Risk Factors For Death In Patients Research Articles

Renal Function at Six Months Is the Most Relevant Risk Factor for Graft Failure at Seven Years after Renal Transplantation

Introduction: To describe the results of renal transplantation in the clinical practice at seven years with special emphasis on risk factors for graft loss and mortality in Spain. Methods: From a database focus on postransplant cardiovascular disease (CDV) we prospectively analyzed the results at seven years of all transplanted patients: 2600 (without exclusions) during 2000-2002 in 14 Spanish units. Results: Donors and recipient age were 46.9±17 and 49.7±13.7 years, 16% were retransplanted and 12.5% hyperimmunized. The most frequent immunosuppressive protocol was Tac+MMF+St.(65%) and acute rejection rate at 1 year was 14.8%. At 7 years patients survival was 85.% and graft survival censored and non-censored death was 78.% and 70 % respectively. The main causes of death were CDV 32.5%, (especially coronary disease) 21% infections and 15 neoplasia. As expected, chronic allograft nephropathy (3.5%) and death with function (27%) were the most important causes of graft loss. Renal function at 7yr (1528 patients) showed SCr was 1.56 ± 0.8 mg/dl and MDRD 53.3ml/min. Interestingly, most of them maintained good renal function: 51% and 30% were on stages II and III of renal disease with the same immunosuppressive protocol (St+TAC+MMF). In the multivariatye analysis, (in patients surviving more than 6 mo.) the most striking finding was that renal function at 6mo. (SCr more than 1.5 mg/ dl) was the most powerful risk factor for graft loss and the second one risk factor for patient death (after pretransplant CDV disease). Conclusion: Our results suggest that in the clinical practice early renal function, SCr more than 1.5 mg/dl at six months, is the most important predictor of graft survival and the second for patient death in the mediumterm after renal transplantation. Measures to early ameliorate renal function could contribute to improve survival figures.

Long-term outcome of Hepatitis B-positive renal allograft recipients after development of antiviral treatment

Hepatitis B virus (HBV) infection can adversely affect the clinical outcome of kidney transplantation (KT). Short-term efficacy of lamivudine has been demonstrated for chronic hepatitis B in KT recipients (KTR). To clarify the long-term impact of antiviral treatment for HBV-positive KTR, we retrospectively reviewed 94 HBV-positive (male 73%) and 282 age/sex-matched HBV-negative patients who underwent KT from February 1997 to November 2009, after lamivudine had come into wide use. Mean follow-up was 75.7 months. 56 patients received antiviral agent for prophylaxis, and other 18 for HBV reactivation. During follow-up, 15 died, with 5 deaths being HBV related. Although the patient survival rate was lower for HBVpositive than HBV-negative KTRs (89% vs. 94% at 5 years, 78% vs. 88% at 10 years, p = 0.031), graft survival was comparable (86% vs. 92% at 5 years, 73% vs. 81% at 10 years, p = 0.113). In multivariate analysis, HBsAg positivity was a significant risk factor for patient death (OR 2.19, 95% CI 1.14 - 4.20, p = 0.019), but not significant for graft loss (OR 1.64, 95% CI 0.94 - 2.86, p = 0.079). Of the 26 hepatitis B e antigen (HBeAg)-positive patients, 14 experienced HBV reactivations, but all survived with stable liver chemistry, except for one who died of hepatocellular carcinoma. Among 57 HBeAg-negative patients, 12 died, whereas the remaining 45 survived without hepatic dysfunction. Long-term outcomes of HBV-positive KTRs may be favorable after antiviral agents have been introduced.

Modern death risk factors in patients with community-acquired pneumonia

Aim. To study death risk factors in patients with community-acquired pneumonia in municipal hospitals in Samara. Methods. 75 cases of deaths of patients hospitalized because of community-acquired pneumonia were studied (study group), 300 convalescent patients with community-acquired pneumonia discharged from the hospital were included in the control group. The retrospective comparative «case control» study was performed. Results. Mean age of the patients who died was 47.4±2.2 years; men were more prevalent (70.6%), time since admission date till death was 6.5±2.5 days, more than a third (36.0%) died before 24 hours after admission. The study group contained significantly higher number of unemployed (72.0%) and intravenous drugs users (16.0%). HIV infection was found in 37.3% of the patients who died, compared to 19.6% prevalence in control group. Multifactorial logistic regression of clinical signs revealed the following death risk factors in patients with community-acquired pneumonia: infiltrates on X-ray involving more than one lung lobe, arterial hypotension (systolic blood pressure ≤100 mm Hg, diastolic blood pressure ≤60 mm Hg), tachypnea (breath rate over 25 per minute). Conclusion. Factors having the highest positive prognostic value for a lethal outcome at patients with community-acquired pneumonia are: late admission, multilobar pneumonia; arterial hypotension; tachypnea; HIV infection, social unemployment and male gender.

Obesity, Surgical Site Infection, and Outcome Following Renal Transplantation

We sought to understand whether obesity imparts detriment in outcome beyond risk of developing surgical site infection (SSI). Obesity is a risk factor for SSI following renal transplantation, and has been implicated in inferior patient and graft survival postoperatively. We conducted a retrospective review of all adult kidney-only transplants performed at the University of Michigan between September 2003 and April 2008. The primary exposure variable was recipient body mass index (BMI). Cox multivariable regression and Kaplan-Meier analysis were used to identify factors associated with SSI, graft loss, and patient death. In total, 869 recipients were studied, including 351 with BMI >30. Multivariate analysis revealed recipient age, delayed graft function, and BMI >30 to be independent risk factors for SSI. SSI was a significant risk factor for graft loss (HR: 2.194, 95% CI: 1.357-3.546) and approached significance as a risk factor for patient death (HR: 1.689, 95% CI: 0.941-3.028). Obesity had no independent effect on graft or patient outcome. SSI is associated with detriment to patient and graft survival following renal transplantation. The prevalence of SSI is higher among obese recipients, but those who avoid SSI have comparable outcomes to nonobese recipients. These findings redemonstrate the importance of SSI prevention following renal transplantation.

L1 Cell Adhesion Molecule Is a Novel Independent Poor Prognostic Factor of Extrahepatic Cholangiocarcinoma

Cholangiocarcinomas (CC) are associated with poor survival, but diagnostic markers and therapeutic targets have not yet been elucidated. We previously found aberrant expression of L1 cell adhesion molecule in intrahepatic CC and a role for L1 in the progression of intrahepatic CC. Here, we analyzed L1 expression in extrahepatic CC (ECC) and evaluated its prognostic significance. We examined L1 expression in tumors from 75 ECC patients by immunohistochemistry. We analyzed the correlations between L1 expression and clinicopathologic factors as well as patient survival. L1 was not expressed in normal extrahepatic bile duct epithelium but was aberrantly expressed in 42.7% of ECC tumors. High expression of L1 was detected at the invasive front of tumors and was significantly associated with perineural invasion (P < 0.01). Univariate analysis indicated that various prognostic factors such as histologic grade 3, advanced pathologic T stage and clinical stage, perineural invasion, nodal metastasis, and high expression of L1 were risk factors predicting patient survival. Multivariate analyses done by Cox's proportional hazards model showed that high expression of L1 (hazard ratio, 2.171; 95% confidence interval, 1.162-4.055; P = 0.015) and nodal metastasis (hazard ratio, 2.088; 95% confidence interval, 1.159-3.764; P = 0.014) were independent risk factors for patient death. L1 was highly expressed in 42.7% of ECC and its expression was significantly associated with perineural invasion. High expression of L1 and nodal metastasis were independent poor prognostic factors predicting overall survival in patients with ECC.

Immunosuppressive Drugs in Kidney Transplantation

Renal transplant recipients have increased mortality rates when compared with the general population. The new immunosuppressive drugs have improved short-term patient survival up to 95% at 1-2 years, but these data have to be confirmed in long-term follow-up. Furthermore, no particular regimen has proved to be superior over others with regard to patient survival. Cardiovascular diseases are the most common cause of mortality in renal transplant recipients and while no immunosuppressive drug has been directly associated with cardiovascular events, immunosuppressive drugs have different impacts on traditional risk factors. Corticosteroids and ciclosporin are the agents with the most negative impact on weight gain, blood pressure and lipids. Tacrolimus increases the risk of new-onset diabetes mellitus. Sirolimus and everolimus have the most impact on risk factors for post-transplant hyperlipidaemia. Modifications in immunosuppression could improve the cardiovascular profile but there is little evidence regarding the beneficial effects of these changes on patient outcomes. Malignancies are also an increasing cause of mortality, overtaking cardiovascular disease in some series. Induction therapy, azathioprine and calcineurin inhibitors (CNIs) are probably the immunosuppressive agents most linked with post-transplant malignancies. Mycophenolate mofetil (MMF) has no negative impact on the incidence of malignancies. Target of rapamycin (mTOR) inhibitors have antioncogenic properties and they are associated with a lower incidence of malignancies. In addition, these agents have been recommended for use to decrease the dose or withdrawal of CNIs in patients with malignancies. Infections are still an important cause of morbidity and mortality in renal transplant recipients. Some immunosuppressive agents such as MMF increase the incidence of cytomegalovirus infection and the need for prophylactic measures in risk recipients. The use of potent immunosuppressive therapy has resulted in the appearance of BK virus nephropathy, which progresses to graft failure in a high percentage of patients. Although first associated with tacrolimus and MMF immunosuppression, recent data suggest that BK nephropathy appears with any kind of triple therapy. In conclusion, reducing risk factors for patient death should be a major target to improve outcomes after renal transplantation. Effort should be made to control cardiovascular diseases, malignancies and infections with improved use of immunosuppressive drugs. Preliminary results with belatacept suggest its safety and efficacy, and open new perspectives in the immunosuppression of de novo renal transplant recipients.

CYP3A5 genotype is associated with longer patient survival after kidney transplantation and long-term treatment with cyclosporine

The CYP3A5*1 allele has been linked to high expression of CYP3A5 and metabolism of cyclosporine. We evaluated the role of CYP3A5*1 for long-term survival in renal transplant patients in a cohort of 399 patients who underwent cadaveric or living donor kidney allograft transplantation. All patients were treated with a similar cyclosporine-based immunosuppressive maintenance therapy protocol. The mean duration of follow-up was 8.6+/-3.7 years. In univariate survival analysis, the presence of the CYP3A5*1 allele in recipients significantly increased patient survival P=0.028 (log-rank), resulting in a hazard ratio (HR) of 0.52 (95% CI=0.29-0.94). When the presence of the CYP3A5*1 allele was included in multivariate Cox regression analyses accounting for major risk factors for patient death, CYP3A5*1 still conferred a protective effect. Further, haplotype analysis at the CYP3A5 locus confirmed that CYP3A5*1 might indeed be responsible for this survival benefit.

Disease Progression and Outcomes in Type 1 Diabetic Kidney Transplant Recipients Based on Posttransplantation CKD Staging

Disease progression rates and outcomes per stage of kidney disease in kidney transplant recipients with type 1 diabetes mellitus are unknown. Single-center retrospective cohort study. 276 kidney transplant recipients with type 1 diabetes mellitus and a functioning graft at 1 year posttransplantation. Stage of chronic kidney disease at 1 year posttransplantation, donor source, and other clinical characteristics (covariates). Slope of creatinine clearance, weighted average slopes of creatinine clearance in a subgroup of 60 patients, death-censored allograft and patient survival rates. The median rate of creatinine clearance decrease after the first posttransplantation year was -1.6 mL/min/y (95% confidence interval [CI], -1.97 to -1.30) during a median follow-up of 8.4 years (95% CI, 8.13 to 8.84). The slope was significantly greater in stages 1 to 2 (-1.7 mL/min/y; 95% CI, -2.2 to -1.4) than stage 3 (-1.2 mL/min/y; 95% CI, -1.9 to -0.6; P = 0.0003). However, chronic kidney disease stage and donor source had no significant effect on death-censored allograft survival and patient survival rates. There were 23 deaths and 31 allograft losses in patients with stages 1 to 2 compared with 19 deaths and 18 allograft losses in those with stage 3. Univariate and multivariable Cox regression analyses showed that semiquantitative proteinuria of 1 or greater, mean arterial pressure, hematocrit of 33% or less, and calcineurin-inhibitor use were associated with decreased allograft survival, and age and hemoglobin A(1c) level of 7% or greater were significant risk factors for patient death regardless of donor type and stage of kidney function. Generalizability to other settings; study power. All forms of kidney transplantation in patients with type 1 diabetes mellitus progressed at similar rates regardless of chronic kidney disease stage at 1 year posttransplantation. Age, anemia, hemoglobin A(1c) level, proteinuria, hypertension, and calcineurin-inhibitor use were associated with decreased allograft and patient outcomes.

Impact of Carotid Atherosclerosis as Assessed by B-Mode Ultrasonography on the Evolution of Kidney Transplantation

Carotid arteriosclerosis is a marker of cardiovascular risk in the general population. Cardiovascular disease is highly prevalent in kidney transplant recipients. This study analyzed the impact of arteriosclerotic carotid lesions on the evolution of renal transplant recipients. Methods This prospective study was performed in 70 patients with renal transplantations (mean age 52 ± 12 years; 67% men ( n = 47). High-resolution B-mode ultrasonography (7.5 MHz) of both carotid arteries was performed at baseline to assess carotid caliber, mean and maximum intima-media thickness (IMT), presence of arteriosclerotic plaques (number and maximum height), and percentage stenosis. We analyzed the impact of carotid arteriosclerosis and various donor-recipient clinical covariables on long-term patient and graft survival. Results Mean follow-up was 9.7 ± 2.5 years (2–14). Atheroma plaques were detected in 74% of patients ( n = 52). The mean number of plaques was 3.96 ± 2.88 and maximum plaque height was 2.49 ± 0.97 mm. IMT was 0.71 ± 0.21 mm (0.4–1.5) with 27% of patients ( n = 19) having an IMT value greater than 0.8 mm. Sonographic signs of occlusion were evident in 13% ( n = 9) and the mean occlusion was 33 ± 11% (range 20%–45%). The presence of plaques was significantly associated with age ( P = .002), hypertension and diabetes ( P = .016), and hypercholesterolemia ( P = .01). There was an association between age and arterial wall thickness ( P = .042). Acute rejection was an independent risk factor for graft loss (OR 8.14, P = .003). The multivariate study identified carotid wall thickness as an independent risk factor for patient death (OR 12.7, P = .017). Conclusion Carotid arteriosclerosis is highly prevalent among renal transplant recipients. Carotid lesions were an independent risk factor for long-term patient death. High-resolution ultrasound imaging of the carotid arteries was a useful, noninvasive diagnostic technique for accurate assessment of cardiovascular risk in renal transplant recipients.

Post-Transplant Lymphoproliferative Disorders Occurring After Renal Transplantation in Adults: Report of 230 Cases From the French Registry

Post-transplant lymphoproliferative disorders (PTLD) are a rare but serious complication after organ transplantation. A French Registry of PTLD was set up in a nationwide population of kidney transplant recipients. We prospectively enrolled all adult kidney recipients developing PTLD between January 1, 1998, and December 31, 2003. We analyzed the incidence, risk and prognostic factors of PTLD by Kaplan-Meier and Cox analyses. Totally 230 cases of PTLD were referred to the French Registry. Cumulative incidence was 1.18% after 5 years. Older age (per year, AHR = 2.19, CI = 1.22-3.94) and recipient Epstein-Barr virus seronegativity (AHR = 3.01, CI = 1.57-5.08) were associated with an increased risk of PTLD. Patients with PTLD had a reduced survival rate (61% at 5 years). Graft PTLD had the best prognosis with an 81% survival rate after 5 years. Infection with hepatitis C or B virus (HCV or HBV), late-onset PTLD, multiple sites involvement and high Ann Arbor staging were risk factors for patient death. Use of azathioprine was associated with a poorer survival rate. PTLD incidence and risk factors in French recipients are in line with the international or American PTLD series. We highlighted the role of HBV or HCV in patient mortality and described the relevant prognosis factors for patients with post-transplant lymphoproliferations.

Effect of donor age on the outcome of living-related kidney transplantation

The study compared the results of kidney transplantation from living-related donors older and younger than 60 years. The 273 kidney graft recipients were divided into group 1 (115 recipients of older grafts) and group 2 (158 recipients of younger grafts). The frequency of acute rejection (AR) episodes was similar in both groups but slow graft function occurred more frequently in group 1. The frequency of chronic renal allograft dysfunction in the first post-transplant year was significantly higher in group 1 than in group 2. Patient and graft survival was significantly worse in group 1. Risk factors for graft loss were the difference between donor and recipient age and AR. Donor age and graft function were risk factors for patient death. Although kidneys from older donors provide a statistically poorer transplant outcome, they are clinically acceptable, especially when waiting time is prolonged and access to dialysis limited.

THE IMPACT OF HYPERLIPIDEMIA ON THE LONG-TERM OUTCOME OF RENAL TRANSPLANT RECIPIENTS.

653 PURPOSE OF THIS STUDY: We tried to clarify the effect of hyperlipidemia on the long-term outcome of renal transplantation. MATERIALS AND METHODS: Of 946 consecutive renal transplant recipients who underwent surgery at our institute between February, 1983, and October, 1996, 787 recipients treated with cyclosporine and with a functioning graft for more than one year, were included in this study. We assessed the effect of lipid levels at one year after renal transplantation for the long-term renal outcome. Cox proportional hazards model was employed to evaluate the effect of lipid levels after adjusting other potential risk factors. The median follow-up time was 9.0 years (range, 1.2-14.9 years). RESULTS: Serum levels of TG, TC, and high density lipoprotein-cholesterol (HDL-C) at one year after transplantation were 184±98 mg/dl (range, 31-777), 228±55 mg/dl (87-663), and 61±17 mg/dl (6-135), respectively. During the subsequent course of the observation, these lipid levels showed little change. 581 recipients (74%) were diagnosed with hypercholesteremia at one year after transplantation. Multivariate analyses showed that the TC level only was an independent risk factor for patient death, whereas TG and HDL-C were not. The hazard ratios for death were increased among the recipients with higher TC levels compared with the patients with normal (≤219 mg/dl) or moderately elevated levels (220-279 mg/dl), as follows: 220-297 mg/dl, 0.99; ≥ 280 mg/dl, 1.97. The hazard ratios for death caused by cardiovascular disease significantly increased among recipients with a higher TC, as follows: ≤219 mg/dl, 1.0, 220-279 mg/dl, 2.61; ≥280 mg/dl, 9.40. Although both TG and HDL-C had a significant effect on long-term survival, TC did not. Multivariate Cox proportional hazards model adjusted by covariates showed that TG and HDL-C were independent risk factors for graft failure. The hazard ratios for graft failure were increased among recipients with higher TG levels compared with the patients with normal (≤149 mg/dl) or moderately elevated levels (150-249 mg/dl), as follows: 150-249 mg/dl, 1.02; ≥250 mg/dl, 1.40. The hazard ratio for graft failure was decreased among the recipients with higher HDL-C levels compared with normal levels (<70 mg/dl), as follows: ≥71 mg/dl, 0.70. CONCLUSIONS: A higher TC level was the independent risk factor for patient death during the long-term follow up, whereas TG or HDL-C were not. Higher TG and lower HDL-C were independent risk factors for long-term graft survival, but TC was not.