Results of 151 renal transplants in Kuwait.
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Biomedical subjects
Publications and source records attributed to M Lao.
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Early diagnosis of CMV infection is very important mainly in transplant recipients because CMV infection is a frequent complication after transplantation. In this work we compared different laboratory methods: ELISA (IgG, IgM), Western blot,shell vial, antigenemia assay (pp65), the immunofluorescent method with epithelial cells from urine (IF), DNA in leukocytes by PCR and DNA in leukocytes by hybridization (HCS) to estimate the most proper method for diagnosis of CMV in renal transplant recipients. This preliminary study showed that HCS, PCR and Western blot are sensitive methods for detecting CMV infection. Using HCS in quantitative variant we obtained a very good correlation between DNA load and clinical symptoms.
OBJECTIVES: Reactivation of Epstein-Barr virus (EBV) infection in renal transplant recipients may cause significant morbidity and mortality. To evaluate factors associated with activation of EBV replication we followed prospectively a group of 65 recipients of cadaveric kidney for 12 months. METHODS: Sera were collected periodically from these patients and analyzed for the presence of specific anti-EBV antibodies. Control group consisted of renal (n=35) and healthy blood donors (n=35). Enzyme-linked immunoassays based on recombinant EBV proteins were used to detect the following antibody specificities: early antigen (EA) IgA, IgM, and IgG, nuclear antigen (EBNA) IgG. RESULTS: During first year after transplantation, primary infection developed in 4 (6.15%) recipients and reactivation occurred in 18 (27.7%) recipients. Analysis did not show the association of reactivation with type of basic immunosuppressive therapy, prophylactic or therapeutic use of anti-lymphocyte antibodies, as well as acute rejection episodes. There was a borderline association (p=0.068) between the incidence of CMV infection and EBV reactivation. CONCLUSIONS: Our data suggest casual relationship between CMV infection and EBV reactivation.
Monoclonal and polyclonal antilymphocyte antibodies have been used successfully in organ transplantation as induction therapy and in the treatment of acute graft rejection. Used for induction the medication is generally given for the first 7-10 days. The aim of this study was to assess the safety and efficacy of single high dose (9 mg/kg) ATG Fresenius S given perioperatively, before revascularization, to kidney allograft recipients. During last twelve months seventy six, first cadaveric kidney adult recipients were included into the study in two centers (center A-64, center B-12). All patients received triple drug immunosuppression (Neoral, steroids and Cellcept which was replaced by azathioprine after 4 months), and were randomized to receive ATG or not. The follow-up period ranged from 1 month up to 1 year. The preliminary results are very promising, the rejection rate in bolus group was significantly lower than in control. No significant side effects or serious adverse events in both groups were observed.
The influence of atherosclerotic lesions of hypogastric and iliac arteries of kidney recipients on intraoperative surgical technique and one-year graft and patient survival was investigated. Among 1553 transplanted kidneys atherosclerotic lesions which required surgical intervention were found in 201 (12.9%) recipients. Thrombendarterectomy (TEA) of hypogastric artery was performed in 142 cases with subsequent anastomosis with the renal artery. Occlusion of hypogastric artery was an indication for renal graft artery to external iliac artery anastomosis in 32 patients. Atherosclerotic changes in external and common iliac artery required TEA in 25 patients and anastomosis between renal artery and external artery was performed. Ilio-iliac bypass or Y-graft simultaneously with kidney transplantation were performed in two cases. One-year survival rate of allografts and patients was 88% and 93%, respectively. No grafts were removed due to kidney artery thrombosis. We conclude that hypogastric artery after TEA provides adequate blood supply to kidney graft.
UNLABELLED: Glutathione S-Tranferases (GST) are the enzymes which are strictly specific for epithelial cells of the proximal and distal tubules in the kidney. These enzymes are detected in the urine when some tubular damage process is found. In healthy people urine GST is hardly detected. The goal of this study was to evaluate the release of two isoenzymes -- alpha and pi GST in the urine of kidney graft recipients during the first week after kidney transplantation, aiming to differentiate the cause of the delayed function (DF) of transplanted kidney. MATERIAL AND METHODS: 50 cadaveric kidneys were procured using standard technique with "in situ" cooling using UW solution. All kidneys were machine perfused. After preservation kidneys were transplanted to 50 ERSD patients. Standard triple drug immunosuppression was applied (steroids, CsA, Cell-Cept or Aza.). Graft function and the release of alpha and pi GST in the urine were measured 1, 3 and 7 days after transplantation. RESULTS: immediate function (IF) was found in 72% (36pts), DF in 28% (14pts). 5 of DF patients had ATN, 4 had acute rejection (REJ) and the remaining 5 had ATN and acute rejection (see table below). CONCLUSIONS: High alpha and pi GST concentrations were found in pts with DF graft function during the first 7 days after Tx. Elevated pi GST and low alpha GST in the urine indicates acute rejection. High alpha and pi GST in pts with DF should raise suspicion of graft rejection.
Pregnancy-induced changes increase hazards associated with cyclosporine (CsA) treatment. Blood CsA trough levels (C0) were estimated in 15 pregnant renal allograft recipients treated with prednisolone + CsA + azathioprine using the TDx Abbott fluorescent polarization immunoassay. Despite therapeutical dose levels of CsA administered during pregnancy (3.52-3.67 and 3.59 mg/kg body weight in the first, second, and third trimesters, respectively), C0 significantly decreased (first trimester 130.8 +/- 36.9, second 92.0 +/- 32.7, and third 99.0 +/- 36.9 ng/ml). The mean increase of patient's body weight in mid-pregnancy was 3.0 +/- 2.19 kg and was associated with a significant (P < 0.05) fall in a hematocrit value (from 42 +/- 4.9% prior to pregnancy to 34 +/- 6% at the 20th week). We postulate that C0 concentration does not reflect the true exposure to CsA as no episodes of acute graft rejection were observed during pregnancy.
The aim of this study was to evaluate the efficacy and safety of interferon-alpha (IFN-alpha) therapy of chronic hepatitis B, C and D (HBV, HCV and HDV, respectively) in renal transplant recipients. A group of 42 patients (30 males, 12 females, mean age 38 years) with documented viraemia and chronic active hepatitis (CAH) were studied, of whom 1 had HBV infection alone, 11 had HCV infection alone, 3 had HBV and HDV infection concomitantly, 12 had HBV and HCV infection concomitantly, and 2 had HBV, HCV and HDV infection concomitantly. Patients received 3 MU IFN-alpha three times weekly for 6 months. After IFN-alpha therapy, 18 patients (43%) achieved normal alanine aminotransferase (ALT) activity and a partial response was observed in 12 (29%) patients. Two patients relapsed (one with HCV and one with HBV + HCV infection) immediately after the cessation of IFN-alpha therapy. Repeated liver biopsy was performed in 16 patients after 6-24 months of therapy and revealed progression to cirrhosis in five patients, remission in two and stable disease in nine. None of the patients cleared HCV RNA, four patients cleared HBeAg (two also HDV), and one both HBV and HCV. Five patients died during IFN-alpha therapy (one as a consequence of liver failure), and four died during the 6 months after therapy (two as a consequence of liver failure). During IFN-alpha therapy renal allograft function remained stable in 31 patients and acute rejection episodes occurred in 7, of whom 5 lost their graft and all had experienced rejection episodes before. In 16 patients normalization of ALT continued during long-term follow-up (median 22 months, range 0-84 months). IFN-alpha seemed to be moderately effective in the treatment of chronic HBV or HCV infections, but cannot be recommended for recipients infected with both HBV and HCV.
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The high prevalence of hypercholesterolemia (HCh) in kidney transplant recipients probably contributes to the high cardiovascular mortality of these patients. Additionally, HCh is a contributing factor to the progression of renal failure. We conducted a prospective, randomised study with low dose Lovastatin in 42 kidney transplant recipients during 32 weeks, focusing on side effect and kidney function 42 consecutive patients with kidney transplanted in our Institute, with stable renal function (creatinine level < 160 mmol/l) treated with ciclosporine, azathioprine, prednisone were enrolled for the study (regardless of the initial cholesterol level). Every second patient was given Lovastatin 20 mg/night. In the Lovastatin group total cholesterol (TC) and LDL concentration were significantly lower after 6 months of treatment (TC was reduced from 242.5 +/- 12.8 to 220 +/- 15.4 mg/dl, p < 0.05) in Lovastatin group whereas in control group it increased nonsignificantly. Similarly LDL in Lovastatin group decreased from 140.0 +/- 7.0 to 121.3 +/- 10.8 mg/dl, p < 0.02 whereas in control group it increased from 143.6 +/- 5.4 to 169.9 +/- 10.3 mg/dl, p < 0.01. HDL and trigliceride concentrations were unchanged. The Lovastatin treatment did not results in more adverse events than the placebo treatment. Notably, the tendency to increase creatinine level in Lovastatin group was observed from 1.59 +/- 0.17 to 1.74 +/- 0.22 in Lovastatin group versus 1.89 +/- 0.22 to 2.21 +/- 0.35 mg/dl (NS). Low dose Lovastatin treatment seems to be safe and efficient cholesterol-lowering procedure. However we did not observe beneficial effect on kidney graft function.
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Neoral (NEO) is claimed to have better pharmacokinetics than standard preparation of cyclosporine (SIM) thus providing more reliable immunosuppression. We estimated safety and tolerability of NEO and compared pharmacokinetic parameters in 20 stable renal allograft recipients (RARs) converted from SIM to NEO treatment. Another 20 stable RARs continuously treated with SIM created a control group. Whole blood through CsA level (C0) did not differ after conversion (SIM: 136.2 +/- 33 ng/ml and NEO: 142.6 +/- 34 ng/ml). During therapy with NEO peak blood concentration (Cmax) was significantly higher (935.6 +/- 368 ng/ml) and occurred earlier (Tmax 1 hr. 36 min. +/- 30 min) as compared to the period on SIM (Cmax 598 +/- 309 ng/ml, p = 0.01), Tmax = 3 hr. +/- 1 h 36 min., (p = 0.01) respectively. AUC increased from 2975.4 +/- 1020 ngxhr/ml to 4236.1 +/- 1188 ngxhr/ml (p < 0.0001). Correlation coefficient between AUC and C0 was higher during NEO (r = 0.52) than SIM therapy (r = 0.32). The only noticeable change in laboratory tests after switch to NEO was slight increase of serum triglyceride concentration (119.5 +/- 44.7 mg/dL vs. 148.4 +/- 67.0 mg/dl). The mean serum creatinine concentration did not change significantly (1.42 +/- 0.32 mg/dL and 1.46 +/- 0.31 mg/dL). Tolerance of NEO was good and 1:1 switch from SIM to NEO is clinically safe. Higher bioavailability of NEO was not associated with decreased tolerability or increased nephrotoxicity. Better correlation between C0 and AUC during NEO administration makes CsA treatment monitoring more reliable.
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Disturbances of lipid metabolism are considered to play a pathogenetic role in glomerulosclerosis. Since intraglomerular have been proposed to be involved in the pathogenesis of the glomerulosclerosis, we have investigated the influence of LDL on the activity of the cellular proteases. Cathepsins B and L were measured with the aid of fluorometry, and 7-amido-4-methylocoumarin derivates were used as substrates; Z-Arg-Arg-AMC for cathepsin B, Z-Phe-Arg-AMC for cathepsins B and L together. Rat mesangial cells cultured 24 h in medium supplemented with LDL revealed inhibition of cathepsin B activity at concentrations of 250 micrograms LDL/ml medium, lower LDL concentrations were without apparent effect. Since the glomerular accumulation of structural and nonstructural proteins plays an important role in glomerulosclerosis, we conclude that the augmented proteolytic activity of mesangial cells might be one of the pathways located by which hyperlipidemia causes an increased susceptibility to glomerular damage.
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