Intrinsic acute kidney injury (glomerular causes): Clinical sciences

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Introduction0:00–0:34

Intrinsic acute kidney injury or AKI refers to a sudden decline in kidney function that results in electrolyte imbalances, extracellular dysregulation, and the accumulation of nitrogenous waste, such as ammonia and uric acid.
The underlying cause of intrinsic AKI can be glomerular, which involves damage to the glomerulus; and non-glomerular, which affects renal components like tubules or the interstitium.

Unstable Patient0:34–1:13

If your patient presents with chief concerns suggesting AKI, first, perform an ABCDE assessment to determine if they’re unstable or stable.
If unstable, stabilize their airway, breathing, and circulation. Next, obtain IV access, which might include dialysis access, and put your patient on continuous vital sign monitoring and cardiac telemetry.
Finally, if you identify hyperkalemia, metabolic acidosis, volume overload, or symptomatic uremia, start emergent hemodialysis!

Stable Patient1:13–2:10

Now, let’s go back and take a look at stable patients. First, obtain a focused history and physical exam, which usually reveals nonspecific signs and symptoms.
For example, history might reveal reduced urine output, bloody urine, or systemic symptoms, like fatigue, malaise, and fever.
Additionally, patients might report taking nephrotoxic medications or having chronic conditions, like systemic lupus erythematosus or malignancy.
Similarly, the physical exam is nonspecific and might reveal blood pressure abnormalities, rash, or periorbital and peripheral edema.
In this case, suspect intrinsic AKI, so be sure to order a basic metabolic panel and urinalysis with microscopy, assess the patient’s urine output over time, and check renal ultrasound!
In all types of AKI, labs will reveal a rise in serum creatinine of 0.3 milligrams per deciliter or more over 48 hours; a rise of serum creatinine 1.5 times the baseline or more in the last 7 days, or urine output less than 0.5 milliliters per kilogram per hour for six hours.

Labs2:10–4:34

However, with intrinsic AKI, the BUN-to-Cr ratio will be less than 20 to 1, and urine sodium will be greater than 20 milliequivalents per liter.
Next, calculate the fractional excretion of sodium, or FENa for short, to check the percentage of sodium filtered by the kidneys into the urine.
Divide the product of urinary sodium and serum creatinine by the product of urinary creatinine and serum sodium and multiply the dividend by 100.
In intrinsic AKI, kidneys fail to reabsorb the sodium from filtered urine, meaning more sodium gets excreted, so the FENa will be greater than 2 percent.
Now, here’s a clinical pearl! In contrast to intrinsic AKI, in prerenal AKI, the kidneys filter less sodium to maintain intravascular volume.
In other words, the FENa will be below 1%. Remember, FENa is not reliable in oliguric individuals with chronic kidney disease because this condition is associated with an impaired ability to concentrate urine and varying baseline plasma sodium levels.
In other words, FENa will not adequately reflect the changes in acute kidney injury. Similarly, FENa is not reliable in oliguric patients who are taking diuretics because these medications promote sodium excretion and can give falsely high FENa values.
Additionally, urinalysis and microscopy often reveal RBC casts, WBC casts, or tubular epithelial casts. Finally, if the renal ultrasound shows normal kidneys and parenchyma with no hydronephrosis, you can diagnose intrinsic AKI, which can occur due to glomerular and non-glomerular causes.

Proliferative glomerulonephritis4:34–6:02

Now, let’s focus on glomerular causes, which include proliferative glomerulonephritis and non-proliferative glomerulonephropathy!
Patients with proliferative glomerulonephritis typically report fever, joint pain, and frankly bloody or dark-colored urine.
Next, the exam will reveal facial or peripheral edema and hypertension, while the urinalysis with microscopy will reveal hematuria, dysmorphic RBCs, and RBC casts.
With these findings, diagnose proliferative glomerulonephritis, more specifically, a nephritic pattern of glomerular injury.
Here’s a clinical pearl! Proliferative glomerulonephritis typically presents with a nephritic pattern of injury.
However, in severe cases, patients might present with nephrotic syndrome, characterized by massive proteinuria and hypoalbuminemia.
Now, to assess the specific type, order additional labs, including CBC, complement C3 and C4, and cryoglobulins. Also, test for autoantibodies, including c-ANCA-, p-ANCA-, anti-glomerular basement membrane-, antinuclear-, and anti-double stranded DNA antibodies.
Finally, order a renal biopsy and assess underlying causes. First, let’s focus on IgA nephropathy, also called Berger disease, which is associated with recurrent episodes of hematuria.

IgA Nephropathy6:02–7:00

Patients might also report a recent upper respiratory infection or a history of liver- or celiac disease. If renal biopsy reveals mesangial deposits of IgA along the basement membrane, diagnose IgA nephropathy.
Treatment focuses on supportive care for AKI. If there’s hypovolemia, start intravenous hydration, and if there’s volume overload, stimulate diuresis with diuretics.
In severe cases, you can begin dialysis to manage potassium, urea, and acid base balance until the kidneys recover. Also, correct any electrolyte disturbances and be sure to control blood pressure.
Finally, don’t forget glucocorticoids for refractory cases. Next up is anti-glomerular basement membrane disease, formerly called Goodpasture syndrome, which is associated with the deposition of anti-GBM antibodies along the glomerular basement membrane.

Anti-GBM Disease7:00–8:03

As a result, the immune system impairs glomerular filtration, causing symptoms like reduced urine output. Remember, these antibodies can also deposit along the alveolar membrane and cause dyspnea, cough, and even massive hemoptysis.
If labs reveal positive anti-GBM antibodies, and the renal biopsy shows linear IgG deposition along the glomerular basement membrane, diagnose anti-GBM disease.
Treatment includes supportive care, glucocorticoids, and immunosuppressants like cyclophosphamide. Finally, if there’s acute hemoptysis or hematuria, consider plasmapheresis to remove circulating antibodies.

Immune-complex mediated proliferative glomerulonephritis8:03–9:41

Moving on to immune complex-mediated proliferative glomerulonephritis. These patients often have a history of a chronic infection, like hepatitis B or C, or HIV; or autoimmune conditions, such as systemic lupus erythematosus.
Labs may reveal low C3 and C4 levels and positive ANA, anti-double-stranded DNA antibodies, or cryoglobulins. With these findings, suspect immune complex-mediated proliferative glomerulonephritis and assess biopsy findings.
If the biopsy reveals mesangial hypercellularity and basement membrane thickening, often described as a tram-track pattern, diagnose membranoproliferative glomerulonephritis.
However, if the biopsy reveals mesangial and endocapillary hypercellularity with a “wire-loop” glomerular capillary appearance, diagnose diffuse proliferative glomerulonephritis.
In both cases, treatment includes supportive care, treating the underlying condition, sometimes in combination with glucocorticoids or immunosuppressants like cyclophosphamide or mycophenolate mofetil.
Now, here’s a clinical pearl! Any patient with glomerulonephritis can develop rapidly progressive crescentic glomerulonephritis, which can quickly progress to end-stage renal disease.
In this case, the biopsy will reveal crescent-shaped glomerular deposits. Next, let’s discuss ANCA-associated vasculitis.

ANCA-Associated vasculitis9:41–12:15

This disease is associated with nonspecific symptoms like fever, malaise, muscle or joint pain, and unintentional weight loss.
If the labs reveal positive c-ANCA or p-ANCA antibodies, suspect ANCA-associated vasculitis and assess underlying causes.
First, let’s focus on granulomatosis with polyangiitis, previously known as Wegener granulomatosis, which is associated with inflammation of small- and medium-sized blood vessels.
In addition to the kidneys, inflammation often affects the upper respiratory tract, causing sinusitis and epistaxis, but also the lower respiratory tract, causing cough and hemoptysis.
If the labs reveal positive c-ANCA antibodies, and the biopsy shows necrotizing granulomatous inflammation with pauci-immune features, characterized by minimal or no immunoglobulin or complement deposition.
If you see these findings, diagnose granulomatosis with polyangiitis. Next, microscopic polyangiitis is associated with inflammation of small-sized blood vessels, which can affect the lower respiratory tract and cause symptoms like cough and hemoptysis.
If the labs are positive for p-ANCA and the renal biopsy reveals necrotizing non-granulomatous inflammation with pauci-immune features, diagnose microscopic polyangiitis.
Finally, eosinophilic granulomatosis with polyangiitis affects small- and medium-sized blood vessels. These patients report a new onset of asthma or rhinosinusitis, while the exam usually reveals skin nodules.
If the labs reveal eosinophilia, with or without positive p-ANCA antibodies, and the biopsy shows microgranulomas, eosinophilic infiltrates, and pauci-immune features, diagnose eosinophilic granulomatosis with polyangiitis.
In all types, treatment includes supportive care, glucocorticoids, and immunosuppressants like methotrexate, cyclophosphamide, or rituximab.
In patients who are presenting with hemoptysis or hematuria, you can also consider plasmapheresis. Now, let’s switch gears and discuss non-proliferative glomerulonephropathy.

Non-proliferative glomerulonephropathy12:15–13:20

During history, you may find unintentional weight gain and foamy urine. On the exam, you will typically identify periorbital or peripheral edema, and sometimes hypertension.
If the urinalysis reveals massive proteinuria greater than 3 grams per 24 hours, diagnose non-proliferative glomerulonephropathy, more specifically, a nephrotic pattern of glomerular injury.
This type of glomerular injury is commonly seen in focal segmental glomerulosclerosis and membranous nephropathy. Next, order a renal biopsy.
Here’s a clinical pearl! Non-proliferative glomerulonephropathy typically presents with a nephrotic pattern of injury.
However, in severe cases, these patients might present with nephritic syndrome, which is characterized by oliguria, hematuria, and hypertension.
If the biopsy reveals focal segmental sclerosis with the fusion of podocyte processes, diagnose focal segmental glomerulosclerosis.

Focal Segmental Glomerulosclerosis13:20–13:46

Management includes supportive care and glucocorticoids, with or without immunosuppressants like calcineurin inhibitors, mycophenolate mofetil, or rituximab.
However, if the biopsy reveals diffuse capillary and glomerular basement membrane thickening without hypercellularity, along with the “spike and dome” appearance of a new extracellular matrix, diagnose membranous nephropathy.

Membranous Nephropathy13:46–14:15

In this case, treatment includes supportive care, glucocorticoids, and immunosuppression with either cyclophosphamide or rituximab.
Alright, as a quick recap… Glomerular causes of intrinsic AKI can be subdivided into proliferative glomerulonephritis, which include conditions like IgA nephropathy, anti-GBM disease, immune complex-mediated glomerulonephritis, and ANCA-associated vasculitis; and non-proliferative glomerulopathies, such as focal segmental glomerulosclerosis and membranous nephropathy.

Review14:15–14:52

In most cases, the management primarily relies on supportive care, treating the underlying cause, glucocorticoids, and immunosuppressants.