USMLE® Step 1 style questions USMLE
A 62-year-old woman comes to the clinic due to progressive fatigue, weight loss, and ankle swelling for the past two months. Physical examination shows 2+ pitting edema around the ankles. Cardiovascular and respiratory examinations are non-contributory. Laboratory results show a serum creatinine level of 3.1 mg/dL, albumin of 2.2 g/dL, and total cholesterol concentration of 290 mg/dL. Urinalysis results show 3+ proteinuria without hematuria or red cell casts. Renal biopsy is performed, and the results are shown below:
Reproduced from: Wikipedia
Which of the following is the most likely explanation for this patient’s condition?
Diabetic nephropathy exam links
Content Reviewers:Rishi Desai, MD, MPH
Contributors:Vincent Waldman, PhD, Tanner Marshall, MS
Diabetic nephropathy refers to the kidney damage caused by both type I and type II diabetes.
Because of the growing number of people affected by diabetes, diabetic nephropathy is currently the leading cause of end-stage renal disease in most developed countries around the world.
Each kidney has millions of nephrons, each of which is served by a tiny capillary bed called a glomerulus.
The tiny arteriole that approaches the glomerulus is called the afferent arteriole - a for approaching, and the arteriole that exits the glomerulus is called the efferent arteriole - e for exits.
The glomeruli are a tiny cluster of capillaries that are physically supported by mesangial cells.
So when blood is filtered it moves through the endothelium lining the capillary, then through the basement membrane, and then through the epithelium lining the nephron, and finally into the nephron itself - at which point its called filtrate.
The endothelium has pores that keep cells from entering the filtrate, and the basement membrane is negatively charged and repels other negatively charged molecules and proteins, like the protein albumin.
The epithelium has of special cell type called a podocyte which looks like an octopus because it has foot processes that wrap around the basement membrane, leaving tiny gaps between its octopus-like projections called filtration slits.
In diabetes mellitus, there’s an excess of glucose in the blood, because it can’t get into cells, and when blood gets filtered through the kidneys, some of that excess glucose starts to spill into the urine, called glycosuria.
In addition, when there’s a lot of glucose in the blood, it also starts sticking to proteins in the blood — a process called non-enzymatic glycation because no enzymes are involved.
Because glucose can get through the endothelium, this process of glycation can also involve the basement membrane of small blood vessels making it thicken. The process particularly affects the efferent arteriole causing it to get stiff and more narrow - a process called hyaline arteriosclerosis.
This creates an obstruction that makes it difficult for blood to leave the glomerulus, increasing pressure within the glomerulus. At the same time, the afferent arteriole dilates, allowing more blood flow into the glomerulus and increasing pressure further.
High pressure in the glomerulus leads to an increase in the glomerular filtration rate--which is simply the amount of blood filtered through per minute. This is the first stage of diabetic nephropathy, called hyperfiltration.
In response to this high-pressure state, the supportive mesangial cells secrete more and more structural matrix expanding the size of the glomerulus. This matrix deposition and mesangial expansion happen uniformly, or it can result in little nodules within the mesangium called Kimmelstiel-Wilson nodules - which are tiny little balls of protein.
The thickening of the basement membrane counterintuitively makes it more permeable—allowing proteins like albumin through that otherwise would have been filtered out.
- "Robbins Basic Pathology" Elsevier (2017)
- "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
- "Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)
- "CURRENT Medical Diagnosis and Treatment 2020" McGraw-Hill Education / Medical (2019)
- "Clinical Manifestations of Kidney Disease Among US Adults With Diabetes, 1988-2014" JAMA (2016)
- "The clinical course of diabetic nephropathy" JAMA: The Journal of the American Medical Association (1976)
- "Genetic Factors in Diabetic Nephropathy" Clinical Journal of the American Society of Nephrology (2007)
- "Update of pathophysiology and management of diabetic kidney disease" Journal of the Formosan Medical Association (2018)