16_HST110 Introduction to Renal Disease II - CKD 2017

Question 1

What % of adults in the US have CKD?

Answer 1

9-13%

Question 2

Patients with CKD and ESRD have a higher risk of mortality, particularly from cardiovascular disease
Survival of patients on dialysis is (X)% at one year, (Y)% at five years

Answer 2

X = 81% 
Y = 34%

Question 3

What are the 2 NKF-K/DOQI definitions of CKD?

Answer 3

Presence of markers of kidney damage for 3 or more months
(Structural or functional abnormalities (pathology, imaging, blood or urine tests) with or without decreased GFR)

OR

Presence of GFR <60 mL/min/1.73m^2 for 3 or more months with or without other signs of kidney damage

Question 4

In Stage 1 CKD, GFR >90 (Kidney damage with normal or high GFR), what is the necessary action?

Answer 4

Diagnosis and treatment
Treatment of comorbid conditions
Slowing progression
CVD risk reduction

Question 5

In Stage 2 CKD, GFR 60-89 (Kidney damage with mild decrease in GFR), what is the necessary action?

Answer 5

Estimating progression

Question 6

In Stage 3 CKD, GFR 30-59 (Moderately decresed GFR), what is the necessary action?

Answer 6

Evaluating and treating complications

Question 7

In Stage 4 CKD, GFR 15-29 (Severe decrease in GFR), what is the necessary action?

Answer 7

Preparation for kidney replacement therapy

Question 8

In Stage 5 CKD, GFR <15 or dialysis (Kidney failure), what is the necessary action?

Answer 8

Replacement (if uremia present)

Question 9

What are the most common causes of ESRD?

Answer 9

Diabetes (44%)
Hypertension (28%)
Glomerulonephritis (6%)
Cystic kidney disease (2%)

Question 10

What 2 conditions account for most cases of non-ESRD CKD?

Answer 10

Hypertension and diabetes

Question 11

What are the 3 general methods CKD develops?

Answer 11

Progressive disease (e.g. diabetes)

Repeated episodes of kidney injury

Secondary disease-independent functional, structural, and metabolic adaptations

Question 12

What are 4 experimental consequences of a 5/6 nephrectomy in rat models?

Answer 12

Renal compensatory hypertrophy and functional adaptation occur

Glomerular sclerosis develops and progresses

Hypertension develops

Rats eventually develop ESRD within 4-6 months

Question 13

Increases in P_GC due to kidney injury and compensation by remaining nephrons leads to podocyte injury and loss, ___ and ____

Answer 13

Effacement, Detachment

Question 14

Sclerotic area formation in damaged kidneys (glomerulus) lead to what 2 conditions?

Answer 14

Glomerulosclerosis and hyalinosis (with obliteration of capillary loops)

Question 15

Podocyte effacement and detachment breaks a critical barrier in proper filtrate formation. What condition can result?

Answer 15

Proteinuria

Question 16

Nephron damage can lead to tubulointerstitial changes leading to what 2 conditions?

Answer 16

Interstitial fibrosis

Tubular atrophy

Question 17

Progression of chronic kidney disease can be prevented by reversing the intraglomerular (X) and (Y) as well as the (Z) due to the increased local convection

Answer 17

X = Hypertension (Antihypertensive therapy)
Y = Hypertrophy
Z = Proteinuria (Dietary protein restriction)

Question 18

GFR varies directly with dietary protein intake

GFR can acutely rise by (X)% after a eating a protein load

Answer 18

X = 15-40

Question 19

In remnant model rats, a low protein diet can do what 3 things?

Answer 19

Prevent intraglomerular hypertension and hypertrophy

Decrease proteinuria

Prevent glomerulosclerosis

Question 20

Intraglomerular pressure can be lowered by lowering (X) blood pressure with medications

Effectiveness and degree of renal protection depends on the class of anti-hypertensive drug used

Answer 20

X = systemic

Question 21

Angiotensin II inhibition as an antihypertensive therapy is effective due to the decrease in (X) resistance

Answer 21

X = efferent

Question 22

ACE inhibitors such as (X) are also effective at decreasing proteinuria and glomerulosclerosis

Answer 22

X = Enalapril

Question 23

ACE inhibitors and ARBs are renoprotective in rats, decreasing what 4 conditions and increasing kidney survival?

Answer 23

Systemic blood pressure, intraglomerular pressure, proteinuria, glomerulosclerosis

Question 24

Dietary protein restriction may protect against the progression of CKD in humans by reducing (X) pressure

Benefits of dietary protein restriction to (Y) g/kg per day on CKD progression is controversial. At best, a small reduction in the rate of GFR decline can be observed with low protein diet

Answer 24

X = intraglomerular
Y = 0.6-0.8

Question 25

Loss of nephrons leads to compensatory (X) and (Y) of surviving nephrons to maintain GFR. These changes over long periods of time result in focal and segmental (Z) (scarring in parts of some but not all glomeruli)

Answer 25

``` X = hypertrophy Y = hyperfiltration Z = glomerulosclerosis ```

Question 26

Antihypertensive treatment with (X) or (Y) have been shown in animals and humans to be renoprotective by lowering intraglomerular pressure

Answer 26

``` X = ACE inhibitors Y = ARBs ```

Question 27

Uremia is a constellation of signs and symptoms that appear in the setting of _____ renal disease

Answer 27

X = advanced

Question 28

Name some of the 8 categories of systems affected in uremia

Answer 28

Musculoskeletal, Hematologic, Electrolytes, Neurologic, Dermatologic, Cardiopulmonary, Endocrine, Gastrointestinal

Question 29

What 3 conditions (decreases in secretion or excretion) are involved in the pathogenesis of uremia?

Answer 29

Decreased excretion of electrolytes and water Decreased excretion of organic solutes (uremic toxins) Decreased renal hormone synthesis

Question 30

What are the 3 categories of uremic toxins?

Answer 30

Small, water-soluble Small, lipid-soluble and/or protein-bound Middle molecules (larger)

Question 31

Name at least 2 examples of small, water-soluble uremic toxins

Answer 31

Urea, guanidines, oxalate, phosphate, polyamines

Question 32

Name at least 3 examples of small, lipid-soluble and/or protein-bound uremic toxins

Answer 32

P-cresol, p-cresyl sulfate, homocysteine, indoles

Question 33

Name at least 1 example of a middle molecule (larger) uremic toxin

Answer 33

β2-microglobulin, PTH, AGEs

Question 34

Patients typically do not complain of common signs and symptoms of uremia (nausea, vomiting, fatigue, anorexia, weight loss, muscle cramps, pruritus, mental status changes, visual disturbances, increased thirst, and bleeding) until GFR falls below (X) mL/min (10% normal)

Answer 34

X = 10-15

Question 35

Name 4 physical findings of uremia

Answer 35

Half-and-half nails Asterixis (jerking hands when in pushing position) Uremic frost on skin Edema

Question 36

What are 3 major complications of CKD?

Answer 36

Hypertension, Anemia, and Mineral Bond Disorders

Question 37

Hypertension in CKD eventually occurs in what percentage of patients?

Answer 37

85-90%

Question 38

What is the mechanism of hypertension in CKD?

Answer 38

Volume expansion (80%) from sodium retention Increased activation of renin-angiotensin-aldosterone system [Primary vascular disease (HTN, vasculitis). Regional renal ischemia induced by scarring]

Question 39

What is the treatment for hypertension in CKD?

Answer 39

Diuretics in patients with volume expansion ACE inhibitors or ARBs

Question 40

What are the blood pressure goals for hypertension of CKD (w/ and w/o proteinuria)?

Answer 40

<130/80 with proteinuria | <140/90 without proteinuria

Question 41

What is the definition of Anemia?

Answer 41

Anemia = hemoglobin or red blood cell count is below normal | Hgb < 13.5 g/dL in men, <12.0 g/dL in women

Question 42

What portion of patients with CKD develop anemia?

Answer 42

Almost all

Question 43

Hemoglobin levels usually begin to fall when GFR is (X)% of normal

Answer 43

40

Question 44

What causes anemia in CKD?

Answer 44

Reduced renal secretion of erythropoietin (EPO)

Question 45

EPO is 34 kDa glycoprotein hormone In adults, produced in kidney by interstitial cells near (X) Produced in response to a decrease in (Y) Binds to EPO receptor on (Z) in the bone marrow and promotes their differentiation and maturation

Answer 45

``` X = peritubular capillaries Y = O2 delivery Z = RBC precursor cells ```

Question 46

Name a few of the 10 factors contributing to anemia of CKD

Answer 46

Deficiency of vitamin B12 and folate High hepicidin level, inflammation, infection Decreased EPO production Absolute iron deficiency (malnutrition and poor absorption) ``` Blood loss Short RBC life span Co-morbidities Bone marrow suppression by uraemia CKD mineral+bone disorder Medication (ACE inhibitors) ```

Question 47

What are the 3 treatments for anemia in CKD (target hemeglobin level of 10-11 g/dL)

Answer 47

Recombinant EPO hormone Iron supplementation Blood transfusions if needed

Question 48

Almost all patients with CKD will develop alterations in bone, called generally (X)

Answer 48

Mineral Bone Disease (MBD)

Question 49

What are the 3 key players in calcium and phosphate homeostasis?

Answer 49

PTH, Vitamin D, FGF-23

Question 50

What are the 3 actions of PTH?

Answer 50

1) Increase renal Ca2+ reabsoption 2) Increase bone resorption 3) Increase calcitriol synthesis (kidney)

Question 51

What is the net effect of PTH?

Answer 51

Increase serum [Ca2+] back to normal

Question 52

What are the 3 actions of 1,25(OH)_2-Vitamin D?

Answer 52

1) Increase intestinal Ca2+ absorption 2) Increase bone resorption 3) Increase renal Ca2+ reabsorption

Question 53

What is the net effect of 1,25(OH)_2-Vitamin D?

Answer 53

Increased serum [Ca2+]

Question 54

Decreased GFR can decrease Phosphate excretion leading to increased serum phosphate. This leads to a decrease in calcitrol and serum [Ca2+]. PTH increases to compensate, leading to (X)

Answer 54

X = Bone resorption

Question 55

Prolonged hyperparathyroidism results in what 2 conditions?

Answer 55

Osteitis fibrosa cystica (renal osteodystrophy) [Skeletal demineralization. Bone cysts. Spontaneous fractures] Metastatic calcifications [Calcium phosphate precipitates out of plasma and deposits in arteries, soft tissues, and viscera. Occurs when [Ca] x [Phosphate] > 60-70]

Question 56

What are 3 treatments for Mineral Bone Disease?

Answer 56

Low phosphate diet Oral phosphate binders Calcitriol (suppress PTH release)

Question 57

What is it called when blood is visually seen in the urine?

Answer 57

Gross hematuria

Question 58

What is is called when RBCS can only been seen in the urine by light microscopy?

Answer 58

Microscopic hematuria (>3 RBCs/hpf)

Question 59

What are causes of heme positive red urine?

Answer 59

Hematuria, hemoglobinuria, myoglobinuria

Question 60

What are causes of heme negative red urine?

Answer 60

Beeturia, drugs (rifampin, pyridium), and acyte porphyria

Question 61

A urine dipstick detects heme. Heme has “(X)-like” activity and reacts with a (X) substrate on the dipstick Will detect RBCs, free hemoglobin, or free myoglobin in the urine

Answer 61

X = peroxidase

Question 62

What could cause a positive heme dipstick reading without RBCs present?

Answer 62

Hemolysis or rhabdomyolysis

Question 63

Urine microscopy can help differentiate glomerular bleeding from (X) bleeding. Dysmorphic RBCs (>(Y)%) or (Z) are consistent with glomerular bleeding

Answer 63

``` X = lower urinary tract Y = 80 Z = RBC casts ```

Question 64

What are 4 common renal causes of hematuria?

Answer 64

``` Stones Infection (UTI) Neoplasm (uroepithelial) Glomerular disease IgA nephropathy Thin base membranes Glomerulonephritis ```

Question 65

What are 3 non-renal causes of hematuria?

Answer 65

Menstruation Vigorous exercise Trauma

Question 66

Adults can excrete up to (X) mg/day of total protein, (Y) mg/day of albumin. Mostly Tamm-Horsfall protein, some (Z)

Answer 66

``` X = 150 Y = 30 Z = immunoglobulins ```

Question 67

What are the 3 classes of proteinuria?

Answer 67

Glomerular proteinuria Tubular proteinuria Overflow proteinuria

Question 68

Glomerular proteinuria: Disruption of the glomerular filtration barrier can result in filtration of high molecular weight plasma proteins (e.g. (X))

Answer 68

X = albumin

Question 69

Tubular proteinuria: Tubular damage or dysfunction results in decreased capacity to reabsorb (Y) proteins

Answer 69

Y = low molecular weight

Question 70

Overflow proteinuria: Increased production of plasma proteins that are filtered by the glomerulus can overwhelm the tubular capacity for reabsorption (e.g. (X))

Answer 70

X = light chain proteins in multiple myeloma

Question 71

The urine dipstick only detects what protein?

Answer 71

Albumin | Does not detect light chain proteins

Question 72

What are the levels of protein content of urine on a dipstick?

Answer 72

``` 1+ = 30 mg/dL 2+ = 100 mg/dL 3+ = 300 mg/dL 4+ = >300 mg/dL ```

Question 73

The urine dipstick can give false positive of proteinuria under what condition?

Answer 73

High urine pH

Question 74

What are the 2 methods of quantification of proteinuria in terms of collection time?

Answer 74

24 hour urine collection | Spot urine protein/creatinine ratio

Question 75

What are the features and limitations of a 24 hour urine collection?

Answer 75

Inaccurate urine collection is greatest source of error Should always simultaneously measure urine creatinine excretion to determine adequacy of sample

Question 76

Spot urine protein/creatinine ratio test Random, single-voided urine sample. Strong correlation of ratio with 24 hour urine collection in a variety of kidney diseases. Ratio of 2 indicates (X) g/day proteinuria

Answer 76

X = 2

Question 77

What is the range for moderately increased proteinuria (microalbuminuria)?

Answer 77

30-300 mg/day

Question 78

What is the range for severely increased proteinuria (macroalbuminuria or overt proteinuria)?

Answer 78

>300 mg/day

Question 79

What is the range for nephrotic range proteinuria?

Answer 79

>3.5 g/day (>3500 mg/day)

Question 80

What are 4 causes of begign proteinuria?

Answer 80

Fever Exercise Seizures Orthostatic (postural) proteinuria

Question 81

What are 2 causes of tubular proteinuria?

Answer 81

Hypertensive nephrosclerosis | Tubulointerstitial disease

Question 82

What is a cause of overflow proteinuria?

Answer 82

Multiple myeloma

Question 83

What are several causes of glomerular proteinuria (under primary glomerulopathy)?

Answer 83

``` Minimal change disease Membranous nephropathy Focal segmental glomerulosclerosis Membranoproliferative GN IgA nephropathy ```

Question 84

What are several causes of glomerular proteinuria (under secondary glomerulopathy)?

Answer 84

Diabetic nephropathy Amyloidosis Collagen vascular disorders Drugs (NSAIDs, heroin, gold)

Question 85

What are 6 treatments for proteinuria?

Answer 85

``` ACE inhibitors Angiotensin receptor blockers (ARBs) Blood pressure management Target <125/75 Smoking cessation Moderate protein restriction Lipid management ```