Renal complications of sickle cell disease

Published on October 31, 2016   31 min

Other Talks in the Series: The Kidney in Health and Disease

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Hello, my name is Claire Sharpe. I'm a consultant nephrologist at King's College Hospital and a senior lecturer at King's College, London. I have been interested in Sickle cell disease in the kidney since 2004, when I've started a joint sickle cell and kidney clinic along with the hematologists at King's College Hospital. I'm going to talk a little bit about pathophysiology of sickle cell and kidney complications, and talk about the clinical manifestations.
The first person to describe sickle cell disease in the western literature was James Herrick, who was working in Boston around 1910. He was looking after a young man from Grenada, who traveled to United States to do a dental degree. This young man had had a sickly childhood, and when he arrived in America, he was suffering with leg ulcers. This paper very clearly describes both the history and the clinical examination of this man. And of note, James Herrick brings out that he had increased urine volume of low specific gravity, which contained a distinct trace of serum albumin. And this very much sums up the sickle cell nephropathy, which we recognize in many of our patients today.
The underlying genetic mutation was first described in Cambridge by Vernon Ingram in 1957. A single point mutation results in a replacement to the glutamine with a valine at the six amino acid, and the beta-chain of adult hemoglobin. This results in the beta hemoglobin becoming less soluble, particularly under hypoxic and acidotic conditions. This results in polymerization of the beta hemoglobin which can form these rope like structures seen here in this middle picture. These structures make the red blood cell rigid and undeformable and it takes on this characteristic sickling shape. This polymerization sickling is initially reversible. However, after many cycles of sickling, the red blood cell becomes irreversibly sickled, and then can spill over into the peripheral circulation that's seen on the right. This is what James Herrick noted and more gave the disease its name.