Renal Disease in Metabolic Syndrome: the Hidden Role of Intrarenal Ischemia.

Introduction: The pathogenesis of renal disease in obesity and metabolic syndrome (MS) is mostly unknown. This is in part because of the limited information about renal morphological changes in these conditions. We evaluated renal histology in subjects with MS and those without MS, who are participants in the European Nephrectomy Biobank (ENBiBA) project. Methods: MS was defined with at least 3 of the following criteria: (i) body mass index (BMI) ≥27 kg/m2; (ii) prediabetes: fasting glucose of 100-125 mg/dl or HbA1c >5.7%; (iii) systolic or diastolic blood pressure >140/90 mm Hg or the use of medications; and (iv) triglycerides >150 mg/dl or high-density lipoprotein cholesterol <40 (in men) or 50 mg/dl (in women). The absence of these criteria defined patients without MS. Exclusion criteria were diabetes or known causes of renal disease. Results: A total of 157 cases were evaluated: 49 without and 108 with MS. Those with MS were older (54 ± 16 vs. 66 ± 11, P < 0.0001), had more prevalent chronic kidney disease (CKD, estimated glomerular filtration rate [eGFR] <60 ml/min): 24% (23%) versus 4% (8%) (P = 0.02), and had higher albumin-to-creatinine ratio (10 [4-68] vs. 4.45 [0-27], P = 0.05) than those without MS. Global sclerosis (3% [1-7] vs. 7% [3-13], P < 0.0001), nodular sclerosis, mesangial expansion, glomerulomegaly; moderate + severe hyalinosis, and arteriosclerosis were more frequent in those with MS than in those without (88 [82] vs. 29 [59]; 83 [77] vs. 30 [61]; P < 0.05). These vascular changes were independent of differences in age. Conclusion: In MS, ischemic renal disease may play a role in renal disease. In addition, some patients may develop lesions compatible with diabetic nephropathy such as increased mesangial expansion and nodular sclerosis. Further analyses are needed to study the consequences of the pandemic of obesity on renal health.

Effects of a Personalized Diet on Nutritional Status and Renal Function Outcome in Nephrectomized Patients with Renal Cancer.

Nutritional therapy (NT) based on a controlled protein intake represents a cornerstone in managing chronic kidney disease (CKD). However, if a CKD patient is at the same time affected by cancer, oncologists and nutritionists tend to suggest a dietary regimen based on high protein intake to avoid catabolism and malnutrition. International guidelines are not clear when we consider onco-nephrological patients and, as a consequence, no clinical shared strategy is currently applied in clinical practice. In particular, no precise nutritional management is established in nephrectomized patients for renal cell carcinoma (RCC), a specific oncological cohort of patients whose sudden kidney removal forces the remnant one to start a compensatory mechanism of adaptive hyperfiltration. Our study aimed to investigate the efficacy of a low-normal-protein high-calorie (LNPHC) diet based on a Mediterranean model in a consecutive cohort of nephrectomized RCC patients using an integrated nephrologist and nutritionist approach. A consecutive cohort of 40 nephrectomized RCC adult (age > 18) patients who were screened for malnutrition (malnutrition screening tool, MST < 2) were enrolled in a tertiary institution between 2020 and 2022 after signing a specific informed consent form. Each patient underwent an initial nephrological and nutritional evaluation and was subsequently subjected to a conventional CKD LNPHC diet integrated with aproteic foods (0.8 g/Kg/die: calories: 30-35 kcal per kg body weight/die) for a period of 6 months (±2 months). The diet was structured after considering eGFR (CKD-EPI 2021 creatinine formula), comorbidities, and nutritional status. MST, body mass index (BMI), phase angle (PA), fat mass percentage (FM%), fat-free mass index (FFMI), body cell mass index (BCMI), extracellular/intracellular water ratio (ECW/ICW), extracellular matrix/body cell mass ratio (ECM/BCM), waist/hip circumference ratio (WHC), lab test exams, and clinical variables were examined at baseline and after the study period. Our results clearly highlighted that the LNPHC diet was able to significantly improve several nutritional parameters, avoiding malnutrition and catabolism. In particular, the LNPHC diet preserved the BCM index (delta on median, ΔM + 0.3 kg/m2) and reduced the ECM/BCM ratio (ΔM - 0.03 *), with a significant reduction in the ECW/ICW ratio (ΔM - 0.02 *), all while increasing TBW (ΔM + 2.3% *). The LNPHC diet was able to preserve FFM while simultaneously depleting FM and, moreover, it led to a significant reduction in urea (ΔM - 11 mg/dL **). In conclusion, the LNPHC diet represents a new important therapeutic strategy that should be considered when treating onco-nephrological patients with solitary kidney due to renal cancer.

Measurement of glomerular filtration rate in patients undergoing renal surgery for cancer: eGFR vs mGFR in the era of precision medicine.

BACKGROUND: In the era of precision medicine, determining reliable renal function assessment remains a critical and debatable issue, especially in nephrology and oncology. SUMMARY: This paper delves into the significance of accurately measured Glomerular Filtration Rate (mGFR) in clinical practice, highlighting its essential role in guiding medical decisions and managing kidney health, particularly in the context of renal cancer (RC) patients undergoing nephrotoxic anti-cancer drugs. The limitations and advantages of traditional GFR estimation methods, primarily using serum biomarkers like creatinine and cystatin C, are discussed, emphasizing their possible inadequacy in cancer patients. Specifically, newer formulae designed for GFR estimation in cancer patients may not perform at best in RC patients. The paper explores various methods for direct GFR measurement, including the gold standard inulin clearance and alternatives like iohexol plasma clearance. KEY MESSAGE: Despite the logistical challenges of these methods, their implementation is crucial for accurate renal function assessment. The paper concludes by emphasizing the need for continued research and innovation in GFR measurement methodologies to improve patient outcomes, particularly in populations with complex medical needs.

Long-term functional outcomes in patients undergoing radical nephrectomy for renal cell carcinoma and tumor thrombus.

BACKGROUND: Up to 15% of patients with locally advanced renal cell carcinoma (RCC) harbors tumor thrombus (TT). In those cases, radical nephrectomy (RN) and thrombectomy represents the standard of care. We assessed the impact of TT on long-term functional and oncological outcomes in a large contemporary cohort. METHODS: Within a prospective maintained database, 1207 patients undergoing RN for non-metastatic RCC between 2000 and 2021 at a single tertiary centre were identified. Of these, 172 (14%) harbored TT. Multivariable logistic regression analyses evaluated the impact of TT on the risk of postoperative acute kidney injury (AKI). Multivariable Poisson regression analyses estimated the risk of long-term chronic kidney disease (CKD). Kaplan Meier plots estimated disease-free survival and cancer specific survival. Multivariable Cox regression models assessed the main predictors of clinical progression (CP) and cancer specific mortality (CSM). RESULTS: Patients with TT showed lower BMI (24 vs. 26 kg/m2) and preoperative Hb (11 vs. 14 g/mL; all-p < 0.05). Clinical tumor size was higher in patients with TT (9.6 vs. 6.5 cm; p < 0.001). After adjusting for potential confounders, the presence of TT was significantly associated with a higher risk of postoperative AKI (OR 2.03, 95% CI 1.49-3.6; p < 0.001) and long-term CKD (OR: 1.32, 95% CI 1.10-1.58; p < 0.01). Notably, patients with TT showed worse long-term oncological outcomes and TT was a predictor for CP (2.02, CI 95% 1.49-2.73, p < 0.001) and CSM (HR 1.61, CI 95% 1.04-2.49, p < 0.03). CONCLUSIONS: The presence of TT in RCC patients represents a key risk factor for worse perioperative, as well as long-term renal function. Specifically, patients with TT harbor a significant and early estimated glomerular filtration rate (eGFR) decrease. However, despite TT patients show a greater eGFR decline after surgery, they retain acceptable renal function, which remains stable over time.

[An Integrated Multidisciplinary Approach to the Care of Renal Cancer Patients Undergoing Nephrectomy].

Kidney cancer is one of the most common cancers globally, ranking 9th and 14th among men and women, respectively. Advances in diagnostic techniques have enabled earlier and potentially less invasive interventions, however, this progress poses a challenge in managing low-malignancy tumors that were previously undiagnosed. To navigate treatment pathways, a deep understanding of the bidirectional relationship between Chronic Kidney Disease (CKD) and Renal Cell Carcinoma (RCC) is essential, influenced by risk factors such as hypertension and obesity. The debate between partial (PN) and radical nephrectomy (RN) continues to be fueled by a rich body of studies in the last two decades, aiming to determine the precise benefits of renal function preservation and overall survival. However, long-term monitoring remains inadequate. There is an urgent need for heightened clinical vigilance, urging meticulous periodic evaluations that include both eGFR and the urinary albumin-creatinine ratio, to identify potential deteriorations early. Furthermore, non-neoplastic renal parenchyma requires equal attention, often overshadowed by the assessment of tumor mass. A nuanced analysis is necessary to identify a range of nephropathies that guide more effective therapeutic strategies. A collaborative strategy that brings nephrologists, urologists, nuclear radiologists, oncologists, and pathologists together on a unified platform, focusing on a personalized medicine approach grounded on a profound analysis of individual risk factors, is pivotal in shaping the future of management and prevention strategies. This approach ensures a detailed therapeutic outlook and facilitates early interventions, marrying vigilance with interdisciplinary cooperation, thereby guarding against late diagnoses and offering patients a robust shield in their battle against kidney afflictions.

Immunonutrition in Radical Cystectomy: State of the Art and Perspectives.

Preoperative nutritional status is a pivotal aspect to consider in patients with cancer undergoing radical cystectomy (RC), as those at risk of malnutrition or already malnourished are more prone to post-surgical complications. The loss of muscle mass is a major consequence of cancer-related malnutrition. It is associated with increased risk of hospital readmission, longer hospitalization, and higher mortality. Nowadays, the close relationship between nutritional and immunological aspects under stressful conditions, such as surgery, represents an emerging scientific and clinical issue. Indeed, the synergistic action of reduced food intake and systemic inflammation generates metabolic derangements with tissue catabolism, including skeletal muscle breakdown, which is, in turn, associated with immune system dysfunction. In order to offer an additional immune-nutritional boost to the post-surgical phase, particularly in malnourished patients, nutritional support may include oral nutritional supplements and/or enteral formulas enriched with specific nutrients such as omega-3 fatty acids, arginine, glutamine, and nucleotides, with acknowledged immune-modulating effects. In the present narrative review, we addressed the state of the art of the available scientific literature on the benefit of immunonutrition in patients undergoing RC for cancer and suggest possible future perspectives to be explored. Although the role of immunonutrition was found to be little explored in the context of urologic oncology, the preliminary available data on radical cystectomy, summarized in the present paper, are promising and suggest that it may improve postoperative outcomes through immunomodulation, regardless of nutritional status before surgery.

Acute kidney injury and acute kidney disease in high-dose cisplatin-treated head and neck cancer.

Background: In locally advanced head and neck squamous cell carcinoma (LA-SCCHN) at least 200mg/m2 (standard dose 300 mg/m2) of cisplatin concomitant with radiotherapy represents the standard of care, both in postoperative and conservative settings. Nevertheless, high dose administration every 3 weeks is often replaced with low dose weekly cisplatin to avoid toxicities like kidney injury, though often failing to reach the therapeutic dose. Our aim was to investigate the incidence of renal impairment in the real-life setting, integrating high dose cisplatin with adequate supportive therapy, and to explore both Acute Kidney Injury (AKI) and Acute Kidney Disease (AKD), a recently described clinical renal syndrome that encompasses functional alterations of the kidney lasting fewer than 3 months. Methods: One hundred and nine consecutive patients affected by LA-SCCHN and treated with at least a cumulative dosage of 200 mg/m2 of cisplatin concomitant with radiotherapy were enrolled in this prospective observational study. Results: AKI was reported in 12.8% of patients, 50% of whom were stage 1 (KDIGO criteria), while 25.7% of the cohort developed AKD. Patients with baseline estimated Glomerular Filtration Rate (eGFR) < 90 ml/min showed a higher incidence of AKD (36.2% vs 17.7%). Hypertension, baseline eGFR, and therapy with Renin-angiotensin-aldosterone system inhibitors proved to be significant factors associated with both AKI and AKD. Conclusion: AKI and AKD are not rare complications of high-dose cisplatin, but an appropriate prevention strategy and accurate monitoring of patients during treatment could lead to a reduction of the burden of these conditions.

Neglected lymph nodal metastases in patients with renal cancer: when to extend the anatomical template of lymph node dissection during nephrectomy.

BACKGROUND: The role of lymph node dissection (LND) in patients with renal cell carcinoma (RCC) is still controversial. However, detecting lymph node invasion (LNI) is key due to prognostic implications and to identify patients who might benefit from adjuvant therapies such as adjuvant pembrolizumab. MATERIALS AND METHODS: Out of 796 patients, 261 (33%) received eLND, of whom 62 (8%) for suspicious lymph node (LN) metastases at preoperative staging (cN1). eLND was divided in 3 anatomical areas: (1) hilar, (2) side-specific (pre-/para-aortic or pre-/para-caval) and (3) inter-aorto-caval nodes. Overall maximum LN diameter was measured by a dedicated radiologist for each patient. Multivariable logistic regression models (MVA) were tested for the effect of maximum LN diameter in predicting the presence of nodal metastases outside the anatomical area of cN1. RESULTS: LNI was confirmed in 50% of cN1, whilst only 13 out of 199 cN0 patients were pN1 at final histology (6.5%; p < 0.001). In a per-patient analysis, of 62 cN1 patients, 24% vs. 18% vs. 8% harboured pN1 disease only inside vs. in-outside vs. only outside the suspicious anatomical field of cN1 at preoperative CT/MRI scan. At MVA, increasing diameter of suspicious LNs was independently associated with risk of finding positive LNs outside the suspicious anatomical field (OR 1.05, 95%CI 1.02-1.11; p = 0.02). CONCLUSIONS: Roughly 50% of cN1 patients undergoing eLND will harbour LN metastases, also outside the suspicious radiological area, and maximum LNs diameter at preoperative imaging correlates with such risk. Thus, an eLND might be justified in patients with large suspicious LN metastases, to better stage this patient population and to improve postoperative treatment management.

Renal Histology in CKD Stages: Match or Mismatch with Glomerular Filtration Rate?

A reliable assessment of renal function is of paramount importance in several clinical assets in order to tailor a personalized medical approach. CKD classification system, created in 2002 by the National Kidney Foundation-sponsored Kidney Disease Outcomes Quality Initiative and then implemented in the following years by the K-DIGO guidelines, offered clinicians a new strategy to better identify nephrological patients at low or high risk to develop renal insufficiency, in order to avoid the progression to end-stage renal disease. However, the criteria used to create this classification did not consider some important aspects related to renal histology and glomerular filtration rate measurement, resulting in a possible over- or underestimation of the real established renal damage. In this mini-review, we will summarize the most relevant shortcomings in the CKD classifications, which can create misleading diagnosis in daily clinical practice.

A comprehensive assessment of frailty status on surgical, functional and oncologic outcomes in patients treated with partial nephrectomy-A large, retrospective, single-center study.

BACKGROUND: Partial nephrectomy (PN) is a challenging procedure, which can be associated with severe complications. In consequence, the search for accurate and independent indicators of unfavorable surgical outcomes appears warranted. We aimed at evaluating the impact of frailty status on surgical, functional and oncologic outcomes in patients undergoing PN for renal cell carcinoma (RCC). METHODS: A retrospective, single-center study including 1,282 patients treated with PN for clinically localized cT1 RCC was performed. The modified Frailty Index (mFI) was used to assess preoperative frailty. Multivariable logistic, Poisson and linear regression analyses(MVA) tested the effect of frailty on complications, acute kidney injury(AKI), renal function decline after PN. Cumulative incidence and competing-risk analyses investigated survival outcomes. RESULTS: Of 1,282 patients, 220 (17%) were frail. Overall, 982 (76%) vs. 123 (9.6%) vs. 171 (13%) patients underwent open vs. laparoscopic vs. robot-assisted PN. Median follow-up was 66 (IQR: 35-107) months. At MVA, frailty status predicted increased risk of complications [Odds ratio (OR): 1.46, 95%CI 1.17-1.84; P < 0.001]. Moreover, frail patients were at higher risk of postoperative AKI (OR: 1.95, 95%CI 1.13-3.35; P = 0.01). In frail patients, renal function permanently decreased over time (P = 0.01) without any renal function plateau or improvement during the follow-up, which were instead observed in the nonfrail cohort. At competing-risks analyses, frailty status predicted higher risk of other-cause mortality [Hazard ratio (HR): 1.67, 95%CI 1.05-2.66; P = 0.02], but not of cancer-specific mortality (P = 0.3). CONCLUSIONS: Frailty status predicts higher risk of adverse surgical outcomes after PN. Moreover, greater renal function decline was observed in frail patients, compared with nonfrail patients. Finally, the risk of OCM significantly overcomes the risk of dying due to RCC in frail patients.

The Impact of a Mediterranean-like Diet with Controlled Protein Intake on the Onco-Nephrological Scenario: Time for a New Perspective.

Chronic kidney disease (CKD) represents a frequent comorbidity in cancer patients, especially for patients affected by urological cancers. Unfortunately, impaired kidney function may limit the choice of adequate oncological treatments for their potential nephrotoxicity or due to contraindications in case of a low glomerular filtration rate. For these patients, tailored nephrological and nutritional management is mandatory. The K-DIGO guidelines do not define whether the nutritional management of CKD could be useful also in CKD patients affected by urological cancer. In fact, in clinical practice, oncological patients often receive high-protein diets to avoid malnutrition. In our study, we investigated the nutritional and nephrological impact of a Mediterranean-like diet with a controlled protein intake (MCPD) on a cohort of 82 stage III-IV CKD patients. We compared two cohorts: one of 31 non-oncological CKD patients and the other of 51 oncological patients with CKD. The use of an MCPD had a favorable impact on both the oncological and non-oncological CKD patients with an amelioration in all the investigated parameters and with a better quality of life, with no cases of malnutrition or AKI.

The Clinical and Molecular Features in the VHL Renal Cancers; Close or Distant Relatives with Sporadic Clear Cell Renal Cell Carcinoma?

Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited cancer syndrome caused by germline mutations in the VHL tumor suppressor gene, characterized by the susceptibility to a wide array of benign and malign neoplasms, including clear-cell renal cell carcinoma. Moreover, VHL somatic inactivation is a crucial molecular event also in sporadic ccRCCs tumorigenesis. While systemic biomarkers in the VHL syndrome do not currently play a role in clinical practice, a new promising class of predictive biomarkers, microRNAs, has been increasingly studied. Lots of pan-genomic studies have deeply investigated the possible biological role of microRNAs in the development and progression of sporadic ccRCC; however, few studies have investigated the miRNA profile in VHL patients. Our review summarize all the new insights related to clinical and molecular features in VHL renal cancers, with a particular focus on the overlap with sporadic ccRCC.

Obesity and Metabolic Traits after High-Fat Diet in Iberian Pigs with Low Birth Weight of Placental Origin.

Intrauterine growth restriction (IUGR) and later obesity and metabolic disorders have classically been associated with maternal malnutrition, but most cases of IUGR are related to placental insufficiency. The current study, using a swine model for IUGR and obesity, aimed to determine the interaction of birth weight (categorized as low birth weight [LBW] or normal birth-weight [NBW]) and postnatal diet (categorized as maintenance diet [MD] or fattening diet [FD]) on body weight, adiposity and metabolic traits. FD induced higher body weight and adiposity (both p < 0.0001), with higher fructosamine levels (p < 0.005) and a trend toward higher HOMA-ß index (p = 0.05). NBW pigs remained heavier than LBW pigs during the early juvenile period (p < 0.005), but there were no differences at later stages. There were no differences in metabolic traits during juvenile development, but there were differences in adulthood, when LBW pigs showed higher glucose and lower insulin levels than NBW pigs (both p < 0.05). These results suggest that (a) FD allows LBW offspring to achieve similar obesity in adulthood as NBW offspring, and (b) glucose metabolism is more compromised in obese LBW than obese NBW pigs. The comparison of our data with previous studies highlights significant differences between offspring with LBW induced by maternal malnutrition or placental insufficiency, which should be considered when studying the condition.

Renal Function Outcomes in Metastatic Non-Small-Cell Lung Carcinoma Patients Treated with Chemotherapy or Immune Checkpoint Inhibitors: An Unexpected Scenario.

Immune checkpoint inhibitors (ICIs) and platinum-based chemotherapy (CT) are effective therapeutic agents for the palliative treatment of metastatic non-small-cell lung cancer (NSCLC); the aim of our study was to investigate the acute and chronic renal toxicities in this setting. We collected data on 292 patients who received cisplatin (35%), carboplatin-based regimens (25%), or ICI monotherapy (40%). The primary and secondary outcomes were compared to the acute kidney injury (AKI) rate and the mean estimated GFR (eGFR) decay between groups, respectively, over a mean follow-up duration of 15 weeks. We observed 26 AKI events (8.9%), mostly stage I AKI (80.7%); 15% were stage II AKI, 3.8% were stage III, and none required renal replacement therapy or ICU admission. The AKI rates were 10.9%, 6.8%, and 8.9% for the cisplatin, carboplatin, and ICI groups, respectively, and no significant differences were observed between the groups (p = 0.3). A global mean eGFR decay of 2.2 mL/min was observed, while for the cisplatin, carboplatin, and ICI groups, the eGFR decay values were 2.3 mL/min, 1.1 mL/min, and 3.5 mL/min, respectively. No significant differences were observed between the groups. Cisplatin/carboplatin-based CT and ICIs resulted in a similar incidence of AKI and eGFR decay, suggesting the safety of their cautious use, even in CKD patients.

Long Non-Coding RNAs as Novel Biomarkers in the Clinical Management of Papillary Renal Cell Carcinoma Patients: A Promise or a Pledge?

Papillary renal cell carcinoma (pRCC) represents the second most common subtype of renal cell carcinoma, following clear cell carcinoma and accounting for 10-15% of cases. For around 20 years, pRCCs have been classified according to their mere histopathologic appearance, unsupported by genetic and molecular evidence, with an unmet need for clinically relevant classification. Moreover, patients with non-clear cell renal cell carcinomas have been seldom included in large clinical trials; therefore, the therapeutic landscape is less defined than in the clear cell subtype. However, in the last decades, the evolving comprehension of pRCC molecular features has led to a growing use of target therapy and to better oncological outcomes. Nonetheless, a reliable molecular biomarker able to detect the aggressiveness of pRCC is not yet available in clinical practice. As a result, the pRCC correct prognosis remains cumbersome, and new biomarkers able to stratify patients upon risk of recurrence are strongly needed. Non-coding RNAs (ncRNAs) are functional elements which play critical roles in gene expression, at the epigenetic, transcriptional, and post-transcriptional levels. In the last decade, ncRNAs have gained importance as possible biomarkers for several types of diseases, especially in the cancer universe. In this review, we analyzed the role of long non-coding RNAs (lncRNAs) in the prognosis of pRCC, with a particular focus on their networking. In fact, in the competing endogenous RNA hypothesis, lncRNAs can bind miRNAs, resulting in the modulation of the mRNA levels targeted by the sponged miRNA, leading to additional regulation of the target gene expression and increasing complexity in the biological processes.

Radiomic and gEnomic approaches for the enhanced DIagnosis of clear cell REnal Cancer (REDIRECt): a translational pilot methodological study.

Background: The combination of radiomic and transcriptomic approaches for patients diagnosed with small clear-cell renal cell carcinoma (ccRCC) might improve decision making. In this pilot and methodological study, we investigate whether imaging features obtained from computed tomography (CT) may correlate with gene expression patterns in ccRCC patients. Methods: Samples from 6 patients who underwent partial nephrectomy for unilateral non-metastatic ccRCC were included in this pilot cohort. Transcriptomic analysis was conducted through RNA-sequencing on tumor samples, while radiologic features were obtained from pre-operative 4-phase contrast-enhanced CT. To evaluate the heterogeneity of the transcriptome, after a 1,000 re-sampling via bootstrapping, a first Principal Component Analyses (PCA) were fitted with all transcripts and a second ones with transcripts deriving from a list of 369 genes known to be associated with ccRCC from The Cancer Genome Atlas (TCGA). Significant pathways in each Principal Components for the 50 genes with the highest loadings absolute values were assessed with pathways enrichment analysis. In addition, Pearson's correlation coefficients among radiomic features themselves and between radiomic features and transcripts expression values were computed. Results: The transcriptomes of the analysed samples showed a high grade of heterogeneity. However, we found four radiogenomic patterns, in which the correlation between radiomic features and transcripts were statistically significant. Conclusions: We showed that radiogenomic approach is feasible, however its clinical meaning should be further investigated.

The Mediterranean Diet as a Source of Bioactive Molecules with Cannabinomimetic Activity in Prevention and Therapy Strategy.

The endocannabinoid system is a complex lipid signaling network that has evolved to be a key regulator of pro-homeostatic pathways for the organism. Its involvement in numerous processes has rendered it a very suitable target for pharmacological studies regarding metabolic syndrome, obesity and other lifestyle-related diseases. Cannabinomimetic molecules have been found in a large variety of foods, most of which are normally present in the Mediterranean diet. The majority of these compounds belong to the terpene and polyphenol classes. While it is known that they do not necessarily act directly on the cannabinoid receptors CB1 and CB2, their ability to regulate their expression levels has already been shown in some disease-related models, as well as their ability to modulate the activity of other components of the system. In this review, evidence was gathered to support the idea that phytocannabinoid dietary intake may indeed be a viable strategy for disease prevention and may be helpful in maintaining the health status. In an era where personalized nutrition is becoming more and more a reality, having new therapeutic targets could become an important resource.

MicroRNA Signatures in the Upper Urinary Tract Urothelial Carcinoma Scenario: Ready for the Game Changer?

Upper urinary tract urothelial carcinoma (UTUC) represents a minor subgroup of malignancies arising in the urothelium of the renal pelvis or ureter. The estimated annual incidence is around 2 cases per 100,000 people, with a mean age at diagnosis of 73 years. UTUC is more frequently diagnosed in an invasive or metastatic stage. However, even though the incidence of UTUC is not high, UTUC tends to be aggressive and rapidly progressing with a poor prognosis in some patients. A significant challenge in UTUC is ensuring accurate and timely diagnosis, which is complicated by the non-specific nature of symptoms seen at the onset of disease. Moreover, there is a lack of biomarkers capable of identifying the early presence of the malignancy and guide-tailored medical treatment. However, the growing understanding of the molecular biology underlying UTUC has led to the discovery of promising new biomarkers. Among these biomarkers, there is a class of small non-coding RNA biomarkers known as microRNAs (miRNAs) that are particularly promising. In this review, we will analyze the main characteristics of UTUC and focus on microRNAs as possible novel tools that could enter clinical practice in order to optimize the current diagnostic and prognostic algorithm.

Renal Oncocytoma: The Diagnostic Challenge to Unmask the Double of Renal Cancer.

Renal oncocytoma represents the most common type of benign neoplasm that is an increasing concern for urologists, oncologists, and nephrologists due to its difficult differential diagnosis and frequent overtreatment. It displays a variable neoplastic parenchymal and stromal architecture, and the defining cellular element is a large polygonal, granular, eosinophilic, mitochondria-rich cell known as an oncocyte. The real challenge in the oncocytoma treatment algorithm is related to the misdiagnosis due to its resemblance, at an initial radiological assessment, to malignant renal cancers with a completely different prognosis and medical treatment. Unfortunately, percutaneous renal biopsy is not frequently performed due to the possible side effects related to the procedure. Therefore, the majority of oncocytoma are diagnosed after the surgical operation via partial or radical nephrectomy. For this reason, new reliable strategies to solve this issue are needed. In our review, we will discuss the clinical implications of renal oncocytoma in daily clinical practice with a particular focus on the medical diagnosis and treatment and on the potential of novel promising molecular biomarkers such as circulating microRNAs to distinguish between a benign and a malignant lesion.

Renal involvement in sarcoidosis: histological patterns and prognosis, an Italian survey.

BACKGROUND: Granulomatous interstitial nephritis in sarcoidosis (sGIN) is generally clinically silent, but in <1% causes acute kidney injury (AKI). METHODS: This Italian multicentric retrospective study included 39 sarcoidosis-patients with renal involvement at renal biopsy: 31 sGIN-AKI, 5 with other patterns (No-sGIN-AKI), 3 with nephrotic proteinuria. We investigate the predictive value of clinical features, laboratory, radiological parameters and histological patterns regarding steroid response. Primary endpoint: incident chronic kidney disease (CKD) beyond the 1°follow-up (FU) year; secondary endpoint: response at 1°line steroid therapy; combined endpoint: the association of initial steroid response and outcome at the end of FU. RESULTS: Complete recovery in all 5 No-sGIN-AKI-patients, only in 45% (13/29) sGIN-AKI-patients (p=0.046) (one lost in follow-up, for another not available renal function after steroids). Nobody had not response. Primary endpoint of 22 sGIN-AKI subjects: 65% (13/20) starting with normal renal function developed CKD (2/22 had basal CKD; median FU 77 months, 15-300). Combined endpoint: 29% (6/21) had complete recovery and final normal renal function (one with renal relapse), 48% (10/21) had partial recovery and final CKD (3 with renal relapse, of whom one with basal CKD) (p=0.024). Acute onset and hypercalcaemia were associated to milder AKI and better recovery than subacute onset and patients without hypercalcaemia, women had better endpoints than men. Giant cells, severe interstitial infiltrate and interstitial fibrosis seemed negative predictors in terms of endpoints. CONCLUSIONS: sGIN-AKI-patients with no complete recovery at 1°line steroid should be treated with other immunosuppressive to avoid CKD, in particular if males with subacute onset and III stage-not hypercalcaemic AKI.