Renal ischemia-reperfusion injury (IRI) is a major cause of acute renal failure. Doxycycline (Dc) belongs to the tetracycline-class of antibiotics with demonstrated beneficial molecular effects in the brain and heart, mainly through matrix metalloproteinases inhibition (MMP). However, Dc protection of renal function has not been demonstrated. We determined whether low doses of Dc would prevent decreases in glomerular filtration rate (GFR) and maintain tubular Na handling in Wistar rats subjected to kidney I/R. Male Wistar rats underwent bilateral kidney ischemia for 30min followed by 24h reperfusion (I/R). Doxycycline (1, 3, and 10mg/kg, i.p.) was administered 2h before surgery. Untreated I/R rats showed a 250% increase in urine volume and proteinuria, a 60% reduction in GFR, accumulation of urea-nitrogen in the blood, and a 60% decrease in the fractional Na excretion due to unbalanced Na transporter activity. Treatment with Dc 3mg/kg maintained control levels of urine volume, proteinuria, GFR, blood urea-nitrogen, fractional Na excretion, and equilibrated Na transporter activities. The Dc protection effects on renal function were associated with kidney structure preservation and prevention of TGFβ and fibronectin deposition. In vitro, total MMP activity was augmented in I/R and inhibited by 25 and 50μM Dc. In vivo, I/R augmented MMP-2 and -9 protein content without changing their activities. Doxycycline treatment downregulated total MMP activity and MMP-2 and -9 protein content. Our results suggest that treatment with low dose Dc protects from IRI, thereby preserving kidney function.
Clinically overt glomerular disease was detected in 6 (1.1%) of 543 patients with HIV infection followed at a Brazilian National Referral Center for AIDS. In 4 cases, glomerulosclerosis was present (focal and segmental in 3, diffuse and global in 1) and rapid progression to terminal renal failure was observed 1-10 months after clinical presentation. The other 2 patients died with normal renal function, and autopsy studies suggested the diagnosis of minimal change disease. Clinically overt glomerular disease was significantly more common among Black patients, whether all the cases with glomerulopathy (p < 0.001) or just the cases with glomerular sclerosis were considered (p = 0.011). Autopsy study of renal fragments from patients without clinical evidence of glomerular disease was additionally performed and revealed the presence of focal and segmental glomerulosclerosis in 3 cases (7.5 %). We concluded that a glomerulopathy with clinicopathological features which match the definition of HIV nephropathy can be found among Brazilian patients with HIV infection. Accordingly to what has been described in American series, Brazilian Black patients seem to be at increased risk of the development of that nephropathy.
Collapsing glomerulopathy is a severe form of glomerular injury, closely associated with HIV infection, characterized by the collapsing feature of glomerular damage with frequent tubulointerstitial involvement and rapid progression to terminal renal failure. The etiopathogenesis in non-HIV infected patients remains obscure. We reported a patient whose diagnosis of collapsing glomerulopathy (CG) and systemic lupus erythematosus (SLE) was done simultaneously and described the diseases characteristics suggesting that SLE could be an etiologic factor for the induction of this glomerulopathy, clinical evolution and treatment.
In order to study the prevalence and the clinical features of renal tuberculosis associated with AIDS, we studied the renal tissue of the necropsies made in 46 AIDS patients under light microscopy. We found renal tuberculous granuloma in 11 (23%) patients (in 3 without previous diagnosis of renal or extrarenal tuberculosis) and only 4 of them presented moderate hematuria or pyuria sterile. As subclinical renal tuberculosis was frequent in this group of AIDS patients, the urine culture for Mycobacterium tuberculosis may be useful for diagnosing tuberculosis in AIDS patients.
BACKGROUND Hemodialysis (HD) patients have an increased incidence of tuberculosis (TB), which may be due to decreased cellular immunity, the presence of malnutrition, and the use of immunosuppressive drugs. Poor living conditions, overcrowding, and human immunodeficiency virus (HIV) infection could be considered added risk factors. This study analyzed the incidence and clinical characteristics of TB among HD patients in an area where TB and HIV infection have a high prevalence. METHODS In this multicenter study, 1266 patients (663 men and 603 women) ages 20–91 years (46.1 ± 16.8 years) from 8 HD centers in different cities of Rio de Janeiro State, Brazil, were studied. HIV‐infected patients were excluded from the study. RESULTS TB was observed in 30 patients (2.3%), the pulmonary type in 11 (36.6%) and the extrapulmonary type in 19 (63.4%). The time of emergence during the HD period was very wide (2–117 months). All patients presented with unexplained fever and general symptoms such as weight loss, fatigue, and malaise in variable frequencies. The purified protein derivative (tuberculin) test was positive in only 16.6% of TB patients. They were treated with a combination of rifampicin (450–6000 mg/day), isoniazid (200–300 mg/day), and pyrazinamide (1.5–2 g/day); only 1 patient died, and 2 underwent a successful renal transplantation after the treatment. CONCLUSIONS TB incidence in HD patients was higher than in the general population (p < 0.0001) with a relative risk (RR) of 19.68 (13.81 < RR < 29.03), which points to the urgent need to investigate TB in all uremic patients with unexplained fever, continuous nonspecific symptoms, or when TB is suspect, whereas the response to therapy is directly dependent on early diagnosis, and the specific treatment may offer HD patients a good prognosis.
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