1. PODCAST TRANSCRIPT:
FOUNDATIONS OF MEDICAL MANAGEMENT OF SHTP
Mohamed G. Atta, MD, MPH
As indicated before it is important to detect this disorder as early as possible to prevent
complications. We are not talking about just osseous or bone complications, which is high
turn-over bone disease, but also we are talking about maintaining the balance in both serum
calcium phosphorus and other complications such as vascular complications, which is related
to the deposition of these disordered minerals in the soft tissue and blood vessels. Vascular
calcification or soft tissue calcification is a main issue now that we are dealing with in
patients with hyperparathyroidism.
It is important to actually start screening those patients early to prevent not just the skeletal
or the bone complications, but also vascular complications, which has been shown in the
past few years to be associated with increased cardiovascular event rates and therefore one
important fact about hyperparathyroidism is that it starts with diffuse hyperplasia and early
nodularity. Those are the stages where actual interventions are helpful and then once those
nodules becomes single nodule that is large enough, those nodules or tertiary what we call
tertiary hyperparathyroidism are resistant to treatment.
The reason they are resistant to treatment is because they lack the receptors for both
vitamin D and calcium sensing receptors. Once the patients reach that level, medical
intervention is not possible and those patients will end up having surgery or
parathyroidectomy to achieve reduction in parathyroid hormone secretion. So, the objective
is really prevention first of osteodystrophy or hyperparathyroidism related bone disease, and
extraosseous complications, which is vascular complications and cardiovascular
complications.
The other aspect of high PTH in kidney patients is mortality which is the solid outcome and it
has been shown at least in some observational studies that high parathyroid hormone across
all levels is associated with increased mortality in kidney patients. Therefore, treatment is
not just to prevent complications and hyperparathyroid bone disease, but also hopefully
decrease mortality. Like every kidney patient I have seen in clinic, those patients are
generally without symptoms. The patients with early kidney disease have no symptoms
related to kidney disease and also they do not have any symptoms related to
hyperparathyroidism.
Obviously it is important that those patients are made aware not just of their kidney disease
but also that they have other disturbances as a result of the kidney disease in the mineral
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2. metabolism, which is the high parathyroid hormone. Communication with the patients about
the disease is really critical in educating our patients about how to address this issue and
also to make the patient feel the importance of this issue and how to address it since those
patients are not expected in the early stage to have any symptoms related to their condition.
It is also important to indicate the cardiovascular implications of high PTH in those patients
and the vascular and soft tissue calcifications.
Make sure that the primary care physicians who are taking care of those patients are aware
of the current condition and the medical complications of hyperparathyroidism, so they can
also reinforce the issue of treatment and the issue of screening and discuss these; they have
the same level of discussion with the patient about the disorder.
The role of the nephrologist… as a nephrologist I would like to obviously see my patients
early on in the disease process and it is also important for me to screen for this disorder
early on rather than wait until the patient has an irreversible condition. Also as a
nephrologist it is important for me to communicate the condition with the primary care
physician, make sure that they know this patient has secondary hyperparathyroidism and
how to screen for it and how often we should screen for it; the implications of the condition
and if there is any intervention at that point of time in the early stage.
How to actually communicate with the patient, so we have the same message directed at the
patient so the patient feels that they are having two physicians, not just the nephrologist is
talking about hyperparathyroidism, which he had not discussed with the primary care
physician.
It is critical for the nephrologist to communicate the message with the primary care
physician, so they can actually have one message directed at the patient care. A critical
aspect of treating patients with CKD is to realize that those patients have a lot of other
comorbid conditions that need to be addressed and not just by the nephrologist but
obviously by the primary care physician. So the fact that we are talking about
hyperparathyroidism as complications of chronic kidney disease should not really discourage
the nephrologist from addressing the other comorbid conditions. That is really important as
well as dyslipidemia, hypertension and glycemic control.
Although the primary care physician is the central physician in taking care of those issues, it
is also important and recommended by the National Kidney Foundation to address those
comorbid conditions in early stages of chronic kidney disease. The National Kidney
Foundation in 2003 came up with the practice guidelines for bone metabolism and chronic
kidney disease patients, and suggested that those patients should be monitored for
phosphorus, calcium and intact PTH. In stage III CKD, which is GFR between 30 and 60 or 30
and 59 mL per minute, those patients should have screening every 12 months. In stage IV,
which is GFR between 16 and 29, every three months. In stage V, which is GFR less than 15
or patients on dialysis should be screened for serum calcium and phosphorus every month.
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educational facilitation by Medikly, LLC
Supported by and unrestricted educational grant from Abbott Laboratories

3. With regard to intact PTH, in stage III, again similar to calcium and phosphorus every 12
months, but in stage IV and stage V, they are similar every three months. Those patients
should be monitored for intact PTH.
In 2009, a global initiative started to ensure that patients with disordered metabolism and
CKD are monitored the same way across the globe. KDIGO, which is Kidney Disease
Improving Global Outcome on mineral and bone disorder workgroup, started clinical practice
guidelines for the diagnosis, evaluation and prevention and treatment of chronic kidney
disease, mineral and bone disorder. Their recommendation slightly differed from the
National Kidney Foundation; with regard to calcium and phosphorus, the recommended
monitoring is between 6 and 12 months for stage III and 3 and 6 months for stage IV and 1 to
3 months for stage V or patients on dialysis. With regard to the intact PTH level monitoring,
at the stage III it is recommended to measure based on the baseline level and CKD
progression.
For instance if the patient’s initial level was elevated, it is important for the treating
physician, whether it is a nephrologist or a primary care physician, to indicate that those
patients may be or are at risk for rapid progression of their parathyroid disease and
therefore they may need more frequent monitoring. In stage IV it is recommended to
monitor intact PTH every 6 to 12 months and in stage V every 3 to 6 months.
The biochemical assessment according to the National Kidney Foundation guidelines is
routine measurement in all patients with GFR less than 60 mL per minute with the PTH,
calcium and phosphorus. The KDIGO, the global initiative, their recommendation for
biological assessment is to measure serum calcium, phosphorus, PTH and alkaline
phosphatase in stage III and repeat testing and measurement of 25-hydroxy vitamin D
dependent on the baseline values and therapeutic interventions. The therapeutic decision
should be not only based on single lab value, it should be based on trends rather than just a
knee jerk reaction to the lab value. You should take into account all available CKD and MBD
assessments.
In regard to the recommendation for screening for vascular calcification, the National Kidney
Foundation had no specific screening recommendation for vascular calcification except for
dialysis patients with severe vascular calcification and or soft tissue calcification; the National
Kidney Foundation recommended the use of non-calcium containing phosphate binders as
the preferred medications of choice. The KDIGO on the other hand suggested that patients
with known vascular or valvular calcification should be considered at the highest
cardiovascular risk factor or risk and it is reasonable to use this information to guide the
management of CKD mineral bone disorder.
The recommendation for the detection of the presence or the absence of valvular
calcification and CKD is using either echocardiogram to detect the valvular calcification and
also a lateral abdominal x-ray to detect the presence or absence of vascular calcifications.
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educational facilitation by Medikly, LLC
Supported by and unrestricted educational grant from Abbott Laboratories

4. There are target levels and ranges for all these biochemical parameters, so according to the
KDOQI in stage III, the target phosphorus is between 2.7 and 4.6 and for the calcium it is
maintained serum calcium within normal for the lab. For stage IV and V, it is to maintain
phosphorus between 2.7 and 4.6 again, so it is like stage III, and in stage V for patients on
dialysis to maintain serum phosphorus between 3.5 and 5.5. With regard to calcium, it is
really maintaining serum calcium within normal limits in both stages III, stage IV, and stage V.
The normal range is considered about 8.4 to 9.5 mg/dL. So that is the recommendation by
the National Kidney Foundation. The KDIGO, or the global initiative guideline, does not differ
completely from the National Kidney Foundation guidelines: regarding phosphorus in stage
III, it is recommended to maintain serum phosphorus within normal limits and stage IV and V
again to maintain the phosphorus within normal limits, and for those patients on dialysis to
maintain serum phosphorus towards normal limitsand regarding calcium, for all levels of CKD
to maintain serum calcium within the normal limits for the lab value.
Again similar recommendations with regard to phosphorus and calcium both by the National
Kidney Foundation and KDIGO guidelines.
What about parathyroid hormone? In the targets for the treatment for stage III there is a
difference between the KDOQI and KDIGO guidelines; the KDOQI recommended in the stage
III to maintain intact PTH between 35 and 70 pg/mL. The KDIGO suggests to maintain PTH at
the upper limits of normal, which is close to the same upper limit that the National Kidney
Foundation recommended, which is 70 pg/mL. For stage IV on the other hand, KDOQI
recommended a PTH range between 70 and 110 pg/mL. The KDIGO recommended an upper
limit of normal, so to still maintain intact PTH at the normal level.
In stage V this clearly is a departure from what a lot of nephrologists have been used to with
the KDOQI guidelines, which initially maintained the PTH between 150 and 300 pg/mL. but
the KDIGO at stage V indicated again the upper limits of PTH normal, but for those patients
on dialysis the initial KDOQI recommendation was to stay at the course similar to stage V
CKD and maintain PTH between 150 and 300 pg/mL. The KDIGO came up with the
recommendation to maintain intact PTH 2 to 9 times the upper limit of normal. Now, an
updated version of the National Kidney Foundation came out to comment on this new
guideline with KDIGO that indicated much higher intact PTH levels.
They suggested actually the upper limit instead of 9 times, they put a cap of 600 pg/mL
level, but also indicated that those target level should be individualized in the sense that in
some patients you may find that at level of intact PTH they may have excessive bone disease
or excessive calcification that you may need to lower PTH less than 600 and keep them at
300 or 400 for instance. So, the idea is to clearly individualize treatment for each specific
patient rather than just blindly follow these target levels.
Developed in collaboration with the Johns Hopkins University School of Medicine, through a strategic
educational facilitation by Medikly, LLC
Supported by and unrestricted educational grant from Abbott Laboratories