Showing posts with label magnesium. Show all posts
Showing posts with label magnesium. Show all posts
Sunday, January 27, 2019
Tuesday, October 2, 2018
Monday, July 28, 2014
Cisplatin-induced acute kidney injury (AKI): Why is magnesium balance important?
Cisplatin is one of the most commonly used chemotherapeutic agents. In the US, there are more than 2000 ongoing clinical
trials investigating cisplatin in patients with ovarian, testicular, bladder,
cervical, and head/neck cancers, among others. Unfortunately, approximately 25-30% of
patients receiving cisplatin suffer nephrotoxicity despite its potency as an
anti-tumor agent. This is a challenge in the oncology clinical setting where either
dose reductions or discontinuation of cisplatin are often required to salvage
the kidneys leaving the patient and clinician with limited options given the efficacy
and affordability of this drug. An
important contributor to cisplatin-mediated nephrotoxicity is the accompanying electrolyte
imbalances, including hypomagnesemia. Magnesium (Mg) is an essential dietary mineral
required for normal body functioning and cellular processes. Surprisingly, Mg consumption (via foods and
supplements) among most Americans, particularly the elderly, is below the recommended
daily allowance. In addition, many medications and disease conditions reduce
the availability of dietary Mg. Therefore, we sought to examine the
effects of Mg deficiency and Mg supplementation following Mg deficiency on
cisplatin-mediated acute kidney injury (AKI) using a mouse model. We observed that Mg deficiency exacerbates
cisplatin-induced AKI, whereas correction of Mg status protects against cisplatin-mediated
AKI. Additional studies detail the cellular
and molecular mechanisms by which Mg provides renoprotection, namely by attenuating
cisplatin-induced inflammation, oxidative stress and apoptosis. In addition, we
show for the first time that Mg supplementation reduces the platinum
accumulation in the kidneys possibly by affecting the efflux of cisplatin by
the renal epithelial cells. While
protecting the kidneys, Mg supplementation did not compromise cisplatin-induced
cytotoxicity using several human cancer cell lines, suggesting the Mg does not
interfere with the chemotherapeutic efficacy of cisplatin in vitro. The results of this study warrant future large scale
clinical studies to better monitor patients’ Mg status prior to and during
cisplatin treatment and to develop improved Mg supplementation protocols that
provide nephroprotection without compromising cisplatin’s potent
chemotherapeutic efficacy.
For full link of paper click below
Post By:
Malvika Solanki, MD
Monday, April 14, 2014
Clinical Case 82: Answers and Summary
Which oral magnesium preparation has the highest amount of elemental magnesium content?
Monday, September 9, 2013
Michelis-Castrillo syndrome
Michelis-Castrillo
syndrome or Familial Hypomagnesemia with hypercalciuria and nephrocalcinosis
(FHHNC)
The other
day, I had dinner with the chief of Nephrology at Lenox Hill hospital in Manhattan,
Dr. Michael Michelis. In the dinner conversation, he was describing his days in
Pittsburg where he had once worked under the direction of Dr. Drash. Interestingly, he was asked to see a family
of siblings with an interesting tubular disorder. At that time he didn’t know
what exactly he was dealing with. He called it “Decreased bicarbonate threshold and renal magnesium wasting in a
sibship with distal renal tubular acidosis : Evaluation of the pathophysiologic role of parathyroid hormone”
and published it in the literature. Since then, over 50 cases of similarfindings have been described: hypomagnesemia,
hypercalciuria, and nephrocalcinosis. He was told by someone else that the
disease has been named after him as Michelis-Castrillo
syndrome. In a recent paper in JASN, it’s quoted as “Gitelman syndrome,
and autosomal recessive familial hypomagnesemia with hypercalciuria and
nephrocalcinosis (FHHNC) are two hereditary hypomagnesemic renal disorders. FHHNC
was first described by Michelis et al. in 1972 (Michelis-Castrillo syndrome). " Dr Castrillo also described this entity later in the Spanish literature (Castrillo JM, Rapado A, Traba ML, Esbrit P, Hernando L: Nefrocalcinosis con hipomagnesemia. Nefrología 3:159–165, 1983), almost 11 years after it was initially described by Dr.Michelis. The disease hence gets its name now as Michelis-Castrillo syndrome.
Since
then, patients of at least 50 different FHHNC kindreds have been reported. FHHNC
is generally complicated by chronic renal failure (CRF) in early childhood or
adolescence. Recurrent urinary tract infections (UTI) and polyuria/polydipsia
are frequent initial symptoms. In addition to marked hypomagnesemia, all
affected individuals exhibit hypercalciuria and nephrocalcinosis. Additional
symptoms at manifestation include nephrolithiasis, abdominal pain, convulsions,
muscular tetany, failure to thrive, incomplete distal renal tubular acidosis
(dRTA), and hypocitraturia. Some authors reported elevated serum parathyroid
hormone (PTH) levels early in the course of the disease, independently of GFR.
Monday, January 31, 2011
CONSULT ROUNDS: Cetuximab therapy and wasting syndromes?
The other day we discussed a case of cetuximab induced hypomagnesemia.
Cetuximab is a monoclonal antibody against the epidermal growth factor receptor (EGFR; also know as c-erb1 or HER1). The EGFR is overexpressed in many epithelial cell cancers, including colorectal, breast, lung, and head and neck cancers.
This agent has been associated with mg and ca wasting syndromes. The relationship between EGFR blockade and magnesium transport may help elucidate important cellular pathways. The protein TRPM6( for Mg transport), a member of the transient receptor potential family of cation channels, has been shown to mediate active transport. Patients with a germline mutation in the TRPM6 gene have severe congenital hypomagnesemia. TRPM6 is localized along the apical membrane of the loop of Henle and the distal convoluted tubule, as well as the brush border of the small intestine. EGFR is also highly expressed in these regions as well. Since this drug blocks EGFR, mg wasting also occurs. Urinary Mg levels usually are high in these patients if they have serum mg that is low suggesting urinary losses. Usually this effect is reversible when chemo is discontinued.
The only caviet is that this medication is usually given with irenotecan, which causes severe diarrhea as well making the diagnosis bit more difficult if the losses are GI or urinary in origin. In the setting of hypomagnesemia, PTH release and the ability of PTH to mobilize calcium from the bone are impaired leading to hypocalcemia as well. For this reason, correction of serum magnesium is usually sufficient to normalize serum calcium levels.
The only caviet is that this medication is usually given with irenotecan, which causes severe diarrhea as well making the diagnosis bit more difficult if the losses are GI or urinary in origin. In the setting of hypomagnesemia, PTH release and the ability of PTH to mobilize calcium from the bone are impaired leading to hypocalcemia as well. For this reason, correction of serum magnesium is usually sufficient to normalize serum calcium levels.
Ref:
Thursday, January 20, 2011
TOPIC DISCUSSION: Magnesium for pre eclampsia?
Magnesium sulphate increased prostacyclin production and that is a potent vasodilator. Some people think this might be the reason for prevention of pre eclampsia and eclampsia where cerebral vasospams and decreased blood flow are thought to be contributory. It prevents seizures by binding to Ca sites and not letting the muscles work as they are supposed to.
Cardiac output usually increases following magnesium administration, compensating for the vasodilatation and minimising hypotension. It is the first-line anticonvulsant for the management of pre-eclampsia and eclampsia, and it should be administered to all patients with severe pre-eclampsia or eclampsia. Magnesium is a moderate tocolytic but the evidence for its effectiveness remains disputed.
What is the data?
1. Two studies randomized showed Mg sulfate over placebo to be preventive of seizures in severe pre eclampsia.
2. Overview of all controlled randomized trials comparing mg sulfate in pre eclampsia as an anticonvulsants show its superiority versus placebo
3. ACOG recommends that use of mg sulfate in women with severe pre eclampsia and that there is lack of consensus as to women in mild pre eclampsia require such treatment or not given small data on that.
Can acute magnesium toxicity occur in the obstetric literature and patients? Magnesium levels when checked are high in these patients getting doses of magnesium but no toxicity is seen. It is rare. Literature has few cases reported but mostly were due to accidental overdosing of the agent.
The normal plasma concentration of magnesium is 0.8-1.0 mmol/L or 1.7 to 2.2 mg/dL. and the suggested therapeutic range in pregnancy 1.7 to 3.5 mmol/L or 4.8-8.4mg/dl. Complicating the interpretation of serum magnesium is that it can be reported in milligrams per decilitre (mg/dL), milliequivalents per litre (mEq/L) or millimoles per litre. As a divalent ion, the latter two are not the same. Deep tendon reflexes are diminished or lost between 3.5 and 5.0 mmol/L, with respiratory paralysis thought to occur at >= 7.5 mmol/L, although significant ventilatory changes occur at lower concentration. Central nervous system depression in conjunction with serious cardiac conduction abnormalities is seen at 7.5 mmol/L and cardiac arrest possible at >=12.5 mmol/L. It also depends on when you draw the level and initially you might get a very high value.
The most common regimen for prevention in pregnant females is a loading dose of 6 g intravenously over 15 to 20 minutes followed by 2 g per hour as a continuous infusion. If someone is in renal failure, lower doses are suggested as main route of clearance is kidney. Following serum magnesium levels is not required if the woman's clinical status is closely monitored for evidence of potential magnesium toxicity. So we don't need to be chasing mg values.
Ref:
Friday, December 10, 2010
Concept Map of Hypomagnesemia
A brief overview of Hypomagnesemia using a concept map model
If not complete, help me complete it!
http://www.ncbi.nlm.nih.gov/pubmed/10405219
Monday, November 29, 2010
Nephsap review: Fluids Electrolytes
Interesting thing we learned at our Nephsap about why hypomagnesemia causing hypokalemia
1. Intracellular Mg has inhibitory effects on the K secretion of ROMK channels in the distal nephron.
2. A decrease in Intracellular Mg will release this inhibitory effect and cause Renal K excretion.
3. Also Low Mg can lead to increase distal Na delivery and increased aldo as well and K excretion increases.
1. Intracellular Mg has inhibitory effects on the K secretion of ROMK channels in the distal nephron.
2. A decrease in Intracellular Mg will release this inhibitory effect and cause Renal K excretion.
3. Also Low Mg can lead to increase distal Na delivery and increased aldo as well and K excretion increases.
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