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Is Calcitriol Produced By The Kidneys

What Happens If I Have Too Little Vitamin D


Vitamin D deficiency is common in the UK, probably due to lifestyle changes and lack of sun exposure. If you have severely low vitamin D levels you are unable to maintain an adequate concentration of calcium in your blood for bone growth. This causes rickets in children and osteomalacia in adults. As the role of vitamin D as a regulator of other functions throughout the body has emerged, it has been suggested that a lack of vitamin D is linked to an inability to fight infections effectively, muscle weakness, fatigue and the development of diabetes, certain cancers, multiple sclerosis, depression, heart disease, high blood pressure, and stroke, although the direct relevance and mechanisms underlying these responses remain unknown.

Oily fish such as sardines, mackerel and salmon are good dietary sources of vitamin D. Calcium can be found in cows milk and dairy products. In the UK, foods such as breakfast cereals and margarine are fortified with vitamin D. Adequate exposure to sunlight is important, especially between April and October, for around 15 minutes daily. Public Health England recommends vitamin D supplements are taken by people in at risk groups .

Enhancing Healthcare Team Outcomes

Calcitriol is a widely prescribed agent by the primary care provider, nurse practitioner, endocrinologist, and internist. However, therapy with the drug requires the efforts of an entire interprofessional healthcare team, including clinicians , nurses, and pharmacists. While calcitriol is relatively safe, it has to be monitored for adverse effects, of which the most common is hypercalcemia. Patients may present with hypertension, renal stones, behavior alterations, and severe constipation. At each clinic visit, the healthcare provider should ask for symptoms of hypercalcemia. In some patients, regular monitoring of calcium levels may be required. Utilizing the interprofessional model, with collaborative activity and open communication when treating patients with calcitriol, will drive improved patient outcomes and help preclude adverse events.

Why Is This Medication Prescribed

Calcitriol is used to treat and prevent low levels of calcium and bone disease in patients whose kidneys or parathyroid glands are not working normally. It is also used to treat secondary hyperparathyroidism and metabolic bone disease in people with kidney disease. Calcitriol is in a class of medications called vitamin D analogs. It works by helping the body to use more of the calcium found in foods or supplements and regulating the body’s production of parathyroid hormone.

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Vdr Analogs In The Treatment Of Shpt

Further research demonstrated that calcitriol decreases PTH gene transcription and cell proliferation and increases parathyroid gland VDR and CaSR expression, supporting its clinical use for the treatment of SHPT. However, calcitriol dose escalation to effectively suppress PTH in more severe cases of SHPT was limited by its narrow therapeutic window . The dose-dependent development of hypercalcemia and hyperphosphatemia with possible consequent soft tissue and vascular calcifications, as well as concerns for the development of adynamic bone disease, prompted the development of calcitriol analogs for PTH suppression with less calcemic activity . Vitamin D analogs activate the VDR differently, when compared with calcitriol, resulting in a different recruitment of coactivators and corepressors which are cell specific . A brief description of analogs commonly used in nephrology follows.

Basic Functions Of The Kidneys:

4. Endocrine Functions of the Kidneys  Functions of Cells ...

The basic 7 functions of kidney includes ACID balance, Electrolyte and Water balance, Toxins removal, Controlling BP, Produce hormones and activates Vitamin D. Lets go into detail one by one, so that we will understand what are the functions of kidney are? And how it works, take a brief look at each of these functions

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Some Side Effects Can Be Serious The Following Symptoms Are Uncommon But If You Experience Any Of Them Call Your Doctor Immediately:

  • feeling tired, difficulty thinking clearly, loss of appetite, nausea, vomiting, constipation, increased thirst, increased urination, or weight loss
  • weakness
  • lack of interest in the things around you
  • hallucination
  • fever or chills
  • yellowing of the skin or eyes
  • runny nose
  • itching
  • difficulty breathing or swallowing

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration’s MedWatch Adverse Event Reporting program online or by phone .

What Do The Kidneys Do

The kidneys have a number of roles in the body

  • The kidneys ensure that the make-up and volume of the fluids in the body is correct.
  • They help control the chemical balance of the blood and regulate the body’s level of sodium, potassium and calcium.
  • The kidneys remove waste products and excess water from the body and so help to regulate blood pressure.
  • They activate vitamin D, which helps to maintain strong bones.
  • They produce erythropoietin, a hormone that is vital for the production of red blood cells.

The kidneys ensure that the make-up and volume of the fluids in the body is correct. They help control the chemical balance of the blood and regulate the body’s level of sodium, potassium and calcium. The kidneys remove waste products and excess water from the body and so help to regulate blood pressure. They activate vitamin D, which helps to maintain strong bones, and produce erythropoietin, a hormone that is vital for the production of red blood cells.

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Renoprotective Roles Of Vdra In Ckd Patients

Calcitriol has long been reported to provide benefits to the human uremic patient by lowering PTH concentration , this has also been reported for dogs and cats., Oral calcitriol has been shown to increase survival in human patients with CKD including those treated prior to dialysis,, and in one placebo-controlled study in dogs with CKD as described earlier.b Various studies that show increased survival can be attributed to the salutary effects of extrarenal tissue VDRA, intrarenal VDRA, and benefits of lowered PTH synthesis and secretion following VDRA in the PTG.

The renin-angiotensin-aldosterone system is a major mediator of progressive renal injury in CKD. The RAAS system is present entirely within the kidney. Juxtaglomerular cells are the most active in initiating RAAS, but the system is present in most renal cells including tubular epithelia. Drugs that target the RAAS, including angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers , have been shown to slow the progression of glomerulosclerosis, tubulointerstitial fibrosis, and proteinuria., Intrarenal Ang II exerts multiple effects on the kidney that promote progression of renal injury.

What Are The Side Effects Of Calcitriol

Thyroid 8- Calcitriol


Excessive vitamin D may lead to hypercalcemia, hypercalciuria , hyperphosphatemia , and bone disease. To avoid complications, vitamin D and its derivatives should be avoided during calcitriol therapy.

Hypercalcemia has been reported in patients treated with calcitriol. Patients should avoid making any sudden changes in their dietary calcium intake and maintain adequate intake of fluid during treatment.

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Monitoring Therapy In The Ckd Patient

Surveillance for routine veterinary CKD patients involves the measurement and analysis of serial serum BUN, and creatinine, phophorus, and tCa. This surveillance is to provide information about the rate of progressive loss of excretory renal functions. Attention to calcium and phosphrous status is even more important during treatment with vitamin D and activated vitamin D compounds in order to provide early detection for the development of hypercalcemia or hyperphosphatemia.

Calcium fractions vary widely in disease and cannot be predicted accurately on the basis of tCa measurement.,,, For accurate assessment of calcium status, iCa must be measured directly. iCa measurement has been shown to be superior to serum tCa measurements in many conditions, especially in HPTH, kidney disease, hypoproteinemia and hyperproteinemia, acid-base disturbances, and critical illnesses.,,, Changes in the magnitude of serum protein concentration, individual protein binding capacity and affinity, serum pH, and complexed calcium all interact to determine the iCa concentration, independent of the tCa concentration.,,

Keeping Blood Pressure In Check

Renin is an enzyme produced by the kidneys. Renin turns angiotensinogen, which is produced in the liver, into angiotensin I, which is then transformed into angiotensin II in the lungs. Angiotensin II causes blood arteries to contract, raising blood pressure. When ones blood pressure is excessively high, on the other hand, the kidneys generate more urine in order to lessen the amount of liquid circulating in the body and somewhat compensate for the high blood pressure.

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Cholecalciferol Therapy Increases 1252d Production In Patients With Esrd

We measured changes in the serum markers of mineral metabolism before and after cholecalciferol therapy. We found that both 25D and 1,252D levels significantly increased from the precholecalciferol to postcholecalciferol time points . Not only did these levels rise in response to therapy, but also the final 1,252D levels fell within the reference range of normal values for the general population. Despite a significant rise in both 25D and 1,252D levels, cholecalciferol therapy resulted in no significant change in the other markers of mineral metabolism, including calcium, phosphorus, fibroblast growth factor 23 , and parathyroid hormone . Two weeks after the discontinuation of cholecalciferol therapy, the levels of 25D remained significantly elevated compared with pretreatment values.

Serum biochemistries for patients who had ESRD and were treated with cholecalciferol and paricalcitol

What Hormones Do The Kidneys Produce

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The kidneys make two main hormones, vitamin D and erythropoietin.

Vitamin D is essential for a number of different functions in the body. Most of the vitamin D that is in the blood is inactive and it is modified by the kidney and other tissues to activate it. Active vitamin D stimulates the uptake of calcium from food, is important for the maintenance of healthy bones and also helps to regulate the response of the immune system to infection.

Erythropoietin is produced when oxygen levels in the blood are low. It acts in bone marrow to stimulate the production of mature red blood cells, to maintain healthy oxygen levels in our tissues.

The kidneys also produce prostaglandins, hormone-like substances, made from lipid . The substances are one way in which the production of renin is stimulated. Renin is an enzyme, also produced by the kidneys, that plays an important role in the reninangiotensinaldosterone hormonal system, which helps to control blood pressure. In addition to making hormones, the kidneys also respond to a number of hormones including vitamin D, aldosterone, prostaglandins, cortisol, parathyroid hormone and calcitonin.

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The Vitamin D Receptor

Calcitriol mediates its genomic effects through the vitamin D receptor , which is a member of the steroid/thyroid superfamily of nuclear receptors. Calcitriol binding to VDR results in changes in transcription rates for those genes that contain vitamin D responsive elements . There are many other facets to this process, the details of which are beyond the scope of this review. Interested readers are directed to other reviews of this topic . Uraemia diminishes the tissue response to calcitriol and this is likely to be due, at least in part, to abnormal regulation and function of the VDR . Down-regulation of VDR content has been demonstrated in the parathyroids of uraemic animals . Uraemic toxins have been shown to decrease the ability of the VDR to bind the VDRE as demonstrated for the osteocalcin gene and it is possible that these effects could be ameliorated by early institution of vitamin D therapies. Experiments in the uraemic rat have shown that administration of either calcitriol or the analogue 22-oxacalcitriol can prevent the decrease in VDR content of the parathyroids .

What Are The 7 Functions Of The Kidney

The fundamental function of the kidneys, as most people know, is to eliminate waste items from the body by washing them out with urine. However, did you know that your kidneys are also responsible for at least six more fantastic functions? The nephrologist from all over the world loves to educate patients about kidney disease so that they can. To assist patients understand how the kidneys work, heres a brief summary of their seven basic tasks.

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Understanding Vitamin D Metabolism & Function

Vitamin D is a steroid hormone involved in the intestinal absorption of calcium and the regulation of calcium homeostasis, bone differentiation and immune response. The term vitamin D refers to several different forms of this vitamin.

There are two major types of vitamin D:

  • Vitamin D2 which is synthesized by plants and is not produced by the human body.
  • Vitamin D3 which is made in large quantities in the skin when sunlight strikes bare skin. It can also be ingested from animal sources.
  • The storage type of vitamin D, namely 25- hydroxy vitamin D, is formed in the liver. The hormone 1,25-dihydroxy vitamin D is formed in a second hydroxylation step in the kidney. The responsible enzyme, the kidney 1 -hydroxylase, is subjected to a rigid control through hormones and its activity is influenced by the serum concentrations of calcium and phosphate.

    How To Use Calcitriol

    Endocrinology – Renal Hormones
  • Take this drug orally once a day, with or without food, or as instructed by your doctor. Use a special measuring spoon or device to measure the dosage if you’re using the liquid form. If you use a regular household spoon, you might not get the right dosage.
  • Dosage is dictated by your medical condition and therapy reaction. Your doctor can begin with a low dose and gradually increase it to find the best dose for you. Follow the doctor’s instructions to the letter. To get the most satisfaction from this drug, take it on a daily basis. Take it at the same time every day to help you remember.
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    Biosynthesis And Its Regulation

    Calcitriol is produced in the cells of the proximal tubule of the nephron in the kidneys by the action of 25-hydroxyvitamin D3 1-alpha-hydroxylase, a mitochondrialoxygenase and an enzyme which catalyzes the hydroxylation of 25-hydroxycholecalciferol in the 1-alpha position.

    The activity of this enzyme is stimulated by PTH. This is an important control point in Ca2+ homeostasis. Additional effects on the production of calcitriol include an increase by prolactin, a hormone which stimulates lactogenesis , a process which requires large amounts of calcium. Activity is also decreased by high levels of serum phosphate and by an increase in the production of the hormone FGF23 by osteocyte cells in bone.

    Calcitriol is also produced outside the kidney in small amounts by many other tissues including placenta and activated macrophages.

    When the drug alfacalcidol is used, 25-hydroxylation in the liver produces calcitriol as the active metabolite. This will produce greater effects than other vitamin D precursors in patients with kidney disease who have loss of the renal 1-alpha-hydroxylase.

    Where Are My Kidneys

    The kidneys are small bean-shaped organs approximately 6 cm wide and 12 cm long and consist of two main layers an inner layer called the medulla and an outer layer called the cortex. Most people have two kidneys that are situated at the back of the abdomen on either side of the spine.

    Graphic showing a section through the right kidney with the main structures labelled.

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    Which Drugs Or Supplements Interact With Calcitriol

    Calcitriol should not be used with other vitamin D products because of the increased risk of additive side effects and toxicity.

    Cholestyramine , colestipol, mineral oil, and orlistat may decrease the intestinal absorption of calcitriol. Separating the administration of these medications and calcitriol may prevent this interaction.

    Phenytoin and phenobarbital may reduce blood concentrations of calcitriol, decreasing treatment effectiveness. Higher doses of calcitriol may be necessary if these drugs are used together with calcitriol.

    Thiazide diuretics may increase the blood levels of calcium. Since calcitriol also increases calcium levels, taking these two types of medications together may cause hypercalcemia .

    Calcitriol should be used cautiously in patients taking digoxin . High levels of calcium may cause symptoms of digoxin toxicity such as irregular heartbeats.

    Ketoconazole may decrease the activity of enzymes responsible for metabolizing or breaking down calcitriol and lead to the side effects of excessive vitamin D.

    Magnesium containing medications should be avoided in patients undergoing chronic renal dialysis who are taking calcitriol. These patients are at high risk of experiencing hypermagnesemia as their kidneys are unable to remove adequate amounts of magnesium from the blood.

    Cholecalciferol Therapy Alters Serum Inflammatory Cytokine Levels

    Calcium Homeostasis and Selected Causes of Hypercalcemia ...

    To evaluate the impact of 25D repletion on the inflammatory phenotype of these patients, we measured serum changes in inflammatory cytokines at three time points: Before cholecalciferol, after cholecalciferol and after paricalcitol restart. We observed a decrease in IL-6, IL-8, and TNF- after 25D repletion with cholecalciferol . After the discontinuation of cholecalciferol and reinitiation of paricalcitol therapy, serum levels of IL-8 and TNF- remained low, whereas IL-6 levels returned to levels near baseline.

    Change in serum IL-8, IL-6, and TNF- levels after cholecalciferol and paricalcitol therapy. To assess the effects of cholecalciferol and paricalcitol therapies on the inflammatory phenotype of patients with ESRD, we measured serum levels of several inflammatory cytokines that are generated by the monocyte lineage. We observed a 55% decrease in serum IL-8 levels , a 30% reduction in IL-6 levels , and a 60% decline in TNF- levels after cholecalciferol therapy. Serum IL-8 and TNF- levels remained lower after the discontinuation of cholecalciferol and restart of paricalcitol, whereas the IL-6 levels seemed to return to near baseline values .

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    What Could Go Wrong With The Kidneys

    When the kidneys are not working correctly, waste products and excess fluid can build up and the levels of sodium, potassium, phosphate and calcium are not regulated correctly. When these substances gather together, this causes the symptoms of kidney disease, which can include high blood pressure, excessive tiredness, fluid retention and possibly lower back pain.

    Kidney damage can occur for a number of reasons diabetes, high blood pressure, infections and a group of diseases that affect the glomerulus. The kidneys also need an adequate supply of blood, so if there is something wrong with the blood vessels to the kidney, such as a narrowing, this will prevent the kidneys from working efficiently.


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