07.01 Renal/Uro

07.01 Renal / Nephro [PDF link]: Acute kidney injury (AKI) – AEIOU (indications for RRT in AKI). Chronic kidney disease (CKD) – Mineral bone disease, CKD-related anaemia. Renal replacement therapy (RRT) – Haemodialysis (HD), Peritoneal dialysis (PD), Renal transplant.

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Elevated creatinine investigations

• Bloods: BBV, serum free light chains, kappa lambda ratio

• Urinalysis + ACR

• US KUB

• Specialist – ?renal biopsy if persisting

Asymptomatic benign creatinine rise a/w trimethoprim, co-trimox, cimetidine, dronedarone, dolutegravir, cobicistat and abemaciclib

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More on renal replacement therapy

• The Comprehensive CRRT Explained Series – 1h 15min video on continuous renal replacement therapy, including a quick review on the physiology of the kidneys, plus what and how CRRT is run.

More on renal transplants

• See also 10.10 on organ transplants in general (including transplant rejection)

• Immunosuppression – induction then maintenance

• Calcineurin inhibitors (CNI), eg tacrolimus, ciclosporin

  • MOA. Calcineurin – phosphatase involved in T-cell activation.

  • Requires monitoring of drug concentrations due to narrow therapeutic window

    • Trough levels (~30min prior to next dose)

  • Side effects: renal vasoconstriction and hypertension, peripheral neuropathy, thrombotic microangiopathy, diabetes, hirsutism, gum hypertrophy

  • Many drug interactions due to CYP450 pathway; avoid grapefruit + check interactions

• Mycophenolate mofetil (MMF)

  • MOA: anti-metabolite; blocks purine nucleotide synthesis by inhibiting enzyme IMPDH → inhibits B and T cell proliferation

  • Usually paired with calcineurin inhibitors

  • Side effects: GI toxicity (nausea, vomiting, diarrhoea), myelosuppression, teratogenic

• Azathioprine

  • MOA: anti-metabolite; blocks purine nucleotide synthesises as a purine analogue

  • Side effects: myelosuppression, ↑risk of skin cancer, interacts with allopurinol

• Sirolimus, everolimus

  • MOA: mammalian target of rapamycin (mTOR) inhibitor – inhibits cytokine-dependent cell proliferation (blocks IL-2 receptor). ?Has anti-cancer effects.

  • Side effects: delayed wound healing, proteinuria, pneumonitis, mouth ulcers, hyperlipidaemia

• Monoclonal antibodies

  • Eg basiliximab and daclizumab (target IL2 receptor [CD25] to block activated T cells), alemtuzumab (promotes T & B cell depletion), etc.

  • Used as induction therapy

  • Side effects: ↑infection risk if non-selective

• Anti-thymocyte globulin (ATG)

  • MOA: polyclonal antibody directed against T cell antigens; acts as a depleting antibody

  • Used in induction therapy, and as treatment of steroid-refractory or vascular rejection

• Parameters to monitor (based on Uptodate article)

  • Baseline bloods including FBC, renal function, LFTs, bone profile, Mg, PO4

  • Tacrolimus / cyclosporin / everolimus / sirolimus levels

  • Fasting blood glucose, HbA1c, fasting lipid profile – every 3 months

  • PTH and 25-vitamin D – immediately post transplant and then every 6-12mo

  • Urinalysis, urinary ACR – every visit

  • BK virus blood and/or urine PCR testing

  • CMV blood PCR testing if not receiving CMV prophylaxis – weekly for first 3 months