Recent advances in the clinical management of autosomal dominant polycystic kidney disease [version 1; referees: 2 approved]

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic systemic disorder causing the development of renal and hepatic cysts and decline in renal function. It affects around 1 in 1,000 live births. Early hypertension and progressive renal failure due to massive enlargement of cysts and fibrosis are hallmarks of the disease. This article reviews recent advances in ADPKD and focuses mainly on diagnosis, management, and prediction of the course of the disease

Recent advances in the clinical management of autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic systemic disorder causing the development of renal and hepatic cysts and decline in renal function. It affects around 1 in 1,000 live births. Early hypertension and progressive renal failure due to massive enlargement of cysts and fibrosis are hallmarks of the disease. This article reviews recent advances in ADPKD and focuses mainly on diagnosis, management, and prediction of the course of the disease

How genomics reclassifies diseases : the case of Alport syndrome

Altres ajuts: The author's research is funded by the Instituto de Salud Carlos III/Fondo Europeo de Desarrollo Regional (FEDER) funds, RETIC REDINREN RD16/0009 FIS FEDER FUNDS.In this issue, Matthews et al. provide a comprehensive review of published cohorts with heterozygous pathogenic variants in COL4A3 or COL4A4, documenting the wide spectrum of the disease. Due to the extreme phenotypes that patients with heterozygous pathogenic variants in COL4A3 or COL4A4 may show, the disease has been referred to in a variety of ways, including 'autosomal dominant Alport syndrome', 'thin basement membrane disease', 'thin basement membrane nephropathy', 'familial benign hematuria' and 'carriers of autosomal dominant Alport syndrome'. This confusion over terminology has prevented nephrologists from being sufficiently aware of the relevance of the entity. Nowadays, however, next-generation sequencing facilitates the diagnosis and it is becoming a relatively frequent finding in haematuric-proteinuric nephropathies of unknown origin, even in non-familial cases. There is a need to raise awareness among nephrologists about the disease in order to improve diagnosis and provide better management for these patients

Safety and efficacy of enzyme replacement therapy in the nephropathy of Fabry disease

Kidney involvement with progressive loss of kidney function (Fabry nephropathy) is an important complication of Fabry disease, an X-linked lysosomal storage disorder arising from deficiency of α-galactosidase activity. Clinical trials have shown that enzyme replacement therapy (ERT) with recombinant human α-galactosidase clears globotriaosylceramide from kidney cells, and can stabilize kidney function in patients with mild to moderate Fabry nephropathy. Recent trials show that patients with more advanced Fabry nephropathy and overt proteinuria do not respond as well to ERT alone, but can benefit from anti-proteinuric therapy given in conjunction with ERT. This review focuses on the use of enzyme replacement therapy with agalsidase-alfa and agalsidase-beta in adults with Fabry nephropathy. The current results are reviewed and evaluated. The issues of dosing of enzyme replacement therapy, the use of adjunctive agents to control urinary protein excretion, and the individual factors that affect disease severity are reviewed

Dietary Aspects and Drug-Related Side Effects in Autosomal Dominant Polycystic Kidney Disease Progression

Autosomal dominant polycystic kidney disease (ADPKD) is the most commonly inherited kidney disease. In the absence of targeted therapies, it invariably progresses to advanced chronic kidney disease. To date, the only approved treatment is tolvaptan, a vasopressin V2 receptor antagonist that has been demonstrated to reduce cyst growth and attenuate the decline in kidney function. However, it has various side effects, the most frequent of which is aquaresis, leading to a significant discontinuation rate. The strategies proposed to combat aquaresis include the use of thiazides or metformin and a reduction in the dietary osmotic load. Beyond the prescription of tolvaptan, which is limited to those with a rapid and progressive decline in kidney function, dietary interventions have been suggested to protect against disease progression. Moderate sodium restriction, moderate protein intake (up to 0.8 g/kg/day), avoidance of being overweight, and increased water consumption are recommended in ADPKD guidelines, though all with low-grade evidence. The aim of the present review is to critically summarize the evidence on the effect of dietary modification on ADPKD and to offer some strategies to mitigate the adverse aquaretic effects of tolvaptan

Why do we keep ignoring sex in kidney disease?

Disparity; Pharmacokinetics; WomenDisparidad; Farmacocinética; MujeresDisparitat; Farmacocinètica; DonesThroughout the history of nephrology, little attention has been paid to the sex and gender differences in kidney disease. This lack of awareness prevents optimal diagnosis and management of kidney disease. In today's world of precision medicine, it is imperative to appreciate the differential factors regarding gender and kidney disease. This editorial summarizes the up-to-date literature regarding sex and gender differences in kidney disease and considers areas where knowledge is incomplete and where further research is needed. We address sex-specific effects on chronic kidney disease epidemiology; risks of dialysis underdosing and medication overdosing in women; unexplained loss of female sex advantage in life expectancy during dialysis, and impact of sex on diagnosis and management of genetic kidney disease. We also aim to highlight the impact of gender on kidney health and raise awareness of disparities that may be faced by women, and transgender and gender-diverse persons when a male-model approach is used by healthcare systems. By understanding the link between sex and kidney disease, kidney specialists can improve the care and outcomes of their patients. In addition, research on this topic can inform the development of targeted prevention and intervention strategies that address the specific needs and risk factors of different populations

Fabry disease : the many faces of a single disorder

In 1898, two dermatologists, William Anderson in England and Johannes Fabry in Germany, separately described a disease characterized by skin lesions, known as angiokera-tomas. This issue contains two reports of Fabry disease (FD) patients presenting with proteinuric chronic kidney disease (CKD) but lacking angiokeratomas [1,2]. These cases illustrate the phenotypic heterogeneity of the disease in females [1] and FD variants [2],theroleof genetic diagnosis [1] and renal biopsy [2] and recent advances in pathophysiology [1]. FD is caused by deficient activity of alpha-galactosidase A (α-GalA) due to mutations in the X-chromosome GLA gene, leading to accumulation of neutral glycolipids and eventual tissue injury and organ dysfunction [3]. In classical FD males, α-GalA activity is absent or nearly absent and there is an early onset of acroparesthesias, angiokeratoma and hypohydrosis followed by life-threatening cardiac, central nervous system and kidney disease leading to end-stage renal disease (ESRD) at a mean age of 40 year

Plan PrEFiNE: Plan estratégico para la enfermedad de Fabry en Nefrología

Background Renal failure is one of the main causes of death in patients with Fabry disease (FD). Due to the low prevalence of FD, delayed diagnosis and misdiagnosis, often the correct diagnosis is made when organ damage is already present. Early recognition of the disease would allow the prevention of severe complications and the premature death of patients with FD. Objective We present here the PrEFiNE project, which includes a wide spectrum of activities with the aim of improve knowledge and diagnosis of FD. The project is sponsored by Shire Iberia (http://shireiberica.com/) Methods From January 2016 to the end of 2017 several activities will be carried out, starting with a survey to evaluate current FD knowledge among nephrologists; in addition some studies to assess prevalence of this disease will be performed. One study will include patients receiving dialysis, another study will cover kidney transplant patients, and a pilot study in chronic kidney disease in stage 3-5 predialysis. Also planned is a pharmacoeconomic study to focus on burden of FD. At the same time medical education activities will be conducted both on line and on site. Plan for dissemination will include medical publications and diffusion to media. PrEFiNE Project will finish with the publication of a compilation book on FD in Nephrology including all planned activities and proposing recommendations based on results and detected unmet needs. PrEfiNE Plan will be coordinated by severa scientific committees, one at national level and 10 other regionals comittees, tha will be responsible to ensure the maximum scientific quality of proposed activities. An advisory board will supervise the project. Discussion PrEfiNE project will evaluate an action plan focused on improving FD knowledge to make necessary recommendations for an early recognition of the disease. In addition will generate a plan to improve previously undetected needs.Justificación: La enfermedad renal es una de las principales causas de muerte entre los pacientes con enfermedad de Fabry (EF). Al tratarse de una enfermedad de baja prevalencia, se realizan con frecuencia diagnósticos erróneos y retrasados, que a menudo se dan cuando ya se ha producido dan˜ o orgánico. El reconocimiento temprano de la enfermedad permitiría evitar las complicaciones graves y la muerte prematura en estos pacientes. Objetivo: Presentamos en este artículo un resumen del plan PrEFiNE, que incluye un abanico amplio de actividades con el objetivo de mejorar el conocimiento y reconocimiento de la EF entre los nefrólogos. Este proyecto está patrocinado por Shire Ibérica (http://shireiberica.com/). Métodos: Desde enero de 2016 y hasta finales del 2017 se iniciarán distintas actividades, comenzando por una evaluación del grado de conocimiento que existe actualmente sobre la EF. Se incluyen 3 estudios de prevalencia de la EF, que abarcan el espectro de los pacientes con enfermedad renal crónica (pacientes en diálisis, pacientes trasplantados renales y un estudio piloto en pacientes con enfermedad renal crónica en estadio 3–5 prediálisis) y un estudio farmacoeconómico, centrado en el impacto de la carga de la enfermedad. Parale- lamente, se realizarán actividades formativas tanto presenciales como on line, y un amplio plan de comunicación mediante publicaciones y difusión a medios. El proyecto culminará con la publicación de un libro blanco de la EF en Nefrología, que recoja el resultado de todas las actividades y que proponga recomendaciones en respuesta a los resultados y a las necesidades detectadas. El plan PrEFiNE estará coordinado por distintos comités científicos, uno nacional y 10 regionales que garantizarán el desarrollo de las acciones con el máximo rigor científico y será supervisado por un comité asesor. Discusión: El plan PrEFiNE nos permitirá evaluar la utilidad de un proyecto dirigido a mejorar el conocimiento de una enfermedad minoritaria como la EF a nivel nacional, y a partir del cual se podrán establecer las recomendaciones necesarias para mejorar su reconocimiento, además de planes enfocados a mejorar las necesidades no cubiertas detectadas durante su desarroll

Genetic kidney diseases as an underrecognized cause of chronic kidney disease : the key role of international registry reports

Inherited kidney diseases (IKDs) are among the leading causes of early-onset chronic kidney disease (CKD) and are responsible for at least 10-15% of cases of kidney replacement therapy (KRT) in adults. Paediatric nephrologists are very aware of the high prevalence of IKDs among their patients, but this is not the case for adult nephrologists. Recent publications have demonstrated that monogenic diseases account for a significant percentage of adult cases of CKD. A substantial number of these patients have received a non-specific/incorrect diagnosis or a diagnosis of CKD of unknown aetiology, which precludes correct treatment, follow-up and genetic counselling. There are a number of reasons why genetic kidney diseases are difficult to diagnose in adulthood: (i) adult nephrologists, in general, are not knowledgeable about IKDs; (ii) existence of atypical phenotypes; (iii) genetic testing is not universally available; (iv) family history is not always available or may be negative; (v) lack of knowledge of various genotype-phenotype relationships and (vi) conflicting interpretation of the pathogenicity of many sequence variants. Registries can contribute to visualize the burden of IKDs by regularly grouping all IKDs in their annual reports, as is done for glomerulonephritis or interstitial diseases, rather than reporting only cystic disease and hiding other IKDs under labels such as 'miscellaneous' or 'other'. Any effort to reduce the percentage of patients needing KRT with a diagnosis of 'nephropathy of unknown etiology' or an unspecific/incorrect diagnosis should be encouraged as a step towards precision nephrology. Genetic testing may be of value in this context but should not be used indiscriminately, but rather on the basis of a deep knowledge of IKDs

Hypertension in autosomal-dominant polycystic kidney disease (ADPKD)

Cardiovascular (CV) complications are the major cause of death in autosomal-dominant polycystic kidney disease (ADPKD) patients. Hypertension is common in these patients even before the onset of renal insufficiency. Blood pressure (BP) elevation is a key factor in patient outcome, mainly owing to the high prevalence of target organ damage together with a poor renal prognosis when BP is increased. Many factors have been implicated in the pathogenesis of hypertension, including the renin-angiotensin-aldosterone system (RAAS) stimulation. Polycystin deficiency may also contribute to hypertension because of its potential role in regulating the vascular tone. Early diagnosis and treatment of hypertension improve the CV and renal complications of this population. Ambulatory BP monitoring is recommended for prompt diagnosis of hypertension. CV risk assessment is mandatory. Even though a nonpharmacological approach should not be neglected, RAAS inhibitors are the cornerstone of hypertension treatment. Calcium channel blockers (CCBs) should be avoided unless resistant hypertension is present. The BP should be <140/90 mmHg in all ADPKD patients and a more intensive control (<135/85 mmHg) should be pursued as soon as microalbuminuria or left ventricle hypertrophy is present