Thursday, November 17, 2011

Sickle cell disease and the kidney

Since moving to Baltimore, a city with a large African-American population, earlier this year, I have had the opportunity to see several interesting patients with sickle cell SS disease and renal complications. Here is a mention of some of the kidney abnormalities that occur with SS disease, as well as some of the clinical manifestations.

The underlying pathology of renal sickle cell disease seems to be from microvascular hypoxemia: when red blood cells acquire a sickle shape and obstruct capillary flow, microinfarcts, chronic ischemic injury and medullary hypoxia can occur. Hemosiderin deposits can also be seen on biopsy. Sequelae can include:

1) hyperfiltration. Hypoxia can lead to increased prostaglandin release, which increases GFR. NO synthase may also be upregulated.

2) increased proximal tubular function. The exact causes are unknown, but the proximal tubular upregulates secretion of creatinine, as well as resorption of phosphorus. Thus, creatinine-based estimations of GFR may overestimate renal clearance in sickle cell patients.

3) microalbuminuria. Unclear if this is secondary to ischemia, or if hyperfiltration plays a role. Can progress to overt proteinuria over time. It is interesting to note that parvovirus B19 has been implicated as a cause of nephrotic syndrome in SS disease patients.

4) hyposthenuria. Otherwise known as inability to concentrate or dilute urine; possibly due to impaired water ADH response, although another possibility is that enhanced clearance of interstitial solute washes out the medullary concentration gradient.

5) impaired distal tubular function. Cause unclear. Can lead to decreased distal H+ and/or K+ secretion, and lead to an imcomplete distal RTA.

6) hematuria. Probably from capillary microinfarcts.

7) renal papillary necrosis. From medullary ischemia.

A collapsing form of FSGS as well as MPGN have been reported in conjunction with SS disease.

Amazing (and awful), that a single genetic mutation can cause so much renal havoc!

1 comment:

Edgar Lerma said...

Interestingly, certain genetic factors, such as polymorphisms in the myosin heavy chain 9 (MHY9) and apolipoprotein L1 (APOL1) genes, are associated with a higher risk of proteinuria and reduced glomerular filtration rate in patients with sickle cell disease. These genes are also associated with kidney disease in black patients without sickle cell disease.
Ashley-Koch AE, Okocha EC, Garrett ME, et al. MYH9 and APOL1 are both associated with sickle cell disease nephropathy. Br J Haematol 2011; 155:386