Chronic Kidney Disease, Dialysis & Transplantation – Comprehensive Lecture Notes

Scenario & Framing Example

Tutor begins with a familiar emergency-room vignette: Friday night, GP already asleep, you receive a patient with a creatinine of 900\,\mu mol!\cdot!L^{-1} (≈10× normal).
Take-home: such a value implies ≤10 % of normal renal function and almost certainly qualifies as severe CKD ± super-added AKI.

Chronicity = ≥ 3 months of:
• Structural/anatomical abnormality (e.g. solitary kidney).
• Functional decline: persistent ↓eGFR.
• Genetic disorder (classic example: autosomal-dominant polycystic kidney disease, ADPKD).
ADPKD recap: cysts in kidney plus liver, gut, ovaries, testes, epiglottis, lungs, heart, brain. High prevalence because carriers live long enough to reproduce.

CKD 1–5 based on eGFR (ml·min⁻¹·1.73 m⁻²).
• \ge 90 (with evidence of damage) → Stage 1.
• 60!\le!eGFR<90 → Stage 2.
• 30!\le!eGFR<60 → Stage 3.
• 15!\le!eGFR<30 → Stage 4.
• <15 or dialysis → Stage 5 (ESKD).
Lecturer: “Stage 5 is just the tip of the iceberg; for every dialysis patient there are ≈5\,000 people in Stage 1–2 walking around undiagnosed.”

Rising prevalence due to:
1. Obesity
2. Poorly-controlled hypertension
3. Neglected diabetes mellitus
Health-system implication: massive hidden burden, limited dialysis slots (Tigerberg Hospital ≈140 chronic HD places).

eGFR formulae (MDRD, CKD-EPI) are fine only in steady state; invalid during rapid creatinine rise/fall (AKI).
Creatinine trajectory example post-nephrectomy: 60 \rightarrow 120 \rightarrow 180 \rightarrow 240\,\mu mol/L does NOT equal linear fall in GFR—because actual function is zero.

Retard progression.
Timely preparation for renal replacement therapy (RRT) and transplantation assessment.
Treat complications (anemia, bone disease, electrolyte/acid–base disorders).

Target:
• Non-diabetics \le 140/80 mmHg.
• Diabetics \le 130/70 mmHg (as long as no orthostatic hypotension).
ACEi or ARB = first-line, but never in combination.

Aim BMI 22!\text{–}!27\,kg!\cdot!m^{-2}. Dialysis is catabolic—avoid under-nutrition.

Smoking doubles rate of residual GFR loss and adds pulmonary comorbidity, jeopardising transplant eligibility.

ACE / ARB for proteinuric states.
Selective aldosterone antagonists (newer mineralocorticoid receptor blockers).
SGLT-2 inhibitors – originally antidiabetic; now proven to delay CKD progression by ≈5–8 years.
Ozempic (semaglutide) under investigation for reno-protection (pharma searching for post-patent indications).

Mineral-bone disorder
• Start phosphate binders (e.g. calcium carbonate) once Stage 3+.
• Correct vitamin D/PTH later.
Anemia of CKD
• Usually emerges when eGFR \le 15.
• Pathophysiology: ↓EPO production.
• Treat with recombinant EPO plus iron (builders & bricks analogy).
Metabolic acidosis – bicarbonate in dialysate or oral.
Nutrition – protein restriction debated; less relevant in low-income public-sector diet.

Progression >5\,ml·min^{-1}·year^{-1}.
Any eGFR
CKD 4 (
First-prize: pre-emptive living-donor transplant once eGFR \le 15 but before dialysis.

Symptomatic CKD with eGFR <15 (anorexia, weight loss, insomnia, cognitive fog).
Asymptomatic but eGFR \le 8.
Early catheter/fistula placement allows patient education (needs repetition; uraemic cognition impaired).

Access:
• Tunnelled dual-lumen catheter (IJ / femoral).
• Arteriovenous fistula (AVF) – artery→vein anastomosis; preferred long-term.
Dialyser: thousands of hollow fibres; counter-current of blood vs. dialysate.
Prescription:
• 4 h × 3 sessions/week (minimum).
• May reduce to twice weekly if small body surface or residual urine >300\,ml/day.
Adequacy monitoring:
• URR (%) and Kt/V.
Complications: stenosis, thrombosis, catheter infection, fistula pseudo-aneurysm, high-output cardiac failure, bone disease, intradialytic hypotension.

Tenckhoff catheter in peritoneal cavity.
Two techniques:
1. CAPD: patient manually exchanges ≈2 L bags 4×/day (morning, noon, evening, bedtime).
2. APD: cycler machine performs exchanges overnight.
Clearance via simple diffusion across peritoneal membrane; ultrafiltration via hypertonic glucose solutions.
Advantages: portable, self-managed, preserves residual function, fewer haemodynamic swings.
Disadvantages: peritonitis (most common), membrane failure after 5–6 years, glucose load (weight gain, worsened diabetes).

Dialysis costs state \approx 250\text{–}350\,000\,R per annum; higher in private.
Limited slots → provincial selection tool:
• Must be transplant-eligible (no incurable malignancy, severe cardiopulmonary disease, or social non-compliance).
• Weekly assessment meeting (e.g. Tuesday at Tygerberg).
• Example: 95-year-old with cirrhosis = accepted in private but not state-funded.

Erythropoiesis-stimulating agents (ESA).
Iron (IV or oral).
Water-soluble multivitamins (lost in dialysis).
Phosphate binders with meals (chewable calcium carbonate).
Average dialysis patient: 6–12 chronic meds—always reconcile lists across specialties.

Leading cause of death in dialysis population is atherothrombotic events (AMI, stroke).
Sepsis second (catheter or access-related, immunosuppression after transplant).
Emphasises need for risk factor control & vaccination.

URR = \dfrac{\text{pre-HD urea} - \text{post-HD urea}}{\text{pre-HD urea}} \times 100\%.
Target Kt/V ≥1.2 per session.
Dialysis vintage median survival: HD 5!\text{–}!7 years; PD ≈5 years (membrane lifespan).
Public HD slot capacity (Tygerberg): \sim140.

Always consider AKI on CKD before attributing creatinine rise to chronicity.
Re-check BP seated & standing to avoid over-treating into orthostasis.
Document single-kidney patients (nephrectomy or donation) as CKD 1—still at lifelong risk.
In multi-prescriber patients, verify nephrotoxic drugs (NSAIDs, iodinated contrast, high-dose PPIs, certain antibiotics).
For every new CKD patient, ask: “Could I slow decline by: BP control? glycaemic control? RAAS blockade? SGLT2?”

Lecture to continue after break with the third leg: transplantation—considered the definitive therapy and preferred over lifelong dialysis.