Review of VA Clinical Guidance for the Health Conditions Identified by the Camp Lejeune Legislation (2015) / Chapter Skim
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2 Characterization of Renal Toxicity
2 Characterization of Renal Toxicity
Pages 21-34
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From page 21... ...
In general, these studies found that high-dose solvent exposures were necessary to produce acute renal effects and that the effects of such exposures were variable among species. The 2009 NRC report concluded that there was limited/suggestive evidence of an association between exposure to mixed solvents and renal toxicity.
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From page 22... ...
Studies of the effects of short-term and long-term solvent exposure on renal function below the threshold of clinical disease provided some support for an association between exposure to high concentrations of solvents and acute tubular necrosis. A series of case-control studies that evaluated chronic glomerulonephritis, an immune-mediated disease, in relation to nonspecific solvent exposure provided inconsistent evidence of an association; however, several reasonably strong studies showed dose–response gradients.
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From page 23... ...
Studies using experimental animals and cultured cells (including human) have shown that, as with other solvents, neither TCE nor PCE itself is toxic, but rather each is metabolized to chemically reactive intermediates.
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From page 24... ...
Thus, the signs and symptoms of renal toxicity will vary depending on an individual's metabolic pattern, which implies that a finding in rats may or may not reliably predict acetylation in humans. Excretion Using an in vitro model of renal tubular epithelium (cell culture)
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From page 25... ...
Finally, in spite of the number of animal studies on the renal toxicity of TCE and PCE, neither the 2009 NRC committee nor this committee identified any animal studies with exposures similar to those that occurred at Camp Lejeune, that is, that assessed long-term renal effects following short-term exposure to the solvents as either immature or adult animals. REVIEW OF RECENT EPIDEMIOLOGICAL STUDIES In reviewing the recent literature related to the renal effects of the drinking water contaminants at Camp Lejeune, the committee identified three new epidemiological studies on TCE and one on PCE.
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From page 26... ...
. The results suggest that the Camp Lejeune cohort did not have an increased risk of chronic renal toxicity leading to death or an increased risk of kidney cancer.
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From page 27... ...
The VA's clinical guidance specifies that CKD, defined as a chronic decrease in kidney function, or proteinuria should be the clinical endpoints of concern for renal toxicity resulting from solvent exposure at Camp Lejeune. The committee finds CKD to be an appropriate endpoint to represent possible kidney damage potentially caused by exposure to contaminated water at Camp Lejeune.
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From page 28... ...
(See Box K.) • HIV-associated nephropathy No • Immune-mediated renal K6 disease • Interstitial renal disease caused by an allergic reaction or Return to Patient accepted into the analgesic agents CORE program • Light-chain disease • Polycystic kidney disease • Prerenal disease, volume depletion, congestive heart failure, liver failure • Renovascular disease FIGURE 2-2 Revised algorithm K
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From page 29... ...
K2 -- Applicant is still administratively eligible for the Camp Lejeune program but does not have evidence of renal toxicity as a covered condition. K3 -- Applicant has a history of renal toxicity or kidney disease concurrent with Camp Lejeune residence or shortly after the time of possible exposure to contaminated water at Camp Lejeune.
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From page 30... ...
Diabetes Diabetes Diabetic kidney disease Hypertension/hypertensive Hypertension Hypertensive kidney disease nephrosclerosis Obstructive uropathy Urinary tract obstruction Urinary tract obstruction Sickle cell kidney disease Sickle cell kidney disease HIV-associated nephropathy HIV-associated nephropathy Drug-induced kidney disease Acute tubular necrosis occurring in the Acute tubular necrosis occurring in the setting of setting of hypotension or nephrotoxic hypotension, rhabdomyolysis, or nephrotoxic agents, such as radiocontrast, agents (e.g., chemotherapeutics, IV radiocontrast antibiotics, or chemotherapy drugs media, immunosuppressives) Acute interstitial nephritis, often due to Interstitial renal disease drugs such as NSAIDs or antibiotics Allergic, analgesic agents Volume depletion, severe heart failure Prerenal disease: volume depletion, congestive heart failure, liver failure Atheroembolic disease Glomerulonephritis IgA nephropathy, post-infection, membranous, membranoproliferative, associated with systemic diseases Immune-mediated renal disease Polycystic kidney disease Vasculitis Light chain disease NOTE: HIV = human immunodeficiency virus; IgA = immunoglobulin A; IV = intravenous; NSAIDs = nonsteroidal anti-inflammatory drugs.
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From page 31... ...
Therefore, the committee finds that the VA's general approach to the guidance and algorithm regarding renal toxicity is appropriate. Neither the guidance nor the original algorithm K includes other indicators of acute renal injury.
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From page 32... ...
2010. Multiple new loci associated with kidney function and chronic kidney disease: The CKDGen consortium.
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From page 33... ...
2012. Elevated urinary levels of kidney injury molecule-1 among Chinese factory workers exposed to trichloroethylene.
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