A case–control study was conducted to identify risk factors for Pneumocystis jirovecii pneumonia (PCP) in renal transplant recipients. Eleven cases of PCP were matched with 22 controls. Cases ...occurred a median of 18 months after transplantation, and none of the recipients was receiving prophylaxis. Univariate analysis showed that graft rejection, duration of steroid use, use of mammalian target of rapamycin (mTOR) inhibitors and lymphocytopenia at the time of prophylaxis discontinuation were risk factors for PCP. In the multivariate model, only graft rejection (OR 8.66, p 0.017) remained significantly associated with PCP. In patients with a history of graft rejection, PCP prophylaxis should be maintained, especially among those with lymphocytopenia.
Background
Kidney transplant recipients are at risk for life‐threatening infections, which may affect the long‐term prognosis.
Methods
We retrospectively included all kidney transplant recipients ...admitted for sepsis, severe sepsis, or septic shock to the medical intensive care unit (ICU) of the Saint‐Louis Hospital, Paris, France, between 2000 and 2010. The main objective was to identify factors associated with survival without graft impairment 90 days after ICU discharge.
Results
Data were available for 83 of 100 eligible patients. The main sites of infection were the lungs (54%), urinary tract (24%), and bloodstream (22%). Among documented infections (55/83), 80% were bacterial. Fungal infections were more common among patients transplanted after 2005 (5% vs. 23%, P = 0.02). Mechanical ventilation was used in 46 (56%) patients, vasopressors in 39 (47%), and renal replacement therapy (RRT) in 34 (41%). In‐hospital and day‐90 mortality rates were 20% and 22%, respectively. On day 90, among the 65 survivors, 39 (47%) had recovered their previous graft function and 26 (31%) had impaired graft function, including 16 (19%) who were dependent on RRT. Factors independently associated with day‐90 survival and graft function recovery were baseline serum creatinine (odds ratio OR for a 10 μmol/L increase 0.94, 95% confidence interval CI 0.88–1.00) and cyclosporine therapy (OR 0.30, 95% CI 0.11–0.79).
Conclusion
Sepsis was chiefly related to bacterial pneumonia or urinary tract infection. Pneumocystis jirovecii was the leading opportunistic agent, with a trend toward an increase over time. Infections often induced severe graft function impairment. Baseline creatinine and cyclosporine therapy independently predicted the outcome.
Kidney transplantation is now considered as a reasonable option for HIV‐infected patients with end‐stage renal disease. We describe here a retrospective study conducted in five transplantation ...centers in Paris. Twenty‐seven patients were included. Immunosuppressive protocol associated an induction therapy and a long‐term treatment combining mycophenolate mofetil, steroids and either tacrolimus or cyclosporine. All the patients had protocol biopsies at 3 months and 1 year. Patient's survival was 100% at 1 year and 98% at 2 years. Graft survival at 1 and 2 years is 98% and 96% at 1 and 2 years, respectively. The mean glomerular filteration rate values at 12 and 24 months were 60.6 mL/min/1.73 m2 (range 23–98) and 65.4 mL/min/1.73m2 (range 24–110), respectively. Acute cellular rejection was diagnosed in four cases (15%). Because of high trough levels of calcineurin inhibitor, protease‐inhibitor therapies were withdrawn in 11 cases. HIV disease progression was not observed. One patient developed B‐cell lymphoma.
In conclusion, our study confirms the safety of renal transplantation in HIV‐infected patients with few adverse events and a low incidence of acute rejection.
Systematic protocol biopsies performed in a cohort of 27 HIV‐infected recipients reveal a low incidence of acute rejection.
Papillary renal‐cell carcinoma (pRCC) is unusual for its occurrence in kidneys with chronic dysfunction, for its frequent multifocality and for its common association with papillary adenoma, a benign ...renal lesion morphologically indistinguishable from pRCC. Concomitant development of papillary adenoma and pRCC in five transplanted kidneys, where donor and recipient characteristics are well established, provided a unique opportunity for molecular studies of de novo pRCC carcinogenesis. We aimed to study this tumor type to determine whether or not the different papillary tumors have the same origin, and whether or not papillary adenomas are precursor lesions of pRCC. We performed XY‐FISH in sex‐mismatched kidney transplants, and polymorphic microsatellite DNA and high‐resolution melting of mitochondrial DNA analyzes in all five patients on laser‐microdissected tumor cells, then compared these molecular profiles to donor and recipient profiles. This study (i) identified the recipient origin of de novo papillary adenomas and pRCCs in a kidney transplant, (ii) demonstrated an identical origin for precursor cells of papillary adenomas and pRCCs and (iii) showed additional genetic alterations in pRCCs compared to papillary adenomas. This molecular approach of papillary tumors developed in transplanted kidney identified successive steps in carcinogenesis of human de novo papillary renal‐cell carcinoma.
Using the unique opportunity provided by the concomitant development of papillary adenoma and papillary renal‐cell carcinoma in kidney transplants, this study demonstrates that papillary renal‐cell carcinoma may arise from recipient cells according to a multistep tumorigenesis process.
The value of estimated glomerular filtration rate (eGFR) in living kidney donors screening is unclear. A recently published web‐based application derived from large cohorts, but not living donors, ...calculates the probability of a measured GFR (mGFR) lower than a determined threshold. Our objectives were to validate the clinical utility of this tool in a cohort of living donors and to test two other strategies based on chronic kidney disease epidemiology collaboration (CKD‐EPI) and on MDRD‐eGFR. GFR was measured using 51Cr‐ ethylene‐diamine tetraacetic acid urinary clearance in 311 potential living kidney donors (178 women, mean age 50 ± 11.6 years). The web‐based tool was used to predict those with mGFR < 80 mL/min/1.73 m2. Inputs to the application were sex, age, ethnicity, and plasma creatinine. In our cohort, a web‐based probability of mGFR <90 mL/min/1.73 m2 higher than 2% had 100% sensitivity for detection of actual mGFR <80 mL/min/1.73 m2. The positive predictive value was 0.19. A CKD‐EPI‐eGFR threshold of 104 mL/min/1.73 m2 and an MDRD‐eGFR threshold of 100 mL/min/1.73 m2 had 100% sensitivity to detect donors with actual mGFR <80 mL/min/1.73 m2. We obtained similar results in an external cohort of 354 living donors. We confirm the usefulness of the web‐based application to identify potential donors who should benefit from GFR measurement.
From two independent cohorts of potential living kidney donors, a web‐based application identifies potential donors with a measured glomerular filtration rate higher than 80 mL/min/1.73 m2 for whom direct GFR measurement can be safely avoided before donation.
The new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-based equation was developed to address the systematic underestimation of the glomerular filtration rate (GFR) by the ...Modification of Diet in Renal Disease (MDRD) Study equation in patients with a relatively well-preserved kidney function. The performance of the new equation for kidney transplant recipients is discussed.
We analyzed the performances of the CKD-EPI equation in comparison with the MDRD Study equation in 825 stable kidney transplant recipients. Bias, precision, and accuracy within 30% of true GFR were determined. GFR was measured by urinary clearance of inulin (n=488) and plasma clearance of Cr-EDTA (n=337).
Mean measured GFR (mGFR) was 50±19 mL/min/1.73 m. On the whole cohort, bias was significantly lower for MDRD Study equation compared with CKD-EPI creatinine. This superiority translates into a better accuracy (80% and 74% for the MDRD and CKD-EPI creatinine, respectively). The best performance of the MDRD Study equation is confirmed both in the subgroups of patients with mGFR <60 mL/min/1.73 m and between 60 and 90 mL/min/1.73 m. For mGFR >90 mL/min/1.73 m, there were no significant differences between the two equations in terms of performance.
The CKD-EPI creatinine equation does not offer a better GFR prediction in renal transplant patients compared with the MDRD Study equation, even in the earlier CKD stages.
The results of the transplantation of marginal donor kidneys remain controversial. This study aimed to investigate the impact of donor risk factors as predictors of kidney-graft outcome.
Allograft ...failure risk factors were studied in 7,209 cadaveric kidney-transplant recipients reporting to the Etablissement français des Greffes (EfG) from 1996 to 2000, of which 544 (7.6%) were from donors aged over 60. Both univariate and multivariate analysis were used to assess the effect of donor risk factors and were stratified according to recipient age.
Overall graft survival was 91.1% (95% confidence interval CI 90.5-91.8) at 1 year, 88.6% (95% CI 87.8-89.4) at 2 years, and 85.6% (95% CI 84.6-86.6) at 3 years posttransplant. Univariate analysis of risk factors showed a significant reduction of graft survival in recipients transplanted with kidneys coming from donors older than 60 years, donors with a history of hypertension, a cerebrovascular cause of death, and a preharvesting serum creatinine greater than 150 micromol/L. Multivariate analysis revealed significantly higher failure rate associated with cerebrovascular cause of death (RR=1.2, P=0.02), history of hypertension (RR=1.2, P=0.04), and elevated serum creatinine (RR=1.3, P=0.03), whereas donor age greater than 60 years was not found as an independent risk factor.
Our results suggest that cerebrovascular cause of death, history of hypertension, and elevated creatinine are significant independent donor risk factors for graft survival, whereas donor age is a statistically significant, but dependent, risk factor. This result is important for the design of allocation and transplantation strategies for kidneys procured in elderly donors.
Purpose Renal cell carcinoma in a renal graft is a rare condition whose incidence will increase in the future. To our knowledge no standardized treatment has been established for this disease. We ...performed a prospective study of nephron sparing surgery for small renal cell carcinoma in renal grafts. Materials and Methods From January 2002 to December 2006, 2,050 renal graft recipients were followed at our transplantation center. Of these patients 7 were diagnosed with histologically confirmed renal cell carcinoma in the renal graft, 5 of whom presented with T1a renal cell carcinoma and prospectively underwent nephron sparing surgery. Results Five patients with 15 to 30 mm (median 20) renal cell carcinoma were included in the study and were treated with nephron sparing surgery. Median operative time was 110 minutes (range 60 to 150). Blood loss was less than 200 ml in each case. All tumors were pT1aN0M0 with negative margins. No postoperative complications were observed (hemorrhage, urinary fistulas, renal failure). Preoperative immunosuppressive treatment was not modified postoperatively. At 3 months after nephron sparing surgery and at a mean of 17.4 months of followup (range 5 to 54) no significant impairment of renal function or recurrence was observed. Conclusions Nephron sparing surgery is a safe and efficient procedure for the treatment of renal cell carcinoma in renal grafts, resulting in the preservation of renal function and in short-term cancer control.
Sirolimus, a promising new immunosuppressive drug for organ transplantation, is currently associated with side effects, such as thrombocytopenia and hyperlipidemia.
Eight renal transplant recipients, ...who developed unexplained interstitial pneumonitis during sirolimus therapy, were extensively re-screened for all causes of pneumonitis.
Interstitial pneumonitis was constantly characterized by bilateral interstitial infiltrates on chest x-rays and lung computed tomography scans, with marked general symptoms in all patients but one. Bronchoalveolar lavage (BAL) disclosed lymphocytic alveolitis (mainly of the CD4 type) in seven patients and alveolar hemorrhage in one. Transbronchial lung biopsies, performed in two patients, showed bronchiolitis obliterans with organizing pneumonia combined with lymphocytic interstitial pneumonitis. Pulmonary infections were ruled out by specific stainings and cultures of BAL, bronchial aspirates, and blood cultures. After the elimination of all possible causes, sirolimus-induced pneumonitis was considered probable. Discontinuation of sirolimus in seven cases and dose reduction in the remaining case dramatically improved clinical and radiological status within a few weeks and led to complete resolution within 3 months.
Sirolimus is very probably responsible for interstitial pneumonitis on the following grounds: (a) occurrence of pneumonitis during sirolimus therapy; (b) absence of any other causes; and (c) resolution within 3 months of sirolimus discontinuation or dose reduction. Sirolimus should now be added to the list of possible causes of pulmonary complications after renal transplantation. Discontinuation or dose reduction of sirolimus led to complete and lasting resolution of symptoms.
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