Chronic Kidney Disease Part 1

Question 1

Hallmark of DM nephropathy

Answer 1

persistent albuminuria > 300 mg/24 hours

dm retinopathy + absence of clinical or laboratory evidence of other kidney or renal tract disease

microalbuminuria=urinary albumin excretion of > 30 mg/24 hours and less than 300 mg/24 hours in 2 of 3 samples

DEFINICAO MICROALBUMINURIA= presnca de albuminuria maior q o valor normal mas nao detectavel no dipstick 30-300mg/dia

According to the American Diabetes Association, for patients with type 2 diabetes mellitus, urine albumin should be assessed annually, starting from the point of diagnosis.

Microalbuminuria is associated with kidney dysfunction and atherosclerotic cardiovascular events.

Healthcare workers need to encourage changes in lifestyle and initiate therapy when microalbuminuria is discovered.

If treatment with an ARB or ACE inhibitor does not sufficiently control proteinuria in patients with chronic kidney disease, further control of proteinuria can be done by adding mineralocorticoid receptor antagonists (MRA), such as spironolactone or eplerenone.

However, MRAs are associated with an increased risk of hyperkalemia.

A new agent finerenone which is a nonsteroidal MRA decreased proteinuria while causing lower rates of hyperkalemia.

The current diagnosis of microalbuminuria also includes a urinary albumin/creatinine ratio (UACR) ranging between 2 to 20 mg.

In addition to the individual variability, one should be cautious that some cases have an elevated UACR at baselines, such as males, African Americans, Asians, smokers, people with higher muscle mass, patients with urinary tract infection, and genital leakage.

Question 2

first pathologic sign in dm nephropathy type 1 dm and proteinuria

Answer 2

glomerular basement membrane thickening

Microalbuminuria develops from a dysfunction of the GBM permitting albumin to enter the urine. inadequate control of blood sugars inhibits this enzyme, reducing the negative charge on GBM and allowing excessive amounts of albumin to leak out. Advanced glycosylation end-products can also neutralize the negative charge of albumin by binding with the proteins of both the GBM and mesangial matrix.[6] Additionally, hyperglycemia initiates the glycation of GBM and podocyte receptors interfering with the charge on GBM.[1][2][6]

The current hypothesis, known as the ‘Steno hypothesis,’ is that systemic vascular endothelial dysfunction initiates the development of microalbuminuria and cardiovascular disease, as there is a strong correlation between these three variables.

Therefore, having comorbidities that cause endothelial damage is considered a risk factor. These include increased age, insulin resistance, dyslipidemia, obesity, hypertension, decreased physical activity, and smoking.[5] Some studies predict a genetic component linking together microalbuminuria, atherosclerosis, and even nephropathy. An increased UAE rate was seen among patients with a deletion-deletion polymorphism of the ACE gene.[6]

Microalbuminuria has been associated with patients who have type 1 or type 2 diabetes. For patients with type 1, the prevalence of microalbuminuria within the first three years after diagnosis is only 6%; however, after five years, it is 41%. In type 2, the prevalence is 20% to 25% for newly diagnosed and long-standing diabetics.[8][9] In patients with uncontrolled hypertension, microalbuminuria was seen in 47.4% of patients; whereas, in patients with controlled blood pressure it was 36.7%.[10]

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Pathophysiology

Microalbuminuria arises when GBM, a complex sieve, leaks an increased amount of albumin. The proposed mechanism is a combination of glomerular size enlargement, GBM thickening, mesangial expansion, and podocyte foot process effacement. Microalbuminuria can also occur via inadequate tubular reabsorption.[2][7]

Dysregulated enzymatic metabolism of the extracellular matrix is the pathogenesis behind developing endothelial damage.[3][8] Thus, at vascular places, other than just the renal system, the albumin can either leak out of or enter the vessel wall. When this happens, albumin can stimulate inflammation, lipid accumulation, and atherosclerosis, which eventually could form fixed albuminuria and decreased kidney function.[7]

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Histopathology

There are structural changes at the level of GBM that lead to microalbuminuria. However, these are heterogeneous and may even be present in patients with normoalbuminuric diabetes. The GBM alterations are typically seen in type 1 diabetes, but not type 2.[8]

Furthermore, researchers found no correlation between increased GBM permeability and any histological changes. Since the majority of the GBM dysfunction is through altered charge selectivity, not size, it would not appear on histology.[2][8]

Question 3

arteriolar hyalinosis usually seen within

Answer 3

3 to 5 years

Question 4

exudative lesions in type 1 DM nephropathy pathology

Answer 4

arteriolar hyalinosis, bowmans capsular drops, hyaline caps

Question 5

45-59 ml/min GFR

Answer 5

stage 3a

Question 6

GFR 30-44

Answer 6

stage 3b

Question 7

GFR 15-29

Answer 7

stage 4

Question 8

GFR less than 15

Answer 8

stage 5

Question 9

BP target in CKD with proteinuria

Answer 9

less than 120/80

Question 10

education on RRT and hepatitis B vaccination

Answer 10

Stage 4

Question 11

AVF creation

Answer 11

stage 5

Question 12

Goal for Acei or ARB treatment

Answer 12

urine protein level < 0.5 g/day

Question 13

target for weight loss in obese patients

Answer 13

5%

Question 14

dietary salt restriction

Answer 14

<5 g (90 meqs sodium per day)

Question 15

protein requirement for normal adults or those with uncomplicated CKD

Answer 15

0.8 g protein/kg/day

Question 16

CKD patients with complications

Answer 16

0.6 g protein/kg/day or 0.3 g/kg + ketoacids or a mixture of aminoacid

Question 17

CKD patients with loss of muscle mass

Answer 17

0.8 g protein/kg/day

Question 18

CKD with proteinuria

Answer 18

< 0.8 g protein/kg/day + 1 g protein/g proteinuria

Question 19

at least 3 episodes of itch in a 2 week period that causes difficulty for the patient or as itch that occurs over a 6 month period in a regular pattern

Answer 19

pruritus

Question 20

associated with hyperparathyroidism or elevated Ca x Phos

Answer 20

calciphylaxis

Question 21

main regulator of systemic iron hoemostasis

Answer 21

hepcidin

Question 22

increase in PTH secretion immediate effects

Answer 22

increase in 1a hydroxylase activity,

bone turnover,

ca reabsoprtion
decrease in renal po4 reabsorption

Question 23

more than 3 rbc/hpf in atleast 2 of 3 freshly voioded midstream clean catch urine

Answer 23

asymptomatic hematuria

Question 24

imaging to localize and control source of bleeding

Answer 24

cystoscopy

Question 25

diagnostic when there is any suspicion of upper tract disease

Answer 25

retrograde pyelography

Question 26

glomerular hematuria + active urine sediment + wbcs/casts

Answer 26

nephritic syndrome

Question 27

hallmark of nephritic syndrome

Answer 27

glomerular hematuria

Question 28

definitive finding in nephritic syndrome

Answer 28

rbc casts

Question 29

principal underlying abnormality in nephrotic syndrome

Answer 29

increased permeability of the glomerular capillaries

Question 30

most common underlying systemic disease causing nephrotic syndrome

Answer 30

Diabetes Mellitus

Question 31

1+ urine dipstick protein is equivalent

Answer 31

30-100 mg/dL

Question 32

most common urine lipid

Answer 32

esterified cholesterol

Question 33

birefingent birght cross like appearance in polarizing microscope

Answer 33

lipiduria

Question 34

type of RTA associated in obstructive uropathy

Answer 34

type 4

Question 35

test of choice to diagnose obstructive uropathy

Answer 35

renal ultrasonography

Question 36

stage 1 hypertension

Answer 36

140-159/90-99

Question 37

benzene ring-shaped cysteine crustals

Answer 37

cystinuria

Question 38

coffin lid crystals

Answer 38

struvite

Question 39

imaging procedure of choice for stones

Answer 39

noncontrast helical CT scan

Question 40

radioopaque stones

Answer 40

calcium, cysteine

Question 41

radiolucent stones

Answer 41

uric acid, indinavir or triamterene stones

Question 42

size of stones that will pass spontaneously

Answer 42

4 mm

Question 43

most important vascular complication in patients with CKD

Answer 43

CAD

Question 44

strongest indicator of possible renal underpefusion

Answer 44

overt hypotension

Question 45

normal blood glucose in OGTT

Answer 45

less than 140 mg/dL

Question 46

impaired glucose tolerance or preDM

Answer 46

OGTT 140-199 mg/dL

Question 47

primary cause of insulin resistance in uremia

Answer 47

impaired tissue sensitivity

Question 48

independent risk factors for cardiovascular complication in patients with ESKD

Answer 48

insulin resistance and hyperinsulinemia

Question 49

uremic dyslipidemia

Answer 49

increased triglycerides, ldl and vldl, decreased hdl cholesterol

Question 50

metformin should be used with caution when eGFR is

Answer 50

less than 60 ml/min

Question 51

when to discontinue metformin

Answer 51

less than 30 ml/min

Question 52

insulin sensitizer, causes lactic acidosis in CKD

Answer 52

metformin

Question 53

T3 levels in CKD

Answer 53

low due to low conversion of T4

Question 54

strong inhibitors of protein binding of T4

Answer 54

urea, creatinine, indoles, phenols ,heparin

Question 55

Increase in GH secretion

Answer 55

fasting, insulin induced hypoglycemia, increase of protein

Question 56

glucose load in growth hormone secretion

Answer 56

decrease GH secretion

Question 57

reason for reduced linear bone growth in CKD

Answer 57

reduced effectiveness of GF and IGF-1

Question 58

primary mediator of effects of GH

Answer 58

IGF-1

Question 59

GH deficiency in GFR and renal plasma flow

Answer 59

decrease GFR and plasma flow

Question 60

reason for GH resistance

Answer 60

decreased GH receptors and post GH receptor defects, decreased IGF-1 synthesis

Question 61

stimulates protein synthesis, decreases urea generation and improves nitrogen balance

Answer 61

recombinant human GH

Question 62

adverse reaction to GH treatment

Answer 62

benign intracranial hypertension, hyperglycemia, fluid retention

Question 63

most abundant steroid hormone

Answer 63

DHEA

Question 64

antifibrotic and antiapoptotic effects in kidney

Answer 64

estrogen

Question 65

responsible for decreased libido, erectile dysfunction, oliospermia and infertility, osteopenia in adults with ESKD

Answer 65

hypogonadism, low testoteron and hyperprolactinemia

Question 66

development of lipid enriched plaques in the intimal layer of the artery

Answer 66

atherosclerosis

Question 67

phenomenon of noncalcified nonatheromatous stiffening of smaller muscular arteries

Answer 67

arteriolosclerosis

Question 68

characterized by medial thickening and heavy calcification without the presence of atheroma

Answer 68

monckerberg’s medial calcific sclerosis

Question 69

LV remodeling occurs as early as

Answer 69

stage 2

Question 70

indirect risk factors of CVD/CKD

Answer 70

DM, obesity

Question 71

partially treated uremia and side effects of dialysis

Answer 71

residual syndrome

Question 72

most abundant solute excreted by kidney

Answer 72

urea

Question 73

uremic toxin that impairs platelet function

Answer 73

guanidosuccinic acid

Question 74

aromatic waste compound normally excreted in the largest quantity

Answer 74

hippurate

Question 75

uremic solute associated with cardiovascular death in patients undergoing hd

Answer 75

p-cresol sulfate

Question 76

Fractional excretion of calcium remains unchanged until gfr

Answer 76

<25 ml/min

Question 77

As GFR decrease Na and Phosphate is maintained by

Answer 77

Decreased reabsorption

Question 78

absence of cellular (osteoblast and osteoclast) activity, osteoid formation and endosteal fibrosis

Answer 78

low turn over (adynamic bone disease)

Question 79

bone biopsies that features secondary hpt and mineralization defect, extensive osteoclastic and osteoblastic activity and increased endosteal peritrabecular fibrosis with more osteoid

Answer 79

mixed uremic osteodystrophy

Question 80

rate of skeletal remodeling: bone resoprtion + formation

Answer 80

turn over

Question 81

how well bone collagen calcified during the formation phase of skeletal remodeling

Answer 81

mineralization

Question 82

amount of bone per unit volume of tissue

Answer 82

volume

Question 83

Dxa to assess fracture risk is recommended/not recommended in

Answer 83

stage 1-3/stage 3b-5

Question 84

LV remodeling occurs

Answer 84

Stage 2-3 CKD

Question 85

primary disease of cardiac muscle assoc with ckd causing systolic dysfunction; interstitial myocardial fibrosis

Answer 85

Uremic cardiomyopathy

Question 86

when is statins recommended in ckd

Answer 86

Stage 3-5 in older than 50 years or less than 50 yo with additional risk factors

Question 87

screening of anemia starts at stage

Answer 87

G3

Question 88

tx of aluminum toxicity

Answer 88

deionized water or chelation with desferrioxamine

Question 89

most effective tx of posttransplantation erythrocytosis

Answer 89

Raas blocker

Question 90

gold standard in assesing iron stores

Answer 90

Bone marrow iron

Question 91

if hit is established, what should be considered

Answer 91

Direct thrombin inhibitors or factor Xa

Question 92

Other tx for uremic bleeding

Answer 92

Ddvap
cryoprecipitate
estrogen

Question 93

primary prevention of stroke

Answer 93

aspirin

Question 94

what benefits would initiation of bicarbonate confer

Answer 94

Delay in progression of her CKD
• Improvement in serum potassium
• Improved bone health
• Reduce muscle wasting

Question 95

As microalbuminuria occurs mostly in the absence of any serious underlying renal disease, more benign and common causes of microalbuminuria should be considered first. The following questions should be asked:

Answer 95

Is this transient - This may be because of physical exertion and fever

Is this orthostatic - Typically seen in tall, thin adolescents or people younger than 30 years; there is an association with severe lordosis; normal renal function and albuminuria is frequently less than 1 g/24 hours[13]

Is nonrenal disease causing it, such as severe cardiac failure, sleep apnea - Normal renal function and albumin loss is less than 1 g/24 hours

Are there any symptoms suggestive of nephrotic syndrome or significant glomerular pathology

Are there any changes in the appearance of urine, such as red/smoky, frothy; is there any correlation of this to a respiratory tract infection

Is there ankle, periorbital, labial, or scrotal edema

Has the patient ever been diagnosed with high blood pressure

Is there a history of high cholesterol levels in the patient’s blood

Has the patient ever had a diagnosis of a multisystem disease or another glomerulopathy

Is there a past or family history of any renal disease

If the patient has diabetes mellitus, for how long; are there any complications, such as retinopathy

Is a family history of diabetic nephropathy present

Are there any multisystem inflammatory diseases present, such as systemic lupus erythematosus (SLE) or rheumatoid arthritis

Are there symptoms like joint discomfort, skin rash, bone pain, fever, weight loss, night sweats, or Raynaud syndrome

Is the patient on any medication, including herbal remedies

Are there any past medical illnesses, such as jaundice, malaria, tuberculosis, syphilis, or endocarditis

Is the patient at risk of HIV infection or hepatitis

Question 96

complicacoes da proteinuria

Answer 96

With progressive disease, patients can develop macroalbuminuria, diabetic kidney disease, and proteinuria.[1] The level of serum albumin is unable to predict the nutritional status of a patient. However, during states of extreme starvation, serum albumin is low, and urine albumin is high.

Other complications of proteinuria are:

Pulmonary edema which is attributable to fluid overload

Acute kidney injury secondary to intravascular depletion and progression of kidney disease

Increased risk of cardiovascular diseases

Increased risk of vascular thrombosis, such as renal vein thrombosis

Increased risk of bacterial infections

Question 97

albuminuria prognostico

Answer 97

The main reason to test the UAE level is to evaluate the patient for possible future complications. However, providers should not merely view microalbuminuria as a kidney damage marker, but as a predictor of kidney dysfunction progression rate and reflect the effect of systemic disorders on the kidney.[1]

It is well known that the glomerular filtration rate (GFR) is useful in staging chronic kidney disease. In comparison to microalbuminuria, GFR is a pure kidney damage marker. Several studies have demonstrated that there is a continuous correlation between microalbuminuria and developing end-stage renal disease. Therefore, when presented with a patient with a reduced GFR classified under stage 3 or 4, the patient with microalbuminuria should be considered very high risk, instead of high risk as per the GFR. This classification ensures that prompt action is taken to prevent further complications, such as macroalbuminuria, diabetic kidney disease, proteinuria, and chronic kidney disease.[5]

Microalbuminuria has links with a high rate of atherosclerotic cardiovascular events (such as coronary artery disease, stroke, and peripheral vascular disease) and subsequently increased morbidity and mortality. The evidence reveals in adults; it is a four to six-fold increase, whereas, in patients with diabetes, it is only two-fold.[3][5][6][9] The risk of cardiovascular events is even higher for patients with macroalbuminuria versus microalbuminuria. Thus, screening and compliance with the treatment of microalbuminuria could prevent macroalbuminuria and even death.[3][6] The UACR range for microalbuminuria starts at 2 mg/day, but data shows that the risk between increased UAE and cardiovascular disease can begin even at 1 mg/day.[3]

Among patients with essential hypertension, microalbuminuria can predict kidney function decline, coronary artery stenosis, and hypertensive retinopathy. Importantly, the latter two are reversible with adequate treatment

Question 98

albuminuria tto

Answer 98

If microalbuminuria is present, aggressive measures should ensue with the ultimate goal of decreasing the risk of cardio-metabolic complications. The first-line treatment is lifestyle modifications to control diabetes and hypertension. Although it seems trivial, this can save retinal function, prevent further kidney damage, decrease the risk of cerebrovascular accidents, and reduce microvascular complications.[5] For patients with type 2 diabetes with microalbuminuria, reports indicate that a normal protein diet of (0.8 g x kg)/(bodyweight x day) was optimal, not a low protein diet.[19] Interestingly, eating chicken, instead of red meat, saw a reduction in urinary albumin excretion of 46% along with decreasing total cholesterol and apolipoprotein B in type 2 diabetic patients with microalbuminuria.[11]

Maintaining an A1c of less than 7% has been shown to decrease the risk of developing not only microalbuminuria but also macroalbuminuria. The evidence shows that rosiglitazone and insulin have the best outcomes and the least side effects.[11] Angiotensin-converting enzyme (ACE) inhibitor, angiotensin receptor blocker (ARB), or vasodilatory beta-blockers can reduce blood pressure. Although many providers commonly believe that ACE inhibitors and ARBs are interchangeable in the treatment method, some data does not support the effectiveness of ARBs.[5] These classes of drugs have an effect on reducing proteinuria separate from their antihypertensive effect.[20] In patients younger than 50 years, the blood pressure goal should be 120/70-75 mmHg, whereas it is slightly higher at 125-130/80-85 mmHg in those older than 50. Moreover, ACE inhibitors are useful in patients with diabetes, even without hypertension. They have a reno-protective effect of decreasing mesangial expansion and preventing the onset of glomerulosclerosis.[6][11][21] The other anti-hypertensives help manage hypertension but have minimal effect in delaying the progression of kidney disease.[3][22] Normalization of blood pressure in hypertensive patients results in a decrease in intraglomerular pressure and albuminuria.[23]

If treatment with an ARB or ACE inhibitor does not sufficiently control proteinuria in patients with chronic kidney disease, further control of proteinuria can be done by adding mineralocorticoid receptor antagonists (MRA), such as spironolactone or eplerenone. However, MRAs are associated with an increased risk of hyperkalemia. A new agent finerenone which is a nonsteroidal MRA decreased proteinuria while causing lower rates of hyperkalemia.[24]

Immunosuppressants, such as cyclophosphamide and azathioprine should be used in patients who have progressive renal insufficiency or who have vasculitic changes on renal biopsy.[25]

Several experimental drugs show promising evidence but require further studies to evaluate if they decrease the long-term cardiovascular disease associated with microalbuminuria. For one of the groups, the mechanism is by decreasing protein glycation. These medications are thiamine, ALT-711 (a cross-link breaker of advanced glycation), and pimagedine (a second-generation inhibitor of advanced glycation). Additionally, ruboxistaurin, a protein kinase C-beta inhibitor, has been implicated in decreasing UAE.[11] Increased vascular endothelial growth factor (VEGF), which regulates vascular permeability and angiogenesis, has been linked with microalbuminuria in patients with type 2 diabetes. Thus, VEGF inhibitors could be helpful in patients with microalbuminuria.[8] Glycosaminoglycans, such as sulodexide, can also decrease albuminuria.[3] Statins, on the other hand, have a well-documented effect in reducing the risk of cardiovascular disease, but their role in decreasing urinary albumin excretion is still controversial. Due to its cardioprotection, it merits inclusion in the treatment regimen.[3]

When considering the associated comorbidities with microalbuminuria, the treatment recommendations should also include weight loss, aspirin, and maintaining low-density lipoprotein cholesterol of less than 100.[11] Finally, the level of microalbuminuria can serve as an indicator of treatment response, especially in patients with hyperinsulinemia, insulin resistance, and hypertension.[1][3]

In terms of specific treatments, sodium-glucose co-transporter 2 (SGLT2) inhibitors, such as canagliflozin and empagliflozin have gained popularity not only in the management of diabetes mellitus but also in reducing the development or further worsening of albuminuria.[26] A meta-analysis observed that the combination therapy with SGLT2 inhibitors and other hypoglycemic agents helps reduce albuminuria.[27]

Non-dihydropyridine calcium channel blockers (NDCCBs), such as diltiazem and verapamil, decrease proteinuria more than dihydropyridine calcium channel blockers (DCCBs) because NDCCBs affect both the afferent and efferent arteriole.[28][29]

Endothelin activation has an association with renal inflammation and fibrosis. Endothelin A (ETA) receptor blockade leads to the dilation of the glomerular capillaries, reducing albumin permeability. Endothelin B (ETB) reduces arterial pressure by decreasing salt and water reabsorption from the kidneys. Experimental ETA-selective antagonists, such as avosentan and atrasentan, have been shown to decrease proteinuria.[30][31]

Question 99

e Brito-Ashurst et al. (6) reported that oral

sodium bicarbonate supplements at a dos-

age of approximately 22 mEq/d (and stan-

dard therapy) slowed the decline in mea-

sured CrCl from 5.9 to 1.9 ml/min per 1.73

m

2

. Fewer patients developed end-stage

kidney disease (6.5 versus 33.0%). Nutri-

tional parameters, including dietary intake,

normalized protein nitrogen appearance,

serum albumin, and mid-arm muscle cir-

cumference, improved in the bicarbonate-

supplemented group