Renal biopsy conference this past Thursday at the Brigham
brought forth an interesting discussion about smoking causing nodular
glomerulosclerosis. It was suggested that there was a strong association
between smoking and glomerulosclerosis. So, what’s the bottom line? Is there a
causal relationship?
One of the first substantive morphologic association study –
and the one frequently cited - was by the group at Columbia, New York by
Glen Markowitz published in Human Pathology.
Markowitz reviewed 5,073 native renal biopsy samples at Columbia University between 1996 and 2001.
They reported that after excluding diabetes mellitus, 0.45%
biopsies or 23 patients had prominent diffuse and nodular mesangial
sclerosis, glomerular basement membrane thickening, arteriosclerosis, and
arteriolosclerosis. Patients with nodular sclerosis were mostly older white men
and the majority had hypertension, renal insufficiency, hypertension, and proteinuria
(nearly 70% had >3 g/d of proteinuria). Hypertension (95.7), smoking (91.3%),
and hypercholesterolemia (90%) were highly prevalent. Follow-up data were
available for 17 patients, 6 of whom reached end-stage renal disease (ESRD)
(35.3%). By Kaplan-Meier estimates, the median time after biopsy to ESRD was 26
months. Predictors of progression to ESRD included continuation of smoking (P
= .0165), lack of angiotensin II blockade (P = .0007), degree of tubular
atrophy and interstitial fibrosis (P = .0517), and degree of
arteriosclerosis (P = .0096). They concluded that idiopathic nodular was
linked to hypertension and cigarette smoking.
There are several small studies that document an
association. Liang et al from the Mayo presented a case in AJKD in 2007:
“In this
report, we describe clinical and kidney biopsy findings for a 66-year-old woman
with a history of long-term heavy cigarette smoking who developed proteinuria
and decreasing renal function. This study also describes clinical and kidney
biopsy findings for 9 patients with a history of smoking. None of these
patients had hypertension, diabetes mellitus, or other risk factors that might
result in vascular injury. Renal biopsy specimens showed a range of long-term
changes with varying degrees of focal segmental or focal global
glomerulosclerosis, nodular glomerulosclerosis, ischemic glomeruli,
interstitial fibrosis and tubular atrophy, and mild to moderate arterial
sclerosis and arteriolar hyalinosis. Electron microscopy often showed
glomerular capillary wall thickening caused by subendothelial expansion by
cellular elements and new basement formation resulting in segments of double contours.
These changes indicate endothelial injury and glomerular capillary wall
remodeling; the lesions mimic those seen in patients with chronic hypertension
and chronic or healed thrombotic microangiopathies.”
Likewise Li
et al in 2008 write:
“Idiopathic
nodular glomerulosclerosis is an enigmatic condition closely resembling
diabetic nodular glomerulosclerosis without evidence of diabetic mellitus or
other specific disease. Idiopathic nodular glomerulosclerosis remains a rare
disease entity with an unclear pathogenesis. Clinicopathologic features of 15
patients with idiopathic nodular glomerulosclerosis were evaluated in a
retrospective review of renal biopsies between 1998 and 2007. Our study cohort
consisted predominantly of older (mean age, 64.2 years) white (73%) women
(67%). Fourteen patients (93%) had a history of hypertension, and 10 (67%) were
active smokers at the time of biopsy. Nine patients (60%) were obese (body mass
index, >30 kg/m(2)) and 4 (27%) were overweight (body mass index, 25-29.9
kg/m(2)). Fourteen patients (93%) presented with renal insufficiency with mean
serum creatinine level of 2.8 mg/dL. All 15 patients presented with proteinuria
(mean urinary protein excretion, 5.6 g/24 h). Eleven patients (73%) presented
with nephrotic-range proteinuria and 8 (53%) with nephrotic syndrome.
Histopathologic findings showed nodular glomerulosclerosis (100%), moderate to
severe arterio-arteriolosclerosis (100%), and glomerular basement membrane
thickening (100%). Immunofluorescence and electron microscopy studies had no
other specific findings. Our results confirm previous studies of a close
association of hypertension and smoking with idiopathic nodular
glomerulosclerosis.”
Do these
papers prove a causal relationship between smoking and glomerulosclerosis – no is
the answer.
