BRCU

Question 1

Presentation:
Gross hematuria - uniformly shaped red blood cells in greater than 100 cells per high power field

Papules on his face and neck - 1-3 mm in size and are nontender

Very slow learner and a poor student.

Imaging of his kidneys reveals some cystic change in both kidneys and a solid-looking vascular mass in the right kidney.

Answer 1

Tuberous sclerosis

Question 2

Star fruit

Answer 2

Associated with oxalate nephropathy

Question 3

Ephedra

Answer 3

Causes hypertension (HTN) and stones

Question 4

Glycerrhizic acid (sweetner)

Answer 4

Apparent” mineralocorticoid excess (AME)
- hypokalemia, HTN, and alkalosis

Question 5

Noni juice

Answer 5

Hyperkalemia

Question 6

Lead effect in kidney

Answer 6

Lead is a cation, and the organic cation transport (OCT) system (not the organic anion transporter) in the proximal tubule

Question 7

Cadmium affects what part of kidney

Answer 7

proximal tubule

Question 8

Metal that causes nephrotic syndrome from membranous disease

Answer 8

Gold

Question 9

______________ compounds cause acute tubular necrosis (ATN) through both apoptosis and necrosis, especially of the proximal tubule, and do not cause interstitial nephritis.

Answer 9

Platinum

Question 10

Urinary crystal has this hexagonal appearance
α-Mercaptopropionylglycine improves solubilization. This is an autosomal recessive disease, and the family needs to be educated

Answer 10

Cystinuria

Question 11

Tubulointerstitial nephritis and uveitis (TINU)
Sarcoid
Wegener’s
Crohn’s disease
Drug-induced acute interstitial nephritis
Tuberculosis (TB)
Behcet’s
and most drugs that result in classic acute interstitial nephritis (AIN)

Answer 11

Associated with granulomatous interstitial nephritis

Question 12

Tenofovir causes:

Answer 12

Proximal tubular injury with AKI and Fanconi syndrome, but Fanconi syndrome could manifest as a proximal RTA which does not lead to stone formation

Question 13

Hallmark on skin biopsy is septal panniculitis

Answer 13

Calcific uremic arteriolopathy

Question 14

Which genetic screening test is likely to detect a mutation in more than 5% of sporadic FSGS in adolescents?

Answer 14

Mutations in the NPHS2 (podocin) gene, including p.R229Q variant

Question 15

Multiple myeloma nephropathy will show:

Answer 15

Fractured tubular casts
Congo red–positive glomerular and tubular deposits
Acute tubular injury/necrosis
Plasma cell infiltrates

Question 16

Fibrillary GN 15 - 30 nm, random arrangement
Immunotactoid GN >30 nm, parallel arrays
Cryoglobulin GN 25-35 nm, curved microtubules
Amyloid 9 - 12 nm

Answer 16

Glomerular deposits characterization depends on three findings that help define the disease:
- Congo red staining
- Immune staining patterns, and
- the diameter of fibrils

Question 17

Which laboratory test would produce the highest yield in determining the role of immunoglobulins in a patient suspected to have a paraproteinemia?

Answer 17

The nephelometric assay for serum free light chains is the best test with highest sensitivity and specificity for a monoclonal gammopathy and thus is preferred over serum or urine immunofixation. Serum protein electrophoresis will miss cases due to its significantly lower sensitivity for monoclonal gammopathies. A kidney biopsy may provide the diagnosis, but it is preferable to confirm the possibility of a paraproteinemia before undertaking the kidney biopsy.

Question 18

31-year-old woman presented to the Emergency Department with severe headache and visual changes. She also described fatigue, a 7-lb weight loss, and low-grade fever for the last month. BP is 219/112 mm Hg in both arms and legs. Blurred optic disc margins and retinal hemorrhages are observed on eye exam. No abdominal bruits were noted. Labs: hemoglobin, 10.7 g/dL; platelet count, 225 × 1000/μl, and peripheral smear without schistocytes. Serum electrolytes: Na, 135 mEq/L; K, 3.1 mEq/L; and HCO3, 26 mEq/L. Blood urea nitrogen level was 45 mg/dL, and serum creatinine was 1.7 mg/dL. Urinalysis: specific gravity, 1.012; pH 6.0, trace protein. Urine microscopy: 2-5 granular casts/LPF and 2-5 RTE cells/HPF.

Answer 18

Classical polyarteritis nodosa (PAN)

Arteriogram demonstrates multiple aneurysms and irregular constrictions in the larger vessels with occlusion of smaller penetrating arteries in the kidneys consistent with PAN

Question 19

mineralocorticoid corticoid receptor mutation (Geller’s syndrome)

Answer 19

The mineralocorticoid corticoid receptor mutation (Geller’s syndrome) is a rare disorder that presents as severe hypertension with metabolic alkalosis and hypokalemia in young women during the second and third trimester of pregnancy when progesterone levels are highest. The mutation is transmitted by an autosomal dominant inheritance, and the MR 810 mutation is activated by progesterone (which blocks the normal aldosterone receptor but has the opposite effect in Geller syndrome), and thus the pregnant woman with this mutation will present like other causes of “apparent mineralocorticoid excess”: hypertension, hypokalemic metabolic alkalosis with suppressed renin, and aldosterone. Spironolactone (also normally an aldosterone receptor blocker) acts like progesterone in this condition in that it normally is also an aldosterone antagonist that becomes an agonist, thereby worsening hypertension and hypokalemia when administered. Urgent management during the third trimester of pregnancy often requires delivery, and subsequent management includes avoidance of spironolactone.

Question 20

Age 23, family history of hypertension. BP 170/100.
Serum sodium: 144 mEq/L
Serum potassium: 3.1 mEq/L
Serum chloride: 107 mEq/L
Serum bicarbonate: 29 mEq/L Serum creatinine: 1.1 mg/dL
Urine potassium: 89 mEq/24 hr
Plasma aldosterone: 6 ng/dL
Plasma renin activity: 0.5

Answer 20

Liddle’s syndrome

Gordon’s syndrome (pseudohypoaldosteronism type II) is typified by hyperkalemia and metabolic acidosis and would not fit this presentation. Gitelman’s syndrome is notable for the absence of hypertension.

The differential diagnosis for a patient with hypertension and renal potassium wasting (as in this case) includes primary aldosteronism (high aldo, low renin), glucocorticoid remediable aldosteronism (high aldo, low renin), malignant hypertension (high renin, high aldo), as well as other syndromes of apparent mineralocorticoid excess (Licorice, Cushing’s syndrome, and Liddle’s syndrome - all with low renin, low aldo as this patient has). The positive family history suggesting autosomal dominant suggests Liddle’s syndrome or glucocorticoid remediable hypertension, but the latter has a high aldosterone level not present in this case. The finding of a plasma aldosterone level of 6 excludes primary aldosteronism. Thus, Liddle’s syndrome is the most likely etiology.

Question 21

SCLC can produce ACTH which then causes hypokalemia, metabolic alkalosis, and hypertension.
How to treat:

Answer 21

Therapy is directed at the tumor, steroid synthesis inhibitors (ketoconazole, metyrapone, and octreotide), and mineralocorticoid receptor blockers/ epithelial sodium channel (eNaC) blockers.

Question 22

Causes:
Fanconi syndrome, with any combination of proximal renal tubular acidosis, glycosuria, potassium and phosphate wasting, nephrogenic diabetes insipidus, and AKI

Answer 22

Ifosfamide

Question 23

What medication is associated with a proximal RTA (and distal RTA) often with calcium phosphate stone formation from the latter.

Answer 23

Topiramate

Question 24

______________ is associated with urinary crystals and nephrolithiasis.

Answer 24

Atazanavir

Question 25

What diuretic is associated with with urinary crystals but not stones?

Answer 25

Triamterene

Question 26

Orlistat is associated with enteric _______ and ________.
crystals.

Answer 26

hyperoxaluria and urinary calcium oxalate crystals

Question 27

Pentamidine, like amiloride, triamterene, and trimethoprim, is associated with hyperkalemia by blocking the __________ in the ________part of the nephron.

Answer 27

epithelial sodium channel in the principal cell
cortical collecting duct

Question 28

Which drug has been associated with the development of lactic acidosis with chronic therapy?

Select one:
Linezolid
Daptomycin
Neomycin
Tigecycline
Aztreonam

Answer 28

Linezolid

Chronic linezolid therapy is associated with lactic acidosis by disrupting mitochondrial function. Remember that propofol and metformin use as well as thiamine deficiency are also associated with lactic acidosis.

Question 29

________ can be associated with hyporeninemic hypoaldosteronism and a type 4 RTA

Answer 29

Ketorolac

Question 30

Differential diagnosis in hypercalcemia with low PTH, normal 25(OH)D, and low 1,25(OH)2D includes :

Answer 30

hyperthyroidism, malignancy, immobilization, Paget’s disease, and milk-alkali syndrome

Question 31

A 50-year-old woman undergoes surgery for a craniopharyngioma. Postoperatively, her urine output is noted to be high for 2 days, and she is given two doses of desmopressin. Replacement doses of hydrocortisone are prescribed, and she is discharged from the hospital. Three days later, she is readmitted with obtundation and a serum sodium of 116 mEq/L.

Which is the MOST likely cause of her hyponatremia?

Answer 31

The correct answer is: Degenerating hypothalamic neurons

Pituitary disease does not cause mineralocorticoid deficiency, and hypoaldosteronism without cortisol deficiency does not cause severe hyponatremia. ACTH deficiency can cause hyponatremia but the patient is receiving hydrocortisone. Desmopressin should no longer be working after 3 days. The patient’s course is suggestive of the first two phases of the classic triphasic response following injury or transection of the pituitary stalk. Initially diabetes insipidus occurs because with interruption of nerve impulses vasopressin cannot be released from nerve terminals. The second phase syndrome of inappropriate antidiuretic hormone secretion (SIADH) results from unregulated release of stored vasopressin from degenerating neurons. Once vasopressin stores are depleted, permanent diabetes insipidus may ensue.

Question 32

Chemo drugs that cause renal salt wasting.

Answer 32

cisplatin
ifosfamide

Cisplatin causes kidney injury with various manifestations, including AKI (acute tubular necrosis), tubulopathies (proximal tubulopathy/Fanconi syndrome, salt wasting, Mg2+ wasting, nephrogenic diabetes insipidus), and CKD.

Question 33

How does cetuximab cause hypomagnesemia?

Answer 33

Cetuximab is a monoclonal antibody against epidermal growth factor receptor (EGFR). Binding of EGF to its receptor is associated with movement of the magnesium channel (TRPM6) to the apical membrane to allow for reabsorption of magnesium in the distal collecting tubule. Cetuximab competes for the receptor and, by doing so, disrupts movement of TRPM6 to the apical membrane, resulting in Mg wasting and hypomagnesemia.

Question 34

How does IVIG cause hyponatremia?

Answer 34

IVIG can cause hyponatremia through two different mechanisms. Because IVIG significantly increases the total protein content of blood, pseudohyponatremia can occur as the solid component of blood increases (the same situation can occur with severe hyperlipidemia). The typical laboratory method of measuring serum sodium (indirect ion selective) will produce a low result. However, the plasma osmolality measurement will be normal (an osmolar gap will be present), and the serum sodium value will be normal if measured by a direct ion selective method.

The other mechanism is related to the vehicle or carrier for the IVIG: sucrose or maltose. These sugars can accumulate in the blood (especially if renal failure is present). Because they do not enter cells, the result can be osmotic disequilibrium between the cellular and the extracellular compartments, pulling water out of cells and diluting the sodium concentration in the extracellular compartment. This is similar to what happens with hyperglycemia, but without an osmolal gap because glucose can be measured and included in the calculated serum osmolality.

Question 35

A postoperative ultrasound is obtained 6 weeks after fistula creation. Which measurement is associated with the MOST likelihood that the fistula will be used successfully for dialysis?

Answer 35

Both the diameter and blood flow of the fistula measured 4-6 weeks postoperatively are predictive of successful use of the fistula for dialysis. The combination of a diameter >4 mm AND access flow >500 mL/min predicts a 95% success rate. A combination of fistula diameter <4 mm AND access flow <500 mL/min predicts a 33% likelihood of fistula success.

Question 36

What BEST manages resistant upper urinary tract infections in patients with PKD and CKD stage V?

Answer 36

Fluoroquinolones
Certain antibiotics are known to penetrate cysts and renal parenchyma in patients with ADPKD. Among these are the fluoroquinolones and trimethoprim/sulfamethoxazole. However, in contrast to fluoroquinolones where minimal dose adjustment is needed, adjusting the trimethoprim/sulfamethoxazole to the level of kidney function will result in low urinary concentrations and low cyst concentrations. If the drug is used, the doses should be normal. Gentamicin and cephaphalosporins do not penetrate cysts well, and bilateral nephrectomies are too radical of a therapy unless there is abscess formation and failure of antibiotic treatment.

Question 37

A 63-year-old man has ESKD secondary to hypertensive nephrosclerosis and has been undergoing treatment with continuous ambulatory peritoneal dialysis (CAPD). His peritoneal dialysis prescription consists of four exchanges of 2.5 L and he is currently anuric. At the time of his most recent assessment of peritoneal dialysis adequacy, the following parameters were obtained:

Serum urea nitrogen: 77 mg/dL
Dialysate urea nitrogen: 72 mg/dL
Total ultrafiltration volume: 1000 mL
Volume of distribution of urea: 40 L

Which represent the CLOSEST approximation of the weekly Kt/Vurea?

Answer 37

To calculate weekly Kt/V, it is necessary to know K, t, and V. K is urea clearance = [(D × V)/P], where D is the dialysate concentration of urea nitrogen (mg/dL), V is the dialysate drain volume per unit time, and P is the serum concentration of urea nitrogen (mg/dL).

The 24-hour peritoneal dialysate drain volume = Volume instilled + Ultrafiltration volume
2500 × 4 each + 1000 = 11,000 mL
K, mL/min = (72/77) × (11,000/1440) = 7.14 mL/min
K, L/week = 7.14 × 10.04 = 71.7 L/wk
t = 1 (wk)
V = volume of distribution of urea = 40
Kt/V = (71.7 × 1)/40 = 1.79

Question 38

Slow accumulation of aluminum over many years can cause _____,______,_____,______,_________.

Answer 38

osteomalacia, bone and muscle pain, iron-resistant microcytic anemia, hypercalcemia, and neurologic abnormalities

Question 39

Removal of aluminum excess among symptomatic patients with aluminum overload includes using deferoxamine; however, side effects such as ______ and __________have been associated with its use.

Answer 39

mucormycosis and neurotoxicity

Question 40

_____________ has been associated with significant hemolytic anemia in ESKD patients receiving this therapy for desensitization and treatment of antibody-mediated rejection. Hemolysis occurs due to passive acquisition of A/B isohemagglutinins from the ___________product. RBCs are coated with antibody and eventually undergo erythrophagocytosis

Answer 40

High-dose IVIG
IVIG

Question 41

In a patient with ESKD on chronic maintenance hemodialysis, which anticoagulant does NOT require dose adjustment?

Select one:
A. Danaparoid
B. Argatroban
C. Fondaparinux
D. Enoxaparin
E. Lephirudin

Answer 41

B. Argatroban
Compared with the other anticoagulants, argatroban is metabolized and cleared by the liver, whereas the rest of the options are cleared by the kidneys and require dose adjustment.

Question 42

Which is the MOST likely cause of hypertension and proteinuria observed in pre-eclampsia?

Answer 42

Decreased vascular endothelial growth factor (VEGF)

VEGF, as well as other factors, is produced in normal pregnancy. VEGF is one of the factors that is required for both systemic and glomerular endothelial function. In the setting of pre-eclampsia, circulating VEGF levels are decreased due to binding by soluble flt, which is a VEGF receptor that is excessively produced in this setting. By binding VEGF, soluble flt causes hypertension via endothelial dysfunction (decreased nitric oxide and increased endothelin) and AKI with proteinuria by disturbing the glomerular endothelium (inducing endotheliosis).

Question 43

What does the photo show?

Answer 43

Uric acid crystals

Question 44

Patient had AKI and crystals after colonoscopy

Answer 44

Calcium phosphate stones

The von Kossa stain (calcium phosphate) in this patient’s renal biopsy will be positive.

This is a typical example of phosphate nephropathy. There will be intense precipitation of calcium phosphate crystals in the medulla, with much less involvement in the cortex. The serum phosphate levels were likely >7 mg/dL, resulting in phosphaturia. The crystals of calcium oxalate are “envelope”-shaped, whereas the ones pictured here are needle-like, typical of calcium phosphate. Uric acid crystals are various shapes (e.g., rhomboid, barrel) but rarely needle-like. The best stain for calcium phosphate is the von Kossa stain, which will not stain calcium oxalate.

Question 45

Lithium causes type 1 or type II RTA?

Answer 45

Type I RTA

Question 46

Which drug causes nephrotoxicity by entering the proximal tubule via binding to megalin/cubilin in the apical membrane?

Answer 46

Gentamicin
Gentamicin enters proximal tubular cells via the apical membrane megalin/cubilin receptor pathway. Tenofovir enters cells via the basolateral organic anion transporter pathway. Ifosfamide, trimethoprim, and cimetidine enter proximal tubular cells via the basolateral organic cation transporter pathway

Question 47

Through which mechanism does Tenofovir cause proximal tubular injury such as AKI and Fanconi syndrome?

A. Mitochondrial dysfunction
B. Na+K+ ATPase inhibition
C. Membrane phospholipid injury
D. Lysosomal dysfunction
E. Golgi apparatus dysfunction

Answer 47

Tenofovir is well described to cause AKI and proximal tubular injury via mitochondrial toxicity. This has been shown in both animals and humans. Mitochondria are distorted and swollen and often present in a lower number with tenofovir toxicity.

Question 48

Which drug can cause the combination of AKI, Fanconi syndrome, and nephrogenic diabetes insipidus?

A. Tenofovir
B. Gentamicin
C. Cisplatin
D. Amphotericin B
E. Mitomycin C

Answer 48

Tenofovir is well described to cause proximal tubular injury with associated AKI and Fanconi syndrome, as well as a nephrogenic diabetes insipidus. Gentamicin is associated with AKI, Fanconi syndrome, and a Bartter-like syndrome. Cisplatin causes AKI, Fanconi syndrome, salt wasting, and magnesium wasting. Amphotericin B causes AKI and a distal renal tubular acidosis (RTA). Mitomycin C causes a thrombotic microangiopathy.

Question 49

Renal magnesium wasting due to defective transport in the _______ is typically associated with hypercalciuria, whereas defects in the early distal tubule are associated with ________ and defects in the late distal nephron are associated with__________urinary calcium excretion.

Answer 49

TAL
hypocalciuria
normal

Question 50

How does warfarin increase risk for calciphylaxis (CUA)?

Answer 50

CUA can develop in the setting of warfarin anticoagulation through inhibition of vitamin K-dependent carboxylation of matrix Gla protein (MGP), a mineral-binding extracellular matrix protein that actively inhibits calcification of arteries and cartilage in an animal model

Question 51

Which activity does fibroblast growth factor-23 (FGF-23) have?

Answer 51

FGF-23 is a key regulator of phosphate homeostasis, and its production by bone osteocytes is stimulated by rises in serum phosphorus that occur in the setting of CKD. FGF-23 then acts on numerous downstream targets in an attempt to normalize serum phosphorus levels. These targets include 1) increases in PTH secretion from the parathyroid gland; 2) decreases in sodium-dependent phosphate reabsorption by the proximal tubule; and 3) decreases in 1-α hydroxylase activity. FGF-23 excess has also been associated with an increased risk for cardiovascular mortality.

Question 52

What does cinacalcet do?

Answer 52

Cinacalcet decreases PTH concentration by an average of 47% even in patients with severe secondary hyperparathyroidism.
Serum phosphorus declines on average by 7%. Calcimimetics such as cinacalcet increase the sensitivity of the calcium-sensing receptor for calcium.
Cinacalcet upregulates the calcium-sensing and vitamin D receptors in the parathyroid gland.

Question 53

Drugs that interact with transplant medications and cause toxicity.

Answer 53

Macrolide antibiotics, antifungal agents such as fluconazole and ketoconazole, and non-dihydropyridine calcium channel blockers all inhibit metabolism and predispose to toxicity and not rejection.

Question 54

Drugs that interact with transplant medications and cause rejection.

Answer 54

Anticonvulsants and rifampin induce the cytochrome P4503A4 isoenzyme and thus often result in subtherapeutic drug levels unless doses are adjusted upward

Question 55

A 25-year-old patient has been diagnosed with relapsing hemolytic uremic syndrome (HUS) and is approaching ESKD. A living-donor transplantation is being considered.

Which gene mutation has the BEST prognosis following renal transplantation?

A. Factor H
B. Factor I
C. CD46 (MCP)
D. C3

Answer 55

CD46 (MCP)

HUS features overactivity of the alternative complement pathway. The most common cause is the loss of function of the complement regulators: Factor H, Factor I, and membrane cofactor. Less often atypical HUS comes from a gain of function mutation of C3 or Factor B. All of the mutations listed above other than CD46 are associated with recurrence of disease after renal transplantation. CD46 is tissue bound, so the new kidney (assuming it is coming from a normal donor) will have normal structure and function of CD46 and hence is not associated with recurrence.

Question 56

6 years post transplant kidney biopsy shows:
Thickened glomerular capillary loops on Periodic Acid-Schiff (PAS), double contours on silver stain, C4d positivity of intertubular capillaries, and multilayering of capillary basement membrane.

What is the MOST likely diagnosis?

Answer 56

Chronic active antibody-mediated rejection

Transplant glomerulopathy is likely present, but the finding of both C4d positivity and multilayering of capillary basement membrane defines the more inclusive diagnosis of chronic active antibody-mediated rejection. The C4d positivity supports a diagnosis of acute humoral rejection, but all of the other findings are more consistent with chronic disease. No evidence is described that supports a diagnosis of acute T cell-mediated rejection. This shows interstitial inflammation, endothelialitis, and arteritis at various degrees.

Question 57

CNIs

________ is known to have less diabetes association. It has more hirsutism, while _______ has alopecia. The hypertension may be higher in _________, but both medications are implicated in this finding. The differences between nephrotoxicity are similar.

Answer 57

Cyclosporin
tacrolimus
cyclosporin

Question 58

On kidney biopsy, by what is acute humoral rejection characterized?

A. Mesangial staining for C4d
B. Interstitial fibrosis
C. Interstitial nephritis
D. Neutrophils in peritubular and/or glomerular capillaries
E. Tubulitis

Answer 58

Neutrophils in peritubular and/or glomerular capillaries

A classical histological finding in acute humoral rejection is the presence of neutrophils in peritubular and/or glomerular capillaries. Mesangial staining for C4d is present in all biopsies and is used as a positive control. Interstitial fibrosis is a chronic nonspecific alteration. Interstitial nephritis is typical of drug hypersensitivity or infection. Tubulitis is seen in acute cell-mediated rejection and is not a feature of humoral rejection.

Question 59

Kidney biopsy showing:
Nuclear inclusions in tubular epithelial cells with acute necrotizing inflammation

Answer 59

Adenovirus

Question 60

Kidney biopsy showing:
Nuclear inclusions in tubular epithelial cells with chronic inflammation

Answer 60

Polyoma virus (BK)

Question 61

Herbals:
________ contains biologically active substances that activate the hepatic P450 system and P-glycoprotein system, enhancing the metabolism of tacrolimus and increasing its secretion, respectively. Grapefruit extracts do the opposite and inhibit the metabolism of calcineurin inhibitors, raising the drug levels.

Answer 61

St. John’s Wort contains biologically active substances that activate the hepatic P450 system and P-glycoprotein system, enhancing the metabolism of tacrolimus and increasing its secretion, respectively (option C). Grapefruit extracts do the opposite and inhibit the metabolism of calcineurin inhibitors, raising the drug levels.

Question 62

Lithium toxicity - indications for dialytic therapy include:

Answer 62

a serum lithium level >4 mEq/L among patients with AKI or CKD or the presence of altered mentation, seizures, or dysrhythmias regardless of lithium levels

Question 63

MPGN classification:

Answer 63

The immunofluorescence (IF) pattern of the biopsy provides clues to the pathogenesis and helps define the subtypes.

Immunoglobulin-positive, complement-positive (these can be monoclonal immunoglobulins as with a plasma cell dyscrasia, or polyclonal as with the case of hepatitis C)

Immunoglobulin-negative, complement-positive (disorders of complement, as with dense deposit disease or C3 glomerulonephritis)

Immunoglobulin-negative, complement-negative (as with a thrombotic microangiopathy)

Question 64

Liddle syndrome

Answer 64

Hypertension, hypokalemia, and metabolic alkalosis is consistent with hyperaldosteronism, but if the the renin level is suppressed and aldosterone level is not elevated then it is consistent with the diagnosis of Liddle syndrome, which is optimally treated with an epithelial sodium channel (ENaC) blocker such as amiloride.

Question 65

____________ and inability to excrete __________ are characteristics of a classic, distal RTA, also known as a type 1 RTA.

Answer 65

Hypokalemia and inability to excrete ammonium

Normal urine anion gap is -20 to - 60. If positive, it means ammonium excretion did not increase as it would have in metabolic acidosis.

Question 66

___________ nephrotoxicity is typically associated with CKD, gout, hypertension, mild proteinuria, and hyperuricemia.

Answer 66

Lead

Question 67

Correcting for Na in hyperglycemia.

Answer 67

Na + (Glc - 100)*1.6/100

Question 68

Free water deficit

Answer 68

0.6 × weight (kg) × ([serum Na / 140] – 1)

Question 69

What disease does the combination of macroglossia, severe nephrotic syndrome, and the small M-spike suggest?

Answer 69

AL amyloidosis

Question 70

How does nephrotic syndrome cause vitamin D deficiency?

Answer 70

Patients with nephrotic syndrome can develop significant vitamin D deficiency because of urinary losses of vitamin D bound to vitamin D-binding protein. Prolonged, severe vitamin D deficiency with serum values <10 ng/mL results in secondary hyperparathyroidism and osteomalacia. In this setting, patients may complain of bone pain and tenderness, and muscle weakness. The spine, pelvis, and lower extremities are most commonly involved.

Question 71

High output CHF

Answer 71

High-output CHF if AVF flow is high (>2L/min). A ratio of the access flow (QA) to the cardiac output (CO) > 0.3 has been identified as a potential risk factor for CHF. If high-output CHF is identified, flow reduction by surgical revision of the AVF is often successful in terms of both symptom improvement and access patency.

Question 72

Circulating _____ is specifically associated with hepatitis B-associated membranous nephropathy, and subepithelial _________ deposition is implicated in the pathogenesis of this disease. Approximately 60–80% of patients with membranous nephropathy associated with hepatitis B will have circulating serum _______; the remainder will have antibodies to __________.

Answer 72

HBeAg

Question 73

______ usually has a bimodal presentation, peaking at the first year and then 7–10 years after transplant.
The most common type is a _________ with approximately 50% exhibiting extra-nodal involvement including the allograft

Answer 73

PTLD
Non-Hodgkin lymphoma

Question 74

The use of _________, a selective T-cell costimulatory blocker, for maintenance therapy for patients who are EBV-naïve has also been associated with higher risk of PTLD.

Answer 74

belatacept

Question 75

_______ dialyzer reactions typically occur 15–30 minutes after treatment is initiated. Characteristic symptoms include chest and back pain, nausea, and hypotension, all of which gradually subside even if dialysis is continued. Complement activation via the alternative pathway by the dialyzer membrane is thought to be the primary cause. These reactions were more common when cellulosic dialyzers were in common use but are infrequent in the era of biocompatible dialyzer membranes.

Answer 75

Type B

Question 76

_______ reactions occur soon after initiation of dialysis, usually within 5–10 minutes. Symptoms range from mild allergic-type symptoms to life-threatening bronchospasm, hypotension, and cardiac arrest. The most severe ______ reactions are triggered by an IgE-mediated reaction to substances such as ethylene oxide that leach from the dialyzer or circuit. Patients with allergies or eosinophilia may be predisposed. When a ________ reaction occurs, dialysis should be discontinued without returning the patient’s blood from the circuit

Answer 76

Type A

Question 77

Patients taking ________ and exposed to a dialyzer composed of acrylonitrile and sodium methallyl sulfonate (AN-69) can experience a similar syndrome related to enhanced generation and impaired metabolism of bradykinin.

Answer 77

ACEi

Question 78

Calculating daily solute excretion.

Answer 78

Daily solute excretion ≈ urine volume × (2 × urine [Na+] mmol/L + 2 × urine [K+]mmol/L) + urine urea mg/day ÷ 60 mg/mmol)

Daily solute excretion = 4 L/day (2 × 10 mmol/L + 2 × 17 mmol/L) + 2400 mg/day ÷ 60 mmol/mg = 256 mmol/day

Alternatively, daily solute excretion ≈ urine volume × urine osmolality = 4 L/day × 65 mOsm/kg = 260 mmol/day (note that 1 L ≈1 kg of water and 1 mOsm ≈ 1 mmol).

Question 79

Test used to confirm proximal RTA

Answer 79

The most appropriate test to confirm a proximal tubulopathy is the fractional excretion of uric acid (FEUA).

Question 80

Factors associated with calciphylaxis.

Answer 80

Factors associated with development of the lesions include obesity, female sex, long dialysis vintage, diabetes mellitus, insulin injections, hypercoagulable states (especially with warfarin use), autoimmune diseases, liver disease, and malignancy. Mineral metabolism disorders such as high levels of serum calcium, phosphate, and PTH have been implicated as well as an elevated calcium-phosphorus product, low serum albumin, and elevated alkaline phosphate levels. Medications associated with development of CUA include corticosteroids, warfarin, calcitriol, calcium-containing supplements and phosphate binders, and IV iron. CUA may be present without any of these laboratory abnormalities or risk factors.

Question 81

Fibril size: AL, or light chain-mediated, amyloidosis

Answer 81

10-nm fibrils

Question 82

Fibril size: Fibrillary GN

Answer 82

20-nm fibrils

Question 83

Fibril size: cryoglobulinemic glomerulopathy

Answer 83

40-nm fibrils (frequently with a “fingerprint” pattern)

Question 84

The most appropriate regimen to prevent graft failure in this patient with a history of graft thrombosis is __________

Answer 84

dipyridamole and aspirin

Question 85

______________ is a congenital disorder characterized by cystic dilation of the terminal collecting ducts. It is commonly associated with nephrocalcinosis and recurrent calcium stones. The diagnosis has historically been made by IV pyelography, which demonstrates pooling of contrast material within the cystic dilations, creating a characteristic appearance that may be compared to a “paintbrush” or a “bouquet of flowers.”

Answer 85

Medullary sponge kidney

Question 86

Nephrocalcinosis is present in up to 75% of patients with Dent disease, which is a proximal tubular disorder characterized by _______, _____________, __________, and ______. The first cases of Dent disease also had hypophosphatemia and rickets. Because inheritance of Dent disease is X-linked recessive, this rare diagnosis is even more uncommon in female patients, although a milder form of the disorder can be present in female carriers

Answer 86

hypercalciuria, low molecular weight proteinuria, nephrolithiasis, and CKD

Question 87

Bartter syndrome can be associated with _______,______ and ______, but the absence of hypokalemic metabolic alkalosis and hypovolemia excludes this diagnosis.

Answer 87

hypercalciuria, nephrocalcinosis, and nephrolithiasis

Question 88

Primary hyperoxaluria is a rare autosomal recessive disorder, which results in overproduction of oxalate. Type 1 is the most common of the three types of primary hyperoxaluria, accounting for approximately 80% of the cases. This disorder is due to deficiency of the _______________. There have been >150 mutations identified of the AGXT gene that encodes AGT. ____________ is a cofactor for AGT and has been shown to significantly decrease urinary oxalate excretion in individuals with 2 of the most common primary hyperoxaluria type 1 mutations.

Answer 88

hepatic peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT)

Pyridoxine

Question 89

________ is an RNA-interference drug (RNAi) that reduces hepatic oxalate synthesis and increases excretion of an oxalate precursor, glycolate. A recent study found significant reduction in oxalate excretion and normalization of oxalate levels without serious adverse effects.

Answer 89

Lumasiran

Question 90

_________is an X-linked lysosomal storage disease that leads to the accumulation of glycosphingolipids (globotriaosylceramide) in multiple organs, including the heart and kidneys.

Answer 90

Fabry disease

Question 91

Treatment for Fabry disease

Answer 91

enzyme replacement therapy with α-galactosidase A

Question 92

Antibiotics to use for treating UTI in pregnancy

Answer 92

Amoxicillin is safe throughout pregnancy, but resistance is common and limits efficacy. Alternative options for resistant organisms include cefpodoxime 100 mg twice daily for 3–7 days or fosfomycin 3 g as a single dose.

Question 93

Tram-track appearance of the GBM, subepithelial and intramembranous immune complex deposits, and possibly cryoglobulins on electron microscopy

Answer 93

HCV mediated MPGN

Question 94

3 methods for diagnosing cystinosis:

Cystinosis causes proximal tubular dysfunction and proximal RTA. This condition usually presents in the first 3–6 months of life, although milder, late-onset (juvenile) and adult forms have been described. The adult form is primarily characterized by ocular manifestations.

Answer 94

Measuring the cystine content of peripheral blood leukocytes and fibroblasts;
Identifying a mutation in cystinosin, a lysosomal cystine transporter;
Or identifying corneal cystine deposits by slit lamp examination.

Question 95

Thyrotoxic hypokalemic PP is an acquired form of the disorder that is common in Asian populations and primarily affects males. It has been associated with defects in the gene encoding Kir2.2, an inwardly-rectifying potassium channel on skeletal muscle that is transcriptionally regulated by thyroid hormone. ____________ has been shown to be effective in thyrotoxic PP but has no role in familial hypokalemic PP.

Answer 95

Propranolol

Question 96

Delta ratio

Answer 96

Delta ratio = (change in anion gap)/(change in bicarbonate) ca. 2007 from @JASN_News #Nephpearls

< 0.4: Normal AG acidosis
0.4-0.8: Mixed high ➕ normal AG acidosis
0.8-2.0: Pure high AG acidosis
> 2.0: High AG acidosis ➕ pre-existing metabolic alkalosis

Question 97

Delta ratio

Answer 97

Delta ratio = (change in anion gap)/(change in bicarbonate) ca. 2007 from @JASN_News #Nephpearls

< 0.4: Normal AG acidosis
0.4-0.8: Mixed high ➕ normal AG acidosis
0.8-2.0: Pure high AG acidosis
> 2.0: High AG acidosis ➕ pre-existing metabolic alkalosis

Question 98

Free water deficit (FWD)

Answer 98

FWD = TBW × [(SNa /140) − 1]

Question 99

CUA management

Answer 99

CUA is associated with significant morbidity and mortality and requires an interdisciplinary treatment plan that includes pain control, wound management, sodium thiosulfate, and targeted therapy to reduce known risk factors. Uncontrolled secondary hyperparathyroidism is a risk factor for CUA in patients with ESRD. Cinacalcet should be initiated in efforts to reduce the PTH level. The EVOLVE trial (Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events) found that patients who received cinacalcet had a significantly lower risk of developing CUA than those treated with placebo.

Question 100

Causes of hypercalcemia

Answer 100

Calcium supplementation
Hyperparathyroidism
Iatrogenic(diuretics, lithium), immobilization
Milk-alkali syndrome, multiple myeloma
Paget’s disease
Adrenal insufficiency
Neoplasms
Zollinger-Ellison syndrome
Excess vit D
Excess vit A
Sarcoidosis

Question 101

Fibroblast growth factor-23 deficiency

Answer 101

Presents with tumoral calcinosis, premature loss of dentition, and hyperphosphatemia with an inappropriately low fractional excretion of phosphorus. In addition, there are features of hereditary tumoral calcinosis, a syndrome usually caused by an inactivating mutation in GALNT3. GALNT3 encodes a glycosyltransferase that prevents degradation of fibroblast growth factor-23 (FGF-23). Defects in this gene therefore lead to increased FGF-23 degradation and low FGF-23 levels. FGF-23 acts to regulate serum phosphorus levels by increasing renal phosphate excretion. Thus, low levels of FGF-23 result in hyperphosphatemia and calcium deposition in the subcutaneous tissues due to a chronically elevated calcium-phosphate product (familial tumoral calcinosis). Early loss of dentition due to abnormal tooth calcification is a characteristic finding. Affected individuals have a normal PTH and serum calcium and have inappropriately normal or elevated calcitriol levels. This condition is inherited as an autosomal recessive disorder. FGF-23 is also elevated in CKD and has been associated with increased mortality. FGF-23 may be an important target for therapy in the future.

Question 102

Klotho

Answer 102

Acts as a co-receptor for FGF-23 and appears to be required for normal FGF-23 signaling. Defects in klotho have also been described as a rare cause of familial tumoral calcinosis. An activating mutation in klotho would lead to renal phosphate wasting and hypophosphatemia. Klotho is also a potential target for future management of bone and mineral disorders in CKD.

Question 103

Dent disease

Answer 103

X-linked recessive syndrome characterized by solute wasting, glycosuria, and low molecular weight proteinuria. Phosphate wasting may lead to childhood rickets in affected individuals. It can be distinguished from Fanconi syndrome by the absence of bicarbonate wasting.

Question 104

Dialysis is an effective treatment for salicylate toxicity but is typically reserved for severe cases. The indications for HD classically include the following:

Answer 104

1. Salicylate levels >100 mg/dL (7.2 mmol/L)
   2. Neurological symptoms
   3. Pulmonary or cerebral edema
   4. Severe AKI
   5. Severe acid-base abnormalities

Question 105

FMD

Answer 105

Beading of renal arteries (PAN you see beaning in small arteries inside kidney)
Severe hypertension

Question 106

Angiomyolipoma genes

Answer 106

TSC1 and TSC2
Tx: mTOR inhibitors

Question 107

A 26 yo complains of polyuria with nocturia. First step:

Answer 107

o 24 hour urine volume
o Then urine Osm: >300 = solute diuresis, <100 is water diuresis, 100 – 300 Partial DI

Question 108

copeptin

Answer 108

surrogate for ADH

Question 109

cetuximab side effects

Answer 109

hypomagnesemia—>hypoCa, hypoK

Question 110

Increased FGF23 levels with low 1,25OH vit D

Answer 110

AD hypophosphatemia - FGF23 mutation
X-linked hypophosphatemia - PHEX mutation
DMP 1 mutation

Question 111

Lysozyme induced kidney injury

Answer 111

AML CMML AMML
Lysozyme is freely filtered at the glomerulus and then reabsorbed in the proximal tubule
K wasting
Over reabsoprtion of lysozyme induces toxic AKI from acute tubular injury which is also associated with tubular proteinuria

Question 112

How Cetuximab, aminoglycosides, PPI cause hypomagnesemia

Answer 112

Cetuximab (DCT) aminoglycosides (PCT) cause renal Mg wasting while PPIs impair GI Mg absorption

Question 113

The Banff criteria for the diagnosis of chronic active AMR include all of the following:

Answer 113

1. Evidence of chronic tissue injury including transplant glomerulopathy.
2. Evidence of current or recent antibody interaction with vascular endothelium including C4d staining in the peritubular capillaries, microvascular inflammation including glomerulitis and peritubular capillaritis, or increased expression of gene transcripts associated with AMR.
3. Presence of HLA or non-HLA DSAs.

Question 114

Bartter syndrome

Answer 114

nephrocalcinosis
hypokalemia
metabolic alkalosis
hypercalciuria
BS refers to a family of genetic disorders all characterized by impaired sodium and chloride transport in the thick ascending limb of the loop of Henle. At least 5 types have been described, with different phenotypes attributed to the precise gene defect. Most presentations are antenatal or perinatal, but occasionally patients are identified during childhood or even as adults. Type 1 BS is an autosomal recessive disorder caused by a defect in the loop diuretic–sensitive Na+/K+/2Cl- (NKCC2) cotransporter. The defect in NaCl reabsorption (evidenced by the relatively high urine Na+ and Cl- concentrations) leads to volume depletion and secondary hyperaldosteronism, which together with increased distal delivery of Na+, leads to excessive K+ and H+ excretion, resulting in hypokalemia and metabolic alkalosis. Clinical features include prematurity, failure-to-thrive growth retardation, and polyuria.

Question 115

Gitelman syndrome (GS)

Answer 115

Mutations in the thiazide-sensitive Na+/Cl- (NCC) cotransporter. The key to differentiating these disorders is the urine calcium value. Hypercalciuria is found in Bartter syndrome, whereas hypocalciuria is found in GS. Paracellular Ca2+ reabsorption in the thick ascending loop of Henle relies on the electrochemical gradient created by NaCl reabsorption via the NKCC2 cotransporter, with subsequent K+ recycling into the lumen. Disruption of this gradient in BS leads to inability to reabsorb calcium, resulting in hypercalciuria. In contrast, the distal tubule NCC cotransporter defect in GS results in low urine Ca2+, possibly because the volume depletion caused by distal NaCl excretion leads to increased proximal Ca2+reabsorption. The urine calcium-to-creatinine ratio varies by age, but this patient’s ratio of 0.25 is well above any age-adjusted normal. The presence of hypercalciuria and nephrocalcinosis in this patient is not consistent with the NCC defect of GS. Patients with GS often display hypomagnesemia, but this overlaps with some forms of BS. Genetic testing and response to diuretic challenges are additional methods available to distinguish BS from GS if this is not apparent by phenotypic difference.

Question 116

Activating mutations in ENaC cause —————–, which is characterized by hypertension, hypokalemia, and metabolic alkalosis, but not hypercalciuria.

Answer 116

Liddle syndrome

Question 117

Autosomal recessive mutations in the V-ATPase cause ___________________, with hypokalemia, hypercalciuria, and kidney stones, as well as sensorineural deafness, but not metabolic alkalosis as seen in this case.

Answer 117

distal renal tubular acidosis

Question 118

__________________ is a rare genetic disorder resulting from mutations in WNK1 and WNK4. WNK4 negatively regulates the Na-Cl co-transporter, so genetic mutations in WNK4 lead to unregulated Na-Cl reabsorption, hypertension, hyperkalemia, and metabolic acidosis.

Answer 118

Pseudohypoaldosteronism type 2 (PHA II, Gordon syndrome)

Question 119

Aldosterone paradox

Answer 119

The ability of aldosterone to stimulate Na reabsorption without K excretion during hypovolemia and to stimulate K excretion without Na retention during hyperkalemia is referred as the aldosterone paradox. Normally, Na reabsorption in the distal nephron generates a negatively charged lumen that favors K excretion through the ROMK channel. Hypovolemia stimulates an appropriate increase in renin, angiotensin II (AT II), and aldosterone, as seen in this case. AT II stimulates the WNK4 (protein kinase “with no lysine” 4) pathway, which inhibits ROMK and allows aldosterone-mediated Na reabsorption without K excretion. Renal K retention is confirmed by the low urine K-to-creatinine ratio (<15 mEq/g).

Question 120

A patient with history of lymphoma undergoing treatment has a positive urine ketone but normal anion gap, albumin and glucose.

Drugs containing free sulfhydryl groups can react with nitroprusside, causing a false positive urine ketone result. Common drugs with free sulfhydryl groups include _______________________________

Answer 120

mesna, captopril, D-penicillamine, dimercaprol, and N-acetylcysteine.

In fact, some authorities have suggested using false positive urine ketone results to confirm compliance with mesna therapy.

Question 121

_______________ nephrotoxicity presents with proximal tubule dysfunction, but also bone pain, fractures, and osteoporosis, and does not fit the exposure history in this case.

Answer 121

Cadmium

Question 122

How long to wait before transplant for the following sized tumors:
Size < 4cm
Size 4- 7 cm
>7 cm

Answer 122

For larger tumors, additional recurrence-free waiting time may be necessary.
Tumors < 4cm with clean margins require 0 wait time
Tumors between 4 and 7 cm in diameter may require 0–2 years of waiting time depending on the tumor grade.
Tumors >7 cm typically require a waiting time of at least 2 years.

Question 123

Therapy with tumor necrosis factor (TNF)-α inhibitors such infliximab, etanercept, and adalimumab have been shown to result in a _________________

Answer 123

drug-induced lupus syndrome.
Skin involvement is predominant in these patients (malar rash and photosensitivity) with findings of positive ANA, anti–double-stranded DNA antibodies, and hypocomplementemia. Kidney manifestations are rare, but proliferative lupus nephritis has been described with these agents

Question 124

Pre-eclampsia definition

Answer 124

The definition of preeclampsia, according to the American College of Obstetrics and Gynecologists (ACOG), is an elevation of BP (systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg on 2 measurements at bed rest, 4 hours apart) in a patient with previously normal BP after 20 weeks of gestation, plus proteinuria or any features of severe preeclampsia. Features of severe preeclampsia include stage 2 hypertension (systolic BP ≥160 mm Hg or diastolic BP ≥100 mm Hg on 2 measurements at bed rest, 4 hours apart), thrombocytopenia, abnormal liver function tests, AKI, pulmonary edema, or new-onset cerebral or visual disturbances. This patient has high BP, but readings improved with bed rest. She has proteinuria, but this finding appears to be chronic. There is no acute indication for delivery, but the patient requires vigilant observation. Current ACOG guidelines state that patients without severe features of gestational hypertension should be managed expectantly until 37 weeks. She also has decreased kidney function, and efforts should be made to determine the level of kidney function prior to and during pregnancy.

Question 125

These qualify for Tolvaptan. Specific guidelines to define rapid progression include the following:

Answer 125

• Total kidney volume >750 mL
• Ultrasound-determined kidney length >16 cm
• Decrease in GFR of ≥5 mL/min/1.73 m2 per year
• Increase in total kidney volume >5% per year

Question 126

Mutations in the gene for α-galactosidase cause ————–, a lysosomal storage disorder. Patients with —————- typically display a variety of systemic manifestations, including neuropathy, skin telangiectasias, and corneal opacities.

Answer 126

Fabry disease

Question 127

Fibrocystin gene mutations cause ———————, a disorder that would typically present in a young adult patient with symptoms and signs related to hepatic fibrosis and progressive CKD; nephrotic syndrome would be atypical.

Answer 127

autosomal recessive polycystic kidney disease