Lenvatinib-induced renal failure : two first-time case reports and review of literature

Introduction: Lenvatinib (LEN) is a multi-kinase anti-angiogenic drug recently approved in several cancers. LEN is not easily manageable due to its complex safety profile. Proteinuria and renal failure (RF) were reported among the most frequent LEN-induced adverse events (AEs), often leading to discontinuations or dose modifications. Understanding the pathogenesis of these AEs could ameliorate the management of LEN-induced renal toxicity. Areas covered: We present two cases of LEN-induced renal failure (LIRF) with different pathogenesis. 1) LIRF with severe proteinuria in a man treated for a metastatic papillary thyroid carcinoma. Kidney biopsy showed a glomerular damage secondary to LEN, having excluded other causes of RF. 2) LIRF without proteinuria in a woman with metastatic adenoid cystic carcinoma of minor salivary gland. A tubulointerstitial nephropathy was supposed by clinical evaluation and laboratory tests. Effective management was obtained by oral steroids without interrupting LEN. Expert opinion: The case 1 presented for the first time the histological picture of LIRF with a classical glomerular damage leading to secondary proteinuria and tubular failure. Case 2 showed an alternative LIRF pattern of likely tubulointerstitial injury without proteinuria. These reports reflect two sides of the same coin, both to be considered in case of LIRF

Uno sforzo isometrico per la diagnosi delle arteriopatie obliteranti croniche degli arti inferiori [An isometric exercise for the diagnosis of chronic obliterating arteriopathies of the lower extremities]

A non-invasive method for the diagnosis of occlusive diseases of the peripheral arteries and the followup of therapy is proposed. The method consists in the performance of an isometric effort of the inferior limbs and Doppler detection of the dorsalis pedis systolic pressure. 41 patients with different degrees of peripheral artery involvement were studied and the results compared with those obtained in a control group of 12 normal subjects, equally matched for age and sex. In the normal subjects, the maximal dorsiflection of the feet for 30 seconds caused a mean increase of the heart rate of 20% and no changes of the systolic blood pressure. In the patients with peripheral artery disease, the isometric effort caused, contemporary to the increase of the heart rate, a decrease of the dorsalis pedis systolic pressure, that varied from 15 to 100% according to the degree of the arterial involvement. A close correlation was found between the degree of the percent reduction of peripheral systolic pressure and the entity of the arterial involvement, as evidenced by other invasive and non-invasive methods. The method proposed appears useful for a proper diagnosis of peripheral vascular diseases in those patients who cannot undergo invasive investigations or the treadmill effort test

Glomerular lesions in HIV-positive patients : a 20-year biopsy experience from Northern Italy

Aim: Glomerular involvement in HIV-positive patients is quite heterogeneous. In the present paper we reviewed 73 renal biopsies performed during a period of more than 20 years in a single Nephrology Unit, Milan, Northern Italy, in order to evaluate the aspects of single types of glomerular lesions (including HIV associated nephropathy- HIVAN), grouped according to histological patterns and clinical presentation. Moreover, in the group of non-HIVAN patients, the possible differences in histological characteristics from non-HIV lesions were investigated. Materials and methods: Renal tissues were obtained by percutaneous biopsies and were studied by light microscopy, immunofluorescence and electron microscopy. For the histological description three histological groups were identified: HIVAN, immune complex glomerulonephritis (GN) and glomerulopathies not related to immune-mediated mechanisms (so-called "various" glomerulopathies). Results: HIVAN was observed in 9 cases, immune complex GNs in 40 cases (10 mesangial proliferative GN, 8 membranoproliferative GN, 5 lupus-like GN, 4 "acute" GN, 2 crescentic GN, 4 IgA nephropathy, 4 membranous GN and 3 immunotactoid GN) and "various" glomerulopathies in 24 cases (13 non-collapsing focal segmental glomerulosclerosis, 3 minimal changes, 3 end-stage renal disease, 4 diabetic nephropathy and one amyloidosis). Conclusions: Our 20-year biopsy series of HIV-related glomerular involvement confirmed the heterogeneity of lesions. In our series, the vast majority of HIV-related GN are the so-called immune complex GNs, with some peculiar aspects, as multiple site location of deposits and a frequent tendency towards sclerosis, in agreement with experimental data regarding HIV and fibrosis

Lung ultrasonography for the assessment of rapid extravascular water variation : evidence from hemodialysis patients

Chest ultrasonography is a useful tool to assess extravascular lung water at bedside. In presence of interstitial-alveolar imbibition, vertical artifacts arising from the pleura are detected; these are called B-lines. Although a positive linear correlation between B-lines and extravascular lung water has been shown in symptomatic heart failure patients, the subclinical phase of pulmonary imbibition and the clearance of B-lines after rapid body fluid removal have been less investigated. The aim of this study was to assess if chest ultrasound could detect lung water imbibition and its variations induced by dialysis, an experimental model of controlled rapid fluid loss. Forty-one patients undergoing hemodialysis were studied. Total number of B-lines from ultrasound chest scanning and vena cava diameters were measured before and after treatment. Before dialysis, most of the patients presented ultrasound signs of pulmonary imbibition despite the absence of dyspnea; the number of B-lines was associated with the accumulated weight before treatment (p < 0.05) as well as with the residual weight after dialysis (p < 0.01); B-lines and end-inspiratory and end-expiratory vena cava diameters were also significantly reduced after dialysis. Moreover, B-lines reduction was significantly related to weight loss. Ultrasound performed at the bedside can detect lung water and intravascular overload and their reduction after dialysis in yet asymptomatic patients. These observations add further evidence regarding the use of lung ultrasound and inferior vena cava measurement in estimating volume overload and monitoring the response to therapy both in hemodialysis and congestive heart failure patients