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EDITORIAL
CURRENT
OPINION Something old, something new, something
borrowed, something black
Myles Wolf a and David A. Bushinsky b
Over the years, we have had the privilege to present
to you, members of the clinical and research com-
munities, a series of contemporary review articles
focused on normal mineral metabolism and its alter-
ations in a variety of disease states, including
chronic kidney disease (CKD). We have used a stand-
ard and consistent approach throughout. Each year,
we set out to identify a set of topics for the next
edition by surveying the year’s literature in search of
new publications of significant scientific interest
that we blend with additional topics of high clinical
relevance. To present the reviews in the most effec-
tive manner, we identify the authors who are best
equipped to integrate advances in the area with their
own opinions of how these advances might impact
the future, both clinically and scientifically. It is this
‘opinion’ in Current Opinion that makes for such a
distinctive publication. Although many journals
mandate that review articles be staid expositions
of the published literature that often allow only
narrow lanes for expression of opinion, we implore
our authors to go beyond the data, to contextualize,
to question, to provoke, and to frame the future.
In the 2017 edition of the Mineral Metabolism
section of Current Opinion in Nephrology and Hyper-
tension, we are pleased to present five new and
prescient articles to you. The issue opens with two
articles that provide an up-to-date review on topics
that fit in the ‘something old’ category. Long before
vitamin D analogs or calcimimetics, surgical para-
thyroidectomy was an established treatment of
refractory secondary hyperparathyroidism in end-
stage renal disease (ESRD). With the development of
new medical therapies to control parathyroid hor-
mone (PTH) levels and a body of preclinical and
epidemiological research that suggested that sup-
pressed PTH may be just as harmful or more harmful
to the bone and vasculature than elevated PTH,
use of surgical parathyroidectomy receded. More
recently, parathyroidectomy is resurgent, perhaps
because of loosening of international guidelines for
PTH control that may be leading to higher rates of
refractory hyperparathyroidism, and the emergence
of a new school of thought on the safety and efficacy
of parathyroidectomy. Although the latter position
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Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
is bolstered by observational human data that
suggest survival benefits of parathyroidectomy,
other clinical observational studies reported signifi-
cantly higher short-term hospitalization and
mortality risks in the early postparathyroidectomy
period. Komaba et al. (pp. 000–000) provide a com-
prehensive and provocative review of the different
sides of the parathyroidectomy controversy, which
will surely continue to rage in the absence of
randomized controlled trials that will undoubtedly
be challenging to implement and virtually imposs-
ible to blind.
Hungry bone syndrome is one of the main com-
plications of the immediate postoperative period
following surgical parathyroidectomy. The syn-
drome is so predictably common, when patients
seem to have avoided the postoperative severe hypo-
calcemia that is its hallmark, it is often because the
parathyroidectomy was incomplete, for example,
because of a supernumerary gland in the mediasti-
num. Jain and Reilly (pp. 000–000) review the
clinical manifestations, mechanisms and contem-
porary management of hungry bone syndrome, and
potential approaches to its prevention. Although
clearly ‘something old’ to clinicians, the review is
especially timely in light of the resurgence of surgi-
cal parathyroidectomy, and its updated insights into
prevention and management.
The present issue’s featured article is a review
that prominently befits the ‘something new’
category. In ‘Molecular Modifiers of Kidney Stones’,
Almani and Rimer (pp. 000–000) review exciting
advances in the prevention of recurrent kidney
stones. Almost 9% of Americans will have a kidney
stone sometime in their lives and about half of them
a
Division of Nephrology, Department of Medicine, Duke University School
of Medicine, Durham, North Carolina and bNephrology Division, Depart-
ment of Medicine and of Pharmacology and Physiology, University of
Rochester School of Medicine, Rochester, New York, USA
Correspondence to Myles Wolf, Duke University School of Medicine, 2
Genome Court, Room 2018, Durham, NC 27710, USA. Tel: +1 919 684
6752; fax: +1 919 684 3011; e-mail: myles.wolf@duke.edu
Curr Opin Nephrol Hypertens 2017, 26:000–000
DOI:10.1097/MNH.0000000000000325
www.co-nephrolhypertens.com
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Mineral Metabolism
will form recurrent stones. In the past, our efforts to
prevent recurrent stones focused on recommending
alterations in diet and fluid intake or instituting
medications such as thiazide diuretics to lower uri-
nary supersaturation of solid crystal phases found in
kidney stones, such as calcium oxalate. Although
this approach is relatively successful, there has been
little progress in actually modifying the crystal
surface to prevent crystal growth let alone induce
dissolution. Crystal growth can be slowed by a
thermodynamic effect where modifier–solute com-
plexation alters solute supersaturation, and by a
kinetic effect incurred by molecule adsorption on
crystal surfaces that physically blocks growth sites.
Almani and Rimer educate us on a newly discovered
mechanism of crystal growth inhibition in which
the modifier adsorbs to the crystal surface and indu-
ces strain on the crystal lattice and ultimately,
robust crystal dissolution. Using advanced tech-
niques such as atomic force microscopy to charac-
terize modifier–crystal interactions and the
mechanisms of crystal growth inhibition they have
shown that L-cystine and several other molecules are
not only far more effective than current therapies in
preventing crystal growth but also lead to dissol-
ution of calcium oxalate crystals. If confirmed in
clinical trials, these compounds have the potential
to fundamentally change our approach to preven-
tion of recurrent kidney stones. In this edition we
planned on fewer articles than usual to provide the
additional space for this important extended review.
Iron deficiency anemia is common in patients
with advanced CKD and ESRD. Outside the neph-
rology and dialysis clinics, iron deficiency is usually
caused by conditions characterized by excessive
blood loss including menorrhagia and gastrointes-
tinal diseases. Due to unremitting blood loss, many
of the latter patients require frequent treatment
with intravenous iron. Since these patients are typ-
ically treated as outpatients, pharmaceutical devel-
opment of new iron formulations that can be given
rapidly in high doses without risk of anaphylactoid
reactions has been a priority. However, as use of
certain of these new agents has proliferated in recent
years, so have cases of intravenous iron-induced
hypophosphatemia. Although hypophosphatemia
following single administrations of these high-dose
intravenous iron formulation was usually asympto-
matic and self-limited in pivotal clinical trials,
emerging reports demonstrate that repeated dosing
can be complicated by severe and protracted hypo-
phosphatemia that culminates in osteomalacia and
debilitating fragility fractures. Zoller et al. (pp. 000–
000) review this emerging syndrome and emphasize
that the underlying pathophysiology of fibroblast
growth factor-23-mediated renal phosphate wasting
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is ‘something borrowed’ from that of autosomal
dominant hypophosphatemic rickets, which is the
prototype condition of phosphate wasting due to
primary excess of fibroblast growth factor-23.
Among the most ominous physical findings in a
patient with ESRD is ‘something black’ on the legs,
abdomen or under the breasts, indicating the pres-
ence of calciphylaxis. Calciphylaxis is a devastating,
excruciatingly painful and often fatal complication
of ESRD that is also encountered rarely in other
clinical settings. The necrotic skin eschars serve as
a nidus for local infection and portal of entry for
invading bacteria to evade the innate immune
barrier of healthy skin. Nigwekar (pp. 000–000)
presents a comprehensive review of the incidence,
risk factors and clinical manifestations of calciphy-
laxis, and recent advances in our understanding of
its pathogenesis. He emphasizes that one of the
main obstacles to progress in prevention and treat-
ment of calciphylaxis has been the lack of infra-
structure and coordination between dialysis
providers that is needed to conduct sufficiently
powered randomized controlled therapeutic trials
in this uncommon condition. Emerging registries
and clinical trial networks that can systematically
evaluate novel therapies could help address this
unmet need.
As always, we thank our group of authors for
their outstanding contributions and thank our read-
ers for your interest in their reviews. We look for-
ward to another year of scientific progress and
discovery that will stimulate next year’s edition.
We also would like to inform our readers that the
2017 edition of the Mineral Metabolism section of
Current Opinion in Nephrology and Hypertension also
marks a bittersweet transition. Following publi-
cation of this issue, Dr Wolf will step down from
his role for the last seven years as co-editor with Dr
Bushinsky in order to focus on his other opportu-
nities and responsibilities in nephrology research
and leadership. Rest assured, that Dr Wolf’s exit
creates an opening for a new incoming expert in
mineral metabolism to help redirect the Mineral
Metabolism section of Current Opinion in Nephrology
and Hypertension with Dr Bushinsky into new direc-
tions and to new heights mirroring continued prog-
ress in our burgeoning field.
Acknowledgements
None.
Financial support and sponsorship
None.
Conflicts of interest
There are no conflicts of interest.
Volume 26  Number 00  Month 2017