Detection of Hepatis C Virus-Related Immunologic Markers and Their Impact on Outcomes of Living-Donor Kidney Transplant Recipients.

OBJECTIVES: Liver disease is an important cause of morbidity and mortality among recipients of transplanted organs. In addition to the liver, hepatitis C virus infection has a significant prevalence among recipients of kidney transplant and is related to worse graft and recipient survival as the kidney is an important component of the hepatitis C virus clinical syndrome. MATERIALS AND METHODS: This retrospective single center study included 336 patients with end-stage renal disease who received a kidney transplant at the Mansoura Urology and Nephrology Center from January 1992 to December 1995. Of 336 patients, 63 were excluded, and the remaining 273 patients were divided into 3 groups: viremic active (72 patients), viremic inactive (108 patients), and nonviremic (93 patients). Division of patients was based on hepatitis C virus RNA complement level (C3 and/or C4 consumption), circulating cryoglobulins, and rheumatoid factor detection. RESULTS: Our study showed insignificant differences regarding patient characteristics and demographic data among the study groups but significantly higher incidence of transaminitis in viremic (active and inactive) patients. Nonsignificant differences were found regarding proteinuria among the 3 groups, including among those who had levels in either nephrotic or nonnephrotic ranges. Biopsy-proven acute rejection episodes among the 3 groups of recipients were statistically comparable, with significantly higher frequency of chronic rejection episodes among viremic active patients. Nonviremic recipients had significantly lower serum creatinine levels than viremic (active and inactive) recipients. Patient and graft survival results were comparable among the groups. CONCLUSIONS: Presence of hepatitis C virus immunologic markers does not have a significant effect on patient and graft survival; however, it may be a clue for long-term incidence of chronic rejection.

Sleep disorders in hemodialysis patients.

The prevalence of sleep disorders is higher in patients with kidney failure than the general population. We studied the prevalence of sleep disorders in 88 (mean age; 41.59 +/- 16.3 years) chronic hemodialysis (HD) patients at the Urology and Nephrology Center, Mansoura University, Egypt over 4-month period. The investigated sleep disorders included insomnia, restless leg syndrome (RLS), obstructive sleep apnea syndrome (OSAS), excessive daytime sleepiness (EDS), narcolepsy and sleep walking, and we used a questionnaire in accordance with those of the International Restless Legs Syndrome Study Group, the Berlin questionnaire, Italian version of Epworth Sleepiness Scale, International Classification of Sleep Disorders, and the specific questions of Hatoum's sleep questionnaire. The prevalence of sleep disorders was 79.5% in our patients, and the most common sleep abnormality was insomnia (65.9%), followed by RLS (42%), OSAS (31.8%), snoring (27.3%), EDS (27.3%), narcolepsy (15.9%), and sleep walking (3.4%). Insomnia correlated with anemia (r=0.31, P= 0.003), anxiety (r=0.279, P= 0.042), depression (r=0.298, P= 0.24) and RLS (r=0.327, P= 0.002). Also, RLS correlated with hypoalbuminemia (r=0.41, P= < 0.0001), anemia (r=0.301 and P= 0.046), hyperphosphatemia (r=0.343 and P= 0.001). EDS correlated with OSAS (r=0.5, P= < 0.0001), snoring (r=0.341, P= 0.001), and social worry (r=0.27, P= 0.011). Sleep disorders are quite common in the HD patients, especially those who are anemic and hypoalbuminemic. Assessment of sleep quality, preferably with polysomnography, is necessary to confirm our results. Interventional studies for management of sleep disorders in HD patients are warranted.

Prognostic value of serum creatinine levels in children with posterior urethral valves treated by primary valve ablation.

PURPOSE: We evaluated the prognostic value of serum creatinine level at presentation and nadir creatinine during follow up for future renal function (RF) in children with posterior urethral valves (PUV). MATERIALS AND METHODS: Between 1987 and 2004, 120 cases of PUV were treated initially at our hospital with valve ablation. Initial assessment included serum creatinine measurement, urine analysis and culture, renal ultrasonography and voiding cystourethrography. After valve ablation, renal ultrasound and serum creatinine measurement were repeated and thereafter during visits until the end of follow up. RESULTS: Follow up ranged from 2 to 12 years (mean=4.4). Renal insufficiency (RI) developed at the end of follow up in 44 patients (36.5%). The mean initial and nadir serum creatinine in the RI group was higher than in the normal RF group (P<0.05). With a cut-off value of 1mg/dl for initial and nadir serum creatinine, the incidence of RI was significantly different (P<0.05). CONCLUSION: Our data confirm the high prognostic value of nadir serum creatinine after relief of valvular obstruction. Further, the serum creatinine level before valve ablation correlates significantly with long-term RF in children with PUV.

Single-center experience with cyclosporine for treatment of idiopathic minimal change nephrotic syndrome in children.

INTRODUCTION: Cyclosporine A is used in the treatment of idiopathic nephrotic syndrome. We conducted this study to evaluate the effect of cyclosporine and its combination with ketoconazole in Egyptian nephrotic children with steroid-resistant and steroid-dependant minimal change. MATERIALS AND METHODS: Forty-eight children with minimal change lesions who received cyclosporine with or without ketoconazole were studied. Their mean age was 5.17 +/- 1.59 years, and they were 31 boys and 17 girls. The mean duration of the disease was 6.22 +/- 3.16 years. Thirty-one of the children were steroid dependent and 17 were steroid resistant. Cyclosporine treatment was commenced after remission was attained and adjusted to a target trough level of 100 ng/mL. The mean cyclosporine therapy at a dose of 2.07 +/- 0.91 mg/kg was administered for a mean of 25.75 +/- 1.95 months. Thirty-three patients received adjunctive ketoconazole therapy. RESULTS: Thirty-eight patients (79.2%) responded well to cyclosporine. Steroid therapy could be discontinued in 43 patients (89.6%), but 9 experienced relapse. Ten patients (20.8%) were resistant to cyclosporine therapy. Fifteen patients received cyclosporine alone, while 33 received concomitant cyclosporine and ketoconazole. The response to cyclosporine was significantly better in those on ketoconazole. The economic effect of ketoconazole therapy was a reduction in the costs of cyclosporine treatment by 47.4% at 1 year of treatment. CONCLUSIONS: Cyclosporine treatment in children with minimal change nephrotic syndrome is effective in preventing relapse and decreasing steroid toxicity. Its combination with low-dose ketoconazole is safe, reduces treatment costs, and improves the response to cyclosporine.

Safe conversion of mycophenolate mofetil to azathioprine in kidney transplant recipients with sirolimus-based immunosuppression.

AIM: Mycophenolate mofetil (MMF) is a powerful immunosuppressive drug with established efficacy and safety. The long-term use of MMF may bring increased risk of for infection and malignancy and also increased cost of transplantation. The search for minimization of immunosuppressive protocol has led to an open randomized clinical trial of conversion from MMF to azathioprine (AZA). METHODS: A total of 50 kidney allograft recipients treated with prednisone, sirolimus and MMF were randomized into two groups: converted (AZA group) and continuing (MMF group). The average duration of MMF therapy prior to conversion was 43 months in each group. Inclusion criteria included: patients with serum creatinine levels of less than 200 micromol/L; no past history of acute vascular rejection or recent acute rejection 6 months before randomization; and normal liver function tests. RESULTS: Baseline demographics were similar in the two groups. During the 12 month observation period, there were no acute rejection episodes in either group. There were no significant differences in overall patient or graft survival or function. AZA-treated patients had a lower incidence of gastrointestinal complications (P=0.03). Daily cost reduction in the AZA group was more than $US8.79/day per patient. CONCLUSION: In general, replacing MMF with AZA in stable renal transplant recipients is well tolerated and was cost effective with no increased risk of rejection. As the this study was on relatively small samples, larger and longer follow-up studies will be needed to confirm these expected advantages for the long-term outcome and to assess the long-term safety of this minimization of immunosuppressive therapy.

Long-term graft outcome in patients with chronic allograft nephropathy after immunosuppression modifications.

BACKGROUND/AIM: This retrospective study was conducted to assess the efficacy and safety of immunosuppression conversion on progression of chronic allograft nephropathy (CAN). METHODS: One-hundred and seventy-four cyclosporin (CsA)-treated renal transplant recipients were studied. Patients were included if they had a biopsy-proven CAN (mild to moderate) with serum creatinine < or =3.5 mg/dL. Patient treatment was switched to either: (A) MMF/reduced dose CsA (MMF for azathioprine (Aza); n = 132); or (B) Aza/Tac for CsA (n = 42). Patient records were checked for graft function and survival, and for co-morbidities after conversion. RESULTS: Mean follow-up before conversion was 52.2 +/- 31.1 and 47.9 +/- 27.4 months for groups A and B, respectively. There was significant deterioration of graft function in group B after five years (P < 0.5). Ten-year actuarial graft survival was 38% in group A and 19% in group B (P = 0.04). Nine patients (five patients and four patients in groups A and B, respectively) started dialysis within 12 months. Tacrolimus-treated patients had a lower insignificant incidence of hyperlipidemia (P = 0.05), but a significantly higher incidence of diabetes mellitus (P = 0.04).There was no significant change or difference in blood pressure between groups. CONCLUSIONS: Our results suggest that in patients with CAN and deteriorating allograft function, CsA minimization and addition of MMF achieved favorable efficacies in retarding the decline of graft function. Further prospective studies with larger cohorts are needed for validation.

Long-term graft outcome in patients with chronic allograft dysfunction after immunosuppression modifications.

BACKGROUND: This retrospective study was conducted to assess the efficacy and safety of immunosuppression conversion on progression of chronic allograft nephropathy (CAN). MATERIAL/METHODS: One hundred-seventy four cyclosporin (CsA)-treated renal transplant recipients were studied. Patients were included if they had a biopsy-proven CAN (mild to moderate) with serum creatinine < or =3.5 mg/dL. Patients were treated with either: (A) MMF/reduced dose CsA [MMF for azathioprine (Aza)] (n=132); (B) Aza/Tac for CsA (n=42). Patient records were checked for graft function and survival, co-morbidities after conversion. RESULTS: Mean follow-up before conversion was 52.2+/-31.1 and 47.9+/-27.4 month in-group A and B, respectively. There was a significant deterioration of graft function in-group B after 5-years (P<0.5). Ten-year actuarial graft survival was 38% in-group A and 19% in-group B (P=0.04). Nine patients started dialysis within 12 months. Tacrolimus-treated patients had a lower insignificant incidence of hyperlipidemia (P=0.05), but a significantly higher incidence of diabetes mellitus (P=0.04).There was no significant change or difference in blood pressure between groups. CONCLUSIONS: Our results suggest that in patients with CAN and deteriorating allograft function, CsA minimization and addition of MMF achieved favorable efficacies in retarding the decline of graft function. Further prospective studies with larger cohorts are needed for validation.

Immunosuppression modifications and graft outcome in patients with chronic allograft nephropathy.

OBJECTIVES: This retrospective study was done to assess the efficacy and safety of immunosuppression conversion on progression of chronic allograft nephropathy. MATERIALS AND METHODS: One hundred seventy-four cyclosporine-treated renal transplant recipients were studied. Patients were included if they had biopsy-proven chronic allograft nephropathy (mild to moderate) with a serum creatinine level of 300 micromol/L or less. The treatments groups were (1) mycofenolate mofetil and reduced-dosage cyclosporine (group MMF/CsA; n=132) and (2) azathioprine and reduced-dosage tacrolimus (group Aza/Tac; n=42). Patient records were checked for graft function, survival, and comorbidities after conversion. RESULTS: Mean follow-up before conversion was 52.2 -/+ 31.1 and 47.9 -/+ 27.4 month in groups MMF/CsA and Aza/Tac, respectively. There was a significant deterioration of graft function in group Aza/Tac after 5 years (P < .05). Ten-year actuarial graft survival in group MMF/CsA was 38%; in group Aza/Tac it was 19% (P = .04). Nine patients started dialysis within 12 months. Tacrolimus-treated patients had a lower insignificant incidence of hyperlipidemia (P = .05) but a significantly higher incidence of diabetes mellitus (P = .04). There were no significant changes or differences in blood pressure between the groups. CONCLUSIONS: Our results suggest that in patientswith chronic allograft nephropathy and deteriorating allograft function, cyclosporine minimization and addition of mycofenolate mofetil achieve favorable effects in retarding the decline of graft function. Further prospective studies with larger cohorts are needed for validation.

Characteristics of recipients whose kidney allograft has functioned for more than 20 years.

OBJECTIVES: To study the characteristics of, and predictors for, survival in renal transplant recipients with an allograft functioning for more than 20 years. MATERIALS AND METHODS: Of 144 renal transplants done between 1976 and 1985, 31 allografts were still functioning for more than 20 years (range, 21- 28.5 years). The characteristics of the patients and determinants of the outcomes were obtained by reviewing the patients' medical records. RESULTS: Fourteen patients were treated with cyclosporine, while 17 patients had primary immunosuppression with azathioprine-based regimens. Episodes of acute rejection occurred in 17 patients (58%), 7 of these experienced 2 or more episodes. At most-recent follow-up, the mean serum creatinine level was 132 +/- 44 micromol/L . Four patients were assessed by graft biopsy 15 or more years after the transplant, revealing 2 cases of mild glomerulosclerosis and 2 cases of moderate chronic allograft nephropathy. The most common complication was hypertension (54%). The independent determinants of long-term graft survival were donor age and source, hypertension both before and after renal transplant, and histopathological findings of chronic allograft nephropathy. CONCLUSIONS: Renal transplant offers a near-normal life to patients with end-stage renal disease soon after transplant and for upwards of 20 years and more. We found no significant benefit to cyclosporine-based immunosuppression on long-term graft survival.

Intercellular adhesion molecules in systemic lupus erythematosus patients with lupus nephritis.

Cardiovascular events are markedly increased in systemic lupus erythematosus (SLE), and the mechanism of atherogenesis remains poorly understood. Several methods have been employed to assess endothelial function, among these is the measurement of biomarkers of endothelial activation and dysfunction [intercellular adhesion molecule (ICAM-1)]. It has been reported that such biomarkers play a more important role than traditional risk factors in cardiovascular disease. The objectives of this study were to determine the level of ICAM-1 as markers of endothelial dysfunction in 40 Egyptian patients who have SLE with various degrees of activity and to investigate their relationship to disease activity. Sixty people (40 with SLE and 20 healthy as the control group) were the subject of this study; their clinical disease activity was scored according to the SLE disease activity index (SLEDAI), and serum sampling was obtained for ICAM-1 level assay. Renal biopsy was carried out and examined by light microscopy by a pathologist blinded to the clinical activity. The mean level of ICAM-1 was significantly higher in SLE patients with active disease (826.05 +/- 367.1 Pg/ml) compared to those with inactive disease (441.33 +/- 225.19 Pg/ml) and the healthy control volunteers (111.5 +/- 17.36 Pg/ml). There was a positive correlation between serum ICAM-1 and SLEDAI (r = 0.66). A high concentration of soluble ICAM-1 in SLE patients with nephritis is reported in this paper. Our finding of increased concentrations of ICAM-1 in SLE patients with nephritis underlines the importance of inflammation and endothelial involvement in this disease, but their predictive value in the disease monitoring need to be further studied.

Colchicine vs. omega-3 fatty acids for prevention of chronic cyclosporine nephrotoxicity in Sprague Dawley rats: an experimental animal model.

BACKGROUND: In view of the high cost of the new immunosuppressive drugs, which represents a challenge for both patients and governmental resources especially in developing countries, trials to prevent side effects of the first calcineurin inhibitor discovered (cyclosporine, Cs) are of particular interest. METHODS: In this prospective randomized experimental study, 60 male Sprague Dawley rats were enrolled. Group 1 served as negative control group and received olive oil. Group 2 received Cs orally 100 mg/kg for 80 days and served as positive control group. Group 3 was given daily colchicine (30 microg/kg/day) in addition to Cs. Group 4 was given omega-3 fatty acids (100 mg/kg/day) in addition to Cs. Animals were subjected every other week to laboratory assessment for serum creatinine, sodium, potassium, and Cs whole-blood through levels. At the end point, the animals were sacrificed, and kidney tissue was examined for histopathological changes. RESULTS: There were no significant differences in serum creatinine, creatinine clearance, and serum sodium and potassium in all groups. Histopathological examination of kidney tissues showed focal tubular atrophy and interstitial fibrosis in inner medulla and inner strip of the outer medulla in all Cs-treated animals. Morphological changes were significantly less in colchicine-treated rats compared to omega-3 fatty acid-treated rats and absent in the negative control group. Furthermore, immunostaining showed positive reactions for vimentin in Cs-treated animals only. CONCLUSIONS: Colchicine and omega-3 fatty acids are protective for the kidney against cyclosporine-induced nephropathy; however, colchicine is more protective than omega-3 fatty acid.