Cinacalcet chloride is efficient and safe in renal transplant recipients with posttransplant hyperparathyroidism.

BACKGROUND: Persistent hyperparathyroidism (HPT) is observed in approximately 50% of kidney transplant recipients one year after transplantation. It may result in hypercalcemia, hypophosphatemia, bone demineralization, vascular calcification, lithiasis, and participate in chronic allograft nephropathy. We evaluated the use of the calcimimetic cinacalcet chloride to correct chronic hypercalcemia in posttransplant HPT, in a prospective single-center study. METHODS: Nine patients with persistent hypercalcemia (>2.6 mmol/L) and stable graft function were treated with cinacalcet (30 mg/day, thereafter adapted to obtain normal serum Ca levels) for six months. Their immunosuppressive schedule included mycophenolate mofetil (MMF), steroids, and cyclosporine A (4), tacrolimus (4), or sirolimus (2). RESULTS: Serum Ca levels significantly decreased from 2.75+/-0.15 to 2.59+/-0.10, 2.42+/-0.29 and 2.44+/-0.25 mmol/L by one, two, and six months, respectively (P<0.02, Wilcoxon test for paired data, for all the data points). Parathyroid hormone (PTH) serum levels decreased from 171+/-102 to 134+/-63 pg/ml by two months (P<0.05) and stabilized thereafter (148+/-99 pg/ml at six months; NS). No changes in glomerular filtration rate (49.8+/-18.6 and 51.3+/-19 ml/min at initiation and six months, respectively) and no variation in serum concentration of the immunosuppressive drugs were observed. Three patients withdrew the treatment because gastrointestinal intolerance. CONCLUSION: Cinacalcet allows the correction of hypercalcemia with no interference in immunosuppressive treatment or renal function. However, whether the increased intolerance observed was due to the association of cinacalcet chloride with other drugs required in renal transplantation (e.g., MMF) needs to be assessed.

[Delayed graft function: a frequent but still unsolved problem in renal transplantation]. / La reprise retardée de fonction: une complication fréquente, non résolue, en transplantation rénale.

Delayed graft function (DGF) is a frequent and well-known complication of renal transplantation, which occurs in 30% of cadaver kidney allografts. It has an economic cost that is the result of prolonged patient hospitalization and the need for hemodialysis sessions; it also increases the risk of acute allograft rejection and may affect long-term graft survival. Lots of risk factors were identified, like donor hemodynamic compromise or prolonged cold ischemia time; however, incidence of DGF remains high due to the frequent use of marginal donors due to organ shortage. Recent advances in the pathophysiology of DGF point the importance of the ischemia-reperfusion injury mechanisms and some therapeutics that may reduce them are under investigation, like the use of new solutions to improve organ preservation and the use of some antioxidant and anti-inflammatory drugs.

Lower incidence of chronic allograft nephropathy at 1 year post-transplantation in patients treated with mycophenolate mofetil.

Chronic allograft nephropathy (CAN) is the main cause of graft failure after the first year of transplantation. This prospective, centrally randomized, open-label study was conducted to examine the possibility that mycophenolate mofetil (MMF) can prevent the emergence of CAN. The incidence of biopsy-proven CAN at 1 year was compared between two cyclosporine-based regimens comprising either mycophenolate mofetil (MMF) or azathioprine (AZA). The AZA group (n = 34) and the MMF group (n = 37) were balanced for all baseline characteristics of donors and recipients, the pre-existence of renal lesions on donor biopsy, the incidence of delayed graft function and acute rejection. Based on an intent-to-treat analysis, the number of patients with CAN at 1 year post-transplantation was significantly reduced in the MMF group (17/37-46%) compared with the AZA group (24/34-71%) (p = 0.03). When observed data were considered, 56/71 (78.8%) patients had a 1-year biopsy, and the number of patients with CAN was significantly lowered in the MMF group (9/29-31%) compared with the AZA group (17/27-63%) (p = 0.01). These results suggest a beneficial effect of MMF on the incidence of CAN at 1 year post-transplantation.

Seasonal modifications in blood pressure are mainly related to interdialytic body weight gain in dialysis patients.

BACKGROUND: Longitudinal studies in dialysis patients have identified seasonal variations in blood pressure that may follow climatic parameters such as external temperature and humidity. We aimed to assess the participation of interdialytic body weight gain variations in the seasonal profile of blood pressure. METHODS: Ninety-nine stable patients (40 F/59 M), 52.9 +/- 1.5 years old, dialyzed in a single satellite dialysis unit between January 7, 1991, and September 30, 1998 were studied. Supine systolic and diastolic blood pressure, body weight, and interdialytic body weight gain were determined at every one of the 38,769 dialyses included, and studied along with climatology data obtained from Météo, France. RESULTS: Blood pressure varied throughout the year, following a cyclic pattern. It increased from the autumn months toward winter, and decreased toward the spring and warmer months. Systolic and diastolic blood pressures were strongly correlated with interdialytic body weight gain (r= 0.925; P < 0.0001 and r= 0.888; P= 0.0001, respectively). Blood pressure was also correlated with the climatic factors: rainfall (r= 0.786; P < 0.003 and r= 0.784; P < 0.003), humidity (r= 0.701; P= 0.011 and r= 0.699; P < 0.012), and day light span (r=-0712; P < 0.01, and r=-0.658; P < 0.02, respectively). Multivariate regression analyses taking blood pressure as a dependent variable retained interdialytic body weight gain as the first variable in the model. CONCLUSION: Our results establish a strong link between blood pressure variations and interdialytic body weight gain, showing the important participation of volume state in modulating blood pressure in this group of patients.

Blood pressure is correlated with vitamin d(3) serum levels in dialysis patients.

BACKGROUND/AIMS: The blood pressure, the most influencing factor in cardiovascular disease in end-stage renal failure patients, follows a seasonal variation during the year. Since vitamin D(3) is known to be related to sun exposure, we wanted to evaluate the putative participation of the vitamin D(3) metabolism in blood pressure modifications. METHODS: We studied 22 stable hemodialysis patients (11 females and 11 males, mean age +/- SD 56 +/- 1 year) who had been continuously treated in our dialysis unit for more than 1 year between 1994 and 1997 and did not receive pulse vitamin D(3) treatment. Supine systolic and diastolic blood pressures were measured before every dialysis session (>12,000 measurements) and the intact parathormone (iPTH), 25-hydroxyvitamin D(3) [25(OH)D(3)], and 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] levels every 3 months (>300 determinations). The mean values of blood pressure per season and per patient were taken for analysis using a 4-year longitudinal study design. RESULTS: The blood pressure varied during the years studied following a seasonal trend. It was highest during autumn and tended to decrease during spring and warmer months. Systolic as well as diastolic blood pressures were significantly correlated with the 25(OH)D(3) levels (p = 0.0291 and p = 0.0327, respectively). No correlation was observed between blood pressure and 1,25(OH)(2)D(3) or iPTH levels. CONCLUSION: There is a link between blood pressure and 25(OH)D(3) level. This interrelation is not secondary to a iPTH modulation. Although it cannot be excluded that vitamin D(3) and blood pressure vary following a third factor with seasonal variations, since vitamin D(3) varies during the year, mainly following sun exposure, we suggest that vitamin D(3) is one of the factors participating in the seasonal variation of the blood pressure. Other factors known to control the blood pressure and particularly the extracellular volume overload may also participate.