Measurement of the intestinal permeability in chronic kidney disease

Table 2 Results considering the intestinal permeability published in the included studies

Ref.	Population	Study size	Marker used to assess intestinal permeability (values provided as mean ± SD)	Results	Part of the intestine evaluated
Shi et al[18]	ESRD (both HD and non-HD) vs healthy controls ESRD group further divided patients with bacterial DNA and without bacterial DNA in their blood samples	ESRD n = 52 (HD n = 22, ND n = 30) Controls n = 10	D-lactate (plasma) Endotoxins (blood) Bacterial DNA (blood)	D-lactate plasma levels higher: ESRD HD vs controls P = 0.039 ESRD non-HD vs controls P = 0.044 HD vs non-HD P > 0.05 ESRD with bacterial DNA vs ESRD without bacterial DNA P < 0.05 ESRD HD with bacterial DNA vs ESRD non-HD with bacterial DNA P > 0.05 Endotoxin significantly higher: ESRD HD vs controls P < 0.05 ESRD non-HD vs controls P < 0.05 ESRD HD 0.95 ± 0.12 EU/mL ESRD non-HD 0.70 ± 0.15 EU/mL Controls 0.17 ± 0.10 EU/mL Presence of bacterial 16S rDNA: ESRD HD 6/22 patients ESRD non-HD 6/30 patients Controls: 0/10 patients	Large intestine Mostly large intestine Mostly large intestine
Wang et al[19]	ESRD patients (non-HD) vs healthy controls ESRD group further divided patients with bacterial DNA and without bacterial DNA in their blood samples	ESRD n = 30 Controls n = 10	D-lactate (plasma) Bacterial 16s rDNA (blood)	Plasma D-lactate higher: ESRD with bacterial DNA vs ESRD without bacterial DNA P = 0.0233 ESRD with bacterial DNA vs controls P =0.067 ESRD with bacterial DNA: 13.53 ± 1.47 μg/mL ESRD without bacterial DNA: 5.71 ± 2.28 μg/mL Controls: 4.82 ± 0.93 μg/mL D-lactate plasma levels both ESRD groups combined: 7.274 ± 2.16 μg/mL1 ESRD: 6/30 bacterial DNA in blood Controls: no bacterial DNA in blood	Large intestine
Bossola et al[24]	HD patients (AVF en CVC) vs healthy controls	HD n = 58 (AVF n = 44, CVC n = 14) Controls n = 30	Bacterial 16S rDNA (blood)	HD patients: 12/58 bacterial DNA in blood (= 20.7%) Healthy controls: No bacterial DNA in blood AVF patients 5/44 (= 15.9%) CVC patients 5/14 (35.7) P = 0.22	Both small and large intestine
McIntyre et al[25]	HD patients, PD patients, CKD patients (stage 3-5) vs healthy controls	HD n = 120 PD n =25 CKD stage 3-5 n = 90 Controls n = 14	Endotoxin level (blood)	Significant higher endotoxin levels in HD vs PD P < 0.008 Dialysis patients (HD + PD) vs CKD P < 0.001 CKD vs controls P > 0.05 HD patients: 0.64 EU/mL PD patients: 0.56 EU/mL HD + PD patients: 0.62 ± 0.37 EU/mL CKD patients: 0.11 ± 0.68 EU/mL Controls: Not provided	Both small and large intestine
Feroze et al[26]	HD patients, follow up for 42 mo	HD n = 303	Endotoxin level (blood)	No significant association between elevated circulating endotoxin levels and mortality Mean endotoxin levels: 2.31 ± 3.10 EU/mL	Both small and large intestine
Zuckerman et al[20]	No control group CAPD patients vs healthy controls	CAPD patients n = 11 (5 with significant urine output) Controls n = 32	Cr-EDTA recovery (24 h urine + dialysate)	Significant less recovery of Cr-EDTA: CAPD vs controls P < 0.0005	Both small and large intestine
Szeto et al[27]	New PD patients vs IgAN patients (mild to moderate CKD) and healthy controls Mean creatinine level IgAN group: 151.2 ± 116.68 μmol/L	PD n = 30 IgAN n = 10 Controls n = 6	LPS (plasma)	CAPD patients: Mean 0.57% (0%-1.24%) Healthy controls: Mean 1.99% (0.59-3.48) Significantly higher LPS levels PD vs IgAN P < 0.0001 PD vs controls P < 0.0001 IgAN vs controls: Not provided PD: 0.44 ± 0.18 EU/mL IgAN: 0.0035 ± 0.009 EU/mL Controls: 0.013 ± 0.007 EU/mL	Both small and large intestine
Cobden et al[17]	CKD patients vs healthy controls CKD group: Serum creatinine levels ranging from 140 to 1050 μmol/L	CKD n = 6 Controls n = 55	Cellobiose and mannitol recovery (urine)	No significant difference recovery cellobiose and mannitol CKD vs controls P > 0.05 Cellobiose: CKD: Recovery range 0.09%-0.44% Controls: Not provided Mannitol: CKD: Recovery range 12.8%-52.3% Controls: Not provided	Small intestine
Magnusson et al[28]	Asymptomatic uremic CKD vs healthy volunteers Mean serum creatinine level IgAN group: 503 μmol/L, range 274-796 μmol/L	CKD n = 9 Controls n = 6	PEGs (urine) Computer model was used to predict the PEG recovery adjusted for eGFR	Significant lower urinary recovery of PEG’s CKD vs controls P < 0.05 More heavy PEG’s were harvest in urine CKD patients: indicating that intestinal permeability in CKD patients is more increased for larger molecules	Both small and large intestine
Kovacs et al[21] and Kovacs et al[23]	IgAN patients (both uremic and non-uremic) vs healthy controls	1989: IgAN patients n = 29: (uremic n = 24 non-uremic n = 5) Controls n = 20	Cr-EDTA recovery (urine)	Significantly higher Cr-EDTA recovery in IgAN patients vs controls P < 0.005, both in 1989 and in follow up after 5 yr	Both small and large intestine
These two studies published results measured in the same patient group. Provided data by the two articles are summarized	Both in 1989 and after a four year follow up in 1994 No mean serum creatinine levels of total IgAN group provided	1996: IgAN patients n = 21 No controls Follow up patients further divided an analyzed in two groups; increased intestinal permeability group vs non-increased intestinal permeability		IgAN (1989): 3.86% ± 0.29% IgAN (1994): 4.57% ± 0.63% Controls: 2.72% ± 0.23% Only in the increased permeability group significant decrease in eGFR (Baseline eGFR 84.4 ± 6.1 mL/min vs 65.4 ± 8.6 mL/min after four years, P < 0.01)
Rostoker et al[22]	Patients with Primary IgA glomerulonefritis and permanent proteinuria (IgA GN), INS IC-GN: Membranous + membranoproliferative) vs healthy controls and alcohol abusers (positive controls)	IgA GN n = 30 INS n = 25 IC-GN n = 20 Controls n = 20 Alcohol abusers n = 5	Cr-EDTA recovery (urine)	Significantly higher Cr-EDTA recovery in IgA GN vs controls P < 0.005 INS vs controls P < 0.005 IC-GN vs controls P < 0.005 Alcohol abusers vs controls P < 0.005 IgA GN: Median 3.25% (0.7-17.8) INS: Median 3.71% (0.82-10) IC-GN: 3.40% (0.30-16) Alcohol abusers: 4.9% (7-30) Controls: 2% (0.4-3.9)	Both small and large intestine
Layward et al[15]	Histologically proven IgAN with proteinuria and microscopic hematuria vs healthy No mean serum creatinine levels provided controls	IgAN patients n = 18 Controls n = 17	Cellobiose/mannitol ratio (urine)	No significant difference cellobiose/mannitol ratio IgA NP patients vs controls P = 0.42 IgA NP: 0.015 ± 0.008 Controls: 0.022 ± 0.015	Small intestine
De Maar et al[14]	Renal transplant patients assessed before transplantation and in the follow up during active CMV infection and CMV negative controls	Permeability assessed before transplantation n = 104 Permeability assessed during active infection n = 12 (primary infections: 5, secondary infections: 7) Controls (CMV-): n = 9	Lactulose/mannitol ratio (urine)	L/M ratio increased during active CMV infection in 9/12 patients P < 0.01 L/M ratio active CMV infection compared to patients without CMV P < 0.01	Small intestine Small intestine
Ponda et al[16]	CKD stadium III patients vs healthy controls CKD patients: mean eGFR: 51 mL/min per 1.73² All patients and controls had a vitamin D deficiency	CKD n = 5 Controls n = 4	Endotoxin activity; expressed as fraction of the maximum response to endotoxin (plasma) Lactulose/mannitol ratio (urine)	No significant difference endotoxin activity CKD vs controls P > 0.05 CKD: 0.23 ± 0.15 Healthy controls: 0.20 ± 0.13 L/M ratio increased with D3 therapy P = 0.02 (reflecting an increase in permeability) L/M ratio not assessed in control group

¹Value not provided in article. Calculated as followed: sqrt((6-1)*1.47^2+(24-1)*2.28^2)/(6-1+24-1). Sp = √(n1 – 1) x S1² + (N2 - 1) x S2²/(n1 - 1 + n2 - 1).

AVF: Arteriovenous fistula; CAPD: Continuous ambulatory peritoneal dialysis; CKD: Chronic kidney disease; CVC: Central venous catheter; ESRD: End stage renal disease; HD: Hemodialysis; IgAN: IgA nephropathy; IgA GN: IgA glomerulonephritis; IC-GN: Immunocomplex glomerulonephritis; INS: Idiopathic nephrotic syndrome; Li: Lithium; LPS: Lipopolysaccharide; PD: Peritoneal dialysis; PEG: Polyethylene glycols; TER: Trans epithelial electrical resistance.