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Onconephrology is a rapidly evolving subspecialty that covers all areas of renal involvement in cancer patients. The complexity of the field may benefit from well-defined multidisciplinary management by a dedicated team. Patients with cancer frequently suffer from concurrent chronic kidney disease (CKD), with a prevalence ranging from 12% to 53% at the time of cancer diagnosis. Taking into account the incidence of cancer and the prevalence of CKD in the Italian population, we estimate that about 44,000 patients suffered from both diseases in 2020. Since there is an increasing necessity to address the needs of this population in dedicated outpatient clinics, it is critical to highlight some basic characteristics and to suggest areas of development. Our experience in the nephrological management of cancer patients clearly suggests the need to implement dedicated multidisciplinary teams and to create onconephrology clinics (at least within larger, referral, hospitals). Furthermore, it must be kept in mind that not only is CKD common in cancer patients, but also that the concomitant presence of these two conditions too often excludes cancer patients from clinical trials, thus limiting their access to therapies that could potentially improve their outcomes. Indeed, the Renal Insufficiency and Cancer Medications (IRMA) study found that cancer patients with CKD or on dialysis are often undertreated, or are exposed to either ineffective or toxic anticancer agents. Finally, the aim of this article is to initiate a debate about what an onconephrology outpatient clinic might look like, in order to ensure the highest quality of care for this growing patient population.

Objectives Obesity is an important risk factor for morbidity and mortality. Vitamin K2 is involved in the production of bone and matrix amino acid g-carboxy-glutamic acid (Gla) proteins (vitamin K-dependent proteins [VKDPs]), regulating bone and vascular calcification (VC). Bone Gla protein (BGP) is involved both in bone mineralization and VCs. We assessed the relationships between vitamin K levels and body mass index (BMI) according to the hypothesis that the impact of BMI on mortality is partly driven by low vitamin K levels. Methods The Vitamin K Italian (VIKI) study included 387 hemodialysis patients from 18 dialysis centers in Italy. We determined plasma levels of bone markers: vitamin K levels, VKDPs, vitamin 25(OH)D, alkaline phosphatase (ALP), parathyroid hormone (PTH), calcium (Ca), phosphorus (P) and routine biochemistry. BMI was classified into the following categories: underweight (BMI 2), normal weight (18.5 ≤ BMI 2), overweight (25 ≤ BMI 2) and obese (BMI ≥ 30 kg/m2). Results 45.2% of patients were overweight or obese. Stratification by BMI demonstrated lower median menaquinone-7 (MK7)/triglycerides levels in obese patients (0.42 ng/mg [0.19, 0.87], p = 0.005). BGP levels were lower in overweight and obese patients (152 mcg/L [83.2, 251] and 104 mcg/L [62.7, 230], p = Conclusions These data are the first to report an inverse relationship between Vitamin K2 levels and BMI in hemodialysis patients. Further studies are needed to confirm these findings and to determine if lower levels of Vitamin K are related to greater morbidity and mortality in this at-risk population.

Highlights • Canakinumab is an IL-1β antibody that neutralizes the activity of IL-1β. • The effects of canakinumab in patients with COVID-19-related pneumonia were studied. • 33 patients received canakinumab and 15 received institutional standard of care. • Treatment with canakinumab rapidly restored normal oxygen status. • Canakinumab was also associated with favorable prognosis versus SoC., Objectives Canakinumab is an IL-1β antibody that neutralizes the activity of IL-1β. We studied the efficacy and safety of canakinumab in patients with moderate COVID-19-related pneumonia. Design The aim of our study was to evaluate the reduction in duration of hospitalization with adequate oxygen status. Forty-eight patients with moderate COVID-19-related pneumonia were asked to participate in the prospective case-control study; 33 patients (Cases) signed informed consent and received canakinumab (Cohort 1); 15 patients (Controls) refused to receive the experimental drug and received institutional standard of care (SoC), (Cohort 2). Results Hospital discharge within 21 days was seen in 63% of patients in Cohort 1 vs. 0% in Cohort 2 (median 14 vs 26 days, respectively; p

The assessment of the vitamin K status and its effects on clinical outcomes in kidney transplantation (KT) patients has sparked interest, but it is still largely unfulfilled. In part, this is due to difficulties in laboratory measurements of vitamin K, especially K2 vitamers. Vitamin K status is currently best assessed by measuring undercarboxylated vitamin-K-dependent proteins. The relative contribution of vitamin K1 and K2 to the health status of the general population and CKD (chronic kidney disease) patients, including KT patients, is also poorly studied. Through a complete and first review of the existing literature, we summarize the current knowledge of vitamin K pathophysiology and its potential role in preventing KT complications and improving organ survival. A specific focus is placed on cardiovascular complications, bone fractures, and the relationship between vitamin K and cancer. Vitamin K deficiency could determine adverse outcomes, and KT patients should be better studied for vitamin K assessment and modalities of effective therapeutic approaches. ispartof: NUTRIENTS vol:12 issue:9 ispartof: location:Switzerland status: published

The global growing number of contrast-enhanced procedures highlights the risk of contrast media–induced renal damage. This review is an effort to define contrast-induced nephropathy and its pathogenesis, weigh its principal risk factors, give some clarifications about kidney function evaluation tools, acquire some clinical relevance prognostic concerns, and bring into focus preventive measures, with special regard to cancer patients. Our final purpose is focused on the request of diagnostic safety in high-risk patients, which may be achieved without unfair differences in this subgroup, too. A second reading of the scientific evidence may offer a chance to tear down the kidney damage ghost, replacing it with the consciousness of a still existing challenge that engages more than one specialty.

e16023 Background: Currently, cisplatin, gemcitabine, paclitaxel (CGP) and MVAC are the most active chemotherapy regimens in mUC. We tested the hypothesis that two sequential non-cross-resistant, dose-dense (DD) regimens may target different cancer cells, avoid drug resistance, and improve response rate. Methods: This is a single institution, explorative trial. The aim is to evaluate the incremental benefit of the two regimens in terms of complete response and long term survival. We treat all consecutive, chemo-naïve mUC patients with 4 cycles of CGP dose-dense every 14 days followed by 4 cycles of MVAC every 14 days. In all cycles we used Pegfilgrastim 6 mg on day 3. Pts were evaluated with CT scan at the baseline, after 4 cycles, at the end of chemotherapy and then every 3 months for 2 years and 6 months thereafter. Results: From 2007 to 2018, 67 consecutive pts were included. Male were 82%; median age 66 years (33-83); Bajorin risk factors was 0 in 31%, 1 in 52%, 2 in 16%. The majority of pts were hospitalized for three days during chemotherapy and received hydration and supportive therapy. After the first 4 cycles of CGP, we observed 7% CR, 46% PR, 31% SD, and 12% PD. After the 4 sequential cycles of MVAC DD we observed a global 25% of CR, 33% PR, 10% SD, and 24% PD. Median TTP was 8.2 months (95% CI, 7.3-10.1) and median OS was 18 months (95% CI, 10.8-26.1). 5 pts are still alive after more than 30 months and maintaining complete response. Main grade 3–4 toxicity included anemia 27%, asthenia 23%, neutropenia 19% (febrile 7%), thrombocytopenia 13%. Conclusions: The sequential use of these two DD regimens is active and leads to an increased number of complete response and possible longer survival. A randomized trial is needed to confirm our results.

Background: Immunoglobulin A (IgA) nephropathy is the most common form of glomerulonephritis worldwide. Familial and sporadic cases are recognized, and a locus associated with the familial form of the disease was mapped to chromosome 6. Recent data suggest the familial IgA nephropathy form may have a poorer outcome than the sporadic form. Methods: We tested the hypothesis of unequal survival rates between the 2 forms of disease by analyzing time from biopsy to end-stage renal disease in patients of Italian ancestry; 589 patients with sporadic and 96 patients with familial IgA nephropathy. Results: Overall 10- and 20-year renal survival probabilities of the cohort as a whole were 71% and 50%, respectively. Macroscopic hematuria was the modality of clinical presentation in 51% of patients with familial IgA nephropathy and 39% of patients with sporadic IgA nephropathy. At univariable analysis, the sporadic form of IgA nephropathy was associated significantly with increased risk for renal death. However, patients with the sporadic form tended to be more hypertensive and diagnosed later, with signs of more advanced renal disease than those with familial disease at baseline. In the regression model, form of disease lost any independent effect. Only male sex, lower baseline glomerular filtration rate, greater proteinuria, and histopathologic score proved to be independent predictors of disease progression. Treatment with steroids or angiotensin-converting enzyme inhibitors was associated with improved outcomes. Conclusion: Our study does not confirm that familial IgA nephropathy has a worse prognosis than the sporadic form. The similar renal phenotype may support a common pathogenic mechanism underlying familial and sporadic IgA nephropathy.

T helper (h) lymphocytes in pathogenic immune response at mucosal effector site play a key role in IgA nephropathy (IgAN). We evaluated the impact of some Th1/Th2/Th3/T(R)-type, and of monocyte/macrophage cytokines on IgAN susceptibility with a family-based association study including 53 patients, 45 complete trios, 4 incomplete trios and 36 discordant siblings. Cytokine gene polymorphisms with a potential regulatory role on their production were investigated using the family-based association test (FBAT): IFNgamma intron-1 CA repeat at position 1349-1373; IL-13 -1055C/T; TGFbeta +915G/C; IL-10 5'-proximal and distal microsatellites; TNFalpha -308G/A, -238G/A. The FBAT multi-allelic analysis showed an association between IFNgamma polymorphism and susceptibility to IgAN (P=0.03). The bi-allelic analysis evidenced that the 13-CA repeat allele was preferentially transmitted to the affected individuals (P=0.006; Bonferroni P-value=0.04). The direct sequencing of IFNgamma amplicons showed a strict association between the 13-CA repeat allele and the A variant of the +874T/A single nucleotide polymorphism (SNP rs2430561) directly adjacent to the 5' end of the microsatellite. The in vitro production of IFNgamma evaluated in peripheral blood mononuclear cells from 10 genotyped patients demonstrated a correlation between the +874A allele and a lower production of IFNgamma (P=0.028 Mann-Whitney test). This SNP affects IFNgamma production lying within a binding site for the transcription factor NF-kappaB. No significant difference was observed in the 15 years renal survival between IgAN patients carrying different IFNgamma gene polymorphisms. This first family-based association study demonstrates that the +874A allele, strictly associated with IFNgamma 13-CA repeat allele, confers susceptibility to IgAN, without influencing renal survival.

Heparin-induced thrombocytopenia (HIT) is an uncommon but severe immunologic adverse effect of heparin therapy, which is associated with an increased thrombotic risk [1]. This syndrome is mediated by platelet-activating antibodies, generally targeting platelet factor 4-heparin (PF4-Hep) complexes, and is characterised by an abrupt onset of thrombocytopenia, and, at the same time, by an abnormal thrombin generation resulting in a hypercoagulable state. A thrombotic complication occurs in over half of the patients affected [1]. The diagnosis of HIT is based both on clinical criteria and laboratory assays, but it is often a difficult diagnosis to make and is frequently delayed [2]. This is a case report of one patient with HIT who developed pulmonary embolism and deep vein thrombosis during haemodialysis. A 83-year-old woman with chronic renal failure started haemodialysis because of worsening of renal function (creatinine = 6.5 mg/dl). During each of the dialysis sessions, lasting 3 h, the patient received unfractionated heparin (UFH), with a bolus of 2,000 U followed by 600 U/h by continuous infusion. To facilitate the dialysis procedures, a venous catheter was inserted in the right common femoral vein. After five sessions of dialysis, 12 days after the first administration of UFH, the patient suddenly developed dyspnea, chest and abdominal pain and right leg swelling. Pulmonary embolism, multiple splenic infarctions and deep vein thrombosis of the right leg (from the popliteal to the external iliac vein) were detected by spiral computer tomography and by color-Doppler ultrasonography. The platelet count dropped to 10,000 platelet/mm. Retrospectively, we observed that a decrease in the platelet counts [50% from baseline was already present after the third session of dialysis (from 236,000 to 44,000/mm). An inferior vena cava filter was placed, and anticoagulant therapy with lepirudin (Refludan, Pharmion Ltd) was started at an initial dose of 0.05 mg/kg/h (i.e. 3.5 mg/h) with the aim of maintaining the aPTT ratio between 1.5 and 2.5. The enzyme-linked immunosorbent assay (EIA, GTIHAT, GTI INC, Brookfield WI) to detect PF4/Hep antibodies showed highly positive results (optical density = 2.77; normal value \0.40). Alternative causes of thrombocytopenia, i.e. disseminated intravascular coagulation and thrombotic thrombocytopenic purpura, were excluded. In the following days, the platelet counts remained low (10–15,000/mm); because of severe renal failure, lepirudin monitoring was extremely difficult, with frequent episodes of overanticoagulation (aPTT ratio [ 3.0), despite a reduced dosage (0.0007 mg/kg/h with average of 1.2 mg/ daily); repeated interruptions of lepirudin administration were necessary. The clinical course of the patient was further complicated by sepsis due to methicillin-resistant Staphylococcus aureus: targeted antibiotic treatment was started. Five days after the beginning of lepirudin therapy, the patient started complaining of left leg pain. A colorDoppler ultrasonography showed a new deep vein thrombosis of the left limb, from the popliteal to the common femoral vein. Therefore, lepirudin was replaced with argatroban (Novastan, Mitsubishi Pharma Europe Ltd). The starting argatroban dose was 2 lg/kg/min (corresponding to 7 ml/h) in order to maintain the aPTT ratio between 1.5 and 3.0. A very quick improvement of the clinical picture A. Alatri (&) O. Paoletti A. Zimmermann S. Testa Haemostasis and Thrombosis Centre, A.O. Istituti Ospitalieri di Cremona, Viale Concordia 1, 26100 Cremona, Italy e-mail: a.alatri@ospedale.cremona.it

Background IgA nephropathy (IgAN) or Berger's disease, is the most common glomerulonephritis in the world diagnosed in renal biopsied patients. The involvement of genetic factors in the pathogenesis of the IgAN is evidenced by ethnic and geographic variations in prevalence, familial clustering in isolated populations, familial aggregation and by the identification of a genetic linkage to locus IGAN1 mapped on 6q22–23. This study seems to imply a single major locus, but the hypothesis of multiple interacting loci or genetic heterogeneity cannot be ruled out. The organization of a multi-centre Biobank for the collection of biological samples and clinical data from IgAN patients and relatives is an important starting point for the identification of the disease susceptibility genes. Description The IgAN Consortium organized a Biobank, recruiting IgAN patients and relatives following a common protocol. A website was constructed to allow scientific information to be shared between partners and to divulge obtained data (URL: http://www.igan.net). The electronic database, the core of the website includes data concerning the subjects enrolled. A search page gives open access to the database and allows groups of patients to be selected according to their clinical characteristics. DNA samples of IgAN patients and relatives belonging to 72 multiplex extended pedigrees were collected. Moreover, 159 trios (sons/daughters affected and healthy parents), 1068 patients with biopsy-proven IgAN and 1040 healthy subjects were included in the IgAN Consortium Biobank. Some valuable and statistically productive genetic studies have been launched within the 5th Framework Programme 1998–2002 of the European project No. QLG1-2000-00464 and preliminary data have been published in "Technology Marketplace" website: http://www.cordis.lu/marketplace. Conclusion The first world IgAN Biobank with a readily accessible database has been constituted. The knowledge gained from the study of Mendelian diseases has shown that the genetic dissection of a complex trait is more powerful when combined linkage-based, association-based, and sequence-based approaches are performed. This Biobank continuously expanded contains a sample size of adequately matched IgAN patients and healthy subjects, extended multiplex pedigrees, parent-child trios, thus permitting the combined genetic approaches with collaborative studies.