Mycophenolate mofetil, an inhibitor of inosine monophosphate dehydrogenase, causes a paradoxical elevation of GTP in erythrocytes of renal transplant patients

2004 ◽  
Vol 107 (1) ◽  
pp. 63-68 ◽  
Author(s):  
David GOLDSMITH ◽  
Elizabeth A. CARREY ◽  
Stephen EDBURY ◽  
Ryszard T. SMOLENSKI ◽  
Piotr. JAGODZINSKI ◽  
...  
Keyword(s):  
Mycophenolate Mofetil ◽  
Renal Transplantation ◽  
Renal Transplant ◽  
Plasma Metabolites ◽  
Renal Transplant Recipients ◽  
Inosine Monophosphate Dehydrogenase ◽  
Inosine Monophosphate ◽  
Transplant Patients ◽  
Renal Transplant Patients ◽  
Monophosphate Dehydrogenase

The immunosuppressant MMF (mycophenolate mofetil) has increasingly replaced AZA (azathioprine) in renal transplantation. MMF is a prodrug of MPA (mycophenolic acid), which inhibits lymphocyte IMPDH (inosine monophosphate dehydrogenase), thereby drastically decreasing GTP concentrations essential to lymphocyte proliferation in vitro and in vivo. Erythrocyte GTP concentrations are commonly elevated in severe renal disease, but normalize following successful engraftment. Consequently, elevated GTP in renal transplant recipients might signal impending loss of immunosuppression and graft failure. In the present study, we compared erythrocyte nucleotides and plasma metabolites in two groups of 25 patients after renal transplantation, both receiving prednisolone and cyclosporin A, but one group receiving MMF and the other AZA. No patients had recent allograft biopsy evidence of rejection. Erythrocyte GTP concentrations at MMF commencement were 50.4±23.4 μmol/l. An increase occurred during the first 3 months after transplant when MMF was used de novo, stabilizing at 146.7±62.9 μmol/l after 4 months. This was significantly higher (P=2.5×10−6) than erythrocyte GTP (40.4±15.9 μmol/l) in the AZA group, which was essentially unchanged from values immediately after successful transplantation. The effect of MMF on erythrocyte GTP levels was reversible, since GTP levels fell when MMF therapy was terminated. The results demonstrate paradoxically high GTP concentrations in erythrocytes of renal transplant patients receiving MMF. MPA may stabilize reticulocyte IMPDH, allowing the protein to persist during erythropoiesis. This behaviour is in marked contrast with the decrease in GTP levels seen in white blood cells of patients on chronic MMF therapy.

Increased Mortality Among Renal Transplant Patients With Invasive Pulmonary Aspergillus Infection

2018 ◽  
Vol 28 (4) ◽  
pp. 349-353 ◽  
Author(s):  
Baran Balcan ◽  
Umit Ozcelik ◽  
Aylin Ozsancakli Ugurlu ◽  
Mehtap Aydin ◽  
Serdar Nalcaci ◽  
...  
Keyword(s):  
Renal Transplantation ◽  
Renal Transplant ◽  
Opportunistic Infections ◽  
Fungal Infections ◽  
Univariate Analysis ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Aspergillus Infection ◽  
Transplant Patients ◽  
Renal Transplant Patients

Introduction: Renal transplantation is the most effective and preferred definite treatment option in patients with end-stage renal disease. Due to long-term immunesuppressive treatment, renal transplant recipients become vulnerable to opportunistic infections, especially to fungal infections. Method: This was a single-center, retrospective observational study of 438 patients who underwent renal transplantation between 2010 and 2016. Results: Thirty-eight renal transplant recipients who had lower respiratory tract infection with median age of 41.5 years were evaluated for invasive pulmonary aspergillus (IPA). Of these, 52.6% were female and 84.2% had living donors. Eleven of 38 lower respiratory patients were found to have IPA infection, 5 with proven infection. Compared to patients who did not have fungal pulmonary infection, patients with invasive aspergillus were older and had high fever, galactomannan levels, and leukocyte counts. Mortality was also higher in those patients. Having fever at the baseline and IPA infection was significantly associated with mortality in univariate analysis and remained related in multivariate model after adjustment for age, gender, and fever. Conclusion: Invasive pulmonary aspergillus infection is highly associated with increased mortality rates in renal transplant patients. Fungal pulmonary infections in immune-suppressed patients should be diagnosed and treated immediately in order to avoid the life-threatening complications and may greatly improve prognosis.

Human BK Polyomavirus Nephropathy (BKVN) In Non- Kidney-Transplant Patients

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S118-S118
Author(s):  
Y Chen Wongworawat ◽  
C Zuppan
Keyword(s):  
Renal Transplant ◽  
Kidney Transplant ◽  
Graft Loss ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Transplant Patients ◽  
Bk Polyomavirus ◽  
Pathologic Features ◽  
Renal Biopsies ◽  
Renal Transplant Patients

Abstract Introduction/Objective Human BK polyomavirus nephropathy (BKVN) occurs in up to 10% of renal transplant recipients, and can result in graft loss. Transplant biopsy is the gold standard to diagnose BKVN, and SV40 immunohistochemical (IHC) staining is helpful in confirming the diagnosis. BKVN is uncommon outside the setting of renal transplantation. To understand more about its occurrence in other contexts, we reviewed our renal biopsies files for cases of BKVN. Methods Our renal biopsy files for the past 20 years were reviewed for all cases with a diagnosis of BKVN or polyoma virus infection, and the clinical characteristics of the affected patients noted. Results Evidence of BKVN was found in 44 renal biopsies, of which 39 (86%) were renal transplant patients. Of the remaining five patients (14%), two had undergone heart transplantation, one lung transplantation, one was undergoing chemotherapy for acute lymphoblastic leukemia, and one patient had active HIV infection. All patients had elevated serum creatinine, and four out of five patients had documented BK viremia. Four of the five biopsies showed typical tubular injury with viral nuclear cytopathic changes (inclusions). In the lung transplant patient, the biopsy showed advanced chronic tubulointerstitial injury without distinct viral inclusions, but SV40 staining confirmed the presence of BK virus antigen. Conclusion The BKVN is distinctly uncommon outside the context of kidney transplantation. In our series, 14% of patients with BKVN were not kidney transplant recipients, but all were immune compromised in some fashion. The pathologic features of BKVN appear similar, regardless of whether the host is a renal transplant recipient or not. Although uncommon, it is important to consider the possibility of BKVN in non-renal transplant patients with persistent or progressive renal dysfunction.

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