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The diagnosis of Anderson-Fabry disease is often delayed or even missed. As severe renal manifestations are a hallmark of alfa-galactosidase A (AGAL) deficiency, we tested the hypothesis that Anderson-Fabry disease is under-recognized among male kidney transplant recipients. This nation-wide study in Austria enrolled 1306 patients (ca 65% of all kidney transplanted males) from 30 kidney centers. AGAL activity was determined from filter paper dried blood spots by a fluorescence assay. A positive screening test was defined by an AGAL activity below 1.5 nmol/h/ml. In patients with a positive blood spot-screening test, AGAL activity was re-examined in peripheral blood leukocytes. Genetic testing for mutations in the GLA gene was performed by sequencing to confirm the diagnosis of Anderson-Fabry disease. Two previously not recognized cases with Anderson-Fabry disease were identified. Our study is the first showing that a diagnosis of Anderson-Fabry disease can be missed even in patients who undergo kidney transplantation. Case-finding strategies may be considered a useful tool for diagnosis of this rare disease that may be somewhat more prevalent among kidney transplant recipients compared with dialysis populations.

In kidney transplant recipients (KTR), C-reactive protein (CRP) has been shown to be associated with increased mortality, but data on this association within the high-sensitivity (hs) range of CRP (5 mg/l) are lacking. We prospectively studied 710 prevalent and stable KTR over6 years. We thawed frozen plasma and measured baseline hs-CRP using an ultrasensitive assay. Detailed clinical and demographic baseline characteristics were available for study. We stratified patients by quartile of hs-CRP within the hs range (5 mg/l), and also included KTRs whose hs-CRP was above the hs range (5-10 and10 mg/l). We used multivariate proportional hazards models to test for independent associations. After careful multivariate adjustment, we found a J-shaped association between hs-CRP and mortality. Compared with KTR whose hs-CRP was in the second lowest quartile of hs-CRP (0.06-1.26 mg/l), patients in the lowest quartile (0.06 mg/l) had more than twice their mortality risk (HR = 2.07; 95% CI: 1.05-4.07), as did patients whose hs-CRP wasor =2.44 mg/l (all HRs2.27). No association was found between hs-CRP and death-censored allograft loss. In contrast to the general population, the association between hs-CRP and mortality in KTRs is not linear, but J-shaped, suggesting that KTRs with very low hs-CRP may also be at increased risk of death.

Summary Disturbances in calcium and phosphate metabolism have been linked to increased mortality in hemodialysis patients, but not in kidney transplant recipients (KTR). We enrolled 733 KTR from the Vienna General Hospital into this study. Detailed demographic, clinical, laboratory, and transplant-related information was collected at baseline. We used the Austrian Dialysis and Transplantation Registry for follow-up. Using multivariate proportional hazard regression, we examined the independent associations between serum calcium, serum phosphate, and calcium phosphate (CaPO4) product with the outcomes of death from any cause and kidney allograft loss. Over a median follow-up of >6 years, 154 patients died and 259 kidney allografts were lost. Associations with serum calcium, phosphate concentrations, and CaPO4 product concentrations were found for allograft loss, but not for patient mortality. Patients in the highest quintile of phosphate concentration and CaPO4 product had an increased risk for allograft loss compared with patients in the lowest quintile of these parameters (hazards ratio, HR = 2.15; 95% confidence interval, CI: 1.36–3.40 and HR = 1.72; 95% CI: 1.10–2.71, respectively). High calcium levels were associated with a reduced risk for allograft loss. Results were even more pronounced for death-censored allograft loss. High concentrations of serum phosphate and CaPO4 product were associated with an increased risk for allograft loss in these KTR, whereas high serum calcium concentrations seemed to lower the risk.