Urine Good Hands: ED Management of Renal Transplant Patients

CASE

History of Present Illness

71yo man with past medical history of hypertension and ESRD status post kidney transplant 9 days ago
Presented to the emergency department (ED) with abdominal swelling and tightness with associated shortness of breath.
Recently discharged from the hospital with a JP drain two days prior with no fluid changes in color, consistency, or volume.
Producing urine with no frank blood, bowel movements are regular, and he has no problems eating.

Physical Exam

Vital signs were significant for a blood pressure of 147/73 and a respiratory rate of 22.
Abdomen is diffusely distended but soft and only tender at the incision site and JP drain. The drain has 25mLs of serosanguinous fluid.

Labs

CBC was significant for hemoglobin of 6.8 (down trending from 9.8 day of transplant).
CMP was significant for a creatinine of 2.8 (down trending from 4.5 2 days prior).
Lactate was within normal limits. Urine analysis was clean.

Imaging

Chest X-ray - mild ill-defined opacities within the right lung base concerning for infectious process, however, superimposed mild edema could not be excluded.
Post void bladder scan - 4ml of urine remaining in the bladder.
Erect abdominal X-ray - no dilated air-filled loops of bowel.
US/vasculature study - right lower quadrant transplant with patent vasculature and a new 1.6cm perinephric hematoma on the lower pole.

Clinical Question: What are some provider considerations in patients presenting to the ED status post renal transplant?

SUMMARY OF EVIDENCE

Introduction

There are numerous reasons why renal transplant patients present in the ED. Most renal issues typically manifest with an increase in creatinine levels. A systematic approach must be taken to build differential diagnoses for renal parenchymal dysfunction. Anything that can impact the native kidney, from prerenal to post renal causes, can also impact the transplanted kidney. The only unique cause of renal failure in renal transplant patients is rejection. Early complications of renal transplants have been significantly reduced by improved surgical technique and the creation of potent immunosuppressive drugs. However, the same immunosuppressive properties of these drugs also increase the risk of developing malignancies and infectious diseases. Additionally, these drugs can also be toxic to the kidney. Three critical transplant specific considerations are rejection, infection, and nephrotoxicity of medications.[1]

Rejection

Hyperacute allograft rejection is caused by preformed antibodies directed against the donor tissue. The onset is immediate and usually presents while still in surgery.

Acute allograft rejection can present from weeks to months after surgery and can only be differentiated through biopsy. They are classified as T cell-mediated acute cellular rejection (ACR) and antibody-mediated acute humoral rejection (AHR). Symptoms to look for include:

● Oliguria and anuria

● Fevers

● Hypertension

● Flank tenderness

● Lethargy

● Fluid retention

● Increased BUN, creatinine, and potassium levels

Chronic allograft rejection will most likely manifest months to years after surgery Biopsy will show with histological findings of interstitial fibrosis and tubular atrophy. Patients that develop ACR have a high likelihood of developing chronic allograft rejection. Chronic rejection typically does not manifest with fever and flank tenderness. Some distinct symptoms to look for include:

● Oliguria

● Nausea and vomiting

● Uremia

● Imbalances in electrolytes

● Proteinuria

● Increased BUN, creatinine, and potassium levels

● Fluid retention

Infection

The most common causes of infection in the first month following transplantation are transplant procedures, catheters, and intubation. The management of these infections are no different from any other immunosuppressed patient.

The infections that can develop between the 1st and 6th month following transplantation are separated into two groups:

Immunomodulator-related viral infections (CMV, Hepatitis B and C, BK polyomavirus, HHV 6, and EBV) and
Opportunistic infections (pneumocystis, listeria, and fungal species).[2]

Infections developing six months and beyond after transplantation are separated into 3 groups:

The first group consists of healthy transplant patients who have not developed any immunomodulator-related viral infections. This group has a slightly elevated sensitivity to community acquired infections.[2]
The second group consists of patients with progressive disease processes caused by immunomodulator-related viral infections and long-term immunosuppression. In these patients, you may see recurrent hepatitis, reactivation of latent VZV or HSV, or primary varicella infection among others.[2]
The third group consists of patients with chronic rejection who need aggressive immunotherapy to save the allograft. These patients are at risk for life-threatening fungal and parasitic disease like candidiasis, aspergillosis, and strongyloidiasis.[2]

Nephrotoxicity of Medications

Calcineurin Inhibitors (CNI), Cyclosporine (Sandimmune) and Tacrolimus (Prograf), are well known to be nephrotoxic with both functional and structural effects. The toxicity is dose dependent. If serum creatinine levels do not improve with reduction of the dose, a renal allograft biopsy is indicated.

Many drugs interact with the calcineurin inhibitors. Mechanisms of action include:

Inhibition of CYP-450 enzyme system increasing the levels of nephrotoxic drugs in the blood and
Synergistic nephrotoxicity of immunosuppressive therapy and co-administered drugs.[5]

Acute CNI nephrotoxicity

Commonly manifests as an acute but typically reversible kidney function impairment.
May be difficult to differentiate from acute rejection as they present with
- Acute increase of creatinine
The presence of rejection does not exclude concomitant CNI toxicity[6]

Chronic CNI nephrotoxicity

Manifests as progressive deterioration of kidney function that is irreversible.[6]
May be difficult to differentiate from chronic rejection as they both present with
- Hemodynamic changes
- Toxic effects on renal tubular epithelial cells and glomerulus

RESOLUTION

The patient was given a unit of blood to increase his hemoglobin level with a goal of 7.0.
Cyclosporine levels were ordered, and the patient was admitted to the Transplant surgery service for observation.
The patient’s abdominal distention was attributed to post-surgical edema. The transplant team noted that edema is common in transplant recipients up to 2 weeks after transplant.

REFERENCES

Emergency Care Institute (ECI). (2020, December 3). Renal Transplant Patients in the ED. Emergency Care Institute (ECI). Retrieved September 7, 2022, from https://aci.health.nsw.gov.au/networks/eci/clinical/clinical-tools/renal/renal-transplant-patients-in-the-ed
Ergin, M., Dal, U., Granit, D., Aslay, S., & Selhanoglu, M. (2015). Management of renal transplant patients in the emergency department. Journal of Academic Emergency Medicine, 14(2), 83–87. https://doi.org/10.5152/jaem.2015.01033
Hardinger, K. (2022). Cyclosporine and tacrolimus nephrotoxicity. UpToDate. Retrieved September 21, 2022, from https://www.uptodate.com/contents/cyclosporine-and-tacrolimus-nephrotoxicity#!
Quaglia, M., Merlotti, G., Guglielmetti, G., Castellano, G., & Cantaluppi, V. (2020). Recent advances on biomarkers of early and late kidney graft dysfunction. International Journal of Molecular Sciences, 21(15), 5404. https://doi.org/10.3390/ijms21155404
Venkat, K. K., & Venkat, A. (2004). Care of the renal transplant recipient in the emergency department. Annals of Emergency Medicine, 44(4), 330–341. https://doi.org/10.1016/j.annemergmed.2004.05.019
Zhong, D., & Liang, S. Y. (2018). Approach to transplant infectious diseases in the emergency department. Emergency Medicine Clinics of North America, 36(4), 811–822. https://doi.org/10.1016/j.emc.2018.06.010