The value of the multidisciplinary team in metastatic renal cell carcinoma: Paving the way for precision medicine in toxicities management.

The new landscape of treatments for metastatic clear cell renal carcinoma (mRCC) is constantly expanding, but it is associated with the emergence of novel toxicities, adding to up to those observed in the tyrosine-kinase inhibitor (TKI) era. Indeed, the introduction of immune checkpoint inhibitors (ICIs) alone or in combination has been associated with the development of immune-related adverse events (irAEs) involving multiple-organ systems which, even if rarely, had led to fatal outcomes. Moreover, due to the relatively recent addition of ICIs to the previously available treatments, the potential additive adverse effects of these combinations are still unknown. A prompt recognition and management of these toxicities currently represents a fundamental issue in oncology, since it correlates with the outcome of cancer patients. Even if clinical guidelines provide indications for the management of irAEs, no specific protocol to evaluate the individual risk of developing an adverse event during therapy is currently available. A multidisciplinary approach addressing appropriate interventions aimed at reducing the risk of any insidious, severe, and/or dose-limiting toxicity might represent the most efficacious strategy to timely prevent and manage severe irAEs, allowing indirectly to improve both patients' cancer-specific survival and quality of life. In this review, we reported a five-case series of toxicity events that occurred at our center during treatment for mRCC followed by the remarks of physicians from different specialties, pinpointing the relevant role of an integrated and extended multidisciplinary team in a modern model of mRCC patient management.

Onconephrology: A New Challenge for the Nephrologist.

Clinical Background: Cancer therapeutics (for both solid and hematological malignancies) have evolved over the last two decades, from traditional chemotherapies to novel treatments. A better supportive care, older patients with comorbidities who receive multiple chemotherapeutic and pharmacological regimens, multiple CT scans with contrast agents, and new therapeutic options are also increasing the number of cancer patients who can develop acute kidney injury (AKI) or chronic kidney disease (CKD). Challenges: Targeted therapies and immunotherapies, which harness the body's own immune system to fight cancer cells have led to improved survival in cancer patients, yet all are associated with many organ toxicities. Renal toxicity is mainly represented by acute tubular-interstitial damage, glomerular lesions, thrombotic microangiopathy, tumor lysis, proteinuria, arterial hypertension, AKI, CKD, and secondary fluid/electrolyte disturbances. On the other hand, it is important to consider how the presence of CKD, AKI, and other renal disorders may affect treatment options for the oncologists and patient's outcome. All these features require a specialized approach. Prevention and Treatment: A new evolving field, namely Onconephrology, has emerged during the last few years, including the broad spectrum of renal disorders that can arise in patients with cancer. Nephrologists have become an indispensable part of the multidisciplinary cancer care teams, but a clear and updated knowledge of solid and hematological malignancies, always new anticancer therapies, and their relationships with kidney function is essential to ensure the highest quality of care. In this chapter, we summarize the principal aspects of this new field of Nephrology.

Serum Free Light Chains Removal by HFR Hemodiafiltration in Patients with Multiple Myeloma and Acute Kidney Injury: a Case Series.

BACKGROUND/AIMS: Multiple myeloma (MM) represents 10% of all haematologic malignancies. Renal involvement occurs in 50% of MM patients; of them, 12-20% have acute kidney injury (AKI), with 10% needing dialysis at presentation. While hemodialysis (HD) has no effect upon circulating and tissue levels of monoclonal proteins, novel apheretic techniques aim at removing the paraproteins responsible for glomerular/tubular deposition disease. High cut-off HD (HCO-HD) combined with chemotherapy affords a sustained reduction of serum free light chains (FLC) levels. One alternative technology is haemodiafiltration with ultrafiltrate regeneration by adsorption on resin (HFR-SUPRA), employing a "super high-flux" membrane (polyphenylene S-HF, with a nominal cut-off of 42 kD). Aim of our pilot study was to analyze the effectiveness of HFR-SUPRA in reducing the burden of FLC, while minimizing albumin loss and hastening recovery of renal function in 6 subjects with MM complicated by AKI. METHODS: Six HD-dependent patients with MM were treated with 5 consecutive sessions of HFR-SUPRA on a Bellco® monitor, while simultaneously initiating chemotherapy. Levels of albumin and FLC were assessed, calculating the rates of reduction. Renal outcome, HD withdrawal and clinical follow-up or death were recorded. RESULTS: All patients showed a significant reduction of FLC, whereas serum albumin concentration remained unchanged. In three, HD was withdrawn, switching to a chemotherapy alone regimen. The other patients remained HD-dependent and died shortly thereafter for cardiovascular complications. CONCLUSION: Our study suggests that HFR-SUPRA provides a rapid and effective reduction in serum FLC in patients with MM and AKI, while minimizing the loss of albumin. When started early in combination with chemotherapy, blood purification by HFR-SUPRA was followed by the recovery of renal function in half of the patients treated.

Hemodialysis in patients requiring 131I treatment for thyroid carcinoma.

PURPOSE: Thyroid malignancies can be treated by surgery followed by ablation of the remnant tissue with 131I. As iodide removal from the body occurs by renal extraction, in patients suffering from end-stage renal disease it is necessary to properly evaluate both timing and method of the extracorporeal treatment.
 METHODS: We present two patients on regular hemodialysis, admitted in isolation to the Nuclear Medicine Department and treated with 131I for thyroid carcinoma diagnosed during the check-up for transplantation. Both patients underwent two hemodialysis sessions with a portable machine for CRRT (continuous renal replacement therapy), 24 and 48 hours after the administration of 50 mCi of 131I. The nursing staff were monitored with a dosimeter. Radioactivity of the patients, dialysate and urines were measured during hemodialysis. 
 RESULTS: The greater reduction was obtained with the first dialysis, but in both patients a further, though shorter, hemodialysis at 48 hours was necessary for reaching a patient's radioactivity compatible with discharge. Radioactivity measured in the dialysate demonstrated the almost total removal of radioiodine by dialysis alone. In both patients, follow-up exams revealed a complete ablation of thyroid tissue, without signs of local recurrence. The dose of radioactivity of the dialysis staff was below allowable limits. 
 CONCLUSIONS: We conclude that a successful reduction of radioactivity, without dispersing its therapeutic efficacy, can be obtained with daily hemodialysis with a CRRT machine in patients in isolation treated with 131I. A therapeutic model is proposed.

Focal segmental glomerulosclerosis as a complication of graft-versus-host disease.

BACKGROUND: A 54-year-old man with multiple myeloma underwent peripheral blood stem cell transplantation (PBSCT) with cells donated by his human leukocyte antigen (HLA)-identical sister. Eight months after PBSCT, the patient experienced chronic graft-versus-host disease with skin involvement (generalized erythema), mucosal ulceration, sicca syndrome, and elevated liver enzymes. Two years after PBSCT, the patient developed nephrotic syndrome with massive proteinuria, which required hospitalization. INVESTIGATIONS: Physical examination, blood and urine analyses, liver function tests, 24 h urinary albumin excretion and renal biopsy. DIAGNOSIS: Focal segmental glomerulosclerosis as a complication of graft-versus-host disease. MANAGEMENT: Prednisone, ciclosporin and an angiotensin-converting-enzyme inhibitor.

Antiendomysial antibodies in Berger's disease.

The finding of increased levels of immunoglobulin A (IgA) against food antigens in patients with IgA nephropathy prompted the hypothesis of an association between IgA nephropathy and celiac disease (CD). Attention was initially directed to antigliadin antibodies, then to IgA antiendomysial antibodies (IgA-EMA). IgG1-EMA have been found in patients with CD with IgA-EMA-negative results. The presence of IgA- and IgG1-EMA was investigated in 36 patients with IgA nephropathy, 15 patients with other primary glomerulonephritis, and 15 patients with lupus nephritis. IgA-EMA and IgG1-EMA were detected by indirect immunofluorescence analysis. At the time of renal biopsy, the following factors were evaluated: history of macroscopic hematuria, serum creatinine level, urinalysis, 24-hour proteinuria, blood pressure, and histological classification of IgA nephropathy. Sixteen of 36 patients with IgA nephropathy (44.4%) showed EMA positivity. Among patients with positive EMA, 12 patients (75%) were IgG1-EMA positive, 2 patients (12.5%) were IgA-EMA positive, and 2 patients (12.5%) were positive for both isotypes. No significant differences were observed between the two groups (EMA positive versus EMA negative) concerning age, serum creatinine level, macroscopic hematuria, blood pressure, 24-hour proteinuria, or degree of renal histological involvement. IgA- and IgG1-EMA were not detected in patients with other primary nephropathies or lupus nephritis. These results, based on the finding of IgG1-EMA, suggest a common pathogenetic pathway for CD and IgA nephropathy. On this basis, the presence of IgG1-EMA and/or IgA-EMA should be investigated in patients with IgA nephropathy. Furthermore, the role of a gluten-free diet in the natural history of IgA nephropathy, at least in EMA-positive patients, needs to be ascertained.