Opportunities in Primary and Enteric Hyperoxaluria at the Cross-Roads Between the Clinic and Laboratory.

Hyperoxaluria is a condition in which there is a pathologic abundance of oxalate in the urine through either hepatic overproduction (primary hyperoxaluria [PH]) or excessive enteric absorption of dietary oxalate (enteric hyperoxaluria [EH]). Severity can vary with the most severe forms causing kidney failure and extrarenal manifestations. To address the current challenges and innovations in hyperoxaluria, the 14th International Hyperoxaluria Workshop convened in Perugia, Italy, bringing together international experts for focused presentation and discussion.

Correction: Stämmler et al. Estimating Glomerular Filtration Rate from Serum Myo-Inositol, Valine, Creatinine and Cystatin C. 2021, , 2291.

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Adjudication of Self-reported Symptomatic Stone Recurrence in the Prevention of Urinary Stones With Hydration Trial.

Objective: To assess accuracy of self-reported stone events in a large clinical trial by adjudication against the weight of documentation for spontaneous stone passage or surgical intervention.

Methods: Participants in the Prevention of Urinary Stones with Hydration (PUSH) trial were randomized to a multi-component behavioral intervention or control arm to increase and maintain high fluid intake. The primary endpoint was urinary stone events including symptomatic stone passage or procedural intervention.

Association between Kidney Stones and CKD: A Bidirectional Mendelian Randomization Study.

Key Points: Common kidney stones are unlikely to be an independent and direct cause of CKD in the general population. CKD may protect against kidney stones because of changes in key urinary factors critical for stone formation.

Background: Kidney stones and CKD are common disorders with a substantial interaction.

The Evolving Role of Genetic Testing in Monogenic Kidney Stone Disease: Spotlight on Primary Hyperoxaluria.

Purpose: Multiple factors are thought to give rise to common, recurrent kidney stone disease, but for monogenic stone disorders a firm diagnosis is possible through genetic testing. The autosomal recessive primary hyperoxalurias (PH) are rare forms of monogenic kidney stone disease. All 3 types of PH are caused by inborn errors of glyoxylate metabolism in the liver, leading to hepatic oxalate overproduction and excessive renal urinary oxalate excretion.

Efficacy and Safety of Lumasiran in Patients With Primary Hyperoxaluria Type 1: Results from a Phase III Clinical Trial.

Introduction: Patients with primary hyperoxaluria type 1 (PH1), a genetic disorder associated with hepatic oxalate overproduction, frequently experience recurrent kidney stones and worsening kidney function. Lumasiran is indicated for the treatment of PH1 to lower urinary and plasma oxalate (POx).

Methods: ILLUMINATE-A (NCT03681184) is a phase III trial in patients aged ≥6 years with PH1 and estimated glomerular filtration rate (eGFR) ≥30 ml/min per 1.

Multiomics Assessment of the Gut Microbiome in Rare Hyperoxaluric Conditions.

Introduction: Hyperoxaluria is a risk factor for kidney stone formation and chronic kidney disease progression. The microbiome is an important protective factor against oxalate accumulation through the activity of its oxalate-degrading enzymes (ODEs). In this cross-sectional study, we leverage multiomics to characterize the microbial community of participants with primary and enteric hyperoxaluria, as well as idiopathic calcium oxalate kidney stone (CKS) formers, focusing on the relationship between oxalate degrading functions of the microbiome.

The role of biomarkers in early identification of acute kidney injury among non-critically ill patients.

Background: Prediction and/or early identification of acute kidney injury (AKI) and individuals at greater risk remains of great interest in clinical medicine. Acute kidney injury continues to be a common complication among hospitalized patients, with an incidence ranging from 6 to 58%, depending on the setting. Aim of this study was to determine the performance of Insulin-like growth factor binding protein-7 (IGFBP7), tissue metallopeptidase inhibitor 2 (TIMP2), and urinary neutrophil gelatinase-associated lipocalin (uNGAL) in early detection of AKI among non-critically ill patients.

American Board of Internal Medicine Nephrology Procedure Requirements for Initial Certification: Time for a Change and Pursuing Consensus in the Nephrology Community.

In 1988, the American Board of Internal Medicine (ABIM) defined essential procedural skills in nephrology, and candidates for ABIM certification were required to present evidence of possessing the skills necessary for placement of temporary dialysis vascular access, hemodialysis, peritoneal dialysis, and percutaneous renal biopsy. In 1996, continuous renal replacement therapy was added to the list of nephrology requirements. These procedure requirements have not been modified since 1996 while the practice of nephrology has changed dramatically.

Clinicopathologic Characteristics, Etiologies, and Outcome of Secondary Oxalate Nephropathy.

Objective: To report the clinicopathologic characteristics, prognostic indicators, prognosis, and transplant outcome of secondary oxalate nephropathy (ON).

Patients And Methods: We performed a retrospective analysis of 113 consecutive patients with secondary ON diagnosed at Mayo Clinic in Rochester, Minnesota, between January 1, 2001, and March 1, 2023.

Results: The incidence of secondary ON among all native biopsies from Mayo Clinic patients over the study period (n=11,617) was 0.

Assessing GFR With Proenkephalin.

Introduction: In clinical practice, kidney (dys)function is monitored through creatinine-based estimations of glomerular filtration rate (eGFR: Modification of Diet in Renal Disease [MDRD], Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]). Creatinine is recognized as a late and insensitive biomarker of glomerular filtration rate (GFR). The novel biomarker proenkephalin (PENK) may overcome these limitations, but no PENK-based equation for eGFR is currently available.

Mayo Clinic Consensus Report on Membranous Nephropathy: Proposal for a Novel Classification.

Membranous nephropathy (MN) is a pattern of injury caused by autoantibodies binding to specific target antigens, with accumulation of immune complexes along the subepithelial region of glomerular basement membranes. The past 20 years have brought revolutionary advances in the understanding of MN, particularly via the discovery of novel target antigens and their respective autoantibodies. These discoveries have challenged the traditional classification of MN into primary and secondary forms.

Mayo Clinic consensus report on membranous nephropathy: proposal for a novel classification.

Membranous nephropathy (MN) is a pattern of injury caused by autoantibodies binding to specific target antigens, with accumulation of immune complexes along the subepithelial region of glomerular basement membranes. The past 20 years have brought revolutionary advances in the understanding of MN, particularly via the discovery of novel target antigens and their respective autoantibodies. These discoveries have challenged the traditional classification of MN into primary and secondary forms.

Natural history of urine and plasma oxalate in children with primary hyperoxaluria type 1.

Background: Primary hyperoxaluria type 1 (PH1) is a rare, severe genetic disease causing increased hepatic oxalate production resulting in urinary stone disease, nephrocalcinosis, and often progressive chronic kidney disease. Little is known about the natural history of urine and plasma oxalate values over time in children with PH1.

Methods: For this retrospective observational study, we analyzed data from genetically confirmed PH1 patients enrolled in the Rare Kidney Stone Consortium PH Registry between 2003 and 2018 who had at least 2 measurements before age 18 years of urine oxalate-to-creatinine ratio (Uox:cr), 24-h urine oxalate excretion normalized to body surface area (24-h Uox), or plasma oxalate concentration (Pox).

Performance of Nuclear Magnetic Resonance-Based Estimated Glomerular Filtration Rate in a Real-World Setting.

An accurate estimate of glomerular filtration rate (eGFR) is essential for proper clinical management, especially in patients with kidney dysfunction. This prospective observational study evaluated the real-world performance of the nuclear magnetic resonance (NMR)-based GFR equation, which combines creatinine, cystatin C, valine, and myo-inositol with age and sex. We compared GFR performance to that of the 2021 CKD-EPI creatinine and creatinine-cystatin C equations (CKD-EPI and CKD-EPI), using 115 fresh routine samples of patients scheduled for urinary iothalamate clearance measurement (mGFR).

End Point Considerations for Clinical Trials in Enteric Hyperoxaluria.

Enteric hyperoxaluria is a medical condition characterized by elevated urinary oxalate excretion due to increased gastrointestinal oxalate absorption. Causative features include fat malabsorption and/or increased intestinal permeability to oxalate. Enteric hyperoxaluria has long been known to cause nephrolithiasis and nephrocalcinosis, and, more recently, an association with CKD and kidney failure has been shown.

The Site and Type of Genetic Variation Impact the Resulting Dent Disease-1 Phenotype.

Introduction: Dent disease is an X-linked recessive disorder associated with low molecular weight proteinuria (LMWP), nephrocalcinosis, kidney stones, and kidney failure in the third to fifth decade of life. It consists of Dent disease 1 (DD1) (60% of patients) because of pathogenic variants in the gene and Dent disease 2 (DD2) with changes in .

Methods: Retrospective review of 162 patients from 121 different families with genetically confirmed DD1 (82 different pathogenic variants validated using American College of Medical Genetics [ACMG] guidelines).

Estimating glomerular filtration rate with new equations: can one size ever fit all?

Glomerular filtration rate (GFR) is thought to be the best overall indicator of kidney health. On an individual patient basis, a working knowledge of GFR is important to understand the future risk for chronic kidney disease (CKD) progression, enhanced risk for cardiovascular disease and death, and for optimal medical management including the dosing of certain drugs. Although GFR can be directly measured using exogenous compounds that are eliminated by the kidney, these methods are not scalable for repeated and routine use in clinical care.