Residents' satisfaction and suggestions to improve nephrology residency in Italy, and comparison with the organization in other European countries.

BACKGROUND: In Italy, nephrology residency is available in twenty-one nephrology schools, each with its own strengths and weaknesses. The present study is aimed at exploring the residents' satisfaction with their training programs. METHODS: Between April 20th and May 19th, 2021, a questionnaire on residency satisfaction consisting of 49 items was sent to 586 residents and 175 recently certified specialists (qualified to practice as nephrologists in 2019 and 2020), with a response rate of 81% and 51%, respectively. The teaching organization was contextualized with a survey involving 13 European nephrology schools. RESULTS: Most residency fellowship programs received a good rating with regard to "satisfaction", in particular for the following items: number of hospitalizations followed-up, chronic hemodialysis training, follow-up of transplanted patients, diagnosis and treatment of glomerulonephritis. The teachings that were identified as being of lower quality or insufficient intensity included vascular access management, ultrasound diagnostics and renal nutrition. The need for improvement in formal teaching programs was underlined. Young nephrologists were rather satisfied with their salary and with the quality of the work they were doing, but only few were interested in an academic career since it was generally held that it is "too difficult" to obtain a university position. Many young nephrologists who filled in the questionnaire felt that lack of experience in peritoneal dialysis and vascular access management was a barrier to finding an ideal job. Compared to other European training programs, the Italian program differs with regard to longer exposure to nephrology (as compared to internal medicine), and greater flexibility for internships in different settings, including abroad. CONCLUSIONS: This first nationwide survey on the satisfaction of residents in nephrology indicates that, despite rather good overall satisfaction, there is room for improvement to make nephrology a more appealing choice and to fulfill the needs of a growing number of renal disease patients.

Evaluation of partial pressure CO2 change in the dialyzer blood inlet during hemodialysis as a measure of vascular access recirculation.

INTRODUCTION: Vascular access recirculation during hemodialysis is associated with reduced effectiveness and worse survival outcomes. To evaluate recirculation, an increase in pCO2 in the blood of the arterial line during hemodialysis (threshold of 4.5 mmHg) was proposed. The blood returning from the dialyzer in the venous line has significantly higher pCO2 , so in the presence of recirculation, pCO2 in the arterial blood line may increase (ΔpCO2 ) during hemodialysis sessions. The aim of our study was to evaluate ΔpCO2 as a diagnostic tool for vascular access recirculation in chronic hemodialysis patients. METHODS: We evaluated vascular access recirculation with ΔpCO2 and compared it with the results of a urea recirculation test, which is the gold standard. ΔpCO2 was obtained from the difference in pCO2 in the arterial line at baseline (pCO2 T1) and after 5 min of hemodialysis (pCO2 T2). ∆pCO2 = pCO2 T2-pCO2 T1. FINDINGS: In 70 hemodialysis patients (mean age: 70.52 ± 13.97 years; hemodialysis vintage of 41.36 ± 34.54, KT/V 1.4 ± 0.3), ∆pCO2 was 4 ± 4 mmHg, and urea recirculation was 7% ± 9%. Vascular access recirculation was identified using both methods in 17 of 70 patients, who showed a ∆pCO2 of 10 ± 5 mmHg and urea recirculation of 20% ± 9%; time in months of hemodialysis was the only difference between vascular access recirculation and non-vascular access recirculation patients (22 ± 19 vs. 46 ± 36, p: 0.05). In the non-vascular access recirculation group, the average ΔpCO2 was 1.9 ± 2 (p: 0.001), and the urea recirculation % was 2.8 ± 3 (p: 0.001). The ΔpCO2 correlated with the urea recirculation % (R: 0.728; p < 0.001). DISCUSSION: ΔpCO2 in the arterial blood line during hemodialysis is an effective and reliable diagnostic tool for identifying recirculation of the vascular access but not its magnitude. The ΔpCO2 test application is simple and economical and does not require special equipment.

Parathyroidectomy and survival in a cohort of Italian dialysis patients: results of a multicenter, observational, prospective study.

BACKGROUND: Severe secondary hyperparathyroidism (SHPT) is associated with mortality in end stage kidney disease (ESKD). Parathyroidectomy (PTX) becomes necessary when medical therapy fails, thus highlighting the interest to compare biochemical and clinical outcomes of patients receiving either medical treatment or surgery. METHODS: We aimed to compare overall survival and biochemical control of hemodialysis patients with severe hyperparathyroidism, treated by surgery or medical therapy followed-up for 36 months. Inclusion criteria were age older than 18 years, renal failure requiring dialysis treatment (hemodialysis or peritoneal dialysis) and ability to sign the consent form. A control group of 418 patients treated in the same centers, who did not undergo parathyroidectomy was selected after matching for age, sex, and dialysis vintage. RESULTS: From 82 Dialysis units in Italy, we prospectively collected data of 257 prevalent patients who underwent parathyroidectomy (age 58.2 ± 12.8 years; M/F: 44%/56%, dialysis vintage: 15.5 ± 8.4 years) and of 418 control patients who did not undergo parathyroidectomy (age 60.3 ± 14.4 years; M/F 44%/56%; dialysis vintage 11.2 ± 7.6 y). The survival rate was higher in the group that underwent parathyroidectomy (Kaplan-Meier log rank test = 0.002). Univariable analysis (HR 0.556, CI: 0.387-0.800, p = 0.002) and multivariable analysis (HR 0.671, CI:0.465-0.970, p = 0.034), identified parathyroidectomy as a protective factor of overall survival. The prevalence of patients at KDOQI targets for PTH was lower in patients who underwent parathyroidectomy compared to controls (PTX vs non-PTX: PTH < 150 pg/ml: 59% vs 21%, p = 0.001; PTH at target: 18% vs 37% p = 0.001; PTH > 300 pg/ml 23% vs 42% p = 0.001). The control group received more intensive medical treatment with higher prevalence of vitamin D (65% vs 41%, p = 0.0001), calcimimetics (34% vs 14%, p = 0.0001) and phosphate binders (77% vs 66%, p = 0.002). CONCLUSIONS: Our data suggest that parathyroidectomy is associated with survival rate at 36 months, independently of biochemical control. Lower exposure to high PTH levels could represent an advantage in the long term.

The Impact of Cholecaciferol Supplementation on Bone Mineral Density in Long-Term Kidney Transplant Recipients.

Although reduced bone mineral density (BMD) is associated with a higher risk of fractures, morbidity, and mortality in kidney transplant patients (KTRs), there is no consensus on optimal treatment for the alterations of BMD in this population. This study aims at assessing the effect of cholecalciferol supplementation on BMD over a follow-up period of 2 years in a cohort of long-term KTRs. Patients with age ≥ 18 years were included and divided into two subgroups based on treatment with bisphosphonate and/or calcimimetics and/or active vitamin D sterols (KTRs-treated) or never treated with the above medications (KTRs-free). BMD was evaluated at lumbar vertebral bodies (LV) and right femoral neck (FN) with standard DEXA at the beginning and end of the study. According to World Health Organization (WHO) criteria, results were expressed as T-score and Z-score. Osteoporosis and osteopenia were defined as T score ≤ -2.5 SD and T score < -1 and >-2.5 SD, respectively. Cholecalciferol was supplemented at a dose of 25,000 IU/week over 12 weeks followed by 1500 IU/day. KTRs-free (n. 69) and KTRs-treated (n. 49) consecutive outpatients entered the study. KTRs-free were younger (p < 0.05), with a lower prevalence of diabetes (p < 0.05) and of osteopenia at FN (46.3 % vs. 61.2 %) compared to KTRs-treated. At the entry none of the study subjects had a sufficient level of cholecalciferol; Z-score and T-score at LV and FN were not different between groups. At the end of the study period, serum cholecalciferol concentration was significantly increased in both groups (p < 0.001); the KTRs-free group presented an improvement in both T-score and Z-score at LV (p < 0.05) as well as a lower prevalence of osteoporotic cases (21.7% vs. 15.9%); in contrast, no changes were recorded in KTR-treated individuals. In conclusion, supplementation with cholecalciferol ameliorated Z-score and T-score at LV in long-term KTRs who had been never treated with active or inactive vitamin D sterols, bisphosphonates, and calcimimetics. Future endeavours are needed to confirm these preliminary findings.

Contrast-Induced Acute Kidney Injury and Endothelial Dysfunction: The Role of Vascular and Biochemical Parameters.

INTRODUCTION: Contrast-induced acute kidney injury (CIAKI) is one of the main causes of acute renal failure in hospitalized patients, following the administration of iodinated contrast medium used for CT scans and angiographic procedures. CIAKI determines a high cardiovascular risk and appears to be one of the most feared complications of coronary angiography, causing a notable worsening of the prognosis with high morbidity and mortality. AIM: To evaluate a possible association between the renal resistive index (RRI) and the development of CIAKI, as well as an association with the main subclinical markers of atherosclerosis and the main cardiovascular risk factors. MATERIALS AND METHODS: We enrolled 101 patients with an indication for coronary angiography. Patients underwent an assessment of renal function (serum nitrogen and basal creatinine, 48 and 72 h after administration of contrast medium), inflammation (C reactive protein (CRP), serum calcium and phosphorus, intact parathormone (iPTH), 25-hydroxyvitaminD (25-OH-VitD), serum uric acid (SUA), total cholesterol, serum triglycerides, serum glucose and insulin). All patients also carried out an evaluation of RRI, intima-media thickness (IMT), interventricular septum (IVS) and the ankle-brachial index (ABI). RESULTS: 101 patients (68 male), with a mean age of 73.0 ± 15.0 years, were enrolled for the study; 35 are affected by type 2 diabetes mellitus. A total of 19 cases of CIAKI were reported (19%), while among diabetic patients we reported an incidence of 23% (8 patients). In our study, patients with CIAKI had significantly higher RRI (p < 0.001) and IMT (p < 0.001) with respect to the patients who did not develop CIAKI. Furthermore, patients with CIAKI had significantly higher CRP (p < 0.001) and SUA (p < 0.006). CONCLUSIONS: We showed a significant difference in RRI, IMT, SUA and CRP values between the population developing CIAKI and patients without CIAKI. This data appears relevant considering that RRI and IMT are low-cost, non-invasive and easily reproducible markers of endothelial dysfunction and atherosclerosis.

Association between Cognitive Impairment and Malnutrition in Hemodialysis Patients: Two Sides of the Same Coin.

Cognitive impairment and malnutrition are prevalent in patients on hemodialysis (HD), and they negatively affect the outcomes of HD patients. Evidence suggests that cognitive impairment and malnutrition may be associated, but clinical studies to assess this association in HD patients are lacking. The aim of this study was to evaluate the association between cognitive impairment evaluated by the Montreal Cognitive Assessment (MoCA) score and nutritional status evaluated by the malnutrition inflammation score (MIS) in HD patients. We enrolled 84 HD patients (44 males and 40 females; age: 75.8 years (63.5-82.7); HD vintage: 46.0 months (22.1-66.9)). The MISs identified 34 patients (40%) as malnourished; the MoCa scores identified 67 patients (80%) with mild cognitive impairment (MCI). Malnourished patients had a higher prevalence of MCI compared to well-nourished patients (85% vs. 70%; p = 0.014). MoCa score and MIS were negatively correlated (rho:-0.317; p < 0.01). Our data showed a high prevalence of MCI and malnutrition in HD patients. Low MoCA scores characterized patients with high MISs, and malnutrition was a risk factor for MCI. In conclusion, it is plausible that MCI and malnutrition are linked by common sociodemographic, clinical, and biochemical risk factors rather than by a pathophysiological mechanism.

Diastolic Pressure and ACR Are Modifiable Risk Factors of Arterial Stiffness in T2DM Without Cardiovascular Disease.

AIM: To evaluate early, before the onset of cardiovascular events and of chronic renal insufficiency, the association between chronic kidney disease (CKD)-mineral bone disorder (MBD) biomarkers and vascular stiffness [Cardio Ankle Vascular Index (CAVI)] in the course of type 2 diabetes (T2DM). METHOD: We evaluated 174 T2DM patients [median age 56 years; male/female (M/F) 100/74] with diabetes duration < 10 years and without decreased estimated glomerular filtration rate (eGFR; ≥60 mL/min/1.73 m2) or macrovascular complications. Thirty-four age-matched healthy subjects [M/F 13/21; age 53.5 (50.0-57.7) years; eGFR 107.5 (97.0-119.7) mL/ min1.73 m2] served as local reference control for CAVI (pathological: ≥8) and the novel CKD-MBD biomarkers. RESULTS: Albumin-to-creatinine ratio (ACR) averaged 8.5 mg/g (5.6-17.2) with 12.6% of the patients showing pathologic values, indicative of incipient diabetic nephropathy. Serum parathyroid hormone, fibroblast growth factor 23, and sclerostin were higher while 1,25-dihydroxyvitamin D and Klotho were lower than a control group. CAVI was normal (<8) in only 54% and correlated positively with age (P < 0.001), hemoglobin 1A1c (P = 0.036), and systolic (P = 0.021) and diastolic blood pressure (DBP) (P = 0.001) and negatively correlated with 25-hydroxyvitamin D (P = 0.046). In multivariate analysis, age, DBP, ACR, and serum Klotho were independent positive predictors of CAVI. CONCLUSION: In the absence of overt cardiovascular disease and of chronic renal insufficiency, CAVI is frequently pathologic in T2DM. DBP and ACR are modifiable risk factors of vascular stiffness in T2DM, thus warranting optimal assessment.

Results of the implementation of a triage system of vascular access performance in haemodialysis patients: experience of a single dialysis centre.

BACKGROUND: Routine systems for monitoring vascular access (VA) performance are lacking. We developed a vascular access triage system to evaluate the monthly performance of the access, developed a specific score and assessed the association between score improvement and clinical outcomes. METHODS: Vascular access was triaged (Green, Yellow or Red) according to a score generated by dialytic and clinical parameters in all patients who, from 1/1/2014 to 31/03/2014, had been receiving haemodialysis treatment for at least 3 consecutive months in our Unit and who were then followed up for 4 years. RESULTS: We enrolled 130 patients, 78 with arteriovenous fistula (AVF) and 52 with tunnelled central venous catheter (CVC). During a median of 29 ± 11 months of follow up (range 3-46 months), 28 deaths and 303 hospitalizations (lasting 16 ± 30 days) were recorded. Vascular access triage scores improved over time (2014 vs 2015 vs 2016 vs 2017) in the population with an AVF (Green from 25% to 58% to 77% to 79%, Yellow from 65% to 39% to 18% to 20% and Red from 10% to 3% to 5% to 1%, respectively; χ2 p < 0.01) but not in the CVC group (Green 58% to 57% to 80% to 92%; Yellow 37% to 36% to 20% to 8%; Red 5% to 7% to 0%; χ2 = n.s). Blood pressure and dialysis efficiency improved in the population as a whole and in the two subgroups (AVF and CVC) separately. AVF and CVC populations, stratified separately according to median VA score, had different event-free follow-up, which was higher (p = 0.0085) in patients with lower scores in the AVF population only. CONCLUSION: The vascular access monitoring system improved the vascular access score as well as some clinical and dialytic parameters. Green triage in AVF patients identify those with better outcomes, in agreement with the commonly recognized clinical value of a well-functioning vascular access.

Oxygen Extraction and Mortality in Patients Undergoing Chronic Haemodialysis Treatment: A Multicentre Study.

Patients on haemodialysis (HD) suffer a high mortality rate linked to developing subclinical hypoxic parenchymal stress during HD sessions. The oxygen extraction ratio (OER), an estimate of the oxygen claimed by peripheral tissues, might represent a new prognostic factor in HD patients. This study evaluated whether the intradialytic change in OER (ΔOER) identified patients with higher mortality risks. We enrolled chronic HD patients with permanent central venous catheters with available central venous oxygen saturation (ScvO2) measurements; the arterial oxygen saturation was measured with peripheral oximeters (SpO2). We measured OER before and after HD at enrolment; deaths were recorded during two-years of follow-up. In 101 patients (age: 72.9 ± 13.6 years, HD vintage: 9.6 ± 16.6 years), 44 deaths were recorded during 11.6 ± 7.5 months of follow-up. Patients were divided into two groups according to a 40% ΔOER threshold (ΔOER < 40%, n = 56; ΔOER ≥ 40%, n = 45). The ΔOER ≥ 40% group showed a higher incidence of death (60% vs. 30%; p = 0.005). The survival curve (log-rank-test: p = 0.0001) and multivariate analysis (p = 0.0002) confirmed a ΔOER ≥ 40% as a mortality risk factor. This study showed the intradialytic ΔOER ≥ 40% was a mortality risk factor able to highlight critical hypoxic damage. Using a ΔOER ≥ 40% could be clinically applicable to characterise the most fragile patients.

Chronic Kidney Disease as a Systemic Inflammatory Syndrome: Update on Mechanisms Involved and Potential Treatment.

Chronic kidney disease (CKD) is characterized by manifestations and symptoms involving systemic organs and apparatus, associated with elevated cardiovascular morbidity and mortality, bone disease, and other tissue involvement. Arterial hypertension (AH), diabetes mellitus (DM), and dyslipidemia, with glomerular or congenital diseases, are the traditional risk factors recognized as the main causes of progressive kidney dysfunction evolving into uremia. Acute kidney injury (AKI) has recently been considered an additional risk factor for the worsening of CKD or the development of CKD de novo. Evidence underlies the role of systemic inflammation as a linking factor between AKI and CKD, recognizing the role of inflammation in AKI evolution to CKD. Moreover, abnormal increases in oxidative stress (OS) and inflammatory status in CKD seem to exert an important pathogenetic role, with significant involvement in the clinical management of this condition. With our revision, we want to focus on and update the inflammatory mechanisms responsible for the pathologic conditions associated with CKD, with particular attention on the development of AKI and AKI-CKD de novo, the alteration of calcium-phosphorus metabolism with bone disease and CKD-MBD syndrome, the status of malnutrition and malnutrition-inflammation complex syndrome (MICS) and protein-energy wasting (PEW), uremic sarcopenia, the status of OS, and the different inflammatory pathways, highlighting a new approach to CKD. The depth comprehension of the mechanisms underlying the development of inflammation in CKD may present new possible therapeutic approaches in CKD and hopefully improve the management of correlated morbidities and provide a reduction in associated mortality.

Focus on the Possible Role of Dietary Sodium, Potassium, Phosphate, Magnesium, and Calcium on CKD Progression.

The impressive estimated number of chronic kidney disease (CKD) patients in the world justifies any possible effort at implementing preventive measures of disease progression. Renal insufficiency is associated with significant changes in the electrolyte handling and body balance of sodium, potassium, phosphate, magnesium, and calcium, all of which are biologically vital molecules. Dietary habits could contribute significantly to the optimal management of possible derangements. In this review, we examined the available evidence recommending dietary prescriptions for these five elements aiming at reducing CKD progression. Clear evidence that specific dietary prescriptions may halt or reduce CKD progression is lacking. However, some practical recommendations are possible to prescribe the best possible therapy to the individual CKD patient.

Oxygen extraction ratio to identify patients at increased risk of intradialytic hypotension.

Intradialytic hypotension (IDH) is a hemodynamic phenomenon recently associated with decreased blood oxygen saturation (SO2). The ratio between peripheral oxygen saturation (SpO2) and central venous SO2 (ScvO2) or Oxygen Extraction Ratio (OER), which represents a roughly estimate of the amount of oxygen claimed by peripheral tissues, might be used to estimate haemodialysis (HD) related hypoxic stress. Aim of this pilot study was to evaluate the relationship between OER increments during dialysis sessions (ΔOER) and episodes of IDH. We enrolled chronic HD patients with permanent central venous catheter (CVC) and no fistula, in whom ScvO2 measurement is at hand. OER ([(SpO2 - ScvO2)/SpO2] × 100) was measured in three consecutive HD sessions (HD OER sessions) before HD, after 15', 30' and 60' min and at the end of HD. Then, a one-year follow-up was planned to record the number of IDH episodes. In the 28 enrolled patients (age 74 ± 2.6 years), during 12 ± 1.2 months of follow up, incidence of IDH was 3.6%. We divided patients into two groups, above or below the median value of ΔOER at the end of HD, which was 36%. In these groups, the average incidence of IDH was 7% and 2% respectively (p < 0.01), while OER values before HD were not different. Notably, in the high ΔOER group the OER increment was evident since after 15' and was significantly higher than in the low ∆OER group (∆OER-15' = 19 ± 3.0% vs. 9.0 ± 3.0%; p < 0.05). By comparison, blood volume changes overlapped in the two groups (average change - 9 ± 0.8%). Values of ∆OER > 19% after only 15' of HD treatment or > 36% at the end of the session characterize patients with higher rates of hypotension. Intradialytic ∆OER, a parameter of tissue hypoxic stress, identifies more fragile patients at greater risk of IDH.

Inflammation, Oxidative Stress, and Bone in Chronic Kidney Disease in the Osteoimmunology Era.

Bone is not only a mineralized and apparently non-vital structure that provides support for locomotion and protection to inner organs. An increasing number of studies are unveiling new biologic functions and connections to other systems, giving the rise to new fields of research, such as osteoimmunology. The bone marrow niche, a new entity in bone physiology, seems to represent the site where a complex crosstalk between bone and immune/inflammatory responses takes place. An impressive interplay with the immune system is realized in bone marrow, with reciprocal influences between bone cells and haematopoietic cells. In this way, systemic chronic inflammatory diseases realize a crosstalk with bone, resulting in bone disease. Thus, pathogenetic links between chronic kidney disease-mineral bone disorders and osteoporosis, cardiovascular disease, and ageing are common. The aim of this narrative review is to provide a general view of the progresses in the field of bone research and their potential clinical implications, with emphasis on the links with inflammation and the connections to osteoimmunology and chemokines.

A new technique for measuring fistula flow using venous blood gas oxygen saturation in patients with a central venous catheter.

BACKGROUND: Doppler ultrasound (DU) monitoring early after arteriovenous fistula (AVF) creation allows the identification of low blood flow (Qa) requiring prompt revision, but it is costly (needs skilled operators and technical instruments) and is not available in all dialysis units. Therefore alternative first-line methods to measure Qa would be welcomed. We reasoned that once an AVF is created, an increment in central venous oxygen saturation (ScvO2) is predictable and proportional to Qa. METHODS: Accordingly, in patients receiving dialysis through a central venous catheter (CVC) in whom an AVF was created, we measured, by means of blood gas analysis, the ScvO2 increment before and after manual compression of the arteriovenous shunt and verified its correlation with DU-measured Qa. RESULTS: We sampled blood gas in 18 patients with CVC and AVF before and after 30 s manual compression of the AVF. ScvO2 averaged 70.5 ± 3% before and 65.2 ± 3% after AVF closure, with an average drop of 5.1 ± 3% (range 1-12). AVF Qa, which was measured within 24 h by means of DU, averaged 635 ± 349 mL/min (range 50-1300) and was strictly and positively correlated with ΔScvO2 (r = 0.954, P < 0.0001). CONCLUSIONS: Therefore we suggest that in patients with CVC and a newly created AVF, it is possible to monitor AVF Qa without DU by simply measuring blood gas and ΔScvO2. This technique is simple, cheap, repeatable, non-invasive and operator independent and represents a new useful screening test to detect delayed AVF access maturation deserving prompt DU measurement and surgical revision. It helps to quickly identify patients in urgent need of DU verification and possible surgical revision. Regrettably, it is applicable only in patients with CVC.

Bone, inflammation and chronic kidney disease.

Increasing knowledge on inflammatory mediators and bone metabolism highlights the relationship between inflammation and bone disease. During acute illness, inflammatory cells and cytokines modulate bone cells activity so as to mobilize calcium seemingly to supply the metabolic requirements for immune response. In case of long lasting, chronic inflammatory states a condition of maladaptive, smouldering inflammation is realized and negatively affects calcium bone balance. Aging, now nicknamed inflammaging, is regarded as a chronic inflammatory condition, characterized by increased circulating inflammatory cytokines, that contributes to the development of osteoporosis, cardiovascular diseases and chronic kidney disease. In patients with renal insufficiency, the development of bone and mineral disorders (so called CKD-MBD "syndrome") is now a recognized pathogenic factor for the seemingly accelerated process of aging and for the increased risk of cardiovascular death in these patients. The adaptive changes in mineral and bone metabolism developing in the early stages of chronic kidney disease could represent a hypothetical model of accelerated aging, osteoporosis and cardiovascular disease.

On the role of skin biopsy in the diagnosis of calcific uremic arteriolopathy: a case-based discussion.

Calciphylaxis is a rare disease characterized by ectopic calcification of skin arterioles resulting in ischemia, thrombosis and necrosis. Since end stage renal disease patients are those mainly affected, the term calcific uremic arteriolopathy (CUA) is also suggested. Early clinical manifestations are subtle, while overt necrotic ulcers may quickly spread and become infected so as to result in ominous outcome. Diagnosis might not be easy due to the number of other ischemic and non-ischemic skin lesions observed in uraemia. Skin biopsy, has been proposed as the diagnostic test and is often considered, but not systematically performed due to the hypothetical risk of further spreading of the lesions. Such ambiguity could be responsible for misdiagnosis or underdiagnosis. We review here five consecutive cases recorded in our Unit, all submitted to skin biopsy but with inconsistent results which generated some clinical frustration. Thus, we decided to carefully re-evaluate all of them together with pathologists and dermatologists. However, even after this ex-post discussion, we could not reach a complete agreement on the final diagnosis. In the meanwhile, papers were published in the literature that started to shed some light on the role of skin biopsy in the diagnosis of CUA.