Post renal transplant hypertension? -

what are you trying to say? post renal transplant can cause hypertension? read what is renal transplant and its complications.... Post transplant complications Khalil ullah, Iftikhar R, Moin S and Badsha S. M.H. Kharian, C.M.H, M.H, A.F.P.G. M.I Rawalpindi, SUMMARY Objective: To review complications, mode of mortality in our patients population and describe autopsy findings. Design: A retrospective data based study of renal transplant complications and autopsy findings in two cases. Place and duration of study: The study was conducted at Military Hospital, Combined Military Hospital and pathology Dept, Army Medical College, Rawalpindi over a period of 23 months. Subjects and methods: Post-transplant complications in 41 patients were studied alongwith autopsy findings of two cases related to some of these complications. Results: Renal disease requiring transplantation were glomerulonephritis (61%), hypertension (24.4%), diabetic nephropathy (4.9%), hypertension with diabetic nephropathy (4.9%), nephrotoxicity (2.4%) and renal calculi (2.4%). Thirty eight of the donors were live related. Complications after transplantation included rejection, jaundice, acute tubular necrosis, diabetes mellitus, renal stones, acute myocardial infarction, hydronephrosis, accidental damage, septicaemia, cardiac failure and urinary fistula. Deaths in 13 cases were due to hyperacute rejection, acute rejection, hepatic failure, cardiac failure, septicaemia, diabetes mellitus and generalized fungal infection. Autopsy findings in one case showed generalized fungal infection and in other renal vessel thrombosis with infarction of allograft kidney. Conclusion: Transplantation is a procedure that needs state of the art approach thoughout this modality of therapy to avoid myriads of complications. Autopsy is educating and helps in understanding its pathophysiology and complications. Key words: Renal Transplantation, Complications, Autopsy INTRODUCTION Renal transplantation is the best solution for end stage renal disease1 though limited in this country due to lack of facilities and non-availability of the kidneys2. Although allograft rejection is the major complication of transplantation3, the problem has been overcome to a larger extent by better HLA matching4 and improved immunosuppressive regimens5. This has resulted in longer graft survival and has thus brought other complications to the forefront which are responsible for mortality and morbidity. The surgical procedure of renal transplant though simple in itself is attended by complications 6 including urological complication7 and vascular complications 8. Infection is another most common complication and is leading cause of morbidity and mortality in both early and late post transplant periods 9. Recurrence of renal disease in transplanted kidney is still another complication 10,11,12. The present study is a report of post transplant complications in 41 recipients and autopsy findings related to some of these complications. MATERIALS AND METHODS Forty one patients who had undergone transplant surgery were studied over a period of 23 months. The clinical and laboratory data was obtained from case files and were evaluated pertaining to age, sex, original renal disease in recipient, type of complications including rejection, cause of death and autopsy findings in two patient dying of post transplant complications. The patients were admitted to a tertiary care facility with signs and symptoms of renal disease and diagnosed on the basis of clinical findings, clinical laboratory investigations and renal biopsy. Patients having end stage renal disease were selected for transplantation on the basis of clinical ground, clinical laboratory examination, radiographic, ultrasonographic and other imaging techniques. These were the patients in whome other methods of management had failed and were maintained on dialysis. Selection criteria of recipients included chronic renal failure with end stage kidneys, absence of any surgical contraindications, cardiopulmonary disease, malignant disease and not being in extreme of age. The donors were selected on the basis of ABO and RH blood grouping and cross matching, HLA typing, antibody screening for cytotoxic antibodies and lymphocyte cross match. Screening for hepatitis was also carried out. Cytomegalovirus screening was not done. Selection also included health of the donor, absence of any cardiopulmonary disease, diabetes mellitus and malignancy. Following tests for pretransplant assessment of recipient and donors were carried out; Urine routine examination (RE) as well as culture and sensitivity (C/S), blood complete picture (CP), serum urea, creatinine, electrolytes, creatinine clearance, liver function tests (LFTs), serum lipid, uric acid, serum calcium and phosphate, X-ray chest, intravenous urography, echocardiographic studies, renal scan and renal angiography. The recipients were prepared by haemodialysis 2-3 times per week, injection Epren and iron preparation to correct low Hb levels and regular physiotherapy. Preoperative, intraoperative and postoperative immunosuppression regimen were followed and prophylactic antibiotics given. Follow-up laboratory investigations included daily urea, creatinine, electrolytes and creatinine clearance and blood cyclosporin levels checked at 2-5 post-operative day and then every 7-10 days. Weekly investigations included plasma and urinary proteins, LFTs, serum calcium and phosphate, blood CP, urine RE and C/S. The follow up was available from 02 months to 21 months after surgery. Needle biopsy of kidney was done if required to monitor the status of transplant and any acute rejection, ATN or cyclosporin toxicity. In two cases autopsies were done. RESULTS AND OBSERVATIONS Forty one patients had renal transplantation for end stage renal disease. The age of the recipients ranged from 14-60 years with a mean age of 32.7 years and a male to female ratio of 7.2:1 (Table-1). The renal diseases in the recipients were glomerulonephritis in 25 cases, hypertension in 10 cases, diabetic nephropathy in 02 cases, hypertension and diabetic nephropathy in 02 cases, nephrotoxicity and renal calculi in 01 case each (Table-2). The age ranged in the donors from 25-50 years with mean age of 42 years (Table-1). Thirty eight donors were related to the recipients while three were unrelated. The relationship of the donors to the recipients varied from mother (14 cases), father (5 cases), brothers (10 cases) and sisters (09 cases) (Table-1). Table 1 Showing Age, Sex distribution and Recipient to Donor Relationship(N: 41) S. No Donors Recipients Age Range 25-50 Yrs 14-60 Yrs Mean Age 42 Yrs 32.7 Yrs Males 18 (43.9%) 36 (87.8%) Female 23 (56.1%) 05 (12.2%) Relationship of Donors to Recipients Sex Donors Recipients Male Father - 05 Son - 17 Female Mother - 14 Daughter - 02 Male Brother - 10 Brother - 17 Female Sister - 09 Sister - 02 Not Related - 03 Not Related - 03 Table 2: Showing Renal Disease in Recipient (N: 41) Disease No % Glomerulonephritis 25 61% Hypertension 10 24.4% Diabetic nephropathy 02 4.9% Hypertension + Diabetic nephropathy 02 4.9% Nephrotoxicity 01 2.4% Renal calculi (Recurrent) 01 2.4% Total 41 100% The complications after transplantation occurred in 25 cases and these complications included hepatitis ( 2 cases), hepatic failure (1 case), acute tubular necrosis (ATN) (2 cases), diabetes mellitus, renal stones, acute myocardial infarction, cardiac failure, hydronephrosis and accidental traumatic damage in 01 case each. While septicaemia, and urinary fistulae were seen in 02 cases each (Table - 3). Eight (8) cases showed rejection with hyperacute rejection in 01 case and acute rejection in 07 cases. Four cases have some degree of rejection alongwith other complications. 29 cases showed no signs of rejection from 1 to 23 months after transplantation (Table 3, 4). Table 3: Showing Complications in Recipients (Dead) S.No Complications Nos Remarks 1. Hyperacute Rejection (HAR) 01 HAR after 2nd transplant and died. First been done in Bombay 2. Episode of Rejection 02 - 3. Hepatitis (HBs Ag+ve) 01 Died 03 months after operation; cause of death unknown 4. Hepatic Failure with Acute Rejection episode 01 - 5. Jaundice + ATN + Septicaemia + Malaria + Acute Rejection 01 - 6. Diabetes Mellitus changes (recurrence in graft) 01 Cause not explainable 7 Septicaemia + Multiple abscesses 01 - 8. Fungal (Cryptococcal) infection + Chronic Rejection 01 Autopsy case No.1 9. Renal infarct due to renal vessel thrombosis + Acute Rejection (mild) 01 Autopsy case No.2 10. Cardiac arrest 01 - 11. Accidental damage to transplant 01 Nephrectomy of damaged kidney and retransplant done but died 12. Unknown 01 Primary disease was hypertension/diabetes. Has no obvious cause of death Total 13 Table 4 Showing complications in Recipients (Alive) S.No Complications Nos Remarks 1. Episode of Rejection 05 - 2. Acute Tubular Necrosis (ATN) 02 - 3. Renal Stones (recurrent) 01 - 4. Acute Myocardial infarction 01 - 5. Urinary fistulae 02 One had accompanying renal vessel Pathology and other had slough ureter 6. Hydronephrosis 01 - Total 12 Graft survival was 90.2% and in three patients the graft was lost due to rejection while in one case the graft was damaged due to physical trauma of accident. The patient s survival was 68.3% and patient mortality was 31.7%. Thirteen Cases died and the causes of death in these cases was hyperacute rejection, acute rejection, hepatic failure, cardiac failure, septicaemia, diabetes mellitus, generalized fungal infection and accident, while in 03 cases the cause of death was not known. Autopsy was performed in two cases and the findings in one case revealed features of chronic rejection in allograft kidney alongwith generalized cryptococcal infection involving most of the organs including heart, lungs, stomach, liver, spleen, lymph nodes, pancreas, recipient as well as donor kidneys. Pericarditis with fibrosis and adhesions, bilateral pulmonary oedema and enlargement of all four parathyroids weighing collectively 820 G was noted. In second case left ventricular hypertrophy, marked bilateral pulmonary oedema with patchy bronchopneumonia and enlargement of all four parathyroids collectively weighing 700 G was noted. The allograft kidney showed multiple infarcts involving cortex and medulla. The lumen of the renal vessels showed stenosis and were occluded with thrombus. DISCUSSION As much complex is the function of the kidney as its structure and so are the diseases which affects it. Many of these diseases end up in chronic renal failure what has been called End-State kidneys. Chronic dialysis though extremely useful carries high rate of morbidity and mortality and is far less successful mode of treatment than transplantation which also has its limitations 2. Forty one patients were followed varying from 1 month to 23 months out of which 13 patients died and 28 were alive at the end of 21 months followed up with overall patient s survival of 68.3%. Hoetle and Ruzany13 followed their transplant patients with non-related living donors kidneys for 1 year with survival rate of 75%. In an other study, 12 patients out of 44 having living unrelated donors grafts died with an overall survival rate of 70% 2. The original diseases in our patients for which transplants were done were glomerulonephritis, hypertension, diabetic nephropathy, hypertension with diabetic nephropathy, nephrotoxicity and renal calculi which are similar to the pattern of disease in other studies from Pakistan2. Renal stones and diabetic renal changes recurred in two of our patients. Patients survival rate in our series was 68.3% while graft survival was 90.2%. Tasneem et al14 reported 87% graft and 90% patients survival. The significance of live unrelated and live related transplants on graft survival and patient survival could not be compared due to small number of unrelated donors. Out of the 4 grafts lost one was due to hyperacute rejection while 2 were due to acute rejection and one was physically damaged during accident. Hyperacute rejection occurs when preformed antidonor antibodies are present in the circulation of the recipient. Such antibodies may be present in a recipient who has already rejected a kidney transplant, multiparous women sensitized by paternal antigens shed by foetus or prior blood transfusions15. In the present case the patient has already rejected a kidney transplant carried out at Bombay - India. Infections resulting in septicaemia, hepatic failure, malaria, generalized fungal infection were other major causes of death in some of our cases. In a study infective complications were seen in 30 out of 51 cases and these included wound, respiratory, urinary tract and gastrointestinal infections16 while in another study2 hepatitis, herpes zoster, tuberculosis, tinea versicolor, urinary tract infections and septicaemia were reported. Noorani17 noted urinary, respiratory, gastrointestinal and wound infection with a wide variety of bacterial, viral, fungal and parasitic organisms many of them common in immunocompromised subjects. Malaria infection and infections of CNS with nocardia and herpes zoster were also seen. Viral infection after transplantation have been observed with hepatitis viruses18 CMV19, human herpervirus, HHV - 1 amp; 2, herpes simplex 1 amp; 2, varicella zoster, Epstein Barr virus, influenza, parainfluenza, adenoviruses and respiratory syncytial virus20. Immunosuppressive drugs promote viral infections and the number is increased with more potent immunosuppression. Assessment of the role of specific immunosuppressive agents in promoting infections is confounded by the use of combination therapy, temporal trends in the condition of patients at the time of transplantation, improvement in the detection of viral infection and advances in antiviral prophylaxis20. The more the sophisticated laboratory procedures are applied, the higher is the detection rate for infections in general and viral infections in particular 20. Major complications in series were episodes of rejection some fatal and other treatable. Minor episodes of rejection in 14 and rejection with loss of graft in 9 was seen by Tahir Shafi2 in his series of 60 patients followed from 1 to 54 months. In his series rejection was the most common cause of graft loss2. Tasneem et al14 noted graft survival of 87%. Renal complications in the form of urinary fistulae, hydronephrosis, ATN, recurrent renal stones and renal artery thrombosis were some other important complications in the present work. One of the two urinary fistulae were associated with pathology of a branch of renal vessels which appear to be due to damage during surgery both to vessel and urinary tract. The other one had slough ureter. In another study surgical complication related to urinary tract included ureteric obstruction in one (1) case and renal artery stenosis was noted in one (1). Donnelly et al noted donor ureteric calculus presenting as acute rejection in a renal transplant recipient21, others noted leakage of ureteroneocystostomy in 3 cases, ureterovesical junction stricture with hydronephrosis in 2 cases and cutaneous lymphatic fistula in 3 cases16. Recurrence of previous disease like recurrent diabetes mellitus and renal stones were noted in present work. Recurrent original disease has been noted by many authors10,11,12 and the risk should be avaluated carefully before transplantation. The mortality rate in relation with primary renal disease in recipients was 28% in glomerulonephritis, 40% in hypertension, 100% in hypertension with diabetes and 50% in diabetes mellitus. Though the number of cases are small diabetes mellitus appears to be a major cause of morbidity and mortality after transplantation. The disease may develope in previously non-diabetics because of the use of corticosteroids and other drugs or the original disease in recipient may be exaggerated by use of these drugs22. Furthermore diabetes mellitus associated with immunosuppressive therapy greatly increase the risk of infection in these post transplant patients which may prove fatal 5. Both autopsy cases are a prototype example where discrepancy amongst clinical diagnosis and findings on autopsy were noted. These two cases outline the crucial need of correct diagnosis and management in these patients receiving immunosuppressive regimens. Great caution is needed and accurate diagnosis is required in such cases as intensive immunosuppression to controle rejection may lead to increas risk of infection. In some cases the cause of death was not discernable at the time of death and autopsy, if performed, would have been the best answer to find out the cause. CONCLUSION A successful and complication-free transplantation depends on meticulous care in selection of the recipient and donor, a thorough pretransplant workup of both recipient and donor, highly skilled surgical procedures and a meticulous post-transplant care and management. To achieve this goal a team-work between urologist, nephrologist, pathologist, radiologist and specialist in nuclear medicine is a pre-requisite. The need for precise diagnosis of post-transplant complication and its careful management can not be over emphasized.

High blood pressure after a kidney transplant. I take .6mg catapres and 50mg lopressor

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