Giuseppe Montagnino

Risk factors for late kidney allograft failure

BACKGROUNDnWhile graft survival rates in the short term have improved dramatically, only a modest improvement has been shown in long-term graft survival rates. We evaluated the causes of late failure in renal allograft recipients treated with cyclosporine A (CsA).nnnMETHODSnA total of 864 adults with a functioning graft at one year were evaluated. The end points were dialysis or death with a functioning graft.nnnRESULTSnThe 13-year patient and graft survival probabilities were 0.82 and 0.64, respectively. The graft half-life was 20.1 years and the pure graft half-life was 31.1 years. At multivariate analysis, plasma creatinine at one year (P = 0.0006; RR 1.72), low-density lipoproteins (LDL) at one year (P = 0.0014; RR 1.65), older age (P = 0.0128; RR 1.50) and delayed graft function (P = 0.0350; RR 1.45) were associated with the end point. Chronic allograft nephropathy was the cause of failure in 97 patients, death in 70, recurrence of glomerulonephritis in 24, other events in 6. Cardiovascular complications were the most frequent cause of death. Post-transplant cardiovascular events were associated with: pre-transplant cardiovascular events (P = 0.0012; RR 2.65), older age (P = 0.0001; RR 2.46), pre-transplant arterial hypertension (P = 0.0249; RR 1.57), smoking (P = 0.0235; RR 1.29), duration of dialysis (P = 0.0229; RR 1.28). Mean serum cholesterol, LDL and triglycerides were each significantly associated post-transplant cardiovascular events.nnnCONCLUSIONSnThe graft half-life was 20 years. Chronic allograft nephropathy was the leading cause of late failure, followed by death. If the data were censored by death, the projected pure graft half-life would be 31.1 years. Pre-transplant selection and preparation of the candidate as well as appropriate life style are recommended to improve life expectancy and extend graft survival.

Cutaneous Lesions in 67 Cyclosporin-Treated Renal Transplant Recipients

Sixty-seven out of 100 kidney transplant recipients treated with cyclosporin and methylprednisolone were evaluated for the presence of dermatological manifestations. Only 2 patients had no dermatological lesions; 80% had iatrogenic lesions, 38% infectious, 13% miscellaneous, 3% cancerous lesions, while 28% had cutaneous manifestations related to previous uremic state. Most of the lesions concerned the pilosebaceous unit: hypertrichosis (60%), epidermal cysts (28%), pilar keratosis (21%), acne (15%), folliculitis (12%) and sebaceous hyperplasia (10%). Among infectious manifestations, viral lesions were the most frequent and were very severe in the first month after transplantation. Two patients developed a squamous-cell epithelioma and a probable cutaneous lymphoma, respectively.

Risk factors for cardiovascular events after successful renal transplantation

Background. Cardiovascular disease is a frequent cause of morbidity after renal transplantation. The aims of this study were to evaluate the incidence of cardiovascular events and to identify the main risk factors for cardiovascular complications and mortality in 2071 white adults with a renal transplant functioning for at least 1 year. Methods. Clinical events, routine biochemistry, and prescribed drugs at month 1, month 6, and yearly after transplantation were analyzed. Results. The incidence of cardiovascular events increased over time. At 15 years after transplantation, only 47% of surviving patients had not experienced any cardiovascular event. Risk factors associated with cardiovascular complications were male gender (P=0.04), age (P<0.0001), arterial hypertension before transplantation (P<0.0001), longer pretransplant dialysis (P<0.0001), cardiovascular event before transplantation (P<0.0001), older era of transplantation (P=0.0009), center-specific effect (P=0.003), posttransplant diabetes mellitus (P=0.01), increased pulse pressure after transplantation (P=0.02), intake of corticosteroids (P=0.016), intake of azathioprine (P=0.016), lower serum albumin after transplantation (P=0.004), and higher serum triglyceride levels after transplantation (P=0.007). The risk of death was increased in patients with low or elevated hematocrit, while it was minimal with values around 38%. Conclusions. The occurrence of fatal and nonfatal cardiovascular events after successful renal transplantation not only relates to baseline cardiovascular risk factors present at transplantation, but also to immunosuppressive drugs and posttransplantation traditional and nontraditional risk factors.

Effects Of Three Immunosuppressive Regimens On Vertebral Bone Density In Renal Transplant Recipients: A Prospective Study

The influence of three different immunosuppressive regimens with cyclosporine (CsA) on the development of osteopenia in renal transplant patients was assessed. Fifty-three adults with first kidney transplants participated in a randomized trial to analyze the efficacy of three different immunosuppressive regimens: CsA alone (group 1), CsA plus steroids (group 2), and CsA plus steroids plus azathioprine (group 3). Lumbar spine bone mineral density was assessed by dual energy x-ray absorptiometry every 6 months for 18 months. The values for trabecular mass were expressed as bone mineral density and as a fraction of the standard deviation of the mean of the normal value for patients sex and decade of age (Z-score). Statistical analysis was performed on Z-score and Z-score change (value after 6 months minus the basal value at transplantation). At the 18th month, the Z-score increased significantly in treatment group 1 without steroids (P=0.006) and decreased significantly in steroid-treated groups 2 (P<0.001) and 3 (P<0.001). Comparing the two genders, Z-score decreased less in premenopausal women than in men (P=0.018). Z-score change did not correlate with steroid dosage, was high in patients with high basal bone mineral density, and was directly associated with the duration of dialysis (P=0.008). In conclusion, premenopausal transplant recipients showed a lower decrease of lumbar bone mineral density than men. In transplant recipients given CsA with steroids, lumbar bone mineral density decreased significantly, while it increased significantly in patients given CsA alone.

Cutaneous abnormalities in uremic patients

94 uremic patients, 68 on regular hemodialysis treatment (RHT) and 26 on chronic ambulatory peritoneal dialysis (CAPD), were followed for up to 20 months in search of dermatological manifestations. 79% of RHT and 76% of CAPD patients had some kind of cutaneous lesion. The most characteristic features of cutaneous involvement in RHT and CAPD patients were: cutaneous xerosis, pruritus, infectious manifestations and disorders of pigmentation. In 4 RHT patients, precancerous and cancerous manifestations were also observed.

Clinical Features and Course of Kaposi’s Sarcoma in Kidney Transplant Patients: Report of 13 Cases

We retrospectively evaluated the prevalence of Kaposis sarcoma (KS) in 820 kidney transplant recipients with a follow-up period of at least 6 months. Thirteen patients developed a KS (1.6%): 2 were under conventional therapy and 11 under ciclosporin A. The onset of KS was 38.7 +/- 38.3 (range 6-124) months after transplantation in the whole population and after 33.9 +/- 19.7 months in the patients treated with ciclosporin A only. Nine were men and 4 women (male/female ratio: 2.25:1). The mean age at KS occurrence was 36.8 +/- 11.1 years. The mean follow-up period since KS diagnosis was 35.9 +/- 19.5 months. Clinical manifestation and severity of KS were heterogeneous: 5 patients had a KS with cutaneous involvement only, 8 patients a KS with multiple skin and mucosal and/or visceral lesions. Only 2 patients from the second group died of peritonitis due to intestinal lesions. In these 2 patients, immunosuppressive therapy had either been increased or reintroduced after a partial regression of KS. In all other patients, therapy was promptly reduced or withdrawn. In 1 patient local radiation therapy plus intralesional bleomycin administration were started and 1 patient received intralesional vincristine. Nine patients had a complete and 2 a partial remission of lesions. After therapy reduction, 4 patients lost their kidney (these patients however, had an already ongoing chronic rejection at KS diagnosis), in 2 there was an improvement of graft function, and in the other patients it remained stable. Our experience confirms that in most cases reduction or withdrawal of immunosuppression halts the evolution of both cutaneous and visceral lesions, without compromising graft function.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypertension After Renal Transplantation

In 212 cyclosporine-treated renal transplant recipients with stable graft function at 1 year and with potential follow-up of 5 years the prevalence of arterial hypertension was 81.6% at 1 year and 81.2% at 5 years. The logistic regression analysis showed that the presence of hypertension before transplantation (P = 0.0001; odds ratio 3.5), a plasma creatinine level higher than 2 mg/dL at 1 year (P = 0.0001; odds ratio 3.8), and a maintenance therapy with corticosteroids (P = 0.008; odds ratio 3.3) were positively associated with hypertension at 1 year after transplantation. The mean number of graft failures between 1 and 5 years was significantly higher and the mean reciprocal of plasma creatinine was significantly worse at 1 and 5 years in patients with noncontrolled hypertension than in normotensive patients or in patients with hypertension well controlled by drugs. We also investigated the potential protective role of nifedipine. The episodes of acute tubular necrosis (four versus three), of acute rejections (28 versus 29), the mean arterial pressure at 1 year (105 +/- 9 versus 104 +/- 9 mm Hg) and 5 years (105 +/- 10 versus 108 +/- 12 mm Hg), and the mean plasma creatinine level at 1 year (1.4 +/- 0.4 versus 1.6 +/- 0.4 mg/dL) and 5 years (1.8 +/- 1 versus 1.9 +/- 1 mg/dL) were similar in 52 patients who were given nifedipine for at least 4 years and 58 hypertensive patients who never took calcium channel blockers.(ABSTRACT TRUNCATED AT 250 WORDS)

Natural history of hepatitis B and C in renal allograft recipients.

Background. In renal allograft recipients, most cases of liver dysfunction are caused by hepatitis B virus and hepatitis C virus (HCV). The natural history of hepatitis C and B was studied in 286 renal allograft recipients who received a kidney allograft between 1972 and 1989 when tests for anti-HCV became available. Methods. In all patients, hepatitis B (HB) surface (s) antigen (Ag) was tested before and anti-HCV (by enzyme-linked immunosorbent assay II) after transplantation. Results. At enrollment in 1989 (5.5±4 years after transplantation), 209 patients were anti-HCV positive (C+), 42 patients were HBsAg-positive (B+), and 35 patients were both B+ and C+ (C+B+). One hundred four patients were receiving azathioprine (AZA) and 182 were on cyclosporine A (CsA). Since transplantation, the median follow-up was 18 years in AZA-treated and 13 years in CsA-treated patients. Liver biopsy showed chronic hepatitis in 73 patients, cirrhosis in 20 patients, and fibrosing cholestatic hepatitis in 2 patients. In 34 patients, liver biopsy was repeated, and progression of fibrosis was observed in 24 patients. The 12-year patient survival rate was similar in B+, C+, and B+C+ patients (67%, 78%, and 71%, respectively; P=not significant). Liver-related death was the first cause of death in B+ and B+C+ infected patients (58% and 72%, respectively), whereas cardiovascular disease was the leading cause of death in C+ patients (40%). Multivariate analysis showed that older age (>40 years) (relative risk [RR], 2.8), B+ status (RR, 2.36), and C+ status (RR, 1.65) were independently associated with a worse patient survival. Conclusions. In the long term, B+ patients had a higher risk of death related to liver disease than C+ patients, and co-infection did not worsen patient survival.

Incidence of cancer after kidney transplant: Results from the north italy transplant program

Background. Patients undergoing kidney transplantation demonstrate a higher risk of developing cancer as the result of immunosuppressive treatment and concurrent infections. Methods. The incidence of cancer in a cohort of patients who underwent kidney transplantation between 1990 and 2000, and who survived the acute phase (10 days), was analyzed as part of the North Italy Transplant program. Results. A total of 3,521 patients underwent transplantation during a 10-year period in 10 of 13 participating centers; the length of follow-up after kidney transplant was 67.7±36.0 months. During the follow-up, 172 patients developed cancer (39 with Kaposi sarcoma, 38 with lymphoproliferative diseases, and 95 with carcinomas [17 kidney, 11 non-basal cell carcinoma of the skin, 10 colorectal, 8 breast, 7 gastric, 7 lung, 6 bladder, and 3 mesothelioma]). The average time to cancer development after transplant was 40.1±33.4 months (range 0–134 months). Twenty-four patients developed cancer within 6 months from the transplant (10 with carcinomas, 7 with Kaposi sarcoma, and 7 with lymphoproliferative diseases). Three patients demonstrated a second primary cancer. The average cancer incidence was 4.9%. The incidence of cancer was 0.01 per year. Independent determinants of cancer development were age, gender, and immunosuppressive protocol including induction. Ten-year mortality was significantly higher in patients with cancer (33.1%) than among patients without cancer (5.3%). The relative risk of death in subjects with cancer was 5.5 (confidence interval 4.1–7.4). Conclusions. These preliminary data underline the importance of long-term surveillance of transplant recipients, choice of immunosuppressive treatment, and careful donor selection.

The recurrence of focal segmental glomerulosclerosis in kidney transplant patients treated with cyclosporine

To evaluate the rate of recurrence of focal segmental glomerulosclerosis (FSGS) in renal transplant patients treated with cyclosporine, we reviewed the outcome of 25 renal Tx performed in 24 patients who had FSGS as their original renal disease. After Tx, 6 patients were treated with steroids and azathioprine (follow-up: 42 +/- 34 months) and 19 with CsA (follow-up: 30 +/- 31 months). Two of 6 Aza treated patients (33%) developed recurrence of FSGS and nephrotic syndrome (NS). Both patients lost their graft because of FSGS 24 and 25 months after Tx. Ten of 19 patients (55%) given CsA showed recurrence of FSGS; one of them had had recurrence in the first graft treated with Aza. One patient lost his graft a few weeks after Tx because of acute rejection and 3 lost their graft because of FSGS 4-28 months after NS developed. One patient with NS died from pneumonia 14 months after Tx when his plasma creatinine was 2.7 mg/dl. Three other patients now have NS and plasma creatinine between 1.9 and 2.4 mg/dl 15-37 months after Tx. The last two patients have NS and normal renal function 10 and 31 months after Tx. In both groups, most patients developed NS within the first week after Tx. The patients with recurrence, given Aza or CsA, tended to be younger at the onset of the disease and to have a shorter duration of the disease, when compared with those without recurrence, but the differences were not statistically significant. In our experience neither CsA nor Aza showed any effect on the outcome of FSGS recurring in the graft.