(1)
Portland Veterans Administration Medical Center, Oregon Health & Science University, 3710 SW US Veterans Hospital Road, P3NEPH, 97239 Portland, OR, USA
Keywords
Acute kidney injuryChronic kidney diseaseChronic kidney disease in HSCTKidney damage is a common complication of hematopoietic stem cell transplantation (HSCT) ; its severity may range from a transient and reversible rise in creatinine to a complete loss of kidney function with need for hemodialytic support. Acute kidney injury (AKI) requiring dialysis in critically ill HSCT recipients is associated with greater than 80 % mortality. Additionally, AKI of any degree of severity confers risk for the development of chronic kidney disease (CKD) . Even in the absence of AKI in the immediate post-HSCT period, HSCT recipients are at high risk for CKD over the long term, and this complication is associated with decreased life expectancy. Thus, nephroprotective measures during the HSCT process are of utmost importance and should not be overlooked. Early diagnosis and treatment of AKI, and early nephrology consultation, should likewise be considered. Long-term follow-up of HSCT patients should include routine surveillance for the development of CKD.
24.1 Definitions of AKI and CKD
1.
AKI: This entity was previously called acute renal failure (ARF). The definition is based on an acute rise in serum creatinine or a fall in urine output or both. There are several expert guidelines describing staging of AKI severity; the most recent is summarized in Table 24.1. In HSCT patients who are cachectic with low muscle mass, the baseline creatinine may be below the reference range for normal; in these patients, a rise in the serum creatinine to a normal level may indicate AKI.
Table 24.1
Stages of AKI
Stage | Serum creatinine | Urine output |
1 | 1.5–1.9 × baseline or > / = 0.3 mg/dL increase | < 0.5 mL/kg/h × 6–12 h |
2 | 2.0–2.9 × baseline | < 0.5 mL/kg/h for > 12 h |
3 | 3.0 baseline or increase to >/ + 4.0 mg/dL or need for dialytic support | < 0.3 mL/kg/h for >/ = 24 h or anuria for >/ = 12 h |
2.
CKD: Previously known as chronic renal insufficiency or failure (CRI or CRF), CKD is a structural or functional renal abnormality that persists for at least 3 months. Reduced glomerular filtration rate (GFR) and persistent albuminuria (proteinuria) are the most common manifestations of chronic kidney injury. Five stages of CKD are defined based on GFR (Table 24.2).
Table 24.2
Stages of CKD
Stage | GFR |
1 | > 90 mL/min/1.73 m2 and proteinuria or structural abnormality |
2 | 60–89 mL/min/1.73 m2 |
3 | 30–59 mL/min/1.73 m2 |
3a | 45–59 mL/min/1.73 m2 |
3b | 30–44 mL/min/1.73 m2 |
4 | 15–29 mL/min/1.73 m2 |
5 | < 15 mL/min/1.73 m2 |
24.2 Kidney Disease in HSCT: Incidence and Risk
1.
AKI:
a.
The incidence of AKI in the days to weeks following HSCT is likely > 50 %, though estimates in the literature range from 15 to 60 %.
b.
Risk factors include:
i.
Pre-transplant CKD and/or hypertension
ii.
Post-HSCT complications
Sepsis
Amphotericin product exposure
Hepatic sinusoidal obstructive syndrome (SOS)
Acute graft-versus-host disease (GVHD)
iii.
The type of HSCT performed influences the risk for SOS and GVHD, and the need for calcineurin inhibitor (CNI) therapy , and therefore the risk of severe AKI.
Myeloablative regimens, with their more intensive conditioning and higher risk for SOS compared with nonmyeloablative regiments, are associated with the highest risk of AKI (estimates range from 36 to 78 %; 20–33 % may require dialysis).
Autologous HSCT patients enjoy the lowest risk for severe AKI, given lack of need for CNIs and decreased incidence of GVHD (incidence of AKI approximately 20 %, with roughly 7 % requiring dialysis).
2.
CKD: Survivorship has improved among HSCT recipients; as a result, long-term complications are becoming more widely recognized.
a.
CKD occurs in about 20 % of patients post-HSCT, a rate more than double that in the general population.
b.
Risk factors
i.
AKI at the time of HSCT
ii.
Total body irradiation as a part of the conditioning regimen
iii.
Certain chemotherapeutic agents (see Table 24.3)
Table 24.3
Drug-induced AKI
Mechanism of injury | Drug | Typical urinary findings |
Prerenal state | ACE inhibitors, angiotensin receptor blockers, NSAIDs, diuretics, calcineurin inhibitors, IV contrast | Urine Na < 10 mmol/L; FeNa < 1 %; Urine sediment w/ hyaline casts |
Ischemic ATN | All of the above if other prerenal factors present, such as hypotension | Urine Na > 20 mmol/L; FeNa > 1 %; Urine sediment w/ granular or “muddy brown” casts |
Nephrotoxic ATN | Vancomycin, aminoglycosides, IVIG, platins | As for ischemic ATN |
AIN | Penicillins, cephalosporins, quinolones, sulfa drugs, furosemide, allopurinol, NSAIDs, rifampin, proton pump inhibitors | Peripheral eosinophilia possible; Eosinophiluria possible; Sterile pyuria common; proteinuria often present |
Crystal formation/obstruction | Acyclovir, methotrexate, foscarnet, ganciclovir | Crystalluria present |
Thrombotic microangiopathy | Calcineurin inhibitors | Hematuria, proteinuria likely |
iv.
Chronic GVHD
v.
Long-term CNI exposure
24.3 General Classification of Causes of AKI and Basic Evaluation
It is useful to consider causes as prerenal (or reduced blood flow to the kidneys), intrinsic renal, and postrenal in order to have a systematic approach to evaluating a patient with AKI.
1.
Prerenal
a.
Causes
i.
Hypotension
ii.
Volume depletion secondary to vomiting, diarrhea, poor fluid intake, etc.
iii.
Hypercalcemia
iv.
Hepatic SOS
v.
Medications (CNIs, nonsteroidal anti-inflammatory drugs (NSAIDs), angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers, diuretics)
vi.
Hypoalbuminemia
b.
If the kidney is otherwise functioning normally, reduced renal blood flow will result in a sodium-avid state. The laboratory hallmark is a low spot urine sodium value (< 10–20 mmol/L) or a FeNa of < 1 %. Patients exposed to diuretics, however, may be volume-depleted with a high urine sodium concentration.
2.
Intrinsic renal
a.
Causes
i.
Acute tubular necrosis (ATN) due to prolonged prerenal state (see above)
ii.
Sepsis or drug toxicity
iii.
Intravenous (IV) contrast-induced nephropathy
iv.
Thrombotic microangiopathy (TM)
v.
Allergic interstitial nephritis (acute interstitial nephritis (AIN), drug reaction)
b.
Urinalysis is often abnormal when there is intrinsic renal damage.
i.
Muddy brown casts are seen in ATN.
ii.
Sterile pyuria with or without white blood cell (WBC) casts is typical for AIN.
iii.
Hematuria and proteinuria can be seen with TM
3.
Postrenal
a.
Causes
i.
Intrarenal obstruction from uric acid, phosphate, or drug crystals
ii.
Extrarenal obstruction from bladder outlet obstruction (prostatic hypertrophy or clot from hemorrhagic cystitis)
4.
Initial evaluation
a.
History, including potential nephrotoxin exposures, and careful physical examination with attention to trends in the vital signs, urine output, and estimated intravascular volume status
b.
Basic chemistries, including calcium, phosphate, and uric acid
c.
Complete blood count (CBC)
d.
Urinalysis and microscopy
e.
Spot urine for sodium, creatinine, and protein
f.
Bladder scan for post-void residual
g.
Renal ultrasound
24.4 Timing and Cause of Renal Injury
1.
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Conditioning regimen (AKI)
a.
Tumor lysis syndrome (TLS)
b.
Stem cell infusion toxicity
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