Renal Replacement Therapy — modality, mechanism and the transplant patient viva

Opening prompt

The examiner opens: "A 60-year-old patient with ESKD asks you to explain the renal replacement options. Walk me through the three modalities, how each clears solutes, what you would choose and why, and then how you would manage a transplant recipient who develops a fever six weeks after the operation."

Key points to defend at viva depth

The examiner will probe each of these. Be ready to defend them with mechanism, dose and named evidence — not labels.

1. Three modalities plus conservative care. Haemodialysis, peritoneal dialysis, kidney transplantation, and conservative (non-dialytic) care as a valid fourth option in the frail elderly.^[1]

2. Mechanisms of clearance — the heart of the question.

   • HD = diffusion across a synthetic semipermeable membrane; blood and dialysate flow counter-current to maximise the gradient; small molecules (urea, creatinine, K+) clear well, middle molecules (beta-2 microglobulin) need high-flux membranes; ultrafiltration removes water by hydrostatic pressure.^[7]
   • PD = the peritoneum as a living membrane. The three-pore model: small pores for solutes, ultrasmall aquaporins for water, large pores for protein; the glucose osmotic gradient (or icodextrin) drives ultrafiltration; dwell time and transport status (PET test) govern efficiency.
   • Transplant restores native filtration; donor kidney in the right iliac fossa (renal artery to external iliac artery, vein to external iliac vein, ureter to bladder).

3. Dialysis adequacy — know the targets. HD: Kt/V at least 1.2 per session (K = dialyser clearance, t = time, V = volume of urea distribution); URR at least 65%; minimum 3-4 h, 3 times/week. PD: total Kt/V at least 1.7/week; preserves residual function longer than HD.

4. Modality choice is patient-centred. PD suits children, heart failure, residual function, home independence; HD suits most adults; transplant is best for survival/QoL if suitable. The AV fistula is the best HD access (matures 6-12 weeks, created 6-12 months ahead); avoid subclavian catheters.

5. Transplant survival and immunosuppression. Transplant halves mortality vs remaining on dialysis (Wolfe 1999).^[8] Standard triple therapy: tacrolimus (CNI) + mycophenolate + prednisolone; induction with basiliximab (low risk) or ATG (high risk).

6. When to start dialysis — symptoms, not numbers. ESKD: start at eGFR around 5-10 with symptoms (IDEAL: no benefit of early start). AKI: start for AEIOU (Acidosis, Electrolytes, Ingestion, Overload, Uraemia); AKIKI and STARRT-AKI showed no mortality benefit of early vs delayed RRT in critically ill AKI.^[4]

7. Post-transplant fever at 6 weeks — the opportunistic infection timeline.

   • 0-1 month: donor-derived, nosocomial (wound, urinary, line).
   • 1-6 months: CMV (the classic — fever, leukopenia, pneumonitis/colitis; D+/R- highest risk), BK nephropathy (rising creatinine, decoy cells), PJP (prevented by co-trimoxazole).
   • After 6 months: community infections, TB reactivation, late opportununist, malignancy (non-melanoma skin cancer 100x, PTLD).
   • Workup: cultures, CMV/BK PCR, urine, CXR; consider biopsy if creatinine rising (rejection vs infection). Management: reduce immunosuppression, start valganciclovir for CMV.

8. Rejection types — be ready to distinguish. Hyperacute (minutes, preformed Ab, graft loss); acute cellular (days-weeks, T-cell, IV methylprednisolone); antibody-mediated (C4d+, DSA, plasmapheresis/IVIG/rituximab); chronic (months-years, fibrosis, irreversible). A rising creatinine is not always rejection — biopsy before assuming (could be CNI toxicity, BK, obstruction, recurrence).

9. PD peritonitis. Cloudy effluent + abdominal pain; fluid WBC over 100/mm3, over 50% neutrophils; commonest organism Staph epidermidis. Treat empirically within 6 h with intraperitoneal gram-positive + gram-negative cover (ISPD 2016).^[9]

10. Pitfalls and pearls. Don't start dialysis for a number (IDEAL/AKIKI/STARRT-AKI). Don't use subclavian catheters. Don't attribute a rising creatinine to rejection without biopsy. Mycophenolate is teratogenic — switch to azathioprine pre-pregnancy. Dialysis disequilibrium: first dialysis of a uraemic patient — start gentle and short.

Likely examiner probes (and crisp answers)

• "What is Kt/V?" — Dialyser urea clearance (K) × time (t) ÷ volume of urea distribution (V, ~total body water). HD target at least 1.2 per session.
• "Why counter-current flow?" — Maintains the maximal blood-to-dialysate concentration gradient along the whole membrane length, maximising clearance.
• "Name a dialysable toxin." — Lithium, salicylate, methanol, ethylene glycol, metformin (in lactic acidosis).
• "How would you treat acute cellular rejection?" — IV methylprednisolone 500 mg-1 g daily for 3 days; ATG if steroid-resistant.
• "What prophylaxis after transplant?" — Co-trimoxazole (PJP), valganciclovir (CMV D+/R-), nystatin/fluconazole, HBV antiviral for HBsAg+ recipients.
• "When is conservative care appropriate?" — Frail elderly or heavy comorbidity, where dialysis burden outweighs benefit; comparable survival in the over-80s, better QoL.

References

1. Villa G, Ricci Z, Ronco C. Renal Replacement Therapy. Crit Care Clin 2015.^[1]
2. Himmelfarb J, Ikizler TA. Hemodialysis. N Engl J Med 2010.^[7]
3. Wolfe RA, et al. Mortality dialysis vs transplant. N Engl J Med 1999.^[8]
4. STARRT-AKI Investigators. Timing of RRT in AKI. N Engl J Med 2020.^[4]
5. Li PK, et al. ISPD Peritonitis Recommendations 2016.^[9]

References5ShowHide

1. [1]Villa G, Ricci Z, Ronco C. Renal Replacement Therapy. Critical Care Clinics, 2015.PMID 26410148
2. [4]Bagshaw SM, Wald R, Adhikari NKJ, et al. Timing of Initiation of Renal-Replacement Therapy in Acute Kidney Injury. N Engl J Med, 2020.PMID 32668114
3. [7]Himmelfarb J, Ikizler TA. Hemodialysis. N Engl J Med, 2010.PMID 21047227
4. [8]Wolfe RA, et al. Comparison of mortality in dialysis patients vs transplant recipients. N Engl J Med, 1999.PMID 10580071
5. [9]Li PK, et al. ISPD Peritonitis Recommendations: 2016 Update. Perit Dial Int, 2016.PMID 27282851