Hyperhomocyst(e)inemia in chronic stable renal transplant patients

Abstract

RHCFAP/3019 MACHADO DJ de B et al. -Hyperhomocyst(e) Purpose:Hyperhomocyst(e)inaemia is an important risk factor for atherosclerosis, which is currently a major cause of death in renal transplant patients. The aim of this study was to assess the influence of immunosuppressive therapy on homocyst(e)inemia in renal transplant recipients.Methods: Total serum homocysteine (by high performance liquid chromatography), creatinine, lipid profile, folic acid (by radioimmunoassay-RIA) and vitamin B12 (by RIA) concentrations were measured in 3 groups. Group I patients (n=20) were under treatment with cyclosporine, azathioprine, and prednisone; group II (n=9) were under treatment with azathioprine and prednisone; and group III (n=7) were composed of renal graft donors for groups I and II. Creatinine, estimated creatinine clearance, cyclosporine trough level, lipid profile, folic acid, and vitamin B12 concentrations and clinical characteristics of patients were assessed with the aim of ascertaining determinants of hyperhomocyst(e)inemia.Results: Patient ages were 48.8 ± 15.1 yr (group I), 43.3 ± 11.3 yr (group II); and 46.5 ± 14.8 yr (group III). Mean serum homocyst(e)ine (tHcy) concentrations were 18.07 ± 8.29 mmol/l in renal transplant recipients; 16.55 ± 5.6 mmol/l and 21.44 ± 12.1 mmol/l respectively for group I (with cyclosporine) and group II (without cyclosporine) (NS). In renal donors, tHcy was significantly lower (9.07 ± 3.06 mmol/l; group I + group II vs. group III, p<0.008). There was an unadjusted correlation (p<0.10) between age (r=0.427; p<0.005) body weight (r=0.412; p<0.05), serum creatinine (r=0.427; p<0.05), estimated creatinine clearance (r=0.316; p<0.10), and tHcy in renal recipients (group I +II). Independent regressors (r 2 =0.46) identified in the multiple regression model were age (coefficient= 0.253; p=0.009) and serum creatinine (coefficient=8.07; p=0.045). We found no cases of hyperhomocyst(e)inemia in the control group. In contrast, 38% of renal recipients had hyperhomocyst(e)inemia: 7 cases (35%) on cyclosporine and 4 (45%) without cyclosporine, based on serum normal levels.Conclusions: Renal transplant recipients frequently have hyperhomocyst(e)inemia. Hyperhomocyst(e)inemia in renal transplant patients is independent of the scheme of immunosuppression they are taking. The older the patients are and the higher are their serum creatinine levels, the more susceptible they are to hyperhomocyst(e)inemia following renal transplantation.

Hypertension, metabolic derangements and renal dysfunction in renal transplant patients using cyclosporine or tacrolimus

“…So far, it can be concluded that the diabetogenic effect of tacrolimus is not of great concern, and it can be managed by reducing the dose of tacrolimus, early corticosteroid withdrawal and avoiding it in hepatits C patients 18 . Hyperhomocysteinaemia was not seen under the use of tacrolimus compared to cycloprin, as previously reported 19,20 . The lower serum creatinine levels at the third month observed in patients receiving tacrolimus compared to cyclosporin with the same doses of azathioprine, MMF and prednisone, suggest that tacrolimus is a better imunossupressor to prevent subclinial acute rejection and is also less nephrotoxic 21,22 .…”

Homocysteine and cardiovascular disease in renal disease

“…Furthermore, we recently demonstrated in a prospective placebo‐controlled study using rats that plasma homocysteine concentration was not significantly elevated in CyA‐treated rats 93 . Our finding, coupled with those of others, 27,28 , 71,91 , 92 strongly suggests that CyA is unlikely to cause the hyperhomocysteinaemia seen in RTR. Therefore, mechanisms explaining the hyperhomocysteinaemia in RTR appear to be the same as those affecting ESRF patients; namely, reduced renal homocysteine metabolism and, possibly, the uraemic environment.…”

“…These suggestions have been refuted by studies showing plasma cysteine, a product of transsulphuration, was not significantly different in CyA‐treated RTR compared with non‐CyA‐treated RTR 25 and plasma homocysteine and red cell folate concentrations are correlated in CyA‐treated RTR 27,28,91 . In addition, plasma homocysteine concentrations in RTR treated with CyA were either 23% lower 92 or not significantly different 27,28,71 compared with concentrations in those RTR not receiving CyA, whereas serum creatinine was the strongest independent determinant of plasma homocysteine concentration in 86 stable RTR and CyA had no influence at all 71 . Differences in methodologies between the studies may account for the contrasting results, with some studies 27,28,71 adjusting for renal function and other determinants of hyperhomocysteinaemia whereas others 25,26 did not.…”

Factors Associated with Hyperhomocysteinemia After Renal Transplantation

“…No significant correlation between the tHcy level and the doses of cyclosporine, prednisolone, and azathioprine was found in our study or in many other studies. [25][26][27] Others reported a significant positive correlation between the levels of serum Hcy and cyclosporine [28] but a lowering effect of mycophenolic acid on total plasma Hcy. [29] Multivariate regression analysis revealed that, besides creatinine clearance, only BW was a significant determinant of elevated total Hcy level in our renal transplant recipients.…”