The Kynurenine Pathway in Acute Kidney Injury and Chronic Kidney Disease

Wee H.N.a · Liu J.-J.b · Ching J.a,c · Kovalik J.-P.a · Lim S.C.b,d,e

doi : 10.1159/000519811

Am J Nephrol 2021;52:771–787

The kynurenine pathway (KP) is the major catabolic pathway for tryptophan degradation. The KP plays an important role as the sole de novo nicotinamide adenine dinucleotide (NAD+) biosynthetic pathway in normal human physiology and functions as a counter-regulatory mechanism to mitigate immune responses during inflammation. Although the KP has been implicated in a variety of disorders including Huntington’s disease, seizures, cardiovascular disease, and osteoporosis, its role in renal diseases is seldom discussed.

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Focal Segmental Glomerulosclerosis Superimposed on Transplant Glomerulopathy: Implications for Graft Survival

Zhu Y.a · Fan Y.a · Xu F.b · Liang S.b · Liang D.b · Li P.b · Xia Y.b · Zhu X.b · Yang F.b · Chen J.b · Zeng C.a,b

doi : 10.1159/000519648

Am J Nephrol 2021;52:788–797

Transplant glomerulopathy (TG) is a morphological lesion resulting from chronic glomerular endothelium injury, and it is strongly associated with poor graft survival. TG coexisting with focal segmental glomerulosclerosis (FSGS) can be found in renal allograft biopsies, but few related studies are available.

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Real-World Assessment: Clinical Effectiveness and Safety of Extended-Release Calcifediol

Fadda G.a · Germain M.J.b · Broumand V.c · Nguyen A.d · McGarvey N.d · Gitlin M.d · Bishop C.W.e · Ashfaq A.e

doi : 10.1159/000518545

Am J Nephrol 2021;52:798–807

The safety and efficacy of extended-release calcifediol (ERC) as a treatment for secondary hyperparathyroidism (SHPT) in adults with stage 3 or 4 chronic kidney disease (CKD) and vitamin D insufficiency (VDI) has been demonstrated in prospective randomized clinical trials (RCTs). ERC (Rayaldee®) was approved by the Food and Drug Administration in 2016 on the basis of these prospective RCTs. The current retrospective study assessed the postlaunch data available with respect to ERC’s efficacy and safety in increasing serum 25-hydroxyvitamin D (25D) and reducing parathyroid hormone (PTH) in the indicated population

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FGFR4 and Klotho Polymorphisms Are Not Associated with Cardiovascular Outcomes in Chronic Kidney Disease

Sellier A.B.a · Seiler-Mußler S.a,b · Emrich I.E.c · Böhm M.c · Fliser D.a · Zawada A.M.a · Heine G.H.a,d

doi : 10.1159/000519274

Am J Nephrol 2021;52:808–816

High plasma fibroblast growth factor 23 (FGF-23) predicts cardiovascular events in chronic kidney disease (CKD) patients. Experimental evidence suggests FGF receptor 4 (FGFR4) activation by FGF-23, and deficiency of the soluble form of its co-receptor Klotho promotes left-ventricular hypertrophy (LVH). To evaluate the clinical relevance of these findings, a Mendelian randomization study analyzed the association of genetic variants of FGFR4 and Klotho with echocardiographic parameters and cardiac events in CKD patients.

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Incidence of Serum Creatinine Monitoring and Outpatient Visit Follow-Up among Acute Kidney Injury Survivors after Discharge: A Population-Based Cohort Study

Barreto E.F.a · Schreier D.J.a · May H.P.a · Mara K.C.b · Chamberlain A.M.c · Kashani K.B.d,e · Piche S.L.a · Wi C.-I.f · Kane-Gill S.L.g · Smith V.T.h · Rule A.D.c,d · For the ACT Study Group

doi : 10.1159/000519375

Am J Nephrol 2021;52:817–826

Acute kidney injury (AKI) affects 20% of hospitalized patients and worsens outcomes. To limit complications, post-discharge follow-up and kidney function testing are advised. The objective of this study was to evaluate the frequency of follow-up after discharge among AKI survivors.

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The Therapeutic Evaluation of Steroids in IgA Nephropathy Global (TESTING) Study: Trial Design and Baseline Characteristics

Wong M.G.a,b · Lv J.c,w · Hladunewich M.A.d · Jha V.e,f,g · Hooi L.S.h · Monaghan H.a · Zhao M.c · Barbour S.i · Reich H.N.j · Cattran D.j · Glassock R.k · Levin A.i · Jardine M.J.l · Wheeler D.C.m · Woodward M.a,f · Billot L.a · Chan T.M.n · Liu Z.-H.o · Johnson D.W.p · Cass A.a,q · Feehally J.r · Floege J.s · Remuzzi G.t · Wu Y.u · Agarwal R.v · Zhang H.c · Perkovic V.a · for the TESTING Study Group

doi : 10.1159/000519812

Am J Nephrol 2021;52:827–836

Despite optimal current care, up to 30% of individuals suffering from immunoglobulin A nephropathy (IgAN) will develop kidney failure requiring dialysis or kidney transplantation. The Therapeutic Evaluation of STeroids in IgA Nephropathy Global (TESTING) study was designed to assess the benefits and risks of steroids in people with IgAN. We report the trial design as well as the baseline characteristics of study participants.

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Mini Review: Reappraisal of Uric Acid in Chronic Kidney Disease

Goldberg A.a · Garcia-Arroyo F.b · Sasai F.c · Rodriguez-Iturbe B.b · Sanchez-Lozada L.G.b · Lanaspa M.A.c · Johnson R.J.c,d

doi : 10.1159/000519491

Am J Nephrol 2021;52:837–844

Hyperuricemia predicts the development of chronic kidney disease (CKD) and metabolic complications, but whether it has a causal role has been controversial. This is especially true given the 2 recently conducted randomized controlled trials that failed to show a benefit of lowering uric acid in type 1 diabetes-associated CKD and subjects with stage 3–4 CKD. While these studies suggest that use of urate-lowering drugs in unselected patients is unlikely to slow the progression of CKD, there are subsets of subjects with CKD where reducing uric acid synthesis may be beneficial. This may be the case in patients with gout, hyperuricemia (especially associated with increased production), and urate crystalluria. Here, we discuss the evidence and propose that future clinical trials targeting these specific subgroups should be performed.

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Guideline-Directed Medical Therapy in Patients with Chronic Kidney Disease Undergoing Peripheral Vascular Intervention

Jelani Q.-U.-A.a · Llanos-Chea F.a · Bogra P.b · Trejo-Paredes C.c · Huang J.d · Provance J.B.a · Turner J.e · Anantha-Narayanan M.f · Sheikh A.B.g · Smolderen K.G.a · Mena-Hurtado C.a

doi : 10.1159/000519484

Am J Nephrol 2021;52:845–853

Guideline-directed medical therapy (GDMT) is imperative to improve cardiovascular and limb outcomes for patients with critical limb ischemia (CLI), especially amongst those at highest risk for poor outcomes, including those with comorbid chronic kidney disease (CKD). Our objective was to examine GDMT prescription rates and their variation across individual sites for patients with CLI undergoing peripheral vascular interventions (PVIs), by their comorbid CKD status.

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Association between Preoperative Monocyte-to-Lymphocyte Ratio and Late Arteriovenous Fistula Dysfunction in Hemodialysis Patients: A Cohort Study

Hu S.a · Wang D.b · Ma T.a · Yuan F.a · Zhang Y.c · Gao X.a · Lei Q.a · Cheng J.a

doi : 10.1159/000519822

Am J Nephrol 2021;52:854–860

Inflammation appears to be at the biological core of arteriovenous fistula (AVF) dysfunction, and the occurrence of AVF dysfunction is related to high death and disability in hemodialysis (HD) patients. Despite several studies on the correlations between AVF dysfunction and inflammatory indicators, how AVF dysfunction is related to the monocyte-to-lymphocyte ratio (MLR) is much unclear. We hypothesize that preoperative MLR is associated with AVF dysfunction in Chinese HD patients. 

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A Scoping Review of Alternative Anticoagulation Strategies for Hemodialysis Patients with a Mechanical Heart Valve

Thomson B.K.A.a,b · Pilkey N.G.b · Monteith B.c · Holden R.M.b

doi : 10.1159/000519921

Am J Nephrol 2021;52:861–870

Patients with end-stage renal disease (ESRD) have high rates of cardiac valvulopathy but can develop contraindications for vitamin K antagonist (VKA) therapy. We explored the evidence for alternative anticoagulation strategies in patients with ESRD with a contraindication for VKA therapy.

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Efficacy and Safety of Molidustat for Anemia in ESA-Naive Nondialysis Patients: A Randomized, Phase 3 Trial

Yamamoto H.a · Nobori K.b · Matsuda Y.b · Hayashi Y.c · Hayasaki T.c · Akizawa T.d

doi : 10.1159/000518071

Am J Nephrol 2021;52:871–883

Molidustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that predominantly induces renal production of erythropoietin (EPO). Molidustat was evaluated for the treatment of anemia associated with chronic kidney disease (CKD) in the “Molidustat Once Daily Improves Renal Anemia by Inducing EPO” (MIYABI) program, which comprises 5 phase 3 clinical trials. The present MIYABI Non-Dialysis Correction (ND-C) study investigated the efficacy and safety of molidustat in Japanese patients with renal anemia who were not undergoing dialysis and were not receiving erythropoiesis-stimulating agent (ESA) treatment.

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Molidustat for Renal Anemia in Nondialysis Patients Previously Treated with Erythropoiesis-Stimulating Agents: A Randomized, Open-Label, Phase 3 Study

Yamamoto H.a · Nobori K.b · Matsuda Y.b · Hayashi Y.c · Hayasaki T.c · Akizawa T.d

doi : 10.1159/000518072

Am J Nephrol 2021;52:884–893

Erythropoiesis-stimulating agents (ESAs) are the current standard of care for anemia due to chronic kidney disease (CKD) in patients not undergoing dialysis. Molidustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, is being investigated as an alternative treatment for renal anemia. Molidustat was evaluated in five phase 3 studies, the molidustat once daily improves renal anemia by inducing erythropoietin (MIYABI) program. The present study investigated the safety and efficacy of molidustat in Japanese patients with renal anemia not undergoing dialysis and previously treated with ESAs. 

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HIF-Prolyl Hydroxylase Inhibitors: Confirmed Efficacy with Uncertain Safety

Roger S.D.a · Coyne D.W.b

doi : 10.1159/000518073

Am J Nephrol 2021;52:894–897

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