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.
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.
Expanded clinical experience with the antivascular endothelial growth factor (VEGF) agents has come with increasing recognition of their renal adverse effects. Although renal histology is rarely ...sought in antiangiogenic-treated cancer patients, kidney damage related to anti-VEGF is now established. Its manifestations include hypertension, proteinuria, and mainly glomerular thrombotic microangiopathy. Then, in nephrology practice, should we continue to perform kidney biopsy, and what should be done with the anti-VEGF agents in case of renal toxicity?
Acute kidney injury (AKI) is a growing problem with untoward economic and medical consequences. Anticancer drug toxicity remains an important and increasing cause of AKI. Importantly, drug-induced ...AKI affects all nephron segments-vasculature, glomerulus, tubules, and interstitium. Recent studies have increased insight into the subcellular mechanisms of drug-induced AKI that include direct cellular toxicity and immune-mediated effects. Identification of patients with high-risk cancer before drug exposure may allow prevention or at least a reduction in the development and severity of nephrotoxicity. Recognition of drug-induced AKI and rapid discontinuation (or dose reduction) of the offending agents, when appropriate, are critical to maximizing kidney function recovery. Preventive measures require understanding patient and drug-related risk factors coupled with correcting risk factors, assessing baseline kidney function before initiation of therapy, adjusting the drug dosage and avoiding use of nephrotoxic drug combinations.
Acute Renal Infarction: A Case Series Bourgault, Marie; Grimbert, Philippe; Verret, Catherine ...
Clinical journal of the American Society of Nephrology,
03/2013, Letnik:
8, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Renal 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.
This 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).
Clinical 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.
This study suggests that the clinical and biologic characteristics of patients can provide valuable information about the causal mechanism involved in renal infarction occurrence.
Chronic myelomonocytic leukemia (CMML) is a hematologic malignancy affecting the bone marrow and resulting in peripheral blood monocytosis. Kidney and urinary tract involvement is common and can ...present dramatically with life-threatening consequences. Kidney involvement can be the result of direct or indirect mechanisms, including prerenal azotemia, glomerular disease, tubulointerstitial involvement, and renovascular disorders. Urinary tract involvement, electrolyte and acid-base disorders, as well as nephrotoxicity from treatment of the disorder can also occur. Given this multifactorial pathogenesis involving several mechanisms concomitantly, nephrologists must exercise heightened awareness and maintain a low threshold for kidney biopsy. There is a pressing need for future research endeavors to elucidate and target the manifestations of CMML that involve the kidneys with the ultimate goal of augmenting overall prognosis and therapeutic outcomes.
Objectives To review the current evidence regarding the value of measuring procalcitonin (PCT) levels in patients with systemic autoimmune diseases, with a focus on the evidence for diagnostic and ...analytical performance of this biomarker. A brief description of the pathophysiological basis of this biomarker is also included. Methods Using PubMed from the National Library of Medicine, relevant English literature on PCT in patients with different systemic autoimmune diseases, from 1990 to 2009, was reviewed. The search used keywords referring to procalcitonin and systemic lupus erythematosus, antineutrophil cytoplasmic antibody-associated systemic vasculitis, Goodpasture syndrome, rheumatoid arthritis, and giant cell arteritis. Results When used in the appropriate clinical setting, the measurement of serum PCT levels is valuable as a marker of severe systemic bacterial and fungal infections and sepsis. Information regarding plasma PCT levels in patients with active underlying systemic autoimmune diseases is limited, primarily from observational studies and case series, with considerable variability of patient characteristics and clinical settings. In the detection of systemic infection concomitant with autoimmune diseases, PCT had a diagnostic sensitivity of 53 to 100% and a specificity of 84 to 97% (depending on the selection criteria) and was superior to other inflammatory markers tested. Most of the studies used a semiquantitative test for PCT measurement (functional assay sensitivity <0.5 ng/mL), which can explain the low sensitivity of the test. PCT levels were not significantly affected by renal function abnormalities or immunosuppressive agents. Although high PCT levels commonly occurred with infection, elevated levels of PCT could be found in patients with vasculitis without evidence of infection, often correlated with high disease activity scores. Conclusions Significantly elevated PCT levels offer good specificity and sensitivity for systemic infection in patients with systemic autoimmune diseases, regardless of the use of corticosteroids or immunosuppressive agents. PCT measurement may add to diagnostic accuracy in patients with systemic autoimmune diseases who present with a febrile illness, especially when highly sensitive PCT assays and specific PCT cutoff ranges are used in a predefined clinical setting (reflecting the likelihood of infection versus an autoimmune disease flare). However, there are limitations when using this biomarker in patients with systemic autoimmune diseases. PCT levels should not replace the necessary extensive diagnostic workup, which should include a thorough history and physical examination, combined with appropriate immunological, microbiological, radiological, and histological data.
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