RENAL DATA FROM THE ARAB WORLD
Year : 2008 | Volume
: 19 | Issue : 4 | Page : 651--657
Early Non-Immunological Post Transplant complications: A Single Center Experience
Wael Latif Jabur, Hareth M Mohammed Saaed, Khalid Abdulla
Department of Nephrology, Al-Karamah Teaching Hospital, Baghdad, Iraq,
Wael Latif Jabur
Department of Nephrology, NMC Specialty Hospital, P.O. Box 7832, Dubai, UAE
To assess non-immunological complications affecting renal transplant patients in the first six months after transplantation in Al-Karama hospital, Baghdad, Iraq, we studied 68 patients (49 males, 19 females) attending the clinic during the year 2006. Forty six (67%) patients received kidneys from related and 22 (33%) from unrelated donors. The patients revealed the following complications: post transplant hypertension in 28 (41%) patient, infection (mostly bacterial) in 27 (37%), new onset diabetes in 11 (16%), calcineurin inhibitor toxicity in 10 (14%), anemia in 8 (12%), surgical complications in 7 (10%), slow graft recovery in 4 (6%), cardiovascular complications in 3 (4%), and Kaposi sarcoma in 2 (2.9%).Transient hyperglycemia, hypertension, infection and diabetes mellitus were the commonest early complications of renal transplantation. The incidence of complications is comparable to the average reported in the literature, especially in this region of the world.
|How to cite this article:|
Jabur WL, Mohammed Saaed HM, Abdulla K. Early Non-Immunological Post Transplant complications: A Single Center Experience.Saudi J Kidney Dis Transpl 2008;19:651-657
|How to cite this URL:|
Jabur WL, Mohammed Saaed HM, Abdulla K. Early Non-Immunological Post Transplant complications: A Single Center Experience. Saudi J Kidney Dis Transpl [serial online] 2008 [cited 2013 May 18 ];19:651-657
Available from: http://www.sjkdt.org/text.asp?2008/19/4/651/41334
Adverse outcome for some transplant recipients, including peri-operative mortality and graft rejection are encountered in various degrees in all centers around the world.  In Iraq, there are several centers for kidney transplantation.
We conducted this study to evaluate shortterm non-immune complications during the first six months after renal transplantation in patients followed up in our center, which is one of the biggest transplant centers in the country.
Patients and Methods
We studied 68 patients (49 (60%) males, 19 (40%) females) who received renal transplantation and attended Al-Karama transplant clinic, Baghdad, Iraq, for follow up in the second half of 2005 and first half of 2006. Sixty one (90%) patients received their allografts in our center. Age of patients ranged from 13 to 50 years. Before transplantation all patients underwent regular hemodialysis for periods ranging from 2 months to 2 years.
In most patients the cause of renal failure was unknown. Otherwise, renal stone disease, diabetes mellitus, systemic lupus erythematosus, polycystic kidney disease and chronic glomerulonephritis were the main causes.
Forty six (67%) patients had related donors with 50% or more HLA histocompatibility, while 22 (32%) patients had unrelated donors with HLA histocompatibility of 25% or zero. No cadaver transplantation is performed in Iraq. We used Basiliximab for induction and triple maintenance therapy that included prednisolone, cyclosporine and azathioprin or prednisolone, tacrolimus and mycophenolate mofetil (MMF) depending on whether the patient is high risk or not. Adjuvant therapeutics for all patients included deltiazem, simvastatin, trimethoprim, gancyclovir, and Alfa-calcidol.
The term slow graft recovery was used to describe grafts that did not function promptly in the immediate days after operation so that serum creatinine remained above 3 mg/dl during the first week, but dialysis was not needed.  On the other hand, delayed graft function was used to describe grafts that did not function properly so that dialysis was needed during the first week after operation. 
Serum levels of cyclosporine and tacrolimus was available only for few patients who could afford doing it outside the country. Our criteria to diagnose calcineurin inhibitor toxicity was renal impairment in the presence of high serum level (C2 level more than 300 ng/ml for cyclosporine and a trough level more than 20 ng/ml for tacrolimus) if available. Otherwise, we depended on the following criteria that included blood urea to creatinine ratio more then 40, improvement of renal function within 2-4 days after decreasing the dose of calcineurin inhibitor, absence of clinical signs of rejection such as local tenderness and oliguria, hyperkalemia, and hypertension.
Two readings of blood pressure above 140/90 within one week indicated post transplant hypertension if the patient was normotensive before operation or was hypertensive but his blood pressure was well controlled by treatment before operation and deteriorated despite continuing the same treatment. ,
We adopted the definition of post transplant diabetes of American Diabetes Association and World Health Organization (WHO), which state that new onset diabetes mellitus (NODM) is diagnosed with two measurements of fasting blood sugar of 126 mg/dl or above.  However, we defined post transplant hyperglycemia as elevated blood glucose during the first few days post transplantation and normalized there-after without additional therapy. In all of them pre operative history of diabetes mellitus was negative.
[Table 1] shows the various complications encountered in the first six months after transplantation. Four (6%) patients had slow graft recovery. There was no case of delayed graft function. Ten patients (14%) were diagnosed as having renal impairment secondary to calcineurin inhibitors; in all of them, renal function normalized after readjustment of dose.
Twenty eight (41%) patients whose blood pressure was well controlled by treatment before surgery developed post transplant hypertension. In most of them, hypertension was moderate to severe requiring two or three antihypertensive drugs. They were treated with calcium channel blocker deltiazem or long acting nifedipine plus angiotensin converting enzyme inhibitors (ACEI) or B-Blockers adjusted to heart rate and renal function. Accelerated hypertension (diastolic blood pressure above 120 mm mercury in the absence of end organ damage) was seen in three (12%) patients. Malignant hypertension (diastolic pressure above 120 mm. mercury with signs of end organ damage) was not encountered.
Eleven (16%) patients developed post transplant diabetes mellitus. In all of them blood sugar was controlled with oral hypocemic agents without insulin; onset was in the 1st week in one patient and during the sixth month in the rest. Thirty five (51%) patients developed hyperglycemia in the first few days after transplantation, which normalized spontaneously. None of the patients in either group was a known diabetic before transplantation.
[Table 2] shows the surgical complications in 7 (10%) patients; urinary leak in 4 patients necessitating re-implantation in one, Lymphocele in 2 (3%), and renal artery thrombosis in one.
[Table 3] shows that 25 (37%) patients developed infection during the first 6 months. Among these, 6 developed acute pyelonephritis; 2 of them associated with renal impairment. In one of these patients the diagnosis was made by renal biopsy performed to exclude rejection. Other cases of infection included 3 patients with herpes zoster, 2 with newly acquired pulmonary tuberculosis, and one who converted to CMV positive state 2 months after transplantation.
Three (4%) patients developed acute coronary syndrome (unstable angina); one in the first post operative day, the other after three weeks, and the third after one month.
Eight (12%) patients were anemic throughout the first six months. Hemoglobin level ranged from 9-11 g/dl. The anemia was normochromic normocytic in 7 patients and macrocytic in one. There was no apparent cause for the anemia.
Two (2.9%) patients developed skin Kaposi sarcoma, and one (l.5%) patient developed hemolytic uremic syndrome. His renal function improved with reduction of cyclosporine dose.
Post transplant hypertension is very common with an incidence of more than 50% in most centers. ,, It is also an important determinant of graft survival.  The incidence of 41% uncontrolled hypertension in our study was not unexpected. In addition, the drugs we used have been shown to have comparable efficacies. 
Our patients who developed NODM were all euglycemic before transplantation. They developed hyperglycemia within the first month after transplantation. The probable risk factors are higher doses of calcineurin inhibitors and steroids in our protocol. A similar incidence was reported by some , and a higher incidence by others.  In USRDS (US Renal Data System) registry  the incidence was 16-24% with significant correlation with a Tacrolimus based immunosuppression protocol.
In our study, 51% developed post-transplant transient hyperglycemia; 4 (11%) of them only developed NODM later on. In Mathew et al  study the glucose tolerance was abnormal in 42% of the patients, of those only 18% developed NODM although they had done the glucose tolerance test 2 6 weeks post-transplantation. Transient hyperglycemia is mostly related to the dose of steroids and cyclosporine. The higher incidence of NODM in Mathew's study probably reflects the higher incidence of diabetes mellitus in the general population in India. We did not perform glucose tolerance tests to exactly assess the prevalence of impaired glucose tolerance. The importance of hyperglycemia and its probable relation to future diabetic state is still debatable and need further study.
The incidence of slow graft recovery in our study was low, and probably related to vascular surgical difficulties due to size incompatibility or vascular anomaly. No case of delayed graft function or acute tubular necrosis was encountered. The fact that we only do live donor transplantation seems to contribute to this result. The incidence of both is higher in centers performing deceased kidney transplantation, even in preemptive transplantation. ,, Incidence of 18% was reported by some. 
Acute reversible calcineurin inhibitor toxicity was observed in 14% of our patients. This high incidence is probably due to the high dose of the calcium inhibitors in our transplant protocol. Renal impairment was accompanied with anemia and hypertension; all were corrected when the dose of calcineurin inhibitors was adjusted.
Acute pyelonephritis was the most frequent infection, accounting for 24% of all infections. A similar incidence was reported by Al-Wakeel  in Saudi Arabia. It occurred early in the  post-transplantation period. Canivet et al  reported reflux in 9 (52%) of their 17 patients with pyelonephritis demonstrated by radioisotope micturating cystography. No ureteric stenosis or vesico-ureteric reflux could be demonstrated by micturating cystography in our patients, and this discrepancy may be related to the higher sensitivity of the radioisotope method compared to the radiological micturating cystography.
Bacterial pneumonia was observed in 3 (12% of the cases with infection) patients. A similar incidence was reported by AlWakeel.  Cholecystitis occurred in one patient and was mild. No stones were encountered, unlike the cases of Sarkio et al  which caused significant morbidity and mortality with and without gallstones.
Cytomegalovirus (CMV) disease was diagnosed in one patient. Other studies reported higher incidence (5-20%).  This is probably attributable to Gancyclovir prophylaxis that we applied to all our patients for the first three months and is comparable to the findings of Sagedal et al  who concluded that pre-emptive treatment of CMV infection is associated with very low risk of CMV disease. It may also be related, as was suggested by some,  to using Basiliximab instead of OKT3 for induction of immunosuppression.
Two patients developed hepatitis and were HBs Ag positive after transplantation, and one patient developed hepatitis C seroconversion. These satisfactorily low rates are probably related to the fact that we only accept virologically negative candidates for transplantation. Finally, post transplant herpes zoster was observed in three patients.
Our results showed a significantly higher incidence of bacterial than viral infections in the first six months after transplantation (77% vs. 28%) which is similar to the experience in Saudi Arabia.  The North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) data demonstrated equal incidence of viral and bacterial infections.  The difference is probably related to the difference in age and geographic location.
Pulmonary tuberculosis was diagnosed in 2 (2%) patients. Although their past history was negative for tuberculosis we feel the condition was more likely a reactivation rather than a new infection because it occurred early after transplantation. In comparison, the incidence was 5% in Al-Wakeel  and Shankar et al studies;  mostly miliary tuberculosis.
Anemia was observed in 8 (12%) patients. In comparison, the incidence was higher in Nampoory et al study  from Kuwait (52%) and the cause was related to erythropoietin deficiency or resistance, which might also be the cause in our patients. Yorgin et al  reported an 80% incidence of anemia in transplanted children and young adults during the first 6 months after transplantation. The causes were multiple including allograft failure, drug effect, iron deficiency and bone disease.
Surgical complications were reported in 7(9%) patients. Al-Wakeel  study found 18.4% incidence of lymphocele and urinary leak, while renal artery thrombosis occurred in one patient. In addition, Samhan et al  found 9.5% incidence of lymphocele in recipients of deceased allografts.
Kaposi sarcoma was diagnosed in 2 (3%) patients; both developed lesions limited to the skin and improved by discontinuation of MMF or azathioprine and optimization of cyclosporine, tacrolimus, and steroids. The incidence was comparable to other regional studies, , however, higher than that in western countries and America; the incidence parallels that of the HHV8 in the general population. 
Calcineurin related hemolytic uremic syndrome incidence was 1.5%, and it was treated conservatively by reducing the dose of cyclosporine and optimization of MMF and prednisolone. Ardalan found 3 14% incidence. 
We conclude that our study found that post transplant hyperglycemia was the commonest early complication of renal transplantation. The incidence of post transplant hypertension and new onset diabetes mellitus was comparable to that in other parts of the Middle East and worldwide. Bacterial infection predominated the early infections after transplantation.
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