BRCU Flashcards
(128 cards)
1
Q
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.
A
Tuberous sclerosis
2
Q
Star fruit
A
Associated with oxalate nephropathy
3
Q
Ephedra
A
Causes hypertension (HTN) and stones
4
Q
Glycerrhizic acid (sweetner)
A
Apparent” mineralocorticoid excess (AME)
- hypokalemia, HTN, and alkalosis
5
Q
Noni juice
A
Hyperkalemia
6
Q
Lead effect in kidney
A
Lead is a cation, and the organic cation transport (OCT) system (not the organic anion transporter) in the proximal tubule
7
Q
Cadmium affects what part of kidney
A
proximal tubule
8
Q
Metal that causes nephrotic syndrome from membranous disease
A
Gold
9
Q
______________ compounds cause acute tubular necrosis (ATN) through both apoptosis and necrosis, especially of the proximal tubule, and do not cause interstitial nephritis.
A
Platinum
10
Q
Urinary crystal has this hexagonal appearance
α-Mercaptopropionylglycine improves solubilization. This is an autosomal recessive disease, and the family needs to be educated
A
Cystinuria
11
Q
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)
A
Associated with granulomatous interstitial nephritis
12
Q
Tenofovir causes:
A
Proximal tubular injury with AKI and Fanconi syndrome, but Fanconi syndrome could manifest as a proximal RTA which does not lead to stone formation
13
Q
Hallmark on skin biopsy is septal panniculitis
A
Calcific uremic arteriolopathy
14
Q
Which genetic screening test is likely to detect a mutation in more than 5% of sporadic FSGS in adolescents?
A
Mutations in the NPHS2 (podocin) gene, including p.R229Q variant
15
Q
Multiple myeloma nephropathy will show:
A
Fractured tubular casts
Congo red–positive glomerular and tubular deposits
Acute tubular injury/necrosis
Plasma cell infiltrates
16
Q
Fibrillary GN 15 - 30 nm, random arrangement
Immunotactoid GN >30 nm, parallel arrays
Cryoglobulin GN 25-35 nm, curved microtubules
Amyloid 9 - 12 nm
A
Glomerular deposits characterization depends on three findings that help define the disease:
- Congo red staining
- Immune staining patterns, and
- the diameter of fibrils
17
Q
Which laboratory test would produce the highest yield in determining the role of immunoglobulins in a patient suspected to have a paraproteinemia?
A
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.
18
Q
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.
A
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
19
Q
mineralocorticoid corticoid receptor mutation (Geller’s syndrome)
A
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.
20
Q
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
A
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.
21
Q
SCLC can produce ACTH which then causes hypokalemia, metabolic alkalosis, and hypertension.
How to treat:
A
Therapy is directed at the tumor, steroid synthesis inhibitors (ketoconazole, metyrapone, and octreotide), and mineralocorticoid receptor blockers/ epithelial sodium channel (eNaC) blockers.
22
Q
Causes:
Fanconi syndrome, with any combination of proximal renal tubular acidosis, glycosuria, potassium and phosphate wasting, nephrogenic diabetes insipidus, and AKI
A
Ifosfamide
23
Q
What medication is associated with a proximal RTA (and distal RTA) often with calcium phosphate stone formation from the latter.
A
Topiramate
24
Q
______________ is associated with urinary crystals and nephrolithiasis.
A
Atazanavir
25
What diuretic is associated with with urinary crystals but not stones?
Triamterene
26
Orlistat is associated with enteric _______ and ________.
crystals.
hyperoxaluria and urinary calcium oxalate crystals
27
Pentamidine, like amiloride, triamterene, and trimethoprim, is associated with hyperkalemia by blocking the __________ in the ________part of the nephron.
epithelial sodium channel in the principal cell
cortical collecting duct
28
Which drug has been associated with the development of lactic acidosis with chronic therapy?
Select one:
Linezolid
Daptomycin
Neomycin
Tigecycline
Aztreonam
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.
29
________ can be associated with hyporeninemic hypoaldosteronism and a type 4 RTA
Ketorolac
30
Differential diagnosis in hypercalcemia with low PTH, normal 25(OH)D, and low 1,25(OH)2D includes :
hyperthyroidism, malignancy, immobilization, Paget's disease, and milk-alkali syndrome
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?
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.
32
Chemo drugs that cause renal salt wasting.
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.
33
How does cetuximab cause hypomagnesemia?
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.
34
How does IVIG cause hyponatremia?
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.
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?
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.
36
What BEST manages resistant upper urinary tract infections in patients with PKD and CKD stage V?
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.
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?
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
38
Slow accumulation of aluminum over many years can cause _____,______,_____,______,_________.
osteomalacia, bone and muscle pain, iron-resistant microcytic anemia, hypercalcemia, and neurologic abnormalities
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.
mucormycosis and neurotoxicity
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
High-dose IVIG
IVIG
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
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.
42
Which is the MOST likely cause of hypertension and proteinuria observed in pre-eclampsia?
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).
43
What does the photo show?
Uric acid crystals
44
Patient had AKI and crystals after colonoscopy
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.
45
Lithium causes type 1 or type II RTA?
Type I RTA
46
Which drug causes nephrotoxicity by entering the proximal tubule via binding to megalin/cubilin in the apical membrane?
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
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
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.
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
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.
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.
TAL
hypocalciuria
normal
50
How does warfarin increase risk for calciphylaxis (CUA)?
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
51
Which activity does fibroblast growth factor-23 (FGF-23) have?
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.
52
What does cinacalcet do?
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.
53
Drugs that interact with transplant medications and cause toxicity.
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.
54
Drugs that interact with transplant medications and cause rejection.
Anticonvulsants and rifampin induce the cytochrome P4503A4 isoenzyme and thus often result in subtherapeutic drug levels unless doses are adjusted upward
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
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.
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?
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.
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.
Cyclosporin
tacrolimus
cyclosporin
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
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.
59
Kidney biopsy showing:
Nuclear inclusions in tubular epithelial cells with acute necrotizing inflammation
Adenovirus
60
Kidney biopsy showing:
Nuclear inclusions in tubular epithelial cells with chronic inflammation
Polyoma virus (BK)
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.
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.
62
Lithium toxicity - indications for dialytic therapy include:
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
63
MPGN classification:
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)
64
Liddle syndrome
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.
65
____________ and inability to excrete __________ are characteristics of a classic, distal RTA, also known as a type 1 RTA.
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.
66
___________ nephrotoxicity is typically associated with CKD, gout, hypertension, mild proteinuria, and hyperuricemia.
Lead
67
Correcting for Na in hyperglycemia.
Na + (Glc - 100)*1.6/100
68
Free water deficit
0.6 × weight (kg) × ([serum Na / 140] – 1)
69
What disease does the combination of macroglossia, severe nephrotic syndrome, and the small M-spike suggest?
AL amyloidosis
70
How does nephrotic syndrome cause vitamin D deficiency?
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.
71
High output CHF
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.
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 __________.
HBeAg
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
PTLD
Non-Hodgkin lymphoma
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.
belatacept
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.
Type B
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
Type A
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.
ACEi
78
Calculating daily solute excretion.
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).
79
Test used to confirm proximal RTA
The most appropriate test to confirm a proximal tubulopathy is the fractional excretion of uric acid (FEUA).
80
Factors associated with calciphylaxis.
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.
81
Fibril size: AL, or light chain-mediated, amyloidosis
10-nm fibrils
82
Fibril size: Fibrillary GN
20-nm fibrils
83
Fibril size: cryoglobulinemic glomerulopathy
40-nm fibrils (frequently with a “fingerprint” pattern)
84
The most appropriate regimen to prevent graft failure in this patient with a history of graft thrombosis is __________
dipyridamole and aspirin
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.”
Medullary sponge kidney
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
hypercalciuria, low molecular weight proteinuria, nephrolithiasis, and CKD
87
Bartter syndrome can be associated with _______,______ and ______, but the absence of hypokalemic metabolic alkalosis and hypovolemia excludes this diagnosis.
hypercalciuria, nephrocalcinosis, and nephrolithiasis
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.
hepatic peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT)
Pyridoxine
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.
Lumasiran
90
_________is an X-linked lysosomal storage disease that leads to the accumulation of glycosphingolipids (globotriaosylceramide) in multiple organs, including the heart and kidneys.
Fabry disease
91
Treatment for Fabry disease
enzyme replacement therapy with α-galactosidase A
92
Antibiotics to use for treating UTI in pregnancy
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.
93
Tram-track appearance of the GBM, subepithelial and intramembranous immune complex deposits, and possibly cryoglobulins on electron microscopy
HCV mediated MPGN
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.
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.
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.
Propranolol
96
Delta ratio
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
97
Delta ratio
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
98
Free water deficit (FWD)
FWD = TBW × [(SNa /140) − 1]
99
CUA management
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.
100
Causes of hypercalcemia
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
101
Fibroblast growth factor-23 deficiency
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.
102
Klotho
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.
103
Dent disease
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.
104
Dialysis is an effective treatment for salicylate toxicity but is typically reserved for severe cases. The indications for HD classically include the following:
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
105
FMD
Beading of renal arteries (PAN you see beaning in small arteries inside kidney)
Severe hypertension
106
Angiomyolipoma genes
TSC1 and TSC2
Tx: mTOR inhibitors
107
A 26 yo complains of polyuria with nocturia. First step:
o 24 hour urine volume
o Then urine Osm: >300 = solute diuresis, <100 is water diuresis, 100 – 300 Partial DI
108
copeptin
surrogate for ADH
109
cetuximab side effects
hypomagnesemia--->hypoCa, hypoK
110
Increased FGF23 levels with low 1,25OH vit D
AD hypophosphatemia - FGF23 mutation
X-linked hypophosphatemia - PHEX mutation
DMP 1 mutation
111
Lysozyme induced kidney injury
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
112
How Cetuximab, aminoglycosides, PPI cause hypomagnesemia
Cetuximab (DCT) aminoglycosides (PCT) cause renal Mg wasting while PPIs impair GI Mg absorption
113
The Banff criteria for the diagnosis of chronic active AMR include all of the following:
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.
114
Bartter syndrome
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.
115
Gitelman syndrome (GS)
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.
116
Activating mutations in ENaC cause -----------------, which is characterized by hypertension, hypokalemia, and metabolic alkalosis, but not hypercalciuria.
Liddle syndrome
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.
distal renal tubular acidosis
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.
Pseudohypoaldosteronism type 2 (PHA II, Gordon syndrome)
119
Aldosterone paradox
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).
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 _______________________________
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.
121
_______________ nephrotoxicity presents with proximal tubule dysfunction, but also bone pain, fractures, and osteoporosis, and does not fit the exposure history in this case.
Cadmium
122
How long to wait before transplant for the following sized tumors:
Size < 4cm
Size 4- 7 cm
>7 cm
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.
123
Therapy with tumor necrosis factor (TNF)-α inhibitors such infliximab, etanercept, and adalimumab have been shown to result in a _________________
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
124
Pre-eclampsia definition
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.
125
These qualify for Tolvaptan. Specific guidelines to define rapid progression include the following:
* 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
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.
Fabry disease
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.
autosomal recessive polycystic kidney disease
128
