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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2014  |  Volume : 25  |  Issue : 1  |  Page : 149-151
Role of fludrocortisone in the management of tacrolimus-induced hyperkalemia in a renal transplant recipient

1 Department of Nephrology, Sri Venkateswara Institute of Medical Sciences, Tirupati, India
2 Department of Urology, Sri Venkateswara Institute of Medical Sciences, Tirupati, India

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Date of Web Publication7-Jan-2014

How to cite this article:
Sivakumar V, Sriramnaveen P, Krishna C, Manjusha Y, Reddy Y S, Sridhar N, Subramanian S. Role of fludrocortisone in the management of tacrolimus-induced hyperkalemia in a renal transplant recipient. Saudi J Kidney Dis Transpl 2014;25:149-51

How to cite this URL:
Sivakumar V, Sriramnaveen P, Krishna C, Manjusha Y, Reddy Y S, Sridhar N, Subramanian S. Role of fludrocortisone in the management of tacrolimus-induced hyperkalemia in a renal transplant recipient. Saudi J Kidney Dis Transpl [serial online] 2014 [cited 2021 Jun 18];25:149-51. Available from: https://www.sjkdt.org/text.asp?2014/25/1/149/124539
To the Editor,

Organ transplant recipients receiving treat­ment with immunosuppressive agents such as cyclosporine A (CsA) or FK506 (tacrolimus) may rarely exhibit alteration in electrolyte levels such as hyperkalemia and metabolic acidosis. These symptoms clinically resemble fea­tures of hypo-aldosteronism despite normal serum aldosterone levels in these patients, and have been directly attributed to the adminis­tration of immunosuppresants. [1],[2] The electro­lyte alterations are believed to be caused by direct inhibitory effects on the ion exchange system of the distal tubule of the nephron, such as Na/K/ATPase and Na/K/2Cl co-transporter activity. [1],[2]

Aldosterone is a key hormone involved in the regulation of ion and water homeostasis by stimulating ion transport in the distal nephron. Its action is mediated by the mineralo-corti-coid receptor (MR), which is a nuclear recaptor belonging to the super family of ligand regulation transcription factor. After hormone binding, the aldosterone-MR complex under­goes a conformational change. During this pro­cess, molecular chaperones bound to MR are liberated and the complex is translocated into the nucleus. Some of the molecular chaperones such as heat shock protein 90 (hsp) are capable of binding proteins called immunophilins. These proteins are known to complex with immunosuppresants; cyp 40 binds CsA or FKBP 51 and FKBP 52 bind FK506. The activated MR complex usually binds in the form of a dimer to the target DNA sequences, thereby modu­lating transcription of hormone-dependent genes. The interaction between immunophilins and nuclear receptors suggests a role for immunosuppresants in the signaling pathway of steroid hormones. The impairment of the MR signa­ling pathway results in ion transport alteration, accounting for the symptoms of secondary pseudo-hypoaldosteronism observed in renal transplant patients. [1],[2],[3]

Interestingly, these electrolyte alterations are reversible on administration of fludrocortisone, an observation that is in favor of potentially impaired aldosterone function. Upon adminis­tration of fludrocortisone, a significant decrease in serum potassium occurs within 48 h, and any intervention for hyperkalemia other than fludrocortisone therapy may not be needed in patients who respond. The dose requirement of fludrocortisone may range from 0.1 to 0.4 mg/ day and the duration may be up to 14 days of therapy. [1],[4],[5]

We herein present a patient who developed hyperkalemia in the early post-renal transplant period while on tacrolimus (FK506) and dis­cuss his evaluation and management.

A 31-year-old male with end-stage renal di­sease, presumed to be due to chronic tubulo-interstitial disease and on maintenance hemodialysis, underwent a living related donor renal transplantation, with his mother being the do­nor. He was managed on triple drug immunosuppressive therapy (prednisolone 20 mg/day, mycophenolate mofetil 2 g/day and tacrolimus 5 mg/day). The serum creatinine reached a nadir value of 1.24 on the seventh post-ope­rative day. On the 14 th post-operative day, the patient developed hyperkalemia (5.8 meq/L), which did not respond despite withdrawal of drugs such as carvedilol and trimethoprim and sulfamethoxazole. The tacrolimus blood level was 10.4 ng/mL, with the dose being 5 mg/day (0.1 mg/kg). In spite of anti-hyperkalemic measures, the patient had persistent hyperkalemia without ECG changes (pseudo-hyper-kalemia was ruled out). Trans-tubular potas­sium gradient (TTKG) was found to be less than five, suggesting the possibility of aldosterone resistance/deficiency [Table 1]. The pa­tient was started on fludrocortisone 0.05 mg/ day as a single dose. As there was no response even after 72 h, the dose of fludrocortisone was increased to 0.1 mg/day and, within 48 h, the serum potassium reached normal levels and, later, the fludrocortisone dose was tapered over ten days [Figure 1].
Figure 1: The response of hyperkalemia to fludrocortisone administration.

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Table 1: Laboratory investigations and relation to fludrocortisone administration in the study patient.

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In conclusion, we report a rare entity of hyperkalemia and metabolic acidosis in a living donor-related renal transplant recipient probably secondary to tacrolimus and its res­ponse to fludrocortisone therapy.

   References Top

1.Deppe CE, Heering PJ, Viengchareun S, Grabensee B, Farman N, Lombes M. Cyclosporine A and KF506 inhibit transcriptional activity of the human mineralocorticoid re­ceptor: A cell based model to investigate partial aldosterone resistance in kidney trans­plantation. Endocrinology 2002;143:1932-41.  Back to cited text no. 1
2.Heering PJ, Kurschat C, Vo DT, Klein-Vehne N, Fehsel K, Ivens K. Aldosterone resistance in kidney transplantation is in part induced by a down regulation of mineralocorticoid recep­tor expression. Clin Transplant 2004;18:186-92.  Back to cited text no. 2
3.Heering PJ, Klein-Vehne N, Fehsel K. Decrease mineralocorticoid receptor expression in blood cells of kidney transplant recipients undergoing immunosuppressive treatment: Cost Efficient Determination by quantitative PCR. J Clin Pathol 2004;57:33-6.  Back to cited text no. 3
4.Dick TB, Raines AA, Stinson JB, Collingridge DS, Harmston GE. Fludrocortisone is effective in the management of tacrolimus - induced hyperkalemia in liver transplant Recipients. Transplant Proc 2011;43:2664-8.  Back to cited text no. 4
5.Higgins R, Ramaiyan K, Dasgupta T, et al. Hyponatremia and hyperkalaemia are more frequent in renal transplant recipients treated with tacrolimus than with cyclosporine, further evidence for differences between cyclosporine and tacrolimus nephrotoxicities. Nephrol Dial Transplant 2004;19:444-50.  Back to cited text no. 5

Correspondence Address:
V Sivakumar
Department of Nephrology, Sri Venkateswara Institute of Medical Sciences, Tirupati
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DOI: 10.4103/1319-2442.124539

PMID: 24434399

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