2011 was remarkable for the progress made in the
understanding of glomerulonephritis.
In the NEJM paper by
Mele, MYO1E mutations were implicated in the etiology of
childhood-onset glucocorticoid-resistant focal segmental glomerulosclerosis.
These observations were based on whole-genome linkage analysis followed by
high-throughput sequencing of the positive-linkage area in a family with
autosomal recessive focal segmental glomerulosclerosis.
In the NEJM paper by
Debiec, a study of 11 patient's, demonstrated that cationic bovine serum
albumin is pathogenic in early childhood membranous nephropathy. The mechanism
is through binding to the anionic glomerular capillary wall and in situ
formation of immune complexes.
In the paper by Clement in Nature
Medicine, podocyte-secreted Angptl4 is demonstrated to have a
key role in nephrotic syndrome.
Also in Nature Medicine, Wei et al
show that circulating urokinase receptor looks like the likely cause of
focal segmental glomerulosclerosis.
The pioneering studies of Richard Bright in re-characterizing dropsy from a cardiac to a renal malady in the mid-1820's laid the foundations of these more recent advances.
The picture shows the kidney of "Mary B, aged 34, a patient of Richard Bright, who was admitted with proteinuria of five years duration. She died from a seizure and at autopsy the heart was healthy and of a moderate size. The kidney is of normal size and has a granular surface. Histologically there is interstitial fibrosis and destruction of the glomeruli." (Source for description and picture of specimen is the Gordon Museum, Kings College. London).
Dr. Richard Bright, one of Guy’s Hospital’s great men, died 153
years ago in December. Incidentally, the other two great men from Guy's (from that period) were Addison and Hodgkin. Bright
is thought of as ‘the father of nephrology’. A detailed history is provided here and here.
Bright had studied medicine at Edinburgh, Guy’s and
Cambridge, qualifying from Edinburgh in 1813.
Early in his medical career, Bright began studying organic
changes in the kidney’s structure. Between 1827 and 1836 Bright published three
works describing and linking dropsy (edema), urine which coagulated on heating
and postmortem changes in the kidneys.
He attributed edema and albuminuia to be the consequence of kidney disease. His work clearly differentiated between renal and cardiac dropsy, i.e. edema and proteinuria in nephrotic syndrome from that observed in cardiac failure.
In the
1825-1827 period, Bright studied 23 patients with albumin in the urine. More
than half of these patients died, and all had kidney disease. These findings,
among others, were published in 1827, and this presentation of kidney disease
was named “Bright’s Disease.”
He attributed edema and albuminuia to be the consequence of kidney disease. His work clearly differentiated between renal and cardiac dropsy, i.e. edema and proteinuria in nephrotic syndrome from that observed in cardiac failure.
In 1972, Weller and Nestor performed histologic examination
of the kidney from three patients with renal disease (BMJ)
that were originally described by Richard Bright between 1827 and 1836 and
preserved at the Gordon Museum. 2 of the 3 cases had membrano-proliferative
glomerulonephritis, whereas the third case had renal amyloidosis.
