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ABSTRACT: Ischaemia/reperfusion induces systemic inflammation and oxidative stress and thereby remote organ injury in the kidney. In a double-blind, placebo-controlled clinical trial of 30 patients undergoing knee arthroplasty with tourniquet, this study evaluated the effect of N-acetylcysteine (NAC) infusion on renal function by measuring urine alpha-1-microglobulin, N-acetyl-beta-D-glucosaminidase (NAG), glutathione-S-transferase-alpha and -phi and serum creatinine and cystatin C concentrations up to 24 h post-operatively. Compared to the baseline, urine alpha-1-microglobulin/creatinine increased in both groups and was higher in the NAC group than in the placebo group at tourniquet deflation and at 3 h thereafter. Urine NAG/creatinine increased at deflation and at 3 h thereafter in the NAC group and the ratio was higher than in the placebo group. The two sensitive indicators of proximal tubular damage and function used in the present study suggest that use of NAC in clinical setting of ischaemia/reperfusion injury may increase the risk of remote kidney injury.
Free radical research 08/2009; 43(7):691-6. · 2.22 Impact Factor
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ABSTRACT: 13-cis-Retinoic acid treatment causes insulin resistance and disturbances in lipid and glucose metabolism. We studied how 13-cis-retinoic acid affects inflammatory factors and adiponectin. A total of 23 healthy patients (age, 24.9 +/- 0.9 years; body mass index, 22.6 +/- 0.7 kg/m(2)) who received 13-cis-retinoic acid treatment of acne participated in the study. The patients were studied before the treatment, after 3 months of therapy, and 1 month after the treatment. Inflammatory parameters were measured, and a 4-hour oral glucose tolerance test was performed at each visit. Treatment with 13-cis-retinoic acid resulted in a significantly elevated serum adiponectin concentration (from 24.9 +/- 2.5 to 29.4 +/- 3.6 mg/L, P < .05), hemoglobin A(1c) (from 5.27% +/- 0.05% to 5.42% +/- 0.06%, P < .01), C-peptide area under the curve (from 314.2 +/- 16.6 to 350.0 +/- 21.0 (nmol . min)/L, P < .05), and triglycerides (from 0.97 +/- 0.06 to 1.29 +/- 0.10 mmol/L, P < .05), whereas high-density lipoprotein cholesterol decreased (from 1.50 +/- 0.07 to 1.38 +/- 0.08 mmol/L, P < .05). The increase in adiponectin during 13-cis-retinoic acid therapy correlated with baseline triglycerides (r = 0.51, P < .02). Many inflammatory markers, which were nonsignificantly elevated during therapy, decreased significantly after cessation of treatment. These were C-reactive protein (median from 1.78 to 1.23 mg/L, P < .05), soluble intercellular adhesion molecule 1 (from 210 +/- 10 to 204 +/- 10 microg/L, P < .02), ceruloplasmin (256 +/- 17 to 231 +/- 17 microg/L, P < .02), and erythrocyte sedimentation rate (from 6.4 +/- 1.3 to 4.7 +/- 0.9 mm/h, P < .02). Interleukin 6 concentration was unaffected by the therapy, but decreased significantly after the treatment (from 2.18 +/- 0.46 to 1.65 +/- 0.43 ng/L, P < .05). In conclusion, although treatment with 13-cis-retinoic acid results in disturbances in glucose and lipid metabolism, paradoxically serum adiponectin concentration increases. 13-cis-Retinoic acid has profound effects on the regulation of inflammatory markers.
Metabolism 06/2007; 56(6):786-91. · 2.66 Impact Factor
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ABSTRACT: Cytomegalovirus (CMV) is a suggested risk factor for chronic allograft nephropathy, and transforming growth factor-beta (TGF-beta) is a key fibrogenic molecule in this process. CMV has been shown to induce the expression of TGF-beta and several cytokines. We analyzed the impact of CMV on urinary excretion of TGF-beta, ICAM-1, TNF-alpha and correlated findings with biopsy histology.
Urine samples from 46 renal transplant recipients were available for the study. Urine samples were taken when CMV infection was suspected, or for controlling of proteinuria or bacteriuria.
CMV was diagnosed by antigenemia and viral cultures. Patients with previous CMV infection were excluded from the analysis. Urine samples were analyzed by ELISA-method to detect the levels of TNF-alpha, ICAM-1 and TGF-beta(1). Banff '97 criteria were used for scoring of protocol biopsies taken 6 months after transplantation.
At the time of the urine collection, 13/46 patients had CMV infection. Eight patients with no CMV infection were used as controls. TGF-beta(1) was significantly increased in the CMV group (samples taken mean 137+/-79 days post-transplantation) compared to controls (samples 139+/-64 days post-transplantation) (51.1+/-28.0 vs. 13.3+/-6.7 ng/mmol crea, p<0.001). No differences in the levels of other molecules were recorded. In the biopsies, interstitial fibrosis was significantly increased in the CMV group compared to controls.
Urinary excretion of TGF-beta(1) was increased in patients during CMV infection. This was associated with increased fibrosis in the biopsies.
Transplant Immunology 01/2006; 15(3):217-21. · 1.46 Impact Factor
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ABSTRACT: To elucidate whether serum adiponectin is associated with renal function, low-grade inflammatory markers, metabolic control, and insulin resistance in type 1 diabetic patients with and without nephropathy.
A total of 189 type 1 diabetic patients from the Finnish Diabetic Nephropathy Study were divided into three groups based on their urinary albumin excretion rate (AER): patients with normal AER (n = 66) had no antihypertensive medication, while patients with microalbuminuria (n = 63) or macroalbuminuria (n = 60) were all treated with an ACE inhibitor. Renal function was estimated with the Cockcroft-Gault formula. Adiponectin was measured by an in-house time-resolved immunofluorometric assay.
Adiponectin concentrations were higher in women than in men, but since there was no significant difference in sex distribution between the groups, data were pooled. Adiponectin concentrations were higher in patients with macroalbuminuria (19.8 +/- 12.0 mg/l) than in patients with microalbuminuria (13.1 +/- 4.8 mg/l) or normoalbuminuria (11.8 +/- 4.2 mg/l). In a univariate analysis, adiponectin was positively associated with creatinine (r = 0.41; P < 0.0001), AER (r = 0.33; P < 0.0001), interleukin-6 (r = 0.22; P = 0.002), systolic blood pressure (r = 0.22; P = 0.004), HbA(1c) (r = 0.17; P = 0.02), total cholesterol (r = 0.16; P = 0.03), and HDL cholesterol (r = 0.16; P = 0.03) and negatively with estimated glomerular filtration rate (GFR; r = -0.52; P < 0.0001) and waist-to-hip ratio (WHR; r = -0.16; P = 0.03). In a multiple linear regression analysis including the above variables, estimated GFR, AER, and WHR were independently associated with adiponectin levels (r(2) = 0.32).
Serum adiponectin concentrations are increased in type 1 diabetic patients with nephropathy, and levels are further associated with renal insufficiency.
Diabetes Care 07/2005; 28(6):1410-4. · 8.09 Impact Factor
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ABSTRACT: Glucose absorbed from conventional peritoneal dialysis (PD) solutions contributes to unfavorable metabolic effects. Its replacement with a glucose-free osmotic agent such as icodextrin (ID) or amino acids (AA) may have some benefit on glucose and lipid metabolism.
Serum lipids, insulin sensitivity and substrate oxidation (calorimetry) were measured before and after 8 weeks use of ID or AA in 22 patients. Calorimetry and blood tests (HbA1c, lipids) were also performed after 8 weeks of simultaneous use of ID and AA in 8 patients.
Cholesterol declined during the use of AA (4.8 +/- 0.3-4.5 +/- 0.3 mmol/l, p = 0.045). Triglycerides decreased during the use of both ID (2.2 +/- 0.2-1.9 +/- 0.1 mmol/l, p = 0.019) and AA (1.9 +/- 0.2-1.6 +/- 0.1 mmol/l, p = 0.024). Free fatty acids declined during the use of AA. There were no significant changes in insulin sensitivity. Glucose oxidation decreased and lipid oxidation increased during the use of ID, the changes in substrate oxidation were accentuated during the simultaneous use of ID and AA.
Replacement of glucose with ID or AA had a benefit on glucose and lipid metabolism.
Blood Purification 02/2005; 23(4):303-10. · 2.10 Impact Factor
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ABSTRACT: Diminishing ultrafiltration and dialysis adequacy may limit the long-term use of peritoneal dialysis (PD). Inflammation may play a role in changes in peritoneal function. This study was designed to evaluate alterations in peritoneal function and soluble factors in dialysate during a 1-year follow-up period.
A personal dialysis capacity test was performed at the start of the study and after 6 and 12 months in 20 patients in order to determine dialysis adequacy and membrane characteristics. Dialysate was collected during the test days for analyses of interleukin-6 (IL-6), soluble intercellular adhesion molecule-1, hyaluronan and cancer antigen 125 (CA125).
There were no significant changes in dialysis adequacy or membrane characteristics during the 1-year follow-up period. The appearance rate of IL-6 in dialysate increased significantly (419.8+/-63.3 at the start, 784.1+/-136.4 after 6 months and 1149.3+/-252.2 ng/24 h after 12 months; p=0.006) during follow-up. Furthermore, the appearance rate of CA125 increased throughout the study in patients using icodextrin, but decreased slightly in patients using only conventional dialysis solutions.
There were no major changes in dialysis adequacy or membrane characteristics during the follow-up period, but increased IL-6 in dialysate may reflect peritoneal inflammation, which may lead to long-term alterations in the peritoneal membrane. Icodextrin may have a preventive effect on the longevity of the peritoneal membrane.
Scandinavian Journal of Urology and Nephrology 02/2005; 39(5):410-6. · 0.99 Impact Factor
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ABSTRACT: Albumin and alpha1-microglobulin (alpha1M) are absorbed by two specific receptors in tubular epithelial cells. Any cell injury will disturb the reabsorption of these proteins, The increased urinary excretions of albumin or alpha1M could thus serve as a marker of subclinical graft lesions and as an early indicator of chronic allograft dysfunction.
We measured 24-hour urinary excretions of albumin, alpha1M, and transforming growth factor (TGF)-beta1 at 6 months after transplantation in 79 renal-graft recipients and recorded the changes in 24-hour creatinine clearance an average 51 (range 14-72) posttransplant follow-up months.
At 6 months from transplantation, 46 of 79 (58%) patients were normoalbuminuric, 25 (32%) microalbuminuric, and 8 (10%) macroalbuminuric. In normoalbuminuric patients, urinary alpha1M/creatinine ratio was 10 times, and TGF-beta1/creatinine ratio approximately 5 times, higher than in the healthy subjects but lower than in albuminuric patients. In all patients, urinary alpha1M correlated with urinary TGF-beta1 (r=0.508, P<0.001), with albumin (r=0.220, P<0.05), and with the annual changes in 24-hour creatinine clearance (r=-0.273, P<0.05). During follow-up, renal function deteriorated in 20 of 33 (60%) patients with alpha1M/creatinine ratio greater than 5 mg/mmol, but only in 1 of 46 (2%) patients whose ratio was less than 5 mg/mmol (P<0.01), giving the ratio 5 mg/mmol or greater a 95% sensitivity to detect patients with poor long-term outcome.
We show proximal tubular injury, measured by increased urinary alpha1M, to be present even in normoalbuminuric patients and to be associated with increased excretion of TGF-beta1 and with the annual deterioration of glomerular filtration rate. These findings show increased alpha1M/creatinine ratio to be an early and sensitive indicator of poor long-term outcome in renal-transplant patients.
Transplantation 09/2004; 78(5):719-24. · 4.00 Impact Factor
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ABSTRACT: Despite effective antibiotic therapy, peritonitis still remains a major problem in peritoneal dialysis (PD). The aim of the present study was to investigate changes of CRP, dialysate leukocytes and IL-6, hyaluronan (HA) and sICAM-1 in dialysate during and after peritonitis and their association to the outcome of peritonitis.
Dialysate IL-6, HA and sICAM-1 were measured at the onset and on day 4, at the end of the treatment and 2 months after onset of peritonitis. Furthermore, CRP and dialysate leukocytes were measured on days 1-4.
All measured soluble factors were higher on the first and fourth day than at the end of the treatment. sICAM-1 and HA were lower at the end of the treatment in patients who later had a relapse/re-infection. IL-6 remained higher 2 months after clinically cured peritonitis. CRP and dialysate leukocytes were higher on day 4 in patients with poor outcome.
Peritonitis causes increased excretion of soluble factors. Low concentrations of sICAM-1 and HA at the end of the treatment were negative prognostic indicators. Higher IL-6 levels after peritonitis could be a sign of ongoing inflammation in the peritoneal membrane. Delayed decrease in CRP and dialysate leukocytes may indicate poor outcome.
Blood Purification 02/2004; 22(4):360-6. · 2.10 Impact Factor
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ABSTRACT: Membranous glomerulonephritis (MGN) has a variable clinical course, and factors that determine the prognosis are unknown. Our previous study suggested that urinary excretion of vascular endothelial growth factor (VEGF) is decreased in active MGN, but normalizes in remission. In the present study, VEGF protein and messenger RNA (mRNA) expression were investigated in this disease.
Twelve patients with clinically active and/or progressive MGN were studied by using urinary assays for VEGF and soluble VEGF receptor-1 (sVEGF-R1), semiquantitative scoring of serial renal biopsy specimens by using immunohistochemical staining for VEGF protein, and in situ hybridization for VEGF mRNA. Results were compared with healthy controls and normal parts of nephrectomized kidneys.
Urinary VEGF excretion was decreased significantly (P < 0.001 versus controls) in MGN, but there was no difference in sVEGF-R1 excretion compared with healthy subjects. VEGF protein expression was diminished significantly in glomerular podocytes (P = 0.008), as well as in extraglomerular small arteries (P = 0.03) and arterioles (P = 0.008) in MGN. Total kidney VEGF score (the sum of scores of individual kidney compartments) also was decreased in MGN (P < 0.05) and remained low in repeated biopsies. Expression of VEGF mRNA localized predominantly to podocytes in normal kidneys was greatly reduced in MGN.
Clinically active MGN is associated with diminished expression of VEGF protein and mRNA, mainly in podocytes, and expression remains depressed in persistently active and/or progressive disease. This is reflected by decreased urinary VEGF excretion. These findings point to potentially reversible podocyte injury and, together with our previous study, suggest that VEGF may have a protective role during the evolution of MGN.
American Journal of Kidney Diseases 12/2003; 42(6):1139-48. · 5.43 Impact Factor
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ABSTRACT: IgA nephropathy (IgAN) and Henoch-Schönlein nephritis (HSN) share many clinical, histological and immunological features. It has been postulated that these two conditions have a common pathogenesis and that HSN might be a systemic form of IgAN. Activity of interleukin-1beta (IL-1beta) in urine has been found to be higher in IgAN and HSN patients than in healthy controls. Interaction between IL-1beta and interleukin-1 receptor antagonist (IL-1ra) plays a significant role in the regulation of inflammatory responses. We studied levels of urinary excretion of IL-1beta and IL-1ra in patients with IgAN and HSN.
Amounts of IL-1beta and IL-1ra excreted in 24-h urine samples collected from 241 IgAN, 26 HSN patients and from 33 healthy controls were determined. Results were expressed as cytokine/creatinine (ng/mmol) ratios.
Urinary IL-1beta excretion by the IgAN and HSN patients was no greater than urinary IL-1beta excretion by healthy controls. Urinary IL-1ra excretion by the IgAN patients was lower than urinary IL-1ra excretion by healthy controls (P < 0.05) and by the HSN patients (P < 0.01). In both patients and controls women had significantly higher IL-1ra, IL-1beta excretion levels and IL-1ra/IL-1beta ratios. The differences in urinary excretions of IL-1ra by the healthy controls and by the IgAN and HSN patients were significant in both sexes. Excretion of IL-1beta or IL-1ra did not correlate with excretion of urinary protein, duration of the disease or any histopathological variable. However, histopathological changes in renal biopsy specimens from patients with IL-1ra/IL-1beta ratios above normal were significantly milder than in renal biopsy specimens from patients with low or normal IL-1ra/IL-1beta ratios.
Urinary IL-1ra levels in IgAN patients were lower than urinary IL-1ra levels in healthy controls or HSN patients, a finding which may indicate that the two diseases have a different pathogenesis. Whether the male predominance in IgAN and HSN and the worse outcomes in males that have been reported previously in IgAN and HSN are connected with the lower excretion of IL-1ra and consequently lower IL-1ra/IL-1beta ratios in male patients than in female patients needs more thorough investigation.
Nephrology Dialysis Transplantation 09/2003; 18(9):1785-91. · 3.40 Impact Factor
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ABSTRACT: Interstitial fibrosis in the protocol biopsy specimens of transplanted kidneys is regarded as the most reliable predictor of future impaired renal function. Type I and III collagens are the main components of renal fibrosis. During the synthesis and deposition of type III collagen, an amino-terminal propeptide (PIIINP) of a molecular weight of 44 kDa is degraded from the collagen and secreted into surroundings. Increased circulating PIIINP has been shown to reflect ongoing fibrotic processes.
The extent of interstitial fibrosis in 6-month protocol biopsy specimens was recorded, and the urinary excretion of PIIINP in 24-hr urine specimens was measured in 79 graft patients. We also measured the urinary excretion of transforming growth factor (TGF)-beta 1, alpha(1)-microglobulin (alpha(1)M), and albumin and recorded the changes in creatinine clearance during 0.5 to 6 (mean, 4.3) posttransplant follow-up years.
The urinary excretion of PIIINP was significantly lower in patients with no interstitial fibrosis compared with patients with mild or moderate interstitial fibrosis (P<0.01). The urinary PIIINP-to-creatinine ratio correlated closely with the extent of interstitial fibrosis (r=0.410, P<0.001), with TGF-beta 1-to-creatinine (r=0.585, P<0.001) and alpha(1)M-to-creatinine (r=0.438, P<0.001) but not with the albumin-to-creatinine ratio. There was a close correlation between urinary TGF-beta 1 and alpha(1)M (r=0.508, P<0.001), whereas no correlation was found between urinary and serum PIIINP or between urinary PIIINP-to-creatinine ratio and glomerular filtration rate (GFR). During the follow-up, the GFR decreased in 42% of patients with a PIIINP-to-creatinine ratio over 100 ng/mmol, but only in 8% of patients with a ratio less than 100 ng/mmol (P<0.01).
These findings show that the urinary PIIINP-to-creatinine ratio reflects the ongoing fibrotic processes in the kidney. Tubular epithelial cell injury may initiate the fibrotic processes, and elevated concentrations of urinary TGF-beta 1 and alpha(1)M may associate with the increased production and deposition of collagen type III in the graft. We conclude that measurements of urinary excretion of PIIINP can be used as an early noninvasive indicator of renal fibrosis after kidney transplantation.
Transplantation 07/2003; 75(12):2113-9. · 4.00 Impact Factor
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ABSTRACT: A double-sandwich enzyme immunoassay method was developed for determination of serum immunoglobulin A (S-IgA) and mucosal secretory immunoglobulin A (sIgA) in duodenal brush samples obtained via endoscopy and the relationship between enteric mucosal sIgA, salivary sIgA and S-IgA in dogs was examined. Twenty healthy dogs underwent routine endoscopy. A brush sample from the duodenal mucosa was obtained and washed in PBS, with a serum sample being taken concurrently. A saliva sample was collected from twelve of these dogs. S-IgA and sIgA with total protein concentrations in the duodenal washings and saliva samples were determined. A significant negative correlation (r = -0.64, P = 0.0059) was found between duodenal sIgA/protein ratios and S-IgA concentrations. Saliva sIgA/protein ratios did not correlate with sIgA/protein ratios of duodenal samples. The method described here allows for direct assessment of duodenal IgA; therefore indirect measures based on serum IgA or salivary IgA can be avoided. In addition, these indirect measures appear to be poor indicators of duodenal sIgA competence in dogs.
Microbiology and Immunology 02/2003; 47(2):155-9. · 1.30 Impact Factor
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ABSTRACT: The bioincompatibility of dialysis solutions and recurrent episodes of peritonitis may alter peritoneal function. Cytokines and growth factors may play a role in inflammatory and fibrotic processes. We therefore investigated whether there is a correlation between peritoneal function and excretion of cytokines and other soluble factors in dialysate.
A personal dialysis capacity test was performed in 40 stable peritoneal dialysis patients. Tumour necrosis factor-alpha, interleukin-6 (IL-6), hyaluronan, soluble intercellular cell adhesion molecule-1 and transforming growth factor-beta1 were analysed from overnight and 24-h dialysates during the test.
We found little evidence for a direct correlation between cytokines and other soluble factors in dialysate and dialysis adequacy. There was, however, a strong correlation between the measured soluble factors and characteristics of the peritoneal membrane. Furthermore, IL-6 correlated with the number of previous episodes of peritonitis.
Soluble factors in dialysate may indicate ongoing inflammatory processes in the peritoneal membrane, which may gradually lead to alterations in peritoneal function.
Scandinavian Journal of Urology and Nephrology 02/2002; 36(6):450-4. · 0.99 Impact Factor
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ABSTRACT: Background. After transplantation, even if the graft starts functioning immediately, there are morphological and functional changes in tubular structures. In addition, acute allograft rejection causes damage in the tubular epithelium, tubular basement membrane, and intertubular connective tissue. It also affects the functional capacity of proximal tubular cells resulting in impaired reabsorption and thus increased urinary excretion of low molecular weight proteins.
Methods. We present a double-antibody radioimmunoassay for determination of the concentration of α1-microglobulin (α1 M) in urine. It was used to measure urinary excretion of α1 M approximately once a week during the first 1-6 posttransplant weeks in 136 consecutive patients: 30 patients developing acute rejection (75 24-hr urine samples) and 106 patients with stable graft function (223 24-hr urine samples). The results are expressed as α1 M/creatinine ratios.
Results. Approximately 8 days after transplantation the mean (±SD) urinary α1 M/creatinine ratio of all patients was 17.0±14.8 mg/mmol, being about the same both in patients with uncomplicated posttransplantation course (16.3±14.0 mg/mmol) and in those who later developed rejection (19.3±15.1 mg/mmol), but about 60-fold higher than in healthy controls (0.27±0.15 mg/mmol). At that time, when all patients were included there was a correlation (r=0.3465, P <0.001) between α1 M/creatinine ratio and duration of cold ischemia. Thereafter, during the second week α1 M/creatinine ratio decreased in 89% of patients with stable graft function, but only in 14% of patients who later developed rejection (P <0.001). On the contrary, a significant increase (P <0.01) of α1 M/creatinine ratio was observed 4 to 1 day before rejection in all 15 patients, who had urines collected at that time. At the end of the follow-up period, α1 M/creatinine ratio in patients with rejection was 3-fold compared with the nonrejecting patients, and 100-fold compared with the healthy controls.
Conclusion. These results show that cadaveric transplantation results in impaired low molecular weight protein reabsorption, the degree of dysfunction relating to the duration of cold ischemia, and suggest that during the posttransplant weeks decreasing α1 M/creatinine ratio in consecutively collected urine samples indicates improved tubular function and in most cases rules out development of acute rejection.
Transplantation 10/2000; 70(8):1154-1159. · 4.00 Impact Factor
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ABSTRACT: Glucose and other bioincompatible factors of conventional peritoneal dialysis solutions may damage the peritoneal membrane. The aim of our study was to investigate whether replacement of glucose with icodextrin (ID) or amino acids (AA) affects inflammatory parameters or cancer antigen 125 (CA125).
Either ID or AA was used, in random order, in one daily exchange during an 8-week period. After the first study period, the patients entered a washout period and then switched to the other study solution for an 8-week period. C-reactive protein (CRP) was measured in serum, and CA125, tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), and hyaluronan (HA) were measured in the overnight dwell dialysates at the beginning and end of the study periods.
A university hospital.
22 patients with duration on peritoneal dialysis of 1.5 - 6.3 months.
Levels of serum CRP and dialysate CA125, IL-6, HA, and sICAM-1 during use of ID and AA were compared to levels during use of glucose-only-based solutions.
CRP increased significantly during use of ID. CA125 increased significantly during 8 weeks' use of AA, from 22.8 (5.4 - 89.0) to 42.9 (7.1 - 92.9) kU/L (p = 0.007). IL-6 increased during 8 weeks' use of AA, from 22.0 (9.0 - 108.0) to 36.5 (14.0 - 93.0) ng/L (p = 0.002) and ID, from 25.5 (8.0 - 82.0) to 40.0 (12.0 - 118.0) ng/L (p = 0.008). TNF-alpha also increased significantly during use of ID, but showed no significant changes during use of AA.
The use of glucose-free solutions, especially AA, may lead to preservation of mesothelial cell mass and host defense. However, activation of systemic and peritoneal inflammation may appear during the use of ID and to a lesser extent during use of AA.
Peritoneal dialysis international: journal of the International Society for Peritoneal Dialysis 25(5):453-60. · 2.10 Impact Factor
