prevention 
and management of complications related to nephrotic syndrome are described.
These guidelines, formulated on the basis of current best practice, are aimed to 
familiarize physicians regarding principles of management of children with
steroid-sensitive nephrotic syndrome.


PMCID: PMC2847730
PMID: 20368921 [PubMed - in process]


3. Indian Pediatr. 2008 Mar;45(3):203-14.

Management of steroid sensitive nephrotic syndrome: revised guidelines.

Indian Pediatric Nephrology Group, Indian Academy of Pediatrics, Bagga A, Ali U, 
Banerjee S, Kanitkar M, Phadke KD, Senguttuvan P, Sethi S, Shah M.

Department of Pediatrics, All India Institute of Medical Sciences, Ansari Nagar, 
New Delhi, India. arvindbagga@hotmail.com

JUSTIFICATION: In 2001, the Indian Pediatric Nephrology Group formulated
guidelines for management of patients with steroid sensitive nephrotic syndrome. 
In view of emerging scientific evidence, it was felt necessary to review the
existing recommendations.PROCESS: Following a preliminary meeting in March 2007, 
a draft statement was prepared and circulated among pediatric nephrologists in
the country to arrive at a consensus on the evaluation and management of these
patients.
OBJECTIVES: To revise and formulate recommendations for management of steroid
sensitive nephrotic syndrome.
RECOMMENDATIONS: The need for adequate cortico-steroid therapy at the initial
episode is emphasized. Guidelines regarding the initial evaluation, indications
for renal biopsy and referral to a pediatric nephrologist are updated. It is
proposed that patients with frequently relapsing nephrotic syndrome should, at
the first instance, be treated with long-term, alternate-day prednisolone. The
indications for use of alternative immunosuppressive agents, including
levamisole, cyclophosphamide, mycophenolate mofetil and cyclosporin are outlined.
The principles of dietary therapy, management of edema, and prevention and
management of complications related to nephrotic syndrome are described. These
guidelines, formulated on basis of current best practice, are aimed to
familiarize physicians regarding management of children with steroid sensitive
nephrotic syndrome.


PMID: 18367765 [PubMed - indexed for MEDLINE]


4. Pediatr Nephrol. 2008 Sep;23(9):1495-502. Epub 2008 Jun 20.

Efficacy of intravenous pulse cyclophosphamide treatment versus combination of
intravenous dexamethasone and oral cyclophosphamide treatment in
steroid-resistant nephrotic syndrome.

Mantan M, Sriram CS, Hari P, Dinda A, Bagga A.

Department of Pediatrics, Maulana Azad Medical College, Delhi, India.

We compared, in a randomized controlled trial, the efficacy of a regimen based on
intravenous (i.v.) cyclophosphamide therapy with a combination of i.v.
dexamethasone and oral cyclophosphamide therapy in inducing remission in patients
with steroid-resistant nephrotic syndrome (SRNS). During April 2001 to December
2003, 52 consecutive patients with idiopathic SRNS, normal renal function and
renal histology findings showing minimal change disease, focal segmental
glomerulosclerosis or mesangioproliferative glomerulonephritis were enrolled into
the study. Patients in group I received i.v. injection of cyclophosphamide once a
month for 6 months and prednisolone on alternate days. Those in group II received
i.v. treatment with dexamethasone (initially on alternate days, later fortnightly
and monthly; total 14 doses), oral cyclophosphamide therapy (for 3 months) and
prednisolone on alternate days. Data from 49 patients (26 in group I, 23 in group
II) were analyzed; their clinical and biochemical features were similar at
inclusion. Following treatment, complete remission was seen in 53.8% and 47.8%
patients in groups I and II, respectively (P = 0.6). Long-term follow up showed
favorable outcome in 14 (53.8%) patients in group I, and 9 (39.1%) in group II.
Chief adverse effects, including cushingoid features and serious infections, were
similar in both groups. Patients receiving i.v. dexamethasone therapy commonly
showed hypertension and hypokalemia, while vomiting and reversible alopecia
occurred in those receiving i.v. treatment with cyclophosphamide. In patients
with SRNS, the efficacy of treatment intravenously with cyclophosphamide and
orally with prednisolone was similar to the combination of dexamethasone
intravenously, orally administered cyclophosphamide and prednisolone.


PMID: 18566839 [PubMed - indexed for MEDLINE]


5. Am J Kidney Dis. 2009 May;53(5):760-9. Epub 2009 Mar 5.

Efficacy and safety of tacrolimus versus cyclosporine in children with
steroid-resistant nephrotic syndrome: a randomized controlled trial.

Choudhry S, Bagga A, Hari P, Sharma S, Kalaivani M, Dinda A.

Division of Nephrology, All India Institute of Medical Sciences, Ansari Nagar,
New Delhi, India.

BACKGROUND: To examine whether tacrolimus is more effective and safe than
cyclosporine (CsA) in inducing remission in patients with steroid-resistant
nephrotic syndrome (SRNS).
STUDY DESIGN: Randomized controlled trial, nonblind, parallel group.
SETTINGS & PARTICIPANTS: Tertiary-care hospital; 41 consecutive patients with
idiopathic SRNS, estimated glomerular filtration rate greater than 60 mL/min/1.73
m(2), and histological characteristics showing minimal change disease, focal
segmental glomerulosclerosis, or mesangioproliferative glomerulonephritis were
randomly assigned to treatment with tacrolimus (n = 21) or CsA (n = 20).
INTERVENTION: Tacrolimus (0.1 to 0.2 mg/kg/d) or CsA (5 to 6 mg/kg/d) for 1 year;
cotreatment with alternate-day prednisolone and enalapril.
OUTCOMES: Patients achieving complete remission (urinary protein-creatinine ratio
< 0.2 g/g and serum albumin > or = 2.5 g/dL) or partial remission (urinary
protein-creatinine ratio, 0.2 to 2 g/g, and serum albumin > or =2.5 g/dL) at 6
and 12 months; time to remission; proportion with relapses; side effects.
RESULTS: No patient was lost to follow-up. After 6 months of therapy, remission
occurred in 18 (85.7%) and 16 patients (80%) treated with tacrolimus and CsA,
respectively (relative risk [RR], 1.07; 95% confidence interval [CI], 0.81 to
1.41). Rates of remission at 12 months were also similar (RR, 1.14; 95% CI, 0.84 
to 1.55). The proportion of patients who experienced relapse was significantly
greater in those receiving CsA compared with tacrolimus (RR, 4.5; 95% CI, 1.1 to 
18.2; P = 0.01). The decrease in blood cholesterol levels was greater with
tacrolimus compared with CsA (difference in mean values, 45.1 mg/dL; 95% CI, 19.1
to 71.2). Persistent nephrotoxicity necessitating stoppage of medicine was seen
in 4.7% and 10% patients, respectively. Cosmetic side effects (hypertrichosis and
gum hypertrophy) were significantly more frequent in CsA-treated patients (P <
0.001).
LIMITATIONS: Single-center study, small sample size, and short duration of
follow-up.
CONCLUSIONS: Tacrolimus or CsA in combination with low-dose steroids show similar
efficacy in inducing remission in patients with SRNS. Therapy with tacrolimus is 
a promising alternative to CsA in view of the lower risk of relapses and lack of 
cosmetic side effects.


PMID: 19268410 [PubMed - indexed for MEDLINE]


6. Pediatr Nephrol. 2009 Aug;24(8):1583-6. Epub 2009 Apr 4.

Efficacy of zinc supplements in reducing relapses in steroid-sensitive nephrotic 
syndrome.

Arun S, Bhatnagar S, Menon S, Saini S, Hari P, Bagga A.

Division of Nephrology, Department of Pediatrics, All India Institute of Medical 
Sciences, New Delhi, India.

Relapses in steroid-sensitive nephrotic syndrome (SSNS) often follow infections
of the respiratory or gastrointestinal tract. Based on data that zinc supplements
reduce the risk of infections, we examined the efficacy of such supplements in
reducing relapse rates in these patients. Eighty-one patients with SSNS (1-16
years old) were stratified into frequent (n = 52) and infrequent (n = 29)
relapsers and randomized to receive 12-months of therapy with the recommended
dietary allowance of zinc (10 mg/day) (n = 40) or placebo (n = 41). Patients with
frequent relapses also received long-term, alternate-day prednisolone. Subjects
receiving zinc showed a 20% lower frequency of relapses, with 44.7% of the
patients having sustained remission compared to 27.5% in the placebo group (P >
0.05). Patients with frequent relapses receiving zinc showed a 28% reduction in
relapse rates and a significantly higher likelihood of sustained remission (P =
0.02). Findings from this double blind, randomized study suggest that zinc
supplementation results in trends towards remission and reduced relapses,
especially in patients with frequent relapses. Prospective, adequately powered
studies are required for confirmation of these findings.


PMID: 19347367 [PubMed - indexed for MEDLINE]


7. Clin J Am Soc Nephrol. 2010 Dec;5(12):2207-12. Epub 2010 Aug 26.

Efficacy and safety of treatment with rituximab for difficult steroid-resistant
and -dependent nephrotic syndrome: multicentric report.

Gulati A, Sinha A, Jordan SC, Hari P, Dinda AK, Sharma S, Srivastava RN, Moudgil 
A, Bagga A.

Division of Pediatric Nephrology, All India Institute of Medical Sciences, Ansari
Nagar, New Delhi, India.

BACKGROUND AND OBJECTIVES: The treatment of idiopathic nephrotic syndrome is
often complicated by a refractory and relapsing course, with risk of drug
toxicity and progressive renal failure. We report the efficacy and safety of
rituximab in patients with steroid-resistant (SRNS) and steroid-dependent
nephrotic syndrome (SDNS) refractory to standard therapy.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a cohort study in
academic, tertiary care centers in India and the United States. Patients with
SRNS or SDNS, not responding to medications or showing calcineurin inhibitor
toxicity, treated with two to four doses of intravenous rituximab, and followed
≥12 months were included. Remission was termed as complete, partial, or no
response.
RESULTS: Thirty-three patients with SRNS (24 initial, 9 late resistance) and 24
with SDNS, with mean ages of 12.7 ± 9.1 and 11.7 ± 2.9 years, respectively, were 
included. Six months after rituximab therapy, 9 (27.2%) patients with SRNS showed
complete remission, 7 (21.2%) had partial remission, and 17 (51.5%) had no
response. At 21.5 ± 11.5 months, remission was sustained in 15 (complete: 7,
partial: 8) patients. Of 24 patients with SDNS, remission was sustained in 20
(83.3%) at 12 months and in 17 (71%) at follow-up of 16.8 ± 5.9 months. The mean 
difference in relapses before and 12 months after treatment with rituximab was
3.9 episodes/patient per year.
CONCLUSIONS: Therapy with rituximab was safe and effective in inducing and
maintaining remission in a significant proportion of patients with difficult SRNS
and SDNS.


PMCID: PMC2994081 [Available on 2011/12/1]
PMID: 20798255 [PubMed - in process]


8. Clin J Am Soc Nephrol. 2011 Jan;6(1):63-9. Epub 2010 Sep 16.

Daily corticosteroids reduce infection-associated relapses in frequently
relapsing nephrotic syndrome: a randomized controlled trial.

Gulati A, Sinha A, Sreenivas V, Math A, Hari P, Bagga A.

Division of Nephrology, Department of Pediatrics, All India Institute of Medical 
Sciences, Ansari Nagar, New Delhi, India.

BACKGROUND AND OBJECTIVES: Relapses of nephrotic syndrome often follow minor
infections, commonly of the upper respiratory tract. Daily administration of
maintenance prednisolone during intercurrent infections was examined to determine
whether the treatment reduces relapse rates in children with frequently relapsing
nephrotic syndrome.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a randomized controlled trial
(nonblind, parallel group, tertiary-care hospital), 100 patients with idiopathic,
frequently relapsing nephrotic syndrome eligible for therapy with prolonged
low-dose, alternate-day prednisolone with or without levamisole were randomized
to either receive their usual dose of alternate-day prednisolone daily for 7 days
during intercurrent infections (intervention group) or continue alternate-day
prednisolone (controls). Primary outcome was assessed by comparing the rates of
infection-associated relapses at 12-month follow-up. Secondary outcomes were the 
frequency of infections and the cumulative amount of prednisolone received in
both groups.
RESULTS: Patients in the intervention group showed significantly lower
infection-associated (rate difference, 0.7 episodes/patient per year; 95%
confidence intervals [CI] 0.3, 1.1) and lower total relapse rates (0.9
episodes/patient per year, 95% CI 0.4, 1.4) without increase in steroid toxicity.
Poisson regression, adjusted for occurrence of infections, showed that daily
administration of prednisolone during infections independently resulted in 59%
reduction in frequency of relapses (rate ratio, 0.41; 95% CI 0.3, 0.6). For every
six patients receiving this intervention, one showed a reduction of relapse
frequency to less than three per year.
CONCLUSIONS: Daily administration of maintenance doses of prednisolone, during
intercurrent infections, significantly reduces relapse rates and the proportion
of children with frequently relapsing nephrotic syndrome.


PMCID: PMC3022249 [Available on 2012/1/1]
PMID: 20847092 [PubMed - in process]


9. Ren Fail. 2011;33(1):102-7.

IgA nephropathy in India: what we do know.

Chacko B.

Department of Nephrology, St John's Medical College Hospital, Bangalore, India.
bobcha@hotmail.com

BACKGROUND: Even though IgA nephropathy (IgAN) is not the most common primary
glomerulonephritis (GN) in India, the outcome of patients with IgAN in India is
poor when compared with other parts of the world, which is a burden in itself.
METHODS: Basic and clinical research work in India on primary IgAN was
systematically reviewed. Comparisons between data from India and those from other
countries were made.
RESULTS: IgAN constitutes between 7% and 16% of most biopsy samples from India,
bearing in mind these figures may represent only the tip of the iceberg.
Nephrotic syndrome and renal failure seem to be common presenting features. The
renal survival rates appear to be dismally low. DD genotype of angiotensin-1
converting enzyme (ACE) gene may predispose the individual to IgAN in Indian
population. As might be expected, IgAN can recur posttransplant though the
posttransplant course is indolent. There are no data on the treatment aspects of 
IgAN.
CONCLUSION: Low incidence but marked severity characterizes IgAN in India. It is 
apparent that IgAN seems to have a poor outcome in India. What we are unsure of
is the reason behind it. In-depth basic studies and multicenter clinical trials
are needed to address this bizarre pattern.


PMID: 21219216 [PubMed - in process]