Nephrology

This is a prospective, multicenter, hybrid cohort study designed to validate a non-contrast functional MRI protocol for the non-invasive, quantitative assessment of graft function in kidney transplant recipients. Primary Objectives: To establish an individualized functional baseline for transplanted kidneys through donor-recipient paired studies, moving beyond population-based reference values to enable a "self-comparison" paradigm for enhanced sensitivity in detecting early graft dysfunction. To validate the standalone capability of non-contrast functional MRI for sensitively monitoring dynamic changes in graft function in a large, independent cohort of recipients without donor baseline data (e.g., from deceased donors). To integrate MRI parameters with body composition analysis and metabolic profiles to build a comprehensive, non-invasive assessment model for early diagnosis, treatment evaluation, and prognosis prediction of graft function. Study Cohorts: Paired Study Cohort: Live or deceased kidney transplant donors who can undergo pre-transplant baseline MRI and their corresponding recipients. Independent Recipient Cohort: Kidney transplant recipients for whom donor baseline data is unavailable (primarily from deceased donors). Key Assessments: MRI Protocol: Includes multiple non-contrast functional sequences (e.g., DWI, ASL, BOLD, MT) to quantitatively evaluate renal perfusion, oxygenation, diffusion, and microstructure. Clinical \& Laboratory Data: Collection of serial serum creatinine, eGFR, uric acid, proteinuria, and other relevant biomarkers. Body Composition Analysis: MRI-based quantification of visceral, subcutaneous, perirenal, sinus renalis fat, and muscle mass. Histopathology: When available, biopsy results (e.g., rejection classification, fibrosis scores) will be collected as a reference standard. Study Procedures: Eligible participants will undergo non-contrast MRI scans at scheduled follow-up visits. Clinical data, laboratory results, and body composition metrics will be collected concurrently. For the paired cohort, donor baseline MRI (pre-transplant) serves as the individual reference. All data will be anonymized and analyzed to correlate MRI parameters with clinical, laboratory, and histopathological outcomes. Sample Size: The planned sample size is 1000 participants. This calculation is based on the inclusion of approximately 80 potential predictor variables (from MRI, clinical, and metabolic data) for multivariate analysis, requiring a sample size at least 10 times the number of variables, with an additional allowance for a 20% drop-out rate. Potential Impact: This study seeks to provide a novel, practical, and individualized solution for the precise monitoring of transplant kidney function, addressing a critical unmet need in clinical management, particularly for recipients of deceased donor organs.

This is a prospective, multicenter sample collection study within a kidney transplant population. Whole blood samples and clinical data will be obtained from each participant at the time of indication biopsy (prior to the biopsy procedure). De-identified leftover retrospective gDNA screening samples from the paired donor(s) will also be obtained.

This research study is being done to learn if an experimental treatment of infusing allogeneic adipose-derived mesenchymal stromal cells (allo-A-MSC ) directly into the renal artery is safe and can help reduce inflammation in the transplanted kidney and treat rejection.

This is a pediatric kidney transplant study comparing the safety and efficacy of an immunosuppressive regimen of belatacept and sirolimus to tacrolimus and Mycophenolate Mofetil (MMF). Two hundred participants will be randomized (1:1) to one of two groups within 24 hours following the transplant procedure. The duration of the study from time of transplant to the primary endpoint is 12-24 months.

The hypothesis of this study is that analyzing the heterogeneity of alloreactive Bmem in patients carrying HLA antibodies under varying HLA immunization intensity conditions (corresponding to varying intensities of exposure to HLA alloantigens) is likely to provide insight into the differential modalities of overall alloreactive B repertoire formation. Two types of patients sensitized to HLA antigens following immunizing events (at least one transplant or pregnancy) awaiting kidney transplantation will be specifically explored: * patients deemed hyperimmunized based on an incompatible graft rate (IGR) ≥ 85%, carrying a broad HLA antibody repertoire * patients immunized with an IGR between 50 and 85%, carrying a more restricted HLA antibody repertoire. These two groups will be characterized by differential intensities of exposure to HLA alloantigens. Patients with a history of immunizing events other than transfusions will not be investigated, due to the lack of detection of alloreactive Bmem in this situation. "Control" patients will also be included: "naïve" patients carrying HLA antibodies in the absence of a classic immunizing event, in whom alloreactive Bmem are not detectable. The exploration of alloreactive Bmem in these two groups aims to identify potential differences in terms of clonality, phenotype, and functionality, which could clarify several aspects of the alloreactive humoral response: The expected impact of this pilot translational study in kidney transplantation is threefold: * the acquisition of fundamental knowledge in the field of alloantigen-specific human Bmem biology * the acquisition of data prior to the subsequent exploration of the characteristics of the alloreactive B cell response during acute or chronic humoral rejection * and ultimately, the identification of phenotypic, clonotypic, or functional markers that could potentially be used to better discriminate the immunological risk associated with the presence of antibodies and HLA-reactive B cells. The low frequency of alloreactive Bmem, estimated at 20-150 per million B lymphocytes (for a given HLA specificity), as well as the number and epitopic diversity of targeted HLA antigens, complicate the direct assessment of their repertoire and functionalities. High-throughput approaches (RNAseq) in single cells, which have become essential for characterizing the heterogeneity of rare cellular contingents, now make it possible to simultaneously interrogate the repertoire and transcriptome of immune cells. In this project, we will take advantage of these recent methodologies to directly and simultaneously explore the clonality (BCR repertoire), the phenotype of membrane markers and the transcriptome of alloreactive Bmem towards a restricted panel of HLA alleles chosen according to the HLA antibody reactivity profile of the patients analyzed. This methodology allows the acquisition of individual characteristics of several hundred alloreactive B lymphocytes per patient and their comparison with polyclonal Bmem from patients or control subjects. This is a pilot study intended to acquire preliminary data prior to studies on a larger number of patients, before and after transplantation.

This study aims to evaluate whether the use of alpha-blockers before flexible ureterorenolithotripsy facilitates the passage of the ureteral access sheath. The trial will enroll adult patients diagnosed with kidney stones who are scheduled for flexible ureteroscopy. Participants will be randomly assigned to receive or not receive alpha-blockers for seven days before surgery. The primary outcome is the rate of successful sheath placement without the need for a second procedure. Secondary outcomes include the incidence of ureteral injuries and the need for additional surgical interventions. The goal is to improve surgical efficiency and patient outcomes in the treatment of kidney stones.

Early diagnosis in children with Alport syndrome (AS) with isolated hematuria opens a "window of opportunity" for early intervention. In the Alport mouse-model, this early intervention with the ACE-inhibitor Ramipril let to a delay of kidney failure by 111%. In order to observe treatment approaches for AS in humans, this registry has been established in 2006 to collect data over several generations of Alport families across Europe. In the meantime, this registry has been expanded to "Alport XXL" via the International Alport Alliance as a global effort across all continents. Small children with AS first develop microscopic hematuria (stage 0), proceeding to microalbuminuria (stage I), overt proteinuria (stage II), impaired kidney function (stage III) and finally can end up with kidney failure (stage IV), leading to impaired quality of life and premature death (stage V). This registry uses these stages to assess if earlier initiation of medications such as ACE-inhibition at earlier stages of disease is more effective than later therapy in delaying the time to disease progression (doubeling or tripeling of albuminuria), delaying loss of estimated glomerular filtration rate (eGFR), and if therapy improves life-expectancy. Untreated children with autosomal-recessive AS, digenic AS, and boys with X-linked AS typically all develop kidney failure early in life. Untreated girls with X-linked AS have a 30-40% risk of kidney failure, typically later in life (40 years or older). Untreated heterozygous patients with COL4A3/COL4A4 variants typically have a less severe phenotype (in former times also called "familial benign hematuria" or "thin basement membrane nephropathy" (TBMN)) and a 1-2% risk of kidney failure. Several interim results of this registry have been published since 2012. Alport XXL is designed and conducted as strictly observational, non-interventional data acquisition with prospective (and in parts retrospective) data analysis. Young patients with AS in disease stages 0,I,II from all over the world are included. The renewed version from 2021 has been re-approved by the Ethics Committee of the University Medical Center Göttingen as "Alport XXL", a further development of the former European Alport Therapy Registry (AZ 10/11/06). "Alport XXL" registry and data storage are in conformity with Good Clinical Practice guidelines. ICH-GCP-conform patient information and data exchange is secured by data transfer and cooperation agreements between all international trial centers and the coordinating principal investigator at University Medical Center Goettingen. At baseline, data collection including retrospective data is performed using a standardized, ICH-GCP-conform and pseudonymized questionnaire assessing age, sex, weight, height, mode of inheritance (X-linked, autosomal, compound heterozygous/homozygous, number of missense variants), family history, albumin in 24-hour or spontaneous urine, serum-creatinine, RAS-blockade with preparation and dose. Follow-up visits include same data than baseline plus blood-pressure, smoking-status, serum-potassium, eGFR, hearing loss and eye involvement, other symptoms such as leiomyomatosis, comorbidities and adverse events (adverse events of special interest defined as hyperkalemia, cough, hypotension, acute renal failure, malignancy, death).

This study will evaluate the efficacy, safety, and tolerability of VX-880 in participants with Type 1 Diabetes (TID) with a kidney transplant.

Open surgery remains one of the procedures used for those patients requiring partial or radical nephrectomy and is associated with a high incidence of severe immediate postoperative pain and chronic pain the months following surgery. Regional anesthesia techniques are frequently recommended for pain control in open nephrectomy as they decrease the need for parenteral opioid and improve patient satisfaction. Although abdominal wall blocks are known to decrease opioid requirements without causing epidural associated hypotension, their role in flank surgeries has been less well-established. The dermatomes that need to be covered in flank incision are T9 to T11. Studies have confirmed that ultrasound-guided (USG) transversus abdominis plane (TAP) block is an effective method of analgesia for upper abdominal surgeries, lower abdominal surgeries and kidney transplantation with minimal side effects. The external oblique intercostal (EOI) block is a novel method providing simple and effective somatic analgesia to the upper abdomen with minimal side effects. Other advantages include easy sonoanatomy (even in obese patients), being performed in the supine position, and no anticoagulation concern

The detection rate of renal masses smaller than 7 cm has increased significantly in recent years. To maximize the preservation of postoperative renal function, guidelines from the European Association of Urology (EAU), the National Comprehensive Cancer Network (NCCN), and others have established partial nephrectomy (PN) as the preferred treatment option for small renal masses. In conventional PN, the renal artery or its segmental branches must be clamped, and the renal defect is typically closed using a multilayer suturing technique to control bleeding, maintain a clear surgical field, and prevent postoperative urinary leakage. The maximum safe duration of warm ischemia time (WIT) remains controversial, though most studies suggest a limit of 20-30 minutes to avoid irreversible renal parenchymal damage. In murine models, renal damage increases steeply after ischemia exceeds 30 minutes. Furthermore, the renorrhaphy suture technique has a steep learning curve, and the suturing process itself can cause additional injury to the renal vasculature, potentially compromising global renal function . Notably, up to 30% of patients with normal preoperative renal function may experience a decline in their estimated glomerular filtration rate (eGFR) to \<60 mL/min/1.73 m² post-surgery, and nearly 10% may suffer a \>50% reduction in renal function . Consequently, the concept of a "zero-ischemia sutureless" approach has gained traction. Its core principle is to avoid renal artery clamping and replace suturing with novel haemostatic methods, thereby maximizing the preservation of healthy renal parenchyma. With the expanding array of haemostatic agents and the widespread adoption of robotic-assisted systems, the zero-ischemia sutureless strategy has become technically feasible for small renal masses with low complexity. Findings from multiple retrospective studies indicate that the zero-ischemia sutureless technique is non-inferior, demonstrating comparable safety and surgical outcomes to standard robot-assisted partial nephrectomy (RAPN). A study by Antonio Franco et al. reported a median decline in overall renal function of only 10 mL/min after zero-ischemia sutureless surgery, supporting its role as a safe procedure that effectively preserves postoperative renal function and reduces complications. In a review, J. C. Moreno Cortés highlighted that replacing traditional artery clamping and suturing with mono- or bipolar electrocautery and new haemostatic agents offers a simpler and faster method for reconstruction. This approach simplifies the surgical steps without increasing the risk of complications. However, it is important to note that current research is predominantly focused on tumours ≤4 cm, is largely retrospective, and often involves small sample sizes. More robust evidence from prospective studies is needed to support the application of this technique for larger or anatomically complex tumours.