Trimethoprim-induced hyperkalemia in renal transplant recipient

Abhijeet S More; Nilesh R Bhange; Kshitija G Gadekar; Sudhir G Kulkarni

doi:10.4103/ijot.ijot_4_18

CASE REPORT

Year : 2018 | Volume : 12 | Issue : 2 | Page : 149-151

Trimethoprim-induced hyperkalemia in renal transplant recipient

Abhijeet S More, Nilesh R Bhange, Kshitija G Gadekar, Sudhir G Kulkarni
Department of Nephrology, MGM Medical College, Aurangabad, Maharashtra, India

Date of Web Publication

29-Jun-2018

Correspondence Address:
Dr. Sudhir G Kulkarni
5^th Floor, Department of Nephrology, MGM Medical College, Aurangabad, Maharashtra
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijot.ijot_4_18

Abstract

Trimethoprim-sulfamethoxazole (TMP-SMX) is an antimicrobial agent used in a variety of infections. Adverse reactions are more common in patients with AIDS but occasionally occur in immunocompetent patients. Renal toxicity is usually a hypersensitivity reaction to the sulfa component and manifests as interstitial nephritis or sulfa crystallization in the renal tubules. Reversible hyperkalemia is a rarely reported side effect of TMP-SMX therapy attributed to TMP inhibition of potassium secretion in the distal renal tubule in a manner similar to the potassium-sparing diuretic, amiloride. We report a case of hyperkalemia associated with TMP-SMX occurring in a 32-year-old renal transplant recipient with no other risk factors for hyperkalemia. He was treated with TMP-SMX (800 mg + 160 mg) two tablets QID for suspected pneumocystis jiroveci pneumonia. He developed severe hyperkalemia on day 9 posttherapy. Hyperkalemia reverted to normal with withdrawal of trimethoprim.

Keywords: Hyperkalemia, kidney transplant, pneumocystis jiroveci pneumonia, trimethoprim

How to cite this article:
More AS, Bhange NR, Gadekar KG, Kulkarni SG. Trimethoprim-induced hyperkalemia in renal transplant recipient. Indian J Transplant 2018;12:149-51

How to cite this URL:
More AS, Bhange NR, Gadekar KG, Kulkarni SG. Trimethoprim-induced hyperkalemia in renal transplant recipient. Indian J Transplant [serial online] 2018 [cited 2021 Apr 10];12:149-51. Available from: https://www.ijtonline.in/text.asp?2018/12/2/149/235595

Introduction

Trimethoprim-sulfamethoxazole (TMP-SMX) is an antibiotic of choice for pneumocystis jiroveci pneumonia (PJP). Adverse reactions that may be experienced include gastrointestinal upset and skin lesions.^[1],[2] Renal toxicity is usually a hypersensitivity reaction to the sulfa component and manifests as interstitial nephritis or sulfa crystallization in the renal tubules.^[3],[4] Reversible hyperkalemia is a rarely reported side effect of TMP-SMX therapy attributed to TMP inhibition of potassium secretion in the distal renal tubule in a manner similar to the potassium sparing diuretic, amiloride.^[5] The occurrence of TMP-SMX-induced hyperkalemia has been reported in patients treated for upper respiratory infections,^[6] PJP in non HIV patients,^[7] PJP in acquired immunodeficiency syndrome ^[1] and as a standard dose prophylaxis in renal transplant recipients.^[8] We present a case of life-threatening TMP-SMX-induced hyperkalemia in a renal transplant recipient.

Case Report

A 32-year-old male underwent second kidney transplant 2 years after failed graft due to biopsy-proven recurrence of immunoglobulin A nephropathy. In the present kidney transplant, the donor was a father-in-law with 5/7 mismatch. The donor's age was 65 years. He received antithymocyte globulin (2 mg/kg/day for 2 days) as induction therapy followed by standard triple immunosuppression. The patient was also given pneumocystis jiroveci prophylaxis with TMP-SMX, which was later omitted because of pancytopenia. Pancytopenia recovered after stopping TMP-SMX. The patient received cytomegalovirus (CMV) prophylaxis with valganciclovir 450 mg orally once a day. The patient was alright for 3-month posttransplant, with creatinine stable at 1.8 mg/dl. He presented with fever and cough for 7 days, for which he had received antibiotic (amoxicillin + clavulanate). In spite of antibiotic course, he developed sudden onset of breathlessness for which he was admitted. Chest X-ray on day 1 of admission showed bilateral opacities [Figure 1]. The patient's serum creatinine was 3.2 mg/dl when he developed PJP. His serum potassium was 3.8 meq/L at that time. ABG parameters were pH – 7.39, HCO3 – 13.2, PCO2 – 22.30, and PO2 – 79.70. Lactate level was not measured. His X-ray chest showed ground-glass opacities in both basilar areas. His serum lactate dehydrogenase levels were elevated to 890 mg/dl. CMV polymerase chain reaction (PCR) was negative. He did not produce sputum initially, and later, when sputum was available, it was sent for pneumocystis jiroveci PCR. The test was negative. He was started on TMP-SMX (two tablets QID). The dose of oral steroid was increased to 15 mg QID. The patient was given noninvasive ventilation as his oxygen saturation levels were low. The patient was maintained on oxygen therapy for 10 days. He showed gradual improvement in general condition. On the 9^th day, his serum creatinine was 2.8 mg/dl, but he had serum potassium of 6.2 meq/L with electrocardiography evidence of hyperkalemia. [Figure 2] the patient was not on any other confounding medications such as angiotensin receptor blockers/angiotensin-converting enzyme inhibitor which could contribute to hyperkalemia. His creatinine was 3.2 mg/dl at the time of admission, but it was improving gradually, so the possibility of hyperkalemia due to graft was not suspected. The possibility of trimethoprim-induced hyperkalemia was entertained, after ruling out tacrolimus as a cause of hyperkalemia. Tacrolimus levels were in normal range (9.76 ng/dl). The dose of TMP-SFX was reduced to two tablets BD. He was treated with intravenous calcium gluconate, glucose-insulin drip, and sodium bicarbonate. His serum potassium levels returned to normal on day 18. His serum creatinine had also come down to 2.5 mg/dl. The patient had symptomatic relief, and chest X-ray showed resolution of pneumonia. [Figure 3] the patient was put on pneumocystis jiroveci prophylaxis once again with TMP-SMX double strength once a day. The dose of mycophenolate was reduced to 500 mg twice a day from 500 mg three times a day. Immunosuppression was restored to previous levels at discharge (tacrolimus 1.5 mg BD, mycophenolate 500 mg TDS, and oral steroid 20 mg BD).

Figure 1: Chest X-ray: Day 1 of admission

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Figure 2: Chest X-ray: Day 14 of admission shows bilateral opacities; original photograph shows clearance

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Figure 3: Electrocardiography: Signs of hyperkalemia

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Discussion

Our patient underwent second kidney transplantation (KT) with antithymocyte globulin as induction therapy. He did not receive pneumocystis jiroveci prophylaxis posttransplant completely due to thrombocytopenia. The donor was a father-in-law who was 65 years of age. The patient had reached serum creatinine of 1.8 mg/dl 15-day posttransplant. Three-month post-KT, his serum creatinine was 1.8 mg/dl. A British study by Akoh and Rana ^[9] showed that transplant patients who had donor above 60 years of age had mean serum creatinine of 2.0 mg/dl at the end of 3 months. Furthermore, our patient had good renal output, DSA was negative, graft rejection was not suspected, and renal biopsy was not performed during his initial 3 months after renal transplant. The patient developed PJP 3 months after transplant. The incidence of PJP in renal transplant recipient has been reported to be around 1%–6% in different studies.^{[10],[11],[12]} The standard treatment for PJP is high-dose sulfamethoxazole-trimethoprim (TMP-SMX).^[10] As bioavailability of co-trimoxazole is excellent, it can be used orally. Up to date, Thomas and Limper ^[13] recommended that co-trimoxazole has excellent bioavailability and oral administration is appropriate for all patients who have a functioning gastrointestinal tract. They also recommended the use of oral steroids in moderate-to-severe PJP. A study by Goto et al.^[14] concluded that dose, duration, and timings of steroids had not been fully studied in transplant patients for treating PJP. Sometimes, hyperkalemia can be life threatening and levels can be as high as >6.5 mE/L, so it is mandatory to monitor potassium in patients receiving sulfamethoxazole + trimethoprim for PJP. The mechanism of hyperkalemia with trimethoprim is blocking of potassium secretion from distal convoluted tubule.^[3],[4]

Conclusion

Potassium levels should be monitored when using high-dose SMX-TMP in patients of PJP. Reduction of dose and proper treatment of hyperkalemia will revert this complication.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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