The Kidney Donor Profile Index (KDPI) of marginal donors allocated by standardized pretransplant donor biopsy assessment: distribution and association with graft outcomes.

Pretransplant donor biopsy (PTDB)-based marginal donor allocation systems to single or dual renal transplantation could increase the use of organs with Kidney Donor Profile Index (KDPI) in the highest range (e.g. >80 or >90), whose discard rate approximates 50% in the United States. To test this hypothesis, we retrospectively calculated the KDPI and analyzed the outcomes of 442 marginal kidney transplants (340 single transplants: 278 with a PTDB Remuzzi score<4 [median KDPI: 87; interquartile range (IQR): 78-94] and 62 with a score=4 [median KDPI: 87; IQR: 76-93]; 102 dual transplants [median KDPI: 93; IQR: 86-96]) and 248 single standard transplant controls (median KDPI: 36; IQR: 18-51). PTDB-based allocation of marginal grafts led to a limited discard rate of 15% for kidneys with KDPI of 80-90 and of 37% for kidneys with a KDPI of 91-100. Although 1-year estimated GFRs were significantly lower in recipients of marginal kidneys (-9.3, -17.9 and -18.8 mL/min, for dual transplants, single kidneys with PTDB score<4 and =4, respectively; p<0.001), graft survival (median follow-up 3.3 years) was similar between marginal and standard kidney transplants (hazard ratio: 1.20 [95% confidence interval: 0.80-1.79; p=0.38]). In conclusion, PTDB-based allocation allows the safe transplantation of kidneys with KDPI in the highest range that may otherwise be discarded.

Family recurrence and oligo-anuria predict uremic restless legs syndrome.

OBJECTIVES: To determine clinical and laboratory predictors of restless legs syndrome (RLS) in patients with end-stage kidney disease (ESKD) undergoing long-term hemodialysis (HD). MATERIALS AND METHODS: One hundred and sixty-two consecutive patients were assessed. History of sleep disturbances, neurological examination, clinical, and laboratory data were collected. Patients with and without RLS were compared, and a logistic regression model described the relations between independent predictors and RLS. RESULTS: Fifty-one patients (32%) currently had RLS (RLS+). RLS+ vs RLS- patients were more frequently women (49% vs 29%, P = 0.012), had first-degree relative with RLS (22% vs 6%, P = 0.004), insomnia (59% vs 36%, P = 0.007), peripheral neuropathy (41% vs 21%, P = 0.006), and low residual diuresis (92% vs 68% with below 500 ml/24 h, P = 0.001). Low (OR = 8.71, CI = 2.27-33.41; P = 0.002) and absent (OR = 4.96, CI = 1.52-16.20; P = 0.008) residual diuresis, peripheral neuropathy (OR = 4.00, CI = 1.44-11.14; P = 0.008), and first-degree relative with RLS (OR = 3.82, CI = 1.21-12.13; P = 0.023) significantly predicted RLS in ESKD patients undergoing HD. CONCLUSION: Positive family history for RLS together with reduced/absent residual renal function and peripheral neuropathy predicts the risk for RLS in ESKD patients undergoing HD. Longitudinal studies are warranted to correlate RLS occurrence with genetic and environmental factors.

Physical performance in kidney transplanted patients: a study on desert trekking.

Physical performance of kidney transplanted patients in challenging environments, such as deserts, has been poorly studied. Six kidney transplanted (T: 5 males, 1 female; 45±6 yrs) and 8 control (C: 5 males, 3 females; 49±13 yrs) subjects participated in a 5-day desert trek. Blood pressure, hydration status (Height2/Rz by bioimpedance), heart rate, energy expenditure (by SenseWear Pro Armband) and walking velocities were recorded during each daily trekking stage (GPS-assisted wearable devices). Systo-diastolic blood pressure did not differ between C (119/77±12/8 mmHg) and T (121/77±10/6 mmHg) groups throughout the study. The hydration status was stable from day 1 (Ht2/Rz: 64±13 cm2/Ohm in T and 59±12 cm2/Ohm in C subjects) to day 5 (66±11 cm2/Ohm in T and 61±13 cm2/Ohm in C subjects) in both groups. Two patients on steroid treatment showed a relative hyperhydration. Mean heart rate did not differ between T (135±10 bpm) and C (136±5 bpm) subjects throughout the study, although a reduction from day 1 to day 5 was observed in T subjects only (p<0.05 vs C group). No differences were found between T and C group in walking velocity (1.7±0.6 km/h in T and 1.7±0.5 km/h in C group); mean intensity of physical activity was 3.4±0.5 METs in T and 3.3±0.6 METs in C group during each trekking stage. Negligible differences were observed in cardiovascular, metabolic and hydration status adaptations to desert trekking between selected T and C individuals. T subjects with creatinine clearance > 55 ml/min showed acceptable physical performance and acclimatization to desert environment, suggesting a good long-term outcome of transplantation.

A very early and acute renal impairment due to polyomavirus allograft nephropathy.

Polyomavirus-associated nephropathy (PVAN) has become an important cause of graft loss in the last few years. The typical course of PVAN is characterized by an asymptomatic period of viruria followed, within weeks, by the development of viremia in the context of stable renal function. The persistence of viral replication characterized by high viremia, leads to parenchymal injuries and causes the development, within months, of PVAN that could lead to deterioration in graft function and graft loss. We reported, in a patient who received a renal transplant, an unusual presentation of PVAN characterized by the development of acute renal failurte earlier than would be expected after transplantation, where the histological presentation alone could be confused with an acute rejection. We underline the importance of the association of histological findings with the viral load in urine and blood and with ancillary techniques such as immunohistochemistry and polymerase chain reaction (PCR) in situ for virus detection. We also want to emphasize that decoy cells and PCR for BK virus DNA research could be considered among the diagnostic tools for possible acute renal failure in kidney transplant.

A case of Paget's disease in hemodialysis.

Paget's disease is the second most common bone disease after osteoporosis and causes an excessive bone turnover. Moreover, chronic kidney failure causes an impairment of bone mineral metabolism and electrolytes and PTH homeostasis. As far as we know, this is the first reported case of Paget's disease in a hemodialysis patient: the patient was also affected by secondary hyperparathyroidism and was successfully treated with clodronate, cinacalcet and paracalcitol. The safety and efficacy of this combined therapy was periodically revised in a 12-month follow-up considering the common markers of bone turnover as well as the dosage of OPG, RANKL, IL-6 and MCSF, involved in the pathophysiology of Paget's disease.

The cardiovascular burden of end-stage renal disease patients.

Patients with end-stage renal disease are 10 to 20 times more at risk of cardiovascular death than the general population. Traditional cardiovascular risk factors are not able to explain the increase in the onset of cardiovascular diseases in dialysis patients. Some of the most important non traditional risk factors in uremic patients are: the inflammatory state of the patients, cytokines and growth factors, hyperhomocysteinemia, the presence of alterations of the calcium phosphorous product which can already be in progress when the glomerular filtration rate decreases to less than 60 mL/min. Clinically, these alterations cause vascular calcifications, calcifications of the heart valves and calcific uremic arteriolopathy or calciphylaxis. The pathogenesis of vascular calcification is complex and cannot be assigned to a simple, passive process: in fact, it includes factors which promote or inhibit calcification. In turn, these pathologic conditions have been found to be highly predictive of general and cardiovascular death. Given the serious clinical consequences that vascular calcifications can cause, it is necessary to carry out an early mapping of the traditional and non traditional risk factors of uremic patients as it seems that therapeutic interventions aimed at reducing or inverting the calcification process can improve the outcome of patients, above all when they are started quickly.

Pharmacokinetics for once- versus twice-daily tacrolimus formulations in de novo kidney transplantation: a randomized, open-label trial.

Tacrolimus, a cornerstone immunosuppressant, is widely available as a twice-daily formulation (Tacrolimus BID). A once-daily prolonged-release formulation (Tacrolimus QD) has been developed that may improve adherence and impart long-lasting graft protection. This study compared the pharmacokinetics (PK) of tacrolimus in de novo kidney transplant patients treated with Tacrolimus QD or Tacrolimus BID. A 6-week, open-label, randomized comparative study was conducted in centers in Europe and Australia. Eligible patients received Tacrolimus QD or Tacrolimus BID. PK profiles were obtained following the first tacrolimus dose (day 1), and twice under steady-state conditions. As secondary objectives, efficacy and safety parameters were also evaluated. Sixty-six patients completed all PK profiles (34 Tacrolimus QD, 32 Tacrolimus BID). Mean AUC(0-24) of tacrolimus on day 1 was approximately 30% lower for Tacrolimus QD than Tacrolimus BID (232 and 361 ng.h/mL, respectively), but was comparable by day 4. There was a good correlation and a similar relationship between AUC(0-24) and C(min) for both formulations. Efficacy and safety data were also comparable over the 6-week period. Tacrolimus QD can be administered once daily in the morning on the basis of the same systemic exposure and therapeutic drug monitoring concept as Tacrolimus BID.

[Clinical evaluation of living donor]. / La valutazione clinica del donatore vivente.

When possible, living donor transplantation represents the best therapeutic strategy for patients suffering from chronic renal failure. Studying the donor allows a complete and thorough clinical, laboratory and instrumental assessment that guarantees good organ function whilst protecting the health of the donor. The main parameters considered within this framework are age, renal function, nephrological complications, comorbidities (diabetes, hypertension, obesity, etc.), malignancies, and infection. Moreover, particular attention is paid to the sociopsychological aspects of the donation, particularly related to the donor, the recipient, and the entire family situation.

[When native arteriovenous fistula is not possible: the permanent catheter is better]. / Quando la fistola artero-venosa con vasi nativi non è possibile: è preferibile un catetere tunnellizzato.

Native arteriovenous fistula is still the vascular access of choice in hemodialysis. Other options are arteriovenous graft or, in patients in whom it is not possible to create a surgical vascular access, a permanent venous catheter. International guidelines on vascular access for hemodialysis recommend an increase in the percentage of arteriovenous fistulas compared to other types of vascular access. An analysis of the data relative to the distribution of the types of vascular access in different countries highlights the difficulty in following this recommendation: the only country to have increased the number of arteriovenous fistulas in recent years is the US, where the percentage of grafts has decreased while the use of permanent catheters has increased. In Italy and the rest of Europe, the number of fistulas has remained stable, there has been a constant reduction in the number of grafts and an increase in the percentage of permanent catheters. The reasons for this distribution of the types of vascular access are multifactorial and include the increased average age of patients, frequent late referrals, and increased incidence of diabetes mellitus, cardiovascular disease, obesity, etc. These factors have brought about technical difficulties for the creation of fistulas and grafts, leading to an increase in the number of catheters used. In relation to the evolution of the clinical characteristics of dialysis patients, the permanent catheter should no longer be considered a last-choice vascular access: in selected patients, it can be a better choice than a surgical fistula or graft.

[Expression of metanephric differentiation markers in human mesenchymal stem cells]. / Marker di differenziamento metanefrico espressi in cellule staminali mesenchimali umane.

Stem cells are a potential source for the regeneration of many tissues, including damaged kidneys. The present study describes the adoption of hyaluronic- butyric acid monoesters (HB) to induce expression of nephrogenic genes by mesenchymal cells isolated from human placental membranes. HB at a concentration of 1 mg/mL induces chromatin opening and increases the expression of the observed markers (cadherin 11, CD24, RAR-alpha, stearoyl-CoA desaturase 2, 14-3-3 0, Ewing sarcoma homolog.). These results open new routes toward cell regeneration after kidney injury.

[Factors determining cardiovascular disease progression after kidney transplant]. / I fattori di progressione della malattia cardiovascolare dopo trapianto renale.

Cardiovascular disease is the leading cause of mortality and morbidity in renal transplant recipients as well as the leading cause of death with a functioning graft. The high cardiovascular risk is attributable to the prolonged exposure to multiple traditional and nontraditional risk factors in the pretransplant and posttransplant period. Particular attention must be paid to cardiovascular screening of candidates for kidney transplantation. After a transplant, treatment and prevention strategies should be focused on the modifiable risk factors including smoking, dietary habits, physical activity, weight control, hypertension, and dyslipidemia. Further studies on these factors are needed to better define the pharmacological approaches (hypotensive or hypolipemic drugs) and therapeutic targets. In view of the role of immunosuppressive therapy in the onset or worsening of several risk factors, it is important to tailor the treatment approach and dosage to the cardiovascular risk profile of the individual patient.

[Preventing and reducing comorbidity in candidates for kidney transplantation for the improvement of post-operative results]. / Prevenire e ridurre le comorbilita' nei candidati al trapianto di rene per migliorare i risultati post-trapianto.

The correct and constant management of transplant waiting lists is necessary for the optimal utilization of the limited number of organs available for transplantation. The guidelines regarding placement on transplant waiting lists (absolute and relative contraindications) are well documented, even though they are in constant development. The criteria for the monitoring of patients on waiting lists, however, are not so well defined; this aspect is subject to careful evaluation on account of the widening of the criteria for transplantation suitability, the increase in the average age of patients, a rise in the number of enrolments and, as a result, prolonged waiting time (in Italy, the average time spent on a waiting list is 37 months). During the waiting period, a greater risk of clinically significant comorbidities and mortality, above all from cardiovascular events, has been noted (the annual mortality is 5-7% in the US, 1.3% in Italy). An in-depth clinical and instrumental study of patients with chronic renal failure is necessary when screening eligible candidates for transplant programs, individualizing therapeutic strategies, and identifying patients for whom the risks outweigh the potential benefits. Clinical and instrumental monitoring, as well as adequate treatment of comorbidities during the waiting period, can help improve the post-transplant outcome. This work examines the study algorithms and monitoring procedures for patients on kidney transplant waiting lists.

[Anti-HLA antibodies after bone graft and their impact on kidney transplant programs]. / Riscontri di anticorpi anti-HLA dopo trapianto di tessuto osseo. Impatto su programmi di trapianto di rene.

Immunological evaluation by panel reactive antibody (PRA) and determination of anti-HLA specificity is an important phase in the assessment of patients awaiting kidney transplant. The main causes of immunization are previous solid organ transplants, blood transfusions, and pregnancy; immunogenicity can also be triggered by vascularized tissue grafts. Immune induction by cryopreserved bone allografts is not yet fully understood. We report the case of a 19-year-old patient with osteosarcoma who underwent resection of the left proximal tibia with reconstruction using human bone in 1997 (donor typing: A3, A29 (19) - B44 (12), Bw4 - DR13 (6), DR7, DR52, DR53). The patient was subsequently placed on the waiting list for a cadaver donor kidney transplant because of chronic kidney failure caused by cisplatin toxicity. Pretransplant immunological screening using the CDC (complement dependent cytotoxicity) technique revealed a PRA of 63% and anti-A3 and anti-A68 antibodies. The presence of IgG antibody specificity against class I and class II donor antigens (specifically anti-A3, B44, DR7 antibodies) was highlighted using flow cytometry (Tepnel-Luminex). Further immunological studies using single HLA specificity analysis (LSA Class I - II - Tepnel-Luminex) detected direct antibodies against all donor antigen specificities. This is the first reported case of immune induction after a bone graft in a kidney transplant candidate. It underlines the importance of the availability of HLA typing data of all human allograft donors.

Hyperimmunized patients awaiting cadaveric kidney graft: is there a quick desensitization possible?

On all kidney waiting lists the 10% to 20% of patients who have antibodies against more than 80% of a panel of HLA antigens (panel reactive antibody [PRA] >80%) are difficult to transplant. The best solution for these patients is to find a compatible donor, ideally a full match, who yields a negative crossmatch test (CMX). If this is not possible, desensitization treatment (high-dose) intravenous immunoglobulin (IVIG) or plasmapheresis (PP) + low-dose IVIG is possible with good results in living donor kidney transplantation mainly if the antibody titer is low. It may also be offered to patients awaiting cadaveric donors too after a long waiting time; however, when applied for several months, it has the obvious disadvantage of giving the patient the risk for long-lasting immunologic weakness without the certitude of finding a kidney. In one of our recent cases of combined liver plus kidney transplantation, a positive CMX became negative 8 hours after the liver operation; the kidney was transplanted with a good result which lasted over 3 years. This observation suggested the possibility of a quick desensitization protocol in selected patients with a large (but not strong) immunization who probably are the majority. Patients sensitized to IVIG and with low titer PRA could be given a single PP + low-dose IVIG (what can be done within the time limit of cadaveric donor kidney transplantation) with good probability of turning an initial positive CMX to negative with the possibility of performing the operation and the advantage of giving the immunosuppression only when the kidney is present.

Mars and Prometheus: our clinical experience in acute chronic liver failure.

INTRODUCTION: In our clinical context, there are two groups that practice blood purification treatments on acute or chronic liver failure (AoCLF) patients: one group used MARS (molecular adsorbent recirculating system) and the other Prometheus. MATERIALS AND METHODS: The MARS group used the lack of response to standard medical treatment after 72 hours of observation as the access criterion. The Prometheus group used the access criteria of the multicenter Helios protocol for patients in AoCLF, as well as those with primary nonfunction (PNF) and secondary liver insufficiency. Both groups performed treatment sessions of at least 6 hours, which were repeated at least every 24 to 36 hours. RESULTS: The 56 treated AoCLF patients underwent 278 treatment sessions; 41 out of 191 procedures with MARS and 16 out of 87 procedures with prometheus, which was also applied in two cases in PNF and four in secondary liver insufficiency. The results showed that both systems accomplished a good purification efficiency and that application to patients enabled reinstatement on the transplant list and grafts in 70% of the cases with either method. CONCLUSION: Treatment led to recovery in dysfunction among patients not destined for transplantation, achieved with a 48.5% 3-month survival in the MARS group and 33.5% in the Prometheus groups. The treatment results were inversely proportional to the MELD at the time of entry; The treatment appeared to be pointless. Among PNF and secondary liver insufficiency cases.

Kidney transplantation combined with other organs in Bologna: an update.

BACKGROUND: We retrospectively reviewed our experience in combined liver-kidney (L-KT) and heart-kidney (H-KT) transplantations. PATIENTS AND METHODS: Between January 1997 and April 2007, we performed 25 L-KT and 5 H-KT. Patient mean age was 51+/-8 years in L-KT and 43+/-11 years in H-KT. The main cause of liver failure was chronic viral hepatitis (14 cases). Etiology of heart failure was dilated cardiomyopathy and hypertrophic cardiomyopathy (4 and 1 patients, respectively). The main causes of renal failure in L-KT were chronic glomerulonephritis (n=8) and polycystic disease (n=7). Etiology of renal failure in H-KT was interstitial nephropathy (n=2), vascular nephropathy (n=2), and chronic glomerulonephritis (n=1). RESULTS: Mean follow-up was 32+/-26 months in L-KT and 24+/-17 months in H-KT. Immunosuppression was cyclosporine-based (n=4) or tacrolimus-based (n=21) in L-KT and cyclosporine-based in H-KT. Acute rejection rate was 8% for both liver and kidney in L-KT; 80% (mild) for heart and 40% for kidney in H-KT. In the L-KT group, there was no primary graft nonfunction (PGNF). Two patients experienced liver delayed graft function (DGF); 1 patient required postoperative dialysis. One-year graft and patient survivals were both 84% and overall graft and patient survival was 76%. In the H-KT group, 3 patients needed postoperative dialysis and 1 required a cardiac assistance device for 48 hours; overall graft and patient survival was 100% with good cardiac and renal functions. CONCLUSION: Our experience confirmed that H-KT and L-KT are safe procedures, offering good long-term results.

Multicenter study on double kidney transplantation.

BACKGROUND: Marginal organs not suitable for single kidney transplantation are considered for double kidney transplantation (DKT). Herein we have reviewed short and long-term outcomes of DKT over a 7-year experience. PATIENTS AND METHODS: Between 2001 and 2007, 80 DKT were performed in the transplant centers of Bologna, Parma, and Modena, Italy. Recipient mean age was 61+/-5 years. The main indications were glomerular nephropathy (n=33) and hypertensive nephroangiosclerosis (n=14). Mean HLA A, B, and DR mismatches were 3.1+/-1.2. Donor mean age was 69+/-8 years and mean creatinine clearance was 75+/-27 mL/min. Almost all kidneys were perfused with Celsior solution. Mean cold ischemia time was 17+/-4 hours and mean warm ischemia time was 41+/-17 minutes. Mean biopsy score was 4.4. Immunosuppression was based on tacrolimus (n=52) or cyclosporine (n=26). RESULTS: Fifty (62.5%) patients displayed good postoperative renal function. Thirty (37.5%) experienced acute tubular necrosis and required postoperative dialysis treatment; 8 acute rejections occurred. Urinary complications were 13.7% with 8/11 requiring surgical revision. There were 6 surgical reexplorations: intestinal perforation (n=2), bleeding (n=3), and lymphocele (n=1). Two patients lost both grafts due to vascular and infectious complications at 7 or 58 days after transplantation. Two patients underwent intraoperative transplantectomy due to massive vascular thrombosis. Four (5%) patients underwent transplantectomy of a single graft due to vascular complications (n=2), bleeding (n=1), or infectious complications (n=1). Graft and patient survivals were 95% and 100% versus 93% and 97% at 3 versus 36 months, respectively. CONCLUSIONS: DKT is a safe approach for organ shortage. The score used in this study is useful to determine whether a kidney should be refused or accepted.

[Chronic allograft dysfunction: role of immunosuppressive treatment]. / Disfunzione cronica del trapianto renale (CAD): ruolo della terapia immunosoppressiva.

Renal transplantation is the treatment of choice for patients with end-stage renal disease. In recent years a major improvement has been observed in short-term graft survival, but there has been no corresponding improvement in long-term survival. Chronic allograft dysfunction (CAD) is an anatomical and clinical alteration that can lead to the loss of the transplanted organ without any specific cause. The pathogenesis of CAD, which still remains to be fully clarified, involves both immunological factors (acute rejection, subclincial rejection, HLA mismatches between donor and recipient, noncompliance, etc) and non-immunological factors (marginal donor ischemia/reperfusion injury, infection, cardiovascular risk factors, nephrotoxicity, etc). Immunosuppressive therapy represents one of the strategies for the prevention of CAD. The introduction into clinical practice of novel immunosuppressive agents with no or lower nephrotoxicity, like mycophenolate mofetile, rapamycin and everolimus, will make therapeutic strategies aimed at decreasing the incidence of CAD feasible.

Acute systemic, splanchnic and renal haemodynamic changes induced by molecular adsorbent recirculating system (MARS) treatment in patients with end-stage cirrhosis.

AIM: To evaluate the acute effect of treatment with the molecular adsorbent recirculating system (MARS) on splanchnic, renal and systemic haemodynamics in patients with end-stage cirrhosis. METHODS: Twelve patients with end-stage cirrhosis, undergoing MARS treatment, were enrolled. The following haemodynamic parameters were measured by means of Doppler ultrasonography and thoracic electrical bioimpedance, before and after each session: portal velocity, renal and splenic resistance indices, cardiac output, cardiac stroke volume, heart rate, mean arterial pressure, systemic vascular resistance. RESULTS: Median portal velocity increased significantly after treatment (23.7 vs. 20.3 cm/s, P < 0.05) while renal resistance index (0.72 vs. 0.75, P < 0.05) and splenic resistance index (0.60 vs. 0.65, P < 0.05) decreased significantly. Mean arterial pressure (83 vs. 81 mmHg, P < 0.05) and vascular resistance (899 vs. 749 dyne. s/cm5, P < 0.05) increased significantly, while cardiac output and stroke volume showed no significant changes. CONCLUSIONS: Data emerging from this investigation suggest that MARS treatment improves significantly various haemodynamic alterations in cirrhotic patients in the short term. The observed decrease in renal vascular resistance and improvement in splenic resistance index, a parameter related to portal resistance, which leads us to hypothesize that these haemodynamic effects are probably mediated by clearance of vasoactive substances during MARS treatment.

Metabolic syndrome after kidney transplantation.

BACKGROUND: Metabolic syndrome (MS) includes some risk factors for development of diabetes and cardiovascular disease, obesity (BMI > 30), high triglycerides, low HDL cholesterol, hypertension and impaired glucose tolerance. Following the definition of the Adult Treatment Panel III criteria, a diagnosis of MS was established when 3 or more factors were present. In renal transplant patients MS has been reported to negatively influence both patient and graft survivals. The present study sought to verify the effect of MS among our cases. METHODS: 298 cadaveric renal transplant recipients operated between January 1, 1996 and December 31, 2001 with absence of diabetes before transplantation, stable renal function 1 year posttransplantation and at least 4 years follow up were retrospectively evaluated from the end of the first post-operative year. RESULTS: 50 patients out of 298 (16,7%) had MS at the beginning of the study, including 37 of them with 3 and 13 with 4 risk factors. Only one patient with MS died of cardiovascular disease. Graft failure was observed in 23.5% MS patients versus 9,7% patients without the Syndrome (p:n.s.) Only Creatinine and the incidence of Cardiovascular Diseases at 4 years were statistically higher in MS patients (P < .001). CONCLUSIONS: These results suggested that MS is a risk factor for increasing CVD morbidity and decreased graft function, but early treatment of risk factors as soon as they become apparent can limit the adverse effects on patient and graft survival.