Approach to Chronic Kidney Disease

Definition of CKD

Decreased kidney function or one or more markers of kidney damage for 3 or more months
History of kidney transplant
GFR < 60. Staging helps risk-stratify pts likely to progress or develop complications of CKD
- CKD IIIa: eGFR 45-60
- CKD IIIb: eGFR 30-44
- CKD IV: eGFR 15-30
- CKD V: eGFR < 15
Markers of kidney damage
- Urine Albumin/Cr ratio
  - Mild: 0-30 mg/g
  - Moderate: 30-300 mg/g
  - Severe: >300 mg/g
- Urine sediment: RBC casts, WBC casts, oval fat bodies or fatty casts, granular casts
- Electrolyte derangements
- Abnormalities on histology
- Structural abnormalities: cysts, hydronephrosis, scarring, masses, renal artery stenosis

eGFR < 45
Persistent urine albumin/creatinine ratio > 300 mg/g
Urine protein/creatinine ratio greater than 500 mg/g
Rapid loss of kidney function (> 30% decline over 4 months)
Hematuria not secondary urologic condition or if there are RBC casts on UA
Inability to identify presumed cause of renal dysfunction
Difficult to manage complications: hyperkalemia, anemia, bone-mineral disease, HTN
Confirmed or presumed hereditary kidney disease (PCKD suspected)

Imbalance of water homeostasis
- As renal mass declines, the ability to both concentrate and dilute the urine is impaired
- This manifests as hyponatremia (no end-organ to respond to ADH) and edema
- Treat this with water restriction, diuretics or, eventually, ultrafiltration

Some data support that correcting serum bicarbonate slows decline in renal function and protects against bone-mineral complications of chronic metabolic acidosis (bone breakdown is an alternate buffer that the body uses in chronic acidemia)
Current KDIGO guidelines recommend bicarb goal 18. However, practice patterns vary. For instance, Dr. Gould starts repletion if bicarb <20 on 2 consecutive BMPs in the outpt setting.
- Sodium bicarb 650 mg TID (8mEq bicarb per 650mg tablet) up to 5850mg/day (70 mEq or 3 tabs TID)
- Sodium citrate (Bicitra): 1mL = 1 mEq * Careful in cirrhosis since citrate cannot be metabolized
- Baking soda (sodium bicarbonate): 1 teaspoon = 59 mEq HCO3 (careful of Na load)

Goal BP < 120/80 (Class 2B recommendation) based on SPRINT trial, ACC/AHA 2017, and KDIGO 2021 guidelines
All comers: diet (e.g. DASH) and lifestyle modifications
CKD without albuminuria or DM:
- Start pharmacotherapy based on ASCVD risk as well as risk for other target organ damage
CKD with moderate to severe albuminuria w/ or w/out DM
- ACEi or ARB titrated to maximally tolerated dose (Class 1B recommendation)
- Thiazide-like diuretics (see CLICK trial for chlorthalidone in advanced CKD)
- Loop diuretics can assist with volume driven HTN in patients with CKD 4-5
HTN in kidney transplant
- CCBs or ARBs are first line (Class 1C recommendation)
Consider stopping ACE-i/ARB if:
- GFR declines >30% over 4 months. Consider evaluation for renal artery stenosis
- K > 5.5 despite low K diet, optimizing dose of diuretics, or adding K-binders

Multifactorial: decreased EPO production, impaired iron absorption, uremic toxins suppressing bone marrow, loss of blood in dialysis circuit, and from GI AVMs
Indications for iron supplementation in non-dialysis patients
- ALL patients with TSAT <20% and ferritin <100 ng/mL
- Patients with Hb <13 and TSAT <30% and ferritin <500 ng/mL
  - Can start with PO supplementation (see Anemia section). Reassess iron levels in 1-3 mos; if not appropriately ↑, consider IV iron repletion
Dialysis patients
- IV iron preferred method of repletion for HD patients with
  - TSAT < 20% and ferritin < 200
  - TSAT <30% and ferritin <500 AND with Hb < 10 OR are on EPO
Dosing: usually administered at HD sessions
- 125 mg ferric gluconate at consecutive HD sessions x 8 doses
- 100 mg iron sucrose at consecutive HD sessions x 10 doses
- Ferumoxytol 510mg at the end of two HD sessions 1-4 weeks apart
Indications for EPO
- Pts with Hb <10 who are not iron deficient (ferritin >500) or whose anemia persists despite adequate iron repletion

Patients with diabetic nephropathy (T4 RTA) and CKD 5-ESRD are at the highest risk
Strategies to mitigate hyperK
- Low K diet (< 40-70 mEq/day or 1500-2700 mg/day)
- Loop diuretics
- GI cation exchangers
  - Patiromer (Veltassa): binds K in colon in exchange for calcium
  - Sodium zirconium cyclosilicate (Lokelma): binds K throughout intestine in exchange for sodium and H+
  - Sodium polystyrene sulfonate (Kayexelate): binds K throughout intestine in exchange for sodium; do not use as chronic therapy due to risk of intestinal ischemia/necrosis
- Treat metabolic acidosis

Individualize A1C goals. Both the ADA and VA-DOD have guidelines for selecting A1C targets
Treatment
- Metformin remains first-line but should be dose-reduced based on eGFR
  - eGFR > 45: Maximum daily dose of 2000mg/day (1000mg bid)
  - eGFR < 45: Reduce max daily dose to 1000mg/day (500mg bid)
  - eGFR < 30: Discontinue if high risk for volume mediated AKI/chronically ill
- SGLT-2 inhibitors for patients with eGFR >25 reduces progression to ESRD and death from renal or cardiovascular causes (Evidence: DAPA-CKD, EMPA-KIDNEY, CREDENCE)
  - Expect a GFR decline of up to 30% after initiation
- Finerenone (non-steroidal MRA): initiate if eGFR >25 and UACR > 30 on maximally tolerated ACEi/ARB + SGLT2i (and pt is not already on other MRA for other indication). Check K in 2 weeks (Evidence: FIDELIO)

Early (CKD3a or 3b) referral to Nephrology has better outcomes
Uremic symptoms: fatigue, sleep disturbance, n/v, decreased appetite, dysgeusia, itching, hiccupping
Refractory hyper K
Refractory hypertension
Plot your patient’s eGFR using the graph function in EPIC or CPRS to determine trajectory (normal age-related decline after age 60 is ~ 1ml/min/m2)