Week 4

Question 1

A 58 year-old patient presents with intense thirst and urine output exceeding 3L/day. The patient has a history of bipolar disorder but no history of diabetes. His serum osmolality is 300 mOsm/kg. On urinalysis his urine specific gravity is 1.0002 and his urine osmolality is 500 mOsmol/kg. After 2-3 hours with no intake of water his serum Na is measured to be 147 mEQ/L, he is given vasopressin and there is no change in urine osmolality after administration. What is the most likely diagnosis for this patient?

1. Central Diabetes insipidus
2. Nephrogenic Diabetes insipidus
3. Primary polydipsia
4. SIADH
5. Urea diuresis

Answer 1

• SM 219: Hypernatremia*
• Learning Objectives covered:*
• 6. Explain that except for hypertonic Na gain, all other hypertonic hypernatremias result from H20 deprivation in the setting of persistent H20 or hypotonic losses [MKS 1a]*
• 7. Explain the differential diagnosis of hypertonic hypernatremia [MKS 1a]*

The correct answer is B. The low urine specific gravity and urine osmolality < 600 mosmol/kg indicate an inability to concentrate urine. Thus, the patient’s polyuria is most likely due to water diuresis. The high serum osmolality points toward diabetes insipidus. The no change in urine osmolality after the water deprivation test with vasopressin administration make nephrogenic DI the most likely diagnosis. Nephrogenic DI is due to a failure to respond to circulating ADH by the kidneys.

A is not correct. In central DI the ADH level is low since it is caused by lack of circulating ADH. After the water deprivation test, the urine osmolality should increase by greater than 50% as the patient responds to the vasopression (ADH analog).

C is not correct. In primary polydipsia, the patient is drinking excessive amounts of water leading to polyuria. In this case patients will have a low serum osmolality due to water overload.

D is not correct. In SIADH the body retains water due to inappropriately high levels of ADH.

E is not correct. Solute diuresis can also cause polyuria as the body gets rid of a solute. This can be seen in diabetic patients with severe hyperglycemia and glucosuria for example. In solute diuresis the urine osmolality is usually greater than 600 mosmol/kg since the body is able to concentrate urine appropriately. Urea diuresis usually happens when urea is given as a therapy for hyponatremia, from glucocorticoid therapy (tissue catabolism), or from a high protein diet.

Question 2

A 20-year-old woman who is in the third trimester has felt minimal fetal movement. Ultrasound shows a markedly decreased amniotic fluid index characteristic of oligohydramnios. She gives birth to a stillborn male fetus.

At autopsy, the fetus has flattening of the facies, deformities of the feet, and pulmonary hypoplasia. The liver shows multiple epithelium-lined cysts and a proliferation of bile ducts. Which of the following best describes the appearance of the kidneys in this fetus?

1. No kidneys
2. Bilaterally enlarged kidneys replaced by 1 to 4 cm, fluid filled cysts
3. Bilaterally shrunken kidneys with uniformly finely granular cortical surfaces
4. Decreased size of right kidney (with cysts and cartilage seen) with normal left kidney
5. Symmetrically enlarged kidneys composed of small radially arranged cysts

Answer 2

• SM 216: Genetic Cystic Disease*
• Learning objective covered: 3. Describe the pathogenesis of cystic diseases of the kidney. MKS 1b*

The correct answer is E). The fetus presented with Potter sequence, which is caused by oligohydramnios (decrease amniotic fluid) leading to the fetus becoming compressed. The fetus will have a flat face with low set ears, defects of the extremities, and lung hypoplasia, leading to a still birth. Potter sequence is associated with bilateral renal agenesis, bilateral dysplastic kidney disease, and autosomal recessive polycystic kidney disease.

In this case, the fetus had autosomal recessive polycystic kidney disease because of the evidence of congenital hepatic fibrosis (proliferation of bile ducts in the liver) and hepatic cysts. Thus the kidneys should be symmetrically enlarged with small radially arranged cysts. Autosomal recessive PKD is associated with a mutation in the PKHD1 gene.

1. is not correct. Although bilateral renal agenesis leads to the Potter sequence, it is not associated with congenital hepatic fibrosis and hepatic cysts.
2. Is not correct. Bilaterally enlarged kidneys with 1 to 4 cm fluid filled cysts is more typical of the autosomal dominant form of polycystic kidney disease, with presents in young adults as hypertension, hematuria, and worsening renal failure. Autosomal dominant PKD is caused by a mutation in the APKD1 or APKD2 gene.
3. Is not correct. This type of bilaterally shrunken kidney is associated with end state renal disease in adults
4. Is not correct. Decreased size of a kidney unilaterally with cysts and cartilage is seen with dysplastic kidney. Unilateral dysplastic kidney is noninherited and not associated with Potter sequence.

Question 3

A 7 year old girl presents to your clinic with increasing fatigue in the last few weeks and puffiness around her eyes. Her temperature is 36.8 °C, her blood pressure is 106/72, and her respiratory rate is 22 breaths/min. Her laboratory findings show serum creatinine of 0.7 mg/dL, blood urea nitrogen level of 12 mg/dL, and albumin of 3.4 g/dL. On urinalysis she has a pH of 6, specific gravity of 1.008, 4+ proteinuria, with no blood, glucose, ketones, or leukocytes. Which of the following is most likely to be seen on electron microscopy?

A) Thinning and splitting of the basement membrane

B) Effacement of podocyte foot processes

C) subepithelial “spike and dome” deposits

D) subepithelial “humps”

Answer 3

SM 218: Pediatric Nephrology

Learning objectives covered:

2. List the most common causes/conditions leading to CKD in the pediatric population, and describe how this list differs from the same list in adult patients with CKD. (MKS 1a)
3. Form a differential/be able to perform initial investigation of common kidney-related pediatric complaints (hematuria, proteinuria, UTI). (MKS 1a)

The correct answer is B. The pediatric patient is presenting with nephrotic syndrome as evidenced by nephrotic range 4+ proteinuria, hypoalbuminemia, edema (puffy eyes), and hypoalbuminemia. She also does not have hematuria, hypertension, or azotemia. The most common cause of nephrotic syndrome in pediatric patients is minimal change disease, where the treatment is corticosteroids.

A is not correct. Thinning and splitting of the basement membrane is seen in Alport syndrome, and inherited defect in type IV collagen. This usually presents as hematuria with sensory hearing loss and ocular disturbances.

C is not correct. Subepithelial “spike and dome” deposits are seen in membranous nephropathy due to immune complex deposition. If the patient is not responsive to steroids after 4 weeks, then membranous nephropathy would be higher on the differential.

D is not correct. Subepithelial “humps” are seen in post-streptococcal glomerulonephritis (PSGN), which is the most common glomerulonephritis seen in children. The patient with PSGN would present with hematuria 2-3 weeks after infection, hypertension, low urine output and periorbital edema.

Question 4

A 5 year old patient presents to the clinic with one month of abdominal pain and nausea and vomiting. Her temperature is 38.1 °C. There is a tender palpable mass on her left side and abdominal CT also shows a solid mass in her left kidney. Her urinalysis shows hematuria with no glucose. What is the most likely diagnosis for this patient?

A) nephropathic cystinosis

B) primary hyperoxaluria

C) Wilms tumor

D) autosomal dominant polycystic kidney disease

Answer 4

• SM 218: Pediatric Nephrology*
• Learning objectives covered:*
• 2. List the most common causes/conditions leading to CKD in the pediatric population, and describe how this list differs from the same list in adult patients with CKD. (MKS 1a)*
• 3. Form a differential/be able to perform initial investigation of common kidney-related pediatric complaints (hematuria, proteinuria, UTI). (MKS 1a)*

The correct answer is C. Wilm’s tumor is the most common renal cancer in children, usually occurring between 2-5 years of age. The clinical presentation of fever, abdominal pain, nausea, and vomiting are typical of Wilm’s tumor. Treatment is nephrectomy.

A is not correct. Nephropathic cystinosis is an autosomal recessive lysosomal storage disorder leading to cystine accumulation within cells. It usually presents as Fanconi Syndrome (reabsorption defect in PCT) and polyuria (excessive urine output) with associated eye and thyroid problems. Of note, cytinosis is different from cystinuria, another autosomal recessive disease.

B is not correct. Primary hyperoxaluria is caused by a mutation in the AGXT gene expressed in the liver. Calcium oxalate stones, nephrocalcinosis, and deposits of oxalate in other organs such as the skin, skeletal muscle, and retina are usually seen. It is also associated with malabsorption. The treatment is both liver and kidney transplants.

D is not correct. In ADPKD macrocysts develop in the kidney, and the age of presentation is usually in adulthood.

Question 5

A 45 year old patient has IgA nephropathy, anemia, and a GFR of 50. Which of the following mechanisms in the pathogenesis of his chronic kidney disease is most likely not amplified/worsened by his anemia?

1. Decreased Vitamin D metabolism
2. Increased hypoxia-inducible factors
3. Generation of reactive-oxygen species
4. Acidosis

Answer 5

• SM 213: Chronic Kidney Disease Pathophysiology*
• Learning objective covered: 3. Explain how this adaptive physiology places new demands on structure and function that may perpetuate or even accelerate further nephron loss. (MKS1a, MKS1b)*

The correct answer is A. Vitamin D metabolism is inhibited in chronic kidney disease, which can lead to dysfunction in calcium regulation and bone disease. Vitamin D metabolism is most likely to not be affected by anemia. Anemia increases the risk of renal hypoxia in chronic kidney disease since the kidney is more likely to be poorly perfused while the oxygen demand per nephron increases.

B is incorrect. Renal hypoxia leads to the production of hypoxia-inducible factors that can promote fibrosis leading to tissue dysfunction and nephron loss.

C is incorrect. Renal hypoxia can also lead to the generation of reactive oxygen species that can cause tissue damage

D is incorrect. Renal hypoxia promotes more anaerobic metabolism leading to acidosis, which increases complement system activation and reactive oxygen species formation.

Question 6

An African American patient with diabetes presents to the clinic for a follow-up visit. Her most recent HbA1C was 7%. Her blood pressure is 142/94. She is currently not taking any medications. What is the best option for management of this patient?

1. More blood glucose control with metformin
2. A calcium channel blocker
3. Recommend changes in her diet and more exercise
4. An ACE-inhibitor and ARB combination
5. Start her on an ACE-inhibitor or an ARB

Answer 6

• SM 215: Diabetic Nephropathy*
• Learning Objectives covered:*
• 6. Describe the key components of treatment of diabetic nephropathy. (MKS1e)*

The correct answer is E. The 2017 ACC/AHA guidelines recommend a blood pressure target <130/80 for patients with diabetes. The optimal blood pressure medication in this case is an ACE-inhibitor or an ARB since by decreasing angiontensin II, glomerular filtration pressure is decreased, reducing hyperfiltration injury. These agents may also reduce fibrosis by decreased expression of certain factors such as TGF- beta.

A is not correct. Her HbA1C is already in the target range so adding metformin is not the best option.

B is not correct. An ACE-I or ARB better preserves GFR as compared to a calcium channel blocker.

C is not correct. Changes in her diet and increased exercise may help lower her blood pressure, but in this case a renoprotective blood pressure medication to control her blood pressure are warranted and the first-line treatment.

D is incorrect. A combination of ACE-I and ARB has shown to lead to more AKI and hyperkalemia and thus is not recommended.

Question 7

A 62 year old patient was diagnosed with Type II diabetes 15 years ago. She underwent a kidney biopsy after 120 mg of albumin/24 hours was detected in her urine. Which of the following most accurately describes the pathogenesis of the kidney disease seen in her biopsy?

Image courtesy of : http://www.ndt-educational.org/ferrariodiabete.html

1. Immune complex deposition
2. Hyperfiltration-induced damage
3. Amyloid deposits in the mesangium
4. Thinning of the basement membrane

Answer 7

SM 215: Diabetic Nephropathy

• Learning objectives covered:*
• 2. Describe the histopathologic manifestations of diabetic nephropathy. (MKS1b)*
• 3. Explain the natural history and clinical stages of diabetic nephropathy. (MKS1d)*
• 4. Explain the historical features, clinical symptoms, and laboratory findings one would expect in a patient with diabetic*
• nephropathy. (MKS1d)*
• 5. Describe key factors thought to be involved in pathogenesis of diabetic nephropathy. (MKS1b)*

The correct answer is B. The patient’s medical history and microalbuminuria is highly suggestive of diabetic nephropathy. The pathogenesis of diabetic nephropathy happens in three phases. In the first phase, high serum glucose leads to nonenzymatic glycosylation of the basement membrane which leads to hyaline arteriolosclerosis, with the efferent arteriole being more affected. There is also hyperfiltration due to vasodilation of the afferent arteriole and vasoconstriction of the efferent arteriole. Hyperfiltration injury then leads to microalbuminuria. As the diseases progresses, sclerosis of the mesangium develops. These are also known as Kimmelstiel-Wilson nodules and are seen when mesangial matric expansion occurs in a nodular pattern during the microalbuminuria stage.

A is incorrect. While a diffuse or nodular pattern of mesangial expansion and a thickening of the basement membrane can be seen in membranoproliferative glomerulonephritis which is caused by immune complex deposition, the patient’s clinical history is more suggestive of diabetic nephropathy. In MPGN we also expect to see granular immunofluorescence.

C is incorrect. While systemic amyloidosis can lead to amyloid deposits in the mesangium, the clinical presentation of the patient is more suggestive of diabetic nephropathy. An apple-green birefringence pattern after staining with Congo Red would also be expected.

D is incorrect. In diabetic nephropathy, thickening of the glomerular basement membrane is seen, not thinning. The podocytes may become fused. Thinning of the basement membrane cane be seen in Alport syndrome due to a defect in type IV collagen.

Question 8

A 36 year old man is awakened at night with severe pain on his left flank that radiates to the groin and comes in waves. The next morning he notices blood in his urine. On physical examination, he is afebrile and has a blood pressure of 110/70 mmHg. Labs show: serum Na+ 142mmol/L; K+ 4 mmol/L; Cl= 96mmol/L; CO2 25 mmol/L, glucose 74 mg/dL, creatinine 1.1mg/dL; calcium 9.1 mg/dL, phosphorus 2.9 mg/dL.

UA shows a pH of 7, specific gravity of 1.020, no protein, glucose, ketones, or nitrite.

Which of the following substances is most likely to be increased in concentration in his urine?

A) Calcium oxalate

B) cysteine

C) magnesium ammonium phosphate

D) mucoprotein

E) Uric acid

Answer 8

• SM 217: Kidney Stones*
• Learning Objective:*
• 1. Describe the epidemiology of kidney stones and identify the most common types of kidney stones. (MKS 1f)*

The correct answer is A. This patient’s is presenting with symptoms typical of nephrolithiasis (kidney stones). He has unilateral flank pain that radiates to the groin, and blood in his urine. Meanwhile, his labs are all normal, ruling out some other causes of abdominal pain related to the kidney, such as pyelonephritis.

Nephrolithiasis is caused by supersaturation of certain ions in the urine leading to precipitation and stone formation. In this case, while there are different types of stones, calcium stones more particularly calcium oxalate stones are the most common type of kidney stone. Thus, the patient is most likely to have increased concentration of calcium oxalate in his urine and a calcium oxalate stone. Hypercalciuria can be caused by systemic hypercalcemia (such as from primary hyperparathyroidism) but the most common cause is idiopathic with normal serum calcium levels.

B) is incorrect because cystine stones are a rare cause of nephrolithiasis. They are most commonly seen in children with cystinuria due to a genetic defect.

C) is incorrect because magnesium ammonium phosphate or struvite stones are the second most common type of kidney stone. The most common cause is infection with urease-positive organisms such as Proteus bacteria.

D) is incorrect because mucoprotein in the urine can lead to hyaline casts and is not associated with nephrolithiasis.

E) is incorrect because uric acid stones are the third most common type of kidney stone. Uric acid stones are radiolucent and a risk facter is hyperuricemia.

Question 9

A 64 year old man with a 20 year history of alcohol abuse presents with new onset nausea and vomiting, a headache, and altered mental status. On physical exam, the patient has a fluid-filled abdomen and peripheral edema. His serum sodium is 126 mmol/L. What is the most likely type of sodium disturbance, and the best treatment?

1. Hypovolemic hyponatremia; stopping diuretics and giving 0.9% saline
2. Euvolemic hyponatremia; exogenous ADH
3. Hypervolemic hyponatremia; liver transplant
4. SIADH; ADH antagonist
5. Diabetes Insipidus; desmopressin

Answer 9

• SM 214: Hyponatremia*
• Learning objectives covered:*
• Explain the differential diagnosis of hypotonic hyponatremia [MKS 1a]*
• Discuss the basic strategy for treatment of hypotonic hyponatremia [MKS 1d]*

The correct answer is C) hypervolemic hyponatremia. The patient’s symptoms of sudden onset nausea and headache are typical of hyponatremia. The patient’s history of alcohol abuse is a major risk factor for cirrhosis. The ascites and peripheral edema point to volume overload from portal hypertension. Thus, the patient most likely has hypervolemic hyponatremia. The best treatment in this case is a liver transplant.

A is not correct. The patient is not volume depleted and so does not have hypovolemic hyponatremia. Some causes of hypovolemic hyponatremia are Addison’s disease, excessive vomiting and diarrhea, diuretics (such as thiazide diuretics which inhibit NaCl reabsorption), and water loss from exercise. The treatment in this case would be stopping diuretics if that is the cause and giving 0.9% saline.

B is not correct. The patient does not have euvolemic hyponatremia, which can be caused by psychogenic polydipsia, potomania, thiazide diuretics, and SIADH. Exogenous ADH is not a treatment for euvolemic hyponatremia, but can cause SIADH as in small cell lung cancer.

D is not correct. SIADH leads to excessive free water retention and euvolemic hyponatremia with continued excretion of urinary Na. Some causes of SIADH include ectopic ADH from small cell lung cancer, CNS disorders/head trauma, pulmonary disease, and drugs such as cyclophosphamide. Treatment for SIADH include 0.9% saline, fluid restriction, and ADH receptor antagonists (conivaptan, tolvaptan).

E is not correct. Diabetes insipidus would cause hypernatremia not hyponatremia, since in DI the patient is unable to concentrate urine due to lack of ADH. Intranasal desmopression along with hydration would be the treatment of choice for central diabetes insipidus.

Question 10

A 64 year old patient in the hospital is increasingly thirsty and lethargic after several episodes of vomiting and diarrhea. His serum Na level is 155 mEq/L. The next day, after treatment with saline infusion and D5W, the patient has a new onset of headaches. His serum Na level is now 145 mEq/L. What has most likely happened in this patient?

1. Development of cerebral edema
2. Development of osmotic demyelination syndrome
3. Development of central diabetes insipidus
4. Development of hypotonic hyponatremia

Answer 10

• SM 219: Hypernatremia*
• Learning Objectives covered:*
• 7. Explain the differential diagnosis of hypertonic hypernatremia [MKS 1a]*
• 8. Describe the basic strategy for treatment of hypertonic hypernatremia [MKS 1d]*

The correct answer is A. The patient has hypertonic hypernatremia (serum Na level 155mEq/L) with thirstiness and lethargy due to non-polyuric causes (vomiting and diarrhea). In this case, treatment was too rapid (SNa decreased by greater than 8 mEq/L in 24 hours) and so the patient has developed cerebral edema as seen with the new onset headache.

B is incorrect. Osmotic demyelination syndrome with acute paralysis, dysphagia, and loss of consciousness is usually caused by correcting hyponatremia, not hypernatremia, too rapidly.

C is incorrect. Central diabetes insipidus can cause hypertonic hypernatremia and does not explain the patient’s clinical situation.

D is incorrect. While the patient’s correction of hypernatremia occurred too rapidly, the patient’s serum Na level is now at normal levels. The patient does not have hypotonic hyponatremia.