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.

In recent decades there has been an increasing prevalence of urolitithiasis in many western countries and at the same time there has been an increasing progression of obesity that has reached epidemic proportions. The aim of the present study was to assess the influence of overweight/obesity on the metabolic risk factors for renal stone formation. We studied 799 renal stone formers (462 men and 337 women) who came to the clinic for metabolic risk factors evaluation. They were all studied with a standard protocol (two 24-h urine collections and serum parameters). They were divided according to their BMI in normal (BMI < 25) overweight (BMI 25-29.9) and obese (BMI > 30). Low-weight individuals were excluded. Overall, 487 of 799 (60.9%) patients had a BMI > 25, including 40.6% overweight and 20.3% obese. Among women 55.2% had normal weight, 25.5 were overweight, and 19.3% were Obese; among men 27.3% had normal weight, 51.7 were overweight, and 21% were obese. Age increased significantly with increasing BMI both in men and women. In women there was a significant increase in the excretion of oxalate, uric acid, phosphorus, creatinine, and sodium with increasing BMI, but no change was observed in calcium, magnesium, citrate, and urine pH. In men there was a significant increase in the excretion of oxalate, uric acid, creatinine, phosphorus, sodium, magnesium, and citrate with increasing BMI, no change in urinary calcium and significant progressive decrease in urinary pH. In this population of stone formers there was a high prevalence of overweight/obesity (60.9%). Both in men and women we found a significant increase in the urinary excretion of two promoters of stone formation, oxalate, and uric acid but no change in urinary calcium. There was either no change or increase in magnesium and citrate, inhibitors of crystallization, and a significant decrease in urine pH only in men.

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.

BackgroundCertain glomerulopathies are associated with increased levels of CD80 (B7-1). We measured the urinary excretion of CD80, podocyturia and proteinuria in controls and in subjects with Fabry disease either untreated or on enzyme replacement therapy (ERT).MethodsCross-sectional study including 65 individuals: controls (n = 20) and Fabry patients (n = 45, 23 of them not on ERT and 22 on ERT). Variables included age, gender, urinary protein/creatinine ratio (UPCR), estimated glomerular filtration rate (eGFR), urinary uCD80/creatinine ratio (uCD80) and podocyturia. CD80 mRNA expression in response to lyso-Gb3, a bioactive glycolipid accumulated in Fabry disease, was studied in cultured human podocytes.ResultsControls and Fabry patients did not differ in age, eGFR and gender. However, UPCR, uCD80 and podocyturia were significantly higher in Fabry patients than in controls. As expected, Fabry patients not on ERT were younger and a higher percentage were females. Non-ERT Fabry patients had less advanced kidney disease than ERT Fabry patients: UPCR was lower and eGFR higher, but uCD80 and podocyturia did not differ between non-ERT or ERT Fabry patients. There was a significant correlation between uCD80 and UPCR in the whole population (r 0.44, p 0.0005) and in Fabry patients (r 0.42, p 0.0046). Lyso-Gb3 at concentrations found in the circulation of Fabry patients increased uCD80 expression in cultured podocytes.ConclusionsFabry disease is characterized by early occurrence of increased uCD80 excretion that appears to be a consequence of glycolipid accumulation. The potential for uCD80 excretion to reflect early, subclinical renal Fabry involvement should be further studied.

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.