4. CKD & End Stage Renal Disease

Endocrine function of kidney

Production of renin, erythropoietin, activate vitamin D, glucose control

Marker of GFR

Creatinine

Most accurate way to measure GFR

24-hour urine creatinine clearance

What is the first sign of kidney damage?

Proteinuria

Stage 1 CKD

Normal GFR with presence of kidney damage

What does proteinuria indication with proteinuria in stage 1 CKD?

Dysfunction to filtration barrier

What lab should be checked in anyone with RF for CKD?

Microalbuminuria

Quantity of proteinuria correlates with...

Risk of progressive decline in renal function

Significance of measuring albuminuria in clinical setting

Used for screening, diagnosis, monitoring for diabetic kidney disease

Leading cause of CKD (+ 2 MCC)

Diabetes; then HTN

What is the main driving force for diabetes epidemic worldwide?

Obesity

General causes of CKD

- AKI without full recovery or recurrent AKI

- Chronic, progressive damage

Categories of potential causes of CKD

- Primary & secondary glomerular disease — Diabetic nephropathy

- Tubulointerstitial nephritis

- Hereditary diseases

- Obstructive nephropathies

- Vascular diseases — HTN nephrosclerosis

Contributing factors of prevalence of CKD

- Lack of awareness

- Epidemic of T2DM, obesity

Efforts to improve under/late diagnosis of CKD

- Standardized reporting of eGFR

- Standardized measure of urine albumin (especially in diabetic)

If ordering A1C for DM, also order...

Urine microalbumin

Efforts to mitigate issues associated access to care of CKD

CKD and ESRD very costly for morbidity, mortality, cost

- Increased support of medicare/medicaid to preventative care

Chronic kidney disease (definition)

GFR

Recommended screening for CKD

ALL patients by PCP

Risk factors of CKD

- PMH of DM, HTN, CVD

- FamHx of CKD

- Smoke

- Obesity

Diagnostic workup for screening of CKD

If ≥1 RF → AM urine albumin/Cr AND serum creatinine and eGFR

Normal: Repeat annually

Abnormal: Repeat x2 (3 times total) within 3 months

Diagnostic workup of confirmed CKD

- Fasting lipid and glucose

- Urine microscopy and culture

- Renal US

- A1C

Indications for nephrologist referral

- AKI

- eGFR

Additional CKD workup for stage 3-5 CKD

Serum Ca, phosphate, PTH, vitamin D, iron studies (eval for complications)

Additional CKD workup for age >40

Serum and urine electrophoresis (eval for multiple myeloma)

Additional CKD workup for persistent/severe proteinuria

Renal biopsy (eval for reversible cause/extent of glomerular damage)

Additional CKD workup for resistant HTN

Renal artery US or angiography (eval for RAS)

Additional CKD workup for rapid deterioration of renal function

Eval for rapidly progressive glomerulonephritis:

- ANA, ANCA, anti-glomerular BM, etc

Managing CKD by reducing risk of cardiac complications

- Lifestyle — exercise, smoking, diet

- Statins

- A1C

Management of BP with CKD

- ACEI or ARB

- Mineralcorticoid receptor antagonist

- SGLT2

**Medications lower proteinuria are slow damage of kidneys

BP recommendation for CKD management

What is the most important component in managing CV and renal risks with CKD?

BP control

Monitoring with initiation of ACEI/ARB

eGFR and K+ 1 week and 4 weeks after initiation

What change to creatinine is acceptable with initiation of ACEI/ARB?

Rise

What K+ level should you d/c ACEI/ARB?

>6 despite low K+ diet

What can be added to ACEI/ARB to enhance BP control?

Loop diuretic and Na+ restriction

Addition of SGLT2 inhibitor to ACEI/ARB to enhance BP control

DECREASE diuretic dose by 1/2

Complications of CKD (4)

- Anemia

- Secondary hyperparathyroidism

- Metabolic acidosis

- Hyperkalemia

Anemia as complication of CKD (cause)

- Decreased erythropoietin production of kidney

- CKD commonly have iron deficiency

Diagnosis of anemia as complication of CKD

r/o other causes of anemia — blood loss, hemolysis, paraproteinemia

Demographic associated with anemia as complication of CKD

CKD stage ≥3B (GFR

Significance of managing anemia complication of CKD

Reduces risk of LVH

Cause of iron deficiency in CKD

Dietary

Cause of iron deficiency in ESRD

Multifactorial — blood loss from dialysis, impaired absorption by stomach

Goal of iron when managing anemia with CKD

Transferring saturation >20% and ferritin >200

**Must replenish iron BEFORE ESA therapy is initiated

Management of iron replacement for anemia with CKD

- PO iron 1-2x/day OR IV iron

- Monitor iron q3 months with ESA therapy

What ADR makes iron administration more ideal IV vs. PO?

Constipation (main factor of compliance)

Contraindications for IV iron

Infection — increased risk of bacteremia

What produces erythropoietin (EPO)?

Endothelial cells near renal tubule

Indications for initiation of ESA therapy

Hgb

Goal Hgb with ESA therapy

10-11.5 g/dl; >13 associated with stroke, MI

Recommendation for monitoring of Hgb with ESA therapy

Every 1-2 months, increased frequency for ESRD on dialysis

What GFR value is associated with secondary hyperparathyroidism?

50-60

Cause of secondary hyperparathyroidism as complication of CKD

Hyperphosphatemia, low vitamin D, low Ca → PTH secretion and gland hypertrophy

Effect of ESRD on PTH (+ clinical significance)

Increased bone resistance of PTH → PTH goal higher in ESRD

Goal of PTH level in ESRD

150-600 pg/ml (vs. 10-65 pg/ml CKD)

Management of secondary hyperparathyroidism as complication of CKD

Correct phosphorus, vitamin D, PTH → decreased risk of vascular calcification and LVH

Recommendation for monitoring secondary hyperparathyroidism as complication of CKD

Monitor Ca, PTH, phosphorus

Stage 3: Every 12 months

Stage 4-5: Every 3 months

Management of hyperphosphatemia with secondary hyperparathyroidism as complication of CKD

- Low phosphorus diet — 800-1,00 mg/day

- Phosphate binders taken with meals (bind to phos in stomach/gut to prevent absorption)

Examples of foods with high phosphorus

Meat, dairy, preservatives/additives

Goal calcium levels with secondary hyperparathyroidism as complication of CKD

Stage 3-4: Normal ranges

Stage 5: Lower end of normal

**Use CORRECTED calcium level

Why is it recommended to maintain serum calcium levels in lower range of normal with stage 5 CKD?

Increased risk of vascular calcification with hyperphosphatemia

Why is it important to correct calcium level in CKD patients?

Hypoalbuminemia common

Target value of 25-D (inactive vitamin D)

30-50 ng/ml

Cause of 25-D (inactive vitamin D) deficiency in CKD patients

Lack of sunlight and adequate dietary intake

Goal of management of serum PTH levels in CKD patients

Minimize parathyroid gland hypertrophy → extreme enlargement of glands is non-suppressible

Management of serum PTH levels in CKD patients

- Calcimimetics

- Maintain phosphorus levels (low levels)

- Vitamin D repletion

Management of metabolic acidosis as complication of CKD

- Na bicarb/citrate PO daily

- Goal bicarb ~22

**Prevents bone from secreting bicarb to neutralize acid

Management of hyperkalemia as complication of CKD

Diet restriction, meds

Example of nephrotoxic medication (+ when is risk elevated)

Radiocontrast-induced nephropathy (CIN) — risk higher in CKD stage ≥3

What imaging must be AVOIDED with eGFR

MRI with gadolinium d/t risk of nephrogenic systemic fibrosis

Renal failure

Advanced CKD stage 4-5 — ESRD

Presentation of advanced CKD (stage 4-5)

- Uremia

- Fluid overload

- Hyper K

- Metabolic acidosis

- Anemia

- Secondary hyperparathyroidism (low Ca, high phosphate)

Indications for dialysis (7)

- Uremia symptoms with low GFR

- Uremic pericarditis

- CKD progression to GFR

Presentation of uremia symptoms with low GFR

- Pruritis

- N/V, poor appetite

- AMS → unresponsiveness

Presentation of uremic pericarditis

Pericardial effusion, friction rub (with uremia)

When should dialysis be discussed with patients with CKD?

Stage 4

**NOT always indicated BUT start to discuss

Hemodialysis

- Solutes passively move across dialysis membrane via diffusion

- H2O move across via active ultrafiltration determined by counter-current flow

**Blood and dialysate move in OPPOSITE directions

Functional unit of dialysis machine

Dialyzer — blood from patient through tubing to dialyzer with waste products from blood pulled into dialysate; blood returned to pt

Frequency of in-center hemodialysis

3x/week about 3-4 hours each

Access to body for hemodialysis

Central venous catheter OR arteriovenous fistula

Home hemodialysis (+ frequency of treatment)

- Requires intensive training by dialysis RN

- 6-7 days/week for 2-3 hours

Benefit of home hemodialysis vs. in-center

Home is more frequent, gradual — similar to physiological removal

How long can central venous catheter be used for dialysis?

3-4 months

Preferred site of central venous catheter

Right internal jugular vein — Tip in SVC near RA junction

If central venous catheter from femoral vein line (LAST RESORT), where must it go in?

Needs to reach IVC

More permanent options for dialysis access

AV fistula & AV graft

AV fistula for dialysis access

Vein directly connected to artery → matures for 4-8 weeks

Pros/cons for AV fistula for dialysis access

- NO synthetic material

- Lasts decades

- NOT ideal for patients with small veins

AV graft for dialysis access

Synthetic material connecting vein to artery → matures for 2-4 weeks

Pros/cons for AV graft for dialysis access

- More ideal for patients with small veins

- Lasts 5-10 years

Complications of catheters for vascular access for dialysis access

Infection, central vein stenosis, blood clots

Complications of AVG/AVF for vascular access for dialysis access

Clotting, stenosis, pseudoaneurysm

**Infection less common than catheters

AV fistula vs. AV graft

Fistula: NO synthetic material, lasts longer

Graft: Synthetic material, shorter time to mature, higher success with small veins

Peritoneal dialysis

Transport of solutes and H2O across peritoneal membrane with:

- Diffusion

- Ultrafiltration

- Absorption

Diffusion (1/3) of peritoneal dialysis

- Uremic solutes and K+ from blood to solution across peritoneal membrane

- Glucose, bicarb, Ca from solution to blood

- Determined by concentration gradient and peritoneal SA

Factors that determine diffusion with peritoneal dialysis

Fluid volume, frequency of dialysis, how long fluid in belly for dialysis

Ultrafiltration (2/3) of peritoneal dialysis

- H2O from hypotonic blood to hypertonic dialysis solution

- Rate determined by osmotic gradient

How is ultrafiltration adjusted?

Percentage fo dextrose in dialysis solution

Absorption (3/3) of peritoneal dialysis

Fluid absorption into lymphatics and abdominal wall tissue