Of the 92 patients with the acquired immunodeficiency syndrome (AIDS) who were seen at our institution over a two-year period, 9 acquired the nephrotic syndrome (urinary protein greater than 3.5 g per 24 hours) and 2 had azotemia with lesser amounts of urinary protein. Five of these 11 patients had a history of intravenous-heroin addiction, but in the remaining six, there were no known predisposing factors for nephropathy. In nine patients (including the six non-addicts) the course of renal disease was marked by rapid progression to severe uremia. Renal tissue examined by biopsy in seven patients and at autopsy in three revealed focal and segmental glomerulosclerosis with intraglomerular deposition of IgM and C3. In the 11th patient, renal biopsy revealed an increase in mesangial matrix and cells, with deposition of IgG and C3 consistent with a mild immune-complex glomerulonephritis, and severe interstitial nephritis. We conclude that focal and segmental glomerulosclerosis may be associated with AIDS and suggest that rapid deterioration to uremia may characterize this renal disease.
Structured Abstract Introduction The detection of mutations in the epidermal growth factor receptor (EGFR) gene, which predict sensitivity to treatment with EGFR tyrosine kinase inhibitors (TKIs), represents a major advance in the treatment of lung adenocarcinoma. KRAS mutations confer resistance to EGFR -TKIs. The prevalence of these mutations in African-American patients has not been thoroughly investigated. Methods We collected formalin-fixed, paraffin-embedded material from resected lung adenocarcinomas from African-American patients at three institutions for DNA extraction. The frequencies of EGFR exon 19 deletions, exon 21 L858R substitutions and KRAS mutations in tumor specimens from African-American patients were compared to data in Caucasian patients (n=476). Results EGFR mutations were detected in 23 of the 121 specimens from African-American patients (19%, 95% CI 13–27%), while KRAS mutations were found in 21 (17%, 95% CI 12−25%). There was no significant difference between frequencies of EGFR mutations comparing African-American and Caucasian patients, 19% vs. 13% (61/476, 95% CI 10–16%) (p=0.11). KRAS mutations were more likely among Caucasians, 26% (125/476, 95% CI 23−30%) (p=0.04). Conclusions This is the largest study to date examining the frequency of mutations in lung adenocarcinomas in African-Americans. Although KRAS mutations were somewhat less likely, there was no difference between the frequencies of EGFR mutations in African-American patients as compared to Caucasians. These results suggest that all patients with advanced lung adenocarcinomas should undergo mutational analysis prior to initiation of therapy.
Between January 1982 and December 1986, among the 750 patients with the acquired immunodeficiency syndrome (AIDS) who were treated at two adjacent hospitals in New York City, 78 (10.4 percent) needed evaluation for renal disorders. Reversible acute renal failure due to nephrotoxic injury, ischemic injury, or both was present in 23 patients (30 percent) (Group I). The remaining 55 (70 percent) had massive proteinuria, azotemia, or both (AIDS-associated nephropathy; Group II), and irreversible uremia developed in 43. In an additional 18 patients, all of whom had a history of intravenous narcotic drug use, AIDS was diagnosed after the initiation of maintenance hemodialysis for chronic renal failure (Group III). Survival for more than six months after the onset of chronic uremia occurred in only two subjects in Group II; all patients in Group III died within three months of the diagnosis of AIDS. Death in the patients in Groups II and III followed a syndrome of "failure to thrive" characterized by inanition unresponsive to intensive nutritional support and hemodialysis. In contrast, 8 of 17 patients with acute renal failure (Group I) and a serum creatinine concentration above 6 mg per deciliter regained renal function (serum creatinine level, less than 2.0 mg per deciliter). Four of the seven lived for 10 to 24 months, whereas the other four died of sepsis within a month. Our observations suggest that maintenance hemodialysis is not effective in prolonging life either in patients with AIDS-associated nephropathy and uremia or in patients with end-stage renal failure in whom AIDS develops during the course of maintenance dialysis. Hemodialysis may be useful in the management of potentially reversible acute renal failure in patients with AIDS.
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