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Kidney transplantation in adults: Evaluation and diagnosis of acute kidney allograft dysfunction

Kidney transplantation in adults: Evaluation and diagnosis of acute kidney allograft dysfunction
Literature review current through: Sep 2023.
This topic last updated: Nov 05, 2021.

INTRODUCTION — One of the most common complications of kidney transplantation is allograft dysfunction, which in some cases leads to graft loss. Prompt recognition and evaluation of allograft dysfunction is vital as it is usually reversible. Persistent dysfunction without timely intervention may lead to irreversible loss of allograft function and, eventually, allograft failure.

The causes of kidney allograft dysfunction vary with the time (usually classified as immediate, early, and late period) after transplantation.

This topic will provide an overview of the evaluation and diagnosis of acute kidney allograft dysfunction among patients who have undergone kidney transplantation. The classification, diagnosis, and treatment of acute kidney allograft rejection, chronic allograft nephropathy (CAN), and BK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN) are discussed in more detail elsewhere:

(See "Kidney transplantation in adults: Clinical features and diagnosis of acute kidney allograft rejection".)

(See "Kidney transplantation in adults: Treatment of acute T cell-mediated (cellular) rejection".)

(See "Kidney transplantation in adults: Prevention and treatment of antibody-mediated rejection".)

(See "Kidney transplantation in adults: Chronic allograft nephropathy".)

(See "Kidney transplantation in adults: BK polyomavirus-associated nephropathy".)

DEFINITIONS

Acute allograft dysfunction – There is no consensus definition for acute allograft dysfunction following kidney transplantation. We define acute kidney allograft dysfunction as one or more of the following:

An increase in serum creatinine of ≥25 percent from baseline within a one-to-three-month time period

Failure of the serum creatinine to decrease following transplantation

Proteinuria >1 g/day

Chronic allograft dysfunction – Chronic kidney allograft dysfunction is characterized clinically by a slow, progressive loss of kidney function, frequently associated with hypertension and varying degrees of proteinuria.

Delayed graft function – Delayed graft function (DGF) is most commonly defined as the need for at least one dialysis treatment within the first week after transplantation. It has also been variably defined as low or absent urine output immediately after kidney transplantation or failure of the serum creatinine to decline by more than 25 percent within 24 hours of transplant surgery. None of these definitions are perfect, as some patients with "slow graft function" avoid the need for dialysis, while others need dialysis for the management of refractory hyperkalemia or pulmonary edema early posttransplantation despite having prompt urine output.

EVALUATION OF ACUTE ALLOGRAFT DYSFUNCTION — Our approach to the evaluation and diagnosis of acute kidney allograft dysfunction depends upon the timing of presentation. A diagnosis can be established in most patients by means of thorough history and physical examination, laboratory and imaging studies, and/or a kidney allograft biopsy.

Allograft dysfunction immediately (<1 week) posttransplantation — Patients who develop acute kidney allograft dysfunction within the first week posttransplantation most commonly present with low urine output or failure of the serum creatinine to decrease after transplantation. Some patients may require dialysis in the first week after transplantation. Such patients are considered to have delayed graft function (DGF). (See 'Definitions' above.)

An understanding of the patient's daily urine output prior to transplantation is important when interpreting urine output in the immediate posttransplant setting. Patients who were previously on dialysis may have low or no daily urine output at baseline, and therefore, urine output after transplantation will continue to be low or fail to increase in those with allograft dysfunction. By contrast, patients who receive a kidney transplant before initiating dialysis are likely to have higher (and even normal) daily urine output at baseline. In such patients with urine output from their native kidneys, allograft dysfunction is more likely to manifest as failure of the serum creatinine to decrease posttransplantation. However, a significant increase in urine output after transplantation is expected among patients with normal urine output pretransplantation; failure of this to occur may also be an indication of allograft dysfunction.

In patients who present with low urine output or failure of the serum creatinine to decrease after transplantation, prompt evaluation and diagnosis of the cause of allograft dysfunction is critical since certain causes of acute allograft dysfunction (such as vascular thrombosis) in the immediate postoperative setting are associated with a high risk of allograft loss. Vascular etiologies of allograft dysfunction within the first week represent a transplant emergency, and it is critical to establish that there is adequate blood flow to the transplanted kidney. Our initial approach is as follows:

We first obtain a history and perform a physical examination to assess for fluid balance, blood loss, or intraoperative hypotension.

We next determine if the Foley catheter is obstructed by visual inspection and irrigation or by replacing the catheter.

We administer a 500 mL bolus of isotonic saline as a fluid challenge and give one to two doses of intravenous (IV) furosemide to try to increase urine output. We typically give 100 mg of furosemide to recipients of a deceased-donor transplant and 20 mg to recipients of a living-donor transplant. The risk of acute tubular necrosis (ATN) is much higher in deceased-donor kidneys versus living-donor kidneys, and therefore, recipients of deceased-donor transplants may need a higher dose of furosemide for response. In patients with hypervolemia, we give IV furosemide without a fluid challenge.

We test for the presence and strength/titer of donor-specific anti-HLA antibodies (DSAs).

We obtain a kidney ultrasound with Doppler and a radionuclide renal scan to rule out obstruction, vascular thrombosis, and a urinary leak. However, some clinicians prefer to obtain only a kidney ultrasound without a radionuclide renal scan and measure fluid creatinine levels from an indwelling surgical drain or from fluid collections that may be seen with an ultrasound. (See 'Fluid collections' below.)

Our subsequent approach is as follows:

In patients who are found to have an abnormality on either kidney ultrasound or renal scan that likely explains the allograft dysfunction (eg, vascular thrombosis, urinary leak, or obstruction), we treat with the appropriate therapy (eg, surgical exploration for arterial or venous thrombosis or urinary leak) and monitor serum creatinine levels and urine output. If the serum creatinine and urine output improve, we resume routine monitoring of the patient. If the serum creatinine and urine output fail to improve despite initial successful therapy of the abnormality, we obtain a kidney allograft biopsy.

In patients who have no abnormalities on either kidney ultrasound or renal scan and have no evidence of new or increasing strength/titer DSAs, the most likely cause of allograft dysfunction is postischemic ATN. A biopsy may still be obtained immediately depending upon the clinical scenario (especially in highly sensitized patients or those with preformed DSA) and prebiopsy probability of identifying an unexpected cause of dysfunction. In most patients, we monitor serum creatinine levels and urine output daily for up to one week. If the serum creatinine and urine output fail to improve after one week, we obtain a kidney allograft biopsy, although some clinicians choose to repeat a renal scan and kidney ultrasound prior to obtaining a kidney biopsy. A kidney biopsy is required to evaluate for acute rejection and other possible etiologies of allograft dysfunction, including early recurrent disease (eg, focal segmental glomerulosclerosis [FSGS]), oxalate deposition, and thrombotic microangiopathy. In addition to a biopsy, clinicians may be testing for the presence of non-human leukocyte antigen (HLA) antibodies (such as anti-angiotensin II type 1 receptor (AT1R) or antiendothelial antibodies), if available.

In patients who have no abnormalities on either kidney ultrasound or renal scan and are found to have a new or increasing strength/titer DSA, we obtain a kidney allograft biopsy immediately to evaluate for active antibody-mediated rejection (ABMR).

Allograft dysfunction >1 week posttransplantation

Patients presenting with an elevated serum creatinine — In kidney transplant recipients who present after the first week posttransplantation with a new increase in serum creatinine of ≥25 percent from baseline or a serum creatinine that is higher than expected (such as in recently transplanted patients whose serum creatinine is continuing to decrease after transplantation), we perform the following initial evaluation (algorithm 1):

Assessment for fever and/or abdominal symptoms and signs (eg, abdominal pain or discomfort, graft tenderness, drainage at the site of the surgical wound).

Assessment of volume status.

Assessment of medication history, including adherence, recently added medications (eg, angiotensin-converting enzyme [ACE] inhibitors, angiotensin receptor blockers [ARBs], nondihydropyridine calcium channel blockers, azole antifungal agents), and recent changes in medication dosing.

Assessment of dietary habits, such as drinking grapefruit juice. (See "Pharmacology of cyclosporine and tacrolimus", section on 'Food and drug interactions'.)

Measurement of blood tacrolimus (or cyclosporine) concentration (if not already completed).

Assessment for the presence and strength/titer of DSAs. (See 'Acute rejection' below.)

Measurement of plasma donor-derived cell-free DNA (dd-cfDNA) level, a biomarker for the detection of acute allograft rejection. However, practice may vary at other transplant centers. Some centers do not yet routinely measure plasma dd-cfDNA levels, while other centers do not begin checking plasma dd-cfDNA levels until after one month posttransplantation. (See "Kidney transplantation in adults: Clinical features and diagnosis of acute kidney allograft rejection".)

Measurement of blood BK polyomavirus (BKPyV) and cytomegalovirus (CMV) viral loads. (See 'Viral infections' below.)

Assessment of characteristics of the donor (eg, cause of death [for deceased donors], age, history of hypertension, history of tobacco use) and the donor kidney (eg, estimated glomerular filtration rate [eGFR] at the time of recovering the kidney, kidney weight, kidney donor profile index [KDPI], kidney biopsy findings). (See "Kidney transplantation in adults: Risk factors for graft failure", section on 'Type of kidney'.)

Assessment of the function of the "mate kidney" (ie, the contralateral kidney of the deceased donor, if also recovered for transplant) and comparison with that of the recipient with allograft dysfunction.

Based upon this initial evaluation, our subsequent approach is as follows:

In patients who have fever, abdominal pain, or graft tenderness, we evaluate for pyelonephritis and treat with antibiotics if evidence of infection is present. We repeat serum creatinine upon completion of antibiotic treatment. (See "Urinary tract infection in kidney transplant recipients".)

In patients with a history and/or physical findings consistent with hypovolemia, we increase oral hydration and repeat serum creatinine in one day. If the patient has symptoms and/or signs suggestive of more severe hypovolemia (eg, orthostasis) or is unable to tolerate an increase in oral fluids (eg, due to nausea and vomiting), we administer a 500 to 1000 mL bolus of IV isotonic saline.

In patients with a history of recently added medications or changes in medication dosing, we discontinue potential offending agents and repeat serum creatinine in two to three days.

In patients with a blood tacrolimus (or cyclosporine) concentration above the therapeutic range, we reduce the dose of the calcineurin inhibitor and repeat the serum creatinine and blood tacrolimus (or cyclosporine) concentration in two to three days. If the serum creatinine remains persistently elevated and the blood tacrolimus (or cyclosporine) concentration is still above the therapeutic range, we further reduce the dose of the calcineurin inhibitor and repeat the serum creatinine and blood tacrolimus (or cyclosporine) concentration in another two to three days. It should be noted that calcineurin inhibitor toxicity may occur at blood concentrations that are within the target range. (See 'Calcineurin inhibitor nephrotoxicity' below.)

In patients with a de novo DSA or patients with a preexisting DSA before transplantation who develop a significant rise in DSA titer, we perform a kidney allograft biopsy to evaluate for ABMR. (See "Kidney transplantation in adults: Prevention and treatment of antibody-mediated rejection", section on 'Patients with de novo DSA after transplant'.)

In patients with a plasma dd-cfDNA level >1 percent or a rising trend in serial dd-cfDNA measurements, we perform a kidney allograft biopsy to evaluate for acute rejection. (See "Kidney transplantation in adults: Clinical features and diagnosis of acute kidney allograft rejection".)

In patients with a plasma BKPyV viral load ≥10,000 copies/mL, a presumptive diagnosis of BKPyV-associated nephropathy (BKPyVAN) is frequently made if no other causes of allograft dysfunction are identified. We generally reduce immunosuppression and monitor viral loads every two to four weeks thereafter, when the clinical picture suggests that BKPyVAN is the most likely cause. However, if the cause of allograft dysfunction is uncertain or kidney function impairment and/or viremia fail to resolve despite reducing immunosuppression, we perform a kidney allograft biopsy. (See "Kidney transplantation in adults: BK polyomavirus-associated nephropathy", section on 'Screening and diagnosis' and "Kidney transplantation in adults: BK polyomavirus-associated nephropathy", section on 'Treatment'.)

In patients who do not have an identifiable potential cause for kidney allograft dysfunction (eg, pyelonephritis, hypovolemia, nephrotoxic medications, calcineurin inhibitor nephrotoxicity, BKPyVAN) or whose serum creatinine does not return to baseline after treatment and resolution of these potential causes of allograft dysfunction, we obtain a kidney allograft ultrasound with Doppler to evaluate for perinephric fluid collections (eg, lymphocele, urinary leak [urinoma], perinephric hematoma), urinary obstruction, or transplant renal artery stenosis. (See 'Fluid collections' below and 'Urinary obstruction' below and 'Transplant renal artery stenosis' below.)

If the ultrasound reveals an abnormality (eg, hydronephrosis, a fluid collection, or Doppler evidence of transplant renal artery stenosis) that could explain the elevation in serum creatinine, then we treat with the appropriate therapy (eg, retrograde or percutaneous placement of a nephroureteral stent, drainage and evaluation of fluid collection, angioplasty of transplant renal artery stenosis) and repeat measurements of the serum creatinine level. If the serum creatinine remains persistently elevated despite initial successful therapy of the abnormality detected by ultrasound, we obtain a kidney allograft biopsy.

If the ultrasound is negative for obstruction or other causality, we perform a kidney allograft biopsy.

Patients presenting with proteinuria — Proteinuria in transplant recipients may originate from either the native kidneys or the allograft. Proteinuria derived from native kidneys generally dissipates over time posttransplantation as the end-stage kidneys undergo progressive sclerosis. New or increasing proteinuria greater than 1 g/day after transplantation is indicative of allograft dysfunction [1-5]. The differential diagnosis for proteinuria after kidney transplantation includes recurrent glomerular disease, ABMR, chronic allograft nephropathy (CAN), and de novo glomerulopathies. We generally perform a kidney allograft biopsy in all kidney transplant recipients who present with proteinuria greater than 1 g/day, regardless of the serum creatinine concentration, if not otherwise contraindicated.

CAUSES OF ACUTE ALLOGRAFT DYSFUNCTION — The differential diagnosis of acute kidney allograft dysfunction changes with the time of presentation after transplantation. Certain causes of acute allograft dysfunction (such as surgical complications) are more common in the immediate-to-early posttransplantation period, whereas other causes (such as viral infections) are more likely to present later. However, there is some overlap among the times of presentation, and some causes of acute allograft dysfunction (such as acute rejection) may present at any time posttransplantation.

Immediate (<1 week) posttransplantation — The principal underlying causes of acute kidney allograft dysfunction immediately following transplant surgery are discussed below.

Postischemic acute tubular necrosis — Postischemic acute tubular necrosis (ATN) or reperfusion injury is the most common cause of delayed graft function (DGF) (picture 1). The reason for the distinction between ATN and reperfusion injury is that classic signs of ATN, such as denuded tubules with mitotic figures, are often absent on early posttransplantation biopsies. The incidence of this complication increases with:

Longer cold ischemia time [6]. (See "Kidney transplantation in adults: Risk factors for graft failure".)

Prior sensitization in retransplanted patients, indicating that, in some cases, DGF may be mediated by immunologic injury.

The type of dialysis performed immediately prior to transplantation. (See "Kidney transplantation in adults: Timing of transplantation and issues related to dialysis".)

The quality of the donor (ie, whether the donor was older or had a history of hypertension, suggesting that a higher perfusion pressure may be needed) may also contribute to early or late kidney allograft dysfunction.

Additional factors that may enhance the risk of ATN include preservation of the allograft in Euro-Collins solution, severe vascular disease in the donor and recipient, administration of mammalian (mechanistic) target of rapamycin (mTOR) inhibitors (sirolimus or everolimus), and possibly laparoscopic donor nephrectomy [7-12] (see "Kidney transplantation in adults: Benefits and complications of minimally invasive live-donor nephrectomy" and "Pharmacology of mammalian (mechanistic) target of rapamycin (mTOR) inhibitors"). Use of dopamine or pump perfusion in donor management may also reduce the incidence of early allograft dysfunction [13,14].

Hyperacute rejection — Hyperacute rejection is caused by preformed donor-specific anti-HLA antibodies (DSAs), such as ABO isoagglutinins, anti-human leukocyte antigen (HLA) antibodies, and rarely, antiendothelial antibodies, that lead to immediate and uncontrollable allograft failure.

The diagnosis of hyperacute rejection is usually made by the surgeon in the operating room as the pink kidney becomes mottled and cyanotic. There is little or no urine output and no renal blood flow as detected by renal scan or duplex Doppler studies. Kidney biopsy shows intrarenal coagulopathy, with thrombi occluding the small arteries and glomeruli, and renal cortical necrosis (picture 2A-D). It can be largely prevented by testing recipients for the presence of preformed, cytotoxic antibodies that react with donor cells (crossmatch test) prior to transplantation. In nonsensitized patients with a negative cytotoxicity crossmatch, hyperacute antibody-mediated rejection (ABMR) is rare. However, the use of "virtual crossmatches" based upon an arbitrary anti-HLA antibody level tested on historic sera may increase the likelihood of hyperacute or accelerated acute rejection (rejection within the first week), particularly if the patient experienced a sensitizing event in the interim [15-17].

Volume depletion — Vasodilatation from anesthesia with or without cytokine release from induction agents such as antilymphocyte agents (eg, antithymocyte globulin, alemtuzumab) predispose to fluid extravasation and intravascular volume depletion. Given this "third-spacing" associated with anesthesia, it is customary that the patient receives 3 to 5 liters of intravenous (IV) fluid intraoperatively to maintain sufficient intravascular volume repletion. A common mistake is not to recognize this phenomenon and limit fluid resuscitation. The central venous pressure (if measured) should therefore be maintained at the higher levels of normal (7 to 11 mmHg), with adequate oxygenation-oxygen saturation >90 percent. Transient (<10 minutes) hypotension with systolic blood pressures of <90 mmHg is common and should only contribute to ATN if the kidney is accustomed to seeing higher blood pressures or the patient has atherosclerosis requiring higher perfusion pressures.

Surgical complications

Vascular thrombosis — Thrombosis may arise with or without rejection (secondary and primary thrombosis, respectively) [18-21]. Primary thrombosis of the allograft is an uncommon event, occurring in 0.5 to 6 percent in most series, which usually leads to loss of the graft [22]. One series of 558 consecutive deceased-donor kidney transplants found that primary thrombosis occurred in 34 patients and was responsible for nearly 45 percent of early graft loss (defined as <90 days posttransplantation) [22].

Thrombosis may result from technical problems, including intimal dissection or kinking of the artery, or angulation or kinking of the vein [21]. Additional risk factors or causes for thrombosis may vary with the vessel involved [21].

Arterial thrombosis of the allograft may result from hypotension, hyperacute or unresponsive acute rejection, a hypercoagulable state, multiple renal arteries, and unidentified intimal flaps. Venous thrombosis of the allograft may result from a hypercoagulable state, hematomas or lymphoceles causing compression, anastomotic stenosis, and extension of a deep venous thrombosis.

As observed in children with congenital nephrotic syndrome, adults with massive proteinuria may also be at increased risk for thrombosis. In this setting, prophylactic native nephrectomy reduces the risk of posttransplant vascular thrombosis.

Another specific risk factor for thrombosis is the presence of antibodies directed against either phospholipids or plasma proteins bound to anionic phospholipids [18]. Thus, patients with lupus nephritis, antiphospholipid antibodies, and a history of thromboembolic events, as well as those with the antiphospholipid syndrome, may benefit from continued anticoagulation after kidney transplantation. If untreated, these patients appear to be at risk for both intrarenal and systemic clotting events. (See "Antiphospholipid syndrome and the kidney".)

Whether inherited thrombophilias predispose to kidney allograft thrombosis has not been well studied [23]. At least two inherited thrombophilias, a prothrombin gene mutation and heterozygosity for the factor V Leiden mutation, may increase the risk of this complication [18,24,25]. (See "Prothrombin G20210A".)

Very limited evidence suggests that the prophylactic administration of low-dose aspirin (75 mg/day for one month posttransplantation) may help prevent renal vein thrombosis. In a retrospective, single-center study, the use of such a regimen decreased the incidence of renal thrombosis from 5.6 to 1.2 percent in all transplant recipients [26]. Whether such therapy has a role in this setting requires further study.

Fluid collections — Fluid collections that can occur after transplantation and cause acute kidney allograft dysfunction include lymphoceles, urinary leaks (urinomas), and perinephric hematomas:

Lymphocele – A lymphocele is a fluid collection resulting from the disruption of lymphatics in the recipient or leaking lymph from the donor kidney that accumulates to form a cystic lesion composed mainly of lymphocytes. Small lymphoceles (containing <100 mL of lymph fluid) are typically asymptomatic and frequently resolve spontaneously without intervention. Larger lymphoceles can present from one week to six months posttransplantation with symptoms related to the compression of the adjacent allograft and bladder. The diagnosis is usually made by kidney ultrasound and can be confirmed by assessing the cell count and differential from the fluid aspirate. Lymphoceles occur in up to 26 percent of kidney transplant recipients and, if they are persistent, recurrent, or symptomatic, are most effectively treated with laparoscopic or open surgery [27].

Urinary leak (urinoma) – A urinary leak (urinoma) from the transplanted kidney typically presents in the first few weeks posttransplantation with abdominal pain, decreased urine output, and an increased serum creatinine. Patients generally appear ill, with fever and allograft or abdominal tenderness. The source of the urinary leak is usually the site of the ureteroneocystostomy; possible causes include ischemic necrosis of the distal ureter and surgical trauma. Urinary leaks can collect around the allograft as urinomas, which can be detected by a kidney ultrasound or radionuclide renal scan. The diagnosis can also be established by measuring the creatinine concentration from fluid aspirated from a urinoma or sampled from a surgical drain; the concentration of creatinine in the fluid will be much higher than the serum creatinine, reflecting levels one would expect to find in the urine.

Perinephric hematoma – Most hematomas in the immediate posttransplantation period are small and do not require intervention. However, some hematomas may progressively expand within the retroperitoneal space and compress the allograft, ureter, and vascular supply, resulting in acute allograft dysfunction. The risk of hematoma is greater among patients who are receiving anticoagulation, particularly those treated with IV heparin [28]. Surgical evacuation of the hematoma is generally performed to improve allograft function and prevent concurrent infection.

Multiple renal arteries — Sometimes, when the donor kidney has multiple renal arteries, reconstruction using conjoined anastomotic technique is performed on equal-sized arteries and end-to-side anastomosis of smaller arteries to larger arteries. The small polar vessels are simply ligated [29]. This may lead to infarction of the polar region of the kidney. In rare instances, ligation of the lower polar artery might cause necrosis of the transplanted ureter, resulting in obstruction or urine leak.

Atheroemboli — Atheroemboli (also called cholesterol crystal emboli) are a rare cause of acute allograft dysfunction. Although atheroemboli can occur in the immediate posttransplantation setting, they can cause kidney allograft dysfunction at any time after transplantation. The source of atheroemboli could be either the recipient's native vascular tree or the donor's aorta [30,31]. A donor source may result in a greater atheromatous load and little likelihood of recovering a significant degree of kidney function [31]. (See "Clinical presentation, evaluation, and treatment of renal atheroemboli".)

Calcium oxalate — Calcium oxalate deposits within the kidney allograft parenchyma can occur with primary or secondary oxalosis and cause acute irreversible kidney injury. The treatment in those patients with primary oxalosis is a combined liver-kidney transplant. Crystalline deposition and ATN may occur in patients with uncontrolled secondary hyperparathyroidism [32]. Secondary oxalosis is common in patients after any bariatric surgery, a history of Crohn disease, or cystic fibrosis [33-35].

(See "Primary hyperoxaluria", section on 'Kidney manifestations' and "Primary hyperoxaluria", section on 'Management' and "Primary hyperoxaluria", section on 'Effects of oxalate deposition'.)

(See "Primary hyperoxaluria", section on 'Kidney manifestations'.)

(See "Primary hyperoxaluria", section on 'Management'.)

Attention to lowering pretransplant oxalate levels through the use of calcium-based phosphorus binders, which bind oxalate better than polystyrene-based binders, and hemodialysis, which clears oxalate better than peritoneal dialysis, is needed to control oxalate in patients with chronic kidney disease (CKD) or end-stage kidney disease (ESKD) [36-39].

Early (1 week to 3 months) and late (>3 months) posttransplantation — The differential diagnosis of acute kidney allograft dysfunction is substantially different in patients with initial graft function who then develop kidney function impairment. The major causes in this setting are discussed below.

Acute rejection — Acute rejection is one of the most common causes of allograft dysfunction in the early posttransplantation period, although the incidence of acute rejection has decreased significantly with contemporary immunosuppressive therapy. It typically manifests within the first 12 months after transplantation but can also occur late in patients who are nonadherent to their immunosuppression regimen. Acute rejection should be suspected among all transplant recipients who present with a creatinine that is increased above the patient's usual baseline, especially if they have associated symptoms such as fever, oliguria, and graft pain or tenderness. There are two principal histologic forms of acute rejection:

Acute T cell-mediated (cellular) rejection, which is characterized by infiltration of the allograft by lymphocytes and other inflammatory cells.

Active ABMR, the diagnosis of which requires morphologic evidence of acute tissue injury, circulating DSAs, and immunologic evidence of an antibody-mediated process (such as C4d deposition in the allograft). Cellular infiltrates may not be present.

The diagnosis and treatment of acute rejection are discussed elsewhere:

(See "Kidney transplantation in adults: Clinical features and diagnosis of acute kidney allograft rejection".)

(See "Kidney transplantation in adults: Treatment of acute T cell-mediated (cellular) rejection".)

(See "Kidney transplantation in adults: Prevention and treatment of antibody-mediated rejection".)

Calcineurin inhibitor nephrotoxicity — The calcineurin inhibitors tacrolimus and cyclosporine are used as part of a maintenance immunosuppression regimen in almost all kidney transplant recipients. While these agents are used to prevent acute rejection, they are associated with nephrotoxicity and are a common cause of acute and chronic allograft dysfunction. Calcineurin inhibitor nephrotoxicity can manifest as either acute azotemia, which typically occurs within the first three months posttransplantation and is largely reversible after reducing the dose, or as chronic progressive kidney disease, which generally occurs after three months posttransplantation and is usually irreversible. Other kidney effects of the calcineurin inhibitors include tubular dysfunction and, rarely, a thrombotic microangiopathy that can lead to acute graft loss. (See "Cyclosporine and tacrolimus nephrotoxicity" and 'Thrombotic microangiopathy' below.)

Thrombotic microangiopathy — Thrombotic microangiopathy in the kidney transplant recipient may be the result of recurrent disease (eg, in patients with a prior history of thrombotic thrombocytopenic purpura or complement-mediated thrombotic microangiopathy), calcineurin inhibitor nephrotoxicity, active ABMR, or a hypercoagulable disorder (such as antiphospholipid syndrome). In addition to acute allograft dysfunction, common clinical features include microangiopathic hemolytic anemia, thrombocytopenia, and increased lactate dehydrogenase levels. However, these hematologic abnormalities may be absent in some cases (ie, "renal-limited" thrombotic microangiopathy), and the diagnosis in these patients can only be established by kidney allograft biopsy. (See "Thrombotic microangiopathy after kidney transplantation" and "Drug-induced thrombotic microangiopathy (DITMA)", section on 'Immunosuppressive agents'.)

Recurrent primary disease — In patients whose primary kidney disease was glomerulonephritis, disease recurrence must be considered as a possible cause of allograft dysfunction. Recurrence rates vary depending upon the specific glomerular disease. Glomerular diseases that commonly recur posttransplantation include primary focal segmental glomerulosclerosis (FSGS), primary membranous nephropathy, membranoproliferative glomerulonephritis, complement-mediated thrombotic microangiopathy, and C3 glomerulopathy. Late recurrence (ie, more than one year posttransplantation) may be seen in many diseases, including FSGS, membranoproliferative glomerulonephritis, immunoglobulin A (IgA) nephropathy, and diabetic nephropathy [40,41]. Biopsy of the kidney allograft is required to establish or exclude a diagnosis.

(See "Kidney transplantation in adults: Focal segmental glomerulosclerosis in the transplanted kidney".)

(See "Membranoproliferative glomerulonephritis: Recurrence of idiopathic disease after transplantation".)

(See "Thrombotic microangiopathy after kidney transplantation".)

(See "C3 glomerulopathies: Recurrence after transplantation".)

Transplant renal artery stenosis — Transplant renal artery stenosis can present with an elevated serum creatinine, typically between three months and two years posttransplantation. It should be considered as a cause of kidney allograft dysfunction, especially among patients with concomitant hypertension or posttransplant erythrocytosis. (See "Hypertension after kidney transplantation", section on 'Evaluation for transplant renal artery stenosis'.)

Urinary obstruction — Urinary obstruction may be a result of urinary bladder dysfunction due to autonomic neuropathy or undiagnosed benign prostatic hyperplasia in older males. It may also occur from ureteral scarring (eg, due to ischemia or BK polyomavirus [BKPyV]) that leads to stenosis and/or ureteral kinking. Sometimes lymphoceles (collections of lymph fluid leakage from severed lymphatics that overlie the iliac vessels) may compress the allograft and cause dysfunction. (See "Clinical manifestations and diagnosis of urinary tract obstruction (UTO) and hydronephrosis".)

Viral infections — Viral infections, particularly with BKPyV and cytomegalovirus (CMV), can cause allograft dysfunction due to interstitial nephritis, glomerulopathy, or cytokine release. In addition, adenoviral infections of the kidney allograft are a rare cause of allograft dysfunction [42-44].

(See "Kidney transplantation in adults: BK polyomavirus-associated nephropathy".)

(See "Clinical manifestations, diagnosis, and management of cytomegalovirus disease in kidney transplant patients", section on 'Clinical manifestations'.)

De novo glomerular disease — Although glomerular diseases that occur in the transplanted kidney are frequently recurrences of the primary disease affecting the native kidneys (see 'Recurrent primary disease' above), de novo glomerular diseases that are unrelated to the original disease in the native kidneys may also occur. The clinical presentation and histologic features of these de novo diseases are generally similar to those observed in patients with primary or secondary glomerular diseases in the native kidneys [45]. These include an increase in serum creatinine, proteinuria, hematuria, and sometimes an active urinary sediment.

Less common causes

Retained ureteral stent – Urinary stents may increase the likelihood of urinary tract infection and BKPyV viremia or may become encrusted and lead to partial or complete obstruction [46-48].

Arteriovenous fistulas after kidney allograft biopsy – Arteriovenous malformations occur sometimes after kidney transplant biopsy but usually do not lead to clinical consequences. When they do, they can cause kidney allograft dysfunction, hypertension, persistent hematuria, and occasionally graft loss [49].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Kidney transplantation".)

SUMMARY AND RECOMMENDATIONS

General principles – One of the more common complications of kidney transplantation is allograft dysfunction, which in rare cases leads to graft loss. Prompt recognition and evaluation of allograft dysfunction is vital as it is usually reversible. Persistent dysfunction without timely intervention may lead to irreversible loss of allograft function and, eventually, allograft failure. The causes of kidney allograft dysfunction vary with the time (usually classified as immediate, early, and late period) after transplantation. (See 'Introduction' above.)

Definitions – There is no consensus definition for allograft dysfunction following kidney transplantation. We define acute kidney allograft dysfunction as one or more of the following: an increase in serum creatinine of ≥25 percent from baseline within a one-to-three-month time period, failure of the serum creatinine to decrease following transplantation, and/or proteinuria >1 g/day. Delayed graft function (DGF) is defined as the need for dialysis within the first week after transplantation. Chronic kidney allograft dysfunction is defined as a condition in which irreversible damage to the kidney allograft occurs over a period of weeks to months. (See 'Definitions' above.)

Evaluation – Our approach to the evaluation and diagnosis of acute kidney allograft dysfunction depends upon the timing of presentation. A diagnosis can be established in most patients by means of thorough history and physical examination, laboratory and imaging studies, and/or a kidney allograft biopsy. (See 'Evaluation of acute allograft dysfunction' above.)

Patients who develop kidney allograft dysfunction within the first week posttransplantation most commonly present with low urine output or failure of the serum creatinine to decrease after transplantation. Some patients (ie, those with DGF) may require dialysis in the first week after transplantation. Prompt evaluation and diagnosis of the cause of allograft dysfunction is critical since certain causes of acute allograft dysfunction (such as vascular thrombosis) in the immediate postoperative setting are associated with a high risk of allograft loss. Vascular etiologies of allograft dysfunction within the first week represent a transplant emergency, and it is critical to establish that there is adequate blood flow to the transplanted kidney. Our approach is discussed above. (See 'Allograft dysfunction immediately (<1 week) posttransplantation' above.)

In kidney transplant recipients who present after the first week posttransplantation with a new increase in serum creatinine of ≥25 percent from baseline or a serum creatinine that is higher than expected (such as in recently transplanted patients whose serum creatinine is continuing to decrease after transplantation), we perform an initial evaluation to assess for potentially reversible causes of kidney allograft dysfunction (eg, pyelonephritis, hypovolemia, nephrotoxic medications, calcineurin inhibitor nephrotoxicity) (algorithm 1). In patients who do not have an identifiable potential cause or whose serum creatinine does not return to baseline after treatment and resolution of these potential causes of allograft dysfunction, we obtain a kidney allograft ultrasound with Doppler to evaluate for perinephric fluid collections (eg, urinary leak [urinoma], perinephric hematoma), urinary obstruction, or transplant renal artery stenosis. (See 'Patients presenting with an elevated serum creatinine' above.)

-If the ultrasound reveals an abnormality that could explain the elevation in serum creatinine, then we treat with the appropriate therapy (eg, drainage and evaluation of fluid collection, angioplasty of transplant renal artery stenosis) and repeat measurements of the serum creatinine level. If the serum creatinine remains persistently elevated despite initial successful therapy of the abnormality detected by ultrasound, we obtain a kidney allograft biopsy.

-If the ultrasound is negative for obstruction or other causality, we perform a kidney allograft biopsy.

Proteinuria greater than 1 g/day after transplantation is an indication of allograft dysfunction. In the early posttransplantation setting, proteinuria may be a sign of recurrent or de novo focal segmental glomerulosclerosis (FSGS) that should prompt further evaluation. We generally perform a kidney allograft biopsy in all kidney transplant recipients who present with proteinuria greater than 1 g/day, regardless of the serum creatinine concentration, if not otherwise contraindicated. (See 'Patients presenting with proteinuria' above.)

Differential diagnosis – The differential diagnosis of acute kidney allograft dysfunction changes with the time of presentation after transplantation. Certain causes of acute allograft dysfunction (such as surgical complications) are more common in the immediate-to-early posttransplantation period, whereas other causes (such as viral infections) are more likely to present later. However, there is some overlap among the times of presentation, and some causes of acute allograft dysfunction (such as acute rejection) may present at any time posttransplantation. (See 'Causes of acute allograft dysfunction' above.)

  1. D'Cunha PT, Parasuraman R, Venkat KK. Rapid resolution of proteinuria of native kidney origin following live donor renal transplantation. Am J Transplant 2005; 5:351.
  2. Myslak M, Amer H, Morales P, et al. Interpreting post-transplant proteinuria in patients with proteinuria pre-transplant. Am J Transplant 2006; 6:1660.
  3. Amer H, Fidler ME, Myslak M, et al. Proteinuria after kidney transplantation, relationship to allograft histology and survival. Am J Transplant 2007; 7:2748.
  4. Knoll GA. Proteinuria in kidney transplant recipients: prevalence, prognosis, and evidence-based management. Am J Kidney Dis 2009; 54:1131.
  5. Tsampalieros A, Knoll GA. Evaluation and Management of Proteinuria After Kidney Transplantation. Transplantation 2015; 99:2049.
  6. Irish WD, Ilsley JN, Schnitzler MA, et al. A risk prediction model for delayed graft function in the current era of deceased donor renal transplantation. Am J Transplant 2010; 10:2279.
  7. Lechevallier E, Dussol B, Luccioni A, et al. Posttransplantation acute tubular necrosis: risk factors and implications for graft survival. Am J Kidney Dis 1998; 32:984.
  8. Bleyer AJ, Burkart JM, Russell GB, Adams PL. Dialysis modality and delayed graft function after cadaveric renal transplantation. J Am Soc Nephrol 1999; 10:154.
  9. Nogueira JM, Cangro CB, Fink JC, et al. A comparison of recipient renal outcomes with laparoscopic versus open live donor nephrectomy. Transplantation 1999; 67:722.
  10. Van Biesen W, Vanholder R, Van Loo A, et al. Peritoneal dialysis favorably influences early graft function after renal transplantation compared to hemodialysis. Transplantation 2000; 69:508.
  11. Torregrosa JV, Campistol JM, Fenollosa B, et al. Role of secondary hyperparathyroidism in the development of post-transplant acute tubular necrosis. Nephron 1996; 73:67.
  12. Lind MY, Zur Borg IM, Hazebroek EJ, et al. The effect of laparoscopic and open donor nephrectomy on the long-term renal function in donor and recipient: a retrospective study. Transplantation 2005; 80:700.
  13. Moers C, Smits JM, Maathuis MH, et al. Machine perfusion or cold storage in deceased-donor kidney transplantation. N Engl J Med 2009; 360:7.
  14. Schnuelle P, Gottmann U, Hoeger S, et al. Effects of donor pretreatment with dopamine on graft function after kidney transplantation: a randomized controlled trial. JAMA 2009; 302:1067.
  15. Jani V, Ingulli E, Mekeel K, Morris GP. Root cause analysis of limitations of virtual crossmatch for kidney allocation to highly-sensitized patients. Hum Immunol 2017; 78:72.
  16. Jackson AM. The Virtual Crossmatch: An Essential Tool for Transplanting Sensitized Patients. Clin Transpl 2014; :131.
  17. Zachary AA, Sholander JT, Houp JA, Leffell MS. Using real data for a virtual crossmatch. Hum Immunol 2009; 70:574.
  18. Kujovich JL. Thrombophilia and thrombotic problems in renal transplant patients. Transplantation 2004; 77:959.
  19. Pérez Fontán M, Rodríguez-Carmona A, García Falcón T, et al. Peritoneal dialysis is not a risk factor for primary vascular graft thrombosis after renal transplantation. Perit Dial Int 1998; 18:311.
  20. Ojo AO, Hanson JA, Wolfe RA, et al. Dialysis modality and the risk of allograft thrombosis in adult renal transplant recipients. Kidney Int 1999; 55:1952.
  21. Humar A, Matas AJ. Surgical complications after kidney transplantation. Semin Dial 2005; 18:505.
  22. Bakir N, Sluiter WJ, Ploeg RJ, et al. Primary renal graft thrombosis. Nephrol Dial Transplant 1996; 11:140.
  23. Irish A. Renal allograft thrombosis: can thrombophilia explain the inexplicable? Nephrol Dial Transplant 1999; 14:2297.
  24. Oh J, Schaefer F, Veldmann A, et al. Heterozygous prothrombin gene mutation: a new risk factor for early renal allograft thrombosis. Transplantation 1999; 68:575.
  25. Wüthrich RP, Cicvara-Muzar S, Booy C, Maly FE. Heterozygosity for the factor V Leiden (G1691A) mutation predisposes renal transplant recipients to thrombotic complications and graft loss. Transplantation 2001; 72:549.
  26. Robertson AJ, Nargund V, Gray DW, Morris PJ. Low dose aspirin as prophylaxis against renal-vein thrombosis in renal-transplant recipients. Nephrol Dial Transplant 2000; 15:1865.
  27. Lucewicz A, Wong G, Lam VW, et al. Management of primary symptomatic lymphocele after kidney transplantation: a systematic review. Transplantation 2011; 92:663.
  28. Kusyk T, Verran D, Stewart G, et al. Increased risk of hemorrhagic complications in renal allograft recipients receiving systemic heparin early posttransplantation. Transplant Proc 2005; 37:1026.
  29. Makiyama K, Tanabe K, Ishida H, et al. Successful renovascular reconstruction for renal allografts with multiple renal arteries. Transplantation 2003; 75:828.
  30. Bolander JE 2nd, Carter CB. Cholesterol embolization in renal allografts. J Am Soc Nephrol 1996; 7:18.
  31. Ripple MG, Charney D, Nadasdy T. Cholesterol embolization in renal allografts. Transplantation 2000; 69:2221.
  32. Sewpaul A, Sayer JA, Mohamed MA, et al. Rapid onset intratubular calcification following renal transplantation requiring urgent parathyroidectomy. Clin Nephrol 2007; 68:47.
  33. Tarplin S, Ganesan V, Monga M. Stone formation and management after bariatric surgery. Nat Rev Urol 2015; 12:263.
  34. Andersson H, Bosaeus I, Fasth S, et al. Cholelithiasis and urolithiasis in Crohn's disease. Scand J Gastroenterol 1987; 22:253.
  35. Lefaucheur C, Nochy D, Amrein C, et al. Renal histopathological lesions after lung transplantation in patients with cystic fibrosis. Am J Transplant 2008; 8:1901.
  36. Lieske JC, Regnier C, Dillon JJ. Use of sevelamer hydrochloride as an oxalate binder. J Urol 2008; 179:1407.
  37. Caravaca F, Ruiz AB, Escola JM, et al. [Either calcium carbonate or sevelamer decreases urinary oxalate excretion in chronic renal failure patients]. Nefrologia 2007; 27:466.
  38. Tang X, Voskoboev NV, Wannarka SL, et al. Oxalate quantification in hemodialysate to assess dialysis adequacy for primary hyperoxaluria. Am J Nephrol 2014; 39:376.
  39. Watts RW, Veall N, Purkiss P. Oxalate dynamics and removal rates during haemodialysis and peritoneal dialysis in patients with primary hyperoxaluria and severe renal failure. Clin Sci (Lond) 1984; 66:591.
  40. Ramos EL. Recurrent diseases in the renal allograft. J Am Soc Nephrol 1991; 2:109.
  41. Chadban S. Glomerulonephritis recurrence in the renal graft. J Am Soc Nephrol 2001; 12:394.
  42. Varma MC, Kushner YB, Ko DS, et al. Early onset adenovirus infection after simultaneous kidney-pancreas transplant. Am J Transplant 2011; 11:623.
  43. Storsley L, Gibson IW. Adenovirus interstitial nephritis and rejection in an allograft. J Am Soc Nephrol 2011; 22:1423.
  44. Barros Silva GE, Muglia VF, Filho NS, et al. Adenovirus pyelonephritis in the late posttransplant period. Kidney Int 2017; 92:520.
  45. Ponticelli C, Moroni G, Glassock RJ. De novo glomerular diseases after renal transplantation. Clin J Am Soc Nephrol 2014; 9:1479.
  46. Wilson CH, Rix DA, Manas DM. Routine intraoperative ureteric stenting for kidney transplant recipients. Cochrane Database Syst Rev 2013; :CD004925.
  47. Brennan DC, Agha I, Bohl DL, et al. Incidence of BK with tacrolimus versus cyclosporine and impact of preemptive immunosuppression reduction. Am J Transplant 2005; 5:582.
  48. Jolly EC, Adshead JM, Farrington K. The retained stent: forgotten but not gone. Kidney Int 2010; 77:260.
  49. Schwarz A, Hiss M, Gwinner W, et al. Course and relevance of arteriovenous fistulas after renal transplant biopsies. Am J Transplant 2008; 8:826.
Topic 7301 Version 27.0

References

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