CKD Case Study 5- Solving the mystery of Zn, Iron, Ca, & Vitamin D deficiency

Patient Profile

Name: Mr. Saeed Ahmad
Age: 63 years
Gender: Male
Diagnosis: CKD ( Chronic Kidney Disease) Stage 4 secondary to long-standing diabetes mellitus and hypertension
Dialysis Status: Not yet on dialysis

Chief Complaints:

• Persistent fatigue and muscle weakness
• Poor appetite and altered taste sensation (“everything tastes metallic”)
• Itchy, dry skin and brittle nails
• Occasional numbness and tingling in extremities
• Bone pain and difficulty in climbing stairs

Current Medications

• Furosemide 40 mg once daily
• Amlodipine 5 mg once daily
• Calcium carbonate 500 mg twice daily
• Erythropoietin injection once weekly
• Multivitamin (without minerals) daily
• Sevelamer carbonate 800 mg with meals

Recent Laboratory Findings

Dietary History

• Limited protein intake due to CKD diet restriction
• Rarely eats red meat or seafood
• Drinks tea multiple times a day
• Avoids dairy due to “stomach heaviness”
• Takes phosphate binder regularly with meals

Clinical Notes

The nephrologist suspects that multiple micronutrient deficiencies are contributing to the patient’s symptoms. However, correction requires careful coordination due to the risk of hypercalcemia, hyperphosphatemia, and drug–nutrient interactions.

Discussion Questions (For Pharmacist Reflection)

1. Zinc Deficiency:
   
   • What clinical and biochemical signs suggest zinc deficiency in this patient?
   • How might low zinc levels worsen CKD-related complications?
2. Calcium and Vitamin D:
   
   • How do the lab results reflect secondary hyperparathyroidism?
   • What could be the reason for low calcium despite supplementation?
   • How might phosphate binders and vitamin D deficiency interplay in this case?
3. Iron Deficiency and Anemia:
   
   • What could explain his low hemoglobin despite erythropoietin therapy?
   • How does zinc status influence erythropoiesis and iron metabolism?
4. Pharmacist’s Role:
   
   • What counseling points should a pharmacist provide to improve nutrient absorption?
   • How can supplementation be balanced to avoid adverse interactions (e.g., between calcium, zinc, and iron)?
   • What follow-up laboratory tests would you recommend?

Pharmacist Workup:

Q.1. What clinical and biochemical signs suggest zinc deficiency in this patient?

• Rarely eats red meat or seafood- This dietary habit can cause zinc deficiency
• Patient is taking diuretic “furosemide 40mg” which can cause zinc deficiency.
• The patient under study is taking calcium carbonate inhibit the absorption of zinc in the body by creating alkaline environment
• Patient is taking tea multiple times a day, tea consists of tannins which also binds to the zinc via chelation and inhibit its absorption.
• Typically zinc deficiency is manifested as: diarrhea (typically in infants), hair loss, nail changes, loss of appetite, slow wound healing, visual impairment, low sperm count and skin rashes or lesions.

The patient under study also has similar symptoms like Itchy, dry skin, metallic taste and brittle nails- which signs towards zinc deficiency

• Additionally, Lab report also suggest that the patient is zinc deficient.

Q.2. How might low zinc levels worsen CKD-related complications?

As we have come to know that the patient is deficient in zinc. So, now it’s the time to look at the complication that have been caused by zinc deficiency.

Q.3 How do the lab results reflect secondary hyperparathyroidism?

If we look at the lab report we observe that:

Serum calcium level is low, serum phosphorus is high, parathyroid hormone level is high and serum vitamin D level is low.

As, we know that during chronic kidney disease, the serum level of phosphate becomes high due to inadequate filtration from the kidneys. High level of phosphate, binds to the free serum calcium leaving less amount of free calcium in the blood which induces the secretion of parathyroid hormone resulting in secondary hyperparathyroidism. High level of parathyroid hormone takes the calcium out of the bone via bone resorption process to normalize the serum calcium level, making the patient vulnerable to bone fracture and other bone disorders.

Additionally, during CKD, the ability of the kidney to activate vitamin D, in the absence of active form of vitamin D in the body, the absorption of the calcium from the intestine decreases resulting in low serum calcium level. This low serum calcium also induces secondary hyperparathyroidism.

This whole mechanism is reflected from the lab report of the patient given above.

📝Read: Clinical Case Study of CKD patient-Vitamin Recommendations

Q.4. What could be the reason for low calcium despite supplementation?

If we look at the diet of this patient, there are some of the factors that can lead to calcium deficiency

• Drinks tea multiple times a day- Contains tannins which can binds to calcium as well as iron
• Avoids dairy due to “stomach heaviness”- contribute to low serum calcium

But he is taking calcium supplements, Still the level of calcium is low, the most possible reason for this is the inadequate amount of vitamin D in the patient. Vitamin D plays significant role in the absorption of calcium.

Additionally, patient is also taking furosemide diuretic which can also cause calcium deficiency.

Q.5. How might phosphate binders and vitamin D deficiency interplay in this case?

This patient is taking sevelamer carbonate as a phosphate binder, the sevelamer not only binds dietary phosphate but also binds to the bile acid and fat-soluble vitamins like Vitamin A, D, E and K. This also contribute towards the deficiency of vitamin D in this patient.

Q.6 What could explain his low hemoglobin despite erythropoietin therapy?

Zinc deficiency is one of the most important causes of suboptimal response of erythropoietin therapy. As when there isn’t enough zinc in the body, certain important proteins in the red blood cell membrane — called Na⁺-K⁺-ATPase and Ca²⁺-ATPase — don’t work properly. These proteins depend on small chemical groups called sulphydryl (–SH) groups to stay active.

If zinc is low, these sulphydryl groups get damaged or reduced in number. As a result:

·        The ATPase enzymes lose their function.

·        The balance of sodium, potassium, and calcium across the membrane gets disturbed.

·        This makes the cell membrane weaker and more brittle.

Because of this weakened membrane, red blood cells break more easily, leading to increased fragility and possibly anemia.

Zinc deficiency can also lower iron level which further inhibit the optimal response of ESA therapy. The serum iron level is low to normal in this patient. But final judgement about iron deficiency will be made after serum ferritin and TSAT test. This will help to better understand the type of iron deficiency (i.e. absolute or functional) and the type of iron therapy (oral or I.V)

Another culprit of low hemoglobin level seems to be low Vitamin b12 and B9 level as patient is having Occasional numbness and tingling in extremities and the patient is on restricted protein diet. Though he is taking multivitamins but still investigation through serum vitamin level or CBC test needs to be done, in which if MCV AND MCH is increased then it will confirm the deficiency of Vitamin B9 and B12.

As multivitamin often contains very small amount of vitamins that are not enough to combat deficiencies, so if a particular vitamin comes out to be deficient in the patient, then more than a little amount of that vitamin will be given.

Q.7. How does zinc status influence erythropoiesis and iron metabolism?

Effect of zinc on Iron Metabolism:

Intestinal absorption of iron at the apical surface of enterocytes involves the duodenal cytochrome B (DcytB)-mediated reduction of ferric iron (Fe³⁺) to ferrous iron (Fe²⁺), which is then transported into the cell through the divalent metal transporter 1 (DMT1). On the basolateral side, ferrous iron is exported by ferroportin (FPN1) and subsequently oxidized back to ferric iron by hephaestin (HEPH). Notably, FPN1 is currently recognized as the only iron exporter.

Previous studies have shown that zinc enhances both the uptake and transcellular transport of iron in intestinal cells by activating the PI3K pathway, which leads to increased expression of DMT1 and HEPH Conversely, zinc deficiency reduces iron absorption and downregulates the expression of DMT1, FPN1, and HEPH. These findings suggest that systemic zinc status plays a key role in regulating intestinal iron absorption, although this hypothesis still requires confirmation through in vivo studies.

📜Read Also: Clinical comparison b/w different forms of iron supplements

Effect of zinc on Erythropoiesis:

Zinc is essential for the activity of enzymes like DNA and RNA polymerases. Without enough zinc, erythroid precursor cells (cells that become RBCs) cannot divide properly. This leads to reduced production of new red blood cells, resulting in anemia-like conditions.

Zinc influences the erythropoietin signaling pathway, which stimulates bone marrow to produce RBCs. Zinc deficiency may reduce the bone marrow’s sensitivity to EPO, slowing down erythropoiesis.

📃Explanation:

During the early stages of erythropoiesis (the process of forming red blood cells), the hormone erythropoietin (EPO) plays a key role in stimulating the growth and survival of immature red blood cell precursors in the bone marrow. This process is regulated by zinc finger transcription factors—a group of proteins that require zinc to maintain their structure and bind to DNA properly. These transcription factors control the expression of genes involved in cell proliferation, differentiation, and protection from apoptosis (cell death), ensuring that developing red blood cells mature normally.

As erythroid cells progress to later stages, zinc continues to be essential for the formation of mature, functional red blood cells. It supports the activity of hormones, vitamins (such as vitamin A and folate), and growth peptides that regulate hemoglobin synthesis, cell membrane stability, and oxygen-carrying capacity. Zinc also contributes to antioxidant defense mechanisms in developing red cells, protecting them from oxidative damage caused by reactive oxygen species.

However, zinc has a competitive relationship with other divalent metal ions such as iron (Fe²⁺) and copper (Cu²⁺). In erythroid precursor cells, zinc can antagonize or reduce the uptake of these metals by competing for shared transport pathways. This balance is important—too much zinc can interfere with iron and copper absorption, while too little zinc impairs the enzymes and transcription factors needed for erythropoiesis.

Copper is required for iron transfer from cells to blood, ensuring dietary iron absorption and systemic iron distribution. So, if there is

·        Copper deficiency → treat with copper first, add zinc later if needed.

·        Zinc deficiency → treat with zinc, but monitor copper to prevent deficiency.

 Overall, zinc plays a dual regulatory role in red blood cell formation: it supports gene regulation and cell development while maintaining proper metal ion balance. Therefore, zinc deficiency can disrupt multiple steps of erythropoiesis, leading to reduced red blood cell production, immature cell development, and increased risk of anemia.

Q.8. What counselling points should a pharmacist provide to improve nutrient absorption?

Firstly, the patient is advised to take multivitamin+ mineral supplements designed especially for renal patient to have adequate amount of mineral like zinc, copper and iron etc.

Secondly, patient is advised to take these multivitamin mineral complexes with meal but with minimum of 2 hrs gap from sevelamer carbonate as it can bind with the Vitamins.

It is also recommended to reduce the amount and frequency of tea and give a gap of at least 2 hr. from meal and multivitamin mineral complex, as it contains tannins, that can bind to the minerals and can also reduce the absorption of vitamins.

Patient will encourage for sun exposure (vitamin D synthesis). Vitamin D supplementation will be recommended in consultation with the nephrologist.

Q.9.How can supplementation be balanced to avoid adverse interactions (e.g., between calcium, zinc, and iron)?

Calcium supplementation should be given in accordance with the recommendation of NKF KDOQI GUIDELINES:

Total elemental calcium intake (including both dietary calcium intake and calcium-based phosphate binders) should not exceed 2,000 mg/day.

It is important to note that the patient is taking calcium carbonate which can make the pH of the stomach alkaline resulting in inadequate absorption of zinc and iron which require acidic pH for absorption. So, a minimum of 2 hr gap will be given between calcium supplement and zinc and iron supplements.

Zinc supplementation are preferred to be given along with copper supplements (1mg).  Zinc gluconate or Zinc amino acid chelate are often recommended, as they are easily absorbed and better tolerated especially by those with compromised digestion.

A general guideline for repletion involves 1-3 mg/kg of zinc daily until deficiency symptoms resolve. Patients who have more severe malabsorption may require higher doses (>50mg) for extended periods. 

It is also crucial to check that whether the patients is on PPIs or antacids, as Zinc is best absorbed at acidic pH and these medications can hinder the absorption of the zinc. So, if the patient is taking any of this medication it may require a change of medications or timings.

Excess of Zinc should be avoided to maintain normal level of iron and copper.

Q.10 What follow-up laboratory tests would you recommend?

Following mentioned laboratory test will be recommended to this patient