Incidence of renal failure and nephroprotection by RAAS inhibition in heterozygous carriers of X-chromosomal and autosomal recessive Alport mutations.

We studied here the clinical course of heterozygous carriers of X-linked Alport syndrome and a subgroup of patients with thin basement membrane disease due to heterozygous autosomal recessive Alport mutations whose prognosis may be worse than formerly thought. We analyzed 234 Alport carriers, including 29 with autosomal recessive mutations. Using Kaplan-Meier estimates and log-rank tests, autosomal and X-linked carriers were found to have similar incidences of renal replacement therapy, proteinuria, and impaired creatinine clearance. Further, age at onset of renal replacement therapy did not differ between X-chromosomal and autosomal carriers. Both groups showed an impaired life expectancy when reaching renal replacement therapy. RAAS inhibition significantly delayed the onset of end-stage renal failure. Not only carriers of X-linked Alport mutations but also heterozygous carriers of autosomal recessive mutations were found to have an increased risk for worse renal function. The risk of end-stage renal disease in both groups affected life expectancy, and this should cause a greater alertness toward patients presenting with what has been wrongly termed 'familial benign hematuria.' Timely therapy can help to delay onset of end-stage renal failure. Thus, yearly follow-up by a nephrologist is advised for X-linked Alport carriers and patients with thin basement membrane nephropathy, microalbuminuria, proteinuria, or hypertension.

Design of an eccentric recumbent ergometer to elicit delayed onset muscle soreness.

INTRODUCTION: Our objective was to design an eccentric bicycle design to elicit delayed onset muscle soreness (DOMS). METHODS: To assess the bicycle designs' ability to elicit DOMS, fourteen, recreationally active, males performed five-minutes of eccentric bicycling at 50% of their individualized power determined from a modified six-second Wingate test. Outcome measures to assess DOMS included the Likert pain scale, creatine kinase, lactate blood concentration, and pressure algometry detection evaluated at four time points (baseline (before the eccentric bicycling), immediate post, 24 hours post, and 48 hours post). RESULTS: The Likert pain scale was different (F = 75.88, p < 0.001) at baseline (0.14 ± 0.36) and immediate post (0.21 ± 0.43), compared to 24 hours post (3.07 ± 0.83), and 48 hours post (2.93 ± 1.07). No changes were reported for creatine kinase (F = 0.7167, p = 0.475), lactate blood concentration (F = 2.313, p = 0.107), or pressure algometry detection. CONCLUSIONS: To understand mechanisms of DOMS, there is a need for a consistent, reliable method for producing DOMS. Our eccentric bicycle design and protocol offers an alternative approach to previous eccentric ergometer designs - demonstrating the potential to elicit DOMS in one, five-minute session.

Outcomes of male patients with Alport syndrome undergoing renal replacement therapy.

BACKGROUND AND OBJECTIVES: Patients with the hereditary disease Alport syndrome commonly require renal replacement therapy (RRT) in the second or third decade of life. This study compared age at onset of RRT, renal allograft, and patient survival in men with Alport syndrome receiving various forms of RRT (peritoneal dialysis, hemodialysis, or transplantation) with those of men with other renal diseases. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients with Alport syndrome receiving RRT identified from 14 registries in Europe were matched to patients with other renal diseases. A linear spline model was used to detect changes in the age at start of RRT over time. Kaplan-Meier method and Cox regression analysis were used to examine patient and graft survival. RESULTS: Age at start of RRT among patients with Alport syndrome remained stable during the 1990s but increased by 6 years between 2000-2004 and 2005-2009. Survival of patients with Alport syndrome requiring dialysis or transplantation did not change between 1990 and 2009. However, patients with Alport syndrome had better renal graft and patient survival than matched controls. Numbers of living-donor transplantations were lower in patients with Alport syndrome than in matched controls. CONCLUSIONS: These data suggest that kidney failure in patients with Alport syndrome is now being delayed compared with previous decades. These patients appear to have superior patient survival while undergoing dialysis and superior patient and graft survival after deceased-donor kidney transplantation compared with patients receiving RRT because of other causes of kidney failure.