Obesity-related glomerulopathy: an emerging epidemic.
BACKGROUND
We report the first large renal biopsy-based clinicopathologic study on obesity-related glomerulopathy.


METHODS
Obesity was defined as body mass index (BMI)> 30 kg/m2. Obesity-related glomerulopathy (ORG) was defined morphologically as focal segmental glomerulosclerosis and glomerulomegaly (O-FSGS; N = 57) or glomerulomegaly alone (O-GM; N = 14).


RESULTS
Review of 6818 native renal biopsies received from 1986 to 2000 revealed a progressive increase in biopsy incidence of ORG from 0.2% in 1986-1990 to 2.0% in 1996-2000 (P = 0.0001). Mean BMI in ORG was 41.7 (range 30.9 to 62.7). Indications for renal biopsy included proteinuria (N = 40) or proteinuria and renal insufficiency (N = 31). Seventy-one patients with ORG were compared to 50 patients with idiopathic FSGS (I-FSGS). Patients with ORG were older (mean 42.9 vs. 32.6 years, P < 0.001) and more often Caucasian (75% vs. 52%; P = 0.003). ORG patients had a lower incidence of nephrotic range proteinuria (48% vs. 66%; P = 0.007) and nephrotic syndrome (5.6% vs. 54%; P < 0.001), with higher serum albumin (3.9 vs. 2.9 g/dL; P < 0.001), lower serum cholesterol (229 vs. 335 mg/dL; P < 0.001), and less edema (35% vs. 68%; P = 0.003). On renal biopsy, patients with ORG had fewer lesions of segmental sclerosis (10 vs. 39%; P < 0.001), more glomerulomegaly (100% vs. 10%; P < 0.001), and less extensive foot process effacement (40 vs. 75%; P < 0.001). Glomerular diameter in ORG (mean 226 mu) was significantly larger than age- and sex-matched normal controls (mean 168 mu; P < 0.001). Follow-up was available in 56 ORG patients (mean 27 months) and 50 idiopathic FSGS controls (mean 38 months). A total of 75% of ORG patients received angiotensin-converting enzyme (ACE) inhibition or A2 blockade while 78% of the I-FSGS patients received immunosuppressive therapy. ORG patients had less frequent doubling of serum creatinine (14.3% vs. 50%; P < 0.001) and progression to ESRD (3.6% vs. 42%; P < 0.001). On multivariate analysis, presenting serum creatinine and severity of proteinuria were the only predictors of poor outcome in ORG.


CONCLUSIONS
ORG is distinct from idiopathic FSGS, with a lower incidence of nephrotic syndrome, more indolent course, consistent presence of glomerulomegaly, and milder foot process fusion. The ten-fold increase in incidence over 15 years suggests a newly emerging epidemic. Heightened physician awareness of this entity is needed to ensure accurate diagnosis and appropriate therapy.
Kambham
N
N
Department of Pathology, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA.
Markowitz
G S
GS
Valeri
A M
AM
Lin
J
J
D'Agati
V D
VD
D000328:Adult; D001706:Biopsy; D015331:Cohort Studies; D004196:Disease Outbreaks; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000453:epidemiology / Q000209:etiology / Q000473:pathology / Q000628:therapy; D006801:Humans; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology / Q000628:therapy; D008297:Male; D015999:Multivariate Analysis; D009765:Obesity / Q000150:complications*; D012016:Reference Values; D016896:Treatment Outcome; D014481:United States