Tag: calcium

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Highest creatinine I have seen in acute kidney injury

We had a patient earlier this month who presented with a creatinine that was 20 mg/dL on admission and rose to 22 on the repeat. That is the highest creatinine I have ever seen in a patient with acute kidney injury. I have a seen two patients with advanced CKD with creatinines in the mid to high thirties. (34 and 37 mg/dL).

When my fellow described the patient I was sure this was going to be CKD until she mentioned, rather triumphantly, that when she examined the patient she palpated a large bladder. She had a Foley placed and the patient voided 1300 mL of urine in the next hour.
Obstructive uropathy in a woman is cervical cancer until proven otherwise. Sure enough, a subsequent CT scan of the pelvis revealed a pelvic mass which was diagnosed as cervical cancer.
The patient was discharged with a creatinine of 1.9 mg/dL.
A few aspects of the case were interesting and surprising:
  • Obstructive uropathy causes an electrogenic type 1 RTA (hyperkalemic type 1 RTA as opposed to the hypokalemic classic type 1 RTA). Because of the RTA, these patients often have hyperkalemia out of proportion to the degree of renal failure. She was not hyperkalemic and presented with a potassium of 4.6 mEq/L.
  • The patient had a pH of 7.2, bicarbonate of 4 and a pCO2 of 8, giving her a metabolic acidosis and a respiratory alkalosis (predicted pCO2 by Winter’s formula is 14±2). I had been taught that patients cannot blow off CO2 below 14 mmHG. I guess she had super lungs. As best we could tell, the respiratory alkalosis was due to anxiety and resolved the following day.
  • My fellow wanted to give bicarbonate for the metabolic acidosis, but I did not. The pH of 7.2 is fine and the patient was hemodynamically stable. Her total calcium was 4.6 and her phosphorous was 10. I was worried that giving bicarbonate would correct the acidosis which at the time was essential to prevent the hypocalcemia from causing tetany or worse. The acidosis shifts bound inactive calcium to the unbound and active ionized form.
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Lecture at Providence Hospital on Electrolytes

I am trying to do a monthly lecture for the Providence internal medicine residents on electrolytes. I gave my second one last Friday. It was an interesting case we had of hypernatremia on the consult service last summer.

I did this lecture in Keynote and I am blown away by how good it presents through SlideShare. Really impressive.

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Klotho information

I went to an afternoon of lectures at ASN on Klotho and its relationship to calcium. I thought they talked about klotho being involved with proximal tubule transcellular calcium reabsorption via TRPV5/6 but after posting a comment about that here, I find that my memory failed me.

It looks like Klotho binds FGF-23 receptor and makes it more specific for binding FGF-23 which then increases the production of calcitriol. Additionally free Klotho in the urine increases expression of TRPV5/6 which enhances DCT and connecting tubule transcellular calcium absorption.

the Recent advances that have given rise to marked progress in clarifying actions of alpha-Klothootho (alpha-Klotho) and FGf23 can be summarized as follows:

  1. alpha-Klotho binds to Na, K-ATPase, and Na, K-ATPase is recruited to the plasma membrane by a novel alpha-Klotho dependent pathway in correlation with cleavage and secretion of alpha-Klotho in response to extracellular Ca.
  2. The increased Na gradient created by Na, K-ATPase activity drives the transepithelial transport of Ca in the choroid plexus and the kidney, this is defective in alpha-Klotho(-/-) mice.
  3. The regulated PTH secretion in the parathyroid glands is triggered via recruitment of Na, K-ATPase to the cell surface in response to extracellular Ca concentrations.
  4. alpha-Klotho, in combination with FGF23, regulates the production of 1,25 (OH) Vitamin D in the kidney. In this pathway, alpha-Klotho binds to FGF23, and alpha-Klotho converts the canonical FGF receptor 1c to a specific receptor for FGF23, enabling the high affinity binding of FGF23 to the cell surface of the distal convoluted tubule where alpha-Klotho is expressed.
  5. FGF23 signal down-regulates serum phosphate levels, due to decreased NaPi-IIa abundance in the apical membrane of the kidney proximal tubule cells.
  6. alpha-Klotho in urine increases TRPV5 channel abundance at the luminal cell surface by hydrolyzing the N-linked extracellular sugar residues of TRPV5, resulting in increased Ca influx from the lumen. 

These findings revealed a comprehensive regulatory scheme of mineral homeostasis that is illustrated by the mutually regulated positive/negative feedback actions of alpha-Klotho, FGF23, PTH and 1,25 (OH) Vitamin D. In this regard, alpha-Klotho and FGF23 might play pivotal roles in mineral metabolism as regulators that integrate calcium and phosphate homeostasis, although this concept requires further verification in the light of related findings. Here, the unveiling of the molecular functions of alpha-Klothootho and FGF23 has recently given new insight into the field of calcium and phosphate homeostasis. Unveiled molecular functions of alpha-Klotho and FGF23 provided answers for several important questions regarding the mechanisms of calcium and phosphate homeostasis that remained to be solved, such as :

  1. What is the non-hormonal regulatory system that directly responds to the fluctuation of extracellular Ca? 
  2. How is Na, K-ATPase activity enhanced in response to low calcium stimuli in the parathyroid glands?
  3. What is the exact role of FGF23 in calcium and phosphorus metabolism?
  4. How is Ca influx through TRPV5 controlled in the DCT nephron?
  5. How is calcium homeostasis regulated in cerebrospinal fluid?

However, several critical questions still remain to be solved. So far reported,alpha-Klotho binds to Na, K-ATPase, FGF receptors and FGF23, and alpha-Klotho hydrolyzes the sugar moieties of TRPV5. Does alpha-Klotho recognize these proteins directly or indirectly?Is there any common mechanism?How can we reconcile such diverse functions of alpha-Klotho?What is the Ca sensor machinery and how can we isolate it?How do hypervitaminosis D and the subsequently altered mineral-ion balance lead to the multiple phenotypes?What is the phosphate sensor machinery and how can we isolate it? How does the Fgf23/alpha-Klotho system regulate phosphorus homeostasis? How are serum concentrations of Ca and phosphate mutually regulated?

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Journal Club: Bicarb for contrast nephropathy and calcitriol for CKD 3 and 4

The first article was a retrospective study on the use of calcitriol in patients with CKD stage 3 and 4. The outcome was mortality and mortality plus dialysis. The authors were able to demonstrate a significant reduction in both outcomes with the use of calcitriol. Some interesting points were the lack of a dose effect and the effect was independent of PTH. The authors suggest that the benefit of activated vitamin D therapy is not due to its affect on PTH.

Association of oral calcitriol with improved survival.

The second article was the latest study on contrast nephropathy.

Sodium bicarbonate vs sodium chloride.

This well done randomized, single-blinded, controlled trial showed no difference between isotonic NaCl and nearly isotonic bicarbonate.

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Calcium and the great case report

I gave my first lecture to the residents at Providence Hospital on Friday before Labor Day. I did a new lecture on calcium. I tried to base this lecture around this incredibly interesting patient I had a few years ago at St. John.

He was a young man who came in with a fracture due in part from his rip-roaring uncontrolled secondary hyperparathyroidism, which had actually progressed to tertiary hyperparathyroidism. We treated his hypercalcemia, got him a parathyroidectomy and then watched in horror as his hypercalcemia switched to hypocalcemia as part of a wicked case of Hungry Bone Syndrome. To cap it off he developed acute symptomatic hypocalcemia after meeting Alonzo Mourning.

On that one admission, in one patient my team got to see and study:

  1. Renal osteodystrophy with skeletal complications
  2. Diagnosis and management of Hypercalcemia
  3. Diagnosis and management of tertiary hyperparathyroidism
  4. Diagnosis of Hungry Bone Syndrome
  5. Management of severe hypocalcemia
  6. Relationship of ionized calcium to pH

I call it the greatest case report ever told and regarding calcium it probably is the best.

Again I provided the resident with a booklet and did the lecture Seder Style. This was the best use of that style yet.

Calcium Case Report

iPhone version