Physician Assistant Exam: Inflammation of the Kidney

The Physician Assistant Exam will expect you to be familiar with conditions of the kidney. The kidneys can become inflame in multiple areas so you will need to be familiar with nephritis and vasculitis.

Acute interstitial nephritis (AIN)

Many commonly prescribed medications can cause a type of inflammatory response in the kidney, leading to acute interstitial nephritis (AIN).

With acute interstitial nephritis, someone generally develops acute renal failure a few days after being placed on an offending medication — common causes are antibiotics, including penicillins and cephalosporins. Other medications that can cause acute interstitial nephritis are trimethoprim/sulfamethoxazole (Bactrim), fluoroquinolones (Cipro), proton-pump inhibitors (PPIs), and NSAIDs.

Pertinent physical exam findings for acute interstitial nephritis can include a fever, and sometimes a skin rash is present. Important labs are an abnormal urinalysis, including pyuria and urine eosinophils. Tubular-range proteinuria may be present. The key to treatment is to withdraw the offending medication. Sometimes prednisone may be used.

Glomerulonephritis (GN)

Glomerulonephritis (GN) is an inflammation of the glomerulus, which in essence is a network of capillaries responsible for kidney filtration. When they get inflamed, bad things can happen. Although glomerulonerphritis isn’t very common clinically, the condition is distinct enough to be terrific fodder for test questions. In addition, some types of glomerulonephritis can worsen kidney function quickly if not properly diagnosed.

Glomerulonephritis has myriad causes. The clinical presentations of glomerulonephritis can vary greatly, depending on the individual. There can be either macroscopic or microscopic hematuria. Proteinuria is almost always present, and the creatinine can be normal or abnormal.

If the complements levels in the blood are low, then think about one potential group of conditions that can cause glomerulonephritis. Causes of glomerulonephritis with low complements include the following (Tip: Think S&M: two S’s and two M’s — strep, systemic, membranoproliferative, and mixed):

  • Post-streptococcal glomerulonephritis (PSGN): This type of glomerulonephritis is seen in young children a few weeks after a strep throat or skin infection (for example, impetigo). The child has a low C3 level that will normalize after 6 weeks. Antibody tests used in the diagnosis of post-strep glomerulonephritis include antistreptolysin (ASO) titer and anti-DNase B titer.

  • Systemic lupus erythematosus (SLE) causing glomerulonephritis: There are actually six different classes of lupus nephritis. They have low complements, and you can use anti-dsDNA antibody to help diagnose and gauge how active it is.

  • Membranoproliferative glomerulonephritis (MPGN): You may see a scenario on the test where a young person has a low C3 that doesn’t normalize after 6 weeks but rather stays persistently low. If so, think membranoproliferative glomerulonephritis. The answer isn’t post-streptococcal because in that case, you’d expect the low C3 to normalize. Membranoproliferative glomerulonephritis is common in young people. In older adults, the most common cause is hepatitis C.

  • Mixed cryoglobulinemia: A cryoglobulin is a protein that precipitates at cold temperatures and dissolves when the temperature warms up. There are three types of cryoglobulins: I, II, and III. For the purpose of glomerulonephritis, we’re talking about Type II. Hepatitis C is a big cause of mixed cryoglubulinemia.

You are seeing a 16-year-old boy for hematuria. He had a sore throat 1 week ago, and now he has developed gross hematuria. Urinalysis is positive for 3+ blood and 2+ protein. His creatinine is 1.6 mg/dL. You order complement levels and note that both C3 and C4 are within normal limits. What is the likely diagnosis?

(A) Post-streptococcal glomerulonephritis
(B) IgA nephropathy
(C) Henoch-Schönlein purpura (HSP)
(D) Minimal change disease (MCD)
(E) Membranous nephropathy

The answer is Choice (B). IgA nephropathy is often preceded by a prior pharyngitis and can present with gross hematuria. The time course of the pharyngitis to the development of the hematuria is often a few hours to a few days.

In contrast, with post-streptococcal glomerulonephritis, Choice (A), the pharyngitis can precede the development of the glomerulonephritis by a few weeks. Another key point in this question is that the complements are normal. They’re normal in IgA nephropathy but low in post-streptococcal glomerulonephritis.

Henoch-Schönlein purpura, Choice (C), is a cause of glomerulonephritis in a young person that can present with arthritis, abdominal pain, acute renal failure, and purpura, usually on the lower extremities. Like IgA, Henoch-Schönlein purpura also has normal complements.

Minimal change disease, Choice (D), is a cause of nephrotic syndrome in kids and does not present with hematuria. It presents only with proteinuria and/or the nephritic syndrome. Membranous nephropathy, Choice (E), is a cause of nephritic syndrome in older adults. Hematuria is not present in this condition.

Vasculitis

Vasculitis is the inflammation of the small blood vessels of the kidney. The three causes of vasculitis that you’ll see in some fashion on the PANCE are Wegener’s granulomatosis, Goodpasture’s disease, and Churg-Strauss syndrome. Recognize that because these conditions inflame blood vessels in addition to the kidney, they can affect other body systems as well.

  • Wegener’s granulomatosis: Wegener’s granulomatosis is associated with the triad of sinusitis, hemoptysis, and kidney involvement. It has a positive anti-neutrophilic cytoplasmic antibody (c-ANCA) more than 80 percent of the time. On kidney biopsy, it shows a “pauci-immune necrotizing vasculitis.” Note that this is a key phrase you may see on the test to help clue you in to the diagnosis.

  • Goodpasture’s disease: Goodpasture’s disease presents with both hemoptysis and acute kidney failure. It’s associated with a positive antiglomerular basement membrane (anti-GBM) antibody. On kidney biopsy, Goodpasture’s shows “linear deposition of IgG along the kidney basement membrane” — this is a key phrase you may see on the test. The treatment can involve steroids and cyclophosphamide (Cytoxan); in addition, plasmapheresis is used.

  • Churg-Strauss syndrome: The typical presentation for Churg-Strauss syndrome is an asthma that keeps relapsing after the patient has finished a course of treatment with steroids. Also, expect a very high serum eosinophil count. In addition to the kidneys and lungs, Churg-Strauss can affect the heart.

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