# Transplant Evaluation and Selection

## Overview

Kidney transplantation offers superior outcomes to dialysis for appropriate candidates: improved quality of life, longer survival, and lower cost per patient-year compared to dialysis \[1\]. Comprehensive pretransplant evaluation identifies absolute contraindications, assesses medical/surgical risk, and screens for malignancy, infection, and cardiovascular disease. Immunologic workup (HLA typing, PRA assessment, crossmatching) guides donor selection and immunosuppression strategy. This guide synthesizes transplant evaluation, donor-recipient matching, immunosuppression regimens, and post-transplant complication management.

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## Key Clinical Pearl

**“The best renal transplant is a preemptive living-donor transplant from a biologically related donor with minimal immunologic mismatch. However, even an older, EBV+ donor kidney in a well-screened recipient with excellent adherence is superior to a lifetime on dialysis.”**

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## Part 1: Transplant Evaluation Framework

### Timing of Referral

**KDIGO Recommendation:** - **G3b CKD (eGFR 30–44):** Offer education on all RRT options (dialysis, transplant, conservative care) - **G4 CKD (eGFR 15–29):** Refer for transplant evaluation if appropriate - **G5 CKD (eGFR \<15):** Complete evaluation and list if transplant-eligible - **Pre-emptive transplant:** Ideal; can occur before dialysis initiation (especially living-donor)

### Goals of Transplant Evaluation

1.  **Determine transplant eligibility:** Identify absolute/relative contraindications
2.  **Optimize health status:** Treat cardiovascular disease, diabetes, infections
3.  **Assess immunologic risk:** HLA sensitization, crossmatch compatibility
4.  **Educate on RRT options:** Living vs deceased donor, risks/benefits
5.  **Assess psychosocial readiness:** Adherence capacity, social support, mental health

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## Part 2: Contraindications to Transplantation

### Absolute Contraindications (Transplant Not Offered)

| Contraindication | Rationale | Duration |
|----|----|----|
| **Active malignancy** | Immunosuppression accelerates tumor growth | Until treatment complete |
| **Active infection (systemic)** | Uncontrolled sepsis; immunosuppression worsens outcome | Until resolved |
| **Active tuberculosis (untreated)** | Immunosuppression causes dissemination | Until fully treated (6 months) |
| **Uncontrolled psychiatric disease** | Risk of non-adherence; transplant failure | Until stabilized |
| **Inability to comply with immunosuppression** | Supports graft survival; nonadherence increases rejection risk | Lifelong |
| **Life expectancy \<5 years (from non-renal disease)** | Risk/benefit unfavorable | N/A |
| **Uncorrected cardiac disease with high operative risk** | Cannot tolerate transplant surgery | Until correctable |
| **Severe hepatic cirrhosis (Child-Pugh C)** | Poor synthetic function; cannot metabolize drugs | Permanent |

### Relative Contraindications (Assessed Case-by-Case)

| Contraindication | Assessment | Decision Pathway |
|----|----|----|
| **History of malignancy** | Type, stage, time since treatment | \>2–5 years cancer-free may be acceptable |
| **Age \>70 years** | Functional status, comorbidities, life expectancy | Chronologic age alone not contraindication |
| **Severe obesity (BMI \>40)** | Surgical risk, graft function, compliance | May accept if motivated; weight loss recommended |
| **Significant proteinuria (\>2 g/day)** | Etiology; assess for GN | May transplant if stable; treat underlying disease |
| **History of nonadherence** | Assess reasons; psychosocial support | Intensive counseling may improve outcomes |
| **Active substance abuse** | Addiction active vs in remission | Usually requires 6 months sobriety |
| **Severe coronary artery disease** | Assess with stress testing; revascularize if possible | May accept high-risk CAD if revascularized |
| **Hepatitis C antibody positive** | HCV RNA+ state; assess liver fibrosis; transplant HCV- donor if possible | Direct-acting antivirals cure HCV; may improve candidacy |
| **Hepatitis B surface antigen+** | Assess HBeAg, HBV DNA; vaccination status | Lamivudine/TDF prophylaxis minimizes progression |

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## Part 3: Immunologic Workup

### HLA Typing

**HLA (Human Leukocyte Antigen):** Polymorphic proteins on cell surface that trigger immune recognition.

**HLA Classes:** - **Class I (HLA-A, -B, -C):** On all nucleated cells; target of acute/chronic rejection - **Class II (HLA-DR, -DQ, -DP):** On antigen-presenting cells; elicit T-helper response

**Clinical importance:** - **Identical twins:** 0 HLA mismatch; no rejection risk (theoretically) - **Haplo-identical (one parent/sibling):** 3 HLA mismatch (one haplotype shared); acceptable - **Unrelated:** Often 6 HLA mismatch (highest rejection risk without sensitization history)

**Effect on graft survival:** Each additional HLA mismatch ~5% reduction in 5-year graft survival.

### Panel Reactive Antibody (PRA) and Sensitization Assessment

**PRA (% panel reactive antibody):** - **Definition:** Percentage of donors in a panel to whom recipient has preformed anti-HLA antibodies - **Measured by:** Flow cytometry, Luminex (most sensitive) - **Interpretation:** - **PRA 0%:** Non-sensitized; low rejection risk; easiest to match - **PRA 1–49%:** Moderately sensitized; acceptable transplant candidates with good matching - **PRA \>50%:** Highly sensitized; need compatible donor or desensitization; longer wait times

**Causes of sensitization:** - **Prior transplant rejection** (most common) - **Multiple blood transfusions** - **Pregnancy (female recipients)** - **Prior exposure to alloantigen** (repeat transfusions, failed prior grafts)

### Donor-Specific Antibodies (DSA)

**Definition:** Antibodies against specific donor HLA antigens (determined after donor identified).

**Test:** Single-antigen Luminex bead assay (identifies exact HLA antibodies).

**Clinical significance:** - **Donor-specific IgG antibodies:** HIGH risk of antibody-mediated rejection (AMR); may necessitate desensitization or declining donor - **Donor-specific IgM antibodies:** Variable risk; typically lower than IgG - **Complement-fixing antibodies:** Higher rejection risk than non-complement-fixing

### Crossmatch Test

**Definition:** In vitro test of recipient serum against donor lymphocytes to detect anti-donor antibodies.

**Test methods (from least to most sensitive):** 1. **Complement-dependent cytotoxicity (CDC):** Gold standard historically; detects IgG/IgM 2. **Flow cytometry crossmatch:** More sensitive; detects low-level IgG; better predictor of rejection 3. **Luminex:** Single-antigen beads; identifies exact HLA antibodies vs donor antigens

**Interpretation:** - **Negative crossmatch:** Safe to proceed (IgG antibody unlikely to cause hyperacute rejection) - **Positive IgG crossmatch:** **CONTRAINDICATION to transplant** (hyperacute rejection risk; graft loss within hours) - **Positive IgM only:** Acceptable; IgM typically clears quickly

### ABO Incompatibility

**Traditional rule:** ABO-incompatible transplants were contraindicated (hyperacute rejection from IgM ABO antibodies).

**Modern approach (ABO-incompatible transplant):** - **Desensitization:** Plasmapheresis, low-dose IVIG, rituximab (anti-CD20) - **Result:** Successful ABO-incompatible transplants now possible (5-year graft survival ~80% vs 85% for ABO-compatible) - **Advantage:** Expands living-donor pool; reduces wait times for O recipients

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## Part 4: Living vs Deceased Donor Selection

| Characteristic | Living Donor | Deceased Donor | Impact on Graft |
|----|----|----|----|
| **Donor evaluation** | Comprehensive; healthy baseline | Variable; often limited pre-mortem history | Living = better outcomes |
| **HLA matching** | Often related (0–3 mismatch) | Usually unrelated (3–6 mismatch) | Each mismatch ~5% 5-yr graft loss |
| **Cold ischemia time** | 0 (immediate transplant possible) | 12–24+ hours | Longer ischemia time = more dysfunction |
| **Delayed graft function (DGF)** | 5–10% | 20–40% | DGF increases acute rejection risk |
| **Acute rejection rate** | 20–30% | 40–45% | Living \> deceased in intermediate-term |
| **Graft survival at 5 years** | 80–85% (living-related); 75–80% (living-unrelated) | 70–75% | Living-related superior |
| **Recipient survival** | Better (better health; pre-emptive options) | Variable | Living donor recipients have better outcomes |
| **Cost analysis** | Higher upfront surgical cost (evaluating donor + surgery) | Lower upfront but more dialysis time before Tx | Long-term cost similar; transplant always cheaper |

### Kidney Paired Donation (KPD)

**Definition:** Cross-matching incompatible recipient-donor pairs to find compatible matches.

**Example:** - Patient A incompatible with Donor A - Patient B incompatible with Donor B - BUT: Patient A compatible with Donor B; Patient B compatible with Donor A - **Solution:** Swap donors → two successful transplants

**Impact:** Increases transplant options for highly sensitized recipients and ABO-incompatible pairs.

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## Part 5: UNOS Allocation System for Deceased Donors

### Kidney Allocation System (KAS) Principles

**Goals:** 1. Maximize graft longevity (longer-surviving grafts to younger recipients) 2. Eliminate transplant list waiting time based solely on time accumulated 3. Achieve better HLA matching when possible 4. Improve equity across geographic regions

### Key Metrics

**Kidney Donor Profile Index (KDPI):** - Composite score (0–100) predicting donor kidney function - **Low KDPI (\<35%):** Better quality; longer expected survival - **High KDPI (\>85%):** Lower quality; shorter expected survival

**Estimated post-transplant survival (EPTS):** - Score predicting recipient’s expected lifespan post-transplant - **Low EPTS (\<20%):** Longer life expectancy; allocated best kidneys - **High EPTS (\>80%):** Shorter life expectancy; lower-quality kidneys may be appropriate

**Allocation priority:** - High-KDPI kidneys → low-EPTS recipients (best match) - Low-KDPI kidneys → can be allocated based on compatibility/geography

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## Part 6: Induction and Maintenance Immunosuppression

### Induction Therapy (At Time of Transplant)

**Goal:** Prevent acute cellular rejection in immediate post-transplant period.

**Options:**

| Agent | Type | Dosing | Use | Mechanism |
|----|----|----|----|----|
| **Basiliximab** | Anti-IL-2R mAb | 20 mg IV day 0, 4 | Standard induction | IL-2 receptor blockade |
| **Daclizumab** | Anti-IL-2R mAb | 1 mg/kg day 0, 4 | Alternative (rarely used) | IL-2 receptor blockade |
| **Alemtuzumab** | Anti-CD52 mAb | 0.3 mg/kg IV day 0 | Highly sensitized; ANCA+ | T-cell and B-cell depletion |
| **Rituximab** | Anti-CD20 mAb | 375 mg/m² day 0 | B-cell targeting; ABO-incompatible Tx | B-cell depletion |
| **Antithymocyte globulin (ATG)** | Polyclonal antibody | 1.5 mg/kg daily × 3–5 days | Induction; steroid-sparing | T-cell depletion |

**Preferred approach:** Basiliximab induction + calcineurin inhibitor + MMF + corticosteroids (standard triple therapy).

### Maintenance Therapy (Long-Term)

**Standard triple therapy:**

| Agent | Class | Dosing | Mechanism | Monitoring |
|----|----|----|----|----|
| **Tacrolimus** | Calcineurin inhibitor | 1–2 mg 2×/day (level 5–12 ng/mL initially) | Inhibits IL-2 T-cell signal | Trough level; renal function; K; Mg |
| **Mycophenolate mofetil (MMF)** | Antimetabolite | 500–1000 mg 2×/day | Inhibits IMPDH; depletes GTP in T/B cells | CBC (monitor for leukopenia) |
| **Prednisone** | Corticosteroid | 5–10 mg daily (taper from 20 mg day 0) | Anti-inflammatory; blocks cytokine production | Weight; glucose; BP; osteoporosis risk |

**Alternative combinations:**

| Scenario | Preferred Regimen | Rationale |
|----|----|----|
| **EBV-negative recipient** | Basiliximab + tac + MMF + pred | Standard |
| **CNI-intolerant (diabetes, nephrotoxicity)** | Basiliximab + sirolimus + MMF + pred | Avoid CNI nephrotoxicity |
| **High immunologic risk (sensitized)** | Alemtuzumab + tac + MMF + pred | More intensive T/B-cell depletion |
| **Older recipient, excellent match** | Lower-intensity (belatacept + pred alone) | Belatacept (T-cell co-stimulation blocker) |

### Calcineurin Inhibitor (CNI) Toxicity

**Tacrolimus and cyclosporine** both cause: - **Nephrotoxicity:** Chronic CNI nephropathy → GFR decline 5–10 mL/min/yr over 5 years - **Hypertension:** 50–80% of recipients (vasoconstriction) - **Hyperkalemia:** Impairs K secretion; requires careful monitoring - **Hypomagnesemia:** Increases cardiac arrhythmia risk - **Diabetes (new-onset):** 15–20% of recipients; glucose intolerance

**Management:** - Monitor trough CNI levels (narrow therapeutic window) - Monitor renal function; decline \>20% warrants assessment - Antihypertensive therapy (aim SBP \<130 mmHg) - Potassium monitoring; restrict K if elevated - Screen for NODAT (new-onset diabetes after transplant)

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## Part 7: Post-Transplant Complications

### Acute Cellular Rejection (ACR)

**Timing:** Usually 1–12 months post-transplant (can occur anytime).

**Pathophysiology:** T-cell mediated infiltration of graft; interstitial inflammation, tubulitis.

**Clinical presentation:** - Rising serum creatinine (30–50% above baseline) - Decreased urine output - Possible fever, graft tenderness, proteinuria

**Diagnosis:** Renal biopsy (gold standard); shows mononuclear infiltrate, tubulitis.

**Treatment:** - **Mild-moderate ACR:** Increase corticosteroid dose (pulse methylprednisolone 500 mg IV daily × 3 days) - **Severe/steroid-resistant:** Antithymocyte globulin (ATG 1.5 mg/kg daily × 3–5 days) OR rituximab

**Outcomes:** 80–90% respond to treatment; steroid resistance associated with worse long-term outcomes.

### Antibody-Mediated Rejection (AMR)

**Pathophysiology:** Donor-specific antibodies (anti-HLA, anti-MICA, anti-endothelial) activate complement; endothelial inflammation.

**Presentation:** - Rising Cr - Proteinuria - May be accompanied by acute cellular rejection (“mixed rejection”)

**Diagnosis:** Renal biopsy with IF shows C4d deposition (along peritubular capillaries); DSA+ serum.

**Treatment:** - **Acute AMR:** Plasmapheresis (remove DSA) + IVIG (inhibit complement) + rituximab (deplete B cells producing antibodies) - **Chronic AMR:** Long-term plasmapheresis, IVIG, rituximab; prognosis poor (median graft survival ~5 years)

### Chronic Antibody-Mediated Rejection (cAMR)

**Definition:** Slower decline in graft function associated with persistent DSA + C4d+ and/or chronic pathologic lesions (transplant glomerulosclerosis, transplant vasculopathy).

**Pathologic features:** - Transplant glomerulosclerosis (TGS): Duplication of GBM, capillary collapse - Transplant vasculopathy: Intimal hyperplasia in arteries - Interstitial fibrosis/tubular atrophy (IF/TA): Secondary to chronic rejection

**Outcomes:** Progressive graft loss; median 5–10 year graft survival with cAMR.

### Infections Post-Transplant

**Timeline and pathogens:**

| Timing | Common Pathogens | Pathophysiology |
|----|----|----|
| **0–1 month** | Bacterial UTI, wound infection, HSV (reactivation) | Post-surgical; high-dose initial immunosuppression |
| **1–6 months** | CMV (primary/reactivation), PCP, Toxoplasma, Cryptococcus, Aspergillus | Peak immunosuppression period; opportunistic |
| **\>6 months** | Community organisms (S. pneumoniae), mycobacteria, late CMV | Immunosuppression lower; community exposure |

**CMV Prophylaxis:** - **High-risk (seropositive donor, seronegative recipient):** Valganciclovir 900 mg daily × 3–6 months - **Lower-risk:** IVIG or valganciclovir based on risk stratification

**PCP Prophylaxis:** - **CD4 \<200 or heavy immunosuppression:** TMP-SMX double-strength daily or 3×/week

**Fungal prophylaxis:** - **Nystatin oral rinse** for first 3 months (Candida) - **Fluconazole** if high-risk or previous fungal infection

### Malignancy Post-Transplant

**Increased risk:** 4–5× higher than general population due to chronic immunosuppression.

**Most common:** 1. **Skin cancer (basal cell, squamous cell, melanoma):** 40% of cancers 2. **Post-transplant lymphoproliferative disorder (PTLD):** EBV-driven B-cell lymphoma; 1–2% of recipients 3. **Renal cell carcinoma:** Native kidney cancer (not graft); slightly elevated risk 4. **Cervical cancer** (women); anal cancer; lung cancer

**Risk factors:** - Duration of immunosuppression - Type of immunosuppression (higher risk with mTOR inhibitors, azathioprine) - EBV serostatus (EBV-negative recipients: higher PTLD risk) - Sun exposure, HPV infection, age

**Screening:** - Annual skin exam (dermatology) - Cervical cancer screening (pap smear annually) - Cancer awareness; report symptoms promptly

**PTLD management:** - **Early lesion:** Reduce immunosuppression + observation - **Advanced/symptomatic:** Rituximab ± chemotherapy (CHOP)

### BK Virus Nephropathy

**Etiology:** BK polyomavirus reactivation in immunosuppressed recipients; direct viral cytopathic effect on tubular epithelium.

**Presentation:** - Rising Cr months 3–12 post-transplant - Often asymptomatic; discovered on lab monitoring - Decoy cells on urine cytology (pathognomonic)

**Diagnosis:** Biopsy shows viral inclusions in tubular epithelium; PCR in urine/serum \>10,000 copies indicates active viremia.

**Treatment:** - Reduce immunosuppression (lower CNI target level; reduce MMF dose) - Antivirals: Cidofovir (nephrotoxic; use with caution) or fluoroquinolones (limited evidence) - Monitor viral load with serum/urine PCR

**Prognosis:** ~50% progress to graft loss despite treatment; early detection improves outcomes.

### CMV Infection/Disease

**CMV viremia vs disease:** - **Viremia:** Positive blood culture/PCR without symptoms; may progress to disease - **Disease:** Viremia + end-organ involvement (colitis, esophagitis, retinitis, pneumonitis)

**Diagnosis:** PCR quantitative (viral load in blood); tissue biopsy with viral culture/histology.

**Treatment:** - **CMV viremia:** Valganciclovir 900 mg 2×/day until PCR negative - **CMV disease:** IV ganciclovir (organ involvement requires higher doses) or valganciclovir

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## Part 8: Long-Term Graft Function and Outcomes

### Determinants of Graft Longevity

| Factor | Impact | Modifiable |
|----|----|----|
| **HLA matching** | Each mismatch ~5% 5-yr loss | No (donor selection) |
| **Donor age** | Older donors → shorter graft lifespan | No |
| **Cold ischemia time** | \>24 hrs associated with slower function recovery | No (deceased donor timing) |
| **Recipient age** | Younger = longer lifespan available for graft | No |
| **Acute rejection** | Any ACR episode associated with worse long-term outcomes | Yes (optimize induction/maintenance) |
| **Serum creatinine trajectory** | Early GFR decline (\>10% first year) = poor prognosis | Yes (monitor CNI levels, BP, proteinuria) |
| **Proteinuria** | Proteinuria \>1 g/day associated with worse outcomes | Yes (RAAS blockade) |
| **Blood pressure control** | SBP \>130 associated with graft loss | Yes (antihypertensives) |
| **CNI minimization** | Long-term CNI toxicity; belatacept-based regimens may extend graft life | Yes (alternative induction/maintenance) |
| **Adherence to immunosuppression** | Nonadherence increases rejection and graft-loss risk | Yes (education, monitoring, psychosocial support) |

### Recurrent and De Novo Glomerulonephritis

**Recurrent GN:** Original disease recurring in transplanted kidney.

**Frequency:** 10–15% depending on primary disease.

**High-risk diseases:** - **IgA nephropathy:** 30–50% recurrence; 10% graft loss at 10 years - **Lupus nephritis:** 5–10% recurrence; often milder - **FSGS:** 20–40% recurrence (very high if primary form); can cause immediate graft dysfunction - **Membranoproliferative GN:** 20–30% recurrence

**De novo GN:** New glomerular disease in transplanted kidney (unrelated to original disease).

**Management:** - Monitor for proteinuria; repeat biopsy if rising Cr + proteinuria - Treat with RAAS blockade - Immunosuppression adjustment based on diagnosis

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## Part 9: Key Warnings

### Warning 1: Nonadherence Increases Graft-Loss Risk

Nonadherence to immunosuppression is associated with rejection and graft loss \[5\]. Assess medication access, adverse effects, regimen complexity, mental health and understanding without assuming a fixed proportion of graft failures or judging adherence from age alone. Build a practical support plan.

**Prevention:** Intensive patient education; psychosocial screening; simplified regimens when possible; consider directly-observed therapy if high-risk.

### Warning 2: Acute Rejection in First 3 Years Predicts Poor Long-Term Outcomes

Any acute rejection episode (ACR or AMR) associated with 2–3× higher risk of chronic rejection and graft loss. Modern approach emphasizes preventing rejection through adequate induction + maintenance immunosuppression.

### Warning 3: Calcineurin Inhibitor Nephrotoxicity Accelerates Chronic Graft Dysfunction

CNI-induced chronic nephropathy causes 30–50% GFR decline over 10 years. However, discontinuing CNI increases acute rejection risk. **Balance:** Monitor CNI levels; keep at lowest effective trough; consider switching to belatacept if CNI toxicity severe and HLA match good.

### Warning 4: Sensitized Recipients Require Special Strategies

PRA \>50%: Higher waiting time; longer time to compatible donor. Options: - **Desensitization:** For living-donor transplants (plasmapheresis + IVIG + rituximab) - **Paired kidney exchange:** Match with compatible donor pair - **Accepting higher-risk donor:** Older/lower-KDPI donor if waiting time prohibitive

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## Related Resources

- ← Back to Transplant Hub
- ← Back to Nephrology Hub
- Back to Medical Education Dashboard

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## References

\[1\] Hariharan S, McBride MA, Cherikh WS, et al. Post-transplant renal function in the first year predicts long-term kidney transplant survival. *Kidney Int*. 2002;62:311–318. [PubMed](https://pubmed.ncbi.nlm.nih.gov/12081593/)

Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant. 2009;9 Suppl 3:S1. [PubMed](https://pubmed.ncbi.nlm.nih.gov/19845597/)

\[3\] Meier-Kriesche HU, Schold JD, Kaplan B. Long-term renal allograft survival: have we made significant progress or is it time to rethink our analytic and therapeutic strategies? *Am J Transplant*. 2004;4(8):1289-1295. [DOI](https://doi.org/10.1111/j.1600-6143.2004.00515.x) \| [PubMed](https://pubmed.ncbi.nlm.nih.gov/15268730/)

\[4\] Loupy A, Haas M, Roufosse C, et al. The Banff 2019 Kidney Meeting Report (I): Updates on and clarification of criteria for T cell- and antibody-mediated rejection. *Am J Transplant*. 2020;20(9):2318-2331. [DOI](https://doi.org/10.1111/ajt.15898) \| [PubMed](https://pubmed.ncbi.nlm.nih.gov/32463180/)

\[5\] Butler JA, Roderick P, Mullee M, et al. Frequency and impact of nonadherence to immunosuppressants after renal transplantation: a systematic review. *Transplantation*. 2004. [PubMed PMID 15021846](https://pubmed.ncbi.nlm.nih.gov/15021846/)

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*Last updated: 2026-02-28* *Board-review quality curriculum for nephrology education.*


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