Nephrolog

What is a “sensitized” potential recipient?
A “sensitized” potential recipient is an individual that has detectable preformed HLA antibodies
that pose considerable future risk to the allograft survival. Patient sensitization is classically
reported as the percent panel reactivity antibody (PRA). PRA is defined as the percentage of
donors expected to react with a patient’s serum based on known antibody activities (i.e., the
patient’s degree of sensitization). Approximately 17% of the patients currently on the deceased
donor waiting list are highly presensitized (defined as .80% percent panel reactivity). Highly
“sensitized” patients often cross-match positive to multiple potential donors and require a zero
antigen mismatch allograft to increase success. Consequently, these “sensitized” patients are
less likely to be transplanted or will spend an extended time on the wait-list pending the
availability of a suitable donor

What are some ways that potential recipients become sensitized?
n Pregnancy
n Exposure to antigens from previous transplants
n Exposure to antigens from blood product exposure (e.g., transfusions)

. What are some methods to desensitize potential recipients who possess
preformed HLA antibodies?
n Intravenous immunoglobulin
n Plasmapheresis
n Rituximab
n Splenectomy

Something about transplantation

1. What are the various categories of living-donor transplants?
n Related donors: Donor and recipient are biologically related.
n Unrelated donors: Donor is not biologically related, but an emotional relationship exists
between the donor and recipient (e.g., coworkers, classmates, friends).
n Directed anonymous donors: Donor has no relationship to the recipient; the donor learned
of the recipient’s situation and decided to donate altruistically.
n Undirected anonymous donors: Donor decides donate his or her kidney to the waiting list.
n Paired exchange donors: A pair of donor–recipient candidates (from the related or
unrelated categories) enters into a scheme in which the donor is exchanged with another
donor–recipient candidate pair so as to achieve donor–recipient biologic compatibility of
the ABO blood group system and/or negative cross-match reactivity.
n Multiple paired exchange donors: A paired exchange donation as described in the preceding
section and involves more than two donor–recipient candidate pairs.
2. What do SCD, ECD, DCD, and DBD stand for?
n SCD 5 standard criteria donor
n ECD 5 expanded criteria donor
n DCD 5 donation after cardiac death
n DBD 5 donation after brain death
3. What is an expanded criteria donor?
An expanded criteria donor is .60 years old or age 50 to 59 years old and has two of the
following: cerebrovascular accident as the cause of death, pre-existing hypertension, or terminal
serum creatinine greater than or equal to 1.5 mg/dL. Expanded criteria donors have a 70%
increased risk of graft failure over standard criteria donors.
Metzger RA, Delmonico FL, Feng S, et al. Expanded criteria donors for kidney transplantation. Am J Transplant
2003;3(Suppl 4):114–125.
4. What is the difference in graft survival among living donor transplants,
standard criteria donor transplants, and expanded criteria donor transplants?
See Figure 56-1.
5. What are some general contraindications for kidney donation?
n Chronic kidney disease (glomerular filtration rate ,80 mL/min/1.73 m2)
n Proteinuria
n Hematuria
n Active infection
n Chronic, active viral infections (e.g., HIV, hepatitis B/C)
n Active malignancy
n Family history of renal cell carcinoma
n Hypertension
n Diabetes
 n Urologic abnormalities, including nephrolithiasis
n Substance abuse
n Obesity (body mass index .35 kg/m2)
n Age younger than 18 years

How is a living kidney donor evaluated to determine suitability?
The evaluation of a potential living kidney generally begins with an assessment of the donor
and recipient blood groups and a cross-match. When a potential donor is identified, a crossmatch
is performed prior to transplantation to evaluate for any evidence of preformed
antibodies against the specific donor (human leukocyte antigens [HLA]) that could result in
hyperacute and/or acute humoral rejection. A final cross-match using fresh serum is
performed in all cases immediately preceding transplantation to ensure compatibility between
the donor and recipient. The methods available for cross-match testing include: enzyme-linked
immunosorbent assay (ELISA), flow cytometry, complement-dependent cytotoxicity, and
single antigen bead assay.
The donor and recipient generally must be ABO compatible. This can occur under one of
the following circumstances: the donor and recipient are ABO identical, the donor has blood
type O (universal donor), or the recipient is blood type AB (universal recipient). Given the
distribution of blood group antigens in the United States, the waiting time on the deceased
donor list is prolonged for patients with blood group O and B. The practice of donor swapping
in the case of ABO mismatches with a willing acceptable donor has gained some favor in the
United States. ABO-incompatible transplantations following desensitization strategies have
been performed successfully at some institutions.
Rh antigens are not expressed in kidney tissue; therefore Rh mismatches are not
considered to play a substantial role in allograft rejection. Female Rh-negative recipients ofchildbearing age are at risk for sensitization when the donor is Rh-positive and should receive
anti-Rh immunoglobulin (RhoGAM) at the time of transplantation.
The major histocompatibility complex (MHC) antigens measured routinely in HLA
laboratories include the class I antigens (A, B, and C) and class II antigens (DP, DQ, DR). HLA
matching is an important predictor of survival of deceased donor allografts. However, with the
use of better immunosuppressive agents, the use of HLA matching in allocation policies has
come under considerable debate. A recent study demonstrated that with each successive year
from 1994 to 1998, ever-increasing degrees of HLA mismatching was required to have a
statistically significant adverse effect on graft failure. It also appears that not all HLA
mismatches confer the same risk. HLA-DR matches have been associated with the most
beneficial effect on long-term allograft survival. As a result, some centers advocate matching
schemes to include kidneys without DR mismatches even if mismatched at the A and B loci.
Given the scarcity of kidneys, the reliance on the number of HLA mismatches to determine the
compatibility of a particular donor/recipient pairing is likely to be replaced by a determination
of the significance of each mismatch on future graft survival.
Why are renal imaging tests performed in living kidney donors prior to
transplantation?
n To ensure the presence of two kidneys
n To exclude malignancy involving the urinary tract
n To exclude anatomic abnormalities of the urinary tract
n To assess the vascular supply to the donor kidney
8. What are some common imaging tests performed to evaluate the donor
kidney?
n Helical computed tomography (CT)
n CT angiogram
n Magnetic resonance angiogram
9. What are the surgical risks to the donor?
Laparoscopic surgical techniques have resulted in shorter hospital stays, reduced incisional
pain, and an earlier return to work for living donors when compared to open nephrectomies.
Conversion to open nephrectomy occurs in approximately 2% of the procedures. The
perioperative mortality reported for living kidney donation is approximately 0.03%. Bleeding
and reoperation are more common in laparoscopic techniques, although they are still relatively
rare (0.45% and 1%, respectively).

Some Nephrolog

Randomized controlled studies consistently demonstrate that normalizing the Hb level
of patients with CKD with ESAs is associated with poorer outcomes than a Hb target in
the 9.0 to 11.5 g/dL range.

The characteristic lipid profile of patients with chronic kidney disease consists of high
triglycerides and low high-density lipoprotein (HDL) cholesterol concentrations,
whereas total and low-density lipoprotein (LDL) cholesterol are normal or even low.

Membranous nephropathy occurs as an idiopathic (75% of cases) or secondary disease
(autoimmune diseases, infection, and malignancies), where up to 70% of patients will
have nephrotic syndrome at the time of presentation. It is a chronic disease, with spontaneous
remission and relapses clearly documented.

 Current data suggest that new therapeutic agents such as rituximab and synthetic
adrenocorticotropic hormone (ACTH) are effective in reducing proteinuria while having
few adverse effects.

. MN can recur after kidney transplantation in approximately 42% of patients, causing
proteinuria, allograft dysfunction, and graft failure. Recurrence most often occurs during
the first year.

 Immunoglobulin A (IgA) nephropathy is the most common biopsy-proven primary
glomerulonephritis in the world.

 The classical presentation is painless gross hematuria 2 to 3 days after an upper respiratory
infection.

Hyponatremia

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Nephrolog

*Use of loop diuretics should be limited to the management of patients with volume
overload and not for AKI or oliguria per se.

* It is not necessary to wait until severe uremia develops to initiate dialytic support; renal
replacement therapy should be used as a supportive therapy in the presence of progressive
azotemia and oliguria, rather than a rescue therapy for late manifestation of AKI.

*It is well established that individuals with CKD have a 10- to 20-fold increased risk for
cardiac death compared to age-matched and gender-matched controls without CKD.

*The weight loss drug orlistat rarely may cause acute kidney injury and nephrolithiasis
because its use may lead to intestinal malabsorption and enteric hyperoxaluria.

*. The antiseizure and migraine drug topiramate is a carbonic anhydrase inhibitor that is
associated with proximal renal tubular acidosis and calcium phosphate stone formation.

*The natural history of the primary nephrotic syndrome depends on the underlying cause.
Thus, patients with minimal change nephrotic syndrome (MCNS) have an excellent
long-term prognosis, in contrast to those with primary focal segmental glomerulosclerosis
(FSGS), in whom nearly 50% will progress to end-stage renal disease (ESRD) over 5 to
10 years of follow-up, and 25% to 30% of these patients may experience recurrent
disease in a kidney transplant.