Aerosolized tacrolimus: a case report in a lung transplant recipient

Long-term outcomes after lung transplantation remain poor mainly to the development of bronchiolitis obliterans syndrome (BOS). Currently, treatment options for BOS are very limited. Strategies to prevent and treat this complication include the use of aerosolized therapy with only cyclosporine used in patients to date. We describe the use of aerosolized tacrolimus in a lung transplant recipient with BOS. The patient demonstrated clinical improvement in functional capacity and oxygenation while receiving tacrolimus by nebulization. Further research is needed to study whether aerosolized tacrolimus is beneficial in lung transplant recipients with BOS.     

The calcimimetic cinacalcet normalizes serum calcium in renal transplant patients with persistent hyperparathyroidism.

BACKGROUND: Treatment of persistent hyperparathyroidism in renal transplant patients resistant to calcium and vitamin D sterols is limited and often requires parathyroidectomy. Given the potential hazards linked to surgery, an alternative approach to manage excess parathyroid hormone (PTH) secretion is needed. Calcimimetics inhibit PTH secretion by modulating the calcium-sensing receptor in the parathyroid. Lowering of the serum calcium concentration with the calcimimetic cinacalcet has previously been demonstrated in patients with primary hyperparathyroidism or with secondary hyperparathyroidism on dialysis. Here we present the first clinical observations of a calcimimetic in patients with persistent hyperparathyroidism. METHODS: A 30 mg dose of cinacalcet was prescribed once daily for 3 months to seven female and seven male stable renal transplant patients, aged 23-65 years, 7 months to 14 years after transplantation, with a serum creatinine ranging from 89 to 229 micromol/l and persistent hyperparathyroidism. Concomitant medication included cyclosporin and low-dose prednisone in all patients. RESULTS: On cinacalcet, serum calcium decreased and normalized in all but two patients (baseline 2.72+/-0.03 mmol/l; 1 month 2.42+/-0.04 mmol/l, P<0.001), whereas serum PTH and phosphate levels did not change significantly. A slight reduction in renal function, as assessed by serum creatinine concentration, was observed at months 2 and 3 (P<0.05). An immunoglobulin-deficient patient developed colitis after 1 week of treatment and cinacalcet was withdrawn. No patient stopped cinacalcet because of other presumed side effects. CONCLUSION: Calcimimetics are a promising therapy in renal transplant patients with persistent hyperparathyroidism. Prospective controlled studies must now be designed focusing on functionally relevant musculo-skeletal end-points and allowing the exclusion of negative effects on long-term renal and general outcome of such patients.     

Acute disseminated encephalomyelitis in a renal transplant recipient: a case report

Acute disseminated encephalomyelitis (ADEM) is an acute demyelinating disorder of the central nervous system, mostly seen in children after viral or bacterial infection and vaccinations. Cases of ADEM, albeit rare, have been reported in renal transplant recipients. The pathophysiology of posttransplant ADEM remains unclear but has been hypothesized to be due to aberrant T-cell reactivity to myelin basic protein triggered by a bacterial or viral infection. We report an unusual case of a 34-year-old white female with ADEM developing 5 years after a living related renal transplant.     

Effect of cinacalcet cessation in renal transplant recipients with persistent hyperparathyroidism.

BACKGROUND: Persistent hyperparathyroidism after renal transplantation affects bone and allografts. Cinacalcet, a calcimimetic, reduces serum calcium and PTH in renal transplant recipients with persistent hyperparathyroidism. Here, we address the question whether this effect of cinacalcet persists after withdrawal. METHODS: Therefore, cinacalcet was stopped after 12 months treatment in 10 stable renal transplant patients. Serum calcium, phosphate, PTH, creatinine and cystatin C were monitored for 3 months. RESULTS: Serum calcium, normalized in nine patients before cessation of cinacalcet (2.32 +/- 0.05mmol/l, mean +/- SEM), increased after 3 months of discontinuation by 0.17 +/- 0.04mmol/l, P < 0.05, but remained within the normal range in eight patients. Compared with the time point of cessation, PTH remained unchanged or decreased further after 3 months without therapy in six patients. Measurements of cystatin C suggested an improvement of the glomerular filtration rate after cessation in 9 out of 10 patients (1.55 +/- 0.09 vs 1.33 +/- 0.12 mg/l, P < 0.01). CONCLUSION: First, a beneficial effect of cinacalcet beyond the duration of a 12-month therapy appears to be present in some patients and second, the previously suspected influence of cinacalcet therapy on renal function is reversible. Thus, it is reasonable to consider a trial of cinacalcet cessation to identify these patients. The optimal time point for such a discontinuation is unknown. The present observations are preliminary. They clearly require a prospective randomized trial for definitive confirmation.     

Therapeutic failure of cinacalcet in a renal transplant patient presenting hyperparathyroidism with severe hypercalcaemia

Sir, In our experience, 10% of renal allograft recipients developsustained hyperparathyroidism and hypercalcaemia during thefirst year following renal transplantation. Persistent hypercalcaemiausually requires parathyroidectomy, which represents the onlydefinitive treatment currently available. Cinacalcet, a calcimimeticdrug, represents from now on an alternative     

Outcome of twin pregnancy in a renal transplant recipient treated with tacrolimus

Our report describes the outcome of a twin pregnancy in a woman who was maintained on tacrolimus after a living related renal transplant. Both babies born at 32 weeks of gestation developed severe respiratory distress requiring ventilator assistance and went on to develop congestive heart failure. Echocardiograms on both babies showed dilated heart chambers. Twin A succumbed to complications, but twin B, who was treated more aggressively with vasopressors, recovered. Autopsy findings on twin A revealed a thrombotic cardiomyopathy with degeneration of cardiac muscle. We believe that the unusual outcome in this set of twins may have been a result of cardiomyopathy secondary to tacrolimus used by the mother during her pregnancy.     

Ramsay Hunt syndrome with atypical progress in a renal transplant recipient: a case report

Ramsay Hunt syndrome is a rare complication of herpes zoster disease in which reactivation of latent varicella zoster virus infection occurs in the geniculate ganglion causing otalgia, unilateral vesicular eruption in a restricted dermatomal distribution, and peripheral facial paralysis. Dermal infections caused by human pathogenic herpes viruses are common in organ transplant recipients. For a transplant surgeon, it is imperative to remember that viral prophylaxis is essential in the follow-up of the transplant patients. Here, we presented a case of renal transplant and Ramsay Hunt syndrome with multiple cranial nerve involvement, with an atypical course. Management and differential diagnosis of this particular case are discussed with a review of the literature.     

Clinical course of a renal transplant recipient with malignant fibrous histiocytoma: a case report

Organ transplant (Tx) recipients are susceptible to develop various malignancies, most of which are uncommon in the general population. We present a case of post-Tx malignant fibrous histiocytoma with complete remission of tumor and excellent allograft function 3 years after cessation of cyclosporine.     

Cytomegalovirus infection in peptic ulcer in renal transplant recipient: a case report

Gastroduodenal ulcers in renal transplant recipients are usually originated from excessive acid secretion or infection of Helicobacter pyroli. Herein, we report a case of cytomegalovirus (CMV)--induced gastric ulcer following cadaveric renal transplantation. The patient was a 48-year-old man with chronic renal failure and received cadaveric renal transplantation. A month later, he had epigastralgia without CMV-positive antigenemia and received gastrointestinal fiberscopy. Endoscopically, gastric ulcer was identified. Histological findings revealed conspicious nuclear enlargement of the non-epithelial cells in the ulcer bed, which indicated CMV infection. The patient was treated with ganciclovir for 2 weeks and the symptom was relieved. He discharged with a good renal function on day 75 posttransplant. CMV infection plays an important role in gastric ulcer after renal transplantation. Antigenemia assay dose not seem feasible for the detection of CMV-induced gastric ulcer.     

Infected solitary renal cyst of the graft in a renal transplant recipient : a case report

A 59-year-old woman with end-stage renal disease of diabetic nephropathy who had been on maintenance hemodialisis for 4 years, underwent a living-unrelated renal transplantation 6 years ago. She was admitted to our hospital, because of a low grade fever and edema. Ultrasonography revealed the cyst with heterogeneity structure in the upper pole of the transplanted kidney. Magnetic resonance imaging showed a high-intensity cystic mass measuring 68×53 mm. As fever and laboratory data did not improve sufficiently by the treatment with antibiotics, echo-guided puncture and drainage were performed for the abnormal structure in the upper pole of the transplanted kidney. In the culture of the purulent aspirate drained from renal cyst, Escherichia coli was isolated. To our knowledge, this is the first report of infected renal cyst of the graft in a renal transplant recipient in the world.     

Successful treatment of hypercalcemia with cinacalcet in renal transplant recipients with persistent hyperparathyroidism.

BACKGROUND: Cinacalcet lowers plasma parathyroid hormone (PTH) levels in primary and secondary hyperparathyroidism. The efficacy and safety of cinacalcet have not been examined in renal transplant patients with persistent hyperparathyroidism. The aim of this study was to evaluate the effect of cinacalcet as a novel therapy for the management of such patients. METHODS: Eleven renal allograft recipients with persistent hyperparathyroidism were treated with cinacalcet. The total study time was 10 weeks. Individual cinacalcet doses were adjusted to obtain a serum calcium in the predefined normal target range of 2.10-2.60 mmol/l. RESULTS: Serum calcium decreased significantly from 2.73+/-0.05 mmol/l to 2.44+/-0.05 and 2.42+/- 0.04 mmol/l after 2 and 10 weeks of treatment, respectively. All patients reached the target range rapidly and remained normocalcaemic throughout the study. Serum PTH significantly decreased 16.1 and 21.8% at study weeks 2 and 10, respectively, compared with week 0. Serum phosphate increased. Renal function remained stable and no allograft rejection was observed. From weeks 2 to 10, daily cinacalcet doses administered were 30 mg (n = 8), 15 mg (n = 1) and 60 mg (n = 1), respectively. CONCLUSION: Cinacalcet was effective in correcting the hypercalcaemia associated with persistent hyperparathyroidism after renal transplantation. It appears to be safe. Thus, cinacalcet represents a promising alternative for parathyroidectomy in these patients.     

Falsely abnormally elevated blood trough concentration of tacrolimus measured by antibody-conjugated magnetic immunoassay in a renal transplant recipient: a case report

This report presents a falsely abnormally elevated blood trough concentration (C_t) of tacrolimus measured by antibody-conjugated magnetic immunoassay (ACMIA) methods in a renal transplant recipient. Because the C_t of tacrolimus was 78.5 ng/mL at day 2 after a 52-year-old man underwent renal transplantation, we stopped the tacrolimus extended-release formulation. However, because the abnormally elevated blood C_t continued in the range of 41.1-59.1 ng/mL, we then measured the tacrolimus concentration in a stored blood sample before renal transplantation, it was 43 ng/mL. Consequently, the day-7 blood sample was measured with both ACMIA and enzyme-linked immunoassay, showing C_t values of 42.8 ng/mL and 0.89 ng/mL, respectively. Because the abnormally elevated C_t was falsely measured by the ACMIA method, we restarted tacrolimus However, the calcineurin inhibitor was subsequently converted to cyclosporine at day 21 after renal transplantation. Although cyclosporine was also measured by ACMIA, there was not an abnormally elevated C_t. Subsequently, the tacrolimus concentration ratio in plasma and whole blood (P/B-tacrolimus concentration ratio) was measured by ACMIA in a posttacrolimus blood sample. The P/B-tacrolimus concentration ratio was 100%. In contrast, the P/B-tacrolimus concentration ratio was <30% in 2 control patients administered tacrolimus. It has been reported recently that there were cases showing falsely slightly elevated C_t of tacrolimus within the therapeutic range of concentrations. Therefore, we must be careful not to reduce the tacrolimus dose falsely. We consider confirmatory methods for a falsely abnormally elevated C_t of tacrolimus measured by ACMIA to (1) measure P/B-tacrolimus concentration ratio, (2) compare ACMIA with another measurement, and (3) evaluate a blood sample stored before tacrolimus administration.     

Isolated primary pulmonary Kaposi's sarcoma in a renal transplant recipient: a case report

Kaposi's sarcoma (Ks) a relatively common malignancy after kidney transplantation, generally presents as characteristic dermatomucosal lesions. Visceral organ involvement is common in conjunction with skin lesions; however, isolated visceral KS is an uncommon disease among kidney recipients. Isolated primary pulmonary KS is a rare finding in this population. Herein we have reported on a 38-year-old renal recipient male with respiratory symptoms and a normal dermatomucosal examination without lymphadenopathy. Chest imaging revealed multiple, bilateral, ill-defined nodular opacities without lymphadenopathy or pleural effusion. Pulmonary KS was documented by histopathological evaluation of samples obtained from an open lung biopsy. The patient died because of severe pneumonia and intra-alveolar hemorrhage. Postmortem evaluation indicated no other organ involvement. This case exemplifies the importance of being aware that pulmonary KS should not be excluded in the absence of dermatomucosal lesions and lymphadenopathy.     

Lansoprazole-induced acute allergic interstitial nephritis in a renal transplant recipient: a case report

Drug-induced interstitial nephritis is one of the causes of graft dysfunction in renal transplant recipients. Although commonly implicated as a cause of drug-induced interstitial nephritis in the general population, proton pump inhibitor-induced interstitial nephritis has not yet been reported in renal transplant recipients. Trimethoprim-sulfamethoxazole is responsible for most cases of interstitial nephritis in this population. Here, we describe the first case of proton pump inhibitor-related interstitial nephritis in a renal transplant recipient.     

Treatment of hyperparathyroidism with cinacalcet in kidney transplant recipients

Background

After successful kidney transplantation, hyperparathyroidism can persist in 10%–50% of patients and can harmfully affect bone metabolism. Calcimimetic cinacalcet is a new treatment option in the management of persistent hyperparathyroidism in these patients.

Methods

This prospective, clinical study of 11 patients included those who had a serum intact parathyroid hormone (iPTH) concentration >65 ng/L, a serum creatinine concentration was <200 μmol/L, stable kidney graft function, and were >1 year since transplantation. Patients were not treated with drugs other than calcitriol that could influence bone metabolism. During the 6-month observation period, in which the stability of measured parameters was determined, and in the 12-month treatment period (cinacalcet 30 mg/d), we followed serum concentrations of calcium, phosphate, iPTH, creatinine, vitamin 25OH D₃, bone-specific alkaline phosphatase (ALP), osteocalcin, collagen degradation fragments (CTX), urinary calcium excretion, and bone mineral density (BMD).

Results

During the treatment period, the serum calcium concentration decreased significantly (from 2.50 ± 0.12 to 2.32 ± 0.12 mmol/L; P < .01). Serum iPTH concentration decreased significantly (from 247 [range, 199–362] at time 0 to 198 [range, 165–233] ng/L after 1 month of treatment; P < .05), but increased slightly thereafter. After 6 months of treatment, the serum concentration of ALP and CTX increased significantly, but decreased thereafter. There were no significant changes in the other parameters assessed. Renal function remained stable during the treatment period. The BMD of the lumbar spine, hip, and forearm did not change during the 12 months of treatment.

Conclusion

Cinacalcet was effective in treating posttransplant hyperparathyroidism, resulting in decreased calcemia and transient decreased iPTH. ALP and CTX transiently increased during therapy, but other markers of bone metabolism remained unchanged. Twelve months of cinacalcet treatment did not result in a change in BMD. Cinacalcet seems to be a safe drug with no negative effect on renal function.