ABO-Incompatible Kidney Transplantation: Low Rates of Infectious Complications and Excellent Patient Survival.

BACKGROUND: A significant gap exists between demand and supply of organs for patients with end-stage renal disease. To increase the donor pool, kidney transplantation is performed across ABO- and HLA-incompatible barriers. ABO-incompatible kidney transplant (ABOi-KT) recipients are at increased risk of antibody-mediated rejection, infection, and mortality. Hypogammaglobulinemia secondary to immunosuppression is highly prevalent after solid organ transplantation, and intravenous immunoglobulin (IVIG) has been reported to reduce the risks of infections in various settings. We use high-dose IVIG in ABOi-KT recipients perioperatively. We aimed to determine the rate of infectious complications along with graft and patient survival in our ABOi-KT recipients. METHODS: We included all adult patients who underwent ABOi-KT from the year 2007 to 2016. Patients received rituximab, plasma exchange, and IVIG (2 g/kg body weight). Thymoglobulin and intravenous methylprednisolone were used as induction treatment. Oral prednisone, mycophenolate mofetil, and tacrolimus were used as maintenance therapy. RESULTS: A total of 77 ABOi-KTs were performed, and the recipients were followed up for a median of 1557 days. Two patients were diagnosed as having BK nephropathy. No patients were diagnosed as having pneumocystis infection, cytomegalovirus disease, herpes simplex, varicella zoster, or fungal infection. One-year graft and patient survival was 94.8% and 100%, respectively. CONCLUSIONS: In our series of ABOi-KTs, we observed a low risk of infectious complications and excellent patient survival. High-dose IVIG might have reduced infections.

Outcomes of kidneys utilized from deceased donors with severe acute kidney injury.

BACKGROUND: Significant numbers of kidneys are discarded due to raised terminal creatinine of the donor. AIM: To determine long-term outcomes of kidneys utilized from donors with severe acute kidney injury (AKI). METHODS: In this retrospective study, we included all patients who received kidneys from deceased donors between years 2000 and 2012. AKI was defined according to the acute kidney injury network (AKIN) classification. The primary outcomes were patient and graft survival and secondary outcomes were renal function at different time points, delayed graft function, acute rejection and length of hospital stay. RESULTS: Two hundred and eighty-four recipients received kidneys from 261 deceased donors. One hundred and fourteen patients (40%) received kidneys from the donors with AKI. Forty-two patients received kidneys from the donors with severe AKI (AKIN-3 category). Mean age of the donor and recipient was 36 and 37 years, respectively. Main cause of death in donors was road traffic accident (34%) followed by cerebrovascular accident (33%). Terminal creatinine was 85 and 262 µmol/l in non-AKI and AKI groups, respectively (P < 0.001). Significantly more patients in the AKI group had delayed graft function (P = 0.006), prolonged hospital stay (P < 0.001) and high creatinine at discharge (P = 0.002). However, acute rejection rates (P = 0.25), 1-, 5- and 10-year graft survival (P = 0.57) and patient survival (P = 0.77) were not different between AKI and non-AKI groups. The outcomes in the AKIN-3 category were comparable with the non-AKI group. CONCLUSIONS: This study has shown favorable long-term outcomes of kidneys utilized from donors with severe AKI. This study may encourage healthcare professionals to consider accepting such kidneys.

Serologic association of human herpesvirus eight with posttransplant Kaposi's sarcoma in Saudi Arabia.

BACKGROUND: This study investigates the association between human herpesvirus eight (HHV8) and Kaposi's sarcoma (KS), the most common cancer occurring in renal transplant recipients in Saudi Arabia. METHODS: A cross-sectional study of seroreactivity to HHV8 antigens in posttransplant KS patients from a tertiary care hospital in Riyadh, Saudi Arabia, and in control subjects without KS was conducted. Seroreactivity rates were determined using immunoblotting assays to detect antibodies to two lytic cycle HHV8 antigens: p40, an antigen found in infected cells, and sVCA, an HHV8-encoded small viral capsid antigen expressed in Escherichia coli. RESULTS: Antibodies to HHV8 p40 and sVCA were present in a significantly higher proportion of renal transplant patients with KS (13 of 14 patients) compared to renal transplant patients without KS (5 of 18; P<0.001) and compared to other control individuals (6 of 44; P<0.001). HHV8 seroreactivity was more common among patients with renal failure (28%) than among other control groups (7%). CONCLUSIONS: The serologic results provide evidence of a strong association between HHV8 and posttransplant KS in Saudi Arabia.

PIP: In Saudi Arabia, Kaposi's sarcoma occurs in 4.1% of renal transplant recipients and accounts for 70% of malignancies in this group. Human herpes virus 8 (HHV8) has been identified in the DNA of many of these patients. The association between HHV8 and Kaposi's sarcoma was investigated further in post-renal transplant Kaposi's sarcoma patients from a tertiary care hospital (King Faisal Specialist Hospital and Research Center) in Riyadh, Saudi Arabia (n = 14), and non-Kaposi's sarcoma controls with renal transplant (n = 18), chronic renal failure (n = 14), other cancers that did not affect renal function (n = 15), and healthy volunteers (n = 15). The median time from transplant to Kaposi's sarcoma was 13 months. A serum sample was assumed to have antibodies to HHV8 if antibody to either p40 or sVCA was detected. The prevalence of HHV8 seroreactivity was 13/14 (93%) in cases, 5/18 (28%) in renal transplants without Kaposi's sarcoma, and 11/62 (18%) in the aggregate control group. HHV8 seroreactivity was significantly more common (p 0.001) among transplant patients with Kaposi's sarcoma than those without this cancer (odds ratio, 33.80; 95% confidence interval, 2.96-904). These findings suggest an etiologic link between HHV8 and Kaposi's sarcoma presumably due to immunologic or cellular factors that influence host-virus interactions.

The effect of extracorporeal high blood flow rate on left ventricular function during hemodialysis--an echocardiographic study.

The effect of increased extracorporeal blood flow rate on left ventricular (LV) function has been studied during volume-controlled bicarbonate hemodialysis. Ten stable patients on chronic hemodialysis, with a mean age of 28 years (range 19-38) were studied using two-dimensional and Doppler echocardiography. The mean time on hemodialysis was 32 months (range 3-60). All patients were investigated during three dialysis sessions on the first day of the week for 3 consecutive weeks. The blood flow rate was chosen randomly as 250, 350, or 450 cc/min. Apart from the time of hemodialysis and blood flow rate, other parameters of the hemodialysis were kept stable during all three sessions. Echocardiographic studies were done before, at mid dialysis, and during the last 15 min of each dialysis session. The following parameters were evaluated: heart rate, mean blood pressure, shortening fraction, ejection fraction, cardiac output, and pre-ejection period/LV ejection time ratio. The changes of the measured cardiac parameters at the beginning, middle and end of each session were not significantly different. Furthermore, the differences in changes between the three different sessions were comparable. Our results indicate that an increase in dialysis blood flow rate up to 450 cc/min does not have an adverse effect on the left ventricle in patients on maintenance hemodialysis and with stable cardiovascular function.

Targeted monitoring of donor-specific HLA antibodies following renal transplantation.

Development of de novo donor-specific anti-HLA antibody (DSA) with antibody-mediated rejection (AMR) is the most important cause of renal allograft loss. Therefore, DSA monitoring might identify grafts susceptible to chronic humoral injury. However, implementing universal monitoring is logistically difficult, costly, and not yet supported by management guidelines, especially in patients with stable graft function. To gain further insight into humoral alloimmunity in transplant patients, we conducted a single center, retrospective study of AMR due to de novo DSA. We excluded patients without full characterization of the HLA specificities by single antigen solid phase immunoassay, and those where the clinical relevance of the DSA could not be determined. The clinical scenarios preceding AMR, HLA mismatches and alloantibody specificities, the histopathological phenotypes, and graft outcome were studied. We identified 44 renal transplant recipients with indication and protocol biopsies (44 biopsies for cause and 2 protocol biopsies), revealing 46 episodes of AMR and DSA (2 episodes in two patients). Most were late (more than 6 months after transplant). Suboptimal immunosuppression was an important prelude, usually due to non-adherence. DSA to DQ was prevalent and most biopsies were C4d positive. In all, 20 graft losses were attributed to AMR. From this study, we propose DSA monitoring in the patients with the following: (1) an episode of late (> 6 months) rejection; (2) history of non-adherence to immunosuppression; (3) immunosuppression minimization; (4) a class II loci (DR and DQ) mismatch transplant; or, (5) history of previous transplants. Close surveillance and protocol biopsies in those who develop de novo DSA is suggested.

Primary antiphospholipid syndrome and self-limited renal vasculitis during pregnancy: case report and review of the literature.

A case of self-limited renal vasculitis during pregnancy in a patient with a history of recurrent fetal loss and with a positive cardiolipin immunoglobulin G antibody test is described. The renal disease manifested as an acute renal failure in the second trimester of the patient's third pregnancy, concurrent with severe pre-eclampsia. Vasculitis is a rare manifestation of antiphospholipid syndrome that has been described mostly in peripheral arteries. Renal vasculitis, however, has not yet been reported in association with this syndrome. The full spectrum of renal involvement in antiphospholipid syndrome is presently being determined, and we suggest that renal vasculitis be included in that spectrum.

Attitudes of commercial renal transplant recipients toward renal transplantation in India.

Renal transplantation offers patients with end-stage renal disease the best opportunity for rehabilitation and long-term survival. However, there is a critical shortage of transplantable kidneys worldwide. This plays well into the hands of transplanters and entrepreneurs involved in commercial renal transplantation, particularly in India. This practice has been condemned by all transplant societies. In our fight against rampant commercialism in renal transplantation, we sought to describe feelings of patients who had received transplants in India, and the difficulties they faced during their stay there. The results show that the two reasons that motivated patients to go to India were lack of living-related donors and the need for prompt transplant. More than half of the patients did not meet their donors. Their experience, however, has been largely positive except for some negative feelings toward the broker and the standard of hospital hygiene. The total cost of the transplant was far less than that in the West but, despite that, some patients felt financially exploited. Communication with them was poor, as most patients did not get adequate pretransplant education and were not informed of possible complications including rejection and graft loss. Furthermore, almost half of the patients were not given medical reports. These results substantiate the impression that CRT in India does not conform to the high standards of renal transplant medicine.

Early posttransplant lymphoproliferative disorder presenting with ureteric obstruction in en bloc kidneys.

We describe a female patient who received double pediatric (en bloc) kidney transplants. She presented initially with fever of unknown origin 3 months after transplantation; 5 months after surgery, she presented with obstruction of one ureter followed by obstruction of the other. After 9 months she developed posttransplant lymphoproliferative disorder in both kidneys. To our knowledge, this is the first case report of this disorder occurring in en bloc kidneys and presenting with bilateral ureteric obstruction.

A volume-independent component to postdiuretic sodium retention in humans.

Net sodium (Na) loss during diuretic administration is limited by postdiuretic renal salt retention. This could be a homeostatic response to extracellular fluid volume (ECV) depletion. However, rats infused with loop diuretics develop structural and functional adaptations in the distal nephron that enhance NaCl reabsorption. Therefore, the hypothesis that postdiuretic Na retention in humans contains a volume-independent component was tested. Normal volunteers were equilibrated to a 120 mmol/24 h Na intake. For the first protocol, subjects received, in random order, a placebo, bumetanide (B), or bumetanide accompanied by an infusion of an electrolyte solution at a rate adjusted to match urine flow and thereby to obviate Na losses (bumetanide plus volume replacement; B + VR). After the completion of B diuresis, there was a positive Na balance that restored 70% of the Na loss within 42 h. However, this positive Na balance was prevented by volume replacement (B + VR). For the second protocol, subjects received, in random order, a placebo injection and a 100-mmol NaCl load (P + NaCl) or a bumetanide injection plus volume replacement in addition to a 100-mmol NaCl load (B + VR + NaCl). Over the ensuing 42 h, 94% of the load was eliminated when it was infused alone (P + NaCl). In contrast, only 9% was eliminated when it was given with bumetanide and volume replacement (B + VR + NaCl). It was concluded that postdiuretic Na retention in normal human subjects is due both to ECV depletion and to volume-independent Na retention manifest as an inability to excrete a modest NaCl load.(ABSTRACT TRUNCATED AT 250 WORDS)

Hand contamination with hepatitis C virus in staff looking after hepatitis C-positive hemodialysis patients.

BACKGROUND: Hepatitis C virus (HCV) is a major cause of hepatitis in hemodialysis (HD) patients. Routes other than blood transfusion play a role in the spread of HCV in HD patients. Molecular studies of HCV implicate nosocomial transmission of the virus in HD units. We conducted a clinicovirological study in our HD unit to investigate if the hands of dialysis personnel could represent a mode of transmission of HCV among HD patients. METHODS: One liter of sterile water was used for each handwashing of dialysis personnel. The washing was collected in a sterile container and tested for HCV-RNA by polymerase chain reaction (PCR) within 3 h of collection. Eighty handwashings from nurses dialyzing HCV-positive patients (groupe A) and 100 handwashing from nurses dialyzing HCV-negative patients (group B) were tested for HCV-RNA. As a control, 60 handwashings were collected from the dialysis personnel before entering the dialysis unit (group C) and tested for HCV-RNA. RESULTS: HCV-RNA was positive in 19 (23.75%) of samples of group A, in 8 (8%) of samples of group B (p < 0.003) and in 2 (3.3%) of samples of group C (p < 0. 35). These two positive samples of group C were from nurses who had dialyzed HCV-negative patients. CONCLUSION: These results indicate the presence of HCV-RNA on the hands of some dialysis personnel in our HD unit, in spite fo adherence to the standard precautions. The hands of dialysis personnel are therefore a potential mode for facilitating transmission of HCV between HD patients.