Anti-HLA Antibodies Complicating Infectious Mononucleosis with Thrombocytopenia and Neutropenia

A case concerning a 21-year-old male college student with thrombocytopenia and neutropenia complicating infectious mononucleosis is presented. Although the patient had no prior history of alloimmunization, a broad spectrum anti-HLA antibody was strongly positive in his serum. Concomitant with resolution of the hematologic abnormalities, the titer of the antibody diminished. This case is unique both in the severity of the thrombocytopenia and neutropenia and for the circulating HLA antibody most likely of viral origin

Allogeneic Whole Pancreas Transplantation in Insulin-Dependent Diabetes Mellitus

A clinical whole organ pancreas transplantation program for patients with insulin-dependent diabetes mellitus complicated by end-stage renal disease was initiated at Henry Ford Hospital in 1987. Five patients have received pancreatic allografts after a previous kidney transplant (phase 1), and six patients had simultaneous pancreas-kidney transplants (phase 2). Ten patients had functioning pancreatic grafts after surgery, and all of them had normal carbohydrate tolerance with appropriate plasma free insulin responses to an oral glucose tolerance test three months after transplantation. As long as 28 months postsurgery six patients remained free of insulin requirements; however, one patient rejected the pancreatic allograft, and three patients died because of cytomegalovirus pneumonia. Two of the latter patients had functioning pancreatic allografts at the time of their demise. These results compare favorably with those of the International Pancreas Transplant Registry which reflects the world experience. Pancreas transplantation is a unique experimental treatment with the potential of restoring euglycemia and improving the prognosis of insulin-dependent diabetic patients

Metabolic Acidosis

A 24-year-old man with Type I Diabetes was found unconscious in his home. He had been depressed recently and was known to have become increasingly non-compliant with his insulin therapy and diet. Lying next to him was a glass bottle without a label on it with only a few drops of liquid in it. When he was brought to the ER he appeared to have labored breathing and a comprehensive blood panel, arterial blood gases, urinalysis, and a chest X-ray were performed. His test results are summarized in Table 12.1

Viral-Associated GN: Hepatitis B and Other Viral Infections

By definition, viral-associated GN indicates the direct pathogenic relationship between active viral replication and the development of acute GN. This definition is in sharp contrast to the semantic label and pathophysiologic foundation behind postinfectious GN that uniquely develops only during a period of resolved and absent active infection. The primary example of postinfectious GN are the glomerular lesions described after a pharyngeal or cutaneous streptococcal infection and do not represent the clinical or immunologic pattern seen with viral-associated GN. Hepatitis B (HBV) is the most common chronic viral infection in the world affecting >400 million people which is more than double the prevalence of chronic HIV and hepatitis C carriers combined. In addition, 10%-20% of HBV patients may be coinfected with hepatitis C and 5%-10% will have coinfection with HIV. Being able to distinguish the different types of GN seen with each viral infection is essential for the practicing clinician as each virus requires its own specific antiviral therapy. HBV-induced immune complex disease with renal injury lies on one end of the spectrum of disorders that occurs after a prolonged chronic carrier state. On the opposite end of the spectrum are renal diseases that develop from acute or subacute viral infections. One important glomerular lesion in this category is the association of collapsing FSGS with acute active cytomegalovirus, Epstein-Barr virus, and parvovirus B19 infection. The data supporting or disproving this relationship for each of these viruses will be discussed. A second renal manifestation of acute viral infections often occurs with many different sporadic or epidemic infections such as dengue and hantavirus and can lead to a transient proliferative GN that resolves upon viral clearance. The complex interplay of HBV and all viruses with the immune system provides conceptual lessons on the pathophysiology of immune complex GN that can be applied to all infection-related renal disease and plays an integral role in developing an approach to therapeutic intervention

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

A Practical Approach to Nephrolithiasis

Detailed metabolic evaluation and prophylaxis for all patients presenting with a first renal stone seems inappropriate. The crucial clinical problem lies in predicting which patients are likely to have a recurrence. Stone composition is an important guide for the physician's decisions concerning investigation and a rational choice of treatment

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