This is the final talk from the 4-part Glomerulonephritis Symposium at the ASN (see the talks by
Drs. Cattran, Appel, and Schnaper that are already posted). Dr. Hebert first reviews the causes of
secondary membranous nephropathy that must be ruled out, and then describes poor prognostic factors,
including increased serum creatinine, heavy proteinuria, and adverse renal histology (scarring) in
the presence of proteinuria. He then describes the Schieppati study in NEJM which suggests to some
that MN does not require aggressive treatment, and places against this the 10-year outcomes from the
Ponticelli study, which suggested that therapy with immunosuppressives gave superior long-term renal
survival and remission rates. He goes on to describe results of a meta-analysis and his own
experience at Ohio State University. Dr. Hebert then details the rationale behind adjunctive
therapy, and presents his own protocol. He includes a discussion of his results suggesting an
adverse effect of high daily urinary volume on renal survival in patients with MN. He then turns to
immunosuppressive protocols, touches on the risks of malignancy associated with use of
cyclophosphamide, and closes with an appeal to not simply treat all patients conservatively in the
assumption that all with MN will have a benign course.
Another talk from the 4-part Glomerulonephritis Symposium at the ASN (see the talks by Dr. Cattran
and by Dr. Schnaper that are already posted). Dr. Appel first reviews prognostic indicators for
lupus nephritis, and emphasizes the recent data suggesting that African Americans respond poorly to
therapy. He then reviews use of cyclophosphamide, plasmapheresis and cyclosporin. In part two of
the talk, newer therapies are discussed, including a new toleragen drug, monoclonal antibodies,
anti-CD40 ligand, and bindarit, a new drug that blocks upregulation of monocyte chemoattractant
protein. Use of mycophenolate mofetil is also discussed.
Another talk from the 4-part Glomerulonephritis Symposium at the ASN (see the talk by Dr. Cattran
that is already posted). Dr. Bill Schnaper, a pediatric nephrologist, discusses management of
nephrotic syndrome in children. He starts out with some basic definitions, reviews the glomerular
filtration barrier, points out that there may be two types of nephrosis based on whether clearance
of macromolecules is increased or reduced. Dr. Schnaper then focuses on minimal change nephropathy,
and points out that response in children is more rapid than in adults. Specific therapy remains
steroids, and resistance can be managed by more steroids, alkylating agents, cyclosporine, or
mycophenolate. He discusses the role of albumin infusion in cases of hypoalbuminemia, use of
diuretics to treat edema, and finishes up with a discussion of associated abnormalities, including
lipid changes, hypercoagulability, and other well-known findings pertaining to hormones, immune
dysfunction, anemia, propensity to infection. A treatment algorithm is given at the end of the
talk.
The third of many talks from the 1999 ASN Miami meetings; this one is from the Renal Week course on
Acute Renal Failure in the ICU. Dr. Palevsky, who is from the mecca of liver transplantation at the
University of Pittsburgh, begins with a discussion of his patient series, recounts the causes of
renal failure in his patients and lists their comorbid conditions. He reviews the effects of renal
failure on liver transplant survival, and indications and relative contraindications for dialysis
therapy. He shows that GFR can be very low in such patients, even when serum creatinine is in the
2-3 mg/l range. He reviews the different modes of renal replacement therapy for liver failure
patients, and reasons why he favors CRRT. The issue of elevated intracranial pressure in liver
failure patients is presented as well as its management. Dr. Palevsky closes with a discussion of
newer methods of extracorporeal liver support including hemodiabsorption and attempts at creating a
bioartificial liver.
The second of many talks from the 1999 ASN Miami meetings. Dr.
Cattran's lecture was part of a four-speaker symposium presented at
the ASN, including Drs. Appel, Schnaper, and Hebert. For logistical
reasons, we are posting these talks individually.
Dr. Cattran first goes over levels of evidence for rating treatment
studies, and keeps this context when discussing various therapeutic
trials for FSGS. He discusses evidence for and against use of
prednisone in FSGS, cytotoxic agents, and cyclosporine, and then
briefly touches on use of plasmapheresis, with and without cytotoxic
therapy and immunoadsorption. He also discusses use of mycophenolate
mofetil, and gives a preview of his experience with cyclosporine, to
be published in Kidney International in the coming month.
The first of many talks from the 1999 ASN Miami meetings. There has been growing realization that,
in both nonuremic and uremic patients, markers of inflammation such as C-reactive protein correlate
with vascular disease and with overall mortality. Dr. Kaysen begins by discussing the central role
of the liver in inflammatory states, and how it can affect and by affected by cytokines such as
interleukin, and how the liver can cause increases in some inflammatory markers (serum amyloid A, C-
reactive protein, fibrinogen), and decreases in others (e.g., albumin). He then covers interleukin-
6 and how it has been shown to be increased in uremia, and describes the utility of IL-1ra as a
marker for increased cytokine activity in uremia. He then discusses serum amyloid A and C-
reactive protein as markers for inflammation in uremia, and also minor acute phase proteins such as
fibrinogen. The role of transport proteins is also discussed. Then he turnes to negative acute
phase proteins, including albumin, transferrin, transthyretin, and Apo A1. Dr. Kaysen presents
data from his own laboratory and that of others showing how serum AA and CRP levels are inversely
correlated with the serum albumin (as is interleukin-6) , and how they relate to mortality. He then
briefly touches on the atherogenic effects of amyloid A, operating via modification of HDL, so that
it fails to protect against LDL oxidation. He also talks about EPO resistance and EPO/Hct ratio as
modulated by cytokine levels.
Dr. Kaysen then presents some interesting sequential data in patients, showing episodic increases in
CRP, SAA, and other acute phase markers, which are not always reflected in the change in serum
albumin levels. He concludes that 30% of dialysis patients at any given time will have elevations
in CRP or SAA, and that this appears to be a marker of increased mortality. Of the various markers
which one can follow, he suggests CRP, based on cost, reliability, and ease of measurement.
Another rerun while we're waiting for a large bolus of talks from the ASN meeting 2 weeks from now.
This is another lecture from the Nordic Nephrology Days (Nordiska Njurdagar) Meeting
held in Lund, Sweden in May of 1997. The meeting was held to commemorate 50 years passing since
Nils Alwall performed the first human dialysis in Sweden at the University of Lund. The soundfile
and some of the graphics from the talk have now been updated.
Dr. John Daugirdas begins with a discussion of why many nephrologists really don't understand urea
kinetic modeling (it is communicated in the language of differential equations), and then presents a
simplified, yet pharmacologically correct approach to the relationship between the URR and the Kt/V.
The basis for the logarithmic relationship is presented, along with the need for a
correction for ultrafiltration. The basic outcomes data linking URR and Kt/V to survival are then
reviewed. The basis of the DOQI recommendations of a single-pool Kt/V of 1.2 (or URR of 65%) is
discussed, as well as the design of the NIH HEMO trial, which will assess possible beneficial
effects of higher levels of Kt/V and URR.
In part two, the issue of urea rebound is discussed. The three phases of rebound are presented,
including access recirculation, cardiopulmonary recirculation, and compartment effects. The
importance of dead space in the arterial line is stressed, and the reasoning behind the 10-20 sec
slow flow method for drawing the postdialysis blood is given. Cardiopulmonary recirculation is
defined, and it is shown how this can confound measurement of access recirculation. Compartment
effects are then addressed, and the physiologic basis is discussed of urea sequestration in poorly
perfused compartments that contain substantial total body water and hence urea. The mathematical
derivation of the "rate equation", which enables one to correct post-dialysis Kt/V to
equilibrated Kt/V is presented. The validation of the rate equation by the NIH Hemo study is
discussed, as well as the role of dialysate side urea kinetic modeling. The effect of cardiac
output and other physiologic factors that may affect urea rebound is discussed.
One issue for HDCN will soon be when to remove a multimedia symposium from the website due to
obsolescence. This particular talk by Dr. Carl Kjellstrand, given at the 1997 Nordic Nephrology
Days (Nordiska Njurdagar) Meeting held in Lund, Sweden in May of 1997, will continue to be useful
and entertaining for many years. As we had no new talk to post this week, the soundfile of Dr.
Kjellstrand's classic review was upgraded along with the graphics. We believe that many of our
subscribers have not had the chance to listen to this wonderful preparation and so are presenting it
as a rerun.
Dr. Kjellstrand starts out paying homage to Dr. Nils Alwall, who performed the first dialysis in
Sweden about 52 years ago. He points out that, for dialysis to become a reality, three factors
were necessary: an anticoagulant, a proper membrane, and some knowledge of uremia. Dr. Kjellstrand
describes the classic experiments of Dr. Thomas Graham which studied diffusion of substances through
parchment paper. Then Dr. Kjellstrand points out how the war industry developed cellulose as an
explosive, and it was from polymerized cellulose that cellulosic dialysis membranes were developed.
Next he describes the synthesis of urea by Wöhler and the treatise of Claude Bernard describing
how the kidneys regulate our internal milieu.
Anticoagulation is next, and Dr. Kjellstrand goes over the history of how hirudin and then heparin
were developed. Finally, all the pieces in place, he discusses the classic dialysis experiments in
animals by Abel, Rowntree and Turner, and also the work of pioneers who came after, including George
Haas, Heinrich Necheles, and William Thalhimer.
This is an excellent and very entertaining talk by one of Nephrology's greats. Please see some of
the other talks from the Lund meeting, also, although those soundfiles are in Real Media 4.0 format,
which sound a bit hollow with the newer 5.0 and G2 players. Also click on the
"Miscellaneous" folder tab at the bottom of the Kjellstrand lecture to access several
other interesting general talks pertaining to dialysis on HDCN.
This is the last of six talks from the Southwest Pediatric Nephrology Study Group Basic Nephrology
Conference on IgA Nephropathy, held in Dallas in May of 1998.
Dr. Sibley, a renal pathologist, covers the various forms of renal injury that can be seen with IgA
nephropathy. The emphasis of the lecture is on light microscopic changes. Dr. Sibley begins by
calling attention to the renal tubules, and presents a normal glomerular biopsy with normal tubules.
He then describes some instances of IgA nephropathy where there is associated tubular damage and
interstitial nephritis. He shows photos of mesangial widening, and then more advanced disease
consisting of mesangial cell proliferation, resulting in closure of the capillary loops. He
describes entry criteria for the ongoing NIH-funded IgA Nephropathy Study, which requires a modest
degree of renal pathology visible by light microscopy. He then goes on to describe fibrinoid
necrosis of a focal nature, and formation of nodules composed or epithelial cells in the urinary
space, progressing to crescents. He describes the natural history of crescent formation and
glomerular scarring. He touches on the findings to-date from patients entered into the North
American IgA Nephropathy study, and emphasizes those pathologic findings that are associated with a
poor prognosis. He ends by citing some literature suggesting a relatively high rate of recurrence
of IgA nephropathy in renal allografts, and a relatively high rate of progression to ESRD in IgA
patients who have received transplants.
This is the last of five talks posted from the Annual Scientific Meeting of the Renal Physicians
Association held in Washington, D.C., March-April, 1999. It was part of a symposium on vascular
access.
Dr. Himmelfarb begins by emphasizing data from the USRDS, that fistulas survive longer than grafts,
especially in younger patients. He then emphasizes that, in the past several years, we have come to
appreciate that the main reason why PTFE grafts fail is intimal hyperplasia distal to the graft-vein
anastomosis. He reviews the cellular mechanisms of intimal hyperplasia and the role of various
growth factors, including PDGF, bFGF, and TGF-beta.
Dr. Himmelfarb then emphasizes that a number of randomized trials have shown that antiplatelet
agents given at the time of AV fistula placement enhance the fistula success rates. His own study,
performed under Dr. Ray Hakim, evaluated the effects of dipyridamole and aspirin on PTFE graft
survival and thrombosis rate. Hakim and colleagues found that graft thrombosis rate was reduced
with dipyridamole, but paradoxically increased (not statistically significant) with aspirin. The
effects were not apparent for 6 months or so. Himmelfarb hypothesized that the results were not due
to antiplatelet effects of aspirin and dipyridamole, and went on to analyze effects of these drugs
in cell culture on VSMC (vascular smooth muscle) proliferation. They found a paradoxic effect of
aspirin that enhanced VSMC proliferation, whereas proliferation was markedly suppressed using
dipyridamole.
Dr. Himmelfarb then discusses his own plans for a multicenter study in this area, and reviews
designs of several other ongoing studies, including one using fish oil and another evaluating use
of aspirin plus clopidogrel. He finishes by some simple cost studies, which show that even costly
drugs, if they are effective, will be very cost-effective, because the expense of vascular access
thrombosis and monitoring is so very high.
This is the third of three talks posted from the 8th Annual Spring Clinical Meetings of the U.S.
National Kidney Foundation held in Washington, D.C., April-May, 1999.
Dr. Silbiger begins by pointing out animal data suggesting that estrogen seems to retard, and
testosterone seems to accelerate, glomerulosclerosis in a number of different models. She then
reviews some literature in humans suggesting that progression to chronic renal disease in patients
also is relatively retarded in females. She shows some preliminary data by one of her renal fellows
who did a meta-analysis of published studies, confirming the gender-protective effect in patients.
Dr. Silbiger then goes through the numerous possible reasons why females may be protected against
glomerulosclerosis, and focuses on the cellular effects of sex hormones, especially on mesangial
matrix synthesis. In her own laboratory, Dr. Silbiger, recognizing the importance of accelerated
mesangial matrix synthesis to renal disease progression, focused on examining the effects of
estradiol on collagen synthesis by renal mesangial cells. She looked at synthesis of both type I
and type IV collagen, and found that estradiol retarded synthesis of both, by different mechanisms.
In the case of type I collagen, the effect of estradiol was mediated by stimulation of AP-1, which
inhibited collagen-I gene transcription. In the case of type IV collagen, estradiol reversed the
stimulatory effects of TGF-beta. Similar effects on collagen type I and IV synthesis were found
for raloxifene, a "designer estrogen" characterized by reduced action on uterus and breast
tissue.
Dr. Silbiger closes by suggesting that estrogens, including the newer selective estrogen receptor
modulators, might conceivably be used in a therapeutic fashion to retard progression of renal
disease.
This is the second of two talks posted from the 10th Annual Meeting of the Polycystic Kidney Disease
Research Foundation. The talk was given to a patient audience, but is quite appropriate for
residents and fellows, as well as nephrologists who are not expert in treating this disorder.
In the first part of the series, Dr. Schrier discusses the high prevalence of hypertension in this
disorder, and explains the thought process that was followed to link hypertension to activation of
the renin-angiotensin system. ADPKD patients with high renal volumes, or with more cysts have a
higher prevalence of hypertension, and hypertension is associated with elevated rates of progression
to chronic renal failure. At first saralasin, an angiotensin antagonist, was found not to lower
blood pressure in ADPKD patients, but Dr. Schrier explains how further work showed that, in renin-
dependent hypertension there is a volume component, and that ACE inhibition or blockade only is
effective when volume overload has been corrected. Dr. Schrier shows evidence that renal vascular
resistance is elevated in ADPKD, and that this can be corrected by ACE inhibition.
In the second part of the talk, Dr. Schrier focuses on left ventricular hypertrophy, and reviews the
effects of LVH on outcome, and points out that the primary cause of death in ADPKD patients is due
to cardiovascular causes, and not to kidney failure. He discusses in detail the study by Ecder et
al where reversal of LVH in ADPKD patients was shown using enalapril over a 7-year follow-up period.
He then discusses the design of a planned new study, which would evaluate (a) degree of BP control,
(b) use of ACE inhibitors vs. other antihypertensive drugs, and (c) concomitant use of potassium
citrate, on preservation of renal function in ADPKD patients. Such a study is still in the
planning stages.
In the third part of his talk, Dr. Schrier reviews the occurrence of liver cysts in ADPKD, points
out that they occur late, often in women, and are linked to use of estrogens in postmenopausal
women. He touches on pain due to renal cysts, and then focuses on kidney stones in ADPKD patients
and the frequent occurrence of hypocitraturia. He closes by reviewing the data pertaining to
intracranial aneurysms and subarachnoid cysts in ADPKD, and points out that most intracranial
hemorrhage in ADPKD patients is related to hypertension and not to aneurysms, emphasizing once again
that control of hypertension in ADPKD patients is paramount.
This is the fifth of six lectures given at the Basic Nephrology Lecture Series meeting on IgA
organized by the Southwest Pediatric Nephrology Study Group in May of 1988. The talks were aimed at
an advanced patient audience, but also are suitable for fellows, generalists, and residents.
Dr. Cattran first reviews some work suggesting that all ACE inhibitors are not identical, in that
some preferentially inhibit tissue ACE, and reviews some work suggesting differential effects on
cardiac ACE and hypertrophy of different ACE inhibitor drugs. He then presents one of his own
patients with IgA nephropathy who had a dramatic response to ACE inhibitors, and then discusses
Toronto GN Registry data published in the Am J Kidney Dis, where hypertensive patients with IgA
nephropathy treated with ACE inhibitors seemed to do better than those treated with other anti-
hypertensives. Dr. Cattran then reviews the design of a European Multicenter Trial now in progress
designed to study the usefulness of ACE in this disease. He finishes with some rather esoteric work
in his own laboratory, suggesting that angiotensinogen genotype, perhaps more than ACE genotype, may
affect the rate of renal deterioration in patients with IgA nephropathy.
This Richard Bright Award Lecture was given by Dr. Bianchi at the May, 1999 Scientific Meeting of
the American Society of Hypertension in New York. For a long time it has been known that ingestion
of a high salt diet can induce hypertension in many animal models. Also, in some hypertension-prone
animals, the propensity to hypertension can be transferred by transplanting kidneys from the
hypertensive strain to the normotensive strain. Dr. Bianchi found this working with Milan
Hypertensive Strain (MHS) and Milan Normotensive Strain (MNS) rats, and then further found that
kidneys from MHS rats were sodium avid, and that this was due to increased activity of Na-K-ATPase
located at the basolateral membrane of renal tubular cells. Moreover, MHS rats were found to have
one of several point mutations in a protein called adducin, which at first was not clearly linked to
Na-K-ATPase pumps. With further research, it became apparent that adducin is somehow involved in
insertion and transport, or "trafficking" of Na-K-ATPase from where it is synthesized and
assembled (ER and Golgi) to the plasma membrane.
Of great interest, Dr. Bianchi has found similar adducin mutations in some populations of
hypertension prone humans, where the hypertensive adducin mutations also cause stimulation of Na-K-
ATPase in cultured cells. A drug has been developed (by Prassis Sigma Tau, called PST2238) that
modulates Na-K-ATPase, and that appears to block the stimulatory effects of hypertensive adducins on
Na-K-ATPase. Dr. Bianchi finishes by emphasizing context dependency, which may explain why not all
hypertensive populations show hypertensive adducin mutations, but preliminary data suggest that
patients with such mutations are salt sensitive and respond especially well to diuretics. Finally,
there may be some interaction with ACE genotypes as well.
This is a complex lecture and may not be easy to follow. If you want to print out a transcript to
read during the lecture without printing out the slides, highlight the whole text with your mouse,
then, if in Windows, press Edit at the top of your menu and then Copy. Then open up your favorite
word processor, press Edit and Paste, and you will, after adjusting margins properly, have a text
copy without the slides for easy reference.
These two lectures are parts 3 and 4 of a six-part symposium that was held in Texas in May of 1998.
Dr. Bryson Waldo from Birmingham first reminds us that IgA can be a serious illness and can manifest
as RPGN (rapidly progressive glomerulonephritis). He reviews the use of pulse methylprednisolone or
plasmapheresis for treatment of aggressive IgA nephropathy. Then Dr. Waldo focuses on chronic IgA
nephropathy, and lists all of the treatments that have been tried in the past. Among them,
phenytoin and antibiotics are now discredited. Danazol may have some utility.
Dr. Waldo reviews evidence for and against tonsillectomy, alternate-day steroids, fish oil, and ACE
inhibitors, although fish oil and ACE inhibitor use are discussed in detail later in the symposium.
Dr. Waldo presents the results of a small, uncontrolled trial of alternate day prednisone to treat
IgA nephropathy done in Birmingham, which gave encouraging results, and the results of a positive
albeit uncontrolled Japanese trial by Kobayashi et al. He then discusses trials in progress,
including the vitamin E trial by Chan and the ACEi trial by Coppo et al. Dr. Waldo finishes by
describing the ongoing NIH-funded North American IgA Nephropathy trial, which is headquartered at
the Southwest Pediatric Nephrology Study Group, host of this symposium.
Dr. Donadio focuses his entire lecture on the potential use of fish oil to treat IgA nephropathy.
He begins with some food chemistry, discussing the metabolism of omega-6 and omega-3 fatty acids,
and how the latter generate DHA and EPA, the two major ingredients of commercially prepared fish oil
extract. Dr. Donadio goes over the content of DHA and EPA in various fish vs. the commercial
products MaxEPA and Omacor, and points out that omega-3 fatty acids are also present in soybeans and
flax. He then shows how DHA and EPA inhibit generation of thromboxane and prostacyclin, and
theorizes how thromboxane might induce mesangial cell proliferation and increased mesangial matrix
production, worsening IgA nephropathy. Dr. Donadio then goes over the 4 major randomized trials of
fish oil, 2 negative and 2 positive, including his positive trial reported in the NEJM in 1994, and
presents long-term follow-up from this study, results that were published in JASN in 1999. He also
describes the design of his new ongoing study of 4 g/day vs. 8 g/day Omacor to treat IgA
nephropathy, where the primary outcome will be change in slope of serum creatinine over time.
These two lectures are the first of a six-part symposium that was held in Texas in May of 1998. In
the introductory lecture, Dr. Jennette goes over renal gross and microscopic anatomy, and then
explains how deposition of IgA immune complexes in the renal mesangium causes glomerular
inflammation and renal injury. Dr. Jennette recounts the list of potential reasons why IgA immune
complexes are generated in some persons more than in others, and why they seem to cause renal injury
in selected patients only.
Dr. Hogg then reviews the different clinical presentations of IgA nephropathy, and calls attention
to differences in presentation by age group and in Western vs. Asian countries. He discusses
indications for renal biopsy, and how different indications in different countries may result in
seemingly disparate clinical presentations and prognoses. Dr. Hogg also describes the Henoch-
Schönlein variant in detail, and then goes on to discuss clinical course. Clinical course may
vary considerably among patients, and Dr. Hogg finishes by discussing both fixed and clinically
modifiable risk factors for a poor prognosis.
This lecture was part of the NKF Spring Clinical Nephrology Meetings held in Washington, D.C., in
April-May of 1999. Dr. Feldman begins by defining the syndrome of analgesic nephropathy based on
early reports from Australia and other countries in the 1970s. Then he reviews the prospective
study out of Switzerland that first documented reduced urinary concentrating ability and increased
serum creatinine levels in women who tested positive for phenacetin metabolites in the urine. He
then reviews the declining incidence of analgesic nephropathy in Europe, and how the change in
various European countries over time may vary with policies on availability of phenacetin and
compound analgesic preparations. Dr. Feldman then turns to the United States, and cites data
suggesting a high prevalence of analgesic nephropathy in the Southeast United States. He reviews in
detail studies from North Carolina and Maryland, and discusses the potential problems of confounding
by indication that must be kept in mind when interpreting results.
This lecture was given to a lay audience at the 10th annual meeting of the PKRF foundation.
Dr. Woodford begins by discussing gross and microscopic anatomy of the kidney, and then the main
clinical differences between ADPKD and ARPKD. She then reviews the inheritance of ADPKD, and then
the effects on the kidneys, focusing on hypertension, cysts, hematuria, and pain. She then
discusses manifestations in other organs, especially the cerebral vasculature and liver. She
touches on some new research suggesting that soy-based diets may retard progression.
In part 2 of the talk, Dr. Woodford focuses on diagnosis by ultrasound and by genetic testing,
first of ADPKD and then of ARPKD. In the course of the discussion, the pathogenesis of both
disorders is discussed from the molecular genetics point of view. Finally, she reviews her own
work on linkage-based prenatal diagnosis of ARPKD.
Although the talk was aimed at a lay audience, there is much to be learned here by fellows and even
by nephrologists who are not specialists in these disorders. We plan to post one additional talk
from this meeting, by Dr. Robert Schrier, on the complications of PKD. Dr. Schrier's talk will be
posted later this summer.
Please see also talks from the 1998 PKRF
meeting by Dr. Greg Germino and by Dr. Ellis Avner.
These 2 lectures complete the round of 6 talks that make up this symposium. Dr. Doug Ford discusses
the use of Synsorb-Pk, a verotoxin binder modeled after the soluble receptor concept, and discusses
the use of this binder in two large ongoing clinical trials, one in Canada and one in the United
States. Dr. Paul Mead explains the CDC approach to HUS, and presents some interesting
epidemiologic data, and then describes the PulseNet consortium of laboratories where DNA
fingerprinting of E. coli O157:H7 is available. Dr. Mead describes how PulseNet was used to help
identify the cause of a recent outbreak of HUS due to contaminated alfalfa sprouts. He also
describes new initiatives in food irradiation and discusses possible approaches to vaccination
against HUS.
To complete the symposium, the question and answer periods addressed to the six lecturers are
appended, along with a very moving closing series of comments by Mr. Robert C. Galler, whose
daughter, Lois Joy, succumbed to HUS six years ago. Mr. Galler, together with his wife and other
interested persons founded the Lois Joy Galler Foundation, which works to further research in the
HUS field.
This is one of four selected lectures that HDCN will be posting from the 1999 NKF Eighth Annual
Spring Clinical Meetings, this one held in Washington, D.C. Dr. Giuseppe Remuzzi, one of the
world's preeminent nephrologists, presents both important basic and clinical data linking
proteinuria to progressive renal injury. It has long been known that, whatever the primary cause of
renal injury, the rate of progression is linked to the degree of interstitial scarring. Recent
evidence also suggests that the amount of proteinuria also affects the rate of deterioration of
renal function. How can proteinuria, interstitial scarring, and progression of renal disease be
linked? Dr. Remuzzi presents his observations that in renal disease associated with proteinuria,
one can demonstrate ingested protein and in particular, albumin, in proximal tubular cells. One now
knows that a long list of cytokines, chemokines, and other inflammatory mediators are linked with
progressive glomerular injury. Indeed, a good review of this topic was provided at the 1998 ASN
meeting by Dr. William Couser, and his talk is reproduced on HDCN at this link.
Dr. Remuzzi reviews his data showing that exposing polarized cultured tubular cells to albumin
induces mRNA for some of these same cytokines and chemokines, including RANTES (Regulated upon
Activation, Normal T cell Expressed and Secreted), MCP-1 (monocyte chemoattractant protein), and ET-
1 (endothelin-1).
Also induced is NF-kappaB (nuclear factor - kappa B), which may regulate RANTES and Endothelin
Converting Enzyme production. Dr. Remuzzi provides a teleological explanation for induction of NF-
kB relating to defense against viral infection. The data regarding NF-kB is exciting because,
theoretically, one could give an inhibitor to NF-kB and retard the rate of progression (e.g., see
Rangan et al, Kidney-Int, July, 1999).
Many of these chemokines are secreted by polarized cultured tubular cells primarily at the
basolateral side, where they can induce macrophage attraction and fibrogenesis. In fact, he shows
very interesting photomicrographs demonstrating attraction of activated macrophages in several
proteinuric animal models. Dr. Remuzzi then goes on to show that use of ACE inhibitors not only
reduces proteinuria, but also reduces generation of many of these cytokines, chemokines, and
activated macrophages.
Part 3 of the 3-part talk reviews the results of the REIN study that was done by the GISEN Group
(composed of Italian Nephrologists) who studied the role of lisinopril in preventing progression of
non-diabetic chronic renal disease. Dr. Remuzzi reviews results suggesting that the degree of
proteinuria was an important determinant of the rate of progression, and of course results showing
that lisinopril retarded the rate of progression. He concludes by proposing proteinuria as a prime
risk factor for progression of renal disease that must be reduced per se, if prolongation of renal
function is to be achieved.
July 18 - 24, 1999
HUS: Aspects of the Clinical Presentation, Differences Between Children, and Current Therapy.
(Dr. Richard Siegler)
Continuation of talks from the Basic Nephrology Lecture Symposium Series sponsored by the SPNSG
(Southwest Pediatric Nephrology Study Group) and cosponsored by the Lois Joy Galler Foundation.
There are six talks in this symposium. We are posting talk no. 4 this week.
Again, from Dr. Hogg's introductory remarks:
"
Dr. Dick Siegler will take us into the second aspect of the
disease as we know it today. What Dr. Siegler will to is to talk
about situations that occur then the child has developed hemolytic
uremic syndrome. Dr.
Siegler will talk about the clinical features in these children,
particularly those who have the so called "classic" or
typical HUS, which is what we see in most of the kids. He will talk
about how the disease varies between one child and another. He will
talk about the complications of HUS, not only in the kidney, but also
in other parts of the body. He'll talk about the prognosis for
children who have this condition and then also a little bit about the
current treatment that's available. "
Implementing DOQI Guidelines for Vascular Access
(Dr. Larry Spergel)
This is a continuation of posting of the talks from the March 1999 Annual Renal Physicians
Association Meeting in Washington D.C. Dr. Spergel focuses on his experience in operationalizing
the DOQI guidelines in the vascular access area. Dr. Spergel discusses the importance of
establishing a multidisciplinary CQI team, and gives illustrative and practical examples and
anecdotes relating to his successful efforts to markedly reduce the vascular access thrombosis rate
in Georgia using a Vascular Access Management Program and access flow measurements. He also
describes his successful results in increasing the usage of AV fistulas and in markedly reducing the
use of subclavian catheters in the targeted group of dialysis units.
July 11 - 17, 1999
How Children Present with HUS, and Events Leading Up to the Diagnosis
(Dr. Phillip Tarr)
Continuation of talks from the Basic Nephrology Lecture Symposium Series sponsored by the SPNSG
(Southwest Pediatric Nephrology Study Group) and cosponsored by the Lois Joy Galler Foundation.
There are six talks in this symposium. We are posting talk 3 this week.
Again, from Dr. Hogg's introductory remarks:
"In the second session, we're going to be talking about the disease
itself and the evolution of the disease as it occurs in the individual
child. Dr. Phil Tarr, a Pediatric Gastroenterologist
from Seattle, from the Children's Hospital and
Regional Medical Center, will talk about the period of time leading up
to the development of the hemolytic uremic syndrome. He'll talk about
a number of aspects of the disease that are seen prior to the actual
development of HUS. His particular topics will be the source of VTEC
in the food chain, and what are the risk factors for VTEC infection.
He'll talk about the diagnosis and management of VTEC before HUS
starts. He'll talk about which children who have VTEC, who have the
diarrhea, will develop HUS. Finally, he will talk in terms of means
of preventing the VTEC infection in the gut, the diarrheal illness;
how can we prevent that from evolving into HUS."
July 4 - 10, 1999
Hemolytic Uremic Syndrome: Definitions, Early History, Pathophysiology.
(Dr. J. Charles Jennette)
Another Basic Nephrology Lecture Symposium Series sponsored by the SPNSG (Southwest Pediatric
Nephrology Study Group) and cosponsored by the Lois Joy Galler Foundation. There are six talks in
this symposium. We are posting 2 of the 6 this week.
The first talk is by Dr. Charles Jennette. As per the introductory remarks by Dr. Ron Hogg:
"Dr. Jennette will deal with the distant past with
regards to HUS. He's going to discuss some aspects of normal renal
anatomy and physiology and he will define a number of vague terms that
some of you have heard before, such as HUS, TMA, VTEC. He will also
provide an overview of what the Hemolytic Uremic Syndrome is, and he
will place particular emphasis on its pathology. In that regard, he
will also talk about some of the prognostic features, which are
important in the pathology of HUS. His main area of the historical
review will be the first 25 years or so since this condition was first
described. "
Hemolytic Uremic Syndrome: 1982 - Present.
(Dr. Gerald S. Arbus)
Again, from Dr. Hogg's introductory remarks:
"The second speaker will be Dr. Gerald Arbus, and Dr. Arbus is from the
Hospital for Sick Children in Toronto. Dr. Arbus will then complete
the historical perspective. He will talk about the Toronto
experience, where VTEC and HUS were further defined. He will give a
historical perspective from the early 1980s up until the present time.
And then he'll talk about certain aspects of why hemolytic uremic
syndrome occurs in certain parts of the world more than in others.
And he'll also talk about a number of epidemics or outbreaks of
hemolytic uremic syndrome, which really provide us with a little bit
of education as to what's going on. "
June 27 - July 3, 1999
Strategies for Repair of Access Malfunction.
(Dr. Gerald A. Beathard)
Dr. Beathard, who gave a lecture on
Early Diagnosis and Treatment of Vascular Access Complications at the 1998 Spring Clinical
Meetings of the NKF (that is posted in the FREE ZONE of HDCN) now continues with a talk at the
March, 1999 meeting of the Renal Physicians Association focusing on how to treat access dysfunction.
The lecture is divided into three parts: AV fistula malfunction and how to treat it, prosthetic AV
graft angioplasty, and treatment of AV graft thrombosis. Please hit "reload" if
the Beathard lecture does not appear on the list of talks at the above hyperlink.
Vascular Access Quality Improvement Project for Networks 9 and 10.
(Dr. Ashwini Sehgal)
There were four talks on vascular access as part of a symposium at the 1999 RPA meeting. Another of
the four, by Dr. Ash Sehgal from Case Western Reserve University, describes a QI project that they
developed to assess the proportion of venous catheters being used at various facilities in the
Midwest. An instrument called the SCR, or Standardized Catheter Ratio, similar in concept to the
USRDS' Standardized Mortality Ratio (SMR) or Standardized Hospitalization Ratio (SHR) was developed
and applied. Patient characteristics predictive of venous catheter use were identified, but even
once these were controlled for, Dr. Sehgal found marked between facility variation in the proportion
of venous catheter use.
June 20 - 26, 1999
Complications of the nephrotic syndrome in adults.
(Dr. William F. Keane)
This is the final lecture from the Proteinuria/Nephrotic Syndrome set of talks that make up part of
the Basic Nephrology Lecture Series organized by Dr. Ron Hogg. In
this lecture, Dr. Keane points out that most cases of nephrotic syndrome in adults, as opposed to
children, are not reversible, and one is faced with a chronic condition. Risk factors for
progression include hypertension, proteinuria, and dyslipidemias. Dr. Keane summarizes findings
from major trials, that the degree of proteinuria per se is a risk factor for progression. He then
details the effects of proteinuria on lipid metabolism that result in increases in LDL, IDL, and
Lp(a), and decreased LDL receptor levels. Dr. Keane presents evidence suggestive of increased
coronary artery disease in nephrotic patients with renal insufficiency, and evidence linking the
degree of albuminuria to coronary artery disease. He then turns to coagulation abnormalities in
nephrotic syndrome, and describes increased synthesis of procoagulant factors, decreased synthesis
of anticoagulant and thrombolytic factors, and discusses renal vein and deep vein thrombosis. Dr.
Keane points out the relationships among proteinuria, progression, and treatment in several major
studies, including the MDRD study and the REIN study, and discusses how treatment of proteinuria can
ameliorate the dyslipidemia in these patients. He finishes by proposing the concept of "
progression promoters" for renal failure, and new approaches to reduce these risk factors in
susceptible patients.
This complete set of six lectures should be extremely useful as a basic review in this area, and
will be followed by similar sets of lectures organized by Dr. Hogg pertaining to IgA nephropathy and
the hemolytic uremic syndrome.
Incidentally, on the list of Proteinuria/Nephrotic syndrome talks, if you don't see the link to Dr.
Keane's talk, please press "Reload" to refresh your browser cache.
June 13 - 19, 1999
Features and treatments of proteinuria and nephrotic syndrome in adults.
(Dr. Daniel C. Cattran)
This is another lecture from the Basic Nephrology Lecture Series put together by Dr. Ron Hogg. In
this lecture, Dr. Cattran focuses on treatment of minimal change disease, focal segmental glomerular
sclerosis, and membranous nephropathy in adults. Strategies are presented both for initial therapy
and for therapy of high risk or resistant cases. In particular, Dr. Cattran summarizes his own data
concerning use of cyclosporin for treatment of FSGS and membranous nephropathy.
June 6 - 12, 1999
Principles of Continuous Quality Improvement (CQI) and Outcomes Analysis
(Dr. W. Ernest Rutherford)
This was the inaugural Louis H. Diamond Lecture at the March 1999 Renal Physicians Association
Annual Meeting held in Washington, D.C. Dr. Rutherford begins by discussing the differences between
Quality Assurance (QA) and Continuous Quality Improvement (CQI), pointing out that QA is a data
gathering exercise, whereas CQI is a management strategy. Specifically, CQI is a fourth generation
management strategy. CQI requires Profound Knowledge, and Dr. Rutherford delineates each of the
four components of Profound Knowledge. He dwells specifically on knowledge about variation, and
details the features of common cause vs. special cause variation. He goes on to cite the utility
of Statistical Process Control and the use of control charts to guide decision making in practical
dialysis-unit relevant situations. Finally, he details the nine principles of CQI.
May 30 - June 5, 1999
What Protein Does in the Body and How it Sometimes Leaks out in the Urine.
(Dr. Robert D. Toto)
Specific Diseases Associated with Proteinuria.
(Dr. J. Charles Jennette)
Here are two more lectures from a symposium held in January of this year in Dallas, and organized by
Dr. Ron Hogg. Although the talks are quite introductory, they would be excellent for medical
students and residents as well as nurses interested in basic renal pathophysiology. In particular,
the excellent slides of Dr. Jennette are a wonderful resource in understanding renal biopsy
interpretation.
May 23 - 29, 1999
Third Factor: A Structure at Last! Endogenous Na,K-ATPase inhibition, cardiorenal physiology, and
pathogenesis of hypertension. (Dr. Garner T. Haupert Jr.)
This is another lecture from the Philadelphia ASN Annual Scientific Meeting in October of 1998. It
chronicles the long search for so-called "third factor", a sodium retaining hormone first
postulated to exist by Dr. Hugh de Wardener in 1961. Several ouabain-like hormones have now been
identified in humans, with putative sources in the hypothalamus or adrenal glands. Dr. Haupert
summarized the animal evidence for existence for such a factor, and the identification of the
structures of several of these factors.
Dr. Haupert then describes Dr. Bianchi's work from Milan (whose 1999 talk at the ASH meetings,
incidentally, will be on HDCN). Dr. Bianchi identified point mutations in the adducin gene, which
affects function of the Na,K-ATPase in hypertension prone rats, and also found a similar mutation
in some salt-sensitive hypertensive patients. Dr. Haupert then describes functional differences
between the "hypothalamic Na,K-ATPase inhibitory factor (HIF)" and ouabain, including a
much greater sensitivity of the medullary thick ascending limb to the effects of HIF. Dr. Haupert
concludes with describing a new drug which is undergoing phase I trials in humans, which reverses
the increased salt-sensitivity associated with the adducin mutation found in Milan hypertensive rats
and which may act similarly in salt-sensitive hypertensive humans.
We have tried to keep the content on HDCN primarily clinical. This is a fairly basic lecture, but
one with obvious clinical implications.
May 16 - 22, 1999
Pathophysiology of Peritoneal Transport
This was the Dominick E. Gentile Memorial Lecture presented at the Charlotte, NC 19 Annual
Conference of Peritoneal Dialysis on February 28, 1999. Dr. Raymond Krediet, from the University of
Amsterdam in The Netherlands, first discusses the paradoxical negative effect of high transport
status on removal of small molecular weight solutes. He then introduces the new knowledge gained
about the importance of aquaporins to peritoneal transport, and discusses how status of aquaporin
transport can be assessed using sodium sieving. He also discusses use and indications of
icodextrin, and the special benefits of icodextrin in high transporters. Dr. Krediet further
discusses the concept of ultrafiltration failure, and presents data suggesting that, with increasing
duration of dialysis, there is increased vascularization of the peritoneal membrane, associated with
increased transport rates for urea and creatinine. This may be induced by glucose, and Dr. Krediet
presents new information from a rat model supporting this concept, as well as new information
presented at the meeting in abstract form about high peritoneal effluent concentrations of growth
factors TGF-beta and VEGF in long-term patients on CAPD.
May 9 - 15, 1999
Can Med Assoc Practice Guidelines: Lifestyle Modification for Hypertension
Proceedings of a Consensus Conference, available in full text in .pdf format from the CMAJ website.
Includes recommendations on obesity and weight loss, alcohol consumption, physical exercise
training, dietary salt, and dietary potassium, magnesium, and calcium, as well as a section on
stress management.
They have more guidelines at the site, 650 all told! Included are a number of guidelines in nephrology and in
cardiology/hypertension.
These are the initial 2 lectures from a series of 6, which deal with aspects of the nephrotic
syndrome in both children and adults. This set of lectures focuses on children and adolescents.
April 18 - 24, 1999
A New Role for PD: Implications of a Shifting Paradigm
of Care for the ESRD Patient
(Dr. Karl Nolph, Dr. David Mendelssohn, Dr. Ram Gokal
(Slide audio satellite symposium from the
Annual PD Meeting in Charlotte, NC, February, 1999. Three talks.)
This week HDCN presents the major satellite symposium given at the Annual CAPD Meeting in Charlotte,
NC in Feburary, 1999. Dr. Nolph discusses the improved patient outcome associated with higher
levels of native renal clearance, and reviews the data in favor of early start dialysis. He also
touches on potential disadvantages of protein restriction in pre-ESRD patients. Dr. Mendelssohn
discusses methods of optimizing pre-ESRD care, and focuses on early referral, problems of non-
referral, and of non-nephrologist care of the pre-ESRD patient. He then reviews efforts by the
Canadian Nephrology Society to educate generalists about the potential benefits of earlier referral
to nephrologists of patients with rising serum creatinine levels. The third speaker, Dr. Gokal, in
a very detailed analysis, discusses a number of issues in modality (HD vs PD) selection, including
survival, morbidity, quality of life, medical factors, and non-medical factors. His conclusion is,
that marked improvements in PD outcomes and technique survival over the past 25 years have now made
PD a potential first dialysis therapy of choice for ESRD.
April 11 - 18, 1999
Tacrolimus in Renal Transplantation
(Dr. Gabe Danovitch)
This week HDCN presents another lecture from ASN 98. Dr. Danovitch first discusses the mechanism of
action of tacrolimus (similar to cyclosporin, in that both are calcineurin inhibitors), and then
goes on to review evidence for a decreased incidence of early rejection using tacrolimus vs.
cyclosporine. He then discusses the difficulty in showing improvement in long-term graft survival
even with therapies that have a marked initial beneficial effect in early graft rejection. He does
a point by point comparison of cyclosporin vs. tacrolimus in terms of both efficacy and side-effects
and cites current UNOS data pertaining to long-term graft survival with the two drugs.
This lecture was part of a 4-talk series given at the meeting, along with lectures by Drs. Neylan,
Halloran, and Helderman. The first two are already posted on HDCN, and deal with the anti-TACs,
sirolimus, and mycophenolate mofetil, whereas Dr. Helderman's talk, to be posted soon, will address
the issue of optimal cyclosporin dosing and monitoring.
April 4 - 10, 1999
Current Issues in Anemia Management
(Drs. Besarab, Fishbane, Nissenson, and Wish)
This week HDCN presents a Satellite Symposium that was sponsored by Schein Pharmaceutical at the
October 1998 Annual Scientific Meeting of the ASN. The talks focus on the use of IV iron
preparations in treating hemodialysis patients, and in particular, explore the potential adverse
consequences of IV iron use, including oxidative and cardiovascular damage and infectious risk. Dr.
Nissenson describes his study, published in last month's AJKD, of sodium ferric gluconate (in
sucrose) injection, or Ferrlecit-®. Ferrlecit-® should be available for use in the US
soon. It was approved by the US FDA in February. Some studies suggest a lower incidence of severe
anaphylactic reactions with Ferrlecit-® vs. iron dextran. The symposium, as usual, is in
slide/audio format.
Still current and useful, by the way, is a similar symposium presented at the 1997 ASN meeting, but
which focused on the NKF-DOQI guidelines. This symposium also had a lot of basic information about
iron metabolism. Speakers at that symposium were Drs. Adamson, Berns, Eschbach, Stivelman, and
Wish. For the 1997 symposium, click
here.
March 28 - April 3, 1999
Metabolic Acidosis: Catabolic Mechanisms that Cause Morbidity
(Dr. William Mitch, MD)
This week HDCN presents another lecture from the 1998 ASN meeting. Dr. William Mitch from Emory
University in Atlanta describes the potential deleterious adverse effects of metabolic acidosis on
nutritional status. He begins by reviewing adverse effects of acidosis on bone. Then he cites some
early evidence that acidosis adversely affects nitrogen balance in uremic patients. Dr. Mitch then
describes a uremic rat model in which amino acid oxidation is increased, and where the increase is
obviated by feeding bicarbonate to correct the acidosis. There appears to be induction of the
enzyme branched chain ketoacid dehydrogenase (BCKAD) in this situation. Similar results were
obtained when studying protein degradation, and Dr. Mitch describes the ubiquitin/proteasome
pathway, and his experimental evidence that this system may be upregulated via increased gene
transcription by both acidosis and glucocorticoids. He finishes by citing a number of patient
studies where muscle amino acid content, amino acid oxidation, and albumin synthesis were all
impaired in acidotic states. As a result of this evidence, Dr. Mitch cites data recommending
optimal minimal levels of serum bicarbonate both for hemodialysis patients and for those being
treated with CAPD.
March 20 - 26, 1999
Hypertension in Women: Are Tailored Approaches Warranted?
(Dr. Ellen Cohen, MD)
This week HDCN presents another lecture from the 1998 ASN meeting. Dr. Ellen Cohen from Albert
Einstein College of Medicine and Montefiore Medical Center in the Bronx, NY, discusses the findings
from NHANES-III regarding prevalence of hypertension in women vs. men as a function of age and race,
and discusses a new "numbers needed to treat" approach to assess the utility of lowering
blood pressure in this population. She then discusses the effects of estrogens on the vasculature,
NO release, and lipids as well as other intermediate substances of relevance to cardiovascular
disease. Dr. Cohen discusses the Nurses' Health Study and the HERS study, the primary information
we have about the utility of using hormone replacement therapy in postmenopausal women to lower
cardiovascular risk. She also talks about the relative advantages/disadvantages of the different
classes of anti-hypertensive agents in women vs. men.
March 14 - 20, 1999
New Drugs for Transplantation. IL-2 Receptor Antibodies and Sirolimus
(Dr. John F. Neylan III, MD)
By the way, the technical problems with the Real Media server have been solved.
This week HDCN presents another lecture from the 1998 ASN meeting. Dr. John Neylan
from Emory University first talks about basiliximab and daclizumab, IL-2 receptor
monoclonal antibodies, and then about sirolimus (Rapamune).
March 7-13, 1999
Walter Reed Army Medical Center Nephrology Lectures and Slidesets
(Dr. Kevin Abbott, MAJ, MC)
No talk this week, due to some technical problems with our Real Media Server (causes long waits for
audio downloads for talks in more than one part). For this reason, Dr. John Neylan's lecture on
IL2-R antibodies and sirolimus is being postponed one week.
Meanwhile, we are pointing readers to an outstanding site developed at the Walter Reed Army Medical
Center, containing about 30 lectures in slide format, about half targeted for nephrologists, and
half toward primary care physicians. One very useful feature is the fact that the power point
slideset for each talk is posted for downloading. Thus, the slidesets can be used as a starting
point for modifying the present talks or for making your own talk.
February 28 - March 6, 1999
Hyperkalemia in dialysis patients
(Dr. Michael Allon, M.D.)
Another talk from the October 1998 ASN Scientific Annual Meeting (more to come!).
Dr. Allon first reviews the standard emergency treatments for hyperkalemia, and then describes his
own work with nebulized albuterol. He discusses the relative insensitivity of ESRD patients to the
hypokalemic effects of epinephrine, as well as the lack of efficacy of bicarbonate administration.
He then talks about some recent work pertaining to fasting induced hyperkalemia and potential
methods of preventing this complication, e.g., in the preparatory period prior to surgery. He also
discusses the recent data calling into question the efficacy of sodium polystyrene sulfonate.
February 21 - 27, 1999
Crescentic glomerulonephritis: New mechanisms with therapeutic potential
(Dr. William G. Couser, M.D.)
Another talk from the October 1998 ASN Scientific Annual Meeting (about 10 more to go!).
Dr. Couser reviews his own initial experience with a patient with Goodpasture syndrome while a
resident, and points out that current therapy is similar to that which was in vogue many years ago.
He then reviews new mechanisms that have been identified with the progression of experimental GN and
work in progress to interfere with some of these pathways. He begins with ANCA, and then the role
of cellular immunity. One strategy is to interfere with complement activation, and use of soluble
CR1 receptors is described. Another concept is to interfere with neutrophil and macrophage
localization, and use of anti ICAM-1, anti-LFA-1, blockers of MIP-2, and anti-MCP1 are discussed.
Soluble PDGF (platelet derived growth factor) receptors also reduce injury in experimental models,
in this case, by interfering with the cell response to injury. Roscovitine, a drug that interferes
with cyclin-dependent kinase (cyclins are compounds that are required for the cell to divide and
proliferate), also can be beneficial, as can IL-1 receptor antagonists and soluble TNF receptors.
Tissue factor mediates fibrin deposition, and its inhibition mitigates glomerular injury. Agents
that non-selectively or selectively interfere with the immune response also are useful in
experimental models, including deoxyspergualine (which inhibits humoral immunity), and IL-4 and IL-
10 (which inhibit cell-mediated immunity). Future approaches that selectively inhibit the immune
response or cause tolerance also are described.
February 14 - 20, 1999
Hyperhomocysteinemia and cardiovascular risk in ESRD
(Dr. Vincent W. Dennis, M.D.)
Another talk from the October 1998 ASN Scientific Annual Meeting (about a dozen more to go!).
Dr. Dennis first reviews the structure of homocysteine and mechanisms of how this compound can cause
vascular injury. Then he reviews evidence that hyperhomocysteinemia is associated with coronary
disease in nonuremics. Increased plasma homocysteine (Hcy) levels in CRF are found, and the
potential reasons for this analyzed. The folate cycle, methionine cycle, and transsulfuration
pathways are presented. The Cleveland Clinic Study of plasma Hcy levels in ESRD is described in
detail, in terms of correlations with B vitamin levels, and in terms of mortality. B vitamin
treatment and its limitations are also described.
February 7 - 13, 1999
Respiratory Acid-Base Disorders
(Dr. Thomas D. Dubose, Jr.)
This talk completes our selection of talks from the 1998 ASN Board Review Course dealing with acid-
base and sodium disorders. We also updated the soundfile on a talk given last year by Dr. Dubose to
the NY Society of Nephrology entitled: "A simplified pathophysiologic approach to renal
tubular acidosis".
Together, these lectures and question and answer sessions comprise 8 hours of continuing medical
education material, and the appropriate amount of Category 1 CME Credit for this course is being
offered through the University of Minnesota. Physicians desiring CME credit for this internet
course will need to print out and complete the CME post-test and evaluation form. There is a charge
of $50.00 US for the CME credits, payable on-line. The post-test and evaluation form are designed
to be filled out electronically. Whereas the post-test is ready now, the electronic answer sheet is
still being programmed, and should be ready by the middle of the week.
January 31 - February 6, 1999
Mycophenolate Mofetil: What are the advantages of its long term use?
(Dr. Phillip F. Halloran)
Another talk from the Annual ASN Scientific Meeting (many more to go!). This was part of a Renal
Transplantation Symposium. For technical reasons we are posting the talks separately. In this
presentation, Dr. Halloran discusses the pharmacology of mycophenolate mofetil and its mechanism of
action, and reviews results of early studies demonstrating reduction in acute renal allograft
rejection episodes. He then discusses the experience with MMF in heart transplantation, and goes on
to evalute its potential use in long-term immunosuppression.
January 24 - 30, 1999
New Vitamin D Analogs (Dr. Jack W. Coburn)
We are taking a break from posting the final acid-base talks from the Board Review Course to
complete testing on our automated CME. Meanwhile, this week we present the first of 12-15 selected
lectures from the 1998 ASN Scientific Meeting in Philadelphia. Dr. Jack Coburn talks about
preliminary data in humans obtained with four new vitamin D analogs: 22-oxacalcitriol,
falecalcitriol, 19-nor, and 1-alpha-D2. Before you start this talk, go to the references at the end
of part 2, and print out the ring structures of vitamin D2 and D3. It will help you understand the
chemistry of these derivatives.
January 17 - 23, 1999
Metabolic Alkalosis (Dr. Thomas D. Dubose, Jr.)
Another talk from the 1998 ASN Board Review Course. Next week we will be posting the final talk
and, if all goes well, an on-line CME credit opportunity for participating in this educational
activity.
As an aside, this week we are posting links to featured articles from the 1999 issue of JASN. In
the past 2 months, JASN has begun to offer several full text featured articles on its websiste every
month, plus links to related UpToDate topic cards. This is a wonderful new educational resource!
January 3 - 9, 1999
1998 Research Update in Polycystic Kidney Disease (slide/audio symposium)
(Dr. Ellis Avner)
(1998 PKRF Foundation Scientific Meeting)
This talk by Dr. Avner summarizes the new animal models of PKD, both for PKD1 and PKD2 that have
been recently developed. Work in localizing the gene for ARPKD is described, along with a new
prenatal diagnostic test. He discusses potential mechanisms for interaction of polycystins 1 and 2
with each other and with a TG737 homologue protein to form a protein complex. The importance of
epidermal growth factor receptor is discussed, along with potential therapeutic implications of EGF
receptor blockers or downstream inhibitors. New evidence suggesting lack of effect of Taxol on
progression of PKD in several animal models is presented, along with encouraging preliminary data on
the effects of a soy protein diet. Finally, the new ARPKD registry is described.
A sister talk by Dr. Gregory Germino, posted in October, is also available from the PKRF annual
meeting.
