Successful kidney transplantation does not reverse the coagulopathy in patients with chronic renal failure on either hemo or peritoneal dialysis.

There is wide disagreement about the measurement of various hemostatic parameters in patients with chronic renal failure (CRF) concerning treatment with either hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). This study aims to characterize the coagulopathy in patients with CRF both before initiating dialysis, when the patients are expected to have a steady hemostatic state and after starting regular HD or CAPD. The measurements were repeated in a group of patients who received a successful renal transplant to see whether the coagulopathy associated with CRF would be corrected by this lasting therapy. The study, which was mainly cross-sectional and prospective, included two groups: 49 patients with CRF with their age ranging from 17 to 67 years were divided as follows: those on regular HD (n=20), CAPD (n=9) and patients after transplant (n=20). The tests were also done on 34 healthy controls. Significant hyper-fibrinogenemia was recorded in all three study groups. The HD group showed significant elevation in the plasma levels of AT III and total protein S and a significant reduction in free protein S and protein C, when compared with healthy controls. These inhibitors, except total PS, displayed similar fluctuations in the CAPD group. In the transplant patients, there was significant elevation of AT III and total protein S, a reduction in free PS and no significant changes in PC levels. A significant elevation was found in the levels of F1+2, TAT and D-Dimer in HD and in transplant patients, when compared with controls. In CAPD patients, only D-Dimer levels showed a significant increase. The tPA and PAI-1 levels in the three study groups were similar to the control group. Our study revealed significant activation of the hemostatic system, more pronounced in patients on HD than CAPD. This coagulopathy remained only partly corrected following successful kidney transplantation.

Platelet surface receptor activation in patients with chronic renal failure on hemodialysis, peritoneal dialysis and those with successful kidney transplantation.

Hemostatic disorders associated with chronic renal failure (CRF) include hemorrhagic and/or thrombotic manifestations, which were ascribed, in part, to uremic platelet dysfunction including abnormalities of expression of platelet glycoprotein receptors. There is, however, still no general agreement on the exact characterization of these platelet abnormalities. This study aims at characterizing the platelet glycoprotein abnormalities associated with CRF, by recording the effect of the three renal replacement therapies, hemodialysis (HD), chronic ambulatory peritoneal dialysis (CAPD), and renal transplantation, on these receptors. The study, which was mainly cross-sectional, included two groups: (i) Patient groups (n = 50): HD patients (n = 20), CAPD patients (n = 10) and successful renal transplant patients (n = 20); (ii) Healthy Controls (n = 34): 23 were men and 11 were women who were age- and sex-matched with the patients. Flow cytometric quantitation of CD41, CD42a, CD42b and CD61 was carried out using a Becton-Dickinson FACScan. The expression of CD41 levels showed a highly significant increase in HD and CAPD patients when compared with the normal control levels. However, levels in transplant patients were comparable to the normal control levels. On the other hand, the expression of CD42a, CD42b, and CD61 showed no significant change in HD and CAPD patients when compared with normal control levels, but there was a significant decrease in transplant patients when compared to the normal control levels. In conclusion, there was evidence of increased expression of one glycoprotein receptor (GpIIb-IIIa) pre-dialysis whether HD or CAPD. In transplant patients, no evidence of platelet activation could be demonstrated.

Value of Doppler ultrasound hemodynamics in the assessment of renal artery stenosis in transplanted kidneys: an assessment of patients after percutaneous transluminal angioplasty.

UNLABELLED: Doppler ultrasound (USS) may allow a non-invasive early diagnosis of transplant renal artery stenosis (TRAS). Adequate Doppler sampling of the transplant renal artery is difficult, time consuming and highly operator dependent. As a result, there has been increased attention focused on the intrarenal vessels and downstream changes that occur secondary to TRAS. We evaluated Doppler USS parameters in nine patients with TRAS confirmed on angiography (significant stenosis defined as > 60% diameter narrowing). Doppler USS correctly identified all the nine stenoses. Mean peak systolic velocity (PSV) was 3.6 m/s + 1.09. Mean end-diastolic velocity (EDV) was 1.75 m/s + 0.25 with an acceleration time (AT) of 0.14 + 0.04 sec and resistivity index (RI) of 0.42 + 0.12. Early systolic peak (ESP) was lost in all cases. Percutaneous transluminal angioplasty (PTA) was successfully done in five patients with significant improvement in Doppler parameters. PSV decreased from 4.04 m/s + 1.35 to 0.76 m/s + 0.42 (p = 0.01). Similarly EDV improved from 1.71 m/s + 0.28 to 0.30 m/s + 0.17 (p = 0.001). AT improved from 0.13 + 0.01 to 0.05 + 0.01 sec (p = 0.001). RI normalized from 0.34 + 0.07 to 0.73 + 0.09 (p = 0.008). ESP was restored in all the patients. IN CONCLUSION: our results show that the Doppler USS analysis of segmental arteries is an excellent tool for the diagnosis of TRAS and follow-up of patients post PTA.

Sustained virological and histological response with pretransplant interferon therapy in renal transplant patients with chronic viral hepatitis C.

Patients who are anti-HCV positive before renal transplantation (Tx) have a significantly increased risk of posttransplant liver disease. We conducted a prospective, controlled study to evaluate the posttransplant outcome of renal graft candidates with HCV-associated chronic hepatitis (n = 30). Patients were randomly assigned to either of two groups. All patients on enrollment underwent liver biopsy, which showed mild-to-moderate hepatitis activity (mean 4.1, range 2-6). Half the patients received interferon-alpha (IFN-a) administered at a dosage of 3 million units three times weekly for 1 year. Liver biopsy was repeated for treated patients at the end of IFN-a treatment. Of these, 11 patients received renal transplant (group A). The other half did not receive IFN-a and to date 10 patients have been transplanted (group B). Renal transplant recipients were prospectively followed for a period of 12 months and a follow-up liver biopsy was also done at the end of this period (end of study). Biochemical and virological responses were evaluated and the histologic activity index (HAI) scoring according to Knodell was assessed. The mean pretreatment serum HCV RNA level was 1.14 +/- 0.84 and 1.0 +/- 0.89 mEq/ml for groups A and B, respectively (bDNA assay sensitivity threshold is <0.2 mEq/ml). HCV RNA became undetectable in 4 patients of group A. At the end of study period the mean quantitative HCV RNA titers were 1.43 +/- 4.07 and 15.18 +/- 11.08 mEq/ml in groups A and B, respectively (p < 0.0001). In group A, the mean HAI score decreased from 4.27 +/- 1.19 to 1.64 +/- 0.67 after IFN-a treatment (p < 0.0001). This score was maintained till the end of the study period with a mean of 1.82 +/- 0.6. Mean HAI score of group B on enrollment was 3.9 +/- 1.2 and at the end of study increased to 5.5 +/- 1.35 (p = 0.01). There was statistically significant difference (p value less than 0.0001) between the HAI scores at the end of the study period between the two groups. These results demonstrate that interferon therapy while on dialysis is associated with less viremia and decreased progression of chronic liver disease in renal transplant patients with hepatitis C.

Effect of vitamin-E-modified dialysers on dialyser clotting, erythropoietin and heparin dosage: a comparative crossover study.

We performed a crossover study to compare the effects of different dialysis membranes on 20 patients with frequent dialyser clotting and requiring > or = 5,000 units of heparin per dialysis session. Low-flux dialysers are C15NL (cellulose - Terumo) and E15NL (vitamin-E-coated - Terumo) while high-flux dialysers were F60 (polysulphone) and EE15NL (vitamin-E-coated - Terumo). Ten patients underwent dialysis for 2 months with C15NL then switched to E15NL for 2 months. Similarly, the other 10 patients were started on the high-flux dialyser F60 and then switched over to EE15NL for 2 months. The following parameters were measured at the beginning of the study, 2 weeks, 1 month and then at 2 months: hemoglobin, prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, protein C, protein S, antithrombin III (ATIII) and factor 12 activity. Dialyser clotting, heparin and erythropoietin requirements were assessed during each dialysis session. There was a significant reduction in clotting with E15NL in comparison to C15NL (22.8 +/- 17 and 44.1 +/- 22.8 (p = 0.0233), respectively). Similarly, heparin requirements were less in the vitamin-E-coated (E15NL) dialysers, 4, 754 +/- 1,427 vs. 6,011 +/- 856 units (p = 0.0281) and erythropoietin usage was also significantly reduced, 4,630 +/- 2,620 vs. 7,850 +/- 4,069 units (p = 0.049). There was a significant increase in hemoglobin with E15NL compared to C15NL, 115 +/- 10.4 vs. 108 +/- 13.1 (p = 0.0343). When the high-flux dialysers were compared there was a tendency towards less dialyser clotting with the EE15NL compared to F60, though this did not achieve statistical significance (p = 0.0561). We could not demonstrate any significant changes between the different dialysers with regards to PT, PTT, fibrinogen factor 12 activity, protein C, protein S and ATIII. In conclusion, we have shown that the use of vitamin-E-modified dialysers is associated with less clotting in patients with persistent clotting problems. In addition, this was associated with less heparin and erythropoietin requirements.

Effect of intravenous cyclophosphamide pulse therapy on renal functions and histopathology in patients with severe lupus nephritis.

Despite the wide use of intravenous cyclophosphamide (IC) in lupus nephritis (LN), there are few published studies showing the effect of this treatment on renal histology. In this prospective study, we report the effect of IC on the evolution of histopathologic features in successive renal biopsies in patients with LN. Thirty patients with class IV or V LN were started on IC (10-15 mg/kg) administered once every month for six months followed by three monthly for another six doses making a total of two years of therapy. The clinical course of the disease, serum creatinine and 24 hours urinary protein and creatinine clearance were tested at entry and subsequently during each follow-up visit. Repeat renal biopsy was performed after completion of two years of therapy. The mean serum creatinine of the study patients was 166.3 + 42 tmol/L at entry which decreased to 104 + 46.4 tmol/L at two years (P + 2.4 g at entry to 1.39 + 1.54 g at two years (P + 31 ml/min at the start of treatment to 64 + 32 ml/min at two years of therapy (P 200 tmol/L, of whom six progressed to variable degrees of chronic renal failure. Repeat renal biopsy was performed in 21 patients. The original biopsy of these patients showed class IV in 17 and class V in four patients. On repeat biopsy, five of class IV disease had progressed to advanced sclerosis, four to class V, and five remained unchanged. The remaining three patients with class IV LN changed to one each of class I, II and III. Of the four patients with class V, one progressed to advanced sclerosis, one changed to class III and two remained the same. There was a significant decrease (P < 0.05) in the activity index although there was a significant increase in the chronicity index (P < 0.001). Multivariat analysis for possible risk factors for progression to chronic renal failure showed initial high serum creatinine to be a powerful predictor of renal failure. In conclusion, IC pulse therapy is effective in improving or stabilizing renal function in patients with class IV or V LN. The only poor prognostic determinant observed was higher initial serum creatinine value.

Successful late conversion to mycophenolate mofetil and prednisone immunosuppression therapy in a renal transplant recipient.

A 35-year old male patient developed elevated transaminases about an year after cadaveric donor renal transplantation maintained on triple immunosuppression therapy. Azathioprine was discontinued and the liver enzymes normalized. Three years later, he showed evidence of cyclosporin (CyA) nephrotoxicity as well as sclerosing cholangitis. The dose of CyA was therefore reduced. This was followed shortly by deterioration of his renal function and mycophenolate mofetil (MMF) (3 gm daily) was therefore introduced. He developed intractable diarrhea, which improved on reducing the dose of MMF to 2 gm per day. Eventually, the patient seemed to stabilize on low dose CyA and prednisone (Pred) along with 2 gm of MMF. Four months later, the patient discontinued CyA on his own but continued with MMF and Pred. Over the following two years, his renal functions have remained stable with serum creatinine of around 120 micromol/L, despite the low immunosuppression being administered.

The spectrum of glomerulonephritis in saudi arabia: the results of the saudi registry.

Only few studies regarding glomerulonephritis, with relatively small numbers of patients, have so far been published from different centers in Saudi Arabia, and have reported conflicting results regarding the patterns, even in the same city. The possible reasons for these differences include the small number of patients in the different studies, differences in the indications for renal biopsies, referral bias, geographical differences, and, sometimes, the non-availability of the necessary diagnostic facilities in the reporting centers. In order to overcome these problems, a registry for glomerulonephropathy was attempted in Saudi Arabia. Six large referral hospitals from different regions of Saudi Arabia participated in this registry. Biopsy reports and clinical information of 1294 renal biopsies were obtained. There were 782 renal biopsies due to glomerulonephritis (GN) accounting for 77.2% of the total biopsies. Five hundred eighty seven (72.6%) were primary glomerulonephritidis. Focal and segmental glomerulosclerosis (FSGS) (21.3%) and membrano-proliferative glomerulonephritis (MPGN) (20.7%) were the most common types found in the primary glomerulonephritidis. Membranous glomerulonephritis (MGN) was present in only 10.6% of the cases. IgA nephropathy was found in 6.5% of the cases. Of the secondary glomerulo-nephritides, systemic lupus erythematosus (SLE) was the most common indication for biopsy (57.0%) and amyloidosis was found in only 3.2% of the biopsies. In conclusion, FSGS and MPGN were the most common forms of primary glomerulonephritis in adult patients in Saudi Arabia. MGN was not as common as in the western world. SLE was the commonest cause of secondary GN. Amyloidosis was not as common as in other Arab countries. There is a need for more centers from Saudi Arabia to join this national GN registry. Similar registries can be established in different Arab countries, which all would, hopefully, lead to a Pan-Arab GN registry.

The Effect of Vitamin E-Modified Dialyzers on Acute Intra-dialytic Symptoms: A Comparative Crossover Study.

We performed a crossover study to compare the effect of vitamin E-modified dialyzers on acute intra-dialytic symptoms, with other membranes. Twenty patients on hemodialysis were studied. They were divided into two equal groups of low-flux (C15NL, E15NL) and high-flux (F60, EE15NL) membrane dialyzers. Within each group, a vitamin E-modified dialyzer was compared with another dialyzer in a crossover design over a two-month period. All study patients were seen during each dialysis session by a physician and the occurrence of intra-dialytic symptoms were recorded. There was a significant overall improvement in the incidence of acute intra-dialytic symptoms with the use of vitamin E-modified dialyzers as compared with the other membranes. This effect was more for cuprophane than polysulfone. The occurrence of hypotensive episodes did not differ. Our study indicates that we can achieve a reduction in the incidence of acute intra-dialytic symptoms with the use of vitamin E-modified membrane as compared to cuprophane and polysulfone.

Interferon-alpha in chronic hepatitis C infection in dialysis patients.

This study assesses the efficacy and adverse effects of interferon-alpha (IFN-alpha) administered at a dosage of 3 million units three times weekly for 1 year in 17 hemodialysis patients with hepatitic C virus (HCV)-associated chronic hepatitis (biopsy proven). The patients were prospectively followed up for a period of 18 months. Liver biopsy was repeated after 6 months of treatment in 13 patients. Patients were classified according to the histological activity index. Biochemical and virological responses were evaluated at the end (end-of-treatment response) and 6 months after completion of therapy (sustained response). HCV RNA became negative in 76% of the patients after 12 weeks of treatment, in 88% after 12 months of treatment, and in 71% of the patients 6 months after completion of therapy. HCV genotype 4 was found in 60% of our population. Alanine aminotransferase (ALT) levels were initially increased in only 6 patients and normalized in 4 of these patients after 12 weeks of therapy, with end-of-treatment and sustained biochemical responses of 83% and 67%, respectively. Of 13 patients who underwent liver biopsies after 6 months of therapy, 11 patients (85%) showed histological improvement. One patient could not tolerate therapy because of marked lethargy and myalgia; the other patients had minor side effects that did not require discontinuation of treatment. Two patients received a cadaveric renal transplant after 1 year of IFN treatment, and they continued to maintain biochemical and virological responses after a follow-up of 17 and 28 months, respectively.

Maintenance intravenous iron therapy in hepmodialysis patients receiving recombinant human erythropoientin.

Iron Supplementation is crucial in raising hematocrit as well as dosage saving for recombinant human erythropoietin therapy (rHuEPO) in maintenance hemodialysis patients. Intravenous iron has proved to be both safe and efficacious in this patient's population. However, the exact iron requirement has not been worked our. In this study we found that 1000 mg of element iron (given as iron saccharate) per moth was effective in maintaining hematocrit and hemoglobin at 33% and 110 gm/L respectively, and reducing the erythropoietin (EPO) dosage by about 20% in maintenance hemodialysis patients who were iron-replete. The serum ferritin increased from 219+/-144 to 320+/-234 microg/L (P< 0.05). There were no major side effects and patients tolerated the monthly iron therapy well. Our study suggests that intravenous iron saccharate (100 mg/month) is effective and safe in patients on maintenance hemodialysis receiving RHUEPO.

Effect of intravenous alfacalcidol on lymphocyte phenotyping in hemodialysis patients.

Chronic renal failure is associated with decreased production of active vitamin D and also results in altered lymphocyte population. We studied the effect of alfacalcidol on lymphocyte phenotype. There were 15 patients (10 males, 5 females) with a mean age of 54.3+/-14.4 years who had been on chronic maintenance haemodialysis for a mean period of 3.2+/-1.5 years. Intravenous alfacalcidol was given three times weekly during dialysis for a duration of 6 months. Our results show a significant increase in NK cells from 0.20+/-0.12 to 0.27+/-0.28 (P=0.001), without a significant change in CD2, CD19, CD4, CD8 population, and CD4/CD8 ratio.

Absence status: an overlooked cause of acute confusion in hemodialysis patients.

Epileptic seizures are a known complication of uremia, but non-convulsive seizures appear to be rare. We describe a patient with absence status presenting with acute confusion who responded well to intravenous diazepam. Attention is drawn to this rare cause of acute confusional state in the hemodialysis population.

Dual-lumen femoral vein catheterization as vascular access for hemodialysis--a prospective study.

Prospectively from January 1991 to January 1993, the efficacy and complications of 104 polyurethane, double-lumen femoral vein catheterizations (FVC) in 96 renal failure patients were studied. Ambulation was allowed in the hospital as well as at home while the catheter was in. There were 53 males and 43 females, with ages ranging from 13 to 87 (mean, 48.3 +/- 19.7) years. Forty-eight patients had chronic renal failure and 48 had acute renal failure. The catheters were used for 1 to 26 days (mean, 8 +/- 5 days). Fifty-two (50%) of the FVC were used for 2 weeks and 14 (13.5%) for 3 weeks or longer. The various complications encountered were infection (n=31), poor blood flow (n=8), displaced catheter (n=6), thrombosis of the catheter (n=4), hematoma (n=4), bleeding (n=3), exit site infection (n=3), ileofemoral vein thrombosis (n=2), and tear in the catheter wall (n=2). On removal, bacterial colonization was present in 34 out of 93 catheter tips (36.5%); Staphylococcus epidermidis (n=12) was the commonest organism grown. There was no significant difference of infection between diabetic and nondiabetic chronic renal failure patients. The duration of catheterization was found to have no relation with either thrombosis or infection. Femoral vein catheters can be used for hemodialysis for 2 to 3 weeks and ambulation during cannulation may be allowed.

Treatment of erectile dysfunction after kidney transplantation with intracavernosal self-injection of prostaglandin E1.

PURPOSE: We evaluate the results of treatment of erectile dysfunction in kidney transplant patients with intracavernosal self-injection of vasoactive drugs. MATERIALS AND METHODS: We evaluated and treated 26 male kidney transplant patients for erectile dysfunction. All patients had stable kidney function 6 to 75 months (mean 26.6 +/- 9) after transplantation. Each patient received an intracavernosal injection of 20 microg. prostaglandin E1 (PGE1), and after 20 to 30 minutes the response was assessed. Nonresponders received 40 microg. PGE1 at another visit, and those who showed no response were reinjected with 40 microg. PGE1 plus 30 mg. papaverine hydrochloride. A total of 21 patients were enrolled in a self-injection program and have been followed between 3 and 21 months (mean 11.6 +/- 2.7). RESULTS: Hormonal alterations were seen in 7 patients with serum testosterone as low as 16.6 ng./ml. (normal 33 to 100), and testosterone injections gave only marginal response in 2. Intracavernosal injection of 20 microg. PGE1 provided good response in 15 patients (57.7%), while 40 microg. PGE1 alone or in combination with 30 mg. papaverine resulted in good response in another 6 and 2 patients, respectively. Among the 21 patients who were enrolled in the self-injection program 19 (90.5%) reported complete satisfaction with no adverse local or systemic complications except for local pain at the injection site in 4. There has been no change in serum creatinine, cyclosporine level or doses of immunosuppression medications during the observation period. CONCLUSIONS: Intracavernosal self-injection of PGE1 is well accepted and tolerated by kidney transplant patients. It poses no apparent risks to the transplanted kidney and could be a good modality to treat erectile dysfunction in kidney transplant recipients.

Peritonitis in Patients on CAPD at King Khalid University Hospital: Less Infection-rate with More Center-experience.

Continuous ambulatory peritoneal dialysis (CAPD) was started at the King Khalid University Hospital in 1986. Peritonitis remains the most significant complication of the procedure. Earlier rates of peritonitis were high, but after gaining sufficient experience, the rates are declining. To evaluate the change in peritonitis trend, 55 new patients who were recruited to our CAPD program between the periods October 1993-October 1996 were analyzed for the development of peritonitis on annual basis. There were 37 (67%) males and 18 (33%) females with a mean age of 43.3 years (range 12-72 years). A total of 34 episodes of peritonitis were recorded with a rate of 1.5 episode/patients year in 1993, 0.5 episode/patient year in 1994 and 0.8 in 1995. only 40% of episodes showed positive cultures whereas 60% remained culture-negative despite use of recommended modified culture techniques. Organisms causing peritonitis included staphylococcus eipdermides (6.7%), E. coli (3.3%), Streptococcus fecalis (3.3%) and pseudomonas (6.7%). Out of 34 episodes of peritonitis, 29 (85.3%) showed response to treatment and five episodes could only be treated after removal of catheter. Of the 29 episodes that responded to treatment, three relapsed and one had recurrent infection . However, all were successfully treated though one responded only after removal of catheter. Thus, a total of six catheters (20%) necessitated removal and replacement. In spite of high diabetic patients population in our series (27.2%) only one died of peritonitis related sepsis and another died of myocardial infarction after clearing the infection. Thus mortality remains low in spite of potential risk. Although we still use straight system CAPD rather than Y system peritonitis rates have declined considerable and we hope that the procedure will gain more acceptability amongst patients with ESRD in Saudi Arabia.

Doppler ultrasound evaluation of hemodialysis vascular access.

Brescia-Cimino arteriovenous fistulas (AVF) ad synthetic grafts are the usual forms of vascular accesses for hemodialysis. Although angiography has been the traditional means of imaging these vascular systems, colour Doppler flow imaging (CDFI) offers a non-invasive method of evaluating AVF dysfunction. We retrospectively evaluated 22 patients with clinical evidence of access dysfunction who were studied by CDFI and of whom 14 also underwent angiography. We analyzed the results of whom the 14 patients who had both CDFI and angiography as angiography was impossible in the remaining eight patients due to difficulty with cannulation. Eight patient had thrombosis on CDFI and angiopraphy in all eight patients confirmed these findings. CDFI showed six stenoses, all of which were proven on angiopraphy. Overall,, CDFI correctly identified all lesions that were seen angiographically ginging a sensitivity and specifificity of 100%. Moreover, CDFI detected two cases of pseudoaneurysms which were missed by angiography. CDFI provides an adequate means of evaluating AVF dysfunction and should be the initial imaging technique of choice.