The patient is a 17 year old boy with a history of a congenital vesicoureteral reflux and other congenital abnormalities of kidney and urinary tract (CAKUT) which gradually caused nephrosclerosis, secondary hypertension and chronic kidney disease (CKD). In April, 2019 he started peritoneal dialysis (PD) because of CKD stage 5. In June, 2019 he received a deceased donor kidney transplant (from a 58 year old female, cause of death - intracerebral hemorrhage. CMV +, EBV +, hepatitis markers - negative, CMV donor + /recipient -). Before KTx induction therapy consisted of Basiliximab - interleukin 2 receptor antibody (IL2Ra) 20 mg IV, mycophenolate mofetil (MMF) 750 mg PO and tacrolimus 3 mg PO. Intraoperatively methylprednisolone 500 mg IV was administered. After KTx patient underwent maintenance therapy with tacrolimus 3 mg PO once daily (o.d.), MMF 750 mg PO twice daily, methylprednisolone 48 mg PO Prophylaxis for Cytomegalovirus (CMV) with valganciclovir 450 mg PO for 6 months as high risk and prophylaxis for Pneumocystis jirovecii TMPSMX 80/400 mg PO was given for 3 months (up to September, 2019). Additionally, patient received treatment with antihypertensives and anticoagulants.
The post-transplant period was mostly uncomplicated with good diuresis, patient had no rejection episodes. Tacrolimus, other immunosuppressant and antihypertensive treatment was tailored a few times in order to achieve either required drug serum concentrations or clinical efficacy, graft function was relatively stable, eGFR ranging from 44,1 to 51,4 mL/min/1.73m2. Darbopoetin alfa 20 mug once every two weeks s/c and folic acid was started due to secondary anemia and continued for 6 months. In July, 2019 the first graft biopsy was performed due to proteinuria and poorly controlled hypertension. Results showed focal mesangioproliferative changes without immunoreactant deposition. Immunosuppresive treatment with tacrolimus and antihypertensive treatment was intensified
In September, 2019 the patient was hospitalised due to leukopenia, neutropenia, diarrhea, loss of apetite. His blood tests showed elevated CMV viremia (up to 8811 copies/ml, while on previous outpatient visits no viremia was detected). MMF was discontinued and valgancivlovir dose was increased up to 450 mg twice daily, for 2 weeks until viral load became undetectable. Patient had fungal toenail infection, topical terbinafine and naftifine were prescribed. Valganciclocvir was discontinued in December, 2019, after completion of 6 months of post-KTx prophylaxis. The last outpatient visit was 12 days before the case of PCP. During the visit the patient had no complaints, his physical examination was unremarkable, graft function was stable with eGFR of 41,4 mL/min/1.73m2 and low CMV viremia of 25 copies/ml (which was below the significant threshold). His immunosuppressive regimen consisted of tacrolimus 6 mg PO o.d., methylprednisolone 8 mg PO o.d. and MMF 500 mg PO twice daily and were not tailored recently.
At the end of June, 2020 patient was admitted to the hospital due to the subfebrile temperature, dry cough, shortness of breath for about 1 week and general fatigue for more than 3 weeks during physical activity. Important to note that additional information about earlier onset of patient's complaints was explicated only after the patient was hospitalized, because at last outpatient visit they did not inform about complaints of fatigue. Patient also lost 4 kg down to 46 kg of weight in the last month. On physical examination the patient was tachycardic (HR - 128 bpm), oxygen saturation (SpO2) was 89% and a subfebrile temperature of 37.2oC. Patient required 2-3 L/min of oxygen to maintain oxygen saturation above 92%. Blood pressure (BP) was 124/80mmHg. There was a reddish, dry maculopapular rash on the upper side of the trunk and around the neck and signs of toenail fungus were seen. Lung auscultation was normal. PCR tests for SARS-CoV-2 from nasopharyngeal swabs were negative twice. No other remarkable findings.
Initial laboratory tests showed decreasing eGFR down to 32 mL/min/1.73m2. C-reactive protein (CRP) was elevated - 79.2 mg/l, tacrolimus concentration - 5.7 ng/ml. Complete blood count, albumin, liver enzymes and electrolytes were normal (laboratory tests are presented in Table 1). Tuberculosis was excluded with both negative Tuberculin skin test (TST) and Interferon-gamma release assay. Atypical bacterial infections were excluded with negative serological testing and negative nasopharyngeal swab PCR. Blood culture was taken. Both EBV and CMV blood tests for PGR were taken and CMV viremia was present at 51 copies/ml.
Chest radiograph (Figure 1) revealed fine bilateral interstitial infiltrates with interstitial edema.
Immunosupressive and antihypertensive treatment was initially unchanged. Topical antifungal treatment was prescribed for suspected fungal etiology of toenail and skin lesions while microbiological tests were ongoing. O2 flow through face mask of 2 l/min was continued.
Chest CT scan (Figure 2) showed bilateral ground glass opacities, pneumatoceles in basal segments and diffuse varying in size centrilobular and peribronchovascular consolidation foci.
On the second day of hospitalisation, while the workup was still in process and bronchoscopy for acquisition of BALF was in line, patient's condition deteriorated, resulting in increased breathing rate, dyspnea and supplemental oxygen demand of up to 12 l/min in order to keep SpO2 >=92%. It was followed by a decrease of kidney function down to eGFR of 27,1 mL/min/1.73m2. Patient was empirically started on TMP-SMX 320 mg IV o.d., Fluconasole 100 mg IV o.d., Sol. Ganciclovir 115mg IV o.d. MMF dose was reduced to 250 mg twice daily, which was later temporarily discontinued. A bronchoscopy was performed and a BALF sample tested positive for P. jirovecii. CMV (3575 copies/ml) and EBV (70000 copies/ml) were detected too. In addition, immunoglobulin G (IgG) was found to be significantly lower - 2,16 g/l, so an IV infusion of 20g IgG was administered.
Over the next days the patient's condition improved, with a reduction of O2 therapy (Figure 3) and a gradual resolution of symptoms - patient reported no fatigue, better general well-being and only occasional coughing. Slight improvement in kidney function was observed with eGFR of 30,9 mL/min/1.73m2 and patient was discharged 2 and a half weeks later after he received IV TMP-SMX for 18 days, and IV ganciclovir for 1 week. Later valganciclovir PO was continued for a total of 1 month and TMP-SMX at a lower dose of 480 mg PO was continued for 3 months in total.
At follow-up his condition has progressively improved, with no signs of infection or respiratory distress, with a markedly improved kidney function and normal inflammation markers as seen in Table 1.
Chest CT. Bilateral ground glass opacities and diffuse centrilobular and peribronchovascular consolidation foci.