Toward Best Practices for Controlling Mammalian Cell Culture Environments.

The characterization, control, and reporting of environmental conditions in mammalian cell cultures is fundamental to ensure physiological relevance and reproducibility in basic and preclinical biomedical research. The potential issue of environment instability in routine cell cultures in affecting biomedical experiments was identified many decades ago. Despite existing evidence showing variable environmental conditions can affect a suite of cellular responses and key experimental readouts, the underreporting of critical parameters affecting cell culture environments in published experiments remains a serious problem. Here, we outline the main sources of potential problems, improved guidelines for reporting, and deliver recommendations to facilitate improved culture-system based research. Addressing the lack of attention paid to culture environments is critical to improve the reproducibility and translation of preclinical research, but constitutes only an initial step towards enhancing the relevance of in vitro cell cultures towards in vivo physiology.

In situ monitoring reveals cellular environmental instabilities in human pluripotent stem cell culture.

Mammalian cell cultures are a keystone resource in biomedical research, but the results of published experiments often suffer from reproducibility challenges. This has led to a focus on the influence of cell culture conditions on cellular responses and reproducibility of experimental findings. Here, we perform frequent in situ monitoring of dissolved O2 and CO2 with optical sensor spots and contemporaneous evaluation of cell proliferation and medium pH in standard batch cultures of three widely used human somatic and pluripotent stem cell lines. We collate data from the literature to demonstrate that standard cell cultures consistently exhibit environmental instability, indicating that this may be a pervasive issue affecting experimental findings. Our results show that in vitro cell cultures consistently undergo large departures of environmental parameters during standard batch culture. These findings should catalyze further efforts to increase the relevance of experimental results to the in vivo physiology and enhance reproducibility.

It takes time after bilateral nephrectomy for better control of resistant hypertension in renal transplant patients.

UNLABELLED: Severe resistant hypertension in end-stage renal disease patients has traditionally been an indication for bilateral nephrectomy (BN) before kidney transplantation. Nevertheless the influence of BN on successful control of hypertension has not been well documented. We sought to clarify the effect of BN on blood pressure patterns and control in renal transplant patients. MATERIALS AND METHODS: We retrospectively reviewed 28 patients who underwent BN between November 2003 and May 2009 before or after kidney transplantation. Nineteen of them were under treatment with 4 or 5 antihypertensives according to the international guide lines; they had BN for resistant hypertension. They were considered as group 1 (G1). Nine patients operated for indications other than resistant hypertension; they constitute group 2 (G2) and considered as a control group. All patients received triple immunosuppression according to our local protocol. BN was done either before, simultaneously or after transplantation. Antihypertensives were recorded before and after BN. We evaluated our patients at 3 months, 1 year, and 3 years. Acute rejection episodes and calcinurein nephrotoxicity were reported. RESULTS: In G1, the mean age was 30.2 years (range, 10-62). In G2, the mean age was 33.6 years (range, 11-61). Before BN, G1 patients used antihypertensive drugs (3.6 +/- 1.05 drugs per day; mean +/- SD), which was significantly higher than in G2 patients (2.0 +/- 1.65 drugs per day; P = .02). Three months after BN, G1 patients used 2.6 + 0.9 drugs per day, with gradual reduction in number of antihypertensives to 1.4 +/- 1.3 drugs per day at 3 years (P = .008). In G2, there was reduction in antihypertensive drug number per day, which was insignificant during the follow-up period. No difference was noted between G1 and G2 drug administered after BN. We conclude that BN is effective to help blood pressure control, in resistant hypertension in renal transplant patients, but it starts to show up 3 months after surgery, and continues to work for a year and more.

Heat inactivation can differentiate between IgG and IgM antibodies in the pretransplant cross match.

The presence of IgG antibodies in the pretransplant cross-match (XM) test results in hyperacute rejection, but IgM antibodies are inconsequential. The XM should be able to differentiate between IgG and IgM antibodies. This study evaluated 3 methods. This study was based on 500 patients for whom XM were performed between 2004 and 2006 with all 3 techniques. Two patient sera were used: normal serum and heat inactivated serum, which was prepared by incubating patient serum at 63 degrees C for 10 minutes to destroy IgM antibodies. The efficiencies of flow cytometry XM (FC-XM), dithiothreitol complement-dependent microlymphocytotoxicity (DTT/CDC-XM), and heat inactivation (HI-CDC-XM) to differentiate between IgG and IgM were evaluated by using both sera. Patients with positive XM, and negative HI-CDC-XM were reported as negative XM. During the study period, there were 70 patients with positive B-cell XM. Forty-nine became negative after HI-XM, and 21 remained positive. Only 34 cases became negative after DTT-CDC-XM and 36 remained positive. HI-CDC-XM was comparable to FC-XM; all patients testing negative with this technique experienced successful renal transplantations without hyperacute, accelerated, or acute rejection episodes. Our study showed that HI-CDC-XM was effective at exclude donor-specific IgM antibodies, a result which was comparable to FCXM to detect only IgG antibodies. HI is simple and rapid and does not involve any extra equipment or cost.

Postrenal transplantation urologic complications.

OBJECTIVES: We sought to explore the incidence, risk factors, clinical presentation, management options, and outcomes of post renal transplant urologic complications. PATIENTS AND METHODS: Between November 1993 and December 2005, we performed 646 renal transplantation procedures in 373 males and 273 females, of whom 81 were children. Kidney grafts were obtained from 461 living and 185 cadaveric donors. The medical records were retrospectively reviewed for urologic complications. Affected patients presented clinically with impaired kidney function: the diagnosis was confirmed by ultrasound scanning, isotope renal scanning, magnetic resonance urography, and/or antegrade urography. Ureteric stricture was managed by percutaneous antegrade ureteric dilatation and stenting, or by surgical reconstruction. Urine leak was treated by prolonged bladder drainage or surgical reconstruction. Renal stones were treated with extracorporeal shockwave lithotripsy. RESULTS: Urologic complications were detected in 31 recipients (4.8%), including 21 males and 10 females, among whom 4 were children. They had received kidney grafts from 19 living and 12 cadaveric donors. Urologic complications were ureteric strictures in 15 (2.58%), urine leaks in 15 (2.58%), and ureteric stone in 1 (0.17%) recipients. There was no graft loss to urologic complications. CONCLUSIONS: The incidence of post-kidney transplant urologic complications was 4.8%. They were more common among male recipients and after cadaveric kidney transplantation. Although ureteric stricture presented late posttransplantation and was more common among children (4.23%), urine leak presented early and was more common in the elderly (4.69%). All urologic complications were successfully managed, with no graft loss.

Kuwait experience in laparoscopic donor nephrectomy: first 80 cases.

INTRODUCTION: Laparoscopic donor nephrectomy (LDN) has been adopted rapidly as it offers less postoperative pain, early recovery, and better cosmetic results compared with the open approach. This prospective study investigated the results of the first 80 LDN performed between May 2005 and May 2006, with regard to donor morbidity and effect on graft function. PATIENTS AND METHODS: LDN was attempted in 80 donors by one surgical team. Donors included 68 men and 12 women, ages 22 to 53 years, with body mass indices of 17.9 to 42.4. According to computed tomographic angiography, left nephrectomy was planned in 75 donors and right nephrectomy in 5. RESULTS: LDN was completed successfully in 74 (92.5%) and converted to open in 6 (7.5%) secondary to technical difficulties and operative bleeding. The mean operating time for LDN was 186.16 minutes (range, 95-260 minutes). Mean warm ischemia time (WIT) was 5.7 minutes (range 2-16 minutes). Mean hospital stay was 5.28 days (range, 3-14 days). Two donors (2.5%) were reexplored for postoperative bleeding. Renal function in all donors was satisfactory within 3 months of surgery. Immediate diuresis occurred in 76 (95%) recipients. Acute cellular rejection was diagnosed in 1 recipient. No association was observed between WIT, graft function, development of acute tubular necrosis (ATN), or rejection. Plasma creatinine normalization was clearly associated with donor age. CONCLUSIONS: LDN was found to be a safe procedure with low postoperative morbidity and short recovery time for donors. It can potentially increase the donor pool.

Renal transplantation in children.

OBJECTIVE: Renal transplantation is the preferred method for the treatment of children in end-stage renal disease (ESRD). In this retrospective study, we analyzed the results at our center. PATIENTS AND METHODS: Between November 1993 and June 2006, 86 children (50 boys and 36 girls) received organs from 50 living donors (LDTx) and 36 cadaveric donors (CDTx). Twenty children were <10 years. In addition to ESRD, some patients had one or more other high-risk factors, eg, abnormal lower urinary tract in 36 recipients (42%). The procedure was a preemptive transplantation in 28, and a retransplantation in 9 recipients. Induction immunosuppression used either antithymocyte globulin (43 cases) or anti-interleukin-2 receptor antibodies (20 cases). RESULTS: Patients were followed for 6 to 150 months. There were 24 surgical complications (28%), 26 acute rejection episodes (33%), and 17 of systemic bacterial or viral infections. Two recipients died at 1 and 21 months. The 14 grafts were lost at 1 day to 87 months. The 1- and 10-year actuarial survival rates were 99% and 98%, respectively, for the recipients, and 88% and 84%, respectively, for the grafts. The 10-year actuarial graft survival rates were 98% in LDTx and 64% in CDTx; 86% in recipients >10 years old and 75% in recipients <10 years old. Abnormal urinary tract, pretransplantation dialysis, and transplant number showed no effect on graft survival. All pediatric recipients with functioning grafts are fully rehabilitated. CONCLUSION: Renal transplantation is the preferred method of treatment for children in ESRD. Higher graft survival rates were achieved in older children and following LDTx.

Hyperinfection strongyloidiasis: an anticipated outbreak in kidney transplant recipients in Kuwait.

BACKGROUND: Hyperinfection strongyloidiasis is a potentially fatal syndrome associated with conditions of depressed host cellular immunity. A high degree of suspicion is required to detect cases early and thereby avoid a fatal outcome. PATIENTS AND METHODS: Three consecutive cadaveric kidney transplant recipients died within 2 months from hyperinfections with strongyloides. All members of the transplant team were involved in a campaign to localize the source of infection, identify and treat affected patients, and provide adequate prophylaxis to other transplant recipients. We reviewed cadaveric donor files and screened 61 hospital personnel, 27 hospital inpatients, and the 87 hospital outpatients transplanted in a year's time before that event for a possible source. The screening test included analysis of fresh stool samples on 3 consecutive days for strongyloides larvae. The anti-helminthic drug albendazol was administered to all patients during screening. They were followed for possible development of the disease during the infectivity period. RESULTS: The first 2 recipients received their kidneys from 1 cadaveric donor, while the third received it from a different donor. Both donors came from areas endemic for strongyloidiasis. The 3 recipients were on tacrolimus-based immunosuppression. The twin recipient of the second kidney was on cyclosporine and did not manifest a disease. All stool samples taken for screening were negative for the infective larvae. None of the other recipients developed the disease. CONCLUSIONS: Cadaveric donors were the possible source for this outbreak. Cyclosporine probably has a protective effect against strongyloides. In our setting, screening of cadaveric donors for strongyloides is mandatory before accepting them for donation, and oral prophylaxis is required for all recipients.

Outcome of renal allografts with multiple arteries.

BACKGROUND: Renal allograft transplantation with multiple arteries (MRA) was always avoided as much as possible as it is technically demanding and carries a higher MSK for complications. This was a single-center study to explore the graft outcomes of kidney transplantation with MRA. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 35 patients who received kidney grafts with MRA for the surgical technique, surgical complications, graft function, and graft survival. The results were compared with those achieved in recipients of kidney grafts with a single renal artery (SRA). RESULTS: Of 35 grafts, there were 2 renal arteries in 30 grafts, and 3 renal arteries in 5 grafts. In the MRA group, there were 7 instances of surgical complications, the mean serum creatinine levels were 122, 139, and 156 micromol/L at 1 month, 1 year, and 5 years, respectively, and the actuarial graft survival rates were 94.3%, 88.6%, and 83% at 1, 5, and 10 years, respectively. In the SRA group, there were 56 instances of surgical complications, the mean serum creatinine levels were 115, 121, and 141 micromol/L at 1 month, 1 year, and 5 years, respectively, and the actuarial graft survival rates were 93.7%, 88.1%, and 84.4% at 1, 5, and 10 years, respectively. CONCLUSION: Although transplantation of MRA grafts might carry a relatively higher risk for complications, it is justified because it gives results comparable with those achieved in SRA.

Renal allograft venous thrombosis is salvageable.

BACKGROUND: Renal vein thrombosis (RVT) is an uncommon but serious complication. It usually occurs early after surgery. While compression of the renal vein is the most common cause, early rejection and hemostatic defects are other known causes. The symptoms are nonspecific and diagnosis is often delayed. Ultrasonography and renal isotope scan findings may resemble acute rejection or acute tubular necrosis. PATIENTS AND METHODS: We retrospectively reviewed the records of 684 recipients who were transplated between November 1993 and May 2006. The diagnosis of RVT was suspected by an unexplained drop in urine output, rise in serum creatinine, or hematuria, and confirmed by Doppler ultrasound and isotope scanning. Urgent exploration was performed in all suspected cases. RESULTS: Seven incidences of biopsy-proven RVT were encountered, including 3 associated with hematoma and 1 with rejection. Four grafts were from cadaveric donors. Three grafts were salvaged. CONCLUSIONS: The incidence of RVT in the present series was 1%. All cases developed in the first 2 weeks after transplantation. It was more common in adults, in female recipients, and in cadaveric grafts. Early diagnosis and intervention were the keys to salvage.

Lymphedema: an unusual complication of sirolimus therapy.

INTRODUCTION: Lymphedema is an increasingly observed complication of sirolimus (SIR) therapy. In this report, we describe four renal recipients with SIR-induced lymphedema of varying severity. CASES REPORTS: Patient 1, a 38-year-old man developed lymphedema of the left upper limb after being exposed to SIR for 30 months (mean daily Rapamune dose, 3 mg; trough level, 10-18 ng/mL). Venography and duplex ultrasound were normal. Lymphangiography was showed delayed lymphatic drainage. SIR was replaced with Prograf with significant improvement in the lymphedema over the next 6 months. Patient 2, a 26-year-old woman, developed lymphedema of the left lower limb at 24 months after starting SIR (mean daily dose, 3 mg; trough level, 10-15 ng/mL). Lymphangiography showed delayed drainage of lymphatics in the left lower limb. The patient was shifted to Prograf and there was some improvement over the next 4 months. Patient 3, a 28-year-old man, developed lymphedema of the left upper limb at 24 months after the start of SIR (mean daily dose, 2 mg, trough level, 6-15 ng/mL). Lymphangiography showed evidence of lymphatic obstruction. SIR was changed to cyclosporine with only mild improvement in lymphedema over the next 6 months. Patient 4, a 46-year-old man, developed lymphedema of the right upper limb at 7 months after starting SIR (mean daily dose, 6 mg; trough level, 10-16 ng/mL). Lymphangiography showed complete blockage of the lymphatic channels. SIR was changed to cyclosporine and there was mild improvement in lymphedema over the next 8 to 10 months. CONCLUSION: The exact mechanism of SIR-induced lymphedema is unknown. The absence of other demonstrable etiologies and spontaneous improvement after discontinuation of SIR suggest that this drug was the responsible factor in these four patients. It occurred 7 to 30 months after transplantation. This is the fourth such report in the literature to the best of our knowledge.

De novo Crohn's disease in a renal transplant recipient.

The prevalence of inflammatory bowel disease (IBD) after renal transplantation is affected by the immune tolerance and the modality of immunosuppression. Mycophenolate mofetil (MMF) may have a promoting effect on the development of posttransplantation erosive enterocolitis and a Crohn's disease-like pattern of colitis. We have presented a 40-year-old man with end-stage renal disease due to chronic glomerulonephritis who commenced hemodialysis for 2 months before receipt of a live unrelated renal transplant. He developed early posttransplantation diabetes mellitus and an anti graft rejection episode, which responded to a methylprednisolone pulse and OKT3 treatment. His immunosuppressive regimen included prednisolone, MMF, and tacrolimus. Three years after transplantation, he developed mild constitutional symptoms, mouth ulcerations, and chronic intermittent bloody diarrhea. Colonoscopy showed active segmental colitis with aphthous ulcers, involving the proximal descending colon and the splenic flexure. Colonic biopsies showed distended and branched crypts in the ascending colon, moderate active chronic colitis with regenerative atypia, skipping appearance, and ulceration in the splenic flexure and descending colon. The edematous crypts were associated with ulcerations in the sigmoid colon and rectum. The features were highly suggestive of Crohn's disease. He was successfully treated with high-dose steroids and 5-aminosalicylic acid. Subsequently, he developed chronic transplant glomerulopathy and restarted hemodialysis. We concluded that de novo Crohn's disease may develop in renal transplant recipients despite immunosuppressive therapy especially with MMF immunosuppression.

Lymphocele following renal transplantation.

We attempt in this retrospective study to evaluate the incidence, clinical presentations, and outcome of lymphocele in renal transplant recipients. 528 patients (313 males and 215 females) have received renal allografts from 384 living and 144 cadaveric donors. Diagnosis of lymphocele was made basically by ultrasound examination, and symptomatic collections were drained either percutaneously or into the peritoneal cavity. There were 50 (9.5%) instances of lymphocele encountered between 2 weeks and 6 months after transplantation. The lymphocele presented clinically predominantly as a single pelvi-abdominal swelling in 28 (56%) cases or as a swelling associated with manifestations of utereric and/or venous compression in 18 (36%) cases, and it was more common after cadaveric transplantation. All the cases of lymphocele were successfully treated with no graft loss. Lymphocele is an uncommon complication after renal transplantation, and is formed during the early post transplantation period. If not treated, it could seriously affect the kidney function. Intraperitoneal drainage is the most effective method for the treatment of symptomatic lymphocele.

Results in 158 consecutive cadaveric renal transplantations.

OBJECTIVES: We investigated the outcome of deceased donor kidney transplantations performed in a single center in a developing country. MATERIALS AND METHODS: A total of 158 patients (69 male and 89 female patients, including 32 children) received kidney grafts obtained from deceased donors between March 1996 and October 2004. Cadaveric renal grafts were transplanted after a cold ischemia time of 4 to 24 hours (mean, 12.5 hours). Retransplantation was performed in 19 recipients. Induction immunosuppression was achieved with antithymocyte globulin. The diagnosis of acute graft rejection was based on histopathological findings. RESULTS: Primary graft function was observed in 77% of cases. Posttransplantation complications were: surgical (n = 60; 38%), systemic bacterial and viral infections (n = 33; 21%), acute rejection (n = 47; 30%), and malignancy (n = 2; 1.3%). Seventeen recipients died with a functioning graft, and 23 more grafts were lost. The 7-year actuarial survival rates were 89% and 75% for recipients and grafts, respectively. CONCLUSIONS: The kidney transplantation program in Kuwait is steadily growing. Kidney grafts obtained from deceased donors contributed 28% of the transplantation activity and were associated with a high rate of primary function. Overall actuarial recipient and graft survival rates were comparable to those reported by larger centers.

The area under the concentration-time curve versus trough and peak blood level monitoring in renal transplant recipients on cyclosporine.

OBJECTIVE: The area under the concentration-time curve of cyclosporine microemulsion is the best measure of the absorption and beneficial effects in renal transplant recipients. We sought to determine the best method of monitoring cyclosporine levels in these patients. METHODS: Prospective evaluation of peak cyclosporine blood levels and area under the curve monitoring were performed for 1 year in 65 renal transplant recipients (study group). Cyclosporine trough levels and peak cyclosporine blood levels were correlated with the calculated area under the curve. Cyclosporine trough levels were monitored in equal numbers of matched controls. RESULTS: There were no significant differences in the incidence of acute rejection, cyclosporine nephrotoxicity, proteinuria, serum creatinine levels, or graft and patient outcomes between the groups (P = .1). Peak cyclosporine blood levels guided by calculating the area under the curve were found to be 27% to 32% lower than previously reported. The correlation coefficient was <70% for cyclosporine trough levels (P < .02) and >90% for peak cyclosporine blood levels (P < .001) when related to the calculated area under the curve. The calculated area under the curve was approximately 6000 ng/mL/h following transplantation, gradually decreasing to approximately 3000 ng/mL/h at 1 year. Both appeared to the acceptable therapeutic values. CONCLUSION: Calculating the area under the curve using trough and peak blood levels versus using isolated readings for either of these levels alone is the most effective method of monitoring cyclosporine in recipients undergoing renal transplant.

Early acute rejection episodes in renal transplantation in relation to immunosuppression protocols: an audit of 100 cases.

INTRODUCTION: Early acute rejection episodes (ARE) have deleterious effects on graft outcomes. The incidence of ARE in the first 3 months has been reported to be <20%. In a recent audit of ARE among 100 renal transplants, we observed the rates to be high (30%). We retrospectively collected details of donor type, induction therapy, immunosuppression medications, drug levels, HLA mismatches, acute tubular necrosis (ATN), and delayed graft function (DGF) to correlate with ARE and response to therapy. RESULTS: Thirty rejection episodes occurred after a mean period of 14.3 days after transplantation. Ninety-one patients had induction treatment with either antithymocyte globulin (ATG) or interleukin 2 receptor antibodies (IL2 Rab). The drugs included cyclosporine, mycophenolate, sirolimus, azathioprine, and prednisolone in these patients. There was no significant difference in ARE among the different drug protocols (30.7%-35.2%). Subjects with 4 or more HLA mismatches displayed more ARE (40.3%) compared with those with 3 or less (23%). Subjects with ATN or DGF immediately posttransplantation had a higher incidence of ARE (39.2%) than those without them (26.3%). Deceased donor recipients had a higher episode of ARE (45.1%) compared with live related donor recipients (25%). On stratifying the known risk factors for ARE, subjects with no risk factors had the least (22.2%) ARE compared with those with one (32.5%) or two (47.6%) risk factors. Subjects who failed to achieve adequate cyclosporine (C2) levels showed significantly higher rates of ARE (86.9%) than those with adequate or higher levels (8.6%). CONCLUSION: Higher HLA mismatches, DGF, deceased donor, and failure to achieve adequate cyclosporine levels were observed to be major risk factors for the development of ARE.

Safety of caspofungin for treating invasive nasal sinus aspergillosis in a kidney transplant recipient.

INTRODUCTION: Invasive fungal sinusitis is a rare but often fatal infection in immunocompromised patients. Aggressive antifungal treatment is mandatory, but is not without risk. Caspofungin, an antifungal agent that is a member of the echinocandin family, an inhibitor of glucan synthesis in the fungal wall, is active against Aspergillus and Candidae infections. Although it works on the fungal wall, it does not affect mammalian cells; hence, its toxicity is minimal. CASE SUMMARY: This report describes a case of invasive Aspergillus sinusitis in a kidney transplant recipient with diabetes mellitus. The infection involved the apex of the right orbit causing optic nerve compression. The patient was treated with transnasal endoscopic decompression of the optic nerve and intravenous AmBisome (liposomal amphotericin B) for 2 weeks without clinical improvement. The combination of caspofungin and AmBisome administered for another 2 weeks yielded partial improvement. The AmBisome had to be discontinued due to deterioration of renal and hepatic function, but the patient completed a further 7-week course of caspofungin alone. Retro-orbital biopsy confirmed a complete response to treatment; the patient's renal and hepatic function returned to normal. CONCLUSION: This case indicates that caspofungin is effective to treat invasive Aspergillus sinusitis in kidney transplant recipients. This agent is well tolerated and safe with respect to renal and hepatic function.

BK virus nephropathy in renal transplant recipients in Kuwait: a preliminary report.

INTRODUCTION: BK virus nephropathy (BKVN) is a significant cause of graft loss among renal transplant recipients. The treatment outcomes of BKVN have been variably reported in the literature. PATIENTS AND METHODS: We prospectively investigated BKV infection and BKVN among a population of renal transplant recipients with suspected BKV infection. The 42 subjects who all had acute allograft dysfunction, were categorized in three groups: those with clinical, laboratory, and histological findings that did not suggest acute rejection, drug toxicity, or obstruction (group 1, n = 24); those with findings that suggested probable acute cellular rejection but did not respond to antirejection treatment (group 2, n = 10); and those whose renal histology suggested BKVN (group 3, n = 8). Polymerase chain reaction analysis was done to detect BKV DNA in urine and blood samples from each subject. BKV DNA was detected in 19 (45%) urine samples with 11 of these subjects (26.1% of total) having BK viremia as well. RESULTS: No evidence of BKVN was detected histologically in seven subjects with isolated BK viruria, while the others proved to be JC virus infections. Among the 11 subjects with BK viremia, eight had BKVN based on renal histology at the time of diagnosis with BKV infection, while the other three subsequently developed histological features of BKVN. BKVN developed after 5.3 +/- 2.5 (2 to 44) months after transplantation. The serum creatinine at time of BKVN diagnosis was 158.9 +/- 58 (87 to 285) micromol/L. All subjects were initially treated with a 50% reduction in immunosuppressive drug doses. Further decreases in immunosuppression were performed in all patients with close monitoring of renal function. All subjects were followed up for a of 18.2 +/- 5 (12 to 26) months. Two grafts were lost not due to BKVN, and one patient was lost to follow-up during this period. The latest serum creatinine in eight recipients is 113 + 20 (81 to 138) micromol/L, which is better than the renal function at diagnosis. CONCLUSION: The prevalence of BKVN in suspected BKV infection was 26%. Although the study period was short (30 months), BK viremia strongly correlated with BKVN, which seemed to be successfully treated with reduction in immunosuppression.

Malignancy in renal recipients.

BACKGROUND: Immunosuppressed organ transplant recipients are more susceptible to cancer than are persons in the general population. If malignancies of the skin are excluded for geographic variation, a cancer incidence of 4% to 7% in transplant recipients is usual. OBJECTIVES: We aimed to find the incidence, histopathological types, and outcome of malignancy in kidney transplant recipients in Kuwait. PATIENTS AND METHODS: Between 1972 and October 2004, more than 1500 kidney recipients were followed. After excluding recipients who left the country soon after transplantation, we reviewed the medical records of the remaining 1171 kidney recipients (724 male and 447 female patients of ages 3 to 76 years) at the time of transplantation. Kidney grafts were obtained from 968 living and 203 deceased donors. Records were retrospectively reviewed for the incidence, clinical presentation, histopathological patterns, and outcome of cancer. RESULTS: Fifty-six malignant lesions (4.8%) were diagnosed in 51 recipients (28 men and 23 women, aged 15 to 66 years), who had received grafts from 44 living and seven cadaveric donors. Malignancy was diagnosed 4 to 288 months after transplantation. The most commonest types were posttransplantation lymphoma and Kaposi's sarcoma. Posttransplantation cancer presented earlier in female and in adult recipients and following decreased donor transplantation. Kaposi's sarcoma appeared earlier than posttransplantation lymphoma or squamous cell carcinoma. Less than 40% of recipients with malignancy are alive.