Kidney function and non-kidney solid organ transplantation

INTRODUCTION — 

As outcomes following non-kidney solid organ transplantation (NKSOT) have improved, chronic kidney disease (CKD) has become an increasingly prevalent complication in this population. CKD occurs despite advancements in immunosuppression and perioperative management, as well as attention to cardiovascular risk factors and infectious complications. The development of CKD is associated with enhanced morbidity and mortality.

This topic will review issues relating to kidney function following NKSOT, including the evaluation of kidney function prior to NKSOT. A review of calcineurin inhibitor nephrotoxicity and kidney disease after hematopoietic cell transplantation is presented separately. (See "Cyclosporine and tacrolimus nephrotoxicity".)

PRETRANSPLANT EVALUATION OF KIDNEY FUNCTION

Initial evaluation in all patients — All candidates for non-kidney solid organ transplantation (NKSOT) should undergo an evaluation of kidney function as part of their pretransplant evaluation. This evaluation is usually performed by the primary transplant team or by a collaborating nephrologist. The primary goal of this evaluation is to establish if the patient has kidney function impairment and, if so, to determine the likelihood of reversibility or progression to end-stage kidney disease (ESKD) after the non-kidney organ transplant. Candidates for NKSOT who have severe kidney function impairment may be considered for a simultaneous kidney transplant (eg, liver-kidney, heart-kidney, lung-kidney transplant) or kidney transplant after NKSOT. (See 'Eligibility for multiorgan transplant including a kidney' below.)

Assessment of prior kidney function — The level of kidney function and duration of kidney disease prior to organ transplantation is an important risk factor for posttransplant chronic kidney disease (CKD). In all NKSOT candidates, we review the patient’s history and laboratory trends over at least the past 90 days to determine the following:

●Baseline serum creatinine level and estimated glomerular filtration rate (eGFR).

●Presence or absence of proteinuria. Persistent proteinuria suggests that the patient has underlying intrinsic kidney disease.

●History of prior acute kidney injury (AKI) or CKD, including the causes, duration, and reversibility of prior insults.

AKI in the setting of worsening heart, liver, or lung disease is often caused by poor effective circulating volume (eg, cardiorenal syndrome or hepatorenal syndrome). In these situations, kidney function may improve after replacement of the non-kidney failing organ. However, protracted or recurrent episodes of AKI can cause irreversible ischemic damage leading to progressive interstitial fibrosis and tubular atrophy, resulting in partial or complete non-recovery of kidney function that is unlikely to improve after NKSOT. (See "Cardiorenal syndrome: Definition, prevalence, diagnosis, and pathophysiology" and "Hepatorenal syndrome: Clinical presentation and diagnosis".)

●Presence of comorbidities known to lead to kidney damage, such as diabetes mellitus, autosomal dominant polycystic kidney disease, or renal atherosclerosis.

Assessment of current kidney function — For all NKSOT candidates, we routinely evaluate current kidney function using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine formula to estimate glomerular filtration rate (GFR) (calculator 1). This formula is the preferred method for estimating GFR in adults in most clinical situations, has been shown to perform better than other creatinine-based estimating equations in the solid organ transplant population, and is widely available [1]. (See "Assessment of kidney function".)

Because the serum creatinine level is affected by muscle mass, creatinine-based eGFR estimates may overestimate GFR in patients with advanced liver disease or advanced heart failure, who frequently have poor nutritional status, low muscle mass, weight loss, and edema [2,3]. In such patients, some studies suggest that serum cystatin C levels may be a more sensitive indicator of kidney function than the serum creatinine level [4-9]. If confirmation of the creatinine-based eGFR is needed, we obtain a cystatin C level and estimate GFR using the 2021 CKD-EPI creatinine-cystatin C equation (calculator 2). Newer methods of assessing GFR such as the fluorescent molecule relmapirazin may be utilized in the near future but are not yet widely commercially available [10]. (See "Assessment of kidney function", section on 'eGFR from cystatin C' and "Assessment of kidney function", section on 'Confirmation of eGFR (when needed)'.)

Urine studies — We obtain the following urine studies:

●Urinalysis with microscopic examination of the sediment – We obtain a urinalysis to assess for proteinuria and microscopic hematuria, which indicate the possibility of glomerular disease. If proteinuria is present, it should be quantified, as discussed below. Microscopic hematuria, especially if accompanied by red blood cell (RBC) casts or dysmorphic RBCs, may also indicate underlying glomerular disease. However, most hematuria is due to other causes and may warrant further evaluation. (See "Urinalysis in the diagnosis of kidney disease" and "Evaluation of hematuria in adults".)

●Spot urine albumin-to-creatinine (UACR) or protein-to-creatinine ratio (UCPR) – Either a spot UACR or UPCR should be obtained to quantify proteinuria. The presence of severely increased proteinuria (>500 mg/g) or albuminuria (>300 mg/g) suggests underlying intrinsic kidney disease and should prompt a full evaluation to elucidate the nature and prognosis of this disease. In addition, even mild albuminuria (>30 mg/g) is associated with significant adverse clinical outcomes in diverse patient populations, and observational studies suggest this is also true in liver, lung, and heart transplant recipients [11-13]. However, while it is presently unknown whether these data can be extrapolated to NKSOT candidates, we advise using this albuminuria threshold (>30 mg/g) to avoid potentially missing an underlying glomerular disorder. (See "Evaluation of proteinuria in adults".)

●Urine electrolytes and osmolality – Urine electrolytes and osmolality are useful for assessing the effective volume status and renal concentrating ability of patients with abnormal kidney function. We check urine sodium or fractional excretion of sodium (FENa), which is usually very low (<10 mEq/L or <1 percent, respectively) in liver transplant candidates with hepatorenal syndrome or heart transplant candidates with cardiorenal syndrome. Such conditions represent situations in which the renal hemodynamic state usually improves rapidly with appropriate organ transplantation. The elimination of the source of the kidney insult may allow subsequent kidney function to likewise undergo some degree of further recovery. (See "Fractional excretion of sodium, urea, and other molecules in acute kidney injury" and "Hepatorenal syndrome: Clinical presentation and diagnosis".)

Kidney imaging — We obtain a kidney ultrasound to evaluate kidney size, echogenicity, and cortical thickness and to exclude obstruction, stone disease, and cysts. Since glomeruli are predominantly in the cortex, echogenic kidneys less than 10 cm in length with cortical thinning usually indicate kidney structural damage. Further evaluation of the renal vasculature may be needed in some patients with extensive atherosclerosis. (See "Radiologic assessment of kidney disease", section on 'B-mode ultrasonography'.)

Role of kidney biopsy — The role of a pretransplant kidney biopsy in NKSOT candidates with impaired kidney function or proteinuria is uncertain. A kidney biopsy may be considered on a case-by-case basis in patients with urinary abnormalities such as microscopic hematuria, proteinuria, or cellular casts or in those in whom the etiology of kidney function impairment is not apparent from routine clinical data. As an example, a kidney biopsy may help to differentiate intrinsic glomerular or tubular disease from kidney hypoperfusion and ischemia. (See "The kidney biopsy", section on 'Indications'.)

Other putative benefits include the ability to determine chronicity, treatability, and the likelihood of future progression or reversibility of kidney disease. Some have suggested using the extent of glomerulosclerosis (>40 percent) and interstitial fibrosis (>30 percent) to guide selection of patients for multi-organ transplantation that includes a kidney [14]. Although this may represent useful information regarding chronicity of kidney injury, there is little data supporting the prognostic value of kidney histology or its advantage over kidney function studies alone. Kidney biopsy findings are not included in the Organ Procurement and Transplantation Network (OPTN) criteria for selection of patients for multiorgan transplantation that includes a kidney. (See 'Eligibility for multiorgan transplant including a kidney' below.)

A kidney biopsy may be performed percutaneously under ultrasound or computed tomography (CT) guidance if the patient’s condition allows, but it may be complicated by bleeding. In one series in which 44 liver transplant candidates with abnormal kidney function of undetermined etiology for less than eight weeks duration underwent percutaneous kidney biopsy, the incidence of bleeding complications requiring at least one unit of blood was 30 percent [15]. More than half of the complications were major, defined by the requirement for two or more units of blood and/or intervention. By multivariable analysis, only International Normalized Ratio (INR) at the time of biopsy was an independent predictor of complication. A transjugular kidney biopsy should therefore be considered in patients with severe coagulopathy or on mechanical ventilation in whom a percutaneous approach may not be feasible or safe [16-18]. (See "The kidney biopsy", section on 'Bleeding' and "The kidney biopsy", section on 'Choice of biopsy method'.)

Glomerulonephritis may be clinically silent in liver transplant candidates, especially those with hepatitis C infection. A single-center study, for example, reported the kidney histology and kidney outcomes of 30 liver transplant patients with hepatitis C virus (HCV) infection who underwent liver transplantation alone and had a kidney biopsy at the time of transplantation [19]. Immune-complex glomerulonephritis was noted in 25 patients, 12 with membranoproliferative glomerulonephritis, seven with IgA nephropathy, and six with mesangial glomerulonephritis; only one patient had a normal kidney biopsy. Of this cohort, 10 patients had normal serum creatinine levels, normal urinalysis results, and normal quantitative proteinuria. For five others, the only kidney abnormality was an increased serum creatinine level. No patient had cryoglobulins in the blood or kidney. This study, together with others [15,20], highlights the lack of correlation between clinical parameters and kidney histology in patients with decompensated liver disease.

Eligibility for multiorgan transplant including a kidney — For patients who have severe kidney function impairment that is unlikely to reverse or improve after NKSOT, multiorgan transplantation including a kidney may be an option but requires careful consideration given the complex medical issues involved. In the United States, patients must meet minimum eligibility criteria established by the OPTN. Candidates who do not qualify or who are not deemed suitable candidates for multiorgan transplantation including a kidney may still be considered for an expedited kidney transplant after NKSOT through the OPTN safety-net policy if there is inadequate recovery of function post-NKSOT. (See "Kidney transplantation in adults: The kidney transplant waiting list in the United States", section on 'Kidney waitlisting for multiorgan transplant candidates' and 'Safety-net policy' below and 'Kidney transplantation' below.)

OPTN eligibility criteria — In 2017, OPTN implemented a new policy that formalized the allocation of simultaneous liver-kidney (SLK) transplants [21]. In 2023, the allocation policy was expanded to include simultaneous heart-kidney (SHK) and lung-kidney (SLuK) transplantation as well. (See "Kidney transplantation in adults: The kidney transplant waiting list in the United States", section on 'Kidney waitlisting for multiorgan transplant candidates'.)

In accordance with OPTN policy, NKSOT candidates who meet one of the following criteria are eligible for a simultaneous kidney allocation, if deemed eligible by the transplant nephrology team:

●Diagnosis of CKD with a measured or calculated GFR of ≤60 mL/min for more than 90 consecutive days and at least one of the following at the time of waiting list registration:

•ESKD on dialysis

•Measured or calculated creatinine clearance or GFR ≤30 mL/min

●Diagnosis of sustained acute kidney injury (AKI) and at least one of the following, for the last six weeks:

•Dialysis at least once every seven days

•Measured or calculated creatinine clearance or GFR of ≤25 mL/min documented at least once every seven days

●Additional eligibility for SLK include a diagnosis of metabolic disease, with an additional diagnosis of at least one of the following:

•Hyperoxaluria

•Atypical hemolytic uremic syndrome from mutations in factor H or factor I

•Familial non-neuropathic systemic amyloidosis

•Methylmalonic aciduria

Safety-net policy — In addition to the above criteria defining eligibility for simultaneous multiorgan transplantation including a kidney, the new UNOS policies include a “safety-net” component to ensure that recipients of liver, heart, or lung alone who remain with advanced kidney disease after their NKSOT would be highly prioritized for subsequent kidney-alone offers, if both of the following conditions are met:

●The candidate is registered on the kidney waiting list between 60 and 365 days after liver, heart, or lung transplantation.

●The candidate is either on chronic dialysis or has a measured or calculated creatinine clearance or GFR of ≤20 mL/min.

The safety-net policy was designed to standardize practices in NKSOT and to mitigate misuse of kidney transplant allocation by decreasing the pressure for prophylactic kidney transplants (whereby kidney allografts are allocated to a recipient whose native kidney function is likely to recover after NKSOT) and futile kidney transplants (whereby kidney allografts are non-functional due to prolonged AKI after kidney transplant).

Establishing eligibility criteria for multiorgan transplants including a kidney has helped to eliminate some of the variability across centers that previously existed. However, we stress that meeting eligibility criteria should not automatically be assumed to qualify a candidate for dual organ transplantation, especially since NKSOT recipients receive very high priority for safety-net kidneys. According to early OPTN data, at three-year follow-up after the safety-net policy implementation, liver outcomes improved for patients who underwent kidney after liver transplant with no increased rejection of the transplanted liver or kidney [22]. From a utilitarian standpoint, we advise that only patients with unequivocal ESKD and a reasonable expected overall prognosis should routinely get a multi-organ transplant including a kidney. For patients in whom non-recovery of native kidney function is less clear for transplant nephrologists to predict, we advise NKSOT alone with safety-net listing for a kidney as soon as it becomes clinically indicated. Although not specifically stated in the OPTN policy, seeking out a live kidney donor should be encouraged for all NKSOT recipients listed for a safety-net kidney.

CHRONIC KIDNEY DISEASE AFTER NON-KIDNEY SOLID ORGAN TRANSPLANT — 

The degree of kidney function impairment posttransplant and the rate of progression of chronic kidney disease (CKD) depends to a large degree on the extent of pretransplant kidney function impairment, the nature of the organ transplanted, the intra- and early postoperative course, and the immunosuppressive regimen and individual clinical features that determine susceptibility to kidney injury. Since more than one of these factors is usually present in any given patient, some degree of CKD is present in most long-term organ recipients.

Epidemiology of CKD — CKD is common after non-kidney solid organ transplant (NKSOT). The best general data on the overall incidence of CKD in this population come from a cohort study of 69,321 recipients of non-kidney transplants (heart, lung, liver, and intestine) in the United States between 1990 and 2000 [23]. In this report, 11,426 patients (17 percent) developed CKD (defined as a glomerular filtration rate [GFR] ≤29 mL/min/1.73 m²) over a median of 36 months. The cumulative incidence of CKD at five years ranged from 21 percent among intestinal transplant recipients to 18 percent among liver transplant recipients, 16 percent among lung transplant recipients, 11 percent among heart transplant recipients, and 7 percent among heart-lung recipients. Among patients who developed CKD, 29 percent progressed to end-stage kidney disease (ESKD) requiring maintenance dialysis or kidney transplantation. Subsequent studies in specific organ transplant populations have also shown high rates of CKD after transplantation [24-29].

The presence of CKD among NKSOT recipients is associated with worse posttransplant outcomes, including a higher risk of mortality [23,25,27,30,31].

Causes and risk factors for CKD — Several factors may contribute to the development and progression of CKD after NKSOT, including traditional risk factors for CKD (such as diabetes, hypertension, and obesity) [32-34] as well as transplant-specific factors. Traditional risk factors for CKD are discussed in detail separately. (See "Early detection of chronic kidney disease", section on 'Risk factors'.)

Transplant-specific causes and risk factors include the following:

●Calcineurin inhibitor (CNI) nephrotoxicity – CNI therapy (cyclosporine or tacrolimus) remains the cornerstone of immunosuppression in most organ recipients and has been implicated as a principal cause of posttransplant CKD [35-43]. The use of CNIs has also been associated with the development of de novo thrombotic microangiopathy after kidney transplantation. The mechanisms and histopathologic features of CNI nephrotoxicity are similar among kidney and non-kidney organ recipients and are reviewed separately. (See "Cyclosporine and tacrolimus nephrotoxicity" and "Thrombotic microangiopathy after kidney transplantation".)

●Preexisting CKD before transplant – Preexisting CKD prior to transplantation is a risk factor for worsening kidney function after transplantation. Common causes of pretransplant CKD in NKSOT recipients include diabetes, hypertension, renovascular disease, viral infection (hepatitis B virus [HBV] or hepatitis C virus [HCV]), and recurrent acute kidney injury (AKI) in the setting of chronic cardiorenal or hepatorenal syndrome.

●Posttransplant acute kidney injury (AKI) – Prolonged and recurrent episodes of AKI with incomplete recovery during the peritransplant period is a risk factor for the development of posttransplant CKD. Perioperative events that may result in AKI include hypotension and hypoperfusion, exposure to nephrotoxic agents, sepsis, and aggressive diuresis. In recipients of a heart transplant, cardiopulmonary bypass and aortic cross-clamping during surgery may also precipitate AKI.

●BK polyomavirus infection – Nephropathy associated with BK polyomavirus (BKPyV) has been reported in NKSOT recipients, but this is uncommon [44-47]

While CKD in NKSOT recipients is often attributed to chronic CNI nephrotoxicity, kidney biopsy studies in this patient population have shown that diagnoses other than CNI nephrotoxicity are common [48-52]. In addition, histologic findings vary among the different types of organ transplantation. As an example, a retrospective study of 105 kidney biopsies performed in a cohort of 101 bone marrow, liver, lung, and heart recipients for acute and chronic indications demonstrated histological findings of primary glomerular disease in 17 percent and thrombotic microangiopathy in 10 percent of patients, in addition to nonspecific chronic changes, hypertension-related damage, and CNI toxicity [49]. Arteriolar hyalinosis was more frequent among lung and heart transplant recipients, whereas primary glomerular disease was more frequent in liver transplant recipients.

Evaluation of CKD — The evaluation of newly identified CKD among NKSOT recipients is similar to that for nontransplant patients with CKD and includes an initial assessment of the onset and duration of kidney disease, followed by an evaluation to identify the cause of CKD (algorithm 1). Careful attention to the perioperative events surrounding the organ transplant is important in the history. In addition, we assess the patient’s blood CNI levels since transplantation to determine if they were consistently elevated for a protracted period of time. Some authors would obtain a quantitative plasma BKPyV polymerase chain reaction (PCR; ie, viral load) to evaluate for the possibility of BKPyV-associated nephropathy. In patients who have heavy proteinuria (urine albumin-to-creatinine ratio >300 mg/g or urine protein-to-creatinine ratio >500 mg/g) or who do not have an identifiable cause of CKD based on the initial evaluation, a kidney biopsy may be warranted. This is discussed in detail separately. (See "Chronic kidney disease (newly identified): Clinical presentation and diagnostic approach in adults" and "Chronic kidney disease in children: Clinical manifestations, evaluation, and diagnosis".)

Management of CKD

General measures for CKD — In general, the approach to the prevention and management of CKD in NKSOT recipients is similar to that for nontransplant patients, as discussed in detail separately. (See "Overview of the management of chronic kidney disease in adults" and "Chronic kidney disease in children: Overview of management".)

Transplant-specific considerations include the following:

●Blood pressure control – We aim to achieve good control of blood pressure. In the absence of specific guidelines for NKSOT recipients, we follow general guidelines for the treatment of hypertension in kidney transplant recipients, which are discussed in detail separately. (See "Hypertension after kidney transplantation" and "Liver transplantation in adults: Long-term management of transplant recipients", section on 'Hypertension'.)

●Renin-angiotensin system (RAS) inhibition – Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are recommended for patients with CKD who have albuminuria to help slow the progression of kidney disease. The effectiveness of ACE inhibitors or ARBs in protecting kidney function among NKSOT recipients with CKD is yet to be established. Until such data are available, we advise RAS blockade in NKSOT recipients who have a cardiac indication for the use of these agents or in those with albuminuria. In both settings, kidney function and serum potassium levels should be carefully monitored after drug initiation and with any subsequent dose titration. (See "Overview of the management of chronic kidney disease in adults", section on 'Patients with albuminuria'.)

Mineralocorticoid receptor antagonists (MRAs) can further reduce albuminuria when added to an ACE inhibitor or ARB, although there are no data on kidney outcomes in NKSOT recipients with CKD. As with ACE inhibitors and ARBs, serum potassium levels must be closely monitored if MRAs are used. (See "Antihypertensive therapy and progression of nondiabetic chronic kidney disease in adults", section on 'Mineralocorticoid receptor antagonists'.)

●Sodium-glucose cotransporter 2 (SGLT2) inhibitors – SGLT2 inhibitors are recommended for patients with CKD and severely increased albuminuria (ie, measured albuminuria ≥300 mg/day or albumin-to-creatinine ratio [ACR] ≥300 mg/g) to slow the progression of CKD. However, their use has not been well studied in NKSOT recipients, and it is unclear whether these agents provide the same kidney protective benefits in this population. (See "Overview of the management of chronic kidney disease in adults", section on 'Patients with albuminuria'.)

Management of immunosuppression — The choice of immunosuppression regimen for NKSOT is made by the primary transplant team and is usually based on an assessment of efficacy and toxicity. The vast majority of NKSOT recipients in the United States receive an immunosuppression regimen consisting of a CNI (tacrolimus), an antimetabolite (mycophenolate), and prednisone at the time of transplant [53]. According to the annual report of the Organ Procurement and Transplant Network (OPTN) and Scientific Registry of Transplant Recipients (SRTR), the majority of patients remain on a tacrolimus-based regimen at one year after transplant. (See "Liver transplantation in adults: Initial and maintenance immunosuppression" and "Heart transplantation in adults: Induction and maintenance of immunosuppressive therapy" and "Maintenance immunosuppression following lung transplantation".)

In NKSOT recipients with CKD, some transplant clinicians attempt to eliminate or reduce exposure to CNIs to delay the progression of kidney disease (see 'Causes and risk factors for CKD' above). The optimal approach is not known. Modification of the immunosuppressive regimen should be individualized to balance the overall risks and benefits of one therapy versus another, especially the risk of compromising the function of the transplanted organ. Collaboration between the primary transplant team and the nephrologist is advised. Possible strategies have included the following:

●CNI withdrawal/elimination – One approach is to switch patients from a CNI to an alternative immunosuppressive agent.

•Conversion from a CNI to an mTOR inhibitor (CNI withdrawal) – Some clinicians try to convert patients from a CNI to a mechanistic (mammalian) target of rapamycin (mTOR) inhibitor, such as sirolimus or everolimus. (See "Liver transplantation in adults: Initial and maintenance immunosuppression", section on 'Modifying the existing regimen' and "Heart transplantation in adults: Induction and maintenance of immunosuppressive therapy", section on 'Kidney function impairment' and "Maintenance immunosuppression following lung transplantation", section on 'Patient selection'.)

Conversion from a CNI to an mTOR inhibitor was evaluated in a meta-analysis of 10 randomized trials in 1927 liver transplant recipients [54]. Patients who were converted from a CNI to an mTOR inhibitor had a modestly higher eGFR at one year compared with those who remained on a CNI. However, there was no difference in graft survival, and patients who switched to an mTOR inhibitor had higher risks of acute rejection (relative risk [RR] 1.8, 95% CI 1.3-2.3) and drug discontinuation due to adverse effects (RR 2.2, 95% CI 1.4-3.4) up to one year posttransplant. Similar findings have been reported in heart transplant recipients [55]. Use of mTOR inhibitors should be avoided in patients with eGFR <40 mL/min/1.7³ m² or proteinuria as this has been associated with an accelerated progression of kidney function impairment. (See "Pharmacology of mammalian (mechanistic) target of rapamycin (mTOR) inhibitors", section on 'Kidney function'.)

•Conversion from a CNI to belatacept (CNI withdrawal) – Another option is to convert patients from a CNI to the costimulatory blocker belatacept. This approach has been used in kidney transplant recipients with evidence of CNI nephrotoxicity. However, there are no randomized trials evaluating this approach in NKSOT recipients, and supportive data comes only from case reports and series [56-59]. (See "Maintenance immunosuppression following lung transplantation", section on 'Belatacept'.)

●CNI minimization – Another approach is to add an immunosuppressive agent, such as an mTOR inhibitor, and continue the CNI at a reduced dose, with the aim of minimizing long-term CNI exposure. Support for this approach comes from a randomized trial in which 282 heart or lung transplant recipients ≥1 year from transplant were randomly assigned to continue standard CNI therapy (CNI, azathioprine or mycophenolate, and prednisone) or to start everolimus with reduced-dose CNI (target cyclosporine trough of <75 mg/mL or tacrolimus trough of <4 ng/mL) [60]. At a mean of 5.6 years, mean measured GFR remained stable in the everolimus group (from 51.3 to 51.4 mL/min) but decreased in the control group (from 50.5 to 45.3 mL/min). Rates of rejection, death, and major cardiac events were similar between the groups, but rates of pneumonia were higher with everolimus.

Kidney replacement therapy — For NKSOT recipients who develop ESKD, kidney replacement therapy (KRT) options include dialysis and kidney transplantation.

Dialysis — NKSOT recipients with ESKD can be treated with either hemodialysis or peritoneal dialysis. We advocate for multidisciplinary collaboration between the nephrologist and the primary transplant team in formulating a dialysis treatment plan to discuss with the patient. Indications for initiating dialysis are the same as in nontransplant patients with ESKD, as discussed separately. (See "Indications for initiation of dialysis in chronic kidney disease".)

●Choice of modality – Both hemodialysis (HD) and peritoneal dialysis (PD) are viable options for NKSOT recipients with ESKD, regardless of organ transplanted. Liver transplant recipients can be candidates for PD if their peritoneal membrane is suitable, while lung transplant recipients interested in PD should have lung function that can tolerate a supine peritoneal volume of approximately 2 liters. There is no high-quality evidence to guide the optimal choice of modality in NKSOT recipients, and decisions about the choice of dialysis modality should be individualized. PD may be better tolerated in patients with low blood pressure or hemodynamic instability.

Data comparing dialysis modalities among NKSOT recipients is very limited. In one single-center study of 26 heart, lung, or heart-lung transplant recipients on dialysis (16 on PD and 10 on HD), patient survival was comparable between PD and HD (90 and 88 percent at 6 months and 80 and 81 percent at one year, respectively) [61]. The rate of hospitalizations was higher with HD, with pulmonary disease and vascular access-related issues being the most common causes of hospitalization.

●Dialysis access – Hemodialysis vascular access options (arteriovenous [AV] fistulas, AV grafts, central venous catheters) are the same for NKSOT recipients as for nontransplant patients. In general, AV fistulas or AV grafts are preferred over central venous catheters, given the risk of infectious complications (exit site/tunnel infections, and bloodstream infections) with the latter. More detailed discussions about access creation for HD and PD are presented separately. (See "Approach to the adult patient needing vascular access for chronic hemodialysis" and "Placement of the peritoneal dialysis catheter".)

●Infection risk – Data are conflicting on the risk of peritonitis in NKSOT recipients on PD. While one study reported an increased risk of peritonitis and PD failure compared with nontransplant patients on PD [62], subsequent studies have found no increased risk [63,64].

Kidney transplantation — For most NKSOT recipients with ESKD, kidney transplantation is the preferred form of KRT because of its improved survival compared with dialysis. NKSOT recipients comprise an increasing proportion of the patients referred and waitlisted for kidney transplantation [65-67]. As of 2024, 4.8 percent of patients on the deceased donor waiting list for kidney transplantation in the United States are prior recipients of heart, liver, or lung transplantation [68]; this has increased from approximately 3 percent a decade ago.

●Timing of referral – Timely referral of medically appropriate NKSOT recipients for kidney transplantation is essential because of the increased risk of death on the kidney waiting list in these patients [69]. Since NKSOT recipients fare poorly on dialysis and most will have very limited priority under the present kidney allocation system, living donation represents the best hope of transplantation for many of these patients. For this reason, we typically refer patients for transplant when the eGFR is between 20 to 25 mL/min/1.73 m² in the hopes of identifying a potential donor and proceeding with preemptive kidney transplantation before their health has deteriorated to the point that they are no longer suitable kidney transplant candidates.

●Safety-net listing – Liver, heart, or lung transplant recipients who have advanced CKD and meet certain conditions can be listed for a “safety-net” kidney transplant. Such patients are highly prioritized for kidney-alone offers under the United Network for Organ Sharing (UNOS) safety-net policy. (See 'Safety-net policy' above.)

●Outcomes – For NKSOT recipients who develop ESKD, as in the general population, kidney transplantation results in superior patient survival than dialysis. This was demonstrated in one study of kidney transplant recipients who had a prior NKSOT [69]:

•At 141 days, the relative risk of death in patients who received a kidney transplant was the same as those on the waiting list.

•Beyond 141 days, the relative risk of death was decreased and maintained until the end of the study duration (five years).

The 10-year patient survival after kidney transplantation was 22 and 27 percent lower for recipients of a prior heart and liver transplant, respectively, compared with recipients of a kidney transplant alone [69]. The risk of death was highest among kidney transplant recipients who had received a prior lung transplant (hazard ratio 4.3, 95% CI 2.8-6.6). At five years post-kidney transplant, death with a functioning kidney allograft accounted for most graft loss in patients who had received a prior NKSOT.

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 – As outcomes following non-kidney solid organ transplantation (NKSOT) have improved, chronic kidney disease (CKD) has become an increasingly prevalent complication in this population. (See 'Introduction' above.)

●Pretransplant evaluation of kidney function – All candidates for NKSOT should undergo an evaluation of kidney function as part of their pretransplant evaluation. The primary goal is to establish if the patient has kidney function impairment and, if so, to determine the likelihood of reversibility or progression to end-stage kidney disease (ESKD) after NKSOT.

•Initial evaluation – The initial evaluation includes an assessment of the patient’s prior and current kidney function, urine studies, and kidney imaging. (See 'Initial evaluation in all patients' above.)

•Role of kidney biopsy – A kidney biopsy may be considered on a case-by-case basis in patients with urinary abnormalities such as microscopic hematuria, proteinuria, or cellular casts or in those in whom the etiology of kidney function impairment is not apparent from routine clinical data. Other putative benefits include the ability to determine chronicity, treatability, and the likelihood of future progression or reversibility of kidney disease. However, there is little data supporting the prognostic value of kidney histology or its advantage over kidney function studies alone in this population. (See 'Role of kidney biopsy' above.)

•Eligibility for multiorgan transplant including a kidney – For patients who have severe kidney function impairment that is unlikely to reverse or improve after NKSOT, multiorgan transplantation including a kidney may be an option but requires careful consideration given the complex medical issues involved. In the United States, patients must meet minimum eligibility criteria established by the Organ Procurement and Transplantation Network (OPTN). Candidates who do not qualify or who are not deemed suitable candidates may still be considered for an expedited kidney transplant after NKSOT through the OPTN safety-net policy. (See 'Eligibility for multiorgan transplant including a kidney' above.)

●Chronic kidney disease after NKSOT – CKD is common after NKSOT, and its presence is associated with worse posttransplant outcomes. (See 'Epidemiology of CKD' above.)

•Causes and risk factors – Several factors may contribute to the development and progression of CKD after NKSOT, including traditional risk factors for CKD (such as diabetes, hypertension, and obesity) as well as transplant-specific factors, such as calcineurin inhibitor (CNI) nephrotoxicity, preexisting CKD before transplant, posttransplant acute kidney injury (AKI), and, less commonly, BK polyomavirus (BKPyV) infection. (See 'Causes and risk factors for CKD' above.)

•Evaluation of CKD – The evaluation of newly identified CKD among NKSOT recipients is similar to that for nontransplant patients with CKD and includes an initial assessment of the onset and duration of kidney disease, followed by an evaluation to identify the cause of CKD (algorithm 1). We also assess the patient’s blood CNI levels since transplantation to determine if they were high at any time. Some authors would evaluate for BKPyV infection. In patients who have heavy proteinuria or who do not have an identifiable cause of CKD based on the initial evaluation, a kidney biopsy may be warranted. (See 'Evaluation of CKD' above.)

•Management of CKD

-General measures – Management of CKD in NKSOT recipients is similar to that for nontransplant patients. Transplant-specific considerations are discussed above. (See 'General measures for CKD' above.)

-Management of immunosuppression – In NKSOT recipients with CKD, some transplant clinicians attempt to eliminate or reduce exposure to CNIs to delay the progression of kidney disease, but the optimal approach is not known. Modification of the immunosuppressive regimen should be individualized to balance the overall risks and benefits of one therapy versus another. (See 'Management of immunosuppression' above.)

-Kidney replacement therapy (KRT) – Both hemodialysis and peritoneal dialysis can be considered in NKSOT recipients who develop ESKD. For most patients, kidney transplantation is the preferred form of KRT because of its improved survival compared with dialysis. (See 'Kidney replacement therapy' above.)