Kidney Transplant
Mona D. Doshi, MD
Options for RRT
Dialysis Pt survival QOL:
3/wk for 4 hours Dietary restriction Travel restriction
Transplant Reduces by 70% Improves QOL
Expensive Rx
Saves $50,000/yr after 3 years
Challenges after transplant
Immunosuppression Maintaining adequate graft function Minimizing Death
Why Immunosuppression?
Kidneys are donated from either living or deceased donor In either case they do not belong to the recipient and therefore is likely to be attacked by recipient‟s immune system i.e REJECTION FOOL IMMUNE SYSTEM WITH IS
Recognition of self from non-self
HLA Class I
HLA Class II
Present on all cells Help to combat viral infections & cancer
Macrophages, APC Bacterial infections
HLA provides the platter to present the antigen to the T-cells to trigger immune system
Antigen Presentation
Cellcept Rapa
CNI
Steroids
Side effects of IS medications
Calcineurin inhibitors
Nausea & Vomiting Renal vasoconstriction- decreased kidney function Headache, tremors Electrolyte issues
Anti-Proliferative (Cellcept/ AZA/ Rapa)
Bone marrow suppression GI
Steroids
ALWAYS ORDER CBC & CHEM-7
Metabolism- Cytochrome P450, 3A4
INCREASED Amiodarone (A) diltiazem/verapamil (BCD) erythromycin/ (E) clarithromycinketocona zole/itraconazole/flucon azole (F) grapefruit juice (G)
DECREASED phenytoin phenobarbital rifampin carbamazepine
PLEASE CALL BEFORE STARTING ANY NEW MEDICATIONS
INFECTIONS
Time table for infections
CMV (40 day fever)
D+/R- after stopping prophylaxis Fever, GI, Pneumonitis, hepatitis Leucopenia CMV PCR or CMV Ag Reduce IS (Cellcept) Valcyte 900 mg bid/Ganciclovir 5mg/kg bid Cytogam 400mg/kg
Complications of CMV
Death Other virus infection
HSV-6 co infection with CMV HSV-8 Kaposi Parvo B-19 red cell aplasia
Increased risk of rejection
BK virus
Present in uroepithelium Rising creatinine Urine decoy or urine/serum PCR Renal allograft biopsy Decrease IS (Cellcept) No effective Rx.. Prevention better than cure
Urinary Tract Infection
Predisposing factors: Women, obesity, stent, prednisone Enterococci is most common within first 6 months. A third were resistant to Vancomycin.
E.coli is the most common pathogen thereafter but again a third were resistant to Bactrim.
Candida glabrata most common in obese females. Quickly progress to pyelonephritis and shock
Pneumonia
CAP common after 6 months PJP, Fungal & Viral pneumonias
Underlying lung disease Snorting cocaine or other drug use
Multiple organisms may be the offenders on some cases due to super-infection
TIPS
Fewer clinical manifestations of infections Less likely diagnosis by conventional radiography
CXR > CT Scan of chest
“Gold standard” is tissue histology Limited usefulness of serological diagnosis-think PCR or ELISA More likely antibiotic resistant organisms Antibiotics not useful with undrained fluid collections
Renal dysfunction
Decline in graft function beyond first week
Pre-renal: decreased po intake Renal:
Acute rejection Recurrent disease Nephrotoxicity of CNI ± Rapa (TTP) BK nephropathy
Obstruction
Acute Rejection
10-15% Fever, graft pain uncommon Rise in creatinine Kidney biopsy
Recurrent disease: FSGS
Presents as sudden onset proteinuria ± allograft dysfunction. Bx normal but EM FP effacement
The overall recurrence rate is 30%. Risk factors for recurrenceyoung patients h/o rapid onset proteinuria h/o rapid progression to ESRD h/o recurrence in the prior graft (70%)
Treatment
1.5 L of plasma to be pheresed every other day for 5-10 days to be replaced with albumin IVIg Rituximab
Recurrent disease - TTP
CNI ± Rapa CSA induced endothelial injury ± CMV Fever, HTN, declining renal function, low platelet, hemolytic anemia
Renal bx: glom & arteriolar thrombi Stop the drug Switch to Prograf/ Rapa PP ± anticoagulation 50% risk for graft loss
BK virus- interstitial nephritis
Present in uroepithelium Rising creatinine Urine decoy or urine/serum PCR Renal allograft biopsy Decrease IS (Cellcept) No effective Rx.. Prevention better than cure
Urinary Obstruction
Extrinsic
lymphocele - may also cause allograft dysfunction without hydronephrosis urinoma hematoma/seroma ureteral stricture - usually ischemic if lower polar artery ligated or missed - may have an infarcted lower pole of kidney) extensive „stripping‟ of distal ureter by donor surgeon anastomotic stenosis clot/stone
Intrinsic
Characteristics of fluid collections
Lymphocele Seroma Urinoma
Creatinine
Same as serum
Same as serum
Higher than serum same as urine
Albumin
Very low
Similar to serum Variable - usually absent Same as blood Same as blood
Cell type (low count in all) Culture
Predominant lymphocytes positive if infected
positive if infected
positive if infected
Donor surgery
Textbook of Surgery, Sabiston, 15th Ed, Fig. 20-12
•In deceased donor harvests, renal arteries are on a Carel patch (aorta) •In en-bloc transplants, both kidneys with a segment of aorta /IVC are used. •In living kidney harvests, no patch of aorta, ureters are shorter.
The „back table‟
Textbook of Surgery, Sabiston, 15th Ed, Fig. 20-14
Transplant surgery
Usually extraperitoneal: •in an isolated kidney transplant (1st or 2nd). Can be intraperitoneal: •if multiple organs, •multiple prior transplants, or •if anastomosis to ‘high vessels’ are required. Textbook of Surgery, Sabiston, 15th Ed, Fig. 20-13
Urine leak
Site: at the anastomosis of ureter to bladder. or at site of ureteral necrosis Usually within the 1st week but may be delayed for several weeks especially if anuric initially. Manifestation: extra peritoneal
fluid drainage from wound perinephric fluid collection hydronephrosis with obstruction from urinoma scrotal swelling new pain over allograft
persistent ileus diffuse abdominal pain rise in serum creatinine
If Intra peritoneal
Investigation for urine leak
Wound fluid creatinine or creatinine from fluid collection. Compare with serum and urine creatinine Isotope renography:
99Tcm
Mag3
perinephric leak peribladder leak
Management:
Conservative - percutaneous nephrostomy, stent placement Definitive
revision of neocystoureterostomy uretero-ureterostomy or pyelo-cystostomy
Other problems
NEPHROTOXICITY GI PTDM BONE METABOLISM LIPIDS ELECTROLYTE DISORDERS
CALCINEURIN INHIBITORS
Afferent arteriole of glomerulus without CyA or FK
AA with CyA or FK present
Potentiate nephrotoxic effects
NSAIDs COX2s Amphotericin B aminoglycosides
Acyclovir ACEIs
GI PROBLEMS POST TRANSPLANT
Nausea, Vomiting, decreased appetite Diarrhea Upper / Lower GI bleeding Esophagitis Cellcept/ Rapamycin induce mucosal changes Pancreatitis
POST TRANSPLANT DM
More likely with tacrolimus than cyclosporine (debate) Steroids increase risk African-Americans, Native Americans(?) at greater risk Hepatitis C and may be CMV Obesity, family history, older age
ELECTROLYTE PROBLEMS POST TRANSPLANT
Na: salt sensitive hypertension vs. salt wasting
K: hyperkalemia (CNI) vs. hypokalemia (Rapa)
HCO3: tubular acidification (type 4 RTA)
Mg: wasting (more with Prograf) Ca: hyperparathyroidism PO4: hyperparathyroidism vs. tubular leak vs. Vit D lack
HEMATOLOGIC PROBLEMS AND RT
RBC
Anemia erythrocytosis Leukopenia: which cell line? The problem with rapamycin
WBC
PLATELETS
POST TRANSPLANT ANEMIA
Erythropoietin levels
Rise w/in first 24 hrs but transient Smaller, sustained rise at 1 week
Drugs
Causes of anemia
MMF, Azathioprine, Sirolimus ACEI/ARB Folate metabolism: SMX-TM
Chronic inflammation Graft dysfunction Iron status Virus: CMV, Parvovirus B19
PTE
DEFINITION First described 1965 10-20% patients-Lower now? Hct>51%, absolute increase in RBC mass Other causes excluded CHARACTERISTICS Associated w/ CyA use ACEI/ARB lower Hct by RBC production
Deaths in renal transplant recipients
Cardiovascular disease Infections
TAKE HOME POINTS
Low threshold to admit Infection: Need microbiological or tissue diagnosis CVD is common Always call a transplant nephrologist before starting new medications Avoid placing femoral line on the side of the allograft