Evolution of secondary hyperparathyroidism in patients following return to hemodialysis after kidney transplant failure.

INTRODUCTION: Severe uncontrolled secondary hyperparathyroidism and kidney transplantation history are both risk factors for fractures in hemodialyzed patients. Moreover, patients who return to dialysis after transplant failure have more severe infections/anemia and higher mortality risk than transplant-naive patients starting dialysis with native kidneys. In this context, our aim was to test the hypothesis that transplant failure patients have more secondary hyperparathyroidism than transplant-naive patients. METHODS: We retrospectively compared 29 transplant failure patients to 58 transplant-naive patients matched for age, sex, chronic kidney disease duration and diabetes condition (1 transplant failure/2 transplant-naive ratio), who started dialysis between 2010 and 2014. Clinical and biological data were collected at baseline, 6 and 12 months. FINDINGS: At baseline, neither serum parathyroid hormone (transplant-naive: 386±286pg/mL; transplant failure: 547±652pg/mL) nor serum 25-hydroxyvitamin D (transplant-naive: 27.8±17.0µg/L, transplant failure: 31.1±14.9µg/L) differed between groups. However, serum parathyroid hormone at 12 months and the proportion of patients with uncontrolled secondary hyperparathyroidism (parathyroid hormone>540pg/mL, KDIGO criteria) were significantly higher in transplant failure than in transplant-naive (parathyroid hormone: 286±205 vs. 462±449, P<0.01; uncontrolled secondary hyperparathyroidism: 30% vs. 13%, P<0.01, respectively). Within the transplant failure group, patients with uncontrolled secondary hyperparathyroidism at 12 months were younger than patients with normal or low parathyroid hormone. DISCUSSION: This retrospective and monocentric study suggests that transplant failure patients are more likely to develop secondary hyperparathyroidism. Thus, finding high serum parathyroid hormone in young transplant failure patients, who are expected to undergo further transplantations, should incite physicians to treat early and more aggressively this complication.

[Acute kidney injury in thromboangiitis obliterans disease]. / Ischémie rénale bilatérale par thrombis de la micro-circulation rénale dans le cadre d'une maladie de Buerger.

Buerger's disease or thombo-angiitis obliterans disease is a small vessel's vasculitis, frequently observed in young and smoker's males. Diagnosis is based on both clinical and radiological arguments. There is no specific treatment designed for this disease. We report the case of 43 years old patient presenting with an acute kidney injury associated with Buerger's disease. We reviewed the different case of kidney disease in this rare disease.

The use of bone mineral density measured by dual energy X-ray absorptiometry (DXA) and peripheral quantitative computed microtomography in chronic kidney disease.

Chronic kidney disease (CKD) is a risk factor for fractures. The current evaluation of fracture risk is based upon the combination of various clinical factors and quantitative imaging of bone. X-ray-based tools were developed to evaluate bone status and predict fracture risk. Dual energy X-ray absorptiometry (DXA) is available worldwide. Longitudinal studies showed that low areal Bone Mineral Density (BMD) measured by DXA predicts fractures in the CKD population as it does in non uremic populations, with good specificity and moderate sensitivity. Peripheral quantitative computed tomography (pQCT) and high resolution pQCT are research tools which measure volumetric BMD at the tibia and radius. They are able to discriminate between the cortical and trabecular envelopes which are differentially affected by renal osteodystrophy. In CKD, a rapid thinning and increased porosity at the cortex is observed which is associated with increased the risk for fracture.

Serum cystatin C is a determinant of central pressure augmentation index measured by oscillometric method in renal transplant recipients.

BACKGROUND: Serum cystatin C (ScysC) may help predicting cardiovascular outcome not only through its ability to detect renal dysfunction but also through its potential connection to others factors that are directly related to cardiovascular diseases. We explored the potential association of ScysC with arterial stiffness--a major contributor to cardiovascular disease--in renal transplant recipients (RTR). METHODS: Traditional and non-traditional cardio-vascular risk factors were collected from 215 stable RTR whom arterial stiffness was evaluated by the measure of the augmentation index of central pressure (AIx) determined by the arteriograph device. Serum creatinine and ScysC were measured the same day using standardized methods. Association between ScysC and AIx was examined in univariate and multivariate linear regression analysis. RESULTS: In univariate analysis, ScysC was strongly associated with AIx. This relationship was not confounded by age, gender, length of time spent on dialysis and transplantation vintage. Adjustment on the level of GFR estimated by the MDRD Study equation attenuated but did not abolish the association between ScysC and AIx. CONCLUSIONS: In conclusion, ScysC is an independent predictor of AIx in RTR. Our data suggest that arterial stiffness may partially mediate the association between ScysC and cardiovascular risk in renal transplantation.

Early conversion from twice-daily tacrolimus to once-daily extended formulation in renal transplant patients before hospital discharge.

BACKGROUND: Although the once-daily formulation of tacrolimus (ADVAGRAF) is approved in renal transplantation to be used immediately after surgery, conventional twice-daily formulation offers better flexibility to adjust the dosage of tacrolimus during the initial period of transplantation. MATERIAL AND METHODS: We retrospectively report here our initial experience with a strategy of an early conversion from PROGRAF to ADVAGRAF before hospital discharge. RESULTS: Forty-eight de novo renal transplant recipients were started on PROGRAF and then switched to ADVAGRAF after a median time of 11 days and 4.5 days, respectively, before discharge. In terms of tacrolimus exposure, great inter-individual heterogeneity was noted, with 56% of patients experiencing a clinically significant modification in post-switch tacrolimus blood trough levels. Modification in post-switch drug exposure was poorly predicted by change in tacrolimus daily dosage. Six-month post-transplant outcome was similar in patients converted to ADVAGRAF to that of patients who had remained on PROGRAF during the same period of time. Our data suggest that an early conversion from PROGRAF to ADVAGRAF during the hospital stay may be safely undertaken, provided tacrolimus exposure is tightly monitored in patients. CONCLUSIONS: This strategy might represent an alternative to the immediate post-transplant introduction of ADVAGRAF and needs to be clinically validated in large-scale controlled trials.

Parathyroid hormone 1-84 targets bone vascular structure and perfusion in mice: impacts of its administration regimen and of ovariectomy.

Bone vessel functions during bone remodeling are poorly understood. They depend on both vessel network structure and vasomotor regulation. Parathyroid hormone (PTH) is a systemic vasodilator that may modulate microvascularization. Moreover, although intermittent PTH is anti-osteoporotic, continuous PTH administration can be catabolic for bone. Finally, ovariectomy (OVX) reduces bone perfusion and vessel density in mice. We reasoned that the effects of PTH on bone vascularization might depend on its administration regimen and be impacted by ovariectomy. A 100-µg/kg PTH 1-84 daily dose was administered for 15 days to 4-month-old female C57BL/6 mice, either as daily sc injection (iPTH) or continuously (cPTH; ALZET minipump). Blood pressure (BP) and tibia bone perfusion were measured in vivo with a laser Doppler device. Histomorphometry of bone and barium-contrasted vascular network were performed on the same tibia. Compared with untreated controls, both iPTH and cPTH increased bone formation but had opposite effects on resorption. Both iPTH and cPTH were slightly angiogenic. Intermittent PTH increased microvessel size (+48%, p < 0.001), whereas cPTH decreased it (-29%, p = 0.009). iPTH increased bone perfusion (27%, p < 0.001) with no change in BP, whereas cPTH did not. The vascular effects of a 15-day iPTH treatment were analyzed in OVX mice and compared with sham-operated and OVX untreated controls. Two other anti-osteoporotic drugs, zoledronate (one injection, 70 µg/kg) and propranolol, (5 mg/kg/d) were tested in OVX mice. Although no change in bone mass was observed, iPTH stimulated bone formation and prevented the OVX-induced reduction in bone perfusion and vessel density. Both zoledronate and propranolol strongly lowered bone turnover, but surprisingly, zoledronate prevented OVX-induced reduction in bone perfusion but propranolol did not. Our integrative approach thus demonstrates that the effects of PTH on bone vessel structure and function depend on its mode of administration as well as on the HPG-axis hormonal status, and that OVX-induced vascular changes are prevented by iPTH.