Hypercalcaemia in Mycobacterium kansasii pulmonary infection.

A gentleman in his 60s with end-stage kidney disease status post kidney transplantation on prednisone and tacrolimus presented with generalised weakness for 7 days, associated with altered mental status. Investigations revealed pancytopenia, acute kidney injury, hypercalcaemia, decreased parathyroid hormone (PTH) and normal calcitriol levels. CT of the chest showed multifocal lung opacities suspicious for malignancy. Bronchoscopy with biopsy yielded no malignant cells, and bronchoalveolar lavage specimens grew Mycobacterium kansasii The patient was treated with bisphosphonates, calcitonin and antibiotics for non-tuberculous mycobacteria pulmonary infection, with improvement in serum calcium levels, and was discharged after 5 weeks of hospitalisation.The work-up for hypercalcaemia begins with PTH measurement, and low PTH levels are consistent with malignancy, immobilisation and granulomatous diseases. Hypercalcaemia in the lattermost is classically caused by overproduction of calcitriol by activated macrophages. However, there are case reports of mycobacterial infections with hypercalcaemia despite normal calcitriol levels, supporting the existence of an additional mechanism of hypercalcaemia in granulomatous infections.

Viral-Associated GN: Hepatitis C and HIV.

Viruses are capable of inducing a wide spectrum of glomerular disorders that can be categorized on the basis of the duration of active viremia: acute, subacute, or chronic. The variable responses of the adaptive immune system to each time period of viral infection results mechanistically in different histologic forms of glomerular injury. The unique presence of a chronic viremic carrier state with either hepatitis C (HCV) or HIV has led to the opportunity to study in detail various pathogenic mechanisms of viral-induced glomerular injury, including direct viral infection of renal tissue and the development of circulating immune complexes composed of viral antigens that deposit along the glomerular basement membrane. Epidemiologic data show that approximately 25%-30% of all HIV patients are coinfected with HCV and 5%-10% of all HCV patients are coinfected with HIV. This situation can often lead to a challenging differential diagnosis when glomerular disease occurs in this dual-infected population and requires the clinician to be familiar with the clinical presentation, laboratory workup, and pathophysiology behind the development of renal disease for both HCV and HIV. Both of these viruses can be categorized under the new classification of infection-associated GN as opposed to being listed as causes of postinfectious GN as has previously been applied to them. Neither of these viruses lead to renal injury after a latent period of controlled and inactive viremia. The geneses of HCV- and HIV-associated glomerular diseases share a total dependence on the presence of active viral replication to sustain renal injury so the renal disease cannot be listed under "postinfectious" GN. With the new availability of direct-acting antivirals for HCV and more effective combined antiretroviral therapy for HIV, successful remission and even regression of glomerular lesions can be achieved if initiated at an early stage.

Impact of antiretroviral therapy on clinical outcomes in HIV + kidney transplant recipients: Review of 58 cases.

Background: Antiretroviral therapy (ART) poses challenging drug-drug interactions with immunosuppressant agents in transplant recipients.  We aimed to determine the impact of specific antiretroviral regimens in clinical outcomes of HIV + kidney transplant recipients.  Methods: A single-center, retrospective cohort study was conducted at a large academic center. Subjects included 58 HIV - to HIV + adult, first-time kidney transplant patients. The main intervention was ART regimen used after transplantation.  The main outcomes assessed at one- and three-years were: patient survival, death-censored graft survival, and biopsy-proven acute rejection; we also assessed serious infections within the first six months post-transplant.  Results: Patient and graft survival at three years were both 90% for the entire cohort. Patients receiving protease inhibitor (PI)-containing regimens had lower patient survival at one and three years than patients receiving PI-sparing regimens: 85% vs. 100% ( p=0.06) and 82% vs. 100% ( p=0.03), respectively. Patients who received PI-containing regimens had twelve times higher odds of death at 3 years compared to patients who were not exposed to PIs (odds ratio, 12.05; 95% confidence interval, 1.31-1602; p=0.02).  Three-year death-censored graft survival was lower in patients receiving PI vs. patients on PI-sparing regimens (82 vs 100%, p=0.03). Patients receiving integrase strand transfer inhibitors-containing regimens had higher 3-year graft survival. There were no differences in the incidence of acute rejection by ART regimen. Individuals receiving PIs had a higher incidence of serious infections compared to those on PI-sparing regimens (39 vs. 8%, p=0.01).  Conclusions: PI-containing ART regimens are associated with adverse outcomes in HIV + kidney transplant recipients.