ICL 2.5: Chronic Kidney Disease

Question 1

LS is a 52 year old male with chronic kidney disease due to hypertension.

he has gradually lost renal function with attendant increases in SCr to 5 mg/dl.

during review of his laboratory studies, it is noted that he has increased serum phosphate and decreased serum calcium concentrations. His Mg concentration is noted to be high.

a parathyroid hormone level is drawn and is noted to be markedly increased.

Answer 1

CKD

serum phosphate is high which means phosphate is binding to calcium and causing calcium deposits and low serum Ca

low vitamin D because decreased renal function

PTH increase because low Ca is stimulus for parathyroid to release PTH and his PTH response to low Ca is also enhanced

high Mg is probably from taking an antacid that can’t be excreted

Question 2

what is the prevalence of CKD?

Answer 2

In the United States, there is a rising incidence and prevalence of Kidney Disease

nearly 350,000 of these are on dialysis

also, there is an increasing prevalence of earlier stages of chronic kidney disease which unfortunately is “under-diagnosed” and “under-treated” in the United States

the incidence of recognized CKD in people ages 65 and older more than doubled between 2000 and 2008

Question 3

what is stage 1-5 CKD?

Answer 3

stage 1: GFR > 90

stage 2: GFR 60-80

stage 3: GFR 30-59

stage 4: GFR 15-29

stage 5: GFR < 15

there is an epidemic of kidney disease and nephrologists dont see patients till late stage 3 or stage 4/5 so there’s tons of patients that dont even get seen for kidney disease!

Question 4

what are the causes of mortality in ESRD patients?

Answer 4

once you get a transplant your mortality risk drops alot

patients with ESRD or on dialysis have significantly increased mortality compared to the general population

there is also an increase death rate, hospitalization, and chronic conditions increases when you have CKD

Question 5

what is the new CKD staging?

Answer 5

it includes albuminuria!!

it’s a risk factor that predicts progression of CKD because sometimes people have normal creatinine and normal grr but there’s maybe microscopic albuminuria!

there’s such a big population of unrecognized CKD….

Question 6

what are the markers of renal function?

Answer 6

1. serum creatinine
2. estimated gFR
3. cystatin C (more accurate but not as commonly used)

Question 7

what are the advantages of using creatinine for kidney function?

Answer 7

it’s freely filtered so it’s easily measured and it’s cheap to measure!

creatinine is also secreted in the kidney though so it technically overestimates GFR a bit

also it’s based on muscle mass so men should have higher GFR – also high protein diet can falsely elevate creatinine level without corresponding GFR

muscle wasting diseases can elevate GFR falsely too

you can’t say someone has a certain GFR if they aren’t at steady stage aka if they have acute kidney injury!

Question 8

which drugs can effect the tubular secretion fo creatinine?

Answer 8

there can be a decrease tubular secretion of creatinine which would decrease GFR when taking certain drugs:

1. trimethoprim
2. cimetidine
3. fenofibrate

Question 9

which facts affect extra-renal elimination of creatinine?

Answer 9

1. dialysis = drops creatinine because it’s been cleared by the machine
2. decrease by inhibition of gut creatinase by antibiotics
3. increased by large volume losses of ECF

Question 10

what can interfere with the creatinine assay and consequently effect GFR?

Answer 10

1. spectral interference like from bilirubin in people with liver failure
2. chemical interferences like glucose and ketones in someone in DKA

Question 11

what is a better measure of renal function than serum creatinine?

Answer 11

estimated GFR; creatinine is effects by so many factors it’s not that accurate

MDRD study equation estimated GFR takes into account things like gender, ethnicity, age, weight

there’s also a Cockcroft-Gault equation but it only takes into consideration the age, weight and gender so MDRD is normally used for GFR on lab reports but the Cockcroft-Fault equation is used for drug dosing

GFR is normally 110-120 mL/min

Question 12

what is the role of cystatin C?

Answer 12

the benefit of using this is that it’s generated by all cells and distributed throughout the ECF whereas creatinine is just generated by muscle cells – also since it’s not effected by muscle it’s not effected by age, race, sex etc – however it’s not excreted in the urine so it’s hard to study

KDIGO suggests measuring cystatin C in adults with eGFR creat 45–59 ml/min/1.73 m2 who do not have other markers of kidney damage if confirmation of CKD is required

if cystatin C is measured, KDIGO suggests that health professionals use a GFR estimating equation to derive GFR from serum cystatin C rather than relying on the serum cystatin C concentration alone

Question 13

what is the importance of proteinuria?

Answer 13

1. marker of kidney damage
2. it’s a clue to the type of CKD
3. it’s a risk factor for adverse outcomes
4. it effects modifiers for interventions
5. hypothesized surrogate outcomes and target for interventions

Question 14

what is the most common cause of proteinuria of CKD in diabetic patients?

Answer 14

diabetic nephropathy

there could be other glomerular diseases going on too though so don’t just assume it’s from the DM!

Question 15

what are the causes of CKD?

Answer 15

1. DIABETES
2. HTN
3. glomerulonephritis
4. cystic kidney disease

Question 16

what are the manifestations of CKD?

Answer 16

1. abnormal sodium-water metabolism –> they’ll present with edema or HTN
2. abnormal acid-base abnormalities –> they’ll present with metabolic acidosis due to uremia or RTA
3. abnormal hematopoiesis –> they’ll present with anemia of CKD
4. cardiovascular abnormalities –> they’ll present with LVH, CAD, diastolic dysfunction
5. abnormal calcium-phosphorus metabolism –> they’ll present with hyperphosphatemia, pruritus, arthralgia
   hyperparathyroidism
   renal osteodystrophy

Question 17

what are the tests for evaluating CKD?1.

Answer 17

1. serum electrolytes
2. urine spot protein analysis (24 hour no longer recommended because they’re not accurate)
3. ANA, C3, C4
4. SPEP, UPEP
5. kidney ultrasound
6. urine sediment analysis
7. biopsy if there’s evidence of glomerular disease without diabetes or sudden onset of nephrotic syndrome or glomerular hematuria

Question 18

what are the risk factors for the development or progression of kidney disease?

Answer 18

1. albuminuria
2. hypertension
3. episodes of acute kidney injury
4. hyperlipidemia
5. high-protein diet
6. metabolic acidosis
7. hyperphosphatemia
8. hyperuricemia
9. hyperglycemia
10. obesity
11. smoking
12. underlying cause of kidney disease (e.g., diabetic nephropathy)
13. elevated plasma soluble urokinase receptor (suPAR)
14. APOL1 alleles
15. black or Native American race
16. male sex
17. older age
18. family history of DM, CKD, or ESRD
19. low birth weight

Question 19

what can reduce the risk of CKD progression?

Answer 19

treat diabetes, hypertension, obesity, metabolic syndrome, hyperlipidemia

things that would likely reduce risk include smoking, cocaine, nephrotoxic exposure, BPH, kidney stones, nephrolithiasis, contrast

things that may lower risk include reducing protein intake, fix obesity, treat metabolic syndrome, low income/education level, chemical and environmental hazards

things you can’t fix are advanced age, gender, ethnicity, family history, low birth weight, prior kidney damage, congenital or acquired solitary kidney

Question 20

how is HTN associated with CKD?

Answer 20

renal survival is better if HTN is controlled! RAAS bloackade is the key

lowering BP reduces renal events in DM too!

adult with HTN and CKD should be treated to a BP goal of less than 130/80

if they have albuminuria too you should add ACEI –> ARB if intolerant

Question 21

what is the benefit of RAAS blockade?

Answer 21

The benefit of decreasing proteinuria using ACEi / ARB has been shown in AASKD, RENAAL (Losartan Vs placebo ), IDNT

RENAAL : Losartan reduced the incidence of a doubling of the serum creatinine concentration (risk reduction, 25 percent; P=0.006) and end-stage renal disease (risk reduction, 28 percent; P=0.002) but had no effect on the rate of death. The benefit exceeded that attributable to changes in blood pressure

the greater the proteinuria, the greater is the benefit of the low blood pressure goal in slowing GFR decline

so it doesn’t just lower BP, it also reduces other risk factors!!

Question 22

what are the first line agents for treating HTN?

Answer 22

Although both ACE inhibitors and ARBs are kidney protective, ACE inhibitors are the first choice because it is not yet clear if ARBs give equivalent cardioprotection

SCr increases are common and can often be tolerated. Obtain SCr and K levels 7–10 days later after initiation of an ACEI or ARB and with changes in anti-RAAS therapy.

increases of SCr 30% above baseline within 3 months of initiating anti-RAAS therapy may be acceptable because over time if reduces BP and causes remodeling so it takes a bit for GFR to get back to normal. Greater elevations should be thoroughly investigated and may require nephrology consult.

for baseline SCr 2.0 mg/dL, SCr increases 1.0 mg/dL may be tolerated.
Combined ACE inhibitor and ARB therapy may be more antiproteinuric than ACE therapy inhibitor or ARB alone

combination ACE inhibitor and ARB therapy should therefore be used with caution in those with evidence of advanced atherosclerotic CV disease, but it may still be warranted, especially if there is heavy proteinuria

Question 23

what are the benefits of controlling protein intake in CKD patients?

Answer 23

reducing dietary protein intake from the usual level (about 1 to 1.5g/kg ideal body weight per day) to about 0.8 g/kg ideal body weight per day (low-protein diet) slows GFR decline in those with proteinuria of more than 1g/day –> so once you get to stage 4 CKD you should limit protein intake

another benefit of the lower protein intake is that it slows proteinuria progression in CKD, even in those who at baseline have low-level proteinuria (e.g., <250mg/day)

for a 70-kg person, ingestion of about 55-60g of protein daily would achieve the dietary goal of 0.8g/kg ideal body weight per day.

Question 24

what is the target lipid level in patients with CKD?

Answer 24

TG: <150 mg/dL

LDL-C: 70-100 mg/dL

non HDL-C: <130 mg/dL

Question 25

how do you treat dyslipidemia in patients with CKD?

Answer 25

1. statin to reduce LDL-C to 70-100

CKD dose adjustments: atorvastatin and pravastatin do not require dose adjustments. It is unknown, if dose adjustments are required for simvastatin and fluvastatin. Lovastatin: a 50% dose reduction recommended, if GFR <60 mL/min/1.73 m2.

2. smoking cessation
3. avoid NSAIDs
4. avoid herbal therapy unless approved because can cause fibrosis
5. treat obesity
6. avoid phosphate cathartics
7. avoid IV bisphosphonates because can exacerbate renal failure
8. give NaHCO3 to correct metabolic acidosis because it also has anti catabolic effects

Question 26

how do you treat gout in CKD patients?

Answer 26

allopurinol!

hydrocholorthiazide isn’t recommended since it can increase hyperuricemia

Question 27

what can cause anemia of chronic kidney disease?

Answer 27

1. Iron deficiency
2. chronic inflammation
3. hyperparathyroidism
4. blood loss
5. ACEi/ARB
6. aluminum toxicity

CKD causes anemia because there’s decreased EPO production but you can’t give too much or else it increases mortality! do not exceed Hb of 13

Question 28

which mineral and bone disorders are associated with CKD?

Answer 28

1. dynamic bone
2. osteitis fibrosa
3. osteomalacia

in CKD you have phosphate retention, low activated vitamin D which causes hypocalcemia which goes back to the parathyroid and causes hyperparathyroidism

treat by reducing phosphate in the diet and give activated vitamin D

Question 29

what is the trade off phenomenon?

Answer 29

as the GFR decreases, there is an increase in phosphate and decrease in calcium

this is because there isn’t activation of vitamin D since the enzyme you need to do that is from the kidney! so without vitamin D you can’t absorb calcium from the gut and phosphate can’t be excreted so there’s an increase in phosphate

specifically the low calcium causes stimulation of parathyroid gland which increases PTH levels and this acts on the kidney and bone to restore phosphorous and calcium levels but this is at the expense of increased PTH! eventually though when you get to EDSR you won’t be able to compensate any more and you get high phosphate and low calcium

Question 30

which immunizations can you get for CKD patients?

Answer 30

1. inactivated influenza A/B vaccine
2. pneumovax HepB vaccine

do NOT give attenuated influenza virus vaccines or tamiflu

Question 31

how do you medically manage DM CKD patients?

Answer 31

once GFR drops below 45 do not give metformin

Question 32

what is nephrogenic fibrosing dermopathy?

Answer 32

a side effect of gadolinium contrast in patients with CKD

it’s swelling of the hands and palmar erythema, blisters and contracture of the fingers

Question 33

when do you refer for kidney transplant?

Answer 33

proteinuria with a drop in GFR that isn’t improving

Question 34

how do you prepare for renal replacement therapy?

Answer 34

CKD education sessions should include options of Dialysis-hemodialysis and peritoneal dialysis & timely referral for Renal Transplantation for Renal Replacement

avoidance of Venu-puncture & Insertion of catheters in peripheral veins of Non-dominant forearm, if the patient opts for Hemodialysis

timely insertion of an internal vascular access and peritoneal dialysis catheter

Question 35

what are the indications for dialysis?

Answer 35

1. uncontrolled hypertension
2. uncontrolled pulmonary edema and fluid overload pericarditis
3. advanced encephalopathy or peripheral neuropathy
4. clinical bleeding
5. persistent anorexia, nausea, and vomiting
6. malnutrition
7. uncontrolled hyperkalemia
8. uncontrolled metabolic acidosis