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Contributors: A Bansal (U of Pennsylvania) | P Dedhia

(U of Cincinnati) | A Elebiary (Lahey Clinic) | X Vela (U
of El Salvador) | D Thomson (ECU) | P Jawa (ECU) | S
Sridharan (Lister Hospital, UK) | F Iannuzsella (IRCCS,
Italy) | D Mitema (Johns Hopkins U) | Malvinder Parmar
(Northern Ontario, Canada) | Wisit Cheungpasitporn
(Mayo)

I ssue 4

Volume 2

Year 2015

URL http://goo.gl/QDSB5B

#Kidney
KONNECTI ON
Editor: Tejas Desai | Chief: Cynthia Christiano | Free subscription by emailing myFellowship@ecu.edu

PROTON-PUMP INHIBITORS LOWER MORE

THAN JUST [H+]

by Francesco Iannuzzella (@caioqualunque )

Let's start with a case. A

73-year-old woman presented to
our outpatient clinic for a
follow-up visit of an established
diagnosis of stage 3 chronic
kidney disease (CKD). She had
no history of smoking or alcohol
abuse. She was a typical CKD
patient with the standard
alphabet-soup medical history:
HTN, HLD, and GERD. The
good patient that she was, she
took amlodipine, lisinopril,
atorvastatin, and lansoprazole (a
proton-pump inhibitor, or PPI)).
Though she arrived for a CKD
follow-up, she mentioned feeling
dizzy & complained of upper
extremity tremors, nausea,
anxiety, anorexia, and muscle
cramps. In the office her blood
pressure was 150/95 mmHg but
the exam wasn't very remarkable.
Blood tests showed hypocalcemia
(6.1 mg/dL), hypokalemia (2.1
mEq/L), and severe
hypomagnesemia (0.3 mg/dL).

After seeing these labs, we began to experience some

of her anxiety and admitted her to our local hospital
for supplementation with intravenous calcium,
magnesium, and potassium. And here's where it gets
really interesting: a measured fractional excretion of
magnesium on a random urine specimen was < 2%.

In 1960, Vallee and coworkers

reported the first description of
symptomatic hypomagnesemia in
a case series of 5 patients.
Hypomagnesemic patients are
usually asymptomatic until serum
magnesium concentrations
Such a low fractional excretion could only mean one
thing: a non-renal source of magnesium losses. When become < 1.2 mg/dL & symptoms
include carpopedal spasms with
you don't have enough evidence to blame the kidney
and you're a nephrologist, what do you do? You blame positive Chvostek & Trousseau
signs, muscle cramps, tremor,
the next best organ....the stomach! This patient had
been taking lansoprazole for ~16 months...replacing it nausea, anorexia, apathy,
convulsions, cardiac conduction
with ranitidine helped control her GERD and
disturbances, and arrhythmias. In
normalized her serum magnesium levels. She's had
patients with severe
normal magnesium levels ever since.
hypomagnesemia (like our case), it
is very common to find other
biochemical abnormalities such as
hypocalcemia, and hypokalemia.
Hypocalcemia seems to be caused
by an impaired PTH secretion.
Hypokalemia has been attributed
to renal potassium-wasting. And
because intracellular magnesium is
an inhibitor of the renal outer
medullary potassium (K +) channel
Presumed mechanism by which PPIs cause increased gastrointestinal losses of
magnesium. Inhibition of the TRPM6/7 receptor activity (by raising the luminal pH)
(ROMK), a reduction in the
prevents absorption of magnesium, resulting in enteric magnesium wasting. From KI
2013; 83:553

(Protons continued from page 1)

former may impair the kidneys ability to conserve the latter. Common causes of
hypomagnesemia are reported in Table. The main distinction between gastrointestinal
and renal losses can be made by measuring the fractional excretion of magnesium on a
random urine specimen, according to the following formula
FEMg= (Urinary Magnesium x plasma creatinine) x 100 /(0.7 x plasma Magnesium) x
Urinary creatinine
(a value > 2% suggests renal magnesium-wasting)
We know that magnesium can be absorbed in the small intestine through both passive &
active transport systems. For unknown reasons and in special circumstances/subjects,
PPIs may affect these transport systems, leading to gastrointestinal magnesium loss.
Hypomagnesemia has been reported to occur 1-2 years after PPI initiation, but most
cases occurred after 5 or more years. The treatment of PPI-induced hypomagnesemia

From Am J Clin Nutr 1964; 15:133-143

consists of magnesium supplementation and discontinuation of PPI. Serum magnesium levels usually normalize within 1-3 weeks
after discontinuation of PPI therapy. Recurrence of hypomagnesemia following reintroduction of another PPI has been reported,
so in these patients histamine 2 receptor antagonists should be used.
Learn more about the effects PPIs have on magnesium by visiting pubmed.org & searching: 13840893, 17804670, or 17065651

LIT IN A MINUTE
THE PA21 STUDY: VEL PHORO VERSUS SEVEL AM ER

You wouldn't believe how many pills a dialysis

patient must take. The pill "burden" is
significant; one study suggesting that the median
daily pill burden is 19 with a maximum > 30
tablets/day. Phosphate binders account for 49%
of the total daily pill burden & this burden
directly contributes to patient non-compliance.
Non-compliance has many disastrous health
consequences, like hyperphosphatemia,
uncontrolled secondary hyperparathyroidism, &
severe bone abnormalities. So any intervention
that help patients achieve better phosphate
control @ a lower pill burden would be of great
interest. Say hello to the PA21 study.
PA21 (VelphoroTM ) is an Fe2+-based, Ca2+-free
phosphate binder. In the PA21 Study,
investigators compared the phosphate-controlling
effects of PA21 against sevelamer carbonate in
1055 randomized hemodialysis patients. PA21
was as efficacious as sevelamer; the former
dropped phosphorous by 0.71 mmol/L & the

latter 0.79 mmol/L. However, the 2 most impressive findings were the tablets required
to achieve parity w/ sevelamer & the overall adherence to the regimen. Patients
needed a mean of 3.1 pills/day of PA21 vs. 8.1 pills/day of sevelamer. This resulted in
an adherence rate w/ PA21 of 82.65 (over the 24-week study period) vs. 77.2% w/
sevelamer.
Pill burden is
a serious
challenge to
overcome.
It's awesome
to see that,
when
compared
head-to-head
against
sevelamer, PA21 was able to achieve a comparable serum phosphate reduction @ a
lower pill burden. Time will tell if the effects of PA21 are as efficienty & efficacious
as many dialysis patients (and their doctors) hope it will be.
Learn more @ Kidney International 2014; 86: 638 (link)