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Objective: To report on a patient with Anderson-Fabry disease whose moderately impaired renal function was stabilized with enzyme treatment. Methodology: Anderson-Fabry disease is an X-linked disorder. Symptoms are caused by a deficiency in lysosomal α-galacosidase A, resulting in defective clearance of glycosphyngolipids. Consequently, these glycophyngolipids accumulate intracelluarly, with particular predilection for endothelial and vascular smooth muscle cells. However, various other cell types are implicated; for example, renal podocytes and myocardial cells. Results: A 36-year old man with Anderson-Fabry disease started enzyme replacement therapy with &alpha-galacosidase (Fabrazyme®) using the infusion protocol described by Eng et al. in 2001. Serum creatinine concentration at the beginning of replacement therapy was 2.78 mg/dL (245 μmoL/L), corresponding to a calculated creatinine clearance of 38.9 mL/min. Prior to treatment, loss of creatinine clearance was 6.4 mL/min/year. During the ensuing 19 months of treatment, the progression of renal failure was significantly slowed: The slope of clearance loss during enzyme replacement was -2.2 mL/min/year at the time of the report. During the entire follow-up period, there was no major change in blood pressure or proteinuria (0.4-0.6 g/L), and initial antihypertensive treatment with lisinopril (5 mg daily, instituted before 1994) was substituted by irbesartan (150 mg daily) because of invalidating chronic cough without any significant blood pressure change. Left ventricular hypertrophy was steadily decreased over 19 months of treatment. In parallel, a decrease in septal thickness was observed. Posterior wall thickness remained stable. [ABSTRACT FROM AUTHOR]

Statins are a well-known and highly effective treatment for hypercholesterolemia in order to prevent cardiovascular disease. Occasionally, patients may experience muscle-related events such as myalgia or muscle cramps. Recently, SINAM (statin-induced necrotizing autoimmune myopathy) has been described in patients using statins. Although very uncommon, it may cause a life-threatening situation associated with rhabdomyolysis. We present a case concerning a 71-year-old woman who presented with muscle fatigue for several weeks. Statin therapy was discontinued but symptoms did not resolve. Further workup led to a diagnosis of SINAM for which treatment with immunosuppressants was started.

Objective: Aseptic meningitis is a rare, but possible severe side effect after SARS-CoV-2 Pfizer/BioNTech vaccination., Case Presentation: Recently, a first case of aseptic meningitis after the first shot of mRNA-BNT162b2 SARS-CoV-2 (Pfizer/BioNTech) vaccine was reported. We present the first case of a 34-year-old woman without relevant medical history developing aseptic meningitis after her 2 nd Pfizer/BioNTech vaccination. She was admitted with severe headache and fever for 5 days prior to her presentation at the emergency department. An extensive work-up of the clinical problem could narrow the differential diagnosis. Symptoms resolved after methylprednisolone therapy., Conclusion: This case highlights a rare but important side effect after vaccination that primary physicians and neurologists should be aware of in order to identify and efficiently manage these patients.

Objectives : Assessing the safety and efficacy of immune checkpoint inhibition in risky cancer patient subgroups: pre-existing organ failure, elderly, presence of auto-immune disease, transplanted patients and brain metastasis treated with immune checkpoint inhibitors. Methods : PubMed, Web of Science and Google scholar databases were searched for English articles published prior to February 2019. Search terms used were organ failure, dialysis, elderly, organ transplant, liver disease, auto-immune disease, immunosuppression, and brain metastasis. Results : Our literature data indicate that immune checkpoint inhibition in the majority of these subpopulations can be administered safely without any loss of efficacy. These data are mostly based on case-reports as only a minority of high-risk patients were included in (the earliest) clinical trials. Validation of these results is necessary on a larger scale. Conclusion : Future trials should not automatically exclude aforementioned patient groups but alter the study design and make their inclusion possible, since more data are needed to answer several remaining questions in these populations. Especially since ICI appears to be safe to administer in these patients.

Purpose: To evaluate equations for estimation of glomerular filtration rate (GFR) and measured urinary creatinine clearance, compared to measured GFR in critically ill patients., Methods: GFR was measured using inulin clearance. Multiple blood samples were collected per patient for determination of serum creatinine, cystatin C and inulin. GFR was estimated by the use of the following estimation equations (eGFR): four commonly used creatinine-based equations [Cockcroft-Gault, Modification of Diet in Renal Disease (both the short and long formula) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)], five cystatin C based estimation equations (Hoek, Larsson, Filler, Le Bricon, CKD-EPIcys) and one equation combining cystatin C and serum creatinine (CKD-EPIcr-cys). In addition we measured urinary creatinine clearance. Bias, precision and accuracy of all estimates were compared to those of the inulin clearance., Results: Data were collected from 83 patients, of whom 68 were considered evaluable. The median age was 58 years [interquartile range (IQR) 39-68]. The median inulin clearance was 80 mL/min/1.73 m(2) (IQR 31-114). Equations based on creatinine had much bias and poor precision and accuracy. Measured urinary creatinine clearances overestimated GFR. Equations based on cystatin C were free of bias, but also had limited precision and accuracy., Conclusions: In this cohort of patients, estimates of GFR had low accuracy and precision. Cystatin C based formulas, especially CKD-EPIcr-cys, showed limited bias; however, the accuracy and precision of these estimates were still insufficient. Measured urinary creatinine clearance overestimates GFR, but may provide a cheap alternative, when this is taken into account.

Background: Anderson-Fabry disease (AFD) is an X-linked condition originating from a deficiency in alpha-galactosidase, a lysosomal enzyme. Multi-organ involvement ensues in early adulthood and vital organs are affected: the kidneys, brain, heart. Several reports however suggest that AFD is underdiagnosed., Methods: We screened a kidney transplant population using a two-tier approach. The first tier was the determination of alpha-galactosidase A (AGALA) activity using a dried blood spot on filter paper (DBFP); in the second tier, patients with the lowest alpha-galactosidase levels were further subjected to mutation analysis of the GLA gene., Results: From the database of 2328 patients, 1233 subjects met the inclusion criteria. Finally, after informed consent, 673 patients were screened (54.5%-395 women and 278 men). DBFP analysis resulted in a mean AGALA of 2.63 +/- 2.48 micromol/L/h (2.5 and 97.5 percentile were 0.0001 and 5.07 micromol/L/h, respectively). Eleven patients were subjected to further genetic analysis. In a male patient a pathogenic missense mutation p.Ala143Thr (c.427A>G) was identified., Conclusions: Our results show that the proposed approach can detect AFD patients in a until now seldomly screened high-risk group: kidney transplant patients. We conclude that screening for AFD in high-risk populations is a cost-effective, technically feasible and clinically valuable objective.

Introduction: Fabry's disease (AFD) is an X-linked lysosomal storage disease, resulting from a deficiency in alpha-galactosidase A (AGALA). Untreated, this leads to precocious failure of vital organ function and death. As enzyme replacement therapy is available, it is of vital importance that affected individuals can be traced., Materials and Methods: We set up a screening in the Flemish haemodialysis population using a two-tier approach. The first tier was a determination of alpha-galactosidase A activity using a dried blood spot on filter paper, in the second tier, patients with the lowest alpha-galactosidase levels were further subjected to mutation analysis of the GLA gene., Results: 1284 patients (1047 women, 237 men) were evaluated for inclusion, eliminating patients with definite renal diagnoses. Total 922 patients (71.8 %) were screened (742 women, 180 men). Fifty seven patients were subjected to further genetic analysis. Three GLA mutation carriers were identified: two apparently nonrelated female patients carry the missense mutation p.Ala143Thr (c.427G > A), a missense mutation p.Trp236Arg (c.706T > C) was identified in a man. While the male patient had been clinically diagnosed with AFD, the female patients had remained unrecognized. Additional family based screening resulted in the identification of nine mutation carriers (four males and five females)., Discussion: We demonstrated that the prevalence of GLA mutation carriers in our haemodialysis population is 0.3%. Our results show that the proposed approach accurately detects AFD patients. We conclude that screening for AFD in high risk populations is a cost-effective, technically feasible and clinically valuable objective.

Phenytoin intoxication can result in major and possibly life-threatening disorders. Furthermore, the hepatic clearance can become saturated, thus, shifting the elimination from first- to zero-order kinetics. This results in a slow elimination of the compound in case of intoxication. The treatment modalities for phenytoin overdose are limited. Taking into account the high level of protein binding, the molecule is not easily eliminated from the body by means of extracorporal epuration. Although reports exist on the use of MARS (molecular adsorbents recirculating system) dialysis, peritoneal dialysis, and standard dialysis for the elimination, in practice, hemoperfusion, is the most often applied technique. The authors report the case of a hypoalbuminemic patient with severe neurologic signs of phenytoin intoxication (total concentration moderately elevated, free fraction high). A combination of high-flux dialysis and hemoperfusion resulted in a considerable extraction of the drug, accelerating the natural clearance from the body and ameliorating clinical signs of intoxication. In selected patients (with a high free fraction of phenytoin), high-flux dialysis may be a valuable alternative or adjuvant to hemoperfusion.

Background: It has been proposed that, once renal function has been restricted in chronic kidney disease, compensatory hyperfiltration results in a compulsory deterioration of renal function., Patients and Methods: In this study, 83 patients originally starting from a serum creatinine (S(crea)) between 2.0 and 5.0 mg/dl were followed for the evolution of renal function. This overall population, with a follow-up (FU) of(M +/- SD) 67 +/- 50 months, was stratified into two groups based upon their slope of 1/S(crea), whereby the median of this slope (-0.0019) was taken as the cut-off value., Results: There was an expected decline of renal function in the group with the lowest slope (group A = progression) whereas renal function remained stable in the group with the highest slope (group B = no progression). This evolution occurred in spite of a similar S(crea) in both groups at the start of the study (group A: 2.45 +/- 0.71 mg/100 ml (n = 41) vs. group B: 2.94 +/- 0.88 mg/100 ml (n = 42); p = ns) and an even higher creatinine clearance in group A (group A: 46.43 +/- 18.65 mg/100 ml(n = 41)vs. group B: 34.03 +/- 20.11 mg/100 ml (n = 42); p = 0.0049). Group B contained a higher number of patients with interstitial nephritis (34/42 = 81% vs. 6/41 = 15%; p < 0.00001) while patients with chronic glomerulopathy could be found especially in group A (23/41 = 56% vs. 8/42 = 19%; p < 0.00001). Proteinuria was continuously higher in group A (start FU: p = 0.0097; FU 72 months: p = 0.0155) and tended to decrease in group B (start FU, 0.89 +/- 1.42 g/l (n = 42) vs. FU 72 months, 0.41 +/- 0.78 g/l (n = 26); p = 0.0474) whereas no significant decrease was observed in group A (start FU, 2.16 +/- 2.83 g/l (n = 41) vs. FU 72 months, 1.77 +/- 0.72 g/l (n = 6); p = ns)., Conclusion: Within the time limit and patient inclusion criteria of this FU, a compromised renal function does not necessarily result in a further decline. This study points more towards a major role for the underlying nature of renal disease.