Background and objectives The calcimimetic cinacalcet reduced the risk of death or cardiovascular (CV) events in older, but not younger, patients with moderate to severe secondary hyperparathyroidism (HPT) who were receiving hemodialysis. To determine whether the lower risk in younger patients might be due to lower baseline CV risk and more frequent use of cointerventions that reduce parathyroid hormone (kidney transplantation, parathyroidectomy, and commercial cinacalcet use), this study examined the effects of cinacalcet in older ($65 years, n=1005) and younger (,65 years, n=2878) patients.Design, setting, participants, & measurements Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) was a global, multicenter, randomized placebo-controlled trial in 3883 prevalent patients on hemodialysis, whose outcomes included death, major CV events, and development of severe unremitting HPT. The age subgroup analysis was prespecified.Results Older patients had higher baseline prevalence of diabetes mellitus and CV comorbidity. Annualized rates of kidney transplantation and parathyroidectomy were .3-fold higher in younger relative to older patients and were more frequent in patients randomized to placebo. In older patients, the adjusted relative hazard (95% confidence interval) for the primary composite (CV) end point (cinacalcet versus placebo) was 0.70 (0.60 to 0.81); in younger patients, the relative hazard was 0.97 (0.86 to 1.09). Corresponding adjusted relative hazards for mortality were 0.68 (0.51 to 0.81) and 0.99 (0.86 to 1.13). Reduction in the risk of severe unremitting HPT was similar in both groups. ConclusionsIn the EVOLVE trial, cinacalcet decreased the risk of death and of major CV events in older, but not younger, patients with moderate to severe HPT who were receiving hemodialysis. Effect modification by age may be partly explained by differences in underlying CV risk and differential application of cointerventions that reduce parathyroid hormone.

Alport syndrome (AS) is an inherited type IV collagen nephropathies characterized by microscopic hematuria during early childhood, the development of proteinuria and progression to end-stage renal disease. Since choosing the right therapy, even before the onset of proteinuria, can delay the onset of end-stage renal failure and improve life expectancy, the earliest possible differential diagnosis is desired. Practically, this means the identification of mutation(s) in COL4A3-A4-A5 genes. We used an efficient, next generation sequencing based workflow for simultaneous analysis of all three COL4A genes in three individuals and fourteen families involved by AS or showing different level of Alport-related symptoms. We successfully identified mutations in all investigated cases, including 14 unpublished mutations in our Hungarian cohort. We present an easy to use unified clinical/diagnostic terminology and workflow not only for X-linked but for autosomal AS, but also for Alport-related diseases. In families where a diagnosis has been established by molecular genetic analysis, the renal biopsy may be rendered unnecessary.

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Liver failure carries a high mortality, both the acute type with no pre-existing liver disease (acute liver failure) and the acute decompensation superimposed on a chronic liver disorder (acute on chronic liver failure). Today, liver transplantation still represents the only curative treatment for liver failure due to end-stage liver diseases. Donor organ shortage is still the major limitation and many patients die while awaiting transplantation. Due to the scarcity of donor organs, liver support technologies are being developed to support patients with severe liver failure until either an organ becomes available for transplantation or their livers recover from injury. Early devices including hemodialysis, hemoperfusion, exchange transfusion, cross-hemodialysis, cross-circulation and plasmapheresis appeared inefficient. In the present day, liver support systems' designs fall into two main categories: cell-based, so-called bioartificial and non-cell-based, also known as artificial systems. Bioartificial liver support systems use either porcine hepatocytes or human hepatoma cell lines housed within a hollow-fiber bioreactor. The system perfuses the patient's whole blood or separated plasma through the luminal space in the bioreactor. Theoretically, these methods should optimally resemble normal hepatic tissue structure and function. However, the existing bioartificial systems are far from ideal solution in terms of immunological, infectological, oncological and financial problems and must still be thought of as experimental. The artificial systems are already available for the clinicians in limited quantities. These non-cell-based devices are intended to remove protein-bound and water-soluble toxins without providing synthetic function, which can be partially replaced with substitution of the failing substances (plasma proteins, coagulation factors). These systems include the hemodiabsorption (Liver Dialysis Unit) which is commercially available in the United States, the albumin dialysis which is available in Europe and the newly developed fractionated plasma separation and adsorption (FPSA) system. The simple method of albumin dialysis is "single pass albumin dialysis" (SPAD), which evolved into the so-called "molecular adsorbent recirculating system"(MARS). Prometheus system combines the FPSA method with high-flux hemodialysis. Although the results of many experimental and clinical trials prove the efficacy of the above mentioned methods, large randomized controlled trials are mandatory to establish the impact on survival benefit of artificial and bioartificial support systems versus standard therapy.