ABSTRACT
OBJECTIVE: To assess 1,25-dihydroxyvitamin D status and the effect of vitamin concentration on transplantation outcome in renal allograft recipients. PATIENTS AND METHODS: Ninety patients underwent renal transplantation between 2002 and 2005. All received alfacalcidol supplementation before surgery. 1,25-Dihydroxyvitamin D concentration was determined on day 3 posttransplantation and at 1-, 6-, 12-, 18-, and 24-month follow-up. RESULTS: Severe 1,25-dihydroxyvitamin D deficiency was noted in 83% of patients immediately posttransplantation. From 1 to 12 months thereafter, concentrations increased almost 3-fold, and remained constant to 24 months. In 50% of patients, the 1,25-dihydroxyvitamin D concentration reached a concentration of more than 30 pg/mL, similar to that in healthy volunteers; in the other 50%, the concentration reached 17.2 pg/mL. A high incidence of delayed graft function was observed in patients with 1,25-dihydroxyvitamin D deficiency (44% vs 6%). There was a negative correlation between the initial 1,25-dihydroxyvitamin D and serum creatinine concentrations at day 3 and month 6 (P < .03). Similarly, the 1,25-dihydroxyvitamin D concentration at 1 month was negatively correlated with creatinine concentration at months 1 through 24 (P < .01). Poor outcome was observed primarily in patients with 1,25-dihydroxyvitamin D deficiency; 2 patients developed cancer, 5 grafts were lost, and 4 patients died of cardiovascular events. CONCLUSIONS: 1,25-Dihydroxyvitamin D deficiency is highly prevalent in renal allograft recipients. Patients with 1,25-dihydroxyvitamin D deficiency are at greater risk of delayed graft function, and the graft is more likely to be lost. These findings suggest the necessity of adequate vitamin D supplementation both before and after transplantation.
Subject(s)
Calcitriol/deficiency , Kidney Transplantation/adverse effects , Vitamin D Deficiency/epidemiology , Adult , Calcium/blood , Creatinine/blood , Female , Follow-Up Studies , Humans , Kidney Transplantation/mortality , Male , Middle Aged , Parathyroid Hormone/blood , Patient Selection , Phosphates/blood , Predictive Value of Tests , Retrospective Studies , Treatment Failure , Treatment Outcome , Vitamin D Deficiency/bloodABSTRACT
Posttransplant bone disease is caused by renal osteodystrophy. We sought to examine bone mineral density (BMD) among 90 renal allograft recipients of mean age 42.7 +/- 11.4 years to identify factors preventing bone loss at 2 years posttransplant. Subjects treated with cyclosporine or tacrolimus plus azathioprine/MMF and prednisone underwent BMD estimates of the lumbar spine (LS) and of the proximal femur using dual energy x-ray absorptiometry (DEXA) at 3 months and every 6 months for 2 years. We assayed markers of bone remodeling: intact parathyroid hormone (iPTH), calcitriol, osteocalcin, and carboxyterminal telopeptide of type I collagen on day 3, as well as month 1 and every 6 months after transplantation. At the initial measurement, we observed osteopenia (OSP) among 35% in the LS and 52% in the femur: there was osteoporosis in 8.3%. The prevalence of OSP increased during the first year, thereafter decreasing to the initial value, but the rate of osteoporosis did not change significantly (8.3% vs 6.0%). BMD and Z-score decreased during the first and increased in the second year; 27% of patients regained initial values and 38% higher ones. BMD gains in the LS and femur were observed among subjects with higher calcitriol levels during the first 6 months (P < .01), higher osteocalcin (P < .05), higher estimated glomerular filtration rate during 1-24 months and in the tacrolimus group. Improvement of LS BMD occurred in younger patients (38 vs 46 years; P < .027); BMD gain in the femur correlated with higher levels of iPTH from 1-12 months (P < .01). The tacrolimus group showed higher Z-scores in the LS and femur at 24 months (P < .05). Two years after transplantation >60% of recipients showed stabilization or gain in bone mass. A sufficient calcitriol level in the early transplant period, an adequate iPTH, good renal function, and tacrolimus therapy prevented BMD disease progression.
Subject(s)
Bone Density/physiology , Bone Diseases/epidemiology , Kidney Transplantation/adverse effects , Postoperative Complications/epidemiology , Adult , Bone Diseases/prevention & control , Calcitriol/blood , Collagen Type I , Creatinine/blood , Female , Humans , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/immunology , Male , Middle Aged , Osteocalcin/blood , Parathyroid Hormone/blood , Peptide Fragments/blood , Peptides , Procollagen/bloodABSTRACT
Calcineurin inhibitors improve kidney allograft survival in the posttransplantation period; however, they may cause nephrotoxicity. The objective of this study was to compare the effect of cyclosporine (CsA) and tacrolimus (Tac) treatment on the transplanted kidney. The study included 219 patients aged 21 to 65 years. Of these, 120 (39 women and 81 men) were treated with CsA and 99 (38 women and 61 men) were treated with Tac. Patients were divided into 4 groups depending on the time since kidney transplantation. We evaluated urine markers of nephrotoxicity: proximal tubular cells lysosomal enzymes (N-acetyl-beta-d-glucosaminidase [NAG] and its isoform NAG-B, beta-d-galactosidase, and beta-glucouronidase) and brush border enzymes (alanyl aminopeptidase and gamma-glutamyl transpeptidase). Urine activities of nephrotoxicity markers were compared in CsA- and Tac-treated patients groups depending on the duration of treatment and allograft function as measured by serum creatinine concentration. Correlation studies between CsA and Tac levels and enzyme activities were performed in both groups and in the entire patient cohort. NAG and its isoform NAG-B seemed to be the most reliable markers of nephrotoxicity. Despite the significant correlation between NAG urine activity and serum creatinine concentration in the CsA group, there were no significant differences in NAG or NAG-B activities between CsA- and Tac-treated graft recipients.
Subject(s)
Cyclosporine/therapeutic use , Kidney Transplantation/immunology , Tacrolimus/therapeutic use , Acetylglucosaminidase/blood , Adult , Aged , Cyclosporine/blood , Female , Follow-Up Studies , Humans , Immunosuppressive Agents/blood , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/pathology , Kidney Transplantation/physiology , Kidney Tubules, Proximal/pathology , Male , Middle Aged , Tacrolimus/blood , Time Factors , Young Adult , beta-Galactosidase/bloodABSTRACT
Antiproliferative and non-nephrotoxic properties of sirolimus have been exploited for treatment of patients with chronic graft dysfunction. In this paper we point to the possible association of nephrotic syndrome and renal impairment with rapid conversion from cyclosporine (CsA) to sirolimus in patients with chronic nephropathy. Five male patients, ages 34 to 56 years, with chronic renal failure in the course of glomerulonephritis, were transplanted between 1997 and 1999. For the first 49 to 65 months, the immunosuppressive regimen consisted of CsA, azathioprine (AZA), and prednisone. Thereafter, due to chronic nephropathy evidenced by biopsy, conversion to sirolimus was performed with sharp withdrawal of CsA. The serum creatinine level prior to conversion was 1.9 +/- 0.3 mg/dL. Trace to 86 mg/dL proteinuria was found in 3 patients, while 2 patients had about 200 mg/dL. After 2 to 4 months of sirolimus treatment the proteinuria progressed (558 +/- 183 mg/dL); edema, hypoproteinemia, hypoalbuminemia, and hyperlipidemia developed; and the serum creatinine increased to 3.5 +/- 0.8 mg/dL. Biopsies performed in three patients revealed new pathologic changes. After 4 to 5 months, we performed reconversion to calcineurin inhibitor. Proteinuria decreased to 0 to 150 mg/dL; nevertheless the serum creatinine was continuously rising. Six to 15 months after the conversion, 3 patients returned to dialysis. The fourth patient, who was earlier reconverted, has a serum creatinine level of 2.0 mg/dL after 15 months. In conclusion, conversion from CsA to sirolimus may induce nephrotic syndrome with progressive deterioration of renal function. Converted patients require careful monitoring of proteinuria and renal function. Early reconversion to calcineurin inhibitor may prevent progressive deterioration of graft function.
Subject(s)
Cyclosporine/therapeutic use , Kidney Transplantation/pathology , Nephrosis/chemically induced , Proteinuria/chemically induced , Sirolimus/adverse effects , Adult , Albuminuria/chemically induced , Azathioprine/therapeutic use , Cholesterol/blood , Creatinine/blood , Drug Therapy, Combination , Humans , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Kidney Function Tests , Kidney Transplantation/immunology , Male , Middle Aged , Nephrosis/urine , Transplantation, Homologous/immunology , Transplantation, Homologous/pathology , Triglycerides/bloodABSTRACT
The aim of the study was to assess impaired tubular phosphate reabsorption and renal function among patients on cyclosporine- or tacrolimus-based immunosuppression for 2 years after kidney transplantation. Among 60 cadaveric kidney allograft recipients observed for 48 months, 40 received cyclosporine, azathioprine, and prednisone (group A and B). Group C consisted of 20 patients receiving tacrolimus with steroid withdrawal at 3 months after transplantation. Renal function and calcium-phosphate metabolism-iPTH, 25-OHD, 1,25(OH)(2)D concentration, phosphate reabsorption (TRP; mmol/L), and tubular maximum phosphate reabsorption per glomerular filtration rate (TmPO(4)/GFR; mmol/L)-were assessed at 1, 6, 12, 18, and 24 months (groups A and C) or 24, 30, 36, 42, and 48 months (group B). Renal function after 24 months of observation was significantly better among tacrolimus-treated patients (serum creatinine concentration mumol/L; C: 94.6 +/- 16.8 vs A: 110.5 +/- 22.1 vs B: 121.1 +/- 30.9; P < .05). Among tacrolimus-treated recipients, TRP and TmPO(4)/GFR remained within normal values during the whole observation period. In groups A and B, TRP improved during the first year of observation; after 2 years it reached values observed in group C (TRP: A: 0.67 +/- 0.1; B: 0.72 +/- 0.13; C: 0.76 +/- 0.07; P = NS), whereas TmPO(4)/GFR remained low in group A after 2 years (A: 0.78 +/- 0.19; B: 0.91 +/- 0.25; C: 0.94 +/- 0.15; P < .05). Tacrolimus-treated patients exhibit significantly faster recovery from tubular phosphate reabsorption impairment compared with cyclosporine-treated recipients. Tacrolimus-based immunosuppression led to better kidney allograft function during 2-year observation.
Subject(s)
Cyclosporine/therapeutic use , Kidney Function Tests , Kidney Transplantation/physiology , Kidney Tubules/metabolism , Phosphates/metabolism , Tacrolimus/therapeutic use , Adult , Cadaver , Calcifediol/blood , Calcitriol/blood , Calcium/blood , Creatinine/blood , Drug Therapy, Combination , Female , Glomerular Filtration Rate , Humans , Immunosuppression Therapy/methods , Kidney Transplantation/immunology , Male , Middle Aged , Phosphates/blood , Retrospective Studies , Tissue DonorsABSTRACT
Secondary hyperparathyroidism and immunosuppressive treatments are the most important pathogenetic factors for bone disease after kidney transplantation. The aim of study was to compare the influence of vitamin D receptor (VDR) genotype on the PTH level and bone mineral density (BMD) in 67 patients, including 45 immunosuppressed with cyclosporine (CsA) and 22 with tacrolimus (Tac) versus 147 healthy volunteers. Two VDR polymorphisms: BsmI and FokI were assayed with RFLP-PCR. Scantibodies were utilized to evaluate 1-84 PTH. BMD was measured by DEXA. Hormone levels were measured on the third day and sixth month after transplantation. BMD was examined at the third and ninth month. The distribution of FokI genotype differed, but the BsmI genotypes did not differ between the transplant patients and the control group. All transplanted patients showed an elevated tPTH at the first examination. The highest PTH values, which were observed in bb genotype, significantly decreased after the transplant procedure. Patients with the FF genotype who were treated with CsA showed higher levels of tPTH than those with the Ff genotype. At 6 months, a decrease in tPTH occurred in both the CsA and the Tac patients. A low BMD at the third month was more frequent among patients of the BB genotype treated with CsA. The Z-score remained low at the third month and at the ninth month. In conclusion, kidney graft recipients show overrepresentation of the Ff genotype. Our preliminary data suggest that the bb genotype exhibits a protective effect on bone loss after renal transplantation.
Subject(s)
Bone Density/physiology , Hyperparathyroidism, Secondary/epidemiology , Kidney Transplantation/adverse effects , Kidney Transplantation/physiology , Polymorphism, Genetic , Receptors, Calcitriol/genetics , Adult , Bone Density/genetics , Cyclosporine/therapeutic use , Follow-Up Studies , Genotype , Graft Rejection/epidemiology , Humans , Hyperparathyroidism, Secondary/genetics , Hyperparathyroidism, Secondary/prevention & control , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/immunology , Middle Aged , Parathyroid Hormone/blood , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Tacrolimus/therapeutic useABSTRACT
The aim of the study was to elucidate whether cyclosporine- and tacrolimus-based immunosuppression impairs tubular reabsorption of phosphate after kidney transplantation. Sixty cadaveric allograft recipients were included in the study. Forty patients receiving triple immunosupression with cyclosporine, azathioprine, and prednisone were studied for 1, 6, 12 months (groups A1 and A2, 20 patients) and for 24, 30, and 36 months (groups B1 and B2, 20 patients) after transplantation. Twenty patients who received tacrolimus with steroid withdrawal after 3 months were included in the study (group C). Recipients from groups A2 and B2 were treated additionally with vitamin D and calcium carbonate. Serum iPTH, 25-OHD, 1.25(OH)(2)D concentrations were determined, and TRP (mmol/L) and TmP/GFR (mmol/L) were calculated using Walton-Bijvoet nomogram. Higher values of total calcium serum concentration in group A were detected. Lower inorganic phosphate serum concentrations were detected in groups A and C, in contrast to group B where they remained within normal values. TmP/GFR values were significantly higher in group C in the first and third examination in comparison with patients of group A. Moreover, TRP index values were significantly higher than analogous values of groups A and B. Tacrolimus-treated patients exhibit significantly faster recovery from tubular phosphate reabsorption impairment compared to cyclosporine-treated recipients. No correlation between iPTH, 25-OHD, 1,25(OH)(2)D concentration, and tubular dysfunction parameters was observed. Amelioration of phosphate handling, in spite of hyperparathyroidism intensity, can follow early steroid avoidance.
Subject(s)
Immunosuppressive Agents/therapeutic use , Kidney Tubules/physiology , Tacrolimus/therapeutic use , Adolescent , Adult , Cadaver , Calcium Carbonate/therapeutic use , Drug Therapy, Combination , Female , Glomerular Filtration Rate/drug effects , Humans , Kidney Tubules/drug effects , Male , Middle Aged , Phosphates/metabolism , Retrospective Studies , Vitamin D/therapeutic useABSTRACT
Our previous study of a group of renal transplant recipients treated with CsA showed a significantly faster development of chronic graft failure among patients with gingival hyperplasia (GH) compared to unaffected patients. The aim of the present research was to establish the impact of CsA dose and blood levels on the incidence of chronic graft nephropathy and gingival overgrowth as well as to assess risk factors for chronic graft nephropathy. The study included 64 renal graft recipients (32 patients with GH and 32 without GH) transplanted between 1989 and 1994. There were no significant differences between the pretransplant demographic and clinical data of the patients with and without GH. Patients with GH received a significantly higher total yearly dosages of CsA compared those without GH (P <.03). Serum creatinine in the first year posttransplant in patients with GH was 1.9 mg/dL versus 1.6 mg/dL in those without GH. During 9 to 14 years follow-up, end-stage renal failure due to chronic nephropathy occurred in 18 patients (56%) with GH and eight patients (25%) without GH. Ten-year renal graft survival was 35% in GH patients and 69% in patients without GH. Ten-year patient survival was 69% in the GH group and 91% in the group without GH. CsA dosage was a risk factor for GH and for graft loss, which implies a role of CsA toxic effects on the pathological mechanisms of GH and of chronic allograft nephropathy.
Subject(s)
Cyclosporine/therapeutic use , Gingival Hyperplasia/epidemiology , Kidney Transplantation/pathology , Adult , Chronic Disease , Female , Follow-Up Studies , Gingival Hyperplasia/drug therapy , Graft Survival/drug effects , Graft Survival/immunology , Humans , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/mortality , Male , Retrospective Studies , Survival Analysis , Time FactorsABSTRACT
Despite the fact that concentrations of mycophenolic acid (MPA) are not routinely measured, accumulating data suggest the usefulness of this monitoring to optimize therapy. The aim of this study was to assess the influence of CsA and tacrolimus on MPA pharmacokinetics. Concentrations of MPA were measured using HPLC. An assay was performed before dose (the C(0)), as well as at 40 minutes and 1, 2, 4, 6, 8, 10, 12 hours after administration of mycophenolate mofetil (MMF). MPA profiles were assessed in 51 patients receiving tacrolimus at a dose of 1.0 g/d and prednisone as well as in 97 patients receiving CsA (2.0 g/d) and prednisone. Significant correlations of MPA levels with serum albumin and GFR were observed in both groups. Women presented with higher levels of MPA than men. C(0) MPA level among the tacrolimus group were significantly higher than those in CsA group: 3.18 +/- 2.21 microg/mL versus 1.68 +/- 1.03 microg/mL (P =.001). The level of MPA AUC((0-12)) in the tacrolimus group was nonsignificantly higher than that in the CsA group. There was no second peak of MPA level in a group of patients receiving CsA. We developed a limited sampling strategy to estimate MPA AUC((0-12)) in both tacrolimus and CsA groups. We observed a correlation between C(0) MPA and C(0) CsA (r =.35; P =.001) as well as, between tacrolimus dose and MPA C(40) and MPA C(max) (r =.24; P =.05; r =.27; P = 0.05, respectively). No relationship between MPA pharmacokinetics and tacrolimus blood concentrations was noticed. Tacrolimus and CsA both affect the pharmacokinetics of MPA; high MPA concentrations in patients treated with tacrolimus justify MMF dose reduction in this group. Alterations of CsA concentrations must be used to guide MMF dose adjustments.
Subject(s)
Calcineurin Inhibitors , Kidney Transplantation/immunology , Mycophenolic Acid/analogs & derivatives , Mycophenolic Acid/pharmacokinetics , Adult , Cyclosporine/therapeutic use , Drug Therapy, Combination , Female , Glomerular Filtration Rate/physiology , Humans , Immunosuppressive Agents/pharmacokinetics , Immunosuppressive Agents/therapeutic use , Male , Metabolic Clearance Rate , Mycophenolic Acid/therapeutic use , Prednisone/therapeutic use , Retrospective Studies , Serum Albumin/metabolism , Tacrolimus/therapeutic use , Time FactorsSubject(s)
Graft Rejection/epidemiology , Kidney Transplantation/immunology , Kidney Transplantation/pathology , Mycophenolic Acid/analogs & derivatives , Mycophenolic Acid/therapeutic use , Adult , Blood Pressure , Cholesterol/blood , Creatinine/blood , Female , Graft Rejection/drug therapy , Humans , Immunosuppressive Agents/therapeutic use , Male , Methylprednisolone/therapeutic use , Transplantation, Homologous/immunology , Transplantation, Homologous/pathology , Treatment Failure , Triglycerides/bloodABSTRACT
Since kidney transplant recipients are at enhanced risk for developing severe upper gastrointestinal disease and Helicobacter pylori (Hp) is an important pathogen in active gastritis and peptic ulcer, we performed gastroduodenoscopic examination, coupled with assessment of Hp colonization in 29 renal allograft recipients complaining of recurrent dyspepsia. Results were compared with those of 25 chronically hemodialyzed patients and 16 subjects free from renal disease, also suffering from upper gastrointestinal symptoms of similar severity. We found that while transplant recipients have had a high prevalence of Hp infection (62 vs. 34.6% in dialysis and 43.6% in control dyspeptic patients), active gastritis was clearly less frequently seen in these patients than in control subjects (transplant group: 6.9%, dialysis 3.8%, control 31.3%) and peptic ulceration was totally absent. Prevalence of Hp colonization was even higher in renal graft recipients on triple posttransplant immunosuppression (82%). In dyspeptic transplant and dialysis patients, colonization with Hp did not account for development of active inflammatory lesions, an association frequently seen in subjects free from renal disease and immunosuppressive therapy.
Subject(s)
Dyspepsia/microbiology , Gastric Mucosa/microbiology , Helicobacter Infections/etiology , Helicobacter pylori/isolation & purification , Kidney Transplantation , Adolescent , Adult , Antibodies, Bacterial/analysis , Biopsy , Dyspepsia/epidemiology , Dyspepsia/pathology , Endoscopy, Digestive System , Enzyme-Linked Immunosorbent Assay , Female , Gastric Mucosa/pathology , Graft Rejection/prevention & control , Helicobacter Infections/epidemiology , Helicobacter Infections/pathology , Helicobacter pylori/immunology , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , RecurrenceSubject(s)
Aortic Valve , Calcinosis/epidemiology , Heart Valve Diseases/epidemiology , Kidney Transplantation , Mitral Valve , Postoperative Complications , Adult , Age Factors , Calcinosis/etiology , Calcinosis/physiopathology , Creatinine/blood , Heart Valve Diseases/etiology , Heart Valve Diseases/physiopathology , Humans , Kidney Transplantation/physiology , Middle Aged , Renal Dialysis , Retrospective StudiesABSTRACT
A 30-year old female underwent kidney transplantation after unsuccessful 3-year dialysis for renal cortex necrosis. Immunosuppression was achieved with cyclosporin followed by azathioprine with prednisone. The patient conceived after 22 months with kidney transplantation. Mild decrease in arterial blood pressure and marked increased in glomerular filtration rate were seen during the first three months of pregnancy. Arterial blood pressure increased but insignificantly at the end of pregnancy. That time, gradual decrease in creatinine clearance was observed. An increase in serum bilirubin and alkaline phosphatase was noted. Pregnancy was terminated by cesarean section on the 38th week. Newborn was female, full-termed, viable, with body weight of 3,300 g. All examined parameters were normalized after delivery. Described case indicates that transplanted kidney functioning during pregnancy is similar to that in healthy women.
Subject(s)
Kidney Transplantation/physiology , Pregnancy/physiology , Adult , Cesarean Section , Female , Glomerular Filtration Rate/physiology , Humans , Infant, Newborn , Postoperative PeriodSubject(s)
Adhesives , Cyanoacrylates , Dental Bonding , Dental Cements , Dental Enamel , Polycarboxylate Cement , Animals , Cattle , Dental Enamel/anatomy & histologySubject(s)
Composite Resins , Biocompatible Materials , Chemical Phenomena , Chemistry , Chemistry, Physical , Rheology , Stress, MechanicalABSTRACT
A study was carried out to verify the clinical usefulness of the elaborated method for the measurement of antistreptococcal antibody in revealing the streptococcal etiology of glomerulonephritis. In 158 patients with glomerulonephritis antistreptococcal antibody (ASA), circulating immune complexes (CIC) and haemolytic activity of the complement were measured. On the basis of immune complex formation it has been concluded that streptococcal infection may cause glomerulonephritis. Serial determinations of ASA and CIC are helpful in establishing the streptococcal etiology of glomerulonephritis and in monitoring the course of the disease.
Subject(s)
Antigens, Bacterial/immunology , Glomerulonephritis/immunology , Streptococcus/immunology , Antibodies, Bacterial/analysis , Antibody Formation , Antigen-Antibody Complex/analysis , Antistreptolysin/analysis , Follow-Up Studies , HumansSubject(s)
Aged , Attitude , Dementia , Depression , Female , Humans , Loneliness , Male , Mental DisordersABSTRACT
143 patients were evaluated clinically on the basis of the renal biopsy. Three methods for detecting circulating immune complexes (CIC) were employed: complement consumption test, inhibition of erythrocyte antibody IgG-EA rosette forming test and optical density of 4% PEG precipitated sera. CIC were present in the sera of all patients with acute poststreptococcal glomerulonephritis (2 weeks after streptococcal infection of the throat). In a group of patients with chronic glomerulonephritis the highest values in positive results were observed in lupus nephritis, chronic proliferative glomerulonephritis and chronic submicroscopic glomerulonephritis. These results were compared with levels of total hemolytic complement, C3, C4 components and serum immunoglobulins (IgA, IgG, IgM).