Podocyturia in Fabry disease: a 10-year follow-up.

BACKGROUND: Fabry disease (FD) is a rare X-linked disorder of sphingolipid metabolism that results in chronic proteinuric nephropathy. Podocytes are one of the most affected renal cells and play an important role in the development and progression of kidney disease. Detached podocytes found in urine (podocyturia) are considered as a non-invasive early marker of kidney injury; however, the dynamics of podocyte loss remains unknown. METHODS: In this 10-year follow-up study, podocyturia and other renal clinical data were evaluated in 39 patients with FD. From 2009 to 2019, podocyturia was assessed in 566 fresh urine samples from 13 male and 26 female FD patients using immunocytochemical detection of podocalyxin. RESULTS: Podocyturia (number of podocytes per 100 mL of urine) was found in 311/566 (54.9%) of the samples, more frequently (68.9 ± 21.9% versus 50.6 ± 25.9%; P = 0.035) and with higher values (364 ± 286 versus 182 ± 180 number of podocytes per gram of creatinine (Cr) in urine; P = 0.020) in males compared with females. The mean number of assessed samples for each patient was 14.5 (range 3-40) and the frequency of samples with podocyturia ranged from 0% to 100% (median 57%). Podocyturia was already present in 42.9% of patients <20 years of age and in 89.5% of normoalbuminuric patients. Podocyturia correlated with albuminuria (urine albumin:Cr ratio) (r = 0.20, P < 0.001) and a higher incidence and values of podocyturia were observed in patients with lower estimated glomerular filtration rate. CONCLUSIONS: Our data demonstrated that podocyturia is an early clinical event in the development of nephropathy. In addition, we found podocyturia to be a discontinuous event with wide variability.

The syndrome of cardiac failure in adults with congenitally corrected transposition.

OBJECTIVES: To assess neurohormonal activation of cardiac failure in adults with congenitally corrected transposition, and to determine the most sensitive marker for recognition of the cardiac failure. BACKGROUND: The onset of morphologically right ventricular dysfunction is unpredictable in patients with congenitally corrected transposition, the combination of discordant atrioventricular and ventriculo-arterial connections, and its markers are unknown. METHODS: We measured amino terminal pro brain natriuretic peptide in 19 patients, aged 35 plus or minus 13.1 years, and in 19 control subjects. Morhologically right ventricular function was assessed by echocardiography, including tissue Doppler echocardiography and magnetic resonance imaging or multislice computed tomography. RESULTS: The patients showed a highly significant increase in the levels of amino terminal pro brain natriuretic peptide, the levels being significantly elevated even in asymptomatic patients. Left atrial dimensions were larger in patients, and significantly lower tissue Doppler echocardiographic velocities were measured at the lateral site of the tricuspid annulus and at the basal segment of the interventricular septum. The ejection fraction of the morphologically right ventricle correlated significantly with the levels of brain natriuretic peptide, and with left atrial dimensions. CONCLUSIONS: Neurohormonal activation is present in patients with congenitally corrected transposition even when they are asymptomatic. It is correlated with left atrial dimensions and tissue Doppler echocardiographic parameters. Levels of brain natriuretic peptide, and peak tricuspid early diastolic annular velocity, are the earliest and most sensitive markers of morphologically right ventricular dysfunction.

Paricalcitol as an Antiproteinuric Agent Can Result in the Deterioration of Renal and Heart Function in a Patient with Fabry Disease.

BACKGROUND Fabry disease is a rare and progressive X-linked inherited disorder of glycosphingolipid metabolism that is due to deficient or absent lysosomal a-galactosidase A activity. Among its other associated signs and symptoms, patients present with renal failure and proteinuria, which are markers of disease progression. Renin-angiotensin-aldosterone system (RAAS) blockers can slow the progression of chronic renal failure and proteinuria. In fact, some studies have shown the beneficial effects of paricalcitol on proteinuria. CASE REPORT We present a case of a female patient with the classic variant of Fabry disease. She was treated with a high dose of paricalcitol as an antiproteinuric agent due to unsatisfactory double-RAAS blockage, which resulted in transient worsening of cardiac and renal function. CONCLUSIONS Despite the positive effects of paricalcitol as an antiproteinuric agent, as previously shown by some authors, our case highlights the possible serious adverse effects associated with the use of high doses of this drug.

Tissue Doppler velocities of mitral annulus and NT-proBNP in patients with heart failure.

BACKGROUND: It has been shown that pulsed wave tissue Doppler velocities of mitral annulus correlate well with left ventricular (LV) diastolic and systolic functions. It is not yet clear whether these velocities can be used to estimate left ventricular dysfunction in an unselected population of patients with clinical signs and symptoms of heart failure (HF). AIM: To determine whether LV mitral annulus velocities measured by tissue Doppler imaging (TDI) correlate with plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in patients with HF. METHODS AND RESULTS: Early diastolic (E(m)) and systolic (S(m)) TDI velocities of septal and lateral mitral annulus were measured in 50 patients with HF together with other conventional echocardiographic parameters, and compared with plasma NT-proBNP levels. Significant correlations were found between NT-proBNP level and E(m) velocity (r=-0.79), S(m) velocity (r=-0.43), early transmitral to E(m) velocity ratio (r=0.38), LV end diastolic diameter (r=0.29), LV ejection fraction (r=-0.44) and tricuspid regurgitant velocity (r=0.31). In multiple regression model (R(2)=0.733), the E(m) velocity was the most important predictor of NT-proBNP level. CONCLUSIONS: Early diastolic mitral annulus velocity measured by TDI correlates strongly with plasma NT-proBNP levels, and provides a simple, accurate and reproducible echocardiographic index of heart failure.

Exocrine pancreatic insufficiency is not a cause of abdominal complaints in patients with Fabry disease.

BACKGROUND: Fabry disease (FD), also called Anderson-Fabry disease, is the second most prevalent lysosomal storage disorder after Gaucher disease. Gastrointestinal (GI) symptoms are very common among male and female individuals, although the age of onset is later among female patients. To our best knowledge, exocrine pancreatic insufficiency (EPI) has not yet been studied in patients with FD as a possible cause of abdominal complaints. The aim of our study was to determine whether exocrine pancreatic function is impaired in patients with FD. PATIENTS AND METHODS: We analysed medical records of patients with FD treated in Fabry Center in Slovenj Gradec General Hospital (Slovenian referral centre for FD) by the evaluation of the following features: gender, age, first symptoms before confirmation of FD diagnosis, time interval between first symptoms and diagnosis, therapy and current abdominal complaints. Diagnosis of FD was established by genetic analysis and confirmation of mutation in the α-galactosidase A gene. Faecal elastase-1 (FE-1) measurements were performed using enzyme-linked immunosorbent assay and the commercial kit ScheBo Biotech, Giessen, Germany. RESULTS: There were 28 adult patients (Slovene, Caucasians) with known FD included in the study: 12 male and 16 female; mean age, 45.6 ± 14.3 (range, 19-75) years. Seventeen patients (63%) were on enzyme replacement therapy (ERT). In seven (25.9%) patients, abdominal complaints (diarrhoea, bloating and feeling of satiety) were present before introduction of ERT. In three out of these seven patients, abdominal complaints resolved after ERT, and in four patients, they were still occasionally present. FE-1 was normal in all patients (547.9 ± 104.5 µg/g). CONCLUSIONS: Our results show that exocrine pancreatic function is normal in all patients with FD and is most likely not a cause of abdominal complaints in this group of patients. Nevertheless, EPI still could not be completely excluded as an aetiology factor for GI problems in patients with FD because all our patients with GI problems were treated with ERT. Therefore, a potential effect of ERT on EPI cannot be excluded. Further studies are necessary to determine the aetiology, especially in the group of naïve male patients.

Cerebral and coronary gas embolism from the inhalation of pressurized helium.

OBJECTIVE: Inhalation of helium, which produces a change in the voice, is frequently used among young rock singers to improve their performance. DESIGN: A case report. SETTINGS: Adult medical intensive care unit in a university hospital. PATIENT: A 23-yr-old singer, who accidentally inhaled helium from a high pressurized tank without pressure reduction, presented with transient loss of consciousness and chest pain. INTERVENTIONS: Electrocardiogram, chest radiograph, biochemical and toxicological analyses, echocardiography, coronary angiography were performed. MEASUREMENTS AND MAIN RESULTS: At admission, the patient slowly regained consciousness. An electrocardiogram showed significant ST elevations in leads I, aVL, and V4-V6. The chest radiograph was consistent with pulmonary congestion and pneumomediastinum. The echocardiogram showed normal sized heart chambers with hypokinesis of the left ventricular lateral wall. Ethanol and urine cannabinoids were present in low concentrations, but no presence of opiates, methadone, cocaine, or amphetamines was documented. Troponin T was positive. Elevation of ST segments gradually disappeared within 30 mins, the drowsiness within 10 hrs, and the thoracic pain within 24 hrs. Coronary angiography showed normal coronary arteries. The patient was discharged on day 3 without any symptoms and with normal electrocardiogram and chest radiograph. CONCLUSION: Accidental inhalation of helium under high pressure can cause symptomatic cerebral and coronary artery gas embolism.