1. Case Study of CKD patient:

Mr. Imran Ahmed, a 58-year-old male, has Stage 4 chronic kidney disease (CKD) secondary to long-standing hypertension and diabetes mellitus.
He presents to the nephrology clinic with fatigue, pallor, and shortness of breath on exertion.

Medications:

• Amlodipine 10 mg daily
• Metformin 500 mg twice daily
• Furosemide 40 mg daily
• Calcium carbonate 500 mg twice daily

Lab Results:

Clinical Notes:

• No evidence of active bleeding or hemolysis.
• No history of transfusion.
• Patient is not on dialysis yet.
• Symptoms are affecting daily activity.

Questions:

1. Based on these findings, what type of anemia is most likely present in this patient?
2. How would you differentiate absolute vs functional iron deficiency in this case?
3. According to KDIGO guidelines, what iron thresholds define iron deficiency in non-dialysis CKD?
4. Would oral or IV iron be preferred in this patient? Why?

PHARMACIST WORKUP:

1. Based on these findings, what type of anemia is most likely present in this patient?

Based on the clinical symptoms of the patients and the lab report findings, it is most likely that patient is suffering from absolute iron deficiency Anemia associated with CKD.

2.      How would you differentiate absolute vs functional iron deficiency in this case?

As we know that:

 And the reports of the patient (NDCKD) show that:

So, the patient (NDCKD) is suffering from Absolute iron deficiency.

3.     According to KDIGO guidelines, what iron thresholds define iron deficiency in non-dialysis CKD?

According to KDIGO guidelines Iron threshold in non-dialysis CKD is:

In people with anemia and CKD not receiving dialysis or treated with peritoneal dialysis (CKD G5PD), we recommend using iron if:

·        Ferritin <100ug/l (<100ng/ml) and transferrin saturation (TSAT) <40% or

·        Ferritin ≥100 ng/ml (≥100 µg/l) and <300ug/l (<300ng/ml) and TSAT <25%

4.     Would oral or IV iron be preferred in this patient? Why?

KDIGO guidelines for the NDCKD patients or for those receiving peritoneal dialysis:

·        “In people with anemia and CKD not receiving hemodialysis in whom iron is initiated, we suggest using either oral or intravenous iron”

·        “Switch from oral to intravenous iron if there is an insufficient effect of an optimal oral regimen after 1 to 3 months”.

As per above guidelines we can use either oral or I.V iron so, before deciding this let’s first observe the difference between oral and iv iron:

 Thus, keeping in view all the above factors and the CRP level in above lab report, the inflammation is confirmed which signs towards the increase in the level of hepcidin and associated inadequate absorption of oral iron. Thus, there will be no benefit of using oral iron in this case. As a result of this we will recommend IV iron in this case.

·       “According To KDIGO: “In people with CKD treated with iron, it is reasonable to test hemoglobin, ferritin, and TSAT every 3 months for those not receiving dialysis or CKD G5PD and every month for those with CKD G5HD”.

So, after initiating iron supplements whether oral or I.V in any case, it is recommended to perform regular test of Hb, ferritin and TSAT as per above KDIGO guideline

Intravenous iron formulations and treatment regimen

As there are different I.V. iron formulation available in the market such as  iron sucrose, ferric gluconate, ferric carboxymaltose & ferumoxytol etc. and each of them has different potencies and respective dosage form. So, it is very important to know about the dosage administration guidelines of each of them. Thus before initiating I.V therapy, following dosage administration guidelines regarding I.V iron should be kept in mind:

 In case Oral iron supplements are to be given in any other case, following points regarding the formulation, treatment regimen and influential factors should be kept in mind:

 For oral iron we can go for Ferric citrate, that is approved to treat iron deficiency anemia in people with CKD not receiving dialysis. It has a favorable safety and efficacy profile and may spare I.V. iron and ESA use, and possibly delay the transition to dialysis. Ferric citrate also improves iron parameters and reduces ESA and I.V iron exposure in people with CKD G5HD. However, its role as an iron-repletion agent in this population remains to be clarified.

Ferric maltol have established improvements in Hb level. Sucrosomial iron proved better tolerability over I.V.

 CKD patients receiving dialysis:

It is believed that many patients with CKD G5HD would prefer I.V  iron over oral iron as it can be administered during dialysis. Those at risk of or particularly worried about hypersensitivity reactions may prefer oral treatment This coincides with KDIGO guideline:

“In people with anemia and CKD G5HD in whom iron therapy is being initiated, we suggest using intravenous iron rather than oral iron.”

Let’s see some more KDIGO guidelines for IV iron therapy:

·        “In people with CKD treated with oral iron, the choice between different formulations and dosing schedules is guided by cost, individual patient preference, tolerability, and efficacy”

·        “In people with CKD treated with intravenous iron, the choice between different formulations is guided by cost, individual preference, and recommended dosing schedules”.

·        In people with CKD treated with iron, consider temporarily suspending iron therapy during systemic infection.

In people with CKD treated with iron, it is reasonable to withhold iron
if ferritin ≥700 ng/ml (≥700 µg/l) or TSAT ≥40%.

·        In people with CKD treated with intravenous iron, considerations pertaining to hypersensitivity reactions to intravenous iron include the following:

•       Intravenous iron should only be administered if there is capability to manage acute hypersensitivity and hypotensive reactions,

•       Intravenous doses of iron should not exceed the maximum dose/administration for the compound (as per above mentioned table),

•       Pretreatment with corticosteroids or antihistamines is not routinely necessary (type 1 histamine [H1]-channel blockers), and

Test doses of intravenous iron are not usually required, because lack of response does not predict the risk of hypersensitivity.