Objective
The long‐term effects of enzyme‐replacement therapy (ERT) in Fabry disease are unknown. Thus, the aim of this study was to determine whether ERT in patients with advanced Fabry disease ...affects progression towards ‘hard’ clinical end‐points in comparison with the natural course of the disease.
Methods
A total of 40 patients with genetically proven Fabry disease (mean age 40 ± 9 years; n = 9 women) were treated prospectively with ERT for 6 years. In addition, 40 subjects from the Fabry Registry, matched for age, sex, chronic kidney disease stage and previous transient ischaemic attack (TIA), served as a comparison group. The main outcome was a composite of stroke, end‐stage renal disease (ESRD) and death. Secondary outcomes included changes in myocardial left ventricular (LV) wall thickness and replacement fibrosis, change in glomerular filtration rate (GFR), new TIA and change in neuropathic pain.
Results
During a median follow‐up of 6.0 years (bottom and top quartiles: 5.1, 7.2), 15 events occurred in 13 patients (n = 7 deaths, n = 4 cases of ESRD and n = 4 strokes). Sudden death occurred (n = 6) only in patients with documented ventricular tachycardia and myocardial replacement fibrosis. The annual progression of myocardial LV fibrosis in the entire cohort was 0.6 ± 0.7%. As a result, posterior end‐diastolic wall thinning was observed (baseline, 13.2 ± 2.0 mm; follow‐up, 11.4 ± 2.1 mm; P < 0.01). GFR decreased by 2.3 ± 4.6 mL min−1 per year. Three patients experienced a TIA. The major clinical symptom was neuropathic pain (n = 37), and this symptom improved in 25 patients. The event rate was not different between the ERT group and the untreated (natural history) group of the Fabry Registry.
Conclusion
Despite ERT, clinically meaningful events including sudden cardiac death continue to develop in patients with advanced Fabry disease.
The recent research findings concerning syndromes of muscle wasting, malnutrition, and inflammation in individuals with chronic kidney disease (CKD) or acute kidney injury (AKI) have led to a need ...for new terminology. To address this need, the International Society of Renal Nutrition and Metabolism (ISRNM) convened an expert panel to review and develop standard terminologies and definitions related to wasting, cachexia, malnutrition, and inflammation in CKD and AKI. The ISRNM expert panel recommends the term ‘protein–energy wasting’ for loss of body protein mass and fuel reserves. ‘Kidney disease wasting’ refers to the occurrence of protein–energy wasting in CKD or AKI regardless of the cause. Cachexia is a severe form of protein–energy wasting that occurs infrequently in kidney disease. Protein–energy wasting is diagnosed if three characteristics are present (low serum levels of albumin, transthyretin, or cholesterol), reduced body mass (low or reduced body or fat mass or weight loss with reduced intake of protein and energy), and reduced muscle mass (muscle wasting or sarcopenia, reduced mid-arm muscle circumference). The kidney disease wasting is divided into two main categories of CKD- and AKI-associated protein–energy wasting. Measures of chronic inflammation or other developing tests can be useful clues for the existence of protein–energy wasting but do not define protein–energy wasting. Clinical staging and potential treatment strategies for protein–energy wasting are to be developed in the future.
Zusammenfassung
Renale Effekte von Empagliflozin und Canagliflozin
In den Jahren 2016 und 2017 wurden 2 große Outcomestudien, EMPA-REG OUTCOME („empagliflozin cardiovascular outcome event trial in ...type 2 diabetes mellitus patients“) und CANVAS („canagliflozin cardiovascular assessment study – renal endpoints“), mit den SGLT-2-Inhibitoren (SGLT: „sodium dependent glucose transporter“) Empagliflozin und Canagliflozin publiziert, die beide renoprotektive Effekte in Hinblick auf die Progression der diabetischen Nierenerkrankung hatten.
Renoprotektion im fortgeschrittenen Stadium der Nierenschädigung
Analysen der EMPA-REG OUTCOME-Studie ergaben zusätzlich, dass Empagliflozin nicht nur bei Diabetespatienten mit einer geschätzten glomerulären Filtrationsrate (eGFR) von >60 ml/min und 1,73 m
2
kardiovaskuläre und renale Endpunkte signifikant reduzierte, sondern auch bei Patienten mit einer eGFR von 30–60 ml/min und 1,73 m
2
die gleichen Effekte aufwies.
Lysosomal storage disorders (LSD) are rare diseases, caused by inherited deficiencies of lysosomal enzymes/transporters, that affect 1 in 7000 to 1 in 8000 newborns. Individuals with LSDs face long ...diagnostic journeys during which debilitating and life-threatening events can occur. Clinical trials and classical descriptions of LSDs typically focus on common manifestations, which are not representative of the vast phenotypic heterogeneity encountered in real-world experience. Additionally, recognizing that there was a limited understanding of the natural history, disease progression, and real-world clinical outcomes of rare LSDs, a collaborative partnership was pioneered 30 years ago to address these gaps. The Rare Disease Registries (RDR) (for Gaucher, Fabry, Mucopolysaccharidosis type I, and Pompe), represent the largest observational database for these LSDs. Over the past thirty years, data from the RDRs have helped to inform scientific understanding and the development of comprehensive monitoring and treatment guidelines by creating a framework for data collection and establishing a standard of care, with an overarching goal to improve the quality of life of affected patients. Here, we highlight the history, process, and impact of the RDRs, and discuss the lessons learned and future directions.
Prevention of heart failure relies on the early identification and control of risk factors. We aimed to identify the frequency and characteristics of individuals at risk of heart failure in the ...general population.
We report cross-sectional data from the prospective Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB) cohort study investigating a representative sample of residents of Würzburg, Germany. Sampling was stratified 1:1 for sex and 10:27:27:27:10 for age groups of 30-39/40-49/50-59/60-69/70-79 years. Heart failure precursor stages were defined according to American College of Cardiology/American Heart Association: stage A (risk factors for heart failure), stage B (asymptomatic cardiac dysfunction). The main results were internally validated in the second half of the participants. The derivation sample comprised 2473 participants (51% women) with a distribution of 10%/28%/25%/27%/10% in respective age groups. Stages A and B were prevalent in 42% and 17% of subjects, respectively. Of stage B subjects, 31% had no risk factor qualifying for stage A (group 'B-not-A'). Compared to individuals in stage B with A criteria, B-not-A were younger, more often women, and had left ventricular dilation as the predominant B qualifying criterion (all P < 0.001). These results were confirmed in the validation sample (n = 2492).
We identified a hitherto undescribed group of asymptomatic individuals with cardiac dysfunction predisposing to heart failure, who lacked established heart failure risk factors and therefore would have been missed by conventional primary prevention. Further studies need to replicate this finding in independent cohorts and characterise their genetic and -omic profile and the inception of clinically overt heart failure in subjects of group B-not-A.
IgA nephropathy (IGAN) rarely can present as a crescent and progressive form leading to end-stage renal disease (ESRD) in a short period of time. Recurrence of IGAN after kidney transplantation is ...frequent, and complement components such as C3, C4d, and C5 seem to be involved. We present a case of a young male patient with ESRD caused by rapidly progressive IGAN and who demonstrated rapid recurrence of crescentic IGAN after kidney donation.
In September 2014, a 28-year-old male patient was hospitalized due to IGAN with 60% of crescents. Cyclophosphamide, steroids, and plasmapheresis did not prevent ESRD. After 8 months of peritoneal dialysis, the patient received a blood group–compatible living donor kidney from his 57-year-old mother. Immunosuppression consisted of tacrolimus, mycophenolic acid, and steroids without induction therapy. Acute graft failure occurred 2 months later, and graft biopsy results revealed recurrence of crescentic IGAN. Cyclophosphamide was added to tacrolimus and steroid treatment, but graft function could not be restored despite viable kidney tissue in repeated biopsy specimens. Rescue therapy with 4 single doses of eculizumab was introduced while hemodialysis had already been initiated. After a cumulative dose of 1800 mg of eculizumab, kidney function did not recover.
In this case, eculizumab was not effective in treating IGAN recurrence after transplantation. Therapy was started late when hemodialysis had already been initiated; an earlier start of therapy might be more effective.
•We report a case of the rare recurrence of crescentic IgA nephropathy (IGAN) after living kidney donation with fatal progression.•Because cyclophosphamide, steroids and plasmapheresis could not prevent graft failure and there is evidence of the involvement of complement components in IGAN, we started therapy with the complement binding antibody eculizumab.•This is the first reported case of rescue therapy with eculizumab in IGAN after kidney transplantation, and although we could not prevent graft loss in this case, we wanted to share the experience.
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