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Introduction: Hyperkalemia, one of the most important electrolyte abnormalities of chronic kidney disease (CKD), often limits the use of renin-angiotensin-aldosterone system inhibitors and can increase in the postprandial period. In this study we report a real-world experience with the new non-adsorbed potassium binder patiromer in stage 3b-4 CKD patients. Moreover, we performed a cross-sectional analysis to evaluate, for the first time, the efficacy of patiromer in the control of postprandial potassium concentrations., Methods: We retrospectively collected data of 40 patients at the time of patiromer initiation (T0), and after 2 (T2), 6 (T6) and 12 (T12) months of treatment. For cross sectional analysis, a blood sample was collected 2 h after the main meal for the evaluation of postprandial potassium concentrations., Results: Eighty-two point five percent of patients (33/40) reached normal potassium concentrations at T2. Serum potassium significantly decreased at T2 compared to T0 (5.13 ± 0.48 vs 5.77 ± 0.41 mmol/L, respectively; p < 0.001) and the reduction remained significant during the follow-up (5.06 ± 0.36 at T6 and 5.77 ± 0.41 at T12; p < 0.001 vs T0). Renin-angiotensin-aldosterone system inhibitors were continued by 93% of patients (27/29). Adverse events were reported in 27.5% of patients and were all mild-to-moderate. Postprandial potassium concentrations did not significantly change compared to fasting state potassium measured at T12 (4.53 ± 0.33 vs 5.06 ± 0.36 mmol/L; p = 0.15)., Conclusions: In a real-world setting of advanced CKD patients, patiromer is a useful treatment for hyperkalemia, since it significantly reduces serum potassium levels over the long term and is able to maintain potassium concentrations in the normal range even in the post-prandial period., (© 2024. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Simple renal cysts are a common finding during abdominal imaging assessment. The incidence increases with age and it is higher in male gender. Parapelvic cysts are a subset of simple cysts that arise within the renal parenchyma, adjacent to the renal sinus, characterized by being generally single, larger, and incompletely surrounded by renal parenchyma. Noteworthy, parapelvic cysts are a rare and understudied condition which, although considered clinically insignificant due to the absence of influence on renal function, still have a controversial aetiopathogenesis. On the other hand, urological management and differential diagnosis have been thoroughly investigated. The aim of our review is to provide an overall vision on this rare condition, usually misdiagnosed and underestimated, on the basis of more recent data. An accurate differential diagnosis of parapelvic cysts can lead to the identification of treatable conditions such as Fabry disease, autosomal dominant polycystic kidney disease, polycystic liver disease and tuberous sclerosis complex disease., (© 2022. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Autosomal dominant polycystic kidney disease (ADPKD) is a heterogeneous genetic disorder included in ciliopathies, representing the fourth cause of end stage renal disease (ESRD), with an estimated prevalence between 1:1000 and 1:2500. It is mainly caused by mutations in the PKD1 and PKD2 genes encoding for polycystin 1 (PC1) and polycystin 2 (PC2), which regulate differentiation, proliferation, survival, apoptosis, and autophagy. The advances in the knowledge of multiple molecular pathways involved in the pathophysiology of ADPKD led to the development of several treatments which are currently under investigation. Recently, the widespread approval of tolvaptan and, in Italy, of long-acting release octreotide (octreotide-LAR), represents but the beginning of the new therapeutic management of ADPKD patients. Encouraging results are expected from ongoing randomized controlled trials (RCTs), which are investigating not only drugs acting on the calcium/cyclic adenosin monoposphate (cAMP) pathway, the most studied target so far, but also molecules targeting specific pathophysiological pathways (e.g. epidermal growth factor (EGF) receptor, AMP-activated protein kinase (AMPK) and KEAP1-Nrf2) and sphingolipids. Moreover, studies on animal models and cultured cells have also provided further promising therapeutic strategies based on the role of intracellular calcium, cell cycle regulation, MAPK pathway, epigenetic DNA, interstitial inflammation, and cell therapy. Thus, in a near future, tailored therapy could be the key to changing the natural history of ADPKD thanks to the vigorous efforts that are being made to implement clinical and preclinical studies in this field. Our review aimed to summarize the spectrum of drugs that are available in the clinical practice and the most promising molecules undergoing clinical, animal, and cultured cell studies., (© 2021. Italian Society of Nephrology.)

Background: Fabry disease (FD) is a rare X-linked genetic disorder of glycosphingolipid catabolism caused by mutations in the GLA gene. Its heterogeneous presentation, the paucity of specific early markers, and the absence of a genotype-phenotype correlation are associated with a delayed or missed diagnosis. The true prevalence of FD remains so far unknown., Methods: A systematic search of FD screening studies in dialysis patients published from January 1995 until January 2019 was performed to reanalyze the prevalence of GLA mutations in this population after assigning their correct phenotype., Results: Twenty five screening studies involving 39,621 dialysis patients were included. Of them, 116 [91 males (0.23%) and 25 females (0.06%)] were positive to the GLA sequencing analysis. 56 (48.2%) had benign variant, 52 (44.8%) a pathogenic GLA mutation (39 classic and 13 late onset mutations) and 8 (6.9%) a mutation of uncertain significance. The overall prevalence of GLA variants was 0.24% [CI 95%, 0.17-0.32] while the overall prevalence recalculated on basis of only pathogenetic mutations was 0.14% [CI 95%, 0.08-0.20]. This difference was significant (P = 0.048)., Conclusions: Although the real prevalence of classic FD is low, the screening in the high-risk renal population remains of primary interest as an early diagnosis is fundamental for a timely specific therapy; moreover, the identification of index cases could allow patients' relatives to be investigated and promptly treated.

Neuroendocrine tumors represent a heterogeneous category of neoplasm, with conflicting diagnostic and therapeutic demands. We here describe the case of a 72-yr-old woman with evidence of a poorly differentiated small-cell neuroendocrine carcinoma (NEC) localized in different endocrine glands and other non-endocrine organs. In particular, a large ovarian mass, multinodular thyroid goiter, right adrenal mass, cystic liver metastases and anterior mediastinum lymph node metastasis were present. The largest thyroid nodule caused tracheal restriction and dyspnea. Diagnosis of poorly differentiated metastasized NEC of unknown origin was made on the basis of histological and immunohistochemical findings, and treatment with etoposide (100 mg/m2 in days 1, 2 and 3) and cisplatinum (45 mg/m2 in days 2 and 3) was initiated. Simultaneously, im administration of octreotide LAR 20 mg every 28 days was started, according to the presence of SS receptors at 111In-octreotide scan. Rapid improvement of dyspnea and a reduction of the largest thyroid nodule, liver metastases and adrenal mass by 50% were observed after 3 months of treatment; the dimensions remained stable thereafter, while the pericardial lymph node disappeared. In conclusion, poorly differentiated NEC of unknown primary site is a well-recognized category, usually with an aggressive behavior, rapid growth rate and wide dissemination. Median survival of these patients is 6 months if left untreated. Our patient is alive 18 months after beginning the treatment, reporting good general condition and quality of life over the whole follow-up period.

Reportedly, most acromegalics are refractory to the growth hormone (GH)-releasing effect of central nervous system-acting stimuli. For instance, the synthetic analogue of met-enkephalin (Enk) viz. FK 33-824 fails to alter the high circulating GH levels of acromegalics. The most likely interpretation of such finding is that circulating GH disrupts, for a negative feedback effect, hypothalamic opioid function and/or GH-releasing hormone (GHRH) producing neurons, through which opioids exert their action. To address this issue, we have evaluated in intact and hypophysectomized male rats the effect of a high-dose GH regimen on the hypothalamic stores of endogenous opioid peptides, beta-endorphin (beta-EP) and met-enkephalin (met-enk). Moreover we have evaluated in intact male rats the effect of exogenous GH on median eminence (ME) GHRH stores and the ability of FK 33-824 to stimulate GH and prolactin (PRL) secretion and of exogenous GHRH to induce GH secretion. Human GH (25 and 250 micrograms bid for 4 days) administered to hypophysectomized rats strikingly reduced beta-EP and met-enk-like immunoreactivity (LI) in the medial basal hypothalamus, the effect being already maximal with the lower hGH dose. The higher dose of hGH diminished, though to a lower extent, hypothalamic beta EP-LI content also in intact rats, and reduced GHRH-LI content in the ME. Despite these profound biochemical alterations, the GH responsiveness to GHRH and FK 33-824 administration was preserved, while the latter drug induced a lower PRL rise in GH-treated than in control rats.(ABSTRACT TRUNCATED AT 250 WORDS)