Approach to Chronic Kidney Disease

Definition of CKD

Decreased kidney function or one or more markers of kidney damage for 3+ months
History of kidney transplant - GFR < 60 Stages (based on eGFR): - > 90 = stage 1 (normal)
60 -89 = stage 2 (mild reduced)
45 – 59 = stage 3a
30 – 44 = stage 3b
15 – 29 = stage 4 (severely reduced)
< 15 = stage 5 (kidney failure)

Markers of kidney injury

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)
Management: Per KDIGO guidelines, bicarb goal 18
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: 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
In absence of albuminuria or DM, start pharmacotherapy based on ASCVD risk
In moderate to severe albuminuria w/wo DM, titrate ACEi or ARB to maximally tolerated dose (Class 1B recommendation)
CLICK Trial: in stage CKD4, chlorthalidone therapy improved blood-pressure control at 12 weeks as compared with placebo
Loop diuretics can assist with volume driven HTN in patients with CKD 4-5
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 eval for RAS
K > 5.5 despite low K diet, diuretic optimization, or use of K-binders

Multifactorial etiology: decreased EPO production, impaired iron absorption, uremic toxins suppressing bone marrow, loss of blood in dialysis circuit, and from GI AVMs
Iron supplementation: indications in non-HD patients
ALL patients with TSAT <20% and ferritin <100 ng/mL
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 and if not appropriately ↑, consider IV iron repletion
Iron supplementation: Indications in HD patients (IV iron preferred):
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

Goal K < 5.5
Patients with diabetic nephropathy (T4 RTA) and CKD 5-ESRD are at the highest risk
Strategies to mitigate risk:
Low K diet (< 40-70 mEq/day or 1500-2700 mg/day)
Loop diuretics
GI cation exchangers
Treat metabolic acidosis
Binders
Sodium zirconium cyclosilicate (Lokelma): binds K throughout intestine in exchange for sodium and H+
Patiromer (Veltassa): binds K in colon in exchange for calcium
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)

Individualize A1C goals (see ADA and VA-DOD guidelines for targets)
Metformin: dose-reduce based on eGFR
eGFR > 45: Max 2000mg/day (1000mg bid)
eGFR < 45: Max 1000mg/day (500mg bid)
eGFR < 30: Discontinue if high risk for volume-mediated AKI/chronically ill x
SGLT-2i in patients with eGFR >25 reduces progression to ESRD and death from renal or cardiovascular causes (Trials: 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 (FIDELIO trial)

Considerations:

Early (CKD3a or 3b) referral to Nephrology has better outcomes
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)

(A) –severe metabolic acidosis (serum pH<7.1) refractory to correcting volume status or other electrolyte derangement
(E) – electrolytes (K > 6.5 not responsive to medication management, e.g. loop diuretics, IV fluids, GI cation exchangers, correcting acidemia, etc.)
(I) – ingestion (e.g., lithium, salicylates, alcohols, valproic acid, phenytoin, barbiturates, carbamazepine, vancomycin, aminoglycosides)
(O) – overload (fluid) refractory to diuretics
(U) – Uremia (AMS, fatigue, sleep disturbance, n/v, decreased appetite, dysgeusia, pruritis, hiccupping, platelet dysfunction, pericarditis)
Stage 5 CKD with intractable nausea, vomiting, or progressive weight loss

If Lasix naïve, administer 1mg/kg as a bolus. If on a loop diuretic, administer 1.5 mg/kg as a bolus
If within the hour they have made 200 cc of urine, then they are likely to regain kidney function