Management of patients with a failed kidney transplant: Dialysis reinitiation, immunosuppression weaning, and transplantectomy

Table 1 Continuation of immunosuppression after a failed transplant

Potential beneficial effects	Potential adverse effects
Preservation of residual kidney function	Metabolic complications (diabetes, hypertension, dyslipidemia)
Decreased incidence of graft intolerance syndrome and the need for allograft nephrectomy	Steroid-associated adverse effects (e.g., diabetes, cataracts, myopathy, and avascular necrosis among others)
Minimization of allosensitization	Cardiovascular complications
Avoidance of overt acute rejection	Increased susceptibility to infection
Prevention of adrenal insufficiency syndrome	Malignancy (especially skin cancers, Kaposi’s sarcoma, non-Hodgkin’s lymphoma, and lip cancers)
Prevention of reactivation of systemic disease (e.g., systemic lupus erythematosus, vasculitis)	Costs (particularly when data supporting continued immunosuppression are lacking)

Table 2 Categorization of cancers in the end-stage kidney disease population

ESKD-related	Kidney
	Urinary tract
	Thyroid
	Myeloma
Immune-deficiency related	Hodgkin’s lymphoma
	Non-Hodgkin’s lymphoma
	Leukemia
	Melanoma of skin
	Kaposi’s sarcoma
	Carcinoma of
	Lip
	Mouth, tongue, tonsil, oropharynx
	Esophagus
	Stomach
	Anus
	Liver
	Larynx
	Lung
	Cervix, uteri, vagina, vulva
	Penis
	Eye, squamous cell carcinoma only
Not-related to	Rectum
immune deficiency	Breast
	Ovary
	Prostate
Of uncertain status	All other cancers

ESKD: End-stage kidney disease.

Table 3 Transplantectomy: Potential risks and benefits and impact on a repeat transplant

	Comments
Potential benefits
A failing graft is a focus of a chronic inflammatory state
May reduce mortality rates	Variable results, further studies are needed
Potential adverse effects
Residual kidney function may allow less stringent fluid restriction
Surgery-related morbidity and mortality	Morbidity 17%-60% in most series reported
	Mortality 1.5%-14% in most series reported
Allosensitization and the potential for future prolonged wait-times for a compatible crossmatch kidney
Impact on a repeat transplant
Mixed reports due to potential confounding factors
Differences among studies in:
Immunosuppression withdrawal protocols
Recipient and donor demographics
Era of transplantation
Indications for transplantectomy
Time on dialysis prior to a repeat transplant
Causes of prior graft loss
Allosensitization associated with blood transfusion
Pre-existing DSA with or without complement-fixing DSA (see text)
HLA matching of subsequent graft
Donor type (living vs deceased)
Others

DSA: Donor-specific antibody.

Table 4 Suggested immunosuppression withdrawal protocols based on maintenance therapy

CNI + antimetabolitea + prednisone	CNI + mTOR inh + prednisone	mTOR inh + prednisone
Discontinue antimetabolite at initiation of dialysis	Discontinue mTOR inh at initiation of dialysis	Taper mTOR inh over 4-6 wkb
Taper CNI over	Taper CNI over	Maintain same steroid dose at initiation of dialysis x 2-4 wk, then taper by 1 mg/mo (starting from 5 mg daily) until off
4-6 wkb	4-6 wkb
Maintain same steroid dose at initiation of dialysis x 2-4 wk, then taper by 1 mg/mo (starting from 5 mg daily) until off	Maintain same steroid dose at initiation of dialysis x 2-4 wk, then taper by 1 mg/mo (starting from 5 mg daily) until off

^aMycophenolate Mofetil (Cellcept^®) or Mycophenolic Acid (Myfortic^®) or Azathioprine (Imuran^®);

^bTaper can be done over a shorter period in slow chronic progressive graft failure but over a longer period when graft failure occurred following recent acute rejection episodes. CNI: Calcineurin inhibitor; mTOR inh: Mammalian target of rapamycin inhibitor.

Table 5 Absolute and relative indications for transplantectomy

Absolute indications (commonly accepted)	Relative indications (controversial)
Primary nonfunction Hyperacute rejection Early recalcitrant acute rejection Early graft loss (generally defined as graft loss within the first year) Arterial or venous thrombosis Graft intolerance syndrome Recurrent urinary tract infections or sepsis/urosepsis Multiple retained failed transplants prior to a repeat transplant	The presence of hematologic or biochemical markers of the chronic inflammatory state Erythropoietin resistance anemia Elevated ferritin level Elevated C reactive protein Elevated erythrocyte sedimentation rate Low prealbumin/albumin Graft loss due to BK nephropathy and high level BK viremia (see text)