Case · Presentation

Every risk factor says high. The assay says low.

A 45-year-old African American woman with a five-year history of dialysis-dependent end-stage renal disease (ESRD) secondary to hypertension underwent a deceased donor kidney transplant one week ago. The donor was a 35-year-old deceased individual, and the kidney had a cold ischemia time of 18 hours. The terminal creatinine was 1.2 mg/dL, and the graft demonstrated immediate function post-transplant.

Her pre-transplant immunologic workup included Panel Reactive Antibody (PRA) testing (peak 30%) and HLA typing, which showed no mismatches. Crossmatching tests were negative.

She was hospitalized for four days postoperatively, during which she received induction therapy with antithymocyte globulin (4.5 mg/kg for 3 days). She was then discharged on standard triple immunosuppressive therapy, including tacrolimus with a target trough level of 8–10 ng/mL, mycophenolate mofetil (MMF) 1000 mg twice daily (total 2000 mg/day) and prednisone 30 mg/day. Her serum creatinine at discharge was 1.5 mg/dL.

She presents today for her first post-transplant clinic visit, three days after discharge, and is feeling well overall. She reports good medication adherence, with no complaints of fever, swelling, oliguria, or graft site tenderness. She denies any gastrointestinal symptoms, infections, or new-onset hypertension. Results of the One Lambda™ PTRA previously ordered are available for review at today’s visit.

Medical history: controlled hypertension, G2P2 (Gravida 2, Para 2), three blood transfusions, no known allergies. No significant family history of kidney disease or autoimmune disorders.

On examination she is conscious, alert and well-oriented x3, albeit nervous, but is not distressed. She is afebrile and anicteric, and she is not pale. There is no swelling or palpable lymph nodes. BP 130/80 mmHg, RR 20 cpm, HR 80 bpm, temperature 36.7 °C. Half-and-half nails are present; no cyanosis or edema; pulses intact bilaterally.

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Case · Workup

Creatinine 1.5 to 1.15. Tacrolimus 11.

These are the investigations ordered at today’s visit, with the findings and the reasoning for each.

• One Lambda™ PTRA Assay · (Ordered at Transplant; Results Available Today)

  Today’s results: The One Lambda™ PTRA Assay result is low risk for early acute rejection.

  It is appropriate to review the results of the One Lambda™ PTRA Assay ordered at the time of her transplant. These results help stratify the likelihood of early acute rejection, guiding initial immunosuppression decisions in conjunction with conventional immunologic risk factors such as the panel reactive antibody level, donor type, and induction strategy. Identifying patients at low risk supports a personalized immunosuppressive approach, potentially reducing unnecessary medication exposure. Recent reviews confirm that pre-transplant blood gene-expression assays can stratify early rejection risk and support safe minimization strategies, such as faster steroid taper and early mycophenolate reduction (Strader & Kant, 2025; Chancharoenthana W, et al. 2023). Conversely, it enables early intervention with intensified immunosuppression for high-risk patients to prevent rejection and improve long-term graft survival. Recent comprehensive reviews summarize multicenter prospective validations of peripheral-blood transcriptomic signatures and outline how high-risk profiles can guide intensified immunosuppression and closer surveillance, including closer laboratory, immunologic, and clinical monitoring (Punukollu R, et al. 2025).

• Tacrolimus Trough Levels

  Today’s results: ↑11ng/mL (target range: 8 - 10 ng/mL)

  It is appropriate to order Tacrolimus Trough levels testing. Close monitoring of calcineurin inhibitor exposure is essential in the early post-transplant period to balance rejection prevention with avoidance of nephrotoxicity, particularly as graft function improves (Hardinger K, et al. 2024).

• Comprehensive metabolic panel (CMP)

  The patient’s renal function is improving, with a decreasing creatinine (1.5 → 1.15 mg/dL). This represents a significant improvement in graft function. Significant rise in eGFR (40 → 81 mL/min/1.73 m²), indicating recovering graft function; electrolytes, glucose, and protein levels remain within normal limits and show no evidence of acute metabolic complications or calcineurin inhibitor–related electrolyte disturbances.

  Test	Value today	Value at discharge 3 days ago	Range (Adult Female)
  Bilirubin (total)	0.5 mg/dL	0.4 mg/dL	0.3–1.0 mg/dL
  Bilirubin (direct)	0.2 mg/dL	0.3 mg/dL	0.1–0.3 mg/dL
  Blood urea nitrogen (BUN)	18 mg/dL	25 mg/dL	8–20 mg/dL
  BUN: creatinine ratio	15.65	16.67	10–20
  Bicarbonate	26 mEq/L	25 mEq/L	23–28 mEq/L
  Calcium	9.3 mg/dL	9 mg/dL	8.6–10.2 mg/dL
  Creatinine	1.15 mg/dL	↑ 1.5 mg/dL	0.50–1.10 mg/dL
  Chloride	101 mEq/L	100 mEq/L	98–106 mEq/L
  Estimated glomerular filtration rate (eGFR)	↓ 81 mL/min/1.73 m2	↓ 40 mL/min/1.73 m2	90–120 mL/min/1.73 m2
  Glucose	83 mg/dL	80 mg/dL	70–99 mg/dL
  Potassium	4.1 mEq/L	4.0 mEq/L	3.5–5.0 mEq/L
  Sodium	139 mEq/L	140 mEq/L	136–145 mEq/L
  Total protein	7.5 g/dL	7 g/dL	6.0-7.8 g/dL

• Complete blood count (CBC)

  Today’s results: The patient’s hematologic profile is improving, with hematocrit (HCT) rising from 30% to 33% and hemoglobin (HGB) increasing from 10 g/dL to 11 g/dL, indicating recovery of anemia commonly observed following kidney transplantation and improved erythropoietin production.

  Test	Value today	Value at discharge 3 days ago	Range (Adult Female)
  WBC	7000/µL	8000/µL	4000–10 000/µL
  Neutrophils	66%	65%	50–70%
  Eosinophils	1%	1%	0–3%:
  Basophils	0%	0%	0–1 %
  Monocytes	2%	1%	0–6%
  Lymphocytes	34%	32%	30–45 %
  HCT	↓ 33%	↓ 30%	36–47%
  HGB	↓ 11 g/dL	↓ 10 g/dL	12–16 g/dL
  MCV	85 fL	90 fL	80–100 fL
  MCH	31 pg	30 pg	28–32 pg
  MCHC	33 g/dL	34 g/dL	33–36 g/dL
  Platelets	300,000/µL	290,000/µL	150 000–450 000/µL

• Urinalysis

  Today’s results: Negative

  It is appropriate to order a urinalysis. Routine urinalysis aids in early detection of hematuria, proteinuria, or pyuria, which may signal acute rejection, urinary tract infection, or recurrent or de novo renal disease (Kadambi PV, et al. 2023).

• Plasma BK Polyomavirus PCR

  Today’s results: Undetectable (negative) BK viremia.

  Routine screening for BK polyomavirus viremia is recommended during the first post-transplant year, particularly in patients receiving lymphocyte-depleting induction therapy. Early detection is critical, as BK polyomavirus–associated nephropathy may mimic acute rejection and requires prompt immunosuppression reduction rather than intensification (Limaye AP, et al. 2022).

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Case · Diagnosis

What is her immunologic risk?

Her traditional risk profile and her assay result disagree. One of them has to lead.

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Case · Treatment

Low risk earns her less drug.

She is on tacrolimus targeted to 8–10 ng/mL, MMF 1 g twice daily and prednisone 30 mg/day. Today’s tacrolimus trough is 11 ng/mL.

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Case · Next steps

What she leaves the clinic with.

Every order below is appropriate unless marked otherwise in its reasoning.

• 01Medication adherence. Medication adherence counseling is essential to improve patient understanding of the immunosuppressive regimen, reinforce correct dosing and timing, and reduce the risk of acute rejection and graft loss associated with nonadherence (KDIGO, 2009; Kasiske BL, et al. 2021).
• 02Follow-up appointment. Follow-up is key to carrying out lab tests and regular checkups. These visits help track the recovery process and detect potential complications early on (KDIGO, 2009). In Anne’s case, follow-up also includes a structured monitoring plan to ensure safety during immunosuppression minimization: weekly tacrolimus troughs for 4–6 weeks, then per center policy; serum creatinine/eGFR and urine protein at each visit; infection prophylaxis per risk (e.g., CMV, PJP) with cytopenia checks given MMF taper. Beyond pre-transplant assays like PTRA, emerging noninvasive post-transplant biomarkers — including blood transcriptomic panels and donor-derived cfDNA — may complement routine labs during follow-up, offering additional surveillance for rejection risk (Strader & Kant, 2025; Punukollu R, et al. 2025).
• 03Patient education. Counseling today's patients about renal transplants, signs of infection and rejection, medical adherence, and follow-up visits is important (Chadban S, et al. 2020).
• 04Compression stockings/muscle pump activators. Compression therapy during the early postoperative period can improve lymph flow, reduce leg edema, and reduce the incidence of lymphocele. / Muscle pump activators also reduce edema and increase total urine output (KDIGO, 2009).
• 05Lifestyle modification counseling. This patient should be counseled on the importance of living a healthy lifestyle, including eating a healthy diet, doing appropriate exercises, avoiding smoking, and maintaining a healthy weight. Lifestyle modification is an integral component of post-transplant care and contributes to improved cardiovascular outcomes, metabolic control, and long-term graft survival (Chadban SJ, et al. 2020; Kasiske BL, et al. 2021).
• 06Donor-specific antibody (DSA). KDIGO 2021 recommends routine DSA monitoring at 3–6 months to detect subclinical alloimmune activation, which can precede clinical rejection. Early detection enables timely immunosuppression adjustment and prevents irreversible graft injury (Kasiske BL et al., 2021).
• 07vaccination review. Ensure the patient is up-to-date on inactivated influenza (yearly), pneumococcal vaccination with PCV20 or PPSV23 (depending on prior vaccinations), hepatitis B vaccine (completion of series if not done pre-transplant), and COVID-19 vaccines/boosters (AST, 2025).
• 08Lipid Monitoring. Per KDIGO 2021, lipid profile should be reassessed within 2–3 months post-transplant to guide long-term cardiovascular risk management, with repeat testing annually thereafter or after any change in immunosuppression (Kasiske BL, et al. 2021).
• 09BK virus polymerase chain reaction. As recommended by KDIGO 2021, monthly plasma BK polyomavirus polymerase chain reaction screening should be performed during the first 6 months post-transplant, particularly in patients who received lymphocyte-depleting induction therapy, to enable early detection of viremia and timely immunosuppression adjustment (Kasiske BL et al., 2021; Limaye AP et al., 2022).
• 10Routine kidney biopsy at 3 months. Not appropriate. According to KDIGO 2021 guidance, protocol biopsies are not routinely required in low-risk kidney transplant recipients with stable graft function, absence of donor-specific antibodies, and reassuring biomarker assessments such as a low-risk PTRA result. Performing unnecessary biopsies increases the risk of complications such as bleeding or arteriovenous fistula formation, without clear evidence of added clinical benefit in this context (Kasiske BL et al., 2021; Brennan DC et al., 2023).

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Case · Takeaways

Objective data, not a risk profile.

Anne, a 45-year-old kidney transplant recipient, is navigating the critical early weeks of post-transplant care. Despite her higher panel reactive antibody (PRA) levels, African American ethnicity, younger age, multiple blood transfusions, and history of two pregnancies—all traditionally associated with a higher risk of acute rejection—her clinical course has been stable, and her graft function remains excellent.

Instead of relying solely on historical risk factors, the One Lambda™ PTRA Assay provided a more precise immune risk assessment, confirming Anne falls into a low-risk category for early acute rejection (GenomeWeb, 2024; Sawitzki B, et al. 2009). This allowed for a safe, proactive immunosuppression minimization strategy, reducing her exposure to unnecessary medication side effects while maintaining strong graft protection (Bamoulid J, et al. 2015).

In alignment with KDIGO 2021, ongoing post-transplant surveillance should also include donor-specific antibody (DSA) monitoring at 3–6 months, BK virus PCR screening monthly for the first 3–6 months, and routine lipid reassessment to reduce cardiovascular risk. These measures complement biomarker-driven immunosuppression adjustment, ensuring safety while minimizing toxicity.

While multiple valid treatment strategies exist, this case demonstrates the value of personalized medicine, where modern diagnostic tools enable a more tailored approach to transplant management. The AST guideline on vaccination emphasizes vaccination and infection prophylaxis as critical components of post-transplant management, reinforcing the role of prevention alongside precision immunosuppression (American Society of Transplantation, 2004). By moving beyond demographic assumptions and utilizing evidence-based immune risk stratification, clinicians can more confidently optimize therapy for each patient, improving clinical outcomes and post-transplant quality of life (Chadban S, et al. 2020; KDIGO, 2009).

This case highlights how precision tools like PTRA can reclassify patients traditionally considered “high risk” into a safer category, enabling immunosuppression minimization and improving quality of life.

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