Death With a Functioning Graft Kidney: A Single-Center Experience of More Than 4 Decades.

OBJECTIVES: Death with graft function is one of the most catastrophic events after kidney transplant. Various pre and posttransplant risk factors have been linked to death with graft function. Characterization of this event is crucial to set successful preventive measures. Here, we reported on death with graft function among living donor kidney transplant recipients seen at the Urology and Nephrology Centre at Mansoura University (Mansoura, Egypt) throughout a period of >4 decades. MATERIALS AND METHODS: This single-center study included 2953 patients who received living donor kidney transplant between March 1976 and December 2018. Patient data were retrospectively analyzed. Patients who had death with graft function were compared with other patients with regard to pre- and posttransplant data. Causes of death with graft function were also studied. RESULTS: Among our patients (1654 male [56%] and 1299 female [44%] patients), death with graft function was reported in 9.9% of patients and responsible for 58.3% of deaths and 24.6% of graft losses. Male sex, pretransplant dialysis and blood transfusion, pre- and posttransplant diabetes and hypertension, high HLA mismatches, antithymocyte globulin induction, steroid and cyclosporine use, steroid dose, acute rejection episodes, and posttransplant infections and malignancy were significantly higher among the death with graft function group. However, multivariate analyses showed that only pretransplant diabetes, steroid dose, and posttransplant infections were risk factors for death with graft function. The most common causes of death with graft function were cardiovascular disease, infections, and malignancy. CONCLUSIONS: Death with graft function remains a significant hindrance to competent kidney transplant outcomes. We found that the most common contributors to this major event were cardiovascular disease, infections, and malignancy. More attention is needed to modify risk factors of cardiovascular disease, to update implementation policies for posttransplant vaccinations, and to conduct increased malignancy surveillance, as well to adopt less aggressive immunosuppression regimens.

Chemical composition of Zamzam water: A comparative study with international standards of drinking water.

Studies conducted on the chemical composition of Zamzam water are conflicting especially for arsenic. Therefore, the aim of our study is to study the composition of tap and bottled Zamzam water and to compare its quality according to international guidelines of drinking water. Six Zamzam tap water samples as well as one bottled sample were analyzed according to standard methods (APHA) for their chemical constituents (pH, TDS, Na, K, Mg, Ca, Fe, Cu, Zn, Cd, Pb, Mn, Al, As, Cl-, SO4 -2, HCO3 - and PO4 -3). The results were compared to guidelines of WHO and EPA for quality of drinking water. All analyzed parameters were below the maximum allowable limits (MAL) of WHO and EPA (p˃0.05), with the exception of TDS. The average values of TDS (814 mg L-1 in tap zamzam water samples and 812 mg L-1 in bottled sample) were below the MAL of WHO (1000 mg L-1) but exceeded the limit that defined by EPA as a non-enforceable guidelines (500 mg L-1) (p˂0.05). Compared to the collected tap zamzam water samples, bottled sample had significantly lower levels of Na, PO4 -3 (p˂0.05) and Cu (p˂0.01). The study concluded that Zamzam water has acceptable chemical composition including arsenic, except for TDS that exceeds the high non-enforceable accepted limit according to EPA.

Outcome of sirolimus-based immunosuppression, fifteen years post-live-donor kidney transplantation: Single-center experience.

In a prospective randomized controlled trial, between May 2001 and January 2003, 132 live-donor kidney transplant recipients were randomized to receive sirolimus primary immunosuppression, either in combination with low dose tacrolimus (Tac group) or in combination with mycophenolate mofetil (MMF group). We have previously reported on 2- and 5-year follow-up results, with favorable patient and graft outcomes obtained in both groups. In view of recent published reports of increased risk of inferior outcomes among sirolimus-treated patients, we herein present results of an observational extension of the previously randomized patients 15 years post-transplantation. Mortality rates were 10.8% and 3% in Tac and MMF groups respectively after mean follow-up period of 11.2-11.8 years. Comparable graft survival rates were obtained in both groups ranging from 60% to 62.7%. The (MMF) group continued to have the advantage of remaining on primary plan of immunosuppression (56.7% of patients) as well as to maintain better graft function in terms of serum creatinine level. Herein, we presented longest term published data for sirolimus-based immunosuppression among live-donor kidney transplants with favorable outcome in terms of survival and graft function.

Impact of Donor Source on the Outcome of Live Donor Kidney Transplantation: A Single Center Experience.

BACKGROUND: Renal transplantation is the ideal method for management of end-stage renal disease. The use of living donors for renal transplantation was critical for early development in the field and preceded the use of cadaveric donors. Most donors are related genetically to the recipients, like a parent, a child, or a sibling of the recipient, but there are an increasing percentage of cases where donors are genetically unrelated like spouses, friends, or altruistic individuals. Donor shortages constitute the major barrier for kidney transplantation, and much effort has been made to increase the supply of living donors. The impact of donor source on the outcome of renal transplantation is not adequately studied in our country. OBJECTIVES: The aim of the study was to evaluate the impact of donor source on the outcome of live donor kidney transplantation. PATIENTS AND METHODS: From March 1976 to December 2013, the number of patients that underwent living renal transplantation sharing at least one HLA haplotype with their donors was 2,485. We divided these patients into two groups: (1) 2,075 kidney transplant recipients (1,554 or 74.9% male and 521 or 25.1% female) for whom the donors were living related, (2) 410 kidney transplant recipients (297 or 72.4% male and 113 or 27.6% female) for whom the donors were living unrelated. All patients received immunosuppressive therapy, consisting of a calcineurin inhibitor, mycophenolate mofetil, or azathioprine and prednisolone. We compared acute rejection and complication rates, as well as long-term graft and patient survival of both groups. Demographic characteristics were compared using the chi-square test. Graft survival and patient survival were calculated using the Kaplan-Meier method. RESULTS: The percentages of patients with acute vascular rejection were significantly higher in the unrelated group, while percentages of patients with no rejection were significantly higher in the related group, but there were no significant differences regarding patient and graft survivals between both groups. CONCLUSIONS: Kidney transplant recipients who received their grafts either from live related donors or live unrelated donors had comparable patient and graft survival outcomes.

Impact of dialyzer membrane flux on metal clearance in hemodialysis patients.

Deficiency of essential trace elements (such as Cu or Zn) and accumulation of potentially toxic trace elements (as Cd or Pb) are both known to have adverse effects in hemodialysis (HD) patients. Up to our knowledge, no studies about the permeability of low and high flux polysulfone membranes on metal ions during hemodialysis are available. Therefore, the aim of the present study was to address this issue. Forty one hemodialysis patients (19 were using high flux polysulfone membrane while the remaining were using low flux one) participated in the study. Blood levels of Cu, Zn, Cd and Pb were determined by graphite furnace atomic absorption spectrometry among HD patients, before and after dialysis session, as well as among matched 40 healthy persons. Blood concentrations of Cu and Zn in the whole hemodialysis group was significantly lower than those of the healthy control group, on the other hand the toxic metals (Cd and Pb) levels were observed to be significantly higher among HD patients compared to the normal persons. Among the hemodialysis group, there were no significant differences between the low and high flux dialyzer groups in terms of pre-dialysis blood levels of Cu, Zn, Cd and Pb. In addition, significantly decreased levels of all metal ions were observed after dialysis sessions using either low or high flux membranes. An exception was Pb which did not show any difference between pre-dialysis and post-dialysis values in the low flux groupIn conclusion Zn and Cu deficiencies should be considered in the treatment of these patients. High flux membranes are more efficient than low flux ones in removing excess Cd and Pb. Therefore, when high flux membranes are used, chelation therapy might not be required for Cd and Pb overload.

Frequency of the Original Kidney Disease and Its Effect on the Outcome of Kidney Transplant in the Urology-Nephrology Center Mansoura University.

OBJECTIVES: Renal allograft function and graft survival depends on many factors, including the source of the graft, immunologic matching between donor and recipient, incidence of acute rejection, and recurrence of the original kidney disease. This work aimed to evaluate the effects of the original kidney disease on patient and graft survival. MATERIALS AND METHODS: This was a retrospective, single-center study that included 2189 kidney transplant recipients who were transplanted at The Urology and Nephrology Centre, Mansoura University, between 1976 and 2010. Of 2189 recipients, 1350 patients with unknown original kidney disease were excluded, with the remaining 839 patients divided into 4 groups according to their original kidney disease. RESULTS: We found pretransplant dialysis and blood transfusion to be statistically significant among the 4 groups. Regarding induction immunosuppressive therapy, a statistical significance was found between the 4 groups regarding the presence and type of induction therapy, with no statistical significance regarding the type of maintenance immunosuppression. There was no statistical significance between the 4 groups regarding the incidence of acute and chronic rejection. We also found recurrence of original kidney disease to be statistically significant in the 4 groups, particularly in the group that included patients with glomerular disease, where the highest rate of recurrence was reported in patients with focal segmental glomerulosclerosis and membranoproliferative glomerulonephritis, and patient and graft survival was also statistically significant. CONCLUSIONS: The original kidney disease has an effect on renal allograft function and graft and patient survival.

Application of Cloud Point Extraction for Cadmium in Biological Samples of Occupationally Exposed Workers: Relation Between Cadmium Exposure and Renal Lesion.

Cadmium (Cd) level in blood and urine of soldering iron workers (n=49) and 41 matched healthy controls has been assessed. Cloud point extraction was employed for preconcentration of Cd. The Cd ions formed hydrophobic complex with 9,10-phenanthraquinone monoethyl thiosemicarbazone that was extracted by surfactant-rich phases in the nonionic surfactant Triton X-114. The surfactant-rich phase was diluted with 1 M HNO3 in methanol prior to its analysis by graphite furnace atomic absorption spectrometry. The parameters affecting the extraction efficiency of the proposed method, such as solution pH, amount of complexing agent, surfactant concentration, temperature, and incubation time, were optimized. Under the optimum experimental conditions, the detection limit and the enrichment factor were 0.04 µg L(-1) and 61, respectively. Relative standard deviation of 10 µg L(-1) Cd was less than 3.0%. The accuracy of the method was examined by analysis of certified reference materials. It was observed that soldering iron workers are liable to Cd overload as indicated by higher levels of Cd in blood and urine when compared with the controls. This exposure may lead to kidney damage indicated by elevation of urinary excretion of both N-acetyl-ß-D-glucosaminidase and ß2-microglobulin.

Determination of Cu(2+), Zn(2+) and Pb(2+) in biological and food samples by FAAS after preconcentration with hydroxyapatite nanorods originated from eggshell.

Hydroxyapatite nanorods (HAPNRs) were prepared from recycled eggshell by using precipitation method. The structure of the HAPNRs was physicochemically and morphologically characterized by X-ray diffraction, transmission electron microscopy and Fourier transform infrared spectroscopy. The resulting HAPNRs were used for solid phase extractive preconcentration of Cu(2+), Zn(2+) and Pb(2+) prior to its determination by flame atomic absorption spectrometry. Experimental variables that influence the quantitative extraction of metal ions were optimized by both batch and column methods. The analytes were quantitatively sorbed on the matrix between pHs6 and 9. The maximum sorption capacity of the HAPNRs has been found to be 2.43, 2.37 and 2.53 mmol g(-1) for Cu(2+), Zn(2+) and Pb(2+), respectively, with the preconcentration factor of 250. The 3σ detection limit and 10σ quantification limit for Cu(2+), Zn(2+) and Pb(2+) were found to be 0.72, 0.55 and 5.12 µg L(-1) and 2.40, 1.83 and 17.06 µg L(-1), respectively. The calibration curves were linear up to 250 µg L(-1) for Cu(2+), 300 µg L(-1) for Zn(2+) and 400 µg L(-1) for Pb(2+). Accuracy of the proposed method was verified using certified reference materials (NCS ZC85006 Tomato, Seronorm Trace Elements Whole Blood L-1, Seronorm Trace Elements Whole Blood L-3 and Seronorm Trace Elements Urine). The present method was successfully applied to the analysis of these metal ions in sea water, biological and food samples.

Postkidney transplant malignancy in Egypt has a unique pattern: a three-decade experience.

The pattern of posttransplant malignancy varies among transplant units. We report on our single-center experience. Between 1976 and 2007, 1866 kidney transplantations were carried out (1390 males and 476 females, mean age 29.84+/-10.47 years). Recipients who developed posttransplant malignancy were evaluated (74 patients, 3.97%). Furthermore, their data were compared with those of the malignancy-free recipients (1792 patients). Kaposi sarcoma was the commonest type (36.8%) and had the shortest transplant-to-malignancy period (mean 2.84 years). The lesions were only cutaneous in 75% of cases. Skin cancers were the fourth among posttransplant malignancies (9.2%) and 85.7% of cases were basal cell carcinoma. In our series, age and prior blood transfusion were identified as independent risk factors for the development of posttransplant malignancy. In conclusion, the prevalence and type of posttransplant malignancy vary because of many factors including environmental and genetic factors. In our series, Kaposi sarcoma was the commonest type and, therefore, needs further evaluation.

Living-donor kidney retransplantation: risk factors and outcome.

OBJECTIVE: To review the results of kidney retransplantation at our centre. PATIENTS AND METHODS: Between March 1976 and January 2002, 1406 kidneys were transplanted; among these, 54 patients received a second graft (39 men, mean age 32.1 years, sd 8.6). The donors were 48 relatives (mean age 35.4 years, sd 10.1). RESULTS: The mean (sd, range) duration of the first graft was 49.1 (45.9, 1-192) months and the main cause of these grafts failing was immunological. The mean duration of graft failure was 17.3 (10.5, 5-62) months. The rate of histocompatibility leukocyte antigen (HLA)-A, -B >3 was 16.7% and of haplotype DR matching was 11%. The immunosuppression regimen was mainly based on cyclosporin (75%). There were 33 episodes of acute rejection in 23 patients. The major complications were hypertension (70%), infections (30%) and hepatitis (11%). The overall graft and patient survival was good; 15 grafts (27%) were lost during the follow-up of 1-17 years. Ten patients died, five with a functioning graft. Multivariate analysis showed that donor relationship, primary immunosuppression, duration of first graft and serum creatinine level at 1 year were predictors of graft survival. CONCLUSION: Renal retransplantation is the treatment of choice in patients who have lost their graft. The use of related living-donors and potent immunosuppression could help to improve the outcome.

Preemptive living-donor kidney transplantation: clinical course and outcome.

BACKGROUND: Dialysis is not only associated with morbidity, it is also expensive. In developing countries, preemptive renal transplantation (Tx) may be a cost-effective option, offering an additional benefit to conventional renal Tx. MATERIALS: Between March 1976 and March 2001, 1,279 first living-donor Txs were performed in our center. The 82 patients (6.4%) who underwent Tx without prior dialysis were compared with 1,197 patients who had been dialyzed before Tx. RESULTS: The dialysis-dependent group received more blood transfusions (65% vs. 30%) before Tx. Actuarial graft and patient survival at 5 years was comparable in both groups (P =0.2 and P =0.8, respectively). The incidence of acute and chronic rejection was not different between the two groups. Mortality rate was also similar in the two groups. The main cause of death with a functioning graft was cardiovascular in the preemptive Tx group and chronic liver disease and infection in the control group. CONCLUSION: In the context of a developing country, preemptive Tx offers comparable patient and graft survival to conventional renal Tx and eliminates the complications, inconvenience, and cost of dialysis.

Evaluation and selection of potential live kidney donors.

PURPOSE: Renal transplantation is an optimal therapy for patients with end stage kidney disease. A thorough evaluation of potential donors is necessary to provide the best functional outcome for recipients and ensure no or minimal morbidity for donors. MATERIALS AND METHODS: Between 1992 and 2001, 1661 ABO compatible potential living donors were evaluated clinically as well as by laboratory and imaging studies. RESULTS: Of 1661 potential donors 814 (49%) were excluded. The reasons for elimination were general medical reasons in 34.4% of cases, nephrological disorders in 25.6%, urological diseases in 11.7% and immunological causes in 16.2%. Exclusion on an ethical basis accounted for 12.2% of cases. CONCLUSIONS: Although kidneys from living donors provide the best functional outcome, 50% of potential candidates must be excluded.

Pulse cyclophosphamide inadequately suppresses reoccurrence of minimal change nephrotic syndrome in corticoid-dependent children.

BACKGROUND: In minimal change nephrotic syndrome (MNCS), the most common primary nephrotic syndrome in children, approximately 95% of cases show excellent responses to steroid therapy. However, responding patients may become steroid dependent and experience serious side effects. Although oral cyclophosphamide has been recommended in these patients, long-term side effects such as gonadal toxicity are an important concern. Therefore, cyclophosphamide pulses given intravenously may provide an option that maintains remission with less-frequent side effects. METHODS: We treated 20 primary steroid-dependent MCNS patients (15 boys and five girls) with intravenous cyclophosphamide. The patients were children with ages ranging from 3 to 15 years of age. Remission was induced by steroids followed by cyclophosphamide at a dose of 500 mg/m2 body surface area per month for 6 months. During this period, we attempted to completely withdraw steroids and maintain patients on cyclophosphamide alone. We monitored the patients for the occurrence of relapse and side effects during this period and for an additional 6 months after withdrawal of cyclophosphamide. RESULTS: At the end of the 6-month cyclophosphamide treatment period (i.e. 4 months after steroid discontinuation), nine patients (45%) were in remission on cyclophosphamide alone. However, patients that maintained treatment-free remission (cyclophosphamide responders) decreased to five (25%), two (10%) and one (5%) at 6 months, 1 year and 2 years, respectively. CONCLUSION: We found that a 6-month course of pulse cyclophosphamide produced unfavourable effects in the majority of paediatric patients with steroid-dependent nephrotic syndrome.

Levamisole: adjunctive therapy in steroid dependent minimal change nephrotic children.

In children with minimal change nephrotic syndrome (MCNS), the steroid dependent group constitutes an especially difficult case for management. Patients in this group are prone to serious steroid side effects. Additionally, alkylating agents commonly fail to maintain remission and expose patients to more side effects. Therapy with the immunostimulant drug levamisole may therefore be another option in the attempt to maintain remission with minimal side effects. We prospectively treated 20 of our steroid dependent primary MCNS patients with levamisole. All patients were children, with an age range of 3-15 years; 16 were boys and 4 were girls. Remission was firstly induced by steroids, then levamisole was added in a dose of 2.5 mg/kg body weight on alternate days for 6 months. During this period we attempted to withdraw steroids completely and maintain patients on levamisole alone. We followed up our patients for the occurrence of relapse and side effects during this period and for a further 6 months after stopping levamisole. In 11 out of 20 children (55%), we successfully stopped steroids for more than 2 weeks. At the end of the 6-month treatment period (i.e. after 4 months of steroid discontinuation), ten patients (50%) were maintaining remission on levamisole alone. At the end of the 12-month study period (i.e. after 6 months of levamisole discontinuation), five patients (25%) were still in remission without any treatment for the previous 6 months. No significant side effects were reported during levamisole therapy. None of the patients developed neutropenia, but the leukocyte count showed a significant reduction in those who responded to levamisole treatment. We concluded that levamisole therapy for 6 months is a safe and perhaps effective therapy in a subset of children with steroid dependent MCNS to enable an otherwise infeasible withdrawal of steroids. This may be worth a trial before other types of more hazardous adjunctive therapies are considered.