Mineral metabolism disorders, vertebral fractures and aortic calcifications in stable kidney transplant recipients: The role of gender (EMITRAL study).

BACKGROUND AND OBJECTIVES: The relationship between mineral metabolism disorders, bone fractures and vascular calcifications in kidney transplant recipients has not been established. METHOD: We performed a cross-sectional study in 727 stable recipients from 28 Spanish transplant clinics. Mineral metabolism parameters, the semi-quantification of vertebral fractures and abdominal aortic calcifications were determined centrally. RESULTS: Vitamin D deficiency (25OHD3<15ng/ml) was more common in female recipients at CKD-T stages I-III (29.6% vs 44.4%; p=0.003). The inverse and significant correlation between 25OHD3 and PTH was gender-specific and women exhibited a steeper slope than men (p=0.01). Vertebral fractures (VFx) with deformity grade ≥2 were observed in 15% of recipients. Factors related to VFx differed by gender; in males, age (OR 1.04; 95% CI 1.01-1.06) and CsA treatment (OR: 3.2; 95% CI: 1.6-6.3); in females, age (OR 1.07; 95% CI: 1.03-1.12) and PTH levels (OR per 100pg/ml increase: 1.27; 95% CI: 1.043-1.542). Abdominal aortic calcifications were common (67.2%) and related to classical risk factors but not to mineral metabolism parameters. CONCLUSIONS: Vitamin D deficiency is more common among female kidney transplant recipients at earlier CKD-T stages, and it contributes to secondary hyperparathyroidism. Prevalent vertebral fractures are only related to high serum PTH levels in female recipients.

[Clinical and pharmacological factors related to the requirements of laser photocoagulation in patients with diabetic nephropathy due to type 2 diabetes mellitus]. / Factores clínicos y farmacológicos relacionados con los requerimientos de fotocoagulación láser en pacientes con nefropatía diabética secundaria a diabetes mellitus tipo 2.

BACKGROUND AND OBJECTIVE: Diabetic retinopathy is a microvascular complication of diabetes mellitus whose prevalence is closely related to the presence of nephropathy and hypertension. The aim was to study clinical and pharmacological factors that are associated with an increased need for laser photocoagulation in patients with diabetic nephropathy and retinopathy. PATIENTS AND METHODS: Cross sectional study of 63 patients followed in the Diabetic Nephropathy consultation. Patients were divided into 2 groups according to whether or not previously have received photocoagulation. In each subgroup were studied demographic variables, anthropometric, laboratory, cardiovascular risk factors and treatment received by each patient for the control of hypertension, diabetes and others diseases. RESULTS: We observed that the group had received photocoagulation had more years of diabetes evolution, more history of cardiovascular disease and a lower creatinine clearance. Similarly, the percentage of patients treated with carvedilol was significantly higher in the subgroup who had not received photocoagulation while the percentage of patients treated with beta-blockers was significantly higher in the subgroup that received photocoagulation; no significant differences was observed in the degree of control blood pressure. CONCLUSIONS: Clinical and pharmacological factors related to the requirements of laser photocoagulation were years of diabetes evolution, history of cardiovascular disease, the stage of kidney disease and the treatment with beta-blockers.

Hypercalcemia secondary to persistent hyperparathyroidism in kidney transplant patients: analysis after a year with cinacalcet.

INTRODUCTION: The most common cause of hypercalcemia in patients with transplanted kidneys is persistent hyperparathyroidism, which presents in 10%-30% of patients with functioning renal grafts. In these patients, the treatment of vitamin D-resistant hyperparathyroidism traditionally required parathyroidectomy. Calcimimetic agents represent a new therapeutic alternative; they inhibit parathyroid hormone (PTH) secretion, increasing the sensitivity of the calcium-sensitive receptor in the parathyroid gland. The objective of this study is to evaluate the efficacy of cinacalcet in renal transplant patients with persistent hyperparathyroidism. METHODS: Cinacalcet 30 mg/day was prescribed to 17 renal transplant patients (6 women, 11 men) with a mean age of 49 years and hypercalcemia secondary to persistent hyperparathyroidism. The treatment started 58.17 ± 35.16 months posttransplant, with 1 year of follow-up. RESULTS: Calcium in serum fell from 10.5 ± 0.74 to 9.4 ± 0.84 mg/dL (p<0.001), whereas phosphorous levels were not significantly altered. The fall in PTH was from 204.79 ± 78 to 148.55 ± 56 pg/mL (p<0.011). Kidney function remained stable, and immunosuppressant drug levels remained unchanged. The dose of cinacalcet was increased to 60 mg in 2 patients. No significant adverse effects were described, and none of the patients had to suspend the treatment. CONCLUSIONS: Calcimimetic agents represent a therapeutic alternative in transplant patients with persistent hyperparathyroidism, as they correct hypercalcemia and reduce PTH levels with no adverse effects on kidney function. Prospective, controlled studies should be designed to evaluate the long-term effects and evolution after suspension of the treatment.

[25 hydroxyvitamin D levels and cardiovascular risk in a cohort of patients with advanced chronic kidney disease]. / Niveles de 25 hidroxivitamina D y riesgo cardiovascular en una cohorte de pacientes con enfermedad renal crónica avanzada.

BACKGROUND: Decreased 25 hydroxyvitamin D serum levels have been related to an increase in cardiovascular morbility and mortality in both general population and chronic kidney disease patients. The aim of this study was to evaluate the relationship between 25 hydroxyvitamin D serum level, cardiovascular risk factors and previous established cardiovascular disease in a group of patients with advanced chronic kidney disease. MATERIAL AND METHODS: We performed a cross-sectional observational study in a cohort of 171 stage 4 and 5 chronic kidney disease outpatients seen in our predialysis clinic, mean age 64.16 +/- 13 years, 59.6% were men, 64.3% had diabetes, 47.3% had obesity, 46.8% had previous cardiovascular disease. 25 hydroxyvitamin D and 1-25 dihydroxyvitamin D were measured, we also determined other routine biochemical parameters. All subjects underwent an echocardiogram and 24 hours ambulatory blood pressure monitoring was also performed. RESULTS: Mean 25 hydroxyvitamin D levels were 22.1 +/- 13 ng/mL, only 18.7% of the patients had adequate levels, levels were insufficient in 58.5% of the patients and deficient in 22.8% of them. Low 25 hydroxyvitamin D levels were significantly related with age, diabetes, female gender, obesity, MDRD glomerular filtration rate and previous cardiovascular disease. Pulse pressure was the Ambulatory Blood Pressure Monitoring parameter that was better correlated with 25 hydroxyvitamin D levels. We could not find any association between vitamin D levels and other bone and mineral metabolism parameters. No relationship was seen between low vitamin D levels and left ventricular hypertrophy. On multivariate analysis lower levels of 25 hydroxyvitamin D were independently associated with female gender, previous cardiovascular disease, MDRD4-GFR and higher pulse pressure. CONCLUSIONS: Our study confirm a high prevalence of 25 hydroxyvitamin D insufficiency and deficiency in advanced chronic kidney disease patients, this was associated with the presence of cardiovascular risk markers and previous established cardiovascular disease. However we could not see any relationship with left ventricular hypertrophy which is a known predictor of future cardiovascular events in this population.

Pre-transplant weight but not weight gain is associated with new-onset diabetes after transplantation: a multi-centre cohort Spanish study.

Background. New-onset diabetes after transplantation (NODAT) is associated with poorer outcomes in kidney transplantation (KT). Thus, identification of modifiable risk factors may be crucial for ameliorating the impact of this entity on transplant outcomes. We assessed the relationships between the weight, body mass index (BMI) and weight gain with NODAT.Methods. We retrospectively analysed 2168 KT performed in Spain during 1990, 1994, 1998 and 2002, with a functioning graft after the first year. At 1 year after KT, three groups were considered: (i) NODAT group (n = 215); (ii) impaired fasting glucose (IFG) group (n = 389); (iii) control group (n = 1564).Results. The incidence of NODAT was 10.8%, 9.9% and 10.0% at 3, 12 and 24 months post-transplantation, respectively. Older recipient age (P < 0.0001) and greater use of tacrolimus (P < 0.0001) were observed in NODAT group. Obesity was more frequent in NODAT group (P < 0.0001), but patients with NODAT had a lower weight gain during the first year after KT (P = 0.038). On multivariate analysis, independent risk factors associated with the development of NODAT were: recipient age [odds ratio (OR): 1.060, P = 0.0001], tacrolimus (OR: 1.611, P = 0.005), triglycerides (OR: 1.511, P = 0.018), positive hepatitis C virus (HCV) status (OR: 1.969, P = 0.001) and pre-transplant body mass index (BMI) (OR: 1.135, P = 0.0001), but not the weight gain.Conclusions. BMI, but not the weight gain at 1 year after transplant, is an independent risk factor for NODAT. Tailoring clinical strategies may minimize the impact of this complication.

Randomized controlled study comparing reduced calcineurin inhibitors exposure versus standard cyclosporine-based immunosuppression.

BACKGROUND: Immunosuppressive regimens based on low doses of cyclosporine A (CsA) or tacrolimus (TAC) may improve short-term outcome after kidney transplantation (KT), but the optimal immunosuppressive protocol is currently unknown. METHODS: This study compared the 24-month efficacy and safety of two immunosuppressive regimens using reduced calcineurin inhibitors (CNIs) exposure with standard dosage of CsA in 240 patients who were randomized into three groups: group A (n=80): Thymoglobulin, CsA (4 mg/kg twice daily) plus azathioprine (1.5 mg/kg once daily); group B (n=80): basiliximab, CsA (2 mg/kg/ twice daily) plus mycophenolate mofetil (MMF; 1 g twice daily); and group C (n=80): basiliximab, TAC (0.05 mg/kg/ twice daily) plus MMF (1 g twice daily). Steroid administration was identical for all groups. RESULTS: A significantly better creatinine clearance at 12 months, estimated by Cockcroft-Gault (57+/-12, 65.2+/-20, 73.5+/-27 ml/min, P=0.044), the Jelliffe-2 (51.5+/-16, 56+/-19, 59.4+/-19 ml/min/1.73 m2, P=0.041) and the Modification of Diet in Renal Disease equations (53+/-17, 58.5+/-20, 61.6+/-22 ml/min/1.73 m2, P=0.035), was observed in group C compared with group A. No significant differences were observed between groups B and C. The incidence of biopsy-proven acute rejection was similar between groups (15%, 13.8%, and 16.3%). In addition, patient and graft survival at 24 months were not different between groups. Adverse effects were similar among groups, but cytomegalovirus infections was significantly higher in group A (41% vs. 20% vs. 25%; P=0.008). CONCLUSIONS: Immunosuppressive regimens with reduced CNI exposure provide similar preservation of renal function compared with standard dose of CsA after KT and do not lead to underimmunosuppression.

Impact of metabolic syndrome on graft function and survival after cadaveric renal transplantation.

BACKGROUND: The prevalence and consequences of metabolic syndrome after renal transplantation are not well established. Our aims are to analyze in a historic cohort of consecutive renal transplant recipients without diabetes: (1) the prevalence of metabolic syndrome and its evolution to de novo posttransplantation diabetes mellitus (PTDM), and (2) its impact on graft function and graft and patient survival. METHODS: We studied 230 transplant recipients with stable graft function at 1 year (baseline) and at least 18 months of follow-up (assessment date). Metabolic syndrome is defined using the Adult Treatment Panel III criteria with a slight modification. RESULTS: Metabolic syndrome was present in 22.6% of transplant recipients at baseline, increasing to 37.7% at assessment date. Transplant recipients with metabolic syndrome at baseline more frequently developed PTDM during follow-up than those without metabolic syndrome (P < 0.001). In multiple linear regression analysis, metabolic syndrome was an independent risk factor for decreasing inverse serum creatinine (1/Cr) during follow-up (P = 0.038). In Cox proportional analysis, the hazard ratio for a 30% decrease in 1/Cr over time was 2.6 (95% confidence interval, 1.3 to 5.1; P = 0.005). Graft survival was significantly lower in the metabolic-syndrome group (P = 0.008) and remained significant in multivariate Cox analysis (hazard ratios, 3 to 4.5 in different models). Patient survival also was significantly lower in the metabolic-syndrome group (P = 0.02). CONCLUSION: Metabolic syndrome is a prominent risk factor for PTDM, chronic graft dysfunction, graft loss, and patient death in renal transplant recipients. Because metabolic syndrome is a cluster of modifiable factors, prompt intervention may prevent its consequences.

Treatment with intermittent calcitriol and calcium reduces bone loss after renal transplantation.

BACKGROUND: Bone loss occurs during the first 6 months after renal transplantation (RT), and corticosteroid therapy plays an important role. Although calcium plus vitamin D administration prevents corticosteroid-induced osteoporosis, its use in RT recipients is limited by the risk of hypercalcemia. METHODS: This double-blind, randomized, and controlled prospective intervention trial examined the effect of intermittent calcitriol (0.5 microg/48 h) during the first 3 months after RT, plus oral calcium supplementation (0.5 g/day) during 1 year with calcium supplementation alone. The primary outcome measure was the change in bone mineral density (BMD) at 3 and 12 months after RT; we also explored whether the effect of calcitriol on BMD was different among vitamin D receptor (VDR) genotypes (BsmI). Forty-five recipients were randomized to calcitriol therapy (CT) and 41 were randomized to placebo (PL). RESULTS: Both groups had a similar degree of pre-existing hyperparathyroidism (197 +/- 229 vs. 191 +/- 183 pg/mL), but a more pronounced decrease of parathyroid hormone (PTH) levels after RT was observed in CT patients (at 3 months: 61.4 +/- 42.2 vs. 85.7 +/- 53.1 pg/mL, P= 0.02; at 12 months: 67.3 +/- 33.7 vs. 82.6 +/- 37 pg/mL; P= 0.08). CT patients preserved their BMD at the total hip significantly better than those on PL (3 months: 0.04 +/- 3.3 vs. -1.93 +/- 3.2%, P= 0.01; 12 months: 0.32 +/- 4.8 vs. -2.17 +/- 4.4%, P= 0.03); significant differences were noted at the intertrochanter, trochanter, and Ward's triangle. Differences did not reach significance at the femoral neck. Two CT patients (4.4%) and 4 PL patients (9.8%) developed a hypercalcemic episode during the first 3 months after RT. The effect of CT on BMD at 3 months was more prominent in recipients with the at-risk allele of the VDR gene (P= 0.03). CONCLUSION: Therapy with low-dose calcium supplements during 1 year, plus intermittent calcitriol for 3 months after RT, is safe, decreases PTH levels more rapidly, and prevents bone loss at the proximal femur; a more pronounced effect is seen in recipients with at least one at-risk allele of the VDR genotype.