Introduction to Clinical Medicine - Nephrology
I. David Weiner, M.D.
Professor of Medicine and Physiology
University of Florida College of Medicine and NF/SGVHS
Please e-mail me, at weineid@ufl.edu,
with your questions. I'll post the question and my answer, with your
permission, here for others to see.
Questions and Answers from 2006
In a renal transplant in which the native kidneys remain in the
patient's body, will those kidneys respond to fluctuations in blood
volume/pressure like a normal kidney? So would having the native kidneys
increase the patient's risk for HTN or an overactive response to decreased blood
volume/pressure (due to the renin-aldo system?
-
Yes, the native kidneys are left in the patient's body. They
can respond to physiologic stimuli, can and do produce renin, which can lead
to activation of the renin-angiotensin system and increases in blood
pressure. In fact, because of poor perfusion of the highly diseased kidneys
in these patients, they frequently result in high levels of renin production
and substantial increases in the person's blood pressure. So why don't we
take kidneys out? The reason is that removing the kidneys is a major
surgical procedure, that results in substantial morbidity to the patient.
Recovery from bilateral nephrectomy is neither easy nor quick. In the past,
we tried removing the native kidneys, but the complications and the
difficulty in recovery after the procedure made it not worthwhile.
I. David Weiner, M.D.
I also wasn't sure about which formulas we needed to know and
which, if any, formulas are provided for us on the test. My notes say that we
should be responsible for calculating creatinine clearance, fractional excretion
of Na, and how much water to give to correct hyperkalemia (sic - you
probably mean hypernatremia).
Am I correct?
Thank you very much for your help!
-
I'm going to be vague, sorry. In general, I think that you
can assume that formulas that I emphasize in lecture are the ones that I
think are the most important. Ones that I put in my handouts, but do not
emphasize in lecture, are also important (otherwise I wouldn't have put them
in the handouts), but probably are not quite as important.
-
Now then, the $100,000 question is whether every question you
get asked on a test relates only to the most important concepts or whether some
are directed at still important, just less important, concepts.
-
What do you think is the answer to that question?
I. David Weiner, M.D.
Why does GFR initially (in the Pre- stage) increase in diabetic nephropathy?
Thank you,
- There are increases in renal plasma flow, glomerular hydrostatic
pressure and glomerular permeability, all of which act synergistically to
increase GFR. They also tend to lose autoregulation of
glomerular filtration, that process which maintains a relatively constant
GFR as BP changes. The mechanism of these changes is not completely
understood, but may involve growth hormone hypersecretion.
I. David Weiner, M.D.
Hello, Dr. Weiner. My name is -------- -----------, and I was in your renal
clinical diagnosis class this year. I have a question. Your equation for
Creatinine Clearance includes "(Time/100)" in the denominator. I understand why
time appears, since the equation derives from Pcr x Clcr x time = Ucr x V, but I
do not understand where the /100 part comes from. Did you just carry this over
from the conc. of creatinine in the plasma that you gave on the slide? Or did it
not come from there? Please let me know when it's convenient. Take care, now.
- The "/100" factor relates to the differing units used in the different
components of the equation. In particular, the plasma creatinine is in
mg/dl, which is equivalent to mg/(100 ml). The typical units for GFR
are ml/min. As a result, to go from "dl" to "ml" one needs to have a
"/100" term in the final equation.
- I hope this helps,
I. David Weiner, M.D.
Dr. Weiner, Can you please elucidate for me the physiology of why hepatic
albumin synthesis causes an increase in serum cholesterol as a sequelae of
proteinuria?
- It doesn't make sense why this should happen, but it does!
- The theory is that proteinuria and nephrotic syndrome lead to decreased
plasma oncotic pressure, that the liver "senses" this and decides to
synthesize more albumin in order to raise plasma oncotic pressure.
Then, so goes the theory, the liver is not "smart enough" to just make
albumin, and so it also makes more cholesterol. This leads to
elevations, sometimes dramatic, in both total cholesterol and LDL
cholesterol.
- There are also defects in LDL clearance mechanisms that further
increases cholesterol and LDL-cholesterol levels.
- Sorry that this answer is not better at explaining why the nephrotic
syndrome and severe proteinuria lead to these changes. I suspect that
the answer is more complicated that just decreases in plasma oncotic
pressure.
I. David Weiner, M.D.
Hi Dr. Weiner,
Two questions about HTN in nephrotic and nephritic syndromes:
1. With respect to CKD: HTN is one cause of the CKD. Are the
proteinuria, HTN, and fluid overload in CKD consistent with nephrotic syndrome?
Should be associating CKD with either a nephrotic or nephritic syndrome?
-
Not necessarily. Nephrotic syndrome requires the presence of
three of the 4 criteria of proteinuria greater than 3.5 gm/d,
hypoalbuminemia, hypercholesterolemia and edema. Hypertension is not one of
the criteria. Hypertension-induced chronic kidney disease usually does not
cause this pattern. In practice, if a patient has nephrotic syndrome they
almost always have something else, in addition to hypertension, that is
causing their renal disease.
2. In the Glomerular diseases lecture, it is mentioned that
glomerulonephritis is frequently associated with HTN. Is that because the
Ab-mediated, cell-mediated, and immune complex deposition events are causing
reactive cellular proliferation in the glomeruli, reduced glomerular bloodflow,
a low rate of filtration, and sodium retention, leading to fluid retention and
HTN? (I'm quoting Dr. Clapp's pathology lecture notes.)
Thank you,
I. David Weiner, M.D.
HI Dr Weiner. Could you explain why esrd is associated with gi
bleeding? Is it just because of elevated bp? THANKS.
-
The increased bleeding is related to platelet dysfunction
due to the renal failure. All of the factors that are involved are not
clear, but this "uremic platelet dysfunction" can be improved by treatment
with either the vasopressin V2 receptor agonist, desmopressin, or with the
blood product, cryoprecipitate. The effect of the desmopressin is rather
short lived, and no longer occurs after approximately 48 hours. A long-term
treatment option is high-dose estrogen therapy. This is, of course, limited
by the complications related to estrogen administration.
I. David Weiner, M.D.
I do not understand how hyperkalemia contributes to acidosis.
Will you please explain this to me? Thanks,
-
Hyperkalemia contributes to metabolic acidosis because of
its effects on ammonia metabolism. As you may remember from freshman
year renal physiology, ammonia metabolism is the primary component of renal
net acid excretion. Remember, the metabolism of proteins and amino
acids results in non-volatile acid production must be excreted by the
kidneys. Another way to think of this is that the acids produced from
protein and amino acid metabolism are buffered by bicarbonate present in
body fluids. This bicarbonate must be replaced. Both acid
excretion and new bicarbonate production occur via the kidney in the process
of net acid excretion. Thus, when net acid excretion is impaired,
metabolic acidosis ensues.
-
Hyperkalemia inhibits renal ammonia metabolism through effects
on multiple sites, probably including the proximal tubule, loop of Henle and the
collecting duct. Thus, metabolic acidosis with hyperkalemia is directly, and
completely, explained by its effects on renal ammonia metabolism.
I. David Weiner, M.D.
1.Angiotensin II slows CKD by Decreasing profusion pressure to the kidney?
-***or better... how does Ang II slow CKD?
- Angiotensin-II plays an important role in the progression of chronic
kidney disease. This occurs through a wide variety of mechanisms. First,
angiotensin-II, increases blood pressure, which directly increases the rate
of progression of chronic kidney disease. Second, angiotensin II, by causing
efferent arteriolar vasoconstriction, increases the glomerular hydrostatic
pressure gradient. The increased gradient contributes to pressure related
glomerular damage. Angiotensin II is also a proinflammatory cytokine.
Angiotensin II stimulates adrenal gland aldosterone production, and
aldosterone is a potent stimulator of renal interstitial fibrosis. Renal
interstitial fibrosis is irreversible and causes progression of kidney
disease. Angiotensin II stimulates production by renal interstitial cells of
monocyte chemoattractant protein 1, a specific proinflammatory cytokine
which stimulates white cell infiltration into the kidney where the white
cells then cause interstitial damage. This is only a partial listing of the
mechanisms through which angiotensin II contributes to the progression of
chronic kidney disease.
One might predict from this that inhibiting the renin-angiotensin system
could slow the progression of chronic kidney disease. In fact, that is
exactly true. The best types of clinical studies, randomized, prospective,
double-blind, placebo-controlled studies have shown that inhibiting the
renin-angiotensin system with ace inhibitors slows the progression of
chronic kidney disease and at this effect is separate from the effect of ace
inhibitors on hypertension. As a result, ace inhibitors are a standard of
care in the treatment of patients with chronic kidney disease. Another class
of medications, angiotensin-receptor blockers are also effective, and have
been shown in similar studies to slow the progression of chronic kidney
disease in patients with adult onset diabetes and renal disease. It is
likely that angiotensin-receptor blockers are effective in other conditions,
we just do not have the best quality studies at this point to prove this.
2.If the total Ca2+ decreases, the free Ca2+ stays constant at the expense
of complexed ot bound Ca2+, right?
- The body attempts to regulate ionized (free) calcium concentrations and
has no mechanism to know what the total calcium level is. Therefore, if the
bound calcium decreases, the body will not "know" that this has happened,
will continue to maintain the ionized calcium level normal, and the total
calcium will decrease. Similarly, if the bound calcium increases, the body
will maintain the ionized calcium normal, and total calcium will increase.
The trouble for the clinician occurs when a disease state results in both
the bound calcium decreasing and the ionized calcium increasing. In this
case, the total calcium may well be normal. It is incumbent that the
clinician should recognize that the bound calcium is low, and use this
information to recognize that if the total calcium is normal, then the
ionized calcium may be elevated. The astute clinician will use the formula:
"corrected" calcium = total calcium + (4.0 - albumin) x 0.8, whenever in the
albumin is less than 4.0. This adjusts the total calcium for the degree of
binding of calcium to albumin. The normal range for the corrected calcium is
the same as for the total calcium, but allows the clinician to recognize
hypercalcemia due to changes in bound calcium.
3. What is the interrelationship b/t inc. K+ and acid in CKD?
- Hyperkalemia commonly leads to metabolic acidosis in patients with
chronic kidney disease. This is because of the interrelationship between
potassium and renal ammonia production and metabolism. Hyperkalemia inhibits
ammonia production and metabolism and excretion by the kidneys. Ammonia,
however, is the primary component of net acid secretion by the kidneys. As a
result, with hyperkalemia there is compared ammonia excretion and, thus, net
acid excretion. This is what leads to metabolic acidosis. Conversely,
hyperkalemia commonly leads to metabolic alkalosis because of stimulation of
ammonia metabolism and excretion and subsequent increases in net acid
excretion.
4. finally, if a pt gets a renal tnspt. do you leave the old ones in
place as in the picture? Or take them out?
- In almost all cases when a patient receives a renal transplant in the
old, or "native, " kidneys are left in place. In rare cases, such as with
autosomal dominant polycystic kidney disease, there may be a need to remove
the native kidneys because of the volume of the abdomen that they are taking
up. However, removing the native kidneys is a substantial addition to the
renal transplant surgical procedure, and it is avoided whenever possible.
The Transplant kidney is not placed where the native kidneys are, but is
placed into the abdomen and anastamosed to the iliac artery and vein.
I. David Weiner, M.D.
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