SGLT2 inhibitors – a potential treatment for Alport syndrome

2020 ◽  
Vol 134 (4) ◽  
pp. 379-388 ◽  
Author(s):  
Holly Mabillard ◽  
John A. Sayer
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Alport Syndrome ◽  
Sglt2 Inhibitors ◽  
Potential Candidate ◽  
Potential Treatment ◽  
Type Iv ◽  
Patients With Diabetes ◽  
Membrane Type ◽  
End Stage

Abstract Alport syndrome is a rare genetic disease that results in disordered basement membrane type IV collagen resulting in occular and auditory defects as well of progressive kidney disease. Although no ‘cure’ currently exists, therapeutic blockade of the renin–angiotensin–aldosterone system can slow the progression to end-stage kidney disease (ESKD). Clinical trials for treatments in preventing chronic kidney disease have largely been negative over the last two decades until recent trials have shown positive cardiovascular and renal outcomes of sodium–glucose co-transporter-2 (SGLT2) inhibitors in patients with diabetes mellitus. Although marketed as medications for Type 2 diabetes, SGLT2 inhibitors have been found to have additional properties that are nephroprotective which makes them a potential candidate for treatment for those with other forms of progressive kidney disease. This review discusses the evidence for the use of SGLT2 inhibitors as a potential treatment in Alport syndrome that may slow the progression of chronic kidney disease and prevent patients reaching ESKD.

scholarly journals A novel variant in the COL4A3 gene: etiology of Alport syndrome type 2 in a 38-year-old male with suspected hereditary kidney disease

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Paula Sienes Bailo ◽  
José Luis Bancalero Flores ◽  
Raquel Lahoz Alonso ◽  
María Santamaría González ◽  
Alex Gutiérrez Dalmau ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Alport Syndrome ◽  
Clinical Symptoms ◽  
Molecular Testing ◽  
Syndrome Type ◽  
Variant Of Uncertain Significance ◽  
Type Iv ◽  
Novel Variant ◽  
End Stage

ABSTRACT Objectives Patients with Alport syndrome develop progressive kidney function deterioration, sensorineural hearing loss, and ocular abnormalities. This condition is caused by mutations in COL4A5 (X-linked inheritance), COL4A3 and COL4A4 (autosomal dominant or recessive inheritance), and encoding type IV collagen α3, α4, and α5, respectively. If left untreated, clinical symptoms progress from microscopic hematuria to proteinuria, progressive kidney failure, and end-stage kidney disease. At present, kidney transplantation is the only effective approach. Next-generation sequencing is the method of choice for the diagnosis of this condition. Case presentation We report the case of a young man with chronic kidney disease who eventually underwent transplantation. Molecular testing made it possible to determine the etiology of his clinical symptoms and autosomal recessive Alport syndrome type 2. The patient was found to be a compound heterozygote for two missense variants (trans configuration) in the COL4A3 gene: A likely pathogenic variant c.4981C>T (p.Arg1661Cys) in exon 52 inherited from the mother (described elsewhere), and another variant of uncertain significance, c.943G>A (p.Gly315Ser), in exon 17 inherited from the father that has not been previously reported in the literature or found in relevant databases. Conclusions Following genetic confirmation, genetic counseling was provided to the patient and his direct relatives.

scholarly journals An Update on the Controversies in Anemia Management in Chronic Kidney Disease: Lessons Learned and Lost

Anemia ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Geoffrey Teehan ◽  
Robert L. Benz
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Randomized Trials ◽  
Lessons Learned ◽  
Patients With Diabetes ◽  
Anemia Management ◽  
Erythropoietin Deficiency ◽  
Stage Renal Disease ◽  
End Stage

Background. Erythropoietin deficiency and anemia occur in Chronic Kidney Disease (CKD) and may be treated with Erythropoietin Stimulating Agents (ESAs). The optimal hemoglobin, in non-End Stage Renal Disease CKD, is controversial.Methods. We review three recent randomized trials in anemia in CKD: CHOIR, CREATE, and TREAT.Results. CHOIR (N=1432) was terminated early with more frequent death and cardiovascular outcomes in the higher Hb group (HR 1.34: 95% C.I. 1.03–1.74,P=.03). CREATE (N=603) showed no difference in primary cardiovascular endpoints. Stroke was more common in the higher Hb group (HR 1.92; 95% C.I. 1.38–2.68;P<.001) in TREAT (N=4038).Conclusions. There is no benefit to an Hb outside the 10–12 g/dL range in this population. To avoid transfusions and improve Quality of Life, ESAs should be used cautiously, especially in patients with Diabetes, CKD, risk factors for stroke, and ESA resistance.

scholarly journals Association of HbA1C Variability and Renal Progression in Patients with Type 2 Diabetes with Chronic Kidney Disease Stages 3–4

2018 ◽  
Vol 19 (12) ◽  
pp. 4116 ◽  
Author(s):  
Mei-Yueh Lee ◽  
Jiun-Chi Huang ◽  
Szu-Chia Chen ◽  
Hsin-Ying Chiou ◽  
Pei-Yu Wu
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Lower Risk ◽  
Glycosylated Hemoglobin ◽  
Diabetic Patients ◽  
Patients With Diabetes ◽  
Cox Analysis ◽  
Stage Renal Disease ◽  
End Stage ◽  
Hba1c Variability

Little is known about the predictive value of glycosylated hemoglobin (HbA1C) variability in patients with advanced chronic kidney disease (CKD). The aim of this study was to investigate whether HbA1C variability is associated with progression to end-stage renal disease in diabetic patients with stages 3–5 CKD, and whether different stages of CKD affect these associations. Three hundred and eighty-eight patients with diabetes and stages 3–5 CKD were enrolled in this longitudinal study. Intra-individual HbA1C variability was defined as the standard deviation (SD) of HbA1C, and the renal endpoint was defined as commencing dialysis. The results indicated that, during a median follow-up period of 3.5 years, 108 patients started dialysis. Adjusted Cox analysis showed an association between the highest tertile of HbA1C SD (tertile 3 vs. tertile 1) and a lower risk of the renal endpoint (hazard ratio = 0.175; 95% confidence interval = 0.059–0.518; p = 0.002) in the patients with an HbA1C level ≥ 7% and stages 3–4 CKD, but not in stage 5 CKD. Further subgroup analysis showed that the highest two tertiles of HbA1C SD were associated with a lower risk of the renal endpoint in the group with a decreasing trend of HbA1C. Our results demonstrated that greater HbA1C variability and a decreasing trend of HbA1C, which may be related to intensive diabetes control, was associated with a lower risk of progression to dialysis in the patients with stages 3–4 CKD and poor glycemic control (HbA1c ≥ 7%).

scholarly journals A patient with MEN1 and end‑stage chronic kidney disease due to Alport syndrome: Decision making on the eligibility of transplantation

2017 ◽  
Author(s):  
Antonio Matrone ◽  
Alessandro Brancatella ◽  
Piero Marchetti ◽  
Enrico Vasile ◽  
Ugo Boggi ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Decision Making ◽  
Kidney Disease ◽  
Alport Syndrome ◽  
End Stage

Alport syndrome

2015 ◽  
Author(s):  
Laurence Heidet ◽  
Bertrand Knebelmann ◽  
Marie Claire Gubler
Keyword(s):  
Renal Failure ◽  
Alport Syndrome ◽  
Chromosome 2 ◽  
Renal Disorder ◽  
End Stage Renal Failure ◽  
Type Iv ◽  
Increased Risk ◽  
Fourth Decade ◽  
Membrane Type ◽  
End Stage

Alport syndrome is an inherited renal disorder characterized by early haematuria, progressing to proteinuria, sensorineural hearing loss, and progressive renal failure typically in the third or fourth decade but with wide variation. It is responsible for about 1% of end-stage renal failure. Over 80% of cases are X-linked and young men are most affected, but heterozygous carriers of the abnormal gene are also at significantly increased risk of end-stage renal failure in their lifetime. Those affected by the autosomal recessive variant are phenotypically very similar. It is caused by mutations in tissue-specific isoforms of basement membrane (type IV) collagen encoded by COL4A5 (X chromosome), COL4A3, and COL4A4 (chromosome 2).

scholarly journals Investigation of the Impact of Endodontic Therapy on Survival among Dialysis Patients in Taiwan: A Nationwide Population-Based Cohort Study

2021 ◽  
Vol 18 (1) ◽  
pp. 326
Author(s):  
Chih-Chien Chiu ◽  
Ya-Chieh Chang ◽  
Ren-Yeong Huang ◽  
Jenq-Shyong Chan ◽  
Chi-Hsiang Chung ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Root Canal ◽  
Dialysis Patients ◽  
Root Canal Therapy ◽  
Risk Of Death ◽  
Stage Renal Disease ◽  
End Stage

Objectives Dental problems occur widely in patients with chronic kidney disease (CKD) and may increase comorbidities. Root canal therapy (RCT) is a common procedure for advanced decayed caries with pulp inflammation and root canals. However, end-stage renal disease (ESRD) patients are considered to have a higher risk of potentially life-threatening infections after treatment and might fail to receive satisfactory dental care such as RCT. We investigated whether appropriate intervention for dental problems had a potential impact among dialysis patients. Design Men and women who began maintenance dialysis (hemodialysis or peritoneal dialysis) between January 1, 2000, and December 31, 2015, in Taiwan (total 12,454 patients) were enrolled in this study. Participants were followed up from the first reported dialysis date to the date of death or end of dialysis by December 31, 2015. Setting Data collection was conducted in Taiwan. Results A total of 2633 and 9821 patients were classified into the RCT and non-RCT groups, respectively. From the data of Taiwan’s National Health Insurance, a total of 5,092,734 teeth received RCT from 2000 to 2015. Then, a total of 12,454 patients were followed within the 16 years, and 4030 patients passed away. The results showed that members of the non-RCT group (34.93%) had a higher mortality rate than those of the RCT group (22.79%; p = 0.001). The multivariate-adjusted hazard ratio for the risk of death was 0.69 (RCT vs. non-RCT; p = 0.001). Conclusions This study suggested that patients who had received RCT had a relatively lower risk of death among dialysis patients. Infectious diseases had a significant role in mortality among dialysis patients with non-RCT. Appropriate interventions for dental problems may increase survival among dialysis patients. Abbreviations: CKD = chronic kidney disease, ESRD = end-stage renal disease, RCT = root canal therapy.

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