Adenovirus disease after kidney transplantation: course of infection and outcome in relation to blood viral load and immune recovery.

Information on the clinical spectrum and management of adenovirus infection after kidney transplantation is limited. From April 2007 to April 2010, 17 kidney transplant recipients were diagnosed with adenovirus disease. The median time to infection was 5 (range, 2-300) weeks after transplantation. Of the 17 patients, 13 (76.5%) presented early, within 3 months posttransplant, and four (23.5%) presented late, more than 3 months after transplant. Besides urinary tract, involvement of other organs was common (63.6%) among patients with adenovirus viremia. Despite reduction of immunosuppression, six patients subsequently had a rise in the level of blood viral load, mostly within a week after diagnosis. However, only three (27.3%) patients with early infection developed disease progression. Compared to the late infection group, patients with early infection had significantly lower absolute lymphocyte counts at week 1 (p = 0.01) and 3 (p = 0.002) after diagnosis. Four patients received intravenous cidofovir. At 6-month follow-up, 10 (90.9%) patients had reversible graft dysfunction. Only one (5.7%) died from bacterial sepsis. Adenovirus disease is a significant complication following kidney transplantation. Early case recognition with reduction of immunosuppression is critical. Serial blood adenovirus viral loads and assessment of lymphocyte recovery are also useful in monitoring the course of infection.

Adenovirus infection after kidney transplantation in Thailand: seasonal distribution and potential route of acquisition.

BACKGROUND: Data on the epidemiology and route of acquisition of adenovirus (ADV) infection after kidney transplantation are limited. From April 2007 to March 2010, there were 17 cases of ADV infection: namely, 2 from April to December 2007; 8 from January to December 2008; 4 from January to December 2009; and 3 from January to March 2010. Most cases occurred in October and November (n = 8; 47.1%), followed by February to April (n = 6; 35.3%) and July (n = 3; 17.6%). METHODS: From April 2007 to August 2009, the diagnosis of ADV infection was made based on patient symptoms. From September 2009 to March 2010, in addition to symptoms, the diagnosis was complemented by urine surveillance for ADV using real-time polymerase chain reaction (PCR) prospectively performed every 1-2 weeks among recipients of living-related kidney, starting at week 2 posttransplantation for a total of 8-12 weeks. Before transplantation, recipients and donors were screened for ADV in urine and also using nasal swab. RESULTS: Only 1 of the 24 patients displayed a positive ADV PCR in the urine surveillance study. A local investigation during a cluster of cases in October 2008 showed 2 patients who developed ADV after sharing a room in the transplant unit. Although nosocomial transmission was probable, the majority of cases were scattered over time rather than clustering in 1 time period. CONCLUSION: These findings suggested that ADV infection cases occurred after exogenous exposure. In a resource-limited country, early diagnosis of ADV is justified for patients with compatible symptoms complemented by intense infection control to prevent nosocomial transmission from a confirmed case.

Treatment of simultaneous acute antibody-mediated rejection and acute cellular rejection with alemtuzumab in kidney transplantation: a case report.

This is a case report of a living related donor kidney transplantation using basiliximab induction and maintenance immunosuppression with cyclosporine, mycophenolate sodium, and steroid. On the second posttransplant day, the patient developed acute antibody-mediated rejection, which was treated with plasmapheresis and intravenous immunoglobulin (IVIG). Five days later, the graft had still not responded to the treatment. Another biopsy revealed additional acute cellular rejection (Banff IIA). As alemtuzumab can rapidly deplete T and B lymphocytes, monocytes, and natural killer cells, the patient was treated with alemtuzumab (30 mg subcutaneously) together with methylprednisolone (500 mg) and two more plasmaphereses. The kidney graft responded within 48 hours, producing more than 4 L of urine per day. The total lymphocyte decreased from 530/microL to 50/microL remaining in the 50 to 220/microL range. The patient received valgancyclovir and cotrimoxazole as infection prophylaxis. The kidney graft responded well to the rescue treatment and the patient was discharged with a serum creatinine of 1.1 mg/mL and has been uneventfully followed in the outpatient clinic for 8 months. Today, with the potent, effective, and selective immunosuppressive regimens, the rate and severity of acute cellular rejection in kidney transplantation has decreased in most centers. However, the rate of acute antibody-mediated rejection has increased to levels greater than those of acute cellular rejection in many centers. Acute antibody-mediated rejection is more difficult and expensive to treat successfully. The treatment of acute antibody-mediated rejection included plasmapheresis and IVIG. Herein we have reported a case of kidney transplantation simultaneously developing acute antibody-mediated and acute cellular rejection; the patient was successfully treated with alemtuzumab.

Influenza A/H1N1 2009 pneumonia in kidney transplant recipients: characteristics and outcomes following high-dose oseltamivir exposure.

We report 2 cases of severe pneumonia due to the novel pandemic influenza A/H1N1 2009 in kidney transplant recipients. Our patients initially experienced influenza-like illness that rapidly progressed to severe pneumonia within 48 h. The patients became hypoxic and required non-invasive ventilation. The novel influenza A/H1N1 2009 was identified from their nasal swabs. These cases were treated successfully with a relatively high dose of oseltamivir, adjusted for their renal function. Clinical improvement was documented only after a week of antiviral therapy. Despite early antiviral treatment, we showed that morbidity following novel pandemic influenza A/H1N1 2009 infection is high among kidney transplant recipients.

Tuberculosis in Thai renal transplant recipients: a 15-year experience.

OBJECTIVE: Tuberculosis (TB) is a leading cause of morbidity and mortality in renal transplant recipients, especially in developing countries. Its incidence and characteristics remain unknown in Thai recipients. This study sought to determine the incidence, characteristics, risk factors, and outcome of TB in Thailand. METHODS: We retrospectively reviewed case records of all renal transplant recipients from 1992 to 2007 to record demographic information, transplant characteristics, median time to diagnosis of TB, and outcomes. RESULTS: Among 270 recipients, 9 (3.84%, 95% confidence interval [CI] 1.18%-5.49%) developed TB. Their median age was 40 years (range = 23-62 years) and median time from transplantation to diagnosis was 36 months (range = 4-115 months). Although pulmonary TB was the most common form (56%), 2 patients (22%) developed extrapulmonary disease. Disseminated TB occurred in 2 patients (22%). The diagnosis was made on respiratory specimen cultures in 3 cases (33.3%) and body fluid cultures in 3 (33.3%). Five patients (55.6%) were successfully treated with four-drug combination therapy. Two of the other subjects (22.2%) who received triple therapy were noncompliant, succumbing to graft failure and sepsis. Blood group AB (odds ratio [OR] 10.95, 95% CI 1.57-76.60) and use of tacrolimus rescue therapy (OR 9.68, 95% CI 2.13-43.94) were associated with an elevated risk of TB. CONCLUSION: TB is common among Thai renal transplant recipients with an incidence 27 times higher than that of the general Thai population. The extrapulmonary form in particular occurs more frequently with an increased risk of mortality.

Malignancies in renal transplant patients: 15 years experience in Thailand.

The increased incidence of malignancies post-renal transplantation is well established. We performed a retrospective review of the 270 renal transplant patients from May 1, 1992 to April 30, 2007, including 18 cases (6.7%) of malignancy. The most common cancer in the study was transitional cell carcinoma of the urinary tract (7/18). The second most common cancer was hepatocellular carcinoma (3/18). In contrast to reports from Caucasian countries, we found only 2/18 patients had posttransplantation lymphoproliferative disease and no report of skin cancer. Among the 18 patients with malignancy, 11 died (mortality rate = 61%). We encourage a more extensive study of malignancy post-renal transplantation at multiple centers with a tumor registry in Thailand.

The pharmacokinetics of mycophenolate mofetil in Thai kidney transplant recipients.

Mycophenolate mofetil, in addition to cyclosporine and prednisolone significantly reduces the rate of acute rejection. The original recommended dose of MMF is fixed at 2 g/day. However, Thai patients cannot tolerate this dose due to gastrointestinal adverse effects. So the majority of patients are maintained on MMF at doses ranging from 0.5 to 2 g/day, according to their tolerability with an acceptable rate of acute rejection episodes. This study sought to determine the steady state pharmacokinetics of MMF in Thai kidney transplant recipients on stable doses of MMF. Forty-six kidney transplant patients more than 3 months on a stable MMF dose of 0.5, 1, 1.5, and 2 g/day together with cyclosporine and prednisolone underwent a single pharmacokinetic blood sampling for 12 hours following the morning dose of MMF. The analysis of plasma concentrations of mycophenolic acid (MPA), the sole pharmacologically active metabolite of MMF, was performed by using an high performance liquid chromatography method. Sparse efficient sampling strategies were employed to optimize the blood sampling schedule. Hence, blood samples were collected at 0, 0.5, 2, 12 hours after the MMF dose. The sampling time was designed to best estimate AUC(0-tau) at steady state. The initial MPA-Bayesian estimator were used for MPA concentrations that would allow the best estimation of Vc, CLt, and Ka. In this study, there is a high interindividual variability in the AUC. The median MPA AUC was 34.3 ug.h/mL (range 14.1-65.4). Thirty-one of 45 (68.9%) patients had a MPA AUC within 20 to 40 ug.h/mL, which is the most reasonable risk: benefit ratio in terms of preventing acute rejection episodes. Forty-one of 45 (91.1%) patients had MPA AUC within 20 to 60 ug.h/mL, which is the MPA therapeutic range. The highest Pearson correlation coefficient of determination between MPA AUC and a single concentration was observed with MPA 2 hours (r = 0.622) Without a fixed dosing regimen, most Thai kidney transplant recipients who receive MMF as part of a maintenance immunosuppressive regimen have the MPA AUC within the therapeutic window. The single drug concentration that correlates well with the AUC is MPA at 2 hours postdose.

The role of anti-IL-2 receptor in high-risk kidney transplant patients.

UNLABELLED: Anti-IL-2 receptor has been proved to be effective in reducing the rate of acute rejection in kidney transplantation and also improving both the rate of graft and patient survival. In this study, we retrospectively review the role of anti-IL-2 receptor as induction immunosuppression in immunologically high-risk kidney transplant patient compared with normally low-risk patients. METHODS: From January 1999 to December 2002, we performed 246 kidney transplantations in two transplant centers in Bangkok. These were divided into two groups: group 1, high-risk group containing 50 patients who had one of the following criteria: (1) high panel reactive antibody (>50%); (2) retransplantation; (3) marginal donor (with expectancy of delayed graft function); (4) spouse donor; (5) >4 HLA mismatch. All group 1 patients receive anti-IL-2 receptor as induction immunosuppression (either Basiliximab (n = 27) or Daclizumab (n = 23).) Group 2 consisted of the control group of 196 patients with normal immunological risk. The following data of both groups were collected and analyzed: patient demography, type of donor, acute rejection incidence, severity, and time. RESULTS: In this study, the anti-IL-2 receptors are 27 cases of Basiliximab and 23 cases of Daclizumab. The rates of acute rejection are not significantly different in both groups, namely, 46 of 194 (23.7%) in group 2 compared with 10 of 50 (20%) episodes in group 1 (P = .602). All rejections in both groups responded to pulse steroid treatment. The mortality rate and rate of graft failure were also not significantly different, i.e., 6 of 196 (3.1%) vs 2 of 50 (4.0%) (P = .666) and 7 of 196 (3.6%) vs 3 of 50 (6.0%) (P = .429) in low risk group versus high risk group, respectively. Kaplan-Meier estimates of the probabilities of acute rejection free, patient survival rate, and graft survival rate also showed no difference between groups. CONCLUSIONS: The use of anti-IL-2 receptor antibodies as induction immunosuppression in immunologically high-risk patients results in the same rate of acute rejection, severity of acute rejection, graft survival, and patient survival as recipients with normal immunological risk.

Crossmatching technique facilitating kidney transplantation.

Accelerated acute cellular rejection (AR) continues to be a serious problem in kidney transplantation (KT), suggesting that undetected presensitization may be encountered. The purpose of this study was to determine the most sensitive crossmatching (XM) technique to detect the preformed antibody (Ab) which may cause AR. One hundred and twenty two sera from 98 patients, on the waiting list for KT at Ramathibodi Hospital were XMed with 23 cadaveric splenic lymphocytes including 2 living related KT (LR-KT). The XM was performed by 3 different techniques namely, standard microlymphocytotoxicity test (standard NIH), antihuman globulin microlymphocytotoxicity test (AHG) and flow cytometric XM (FCXM). The XM results revealed that 8 out of 75 (10.7%) tests were negative by standard NIH, i.e., 5 tests were positive by AHG only and 1 test was positive by FCXM only and 2 tests were positive by both AHG and FCXM. In addition, the patients who had the AHG technique were not done, 5 out of 47 (10.7%) tests were also negative by standard NIH but were positive by FCXM. The sensitivity of the techniques was done by titrations of anti HLA-A2. It was found that FCXM was the most sensitive technique, followed by AHG and standard NIH, consecutively. In the retrospective study of LR-KT, case #1, the standard NIH for XM using pre-KT blood sample was negative while AHG and FCXM were strongly positive. The patient had AR at day 2 post-KT which confirmed by needle biopsy. The serum at day 11 and day 116 post-KT were tested again and were positive by the 3 techniques. Case #2, pre-KT blood sample showed negative T-XM by the 3 techniques while auto-B and B-XM were positive by standard NIH and AHG but negative by FCXM. This patient had rejection at day 16 after KT. The post-KT blood sample at day 30 showed positive auto T/B and T/B-XM by standard NIH and AHG whereas it was still negative by FCXM. It was also noted that Ab to donor B cell was better detected by standard NIH and AHG than FCXM. In conclusion, FCXM is more sensitive than standard NIH and AHG, however this technique is limited in detecting IgM T and B cell Ab. AHG technique can detect both IgG and IgM antidonor T and B cell Abs. In addition, AHG technique is more sensitive than standard NIH and does not require sophisticated equipment. AHG technique should be appropriate for routine XM, especially, in LR-KT and sensitized patients.

Bartter's syndrome: evidence suggesting a distal tubular defect in a hypocalciuric variant of the syndrome.

Renal tubular function was examined in 5 adult patients aged 18-30 years with Bartter's syndrome associated with renal magnesium wasting and hypocalciuria. In the 3 patients studied during hypotonic saline diuresis, distal tubular fractional chloride reabsorption was lower than that reported in normal subjects. In response to a single intravenous dose of furosemide (40 mg), the increment in the excretion of sodium, chloride, and magnesium was equal to or greater than in normal subjects, while in 2 patients, in response to intravenous chlorothiazide (500 mg), the increment in sodium excretion was less than in normal subjects. Magnesium chloride infusion was undertaken in 2 patients in order to compare magnesium and calcium excretions at similar plasma magnesium levels in patients and in normal subjects. The patients exhibited magnesium wasting only at normal or low plasma magnesium levels, while calcium excretion was reduced in the patients at normal and elevated plasma magnesium levels. We conclude that in these patients the enhancement of renal magnesium reabsorption by hypomagnesemia is defective, and the hypomagnesemia is not the cause of the hypocalciuria. The tubule defect responsible for these abnormalities of magnesium and calcium excretion may be located beyond the side of action of furosemide, in the thiazide-sensitive segment of the distal convoluted tubule.

Renal magnesium wasting and hypocalciuria in chronic cis-platinum nephropathy in man.

1. The renal handling of calcium and magnesium was studied in six patients with persistent hypomagnesaemia after cis-platinum treatment for testicular tumours. 2. In comparison with normal subjects, the patients showed hypomagnesaemia (mean 0.54 mmol/l), which was associated with a normal urinary magnesium excretion (mean 4.83 mmol/24 h). Urinary calcium excretion was significantly lower in the patients than in the normal subjects (mean 2.05 vs 5.15 mmol/24 h, respectively; P less than 0.01), despite slightly higher total serum calcium levels (2.53 vs 2.38 mmol/l, respectively; P less than 0.05). During magnesium chloride infusion, when serum magnesium levels were comparable in patients and controls, urinary calcium excretion remained lower in the patients, indicating that hypomagnesaemia was not the cause of the hypocalciuria. 3. Dietary magnesium supplementation resulted in a significant increase in the serum magnesium levels in the patients, while dietary magnesium deprivation resulted in a comparable decrease in urinary magnesium excretion in patients and controls (to 1.46 and 2.00 mmol/day, respectively), although the serum magnesium level fell further (to 0.46 mmol/l) in the patients. 4. The dissociation of renal calcium and magnesium excretion appears to be part of the intrinsic tubular defect caused by cis-platinum. This dissociation of urinary calcium and magnesium excretion, which resembles that seen in Bartter's syndrome, may result from a lesion in the distal convoluted tubule.

Continuous peritoneal dialysis in acute renal failure from severe falciparum malaria.

Severe falciparum malaria complicated by acute renal failure resulted in very high mortality. Ten patients with acute renal failure from falciparum malaria (infected rbc up to 80%) were continuously dialysed using Tenckhoff peritoneal catheter. Five were oliguric and BUN was maintained between 60 to 80 mg/dl (21.4 to 28.6 mmol/l) by hourly 1 to 1.5 liter dialysate exchange during the acute phase. The peritoneal urea clearance (mean +/- SD) was 12.1 +/- 1.2 ml/min with urea nitrogen removal of 13.4 +/- 2.3 g/day. In nonoliguric cases dialysis was also needed for additional removal of waste products since the remaining renal function could not cope with the hypercatabolic state. Peritoneal glucose absorption (135 to 565 g/day) gave considerable caloric supply without volume load and also contributed to the prevention of hypoglycemia. Varying degree of acute respiratory failure developed in all patients with 5 cases (2 oliguric and 3 nonoliguric) progressing to pulmonary edema. Swan-Ganz catheterization and hemodynamic study suggested the role of increased capillary permeability and volume overload from endogenous water formation in the development of pulmonary complication. Continuous removal of fluid and waste products minimized these problems and may prevent the progression of respiratory failure. One patient died of severe sepsis and the other nine survived. This study showed the beneficial contribution of continuous peritoneal dialysis in the management of acute renal failure from severe falciparum malaria.