Erythrocyte sodium lithium countertransport in renal transplant recipients with mycophenolate mofetil and low-dose cyclosporine

Hypertension, a common complication after renal transplantation, has many potential etiologies. Erythrocyte sodium lithium countertransport (Na/LiCT) is a sensitive membrane protein that has been observed to be abnormal in several hypertension-related diseases. We have shown that the kinetics of Na/LiCT were abnormal in renal transplant recipients treated with usual dose of cyclosporine (CsA). We postulated that CsA might be a cause of post-renal transplantation hypertension. There is evidence showing that the severity of CsA nephrotoxicity is dependent on the dose. Mycophenolate mofetil (MMF) may allow CsA dose reduction without increasing the risk of rejection. We studied the impact of CsA dose reduction in association with MMF on the kinetics of erythrocyte Na/LiCT in renal transplants. In 15 renal allograft recipients, 2 g/d MMF were introduced and the CsA dose reduced to reach whole-blood levels between 70 and 100 ng/mL within 1 month. CsA doses and levels, renal function parameters, blood pressure, and the kinetics of Na/LiCT were evaluated before and 6 months after CsA dose reduction. Overall, renal transplant recipients with usual doses of CsA showed a lower Km with a higher Vmax/Km ratio for erythrocyte Na/LiCT than normal controls (Km, 40 +/- 4 vs 74 +/- 11; P <.05; Vmax/Km, 10.2 +/- 1.7 vs 6.1 +/- 0.9; P <.05). After 6 months of CsA dose reduction, the Km and Vmax/Km of Na/LiCT were similar to those of normal controls (Km, 66 +/- 8 vs 74 +/- 11; P >.05; Vmax/Km, 5.7 +/- 1.2 vs 6.1 +/- 0.9; P >.05). These results demonstrate that reduction of CsA dose in combination with MMF may improve the kinetics of Na/LiCT and lessen the long-term side effects of CsA without increasing the risk of rejection.     

Role of Urinary Neutrophil Gelatinase–Associated Lipocalin for Predicting the Severity of Renal Functions in Patients With Autosomal-Dominant Polycystic Kidney Disease

Background

Autosomal-dominant polycystic kidney disease (ADPKD) has a feature of disruption of tubular integrity with increased cellular proliferation and apoptosis. There are several known tubular membrane proteins in the pathogenesis of ADPKD, and one of these proteins is the neutrophil gelatinase-associated lipocalin (NGAL). NGAL is a protein expressed on renal tubular cells of which production is markedly increased in response to harmful stimuli such as ischemia or toxicity.

Effect of methotrexate on serum levels of IL-22 in patients with psoriasis

Interleukin-22 (IL-22) is the effector molecule of T-helper subset 22 (Th-22) lineage that promotes keratinocyte proliferation and dermal inflammation in psoriasis. Methotrexate is widely used as a first-line treatment in moderate to severe psoriasis. Methotrexate inhibits inflammatory and cytokinetic processes via various mechanisms, but the relevance of these to psoriasis is limited and whether methotrexate is specifically able to down-regulate Th22 cytokines is unknown. To determine if methotrexate reduces IL-22 in cases of psoriasis. Nineteen patients with moderate to severe psoriasis were given methotrexate 15 mg per week for up to 12 weeks. Serum levels of IL-22 were determined by enzyme-linked immunosorbent assay (ELISA) before and after treatment. Eleven of 19 patients (57.8%) achieved a 75% PASI score reduction. IL-22 levels were significantly higher in untreated psoriasis patients (56.63 ± 60.73 pg/mL) than in controls (12.58 ± 12.59 pg/mL). Methotrexate significantly reduced serum levels of IL-22 in psoriasis patients to 5.91 ± 7.97 pg/mL (p<0.001). Moreover, there was a significant positive correlation between IL-22 levels and PASI (r=0.63, p=0.004). Methotrexate significantly reduces serum IL-22 levels in cases of psoriasis. This is a novel mechanism by which methotrexate acts in the treatment of this disease.     

Detection of Hpdel among Thais, a deleted allele of the haptoglobin gene that causes congenital haptoglobin deficiency

BACKGROUND: Congenital haptoglobin deficiency is a risk factor for anaphylactic nonhemolytic transfusion reactions in Japan. The deleted allele of the haptoglobin gene, Hp(del), which causes congenital haptoglobin deficiency, has also been observed in other Northeast Asian populations, such as Korean and Chinese persons. It has not been reported in several African and European-African populations, however, or investigated in other countries. STUDY DESIGN AND METHODS: To investigate the distribution of congenital haptoglobin deficiency in Southeast Asian countries, blood samples collected from 200 randomly selected healthy Thai volunteers were analyzed for serum haptoglobin and the haptoglobin gene. Plasma haptoglobin concentration was measured to identify haptoglobin deficiency. Haptoglobin phenotyping was performed with sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by Western blotting. The presence of the Hp(del) allele was determined with genomic DNA by an Hp(del)-specific polymerase chain reaction (PCR) method. RESULTS: There were no haptoglobin-deficient subjects detected among the 200 Thais. Their haptoglobin phenotypes were as follows: Hp 1-1 in 10, Hp 2-1 in 81, and Hp 2-2 in 109. Six individuals heterozygous for Hp(del) were detected. The frequency of the Hp(del) allele was calculated to be 0.015. The prevalence of haptoglobin deficiency caused by Hp(del) homozygosity was estimated to be approximately 1 in 4000. CONCLUSION: Congenital haptoglobin deficiency caused by Hp(del) homozygosity is presumed to be present in Thailand as a risk factor for anaphylactic transfusion reactions with a frequency similar to that in Japan. The causative deleted allele of the haptoglobin gene, Hp(del), is distributed among Southeast Asian populations as well as among Northeast Asian populations.     

Prevalence of Melioidosis in Patients with Suspected Pulmonary Tuberculosis and Sputum Smear Negative for Acid-Fast Bacilli in Northeast Thailand

The clinical and radiological features of pulmonary melioidosis can mimic tuberculosis. We prospectively evaluated 118 patients with suspected pulmonary tuberculosis who were acid-fast bacilli (AFB) smear negative at Udon Thani Hospital, northeast Thailand. Culture of residual sputum from AFB testing was positive for Burkholderia pseudomallei in three patients (2.5%; 95% confidence interval [CI] 0.5–7.3%). We propose that in melioidosis-endemic areas, residual sputum from AFB testing should be routinely cultured for B. pseudomallei.Melioidosis is a serious infectious disease caused by the Tier 1 Select Agent and Gram-negative bacillus, Burkholderia pseudomallei.¹ Naturally acquired melioidosis is highly endemic in northeast Thailand where it is the third most common cause of death caused by infectious diseases after human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) and tuberculosis,² and in northern Australia where it is the commonest cause of fatal community-acquired bacteremic pneumonia.³ Melioidosis is also increasingly reported from many countries across Asia, regions of South America, various Pacific and Indian Ocean islands, and some countries in Africa including Nigeria, Gambia, Kenya, and Uganda.¹ Death from melioidosis reaches 80% in those who are not treated with effective antimicrobial drugs.⁴Melioidosis can manifest with a variety of clinical presentations including sepsis, pneumonia, arthritis, and internal organ abscesses, and has been termed “the great mimicker” because it can be confused with a range of diseases. The most notable example is tuberculosis, with an estimated 10% of melioidosis patients presenting with chronic respiratory symptoms and chest radiography mimicking pulmonary tuberculosis.⁵ In reported cases, failure of clinical improvement after the administration of anti-tuberculosis drugs led to bacteriological culture of sputum, broncho-alveolar lavage, or blood and the detection of B. pseudomallei.^6–8 Although it is clear that melioidosis can mimic clinical features of tuberculosis, patients presenting with suspected tuberculosis in Thailand where melioidosis is highly endemic are not systematically screened for melioidosis. Here, we evaluated the use of culturing sputum samples taken from individuals in Thailand with suspected tuberculosis that were smear negative for acid-fast bacilli (AFB) to detect B. pseudomallei.     

Rapid diagnosis of scrub typhus in rural Thailand using polymerase chain reaction

The aim of this study was to evaluate the use of polymerase chain reaction (PCR) amplification of the O. tsutsugamushi 16S rRNA gene for the diagnosis of scrub typhus in rural Thailand. A prospective study of acute febrile illness in Udon Thani, northeast Thailand, identified 183 patients as having scrub typhus on the basis of immunofluorescent antibody testing (IFA) of paired sera. A further 366 febrile patients admitted concurrently with a range of other diagnoses acted as negative controls. Diagnostic sensitivity and specificity of 16S rRNA PCR was 44.8% and 99.7%, respectively, compared with IFA. PCR positivity was related to duration of symptoms and presence of eschar (P < 0.001, both cases). PCR using primers to amplify a fragment of the 56-kd gene had a sensitivity and specificity of 29.0% and 99.2%, respectively. PCR has a high specificity but low sensitivity for the rapid diagnosis of scrub typhus in this endemic setting.