Bortezomib-based therapy combined with high cut-off hemodialysis is highly effective in newly diagnosed multiple myeloma patients with severe renal impairment.

Multiple myeloma (MM) is often associated with renal insufficiency (RI) which adversely influences the prognosis. Several studies demonstrated that bortezomib can improve both renal function and outcome. We prospectively evaluated 21 newly diagnosed MM patients with severe renal impairment secondary to tubular-interstitial damage, most of them due to myeloma kidney, who were primarily treated with bortezomib-based therapy combined with high cut-off hemodialysis (HCOD). The median serum creatinine level at baseline was 6.44 mg dL(-1) and calculated median estimated glomerular filtration rate (eGFR), according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation, was 8 mL/min/1.73 m(2) . Serum free light chain (sFLC) median concentration was 6,040 mg L(-1) . Post induction and best stringent complete response rates were 19 and 38%, respectively. Responses were fast, occurring within a median of 1.4 months. The combination of bortezomib and HCOD led to a prompt and remarkable (>90%) decrease in sFLC levels. Sixteen patients (76%) became dialysis independent within a median of 32 days. With a median follow up of 17.2 months, the 3-year PFS and OS were 76 and 67%, respectively. No early deaths were observed. This study demonstrates that incorporation of bortezomib into induction therapy combined with HCOD is a highly effective strategy in rescuing renal function and improving outcomes in patients with MM and RI.

3D FIESTA pulse sequence for assessing renal artery stenosis: is it a reliable application in unenhanced magnetic resonance angiography?

OBJECTIVES: To assess the capability of the three-dimensional (3D) Fast Imaging Employing Steady-State Acquisition (FIESTA) sequence in evaluating renal artery stenosis (RAS). METHODS: We retrospectively analysed 79 patients referred for suspected RAS, examined by 3D FIESTA and contrast-enhanced magnetic resonance angiography (CE-MRA), using a 1.5T whole-body scanner. Image quality was assessed as well as the presence and grade of RAS. Patients with RAS ≥ 50% were evaluated for possible digital subtraction angiography (DSA). Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy of 3D FIESTA were calculated with ROC analysis using CE-MRA and DSA as the standard of reference. RESULTS: A total of 186 renal arteries were assessed; 36 had RAS ≥ 50 % demonstrated by CE-MRA. Ten patients underwent DSA, for a total evaluation of 22 arteries. Sensitivity, specificity, NPV, PPV, and accuracy of 3D FIESTA were 91.7%, 100%, 98%, 100%, and 98%, respectively, as compared to CE-MRA, and 88.2%, 100%, 71.4%, 100%, and 91%, respectively, as compared to DSA. The area under the ROC curve (AUC) of 3D FIESTA as compared to CE-MRA and DSA was 0.958 and 0.941, respectively. CONCLUSIONS: Our study demonstrated the capability of the 3D FIESTA sequence in evaluating RAS, with high-quality images and good diagnostic accuracy. KEY POINTS: The 3D FIESTA sequence provides a robust evaluation of RAS. The 3D FIESTA sequence allows non-invasive evaluation of the renal arteries. The 3D FIESTA sequence could be a useful tool in evaluating RAS.

[Renal involvement in monoclonal gammopathy and multiple myeloma]. / Il coinvolgimento renale nelle gammopatie monoclonali e nel mieloma.

Lymphoproliferative disorders often involve the kidney either by direct cell infiltration (lymphoma) or by deposition of paraproteins (monoclonal gammopathy, multiple myeloma, LCDD, amyloidosis). Nowadays the latter phenomenon seems to be the most common as a result of the growing number of elderly people affected by monoclonal gammopathies. The nephrotoxic potential of monoclonal immunoglobulins and amyloidogenic proteins make monoclonal gammopathies clinical entities of considerable interest in nephrology. Renal involvement presents different clinicomorphological patterns depending on the qualitative and quantitative characteristics of the paraproteins. Tubulointerstitial toxicity is frequent, while vascular and glomerular lesions resulting from non-inflammatory reactions due to immunoglobulin deposition are less common. Acute kidney failure may complicate the clinical course; this could be due to tubular obstruction by paraproteins or to hypovolemia induced by chemotherapy in association with diuretics. Early diagnosis of renal involvement will allow prophylactic interventions to prevent renal complications. At the same time, the increased number of therapeutic tools has enabled better management of kidney complications in lymphoproliferative disorders.

Acute renal failure in a young woman with Fisher-Evans' syndrome.

A young female with Fisher-Evans' syndrome and a previous melanoma developed acute renal failure with generalized lymphoadenopathy and fever. The appearance of renal lesions is common in the course of several hematological disorders, but is unusual in Fisher-Evans' syndrome. Fisher-Evans' syndrome, defined as Coombs' positive hemolytic anemia and immune thrombocytopenia, is more frequently associated with the other autoimmune diseases, but not with renal involvement. In our case report, having excluded amyloidosis, myeloma, interstitial nephritis and sepsis, the rapid involvement of renal function with enlarged renal size seemed to suggest renal lymphoma. However, the lack of a monoclonal T-lymphocyte population in the renal tissue and peripheral blood, along with a clinical course characterized by a rapid reversibility of acute renal failure made this diagnosis rather an unlikely one. Polyclonal lymphocyte infiltration in a patient with a persistent autoimmune disease made us suspect a hyperimmune reaction. This syndrome is a non-neoplastic proliferation of B-cells involving an exaggeration of lymphocyte transformation. However, the clinical course is progressive and fatal, and can trigger a lymphoproliferative systemic disease. In our patient, two elements led us to suspect it was not a typical hyperimmune syndrome: first, polyclonal lymphocytes had massively infiltrated the kidney and, secondly, the clinical outcome was extremely favorable. Therefore, we were faced with an "atypical" and "singular" hyperimmune reaction with renal involvement, polyclonal proliferation of T-lymphocytes that had exhausted itself over time. Infective or toxic agents or drugs such as cyprofloxacin could have triggered the phenomenon, in the presence of a favorable condition such as Fisher-Evans' syndrome.

An unusual cardiac manifestation in autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease is a common hereditary disorder characterized by renal and extrarenal, cystic and noncystic manifestations. Connective tissue defects, including cerebral aneurysm, meningeal diverticula, abdominal wall hernias, intestinal diverticula, and cardiac valvular abnormalities, are widely known manifestations. Instead intracardiac aneurysms have never been reported in adults with autosomal dominant polycystic kidney disease. We describe a 65-year-old patient with end-stage renal disease due to autosomal dominant polycystic kidney disease and an atrial septum aneurysm associated with platypnoea-orthodeoxia syndrome.