Hannes Cash

Interleukin 6 (IL-6) deficiency delays lupus nephritis in MRL-faslpr mice: the IL-6 pathway as a new therapeutic target in treatment of autoimmune kidney disease in systemic lupus erythematosus

Objective. To investigate the pathophysiological effect of interleukin 6 (IL-6) on lupus nephritis in MRL-Faslpr mice. Methods. We generated IL-6-deficient MRL-Faslpr mice using a backcross/intercross breeding scheme. Renal pathology was evaluated using immunohistochemistry detection for macrophages, lymphocytes, vascular cell adhesion molecule-1 (VCAM-1), and TUNEL (terminal deoxynucleotide transferase-mediated dUTP nick end-labeling) for apoptotic cells, and renal IgG and C3 deposition by immunofluorescence staining. Expression of inflammatory markers in the spleen was analyzed by quantitative real-time reverse transcription-polymerase chain reaction. Serum cytokine concentrations were detected by FACS analysis. Results. IL-6 deficiency was highly effective in prolonging survival and ameliorating the clinical, immunological, and histological indicators of murine systemic lupus erythematosus. During the study period of 6 months, MRL-Faslpr IL-6 −/− mice showed delayed onset of proteinuria and hematuria compared to IL-6-intact control mice. Survival rate was 100% in IL-6-deficient MRL-Faslpr mice and 25% in the control group at 6 months of age. The absence of IL-6 resulted in significant reduction of infiltrating macrophages in the kidney (p < 0.05), a decrease in renal IgG and C3 deposition, and a reduction of CD4+ and CD8+ lymphocytes. The parenchymal adhesion molecule VCAM-1 was found to be downregulated in kidneys of MRL-Faslpr IL-6 −/− compared to IL-6-intact mice. We found elevated serum levels of IL-10 and interferon-γ in IL-6-deficient mice, while splenic mRNA showed an overall downregulation of immunoregulatory genes. Conclusion. IL-6 is a strong promoter of lupus nephritis and may be a promising new therapeutic target in the treatment of human lupus nephritis.

Prostate cancer detection on transrectal ultrasonography-guided random biopsy despite negative real-time magnetic resonance imaging/ultrasonography fusion-guided targeted biopsy: reasons for targeted biopsy failure

To examine the value of additional transrectal ultrasonography (TRUS)‐guided random biopsy (RB) in patients with negative magnetic resonance imaging (MRI)/ultrasonography (US) fusion‐guided targeted biopsy (TB) and to identify possible reasons for TB failure.

Added Value of Multiparametric Ultrasonography in Magnetic Resonance Imaging and Ultrasonography Fusion–guided Biopsy of the Prostate in Patients With Suspicion for Prostate Cancer

OBJECTIVE To analyze whether magnetic resonance imaging-ultrasonography (MRI-US) fusion-guided biopsy detects more and clinical significant prostate cancer (PCa) in comparison to conventional transrectal US-guided prostate biopsy (PBX) and to investigate if multiparametric (mp) US during MRI-US fusion can further characterize mpMRI-suspected lesions according to the prostate MRI reporting and data system (PI-RADS). METHODS From January 2012 to January 2014, 169 patients with a median of 2 negative conventional PBX and/or initially or consistently elevated prostate-specific antigen levels were prospectively included and underwent 3 T mpMRI. Real-time MRI-US fusion scan was used to biopsy the mpMRI-targeted lesions (n = 316). Scanning by mpUS, including B-mode, power Doppler, strain elastography, and contrast-enhanced US was performed to further characterize those lesions and to score by US modalities resulting in an mpUS score. Afterward, a conventional 10-core PBX was performed. PCa detection based on the results of targeted and conventional PBX was estimated. Performances of single US modalities were analyzed. The mpUS score was also investigated for PCa and PI-RADS score prediction. RESULTS Among 169 patients, 71 PCa (42%) were detected. From these 71 cases, clinically significant PCa (Gleason score ≥7) were detected exclusively by MRI-US fusion in 31 from 46 cases (67.4%). The highest sensitivity was observed in contrast-enhanced US (85%) and elastography (80%). The mpUS score predicts PCa and PI-RADS score with an overall accuracy of 86% and 80%, respectively. CONCLUSION MRI-US fusion-guided PBX detects more clinically significant PCa compared with conventional TRUS. The mpUS score correlates with PI-RADS in PCa prediction.

Impact of surgeon experience on complication rates and functional outcomes of 484 deceased donor renal transplants: a single-centre retrospective study

Study Type – Therapy (outcomes)

New perspectives on the renal slit diaphragm protein podocin

Podocin is a critical component of the glomerular filtration barrier, its mutations causing recessive steroid-resistant nephrotic syndrome. A GenBank analysis of the human podocin (NPHS2) gene resulted in the possible existence of a new splice variant of podocin in the kidney, missing the in-frame of exon 5, encoding the prohibitin homology domain. Using RT–polymerase chain reaction and immunoblotting followed by sequence analysis, we are for the first time able to prove the expression of a novel podocin isoform (isoform 2), exclusively and constitutively expressed in human podocytes. Furthermore, we reveal singular extrarenal podocin expression in human and murine testis. Our data show the Sertoli cells of the seminiferous tubules to be the origin of testicular podocin. Confocal laser microscopy illustrates the co-localization of podocin with filamentous actin within Sertoli cells, suggesting a role of podocin in the blood/testis barrier. These results led to the rationale to examine podocin expression in testes of men with Sertoli cell-only syndrome, a disorder characterized by azoospermia. Interestingly, we observed a complete down-regulation of podocin mRNA in Sertoli cell-only syndrome, indicating a possible role of podocin in the pathogenesis of this germinal aplasia. Men with Sertoli cell-only syndrome show normal renal podocin expression, suggesting an alternate regulation of the testicular promoter. Our findings may change the perception of podocin and give new insights into the ultrastructure of glomerular slit diaphragm and the blood/testis barrier.

Erratum to: No need for systemic heparinization during laparoscopic donor nephrectomy with short warm ischemia time

Purpose Systemic heparin administration during laparoscopic donor nephrectomy (LDN) may prevent microvascular thrombus formation following warm ischemia. We herein present our experience with and without systemic heparinization during LDN.

Outcomes after laparoscopic living donor nephrectomy: comparison of two laparoscopic surgeons with different levels of expertise.

Laparoscopic living donor nephrectomy has evolved as the procurement method of choice for living kidney donation. Given that this is a technically challenging procedure with potential risks for the healthy donor, skills transfer from an experienced laparoscopist to a novice is critical. The present study investigates donor and recipient outcomes during a novices early experience with this procedure. Previous training in laparoscopic renal surgery and mentoring by the expert helps the novice to generate acceptable outcomes. However, longer warm ischaemia times during the learning phase may affect short‐term graft function.

Fate of finally transplanted deceased donor kidneys initially rejected at other kidney transplantation centers.

Objective: We conducted this study to determine whether it is justifiable for transplant centers to reject cadaveric donor organs based on marginal organ quality. There is a growing discrepancy between the demand for renal transplants and the number of transplants conducted. For the many patients on the renal transplant waiting list, this translates into increased dialysis-associated morbidity, mortality and a reduced quality of life. Patients and Methods: In our retrospective analysis, we focused on deceased donor kidneys that had been rejected in other transplant centers because of poor organ quality (111 patients) and then accepted for transplantation at our center, compared with a control group consisting of 343 patients. Results: Cold ischemia time was statistically significantly shorter in the control group (11 vs. 12.5 h, p = 0.005). Also, delayed graft function occurred significantly (p = 0.004) more often in the study group (45.9-30.3%). Parameters regarding perioperative data and recipient outcome did not show significant differences and except for 2 time points at 1 week and 3 months, graft function did not differ either. Conclusions: We propose that acceptance criteria for marginal donor kidneys should be expanded. Centers should reconsider their acceptance criteria in the light of these findings as the results of these transplantations may even be much better if the delay due to reallocation and retransport can be spared.

Extracorporeal Shock Wave Lithotripsy (ESWL) of a Renal Calculus in a Liver Transplant Recipient: Report of a Severe Complication—A Case Report

INTRODUCTION Extracorporeal shock wave lithotripsy (ESWL) has evolved as a standard treatment modality for calculi of the upper urinary tract. Noninvasive ESWL shows rare life-threatening complications. Herein we have reported the case of a liver transplant recipient who developed severe renal hemorrhage after ESWL of a renal calculus. Transfusion of erythrocytes and platelets led to anaphylactic shock with acute renal failure requiring intensive care. The patient fully recovered shortly thereafter and was discharged home with a residual left kidney stone measuring 8 mm. CASE PRESENTATION A 55-year-old man with a single left kidney underwent ESWL due to symptomatic left nephrolithiasis. He had undergone successful liver transplantation 11 years earlier. At the time of ESWL his liver functions were normal and his serum creatinine level was 1.3 mg/dL. Two weeks before the treatment a double pigtail ureteral stent was inserted because of a symptomatic left hydronephrosis. Several hours after ESWL treatment the patient complained of left-sided flank pain. An ultrasound revealed a large subcapsular hematoma of the left kidney, which was confirmed using abdominal computed tomography (CT). With the patient being hemodynamically stable, we opted for conservative management. Despite postinterventional complications, the patient made a fast recovery. CONCLUSION ESWL is a noninvasive, safe, and efficient method to treat renal calculi. Patients who are at risk for hemorrhage should undergo close postinterventional monitoring, including red blood cell count and renal ultrasound.

Is the Ellipsoid Formula the New Standard for 3-Tesla MRI Prostate Volume Calculation without Endorectal Coil?

Prostate volume in multiparametric MRI (mpMRI) is of clinical importance. For 3-Tesla mpMRI without endorectal coil, there is no distinctive standard for volume calculation. We tested the accuracy of the ellipsoid formula with planimetric volume measurements as reference and investigated the correlation of gland volume and cancer detection rate on MRI/ultrasound (MRI/US) fusion-guided biopsy. One hundred forty-three patients with findings on 3-Tesla mpMRI suspicious of cancer and subsequent MRI/US fusion-guided targeted biopsy and additional systematic biopsy were analyzed. T2-weighted images were used for measuring the prostate diameters and for planimetric volume measurement by a segmentation software. Planimetric and calculated prostate volumes were compared with clinical data. The median prostate volume was 48.1 ml (interquartile range (IQR) 36.9-62.1 ml). Volume calculated by the ellipsoid formula showed a strong concordance with planimetric volume, with a tendency to underestimate prostate volume (median volume 43.1 ml (IQR 31.2-58.8 ml); r = 0.903, p < 0.001). There was a moderate, significant inverse correlation of prostate volume to a positive biopsy result (r = -0.24, p = 0.004). The ellipsoid formula gives sufficient approximation of prostate volume on 3-Tesla mpMRI without endorectal coil. It allows a fast, valid volume calculation in prostate MRI datasets.