JC79 (Medicine) - Chronic kidney diseases Flashcards
Clinical definition of CKD
- GFR < 60 mL/min/1.73m2 for ≥ 3 months (Normal range = 90 – 120 mL/min/1.73m2)
- Evidence of kidney damage such as albuminuria for ≥ 3 months
- Abnormal findings on renal imaging present for ≥ 3 months
Define range of GFR for 5 stages of renal failure
Stage 1 - Normal >90 Stage 2 - Mild decrease 60-89 Stage 3 - Moderate decrease 45-59 Stage 3b - moderate to Severe decrease 30-44 Stage 4 - Severe decrease 15-29 Stage 5 - End-stage - <15
** must be sustained for >90 days **
How does albuminuria affect prognosis of CKD
Higher persistent albuminuria = worse prognosis and higher risk of progression in CKD
Basic functions of nephron unit
Remove nitrogenous waste product
Conserve Sodium and water
Maintain electrolyte balance
Maintain acid-base balance
Albuminuria
- Cut-offs for normal vs diabetic pt.
Urine Albumin-creatinine ratio > 30mg/mmol = significant albuminuria in normal pt.
Urine ACR >3mg/mmol = microalbuminuria in diabetic pt., need ACEI or ARB
3 formulas for estimated GFR
Cockcroft and Gault Creatinine Clearance: age, serum creatinine, weight
Modification of Diet in Renal Disease Study (MDRD)
CKD- EPI or CKD- EPIcys
Most common causes of CKD
- DM nephropathy (45%) **
- Hypertension/ Renal artery stenosis (RAS) (27%)
- Chronic Glomerulonephritis (10%)
- Chronic pyelonephritis
- Interstitial disease (5%)
- Polycystic kidney disease (2%)
- Drug induced (TCM)
- Myeloma (CARB), Vasculitis, SLE
- Obstruction, nephrolithiasis
- Hereditary diseases (e.g. Alport’s)
Define pre-renal causes of CKD
Hypovolemia
• Hemorrhage
• Vomiting/ Diarrhea
• Diuretics
Hypervolemia but low effective circulating volume
• Heart failure with reduced ejection fraction (HFrEF)
(Cardiorenal syndrome)
• Decompensated liver disease with portal hypertension (Hepatorenal syndrome)
Low Afferent arteriole vasodilatation
• NSAIDs - Inhibits COX enzymes and thus decreased synthesis of prostaglandins (PG)
• ACEI/ ARB
• Cyclosporine
Define renal causes of CKD
Renal vascular disease:
Hypertensive nephrosclerosis
Ischemic nephropathy - Renal artery stenosis
Glomerular disease:
Proliferative glomerulonephritis (Nephritic pattern)
Non-proliferative glomerulonephritis (Nephrotic pattern)
Tubular-interstitial diseases: Polycystic kidney disease (PKD) Reflux nephropathy Nephrocalcinosis - Result of hypercalcemia or hypercalciuria Sarcoidosis
List proliferative and non-proliferative primary glomerulonephritis
Proliferative glomerulonephritis (Nephritic pattern)
• Post-streptococcal glomerulonephritis (PSGN)
• IgA nephropathy
• Membranoproliferative glomerulonephritis
Non-proliferative glomerulonephritis (Nephrotic pattern)
• Minimal change disease (children)
• Focal segmental glomerulosclerosis
• Membranous nephropathy (adult)
Post-renal causes of CKD
Obstructive uropathy
Prostatic disease
• Benign prostatic hyperplasia
• Prostatic cancer
Metastatic disease
+ other obstructive pathologies…etc
Common renal symptoms between AKI and CKD
How to distinguish from AKI
Edema (hypoalbuminemia and RAAS activation)
Hypertension (fluid retention and low plasma volume triggers compensatory RAAS activation for salt and water retention
Oligouria
"”CKD has complications in CVD, Neuro, Haemat, endocrine…etc””
Anuria is never observed in CKD alone, always indicate AKI
Determinants of CKD progression
Typical GFR deterioration rate
Underlying cause
Baseline serum creatinine and severity of proteinuria
Hypertension severity
Renal fibrosis and aging
Rate: From 1ml/min to 7ml/min over 1 year
Mild CKD does not require management as it does not correlate with mortality.
True or False?
False
Mild CKD and albuminuria increases risk of cardiovascular death
Cardiovascular complications of CKD
Uremic pericarditis*/ Hypertension/ Hyperlipidemia/ Cardiomyopathy/ Accelerated atherosclerosis/ Volume overload/ Congestive heart failure
Neurological complications of CKD
Uremic encephalopathy* (Mental status change/ Coma/ Decreased in memory and attention)/ Neuropathy/ Seizure/ Impaired sleep
Hematological and endocrine complications of CKD
Hematological
Uremic bleeding* (Platelet dysfunction and EPO deficiency)/ Anemia
Endocrinological
Hyperkalemia/ Hyperphosphatemia/ Hypocalcemia/ Metabolic acidosis/ Secondary hyperparathyroidism/ Renal osteodystrophy
Dermatological complications of CKD
Dermatological
Pruritus*/ Calciphylaxis/ Nephrogenic systemic fibrosis (NSF)/
Uremic frost (white crystals in and on the skin)
Constitutional symptoms of CKD
Fatigue/ Anorexia/ Nausea and vomiting*/ Metallic taste/ Fetor uremicus
Nocturia/ thirst
Outline history taking for CKD
Medical history
• Hypertension (Hypertensive nephrosclerosis)
• DM (DM nephropathy)
• Previous AKI
• Cardiovascular/ Cerebrovascular/ Peripheral vascular disease for renovascular disease
Drug history
• NSAIDs/ Cisplatin/ Cyclosporine
Family history • Polycystic kidney disease • IgA nephropathy • Hereditary nephropathy • C3 glomerulonephritis
Drug-induced kidney failure
- Define time cut-off for acute, subacute and chronic
- Pathogenesis pathways
Acute = <7 days Subacute = 7-90 days Chronic = >90 days
Pathogenesis pathways:
- Hypersensitivity
- Vasoconstriction and hypoxic damage
- Glomerular disease
- Tubular toxicity
- Nephrolithiasis and Crystalluria
List example of drug-induced AKI
Protease inhibitor Cisplatin Aminoglycosides Acyclovir Calcineurin inhibitor ...etc
Major clinical features of CKD
Constitutional: Fatigue, Nocturia and thirst, fluid retention and edema, General pruritis
CVS: Hypertension, LVH, Congestive HF
Anaemia (NcNc)
CKD- Mineral bone disorder: includes abnormal PTH, bone biochemistry, vascular calcification
Diagnostic investigations for CKD
- Ultrasound Kidney: Small/dysplastic/shrunken kidney
- CT angiogram for vascular causes of CKD
- Renal biopsy with histological diagnosis
Treatment targets for CKD (what needs to be treated/controlled in CKD)
- Delay renal failure
- Treat cardiac, neurological, vascular risk, prevent CKD complications
- Control albuminuria by ACEi or ARB
- Control DM, HTN
- Correct electrolyte and acid-base disturbance
- Correct Lipid profile
Typical CBC, Lipid, Electrolyte, ABG, PTH, RFT profile in CKD
CBC - NcNc anaemia
Lipid - Hypertriglyceridemia (reactive to low albumin)
HypoNatremia
HyperKalemia (K+ shift due to metabolic acidosis)
HypoCalcemia (low Calcitriol production, sec. to hyperphosphatemia)
HyperPhosphatemia (low renal excretion)
ABG: Metabolic acidosis + ↑ Anion gap
PTH: ↑ PTH level due to secondary hyperparathyroidism
RFT: ↑ Urea/ BUN and creatinine level; ↓ GFR
List all serological and urine tests for CKD
CBC with diff. Lipid profile Electrolyte with Ca and PO4 ABG Serum PTH RFT: Urea/ BUN and creatinine, GFR Urinalysis: quantitative protein test
Autoimmune markers: ANA/ anti-dsDNA/ C3/4/ ANCA/anti-GBM
Serum free light chain assays
Serum/ Urine protein electrophoresis with immunofixation
LFT: hepatorenal syndrome, high ALP
HBV and HCV (urgent HD)
Imaging and sampling Ix for CKD
Renal biopsy for histological Dx with light microscopy, EM and immunofluorescence
Imaging:
X-ray or CT KUB
USG kidney
***MRI avoided- administration of gadolinium is associated with potentially severe syndrome of nephrogenic systemic fibrosis (NSF) **
Dietary modifications for CKD
Calories: 30 – 35 kcal/kg/day
Vitamins: Ascorbic acid, Folate, Calcitriol
Low Sodium: reduce to <2g (<90mmol) for Hypertensive
Low Potassium: < 1 mmol/kg/day
Low PO4: < 800 mg/day
Low protein:
- for CKD stage 3-5: reduce uremic toxins and clinical symptoms
- Diabetic Nephropathy: 0.8g/kg
Lipid control for CKD
- Drug option
- Indication
- Risk of no control
Indications:
- > 50 years old
- CKD 3-5
Drugs: Statin +/- Ezetimibe
Risk: 10% CVD risk in 10 years
Diabetic control in CKD
- Treatment/ drug options
- eGFR cut-offs for different treatments
- Lifestyle control: physical activity, nutrition, weight loss
- First-line:
- Metformin**
- SGLT2 inhibitor ** - Additional drugs:
- GLP-1 receptor agonist preferred
- DPP-4 inhibitor
- Insulin
- Sulphonylurea
- TZD
- Alpha- glucosidase inhibitor
Cut-off:
- Discontinue/ do not initiate Metformin or SGLT2 inhibitor if eGFR <30
- Stop Metformin or SGLT2 inhibitor if on dialysis
Electrolyte and acid-base correction therapy for CKD
Hyperkalemia
• Calcium gluconate/ Dextrose-insulin infusion/ Sodium bicarbonate/ Resonium C
• Restriction of dietary K+ intake, discontinuation of ACEI/ ARB
Hypocalcemia
• Calcium gluconate or calcium carbonate if symptomatic
• Restriction of dietary PO43- intake
Hyperphosphatemia
• PO43- binding agents
Metabolic acidosis
• Sodium bicarbonate or sodium citrate
• Initiation of dialysis
Anaemia treatment in CKD
- Target Hb
- Tx options
Symptomatic anemia
• Target Hb = 10-11 g/dL
Treatment:
• Blood transfusion preferably during dialysis using packed cells
• Erythropoiesis stimulating agents/ ESA (EPO therapy) in refractory anemia
• Iron supplementation (transferrin saturation >20%)
CKD- Bone mineral disease
- Tx options
Active vitamin D analogues - Alfacalcidol
Calcimimetics
Parathyroidectomy
Phosphate Binders and dietary phosphate restriction
Outline Vitamin D metabolism in skin, liver and kidney
CKD-MBD
- Features
- Pathogenesis
Definition:
• Abnormalities of Ca2+, PO43-, PTH and vitamin D metabolism
• Abnormalities in bone turnover, mineralization, volume linear growth or strength
Pathogenesis:
- Hyperphosphatemia + Vitamin D deficiency (1a hydroxylase) + Secondary hyperparathyroidism
Phosphate binding agents for CKD
- Types
- Indication of use for each type
Main types: Calcium binding and Non-calcium binding
Indications:
LOW Ca2+ = Calcium acetate or calcium carbonate
HIGH Ca2+ = Sevelamer (Renagel)/ Lanthanum (Fosrenol) - NON-calcium-NON-aluminium containing binders
MoA of non-calcium containing phosphate binding agents
Sevelamer is a non-absorbable cationic polymer that bind PO43- in intestinal lumen through ion exchange limiting absorption
Lanthanum is a rare-earth element that lowering PO43- level
Clinical manifestations of CKD-BMD
Bone: Ostetis fibrosa cystica Adynamic bone disease Osteoporosis Mixed uremic osteodystrophy Gout and pseudogout
Vascular calcification:
Coronary artery calcification (death)
Calciphylaxis (small vessel calcification in fat and skin)
Pathogenesis of Osteitis fibrosa cystica, Adynamic bone disease, Osteomalacia and Mixed uremic osteodystrophy in CKD-BMD
Osteitis fibrosa cystica
o (↑ PTH) High bone turnover due to secondary hyperparathyroidism
Adynamic bone disease
o (↔/↓ PTH) Low bone turnover, reduced bone volume and mineralization
o Due to excessive suppression of parathyroid gland by vitamin D use, calcium-based phosphate binder or calcium-dialysis solution
Osteomalacia
o (↔/↓ PTH) Low bone turnover and abnormal mineralization
o Due to use of aluminum-based phosphate binder
Mixed uremic osteodystrophy
o High or low bone turnover and abnormal mineralization
List bone abnormalities caused by CKD-BMD
Subperiosteal resorption
Fracture
Bone pain
Metastatic calcifications
Management options of CKD-BMD
- Low dietary PO4 intake
- Calcium-containing PO4 binding agents such as calcium acetate
- Calcitriol or vitamin D analogues
- Calcimimetics (stimulate parathyroid CaSR to decrease PTH secretion) - e.g. Cinacalcet
- Total parathyroidectomy with autotransplantation
Calciphylaxis
Definition
Ix
Tx
Calcification of media of small-to-medium-sized vessels of dermis and subcutaneous fat, causes skin ischemia and necrosis with painful lesions
Ix: Skin biopsy
Tx:
Sodium thiosulfate* (IV/ Intralesional)
Cinacalcet or parathyroidectomy for hyperparathyroidism
NON-calcium-containing phosphate binder for hyperphosphatemia
Which treatment for CKD-BMD is appropriate if there is Calciphylaxis
Which treatment is not indicated
Aim for lower Ca: Canacalcet** (Calcimimetics)
Lower Ca, PTH, PO4
Not indicated:
Calcium-containing phosphate binding agents
Vitamin D analogues/ Calcitriol
What causes of abnormal skin complexion in CKD
Coexistence of anemia and retention of β-melanocyte-stimulating hormone
Pigment deposition (urochromogens)
Indications for emergency dialysis in CKD
- Respi: Acute pulmonary edema
- CVS: Uremic pericarditis or cardiac tamponade
- CNS: Uremic encephalopathy
- Endo: Severe metabolic acidosis
- Endo: Hyperkalemia
