Kidney Disease Marta Crespo and Clara Barrios

Pathophysiology, Risk Factors and Biomarkers in Kidney Diseases

Study of the cardiovascular profile, renin-angiotensin-aldosterone system, endothelial dysfunction and inflammation in normotensive patients suffering from autosomal dominant polycystic kidney disease without kidney failure.

ADPKD patients have a high prevalence of hypertension which significantly conditions their life prognosis as it favours the progression of kidney disease and is the main cardiovascular risk factor. Nowadays, there are large gaps in relation to knowledge about its onset. The possible change in circadian rhythm before the morning rise in blood pressure (BP) and the presence of subclinical damage in various target organs are some of the hypotheses.

We propose investigating to see if there is a relation between BP level and its circadian rhythm and subclinical target organ damage and kidney size in patients with autosomal dominant polycystic kidney disease and normal kidney functioning. We also propose going deeper into what is already known about RAAS hyperactivity and evaluating endothelial dysfunction in the initial stages of disease.

Early biomarkers of acute kidney failure

Acute kidney failure (AKF) is an increasingly common and fatal complication among hospitalised patients. Current diagnostic tests for AKF include Seric Creatinine (SCr) and Blood Urea Nitrogen (BUN), biomarkers which were identified and included in clinical practice decades ago. Nowadays, it is widely acknowledged that these parameters are sub-optimal markers for the diagnosis of acute kidney failure. Therefore, more sensitive and specific biomarkers are needed for the diagnosis.

We propose validating NGAL, KIM-1 and IL-18 as early biomarkers of acute kidney failure. In addition, we aim to study other inflammatory markers such as tumour necrosis factor and interleukin-6. Early and accurate diagnosis of acute kidney failure will enable us to perform interventional studies quickly and at the right time, which is needed for developing new preventive and treatment strategies for improving acute kidney failure prognosis.

Cardiovascular disease and uraemia: analysis of the prevalence and relevance of cardiovascular risk factors.

Patients on a haemodialysis programme present a very high cardiovascular risk and mortality caused by these risks is between 10 and 20 times greater than that of the general population. The high prevalence of the classic cardiovascular risk factors (Framingham) in these patients is not enough in itself to explain this high cardiovascular risk. Therefore, new factors contributing to increasing this risk have been proposed: lipoprotein (a), hyperhomocysteinemia, oxidative stress, inflammation, high ADMA or troponin levels, among others, factors specific to chronic kidney failure (anaemia, volume overload, changes in calcium-phosphorous product, hyperparathyroidism and malnutrition). We will also study the possible association of classic cardiovascular risk factors and new ones with the cardiovascular changes present in uraemia (left ventricular hypertrophy, intima-media thickness/carotid atherosclerosis, arterial rigidity, etc.). We are planning to analyse if the TGF-beta codon 10 (Leu-Pro) polymorphism is connected to overall and cardiovascular mortality, as well as cardiovascular morbidity in the haemodialysis population.

Usefulness of imaging techniques and biomarkers in predicting cardiovascular risk in patients with chronic kidney disease in Spain: the NEFRONA Project*

Cardiovascular Disease (CD) is the first cause of mortality in chronic kidney disease patients (CKD). Cardiovascular risk assessment using traditional factors is not very useful in this population due to the phenomenon of “reverse epidemiology” and the existence of specific factors stemming from uraemia. The Nefrona project is a prospective study aiming to assess the usefulness of imaging techniques and biomarkers in predicting CD and CKD. In November 2009, the project began recruiting over 2,500 asymptomatic adult patients with CKD (stage 3-5D) coming from kidney outpatient visits and dialysis centres from all over Spain (over 50 centres). In addition, almost 1,000 non-CKD patients are included (control group). The onset of cardiovascular events and mortality are registered on a semi-annual basis. A travelling team performs a carotid ultrasound to assess intima-media thickness and the presence of plaques, and determines the ankle-brachial index for classifying atheromatous disease. A score based on the presence of calcifications in the carotid, femoral and brachial arteries and in the heart valves, detected via ultrasound, is used in the study of vascular calcifications. Finally, blood samples are collected for determining biomarkers, thus generating the most important biobank known for this type of patient . This biobank will serve to generate high-level research projects. Therefore, the project will evaluate the usefulness of imaging techniques and biomarkers in the assessment of atheromatous disease and its predictive value in the Spanish CKD population. The Kidney Disease Research Unit (UREN, Unitat de Recerca en Nefropaties) is participating in this project by studying and including 100 patients, and is one of the three main recruitment centres.