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      Clinical profile of patients having pulmonary tuberculosis and renal amyloidosis

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          Abstract

          Objectives:

          This study was planned to define the clinical profile of pulmonary tuberculosis (PTB) patients having renal amyloidosis, to identify the factors responsible for development of amyloidosis, to detect the time period between onset of amyloidosis and PTB, and analyze clinical features of amyloidosis in PTB patients for early diagnosis and timely assessment.

          Materials and Methods:

          Patients of PTB having pedal edema, proteinuria, and grossly diseased kidneys on ultrasound abdomen were subjected to renal biopsy and appropriate biochemical investigations. Clinical profile of biopsy proven amyloidosis cases was analyzed.

          Results:

          There were 43 patients (32 males, 11 females, age range 20–65 years) having PTB with pedal edema, proteinuria, and renal medical disease on abdominal ultrasound where amyloidosis was confirmed by renal biopsy. The total duration of illness ranged from two months to seven years (mean 2.25 years) and was less than five years in 93% patients. All patients had significant proteinuria. Nephrotic syndrome was seen in 23, hypertension in 19, hypoalbuminemia in 33, hypercholesterolemia in 29, and deranged renal functions in 32 patients. Ninety percent patients had moderate to far advanced pulmonary lesions on chest radiography with smear positivity in 21 patients.

          Conclusions:

          Renal amyloidosis is an important complication of PTB and should be suspected clinically in patients presenting with a triad of pedal edema, proteinuria, and medical renal disease on ultrasound. Contrary to general belief, renal amyloidosis may occur in PTB patients having disease for relatively shorter duration, and even if adequately treated.

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          Most cited references26

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          Amyloidosis.

          Mark Pepys (2006)
          Amyloidosis is a clinical disorder caused by extracellular deposition of insoluble abnormal fibrils, derived from aggregation of misfolded, normally soluble, protein. About 23 different unrelated proteins are known to form amyloid fibrils in vivo, which share a pathognomonic structure although they are associated with clinically distinct conditions. Systemic amyloidosis, with amyloid deposits in the viscera, blood vessel walls, and connective tissue, is usually fatal and is the cause of about one per thousand deaths in developed countries. This rarity and the variable involvement of different organs and tissues are often responsible for missed or delayed diagnosis, and amyloidosis remains a considerable clinical challenge. However, recent elucidation of important aspects of pathogenesis, as well as developments in diagnosis, monitoring, and treatment, have greatly improved outcomes, especially when patients are managed in specialist centers.
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            Regulation of cytokines, cytokine inhibitors, and acute-phase proteins following anti-TNF-alpha therapy in rheumatoid arthritis.

            Treatment with a chimeric mAb to TNF-alpha has been shown to suppress inflammation and improve patient well-being in rheumatoid arthritis (RA), but the mechanisms of action of such treatment have not been fully explored. Here we show that in vivo administration of anti-TNF-alpha Ab, using a longitudinal analysis, results in the rapid down-regulation of a spectrum of cytokines, cytokine inhibitors, and acute-phase proteins. Marked diurnal variation in the serum levels of some of these were detected. These results were consistent with the concept of a cytokine-dependent cytokine cascade, and the degree of clinical benefit noted after anti-TNF-alpha therapy is probably due to the reduction in many proinflammatory mediators apart from TNF-alpha, such as IL-6, which reached normal levels within 24 h. Serum levels of cytokine inhibitors such as soluble p75 and p55 TNFR were reduced as was IL-1 receptor antagonist. Reductions in acute-phase proteins occurred after serum IL-6 fell and included serum amyloid A, haptoglobin, and fibrinogen. The latter reduction could be of importance, as it is a risk factor for atherosclerosis, which is augmented in RA patients.
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              Secondary systemic amyloidosis: response and survival in 64 patients.

              From 1956 through 1989, 38 men and 26 women were seen at the Mayo Clinic with biopsy-proven AA. The underlying disorder was rheumatic disease in 42, infectious disease in 11, inflammatory bowel disease in 6, and other causes in 5. All patients were symptomatic at the time of diagnosis. Fifty-eight of the 64 patients had proteinuria or renal insufficiency. Fourteen also had significant symptoms of gastrointestinal amyloid, and 6 had amyloid goiter. None of the patients had symptomatic cardiac involvement, and only 3 had palpable hepatomegaly. Renal, gastric, rectal, fat, and marrow biopsies were positive for amyloid in 100%, 94%, 82%, 58%, and 46% of tested patients, respectively. The median survival of the entire group was 24.5 months. Thirty-five of the 47 deceased patients died as a direct result of their amyloidosis, primarily from complications of renal failure. Nine were successfully treated and had regression of the disease. Two with bronchiectasis responded to long-term cyclic antibiotic therapy, as did 1 patient with osteomyelitis. One patient with inflammatory bowel disease responded to surgical resection, and 1 with familial Mediterranean fever responded to colchicine. Four patients with rheumatic disease were treated with cyclophosphamide (in 2) and methotrexate (in 2), with complete resolution of their renal disease. All 9 successfully treated patients are alive, with a median follow-up of 58 months. Statistical analysis revealed that creatinine values greater than or equal to 2.0 mg/dl (P less than 0.003) and a serum albumin value less than 2.5 g/dl (P less than 0.02) were associated with a poorer survival. The single strongest variable associated with poor survival was a serum creatinine level greater than 2 mg/dl at presentation, with a median survival of 11.2 months compared to patients with a creatinine level less than 2.0 mg/dl, with a median survival of 56.9 months.
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                Author and article information

                Journal
                Lung India
                LI
                Lung India : Official Organ of Indian Chest Society
                Medknow Publications (India )
                0970-2113
                0974-598X
                Apr-Jun 2009
                : 26
                : 2
                : 41-45
                Affiliations
                Department of Pulmonary Medicine, JLN Medical College, Ajmer, India
                [1 ] Department of Pathology, JLN Medical College, Ajmer, India
                [2 ] Department of Medicine, Gandhi Medical College, Bhopal, India
                Author notes
                Address for correspondence: Dr. Ramakant Dixit, 381/26, Ramganj, Ajmer-305 001, India. E-mail: dr.ramakantdixit@ 123456gmail.com
                Article
                LI-26-41
                10.4103/0970-2113.48896
                2860413
                20440393
                c36741a5-1941-425a-b3ba-d08e81e18e26
                © Lung India

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Original Article

                Respiratory medicine
                tuberculosis,disease duration,complication,amyloidosis
                Respiratory medicine
                tuberculosis, disease duration, complication, amyloidosis

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