J.J. Villafruela

Influence of immunosuppression on the prevalence of cancer after kidney transplantation.

The prevalence of cancer in renal transplant patients is greater than in the general population. It is influenced by demographic and ethnic characteristics. We performed a retrospective study of 793 patients who received 872 kidney transplants at our center during 23 years. The age at transplantation was 41.4+/-14.0 years, the follow up 75.4+/-69.4 months. The cohorts include 203 patients treated with azathioprine-prednisone; 510, cyclosporine-based therapy; and 159, tacrolimus-based therapy. There were 95 patients (10.9%) who developed at least one neoplasm with 9 having more than one type of tumor. The incidence was of 17.3 cases per 1000 patients-years. Forty-four (46.3%) had skin cancer, 8 (8.4%) Kaposi sarcoma and 43 (45.3%) a non-skin cancer. Seven of eight patients with Kaposi sarcoma were on CsA therapy. The risk of developing a neoplasm at 5, 10, and 15 years was 8%, 17%, and 30% respectively. In a multivariate analysis, the risk factors associated with neoplastic diseases were older age (OR=1.061; 95% CI 1.039-1.084; P=.000), male sex (OR=2.658; 95% CI 1.536-4.599; P=.000), length of follow-up (OR=1.121; 95% CI 1.073-1.172; P =.000), and immunosuppression with CsA (OR=4.448; 95% CI 1.334-14.764; P=.015). Cancer was the cause of death in 26 patients, the fourth most common cause after cardiovascular disease, infection, and liver failure. We conclude that malignancies are an important cause of morbidity and mortality among transplant patients. Special attention must be devoted to older male patients with a long-term follow up to develop preventive and surveillance strategies.

Epidemiology of Symptomatic Hypotension in Hemodialysis: Is Cool Dialysate Beneficial for All Patients?

A prospective study on hypotension in hemodialysis was performed in 60 nondiabetic patients at two different dialysate temperatures during 12 months. A 37 degrees C bath (3,723 sessions) was used and after the first 6 months the temperature was changed to 35 degrees C (4,019 sessions). The prevalence of symptomatic hypotension was 15.3% and it was closely correlated with the presence of other symptoms. The most affected populations were women, patients over 55 years of age, patients with low body surface area and patients with a cardiovascular disease. A slight but significant decrease of symptomatic hypotension was seen by using a 35 degrees C dialysate (16.4 vs. 14.3%, p less than 0.01). In patients with frequent hypotension (in up to 30% of sessions), cool dialysate significantly reduced the incidence of the symptom (44.2 vs. 34.1%, p less than 0.001). These results were obtained in spite of a greater interdialysis weight gain at low temperature (2 +/- 0.6 vs. 1.9 +/- 0.7 kg, p less than 0.001). We consider that low-temperature dialysis is a simple, useful and economic procedure, especially for highly symptomatic patients. The association of cooling dialysate with higher sodium concentration, bicarbonate and special membranes could reduce dialysis symptoms dramatically.

Outcome of cadaveric renal transplant patients treated for 10 years with cyclosporine : Is chronic allograft nephropathy the major cause of late graft loss?

Background. The introduction of cyclosporine (CsA) has improved the short-term outcome of renal transplantation, but its effect on the long-term survival is not well known. Methods. We analyzed 128 cadaveric first renal transplant recipients with CsA and prednisone as basal immunosuppression followed for at least 10 years, and we have compared them with a group of 185 historical patients treated with azathioprine (Aza) and prednisone. Results. The 1-year graft survival was 83% in the CsA-treated patients and 68% in the Aza-treated patients (P <0.025), and the differences were significant for 3 years. Acute rejection accounted for the 10.9% of losses in CsA-treated patients and for 23.8% of losses in Aza-treated patients (P =0.046). Chronic allograft nephropathy was the cause of graft losses in 40.6% and 16.8% of cases (P =0.008). Patient survival at 5 years was 88% in CsA-treated patients and 79% in the Aza-treated patients (P <0.025). When analyzing the data of the 64 CsA-treated patients and the 84 Aza-treated patients with one functioning graft at 10 years, mean serum creatinine values were significantly higher in the CsA-treated patients at all time points but the increases were not significantly different. At 10 years, mean blood pressure was higher (P =0.002), and hypercholesterolemia (P =0.011) and hyperuricemia (P =0.000) were more prevalent in the CsA-treated patients. Conclusions. CsA resulted in a better short-time patient and graft survival that was not maintained in the long-term outcome. Chronic allograft nephropathy was the leading cause of graft loss in CsA-treated patients. Graft function was poorer in the CsA-treated patients, but its decline was similar in the two groups.

Evolution of Serum Erythropoietin after Androgen Administration to Hemodialysis Patients: A Prospective Study

A prospective study of the evolution of serum erythropoietin level after androgen therapy was carried out in a group of 25 male patients on chronic hemodialysis treatment with nonferropenic anemia (serum ferritin > 50 ng/ml). The androgen used was nandrolone decanoate (200 mg/week intramuscularly, for 6 months). There was an increase of serum erythropoietin, that reached statistical significance in the 2nd week of treatment (8.6 +/- 6.4 vs. 14.2 +/- 9.8 mIU/ml, p < 0.05), and a stabilization after 1 month (1 month: 17.8 +/- 11.2 mIU/ml, 6 months: 19.6 +/- 14.9 mIU/ml). The hemoglobin also experienced a parallel increase to that observed in serum erythropoietin (basal value: 8 +/- 0.9 g/dl; at 1 month postandrogen: 9.2 +/- 1.3 g/dl, p < 0.001; at 6 months: 10.7 +/- 1.8 g/dl, p < 0.001). According to their response of serum erythropoietin the patients were divided into responders (15 patients) and nonresponders (10 patients). There were no differences between them concerning age, basal levels of serum erythropoietin and hemoglobin, and dose of nandrolone decanoate in relation to body weight. The evolution of hemoglobin was similar in both groups, and a correlation between serum erythropoietin and hemoglobin was not observed in the responder group. Fourteen patients were studied after androgen was discontinued. The serum erythropoietin returned to basal levels 6 weeks after the last dose of nandrolone decanoate (7.7 +/- 5.4 mIU/ml). However, hemoglobin was above the basal levels 16 weeks after discontinuing androgen (9.5 +/- 1.1 g/dl, p < 0.05), with no differences between the responder and nonresponder group.(ABSTRACT TRUNCATED AT 250 WORDS)

Lumbar bone mineral density in renal transplant patients on neoral and tacrolimus: a four-year prospective study.

Background. This prospective study was designed to investigate the long-term evolution of bone mineral density (BMD) in kidney transplant recipients. Methods. In 86 patients with functioning grafts, 65 on tacrolimus-based immunosuppression and 21 on cyclosporine-based immunosuppression, laboratory parameters and BMD measurements in lumbar spine (L2–L4) and femoral neck (FN) were performed by DEXA in the first month after transplantation (baseline) and yearly thereafter up to the fourth year. Results. BMD did not change at 12 months in lumbar spine nor in the FN. Detailed analysis identified three patterns of BMD in lumbar spine at 12 months: BMD remained stable in 27 patients (31.4%), decreased >2% in 31 (36.0%) and increased >2% in 28 (32.6%). Patients with no change or gain presented a parallel increase of BMD in FN (P<0.001 in both groups). On multivariate analysis, the variables associated with no change or lumbar BMD loss were total prednisone dose in grams at 12 months (OR 1.402; 95% CI 1.038–1.893; P=0.028), calcitriol levels at 12 months (OR 0.936; 95% CI 0.892–0.982; P=0.007) and lumbar BMD at baseline (OR 1.006; 95% CI 1.002–1.010; P=0.002). Late treatment with calcium supplements and calcitriol did not improve osteopenia. Conclusions. One third of patients had bone loss mainly during the first year of follow-up. Bone loss was associated to higher baseline BMD, high steroid dose, and lower calcitriol levels at 1 year. Late administration of calcitriol and calcium supplements did not improve posttransplant osteopenia. More than 50% of patients were osteopenic 4 years after transplantation.

Chronic Increase of Bone Turnover Markers After Biliopancreatic Diversion is Related to Secondary Hyperparathyroidism and Weight Loss. Relation with Bone Mineral Density

BackgroundBiliopancreatic diversion (BPD) is the most effective bariatric procedure. Around 70% of these patients have secondary hyperparathyroidism (SH) in the long term as a consequence of calcium and vitamin D malabsorption. This work was aimed to study the influence of SH on bone turnover and its relationship with bone mineral density (BMD).MethodsBone turnover markers were determined in 63 BPD patients and 34 morbidly obese controls. In the BPD group, we also studied the influence of age, loss of weight, common channel length, PTH, vitamin D, and serum calcium on bone turnover as well as its relation with BMD.ResultsBPD patients showed significantly higher PTH, osteocalcin, and β-CTx levels than controls. In the multivariate regression analysis, only PTH (β = 0.42; P = 0.0002), menopausal status (β = 0.31; P = 0.007) and the percentage of lost BMI (β = −0.24; P = 0.03) significantly predicted the osteocalcin level (R2 = 0.33; F = 9.56; P < 0.0001). Similarly, only PTH (β = 0.39; P = 0.0005), menopausal status (β = 0.37; P = 0.001) and the percentage of lost BMI (β = −0.23; P = 0.04) significantly predicted the β-CTx level (R2 = 0.33; F = 9.82; P < 0.0001). Osteocalcin and β-CTx levels correlated negatively with BMD at lumbar spine (r = −0.38, P = 0.002 and r = −0.30, P = 0.02, respectively).ConclusionsChronic SH and the loss of weight determine a high rate of bone turnover that is associated with decreasing BMD in BPD patients.

Nonenzymatic Glycosylation of Hemoglobin and Total Plasmatic Proteins in End-Stage Renal Disease

In order to ascertain whether there are abnormalities of nonenzymatic glycosylation in uremia, the levels of nonenzymatically glycosylated hemoglobin (GHb), and total plasmatic glycosylated proteins (PGP) were studied using the thiobarbituric acid (TBA) method, a procedure not interfered with by carbamylation. Total hemoglobin A1 (HbA1) and the A1c fraction were also determined by ion exchange chromatographic methods. Sixty-six end-stage renal disease patients (29 nondiabetic and 8 diabetic uremic patients on conservative treatment, 29 nondiabetic hemodialysis patients) and 56 controls (32 nonuremic diabetic patients and 24 healthy controls) were studied. High levels of GHb and total PGP were found in the nondiabetic uremic group on conservative treatment with all the methods used, but the persistence of high chromatographically determined HbA1 levels in hemodialysis patients contrasts with the results obtained with the other techniques, which showed lower values on hemodialysis. Nondiabetic uremic patients with abnormal oral glucose tolerance curves had significantly higher levels of TBA-determined GHb and PGP. Uremic diabetic patients had the highest glycosylation levels of all the studied groups. We conclude that there is an abnormal nonenzymatic glycosylation of proteins in uremia, independent of carbamylation reactions and partially corrected by hemodialysis.

Influence of laparoscopic live donor nephrectomy in ischemia–reperfusion syndrome and renal function after kidney transplantation: an experimental study

The increase of intra-abdominal pressure during laparoscopic techniques provokes oliguria and reduction of the renal blood flow (RBF). The aim of this study is to evaluate this effect during living donor nephrectomy and its influence in the ischemia-reperfusion syndrome and renal function after kidney transplantation. Autotransplantation was performed using 22 pigs (15 after conventional open nephrectomy and 7 after laparoscopic nephrectomy). During donor nephrectomy a significant reduction in RBF was observed in the laparoscopic group (70 mL/min) vs the open group (260 mL/min) (P<.05). After a cold ischemia period of 24 hours an autotransplantation was performed. During the first hour after revascularization RBF was lower for the laparoscopic than for the open group: 60 vs 180 mL/s at 1 minute and 160 vs 400 mL/s at 60 minutes (P<.05). The decrease of creatinine was slower for the laparoscopic than for the open group during the first posttransplant week (2 vs 1.3 mg/dL on the first day and 1.4 vs 0.8 mg/dL on the seventh day posttransplant, respectively) (P<.05).

Renal transplant recipient outcome after losing the first graft

Renal transplantation is the optimal therapy for end-stage renal failure and considerable attention has been given to graft and patient survival and the effectiveness of immunosuppressive regimens. However, little attention has been given to outcome for patients who lose their grafts. We retrospectively reviewed the outcomes of the 793 first renal transplants performed at our institution between November 1979 and December 2001. A total of 348 patients lost their grafts, 116 by death with a functioning graft (33.3%) and 232 patients for other causes (66.7%). Eighty-six patients (37.1%) received a second transplant 3.5+/-2.4 years after returning to dialysis and the remainder continued on dialysis. Retransplanted patients were younger at the time of the first transplant (P=.000), and both time on dialysis (P=.012) and duration of graft function (P=.057) were shorter than for those remaining on dialysis. Therefore, retransplant patient survival at 1, 5, and 10 years was better than among those patients on dialysis not included on the waiting list (P<.001), but when compared with the relisted patients the survival rate was almost identical (96%, 85%, and 67% vs 97%, 82%, and 67%; P=NS). Almost 40% of patients who lost their first grafts were retransplanted. We did not observe differences in patient survival between retransplant and relisted patients. Because the number of cases is limited, our results need to be confirmed by larger series.

Are low levels of 25-hydroxyvitamin D a risk factor for cardiovascular diseases or malignancies in renal transplantation?

BACKGROUND Observational studies in healthy people suggest an inverse relationship between 25-hydroxy-vitamin D (25(OH)D levels) and cardiovascular diseases and malignancies. We performed an observational prospective study in renal transplant recipients to investigate the effects of vitamin D deficiency on cardiovascular and malignancy risks. METHODS From 389 renal transplant recipients, 331 with a functioning graft at 12 months were included in the study. Mineral metabolism parameters were measured at 1, 3, 4 and 12 months. Information regarding the cardiovascular events and malignancies were collected from an electronic database. RESULTS According to the 1-year mean of 25(OH)D levels, 75 recipients (22.7%) had a normal vitamin D status, 161 (48.6%) had insufficiency and 95 (28.7%) had deficiency in vitamin D levels. During the follow-up, 80 recipients presented at least one cardiovascular event. The total cardiovascular diseases included: 27 patients with coronary diseases, 25 with cardiac failure, 18 with arrhythmia, 11 with acute cerebrovascular events and 19 with peripheral vascular disease. Cardiovascular events were not associated with 25(OH)D levels or vitamin D status, and the 10-year cumulative incidence was 29.3% for normal vitamin D status and 31.6% for insufficiency and 51.9% for deficiency (P = 0.216). Furthermore, Cox univariate analysis showed no association between cardiovascular events and vitamin D levels or vitamin D status. In addition, 53 recipients presented at least one malignancy: 33 non-melanoma skin malignancies and 20 non-skin malignancies (5 prostate, 3 kidney and urinary tract, 2 colon, 2 lung, 2 lymphoma, 2 breast and 4 from other locations). The cumulative incidence of malignancies was 21.3% for normal vitamin D status, 22.7% for insufficiency and 16.7% for deficiency (P = 0.818). CONCLUSIONS Our data suggested that low vitamin D levels were not associated with an increased risk of cardiovascular diseases or malignancies. However, due to the small number of patients and events, the results should not be considered as definitive. Additional studies with a higher number of patients are required to elucidate the true impact of vitamin D status on cardiovascular and malignancy risks.