Renal Pathology Practice Questions

Q: Dent disease is due to a defect in which of the following channels?

Chloride channel. **Explanation:** **Dent disease** is an X-linked recessive disorder characterized by proximal renal tubular dysfunction (Fanconi syndrome), hypercalciuria, nephrocalcinosis, and progressive renal failure. 1. **Why Chloride Channel is correct:** The disease is primarily caused by mutations in the **CLCN5 gene**, which encodes the **ClC-5 chloride channel**. This channel is a chloride/proton antiporter located in the endosomes of proximal tubular epithelial cells. It is essential for maintaining the acidic environment required for endocytosis. A defect in ClC-5 impairs the reabsorption of low-molecular-weight proteins (like $\beta$2-microglobulin), leading to the hallmark clinical finding of **low-molecular-weight proteinuria**. 2. **Why other options are incorrect:** * **Sodium channel:** Defects in the ENaC (epithelial sodium channel) lead to Liddle syndrome (gain of function) or Pseudohypoaldosteronism type 1 (loss of function). * **Potassium channel:** Mutations in ROMK (renal outer medullary potassium channel) are associated with Type II Bartter syndrome. * **Calcium channel:** While Dent disease causes hypercalciuria and nephrocalcinosis, the primary molecular defect is not in a calcium channel, but rather a secondary consequence of tubular dysfunction. **High-Yield Clinical Pearls for NEET-PG:** * **Inheritance:** X-linked Recessive (affects males). * **Classic Triad:** Low-molecular-weight proteinuria, hypercalciuria, and nephrocalcinosis/nephrolithiasis. * **Genetics:** **CLCN5** (Dent Disease 1) or **OCRL1** (Dent Disease 2; also associated with Lowe syndrome). * **Distinction:** Unlike other causes of nephrocalcinosis, Dent disease specifically presents with proteinuria consisting of proteins smaller than albumin.

Q: Most common mutation in Alport syndrome is in COL4A5, which is transmitted as?

X-linked. **Explanation:** Alport Syndrome is a hereditary nephritis caused by mutations in the genes encoding the **Type IV collagen** chains, which are essential components of the glomerular basement membrane (GBM), cochlea, and lens [1]. **1. Why X-linked is correct:** The most common form of Alport Syndrome (approximately **80% of cases**) is caused by a mutation in the **COL4A5** gene, located on the **X chromosome** [1]. This gene encodes the $\alpha$5 chain of Type IV collagen. Because it is X-linked, males are typically more severely affected, often progressing to end-stage renal disease (ESRD), while females are often carriers with milder symptoms (like isolated hematuria) [1]. **2. Why other options are incorrect:** * **Autosomal Recessive (Option B):** This accounts for about 15% of cases and involves mutations in **COL4A3 or COL4A4** (located on Chromosome 2). It presents with early-onset renal failure in both genders. * **Autosomal Dominant (Option A):** This is the rarest form (approx. 5%) and also involves mutations in **COL4A3 or COL4A4**, but follows a dominant inheritance pattern with slower progression. * **Variable (Option D):** While Alport syndrome is genetically heterogeneous, the specific question asks for the transmission of the **COL4A5** mutation, which is strictly X-linked. **High-Yield Clinical Pearls for NEET-PG:** * **Classic Triad:** Hereditary nephritis (hematuria/ESRD), Sensorineural deafness, and Ocular defects (e.g., **Anterior Lenticonus**). * **Electron Microscopy (Gold Standard):** Shows characteristic **"Basket-weave appearance"** due to irregular thickening, thinning, and splitting of the lamina densa. * **Immunofluorescence:** Shows a "negative" or "loss of expression" for $\alpha$3, $\alpha$4, and $\alpha$5 collagen chains in the GBM [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Kidney, pp. 929-930.

Q: Alport syndrome is due to defective-

Collagen. **Explanation:** **Alport Syndrome** is a hereditary nephropathy caused by mutations in the genes encoding the **Type IV collagen** chains (specifically α3, α4, or α5) [1]. Type IV collagen is a crucial structural component of the basement membranes in the glomerulus, the cochlea, and the lens of the eye. 1. **Why Collagen is Correct:** The defect leads to an abnormal glomerular basement membrane (GBM). Under electron microscopy, this manifests as a characteristic **"basket-weave" appearance** due to irregular thinning and thickening with longitudinal splitting of the lamina densa. 2. **Why other options are incorrect:** * **Elastin:** Defects in elastin are associated with conditions like Williams syndrome or cutis laxa, not Alport syndrome. * **Fibrillin:** Mutations in Fibrillin-1 lead to **Marfan Syndrome**, characterized by skeletal, ocular (ectopia lentis), and cardiovascular issues. * **Proteoglycan:** While proteoglycans are part of the extracellular matrix, they are not the primary structural defect in Alport syndrome. **High-Yield Clinical Pearls for NEET-PG:** * **Inheritance:** Most commonly **X-linked Dominant** (COL4A5 mutation) [1]. * **Classic Triad:** 1. **Hereditary Nephritis:** Progressing to end-stage renal disease (ESRD) [1]. 2. **Sensorineural Hearing Loss:** Bilateral, high-frequency [1]. 3. **Ocular Defects:** Anterior lenticonus (pathognomonic) and maculopathy. * **Diagnosis:** Electron microscopy is the gold standard (Basket-weave appearance). Immunohistochemistry showing absence of α5 collagen staining in the GBM can also be helpful [1]. * **Note:** If the question asks for the specific collagen type, it is **Type IV** ("Can't see, can't pee, can't hear a high-C"). **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Kidney, pp. 929-930.

Question 1

An adult patient presents with normal or enlarged kidneys and massive proteinuria. What is the most likely cause?

Accepted Answer

Amyloidosis

Answer

Chronic pyelonephritis

Answer

Chronic glomerulonephritis

Answer

Renal artery stenosis

Question 2

Dent disease is due to a defect in which of the following channels?

Accepted Answer

Chloride channel

Answer

Sodium channel

Answer

Potassium channel

Answer

Calcium channel

Question 3

Most common mutation in Alport syndrome is in COL4A5, which is transmitted as?

Accepted Answer

X-linked

Answer

Autosomal dominant

Answer

Autosomal recessive

Answer

Variable, autosomal dominant or autosomal recessive

Question 4

Alport syndrome is due to defective-

Accepted Answer

Collagen

Answer

Elastin

Answer

Fibrillin

Answer

Proteoglycan

Question 5

Which of the following conditions is characterized by Type III Rapidly Progressive Glomerulonephritis (RPGN)?

Accepted Answer

Granulomatosis with polyangitis

Answer

Systemic Lupus Erythematosus (SLE)

Answer

IgA nephropathy

Answer

Cryoglobulinemia

Question 6

Medullary cystic disease of the kidney is best diagnosed by:

Accepted Answer

Biopsy

Answer

Ultrasound

Answer

Nuclear scan

Answer

Urography

Question 7

What is the most common lesion in diabetic nephropathy?

Accepted Answer

Diffuse glomerulosclerosis

Answer

Fibrin caps

Answer

Capsular drops

Answer

Kimmelstiel Wilson nodule

Question 8

Salt losing nephritis is most commonly due to which of the following conditions?

Accepted Answer

Interstitial nephritis

Answer

Lupus nephritis

Answer

Streptococcal infection

Answer

Goodpasture's syndrome

Question 9

A 74-year-old man presents with fatigue, shortness of breath on exertion, and back and rib pain, which is made worse with movement. Investigations reveal he is anemic, calcium, urea, and creatinine are elevated. X-rays reveal multiple lytic lesions in the long bones and ribs, and protein electrophoresis is positive for an immunoglobulin G (IgG) paraprotein. Which of the following is the most likely mechanism for the renal injury?

Accepted Answer

Tubular damage by light chains

Answer

Plasma cell infiltrates

Answer

Glomerular injury

Answer

Vascular injury by light chains

Question 10

A 37-year-old man develops pulmonary hemorrhage and glomerulonephritis. Lung biopsy with immunofluorescence demonstrates IgG deposition along the basement membrane. These antibodies are most likely directed against which of the following types of collagen?

Accepted Answer

Type IV

Answer

Type I

Answer

Type II

Answer

Type III

Renal Pathology — MCQs

Renal Pathology — MCQs

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