Immunohistochemical Evaluation of Renal Biopsy with Anti-PD1 and p53 to Solve the Dilemma between Platinum- and Pembrolizumab-Induced AKI: Case Report and Review.

Introduction: The combination therapy of platinum and pembrolizumab looks like a promising treatment in advanced non-small-cell lung cancer. However, both platinum-based chemotherapy and pembrolizumab can lead to AKI. AKI can occur due to acute tubular necrosis or interstitial nephritis. It is essential to identify the drug responsible for renal damage. For this purpose, we used new immunohistochemistry markers (p53 and anti-PD1 analysis). Case Description: A 77-year-old female patient with advanced non-small-cell lung cancer received the PD-1 inhibitor pembrolizumab and platinum-based chemotherapy carboplatin. The patient, after 60 days, experienced AKI. A kidney biopsy was performed, and two new immunohistochemical techniques for p53 (experimental markers of ATN from platinum) and anti-PDL1 (experimental markers of PD-1 inhibitors nephritis) were employed. Renal biopsies revealed severe tubular damage. No infiltration was detected, and the immunohistochemical assessment of PDL-1 was negative. The expression of p53 was positive. The renal biopsy suggested platinum-induced acute tubular necrosis. After discontinuing steroids and reducing carboplatin, the patient continued with pembrolizumab, and their renal function returned to normal within two months. Discussion: Combining checkpoint inhibitors and platinum-based therapies may result in AKI. The standard method of examining kidney tissue may not provide sufficient information about the effects of these drugs on the kidneys. To address this issue, we recommend incorporating an assessment of the analysis of the expression of PDL1 and p53. This personalized approach will help identify the best treatment option for the patient while ensuring the best possible cancer treatment plan.

Using Renal Elastography to Predict the Therapeutic Response of Nephrological Patients.

BACKGROUND: The standard method for assessing chronic renal damage is renal biopsy, which has limitations due to its invasiveness. Ultrasound elastography is a non-invasive technique that quantifies tissue elasticity and can be used to determine Young's modulus (YM). Although this breakthrough technology has been successfully employed to evaluate liver stiffness and the extent of fibrosis, its application in kidney-related conditions still needs improvement. METHODS: Our study aimed to verify the correlation between renal elastography and the chronic histological score determined via renal biopsy, evaluate the correlation between elastography and response to treatment in the short-term follow-up (6 months), and compare elastography data between renal disease patients (AKD-P) and healthy controls (HP). RESULTS: The analyzed population consisted of 82 patients (41 HP and 41 AKD-P). The AKD-P were divided into responders (R) or non-responders (NR) based on the criteria established by the guidelines. No association was found between renal stiffness and chronic histological score. Elastography data revealed median YM values of 6.15 kPa for AKD-P and 12.2 kPa for HP, with a statistically significant difference. The median YM values of the R and NR groups were 7.4 KPa and 5.6 KPa, respectively (p = 0.037). CONCLUSIONS: Patient responsiveness was associated with YM, with lower values observed in the NR group. We also found that the healthy controls exhibited significantly higher YM values than the renal disease population.

Rationale for the evaluation of renal functional reserve in allogeneic stem cell transplantation candidates: a pilot study.

Background: The main purpose of our study was to evaluate the ability of renal functional reserve (RFR) to stratify the risk of acute kidney injury (AKI) occurrence within 100 days of hematopoietic stem cell transplantation (HSCT) and to predict any functional recovery or the onset of chronic kidney disease. A secondary aim was to identify the clinical/laboratory risk factors for the occurrence of AKI. Methods: The study design is prospective observational. We enrolled 48 patients with normal basal glomerular filtration rate (bGFR) who underwent allogenic HSCT. A multiparameter assessment and the Renal Functional Reserve Test (RFR-T) using an oral protein load stress test were performed 15 days before the HSCT. Results: Different RFRs corresponded to the same bGFR values. Of 48 patients, 29 (60%) developed AKI. Comparing the AKI group with the group that did not develop AKI, no statistically significant difference emerged in any characteristic related to demographic, clinical or multiparameter assessment variables except for the estimated GFR (eGFR). eGFR ≤100 mL/min/1.73 m2 was significantly related to the risk of developing AKI (Fisher's exact test, P = .001). Moreover, RFR-T was lower in AKI+ patients vs AKI- patients, but did not allow statistical significance (28% vs 40%). In AKI patients, RFR >20% was associated with complete functional recovery (one-sided Fisher's exact test, P = .041). The risk of failure to recover increases significantly when RFR ≤20% (odds ratio = 5.50, 95% confidence interval = 1.06-28.4). Conclusion: RFR identifies subclinical functional deterioration conditions essential for post-AKI recovery. In our cohort of patients with no kidney disease (NKD), the degree of pre-HSCT eGFR is associated with AKI risk, and a reduction in pre-HSCT RFR above a threshold of 20% is related to complete renal functional recovery post-AKI. Identifying eGFR first and RFR second could help select patients who might benefit from changes in transplant management or early nephrological assessment.

Idiopathic nephrotic syndrome relapse following COVID-19 vaccination: a series of 25 cases.

Background: Several cases of idiopathic nephrotic syndrome (INS) relapse following the administration of coronavirus disease 2019 (COVID-19) vaccines have recently been reported, raising questions about the potential relationship between the immune response to COVID-19 vaccination and INS pathogenesis. Methods: We performed a retrospective multicentre survey describing the clinical and biological characteristics of patients presenting a relapse of INS after COVID-19 vaccination, with an assessment of outcome under treatment. Results: We identified 25 patients (16 men and 9 women) presenting a relapse within 1 month of a COVID-19 vaccine injection. The glomerular disease was of childhood onset in half of the patients and most patients (21/25) had received at least one immunosuppressive drug in addition to steroids for frequently relapsing or steroid-dependent nephrotic syndrome (NS). All patients were in a stable condition at the time of injection and 11 had no specific treatment. In five patients, the last relapse was reported >5 years before vaccine injection. The Pfizer-BioNTech (BNT162b2) vaccine was used in 80% of the patients. In 18 cases, INS relapse occurred after the first injection, a mean of 17.5 days after vaccination. A second injection was nevertheless administered in 14 of these patients. Five relapses occurred after administration of the second dose and two relapses after the administration of the third dose. All but one of the patients received steroids as first-line treatment, with an additional immunosuppressive agent in nine cases. During follow-up, complete remission was achieved in 21 patients, within 1 month in 17 cases. Only one patient had not achieved at least partial remission after 3 months of follow-up. Conclusions: This case series suggests that, in rare patients, COVID-19 vaccination may trigger INS relapse that is generally easy to control. These findings should encourage physicians to persuade their patients to complete the COVID-19 vaccination schedule.

Monoclonal gammopathy of renal significance (MGRS): Real-world data on outcomes and prognostic factors.

Monoclonal gammopathy of renal significance (MGRS) is a recognized clinical entity. Literature regarding treatment and its outcomes in MGRS is sparse due to the rarity and misdiagnosis of MGRS. We retrospectively analyzed 280 adults with an MGRS diagnosis from 2003 to 2020 across 19 clinical centers from 12 countries. All cases required renal biopsy for the pathological diagnosis of MGRS. Amyloidosis-related to MGRS (MGRS-A) was present in 180 patients; nonamyloidosis MGRS (MGRS-NA), including a broad spectrum of renal pathologies, was diagnosed in 100 patients. The median overall survival in the studied cohort was 121.0 months (95% CI: 105.0-121.0). Patients with MGRS-A had a shorter overall survival than patients with MGRS-NA (HR = 0.41, 95%CI: 0.25-0.69; p = 0.0007). Both hematologic and renal responses were associated with longer survival. Achievement of ≥VGPR was generally predictive of a renal response (OR = 8.03 95%CI: 4.04-115.96; p < 0.0001), one-fourth of patients with ≥VGPR were renal nonresponders. In MGRS-A, factors associated with poor prognosis included elevated levels of creatinine, beta-2-microglobulin, and hemodialysis at diagnosis. In MGRS-NA, only age >65 years was associated with increased risk of death. Treatments provided similar hematologic response rates in both types of MGRS. Autologous stem cell transplantation led to better response than other treatments. This multicenter and international effort is currently the largest report on MGRS.

[The genetic basis of post-bone marrow transplant thrombotic microangiopathy: is this the last piece of the puzzle?]

Transplant-associated thrombotic microangiopathy (TA-TMA) is a complication of hematopoietic stem cell transplantation (HSCT) associated with kidney injury and significant mortality. Recent studies indicate that dysregulation of the alternate complement pathway may be at the basis of the development of TA-TMA. Currently, there are no pre-transplant screening tools to identify patients at risk. To explore the mechanism of TA-TMA, we performed a genetic study that allowed us to identify the deletion of the CFHR3-CFHR1 region in homozygosity. We report the clinical case of a 47-year-old woman who underwent haploidentical HSCT complicated by TA-TMA confirmed by renal biopsy. The patient discontinued treatment with calcineurin inhibitors (potential inducers of TA-TMA) with a brief introduction of prednisone until complete resolution of renal damage and microangiopathy. Identifying genetic variants that affect the mechanism of the alternate complement pathway could help in the stratification of the risk of TA-TMA and in implementing a personalized therapeutic approach.

Brief Communication PD1-related Nephrotoxicity: Optimizing Its Clinical Management Through Histopathologic Features.

Immune-related nephrotoxicity (ir-N) is a rare adverse event of immune-checkpoint(s) inhibitors (ICI) therapy and its clinical management is still debated. Among 501 consecutive ICI-treated patients at our Institution, 6 who developed an ir-N with clinical signs suggestive for an acute kidney injury underwent kidney biopsy. Histology showed an acute tubule-interstitial nephritis, simulating the scenario of acute T-cell-mediated kidney transplant rejection. Thus, the management of allograft kidney rejection routinely utilized at our clinic was implemented, leading to rapid renal function improvement. Histologic features supporting the definition of an immune-mediated acute kidney injury in ICI-treated patients may help optimizing the clinical management of ir-N.

Inflammatory muscle involvement in systemic vasculitis: A systematic review.

Vasculitis are severe systemic autoimmune diseases which may involve different organs and systems. Conversely, muscles do not represent an organ commonly involved by systemic vasculitis and myositis is not include among any classification or diagnostic criterion of vasculitis. In this regard, we aimed to review the literature in order to report all the available evidence concerning the inflammatory involvement of muscle in patients affected by systemic vasculitis. We collected a total of 108 papers, for a sum of 395 patients affected by muscle vasculitis. Most of them suffered from medium and small vessels vasculitis (mainly polyarteritis nodosa and ANCA-associated vasculitis) or from vasculitis secondary to rheumatoid arthritis. Conversely, muscle involvement in case of large vessel vasculitis occurred seldom, while only few papers reported such occurrence in Kawasaki or Behçet's disease. Histological findings may differ, but the most common ones displayed a necrotizing vasculitis of perimysium vessels, while granulomatous vasculitis was assessed only in case of ANCA-associated vasculitis patients. Creatine kinase were usually within normal range, seldom elevated, while imaging findings were generally undistinguishable from the ones found in idiopathic inflammatory myopathies: magnetic resonance imaging displays signal hyperintensity in T2 and STIR scans, while few data exist for positron emission tomography. The presentation of the disease may be fearsome and severe, sometimes life-threatening, but an overall good response to conventional immunosuppressants and/or glucocorticoids has been reported.

Biologic drugs in the treatment of polyarteritis nodosa and deficit of adenosine deaminase 2: A narrative review.

Polyarteritis nodosa (PAN) is a medium vessels vasculitis variously involving different organs and systems, sometimes with an aggressive course, leading to death or disability in a significant number of cases. First-line treatment usually relies on steroids and classical immunosuppressants, but a growing number of case reports and small case series shows the potential role of biologic drugs, mostly anti-tumor necrosis factor (TNF)-α agents, in inducing and maintaining remission in patients affected by PAN. Similarly, the recently described autoinflammatory disease named deficit of adenosine deaminase 2 (DADA2), considered by several experts as a more precocious and aggressive variant of PAN, seems to respond to a prompt treatment with TNF-α inhibitors. The aim of this review is to collect all existing evidences about the use of biologic drugs in PAN and DADA2. Fifty-one articles published during the last 15 years were retrieved, including 58 and 76 patients affected by PAN and DADA2, respectively, and treated with biologic drugs. The majority of subjects was treated with TNF-α inhibitors, whose effectiveness was reported in the treatment of such difficult-to-manage diseases, particularly in DADA2. Among the other biologic drugs, Tocilizumab was successfully employed in some subjects affected by PAN who did not respond to TNF-α inhibitors, while Rituximab did not give substantial benefits neither in PAN nor in DADA2. Only few data exist about the role of Janus-kinase inhibitors and anti-IL1 agents. This study provides the first comprehensive assessment of biologic agents in both PAN and DADA2, with encouraging results especially in the context of TNF-α inhibitors. Nevertheless, due to the lack of prospective, randomized, case control studies, further efforts should be made in order to fully elucidate the role of these drugs in such rare and life-threatening conditions.

2017 Marathon of Rome: Anthropometry and Sport Profile in 350 Runners and Association With Achilles and Patellar Tendinopathy.

BACKGROUND: Achilles and patellar tendinopathy are common in runners. Despite the relevance of the problem, causative factors remain poorly understood. This cross-sectional study evaluated the association between Achilles and patellar tendinopathy and age, sex, weight, height, number of marathons, and impact profile in runners who participated in the 2017 Marathon of Rome. METHODS: At the 2017 Marathon of Rome, 350 athletes (256 men and 94 women; mean age: 44.8 years, range 12-80 years) filled in the VISA-A and VISA-P questionnaires. A fully trained orthopedic surgeon made a diagnosis of Achilles and patellar tendinopathy according to clinical criteria. RESULTS: Ninety-five participants were diagnosed with Achilles tendinopathy and 96 with patellar tendinopathy. There was evidence of a statistically significant positive association between age and Achilles and patellar tendinopathy, with no effect of sex, weight, and height on the presence of Achilles tendinopathy. There was no evidence of a statistically significant positive association between the number of marathons and impact profile and VISA-A score. There was a statistically significant association between VISA-P score and impact profile. Finally, there was evidence of a statistically significant positive association between VISA-A score and VISA-P score (P = 0.007). CONCLUSIONS: In marathon runners, there was no evidence of a statistically significant association between sex, weight, height, number of marathons, and Achilles and patellar tendinopathy. However, age was associated with Achilles and patellar tendinopathy, and impact profile was associated with patellar tendinopathy.

SARS-CoV-2 in pleural fluid in a kidney transplant patient.

Coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has quickly spread all over the globe from China. Pleural involvement is not common; around 5-10% of patients can develop pleural effusion and little is known about the involvement of pleural structures in this new infection.A 61-year-old male kidney transplant patient with a history of multiple biopsy-confirmed acute rejections and chronic allograft rejection was admitted to our COVID-19 Unit with dry cough, exertional dyspnea, oliguria, and abdominal distension. Lung ultrasound imaging, chest X-ray, and CT scan showed left pleural effusion and atelectasis of the neighboring lung parenchyma. RT-PCR was positive for SARS-CoV-2 in the pleural fluid and cytology showed mesothelial cells with large and multiple nuclei, consistent with a cytopathic effect of the virus.This is one of few reports describing detection of SARS-CoV-2 in the pleural fluid and to the best of our knowledge, is the first to document the simultaneous presence of a direct cytopathic effect of the virus on mesothelial cells in a kidney transplant patient with COVID-19 pneumonia. The pleura proved to be a site of viral replication where signs of a direct pathological effect of the virus on cells can be observed, as we report here. RT-PCR for SARS-CoV-2 should be part of routine examination of pleural effusion even in patients with mild respiratory symptoms or with comorbidities that seem to explain the cause of effusion.

Diagnostic accuracy of anti-phospholipase A2 receptor (PLA2R) antibodies in idiopathic membranous nephropathy: an Italian experience.

BACKGROUND: Autoantibodies against-phospholipase A2 receptor (PLA2R) are specific markers of idiopathic membranous nephropathy (iMN). Enzyme-linked immunosorbent assay (ELISA) is becoming the preferred method in many laboratories for the determination of anti-PLA2R antibodies, because it provides quantitative results, and is not prone to subjective interpretation, as is the case with indirect immunofluorescence assay. METHODS: The purpose of our study was to determine the diagnostic performance of serum PLA2R antibodies detected by commercially available ELISA in a large Italian multicenter cohort of patients with biopsy-proven iMN and in patients with other renal diseases, with special focus on evaluating the optimal cut-off value to discriminate positive and negative results. A total of 495 consecutive patients were recruited. Renal biopsies were performed in all patients, and blood samples were taken before the initiation of immunosuppressive treatment. RESULTS: According to the clinical diagnosis and to kidney biopsy, 126 patients were diagnosed with iMN and 369 had other non-membranous nephropathies. Anti-PLA2R autoantibodies were detected using a commercial anti-PLA2R ELISA. At a cut-off value of 20 relative units (RU)/ml indicated by the manufacturer for positive classification, sensitivity was 61.1% and specificity 99.7%. At a cut-off value of 14 RU/ml indicated by the manufacturer for borderline results, sensitivity was 63.5% and specificity remained the same (99.7%). At a cut-off of 2.7 RU/ml, selected as the optimal cut-off on the basis of ROC curve analysis, sensitivity was 83.3% and specificity 95.1%. The best overall efficiency of the test was observed at 2.7 RU/ml; however, the highest positive likelihood ratio and diagnostic odds ratio were achieved at 14 RU/ml. A cut-off threshold higher than 14 RU/ml or lower than 2.7 RU/ml entailed worse test performance. CONCLUSION: Depending on the clinical use (early diagnosis or as a support to confirm clinical diagnosis), nephrologists may take advantage of this evidence by choosing the most convenient cut-off. However, renal biopsy remains mandatory for the definitive diagnosis of iMN and for the assessment of disease severity.

Detection of Cryptic Mosaicism in X-linked Alport Syndrome Prompts to Re-evaluate Living-donor Kidney Transplantation.

BACKGROUND: Alport syndrome is a hereditary nephropathy caused by mutations in collagen IV genes and characterized by ultrastructural lesions of the glomerular basement membrane. Some patients have a negative family history with apparently de novo mutations. Although somatic mosaicism has been postulated, as cryptic mosaicism cannot be detected from mutational screening on peripheral blood samples, cases in kidney-confined mosaic form have been missed. METHODS: We report the case of a 24-year-old male patient with X-linked Alport syndrome diagnosis due to a COL4A5 pathogenic mutation (c.3334_3337dup [p.Gly1113Alafs25]). The same mutation had not been previously detected on a peripheral blood sample of maternal DNA. However, the mother, who was undertaking a clinical re-evaluation to take in consideration the possibility of a living-kidney transplantation, had experienced persistent microhematuria since the age of 10 years. RESULTS: A next-generation sequencing approach performed on maternal DNA from both peripheral blood sample and urine-derived podocyte-lineage cells unmasked the COL4A5 mutation only in the podocyte-lineage cells. CONCLUSIONS: This finding unveils an early postzygotic event which can explain both the renal involvement and germline mosaicism. It changes the inheritance risk for each pregnancy raising it to 50% and underlines the need for different clinical management in the mother. This seems to indicate that a case-by-case more cautious approach is needed with mother-to-son kidney transplants.

Genetic basis of rotator cuff injury: a systematic review.

BACKGROUND: Rotator cuff disease is a widespread musculoskeletal pathology and a major cause of shoulder pain. Studies on familial predisposition suggest that genetic plays a role in the pathogenesis of rotator cuff disease. Several genes are responsible for rotator cuff disease. The aim of this study was to perform a systematic review on genetic association between rotator cuff disease and genes variations. METHODS: A systematic review of the literature was performed, in accordance with the PRISMA guidelines. PubMed, Medline, CINAHL, Cochrane, Embase and Google Scholar databases were searched comprehensively using the keywords: "Rotator cuff", "Gene", "Genetic", "Predisposition", "Single-nucleotide polymorphism" and "Genome-wide association". RESULTS: 8 studies investigating genes variations associated with rotator cuff tears were included in this review. 6 studies were case-control studies on candidate genes and 2 studies were GWASs. A significant association between SNPs and rotator cuff disease was found for DEFB1, FGFR1, FGFR3, ESRRB, FGF10, MMP-1, TNC, FCRL3, SASH1, SAP30BP, rs71404070 located next to cadherin8. Contradictory results were reported for MMP-3. CONCLUSION: Further investigations are warranted to identify complete genetic profiles of rotator cuff disease and to clarify the complex interaction between genes, encoded proteins and environment. This may lead to individualized strategies for prevention and treatment of rotator cuff disease. LEVEL OF EVIDENCE: Level IV, Systematic Review.

First case report of using Ofatumumab in kidney transplantation AB0 incompatible. / PRIMO CASE REPORT DI UTILIZZO DELL' OFATUMUMAB NEL TRAPIANTO RENALE AB0 INCOMPATIBILE.

Modern methods for desensitization protocol rely heavily on combined apheresis therapy and Rituximab, a chimeric (murine and human) anti-CD20 antibody used in AB0 incompatible kidney transplants. Severe infusion related reactions due to the administration of Rituximab are reported in 10% of patients. These adverse reactions may hinder the completion of the desensitization protocol. Therefore, it's useful to test alternative B cell depleting therapies. Our clinical case focuses on a 41-year-old male who developed an adverse infusion reaction following the administration of Rituximab and was given Ofatumumab as an alternative treatment. Ofatumumab is a fully humanized monoclonal anti-CD20 antibody. As a fully humanized antibody, Ofatumumab may avoid immunogenic reactions. The patient tolerated the administration of the drug showing no signs of adverse side effects and with good clinical efficacy. Our case report suggest that Ofatumumab is a valid alternative B cell depleting agent.

Parathyroidectomy Halts the Deterioration of Renal Function in Primary Hyperparathyroidism.

OBJECTIVE: Decreased renal function has been consistently included among factors prompting recommendation for surgery in primary hyperparathyroidism (PHPT). However, most retrospective studies addressing this issue did not show an improvement in renal function after parathyroidectomy (PTX). The aim of this study was to investigate changes in renal function after PTX in PHPT patients subdivided according to renal function at diagnosis. DESIGN: This was a retrospective cross-sectional study. PATIENTS AND METHODS: We studied 109 consecutive PHPT patients before and after PTX. Biochemical evaluation included fasting total and ionized serum calcium, phosphate, creatinine, immunoreactive intact PTH, and 25-hydroxyvitamin D3 levels. Glomerular filtration rate (GFR) was assessed with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. RESULTS: Mean (± SD) CKD-EPI estimated GFR (eGFR) at diagnosis was 82.4 ± 19.3 mL/min/1.73 m(2) (median, 84.8 mL/min/1.73 m(2); interquartile range, 68.5-94.2 mL/min/1.73 m(2)). Patients with eGFR equal to or higher than 60 mL/min/1.73 m(2) (group 1, n = 95) were significantly younger than patients with eGFR lower than 60 mL/min/1.73 m(2) (group 2, n = 14; P < .0003). After PTX, eGFR did not change in patients of group 2 (P = .509), whereas it was significantly reduced in patients of group 1 (P < .0002). The difference in eGFR between baseline and post-PTX values was correlated negatively with baseline serum creatinine (R = -0.27; P = .0052) and positively with baseline CKD-EPI eGFR (R = 0.32; P = .00062). At multiple regression analysis, only systolic blood pressure and baseline CKD-EPI eGFR were independent predictors of GFR variation. CONCLUSION: Surgical cure of PHPT halts renal function deterioration in patients with coexisting renal disease. Our study thus supports the indication for surgery in patients with eGFR less than 60 mL/min/1.73 m(2), as recommended by current guidelines. Moreover, our data show that presurgical renal function is a relevant predictor of renal function after PTX.

Silent renal stones in primary hyperparathyroidism: prevalence and clinical features.

OBJECTIVE: (1) To evaluate the prevalence of silent nephrolithiasis in patients with primary hyperparathyroidism (PHPT) compared with controls, and (2) To characterize clinically PHPT patients with silent renal stones. METHODS: We reviewed clinical data for 141 patients with PHPT and without symptoms or history of nephrolithiasis in whom renal ultrasonography was performed at diagnosis. A total of 141 sex- and age- matched subjects with abdomen ultrasonography obtained for reasons different from urinary symptoms served as controls. RESULTS: Silent nephrolithiasis was more prevalent in PHPT patients than in controls (11.35% vs. 2.13%; P = .003). Among patients with PHPT, those with silent renal stones showed higher serum calcium and parathyroid hormone levels and met surgical criteria, regardless of nephrolithiasis, more frequently than those without renal stones. CONCLUSION: The prevalence of silent nephrolithiasis is increased in patients with PHPT as compared with controls. Moreover, it seems likely that silent renal stone disease could identify a subset of PHPT patients with more severe disease. Accordingly, we suggest ultrasonographic screening of nephrolithiasis in all PHPT patients. Further studies are needed to better characterize this clinical entity.

[Renal biopsy practice in Piedmont and Valle d'Aosta]. / Indagine sulle modalità di esecuzione delle biopsia renale in Piemonte e Valle d'Aosta.

In 2010 a questionnaire was administered to the renal units of Piedmont and Valle d'Aosta to analyze their procedures for renal biopsy (RB). Seventy-eight percent of units performed RBs, 57% for more than 20 years, but only 43% performed at least 20 BRs per year. 20/21 units performed RB in an inpatient setting and 1/21 in day hospital with the patient remaining under observation the night after. Thirty-two percent did not consider a single kidney as a contraindication to RB, 59% considered it a relative contraindication and 9% considered it an absolute contraindication. In 90.5% of units there was a specific protocol for patient preparation for RB and 86% used a specific informed consent form. Ninety-five percent of units performed ultrasound-guided RB, 60% of them using needle guides attached to the probe. In 81% of units the left side was preferred; 71% put a pillow under the patient's abdomen. All units used disposable, automated or semi-automated needles. Needle size was 16G in 29%, 18G in 58%, and both 16G and 18G in 14% of units; 1 to 3 samples were drawn. One third of units had a microscope available for immediate evaluation of specimen adequacy. After RB, 86% of units kept patients in the prone position for 2-6 hours and all prescribed a period of bed rest (at least 24 hours in 90.5%). 90.5% of units followed a specific postbiopsy observation protocol consisting of blood pressure, heart rate and red blood cell measurements at different times, and urine monitoring and ultrasound control within 12-24 hours (only half of them also employing color Doppler). One third of all units discharged patients after 1 day and two thirds after 2-3 days; all prescribed abstention from effort and from antiplatelet drugs for 7-15 days. In 9 units both RB and tissue processing and examination were done in the same hospital, while 12 units sent the samples elsewhere. 76% obtained results in 2-4 days, 19% in 6-7 days, and 5% in 10-15 days. Less than 20% of the interviewed operators were fully familiar with the clauses of hospital insurance securing their activity. Use of RB is widespread in Piedmont and Valle d'Aosta but its practice shows variation between centers.