Change in serum creatinine levels between 6 and 12 months and kidney graft survival: influence of proteinuria.

Renal function within the first year after transplantation has been shown to be an important parameter influencing long-term survival. In this study, we examined the relationship between long-term outcome in 365 renal transplants and renal function in the first year, expressed as serum creatinine (SCr) level at 6 months and at 1 year as well as namely deltaCr, the change in SCr between 6 months and 1 year. In addition, we examined the influence of the presence of proteinuria as a predictive factor for a worse evolution. Graft survival was worse among patients with higher deltaCr, especially among those who developed proteinuria. In a Cox regression analysis of long-term graft survival, both deltaCr and proteinuria were important predictors of half-life. The risk of graft loss when deltaCr >0.3 was 2.65 (1.8-3.8; P < .000), whereas the risk increased to 5.67 (3.3-9.4; P < .00) when proteinuria was present. In conclusion, deltaCr values predict long-term graft survival. Patients who developed proteinuria were at higher risk for graft loss compared with those without proteinuria. By using a combination of SCr and deltaCr with proteinuria, it is possible to identify a subset of transplant recipients with a predictably shortened half-life.

The macrophage infiltration index and matrix metalloproteinase-II expression as a predictor of chronic allograft rejection.

The presence of macrophages on renal biopsy specimens is considered an important cofactor in the development of chronic allograft nephropathy (CAN). Macrophages can activate the expression of matrix metalloproteinases (MMP), which induce glomerulosclerosis, arteriosclerosis, and interstitial fibrosis. The aim of our study was to demonstrate if they were related to the development of CAN. We analyzed matrix metalloproteinase (MMP) expression with specific monoclonal antibodies on 53 kidney biopsies performed due to the suspicion of a first acute rejection (AR) episode: 24 of the grafts have been lost due to CAN and the rest are still functioning. The group with CAN showed worse graft function and greater proteinuria from the beginning. The macrophage infiltration index (MI) expression was significantly higher in that group also (18.8 +/- 12 vs 12.5 +/- 9.15; P < .05), with a more important presence of macrophages in the interstitium and tubules. We observed a positive correlation between MI and tubular infiltration (r(2) = 0.52; P < .001) and between MMP-II and MI in the interstitium (r(2) = 0.3; P < .05) and with the global MI (r(2) = 0.3; P < 0.05). The last correlation was more powerful in the group with CAN (r(2) = 0.4; P < .05). According to our experience, global MI and tubular infiltration during an AR episode are good markers of long-term graft survival. The correlation between MI and MMP-II supports the role of macrophages in the development of CAN, although further studies are needed to clarify the nature of this relationship.

Effect of early graft function on patient survival in renal transplantation.

The influence of early graft function on long-term graft survival has been widely reported but its association with patient survival has received less attention. We investigated the effect of early renal function on patient survival and on cardiovascular disease after renal transplantation among 532 transplant patients who had grafts functioning for >1 year. Patients were classified into two groups, depending on the early creatinine clearance (< or >60 mL/min). We analyzed graft and patient survival, posttransplant cardiovascular disease, and the principal causes of death. Five- and 10-year graft and patient survival were lower among the group with worse early renal function. The main cause of death was vascular disease. Poorer early renal function increased the risk (RR) of patient death by 2.2-fold, and also the presence of posttransplant cardiovascular disease. In conclusion, patients with poor levels of early graft function are at an increased risk of death. These high-risk groups should be targeted for interventional studies to improve patient survival.

Pulse pressure is an independent risk factor of cardiovascular disease in renal transplant patients.

Elevated pulse pressure in the general population has been shown to be associated with cardiovascular disease, which is the main cause of death in renal transplant patients. We investigated the effects that a wide pulse pressure has on cardiovascular disease after renal transplantation in a cohort of 532 transplant patients with functioning grafts for more than one year. Patients were classified into two groups depending on whether the one-year pulse pressure was less than or greater than 65 mm Hg. We analyzed patient survival, posttransplant cardiovascular disease and principle causes of death. Five- and ten-year patient survival were lower among the group with higher pulse pressures. The main cause of death was vascular disease in both groups. The presence of posttransplant cardiovascular disease was higher among the group with higher pulse pressures (RR=1.73). In addition, the incidence of an elevated pulse pressure was directly associated with recipient age and posttransplant diabetes mellitus. In conclusion, pulse pressure represents an independent risk factor for increased cardiovascular morbidity and mortality in renal transplant patients.

Factores de riesgo cardiovascular en el trasplante renal: marcadores clínicos / Cardiovascular risk factors in renal transplantation: clinical markers

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Informe de diálisis y trasplante de la Sociedad Española de Nefrología y Registros Autonómicos, año 2000 / Rapport of the dialysis and transplant registry in Spain. The Spanish Society of Nephrology and Regional Registries

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Hypertension and long-term renal allograft survival: effect of early glomerular filtration rate.

BACKGROUND: For many years, hypertension has been related to long-term survival of patients and kidney grafts, although the nature of this relationship has not been completely defined. The aim of this study was to analyse the influence of early glomerular filtration rate on post-transplant hypertension and on graft survival. METHODS: A total of 432 kidney transplanted patients on cyclosporin therapy, with a functioning graft for at least 1 year, were studied. They were divided into two groups depending on their early creatinine clearance: group A [<60 ml/min (n=270)] and group B [>60 ml/min (n=162)]. RESULTS: There were no differences in sex, aetiology of renal failure, number of retransplants, PRA, HLA mismatches and pre-transplant blood pressure. One year after transplantation, blood pressure was higher in group A (systolic BP 148/diastolic BP 86/mean BP 117) than in group B (systolic BP 140/diastolic BP 82/mean BP 111) (P<0.003). We observed a negative correlation between early creatinine clearance and 1-year blood pressure (P<0.01). Five and 10 year graft survival was 60 and 37% in group A and 87 and 69% in group B, respectively (P<0.000). A multivariate Cox analysis showed that 1-year blood pressure (P<0.0029, RR=1.76) and early creatinine clearance (P<0.000, RR=3.27) had a significant influence on graft survival. CONCLUSIONS: The 1-year post-transplant blood pressure is a non-immunological risk factor in long-term graft survival. Patients with a lower initial glomerular filtration rate are more susceptible to the development of secondary hypertension and worse graft survival.

Circulating levels of matrix metalloproteinases MMP-3 and MMP-2 in renal transplant recipients with chronic transplant nephropathy.

BACKGROUND: Chronic transplant nephropathy remains the major cause of graft loss after the first year post transplant, with the exception of death with functioning graft. The histological hallmark of chronic kidney rejection is progressive fibrosis in which extracellular matrix turnover plays an important role. This turnover is regulated by several systems of connective tissue proteases, the matrix metalloproteinases family being one of them. Every metalloproteinase exerts a different function over extracellular matrix proteins and can contribute to the pathogenesis of several diseases, such as rheumatoid arthritis and glomerulonephritis. The role of metalloproteinases in the pathogenesis of chronic transplant nephropathy and in kidney transplantation has not yet been addressed. METHODS: We measured the serum levels of proMMP-1, proMMP-2 and proMMP-3 by ELISA in 40 patients with chronic transplant nephropathy, 30 with acute rejection, 30 with stable graft function for a time equivalent to chronic transplant nephropathy, 30 with stable graft function for a time equivalent to acute rejection, and 30 healthy age-paired blood donors. RESULTS: Serum proMMP-2 and proMMP-3 were significantly higher in patients with chronic transplant nephropathy than in patients with acute rejection, stable graft function and healthy donors. The most striking finding was the significant positive correlation observed between serum levels of proMMP-3 and serum creatinine, and between circulating levels of proMMP-2 and proteinuria. Serum concentration of proMMP-1 was increased in patients with acute rejection compared with those with stable graft function and healthy donors. CONCLUSIONS: Serum proMMP-2 and proMMP-3 reflect the changes of glomerular and interstitial extracellular matrix in chronic transplant nephropathy, suggesting that they could play a role in the pathogenesis of this condition. Acute rejection is associated with increased levels of proMMP-1, which could be a reflection of the stimulation induced by a number of inflammatory cytokines produced in such a process.