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Saudi Journal of Kidney Diseases and Transplantation
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LETTER TO THE EDITOR Table of Contents   
Year : 1996  |  Volume : 7  |  Issue : 3  |  Page : 315-316
Cyclosporine A Induced Hyperkalemia in a Renal Allograft Recipient

Renal Unit, King Hussein Medical Center, P.O. Box 540708, Amman, Jordan

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How to cite this article:
Ghnaimat M, Akash N, El-Lozi M. Cyclosporine A Induced Hyperkalemia in a Renal Allograft Recipient. Saudi J Kidney Dis Transpl 1996;7:315-6

How to cite this URL:
Ghnaimat M, Akash N, El-Lozi M. Cyclosporine A Induced Hyperkalemia in a Renal Allograft Recipient. Saudi J Kidney Dis Transpl [serial online] 1996 [cited 2022 Jun 25];7:315-6. Available from: https://www.sjkdt.org/text.asp?1996/7/3/315/39498
To the Editor:

Cyclosporine A (CsA) is a fungal peptide that is widely used to reduce the incidence of rejection following renal and other organ transplantations [1] . It has also been used in a variety of auto-immune diseases, such as rheumatoid arthritis, uveitis and insulin dependent diabetes mellitus. The principal action of CsA appears to result from the preferential inhibition of helper (T4 positive) T cell activation, thereby blocking interleukin II (IL-2) production [1] . Although CsA therapy has improved overall graft survival, its use is limited by the development of nephrotoxicity [2] and hyperkalemia [3] . In this report, we describe a renal transplant recipient who developed life threatening hyperkalemia induced by CsA therapy. To the best of our knowledge this is the first reported case of sustained severe hyperkalemia following CsA administration from Jordan. Although well known, this report is meant to highlight this potentially lethal side effect of CsA.

A 30 year old non-diabetic man with end­stage renal disease secondary to chronic glomerulonephritis received a living related renal allograft from his sister. Following transplantation, he was put on triple drug immunosuppressive therapy [CsA, 250 mg twice a day (10 mg/kg/day), azathioprine 50 mg twice a day (2 mg/kg/day) and prednisolone 50 mg once daily]. His post-transplant course was complicated by mild non-oliguric graft dysfunction which improved within five days and hypertension for which hydralazine was given. On the seventh post-operative day the patient was well, his blood pressure was adequately controlled, the urine output was about five liters daily; the blood urea nitrogen was 7 mmol/L, serum creatinine was 110 µmol/L and serum potassium was 4.6 mmol/L.

Two days later, the patient started to complain of generalized weakness and par­esthesia involving both upper and lower limbs. Findings on physical examination were unremarkable. His initial investigations revealed hyperkalemia (7.9 mmol/L) which was confirmed by abnormal electrocardiogram (peaked T-waves, prolonged PR interval and wide QRS complexes). Spurious elevation of serum potassium level due to hemolysis, thrombocytosis and leukocytosis was excluded. Other laboratory parameters including serum creatinine, blood glucose, calcium and magnesium levels, serum chloride, bicarbonate, blood and urine pH were all within normal limits. The whole blood CsA level was 213 ng/ml, 24 hour urinary potassium excretion was 36 mmol/L and glomerular filtration rate was 76 ml/min.

The patient was initially managed with calcium gluconate, glucose with insulin, sodium bicarbonate, loop diuretics and dietary potassium restriction. In spite of all these measures, his serum potassium level continued to be in the range of 6.9-7.6 mmol/L, and hence a decision was made to discontinue CsA. One day later his serum potassium concentration dropped to 6.2 mmol/L, and continued to drop further. The patient was discharged within four days with a serum potassium of 5.1 mmol/L, and when seen after one week in the out-patient clinic, the serum potassium was 4.8 mmol/L.

Hyperkalemia during CsA therapy is a major clinical problem for patients with auto-immune diseases and following organ transplantation [4] . In a study by Bantle, et al, 25% of those receiving CsA had hyperkalemia sufficient to warrant treatment, whereas only 6% of patients receiving azathioprine needed such treatment [5] . The higher concentration of potassium in CsA treated patients does not appear to be related to impairment of glomerular function, the donor source of the kidney, the sex of the patient or the underlying disease condition initially causing the renal failure [6] .

Whether CsA-induced hyperkalemia is a dose dependent phenomenon remains controversial. Adu, et al [3] and Foley, et al [6] found no correlation with drug levels in contrast to Gupta, et al who found that hyperkalemia and hyperuricemia did correlate with CsA levels in patients receiving CsA for the treatment of psoriasis [7] . The pathophysiology of CsA-induced hyperka­lemia is not well understood. Adu, et al [3] reported seven of 43 renal transplant patients receiving CsA who developed sustained hyperkalemia; all had hyperchloremic acido­sis and six of them were receiving beta blockers for hypertension. Plasma renin level was low in five of the seven patients while plasma aldosterone was normal in five and raised in two. They suggested type IV renal tubular acidosis (hypo-reninemic hypo-aldos­teronism) as a possible mechanism. The same theory was supported by Bantle, et al [5] who, in addition, found that CsA treated patients excreted 52% of the potassium load versus 67% in azathioprine treated patients, suggesting that CsA may also induce partial tubular insensitivity to aldosterone.

Other mechanisms, based on the fact that normal functioning of Na+/K+ATPase is necessary for the regulation of potassium excretion in the distal nephron, was studied by Tumlin, et al [8] . They concluded that CsA, at a toxic concentration, significantly inhibits Na + /K + ATPase in the cortical collecting ducts; this leads to decreased K"1" secretion and contributes to clinical hyperkalemia. At a later stage, Ling, et al [9] demonstrated that CsA inhibits apical K"1" channels in rabbit principal cells, thus leading to decreased kaliuresis and hyperkalemia, a process that is mediated by Ca+" dependent protein kinase C.

In conclusion, hyperkalemia is a common manifestation in patients receiving CsA therapy and can be life threatening. It is worth re-emphasizing that the serum concentration of potassium should be carefully monitored when CsA is administrated; this is especially true for patients with diabetes mellitus, patients on beta-blockers, potassium sparing diuretics, angiotensin converting enzyme inhibitors, non-steroidal antiinflammatory drugs and those with impaired renal function.

   References Top

1.Cohen DJ, Loertscher R, Rubin MF, Tilncy NL, Carpenter CB, Strom TB. Cyclosporine: a new immunosuppressive agent for organ transplantation. Ann Intern Med 1984;101:667-S2.  Back to cited text no. 1    
2.Mycr BD, Ross J, Newton L, Luetscher J, Perlrath M. Cyclosporine associated nephropathy. N Engl J Med 1984;311:699-­705.  Back to cited text no. 2    
3.Adu D, Turney J, Michael J, McMaster P.Hyperkalemia in cyclosporin-treated renal allograft recipients. Lancet 1983;2:370-2.  Back to cited text no. 3    
4.Kamel KS, Ethier JH, Quaggin S, et al. Studies to determine the basis for hyperkalemia in recipients of a renal transplant who are treated with cyclosporine. J Am Soc Nephrol 1992;2:1279-84.  Back to cited text no. 4    
5.Bantle JP, Nath KA, Sutherland DE, Najarian JS, Ferris TF. Effects of cyclosporine on the reninangiotensin­aldosterone system and potassium excretion in renal transplant recipients. Arch Intern Med 1985;145:505-8.  Back to cited text no. 5    
6.Foley RJ, Hamner RW, Weinman EJ. Serum potassium concentrations in cyclosporine and azathioprine-treated renal transplant patients. Nephron 1985;40:280-­5.  Back to cited text no. 6    
7.Gupta AK, Rocher LL, Schmaltz SP, et al. Short term changes in renal function, blood pressure and electrolyte levels in patients receiving cyclosporine for dermatologic disorders. Arch Intern Med 1991;151:356­-62.  Back to cited text no. 7    
8.Tumlin JA, Sands JM. Nephron-segment­ specific inhibition of Na + /K + ATPase activity by cyclosporine A. Kidney Int 1993;43(1):246-51.  Back to cited text no. 8    
9.Ling BN, Eaton DC. Cyclosporine A inhibits apical secretory K channels in rabbit cortical collecting tubule principal cells. Kidney Int 1993;44:974-84.  Back to cited text no. 9    

Correspondence Address:
Mohamad Ghnaimat
Renal Unit, King Hussein Medical Center, P.O. Box 540708, Amman
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Source of Support: None, Conflict of Interest: None

PMID: 18417951

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