Survival Benefit From Kidney Transplantation Using Kidneys From Deceased Donors Aged ≥75 Years: A Time-Dependent Analysis.

Patients with end-stage renal disease have longer survival after kidney transplantation than they would by remaining on dialysis; however, outcome with kidneys from donors aged ≥75 years and the survival of recipients of these organs compared with their dialysis counterparts with the same probability of obtaining an organ is unknown. In a longitudinal mortality study, 2040 patients on dialysis were placed on a waiting list, and 389 of them received a first transplant from a deceased donor aged ≥75 years. The adjusted risk of death and survival were calculated by non-proportional hazards analysis with being transplanted as a time-dependent effect. Projected years of life since placement on the waiting list was almost twofold higher for transplanted patients. Nonproportional adjusted risk of death after transplantation was 0.44 (95% confidence interval [CI] 0.61-0.32; p < 0.001) in comparison with those that remained on dialysis. Stratifying by age, adjusted hazard ratios for death were 0.17 (95% CI 0.47-0.06; p = 0.001) for those aged <65 years, 0.56 (95% CI 0.92-0.34; p = 0.022) for those aged 65-69 years and 0.82 (95% CI 1.28-0.52; p = 0.389) for those aged ≥70 years. Although kidney transplantation from elderly deceased donors is associated with reduced graft survival, transplanted patients have lower mortality than those remaining on dialysis.

Endothelial progenitor cells are reduced in refractory hypertension.

Circulating endothelial progenitor cells (EPCs) play a key role in the maintenance of endothelial homoeostasis and promote vascular repair. They may also be of predictive value for cardiovascular events. Reduced EPC number and functional activity have been associated with several cardiovascular risk factors, but their relationship with hypertension remains unclear. The objective of this study was to investigate if number and function of circulating EPCs are reduced in patients with refractory hypertension (RHT). Circulating EPCs (CD34+ CD133+/CD45+) were isolated from peripheral blood by flow cytometry in 39 RHT and 30 normotensive controls. EPC number was also determined in vitro after 7 days in culture. After age adjustment, EPC concentration was significantly reduced in RHT as compared with controls (mean (95% CI), 33.8 (18.1-49.6) vs 69.1 (50.7-87.5) EPCs per 10(5) peripheral mononuclear cells (MNCs), respectively; P=0.014). After in vitro culture, EPCs were also reduced in patients as compared with controls (mean (95% CI), 142.3 (49.5-235.0) vs 611.0 (480.2-741.8) EPCs per field, respectively, P<0.001). In multiple linear regression analysis, circulating EPCs were significantly reduced by 56.3% in RHT as compared with control (P=0.006), independently of all other known risk factors. Moreover, RHT had a high independent predictive value for lower EPC proliferation. The number of EPCs per field was reduced by 76.7% in RHT with respect to controls (P<0.001). In summary, the number of circulating EPCs after culture is reduced in patients with RHT, which may be related to the increased rate of endothelial dysfunction, atherosclerotic disease and cardiovascular events observed in this population.

Phospholipases A1 and A2 in subcellular fractions and plasma membranes of Krebs II ascites cells.

A method is described for the localization and characterization of phospholipases A1 and A2 (EC3.1.1.4) in Krebs II ascites cells, particularly in the plasma membranes. Cells were lysed with a Dounce homogenizer in an isotonic sucrose medium. Plasma membranes sediment with mitochondria and lysosomes during subcellular fractionation and are finally isolated on a continuous sucrose gradient. The membranes are localized at two levels in the gradient, at densities of 1.06 and 1.15, in which 5'-nucleotidase (EC 3.1.3.5) activity exhibits a 9- and 21-fold purification, respectively. Total contamination by endoplasmic reticulum, lysosomes, and mitochondria is 17 percent for the low-density membrane fraction and 25 percent for the high-density fraction. The phospholipases A present in Krebs II cells are active at pH 4.0 and pH 7.5. At the 2 pH values, they have A1 and A2 specificities. The intracellular distribution of acidic forms is comparable to that of acid phosphatase (EC 3.1.3.1), while neutral forms are localized like lactate dehydrogenase (EC 1.1.1.27). A small proportion of neutral phospholipase A2 has the same repartition on the sucrose gradient as nicotinamide adenine dinucleotide diaphorase (EF 1.6.4.3), an endoplasmic reticulum marker, and as 5'-nucleotidase, a plasma membrane marker.

Interaction of DNA with lysine-rich polypeptides and proteins. The influence of polypeptide composition and secondary structure.

Using X-ray diffraction we have studied fibres obtained from complexes of DNA with lysine-rich polypeptides and with proteins that have different conformations, to ascertain whether the conformations of the polypeptides and the DNA are maintained upon interaction. Substances investigated include N-acetyl-Lys-Ala-Tyr-Ala-Lys-ethylamide, random poly(Leu50, Lys50), sequential poly(Leu-Lys), poly(Val-Lys), poly(Ala-Lys), poly(Lys-Ala-Ala-Lys), poly(Lys-Ala-Ala), poly(Lys-Leu-Ala), poly(Lys-Ala-Gly), protein phi 0 from sea cucumber spermatozoa, histone H1 and two fragments of this protein obtained by chemical cleavage. In general, the B form of DNA with ten base-pairs per helical turn is maintained upon interaction at high levels of humidity. The A form is never observed; it appears to be forbidden in a protein environment. No evidence for transition into any novel DNA conformation has been observed, although the B form is altered in some cases, in particular upon dehydration. Such alteration occurs always in the sense of tightening the double helix, so that the number of base-pairs per helical turn diminishes. The polypeptides may interact with DNA in both the alpha and beta conformations. We have found different types of complexes in which either a monolayer or a double layer of beta-pleated sheets is intercalated between layers of DNA molecules. Alternatively, the polypeptide chain may be wrapped around the DNA, following one of the grooves. The polypeptide conformation may be either maintained or changed upon interaction. The charge density of the polypeptide is an important parameter of the interaction. When it matches the charge density of the DNA, the polypeptide conformation is maintained in most cases; otherwise it is modified. The globular part of histone H1 gives a unique X-ray pattern upon interaction, indicative of a loss of order of DNA in the complex. On the other hand, the C-terminal part of histone H1 gives a very well-ordered complex, similar to a nucleoprotamine, in spite of its lower charge density.

Recurrence of IgA nephropathy and Henoch-Schönlein purpura after kidney transplantation: risk factors and graft survival.

BACKGROUND: IgA nephropathy (IgA) is one of the most common glomerulonephritis. Renal transplantation is the treatment of choice for patients with ESRD due to any kind of glomerulopathy, including IgA and Henoch-Schönlein purpura nephritis (H-SP), but original disease recurrence is now the third most frequent cause of allograft loss. METHODS: Eighty-seven cases of glomerulonephritis as the original disease were divided in two groups: group A--37 affected with 31 IgA and 6 H-SP; and group B--50 with other glomerulopathies. We compared patient and graft survivals at 5 years. To assess the presence of IgA or H-SP recurrence in group A patients, we performed an allograft biopsy in the presence of microhematuria, proteinuria, or an increased plasma creatinine. Known risk factors influencing recurrence rate were also analyzed. RESULTS: Five-year patient (97% vs 95%) and graft survivals (81% vs 78%) were not significantly different between groups A and B. Patients with crescentic glomerulonephritis (CGN) at the moment of diagnosis of IgA or H-SP showed a 5-year graft survival of 71% in contrast with 100% graft survival among those with mesangial or focal and segmental glomerulosclerosis pattern (P = .03). Histological recurrence was diagnosed in eight patients: six IgA and two H-SP. Women (P = .013) and a good HLA match (P = .029) were significantly associated with the risk of recurrence. CONCLUSIONS: When compared with other glomerulonephritis patients, with IgA or S-HP showed similar 5-year graft and patient survivals. Nevertheless, graft survival was shorter among patients with crescentic glomerulonephritis at the moment of diagnosis. Thus, the disease prognosis after grafting may be linked to the initial histological aggressiveness. Women and those patients transplanted with a good HLA match were prone to develop disease recurrence with a tendency toward a lower 5-year graft survival.

Mycobacterial infections in renal transplant recipients. Seven cases and a review of the literature.

During an 11-year period, 1,069 patients received renal allografts at the University of Minnesota Hospital, Minneapolis, and infections developed in seven (0.65%) due to mycobacteria (Mycobacterium tuberculosis and M kansasii). The primary infection was in joint or subcutaneous tissue in six patients and pulmonary (miliary) in one. Infections in joint or skin shared common features regardless of the species of Mycobacterium and usually mimicked acute pyogenic bacterial infection; all responded to antimycobacterial drugs. The clinical manifestations in our patient in miliary tuberculosis were compared with those of 19 other patients described in the literature. Although their systemic manifestations were more severe, the symptoms were often ill-defined and the diagnosis overlooked. Five of these 20 patients (25%) died of uncontrolled infection.

The in vivo and in vitro effect of 15-deoxyspergualin on pancreatic islet function.

15-deoxyspergualin (DSG) is a novel immunosuppressive agent that has been shown to prolong the function of islet allografts in both small and large animal models. The purpose of this study was to investigate the effect of DSG on in vitro glucose-induced insulin secretion by isolated islets and on glucose disposal in vivo. Incubation of human or rat islets for 24 hr in the presence of DSG (1, 2, 5 or 10 micrograms/ml) did not effect their secretory capacity. In addition, glucose disposal and insulin secretion by normal rats was unaffected by the daily administration of DSG (1, 4, or 10 mg/kg) for 1 week. In contrast to cyclosporine, prednisone, and FK506, DSG does not appear to be associated with altered beta cell function or disordered glucose disposal and is an attractive alternative with potential usefulness in clinical islet allo-transplantation.

Total pancreatectomy in the pig for islet transplantation. Technical alternatives.

Pigs appear to be a suitable biological and logistical animal donor of islets for xenotransplantation in human diabetic type I recipients. To improve the islet isolation technique in this species, to evaluate the islet function in vivo, and to assess the toxic effects of various immunosuppressive regiments on transplanted islets will necessitate a model of the pancreatectomized pig suitable for islet autotransplantation. We describe three techniques of total pancreatectomy in pigs. The first removed the pancreas in order to study postoperative management and pig survival; no attempt was made to preserve the pancreas for islet isolation. The second consisted of a pancreatectomy in a surviving pig, with careful preservation of the whole pancreas for subsequent islet isolation. The third was rapid en bloc procurement of the pancreas and duodenum, to obtain a pancreas solely for the purpose of islet isolation. We conclude that pigs tolerate and survive a total pancreatectomy--they are suitable animals for islet isolation and possible autotransplantation. The result of islet isolation does not appear related to the pancreas procurement technique; however, the islet yield must be improved before autotransplantation can be functionally successful.

Reflex sympathetic dystrophy syndrome of the lower limbs in a renal transplant patient treated with tacrolimus.

BACKGROUND: Recently, a previously unrecognized posttransplant syndrome known as reflex sympathetic dystrophy syndrome of the lower limbs has emerged in patients receiving cyclosporine as immunosuppression. We describe herein this complication observed in a patient treated with tacrolimus after kidney transplantation. METHODS: A 49-year-old man received a kidney transplant from a cadaver donor and was treated with tacrolimus. Three months later, the patient complained of severe pain in the lower limbs that affected both knees and ankles. Bone scintigraphy and magnetic resonance were consistent with reflex sympathetic dystrophy syndrome. RESULTS: Laboratory tests that included creatinine, glomerular filtration rate, calcium, phosphate, urate, alkaline phosphatase, and parathormone were normal or near normal. Tacrolimus levels were around 13 microg/ml. Clinical improvement appeared slowly and spontaneously during the following 3 months, without appreciable changes in the tacrolimus level. CONCLUSIONS: In kidney transplant patients, tacrolimus could be a risk factor for the development of a reflex sympathetic dystrophy syndrome.

An in vitro study of hemicholinium-3 on phospholipid metabolism of Krebs II ascites cells.

With [Me-14C]choline as marker and after separation of choline and phosphocholine by ion-exchange column chromatography or thin layer chromatography on alumina, it is shown that 40 microM hemicholinium-3 (HC-3) inhibits the cytosolic choline-kinase of rat liver and Krebs cells. This inhibition is competitive (Km different, Vm similar) in the first case and mixed in the second (Km and Vm different). Despite this general inhibition of the phosphocholine formation, the synthesis of phosphatidylcholine (PC) by post-nuclear supernatants of rat liver and Krebs cells is different when tested with HC-3. It is unaffected in rat liver; however, HC-3 induces a PC deficiency in Krebs cells which is time-course dependent between 15 and 120 min and proportional to the drug concentrations in the interval 5-40 microM. Incorporation of AT-[gamma 32P] or [2-14C]ethanolamine into phospholipids shows that the sequential methylation pathway is not detectable in Krebs cells. These results are discussed in relation to those established concerning HC-3 action on phospholipid metabolism in other tissues.

Action of hemicholinium-3 on phospholipid metabolism in Krebs II ascites cells.

Incorporation of [Me-14C]choline or/and [2-14C]ethanolamine into phospholipids of Krebs II ascites cells in toto have been tested in the presence of hemicholinium-3. With [Me-14C]choline, labelling of cell pellet, intracellular choline, phosphocholine and total lipid extract is inhibited by hemicholinium-3 in a dose-dependent way between 6.25 X 10(-6) M and 10(-3) M. These effects are caused by a diminution of the choline or/and ethanolamine transport across the cell membrane and by a choline-kinase inhibition. In Krebs cells, choline is taken up by a low affinity Na+ sensitive uptake system (KT = 46 X 10(-6) M) which is competitively inhibited by hemicholinium-3 (KTi = 161 X 10(-6) M). Krebs cells exert a counter-transport (i.e. an exchange of choline across the membrane) against a concentration gradient of 10 mM choline whereas 10 mM hemicholinium-3 has no effect. Choline-kinase is also inhibited (I50 = 57 X 10(-6) M) in Krebs cells in toto and time-course data suggest that choline transport and phosphorylation might be tightly coupled. Specific radioactivities of phosphocholine and choline-glycerophospholipids decrease owing to the effect of the drug on the uptake and phosphorylation system. With 4 X 10(-5) M hemicholinium-3 and [Me-14C]choline as a marker, labelled choline-glycerophospholipids are decreased by 22%. With [2-14C]ethanolamine, labelled ethanolamine-phospholipids are decreased by 26% and choline-glycerophospholipids remain unlabelled. With the two markers, the additional effect produces a 35% decrease. It is concluded that hemicholinium-3 might be able to induce a depression of the intracellular choline and phosphocholine pool which could provoke a serious quantitative deficiency of major phospholipids in Krebs cells.

Evolution of untreated mild rejection in heart transplant recipients.

To elucidate whether mild rejection requires treatment, we retrospectively examined the spontaneous natural history of this histologic feature without an increase of immunosuppression. During a 4-year period, 55 heart transplantations were performed in 54 patients on whom 958 endomyocardial biopsies were performed. Among these biopsies, 162 specimens showed features of mild rejection. We studied the results of subsequent biopsies performed 7 to 10 days later, without any change in immunosuppression. These revealed regression of lesions to minimal rejection in 51 cases (31%), the same histologic feature in 82 cases (51%), or progression to moderate or severe rejection in 29 cases (18%). In 82% of these cases, therefore, no aggravation of histologic feature was observed. We separated the cases in which current-study biopsies showed mild rejection into three groups according to the result of the most recent biopsy, that is, minimal, mild, or moderate-severe rejection. The percentage of good outcome was not modified by the nature of the previous biopsy specimen: 84%, if minimal rejection was preceding the study biopsy; 82%, in the cases of mild rejection; and 77%, for moderate or severe rejection. We did not find significant differences in this evolution between patients with fewer or more than two moderate or severe acute rejections in the first 4-month period after heart transplantation (respectively, 15% or 24% progression to moderate or severe acute rejection after nontreated mild rejection).(ABSTRACT TRUNCATED AT 250 WORDS)

Free intraperitoneal islet autografts in pancreatectomized dogs--impact of islet purity and posttransplantation exogenous insulin.

BACKGROUND: We compared the ability of impure, dispersed pancreatic islet tissue (DPIT) and purified islets to engraft in the peritoneal cavity of dogs. We also tested whether posttransplantation insulin therapy affects islet engraftment. METHODS: Thirty-two dogs underwent total pancreatectomy. DPIT was autotransplanted intraperitoneally in nine dogs. Purified islets were autotransplanted intraperitoneally in 13 dogs and intraportally in seven dogs. Dogs received comparable islet mass. One half of the recipients of intraperitoneal grafts received 12 days of posttransplantation exogenous insulin. Three dogs did not undergo transplantation. Intravenous glucose tolerance tests were done at 60 and 180 days. RESULTS: The long-term graft functional survival rate of intraperitoneal DPIT graft was significantly better than the rate of intraperitoneal purified islets (p < 0.01) and was as good as the rate of intraportal purified islets. Purified islets transplanted intraperitoneally failed early compared with other groups, with only 46% functioning at 3 weeks (p = 0.05); exogenous insulin reduced this early failure rate (p = 0.05). At 6 months 67% of intraperitoneal DPIT and 86% of intraportal purified grafts were functioning. Glucose disposal did not differ between groups. CONCLUSIONS: The peritoneal cavity is a safe, practical site for islet transplantation, particularly for high-volume DPIT grafts. DPIT may provide a larger, more viable beta-cell mass than purified islets, or the acinar-ductal tissue may have a positive effect on engraftment. Exogenous insulin may promote engraftment of transplanted islets with a marginal beta-cell mass.

Evaluation of intrathymic islet transplantation in the prediabetic period.

BACKGROUND: Beta-cell destruction in type I diabetes mellitus results from a chronic autoimmune process. Exposure of thymic T cells to islet antigens during the prehyperglycemic phase of diabetes may alter the likelihood of autoimmune damage to beta cells in the native pancreas. Thus we evaluated whether prophylactic major histocompatibility complex (MHC)-incompatible intrathymic islet allografts could prevent hyperglycemia and native pancreatic beta-cell destruction. METHODS: At 4 to 6 weeks of age, diabetes-prone BioBreeding rats received intrathymic injection of 1500 to 2000 noncultured MHC-incompatible Lewis islets. No immunosuppression was administered. Age-matched littermates underwent intrathymic injection of saline solution. RESULTS: None of 13 BioBreeding rat recipients of prophylactic intrathymic Lewis islet allografts became hyperglycemic versus 13 of 13 control rats (p less than 0.001). The age at onset of diabetes in the control group ranged from 77 to 104 days (mean, 86 days). Normoglycemia in recipients of intrathymic islet allografts persisted for greater than 8 months after transplantation, and thymectomy (graft removal) did not precipitate hyperglycemia. CONCLUSIONS: Prophylactic intrathymic MHC-incompatible islet allografts effectively prevent hyperglycemia and native beta-cell destruction in an animal model of autoimmune diabetes. Rejection and autoimmune destruction of intrathymic MHC-incompatible islet allografts were not seen after transplantation in the prediabetic (prehyperglycemic) period. Intrathymic islet allografts at an early age (before puberty) preserve native beta-cell function and may prevent or retard thymic atrophy.

Combined liver kidney transplantation in primary hyperoxaluria type I. Prevention of the recidive of calcium oxalate deposits in the renal graft.

We report the case of a 31-year-old patient who underwent combined liver and kidney transplantation for primary hyperoxaluria type I. Intensive hemodialysis was performed before the intervention and post-operatively in order to maintain plasma oxalate levels near the normal range. In spite of the correction of the liver enzyme deficiency, oxalate removal from the tissular stores led to prolonged hyperoxaluria, more longer than one year after the transplantation, as already reported. This increased urinary oxalate excretion exposes the renal graft to the risk of recurrence of calcium oxalate deposits and stone formation during a prolonged period. Hemodialysis in the postoperative period and fluid intake allowing a large urine volume might be able to decrease the concentration of urinary oxalate under the critical value of 300 mumol/l, at which supersaturation of urine in respect of calcium oxalate occurs.

Hypertension and nephrotoxicity in the rate of decline in kidney function in diabetic nephropathy.

Serum creatinine levels were determined prospectively every 2 to 3 months in 40 patients with diabetic nephropathy for a global observation period of 864 months. The monthly creatinine increasing rate was significantly lower in normotensive periods, mean arterial pressure (MAP) less than 115 mmHg, when compared with hypertensive periods, MAP greater than 125 mmHg. No significant difference was shown in periods with borderline hypertension (MAP between 115-124 mmHg). The mean creatinine increases were of 0.036 mg/dl/month, 0.3 mg/dl/month and 0.046 mg/dl/month respectively. Normotension was associated with a slowing down of the rate of decline in renal function in this group of moderate kidney failure with an initial mean serum creatinine of 2.26 mg/dl. The exposure of patients to nephrotoxics (aminoglycosides, and possibly anesthesia) significantly accelerated the decline in renal function: 0.39 mg/dl/month and 0.17 mg/dl/month respectively according to the concomitance or not of toxics and hypertension. The reported protective effect of diabetes against aminoglycosides nephrotoxicity in experimental conditions was not reflected in our clinical results. On the contrary, we suggest a possible enhanced sensibility of the diabetic patient with diabetic nephropathy to aminoglycosides leading to an acceleration of the progression of renal failure.

Use of cyclosporine in renal transplantation.

The first cyclosporine trials in renal transplantation began in Cambridge in 1978. Between 1982 and 1985 several large multicenter trials and the reports from large series of patients evidenced that cyclosporine was a major advance in the prevention of acute rejection episodes and in improving short-term and long-term graft survival. Cyclosporine also showed the capacity to mitigate immunologic risk factors, HLA mismatching, and lack of pretransplant transfusions. However, cyclosporine has the serious defect of being nephrotoxic. Induction therapy with OKT3, polyclonal antibodies, and more recently with anti IL-2R monoclonal antibodies allowed the delay of introduction cyclosporine in patients showing posttransplant graft dysfunction. Other relatively unsuccessful attempts for overcoming cyclosporine nephrotoxicity were made before the association of new xenobiotics such as mycophenolate mofetil or sirolimus permitted cyclosporine doses to be reduced. These combinations reduce acute rejection incidence to below 20%, with its consequent positive impact on long-term graft outcome and also allow a safer steroid sparing and withdrawal early posttransplantation. Also, the association of cyclosporine with other new compounds such as the lymphocyte homing FTY20 or the peripheral lymphocyte-depleting Campath-1-IgG is currently under clinical investigation. Cyclosporine's future place is yet to be established in the new era of immunosuppression.

Efficacy and safety of doxazosin GITS in hypertensive renal transplant patients: comparison of 8 and 4 mg.

BACKGROUND: Hypertension (HT), a prevalent complication in renal transplant patient (RT), must be accurately treated because cardiovascular disease is the leading cause of death and of chronic graft dysfunction. Sympathetic activity may contribute to HT in RT, yielding the rationale to suspect that doxazosin, an alpha1-adrenergic receptor inhibitor, may lower blood pressure (BP). The aim of this study was to evaluate the efficacy and safety of doxazosin GITS (4 and 8 mg) in RT. METHODS: Twenty-three hypertensive RT received doxazosin 4 mg once daily for 4 weeks (W4) followed by a 4-week washout (W0) and 17/23 treated with doxazosin 8 mg for 4 more weeks (W8) due to persistent HT. All patients underwent 24-hour ambulatory blood pressure monitoring (ABPM) after W0, W4, and W8. Laboratory tests were performed, adverse events recorded, and prostatic symptomatology examined. Statistical analysis included Saphiro-Wilks, Student t, ANOVA, Wilcoxon, or Friedman tests. RESULTS: The systolic, diastolic, and mean BP were significantly lowered at W4 in awake (P<.001) and 24 hour period (P<.005) but not sleep recordings. Doxazosin 8 mg had no significant additional effect to lower BP at any period. Normotension was reached in 13% and 21.7% of patients at W4 and W8, respectively. Palpitations were the only reported adverse event after treatment (incidence similar to placebo). There was no significant change in the laboratory values. CONCLUSIONS: Doxazosin (-4 mg) effectively decreased BP in awake and 24-hour periods without a significant improvement during sleep. A double dose of the drug added little benefit. Optimal BP was reached by an insufficient number of patients. Doxazosin proved to have a good tolerance and safe profile. This results suggest that doxazosin should be considered a good add-on treatment to other antihypertensive drugs in RT.

Ambulatory blood pressure monitoring in renal transplant patients: modifiable parameters after active antihypertensive treatment.

BACKGROUND: Hypertension (HT) accounts for nearly 60% to 80% of renal transplant patients (RT). It is one of the most important risk factors for cardiovascular diseases and may cause chronic graft dysfunction. Therefore, it is important to accurately detect and treat HT. We aimed to evaluate the changes in ambulatory blood pressure monitoring (ABPM) parameters among hypertensive RT after active treatment compared with baseline values. METHODS: Thirty seven RT (25 men, 12 women, aged 49.4 +/- 11.2 year) diagnosed with mild to moderate HT underwent 24-hour ABPM after a 4-week washout period (W0). For the 23 RT with confirmed HT of a second 24-hour ABPM was recorded after 4 weeks of treatment with doxazosin GITS (-4 mg once daily in the morning), a new formulation of an alpha1-receptor inhibitor (W4). Nondippers were considered when mean blood pressure (BP) showed a < or = 10% reduction during sleep. Statistical analyses included Saphiro-Wilks test, Student t test, and ANOVA. RESULTS: After active treatment systolic, diastolic, and mean BP (SBP, DBP, MBP) significantly decreased during diurnal and 24 hours but not the nocturnal period. No significant change was observed for heart rate nor for pulse pressure during any period. The prevalence dippers increased from 0% to 17% after treatment. After placebo administration 8 among 37 RT with HT diagnosed according to casual BP remained hypertensive at nighttime (but not at daytime) according to 24-hour ABPM. CONCLUSIONS: Diurnal and 24-hour periods of ABPM showed significant changes in SBP, DBP, and MBP after active treatment with doxazosin GITS. No significant BP changes were observed in the nocturnal period or in dipper status. Further studies using ABPM must be undertaken to determine the optimal dosage and time of administration of antihypertensive drugs in RT.

Posttransplant lymphoproliferative disease: treatment and outcome in renal transplant recipients.

UNLABELLED: Posttransplant lymphoproliferative disorders (PTLD) are a heterogeneous group of lymphoid diseases that occur after solid organ and bone marrow transplantation. We performed a retrospective study to assess the incidence, response to treatment, and patient and graft survival after PTLD. PATIENTS: Between January 1980 and December 2002, 1.96% (n=10) of 509 renal transplant recipients developed PTLD. Seventy percent were men. Mean age was 40 years (range 21-65). They were classified into four groups based upon the type of PTLD: group I, early lesion (n=1); group II, polymorphic PTLD (n=1); group III, monomorphic PTLD (n=7) including five non-Hodgkin lymphoma [NHL] and two Burkitt (BL); and group IV, Hodgkin lymphoma (HL) (n=1). The mean time from transplantation to diagnosis was 77 months (range 4-138). Although only 20% of cases were early presentation, Epstein-Barr virus (EBV) was found in the tumor cells of seven cases. Treatment was individualized according to PTLD type: for group I, immunosuppression reduction (IR); group II, IR plus acyclovir; group III, withdrawal or IR plus chemotherapy and/or surgery in all but one patient who was also treated with anti-CD20 monoclonal antibody and radiotherapy. Interferon was also used in one patient. For group IV, treatment was IR plus radiotherapy. RESULTS: A complete response was achieved in nine cases (90%) with one recurrence. Three patients returned to dialysis. One patient with BL died. CONCLUSIONS: The incidence of PTLD in our center was 1.96%. Patient survival after PTLD was 90%, with 60% maintaining allograft function. Individualized treatment according to extension, histology, and location is mandatory to obtain a high survival rate.