Overview
Chronic kidney disease is defined as kidney damage or decreased kidney function of < 60ml/min for > 3 months. It may be caused by glomerular, tubular or vascular injury which may be detected on urinalysis, ultrasound or renal biopsy. Classification is based on the glomerular filtration rate (GFR), presence of albuminuria (as a marker of kidney injury) and the cause of kidney disease.
GFR can be estimated using creatinine or cystasin C clearance. The weight, age, gender, ethnicity, and protein intake are important variables. Formulas such as Cockroft Gault, Modified MDRD, and CKD-EPI exist for estimating the GFR. Normal GFR is 90- 120 ml/ min per 1.73 m² surface area. GRF of > 60 is considered CKD if there is evidence of kidney damage, proteinuria/hematuria, transplant, tubule disorders or pathology on biopsy or imaging. CKD usually becomes symptomatic at GFR < 30.
The most common causes of CKD include diabetes mellitus, glomerulonephritis, and hypertension/renovascular diseases. Low GFR and albuminuria are independently associated with mortality in chronic kidney disease. Patients with CKD are more likely to die from cerebrovascular disease than reuire renal replacement therapy.
Classification of CKD by GFR
| Category | GFR | Description |
|---|---|---|
| G1 | > 90 | Only CKD if there is evidence of kidney damage, proteinuria, hematuria, pathology on biopsy/imaging, tubule disorder or transplant |
| G2 | 60 – 89 | Only CKD if there is evidence of kidney damage, proteinuria, hematuria, pathology on biopsy/imaging, tubule disorder or transplant |
| G3a | 45 – 59 | Mild-modeate reduction in GFR |
| G3b | 30 – 44 | Moderate-severe reduction in GFR |
| G4 | 15 – 29 | Severe reduction in GFR. Requires renal replacement therapy. |
| G5 | < 15 | Kidney failure (End stage renal disease) |
Classification of CKD by albuminuria
| Category | Albumin excretion (mg/24 hours) | Albumin:creatinine (A:Cr) in mg/mmoL | Description |
|---|---|---|---|
| A1 | < 30 | < 3 | Optimal and high-normal |
| A2 | 30 – 300 | 3 – 30 | High |
| A3 | > 300 | > 30 | Very high and nephrotic |
Approximate equivalent values
| ACR (mg/mmol) | PCR (mg/mmol) | 24 hour urinary protein excretion (g/24 h) |
|---|---|---|
| 30 | 50 | 0.5 |
| 70 | 100 | 1 |
- Causes of CKD
- Hypertension
- Diabetes mellitus
- Inherited causes e.g. polycystic kidney disease
- Glomerular diseases
- Interstitial diseases
- Systemic inflammatory diseases (SLE, vasculitis)
- Progression of AKI
- Infections e.g. HIV, Hepatitis C, group B Streptococcus
- Nephrotoxins
- Kidney stones
- Malignancy
- Obstructive uropathy
Pathophysiology
- Pathophysiology of bone and mineral disease in CKD
- ↓ Hydroxylation of calcifediol (25-hydroxycalciferol) by the kidneys → ↓ production of calcitriol with ↓ excretion of phosphate → ↓ serum Ca2+ (reduced GI absorption of Ca, reduced osteoclast activity)→ ↑ PTH
- Parathyroid hormone increases bone resorption to mobilise calcium from the bone leading to hypercalcemia with tissue calcification
- Manifests as weak bones and bone pain
- Pathophysiology of anemia in CKD
- Anemia in chronic kidney disease is usually normocytic normochromic anemia. On CBC, findings are decreased HCt, Hb, normal RBC count and TIBC.
- Decreased erythropoietin production by interstitial fibroblasts
- Decreased hematopoeiesis due to circulating cytokines caused by uraemia
- Increased hepcidin production due to uraemia leading to anaemia of chronic disease
- Reduced RBC lifespan to 70 – 80 days caused by uraemia
- Gastrointestinal bleeding due to platelet dysfunction secondary to uraemia
- Obliteration of the bone marrow due to osteitis fibrosa cystica
Clinical Features
- Patient history
- Evidence of chronicity for > 3 months
- History of UTI, LUTS
- Past medical history of hypertension, diabetes, ischemic heart diesease, renal colic or other systemic disorders
- Drug history
- Family history of renal disease and subarachnoid hemorrhage
- Signs and symptoms
- Fluid overload due to sodium retention: shortness of breath and peripheral oedema
- Urinary symptoms: polyuria, oliguria
- Arrhythmias: hyperkalemia
- Anorexia
- Nausea and vomiting
- Resless legs
- Fatigue
- Weakness
- Pruritus
- Pallor and fatigue due to anaemia
- Bone pain and pathological fractures due to bone and mineral disease
- Amenorrhoea
- Impotence
Potential physical exam findings in a patient with CKD
| Category | Findings |
|---|---|
| Peripheries | Peripheral odema, vasculitic rash, signs of peripheral vascular disease or neuropathy, gouty tophi, joint disease, arteriovenoous fistula (thrill), signs of immunosuppression, bruising, skin malignancy, uraemic flap or encephalopathhy |
| Face | conjunctival pallor, xanthelasma, yellow tinge (uraemia), jaundice (hepatorenal), gum hypertrophy (cyclosporin), cushingoid moon facies (steroids), periorbital oedema (nephrotic syndrome), taut skin and telangiectasia (scleroderma), facial lipodystrophy (glomerulonephritis) |
| Neck | JVP for fluid state, tunnelled line, scar from parthyroidectomy, lymphadenopathy |
| Cardiovascular | Hypotension or hypertension, sternotomy, cardiomegaly, stigmata of endocarditis, JVP may not indicate fluid state if righ-heart failure of tricuspid regurgitation |
| Respiratory | Pulmonary oedema, pulmonary effusion |
| Abdomen | Peritonela dialysis catheter or scar, signs of previous transplant, ballotable polycystic kidney, palpable liver |
Signs and symptoms of uremia
| Category | Signs and symptoms |
|---|---|
| Constitutional | Fatigue, weakness, headache |
| Gastrointestinal | Nausea and vomiting, anorexia, uremic fetor |
| Dermatological | Pruritus, hyperpigmentation, uremic frost |
| Serositis | Uremic pericarditis, pleuritis |
| Neurological symptoms | Asterixis, uremic encephalopathy (seizures, somnolence, coma), peripheral neuropathy |
| Haematologic | Anaemia, recurrent infections, coagulopathy |
- Evaluation
- History and physical exam
- Serum biochemistries: Cr, UECs, blood gas analysis
- Urinalysis
- Renal ultrasound
- Parathyroid hormone levels
- ECG: in hyperK, will show peaked T waves (if taller than 5 mm on limb leads, greater than 1cm on precordial leads)
- Investigate possible etiologies: blood sugar, HIV
Treatment
Treatment of CKD requires
- Approprite referral to a nephrologist
- Treatment to slow renal disease progression
- Treatment of renal complicatios of CKD
- Treatment of other complications of CKD
- Renal replacement therapy
- Long term mangement of CKD
- Diet containing low K+, low Na+, and low phosphate
- Fluid intake restriction
- Avoid NSAIDs and aminoglycosides
Referral
- Indications for referral to a nephrologist
- Stage G4 and G5 CKD
- Moderate proteinuria (A:Cr > 70 mg/mmol) unless due to diabetes that is being treated
- Proteinuria A:Cr > 30 mg/mmol with hematuria
- Reduction in eGFR by ≥ 25% or sustained reduction of ≥ 15 % within 12 months
- Hypertension that is poorly controlled despite ≥ 4 antihypertensives at therapeutic doses
- Known or susepcted rare or genetic cause of CKD
Treatment to slow disease progression
- Control blood pressure using ACEi or ARBs (renal protective)
- Tartet systolic or 120 – 139 mmHg and diastolic < 90 mmHg
- Target systolic < 120 – 129 and diastolic < 70 if diabetic or A:Cr > 70
- Watch for hyperkalemia and stop ACEi/ARBs if K+ > 6 mmol/L, drop in eGFR > 35%, or increase in creatinen > 25%
- Control blood sugar
- Target HbA1c of 7%
- Lifestyle modifications
- Exercise
- Healthy weight
- Smoking cessation
- Salt intake < 2 g of sodium per day (< 5 g sodium chloride per day)
Treatment of renal complications
- Treatment of anaemia
- IV iron replacement therpy
- IV or SC erythropoietin. Watch for pure red cell aplasia due to anti-erythropoietin antibodies (presents as Hb < 6 g/dL)
- Oral folate
- Treatment of acidosis
- Sodium bicarbonate supplements for eGFR < 30 and low serum bicarbonate (< 20 mmol/L)
- Treatment of oedema
- Restrict fluid intake to 500 – 1000 ml per day
- Restrict sodium intake < 2g/day
- Restrict protein intake to < 2.5 g/kg/day
- Diuretics (high dose loop diuretics may be needed)
- Treatment and prevention of hyperkalemia
- Expert dietary advice to avoid K+ rich foods such as oranges, tomatoes, bananas, and greens
- Bind K+ usin K+ cation exchanges such as Kayexelate, K check, and resonium
- Treatment of bone and mineral disorders
- Treatment of hyperphosphatemia (> 1.5 mmol/L or 1.7 mmol/L if RRT) with dietary restriction (dairy products) and phosphate binders (calcium carbonate, sevalamer and lanthanum)
- Treatment of vitamin D deficiency with calcitriol
- Calcimimetics (calcimet and cinacalcet) to reduce PTH by increasing calcium receptor sensitivity
Treatment of other complications
- Treatment of cardiovascular disease
- Low-dose aspirin
- Statin
Renal Replacement Therapy
- Indications for renal replacement therapy (RRT)
- GFR <15ml/ minute (stage 5) can start dialysis at any point depending on complicatuins
- Uremia
- Bleeding diasthesis
- Fluid overload/ hypertension refractory to treatment with diuretics
- Metabolic disturbances refractory to treatment
- Marked malnutrition
- Indications for dialysis Choice for dialysis is dependent on the patient’s symptoms (AEIOU)
- Acidemia– metabolic acidosis
- Electrolyte abnormalities (especially hyperK) with ECG changes
- Intoxication (salicylate, lithium, isopropanol, methanol, ethylene glycol)
- Overload of fluids unresponsive to diuretics
- Uremic symptoms (pericarditis (irritation), AMS, encephalopathy(irritation), myoclonus, severe bleeding diathesis especially GI (platelet dysfunction), increased risk of ixn (WBCs can’t degranulate))
