Correlation of X chromosome inactivation with clinical presentation of Fabry disease in a case report.

Fabry disease or also called Anderson-Fabry disease (FD) is a rare disease caused by pathogenic variants in the GLA gene, located on the X chromosome. This gene is involved in the metabolism of glycosphingolipids and its pathogenic variants cause a deficit or absence of α-galactosidase A causing the deposition of globotriaosylceramide throughout the body. Females have a variable phenotypic expression and a better prognosis than males. This is due to the X chromosome inactivation phenomenon. We present a clinical case of Fabry disease in a female with predominantly renal involvement and demonstrate how the X chromosome inactivation phenomenon is tissue dependent, showing preferential inactivation of the mutated allele at the renal level.

Creatine Kinase Elevation in Autosomal Dominant Polycystic Kidney Disease Patients on Tolvaptan Treatment.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary cause of end-stage kidney disease. Currently, tolvaptan is the only treatment that has proven to delay disease progression. The most notable side effect of this therapy is drug-induced liver injury; however, recently, there have been two reports of creatine kinase (CK) elevation in ADPKD patients on tolvaptan treatment. We set out to monitor and determine the actual incidence of CK elevation and evaluate its potential association with other clinical factors. METHODS: This is an observational retrospective multicenter study performed in rapidly progressive ADPKD patients on tolvaptan treatment from Barcelona, Spain. Laboratory tests, demographics, treatment dose, and reported symptoms were collected from October 2018 to March 2021. RESULTS: Ninety-five patients initiated tolvaptan treatment during follow-up. The medication had to be discontinued in 31 (32.6%) patients, primarily due to aquaretic effects (12.6%), elevated liver enzymes (8.4%), and symptomatic or persistently elevated CK levels (3.2%). Moreover, a total of 27 (28.4%) patients had elevated CK levels, with most of them being either transient (12.6%), mild and asymptomatic (4.2%), or resolved after dose reduction (3.2%) or temporary discontinuation (2.1%). CONCLUSION: We pre-sent the largest cohort that has monitored CK levels in a real-life setting, finding them elevated in 28.4% of patients. More research and monitoring will help us understand the clinical implications and the pathophysiological mechanism of CK elevation in this population.

Acute renal failure associated to paroxysmal nocturnal haemoglobinuria leads to intratubular haemosiderin accumulation and CD163 expression.

Decreased renal function has been observed in diseases with intravascular haemolysis, including paroxysmal nocturnal haemoglobinuria (PNH). However, the mechanisms via which haemoglobin enhances renal damage in this pathology are not fully known. We report a case of acute renal failure associated to PNH and extensive haemosiderin deposits in tubular cells. Renal biopsy also revealed a strong immunostaining of CD163 (a haemoglobin scavenger receptor expressed in macrophages) and oxidative stress markers (NADPH-p22 phox and haeme oxigenase-1) in areas with deposits of iron. This fact provides evidence for a pathogenic role for free haemoglobin in tubulointerstitial renal injury in human PNH disease.

[Sodium transporters and aquaporins: future renal biomarkers?]. / Transportadores de sodio y aquaporinas: futuros biomarcadores renales?

Renal sodium and water reabsorption is mediated by renal sodium transporters and water channels or aquaporins which are localized in the apical and basolateral membranes of tubular epithelial cells. The main apical sodium transporters and water channels located along the nephron are: sodium-proton exchanger subtype 3 (NHE-3) which reabsorbs most of the sodium coming from the glomerular filtrate, sodium-phosphate type II cotransporter (NaPiII) and aquaporin-1, all of which are located in the proximal tubule; sodium-potassium-2 chloride cotransporter (NKCC2) which plays a key role in sodium reabsorption in the thick ascending limb; the sodium-chloride cotransporter (NCC) in the distal tubule; and the epithelial sodium channel (ENaC) and aquaporin-2 located in the collecting tubule. There are some experimental studies in which the role of these proteins has been associated with the pathophysiology of several sodium and water balance disorders. In humans, urine is the perfect source to obtain biomarkers useful for the diagnosis of kidney diseases and the assessment of disease progression without the use of invasive procedures. Thus, some of the renal sodium transporters or the aquaporins located in the apical membrane which are excreted in the tubular lumen and detected in urine could become biomarkers of some sodium and water balance disorders. Nowadays there are many studies investigating the role of these proteins in humans in clinical settings.

A review on autosomal dominant tubulointerstitial kidney disease. / Revisión de la nefropatía tubulointersticial autosómica dominante.

In recent years there has been a reclassification of hereditary tubulointerstitial renal diseases. The old concepts of nephronoptisis or medullary cystic disease have been reordered based on the discovery of new genes. The 2015 KDIGO guidelines proposed a unification of terminology, diagnostic criteria and monitoring. So far 4genes causing autosomal dominant tubulointerstitial kidney disease have been described: MUC1, UMOD, HNF1B and REN. Although the mutation in each of them causes distinctive features in how they present, all have in common the progressive tubulointerstitial damage and renal fibrosis. In this article, we present a review of the guidelines and the literature, and some practical recommendations for dealing with this disease.

Effects of rapamycin on angiomyolipomas in patients with tuberous sclerosis.

BACKGROUND: Tuberous sclerosis (TS) is a systemic disease, with an autosomal dominant pattern of inheritance caused by mutations in two genes (TSC1 and TSC2) that cause tumours (angiomyolipomas [AML], angiofibromas, astrocytomas). Constant and inadequate proliferation occurring in TS may be blocked by mTOR inhibitors (mammalian target of rapamycin), such as rapamycin. MATERIAL AND METHODS: At present, our study includes 17 patients with TS. All had at least one AML greater than 2cm in diameter diagnosed by MRI. They received rapamycin during 12 months. Plasma levels remained stable between 4-8ng/dl. The AML size was monitored every six months by abdominal MRI. RESULTS: At 12 months of inclusion, MRI indicated a decrease in the size of AML in all patients showing at least a 50% reduction in 82.4% (14/17, 95% CI [56.57%, 96.20%]). The mean percent reduction was 66.3% (95% CI [56.9%, 75.6%], P<.0001). The major side effects observed were: oral aphthous ulcers (5/17); hypertriglyceridemia (3/17); microcytosis and hypochromia (3/17); diarrhea (2/17); acne (1/17); acute pyelonephritis (1/17); and proteinuria (1/17). CONCLUSIONS: These preliminary clinical data suggest that rapamycin can play a beneficial role in the treatment of TS. Our experience in 17 patients treated for 12 months demonstrates safety and efficacy in reducing AML volume.