Table 1 Overview of study characteristics, ordered alphabetically by rare renal disease type
From: Differential methylation as a diagnostic biomarker of rare renal diseases: a systematic review
First author, year and rare kidney disease featured. | Methylation measurement method | Participant information. | Outcome |
|---|---|---|---|
Fujino, Takayuki. 2016 Disease: Membranous Nephropathy | ChIPa assays and H3K4me3b localisation. | Renal biopsies from patients (n = 6) diagnosed with nephrotic syndrome caused by membranous nephropathy compared to controls with other causes of nephrotic syndrome. Two additional control comparisons were participants with microhematuria but no glomerulonephropathy (n = 3) and a single age matched healthy control. Also murine models with induced proteinuria. | The association of increased H3K4me3 and cathepsin L as well as decreased synaptopodin levels and proteinuria in membranous nephropathy. |
Hayashi, K. 2014 Disease: Proteinuria | Micro-array based genome wide DNAcmethylation profiling system, MSPd and bisulphite sequencing. | Murine models of proteinuric disease, including FSGSe (n = 11), minimal change disease (n = 10), diabetic nephropathy (n = 9) and normal controls (n = 9). Human renal biopsies from the same proteinuric diseases, number not stated. | Elucidation of a potential novel therapeutic target of proteinuria, the gene KLF4, including investigation of promoter CpG methylation. |
Hayashi, K. 2015 Disease: Proteinuria | Bisulphite treatment of DNA and MSP. | Murine models of adriamycin nephropathy, (n = 5 in each treatment group). Samples from patients with proteinuric glomerular diseases including FSGS (n = 8), minimal change disease (n = 9), diabetic nephropathy (n = 8) and normal controls (n = 8). Immortal human podocyte cell lines. | Identification of KLF4 as a potential therapeutic target of proteinuria and angiotensin receptor blockers as a treatment which exerts effects on methylation. |
Ito, Y. 2017 Disease: Proteinuria | ChIP assays of histone methylation. | Human embryonic kidney cell lines as well as murine and zebrafish models of proteinuria. | The role of WHSC1L1-L1 in epigenetically modifying the expression of nephrin, with implications for both congenital nephrotic syndrome (rare) and acquired nephrotic syndrome (non-rare). |
Jin, M. 2014 Disease: Congenital renal agenesis | Reduced representation bisulphite sequencing to allow analysis of differentially methylated regions. | Chinese female monozygotic twins discordant for congenital renal agenesis. | Genomic/epigenomic changes, including methylation, which may be correlated with congenital renal agenesis in discordant monozygotic twins. |
Li, LX. 2017 Disease: ADPKDf | ChIP with anti-H3K4me2g antibodies and anti-SMYD2 antibodies. Methylation sites localised using a flag-tagged protein. | Double conditional knockout of Pkd1 and Smyd2 in murine models of ADPKD (n = 12) compared to single knockout of Pkd1 (n = 14). Treatment of mice (n = 12) of ADPKD (Pkd1 knockouts) with AZ505 compared to DMSOh injected controls (n = 12) and in conditional Pkd1 knockouts (n = 14) compared again to DMSO injected controls (n = 14). Human ADPKD cells were also utilised and compared to normal kidney cells. | SMYD2’s potential role in ADKPD cyst formation, including differential methylation. |
Majumder, Syamantak. 2018. Disease: Proteinuria | Immunohistochemical staining, RT-qPCRi and ChIP assays of H3K27me3j. | Murine models with induced glomerular injury compared to controls. Kidney samples of human participants with diabetic glomerulosclerosis (n = 12) compared to age matched healthy controls (n = 12) and FSGS (n = 10) compared to non-FSGS tissue biopsies taken at the time of kidney transplantation (n = 9). | Reduced H3K27me3 and subsequent upregulation of the Notch pathway as a contributor to albuminuria in glomerular disease. |
Qi, S. 2012 Disease: IgANk | ChIP microarray and real time quantitative MSP. | PBMCsl from IgAN patients (n = 15) and healthy controls (n = 15). | Identification of H3K4me3 as a potential contributor to IgAN. |
Sallustio, F. 2016 Disease: IgAN | Whole genome microarray analysis of CD4+ T cells, followed by pyrosequencing for validation. | Renal biopsies from IgAN patients (n = 24) and normal controls (n = 24). | Differential methylation in CD4+ T-cells as a potential contributor to IgAN pathogenesis. |
Sui, WG. 2014 Disease: Membranous nephropathy | ChIP-sequencing of H3K9me3m followed by Model-based Analysis of ChIP-sequencing which identified enriched H3K9me3 peaks. | PBMCs from membranous nephropathy patients (n = 10) and healthy controls (n = 10). | Identification of H3K9me3 alterations, including differential methylation, as a potential contributor to membranous nephropathy pathogenesis and a potential biomarker. |
Sun, Q. 2015 Disease: IgAN | MSP of bisulphite treated Cosmc gene promoter regions. | PBMCs from paediatric patients with IgAN (n = 26), other renal diseases (n = 11) and healthy control children (n = 13). | Differential methylation in the Cosmc gene as a potential contributor to aberrantly glycosylated IgA1 in IgAN patients. |
Woo, YM. 2014 Disease: ADPKD | MIRA-seqn and ChIP-qPCR. | Cystic renal cortex samples from ADPKD patients (n = 3) and non-ADPKD samples from renal cell carcinoma patients (n = 3) used as a normal control. Madin-Darby Canine Kidney cells also used. | Differential methylation in ADPKD cyst formation and the role of methylation inhibitors in repression of cyst formation. |
Woo, YM. 2015 Disease: ADPKD | MIRA-seq, methylation-sensitive high-resolution melting and validation using EpiTYPER assay. | Renal tissue from ADPKD patients (n = 3) and non-ADPKD healthy renal tissue from renal cell carcinoma patients (n = 3). Urine samples of ADPKD patients evaluated over a period of 21 months (n = 53). | Identification of differentially methylated MUPCDH as a potential prognostic biomarker of ADPKD. |