Membranous Nephropathy - Indian Studies

1. Nephrol Dial Transplant. 2008 Jun;23(6):1926-30. Epub 2007 Nov 7.

Mycophenolate mofetil or standard therapy for membranous nephropathy and focal
segmental glomerulosclerosis: a pilot study.

Senthil Nayagam L, Ganguli A, Rathi M, Kohli HS, Gupta KL, Joshi K, Sakhuja V,
Jha V.

Department of Nephrology, Postgraduate Institute of Medical Education and
Research, Chandigarh, India.

Comment in:
    Nephrol Dial Transplant. 2008 Jun;23(6):1793-6.

BACKGROUND: The current treatment regimes for patients with nephrotic syndrome
due to idiopathic membranous nephropathy (MN) and focal segmental
glomerulosclerosis (FSGS) are based on steroids and/or cytotoxic agents. Data on 
the effect of mycophenolate mofetil (MMF) for these conditions are scarce and
confounding.
METHODS: We compared the efficacy of an MMF-based therapy with standard therapies
in inducing remission in adult nephrotics with MN and FSGS in a randomized pilot 
study. MMF was given at 2 g/day for 6 months along with prednisolone at 0.5
mg/kg/day for 2-3 months. Conventional therapy was prednisolone 1 mg/kg/day for
3-6 months for FSGS and alternating monthly cycles of steroids and
cyclophosphamide for 6 months for MN. The primary end point was change in urinary
protein/creatinine ratio.
RESULTS: A total of 54 patients (21 MN and 33 FSGS) were recruited; 28 were
randomized to receive MMF (group A) and 26 were on conventional treatment (group 
B). There was no difference in the proportion of patients achieving remission in 
two groups (64 and 80% in MN and 70 and 69% in FSGS). The frequency of relapses
and incidence of infections was also similar. FSGS patients in group A achieved
remission faster and received a lower cumulative steroid dose.
CONCLUSIONS: A 6-month treatment with MMF is as effective as the conventional
treatment for primary treatment of MN and FSGS in the short term. It induces
remission faster and reduces steroid exposure in FSGS patients. Studies with more
cases and longer follow-up are required to evaluate its impact on preservation of
kidney function.


PMID: 17989103 [PubMed - indexed for MEDLINE]


2. J Am Soc Nephrol. 2007 Jun;18(6):1899-904. Epub 2007 May 9.

A randomized, controlled trial of steroids and cyclophosphamide in adults with
nephrotic syndrome caused by idiopathic membranous nephropathy.

Jha V, Ganguli A, Saha TK, Kohli HS, Sud K, Gupta KL, Joshi K, Sakhuja V.

Department of Nephrology, Postgraduate Institute of Medical Education and
Research, Chandigarh 160 012 India. vjha@pginephro.org

Comment in:
    Nat Clin Pract Nephrol. 2007 Oct;3(10):534-5.

Idiopathic membranous nephropathy (IMN) is the most common cause of nephrotic
syndrome in adults. Universal consensus regarding the need for and the modality
of therapy has not been formed because of a lack of controlled trials of
sufficient size, quality, and duration. This study compared the effect of a 6-mo 
course of alternating prednisolone and cyclophosphamide with supportive treatment
in adults with nephrotic syndrome caused by IMN on doubling of serum creatinine, 
development of ESRD, and quality of life in a randomized, controlled trial.
Patients were followed up for 10 yr. Data were analyzed on an intention-to-treat 
basis. A total of 93 patients completed the study. Of the 47 patients who
received the experimental protocol, 34 achieved remission (15 complete and 19
partial), compared with 16 (five complete, 11 partial) of 46 in the control group
(P < 0.0001). The 10-yr dialysis-free survival was 89 and 65% (P = 0.016), and
the likelihood of survival without death, dialysis, and doubling of serum
creatinine were 79 and 44% (P = 0.0006) in the two groups. Treated patients
exhibited significantly lower prevalence of edema, hypertension, hypoalbuminemia,
hyperlipidemia that required therapy, angiotensin-converting enzyme
inhibitor/angiotensin II receptor blocker use, and better quality of life on
follow-up. The incidence of infections was similar in the two groups. In
conclusion, untreated IMN with nephrotic syndrome is associated with a high risk 
for deterioration of renal function. A 6-mo regimen of cyclophosphamide and
steroids induces remissions in a high proportion, arrests progression of renal
insufficiency, and improves quality of life.


PMID: 17494881 [PubMed - indexed for MEDLINE]


3. Pediatr Nephrol. 2003 Jul;18(7):657-60. Epub 2003 May 13.

Histopathological spectrum of childhood nephrotic syndrome in Indian children.

Kumar J, Gulati S, Sharma AP, Sharma RK, Gupta RK.

Department of Nephrology, Sanjay Gandhi Post Graduate Institute of Medical
Sciences, Raebareli Road, Lucknow 226014, India.

Nephrotic syndrome in children is a clinical manifestation of different
histopathological subtypes. There is a paucity of recent large studies dealing
with the histopathological spectrum from developing countries. A prospective
study was performed from January 1990 to December 2000 at our center, involving
600 children (with age of onset up to 16 years) with idiopathic nephrotic
syndrome (INS). The objectives were: (1) to study the histopathological
distribution of different subtypes of INS and (2) to compare the clinical and
biochemical parameters at the time of diagnosis of minimal change disease (MCD)
with non-MCD subtypes. For the purpose of this study we analyzed only those
children with INS who underwent biopsies. The study group included 290 children
in which adequate biopsy reports were available. There were 213 males and 77
females. Mean age at onset of INS was 7.9+5.1 years. Facial edema was found in
286 (98.6%), microhematuria in 120 (41.3%), gross hematuria in 7 (2.5%), and
hypertension in 77(26.8%) patients. All patients of the study group were
seronegative for HBsAg and HIV. Focal and segmental glomerulosclerosis (FSGS) was
the most common histopathological subtype, occurring in 110 of 290 children
(38%). Other subtypes included MCD in 95 children (32%), membranoproliferative
glomerulonephritis (MPGN) in 44 children (15%), mesangioproliferative
glomerulonephritis in 33 children (11%), membranous glomerulonephritis in 5
children (2%), and diffuse mesangial sclerosis in 3 children (1%). In children
under 8 years of age, MCD was the most common entity, whereas FSGS predominated
in children with age at onset greater than 8 years. The age at onset of nephrotic
syndrome was significantly higher in the non-MCD group than the MCD group. The
incidence of hypertension, microhematuria, and gross hematuria was significantly 
lower in the MCD group. MCD remains the most common histopathological subtype in 
Indian children with INS and onset under 8 years of age. The incidence of MPGN
continues to be high. MCD can be differentiated from non-MCD subtype by younger
age at onset, absence of hypertension, and absence of microscopic hematuria.


PMID: 12743793 [PubMed - indexed for MEDLINE]


4. Pediatr Nephrol. 2002 Jun;17(6):404-8.

Do current recommendations for kidney biopsy in nephrotic syndrome need
modifications?

Gulati S, Sharma AP, Sharma RK, Gupta A, Gupta RK.

Department of Nephrology, Sanjay Gandhi Post Graduate Institute of Medical
Sciences, Raebareli Road, Lucknow 226014, India. sgulati@sgpgi.ac.in

The current recommendations of kidney biopsy in childhood idiopathic nephrotic
syndrome (CINS) were put forward to minimize unnecessary kidney biopsies in
underlying minimal change disease (MCD). However, there remains a diversity of
opinion about the criteria for biopsying children with idiopathic nephrotic
syndrome. This study was conducted to prospectively study their usefulness in
avoiding biopsies in MCD and to evaluate further modifications for minimizing
biopsies in CINS. Of 400 consecutive CINS patients, 222 patients were subjected
to kidney biopsy according to the current recommendations. The histopathology
spectrum of these selectively biopsied children revealed focal segmental
glomerulosclerosis (FSGS) in 39%, MCD in 34.2%, membranoproliferative
glomerulonephritis (MPGN) in 16.2%, mesangioproliferative glomerulonephritis
(MesPGN) in 7.6%, membranous nephropathy (MN) in 1.8%, and diffuse mesangial
sclerosis (DMS) in 0.9%. We observed that despite the current recommendations and
efforts to minimize biopsy, 34% of children had MCD on histopathology. Two or
more clinical (hematuria and hypertension) or biochemical (renal insufficiency)
parameters were present in all children with MPGN. Low C3 was present only in
children with MPGN. All the steroid responders were found to have MCD, FSGS, or
MesPGN on biopsy. Cyclophosphamide response correlated better with steroid
responsiveness ( P=0.02) than with histo- pathology ( P=0.80) in MCD, FSGS, and
MesPGN. Based on these observations, we suggest some modifications in current
recommendations for kidney biopsy to minimize biopsying children with MCD. These 
are (1) biopsies in children (age 1-16 years) should be restricted (a) to a
subgroup with two or more clinical and biochemical parameters and (b) in steroid 
non-responders, (2) the decision to administer cyclophosphamide should be based
on steroid response pattern without requiring a prior routine biopsy.


PMID: 12107803 [PubMed - indexed for MEDLINE]