Clinic-Pathologic Features and Renal Outcome of Fabry Disease: Data from a Chinese Cohort

2018 ◽  
Vol 48 (2) ◽  
pp. 137-146
Author(s):  
Dan Zhang ◽  
Jiong Zhang ◽  
Shaoshan Liang ◽  
Jinquan Wang ◽  
Zhihong Liu
Keyword(s):  
Renal Function ◽  
Survival Rate ◽  
Fabry Disease ◽  
Left Ventricular ◽  
Renal Outcome ◽  
Characteristic Analysis ◽  
Renal Function Deterioration ◽  
Renal Prognosis ◽  
Stable Renal Function ◽  
Fabry Nephropathy

Background: Fabry disease (FD) with life-threatening complications occurs as a result of organ damage in kidneys, heart, and brain. Only a few studies, especially from Asia, report their long-term outcome. Methods: In this monocentric study, patients with Fabry nephropathy confirmed by renal biopsy were clinically investigated in a comprehensive manner. The clinic-pathological features, progression, and risk factors for the outcome were analyzed. Results: Thirty-one patients were recruited, after median 62 months (range 8–156 months) follow-up, 23 of them had stable renal function while 8 underwent renal function deterioration. Frequent presenting symptoms included acroparesthesia (58.1%), edema (51.6%), hypo- or anhidrosis (38.7%), and angiokeratoma (32.3%). Left ventricular hypertrophy was present in 62.5% patients with renal function deterioration and 17.4% patients with stable renal function (p = 0.03). The renal cumulative survival rate of all patients was 64.5% in 10 years. Mainz Severity Score Index (MSSI) and segmental sclerosis are independent predictive factors for a more rapid progression of Fabry nephropathy. The receiver operating characteristic analysis demonstrated that the area under the curve for the prediction of renal function progression on the basis of MSSI and segmental sclerosis levels in patients with FD was 0.845 and 0.780, respectively. MSSI score ≥18 or segmental sclerosis ≥3.9% in patients with FD positively correlated with poor renal prognosis. Conclusions: FD’s clinical manifestations are heterogeneous and nonspecific. The ­10-year cumulative renal survival rate was low in Chinese patients. MSSI score and segmental sclerosis levels predict the renal prognosis of patients with FD sensitively.

P0076HOMOARGININE ASSOCIATES WITH RENAL AND CARDIAC FUNCTION IN FABRY DISEASE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Christiane Drechsler ◽  
Andreas Menitzer ◽  
Winfried Maerz ◽  
Lena Gutjahr-Lengsfeld ◽  
Daniel Oder ◽  
...  
Keyword(s):  
Renal Function ◽  
Fabry Disease ◽  
Clinical Symptoms ◽  
Controlled Trial ◽  
Cardiac Contractility ◽  
Left Ventricular ◽  
Amino Acid Derivative ◽  
Cerebral Stroke ◽  
Cross Sectional ◽  
Lv Mass

Abstract Background and Aims Patients with Fabry disease frequently develop progressive Fabry nephropathy, hypertrophic cardiomyopathy with arrhythmias and subsequent death, transient ischemic attacks and early cerebral stroke. Homoarginine is an amino acid derivative, mainly produced in the kidney from its precursor lysine. Homoarginine may increase nitric oxide availability, decrease the release of cytokines, modulate the renin-angiotensin-aldosterone system and improve cardiac contractility. We hypothesize that high homoarginine levels associate with less clinical symptoms and better renal function in patients with Fabry disease. Method This study investigated the homoarginin status and its association with renal function, left ventricular (LV) mass and adverse clinical symptoms in patients with Fabry disease. Homoarginine was measured by high-performance liquid chromatography in 162 patients who were genetically proven to have Fabry disease. GFR was determined by DTPA clearance. LV mass and cardiomyopathy were assessed by magnetic resonance imaging and echocardiography. In cross-sectional analyses, associations with adverse clinical outcomes were determined by linear and binary logistic regression analyses, respectively, and were adjusted for age, sex, and BMI. Results Patients had a mean age of 39±14 years and 41% were male. The mean homoarginine concentration was 2.0±1.0 µmol/l. Patients had a mean BMI of 23.7±4.5 kg/m2 and a mean GFR of 93±37 ml/min. Homoarginine was significantly correlated with GFR and proteinuria. The better the homoarginine status of the patients, the higher was their GFR (r=0.20, p=0.04) and the lower proteinuria (r=-0.21, p=0.03). Furthermore, LV mass was significantly higher with lower homoarginine levels (r=-0.30, p<0.01). Patients of the lowest homoarginine tertile had a 4-fold higher risk of myocardial hypertrophy (OR 4.17, 95% CI 1.44-12.02), especially with septal and posterior hypertrophy, compared to those of the upper tertiles. Similarly, patients of the lowest homoarginine tertile had a higher rate of angina pectoris (OR 4.2, 95% CI 1.3-13.3) and chronic pain (OR 4.1, 95% CI 1.7-10.1), compared to patients of the upper tertiles. At lower homoarginine status, the median levels of proteinuria increased, as well as the prevalence rates of heart failure and the need for analgesic therapy. Conclusion In conclusion, low homoarginine status was strongly associated with cardiomyopathy, renal function and adverse clinical symptoms in patients with Fabry disease. Whether homoarginine supplementation improves complications of Fabry disease, requires a randomized controlled trial.

scholarly journals Kidney Transplant in Fabry Disease: A Revision of the Literature

Medicina ◽  
2020 ◽  
Vol 56 (6) ◽  
pp. 284 ◽  
Author(s):  
Irene Capelli ◽  
Valeria Aiello ◽  
Lorenzo Gasperoni ◽  
Giorgia Comai ◽  
Valeria Corradetti ◽  
...  
Keyword(s):  
Renal Function ◽  
Kidney Transplantation ◽  
Fabry Disease ◽  
Therapeutic Option ◽  
Gene Mutations ◽  
Disease Recurrence ◽  
Long Term Effects ◽  
Enzyme Replacement ◽  
Fabry Nephropathy

Fabry disease is classified as a rare X-linked disease caused by a complete or partial defect of enzyme alpha-galactosidase, due to GLA gene mutations. This disorder leads to intracellular globotriaosylceramide (Gb3) deposition associated with increased Gb3 plasma levels. Most of the symptoms of the disease, involving kidneys, heart and nervous system, result from this progressive Gb3 deposition. The incidence is estimated in 1/50,000 to 1/117,000 in males. Fabry nephropathy begins with microalbuminuria and/or proteinuria, which, in the classic form, appear from childhood. Thus, a progressive decline of renal function can start at a young age, and evolve to kidney failure, requiring dialysis or renal transplantation. Enzyme replacement therapy (ERT), available since 2001 for Fabry disease, has been increasingly introduced into the clinical practice, with overall positive short-term and long-term effects in terms of ventricular hypertrophy and renal function. Kidney transplantation represents a relevant therapeutic option for Fabry nephropathy management, for patients reaching end-stage renal disease, but little is known about long-term outcomes, overall patient survival or the possible role of ERT after transplant. The purpose of this review is to analyze the literature on every aspect related to kidney transplantation in patients with Fabry nephropathy: from the analysis of transplant outcomes, to the likelihood of disease recurrence, up to the effects of ERT and its possible interference with immunosuppression.

scholarly journals Copious Podocyturia without Proteinuria and with Normal Renal Function in a Young Adult with Fabry Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
H. Trimarchi ◽  
R. Canzonieri ◽  
A. Muryan ◽  
A. Schiel ◽  
A. Araoz ◽  
...  
Keyword(s):  
Renal Function ◽  
Kidney Disease ◽  
Fabry Disease ◽  
Renal Damage ◽  
Dual Problem ◽  
Clinical Signs ◽  
Enzyme Replacement ◽  
Cardiovascular Morbidity And Mortality ◽  
Initiation Of Therapy ◽  
Fabry Nephropathy

The time for starting a patient with Fabry disease on enzyme replacement therapy is still a matter of debate, particularly when no overt classical clinical signs or symptoms are present. With respect to Fabry nephropathy, a dual problem coexists: the reluctance of many nephrologists to start enzyme replacement infusion until signs of renal disease appear as the appearance of proteinuria or an elevation in serum creatinine and the lack of validated biomarkers of early renal damage. In this regard, proteinuria is nowadays considered as an early and appropriate marker of kidney disease and of cardiovascular morbidity and mortality. However, in this report we demonstrate that podocyturia antedates the classical appearance of proteinuria and could be considered as an even earlier biomarker of kidney damage. Podocyturia may be a novel indication for the initiation of therapy in Fabry disease.

scholarly journals Glomerulonephritis with Crescents in Children: Etiology and Predictors of Renal Outcome

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
K. Alsaad ◽  
N. Oudah ◽  
A. Al Ameer ◽  
K. Fakeeh ◽  
A. Al Jomaih ◽  
...  
Keyword(s):  
Renal Function ◽  
Crescentic Glomerulonephritis ◽  
Clinicopathological Features ◽  
Renal Outcome ◽  
Histological Features ◽  
Younger Age ◽  
Renal Prognosis ◽  
The Mean ◽  
Nephrotic Range Proteinuria ◽  
Observation Period

Objective. To investigate the clinicopathological features and outcome of glomerulonephritis with crescents among Saudi children. Method. This is a retrospective study of cases of crescentic glomerulonephritis (CrGN) seen over a 9-year period. Histological features and renal function were recorded. Results. Thirty-seven cases were enrolled. The mean percent of glomeruli with crescents was 39% (±19). Lupus nephritis (LN) was the commonest etiology (54.1%). At presentation, the serum creatinine (SCr) was 218.2 (±174.3) umol/l, and 57.1% of the cases had nephrotic range proteinuria. By the end of the observation period, SCr dropped to 81.0 (±67.7) umol/l (P=0.001). Worsening renal function was associated with younger age (P=0.002), non-LN etiology (P=0.01), more crescents (P=0.019), and ATN (P=0.05). At the end of the followup, more patients in the LN group were dialysis-free (P=0.017) and had improved renal function (0.01) than in the non-LN group. Using multivariate analysis, the only independent factor found to predict need for dialysis or change in SCr level was percent of globally sclerosed glomeruli (P=0.034). Conclusion. LN is the main cause of CrGN in our cohort of children. The LN group had less globally sclerorsed glomeruli and better renal prognosis than the non-LN group.

scholarly journals Modifiable factors affecting renal preservation in type I glycogen storage disease after liver transplantation: a single-center propensity-match cohort study

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yi-Chia Chan ◽  
Kai-Min Liu ◽  
Chao-Long Chen ◽  
Aldwin D. Ong ◽  
Chih-Che Lin ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Renal Function ◽  
Glycogen Storage Disease ◽  
Storage Disease ◽  
Glycogen Storage ◽  
Renal Outcome ◽  
Type I ◽  
Long Term Outcome ◽  
Renal Prognosis

Abstract Background and aims Glycogen storage disease type I (GSD-I) is an autosomal recessive disorder of carbohydrate metabolism, resulting in limited production of glucose and excessive glycogen storage in the liver and kidneys. These patients are characterized by life-threatening hypoglycemia, metabolic derangements, hepatomegaly, chronic kidney disease, and failure to thrive. Liver transplantation (LT) has been performed for poor metabolic control and delayed growth. However, renal outcome was diverse in pediatric GSD patients after LT. The aim of this study was to investigate the long-term outcome of renal function in pediatric GSD-I patients after living donor LT (LDLT), and to identify modifiable variables that potentially permits LT to confer native renal preservation. Methods The study included eight GSD-Ia and one GSD-Ib children with a median age of 9.0 (range 4.2–15.7) years at the time of LT. Using propensity score matching, 20 children with biliary atresia (BA) receiving LT were selected as the control group by matching for age, sex, pre-operative serum creatinine (SCr) and pediatric end-stage liver disease (PELD) score. Renal function was evaluated based on the SCr, estimated glomerular filtration rate (eGFR), microalbuminuria, and morphological changes in the kidneys. Comparability in long-term renal outcome in terms of anatomic and functional parameters will help to identify pre-LT factors of GSD-I that affect renal prognosis. Results The clinical and biochemical characteristics of the GSD and BA groups were similar, including immunosuppressive regimens and duration of follow-up (median 15 years) after LT. Overall, renal function, including eGFR and microalbuminuria was comparable in the GSD-I and BA groups (median eGFR: 111 vs. 123 ml/min/1.73m2, P = 0.268; median urine microalbuminuria to creatinine ratio: 16.0 vs. 7.2 mg/g, P = 0.099, respectively) after LT. However, in the subgroups of the GSD cohort, patients starting cornstarch therapy at an older age (≥ 6-year-old) before transplantation demonstrated a worse renal outcome in terms of eGFR change over years (P < 0.001). In addition, the enlarged kidney in GSD-I returned to within normal range after LT. Conclusions Post-LT renal function was well-preserved in most GSD-I patients. Early initiation of cornstarch therapy before preschool age, followed by LT, achieved a good renal prognosis.

scholarly journals Determinants of renal outcome in anti-myeloperoxidase-associated necrotizing crescentic glomerulonephritis.

1998 ◽  
Vol 9 (10) ◽  
pp. 1915-1923 ◽  
Author(s):  
C F Franssen ◽  
C A Stegeman ◽  
W W Oost-Kort ◽  
C G Kallenberg ◽  
P C Limburg ◽  
...  
Keyword(s):  
Renal Function ◽  
Crescentic Glomerulonephritis ◽  
Clinical Laboratory ◽  
Response To Treatment ◽  
Renal Outcome ◽  
Necrotizing Crescentic Glomerulonephritis ◽  
Stable Renal Function ◽  
Relapse Group

Patients with anti-myeloperoxidase (MPO)-associated necrotizing crescentic glomerulonephritis (NCGN) may develop chronic renal failure (CRF) leading to end-stage renal disease despite an initially favorable response to treatment. The aim of this study was to determine the prognostic value of clinical, laboratory, and histopathologic features at the time of presentation and during follow-up for the development of CRF in 21 consecutive anti-MPO-positive patients with NCGN. Renal function did not recover in two of five patients who were dialysis-dependent at presentation. The remaining 19 patients all went into remission and were off dialysis at 3 mo after diagnosis. At long-term follow-up, nine of these patients had stable renal function and did not relapse (group A), five patients developed CRF without signs of relapse (group B), and five patients relapsed (group C). At diagnosis, serum creatinine, C-reactive protein, and anti-MPO levels did not differ between groups A, B, and C. Microscopic erythrocyturia resolved in all patients within 4 mo of treatment. BP at presentation and during follow-up did not differ between groups A, B, and C. Proteinuria at diagnosis and in the first 6 mo after diagnosis was higher in patients who developed CRF than in patients with a stable renal function. Anti-MPO levels at 3 mo had decreased compared with anti-MPO levels at diagnosis in groups A and C, whereas anti-MPO levels did not fall significantly in patients who developed CRF. The predictive value of a renal biopsy at diagnosis on long-term renal outcome was limited. In conclusion, a higher degree of proteinuria at diagnosis and during follow-up as well as persistently elevated anti-MPO levels after induction of remission are associated with the development of CRF and are predictive of poor renal outcome in anti-MPO-associated NCGN.

scholarly journals P0055GALECTIN-3 STRONGLY ASSOCIATES WITH RENAL FUNCTION, CARDIOMYOPATHY AND FIBROSIS IN PATIENTS WITH FABRY DISEASE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Christiane Drechsler ◽  
Rudolf De Boer ◽  
Daniel Oder ◽  
Lena Gutjahr-Lengsfeld ◽  
Nurcan Üçeyler ◽  
...  
Keyword(s):  
Renal Failure ◽  
Renal Function ◽  
Cardiac Hypertrophy ◽  
Fabry Disease ◽  
Left Ventricular Mass ◽  
Odds Ratio ◽  
Cardiac Fibrosis ◽  
Clinical Symptoms ◽  
Left Ventricular ◽  
Galectin 3

Abstract Background and Aims Patients with Fabry disease frequently develop cardiac hypertrophy and progressive Fabry nephropathy. The progress of cardiac hypertrophy can lead to replacement fibrosis and heart failure. Galectin-3 is expressed in the heart, kidneys, blood vessels, and macrophages. It marks activated macrophages in failure-prone hypertrophied hearts and contributes to cardiac dysfunction. Experimental data suggest that galectin-3 is involved in fibrosis and inflammation also associated with renal failure. Galectin-3 inhibitor therapy tested in a phase 2 clinical trial in chronic kidney disease lead to an improvement of the estimated glomerular filtration rate. Given the role of Galectin-3 in cardiac hypertrophy, heart and renal failure, we hypothesized that it may be of potential relevance particularly for Fabry disease patients. Method This study investigated the galectin-3 concentrations in 172 patients with genetically proven Fabry disease. We studied the association of galectin-3 concentrations with renal function, left ventricular mass, and adverse clinical symptoms in patients with Fabry disease. Galectin-3 was measured by FDA-approved ELISA. GFR was determined by DTPA clearance. Left ventricular mass and cardiomyopathy were assessed by magnetic resonance imaging and echocardiography. In cross-sectional analysis, associations with adverse clinical outcomes were determined by correlation analysis and linear and binary logistic regression analysis, respectively. Data was adjusted for age and sex. Results Patients had a mean age of 39±14 years and 41% were male. The mean galectin-3 concentration was 17±12 ng/mL (normal value is approx. 11 ng/mL). Patients had a mean BMI of 23.7±4.5 kg/m2 and a mean GFR of 92±38 ml/min. Galectin-3 was strongly correlated with GFR, creatinine and urea. With higher galectin-3 concentrations of the patients, their GFR was lower (r=-0.63, p&lt;0.001) and creatinine and urea were higher (r=0.68 and r=0.53, respectively, both p&lt;0.001). Furthermore, cardiac hypertrophy was significantly higher with higher concentrations of galectin-3. The correlation coefficient for septal hypertrophy was r=0.43 (p&lt;0.001) and for posterior hypertrophy r=0.39 (p&lt;0.001), respectively. Similarly, cardiac fibrosis was significantly higher with higher galectin-3 levels (r=0.34, p&lt;0.001). Patients of the highest galectin-3 tertile furthermore had significantly higher risks of adverse clinical symptoms. The adjusted odds ratio to suffer from angina pectoris was increased &gt; 6-fold and the odds ratio to suffer from neuropathic pain was increased &gt; 3-fold for patients of the highest galectin-3 tertile as compared to patients of the lowest galectin-3 tertile. Conclusion Increased galectin-3 concentrations were strongly associated with cardiac hypertrophy, cardiac fibrosis, decreased renal function, and adverse clinical symptoms in patients with Fabry disease. Galectin-3 can be useful as biomarker for cardiac and renal complications in Fabry disease. Galectin-3 inhibitor treatment may reduce complications of Fabry disease, and requires a randomized controlled trial.

MO462TIME-TRAJECTORIES OF RENAL FUNCTION AND OUTCOMES IN ELDERLY INDIVIDUALS WITH CKD OF VARIOUS ETIOLOGY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Mariateresa Zicarelli ◽  
Alessandro Comi ◽  
Gemma Patella ◽  
Paola Cianfrone ◽  
Giuseppe Coppolino ◽  
...  
Keyword(s):  
Renal Function ◽  
Kidney Disease ◽  
Left Ventricular ◽  
Renal Outcome ◽  
Hypertensive Retinopathy ◽  
Ckd Progression ◽  
Elderly Individuals ◽  
Older Populations ◽  
The Impact

Abstract Background and Aims Despite hypertension ranks among the leading causes of chronic kidney disease (CKD), the impact of chronic hypertensive nephropathy, the so-called “nephrosclerosis” (NS), on CKD progression towards end-stage kidney disease (ESKD) is often unpredictable, particularly in older populations. We run a prospective, observational study to define renal function patterns and outcomes in elderly individuals with or without NS-related CKD. Method 304 elderly patients with already established CKD (mean age 69±4 y; mean eGFR 44.2±19.6 mL/min/1.73 m2; male= 64.1%), followed in our outpatients’ clinic were categorized according to the etiology of CKD. NS was defined as the presence of CKD associated with long-term essential hypertension, hypertensive retinopathy, left ventricular hypertrophy and minimal proteinuria. Time-trajectories in eGFR (CKD-Epi) were computed over a 4-year follow-up. In addition, we analysed the occurrence of a composite outcome of doubling of serum creatinine, eGFR reduction≥ 25% and/or ESKD needing dialysis or kidney transplantation. Results CKD was secondary to nephrosclerosis (CKD-NS) in 220 (72.3%) patients. Among the remaining 84 (27.7%), glomerular/diabetic diseases were the most frequent cause of CKD (47.6%). In the whole cohort, the average estimated annual GFR slope was of 1.8 mL/min/1.73 m2. eGFR decline was slower in CKD-NS as compared with the one of others (1.4 vs. 3.4 mL/min/1.73 m2; p&lt;0.001. Figure 1). The composite renal outcome during follow-up (median 36 mo.; range 6-48) occurred less frequently among elderly with CKD-NS (16/204 vs 14/70; p=0.01 Crude HR 0.43, 95%CI 0.22-0.85) and was associated at logistic analyses with etiology of CKD, serum total cholesterol, serum LDL cholesterol levels and glycemia (p ranging from 0.01 to 0.04). Conclusion Despite being highly prevalent in the elderly, NS is associated with a more favorable renal disease course as compared with other conditions. Therapeutic efforts to delay CKD progression in older populations should go beyond just optimizing blood pressure control and focus more on concomitant diseases.

scholarly journals Emerging Urinary Markers of Renal Injury in Obstructive Nephropathy

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Giuseppe Lucarelli ◽  
Vito Mancini ◽  
Vanessa Galleggiante ◽  
Monica Rutigliano ◽  
Antonio Vavallo ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Injury ◽  
Renal Damage ◽  
Interstitial Fibrosis ◽  
Renal Outcome ◽  
Obstructive Nephropathy ◽  
Tubulointerstitial Injury ◽  
Tubular Atrophy ◽  
Renal Function Deterioration

The effects of obstruction on renal function are the consequence of many factors that profoundly alter all components of glomerular function. Besides the acute effects on glomerular filtration rate and tubule function, a chronic obstruction induces tubular and interstitial injury that results from the activation of different pathways. The progression of tubulointerstitial injury leads to chronic renal damage characterized by tubular atrophy, inflammatory cell infiltration, and interstitial fibrosis. Obstructive nephropathy is an evolving disease in which the renal damage continues even after relief of the obstruction. In particular, it has been demonstrated that the time of relief is the most important factor in predicting long-term renal function deterioration. In this setting, the EGF/MCP-1 ratio, urinary NGAL, and urinary KIM-1 are useful early biomarkers of progressive renal damage and could have a potential role in predicting the long-term renal outcome. This minireview summarizes the role of these emerging urinary biomarkers of obstructive nephropathy based on the current understanding of the pathophysiology of renal injury.

Sign in / Sign up

Export Citation Format

Share Document