Hassan Izzedine

Acute Renal Infarction: A Case Series

BACKGROUND AND OBJECTIVESnRenal infarction is an arterial vascular event that may cause irreversible damage to kidney tissues. This study describes the clinical characteristics of patients with renal infarction according to underlying mechanism of vascular injury.nnnDESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSnThis study retrospectively identified 94 patients with renal infarction diagnosed between 1989 and 2011 with the aim of highlighting potential correlations between demographic, clinical, and biologic characteristics and the etiology of renal infarction. Four groups were identified: renal infarction of cardiac origin (cardiac group, n=23), renal infarction associated with renal artery injury (renal injury group, n=29), renal infarction associated with hypercoagulability disorders (hypercoagulable group, n=15), and apparently idiopathic renal infarction (idiopathic group, n=27).nnnRESULTSnClinical symptoms included abdominal and/or flank pain in 96.8% of cases; 46 patients had uncontrolled hypertension at diagnosis. Laboratory findings included increase of lactate dehydrogenase level (90.5%), increase in C-reactive protein level (77.6%), and renal impairment (40.4%). Compared with renal injury group patients, this study found that cardiac group patients were older (relative risk for 1 year increase=1.21, P=0.001) and displayed a lower diastolic BP (relative risk per 1 mmHg=0.94, P=0.05). Patients in the hypercoagulable group had a significantly lower diastolic BP (relative risk=0.86, P=0.005). Patients in the idiopathic group were older (relative risk=1.13, P=0.01) and less frequently men (relative risk=0.11, P=0.02). Seven patients required hemodialysis at the first evaluation, and zero patients died during the first 30 days.nnnCONCLUSIONSnThis study suggests that the clinical and biologic characteristics of patients can provide valuable information about the causal mechanism involved in renal infarction occurrence.

Cardiac side effects of molecular targeted therapies: Towards a better dialogue between oncologists and cardiologists

Molecular targeted therapies (MTTs) have become a major component of modern management of various hematological and solid malignancies. However, some MTTs have been associated with cardiotoxicity. MTT-induced cardiovascular side effects include left ventricular systolic dysfunction, heart failure, conduction abnormalities, acute coronary syndrome, and hypertension. One of the most threatening complications of MTT, and notably of angiogenic inhibitors, is QT prolongation with the risk of torsades de pointe and sudden death. The precise incidence of cardiovascular events associated with MTT as well as their reversibility are unknown. Here, we summarize what is known about the cardiotoxicity of MTT, emphasizing MTTs that target tyrosine kinases. We have tried to provide both the basic mechanisms underlying specific cardiotoxicities (such as the interruption of specific signaling pathways leading to cardiomyocyte dysfunction and/or death), and offer guidance regarding the optimal way to detect and treat these cardiotoxicities.

Thrombotic Microangiopathy, Cancer, and Cancer Drugs

Thrombotic microangiopathy (TMA) is a complication that can develop directly from certain malignancies, but more often results from anticancer therapy. Currently, the incidence of cancer drug-induced TMA during the last few decades is >15%, primarily due to the introduction of anti-vascular endothelial growth factor (VEGF) agents. It is important for clinicians to understand the potential causes of cancer drug-induced TMA to facilitate successful diagnosis and treatment. In general, cancer drug-induced TMA can be classified into 2 types. Type I cancer drug-induced TMA includes chemotherapy regimens (ie, mitomycin C) that can potentially promote long-term kidney injury, as well as increased morbidity and mortality. Type II cancer drug-induced TMA includes anti-VEGF agents that are not typically associated with cumulative dose-dependent cell damage. In addition, functional recovery of kidney function often occurs after drug interruption, assuming a type I agent was not given prior to or during therapy. There are no randomized controlled trials to provide physician guidance in the management of TMA. However, previously accumulated information and research suggest that endothelial cell damage has an underlying immunologic basis. Based on this, the emerging trend includes the use of immunosuppressive agents if a refractory or relapsing clinical course that does not respond to plasmapheresis and steroids is observed.

Renal involvement in Castleman disease

BACKGROUNDnCastleman disease (CD), or angiofollicular lymph-node hyperplasia, is an atypical lymphoproliferative disorder with heterogeneous clinical manifestations. Renal involvement in CD has been described in only single-case reports, which have included various types of renal diseases.nnnMETHODSnNineteen patients with histologically documented CD and renal biopsies available were included. Clinical features and renal histological findings were reviewed, and the available samples were immunolabelled with anti-vascular endothelial growth factor (VEGF) antibody.nnnRESULTSnNineteen CD cases were identified: 89% were multicentric, and 84% were of the plasma-cell or mixed type. Four cases (21%) were associated with human immunodeficiency virus (HIV) infection. Among HIV-negative patients, two main patterns of renal involvement were found: (i) a small-vessel lesions group (SVL) (60%) with endotheliosis and glomerular double contours in all patients and with superimposed glomerular/arteriolar thrombi or mesangiolysis in most; and (ii) AA amyloidosis (20%). Renal histology was more heterogeneous among HIV-positive patients. Decreases in glomerular VEGF were observed only in some patients with SVL, whereas VEGF staining was normal in all other histological groups. Interestingly, glomerular VEGF loss associated with SVL was correlated with plasma C-reactive protein levels, a marker of CD activity.nnnCONCLUSIONSnSmall-vessel lesions are the most frequent renal involvement in CD, whereas loss of glomerular VEGF is correlated with CD activity and could have a role in SVL pathophysiology.

MR imaging features of acute bilateral renal cortical necrosis

Bilateral renal cortical necrosis (BRCN) is an uncommon cause of acute renal failure. Kidney biopsy, arteriography, and contrast-enhanced computed tomography (CT) are usually used to diagnose BRCN. However, these methods can have potentially serious side effects. We report two cases in which magnetic resonance imaging (MRI) evidenced characteristic features of BRCN, which were confirmed by histological findings and arteriography and correlated with clinical evolution. In the first case report, the diagnosis of a massive and complete cortical necrosis variety was suggested on MRI that showed a thin rim of low signal intensity along border of kidneys. It was confirmed on kidney biopsy, and the renal function did not recover. The second case is an incomplete form with cortical patchy areas of low signal intensity. In these two patients, MRI helped to establish an early diagnosis of BRCN with characteristic representative findings, without the potential nephrotoxic effects of iodinated contrast that has to be used in CT and arteriography. Kidney biopsy, besides the risks of complications, provides only a parceled analysis of the renal tissue and therefore does not allow any conclusion as to the extension of cortical necrosis. MRI may be of great help for the diagnosis and follow-up of acute renal cortical necrosis.

QT interval prolongation among patients treated with angiogenesis inhibitors.

Among toxicities associated with molecular targeted agents (MTA), cardiovascular toxicities remain largely unknown or underestimated. Their frequency is variable and dependent on the compound. A high incidence of hypertension, symptomatic or asymptomatic left ventricular systolic dysfunction, acute coronary syndrome, arterial and venous thrombosis has been observed in patients receiving MTA. One of the most threatening complications of angiogenic inhibitors (AI) could be QT prolongation with the risk of torsade de pointes (TdP) and sudden death. QT prolongation and torsade de pointes accounted for 29% of cardiac and non-cardiac post-marketing withdrawals. The assessment of the effects of drugs on cardiac repolarization is the subject of recent guidelines and recommendations. Regulatory agencies now require practically every new pharmaceutical compound to undergo a thorough investigation of its propensity to modify cardiac repolarization. To reduce the incidence of QT prolongation and torsade de pointes in patients receiving AI, cancer patients should be closely monitored while receiving AI.

New drug toxicities in the onco-nephrology world

New anticancer medications are rapidly entering the clinical arena offering patients with previously resistant cancers the promise of more effective therapies capable of extending their lives. However, adverse renal consequences develop in treated patients with underlying risk factors, requiring the nephrology community to be familiar with the nephrotoxic effects. The most common clinical nephrotoxic manifestations of these drugs include acute kidney injury, varying levels of proteinuria, hypertension, electrolyte disturbances, and at times chronic kidney disease. Thus, to practice competently in the onco-nephrology arena, nephrologists will garner benefit from an update on older drugs with newly recognized nephrotoxic potential as well as newer agents, which may be associated with kidney injury. With that in mind, this brief update is meant to provide clinicians with the currently available evidence on the nephrotoxicity of a group of anticancer medications.

Changing Electrolyte and Acido-Basic Profile in HIV-Infected Patients in the HAART Era

Background: HIV-infected patients may develop a variety of underreported metabolic abnormalities that may be classified into HIVAN, specific HIV abnormalities, coincidental renal disorders and anti-retroviral-treatment-induced side effects. Methods: Our descriptive cross-sectional study evaluates the prevalence of electrolyte and acid base disorders in HIV patients in the HAART era in a tertiary care teaching hospital. All consecutive HIV-infected patients (n = 1,232) presenting at our Department of Infectious Disease over 3 months were included. Measurements: All available biochemical data obtained at admission or on the day of the visit were analyzed. We identified risk factors for electrolyte and acid base disorders with univariate regression analysis and multivariate stepwise regression analysis. Variables tested for significance included age, sex, absolute CD4 and CD8 counts, hepatitis B and C antibodies, and use and type of anti-retroviral medication. Results: Most frequent and clinically relevant abnormalities were hyperuricemia in 41.3%, hypophosphatemia in 17.2% and low bicarbonate level in 13.6% of HIV-tested patients. Plasma magnesium was out of the normal range in 38.9% and blood glucose in 25.3% of the tested patients. When CD4 count was below 200/mm3, 9.2% of tested patients experienced low serum calcium (vs. 0.5% if CD4 count >200/mm3, p < 0.002), 11.4% increased creatinine plasma level (vs. 2.3% if CD4 count >200/mm3, p < 0.0001) and 24.5% low serum bicarbonate (vs. 13.7% if CD4 count >200/mm3, p < 0.0001). Protease inhibitor treatment was a significant risk factor of hyperuricemia (p < 0.003). Non-nucleoside reverse transcriptase inhibitor therapy was significantly associated with less hyperuricemia (OR = 0.6, 95% CI 0.38–0.96) and with hypophosphatemia (OR = 2.0, 95% CI 1.1–3.4). Conclusions: The profile of biochemical abnormalities in HIV-infected patients has changed, hyperuricemia and hypophosphatemia being the most prevalent. Causes are poorly understood. Interpretation of drug-induced side effects in the HIV patient is only meaningful if performed versus a control group of patients.

Drug-induced glomerulopathies

Normal renal function depends upon an intact glomerular apparatus. Many drugs and chemicals are capable of damaging the glomerulus, causing its increased permeability to large molecules. Glomerular lesions are usually responsible for proteinuria and the nephrotic syndrome. This also holds true for the drug-induced glomerulopathies, of which membranous glomerulo-nephritis is the most frequent type of lesion encountered. Apart from this, several cases of different glomerular changes such as focal segmental glomerulosclerosis and crescentic glomerulonephritis have also been reported. The drug-induced glomerulopathies are probably immune mediated. This is, for instance, reflected in the fact that patients with drug-induced nephritic syndrome frequently have the HLA-B8 and DR3 antigens. In depth information is provided for the previously mentioned disorders.

The renal effects of ALK inhibitors

SummaryAnaplastic lymphoma kinase 1 (ALK-1) is a member of the insulin receptor tyrosine kinase family. In clinical practice, three small molecule inhibitors of ALK-1 are used, namely crizotinib, ceritinib and alectinib. Several more agents are in active pre-clinical and clinical studies. Crizotinib is approved for the treatment of advanced ALK-positive non-small cell lung cancer (NSCLC). According to the package insert and published literature, treatment with crizotinib appears to be associated with kidney failure as well as an increased risk for the development and progression of renal cysts. In addition, this agent is associated with development of peripheral edema and rare electrolyte disorders. This review focuses on the adverse renal effects of Crizotinib in clinical practice.