Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pembrolizumab is an immune checkpoint inhibitor that targets the programmed cell death protein 1 (PD-1) antigen and induces an immune response against tumor tissues. It has been successful in inducing remission in patients with severe metastatic disease, often refractory to other chemotherapeutic agents. The risk of injury of other organ systems has been noted with reported cases of glomerular disease and endocrine disease. In addition, hypophysitis as well as dermatological and gastroenterological side effects have been reported. Renal injury with immune checkpoint inhibitors like nivolumab and pembrolizumab is usually mediated via interstitial nephritis, though glomerular disease presentations like anti-neutrophil cytoplasmic antibody-associated vasculitis, immune complex disease, and thrombotic microangiopathy have also been reported. We report a 70-year-old Caucasian male who underwent treatment with pembrolizumab for adenocarcinoma of the lung. He developed acute adrenal insufficiency and concomitant severe hypotension upon presentation. He did not require renal replacement therapy, rather his severe acute kidney injury resolved with hydration, normalization of blood pressures with vasopressors, and treatment with high-dose corticosteroids. His urinary indices (fractional excretion of urea, FEUrea) and clinical course were highly suspicious for acute tubular necrosis that resolved quickly after treating his underlying adrenalitis. The urinary sediment, proteinuria, and clinical course were not typical for the usually expected renal lesion of interstitial nephritis in patients treated with immune checkpoint inhibitors.
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PMID:Acute Kidney Injury after Pembrolizumab-Induced Adrenalitis and Adrenal Insufficiency. 3019 6

While systemic lupus erythematosus (SLE) is an autoantibody and immune complex disease by nature, most of its organ manifestations are in fact inflammatory. SLE activity scores thus heavily rely on assessing inflammation in the various organs. This focus on clinical items demonstrates that routine laboratory markers of inflammation are still limited in their impact. The erythrocyte sedimentation rate (ESR) is used, but represents a rather crude overall measure. Anemia and diminished serum albumin play a role in estimating inflammatory activity, but both are reflecting more than one mechanism, and the association with inflammation is complex. C-reactive protein (CRP) is a better marker for infections than for SLE activity, where there is only a limited association, and procalcitonin (PCT) is also mainly used for detecting severe bacterial infection. Of the cytokines directly induced by immune complexes, type I interferons, interleukin-18 (IL-18) and tumor necrosis factor (TNF) are correlated with inflammatory disease activity. Still, precise and timely measurement is an issue, which is why they are not currently used for routine purposes. While somewhat more robust in the assays, IL-18 binding protein (IL-18BP) and soluble TNF-receptor 2 (TNF-R2), which are related to the respective cytokines, have not yet made it into clinical routine. The same is true for several chemokines that are increased with activity and relatively easy to measure, but still experimental parameters. In the urine, proteinuria leads and is essential for assessing kidney involvement, but may also result from damage. Similar to the situation in serum and plasma, several cytokines and chemokines perform reasonably well in scientific studies, but are not routine parameters. Cellular elements in the urine are more difficult to assess in the routine laboratory, where sufficient routine is not always available. Therefore, the analysis of urinary T cells may have potential for better monitoring renal inflammation.
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PMID:Inflammatory markers in systemic lupus erythematosus. 3181 31

Chronic kidney disease (CKD) is a comorbidity of major clinical significance amongst people living with HIV (PLWHIV) and is associated with significant morbidity and mortality. The prevalence of CKD is rising, despite the widespread use of antiretroviral therapy (ART) and is increasingly related to prevalent non-infectious comorbidities (NICMs) and antiretroviral toxicity. There are great disparities evident, with the highest prevalence of CKD among PLWHIV seen in the African continent. The aetiology of kidney disease amongst PLWHIV includes HIV-related diseases, such as classic HIV-associated nephropathy or immune complex disease, CKD related to NICMs and CKD from antiretroviral toxicity. CKD, once established, is often relentlessly progressive and can lead to end-stage renal disease (ESRD). Identifying patients with risk factors for CKD, and appropriate screening for the early detection of CKD are vital to improve patient outcomes. Adherence to screening guidelines is variable, and often poor. The progression of CKD may be slowed with certain clinical interventions; however, data derived from studies involving PLWHIV with CKD are sparse and this represent an important area for future research. The control of blood pressure using angiotensin converting enzyme inhibitors and angiotensin receptor blockers, in particular, in the setting of proteinuria, likely slows the progression of CKD among PLWHIV. The cohort of PLWHIV is facing new challenges in regards to polypharmacy, drug-drug interactions and adverse drug reactions. The potential nephrotoxicity of ART is important, particularly as cumulative ART exposure increases as the cohort of PLWHIV ages. The number of PLWHIV with ESRD is increasing. PLWHIV should not be denied access to renal replacement therapy, either dialysis or kidney transplantation, based on their HIV status. Kidney transplantation amongst PLWHIV is successful and associated with an improved prognosis compared to remaining on dialysis. As the cohort of PLWHIV ages, comorbidity increases and CKD becomes more prevalent; models of care need to evolve to meet the new and changing chronic healthcare needs of these patients.
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PMID:Contemporary issues and new challenges in chronic kidney disease amongst people living with HIV. 3217 87


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