Association between acute graft pyelonephritis and kidney graft survival: A single-center observational study.

The association between acute graft pyelonephritis (AGPN) and graft failure in kidney transplant recipients (KTR) remains controversial. In this single-center observational study, we aimed to assess the incidence of AGPN as a time-dependent posttransplantation event. We also examined the association between the diagnosis of AGPN and graft outcomes. In total, we evaluated 1480 patients who underwent kidney transplantation between January 2007 and December 2017. During a median follow-up of 5.04 years, we observed 297 AGPN episodes that occurred in 158 KTR. To evaluate the association between AGPN and clinical outcomes, we performed Cox proportional hazards regression analyses in which AGPN was entered as a time-dependent covariate. AGPN was independently associated with an increased risk of graft loss (hazard ratio = 1.66; 95% confidence interval [CI]: 1.05-2.64, p < .03) and a persistently decreased eGFR (fixed effect on intercept: -2.29 ml/min/1.73 m2 ; 95% CI: from -3.23 to -1.35, p < .01). However, neither mortality nor biopsy-proven acute rejection was found to correlate with AGPN. Moreover, recurrent AGPN episodes did not appear to have an additive detrimental impact on graft loss. These data represent a promising step in understanding whether AGPN prevention may decrease the risk of graft loss in KTR.

Successful Reuse of Kidney Graft After Early Recurrence of Primary Focal and Segmental Glomerulosclerosis.

Primary focal and segmental glomerulosclerosis (FSGS) frequently recurs after transplantation and is associated with a poor prognosis. We describe here the successful kidney graft reuse in an adult recipient, 8 months after early primary FSGS recurrence resistant to all available therapeutics. Patient 1, a 23-year-old man, followed for kidney failure secondary to primary FSGS, was first transplanted in 2018 with a deceased donor graft. Unfortunately, we observed an immediate recurrence of biopsy-proven primary FSGS. After 4 lines of treatment (intravenous cyclosporine+corticosteroids, plasma exchanges, immunoadsorption, and rituximab), the patient was still highly nephrotic and kidney function was slowly deteriorating. After approval from both the patient and the health authority (Biomedicine Agency), the graft was detransplanted 8 months after transplantation and reimplanted in patient 2, a 78-year-old nonimmunized and anephric recipient (bi-nephrectomy 2 years previously for bilateral renal carcinoma). We observed immediate kidney function and progressive resolution of proteinuria (serum creatinine of 1.2mg/dL and proteinuria of 0.1 g/d 1 year later). Biopsies performed after surgery showed persistent FSGS lesions with a decrease in overall foot-process effacement. To our knowledge, this is the first reported case showing that kidney graft transfer may still be a viable option for refractory primary FSGS several months after transplantation.

Autotransplantation or In Situ Surgical Treatment of Complex Renal Artery Aneurysm: Surgical Technique and Outcomes.

Background and objective: Renal artery aneurysm (RAA) is a rare condition. Our study investigates the effectiveness and outcomes of surgical treatments for complex RAA, comparing the in situ (IS) and ex vivo autotransplantation (AT) methods. Methods: We conducted a retrospective study from June 2015 to March 2023, including all consecutive patients treated surgically for complex RAA in our center. We focused on patients with complex RAA locations requiring open surgical multidisciplinary treatment, excluding those with simple aneurysms or who were treated endovascularly. Preoperative data including demographics, comorbidities, and cardiovascular risk factors were collected. The measured primary outcome was the absence of residual aneurysm and main renal arterial thrombosis after surgery. The secondary outcomes included pre- and postoperative kidney perfusion analyses and surgical complications as per Clavien-Dindo classification. Differences between AT and IS were assessed by Wilcoxon, chi-square, or Fischer's exact test. Key findings and limitations: Twenty-seven aneurysms were treated in 25 patients. No residual aneurysm or main artery thrombosis was found after surgery. Ten (40%) patients underwent AT surgery. The median kidney perfusion differences were 2 cc (-12; 13), 0 cc (-13; 10), and 2 cc (-10; 13; p = 0.41) in the whole, AT, and IS cohorts, respectively. Clavien-Dindo grade 1 and 2 complications occurred in 11% and 30% of patients, respectively, with no grade 3 or 4 complications observed. Conclusions and clinical implications: Complex RAA can be managed effectively through open surgery, ensuring good ipsilateral renal preservation and tolerable toxicity. Both AT and IS surgeries yielded similar outcomes. Further multicenter studies are warranted to confirm our findings. Patient summary: This study explored the treatment of a rare kidney blood vessel condition called renal artery aneurysm using two surgical approaches. Our findings suggest that both surgical techniques are effective in treating this condition without major complications, ensuring good kidney preservation. These promising results need further confirmation through larger studies across different medical centers.

Day-Time Declamping Is Associated with Better Outcomes in Kidney Transplantation: The Circarein Study.

Despite improvements in organ preservation techniques and efforts to minimize the duration of cold ischemia, ischemia-reperfusion (IR) injury remains associated with poor graft function and long-term survival in kidney transplantation. We recently demonstrated a clinically significant day-time variation in myocardial tolerance to IR, transcriptionally orchestrated by the circadian clock. Patient and graft post-transplant survival were studied in a cohort of 10,291 patients first transplanted between 2006 and 2017 to test whether kidney graft tolerance to IR depends on the time-of-the-day of clamping/declamping, and thus impacts graft and patient survival. Post-transplant 1- and 3-year survival decreased with increasing ischemia duration. Time-of-the-day of clamping did not influence outcomes. However, night-time (vs. day-time) declamping was associated with a significantly worse post-transplant survival. After adjustment for other predictors, night-time (vs. day-time) declamping remained associated with a worse 1-year (HR = 1.26 (1.08-1.47), p = 0.0028 by Cox multivariable analysis) and 3-year (HR = 1.14 (1.02-1.27), p = 0.021) outcome. Interestingly, the deleterious impact of prolonged ischemia time (>15 h) was partially compensated by day-time (vs. night-time) declamping. Compared to night-time declamping, day-time declamping was associated with a better prognosis of kidney transplantation despite a longer duration of cold ischemia.

Impaired renal function before kidney procurement has a deleterious impact on allograft survival in very old deceased kidney donors.

As the use of elderly kidney donors for transplantation is increasing with time, there is a need to understand which factors impact on their prognosis. No data exist on the impact of an impaired renal function (IRF) in such population. 116 kidney recipients from deceased kidney donors over 70 years were included from 2005 to 2015 in a single-center retrospective study. IRF before organ procurement was defined as a serum creatinine above 1.0 mg/dl or a transient episode of oligo-anuria. Mean ages for donors and recipients were respectively 74.8 ± 3.5 and 66.7 ± 8.0. Graft survival censored for death at 5 years was of 77%. Using a multivariate analysis by Cox model, the only predictor of graft loss present in the donor was IRF before organ procurement (HR 4.2 CI95[1.8-9.7]). IRF was also associated with significant lower estimated glomerular filtration rates up to 1 year post-transplantation. By contrast, KDPI score (median of 98 [96-100]), was not associated with the risk of graft failure. Then, IRF before kidney procurement may define a risk subgroup among very-old deceased kidney donors, in whom pre-implantatory biopsies, dual kidney transplantation or calcineurin inhibitor-free immunosuppressive regimen could help to improve outcomes.

De novo renal carcinoma arising in non-functional kidney graft: a national retrospective study.

AIM: Characteristics of renal carcinoma arising in non-functional graft in renal transplant recipients (RTR) are unknown. We studied a large national retrospective cohort to analyze circumstances of diagnosis, treatment and outcome compared to the literature. METHODS: Study included all RTR presenting with kidney graft tumors irrespective of the histology, except those with lymphoma and including those tumors arising in non-functional renal graft. Between January 1988 and December 2018, 56,806 patients had renal transplantation in the 32 centers participating in this study. Among this cohort, 18 renal graft tumors were diagnosed in non-functional grafts. RESULTS: The median patient age at the time of diagnosis was 42.1 years (31.7-51.3). Median age of kidney grafts at the time of diagnosis was 56.4 (23.2-63.4). Eight (44.4%) tumors were discovered fortuitously on renal graft histologic analysis. Fourteen tumors (77.8%) were papillary carcinomas. Two patients had clear cell carcinomas and one patient had a pTa high-grade multifocal urothelial carcinoma in the graft of the upper tract with an in situ carcinoma. CONCLUSION: Renal carcinomas in non-functional grafts are rare entities and most of them are diagnosed fortuitously. Despite the fact that these tumors are small, low grade and with a good prognosis, regular monitoring of non-functional grafts should be performed with at least an annual ultrasonography.

Peripheral zone prostate cancers: location and intraprostatic patterns of spread at histopathology.

BACKGROUND: To describe the precise location of peripheral zone (PZ) prostate cancers at various stages of development and to demonstrate their pattern of intraprostatic spread from their site of origin. METHODS: PZ cancers defined as cancers located in peripheral zone (PZ) including the anterolateral part of PZ, were identified from radical prostatectomy specimens. PZ cancers morphometric histopathological study included largest surface area, volume and spatial distribution. RESULTS: Out of 188 PZ cancers, 179 were <4 cm(3) and 168 <2 cm(3). PZ cancers were still confined to their zone of origin for volumes <2 cm(3). Between 2 and 4 cm(3), some cancers partially spread into the transition zone or anterior fibromuscular stroma. Sixty-four and 90% of PZ cancers <4 cm(3) were located in the lower and posterior half of the gland respectively. Ten percent were located in the anterior horn of PZ. Overall, non-index (second) cancers were located in the ipsi and contolateral side of the index cancer (largest) in 31% and 69% of cases, respectively. Cancers <2 cm(3) were confined to one lobe in 164 of 168 (98%) cases and not confined in 3 out of 11 (27%) cancers 2-4 cm(3). On vertical axis, only cancers >or=2 cm(3) involved both apex and base. CONCLUSIONS: PZ cancers contours and locations are predictable and conform to histological zone boundaries if <2 cm(3) in volume. Knowledge of PZ cancers origin and pattern of spread in PZ are of importance for imaging diagnosis, guidance for biopsy and focal therapy.

Transition zone and anterior stromal prostate cancers: zone of origin and intraprostatic patterns of spread at histopathology.

BACKGROUND: To describe the precise location of transition zone (TZ) and anterior fibromuscular stroma (AFMS) prostate cancers (TZ/AFMS) within histological zones at various stages of development and to demonstrate their pattern of intraprostatic spread from their site of origin. METHODS: Anterior TZ/AFMS cancers excluding the anterolateral part of peripheral zone, were identified from radical prostatectomy specimens. Morphometric histopathological study included largest surface area, volume and spatial distribution. RESULTS: Out of 91 TZ/AFMS cancers, 79 were <4 cm3 and 69 <2 cm3. Fifty percent and 70% of cancers <4 cm3 were located in the anterior third and inferior half of TZ and/or AFMS, respectively. Cancers <2 cm3 could be classified into three types according to their location related to histologic zone boundaries: TZ type 1 (40%) for cancers confined to one TZ lobe; TZ type 2 (35%) for cancers most represented in one TZ lobe but crossing its anterior boundary; type AFMS (25%) for cancers confined to AFMS. These results form the rationale for the hypothesis that AFMS cancers originate from anterior and medial TZ and due to benign prostatic hypertrophy they become excluded from TZ, anteriorly into AFMS. TZ anterior limit would then act as a barrier to their posterior extension. CONCLUSIONS: TZ/AFMS cancers contours and locations are predictable and conform to histological zones boundaries. Knowledge of these cancer origin and pattern of spread in TZ and AFMS are of importance for imaging diagnosis, guidance for biopsy and focal therapy.

Dynamic contrast-enhanced MRI of anterior prostate cancer: morphometric assessment and correlation with radical prostatectomy findings.

The purpose of the study was to relate morphometric features of prostate cancers in the anterior compartment of the prostate by dynamic contrast-enhanced (DCE) MRI to subsequent histopathologic findings. We prospectively performed DCE-MRI before biopsy in patients with suspected prostate cancer and selected those showing both a suspicious lesion at MRI and positive biopsies in the anterior compartment of the gland. Tumor contours, margins, largest surface areas and volumes were assessed at MRI and histopathology, when available. Anterior compartment tumors were classified according to transition zone (TZ) boundaries with the peripheral zone (PZ) or with the anterior fibromuscular stroma (SFMA). Forty-three patients were included in this study [median PSA 12.7 ng/ml (3.6-72)]. Whole-mount radical prostatectomy specimens were available in 27 cases. Of the anterior cancers, 89% had ill-defined margins at T2-weighted MRI. Cancer location and contour established at MRI agreed well with histopathology in the 27 cases. Median largest surface area and volume were 1.38 cm(2) (0.35-5.82) and 1.01 cc (0.15-7.4) for MRI versus 1.86 cm(2) (0.2-14) and 2.84 cc (0.33-28.92) for histopathology with respective correlation coefficients (r(2)) of 0.73 and 0.69. The site of origin could be accurately determined for the 15 tumors of less than 3 cc. We found a good relationship between DCE-MRI and histopathology for localization, morphologic description and volume assessment of anterior prostate cancers.

[What is prostate cancer?]. / Qu'est-ce que le cancer de la prostate.

Prostate cancer can be diagnosed by individual screening (digital examination and PSA assay at age > 50 y) when still localized and asymptomatic. The diagnosis is confirmed by staged biopsies and by magnetic resonance imaging (MRI) with targeted biopsies. A better knowledge of the natural history of prostate cancer, together with improvements in MRI, can help to predict the location, volume, local extension and prognosis prior to treatment. This is particularly important for focal or partial treatment, aimed at removing the cancer without creating functional urinary or sexual disorders.

Increased circulating miR-21 levels are associated with kidney fibrosis.

MicroRNAs (miRNAs) are a class of noncoding RNA acting at a post-transcriptional level to control the expression of large sets of target mRNAs. While there is evidence that miRNAs deregulation plays a causative role in various complex disorders, their role in fibrotic kidney diseases is largely unexplored. Here, we found a strong up-regulation of miR-21 in the kidneys of mice with unilateral ureteral obstruction and also in the kidneys of patients with severe kidney fibrosis. In addition, mouse primary fibroblasts derived from fibrotic kidneys exhibited higher miR-21 expression level compared to those derived from normal kidneys. Expression of miR-21 in normal primary kidney fibroblasts was induced upon TGFß exposure, a key growth factor involved in fibrogenesis. Finally, ectopic expression of miR-21 in primary kidney fibroblasts was sufficient to promote myofibroblast differentiation. As circulating miRNAs have been suggested as promising non-invasive biomarkers, we further assess whether circulating miR-21 levels are associated with renal fibrosis using sera from 42 renal transplant recipients, categorized according to their renal fibrosis severity, evaluated on allograft biopsies (Interstitial Fibrosis/Tubular Atrophy (IF/TA). Circulating miR-21 levels are significantly increased in patients with severe IF/TA grade (IF/TA grade 3: 3.0±1.0 vs lower grade of fibrosis: 1.5±1.2; p = 0.001). By contrast, circulating miR-21 levels were not correlated with other renal histological lesions. In a multivariate linear regression model including IF/TA grade and estimated GFR, independent associations were found between circulating miR-21 levels and IF/TA score (ß = 0.307, p = 0.03), and between miR-21 levels and aMDRD (ß = -0.398, p = 0.006). Altogether, these data suggest miR-21 has a key pathogenic role in kidney fibrosis and may represent a novel, predictive and reliable blood marker of kidney fibrosis.