Deceased donor urinary Dickkopf-3 associates with future allograft function following kidney transplantation.

Predicting future kidney allograft function is challenging. Novel biomarkers, such as urinary Dickkopf-3 (uDKK3), may help guide donor selection and improve allograft outcomes. In this prospective multicenter pilot trial, we investigated whether donor uDKK3 reflects organ quality and is associated with future allograft function.

Hybrid Immunity Protects against Antibody Fading after SARS-CoV-2mRNA Vaccination in Kidney Transplant Recipients, Dialysis Patients, and Medical Personnel: 9 Months Data from the Prospective, Observational Dia-Vacc Study.

(1) Background: Compared to medical personnel, SARS-CoV-2mRNA vaccination-related positive immunity rates, levels, and preservation over time in dialysis and kidney transplant patients are reduced. We hypothesized that COVID-19 pre-exposure influences both vaccination-dependent immunity development and preservation in a group-dependent manner. (2) Methods: We evaluated 2- and 9-month follow-up data in our observational Dia-Vacc study, exploring specific cellular (interferon-γ release assay = IGRA) and/or humoral immune responses (IgA/IgG/RBD antibodies) after two SARS-CoV-2mRNA vaccinations in 2630 participants, including medical personnel (301-MP), dialysis patients (1841-DP), and kidney transplant recipients (488-KTR).

Immunosuppression with cyclosporine versus tacrolimus shows distinctive nephrotoxicity profiles within renal compartments.

Aim: Calcineurin inhibitors (CNIs) are the backbone for immunosuppression after solid organ transplantation. Although successful in preventing kidney transplant rejection, their nephrotoxic side effects contribute to allograft injury. Renal parenchymal lesions occur for cyclosporine A (CsA) as well as for the currently favored tacrolimus (Tac).

Low-cost simulation model for ultrasound-guided punch biopsy and puncture: Construction manual and photo examples.

Purpose: Ultrasound-guided puncture and punch biopsy pose a particular challenge in ultrasound examination training. These techniques should be learned and performed several times using a simulation model that is as realistic as possible before being applied to patients. While the use of agar-agar-based models is extensively documented in the literature, there is a discernible gap in publications specifically addressing their use in punch biopsy and puncture.

HYDROchlorothiazide versus placebo to PROTECT polycystic kidney disease patients and improve their quality of life: study protocol and rationale for the HYDRO-PROTECT randomized controlled trial.

Background: Autosomal dominant polycystic kidney disease (ADPKD) leads to progressive renal cyst formation and loss of kidney function in most patients. Vasopressin 2 receptor antagonists (V2RA) like tolvaptan are currently the only available renoprotective agents for rapidly progressive ADPKD. However, aquaretic side effects substantially limit their tolerability and therapeutic potential.

9-Month observational Dia-Vacc study of vaccine type influence on SARS-CoV-2 immunity in dialysis and kidney transplant patients.

Background: SARS-CoV-2mRNA vaccination related seroconversion rates are reduced in dialysis and kidney transplant patients.

Methods: We evaluated nine months follow up data in our observational Dia-Vacc study exploring specific cellular (interferon-γ release assay) or/and humoral immune responses after 2x SARS-CoV-2mRNA vaccination in 880 participants including healthy medical personnel (125-MP), dialysis patients (595-DP), kidney transplant recipients (111-KTR), and apheresis patients (49-AP) with positive seroconversion (de novo IgA or IgG antibody positivity by ELISA) after eight weeks.

Findings: Nine months after first vaccination, receptor binding domain (RBD) antibodies were still positive in 90 % of MP, 86 % of AP, but only 55 %/48 % of DP/KTR, respectively.

Efficacy and safety of a targeted-release formulation of budesonide in patients with primary IgA nephropathy (NefIgArd): 2-year results from a randomised phase 3 trial.

Background: IgA nephropathy is a chronic immune-mediated kidney disease and a major cause of kidney failure worldwide. The gut mucosal immune system is implicated in its pathogenesis, and Nefecon is a novel, oral, targeted-release formulation of budesonide designed to act at the gut mucosal level. We present findings from the 2-year, phase 3 NefIgArd trial of Nefecon in patients with IgA nephropathy.

Annexin A1 exerts renoprotective effects in experimental crescentic glomerulonephritis.

Non-resolving inflammation plays a critical role during the transition from renal injury towards end-stage renal disease. The glucocorticoid-inducible protein annexin A1 has been shown to function as key regulator in the resolution phase of inflammation, but its role in immune-mediated crescentic glomerulonephritis has not been studied so far. Acute crescentic glomerulonephritis was induced in annexin A1-deficient and wildtype mice using a sheep serum against rat glomerular basement membrane constituents.

Results from part A of the multi-center, double-blind, randomized, placebo-controlled NefIgArd trial, which evaluated targeted-release formulation of budesonide for the treatment of primary immunoglobulin A nephropathy.

The therapeutic potential of a novel, targeted-release formulation of oral budesonide (Nefecon) for the treatment of IgA nephropathy (IgAN) was first demonstrated by the phase 2b NEFIGAN trial. To verify these findings, the phase 3 NefigArd trial tested the efficacy and safety of nine months of treatment with Nefecon (16 mg/d) versus placebo in adult patients with primary IgAN at risk of progressing to kidney failure (ClinicalTrials.gov: NCT03643965).

Urinary CD8+HLA-DR+ T Cell Abundance Non-invasively Predicts Kidney Transplant Rejection.

Early detection of kidney transplant (KT) rejection remains a challenge in patient care. Non-invasive biomarkers hold high potential to detect rejection, adjust immunosuppression, and monitor KT patients. So far, no approach has fully satisfied requirements to innovate routine monitoring of KT patients.

MMF/MPA Is the Main Mediator of a Delayed Humoral Response With Reduced Antibody Decline in Kidney Transplant Recipients After SARS-CoV-2 mRNA Vaccination.

Kidney transplant recipients (KTR) show significantly lower seroconversion rates after SARS-CoV-2 mRNA vaccination compared to dialysis patients (DP). Mycophenolate mofetil or mycophenolic acid (MMF/MPA) in particular has been identified as a risk factor for seroconversion failure. While the majority of all KTR worldwide receive MMF/MPA for immunosuppressive therapy, its impact on antibody decline in seroconverted KTR still remains unclear.

Risk of strong antibody decline in dialysis and transplant patients after SARS-CoV-2mRNA vaccination: Six months data from the observational Dia-Vacc study.

Background: Vulnerable dialysis and kidney transplant patients show impaired seroconversion rates compared to medical personnel eight weeks after SARS-CoV-2mRNA vaccination.

Methods: We evaluated six months follow up data in our observational Dia-Vacc study exploring specific cellular (interferon-γ release assay) or/and humoral immune responses after 2x SARS-CoV-2mRNA vaccination in 1205 participants including medical personnel (125 MP), dialysis patients (970 DP) and kidney transplant recipients (110 KTR) with seroconversion ( IgA or IgG antibody positivity by ELISA) after eight weeks.

Findings: Six months after vaccination, seroconversion remained positive in 98% of MP, but 91%/87% of DP/KTR ( = 0·005), respectively.

10-Year Evaluation of Adherence and Satisfaction with Information about Tolvaptan in ADPKD: A Single-Center Pilot Study.

Purpose: Tolvaptan is the only approved drug for the treatment of autosomal dominant polycystic kidney disease (ADPKD) and causes significant polyuria with secondary polydipsia. Up to now, there is no study that examines tolvaptan adherence and satisfaction with information received about tolvaptan in ADPKD patients 10 years after starting tolvaptan therapy.

Patients And Methods: This pilot study includes 12 ADPKD patients that were formerly enrolled in the tolvaptan registration trials and have continued to use tolvaptan thereafter.

Cellular and Humoral Immune Responses After 3 Doses of BNT162b2 mRNA SARS-CoV-2 Vaccine in Kidney Transplant.

Supplemental Digital Content is available in the text.

Humoral and cellular immunity to SARS-CoV-2 vaccination in renal transplant versus dialysis patients: A prospective, multicenter observational study using mRNA-1273 or BNT162b2 mRNA vaccine.

Background: Dialysis and kidney transplant patients are vulnerable populations for COVID-19 related disease and mortality.

Methods: We conducted a prospective study exploring the eight week time course of specific cellular (interferon-γ release assay and flow cytometry) or/and humoral immune responses (ELISA) to SARS-CoV-2 boost vaccination in more than 3100 participants including medical personnel, dialysis patients and kidney transplant recipients using mRNA vaccines BNT162b2 or mRNA-1273.

Results: SARS-CoV-2-vaccination induced seroconversion efficacy in dialysis patients was similar to medical personnel (> 95%), but markedly impaired in kidney transplant recipients (42%).

Kidney transplant monitoring by urinary flow cytometry: Biomarker combination of T cells, renal tubular epithelial cells, and podocalyxin-positive cells detects rejection.

Creatinine and proteinuria are used to monitor kidney transplant patients. However, renal biopsies are needed to diagnose renal graft rejection. Here, we assessed whether the quantification of different urinary cells would allow non-invasive detection of rejection.

Vasopressin Increases Urinary Acidification V1a Receptors in Collecting Duct Intercalated Cells.

Background: Antagonists of the V1a vasopressin receptor (V1aR) are emerging as a strategy for slowing progression of CKD. Physiologically, V1aR signaling has been linked with acid-base homeostasis, but more detailed information is needed about renal V1aR distribution and function.

Methods: We used a new anti-V1aR antibody and high-resolution microscopy to investigate Va1R distribution in rodent and human kidneys.

The pathological features of regulated necrosis.

Necrosis of a cell is defined by the loss of its plasma membrane integrity. Morphologically, necrosis occurs in several forms such as coagulative necrosis, colliquative necrosis, caseating necrosis, fibrinoid necrosis, and others. Biochemically, necrosis was demonstrated to represent a number of genetically determined signalling pathways.

NFAT5 regulates renal gene expression in response to angiotensin II through Annexin-A2-mediated posttranscriptional regulation in hypertensive rats.

The aim was to identify new targets that regulate gene expression at the posttranscriptional level in angiotensin II (ANGII)-mediated hypertension. Heparin affinity chromatography was used to enrich nucleic acid-binding proteins from kidneys of two-kidney, one-clip (2K1C) hypertensive Wistar rats. The experiment was repeated with 14-day ANGII infusion using Alzet osmotic mini pumps, with or without ANGII receptor AT1a inhibition using losartan in the drinking water.

Con: Tolvaptan for autosomal dominant polycystic kidney disease-do we know all the answers?

According to recent literature, tolvaptan ameliorates the natural decline of renal function in autosomal dominant polycystic kidney disease. Tolvaptan is an orally available vasopressin V2 receptor antagonist. We describe herein the remaining questions and problems: it is unclear from the published work what influence tolvaptan has on total kidney volume.

AVP dynamically increases paracellular Na permeability and transcellular NaCl transport in the medullary thick ascending limb of Henle's loop.

The medullary thick ascending limb of Henle's loop (mTAL) is crucial for urine-concentrating ability of the kidney. It is water tight and able to dilute the luminal fluid by active transcellular NaCl transport, fueling the counter current mechanism by increasing interstitial osmolality. While chloride is exclusively transported transcellularly, approx.

Vasopressin lowers renal epoxyeicosatrienoic acid levels by activating soluble epoxide hydrolase.

Activation of the thick ascending limb (TAL) Na-K-2Cl cotransporter (NKCC2) by the antidiuretic hormone arginine vasopressin (AVP) is an essential mechanism of renal urine concentration and contributes to extracellular fluid and electrolyte homeostasis. AVP effects in the kidney are modulated by locally and/or by systemically produced epoxyeicosatrienoic acid derivates (EET). The relation between AVP and EET metabolism has not been determined.

Demonstration of the functional impact of vasopressin signaling in the thick ascending limb by a targeted transgenic rat approach.

The antidiuretic hormone vasopressin (AVP) regulates renal salt and water reabsorption along the distal nephron and collecting duct system. These effects are mediated by vasopressin 2 receptors (V2R) and release of intracellular Gs-mediated cAMP to activate epithelial transport proteins. Inactivating mutations in the V2R gene lead to the X-linked form of nephrogenic diabetes insipidus (NDI), which has chiefly been related with impaired aquaporin 2-mediated water reabsorption in the collecting ducts.

Advances in pharmacotherapy to treat kidney transplant rejection.

Introduction: Current immunosuppressive combination therapy provides excellent prevention of T-cell-mediated rejection following renal transplantation; however, antibody-mediated rejection remains of high concern and accounts for a large number of long-term allograft losses. The recent development of protocol biopsies resulted in the definition of subclinical rejection (SCR), showing histologic evidence for rejection but unremarkable clinical course.

Areas Covered: This review describes the current knowledge and evidence of pharmacotherapy to treat kidney allograft rejections and covers SCR treatment options.

Sex-dependent hypertension and renal changes in aged rats with altered renal development.

Numerous studies have evaluated blood pressure (BP) and renal changes in several models of developmental programming of hypertension. The present study examined to what extent BP, renal hemodynamic, and renal structure are affected at an old age in male and female animals with altered renal development. It also evaluated whether renal damage is associated with changes in cyclooxygenase (COX)-2 and neuronal nitric oxide synthase (NOS1) expression and immunoreactivity.