Nephrectomy in Autosomal Dominant Polycystic Kidney Disease: A consensus statement of the ERA Genes & Kidney Working Group.

A substantial number of patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD) undergo a nephrectomy, especially in work-up for a kidney transplantation. Currently, there is no evidence-based algorithm to guide clinicians which patients should undergo nephrectomy, the optimal timing of this procedure, or the preferred surgical technique. This systematic review-based consensus statement aimed to answer important questions regarding nephrectomy in ADPKD.

Increased expression of SCARF genes favoring SARS-CoV-2 infection in key target organs in CKD.

Background: Chronic kidney disease (CKD), especially diabetic CKD, is the condition that most increases the risk of lethal coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the underlying molecular mechanisms are unclear. SARS-CoV-2 and coronavirus-associated receptors and factors (SCARFs) regulate coronavirus cell entry and/or replication.

Sodium zirconium cyclosilicate and metabolic acidosis: Potential mechanisms and clinical consequences.

Metabolic acidosis is frequent in chronic kidney disease (CKD) and is associated with accelerated progression of CKD, hypercatabolism, bone disease, hyperkalemia, and mortality. Clinical guidelines recommend a target serum bicarbonate ≥ 22 mmol/L, but metabolic acidosis frequently remains undiagnosed and untreated. Sodium zirconium cyclosilicate (SZC) binds potassium in the gut and is approved to treat hyperkalemia.

The association of urinary epidermal growth factors with ADPKD disease severity and progression.

Background: The epidermal growth factor receptor (EGFR) pathway is involved in kidney tissue repair and growth. Preclinical interventional data and scarce human data have suggested a role for this pathway in the pathophysiology of autosomal dominant polycystic kidney disease (ADPKD), while other data have suggested that its activation is causally linked to repair of damaged kidney tissue. We hypothesize that urinary EGFR ligands, as a reflection of EGFR activity, are associated with kidney function decline in ADPKD in the context of tissue repair following injury, and as the disease progresses as a sign of insufficient repair.

Consensus document on autosomal dominant polycystic kindey disease from the Spanish Working Group on Inherited Kindey Diseases. Review 2020.

Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent cause of genetic renal disease and accounts for 6-10% of patients on kidney replacement therapy (KRT). Very few prospective, randomized trials or clinical studies address the diagnosis and management of this relatively frequent disorder. No clinical guidelines are available to date.

Who killed Bruce Lee? The hyponatraemia hypothesis.

Bruce Lee brought attention to martial arts in the Western world and popularized the quote 'Be water, my friend'. Lee died at the age of 32 years in Hong Kong on 20 July 1973, under mysterious circumstances. The cause of death is unknown, although numerous hypotheses have been proposed, from assassination by gangsters to the more recent suggestion in 2018 that he died from heatstroke.

Gain-of-function and loss-of-function gene variants identify a novel pathway for Mendelian lupus and lupus nephritis.

Systemic lupus erythematosus (SLE) is a chronic and inflammatory autoimmune disease of unknown origin that may cause kidney disease, i.e. lupus nephritis (LN).

The mysterious death of the beer drinking champ: potential role for hyperacute water loading and acute hyponatremia.

Hyponatremia is acute when present for <48 h. Most cases of acute hyponatremia involve both excess free water intake and an at least partial urinary free water excretion defect. By contrast, hyperacute water intoxication may result from a large excess electrolyte-free water intake in such a short time that properly working urinary free water excretion mechanisms cannot cope.

Growth differentiation factor-15 preserves Klotho expression in acute kidney injury and kidney fibrosis.

Growth differentiation factor-15 (GDF15) is a member of the GDF subfamily with potential kidney protective functions. Here, we explored the impact of GDF15 on the expression of the kidney protective factor Klotho in models of acute kidney injury and kidney fibrosis in mice. GDF15 was the most upregulated GDF family gene in experimental toxic acute kidney injury and in kidney fibrosis transcriptomics.

Autosomal dominant polycystic kidney disease: possibly the least silent cause of chronic kidney disease.

Pain is the highest prioritized patient-reported outcome in people with autosomal dominant polycystic kidney disease (ADPKD) but it remains infrequently and inconsistently measured across countries, studies and trials. The study by El-Damanawi integrated a network of ADPKD expert clinicians, pain specialists, researchers and patient representatives from the national UK PKD charity, with the aim of addressing the lack of validated ADPKD-specific pain assessment tools (APATs). The APAT designed by the authors included several pain measurement tools and was tested in ADPKD patients, although further validation through assessment in larger cohorts is needed.

Milestones of Precision Medicine: An Innovative, Multidisciplinary Overview.

Although the concept of precision medicine, in which healthcare is tailored to the molecular and clinical characteristics of each individual, is not new, its implementation in clinical practice has been heterogenous. In some medical specialties, precision medicine has gone from being just a promise to a reality that achieves better patient outcomes. This is a fact if we consider, for example, the great advances made in the genetic diagnosis and subsequent treatment of countless hereditary diseases, such as cystic fibrosis, which have improved the life expectancy of many of the affected children.

TWEAK Signaling Pathway Blockade Slows Cyst Growth and Disease Progression in Autosomal Dominant Polycystic Kidney Disease.

Background: In autosomal dominant polycystic kidney disease (ADPKD), cyst development and enlargement lead to ESKD. Macrophage recruitment and interstitial inflammation promote cyst growth. TWEAK is a TNF superfamily (TNFSF) cytokine that regulates inflammatory responses, cell proliferation, and cell death, and its receptor Fn14 (TNFRSF12a) is expressed in macrophage and nephron epithelia.

Phosphate, Microbiota and CKD.

Phosphate is a key uremic toxin associated with adverse outcomes. As chronic kidney disease (CKD) progresses, the kidney capacity to excrete excess dietary phosphate decreases, triggering compensatory endocrine responses that drive CKD-mineral and bone disorder (CKD-MBD). Eventually, hyperphosphatemia develops, and low phosphate diet and phosphate binders are prescribed.

Urinary Growth Differentiation Factor-15 (GDF15) levels as a biomarker of adverse outcomes and biopsy findings in chronic kidney disease.

Background: Growth Differentiation Factor-15 (GDF15) is a member of the TGF-β superfamily. Increased serum GDF15 has been associated with increased risk of chronic kidney disease (CKD) progression. However, no prior studies have addressed the significance of urinary GDF15 in adult CKD.

The dirty little secret of urate-lowering therapy: useless to stop chronic kidney disease progression and may increase mortality.

Hyperuricaemia is frequent in chronic kidney disease (CKD). Observational studies have shown an association with adverse outcomes and acquired hyperuricaemia (meaning serum urate levels as low as 1.0 mg/dL) in animal models induces kidney injury.

Urine proteomics for prediction of disease progression in patients with IgA nephropathy.

Background: Risk of kidney function decline in immunoglobulin A (IgA) nephropathy (IgAN) is significant and may not be predicted by available clinical and histological tools. To serve this unmet need, we aimed at developing a urinary biomarker-based algorithm that predicts rapid disease progression in IgAN, thus enabling a personalized risk stratification.

Methods: In this multicentre study, urine samples were collected in 209 patients with biopsy-proven IgAN.

Pelacarsen for lowering lipoprotein(a): implications for patients with chronic kidney disease.

Chronic kidney disease (CKD) patients are at an increased risk of cardiovascular disease (CVD) and statins may not be protective in advanced CKD. The reasons for the limited efficacy of statins in advanced CKD are unclear, but statins may increase plasma levels of the highly atherogenic molecule lipoprotein(a), also termed Lp(a), as well as PCSK9 (protein convertase subtilisin/kexin type 9) levels. Lp(a) has also been linked to calcific aortic stenosis, which is common in CKD.

Megalin/lipoprotein receptor-related protein 2 autoimmunity and kidney disease.

In this issue of , Gamayo describe two cases of anti-low-density lipoprotein receptor-related protein 2 (LRP2) nephropathy. This is a recently described entity that has features of both tubulointerstitial disease and segmental membranous nephropathy. The originality of the present report consists of the association of a disease thought to be rare (only 13 in prior described patients, 11 in the past year) with B-cell lymphoproliferative disease.

Evaluation of the optical and biomechanical properties of bioengineered human skin generated with fibrin-agarose biomaterials.

Significance: Recent generation of bioengineered human skin allowed the efficient treatment of patients with severe skin defects. However, the optical and biomechanical properties of these models are not known.

Aim: Three models of bioengineered human skin based on fibrin-agarose biomaterials (acellular, dermal skin substitutes, and complete dermoepidermal skin substitutes) were generated and analyzed.

Aliskiren and the dual complement inhibition concept.

In this issue of , Plasse . report on the use of high-dose aliskiren as an adjunct therapy in a patient treated with eculizumab for haemolytic uraemic syndrome (HUS). This follows the recent description of the complement factor 3 (C3) activating activity of the enzyme renin and the successful therapeutic use of the direct renin inhibitor aliskiren in three cases of C3 glomerulopathy/dense deposit disease.

Design and optimization strategies for the development of new drugs that treat chronic kidney disease.

: Chronic kidney disease (CKD) is characterized by increased risks of progression to end-stage kidney disease requiring dialysis and cardiovascular mortality, predicted to be among the five top causes of death by 2040. Only the design and optimization of novel strategies to develop new drugs to treat CKD will contain this trend. Current therapy for CKD includes nonspecific therapy targeting proteinuria and/or hypertension and cause-specific therapies for diabetic kidney disease, autosomal dominant polycystic kidney disease, glomerulonephritides, Fabry nephropathy, hemolytic uremic syndrome and others.

MYH9-related disease: it does exist, may be more frequent than you think and requires specific therapy.

In this issue of , Tabibzadeh report one of the largest series of patients with mutations and kidney disease. The cardinal manifestation of MYH9-related disease is thrombocytopenia with giant platelets. The population frequency of pathogenic mutations may be at least 1 in 20 000.