Domenico Trimboli

Relaxin: New Pathophysiological Aspects and Pharmacological Perspectives for an Old Protein

Human relaxin‐2 (hereafter simply defined as “relaxin”) is a 6‐kDa peptidic hormone best known for the physiological role played during pregnancy in the growth and differentiation of the reproductive tract and in the renal and systemic hemodynamic changes. This factor can also be involved in the pathophysiology of arterial hypertension and heart failure, in the molecular pathways of fibrosis and cancer, and in angiogenesis and bone remodeling. It belongs to the relaxin peptide family, whose members comprehensively exert numerous effects through interaction with different types of receptors, classified as relaxin family peptide (RXFP) receptors (RXFP1, RXFP2, RXFP3, RXFP4). Research looks toward the in‐depth examination and complete understanding of relaxin in its various pleiotropic actions. The intent is to evaluate the likelihood of employing this substance for therapeutic purposes, for instance in diseases where a deficit could be part of the underlying pathophysiological mechanisms, also avoiding any adverse effect. Relaxin is already being considered as a promising drug, especially in acute heart failure. A careful study of the different RXFPs and their receptors and the comprehension of all biological activities of these hormones will probably provide new drugs with a potential wide range of therapeutic applications in the near future.

From Water to Aquaretics: a Legendary Route

Man is water. When life appeared on earth, the primordial cell had a simple structure and could immediately ascertain from the surrounding aquatic environment the substances for nutrition and oxygen, without any need for structural complexity. As part of evolution, during the transition from aquatic to terrestrial life, vertebrates had to fight against dehydration as well as fish in the sea. In this complex mechanism of osmoregulation, the structure and function of some osmoregulatory hormones have been maintained during the evolution of species, from fish to man. Within the homeostatic mechanism, the renin-angiotensin-aldosterone system (RAAS) is crucial in the regulation of renal reasorption of water and sodium. It is also involved in the regulation of renal plasma flux, blood volume and blood pressure. Vasopressin plays a hormonal function in the mechanisms of water homeostasis acting through Aquaporins (AQP), channel-proteins that allow bi-directional water transport across cell membranes.

3 Tesla-Diffusion Tensor Imaging in Autosomal Dominant Polycystic Kidney Disease: The Nephrologist's Point of View

Background/Aims: CT, MRI and ultrasound are currently used for screening and follow-up of individuals affected by autosomal dominant polycystic kidney disease (ADPKD). Dynamic contrast-enhanced MRI studies renal perfusion after gadolinium administration, with possible side effects, such as nephrogenic systemic fibrosis. The aim of our study was to evaluate the clinical application of 3 Tesla (3T)-diffusion tensor image (DTI) in ADPKD patients, correlating its parameters, such as fractional anisotropy (FA), and apparent diffusion coefficient (ADC) with kidney function tests. Methods: Eight ADPKD patients and 6 healthy volunteers (HS) were enrolled. FA and ADC mean values were calculated. And correlations between DTI-parameters, creatinine and estimated glomerular filtration rate (eGFR) were evaluated. Results: Parenchymal FA was significantly lower in ADPKD than HS (FA: 0.17 ± 0.03 vs. 0.22 ± 0.01; p = 0.02), whereas parenchymal ADC was higher in patients than controls (2.48 (×10-3) ± 0.16 vs. 2.28 (×10-3) ± 0.09), but a statistically significant difference was not achieved (p = 0.27). Direct correlations were revealed between eGFR and FA (r = 0.82; p = 0.0003), whereas an inverse correlation was found with creatinine (r = -0.77; p = 0.001). Similarly, ADC closely correlated with creatinine (r = 0.79; p = 0.0006) and eGFR (r = -0.620; p = 0.01). Conclusion: 3T-DTI is a promising radiological tool that could be used by nephrologists to evaluate ADPKD patients, highlighting early micro-structure alterations, without side effects and contrast agent administration.

Unexpected hypercalcemia in a diabetic patient with kidney disease

We report a case of a diabetic patient with progressive chronic kidney disease and unexplained hypercalcemia. This unusual presentation and the investigation of all possible causes led us to perform a renal biopsy. The systemic sarcoidosis diagnosis was confirmed by the presence of interstitial multiple granulomas composed of epithelioid and multinucleated giant cells delimited by a thin fibrous reaction, and by pulmonary computed tomography finding of numerous lumps with ground-glass appearance. Sarcoidosis most commonly involves lungs, lymph nodes, skin and eyes, whilst kidney is less frequently involved. When it affects males it is characterized by hypercalcemia, hypercalciuria, and progressive loss of renal function. Early treatment with steroids allows for a gradual improvement in renal function and normalization of calcium serum values. Otherwise, the patient would quickly progress to end stage renal disease. Finding of hypercalcemia in a patient with renal failure must alert physicians because it may be a sign of several pathological entities.