To analyze the clinical features and to identify factors associated with the development of Raynaud's phenomenon (RP) in patients receiving chemotherapy for human immunodeficiency virus (HIV) related ...Kaposi's sarcoma.
A retrospective cohort study of all patients with Kaposi's sarcoma treated with chemotherapy at Toronto-Sunnybrook Regional Cancer Centre from 1987 to 1995. Patients who developed RP were compared with those who did not with respect to age, CD4 cell count, Acquired Immune Deficiency Syndrome Clinical Trials Group (ACTG) stage, smoking history, type and dose of chemotherapy, and previous treatment with interferon and radiation therapy.
Eighty-seven patients with Kaposi's sarcoma were treated with chemotherapy between 1987 and 1995. Five developed RP, which progressed to digital gangrene. Median age, proportion of smokers, proportion defined as ACTG poor risk, median CD4 count, and history of opportunistic infections were equal in the 2 groups. All patients with RP received vinblastine followed by bleomycin. No cases of RP occurred in 27 patients treated with vinblastine alone or in 24 patients treated with bleomycin without previous vinblastine. Patients developing RP tended to have received higher cumulative doses of chemotherapy including bleomycin (p = 0.067) and previous treatment with either local radiation or interferon (p < 0.009, p < 0.001, respectively).
Sequential chemotherapy with vinblastine followed by bleomycin was associated with the development of RP in patients with HIV related Kaposi's sarcoma. Bleomycin alone was not associated with RP.
BACKGROUNDPregnancy in patients on chronic hemodialysis therapy, though unlikely, does happen rarely. Intensive hemodialysis is thought to offer a better survival advantage to the unborn child. ...Circulating angiogenic factors are helpful for prognostication of pregnant patients with chronic kidney disease who are not on dialysis. Data on their utilization in dialysis patients, however, are limited. CASE PRESENTATIONWe report the case of a patient with a history of interstitial nephritis who had a kidney transplant that failed after 8 years due to membranous nephropathy. She was initiated on hemodialysis three sessions per week and conceived after being on dialysis for 6 weeks. She was switched to intensive hemodialysis at 8 weeks of gestation and had a C-section because of hypertension at 35 weeks, with delivery of a healthy girl weighing 2012 g. Serum angiogenic factors (placental growth factor and soluble fms-like tyrosine kinase) were measured at 32, 33, and 34 weeks of gestation and at 1, 2, and 3 weeks postpartum. Serum angiogenic factors were similar to what has been reported for patients with chronic kidney disease and were not consistent with preeclampsia. CONCLUSIONSOur case report expands on the literature regarding intensive hemodialysis and angiogenic factor utilization in pregnant dialysis patients. Our case report suggests that starting intensive dialysis early in pregnancy is safe and concentration of angiogenic factors are similar to those reported for patients without kidney disease, except for PIGF levels, which are somewhat higher.
Acute renal failure remains a common, devastating complication of the postoperative period and in the critically ill patient. The most common cause is the progression of prerenal insufficiency to ...ATN. Despite improved understanding of the pathogenic mechanisms, including impaired hemodynamic autoregulation, medullary hypoxia, and proximal tubular obstruction and transtubular backleak, the treatment, to date, remains largely supportive. Avoidance by ensuring hemodynamic stability, with provision of adequate renal perfusion, provides the best means for minimizing the complications of this organ dysfunction.
risk variants are associated with increased risk of kidney disease in patients of African ancestry, but not all individuals with the
high-risk genotype develop kidney disease. As APOL1 gene ...expression correlates closely with the degree of kidney cell injury in both cell and animal models, the mechanisms regulating APOL1 expression may be critical determinants of risk allele penetrance. The APOL1 messenger RNA includes Alu elements at the 3' untranslated region that can form a double-stranded RNA structure (Alu-dsRNA) susceptible to posttranscriptional adenosine deaminase acting on RNA (ADAR)-mediated adenosine-to-inosine (A-to-I) editing, potentially impacting gene expression. We studied the effects of ADAR expression and A-to-I editing on APOL1 levels in podocytes, human kidney tissue, and a transgenic APOL1 mouse model. In interferon-γ (IFN-γ)-stimulated human podocytes, ADAR down-regulates APOL1 by preventing melanoma differentiation-associated protein 5 (MDA5) recognition of dsRNA and the subsequent type I interferon (IFN-I) response. Knockdown experiments showed that recognition of APOL1 messenger RNA itself is an important contributor to the MDA5-driven IFN-I response. Mathematical modeling suggests that the IFN-ADAR-APOL1 network functions as an incoherent feed-forward loop, a biological circuit capable of generating fast, transient responses to stimuli. Glomeruli from human kidney biopsies exhibited widespread editing of APOL1 Alu-dsRNA, while the transgenic mouse model closely replicated the edited sites in humans. APOL1 expression in mice was inversely correlated with Adar1 expression under IFN-γ stimuli, supporting the idea that ADAR regulates APOL1 levels in vivo. ADAR-mediated A-to-I editing is an important regulator of APOL1 expression that could impact both penetrance and severity of APOL1-associated kidney disease.
Apolipoprotein L1 (APOL1)-associated focal segmental glomerulosclerosis (FSGS) is the dominant form of FSGS in Black individuals. There are no targeted therapies for this condition, in part because ...the molecular mechanisms underlying APOL1’s pathogenic contribution to FSGS are incompletely understood. Studying the transcriptomic landscape of APOL1 FSGS in patient kidneys is an important way to discover genes and molecular behaviors that are unique or most relevant to the human disease. With the hypothesis that the pathology driven by the high-risk APOL1 genotype is reflected in alteration of gene expression across the glomerular transcriptome, we compared expression and co-expression profiles of 15,703 genes in 16 Black patients with FSGS at high-risk vs 14 Black patients with a low-risk APOL1 genotype. Expression data from APOL1-inducible HEK293 cells and normal human glomeruli were used to pursue genes and molecular pathways uncovered in these studies. We discovered increased expression of APOL1 and nine other significant differentially expressed genes in high-risk patients. This included stanniocalcin, which has a role in mitochondrial and calcium-related processes along with differential correlations between high- and low-risk APOL1 and metabolism pathway genes. There were similar correlations with extracellular matrix- and immune-related genes, but significant loss of co-expression of mitochondrial genes in high-risk FSGS, and an NF-κB-down regulating gene, NKIRAS1, as the most significant hub gene with strong differential correlations with NDUF family (mitochondrial respiratory genes) and immune-related (JAK-STAT) genes. Thus, differences in mitochondrial gene regulation appear to underlie many differences observed between high- and low-risk Black patients with FSGS.
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