Nephrology JC079: Chronic Kidney Disease And Its Complications Flashcards
Basic function of a nephron
- Get rid of nitrogenous waste products
- Conserve Na, H2O
- Maintaining electrolyte balance
- Maintaining acid-base balance
Structures:
- Bowman capsule
- Tubules
- LoH
- Collecting duct
Processes:
- Filtration
- Absorption
- Transport
- Secretion
- Concentration gradient
- Receptors / Channels
- Enzymes (Na/K-ATPase)
Albuminuria
- Proteinuria (Dipstix) >300 mg/day —> associated with Chronic GN, Renal HT, Parenchymal disease
Urine Albumin-Creatinine ratio (ACR):
- >30 mg/mmol is considered “significant” in non-DM
- >3 mg/mmol is considered microalbuminuric in DM —> require ACEI / ARB
Causes:
1. **CKD
2. **HT
3. **High protein diet
4. **Exercise
5. Fever
6. ***UTI
7. CCF
Estimated GFR (eGFR)
How to estimate GFR:
1. 24 hour urine: measure urine Cr (U), plasma Cr (P), total urine volume (V) —> ***24 hour Cr clearance (UV / P)
2. Cockcroft and Gault CrCl = 88 x (145-age) / Serum Cr x weight / 70 - 3
3. MDRD equation (Modification of Diet in Renal disease study) per 1.73 m^2
- CKD-EPI (per 1.73 m^2)
- CKD-EPIcys
Chronic kidney disease (CKD)
Definition:
- **Slow **irreversible loss of renal function over time usually without symptoms until damage is advanced
記: 90, 60, 45, 30, 15
Staging of CKD (sustained for **>90 days (3個月)):
Stage 1: >90 (normal GFR with **another kidney abnormality)
Stage 2: 60-89 (mild ↓ GFR with ***another kidney abnormality)
Stage 3a: 45-59 (moderate ↓ GFR)
Stage 3b: 30-44 (moderate ↓ GFR)
Stage 4: 15-29 (severe ↓ GFR)
Stage 5: <15 / dialysis (ESRD)
KDIGO:
- Insert Albumin : Creatinine ratio (ACR) into CKD classification to make it predictable of progression (i.e. match Cr with ***Albuminuria level —> low eGFR + severe Albuminuria —> more likely to progress)
Role of Nephrologist
- Diagnosis of cause of CKD
- Management of complications of CKD
- Preparation for dialysis
- Preparation for kidney transplantation
- Palliative care for ESCKD
Patients journey of CKD
CKD diagnosis:
- Blood test, USG scans, Kidney biopsy
Stage 1-4 CKD:
- ***BP control
ESRD:
- Control renal **anaemia
- Control **acidosis
- Cardiac tests
- Live donor workup
- Fistula
Renal replacement therapy
1. Conservative / Palliative care
2. PD / HD
3. Transplantation
***Causes of CKD
- ***DM
- HT / Vascular
- Chronic GN (e.g. IgAN)
- Chronic pyelonephritis
- Polycystic kidney disease
- Drug induced, TIN, TCM
- Myeloma (CRAB), Vasculitis, SLE
- Obstruction, Kidney stones
- Alport syndrome / other hereditary diseases
Progressive CKD
Progression rate determined by:
1. **Causes
2. **Baseline Serum Cr, Proteinuria
3. **HT severity
4. **Renal fibrosis / Aging
Rate: 1-7 ml/min per year
Mild CKD:
- mild CKD / Albuminuria ↑ risk of CVS death
- finding + treating cause —> delaying progression + long-term follow-up + ***CVS protection are ALL important
Drug-induced kidney disease
Types:
1. Acute (<7 days)
2. Subacute (7-90 days)
3. Chronic (>90 days)
Mechanism:
1. Hypersensitivity
2. Vasoconstriction
3. Glomerular disease
4. Tubular toxicity
5. Nephrolithiasis
6. Crystalluria
Examples:
- Aminoglycosides —> AKI
- Aciclovir —> Nephrolithiasis
- Calcineurin inhibitor —> AKI-CKD
- Cisplatin —> Tubular
- Colistin —> AKI
- Protease inhibitor —> Nephrolithiasis, AKI
***S/S of CKD
- Fatigue
- Nocturia
- Thirst (∵ acidosis, hyperventilation, mouth-breathing)
- Fluid retention
- Itch
Clinical features:
1. **Acidosis
2. **HT, LVH
3. **CHF
4. **Anaemia (Normochromic normocytic ∵ lack of erythropoietin)
5. ***CKD-MBD (mineral bone disorder): high / low PTH, low turnover bone disease, bone biochemistry abnormality, vascular calcification
Kidney sizes on USG
- Normal size 10-12cm + symmetrical
Small kidneys in CKD:
- Dyplastic
- **Scarred
- **Shrunken
Large kidneys:
- **Polycystic kidney disease
- **Infiltration (e.g. Amyloid)
- ***Obstruction
Other investigations
- Renal angiogram
- CT angiogram
- MRI of renal artery
—> can be used to demonstrate renal artery stenosis
***Therapy aim for CKD
- ***Delay kidney failure, treat cardiac risk, treat CKD complications
- ***Control HT
- ***Reduce Albuminuria by ACEI / ARB
- Tackling ***glycaemic control HbA1c in DN
- Treat any ***acidosis, high K, Ca/P/PTH
- Control lipids
KDIGO 2021 guideline of Hypertension target
HT patients with CKD: Target ***<120 / 80
- ***ACEI / ARB
- ↓ Albuminuria
- Monitor U/E - β-blocker
- Cardioprotection - CCB
- SE: ankle edema - Diuretics
- ***Overdiuresis can lead to worsening renal function - α-blocker
- if have prostate symptoms
Dietary recommendation in CKD
HT patients:
- ↓ Na intake ***<2 g daily (<90 mmol)
- ↓ NaCl intake <5 g daily
- ∵ high salt intake —> more likely ↑ CVD events in CKD patients
CKD stage 3-5:
- moderate restriction of dietary protein
—> possibly ↓ uraemic toxins + hyperfiltration + ↓ clinical symptoms + delay maintenance dialysis
DN:
- daily protein recommendation: ***0.8 g/kg
Hyperlipidaemia in CKD
> 50 yo with CKD**3-5:
- >10% 10-year risk of coronary deaths regardless of cholesterol level
- **Statin / ***Statin + Ezetimibe recommended
New + Old Diabetic drugs
Old drugs:
1. Metformin
2. Acarbose
3. Sulphonylureas
4. PPAR-γ agonists (Thiazolidinediones)
New drugs:
1. DPP4 inhibitors (Gliptins)
2. Repaglinide
3. GLP1 receptor agonists (Exenatide, Liraglutide)
4. Analogue insulin
5. ***SGLT2 inhibitor (Gliflozins) —> improve DM control + reduce kidney disease progression
Diabetic kidney disease KDIGO guideline
- Lifestyle therapy
- Physical activity
- Nutrition
- Weight loss - Metformin / SGLT2 inhibitor / combination
- **eGFR <45 —> ↓ Metformin dose
- **eGFR <30 —> Stop Metformin
- ***do not initiate SGLT2 inhibitor if eGFR <30
- discontinue SGLT2 inhibitor in dialysis patient - Addition drug therapy for more severe CKD
- GLP1 receptor agonists (preferred)
- DPP4 inhibitor
- Insulin
Complications of CKD
- Fluid retention
- Metabolic acidosis
- HT
- Normochromic normocytic anaemia
- Secondary hyperparathyroidism
- Bone disease
***Drug therapy for CKD
- Diuretic
- Anti-HT
- Oral NaHCO3 (for acidosis)
- Phosphate binder (for hyperPO4)
- Active Vit D analogues (alfacalcidol)
- Calcimimetics
- Erythropoiesis stimulating agents (ESAs)
Renal Anaemia guideline
***Replenish Fe first before Hb
Fe saturation should be ***>20%
Fe supplement (aim Fe saturation >20%):
1. Oral Fe
2. Fe dextran
3. Fe sucrose (venofer)
4. Fe carboxymaltose (ferinject)
Best Hb level for renal patients: 10-11
—> ↓ EPO if Hb 12
1. ESA
- ↑ Hct
- injection form
- HIF-PH inhibitor (Roxadustat)
- HIF (hypoxic-induced factor): stimulate erythropoiesis
- HIF-PH (proline hydroxylase): enzyme degrading HIF
—> HIF-PH inhibitor
—> stop degradation of HIF
—> more erythropoiesis
Causes of Resistance to ESA:
1. **Inflammation, neckline, failed allograft
2. HD vs PD
3. **Functional Fe deficiency (hypochromic RC)
4. Chemotherapy, IFN for Hep C
5. Bleeding
6. ***Marrow failure
7. Aluminium toxicity
8. Severe hyperparathyroidism
Treatment of HyperK acidosis
- ***Low K diet
- ***Oral HCO3 (to control acidosis + slow down kidney deterioration)
- Adjust medication (e.g. ACEI, ARB)
- Other oral K lowering drugs
- Exchange resins / Cation exchanges / K binder
—> ***Calcium resonium, Patiromer, Sodium Zirconium Cyclosilicate
***CKD-MBD (mineral bone disorder)
Clinical features:
1. **Hyperphosphataemia
2. **Vit D deficiency (1α-hydroxylase)
3. **Secondary hyperparathyroidism
4. **Osteitis fibrosa cystica (characterised by high bone turnover due to secondary hyperPTH (UpToDate))
5. ***Adynamic bone disease (i.e. low turnover bone dsease)
6. Osteoporosis (pelvic fracture)
7. Gout, Pseudogout
Coronary artery calcifications ↑ with years of dialysis
***HyperCa
Mortality in dialysis patients (100x higher risk than general population)
Calciphylaxis:
- aka Calcific uraemic arteriolopathy (wiki)
- affect small blood vessels supplying skin —> painful skin ulcer
