Renal & Urinary

CKD: renal transplant evaluation and referral

Clinical Overview and When to Suspect Transplant Candidacy

— All patients with CKD G4–G5 (eGFR <30 mL/min/1.73 m²) that is progressive and irreversible

— Patients on dialysis, regardless of modality (HD or PD)

— Patients with rapidly declining eGFR expected to reach <20 within 6–12 months

— Diabetic nephropathy (most common cause of ESRD in the US)

— Hypertensive nephrosclerosis

— Glomerulonephritides (IgA, FSGS, lupus nephritis)

— Polycystic kidney disease

— Reflux/obstructive uropathy

— Living donor transplant > deceased donor transplant > dialysis

— Even older patients (≥65) often benefit if otherwise reasonable surgical candidates

Kidney transplantation is the renal replacement therapy of choice for most patients with advanced CKD or ESRD — confers superior survival, quality of life, and cost-effectiveness compared with maintenance dialysis

Who should be evaluated:

Preemptive transplantation (before dialysis initiation) is associated with the best graft and patient survival — refer when eGFR approaches 30, list when eGFR ≤20

Common underlying diagnoses prompting evaluation:

Step 3 management: When you see a CKD patient with eGFR trending below 30, the next best step is referral to a transplant center for evaluation — do not wait for dialysis initiation. Early referral is a quality metric.

Survival advantage:

Board pearl: Preemptive living donor transplant is the gold standard — avoids dialysis-associated cardiovascular morbidity, vascular access complications, and dialysis-related mortality risk that peaks in the first 90 days after starting HD

Patients with acute kidney injury superimposed on CKD should not be referred until baseline function is established

Health system context: Medicare covers transplant evaluation and surgery for ESRD patients regardless of age (ESRD Medicare benefit). Eligibility for the deceased donor waitlist requires formal multidisciplinary evaluation and active listing — waitlist time often 3–7 years depending on region and blood type

Presentation Patterns and Key History

— Cause of native kidney disease — recurrence risk in graft (FSGS ~30%, MPGN, primary hyperoxaluria, atypical HUS)

— Duration on dialysis — longer time on dialysis worsens post-transplant outcomes

— Prior transplants — sensitization, PRA elevation

— Transfusion history, pregnancies — sources of HLA sensitization

— Cardiovascular: prior MI, CABG/PCI, CHF, angina, claudication

— Malignancy history: required waiting periods after curative treatment (typically 2–5 years; some skin cancers and incidental RCC have no wait)

— Infections: HIV, HBV, HCV, TB exposure, endemic mycoses, prior CMV/EBV serostatus

— Substance use: tobacco, alcohol, illicit drugs — active use is often a relative contraindication

— Psychiatric history and medication adherence track record

— Reliable caregiver support

— Insurance/financial means to afford lifelong immunosuppression (~$10–20k/yr)

— Transportation to frequent post-op visits

— Stable housing

Transplant candidates rarely present "for transplant" — they present in CKD clinic, dialysis units, or nephrology follow-up where the referral decision is made

Key history elements that drive candidacy:

Comorbidity screening (must document):

Social history is decisive:

Board pearl: Active nonadherence to dialysis, medications, or appointments is one of the strongest predictors of graft loss and is a legitimate basis for delaying listing — not discrimination

Key distinction: Absolute contraindications are few — active malignancy, active untreated infection, severe irreversible cardiopulmonary disease, active substance use, demonstrated nonadherence. Relative contraindications (age, obesity BMI >35–40, frailty) require individualized assessment

Step 3 management: When a 58-year-old with diabetic ESRD on HD asks about transplant, the right answer is referral for evaluation now — do not screen out based on age or diabetes alone. Diabetes is the leading indication, not a contraindication

Physical Exam Findings and Functional Assessment

— Blood pressure in both arms, orthostatics

— Carotid bruits (screen for cerebrovascular disease)

— Peripheral pulses — femoral, popliteal, DP/PT — iliac vessel patency is critical for graft anastomosis

— Abdominal bruits suggesting renovascular disease

— JVP, S3, edema (volume status, occult HF)

— Prior surgical scars (multiple abdominal surgeries complicate placement)

— Palpable PKD kidneys — may need native nephrectomy if no room

— Hernias, ascites

— Document AV fistula/graft site and function

— Assess for steal syndrome, aneurysm, infection

— Gait speed, grip strength, sit-to-stand

— Fried frailty phenotype is increasingly used

— Karnofsky performance status — typically need ≥60–70

— Prostate exam in older men (BOO can complicate post-transplant urology)

— Pelvic exam per age-appropriate screening

— Active dental infection must be cleared before immunosuppression — refer to dentist

— Baseline survey for premalignant lesions; immunosuppression accelerates NMSC

Transplant evaluation exam targets surgical candidacy, vascular access for the allograft, and frailty

Cardiovascular exam:

Abdominal exam:

Vascular access exam:

Functional/frailty assessment:

Genitourinary exam:

Dental/oral exam:

Skin exam:

Board pearl: A frail dialysis patient with poor functional status may be denied listing — pre-habilitation programs can rescue candidacy. Document the rationale clearly.

Step 3 management: A patient being evaluated for transplant who has a carotid bruit — next step is carotid duplex, not proceeding directly with workup. Symptomatic carotid stenosis must be addressed pre-transplant.

Key distinction: BMI >40 is a relative contraindication at most centers due to wound complications and graft loss; bariatric surgery before transplant is a legitimate pathway

Diagnostic Workup — Initial Labs, Imaging, and Cardiac Screening

— CBC, CMP, LFTs, coagulation, lipid panel, HbA1c

— PTH, calcium, phosphorus, vitamin D, iron studies

— Urinalysis, 24-hr urine protein (if making urine)

— Blood type (ABO) — central to matching

— HLA typing (A, B, DR, DQ loci)

— Panel reactive antibody (PRA) and detailed antibody screen — quantifies sensitization

— HIV, HBsAg/anti-HBs/anti-HBc, anti-HCV (and HCV RNA if positive)

— CMV IgG, EBV IgG, VZV IgG, HSV

— Syphilis (RPR), Toxoplasma (heart candidates esp.), Strongyloides if endemic exposure

— TB screening: IGRA or PPD — treat LTBI before transplant

— Endemic: coccidioides, histoplasma, Trypanosoma cruzi (Chagas) per geography

— Mammography, cervical cytology, colonoscopy, low-dose chest CT if smoker

— PSA discussion in men

— Skin exam

— ECG and TTE for everyone

— Stress testing (pharmacologic nuclear or stress echo) for diabetics, age >50, prior CAD, or multiple risk factors

— Coronary angiography if stress test abnormal or high pretest probability

— Iliac vessel imaging (CT or duplex) in patients with PVD, prior pelvic surgery/radiation

— Renal/native kidney imaging if PKD or suspected malignancy

Transplant evaluation is multidisciplinary and standardized; the nephrologist's job is to ensure these are completed before listing

Core laboratory panel:

Infectious serologies (must obtain):

Cancer screening (age- and risk-appropriate):

Cardiac evaluation:

Imaging:

Board pearl: EBV-seronegative recipients receiving an EBV-seropositive organ are at high risk for post-transplant lymphoproliferative disorder (PTLD) — document and counsel

Step 3 management: Diabetic ESRD patient being evaluated for transplant → pharmacologic stress test is the right initial cardiac screen; routine cath without an indication is wrong

CCS pearl: Order serologies, HLA typing, and PRA early — results take weeks

Diagnostic Workup — Advanced/Confirmatory and Crossmatch

— ABO compatibility — required (or ABO-incompatible protocol at specialized centers)

— HLA typing of recipient + donor — fewer mismatches = better outcomes but not mandatory

— Crossmatch:

– Complement-dependent cytotoxicity (CDC) crossmatch — historical gold standard; positive = absolute contraindication

– Flow cytometric crossmatch — more sensitive for low-titer antibodies

– Virtual crossmatch — uses solid-phase antibody data (Luminex) vs. donor HLA

— Donor-specific antibodies (DSA) — preformed DSA increases risk of antibody-mediated rejection

— Longer wait times

— Candidates for desensitization (plasmapheresis, IVIG, rituximab) or paired kidney exchange

— Left heart catheterization if abnormal stress test

— Revascularization (PCI or CABG) before listing if obstructive disease found — though benefit of routine revascularization in stable CAD pre-transplant is debated (ISCHEMIA-CKD informs this)

— PFTs and chest CT if smoking history or symptoms

— HCV RNA, fibroscan/liver biopsy in chronic HCV or NAFLD

— Treat HCV (DAA therapy) — HCV+ kidneys can now be transplanted into HCV– recipients with planned DAA treatment

— Voiding cystourethrogram if reflux/neurogenic bladder

— Urodynamics if obstructive symptoms

Once initial workup clears, candidates move toward listing or living donor pairing

Immunologic compatibility testing:

Highly sensitized candidates (cPRA >80%):

Advanced cardiac workup:

Pulmonary:

GI/Hepatic:

Urologic:

Board pearl: A positive CDC crossmatch is an absolute contraindication to proceeding with that donor. A positive flow crossmatch with no DSA is workable; with DSA, requires desensitization or alternative donor.

Key distinction: HLA matching influences long-term graft survival; ABO matching and crossmatch are immediate go/no-go decisions

Step 3 management: Highly sensitized patient (cPRA 95%) waiting years on the list → next best step is enrollment in paired kidney exchange or desensitization program, not continued passive waiting

Risk Stratification and Candidacy Decision Logic

— Active malignancy (with rare exceptions like incidental small RCC, non-melanoma skin cancer)

— Active uncontrolled infection

— Severe irreversible cardiopulmonary disease without intervention option

— Active substance use disorder

— Demonstrated severe nonadherence

— Limited life expectancy <2–5 years from non-renal causes

— Advanced age — outcomes good for fit septuagenarians; chronological age alone not disqualifying

— Severe obesity (BMI >40)

— Frailty

— Recurrent disease risk (primary FSGS, primary hyperoxaluria, atypical HUS)

— Recent malignancy within waiting period

— Most solid tumors: 2–5 years of disease-free survival

— Non-melanoma skin cancer: no wait after treatment

— Renal cell carcinoma (small, incidental): no wait

— Breast, colon: 2–5 years depending on stage

— Melanoma, advanced cancers: often 5+ years

— Uses age, diabetes status, prior transplant, time on dialysis

— Top 20% EPTS get priority access to top 20% Kidney Donor Profile Index (KDPI) kidneys — longevity matching

— Shorter wait, scheduled surgery, better HLA matching feasible, longer graft half-life (~15–20 yr vs. 10–12 yr deceased)

Transplant centers use a multidisciplinary committee (nephrology, surgery, social work, psychiatry, pharmacy, financial counseling) to determine listing

Absolute contraindications:

Relative contraindications (case-by-case):

Cancer waiting periods (KDIGO/AST guidance, examples):

Estimated Post-Transplant Survival (EPTS) score:

Living donor pathway is preferable when available:

Board pearl: Time on dialysis is the single strongest modifiable predictor of post-transplant outcome — every year on dialysis worsens graft and patient survival. This is why preemptive transplant is so valuable.

Step 3 management: A 45-year-old with newly diagnosed CKD G4 (eGFR 25) and a willing sister donor → refer now for preemptive living donor transplant evaluation. Do not start dialysis first.

Key distinction: Listing ≠ active status. Patients can be listed but inactive (accruing wait time) while completing workup or addressing transient issues

Pharmacotherapy — Pre-Transplant Optimization and Induction Overview

— BP target <130/80; ACEi/ARB if proteinuric (continue until eGFR very low or hyperkalemia precludes)

— SGLT2 inhibitors for CKD with proteinuria (eGFR ≥20) — slow progression, may delay dialysis and extend window for preemptive transplant

— Statin therapy for ASCVD risk reduction (per KDIGO, adults ≥50 with CKD)

— Anemia: ESA if Hb <10; iron repletion

— CKD-MBD: phosphate binders, vitamin D analogs, calcimimetics for secondary hyperparathyroidism — parathyroidectomy occasionally indicated pre-transplant for severe disease

— Hepatitis B series (with higher-dose schedule for CKD; check anti-HBs titer, boost as needed)

— Pneumococcal (PCV20 or PCV15+PPSV23)

— Influenza annually

— COVID-19 series

— MMR, varicella, zoster (live) — must give pre-transplant if non-immune

— HPV in age-eligible patients

— Basiliximab (IL-2 receptor antagonist) — low immunologic risk

— Anti-thymocyte globulin (ATG, rabbit) — high immunologic risk, sensitized, retransplant, AA recipients

— Alemtuzumab — alternative

— Calcineurin inhibitor (tacrolimus > cyclosporine)

— Antimetabolite (mycophenolate > azathioprine)

— Corticosteroid (prednisone — some centers steroid-free)

Pre-transplant medication management is part of the nephrologist's longitudinal role

Optimize CKD comorbidities aggressively:

Vaccinations BEFORE transplant (live vaccines contraindicated post-transplant):

Induction immunosuppression (administered at time of transplant — knowledge-level for Step 3):

Maintenance immunosuppression triple therapy:

Board pearl: Live vaccines (MMR, varicella, live zoster, yellow fever) are contraindicated post-transplant — get them done during evaluation. The new recombinant zoster vaccine (Shingrix) is non-live and safe post-transplant.

Step 3 management: CKD G4 patient being evaluated → give Hep B series, pneumococcal, and any needed live vaccines now, before immunosuppression closes the window

Procedural Considerations and the Transplant Operation

— Living donor: scheduled, often laparoscopic donor nephrectomy; donor evaluated independently for kidney function, anatomy, psychosocial readiness

— Deceased donor: organ allocated via UNOS based on KAS (Kidney Allocation System) — factors include wait time (from dialysis start or eGFR ≤20), CPRA, pediatric status, prior living donor status, EPTS/KDPI matching

— Heterotopic placement in iliac fossa (retroperitoneal)

— Renal artery → external/internal iliac artery

— Renal vein → external iliac vein

— Ureter → bladder (ureteroneocystostomy, often with stent)

— Native kidneys usually left in place unless symptomatic PKD, chronic infection, or intractable HTN

— For incompatible donor-recipient pairs (ABO or crossmatch)

— Donor of pair A gives to recipient of pair B and vice versa

— National registries (e.g., NKR, UNOS KPD)

— Plasmapheresis + IVIG ± rituximab for sensitized recipients with available donor

— Now routine with DAA prophylaxis — expands donor pool significantly

— Two kidneys, normal function, normal anatomy, no transmissible disease

— Psychosocial: voluntary, no coercion, no financial inducement

— Independent donor advocate required by UNOS

Living vs. deceased donor logistics:

Surgical approach (recipient):

Paired kidney exchange (KPD):

Desensitization:

HCV+ donor → HCV– recipient:

Increased risk donors (PHS increased risk — IV drug use, MSM, incarceration): require informed consent; window-period testing with NAT minimizes residual risk

Donor evaluation (for living donors) — key principles:

CCS pearl: When admitting a post-transplant patient, standing orders include tacrolimus level (trough), CBC, BMP, CMV PCR, BK virus PCR (after week 4), and PJP prophylaxis with TMP-SMX

Board pearl: Delayed graft function (DGF) — need for dialysis in first week post-transplant — is more common with deceased donor, prolonged cold ischemia, and high-KDPI kidneys; usually recovers but predicts worse long-term outcomes

Special Populations — Elderly and Hepatic Impairment

— Fastest-growing transplant demographic

— Chronological age alone is not a contraindication — biological/physiological age matters

— Outcomes: still survival advantage over dialysis for fit elderly

— EPTS-KDPI matching typically allocates higher-KDPI (older/marginal) kidneys to older recipients to optimize organ utility

— Higher perioperative cardiovascular risk → rigorous cardiac evaluation

— Higher infection and malignancy risk on immunosuppression → may use reduced-intensity regimens, steroid-free protocols

— Frailty assessment critical: gait speed, grip strength, Fried criteria

— Chronic HBV: must be on antiviral suppression (entecavir or tenofovir) before and indefinitely after transplant; HBV reactivation risk is significant

— Chronic HCV: treat with DAAs — virtually all candidates can achieve SVR; HCV is no longer a barrier

— Cirrhosis with portal hypertension: consider simultaneous liver-kidney transplant (SLK) — strict criteria via UNOS

— NAFLD/NASH: increasingly common; assess fibrosis (Fibroscan, biopsy)

— Patients on dialysis: review all meds for dialyzability and dose adjustment

— Gabapentin, allopurinol, metformin, digoxin, many antibiotics — common culprits for accumulation

Elderly candidates (≥65, increasingly ≥70):

Pre-habilitation programs (exercise, nutrition, smoking cessation) can convert "borderline" candidates to acceptable

Hepatic impairment:

Renal-specific drug dosing during evaluation:

Board pearl: A patient with HCV-related cirrhosis and ESRD with significant portal hypertension/decompensation should be evaluated for simultaneous liver-kidney transplant, not kidney alone — isolated kidney transplant under cirrhosis carries high mortality

Step 3 management: 72-year-old, otherwise fit, with diabetic ESRD on HD for 2 years → refer for transplant evaluation. Do not assume age disqualifies. Document functional status and shared decision-making.

Key distinction: SLK criteria (UNOS): sustained AKI on dialysis ≥6 wk, CKD eGFR ≤60 for ≥90 days with current eGFR ≤30, or metabolic disease — formal thresholds matter

Special Populations — Pregnancy, Pediatrics, and Other Subgroups

— Pregnancy is generally not recommended on dialysis (poor maternal and fetal outcomes) — transplant restores fertility and dramatically improves pregnancy outcomes

— Wait ≥1 year post-transplant before conception (graft function stable, immunosuppression minimized)

— Mycophenolate is teratogenic (FDA category D; REMS program) — must switch to azathioprine before conception

— Tacrolimus, cyclosporine, prednisone, azathioprine are acceptable in pregnancy

— Pre-conception counseling is essential

— Document contraception plan; mycophenolate REMS counseling

— Pregnancy test at listing

— Allocated priority in KAS (faster wait times)

— Growth, development, school attendance considerations

— Living donor (often parental) is highly preferred

— Bladder dysfunction (posterior urethral valves) common — urologic prep critical

— Priority in allocation

— Paired kidney exchange and desensitization protocols

— Acceptable if CD4 >200, undetectable viral load, no recent opportunistic infections

— HIV+ to HIV+ transplantation now permitted (HOPE Act)

— Drug-drug interactions between ART and CNIs are significant (esp. protease inhibitors with tacrolimus)

— Simultaneous pancreas-kidney (SPK) is preferred when feasible — single surgery, normoglycemia, better outcomes than kidney alone

— Pancreas-after-kidney (PAK) is alternative

Pregnancy considerations:

Women of reproductive age in evaluation:

Pediatric candidates:

Highly sensitized patients (cPRA >80–98%):

HIV+ candidates:

Diabetic patients with type 1 DM:

Board pearl: Mycophenolate must be stopped and switched to azathioprine ≥6 weeks before conception in transplant recipients planning pregnancy — high risk of orofacial clefts, microtia, cardiac defects

Step 3 management: 28-year-old transplant recipient, 2 years post-op, stable graft, asks about pregnancy → counsel: switch mycophenolate to azathioprine, confirm stable graft, then plan conception after 3-month washout

Key distinction: SPK is for type 1 DM with ESRD; type 2 DM patients usually get kidney alone (rare SPK exceptions)

Complications and Adverse Outcomes Relevant to Evaluation

— Delayed graft function (need for dialysis in first week) — 20–40% of deceased donor grafts

— Vascular: renal artery/vein thrombosis (rare but graft-fatal), stenosis

— Urologic: leak, obstruction at ureteroneocystostomy

— Lymphocele

— Wound infection, dehiscence (higher with BMI >35)

— Hyperacute (minutes-hours, preformed antibodies, now rare with crossmatch)

— Acute cellular rejection (days-months, T-cell mediated) — treat with pulse steroids ± ATG

— Antibody-mediated rejection (de novo or recurrent DSA) — plasmapheresis, IVIG, rituximab

— Chronic allograft injury — leading cause of late graft loss

— Month 1: nosocomial, surgical

— Months 1–6: opportunistic — CMV, BK virus, PJP, Candida, Aspergillus

— >6 months: community-acquired + late opportunistic

— Non-melanoma skin cancer (most common; counsel sun protection)

— PTLD (EBV-driven, esp. EBV-mismatched)

— Kaposi sarcoma (HHV-8)

— Increased rates of solid tumors

— Tacrolimus > cyclosporine for diabetogenicity

— Steroids contribute

— Screen with fasting glucose, HbA1c

Recognizing post-transplant complications helps inform pre-transplant counseling and candidate selection

Surgical/early complications:

Rejection:

Infections (timeline-based):

Malignancy:

Cardiovascular disease remains leading cause of death with functioning graft — must continue aggressive ASCVD prevention

New-onset diabetes after transplant (NODAT):

Bone disease: persistent hyperparathyroidism, steroid-induced osteoporosis

Board pearl: BK virus nephropathy — viruria → viremia → biopsy-proven nephropathy. Treatment is reduction of immunosuppression (not antivirals; cidofovir/leflunomide are last-resort). Monitor with serum BK PCR monthly for the first 6 months.

Step 3 management: Transplant patient at 3 months with rising creatinine, BK PCR positive in blood → reduce mycophenolate first, then tacrolimus if needed; biopsy if creatinine continues to rise

CCS pearl: All transplant recipients need TMP-SMX for PJP prophylaxis (6–12 months) and valganciclovir for CMV prophylaxis (3–6 months for at-risk D+/R– pairs)

When to Escalate Care — Referral Triggers and Consult Logic

— eGFR <30 mL/min/1.73 m² (CKD G4) — refer to nephrology if not already followed

— Albuminuria >300 mg/g with declining function

— Rapidly declining eGFR (>5 mL/min/yr)

— Unclear etiology of CKD

— eGFR ≤30 with progressive disease — start the evaluation

— eGFR ≤20 — can be listed for deceased donor wait time accrual (UNOS rule)

— Dialysis initiation — start of wait-time accrual if not previously listed

— Identification of a potential living donor at any stage

— Cardiology — risk stratification, stress testing, revascularization decisions

— Social work — psychosocial assessment, caregiver, financial

— Psychiatry/psychology — depression, substance use, adherence history

— Nutrition — BMI optimization

— Dentistry — clear active dental disease

— Hepatology — if HBV, HCV, NAFLD, cirrhosis

— Gynecology/urology as needed for cancer screening

— Vascular surgery — if severe PVD, prior pelvic surgery

— Rising creatinine → urgent transplant nephrology evaluation; allograft ultrasound with Doppler; consider biopsy

— Fever in transplant recipient → infectious workup, blood/urine cultures, CMV PCR, chest imaging; admit if unstable

— Tacrolimus toxicity (tremor, AKI, confusion) → check trough level, hold dose, evaluate drug interactions

Trigger thresholds for nephrology referral in CKD:

Trigger thresholds for transplant center referral:

Multidisciplinary consults to obtain during evaluation:

Inpatient/urgent escalation post-transplant:

Board pearl: A patient on dialysis who has never been referred for transplant evaluation at any time — this is a quality-of-care gap. Every dialysis patient deserves the conversation, even if not a candidate.

Step 3 management: Patient with eGFR 22, stable, no symptoms — refer to transplant center now, do not wait for dialysis. List passively while completing workup.

Key distinction: Referral (initiating evaluation) vs. listing (active on UNOS waitlist accruing time) vs. active status (ready to receive offers) — all distinct administrative steps

Key Differentials — Other Renal Replacement Modalities

— In-center HD (3x/week, 3–4 hr sessions) — most common US modality

— Home HD (more frequent, better outcomes but resource-intensive)

— Requires vascular access: AV fistula preferred > AV graft > tunneled catheter (highest infection risk)

— Pros: established, supervised

— Cons: cardiovascular stress, dietary/fluid restrictions, time burden, access complications

— CAPD (manual exchanges) or APD (cycler at night)

— Pros: home-based, preserves residual function longer, gentler hemodynamics, flexible

— Cons: peritonitis risk, catheter complications, membrane failure over years, contraindicated with prior extensive abdominal surgery or large hernias

— Appropriate for elderly, frail, or those with limited life expectancy where dialysis would not meaningfully extend quality life

— Symptom-focused care, often with palliative care co-management

— Survival difference between dialysis and conservative care is modest in patients >80 with significant comorbidities

— Transplant: ~10–15 year median graft survival (living), ~10–12 yr (deceased); patient survival often >20 yr post-transplant

— Dialysis: 5-year survival ~40% (varies widely with age/comorbidity)

— Patient preference (autonomy is paramount)

— Comorbidities, frailty

— Home environment, support system

— Vascular anatomy (PD if vessels poor)

— Distance from dialysis center

When discussing transplant candidacy, must contrast with alternative renal replacement options — shared decision-making is required

Hemodialysis (HD):

Peritoneal dialysis (PD):

Conservative (non-dialytic) management:

Transplant vs. dialysis survival:

Modality selection factors:

Board pearl: Education on all modalities (transplant, HD, PD, conservative care) is a CMS quality metric for late-stage CKD — patients should not be defaulted into in-center HD without informed choice

Step 3 management: 70-year-old with CKD G5, eGFR 12, frail with metastatic cancer and limited life expectancy → discuss conservative kidney management as a valid option; not all patients benefit from dialysis

Key distinction: Transplant is the only modality that restores most kidney functions including erythropoiesis, vitamin D activation, and acid-base homeostasis

Key Differentials — Reversible Causes of Apparent ESRD

— Volume depletion

— Nephrotoxic medications (NSAIDs, contrast, aminoglycosides)

— Obstruction (BPH, stones, retroperitoneal fibrosis)

— Acute interstitial nephritis

— Bilateral renal artery stenosis or stenosis to a solitary functioning kidney

— Suspect with HTN, flash pulmonary edema, ACE-i induced AKI, asymmetric kidneys

— Workup: renal duplex, MRA, CTA

— Lupus nephritis flare

— ANCA vasculitis (untreated)

— Anti-GBM disease

— Cryoglobulinemic GN (HCV)

— Membranous nephropathy with anti-PLA2R

— Multiple myeloma (cast nephropathy) — bone marrow biopsy, SPEP/UPEP, free light chains

— TMA (TTP, HUS, atypical HUS) — plasma exchange, eculizumab

— Scleroderma renal crisis — ACE-i (counterintuitive but standard)

— Always rule out with renal ultrasound before declaring ESRD — hydronephrosis is treatable

— IgA, FSGS, lupus, ANCA can have superimposed acute on chronic flares

— Long-standing NSAID use, lithium, calcineurin inhibitors (in other transplant recipients), proton pump inhibitor-related interstitial nephritis

Before listing for transplant, ensure the kidney disease is truly irreversible — missing a reversible cause is a major error

Acute on chronic kidney injury — may recover function:

Renovascular disease:

Active glomerular disease that may respond to therapy:

Treatable systemic disease causing renal failure:

Obstructive uropathy:

Recurrent disease in native kidneys:

Drug-induced:

Board pearl: Every patient at eGFR <30 needs a renal ultrasound at minimum to exclude obstruction and assess kidney size/echogenicity. Small echogenic kidneys = chronic, irreversible. Normal-sized kidneys = consider biopsy or reversible causes.

Step 3 management: Patient with eGFR 18 and bilateral hydronephrosis on US → relieve obstruction first (Foley, nephrostomy, urology consult) before any transplant discussion. Function may recover substantially.

Key distinction: Anuria for >3 weeks with established ESRD is generally irreversible; oliguria with declining function may still have recoverable disease

Long-Term Plan — Listing, Wait Management, and Post-Transplant Lifelong Care

— Re-evaluate cardiac status periodically (stress test every 1–2 years for high-risk candidates)

— Update cancer screening per age guidelines

— Maintain vaccinations

— Recheck PRA/DSA every 3 months (sensitization events: transfusions, pregnancy, infections)

— Annual transplant center visits at minimum

— Maintain BMI in acceptable range

— Tobacco/substance cessation must be sustained

— Continue dialysis as needed

— Continue CV risk reduction: statin, antihypertensives, antiplatelet if indicated

— Avoid nephrotoxins to preserve any residual function

— Immunosuppression lifelong — typically tacrolimus + mycophenolate + prednisone (or steroid-free)

— TMP-SMX for PJP prophylaxis 6–12 months (longer if heavy immunosuppression)

— Valganciclovir for CMV prophylaxis based on D/R serostatus (3–6 months)

— Anti-fungal prophylaxis sometimes (nystatin oral)

— HBV antiviral lifelong if HBsAg+

— Aspirin often continued for graft thrombosis prevention in early period and CV risk long-term

— Statin for ASCVD prevention — leading cause of death post-transplant is CV disease

— Annual full skin exam by dermatology

— Routine age-appropriate cancer screening, often more aggressive

While waiting on the list, the patient needs ongoing optimization:

Pre-transplant medication adjustments:

Post-transplant long-term plan (knowledge level for Step 3):

Cancer surveillance post-transplant:

Bone health: DEXA, vitamin D, calcium; bisphosphonates if osteoporotic

Board pearl: Cardiovascular disease remains the #1 cause of death in transplant recipients with a functioning graft — aggressive secondary prevention is mandatory, not optional

Step 3 management: Stable 5-year post-transplant patient at routine visit: check tacrolimus trough, creatinine, CBC, UA, BP, A1c, lipid panel, update vaccines (no live), reinforce skin exam and sun protection

Key distinction: Immunosuppression is lifelong — discontinuation almost always results in rejection and graft loss, even years out

Follow-Up, Monitoring, and Counseling Cadence

— Initial evaluation: 1–2 day visit at transplant center

— Workup completion: typically 2–6 months

— Reassessment annually while waitlisted (more often if comorbidities)

— PRA/HLA antibody screen every 3 months

— Week 1: daily or every other day labs (creatinine, tacrolimus, electrolytes, CBC)

— Weeks 2–4: 2–3x/week

— Months 2–3: weekly to biweekly

— Months 3–6: every 2–4 weeks

— Months 6–12: monthly

— Year 1+: every 2–3 months, then quarterly for stable patients

— Creatinine, eGFR — primary graft function marker

— Tacrolimus trough level (target 8–10 ng/mL early, 5–8 later)

— CBC (mycophenolate causes leukopenia)

— Electrolytes (CNIs cause hyperkalemia, hypomagnesemia)

— Urinalysis with proteinuria

— Glucose/A1c (NODAT surveillance)

— Lipids

— BK virus PCR: monthly months 1–6, then every 3 months

— CMV PCR: with symptoms or per prophylaxis protocol

— BP — target <130/80

— Medication adherence is life-or-death — missed immunosuppression → rejection

— Sun protection (broad-spectrum SPF, hats, dermatology annually)

— Food safety (avoid unpasteurized products, undercooked meats — listeria/toxoplasma risk)

— Pet safety (no reptiles, careful with cat litter)

— Travel counseling (no live vaccines, avoid endemic regions when possible)

— Pregnancy planning (mycophenolate → azathioprine ≥6 wks before conception)

Pre-transplant evaluation cadence:

Post-transplant follow-up cadence (typical):

Monitoring parameters at each visit:

Counseling priorities:

Board pearl: Tacrolimus drug interactions are major — azoles, macrolides (not azithromycin), diltiazem, verapamil, grapefruit increase levels; rifampin, phenytoin, carbamazepine decrease levels. Always check before any new prescription.

Step 3 management: Stable transplant patient prescribed fluconazole for vaginitis → anticipate tacrolimus level rise; reduce tacrolimus dose and recheck trough, or use a non-interacting alternative

CCS pearl: Ambulatory follow-up orders for post-transplant: BMP, CBC, tacrolimus trough, UA — same panel weekly tapered to monthly

Ethical, Legal, and Patient Safety Considerations

— Risk of surgery and anesthesia

— Risk of graft loss, rejection

— Lifelong immunosuppression with infection and malignancy risks

— NODAT, cardiovascular risk

— Alternative therapies (HD, PD, conservative care)

— Risk of donor-derived disease (infection, malignancy) — including risks from increased-risk donors and HCV+ donors

— Expected wait time and possibility of dying on the waitlist

— Voluntary, free of coercion, no financial gain (reasonable expenses may be reimbursed; payment for organs is illegal under NOTA — National Organ Transplant Act 1984)

— Independent donor advocate required (cannot be the recipient's physician)

— Donor evaluation prioritizes donor safety, not recipient need

— Donors must be able to withdraw at any time without recipient knowing reason

— UNOS allocation is regulated to minimize disparities

— Documented disparities persist: African Americans, women, low-income patients are referred and listed less frequently — actively counter this in your practice

— Cannot deny based on race, sex, disability per se

— Substance use, adherence, social support are legitimate medical factors but must be applied consistently

— Document rationale carefully

— Post-transplant patient discharged from transplant center back to community nephrologist — medication reconciliation is critical

— Tacrolimus dosing errors, drug interactions, missed doses are common preventable harms

— Ensure explicit handoff with medication list, follow-up plan, when to call/return

— Suspected coercion in living donation must be reported

— Suspected organ trafficking — federal crime

Informed consent for transplant is uniquely complex — must cover:

Living donor ethics:

Allocation justice:

Listing decisions and discrimination:

Transition-of-care risks (Step 3 high-yield):

Mandatory reporting:

Brain death determination for deceased donors: governed by Uniform Determination of Death Act; family consent (or registered donor status) required for procurement

Board pearl: Payment for organs is illegal in the US (NOTA); paired exchange and reimbursement of donor expenses are legal alternatives

Step 3 management: Family member offers cash to "thank" a living donor → counsel that this violates federal law (NOTA) and would disqualify donation; refer to social work

High-Yield Associations and Rapid-Fire Clinical Facts

Refer to transplant center when eGFR ≤30; list when eGFR ≤20 (UNOS wait-time accrual threshold)

Time on dialysis is the strongest modifiable predictor of post-transplant outcome → preemptive transplant is best

Living donor > deceased donor for graft survival; HLA-identical sibling is the immunologic gold standard

Crossmatch types: CDC (historical), flow cytometry (sensitive), virtual (Luminex + donor HLA typing)

Positive CDC crossmatch = absolute contraindication to that donor

Cancer waiting periods: most solid tumors 2–5 years disease-free; NMSC and incidental small RCC: no wait

Vaccines pre-transplant: complete all live vaccines (MMR, varicella, live zoster, yellow fever) — contraindicated post-transplant

Mycophenolate is teratogenic — switch to azathioprine ≥6 weeks before conception

Tacrolimus interactions: azoles, macrolides, diltiazem ↑; rifampin, phenytoin ↓

BK virus nephropathy: treat by reducing immunosuppression

PJP prophylaxis: TMP-SMX for 6–12 months

CMV prophylaxis: valganciclovir, especially D+/R– (highest risk)

PTLD: EBV-driven, especially EBV-mismatched (D+/R–)

NODAT: tacrolimus and steroids; screen with HbA1c

Leading cause of death with functioning graft: cardiovascular disease

Leading cause of late graft loss: chronic allograft injury (formerly "chronic rejection")

HCV+ kidney → HCV– recipient: now standard practice with DAA prophylaxis

HIV transplantation: requires CD4 >200, undetectable VL, no recent OIs; HIV+ to HIV+ allowed (HOPE Act)

Simultaneous pancreas-kidney (SPK): type 1 DM with ESRD

Simultaneous liver-kidney (SLK): per UNOS metabolic/sustained AKI/CKD criteria

Paired kidney exchange: solution for ABO/crossmatch incompatible pairs

Surgical site: heterotopic, iliac fossa; native kidneys usually left in place

Delayed graft function: dialysis needed in first week; more common with deceased donor, high KDPI, long cold ischemia

Board pearl: EPTS top 20% recipients matched with KDPI top 20% kidneys (longevity matching) under current Kidney Allocation System

Step 3 management: Any CKD G4 patient — ask "have they been referred for transplant evaluation?" If not, refer now

Board Question Stem Patterns

— Stem: "62-year-old man with diabetic CKD, eGFR 28, stable. What is the next best step?"

— Answer: Refer to transplant center for evaluation (not "start dialysis," not "wait until eGFR <15")

— Stem: "45-year-old with CKD G4 eGFR 22 and a healthy HLA-matched sibling willing to donate. Best management?"

— Answer: Proceed with preemptive living donor transplant evaluation — do not initiate dialysis first

— Stem: "Patient being evaluated for transplant, non-immune to varicella. What now?"

— Answer: Administer varicella vaccine now (live vaccine, must be given before transplant)

— Stem: "Transplant patient on tacrolimus started on clarithromycin develops AKI and tremor."

— Answer: Tacrolimus toxicity from CYP3A4 inhibition — hold tacrolimus, check trough, use alternative antibiotic (e.g., azithromycin)

— Stem: "28-year-old, 2 years post-transplant, wants to conceive."

— Answer: Switch mycophenolate to azathioprine ≥6 weeks before conception

— Stem: "3 months post-transplant, creatinine rising, BK PCR positive in blood."

— Answer: Reduce immunosuppression (start with mycophenolate)

— Stem: "Patient with metastatic colon cancer 6 months ago, now ESRD, wants transplant."

— Answer: Active malignancy is absolute contraindication; wait per cancer-specific guidelines (typically 2–5 yrs disease-free)

— Stem: "Patient with cPRA 98% on waitlist 6 years. Best strategy?"

— Answer: Paired kidney exchange or desensitization protocol

— Stem: "Diabetic on HD being evaluated. Next cardiac test?"

— Answer: Pharmacologic stress test (not routine cath without indication)

— Stem: "Recipient offers donor $20,000."

— Answer: Violates NOTA; disqualifies donation; refer to social work

Pattern 1 — When to refer:

Pattern 2 — Preemptive transplant:

Pattern 3 — Vaccinations:

Pattern 4 — Drug interaction:

Pattern 5 — Mycophenolate and pregnancy:

Pattern 6 — BK virus:

Pattern 7 — Contraindication:

Pattern 8 — Allocation/sensitization:

Pattern 9 — Cardiac workup:

Pattern 10 — Live donor ethics:

Board pearl: Step 3 favors outpatient longitudinal management — "refer now," "schedule vaccine," "switch drug," "counsel on adherence" — over inpatient heroics

One-Line Recap

— Referral threshold eGFR ≤30; listing threshold eGFR ≤20; living donor preemptive transplant is the gold standard, and time on dialysis is the single strongest modifiable predictor of post-transplant outcome

— Workup essentials: ABO/HLA/PRA, crossmatch, infectious serologies (HIV/HBV/HCV/CMV/EBV/TB), age-appropriate cancer screening, cardiac stress testing in high-risk patients, dental clearance, psychosocial evaluation, and complete all live vaccines before transplant (MMR, varicella, live zoster)

— Absolute contraindications are limited: active malignancy, active untreated infection, severe irreversible cardiopulmonary disease, active substance use, demonstrated severe nonadherence — age and diabetes alone are NOT contraindications

— Tacrolimus toxicity → check trough, review interactions (azoles, macrolides, diltiazem ↑)

— BK viremia → reduce immunosuppression (mycophenolate first)

— Pregnancy planning → mycophenolate to azathioprine ≥6 weeks before conception

— Highly sensitized (cPRA >80%) → paired exchange or desensitization

Bottom line: Every patient with progressive CKD reaching eGFR ≤30 deserves prompt referral to a transplant center for multidisciplinary evaluation, because preemptive living donor transplantation — performed before dialysis when possible — provides the longest, healthiest life of any renal replacement option.

Three high-yield recap pearls:

Four management triggers to memorize:

Board pearl: When in doubt on Step 3, the answer involves early referral, complete pre-transplant vaccination, aggressive cardiovascular prevention, and meticulous medication reconciliation — these are the longitudinal management decisions that define renal transplant evaluation at the Step 3 level.