Screening for primary aldosteronism without discontinuing hypertensive medications: plasma aldosterone-renin ratio.

The traditional workup for primary aldosteronism is cumbersome and requires discontinuing antihypertensive medications, which is inconvenient and potentially dangerous. A simple and accurate screening test that can be used without modifying medications is needed. The plasma aldosterone-renin ratio (ARR) is a valid screening assay for primary aldosteronism, but antihypertensives are usually discontinued before obtaining this ratio, limiting its utility. The present prospective study is designed to examine the validity of the ARR as a screening test for primary aldosteronism if the ratio is measured randomly while patients continue antihypertensive therapy. During the 18-month study period, 90 patients were referred to the hypertension clinic with poorly controlled hypertension. ARR was measured in random blood samples in all 90 patients while maintaining their prescribed antihypertensive medications. Those with elevated ARRs (>100 ng/dL / ng/mL/h) underwent further diagnostic workup, including adrenal computed tomography and/or magnetic resonance imaging and adrenal iodine 131 norcholesterol uptake scan. Fifteen patients (17%) had elevated ARRs greater than 100:1. Ten of 15 patients were found to have adrenal adenoma on diagnostic workup, and adenoma was later confirmed by histological examination after surgical removal in these 10 patients. Five patients were found to have adrenal hyperplasia; all 5 patients responded to antialdosterone treatment. Thus, all 15 patients had good control of blood pressure after surgery and/or antialdosterone medications. No patient showed a falsely elevated ARR. Data suggest that the ARR is a valid screening assay for primary aldosteronism in patients with poorly controlled blood pressure, and discontinuation of antihypertensive medications is not needed for this test.

Reversible acute renal allograft dysfunction due to gabapentin.

BACKGROUND: The use of gabapentin as an effective analgesic agent for neuropathic pain has expanded considerably. Its lack of both anticholinergic side effects and interference with the metabolism of drugs via the cytochrome P450 pathway make it especially useful for transplant recipients. METHODS AND RESULTS: We describe the case of a renal transplant recipient with a long-term stable functioning allograft who developed reversible acute renal dysfunction after beginning gabapentin therapy for chronic pain due to diabetic neuropathy. CONCLUSIONS: We suggest that gabapentin may cause acute renal dysfunction by a mechanism involving renal afferent vasoconstriction. Caution should be employed when considering the use of gabapentin in transplant recipients, especially when combined with other agents that may potentiate renal vasoconstriction.

Chronic modulation of the TCR repertoire in the lymphoid periphery.

Using TCR V beta 5 transgenic mice as a model system, we demonstrate that the induction of peripheral tolerance can mold the TCR repertoire throughout adult life. In these mice, three distinct populations of peripheral T cells are affected by chronic selective events in the lymphoid periphery. First, CD4+V beta 5+ T cells are deleted in the lymphoid periphery by superantigens encoded by mouse mammary tumor viruses-8 and -9 in an MHC class II-dependent manner. Second, mature CD8+V beta 5+ T cells transit through a CD8lowV beta 5low deletional intermediate during tolerance induction by a process that depends upon neither mouse mammary tumor virus-encoded superantigens nor MHC class II expression. Third, a population of CD4-CD8-V beta 5+ T cells arises in the lymphoid periphery in an age-dependent manner. We analyzed the TCR V alpha repertoire of each of these cellular compartments in both V beta 5 transgenic and nontransgenic C57BL/6 mice as a function of age. This analysis revealed age-related changes in the expression of V alpha families among different cellular compartments, highlighting the dynamic state of the peripheral immune repertoire. Our work indicates that the chronic processes maintaining peripheral T cell tolerance can dramatically shape the available TCR repertoire.

Glomerulonephritis in renal allografts associated with hepatitis C infection: a possible relationship with transplant glomerulopathy in two cases.

Chronic infection with hepatitis C virus (HCV) has been identified as a cause of type I membranoproliferative glomerulonephritis (MPGN). HCV infection is common in patients with end-stage renal disease and may persist in renal allograft recipients. MPGN in the allograft may therefore be a manifestation of persistent HCV infection. We report two cases of glomerulopathy with features of both MPGN and transplant glomerulopathy in renal transplant patients chronically infected with HCV. We discuss the course of interferon alfa therapy in both patients as well as a possible relationship of HCV infection with transplant glomerulopathy.