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| Year : 2002 | Volume
: 13
| Issue : 1 | Page : 50-54 |
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| Post Transplant Acute Tubular Necrosis - How Long you can Wait?: A Case Report |
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Sameer Huraib, W Al Khudair, G Al Ghamdi, A Iqbal
Department of Medicine, King Fahd National Guard Hospital, Riyadh, Saudi Arabia
Click here for correspondence address and email
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 Abstract | | |
Delayed graft function (DGF) is a common clinical problem occurring after cadaveric renal transplantation. Acute tubular necrosis (ATN) is one of the main causes of the DGF. Protracted recovery from ATN may continue for several weeks. We describe a case of prolonged oliguric ATN that lasted for more than three months with complete recovery of renal function. We discuss the contributing factors to the lengthy course of ATN and the known prophylactic and treatment strategies.
How to cite this article:
Huraib S, Al Khudair W, Al Ghamdi G, Iqbal A. Post Transplant Acute Tubular Necrosis - How Long you can Wait?: A Case Report. Saudi J Kidney Dis Transpl 2002;13:50-4 |
How to cite this URL:
Huraib S, Al Khudair W, Al Ghamdi G, Iqbal A. Post Transplant Acute Tubular Necrosis - How Long you can Wait?: A Case Report. Saudi J Kidney Dis Transpl [serial online] 2002 [cited 2021 Jan 19];13:50-4. Available from: https://www.sjkdt.org/text.asp?2002/13/1/50/33202 |
| Introduction | |  |
Delayed graft function (DGF) is a common clinical problem occurring after cadaveric renal transplantation. DGF occurs in more than half of the cadaver grafts. [1],[2] Acute tubular necrosis (ATN) is one of the main causes of the DGF with an incidence varying from 20% to 50% in the cyclosporine era. [2],[3] Protracted recovery of ATN may continue for several weeks. Persistence of oliguria in ATN is an ominous sign that usually results in allograft loss or chronic renal insufficiency. [4] Here, we describe a case of prolonged oliguric ATN that lasted for more than three months with complete recovery of renal function.
| Case Report | | |
This is a case report of a 43-year-old Saudi female who was started on dialysis in 1991. She had developed renal failure due to focal segmental glomerulosclerosis. The patient received a zero-antigen match cadaveric renal transplant on March 9, 1995. The donor was a 27-year-old man, a victim of a road traffic accident with severe brain trauma. Euro-Collins solution was used for in-situ perfusion of the donor kidney with an estimated cold ischemia time of 26 hours. There was no appreciable urine output recorded after relief of the vascular clamp at the end of the graft implantation.
As per our immunosuppressive protocol in case of oliguric ATN, the patient received anti-thymocyte globulin (ATG) and prednisone for induction of immunosuppression. The ATG was given at a dose of 10 mg/kg/ day intravenously (IV) for 14 days in the immediate post transplant period. The steroid was administered at a dose of 0.5 g intravenous methylprednisolone intraoperatively. Thereafter, the steroids were continued orally as 1 mg/kg/day prednisone, and tapered off to a final dose of 20 mg/day by decrements of 5 mg/week.
The urine output on the first postoperative day (POD) was less than 100 cc. Color Doppler and spectral analysis by ultrasonography showed increased resistive indices, suggestive of ATN or acute rejection. Additionally, it was noticed that there was a narrowing of the extrarenal segment of the renal vein and an obstructive thrombus could not be ruled out. Renal venogram was done on POD #2 to elucidate the Doppler findings. The venogram did not show occlusion of the transplanted renal vein. The patient remained oligo-anuric requiring dialytic support post operatively.
An allograft biopsy was performed on POD #7. The biopsy findings were consistent with ATN; degenerative changes in the tubules with multiple scattered hyaline casts, a slight increase in the mesangial matrix and cellularity, congested blood vessels and interstitial edema.
The patient was started on cyclosporine by the end of second week and ATG was discontinued after completing the protocol. The cyclosporine blood level was maintained between 200-250 µg/ml by the fluorescence polarization assay (TDX assay).
On POD #17 the patient developed productive cough and her chest radiograph showed extensive alveolar densities. She was intubated for severe hypoxia and required vasopressor support for low blood pressure. Bronchoalveolar lavage was positive for pseudomonas and serratia that required antibiotics including aminoglycosides. Eventually, she was discharged from the intensive care unit without improvement of renal function.
The repeated renal ultrasound showed increased echogenicity of the renal parenchyma and loss of the cortico-medullary junction; there was no perinephric fluid collection or hydronephrosis. Doppler studies ruled out the possibility of venous thrombosis. Renogram showed high perfusion index with severe reduction in both the early vascular blush and the uptake of the transplanted kidney. The renal biopsy was repeated on POD #31 and showed findings of recovering ATN and acute cellular rejection.
Based on the biopsy results, the patient was pulsed with methylprednisolone 0.5 g IV for three days with a subsequent gradual tapering of steroids.
The patient remained anuric. A third allograft biopsy was performed on POD #55 prior to discharge, which showed tubules with variable stages of necrosis and regenerative changes, normal glomeruli and unremarkable arterioles and small arteries. The patient was closely monitored in the outpatient dialysis unit and cyclosporine blood level was maintained between 150-200 µg/ml.
On the 80 th POD, the patient noticed an increase in urinary output, ranging from 300 to 700 ml/day. Her blood urea nitrogen, serum creatinine and creatinine clearance began to improve. Hemodialysis was discontinued on POD #104. The serum creatinine level decreased to 426 µmol/L on
POD #123 and 377 µmol/L on POD #137. In December 1995, the serum creatinine was 155 µmol/L and 67 µmol/l in February
1996. The renal function stabilized to blood urea nitrogen of 7-9 mmol/L and creatinine in the range of 55-78 µmol/L without proteinuria during the years 1997 and 1998. On the last follow-up in January 1999, the serum creatinine was 69 µmol/L with proteinuria quantified to 0.43 gram/day and her maintenance immunosuppression included microemulsion cyclosporin 250 mg/day in two divided doses and prednisone 7.5 mg per day.
| Discussion | | |
Renal failure persisting after renal transplantation is called delayed graft function (DGF). The definition of DGF is varied in different studies, but generally refers to anuria or requirement for dialysis after the first week post transplantation. Less than 5 percent of the kidneys with DGF never function (primary nonfunctioning). The frequency of DGF may be as low as 10% and as high as 70% in some series. [1],[2]
The major causes of DGF are acute tubular necrosis (ATN), hyperacute rejection, accelerated rejection superimposed on ischemic ATN, urinary tract obstruction or, very rarely, atheroembolic or thrombosis of the renal artery or vein.
ATN is the most common cause of DGF with an incidence varying from 20% to 50% in the cyclosporine era. [2],[3] Causes that have been implicated in the etiology of ATN include renal ischemia due to hypoperfusion in the donor, prolonged warm and cold ischemia times, harvesting conditions, surgical procedures and cyclosporine given immediately following transplantation. [5] Cyclosporine (especially at doses above 10 mg/kg per day) and prior sensitization in the retransplanted patients, have been shown to increase the incidence and duration of ATN. [6]
The majority of recipients experiencing ATN is oliguric and may require dialytic support. Onset of diuresis heralds recovery of renal function. Oliguria in reversible ATN usually lasts for 1-60 days.[7],[8] However, it may last as long as 90 days as recorded by Canafax et al. [8]
Hall et al [9] defined the onset of adequate renal function as the day post transplant on which the serum creatinine fell below 400 µmol/l without dialysis. Based on this criterion, the median time in the cyclosporine-treated patients was 25.5 days (range of 10-98 days) compared to 11.5 days (range of 1-42 days) in the azathioprine treated patients.
Chung et al [7] described a case of nonoliguric ATN associated with high dose vitamin K in which ATN lasted for 113 days. The patient was placed on dual therapy of cyclosporine 2.5 mg/kg and steroids. In our case, ATN lasted for 137 days according to Hall et al. [9] In addition, there was complete recovery of renal function in spite of the severe prolonged oligo-anuric renal failure.
Detrimental effects secondary to DGF on graft survival are subject to controversy. Some series report greater than 20% reduction in one-year graft survival, [10] whereas others reported no deleterious effect. [11],[12][,[13],[14]
Some renal transplant programs modify their immunosuppressive protocols in the presence of ATN, usually on the premise that cyclosporine or tacrolimus administration should be avoided or minimized in this situation. Various induction regimens including full and low dose cyclosporine, and protocols involving anti-lymphocytic globulin (ALG) and murine monoclonal antibody (OKT3) have been used in DGF with variable success.
Some investigators have reported an increased risk of delayed graft function following transplantation in the cyclosporine treated patients. [6] However, others have failed to document any difference in the rate of DGF with the conventional immunosuppressive drugs. [8],[11] ATN tends to become prolonged when cyclosporine is used in these settings. [15]
Administration of calcium channel blockers can prevent the acute renal vasoconstriction induced by cyclosporine. [16],[17] The long-term reno-protective effects of these agents have yet to be proven. [18],[19] Chung et al [7] treated 13 patients with DGF and ATN with a low dose cyclosporine and found no significant decrease in the one-year survival rates. However, he found that poor functional recovery of ATN or non-ATN condition could predict poor one-year allografts survival rate.
The most dangerous potential risk of the low dose cyclosporine used in the patients with DGF was the increased incidence of rejection that results in poor graft survival. On the other hand, the episodes of infection were significantly lower. Toussaint et al [15] have proposed that low dose cyclosporine in the early postoperative course of DGF was an alternative to ALG or OKT3. Others suggested the sequential use of ALG and cyclosporine. [20],[21] The cost and side effects related to the anti-lymphocyte therapy have to be considered in this approach.
In our patient, the prolonged ischemia time resulted in primary nonfunctioning allograft. Cyclosporine was not included in the induction regimen in an attempt to decrease the duration of the DGF. The initial ischemic tubular injury was worsened by the contrast media-induced nephrotoxicity. Angiogram had to be performed to rule out vascular occlusion as was evident on Doppler ultrasound. The fulminant chest infection with pulmonary failure obligated the use of aminoglycosides, adding further to the tubular injury. Furthermore, the biopsy of renal allograft was resorted to on three different occasions to evaluate the delayed function and to rule out acute rejection. These repeated and continued insults to the allograft might have contributed to the lengthy ATN that required the prolonged dialytic support.
DGF complicates management because it masks the clinical detection of post transplant events. The diagnosis of rejection is difficult to establish in patients experiencing ATN. The renal allograft biopsy remains the only definitive procedure for diagnosis, but carries the risk of hemorrhage, development of arteriovenous fistulae and possible graft loss. Brophy et al and Flechner et al[12],[13] suggested that one should be conservative in performing invasive studies in the patients with DGF. However, the core biopsy is performed in some centers at fixed intervals to ensure that the ATN is not complicated by rejection. The allograft biopsy may be especially useful in poorly functioning kidneys, particularly after 14 days of established ATN, or in the presence of signs that suggest rejection. [13] The graft with ATN usually begins to function without the requirement for any therapy more than the dialytic support and the close monitoring of renal function. [11] The criteria for dialysis and dietary management during this period are the same as any other postoperative renal failure. Care should be given to avoid hypotension and excessive fluid removal to avoid graft hypoperfusion.
| References | | |
| 1. | Taylor RJ, Zheng S, Ptachinski R, Rosenthal JT, Hakala TR. Cyclosporine therapy independent of graft diuresis in cadaveric renal transplants. Transplant Proc 1986;18(Suppl 1):5-7.  |
| 2. | Toledo Pereyra-LH, Whitten JI. Comparison of the incidence and effect of ATN in the cyclosporine and ALG eras. Transplant Proc 1988;20:910-2. |
| 3. | Chung YC, Huang MT, Chang CN, et al. Prolonged nonoliguric acute renal failure associated with high-dose vitamin K administration in a renal transplant recipient. Transplant Proc 1994;26:2129-31. [PUBMED] |
| 4. | Traindl O, Langle F, Reading S, et al. Secondary hyperparathyroidism and acute tubular necrosis following renal transplantation. Nephrol Dial Transplant 1993;8:173-6. |
| 5. | A randomized clinical trial of cyclosporine in cadaveric renal transplantation. N Engl J Med 1983;309:809-15. |
| 6. | Taylor RJ, Landreneau MD, Makowda LL, et al. Cyclosporine immunosuppression and delayed graft function in 455 cadaveric renal transplants. Transplant Proc 1987;19: 2100-3. |
| 7. | Chung YC, Lee PH, Hu RH, et al. The outcome and delayed graft function in cadaveric renal transplants treated with low dose cyclosporine. J Formos Med Assoc 1991;90:975-80. [PUBMED] |
| 8. | Canafax DM, Torres A, Fryd DS, et al. The effects of delayed function on recipients of cadaver renal allografts. A study of 158 patients randomized to cyclosporine or ALGazathioprine. Transplantation 1986;41:177-81. |
| 9. | Hall BM, Tiller DJ, Duggin GG, et al. Post-transplant acute renal failure in cadaver renal recipients treated with cyclosporine. Kidney Int 1985;28:178-86. [PUBMED] |
| 10. | Najarian JS, Fryd DS, Strand M, et al. A single institution, randomized, prospective trial of cyclosporine versus azathioprineantilymphocyte globulin for immunosuppression in renal allograft recipients. Ann Surg 1985;201:142-57. [PUBMED] [FULLTEXT] |
| 11. | Fischer J, Kirste G, Keller H, Wilms H. Does ATN influence renal transplant function negatively? Transplant Proc 1988;20:908-9. [PUBMED] |
| 12. | Brophy D, Najarian JS, Kjellstrand CM. Acute tubular necrosis after renal transplantation. Transplantation 1980;29:245-8. [PUBMED] |
| 13. | Flechner SM, Payne WD, van-Buren C, Kerman R, Kahan BD. The effect of cyclosporine on early graft function in human transplantation. Transplant 1983;36:268-72. |
| 14. | Belitsky P, McDonald AS, Gajewski J, et al. Significance of delayed function in cyclosporine-treated cadaver kidney transplants. Transplant Proc 1987;19:2096-9. |
| 15. | Toussaint C, Kinnaert P, De Pauw L, et al. Comparison of low doses of cyclosporine with azathioprine immunosuppression during the first year following transplantation. Transplant Proc 1986;18:1256-8. |
| 16. | Ruggenenti P, Perico N, Mosconi L, et al. Calcium channel blockers protect transplant patients from cyclosporine induced daily renal hypoperfusion. Kidney Int 1993;43: 706-11. [PUBMED] |
| 17. | Palmer BF, Dawidson I, Sagalowsky A, Sandor Z, Lu CY. Improved outcome of cadaveric renal transplantation due to calcium channel blockers. Transplantation 1991;52:640-5. [PUBMED] |
| 18. | Chrysostomou A, Walker RG, Russ GR, et al. Diltiazem in renal allograft recipients receiving cyclosporine. Transplantation 1993;55:300-4. [PUBMED] |
| 19. | Ladefoged SD, Pedersen E, Hammer M, et al. Influence of diltiazem on renal function and rejection in renal allograft recipients receiving triple-drug immunosuppression: a randomized, double-blind, placebo-controlled study. Nephrol Dial Transplant 1994;9:543-7. [PUBMED] [FULLTEXT] |
| 20. | Sollinger HW, Deierhoi M, Kalayoglu M, Belzer FO. Sequential antilymphocyte globulin cyclosporine therapy in cadaver renal transplantation. Transplant Proc 1986;18:16-8. |
| 21. | Sommer BG, Henry ML, Ferguson RM. Sequential conventional immunotherapy with maintenance cyclosporine following renal transplantation. Transplant Proc 1986;18:69-75. |
Correspondence Address:
Sameer Huraib
Department of Medicine, King Fahd National Guard Hospital, P.O. Box 22490, Riyadh 11426
Saudi Arabia
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PMID: 18209413 
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