16_HST110 Introduction to Renal Disease II - CKD 2017 Flashcards
What % of adults in the US have CKD?
9-13%
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
X = 81% Y = 34%
What are the 2 NKF-K/DOQI definitions of CKD?
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
In Stage 1 CKD, GFR >90 (Kidney damage with normal or high GFR), what is the necessary action?
Diagnosis and treatment
Treatment of comorbid conditions
Slowing progression
CVD risk reduction
In Stage 2 CKD, GFR 60-89 (Kidney damage with mild decrease in GFR), what is the necessary action?
Estimating progression
In Stage 3 CKD, GFR 30-59 (Moderately decresed GFR), what is the necessary action?
Evaluating and treating complications
In Stage 4 CKD, GFR 15-29 (Severe decrease in GFR), what is the necessary action?
Preparation for kidney replacement therapy
In Stage 5 CKD, GFR <15 or dialysis (Kidney failure), what is the necessary action?
Replacement (if uremia present)
What are the most common causes of ESRD?
Diabetes (44%)
Hypertension (28%)
Glomerulonephritis (6%)
Cystic kidney disease (2%)
What 2 conditions account for most cases of non-ESRD CKD?
Hypertension and diabetes
What are the 3 general methods CKD develops?
Progressive disease (e.g. diabetes)
Repeated episodes of kidney injury
Secondary disease-independent functional, structural, and metabolic adaptations
What are 4 experimental consequences of a 5/6 nephrectomy in rat models?
Renal compensatory hypertrophy and functional adaptation occur
Glomerular sclerosis develops and progresses
Hypertension develops
Rats eventually develop ESRD within 4-6 months
Increases in P_GC due to kidney injury and compensation by remaining nephrons leads to podocyte injury and loss, ___ and ____
Effacement, Detachment
Sclerotic area formation in damaged kidneys (glomerulus) lead to what 2 conditions?
Glomerulosclerosis and hyalinosis (with obliteration of capillary loops)
Podocyte effacement and detachment breaks a critical barrier in proper filtrate formation. What condition can result?
Proteinuria
Nephron damage can lead to tubulointerstitial changes leading to what 2 conditions?
Interstitial fibrosis
Tubular atrophy
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
X = Hypertension (Antihypertensive therapy) Y = Hypertrophy Z = Proteinuria (Dietary protein restriction)
GFR varies directly with dietary protein intake
GFR can acutely rise by (X)% after a eating a protein load
X = 15-40
In remnant model rats, a low protein diet can do what 3 things?
Prevent intraglomerular hypertension and hypertrophy
Decrease proteinuria
Prevent glomerulosclerosis
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
X = systemic
Angiotensin II inhibition as an antihypertensive therapy is effective due to the decrease in (X) resistance
X = efferent
ACE inhibitors such as (X) are also effective at decreasing proteinuria and glomerulosclerosis
X = Enalapril
ACE inhibitors and ARBs are renoprotective in rats, decreasing what 4 conditions and increasing kidney survival?
Systemic blood pressure, intraglomerular pressure, proteinuria, glomerulosclerosis
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
X = intraglomerular Y = 0.6-0.8
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)
X = hypertrophy Y = hyperfiltration Z = glomerulosclerosis
Antihypertensive treatment with (X) or (Y) have been shown in animals and humans to be renoprotective by lowering intraglomerular pressure
X = ACE inhibitors Y = ARBs
Uremia is a constellation of signs and symptoms that appear in the setting of _____ renal disease
X = advanced
Name some of the 8 categories of systems affected in uremia
Musculoskeletal, Hematologic, Electrolytes, Neurologic, Dermatologic, Cardiopulmonary, Endocrine, Gastrointestinal
What 3 conditions (decreases in secretion or excretion) are involved in the pathogenesis of uremia?
Decreased excretion of electrolytes and water
Decreased excretion of organic solutes (uremic toxins)
Decreased renal hormone synthesis
What are the 3 categories of uremic toxins?
Small, water-soluble
Small, lipid-soluble and/or protein-bound
Middle molecules (larger)
Name at least 2 examples of small, water-soluble uremic toxins
Urea, guanidines, oxalate, phosphate, polyamines
Name at least 3 examples of small, lipid-soluble and/or protein-bound uremic toxins
P-cresol, p-cresyl sulfate, homocysteine, indoles
Name at least 1 example of a middle molecule (larger) uremic toxin
β2-microglobulin, PTH, AGEs
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)
X = 10-15
Name 4 physical findings of uremia
Half-and-half nails
Asterixis (jerking hands when in pushing position)
Uremic frost on skin
Edema
What are 3 major complications of CKD?
Hypertension, Anemia, and Mineral Bond Disorders
Hypertension in CKD eventually occurs in what percentage of patients?
85-90%
What is the mechanism of hypertension in CKD?
Volume expansion (80%) from sodium retention
Increased activation of renin-angiotensin-aldosterone system
[Primary vascular disease (HTN, vasculitis). Regional renal ischemia induced by scarring]
What is the treatment for hypertension in CKD?
Diuretics in patients with volume expansion
ACE inhibitors or ARBs
What are the blood pressure goals for hypertension of CKD (w/ and w/o proteinuria)?
<130/80 with proteinuria
<140/90 without proteinuria
What is the definition of Anemia?
Anemia = hemoglobin or red blood cell count is below normal
Hgb < 13.5 g/dL in men, <12.0 g/dL in women
What portion of patients with CKD develop anemia?
Almost all
Hemoglobin levels usually begin to fall when GFR is (X)% of normal
40
What causes anemia in CKD?
Reduced renal secretion of erythropoietin (EPO)
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
X = peritubular capillaries Y = O2 delivery Z = RBC precursor cells
Name a few of the 10 factors contributing to anemia of CKD
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)
What are the 3 treatments for anemia in CKD (target hemeglobin level of 10-11 g/dL)
Recombinant EPO hormone
Iron supplementation
Blood transfusions if needed
Almost all patients with CKD will develop alterations in bone, called generally (X)
Mineral Bone Disease (MBD)
What are the 3 key players in calcium and phosphate homeostasis?
PTH, Vitamin D, FGF-23
What are the 3 actions of PTH?
1) Increase renal Ca2+ reabsoption
2) Increase bone resorption
3) Increase calcitriol synthesis (kidney)
What is the net effect of PTH?
Increase serum [Ca2+] back to normal
What are the 3 actions of 1,25(OH)_2-Vitamin D?
1) Increase intestinal Ca2+ absorption
2) Increase bone resorption
3) Increase renal Ca2+ reabsorption
What is the net effect of 1,25(OH)_2-Vitamin D?
Increased serum [Ca2+]
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)
X = Bone resorption
Prolonged hyperparathyroidism results in what 2 conditions?
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]
What are 3 treatments for Mineral Bone Disease?
Low phosphate diet
Oral phosphate binders
Calcitriol (suppress PTH release)
What is it called when blood is visually seen in the urine?
Gross hematuria
What is is called when RBCS can only been seen in the urine by light microscopy?
Microscopic hematuria (>3 RBCs/hpf)
What are causes of heme positive red urine?
Hematuria, hemoglobinuria, myoglobinuria
What are causes of heme negative red urine?
Beeturia, drugs (rifampin, pyridium), and acyte porphyria
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
X = peroxidase
What could cause a positive heme dipstick reading without RBCs present?
Hemolysis or rhabdomyolysis
Urine microscopy can help differentiate glomerular bleeding from (X) bleeding. Dysmorphic RBCs (>(Y)%) or (Z) are consistent with glomerular bleeding
X = lower urinary tract Y = 80 Z = RBC casts
What are 4 common renal causes of hematuria?
Stones Infection (UTI) Neoplasm (uroepithelial) Glomerular disease IgA nephropathy Thin base membranes Glomerulonephritis
What are 3 non-renal causes of hematuria?
Menstruation
Vigorous exercise
Trauma
Adults can excrete up to (X) mg/day of total protein, (Y) mg/day of albumin. Mostly Tamm-Horsfall protein, some (Z)
X = 150 Y = 30 Z = immunoglobulins
What are the 3 classes of proteinuria?
Glomerular proteinuria
Tubular proteinuria
Overflow proteinuria
Glomerular proteinuria:
Disruption of the glomerular filtration barrier can result in filtration of high molecular weight plasma proteins (e.g. (X))
X = albumin
Tubular proteinuria:
Tubular damage or dysfunction results in decreased capacity to reabsorb (Y) proteins
Y = low molecular weight
Overflow proteinuria:
Increased production of plasma proteins that are filtered by the glomerulus can overwhelm the tubular capacity for reabsorption (e.g. (X))
X = light chain proteins in multiple myeloma
The urine dipstick only detects what protein?
Albumin
Does not detect light chain proteins
What are the levels of protein content of urine on a dipstick?
1+ = 30 mg/dL 2+ = 100 mg/dL 3+ = 300 mg/dL 4+ = >300 mg/dL
The urine dipstick can give false positive of proteinuria under what condition?
High urine pH
What are the 2 methods of quantification of proteinuria in terms of collection time?
24 hour urine collection
Spot urine protein/creatinine ratio
What are the features and limitations of a 24 hour urine collection?
Inaccurate urine collection is greatest source of error
Should always simultaneously measure urine creatinine excretion to determine adequacy of sample
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
X = 2
What is the range for moderately increased proteinuria (microalbuminuria)?
30-300 mg/day
What is the range for severely increased proteinuria (macroalbuminuria or overt proteinuria)?
> 300 mg/day
What is the range for nephrotic range proteinuria?
> 3.5 g/day (>3500 mg/day)
What are 4 causes of begign proteinuria?
Fever
Exercise
Seizures
Orthostatic (postural) proteinuria
What are 2 causes of tubular proteinuria?
Hypertensive nephrosclerosis
Tubulointerstitial disease
What is a cause of overflow proteinuria?
Multiple myeloma
What are several causes of glomerular proteinuria (under primary glomerulopathy)?
Minimal change disease Membranous nephropathy Focal segmental glomerulosclerosis Membranoproliferative GN IgA nephropathy
What are several causes of glomerular proteinuria (under secondary glomerulopathy)?
Diabetic nephropathy
Amyloidosis
Collagen vascular disorders
Drugs (NSAIDs, heroin, gold)
What are 6 treatments for proteinuria?
ACE inhibitors Angiotensin receptor blockers (ARBs) Blood pressure management Target <125/75 Smoking cessation Moderate protein restriction Lipid management
