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Table 2 Characteristics of included studies

From: The gut microbiota profile of adults with kidney disease and kidney stones: a systematic review of the literature

Reference Country Demographics of patients Demographics of controls Stool collection, temp. & storage Antibiotic use Medications Taxonomy database Microbiota analysis technique Diversity metrics Dietary assessment
ADULTS WITH KIDNEY STONES (n= 6 articles)
 Ticinesi 2018 [50] Italy N = 52 recurrent idiopathic calcium stones
Age: 48 ± 11yrs, 60% male; ethnicity not reported
N = 48
Age: 47 ± 13yrs, 58% male; ethnicity not reported.
Self-sampled; Delivered to clinic within 2 hours from collection and stored at -22°C; Processed ≤ 2 weeks of receipt Excluded if taken in prior 30 days. Not reported SILVA (16S rRNA), whole NCBI nr (shotgun) 16S ribosomal RNA gene sequencing
(V3 region)
Illumina MiSeq &
shotgun metagenomics on sub-sample (n=10)
Illumina NextSeq
↓ α-diversity in KS group vs. controls (Chao1 index; p<0.05);
β-diversity significantly different between groups (p=0.002 with PERMANOVA and p=0.004 with Adonis test based on Bray-Curtis and weighted UniFrac metrics)
EPIC FFQ delivered by a nutritionist; Calcium intake lower in adults with KS (p<0.04). Calcium intake considered as a covariate in the analysis of gut microbiota data.
 Stern 2016 [58] USA N = 23; all stone types included
Age: 53.7 ± 15.4yrs, 22% male; 13% African American, 35% Hispanic, 52% Caucasian.
N = 6
Age: 53.5 ± 16.0yrs, 67% male; 50% African American and 50% Caucasian.
Self-sampled; Flash-frozen with dry ice & stored -80°C Excluded if taken in prior 2 weeks. Not reported Greengenes 16S ribosomal RNA gene sequencing
(V4 region)
Illumina MiSeq
Not reported Not reported
 Tang 2018 [53] China N = 13; stone types not reported.
Age: 52.25 ± 7.25yrs, 38% male; 100% Chinese.
N = 13
Age: 55.81 ±5.79yrs,
38% male; 100% Chinese.
Self-sampled; Immediately frozen & stored -80°C. (DNA samples stored at -20°C) Control group did not have antibiotics in prior 3 months; unclear if this was the same for kidney stone group. None of the adults with kidney stones were reported to be on any medications before sample collection. RDP 16S ribosomal RNA amplicon sequencing
(V4 region)
Illumina Hiseq 2500 platform
α-diversity reported not significantly different (Chao1, Shannon, Simpson’s and Good’s coverage indices, p>0.05)
Overall, β-diversity was distinct but not significantly different (p=0.096 with ANOSIM and p=0.058 with MPRR based on Bray-Curtis distance metric)
Not reported
 Suryavanshi 2016 [38] India N = 24 recurrent calcium oxalate stones.
Age: 22-50yrs, 100% male; ethnicity not reported.
N = 15
Age: 22-52yrs, 100% male; ethnicity not reported.
Self-sampled; Stored -80°C Excluded if taken in prior 3 months. Not reported Greengenes (16S rRNA) & M5NR database (frc-gene) 16S ribosomal RNA gene and frc-gene amplicon sequencing; quantitative polymerase chain reaction & PCR-DGGE
(V3 region of 16S rRNA gene)
Iron Torrent PGM system
α-diversity reported not significantly different (Chao1, observed species/OTUs, phylogenetic diversity, Shannon and Simpson’s indices)
β-diversity metrics reported to reveal compositional differences between groups (PCoA plots of weighted and unweighted UniFrac results; statistical test and p-value not reported).
Reported number of participants who follow a vegetarian diet; dietary intake results and assessment methods not reported.
 Suryavanshi 2018 [37] India Same as the population above
N = 24 recurrent calcium oxalate stones.
Age: 22-50yrs, 100% male; ethnicity not reported.
N = 48
(Additional n = 33 controls recruited).
Age and gender only reported for a subset of n =15 (as above); ethnicity not reported.
Not reported Not reported Not reported Greengenes Targeted sequencing (frc-, but- and buk-, 16S and 18S ribosomal RNA genes as well as fungal ITS1 region) & quantitative polymerase chain reaction
Iron Torrent PGM system
α-diversity investigated in selected sub-sample
(n = 7 KSD, n = 7 controls); authors reported significant decrease observed in KSD group (Chao1, Shannon and Simpson’s indices; p-value not reported).
β-diversity not reported.
Not reported
 Tavasoli 2019 [49] Iran N = 58 (majority confirmed to have calcium stones)
n = 29 recurrent stones with hyperoxaluria
Age: 44.21 ± 9.58yrs,
62.1% male.
n = 29 recurrent stones without hyperoxaluria
Age: 48.07 ± 9.20yrs, 72.4% male.
Ethnicity not reported
N = 29
Age: 41.42 ± 11.48yrs,
89.7 % male; ethnicity not reported.
Self-sampled; stored -20°C Excluded if taken in prior 2 months. Medications not reported; individuals excluded from the study if taking calcium, magnesium, potassium or pyridoxine supplementation. N/A Real-time polymerase chain reaction N/A Not reported
ADULTS WITH KIDNEY DISEASE (n=19 articles)
Individuals not reported to be undertaking a renal replacement therapy (n=10)
  Al-Obaide 2017 [42] USA N = 20 CKD* (CKD stage not reported, all were reported to have T2DM) eGFR: 16.54 ± 3.01; Age: 64.4 ± 2.3yrs.
Gender and ethnicity not reported.
*Stool samples of n=18/20 were analysed to identify the gut microbial profile
N = 20
Age:54.3±3.2yrs;
eGFR, gender and ethnicity not reported.
Self-sampled;
Processed ≤24hrs of receipt
Excluded if taken for atleast 3 consecutive days in the prior month Participants of the T2DM-CKD group treated with insulin, OHAs, ranitidine, PPI, ACEi, ARBs, statin therapy Curated database from Greengenes, RDPII & NCBI 16S ribosomal RNA gene sequencing
(V3-V4 region)
Illumina MiSeq
Not reported. Dietary assessment methods not stated.
Macronutrient data presented as a percentage of total energy intake; protein intake higher in controls (p<0.05) and fat intake higher in CKD group (p<0.01)
  Barrios 2015 [61] UK N = 62 (CKD stage not reported).
eGFR: reported ≤60;
Age, gender and ethnicity not reported for sub-sample.
N = 793
eGFR >60;
Age, gender and ethnicity not reported for sub-sample.
Self-sampled;
Refrigerated up to 2 days prior to clinic visit; Stored at -80°C
Data on antibiotics usage was collected for the prior month; data available for only 11% of study participants. Not reported Greengenes 16S ribosomal RNA gene sequencing
(V4 region)
Illumina MiSeq
Not reported Dietary scores were obtained from EPIC FFQ generated through PCA. Diet scores were considered as covariates in the linear mixed effects regression models; no significant results reported.
  De Angelis 2014 [39] Italy N = 32 IgAN (CKD stage not reported)
n = 16 non-progressors,
eGFR: 76 ± 15;
Age: 41 ± 10yrs, 69% males.
n=16 progressors,
eGFR: 30±18;
Age:45 ± 6 yrs, 63% male. 100% Caucasian.
N = 16
eGFR: 96 ± 7;
Age: 43 ± 8yrs, 60% male. 100% Caucasian
Self-sampled; Stored -80°C Excluded if taken in prior 3 months. All IgAN participants treated with ACEi. Other medications undefined; no remarkable changes reported to medications in prior month. RDP Bacterial tag-encoded FLX-titanium amplicon pyrosequencing bTEFTAP
(V1-V3 region)
454 FLX Sequencer
↓ α-diversity in IgAN group vs. controls (Chao1, observed species/OTUs and Shannon indices; p<0.05)
β-diversity not reported.
Reported no remarkable changes to participant’s diet in prior month. Dietary assessment method or results not reported.
  Jiang 2016 [47] China N = 65 (CKD stage 1-5 )
eGFR: 55.61 ± 52.55;
Age: 43.45 ± 16.90 yrs, 46% male. 100% Chinese
N = 20
eGFR: 104.99 ± 19.82; Age: 43.05 ± 9.88yrs,
30% male. 100% Chinese
Self-sampled;
Stored at -80°C
Excluded if taken in prior 4 weeks. Not reported N/A Quantitative polymerase chain reaction N/A Not reported
  Xu 2017 [56] China N = 32 (CKD stages 4-5)
eGFR: reported <30; Age: 53.34 ± 14.47yrs, 50% male; 100% Chinese
N = 32
eGFR: reported ≥90; Age: 55.03 ± 10.38yrs,
50% male; 100% Chinese
Sample collection method unclear; Stored at -40°C Excluded if taken in the prior month. Not reported Not reported 16S rDNA and rRNA sequencing
(V4 region)
Illumina MiSeq
↓ α-diversity in CKD group vs. controls (phylogenetic diversity and Shannon indices; p<0.001)
β-diversity significantly different between groups (ADONIS analysis based on unweighted UniFrac metric, p<0.001)
Not reported
  Wang 2012 [44] China N = 30 (reported ESKD)
Age: 54 (37-71) yrs, 53% male. eGFR and ethnicity not reported.
N = 10
Age: 55 (41-67yrs) yrs, 50% male. eGFR and ethnicity not reported.
Not reported Excluded if taken in prior 3 weeks. Medications not reported; Corticosteroids, statins, or cytotoxic drugs were not taken in the prior 3 weeks. SILVA 16S ribosomal RNA gene pyrosequencing
(V1-V3 region)
Sequencing platform not reported
↑ α-diversity ESKD vs. controls (observed species/OTUs index; p=0.017).
β-diversity not reported.
Not reported
  Jiang 2017 [51] China N = 52 (CKD stage 5)
eGFR: 6.86 ± 2.87;
Age: 51.58 ± 18.33yrs, 56% male. 100% Han Chinese nationality.
N = 60
eGFR: 98.03 ± 27.32; Age:52.53 ± 13.98yrs, 42 % male. 100% Han nationally Chinese
Self-sampled; Stored at -80°C Excluded if taken in prior 4 weeks. ESKD participants treated with phosphate
binders, anti-hypertensives and various vitamin and/or mineral supplementation (iron, calcium and vitamin D)
Not reported Quantitative polymerase chain reaction
&
16S ribosomal RNA gene pyrosequencing in sub-sample
(n = 27 ESKD and n = 26 controls)
(V4-V6 region)
Illumina GAII
α-diversity reported not significantly different (Chao1, observed species/OTUs, Shannon and Simpson’s indices).
No difference in β-diversity reported between groups (PCoA plot based on UniFrac metric, statistical test or p-value not reported).
Not reported
  Gradisteanu 2019 [41] Romania N = 9 DN (CKD stage not reported)
eGFR, age, gender and ethnicity not reported .
N = 5
eGFR, age, gender and ethnicity not reported.
Self-sampled;
Stored at -20°C
Not reported Not reported N/A Real-time polymerase chain reaction
(Bacterial and fungal group-specific primers were also used)
N/A Not reported
  Tao 2019 [40] China N = 14 DN (CKD stage not reported)
eGFR: 93.26 ± 17.0;
Age:52.93 ± 9.98 yrs, 64% male. 100% Chinese.
N = 28
n = 14 healthy controls
eGFR: 96.01 ± 9.29; Age: 52.86 ± 9.91yrs, 64% male.
n = 14 T2DM controls without CKD
eGFR: 93.48± 13.02; Age: 53.29yrs ± 9yrs, 64% male.
100% Chinese.
Self-sampled; stored at -80°C Excluded if taken in the prior 30 days. Not reported SILVA 16S ribosomal RNA gene pyrosequencing
(V3-V4 region)
Illumina MiSeq
↑ α-diversity richness DN vs. T2DM controls (observed species/OTUs index, p= 0.023; but no difference found for other α-diversity indices)
β-diversity significantly different between groups (PERMANOVA based on Bray-Curtis metric, p = 0.02).
Excluded if following restrictive diets. Reported similar/same eating habits across some of their groups; however, no formal dietary assessment was undertaken.
  Li 2019 [52] China N = 50 (CKD stage not reported)
eGFR: 22.39 ± 15.56;
Age:52.4 ± 13.49yrs, 54% male. 100% Chinese.
N = 22
eGFR: 97.06 ± 12.98;
Age:50.27 ± 7.77yrs, 55% male. 100% Chinese
Self-sampled; transported on ice and stored at -80°C Excluded taken in prior 3 months. Medications not reported; Immunosuppressive drugs not to be taken in prior 3 months. RDP 16S ribosomal RNA gene pyrosequencing
(V3-V4 region)
Illumina HiSeq
↓ α-diversity in CKD group vs. controls (Phylogenic diversity whole-tree index), p<0.05, and reduced but not significant for Shannon or Simpson’s indices p> 0.05).
β-diversity significantly different between groups (ANOSIM test based on unweighted UniFrac, p= 0.001)
Not reported
Individuals undertaking a renal replacement therapy: Haemodialysis (n=3 articles)
  Vaziri 2013 [48] & Wong 2014 [36] USA N = 24
eGFR not reported.
Dialysis vintage: ≥3 months, Kt/V =1.5 ± 0.3.
Age: 57 ± 14 yrs, 25% male.
38% Caucasian, 54% Hispanic, and 8% Asian.
N = 12
eGFR not reported.
Age: 51 ± 12 yrs,
33% male.
33% Caucasian, 58% Hispanic, and 8% Asian.
Not reported Excluded if taken in prior 3 months. HD patients were treated with phosphate binders, ESAs (Darbopoetin), vitamin & mineral supplementation. Immunosuppressive drugs not to be taken in prior 3 months. Greengenes (Wong) Microarray sequencing; 16S ribosomal RNA gene PhyloChip analysis Relative richness (assessed for subfamilies at subphylum level) was reported to be similar between groups (p-value not reported).
β-diversity revealed tighter clustering in the control group than HD group (NMDS figure based on Bray-Curtis distance metric; statistical test or p-value not reported)
Strict fluid and dietary sodium, phosphorus, and potassium restrictions; Nutrition prescription, education or counselling methods and results not reported.
  Miao 2018 [45] China N = 21
Dialysis vintage: ≥3 months, spKt/V reported >1.2 and regularly monitored.
Age: 53.0 ± 9.0yrs, 57% male.
eGFR and ethnicity not reported.
N = 20 (Unit staff)
Age:31 ± 9.1yrs, 50% males.
eGFR and ethnicity not reported.
Self-sampled; storage not reported. Not reported Medications at baseline not reported; HD patients had not taken lanthanum carbonate in prior 3 months. RDP, BLAST 16S ribosomal RNA gene pyrosequencing
(V1-V3 region)
Sequencing platform not reported
α-diversity not significantly different (Shannon index; p=0.429).
β-diversity not reported.
Diet reported being ‘controlled for’, although methods and results were not reported.
Individuals undertaking a renal replacement therapy: Peritoneal dialysis (n=1 article)
  Wang 2012 [43] Taiwan N = 29
eGFR: reported <15;
Dialysis vintage: 49.7 ± 35.4 months, Kt/V not reported; Age: 53.7 ± 11.7yrs, 34% male. Ethnicity not reported.
N = 41
Age: 58.2 ± 12.8yrs, 37% male.
eGFR and ethnicity not reported.
Self-sampled; Immediately put on ice; Processed ≤1hr of defecation Excluded if taken in prior 30 days. Not reported N/A Real-time polymerase chain reaction N/A Not reported
Mixed cohorts of individuals with chronic and end-stage kidney disease including those undertaking different renal replacement therapies (n= 5 articles)
  Shi 2014 [55] China N = 52
n = 22 HD group
Dialysis vintage: 6-40 months, Kt/V not reported.
n = 30 reported ESKD not undertaking dialysis.
eGFR, age, gender and ethnicity not reported.
N = 10
eGFR, age, gender and ethnicity not reported.
Details of sample collection not reported; Samples immersed in 90% alcohol and stored at -20°C Excluded if taken in prior 3 weeks. Medications not reported; Corticosteroids, statins, cytotoxic drugs not taken in prior 3 weeks. SILVA 16S ribosomal RNA gene
Pyrosequencing
(V1-V3 region)
Sequencing platform not reported
↑ α-diversity in HD group vs. controls (average OTUs/ species, p=0.044) and Chao1 index higher in three HD samples (p-value not reported).
β-diversity not reported between study groups. However, PCA plot of Unifrac data from selected samples at the genus level exhibited a large separation in the same three HD samples vs. the other selected samples (p-value or statistical test not report).
Not reported
  Stadlbauer 2017 [57] Austria N = 30
n = 15 PD group
GFR (ml/min): 7.9 (7.3; 14.0); Dialysis vintage: 25 (15-74) months.
Age: 62yrs (54-69), 80% male.
n = 15 HD group
GFR (ml/min): 6.0 (5.9; 9.3); Dialysis vintage: 70 (40-197) months, Kt/V not reported.
Age: 61yrs (54-71), 67% male;
Ethnicity not reported.
N = 21
GFR (ml/min): 77.6 (73.4; 86.6).
Age: 58 yrs (53-62),
43% male. Ethnicity not reported.
Self-sampled; Stored at -80°C Not reported Participants from HD and PD groups treated with phosphate binders, PPI, immunosuppressive drugs. Small number of controls (n=2) also treated with PPI. SILVA 16S ribosomal RNA gene sequencing
(V1-V2 region)
Illumina MiSeq
↓ α-diversity in PD and HD group compared to controls (Chao1 index, p<0.05, similar results reported for observed species/OTUs and phylogenic diversity)
β-diversity significantly different between HD vs. controls p=0.012 and PD vs. controls p=0.003 (ANOSIM test based on Bray Curtis, weighted and unweighted UniFrac metrics)
Not reported
  Lun 2019 [60] China N = 49 (n =13 treated with HD)
Age: 54 ±14 yrs, 76% male; eGFRand ethnicity not reported.
N = 24
Age: 56 ± 9 yrs, 67% males; eGFR and ethnicity not reported.
Self-sampled; Stored at -80°C Excluded taken in prior 3 months. Not reported Not reported 16S ribosomal RNA gene sequencing
(V3-V4 region)
Illumina HiSeq (PE250)
α-diversity not reported.
β-diversity reported being distinct between CKD vs. controls; unclear if statistically significant (PCA plot based on the Euclidean distance & NMDS based on the UniFrac distance metric; statistical test or p-value not reported)
Not reported
  Li 2019 [62] China N = 53
n = 29 HD group
eGFR: 5.75 (4.35–8.26);
Dialysis vintage and Kt/V not reported.
Age: 54yrs (41.5-69), 59% male.
n = 24 ESKD group (stage 5) not undertaking dialysis.
eGFR: 5.33 (4.31–7.72);
Age: 55.5 yrs (48.25-64.5), 50% male.
Ethnicity not explicitly reported.
N = 69
eGFR: 126.07 (102.80–148.65);
Age: 51yrs (39.5-64), 39 % male.
Ethnicity not explicitly reported.
Collected in sterile 2mL tube on ice, containing pure ethanol and frozen within 30 minutes; Stored at -80°C Excluded if taken in prior 4 weeks. HD and CKD participants were treated with phosphate binders. Medication history of the last month was collected, but results were not reported. Greengenes 16S ribosomal RNA gene sequencing
(V1-V2 region)
Illumina HiSeq 2500 system
↓ α-diversity in CKD and HD group vs. controls (Chao1, ACE and Shannon indices p<0.001).
β-diversity reported being different between groups (PCoA plot presented data based on weighted and unweighted UniFrac metrics, ANOSIM test, p-value not reported)
Reported similar eating habits across the cohort, although methods and results were not reported.
  Guirong 2018 [46] China N = 100
n = 16 KT recipients (sampling reported within the first month after transplantation)
Age: 42.8±11.5yrs.
n = 84 CKD group (stage 3-4)
Age: 55.9±18.2 yrs.
eGFR, gender and ethnicity not reported.
N = 53
Age: 54.7 ± 12.8yrs; eGFR, gender and ethnicity not reported.
Collection and storage not reported. None taken in prior 3 months. Not reported Not reported 16S ribosomal RNA gene sequencing
(V3 region)
Ion Personal Genome Machine system
↓ α-diversity in RT and HD vs. controls (Chao1 index p<0.001).
β-diversity reported being different between groups (PERMANOVA based on Bray-Curtis metric, p<0.01)
Not reported
  1. Legend: ESKD End-stage kidney disease, HD Haemodialysis, HC Healthy controls, PD Peritoneal dialysis, KS Kidney stones, KT Kidney transplant, DN Diabetic nephropathy, OTU Operational Taxonomic Units, Wt Weight, Ht Height, WC Waist circumference, KSD Kidney stone disease, T2DM Type 2 diabetes mellitus, PPI Protein pump inhibitors, ESA Erythropoiesis-stimulating agents, ACEi Angiotensin-converting-enzyme inhibitors, ARBs Angiotensin II receptor blockers, OHA Oral hypoglycaemic agents, eGFR Estimated glomerular filtration rate (ml/min/1.73m2), GFR Glomerular filtration rate (ml/min), vs. versus; ↓= decreased, ↑= increased