Ep 46: A 50-year-old with proteinuria

Her physical examination discloses a height of 168 cm, which is about 5 feet, 6 inches, a weight of 91 kilograms, or about 200 pounds, a blood pressure of 130/80, and she also is noted to have an elevated jugular venous pressure, a fourth heart sound, and trace pedal edema. (Cathy) That translates to a BMI of 32, so in the obese category, which starts at a BMI of 30. And it also sounds like she's pretty volume overloaded with some heart failure.

(Charlie) Okay, let me tell you about her laboratory values. So, her serum creatinine is 1.2 mg/dL, her BUN is 18, her creatinine clearance is 87 mL/min. She has a urinalysis which shows a spot pH of 5.0, a specific gravity of 1.018, a dipstick protein of 3+. Notably, there's no glucose, and on microscopic examination she has occasional course granular casts and no red blood cells. She has a 24-hour urine collection, which yields a protein excretion of 5.9 g in 24 hours.

(Cathy) Okay, so she has nephrotic-range proteinuria, the cut-off for that being over 3.5 g/day. She doesn't have any hematuria or red blood cells noted on the urinalysis so we're dealing purely with nephrotic-range proteinuria. (Charlie) Would you perform a renal biopsy based on what you know now? (Cathy) Probably. She doesn't have an underlying disease. We didn't hear anything about diabetes that would obviously be causing her proteinuria. And it sounds like this is new compared to a year ago.

The hypertension that we did hear about she has-- typically, that doesn't cause nephrotic-range proteinuria, so in this case I would refer for a biopsy. (Charlie) Okay, so the question states that she undergoes a renal biopsy, which demonstrates that 60% of the glomeruli, mostly in the corticomedullary junction, have segmental scarring by light microscopy. The remainder of the glomeruli appear unremarkable. Based on this finding, what is the most likely diagnosis?

Option A is focal segmental glomerulosclerosis; option B is hypertensive nephrosclerosis; option C is Minimal Change Disease; option D is membranous glomerular nephropathy; and option E is crescentic glomerulonephritis. (Cathy) So, the option here is Option A, which is FSGS. Now, the characteristic pattern that you see is what you mentioned. So, it's focal, meaning that not all the glomeruli are involved, and it's also segmental, so that means that the entire glomerulus isn't involved.

The history and laboratory features that you mentioned are also consistent with this lesion. There's some associated hypertension, there's a decrease in her creatinine clearance, and a relatively inactive urine sediment. (Charlie) What's the etiology? What do you think about the etiologies of FSGS? (Cathy) You can have primary or secondary causes of FSGS, and there are a large number of secondary causes. So, you have to think about viral infections, such as HIV or hepatitis.

Hypertension can lead to FSGS. Certain drugs, like heroin or bisphosphonates, and sickle cell disease can also lead to FSGS. Now, there are other less common causes and even genetic causes, but if the secondary causes are eliminated then the remaining patients are considered to have primary FSGS. (Charlie) How common is it? (Cathy) The prevalence is increasing, and it's more common in African-Americans. It now represents up to one third of cases of nephrotic syndrome.

(Charlie) What's the expected outcome for patients like this? (Cathy) It rarely remits spontaneously, but you can have treatment-induced remission of the proteinuria, and that would significantly improve her prognosis. Treatment of patients with primary FSGS should include inhibitors of the renin-angiotensin system and the treatment of secondary FSGS typically involves treating the underlying cause and controlling the proteinuria.

There's no role for steroids or other immunosuppressive agents in secondary FSGS. (Charlie) So, the central aspect to treatment is with ACE inhibitors or ARBs, it sounds like. (Cathy) Yes, to control the proteinuria. And there are risk factors that are associated with poorer outcomes, so that would include, once you get to the nephrotic-range proteinuria, African-American race, and renal insufficiency.

And up to half of those patients will reach frank renal failure in six to eight years after diagnosis. (Charlie) What about the other options? What would you expect to see on kidney biopsy if a renal disease was due to one of the other causes? (Cathy) Option B talks about hypertensive nephrosclerosis. And this exhibits more prominent vascular changes and patchy ischemic, totally sclerosed glomeruli.

In addition, you also don't see nephrosclerosis associated with nephrotic-range proteinuria, usually. Option C mentions Minimal Change Disease, and that's usually associated with symptomatic edema, but normal-appearing glomeruli on light microscopy. Option D talks about membranous nephropathy, which the patient's presentation is consistent, but the biopsy is not. So, in membranous glomerular nephropathy, all glomeruli are uniformly involved with subepithelial dense deposits.

And Option E is not supported by this case because there are no features of crescentic glomerular nephritis here. (Charlie) Okay, so the teaching point in this case is that FSGS, or focal segmental glomerulosclerosis, is one of the major causes of proteinuria in adults. On renal biopsy you'll see a characteristic pattern of focal and segmental glomerular scarring.

There are a bunch of primary disorders that can lead to secondary FSGS, or, in the absence of a precipitating cause, it can be primary. Treatment centers around treating the underlying cause, when there is one, and treating the proteinuria with ACE inhibitors and ARBs. (Cathy) And to learn more about this you can read in Harrison's chapter on Renal Disorders. ♪ (music) ♪