Kidney International Reports
ISSN / EISSN : 2468-0249 / 2468-0249
Current Publisher: Elsevier BV (10.1016)
Total articles ≅ 4,275
Latest articles in this journal
Kidney International Reports, Volume 6, pp 1368-1378; doi:10.1016/j.ekir.2021.01.023
Introduction Disease causing mutations in the protocadherin FAT1 have been recently described both in patients with a gomerulotubular nephropathy and in patients with a syndromic nephropathy. Methods We identified four patients with FAT1 associated disease, performed clinical and genetic characterization and compared our findings to the previously published patients. Patient-derived primary urinary epithelial cells were analyzed by qPCR and immuno-blotting to identify possible alterations in Hippo signaling. Results Here we expand the spectrum of FAT1-associated disease with the identification of novel FAT1 mutations in four patients from three different families (homozygous truncating variants in three, compound heterozygous missense variants in one patient). All patients show an ophthalmological phenotype together with heterogeneous renal phenotypes ranging from normal renal function to early onset end-stage kidney failure. Molecular analysis of primary urine-derived urinary renal epithelial cells revealed alterations in the Hippo signaling cascade with a decreased phosphorylation of both the core kinase MST and the downstream effector YAP. Consistently, we found a transcriptional upregulation of bona fide YAP target genes. Conclusion A comprehensive review of the here identified patients and those previously published indicates a highly diverse phenotype in patients with missense mutations but a more uniform and better recognizable phenotype in the patients with truncating mutations. Altered Hippo signaling and de-repressed YAP activity might be novel contributing factors to the pathomechanism in FAT1-associated renal disease.
Kidney International Reports, Volume 6; doi:10.1016/j.ekir.2021.03.881
We read the article “Prognostic Value of FGF23 in Autosomal Dominant Polycystic Kidney Disease” by EI Ters and colleagues with great interest.1El Ters M. et al.Prognostic Value of FGF23 in Autosomal Dominant Polycystic Kidney Disease.Kidney Int. Reports. 2021; https://doi.org/10.1016/j.ekir.2021.01.004Abstract Full Text Full Text PDF Scopus (0) Google Scholar EI Ters et al. provided an important demonstration that serum FGF23 was a prognostic biomarker for kidney volume and renal outcomes or death in patients with early ADPKD. However, early elevation of FGF23 in ADPKD is complicated and remains inconclusive. FGF23 is secreted primarily by the bone followed by the thymus, heart, and other tissues in low levels. However, experimental studies in PKD rodents revealed high FGF23 expression in the cyst-lining epithelium of kidneys but not in bone.1El Ters M. et al.Prognostic Value of FGF23 in Autosomal Dominant Polycystic Kidney Disease.Kidney Int. Reports. 2021; https://doi.org/10.1016/j.ekir.2021.01.004Abstract Full Text Full Text PDF Scopus (0) Google Scholar As kidney FGF23 does not contribute to the elevation of its circulating levels in uremia2Mace M.L. et al.Kidney fibroblast growth factor 23 does not contribute to elevation of its circulating levels in uremia.Kidney Int. 2017; 92: 165-178Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar, there may be other sources of high FGF23 in early ADPKD. Because ADPKD is a systemic disease, we assume that PKD mutations in different organs and tissues may produce FGF23 and lead to serum FGF23 elevation in humans. Indeed, severely polycystic livers were proved to produce and increase circulating FGF23 in ADPKD patients.3Bienaimé F. et al.Hepatic Production of Fibroblast Growth Factor 23 in Autosomal Dominant Polycystic Kidney Disease.J. Clin. Endocrinol. Metab. 2018; 103: 2319-2328Crossref PubMed Scopus (5) Google Scholar Overall, this study was very important, for it not only filled up the gap that was not proven by HALT-PKD Study which only supported FGF23 use in late ADPKD4Chonchol M. et al.Fibroblast Growth Factor 23 and Kidney Disease Progression in Autosomal Dominant Polycystic Kidney Disease.Clin. J. Am. Soc. Nephrol. 2017; 12: 1461-1469Crossref PubMed Scopus (8) Google Scholar, but also showed predictive roles of FGF23 in ADPKD progression independent of CKD. More mechanisms about FGF23 elevation in ADPKD will need to be studied.
Kidney International Reports, Volume 6, pp 1205-1207; doi:10.1016/j.ekir.2021.03.890
Facebook’s corporate mission is, “to give people the power to build community and bring the world closer together. People use Facebook to stay connected with friends and family, to discover what's going on in the world, and to share and express what matters to them.”1 Facebook groups are communities within the Facebook network that have shared interests. While most of Facebook is about seeing what people you know in the real world are doing and thinking, Facebook Groups is about interacting with people that have similar interests. These groups are user -created and administered. The discussions and postings are driven by participant interest. Groups can be open, closed, or secret. Open groups are available by searching and anyone can join, whereas closed groups are visible by search but potential members must obtain permission from an administrator of the group. Secret groups are invisible and people can only join after being invited by a group administrator.
Kidney International Reports, Volume 6, pp 1203-1204; doi:10.1016/j.ekir.2021.03.895
The immediate consequences of acute, severe hyperkalemia are well recognized in medicine. High extracellular potassium levels result in decreased cardiac membrane potential resulting in fatal arrhythmias, including ventricular fibrillation, asystole and cardiac arrest. Chronic kidney disease, diabetes mellitus, heart failure and their associated medications that interfere with the renin-angiotensin-aldosterone system (RAAS), predispose patients to hyperkalemia and associated acute adverse outcomes. While the association between severe hyperkalemia and increased mortality is well established, the clinical significance of mild hyperkalemia remain poorly described1Collins A. Pitt B. Reaven N. et al.Association of Serum Potassium with All-Cause Mortality in Patients with and without Heart Failure, Chronic Kidney Disease, and/or Diabetes.Am J Nephrol. 2017; 46: 213-221Crossref PubMed Scopus (109) Google Scholar. Part of the challenge has been the confounding that results from the presence of comorbidities that confer worse outcomes, as well as the adverse consequences associated with the initiation of potassium lowering treatments such as sodium polystyrene sulfonate or the discontinuation of RAASi medications.
Kidney International Reports, Volume 6, pp 1355-1367; doi:10.1016/j.ekir.2021.01.012
Introduction Albuminuric and nonalbuminuric pathways contribute to diabetic kidney disease. Proximal tubule and inflammation play important roles in these processes. Urinary biomarker(s) to detect early kidney damage and predict progression are needed. Methods Nine urinary biomarkers were measured at baseline in 400 patients with diabetes. Correlation and multivariate logistic and linear regression analyses were performed to assess the association of biomarkers with chronic kidney disease and progression. Results In the albumin/creatinine ratio (ACR) <3 cohort, the only biomarker significantly associated with estimated glomerular filtration rate < 60 ml/min was N-acetyl-β-d-glucosaminidase. A combination of ACR and monocyte chemotactic protein 1 (MCP1) were significantly associated with stage 2 chronic kidney disease in this cohort. Logistic models showed that in patients with all levels of albuminuria, ACR, retinol binding protein (RBP), and MCP1 were associated with progression. A model including MCP1, interleukin 6, and neutrophil gelatinase-associated lipocalin showed significant association with progression to chronic kidney disease 3/4 in the ACR <3 cohort. Linear mixed-model regression analyses demonstrated MCP1, RBP, and ACR as significant proteins associated with progression to stage 3 or worse, whereas MCP1 was the only significant biomarker in the ACR <3 cohort. Time-to-event and Cox proportional hazard models confirmed significant hazard ratios for progression for ACR, RBP, and MCP1, with significant differences noted between quantiles of biomarkers for ACR, RBP, and MCP1. Conclusion In this study of diabetic patients with single baseline measurements of urinary biomarkers, albumin, RBP, and MCP1 were significantly associated with chronic kidney disease progression at all levels of albuminuria. Inflammatory cytokines, neutrophil gelatinase-associated lipocalin, and MCP1 were associated with progression in patients without albuminuria. N-acetyl-β-d-glucosaminidase demonstrated a significant association with an estimated glomerular filtration rate < 60 ml/min in the ACR <3 cohort.
Kidney International Reports, Volume 6, pp 1211-1224; doi:10.1016/j.ekir.2021.02.003
We discuss the use urine electrolytes and osmolality in the clinical diagnosis in patients with fluid, electrolytes and acid-base disorders, emphasizing their physiological basis, their utility and the caveats and limitations in their use. While our focus is on information obtained from measurements in the urine, clinical diagnosis in these patients must integrate information obtained from the history, the physical examination and other laboratory data.
Kidney International Reports, Volume 6, pp 1437-1443; doi:10.1016/j.ekir.2021.02.004
The prevalence of chronic kidney disease (CKD) has increased by 29·3% and the all-age mortality rate from CKD has increased by 41·5% since 1990 worldwide.1Global regional , and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.Lancet. 2020; 395: 709-733Abstract Full Text Full Text PDF Scopus (187) Google Scholar The overwhelming fatigue, complex treatment regimens and diet restrictions constraining CKD patients' lives increase their psychological distress,2Tong A. Sainsbury P. Chadban S. et al.Patients' experiences and perspectives of living with CKD.Am J Kidney Dis. 2009; 53: 689-700Abstract Full Text Full Text PDF PubMed Scopus (111) Google Scholar which can induce hyperactivity of the hypothalamus – pituitary – adrenal axis, the commonest neurobiological change observed in depressive patients.3Yang L. Zhao Y. Wang Y. et al.The Effects of Psychological Stress on Depression.Curr Neuropharmacol. 2015; 13: 494-504Crossref PubMed Scopus (4) Google Scholar The lifetime prevalence of depression is 10.8% in the general population4Lim G.Y. Tam et al.Prevalence of Depression in the Community from 30 Countries between 1994 and 2014.Sci Rep. 2018; 8: 2861Crossref PubMed Scopus (211) Google Scholar whereas in CKD stage VD patients, it is 22.8% based on interview method and 39.3% based on self- or clinician-administered rating scales, as per a meta-analysis in 2013.5Palmer S. Vecchio M. Craig J.C. et al.Prevalence of depression in chronic kidney disease: systematic review and meta-analysis of observational studies.Kidney Int. 2013; 84: 179-191Abstract Full Text Full Text PDF PubMed Scopus (293) Google Scholar
Kidney International Reports, Volume 6, pp 1346-1354; doi:10.1016/j.ekir.2021.02.005
Introduction Recently, nephronophthisis (NPH) has been considered a monogenic cause of end-stage renal disease (ESRD) in adults. However, adult-onset NPH is difficult to accurately diagnose and has not been reported in a cohort study. In this study, we assessed the genetic background and clinicopathologic features of adult NPH. Methods We investigated 18 sporadic adult patients who were suspected as having NPH by renal biopsy. We analyzed 69 genes that cause hereditary cystic kidney disease and compared clinicopathologic findings between patients with and without pathogenic mutations in NPH-causing genes. Results Seven of 18 patients had pathogenic NPH-causing mutations in NPHP1, NPHP3, NPHP4, or CEP164. Compared with patients without pathogenic mutations, those with pathogenic mutations were significantly younger but did not significantly differ in the classic NPH pathologic findings, such as tubular cysts. On the other hand, the number of tubules with thick tubular basement membrane (TBM) duplication, which was defined as >10-μm thickness, was significantly higher in patients with genetically proven adult NPH than in those without pathogenic mutations. α-Smooth muscle actin (α-SMA)-positive myofibroblasts were detected inside thick TBM duplication. Conclusions In adult patients with NPH, thick TBM duplication was the specific finding. Our analysis also suggested that older patients tended to have no pathogenic mutations, even when they were suspected to have NPH by renal biopsy. These findings could be the novel clinical clue for the diagnosis of NPH in adult patients.
Kidney International Reports, Volume 6, pp 1411-1415; doi:10.1016/j.ekir.2021.02.007
Kidney International Reports, Volume 6, pp 1280-1288; doi:10.1016/j.ekir.2021.02.010
Introduction Impaired physical fitness is prevalent in people with chronic kidney disease (CKD), associating with an increased risk of mortality, falls and hospitalization. A plethora of physical fitness outcomes have been reported in randomized trials. This study aimed to assess the scope and consistency of physical fitness outcomes and outcome measures reported in trials in CKD. Methods A systematic review of randomized trials reporting physical fitness outcomes in adults with CKD (not requiring kidney replacement therapy), receiving hemodialysis or peritoneal dialysis, and kidney transplant recipients was conducted. Studies were identified from MEDLINE, Embase and the Cochrane Library from 2000 to 2019. The scope, frequency and characteristics of outcome measures were categorized and analyzed. Results From 111 trials, 87 tests/measurements were used to evaluate 30 outcomes measures that reported on 23 outcomes, categorized into five domains of physical fitness: neuromuscular fitness (reported in 76% of trials), exercise capacity (64%), physiological-metabolic (49%), body composition (36%) and cardiorespiratory fitness (30%). Neuromuscular fitness was examined by 37 tests/measurements including the physical function component of questionnaires (27%), 1-repetition maximum (9%) and hand-grip strength (9%). Outcome measures were assessed by lab-based (58% of all trials), field-based (31%) and patient-reported measures (11%), and commonly evaluated at 12 (30%), 26 (23%) and 52 weeks (10%). Conclusions There is large heterogeneity in the reporting of physical fitness outcomes, with inconsistencies particularly in the definitions of outcome measures. Standardization in the assessment of physical fitness will likely improve the comparability of trial outcomes and enhance clinical recommendations.