Pulse contour analysis: a valid assessment of central arterial stiffness in children?

In adults the contour analysis of peripheral pressure waves in the upper limb reflects central aortic stiffness. Here, we wanted to demonstrate the appropriateness of pulse contour analysis to assess large artery stiffness in children. Digital volume pulse analysis, with the computation of the stiffness index and pulse wave velocity between carotid and femoral artery, were simultaneously determined in 79 healthy children between 8years and 15years (mean age 11.4years, 32 girls). The stiffness index of 42 healthy adults (mean age 45.6years, 26 women) served as control. Pulse wave velocity between carotid and femoral artery was directly correlated with systolic pressure and mean blood pressure, as well as with pulse pressure. The results from the stiffness index of children revealed the expected values extrapolated from the linear regression of adulthood stiffness index vs. age. Childhood stiffness index positively correlated with pulse wave velocity (r2 = 0.07, P = 0.02) but not with blood pressure parameters. The exclusion of individuals with an increased vascular tone, as indicated by a reflexion index >90%, improved the correlation between stiffness index and pulse wave velocity (r2 = 0.13, P = 0.001). Our data indicate that digital volume pulse-based analysis has limitations if compared with pulse wave velocity to measure arterial stiffness, mostly in patients with a high vascular ton

The calcimimetic cinacalcet normalizes serum calcium in renal transplant patients with persistent hyperparathyroidism

Background. Treatment of persistent hyperparathyroidism in renal transplant patients resistant to calcium and vitamin D sterols is limited and often requires parathyroidectomy. Given the potential hazards linked to surgery, an alternative approach to manage excess parathyroid hormone (PTH) secretion is needed. Calcimimetics inhibit PTH secretion by modulating the calcium-sensing receptor in the parathyroid. Lowering of the serum calcium concentration with the calcimimetic cinacalcet has previously been demonstrated in patients with primary hyperparathyroidism or with secondary hyperparathyroidism on dialysis. Here we present the first clinical observations of a calcimimetic in patients with persistent hyperparathyroidism. Methods. A 30 mg dose of cinacalcet was prescribed once daily for 3 months to seven female and seven male stable renal transplant patients, aged 23-65 years, 7 months to 14 years after transplantation, with a serum creatinine ranging from 89 to 229 µmol/l and persistent hyperparathyroidism. Concomitant medication included cyclosporin and low-dose prednisone in all patients. Results. On cinacalcet, serum calcium decreased and normalized in all but two patients (baseline 2.72±0.03 mmol/l; 1 month 2.42±0.04 mmol/l, P<0.001), whereas serum PTH and phosphate levels did not change significantly. A slight reduction in renal function, as assessed by serum creatinine concentration, was observed at months 2 and 3 (P<0.05). An immunoglobulin-deficient patient developed colitis after 1 week of treatment and cinacalcet was withdrawn. No patient stopped cinacalcet because of other presumed side effects. Conclusion. Calcimimetics are a promising therapy in renal transplant patients with persistent hyperparathyroidism. Prospective controlled studies must now be designed focusing on functionally relevant musculo-skeletal end-points and allowing the exclusion of negative effects on long-term renal and general outcome of such patient

Effect of cinacalcet cessation in renal transplant recipients with persistent hyperparathyroidism

Background. Persistent hyperparathyroidism after renal transplantation affects bone and allografts. Cinacalcet, a calcimimetic, reduces serum calcium and PTH in renal transplant recipients with persistent hyperparathyroidism. Here, we address the question whether this effect of cinacalcet persists after withdrawal. Methods. Therefore, cinacalcet was stopped after 12 months treatment in 10 stable renal transplant patients. Serum calcium, phosphate, PTH, creatinine and cystatin C were monitored for 3 months. Results. Serum calcium, normalized in nine patients before cessation of cinacalcet (2.32 ± 0.05mmol/l, mean ± SEM), increased after 3 months of discontinuation by 0.17 ± 0.04mmol/l, P < 0.05, but remained within the normal range in eight patients. Compared with the time point of cessation, PTH remained unchanged or decreased further after 3 months without therapy in six patients. Measurements of cystatin C suggested an improvement of the glomerular filtration rate after cessation in 9 out of 10 patients (1.55 ± 0.09 vs 1.33 ± 0.12 mg/l, P < 0.01). Conclusion. First, a beneficial effect of cinacalcet beyond the duration of a 12-month therapy appears to be present in some patients and second, the previously suspected influence of cinacalcet therapy on renal function is reversible. Thus, it is reasonable to consider a trial of cinacalcet cessation to identify these patients. The optimal time point for such a discontinuation is unknown. The present observations are preliminary. They clearly require a prospective randomized trial for definitive confirmatio

Influence of Immunosuppressive Regimen on Diffusivity and Oxygenation of Kidney Transplants-Analysis of Functional MRI Data from the Randomized ZEUS Trial.

The ZEUS study was a multi-center randomized controlled trial investigating the effect of early conversion from a ciclosporin-based to an everolimus-based regimen on graft function twelve months post-transplantation. In this investigator-initiated sub-study, functional magnetic resonance imaging (fMRI) of kidney grafts was prospectively performed to non-invasively assess differences in graft oxygenation, diffusion and perfusion between groups and time-points using diffusion-weighted imaging (DWI) and blood oxygen level-dependent (BOLD)-MRI. Sixteen patients underwent DWI and BOLD-MRI at months 4.5 and 12 post-transplantation on a 3 Tesla and 1.5 Tesla (n = 3) MR scanner. After exclusion due to image quality, outlier values or missing data, DWI was analyzed for ten subjects; BOLD for eight subjects. The diffusion coefficient ADCD decreased in the CsA-treated group over time, whereas it increased in the EVE group (p = 0.046, medulla). The change in ADCD from months 4.5 to 12 significantly differed between groups in the cortex (p = 0.033) and medulla (p = 0.019). In BOLD, cortico-medullary transverse relaxation rate R2* increased (decreased tissue oxygen) in the CsA-treated and decreased in EVE-treated groups over time. Similarly, R2* values at month 12 were higher in the CsA-treated group compared to the EVE-treated group. There was no significant difference for the perfusion fraction FP. In conclusion, this prospective sub-study of the ZEUS trial suggests an impact of immunosuppressive regimen on fMRI parameters of the kidney graft

PTH and 1.25 vitamin D response to a low-calcium diet is associated with bone mineral density in renal stone formers

Background. Renal calcium stones and hypercalciuria are associated with a reduced bone mineral density (BMD). Therefore, the effect of changes in calcium homeostasis is of interest for both stones and bones. We hypothesized that the response of calciuria, parathyroid hormone (PTH) and 1.25 vitamin D to changes in dietary calcium might be related to BMD. Methods. A single-centre prospective interventional study of 94 hyper- and non-hypercalciuric calcium stone formers consecutively retrieved from our stone clinic. The patients were investigated on a free-choice diet, a low-calcium diet, while fasting and after an oral calcium load. Patient groups were defined according to lumbar BMD (z-score) obtained by dual X-ray absorptiometry (group 1: z-score 0.5, n = 28). The effect of the dietary interventions on calciuria, 1.25 vitamin D and PTH in relation to BMD was measured. Results. An inverse relationship between BMD and calciuria was observed on all four calcium intakes (P = 0.009). On a free-choice diet, 1.25 vitamin D and PTH levels were identical in the three patient groups. However, the relative responses of 1.25 vitamin D and PTH to the low-calcium diet were opposite in the three groups with the highest increase of 1.25 vitamin D in group 1 and the lowest in group 3, whereas PTH increase was most pronounced in group 3 and least in group 1. Conclusion. Calcium stone formers with a low lumbar BMD exhibit a blunted response of PTH release and an apparently overshooting production of 1.25 vitamin D following a low-calcium die

Evaluation of renal allograft function early after transplantation with diffusion-weighted MR imaging

Aims: To determine the inter-patient variability of apparent diffusion coefficients (ADC) and concurrent micro-circulation contributions from diffusion-weighted MR imaging (DW-MRI) in renal allografts early after transplantation, and to obtain initial information on whether these measures are altered in histologically proven acute allograft rejection (AR). Methods: DW-MRI was performed in 15 renal allograft recipients 5-19days after transplantation. Four patients presented with AR and one with acute tubular necrosis (ATN). Total ADC (ADCT) was determined, which includes diffusion and micro-circulation contributions. Furthermore, diffusion and micro-circulation contributions were separated, yielding the "perfusion fraction” (FP), and "perfusion-free” diffusion (ADCD). Results: Diffusion parameters in the ten allografts with stable function early after transplantation demonstrated low variabilities. Values for ADCT and ADCD were (×10−5mm2/s) 228 ± 14 and 203 ± 9, respectively, in cortex and 226 ± 16 and 199 ± 9, respectively, in medulla. FP values were 18 ± 5% in cortex and 19 ± 5% in medulla. FP values were strongly reduced to less than 12% in cortex and medulla of renal transplants with AR and ATN. FP values correlated with creatinine clearance. Conclusion: DW-MRI allows reliable determination of diffusion and micro-circulation contributions in renal allografts shortly after transplantation; deviations in AR indicate potential clinical utility of this method to non-invasively monitor derangements in renal allograft

ANCA-negative pauci-immune renal vasculitis: histology and outcome

Background. Pauci-immune renal vasculitis with focal glomerular necrosis and crescent formation is usually associated with anti-neutrophil cytoplasmic antibodies (ANCAs). However, ANCA's are absent in up to 10% of cases, which constitutes a rarely studied variant of renal vasculitis. Methods. This retrospective multicentre cohort study analyzed the presenting features, renal histology and outcome in 20 patients with pauci-immune crescentic necrotizing renal vasculitis in whom indirect immunofluorescence did not detect ANCA. Results. Renal histology revealed a high percentage of active glomerular lesions (50%), mainly cellular crescents, 28% of them with glomerular necrosis. Chronic tissue damage with glomerulosclerosis (21%) and diffuse interstitial fibrosis (40%) was already present at diagnosis, more prominent than in historical PR3-positive patients. Infiltrates of polymorphonuclear neutrophils in glomerular capillary loops were observed in 40% of all biopsies, mainly in necrotic lesions. The subsets of interstitially infiltrating leukocytes similar to ANCA-associated disease. Microscopic polyangiitis was diagnosed in 17 patients, Wegener's granulomatosis in two and renal-limited vasculitis in one. The patients median disease extent index (DEI) of 5 (range 4-11) reflected a systemic vasculitis. ANCA-negative vasculitis was not associated with infection or malignancy. Renal outcome was correlated to DEI (P = 0.032) and serum creatinine at diagnosis (P = 0.04). The mortality rate was high (35%) and closely related to age above 65 years at diagnosis (P = 0.014). Conclusions. The histological findings and prognosis in ANCA-negative renal vasculitis are comparable with those of ANCA-positive disease. Our data underline the importance of the exact diagnosis in an active vasculitic disease process even in the absence of ANCA

Heritability, determinants and reference values of renal length: a family-based population study

Objectives: In this population-based study, reference values were generated for renal length, and the heritability and factors associated with kidney length were assessed. Methods: Anthropometric parameters and renal ultrasound measurements were assessed in randomly selected nuclear families of European ancestry (Switzerland). The adjusted narrow sense heritability of kidney size parameters was estimated by maximum likelihood assuming multivariate normality after power transformation. Gender-specific reference centiles were generated for renal length according to body height in the subset of non-diabetic non-obese participants with normal renal function. Results: We included 374 men and 419 women (mean ± SD, age 47 ± 18 and 48 ± 17years, BMI 26.2 ± 4 and 24.5 ± 5kg/m2, respectively) from 205 families. Renal length was 11.4 ± 0.8cm in men and 10.7 ± 0.8cm in women; there was no difference between right and left renal length. Body height, weight and estimated glomerular filtration rate (eGFR) were positively associated with renal length, kidney function negatively, age quadratically, whereas gender and hypertension were not. The adjusted heritability estimates of renal length and volume were 47.3 ± 8.5% and 45.5 ± 8.8%, respectively (P < 0.001). Conclusion: The significant heritability of renal length and volume highlights the familial aggregation of this trait, independently of age and body size. Population-based references for renal length provide a useful guide for clinicians. Key Points: • Renal length and volume are heritable traits, independent of age and size. • Based on a European population, gender-specific reference values/percentiles are provided for renal length. • Renal length correlates positively with body length and weight. • There was no difference between right and left renal lengths in this study. • This negates general teaching that the left kidney is larger and longe

Serum calcification propensity is independently associated with disease activity in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is associated with severe cardiovascular complications. The T50 score is a novel functional blood test quantifying calcification propensity in serum. High calcification propensity (or low T50) is a strong and independent determinant of all-cause mortality in various patient populations. A total of 168 patients with ≥ 4 American College of Rheumatology (ACR) diagnostic criteria from the Swiss Systemic lupus erythematosus Cohort Study (SSCS) were included in this analysis. Serum calcification propensity was assessed using time-resolved nephelometry. The cohort mainly consisted of female (85%), middle-aged (43±14 years) Caucasians (77%). The major determinants of T50 levels included hemoglobin, serum creatinine and serum protein levels explaining 43% of the variation at baseline. Integrating disease activity (SELENA-SLEDAI) into this multivariate model revealed a significant association between disease activity and T50 levels. In a subgroup analysis considering only patients with active disease (SELENA-SLEDAI score ≥4) we found a negative association between T50 and SELENA-SLEDAI score at baseline (Spearman's rho -0.233, P = 0.02). Disease activity and T50 are closely associated. Moreover, T50 levels identify a subgroup of SLE patients with ongoing systemic inflammation as mirrored by increased disease activity. T50 could be a promising biomarker reflecting SLE disease activity and might offer an earlier detection tool for high-risk patients