Patients with Fabry disease display heavy podocyturia; those untreated present significantly higher podocyturia, lower proteinuria and better renal function than those who are treated, suggesting that therapy may be started at advanced stages. Podocyturia may antedate proteinuria, and enzyme therapy may protect against podocyte loss.

At GFR <60 ml/min, CKD-EPI and Hoek equations appeared to best correlate with (99m)TcDTPA. In controls and at early stages of CKD, creatinine-based equations correlated better with (99m)Tc-DTPA, with CKD-EPI being the one with the best degree of agreement.

Background. Despite enzyme replacement therapy, Fabry nephropathy still progresses. Podocyturia is an irreversible event that antedates proteinuria and leads to chronic renal failure. We evaluated a potential mechanism of podocyte detachment via the expression of the urokinase-type Plasminogen Activator Receptor (uPAR) in urinary podocytes of Fabry patients. Methods. This is a cross-sectional study that included controls (n = 20) and Fabry patients (n = 44) either untreated (n = 23) or treated with agalsidase-β (n = 21). Variables. Variables are estimated glomerular filtration rate (eGFR), urinary protein : creatinine ratio, and urinary uPAR+ podocyte : creatinine ratio. uPAR mRNA expression in response to lyso-Gb3, a bioactive glycolipid accumulated in Fabry disease, was studied in cultured human podocytes. Results. Controls and Fabry patients had similar age, gender, and renal function. Urinary uPAR+ podocytes were higher in patients than in controls. Untreated patients were significantly younger; had more females, and presented lower urinary protein : creatinine ratios and significantly higher urinary uPAR+ podocytes than treated subjects. In treated patients, urinary uPAR+ podocytes correlated with urinary protein : creatinine ratio (ρ = 0.5; p = 0.02). Lyso-Gb3 at concentrations found in the circulation of Fabry patients increased uPAR expression in cultured podocytes. Conclusions. Urinary podocytes expressing uPAR are increased in Fabry patients, especially in untreated patients. The potential contribution of uPAR expression to podocyte detachment merits further studies.

Patients with Fabry disease present a higher risk of cardiovascular and kidney morbidity. We present a patient with a past history of biopsy-proven Fabry disease and stage 3 chronic kidney disease. Proteinuria partially dropped from 6.8 g/day to 2.1 g/day despite an aggressive regime which consisted of low-salt diet, agalsidase beta infusions, dual blockade of the renin-angiotensin system, and low-dose maintenance of steroids. As proteinuria is considered a risk marker of cardiovascular disease and of progression of kidney disease, we added amiloride 5 mg/day, a drug with proven effects in podocyte stabilization and proteinuria actions at the distal convoluted tubule. Proteinuria finally decreased to 0.8 g/day. This report highlights the relevance of intervening on proteinuria in a multitarget approach in order to reduce it as much as possible. Due to this pharmacological response, we suggest that although agalsidase beta specific treatment protects the endothelium, the podocyte, and the tubule in Fabry disease and secondary haemodynamic and immunologic pathways are treated with inhibition of the renin-angiotensin system and steroids, amiloride may act as a complementary tool in podocyte stabilization and in proteinuria effects at the distal tubule.

BackgroundCardiovascular disease is the leading cause of morbidity and mortality in hemodialysis (HD) patients, the main etiologies being diabetes and hypertension. Cardiac and inflammatory biomarkers are usually employed to assess risk or damage, or during follow-up. Proteinuria is considered a strong predictor of morbidity, a cause of inflammation, oxidative stress, hemodynamic alteration, and progression of chronic kidney disease. However, proteinuria is rarely considered in the clinical assessment of HD patients.MethodsThis was a concurrent, cohort-observational, cross-sectional study in which 52 chronic HD subjects were divided into three groups according to the degree of proteinuria: Group (G) A: <1 g/day, n = 25; GB: 1–3 g/day, n = 13; GC: >3 g/day, n = 14. Baseline hemoglobin, albuminemia, cholesterol, body mass index, Malnutrition-Inflammatory Score, pro-B-type natriuretic peptide, troponin T, C-reactive protein (CRP), and ultrafiltration rates were analyzed.ResultsThere was no difference between groups in terms of baseline age, gender, hypertension, cause of renal failure, hemoglobin, cholesterol, albumin, CRP levels, cardiac biomarkers, adiponectin, body mass index, or Malnutrition-Inflammatory Score. Time on HD: GA, 34.56 ± 23.3 (range [r]: 6–88); GB, 25.15 ± 19.40 (r: 6–58); GC, 18.21 ± 9.58 (r: 6–74) months; P = 0.048. Proteinuria: GA, 0.33 ± 0.30 (r: 0.0–0.88); GB, 1.66 ± 0.54 (r: 1.03–2.75); GC, 7.18 ± 2.80 (r: 3.04–21.5) g/day; P < 0.001. Mean ultrafiltration rates were significantly different: GA, 2.80 ± 0.73; GB: 1.85 ± 0.96 liters/session; P = 0.003. Fourteen diabetic patients were identified (27%): GA, 3 (12%); GB, 3 (23%); GC, 8 (57%); P = 0.009. A positive and significant correlation was observed between diabetes and proteinuria >3 g/day: rho 0.438, P = 0.027. Although troponin T, pro-B-type natriuretic peptide, adiponectin, and CRP were not different among groups, the positive correlation between troponin T and CRP elevated significantly as proteinuria increased: GA, rho 377, P = 0.063; GB, rho 663, P = 0.013; GC, rho 687, P = 0.007.ConclusionIn chronic HD, nephrotic-range proteinuria was significantly higher in diabetic nephropathy patients versus other causes. This was associated with inflammation and cardiac stress and was independent of fluid removal. Proteinuria >3 g/day was associated with shorter time on HD. Whether severe proteinuria is associated with shorter survival in HD, independent of diabetes, is to be determined. Proteinuria should be considered in the assessment of cardiovascular and inflammatory states in HD patients.

Central venous disease (CVD) is a serious complication in hemodialysis patients. Neurological manifestations are rare. We describe a female with end-stage renal disease with throbbing headache accompanied by paresthesia, weakness, and abnormal posture of her right hand during dialysis sessions. Motor symptoms completely resolved after each dialysis session, although the headaches persisted for several hours. No neurological deficit was evidenced on physical examination. Digital subtraction angiography identified an incomplete thrombosis of the left brachiocephalic vein with retrograde flow in the internal jugular vein, sigmoid sinus, and transverse sinus on the left side. This case illustrates that cerebral venous congestion due to CVD can produce neurological symptoms. Furthermore, we systematically review the literature to identify the characteristics of the cases described so far. This allows clinicians to know the entity and have a high index of suspicion in a hemodialysis patient who develops neurological symptoms.

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.

Focal and segmental glomerulosclerosis is classified as either primary or secondary. We present a patient with a past history of biopsy-proven focal and segmental glomerulosclerosis. Despite initial response to dual blockade and steroids, proteinuria raised when steroids were decreased. After the patient was restarted on steroids, proteinuria did not improve. Another biopsy confirmed the previous diagnosis but suggested Fabry's disease, later confirmed by electron microscopy, α-galactosidase A serum and leukocyte deficiency as well as genetic studies. Proteinuria decreased when agalsidase β was prescribed in parallel with steroid tapering, increased with steroid discontinuation and improved with meprednisone administration. This report highlights the relevance of electron microscopy in kidney biopsy. In glomerulosclerosis, despite specific treatment, secondary hemodynamic and immunologic pathways may contribute to the development of proteinuria and accelerate the renal disease progression due to the primary disease. We discuss possible pathophysiologic pathways involved in proteinuria in Fabry's disease according to the biopsy and the therapeutic response.