Pneumocystis jirovecii pneumonia with an atypical granulomatous response after kidney transplantation.

Pneumocystis jirovecii pneumonia (PCP) continues to be a leading cause of morbidity and mortality in kidney transplant recipients. Granulomatous PCP is an unusual histological presentation that has been described in a variety of immunosuppressive conditions. Previous studies have demonstrated an association between granulomatous disorders and hypercalcemia, the purported mechanism of which is extrarenal production of 1,25-dihydroxyvitamin D by activated macrophages. Here, we report a case of granulomatous formation in a kidney transplant recipient with PCP who presented with hypercalcemia and suppressed parathyroid hormone, both of which resolved after successful treatment of the pneumonia. In immunocompromised patients, pulmonary infection associated with hypercalcemia should raise the suspicion of PCP and other granulomatous disorders.

Malakoplakia after renal transplantation in the current era of immunosuppressive therapy: case report and literature review.

Malakoplakia is a rare chronic granulomatous disease of unknown cause. It is thought to be caused by an acquired bactericidal defect of macrophages. Malakoplakia is associated with chronic infections and immunosuppression. Although it occurs mainly in the urinary tract, it has already been reported in almost every organ system. The isolation of bacteria, especially Escherichia coli, is common in malakoplakia patients. Here, we present a case of primary cutaneous malakoplakia in a kidney transplant recipient who had been taking prednisone, tacrolimus, and mycophenolate. Culture of a lesion grew Burkholderia cepacia complex. Treatment with high doses of trimethoprim-sulfamethoxazole was successful. We also present a systematic review of the literature, identifying 4 previously reported cases of malakoplakia after renal transplantation under similar immunosuppressive therapy, most occurring in the urinary tract or perineum and following benign courses to cure. Data in the literature suggest that malakoplakia has become even rarer since changes were made in the immunosuppressive therapy employed after kidney transplantation.

Critical points and potential pitfalls of outbreak of IMP-1-producing carbapenem-resistant Pseudomonas aeruginosa among kidney transplant recipients: a case-control study.

BACKGROUND: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) infection after kidney transplantation (KT) is associated with high mortality. AIM: To analyse an outbreak of infection/colonization with IMP-1-producing CRPA on a KT ward. METHODS: A case-control study was conducted. Cases were identified through routine surveillance culture and real-time polymerase chain reaction for carbapenemase performed directly from rectal swab samples. Controls were randomly selected from patients hospitalized on the same ward during the same period, at a ratio of 3:1. Strain clonality was analysed through pulsed-field gel electrophoresis (PFGE), and whole-genome sequencing was performed for additional strain characterization. FINDINGS: CRPA was identified in 37 patients, in 51.4% through surveillance cultures and in 49.6% through clinical cultures. The median persistence of culture positivity was 42.5 days. Thirteen patients (35.1%) presented a total of 15 infections, of which seven (46.7%) were in the urinary tract; among those, 30-day mortality rate was 46.2%. PFGE analysis showed that all of the strains shared the same pulsotype. Multilocus sequence typing analysis identified the sequence type as ST446. Risk factors for CRPA acquisition were hospital stay >10 days, retransplantation, urological surgical reintervention after KT, use of carbapenem or ciprofloxacin in the last three months and low median lymphocyte count in the last three months. CONCLUSION: KT recipients remain colonized by CRPA for long periods and could be a source of nosocomial outbreaks. In addition, a high proportion of such patients develop infection. During an outbreak, urine culture should be added to the screening protocol for KT recipients.

Multifocal renal allograft biopsy: impact on therapeutic decisions.

OBJECTIVE: There are no data to support the suggestion that samples removed from one segment of the transplanted kidney are representative of the whole graft. The aim of this study was to compare the histological differences between biopsies obtained from different portions of the renal allograft and their impact on treatment recommendations. PATIENTS AND METHODS: Two hundred percutaneous biopsies were performed on kidney allografts and samples were collected from the upper and lower poles (100 kidneys). All samples were randomized and blindly reviewed. We obtained the discordance rates between the poles for the grading of acute rejection and for the diagnosis of nephrotoxicity due to immunosuppression. We also checked if the differences found were sufficient to call for different clinical recommendations. These values were compared with the intrapathologist variation rates. RESULTS: In 70 kidneys adequate sampling was obtained from both poles. The diagnosis of acute rejection were made in 17. The discordance rate between the upper and lower poles was 82.3% (kappa = 0.34), higher than the intrapathologist variation (P = .002). Nephrotoxicity was found in 14 kidneys. The discordance rate between the upper and lower poles was 28.6% (kappa = 0.88), with no difference compared with the intrapathologist variation. In 14 of the 70 kidneys (25.7%), discordances between poles had impact on clinical recommendations, most of these cases due to different gradings of acute rejection (78%). This number was higher than the intrapathologist variation (P = .04). CONCLUSIONS: The histopathological changes in the kidney allograft are not always homogeneous. This heterogeneity may affect the therapeutic recommendations.

Critical points and potential pitfalls of outbreak of IMP-1-producing carbapenem-resistant Pseudomonas aeruginosa among kidney transplant recipients: a case-control study

Background Carbapenem-resistant Pseudomonas aeruginosa (CRPA) infection after kidney transplantation (KT) is associated with high mortality. Methods We analysed an outbreak of infection/colonization with IMP-1-producing CRPA on a KT ward, conducting a case-control study. Cases were identified through routine surveillance culture and real-time polymerase chain reaction (PCR) for carbapenemase performed directly from rectal swab samples. Controls were randomly selected from patients hospitalized on the same ward during the same period, at a ratio of 3:1. Strain clonality was analysed through pulsed-field gel electrophoresis (PFGE), and whole-genome sequencing was performed for additional strain characterization. Results CRPA was identified in 37 patients, in 51.4% through surveillance cultures and in 49.6% through clinical cultures. The median persistence of culture positivity was 42.5 days. Thirteen patients (35.1%) presented a total of 15 infections, of which 7 (46.7%) were in the urinary tract, among those, 30-day mortality rate was 46.2%. PFGE analysis showed that all of the strains shared the same pulsotype. Multilocus sequence typing analysis identified the sequence type as ST446. Risk factors for CRPA acquisition were hospital stay > 10 days, re-transplantation, urological surgical re-intervention after KT, use of carbapenem or ciprofloxacin in the last three months and low median lymphocyte count in the last three months. Conclusions KT recipients remain colonised by CRPA for long periods and could be a source of nosocomial outbreaks. In addition, a high proportion of such patients develop infection. During an outbreak, urine culture should be added to the screening protocol for KT recipients.

Donor transmission intestinal carcinoma after kidney transplantation: case report.

Tumor transmission is a rare complication of organ transplantation. Despite several improvements in excluding donor malignant disease, there continue to be reports of unknown tumors in the donors. The risk of having a donor with an undetected malignancy ranges between 1.3% and 2%. The cases of two kidney transplant recipients who had intestinal carcinoma transmitted from the same deceased donor are described. The clinical presentation, previous data, and management options are discussed. As a result of the increase in the overall donor pool, using extended criteria donors, donors of extreme ages, donors with prolonged intensive care admission, and donors who may potentially transmit disease to their recipients, the risk of tumor transmission and also infections should be considered.

The impact of azathioprine on chronic viral hepatitis in renal transplantation: a long-term, single-center, prospective study on azathioprine withdrawal.

BACKGROUND: In transplanted patients, viral hepatitis progresses to chronic liver disease and patient's death after many years of transplantation. Also, it is well known that azathioprine (AZA) is harmful to the liver of these patients. However, it is unclear whether a low dose of AZA still represents a threat to the viral liver disease. METHODS: A total of 79 patients with hepatitis C, B, or both, transplanted between 1973 and 1990, were grouped according to whether they had AZA either withdrawn from the immunosuppressive regimen [group (G) I, n=45] or a dosage reduction only (group II, n=34). The decision to remove or to keep AZA was restricted to the patient's doctor. Patients records were reviewed by April 1997. RESULTS: After an equal time of follow-up, after the AZA changing (64+/-26 vs. 58+/-29 months), patients in GI showed a significant decrease in the serum liver parameters when compared to baseline [alanine aminotransferase (ALT): P=0.001; gamma-glutamyl transferase (gamma-GT): P=0.001 and total bilirubin: P=0.002], whereas in GII only ALT decreased (P=0.04) although gamma-GT and total bilirubin did not. Compared to baseline, serum creatinine (SCr) increased only in GI (P=0.001) but, at last follow-up, did not differ from GII. The intention-to-perform liver biopsies was equal in GI and GII (16 vs. 14) but the hystological findings of severe chronic liver disease (either chronic active hepatitis or cirrhosis) were more frequent in GII (P=0.004). Death with a functioning graft was much more frequent in GII than in GI (P=0.001). Infection and cirrhosis were more common as a cause of death in GII than in GI. CONCLUSIONS: The use AZA is harmful to renal transplantation patients with both chronic hepatitis C and B and, therefore, should be avoided. AZA withdrawal, but not dose adjustments, diminishes the serum liver enzymes and the progression rate of the chronic viral liver disease as well as the rate of death secondary to infection and cirrhosis.

Histological outcome of acute cellular rejection in kidney transplantation after treatment with methylprednisolone.

BACKGROUND: Several studies comparing the response of acute cellular rejection (ACR) episodes to different corticosteroid regimens have been conducted. However, in most of them, the histological evaluation of the infiltrate and its correlation with clinical response was not studied. The clinical and histological outcomes of 37 episodes of ACR treated with methylprednisolone (MP) were studied, with the aim to determine how long the infiltrate takes to be cleared after therapy. METHODS: A total of 37 patients with biopsy-proven ACR were treated with 8 or 16 mg of MP/kg/day. Allograft biopsies were repeated at 5 and 10 days after the end of corticotherapy. Clinical and histological outcomes were compared. RESULTS: Six patients were excluded; 15 (48.4%) patients responded to therapy; the mean serum creatinine of these patients reached normal levels in the 2 weeks that followed treatment. Nine patients (60%) of this group had signs of ACR on biopsies done 5 days after corticotherapy, and four (26.7%) maintained them on the 10th day. Among 16 patients with no clinical response, none reached normal serum creatinine levels; 15 (93.7%) had signs of rejection 5 days after treatment and maintained them on the 10th day. Histological signs of ACR disappeared in 73.3% of patients with clinical response 10 days after therapy, but in only 6.3% of patients with no response (P=0.001). CONCLUSIONS: Biopsies performed 5 days after treatment show a high incidence of features of ACR; such features take on average 10 days to disappear in nearly 75% of cases with successful therapy with MP.

Sacral agenesis: why is it so frequently misdiagnosed?

Thirty-four patients with sacral agenesis were seen from 1954 to 1983, cases of meningomyelocele excluded. Five recognizable and consistent patterns of bone malformation were identified. Urodynamic examinations were done in 10 of the 34 patients. Their evaluation and response to treatment are analyzed; we tried to determine and establish the possible causes for its late diagnosis and consequences regarding the upper urinary tract.

Prosthetic repair of incisional hernia in kidney transplant patients. A technique with onlay polypropylene mesh.

The employment of synthetic mesh for incisional hernia repair in kidney-transplanted patients is rarely reported in the present literature. Many authors believe that mesh employment in such conditions is not safe due to fear of mesh related complications. From 1965 through 1999, a total of 1685 kidney transplants were performed at our Kidney Transplant Unit and 19 patients developed eventrations in the kidney transplant incision, an incidence of 1.1%. From September 1996 eight of these patients had prosthetic repair of the abdominal wall with onlay polypropylene mesh. All patients were under immunosuppressive therapy with prednisone, ciclosporine and azathioprine. Mean age was 48.8 years, mean body mass index was 22.5 and mean number of previous abdominal operations was 2.5. A large polypropylene mesh (Marlex mesh) was fixed over the aponeurosis after primary closure of the aponeurotic borders, as an onlay graft. There was neither morbidity nor mortality associated to the surgical procedure. No recurrences or long-term complications associated with mesh employment were verified after a follow-up ranging from one year to three years. We concluded that prosthetic repair of incisional hernia in transplanted patients can be performed routinely.

Induction versus noninduction therapy in kidney transplantation: considering different PRA levels and different induction therapies.

To evaluate the rate of acute cellular rejection (ACR) and long-term results in different levels of anti-HLA sensitization, using noninduction or different induction therapies, 763 patients who underwent transplantation from January 1995 to December 2001 were evaluated: 213 patients received induction therapy, 71 received Thymoglobulin (Thymo), 66 Simulect, and 44 OKT3. Follow-up time was at least 1 year for all groups. The Simulect group included older recipients and the OKT3 group had more female patients. Simulect and OKT3 groups had more black patients; Thymo and OKT3 groups had more retransplantations. PRA was low in the noninduction group (mean, 7%) and about the same in the Simulect and Thymo groups (mean, 30%). OKT3 was the most sensitized group (mean = 59%). Dialysis during the first posttransplantation week was more frequent among the induction groups (43% vs 65%; P <.005). Fewer patients experienced rejection episodes in the Thymo group (20% vs 50%; P =.02). Patients were classified according to their level of sensitization, and the Thymo group showed the lower rejection rates in all levels (mean, 20%; P =.001). When analyzing PRA >50%, the Thymo group showed lower rejection rates (12% vs 50%; P =.02). At this level of sensitization, there was no significant difference on graft loss and death with a functioning graft. There was a trend to more cytomegalovirus (CMV) disease in the Thymo group (33% vs 23%; P =.08). Two PTLD were diagnosed, both in the noninduction group. Renal function was better in the Thymo group (1.3 mg/dL). In conclusion, Thymo showed lower ACR rates in all PRA groups. No significant differences in CMV infection, tumors, and patient survival were observed.

Identifying cyclosporine blood levels associated with the prevention of renal transplant rejection: a single-center, randomized prospective study.

Multiple-drug therapy may allow reduced individual drug doses with fewer side effects. Blood levels of cyclosporine (CsA) necessary to avoid rejection may vary with different drug combinations. Fifty-eight kidney transplant patients were randomized into two groups: 25 subjects were assigned to the 4-hour area under the curve (AUC(0-4)) Cohort-the "high arm" (4500 to 5500 ng . h/mL)--1 and 33 to the AUC(0-4) "low arm" (2400 to 3400 ng . h/mL). After CsA introduction, AUC(0-4) was drawn on days 4, 7, 14, 21, 28, 42, 56, 70, 84, 90. We compared the proportion of rejection versus rejection-free patients, according to the CsA exposure. Logistic regression analysis showed that an AUC(0-4) of > or =4000 ng . h/mL or a 2-hour cyclosporine level (C(2)) of > or =1450 ng/mL predicted a rejection-free course among patients not receiving induction therapy. When either basiliximab or thymoglobulin was administered, a C(2) and AUC(0-4) of 1043 +/- 151 ng/mL or 3146 +/- 262 ng . h/mL, respectively, were associated with a rejection-free course. Our findings confirm the need for different CsA levels to prevent rejection according to induction therapy. Induction with either basiliximab or thymoglobulin allows reduced CsA levels during the first 3 months after renal transplantation.

Reducing cross-clamping duration in aortoiliac reconstruction after renal transplantation. A case report.

A fifty-two-year-old male renal transplant patient underwent aortoiliac reconstruction with a bifurcated prosthesis for treatment of hypertension and deteriorating allograft function. A modified technique was used that reduced aortic cross-clamping time to twelve minutes. This simple technique is applicable to most patients, reduces warm ischemia to a minimum, and saves time for a careful aortoiliac reconstruction.

Transplantation of horseshoe kidney en bloc.

Horseshoe kidney is probably the most common renal fusion anomaly. With the continuous donor shortage, transplant surgeons tend to accept donors previously considered unsuitable. We present a successful case of en bloc horseshoe kidney transplant in a single recipient. The literature is reviewed. The use of horseshoe kidneys in transplantation is recommended in selected cases.

Catheter-associated urinary infection in kidney post-transplant patients.

CONTEXT: There is still controversy as to the use and dosage of antimicrobial prophylaxis of the urinary infection associated with urethral catheterization in the post renal transplant period. OBJECTIVE: To determine whether patients develop urinary infection during short-term urethral catheterization after renal transplant without routine antimicrobial prophylaxis. DESIGN: Prospective study. SETTING: Kidney Transplantation Unit. SAMPLE: 20 patients submitted to non-complicated kidney transplant, with a normal urinary tract and no risk factors present regarding urinary infection. Aged 15 to 65 years. MAIN MEASUREMENTS: Before the transplant, material from the urethral meatus and urine were collected for culture. After the transplant, in the period during which the patient was with short-term urethral catheterization (4 to 5 days), material from the urethral meatus and urine from the bladder and the collecting bag were taken daily from all recipients for culture. RESULTS: There was a predominance of coagulase-negative Staphylococcus and S. viridans in the normal urethral meatus flora and in the first two days of urethral catheterization. After the second day, there was a predominance of E. coli and E. faecalis. Urinary infection did not occur during the period of urethral catheterization. In the follow up only one female patient (7%) had asymptomatic bacteriuria caused by E.coli after the withdrawal of the urethral catheter. CONCLUSIONS: Infection urinary does not occur during the period of urethral catheterization in kidney post-transplant patients. Thus, antimicrobial prophylaxis is not recommended for these patients to prevent urinary infection.

[Comparison of clinical and histological diagnosis in kidney post-transplantation period]. / Comparação entre diagnósticos clínicos e histológicos no pós-transplante renal.

PURPOSE: To assess the agreement between clinical and histopathological diagnosis in a renal transplantation center, 40 episodes of acute renal failure were studied. METHODS: Kidney biopsies were performed at the moment that a clinical diagnosis was made by the staff. RESULTS: Nineteen episodes of acute tubular necrosis (ATN), eighteen episodes of acute cellular rejection (ACR), 2 humoral rejections and 1 acute cyclosporin nephrotoxicity episodes were diagnosed. ATN episodes were confirmed by renal biopsy in 84.21%, ACR episodes in 83.33%, humoral rejections in 100%. Renal biopsy showed ATN in the occurrence of clinical cyclosporin nephrotoxicity. Total agreement was 82.5%. CONCLUSION: There is a good relationship between clinical and histopathological diagnosis in the post-transplantation period. Diagnostic mistakes occurred mainly when oliguria was present.

Single center experience with elective surgical patients as living kidney donors.

PURPOSE: To report a single center experience with elective surgical patients as living kidney donors. METHODS: We retrospectively analyzed a prospective database of 458 living kidney donors from September 2005 to May 2011. Fifteen (3.2%) of them were elective surgical patients simultaneously undergoing living donor nephrectomy. We reviewed age, gender, operative time, intraoperative blood transfusion, intra- and postoperative complications, as well as length of hospital stay. Recipients were evaluated for delayed graft function. Four hundred forty-three patients undergoing living donor nephrectomy alone composed the control group. RESULTS: Among the elective surgical patients group, the mean (range) operative time was 155 (90 to 310) minutes and mean (range) length of hospital stay was 3 (2 to 9) days. One (6.7%) recipient displayed delayed graft function. Among the regular living kidney donors group, the mean (range) operative time was 100 (70 to 150) minutes, mean (range) length of hospital stay was 3 (2 to 5) days, and delayed graft function was observed in 5.6% of recipients. Only operative time (P = .03) was significantly different between the groups. CONCLUSIONS: Elective surgical patients are potential donors who may be treated at the same time as the living donor nephrectomy.

De novo thrombotic microangiopathy after kidney transplantation: clinical features, treatment, and long-term patient and graft survival.

INTRODUCTION: Posttransplant thrombotic microangiopathy (TMA)/hemolytic uremic syndrome (HUS) can occur as a recurrent or de novo disease. METHODS: A retrospective single-center observational study was applied in order to examine the incidence and outcomes of de novo TMA/HUS among transplantations performed between 2000 and 2010. Recurrent HUS or antibody-mediated rejections were excluded. RESULTS: Seventeen (1.1%) among 1549 kidney transplant recipients fulfilled criteria for de novo TMA. The mean follow-up was 572 days (range, 69-1769). Maintenance immunosuppression was prednisone, tacrolimus (TAC), and mycophenolic acid in 14 (82%) patients. Mean age at onset was 40 ± 15 years, and serum creatinine was 6.1 ± 4.1 mg/dL. TMA occurred at a median of 25 days (range, 1-1755) after transplantation. Nine (53%) patients developed TMA within 1 month of transplantation and only 12% after 1 year. Clinical features were anemia (hemoglobin < 10 g/dL) in 9 (53%) patients, thrombocytopenia in 7 (41%), and increased lactate dehydrogenase in 12 (70%). Decreased haptoglobin was observed in 64% and schistocytes in 35%. Calcineurin inhibitor (CNI) withdrawal or reduction was the first step in the management of 10/15 (66%) patients, and 6 (35%) received fresh frozen plasma (FFP) and/or plasmapheresis. TAC was successfully reintroduced in six patients after a median of 17 days. Eight (47%) patients needed dialytic support after TMA diagnosis and 75% remained on dialysis. At 4 years of follow-up, death-censored graft survival was worse for TMA group (43.0% versus 85.6%, log-rank = 0.001; hazard ratio = 3.74) and there was no difference in patient survival (53.1% versus 82.2%, log-rank = 0.24). CONCLUSION: De novo TMA after kidney transplantation is a rare but severe condition with poor graft outcomes. This syndrome may not be fully manifested, and clinical suspicion is essential for early diagnosis and treatment, based mainly in CNI withdrawal and FFP infusions and/or plasmapheresis.

Protective effect of N-acetylcysteine on early outcomes of deceased renal transplantation.

We investigated the effects of the antioxidant N-acetylcysteine (NAC) on early outcomes of deceased donor renal transplantation. Between April 2005 and June 2008, adult primary graft recipients of deceased renal donors were assigned to treatment (n = 38) or control (n = 36) groups and evaluated for 90 days and one year after renal transplantation. The treatment group received NAC orally (600 mg twice daily) from day 0 to 7 postoperatively. Renal function was determined by serum creatinine, MDRD and Cockcroft-Gault estimated GFR (eGFR), delayed graft function (DGF) and dialysis free Kaplan-Meier estimate curve. Serum levels of thiobarbituric acid reactive substances (TBARS), were employed as markers of oxidative stress. The NAC group displayed a lower mean serum creatinine during the first 90 days (P = .026) and at 1 year after transplantation (P = .005). Furthermore, the NAC group showed a higher mean eGFR throughout the first 90 days and at 1 year. DGF was lower among the NAC group (P = .017) and these recipients required fewer days of dialysis (P = .012). Oxidative stress was significantly attenuated with NAC (P < .001). Our results suggested that NAC enhanced early outcomes of deceased donor renal transplantation by attenuating oxidative stress.

Non-human leukocyte antigen antibodies reactive with endothelial cells could be involved in early loss of renal allografts.

Preformed donor-specific human leukocyte antigen (HLA) antibodies have been associated with allograft dysfunction and failure. However, recipients of HLA-identical kidneys can develop acute humoral rejection, implicating putative pathogenic antibodies that are directed against non-HLA antigens. We investigated the presence of endothelial cell-reactive antibodies in 11 patients who experienced early loss of their transplanted kidneys owing to humoral rejection and 1 loss from renal venal thrombosis. We examined the potential efficacy of intravenous immunoglobulin to block the binding of these antibodies, as previously suggested for anti-HLA antibodies.