Treatment of hyper-IgG4 disease with sequential corticosteroids and tamoxifen - case report and review of the literature.

We report a patient with multifocal fibrosclerosis presenting as sialadenitis, hepatic fibrosis, and retroperitoneal fibrosis with renal failure. His medical management consisted of prednisone (4 months at 40 mg daily, then tapered down to 5 mg daily for another 14 months) and 18 months of tamoxifen. He responded clinically and radiographically to this regimen, and remains in clinical remission 10 months after discontinuing medical therapy. Subsequent histologic examination of submandibular gland tissue revealed strong staining for IgG4-positive plasma cells. To our knowledge, this is the first case of confirmed multifocal hyper-IgG4 disease to be successfully treated with sequential corticosteroids and tamoxifen.

Intravenous iron sucrose changes the intraperitoneal homeostasis.

BACKGROUND/AIMS: Intravenous iron infusion is the accepted way of supplementation of that compound in uremic patients. The aim of the study was to evaluate whether this treatment affects intraperitoneal homeostasis in patients on peritoneal dialysis. METHODS: Blood and peritoneal dialysate samples were collected from 10 patients treated with continuous ambulatory peritoneal dialysis who were given 100 mg iron sucrose (IS) intravenously. Systemic and peritoneal permeability as well as transperitoneal transport were studied. The effect of spent dialysate was tested in vitro on human peritoneal mesothelial cells (MCs). RESULTS: Dialysate total iron was increased (+19%, p < 0.01) during intravenous infusion of IS. Immediately after infusion the concentration of 8-OHdG was increased in plasma (+10%, p < 0.01) and in dialysate (+5%, p < 0.05). IS infusion caused a transient decrease in peritoneal permeability to protein (-42%, p < 0.05) and glucose (-30%, p < 0.01) and a reduction in dialysate cell count (-58%, p < 0.05). During the exchange dialysate hyaluronan was increased by 27% (p < 0.01). Spent dialysate, tested ex vivo on cultured MC, induced oxidative stress (+39%, p < 0.01), slowed their proliferation (-20%, p < 0.01), and stimulated MCP-1 synthesis (+46%, p < 0.01). Iron content in MCs exposed to dialysate obtained after IS infusion was increased by 32% (p < 0.01). CONCLUSION: Intravenous infusion of IS causes oxidative stress and inflammation within peritoneal MCs which may impair viability of the peritoneum.

The effect on renal structure and function of late-life-introduced caloric restriction (CR) in rats.

Previous studies have shown that life-long caloric restriction in rats protects the kidneys from age-dependent injury. In this study, we analyzed whether late-life-introduced caloric restriction has a similar effect. The study lasted 12 months. Three groups of animals were analyzed: rats fed "ad libitum" (AD, n = 9), rats on 60% caloric restriction (CR, n = 9), and rats fed "ad libitum" for the first six months of their life then switched to 60% caloric restriction thereafter (LCR, n = 9). At the end of the study kidney function was assessed and kidney samples were analyzed histologically. Serum creatinine and urine albumin were higher in AD than in both CR and LCR (P < 0.001). Creatinine clearance (Cl(cr)) corrected for body weight was lowest in AD and comparable in CR and LCR. Similarly Cl(cr) corrected for kidney weight was lower in AD than in both CR and LCR (P < 0.05). Severe albuminuria was observed only in AD. In CR and LCR the amount of albumin excreted was comparable (AD vs. CR, P < 0.0001; AD vs. LCR, P < 0.001). In morphometric analysis, the mean size of the glomeruli was higher in AD than in both CR and LCR (P < 0.01). Similar results were found for the mesangial area (AD vs. CR, P < 0.001; AD vs. LCR, P < 0.01) and for mesangial cell counts (AD vs. CR, P < 0.001; AD vs. LCR, P < 0.05). No difference was found between CR and LCR in morphometry. In conclusion, our study indicates that late-life introduction of caloric restriction reverses most of the structural and functional changes observed in the kidneys of "ad libitum"-fed rats.

Vascular complications of the lower extremities in diabetic patients on peritoneal dialysis.

BACKGROUND: Diabetic patients with end-stage renal disease (ESRD) are at high risk for developing foot complications and few have studied this complication in the diabetic patients treated with peritoneal dialysis (PD). The purpose of this study was to examine peripheral vascular disease (PVD) in diabetic patients with ESRD, who are being treated with PD, and to identify those factors that may contribute to its development. PATIENTS: We reviewed retrospectively the charts of 71 diabetic patients who started PD between January 1999 and January 2006, inclusive, and recorded their demographic data, their treatment regimens, their complications and the results of biochemical investigation(s) at the beginning and throughout their follow-up period. All patients were under the care of a chiropodist who examined them at regular intervals and more often when needed. We divided the patients into two groups with respect to the presence of complications in the lower extremities, such as ulcers, open wounds, osteomyelitis, necrotizing or gangrenous lesions, and amputations, intermittent claudication and/or the presence on an imaging examination of changes in the leg vessels consistent with vascular disease. RESULTS: 33 of the 71 patients had some type of a foot lesion. There were 8 amputations in the course of 176 patient-years (2 double amputations), or 1 amputation per 30 PD patient-years. Those patients with foot complications were treated more frequently with CCPD (p<0.05), more often had peripheral neuropathy (p<0.002), as well as coronary artery disease (p<0.044). They had lower serum albumin (p<0.005), significantly higher serum phosphorus (p<0.047) and they received higher doses of erythropoietin (p<0.042). There was no statistically significant difference between the groups regarding sex, age at initiation of PD, type of diabetes, use of insulin, levels of HbA(1c), body mass index (BMI), presence of retinopathy, cerebral vascular disease, hyperlipidemia, smoking, rate of transplantation, rate of drop-out from PD, time-averaged Kt/V, creatinine clearance, serum calcium, Ca x P and intact PTH. In a multiple logistics regression model, only peripheral neuropathy and hypoalbuminemia were independently associated with the development of lower-extremity complications (p<0.0066 and p <0.026, respectively). One-, two- and three-year cumulative survival of the whole group was 91.5%, 78.8% and 69%, respectively. Patients with foot lesions had a lower survival than those without. Interestingly though, those patients, who had had an amputation, survived as long as those patients, who did not have foot complications at all. CONCLUSION: In conclusion, compared to reports in the literature, our diabetic patients on PD had a lower rate of foot complications and amputation probably because of early intervention by our chiropodist. This fact stresses the need for constant and expert monitoring of the condition of the diabetic patient's feet, especially in those with low serum albumin and peripheral neuropathy.

Phosphorus control in peritoneal dialysis patients.

Hyperphosphatemia is independently associated with an increased risk of death among dialysis patients. In this study, we have assessed the status of phosphate control and its clinical and laboratory associations in a large international group of patients on chronic peritoneal dialysis (PD) treatment. This cross-sectional multicenter study was carried out in 24 centers in three different countries (Canada, Greece, and Turkey) among 530 PD patients (235 women, 295 men) with a mean+/-s.d. age of 55+/-16 years and mean duration of PD of 33+/-25 months. Serum calcium (Ca(2+)), ionized Ca(2+), phosphate, intact parathyroid hormone (iPTH), 25-hydroxy vitamin D(3), 1,25-dihydroxy vitamin D(3), total alkaline phosphatase, and bone alkaline phosphatase concentrations were investigated, along with adequacy parameters such as Kt/V, weekly creatinine clearance, and daily urine output. Mean Kt/V was 2.3+/-0.65, weekly creatinine clearance 78.5+/-76.6 l, and daily urine output 550+/-603 ml day(-1). Fifty-five percent of patients had a urine volume of <400 ml day(-1). Mean serum phosphorus level was 4.9+/-1.3 mg per 100 ml, serum Ca(2+) 9.4+/-1.07 mg per 100 ml, iPTH 267+/-356 pg ml(-1), ionized Ca(2+) 1.08+/-0.32 mg per 100 ml, calcium phosphorus (Ca x P) product 39+/-19 mg(2)dl(-2), 25(OH)D(3) 8.3+/-9.3 ng ml(-1), 1,25(OH)(2)D(3) 9.7+/-6.7 pg ml(-1), total alkaline phosphatase 170+/-178 U l(-1), and bone alkaline phosphatase 71+/-108 U l(-1). While 14% of patients were hypophosphatemic, with a serum phosphorus level lower than 3.5 mg per 100 ml, most patients (307 patients, 58%) had a serum phosphate level between 3.5 and 5.5 mg per 100 ml. Serum phosphorus level was 5.5 mg per 100 ml or greater in 28% (149) of patients. Serum Ca(2+) level was > or =9.5 mg per 100 ml in 250 patients (49%), between 8.5 and 9.5 mg per 100 ml in 214 patients (40%), and lower than 8.5 mg per 100 ml in 66 patients (12%). Ca x P product was >55 mg(2)dl(-2) in 136 patients (26%) and lower than 55 mg(2)dl(-2) in 394 patients (74%). Serum phosphorus levels were positively correlated with serum albumin (P<0.027) and iPTH (P=0.001), and negatively correlated with age (P<0.033). Serum phosphorus was also statistically different (P = 0.013) in the older age group (>65 years) compared to younger patients; mean levels were 5.1+/-1.4 and 4.5+/-1.1 mg per 100 ml, respectively, in the two groups. In our study, among 530 PD patients, accepted uremic-normal limits of serum phosphorus control was achieved in 58%, Ca x P in 73%, serum Ca(2+) in 53%, and iPTH levels in 24% of subjects. Our results show that chronic PD, when combined with dietary measures and use of phosphate binders, is associated with satisfactory serum phosphorus control in the majority of patients.

Patient and technique survival of diabetics on peritoneal dialysis: one-center's experience and review of the literature.

BACKGROUND: Diabetes is the leading cause of end-stage renal disease (ESRD). This retrospective study investigated the long-term patient and technique survival and sought to identify the predictors of mortality in diabetic patients receiving PD. METHODS: Patients, aged 17 years or more who commenced home PD between January 31, 1994, and December 31, 2001 were included. Clinical data were available for 358 patients out of 418 total patients who started PD during this period. They were followed until cessation of PD, death, or to January 31, 2003. Survival probabilities were generated according to the Kaplan-Meier method, and multivariate Cox proportional hazards models were used to assess predictors of survival. RESULTS: A total of 358 patients were enrolled in the study. Among them, 139 patients (38.8%) were diabetics. The 1-, 2-, 3- and 5-year patient survival rates were 91%, 76%, 66% and 47% in diabetics and 94%, 89%, 84% and 69% in non-diabetics, respectively. Median actuarial patient survival for diabetic patients (51.8 months; 95% CI 36.0 â 67.5 months) was significantly shorter than that of non-diabetic patients (log rank 14.117, p < 0.001). Death-censored technique survival rates at 1-, 2-, 3- and 5-year were 90%, 83%, 67% and 58% in diabetic, and 94%, 87%, 77% and 70% in non-diabetic patients, respectively. Similar to patient survival, the median technique survival time was significantly shorter for diabetic patients (63.9 months; 95% CI 35.7 - 92.2 months) than that of non-diabetic patients (log rank 4.884, p = 0.027). Multivariate Cox regression analysis showed that advancing age was the only independent predictor of death in the diabetic patients, whereas higher age and wider pulse pressure were associated with mortality in non-diabetic patients. CONCLUSION: Long-term patient and technique survival for diabetic patients on PD seem to be improved compared to our previous report and other studies. The mortality of diabetic patients was predicted predominantly by advancing age. PD remains a viable form of long-term renal replacement therapy for diabetic patients with ESRD.

Duplicate use of angiotesin-converting enzyme (ACE) inhibitors in a community-dwelling elderly population in Poland.

In this paper the data on the duplicate use of ACE inhibitors among a community-dwelling elderly population are presented. Using a questionnaire, 1000 subjects were interviewed concerning the use of drugs, 654 females, mean+/-SD age: 72.6+/-6.5 years. They were divided into two groups: Group A (5%) taking at least two ACE inhibitors (n=50) and Group B: those who used either a single ACE inhibitor or no ACE inhibitor (n=950). In Group A, 49 individuals were taking two different ACE inhibitors concomitantly and one was using three. The most commonly used ACE inhibitor was enalapril (29 of 50 subjects). Subjects in Group A consumed significantly more drugs, both of prescription (Rx) and nonprescription (OTC), compared to those in Group B (total means: 8.4+/-2.8 vs. 6.7+/-3.2; p<0.01, Rx means: 6.3+/-2.5 vs. 5.2+/-2.8, p<0.05, OTC means: 2.0+/-1.6 vs. 1.6+/-1.5, p<0.05). Also, they were more likely to have consulted a cardiologist (17/50 vs. 201/950, p<0.05). The duplicate use of ACE inhibitors in 5% of a population of community-dwelling elderly patients seems to be caused by both poor doctor-doctor communication and polypharmacy. This phenomenon could possibly be dangerous especially when potential additive adverse effects are taken into account.

Severe vitamin D deficiency in chronic renal failure patients on peritoneal dialysis.

UNLABELLED: The aim of this study was to evaluate the prevalence of vitamin D deficiency in chronic renal failure (CRF) patients on peritoneal dialysis (PD) and to correlate the findings with various demographic and renal osteodystrophy markers. METHOD: This cross-sectional, multicenter study was carried out in 273 PD patients with a mean age of 61.7 +/- 10.9 years and mean duration of PD 3.3 +/- 2.2 years. It included 123 female and 150 male patients from 20 centers in Greece and Turkey, countries that are on the same latitude, namely, 36-42 degrees north. We measured 25(OH)D3 and 1.25(OH)2D3 levels and some other clinical and laboratory indices of bone mineral metabolism. RESULTS: Of these 273 patients 92% (251 patients) had vitamin D deficiency i.e. serum 25(OH)D3 levels less than 15 ng/ml, 119 (43.6%) had severe vitamin D deficiency i.e., serum 25(OH)D3 levels, less than 5 ng/ml, 132 (48.4%) had moderate vitamin D deficiency i.e., serum 25(OH)D3 levels, 5-15 ng/ml, 12 (4.4%) vitamin D insufficiency i.e., serum 25(OH)D3 levels 15 - 30 ng/ml and only 10 (3.6%) had adequate vitamin D stores. We found no correlation between 25(OH)D3 levels and PTH, serum albumin, bone alkaline phosphatase, P, and Ca x P. In multiple regression analyses, the independent predictors of 25(OH)D3 were age, presence of diabetes (DM-CRF), levels of serum calcium and serum 1.25(OH)2D3. CONCLUSION: We found a high prevalence (92%) of vitamin D deficiency in these 273 PD patients, nearly one half of whom had severe vitamin D deficiency. Vitamin D deficiency is more common in DM-CRF patients than in non-DM-CRF patients. Our findings suggest that these patients should be considered for vitamin D supplementation.

Time to reconsider saline as the ideal rinsing solution during abdominal surgery.

BACKGROUND: Peritoneal mesothelial cells lining the peritoneal cavity play a primary role in prevention of formation of peritoneal adhesions, which depends mainly on their fibrinolytic activity. During surgical procedures, the abdominal cavity is in most cases rinsed with normal saline solution, which may modify the fibrinolytic activity of the peritoneal mesothelium and predispose to formation of adhesions. The goal of our experiments was to evaluate how normal saline and other solutions affect the fibrinolytic properties of the peritoneal mesothelial cells. MATERIAL AND METHODS: Experiments were performed on in vitro cultures of human peritoneal mesothelial cells. Mesothelial monolayers were exposed during 6 hours to the following solutions: culture medium (control), .9% NaCl, Hanks solution, Earles solution, new peritoneal dialysis fluid with low glucose degradation products (GDP) concentration (PDF), and peritoneal dialysis fluid with high concentration of GDP (PDF-GDP). Afterwards, morphology of the cells as well as leakage of lactate dehydrogenase (LDH) from their cytosol were evaluated. During the next 24 hours when the cells were cultured in standard medium synthesis of interleukin-6 (IL-6), tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) were studied. RESULTS: Mesothelial monolayers exposed to .9% NaCl or to PDF-GDP showed destruction of their morphology after 6 hours incubation and in case of PDF-GDP release of LDH from the cytosol was increased by 275% versus the control (P<.05). During subsequent culture of all cells in standard medium, the release of IL-6 was decreased in cases of cells pretreated with .9% NaCl (-58%, P<.05) or PDF-GDP (-93%, P<.001). The release of t-PA was also reduced from cells pretreated with .9% NaCl (-71%, P<.01) or with PDF-GDP (-74%, P<.01) but increased after exposure of these cells to PDF (+35%, P<.05). Statistically significant decrease of PAI-1 synthesis was observed in cells preexposed to .9% NaCl (-69%, P<.01) or to PDF-GDP (-82%, P<.05). When changes in the PAI-1/t-PA ratio were calculated, a strong tendency for increase of that value was seen in cells pretreated with .9% NaCl or Earles salts solution but not with PDF. However, in cases of Hanks solution, a significant increase in the PAI-1/t-PA ratio was observed (+104%, P<.01). CONCLUSION: Exposure of the peritoneal mesothelial cells to .9% NaCl, Hanks, Earles salts solution, or PDF-GDP results either in reduction of their viability or in loss of their fibrinolytic activity. Peritoneal dialysis fluid with a low content of glucose degradation products appears to be the optimal solution causing the least damage to mesothelial cells and therefore may be the ideal solution for rinsing the abdominal cavity with low risk of inducing deterioration of the mesothelial cells fibrinolytic activity and formation of adhesions. We postulate therefore that such hypertonic peritoneal dialysis fluids should be used not only during peritoneal dialysis but also for rinsing the abdominal cavity during any surgical procedures.

Difference in estimated GFR with two different formulas in elderly individuals.

The aim of this study was to characterize the differences between the prediction of GFR with Cockcroft-Gault formula (CG=(140-age)/(72 x PCr (mg/ml), for females multiplied by 0.85) and the new formula based on the multicenter trial of the Modification of Diet in Renal Diseases (MDRD=186 x P (Cr) (-1.154) x age(-0.203); 0.742 if patient is female) in elderly subjects. The study involved 100 individuals aged 65-111 years (mean age 88.3+/-14.7; 79 females and 21 males). In all subjects GFR was estimated according to both formulas mentioned above and expressed in ml/min/1.73 m2. Thereafter we calculated the difference between MDRD and CG (MDRD-CG) and analyzed its determinants in every subject. Mean GFR, obtained with MDRD was 76.0+/-24.0, whereas according to CG 67.9+/-18.6 (p < 0.0001). However, the mean MDRD-CG was up to 30.0+/-26.6 which means that MDRD results were much higher in comparison with CG. Using the multiple linear regression analysis we showed that MDRD-CG strongly depend on age (p < 0.0001), BMI (p < 0.0001) and serum creatinine concentration (p<0.0001). However, the gender has not effect on MDRD-CG value. The values of MDRD-CG strongly and positively correlated with age (r=0.7027, p < 0.0001) and negatively both with body mass index (r=-0.7171, p < 0.0001) and serum creatinine (r=-0.5590, p < 0.0001). In summary, our results show that the difference between MDRD and CG strongly depends on age, BMI and Scr. Investigators should be aware of these differences and take it into account in elderly.

N-acetylglucosamine reduces inflammatory response during acute peritonitis in uremic rats.

BACKGROUND: Peritoneal dialysis (PD) induces intraperitoneal inflammation and that process may be uremia. The goal of this study is to evaluate the effect of uremia on the kinetics of peritonitis and furthermore test the anti-inflammatory potential of N-acetylglucosamine (NAG) in a uremic environment. METHODS: Experiments were performed on healthy Wistar rats and on animals with impaired renal function. Acute PD was performed in all animals with dialysis fluid containing either glucose (GLU) or NAG as osmotic solutes. Peritonitis was induced by addition of lipopolysaccharide from Escherichia coli (LPS) to the dialysis fluid. Transperitoneal transport of water and solutes as well as intraperitoneal and systemic inflammation were evaluated. RESULTS: Uremia reduces peritoneal permeability to total protein during peritonitis (-33% vs. control, p < 0.001) and increases net ultrafiltration (+2.5 +/- 2.2 vs. -2.7 +/- 3.2 ml in control, p < 0.001). In uremic rats with peritonitis, reduced dialysate levels of the following inflammatory mediators were detected as compared to healthy animals: MCP-1 (-15%, p < 0.01); IL-1beta (-53%, p < 0.001), and elastase (-28%, p < 0.02). In the serum of uremic rats, the increase in TNFalpha and MCP-1 concentrations was smaller than in control rats: -44% (p < 0.02) and -39% (p < 0.001), respectively. NAG used as an osmotic solute in rats with preserved renal function decreases intraperitoneal and systemic inflammation during acute peritonitis. Drained dialysate volume was increased in the NAG group by 32% (p < 0.001) and transperitoneal loss of protein was reduced by 21% (p < 0.002). When NAG was used as the osmotic solute instead of GLU, intraperitoneal inflammation in uremic animals was further reduced: TNFalpha (-40%, p < 0.05); IL-1beta (-49%, p < 0.005); MCP-1 (-21%, p < 0.005). The presence of NAG also reduced the increased blood level of IL-1beta (-47%,p < 0.02) and MCP-1 (-36%, p < 0.02). CONCLUSIONS: Intensity of acute peritonitis is reduced during uremia. NAG exerts a systemic and peritoneal anti-inflammatory action under conditions of uremia that confirms the potential use of this compound as an osmotic agent in the PD fluids that also decreases inflammation.

The Toronto Western Hospital catheter: one center's experience and review of the literature.

BACKGROUND: We report our center's experience with the Toronto Western Hospital (TWH) catheter, and discuss our catheter survival and complication rates. METHODS: Retrospective chart review of patients receiving peritoneal dialysis therapy via a TWH catheter. Catheter complication rates of peritonitis, exit site infection, obstruction, leak, and malfunction were assessed. A catheter was considered failed if removed because of exit site infection, obstruction, or malfunction. All other catheters, even if removed for other reasons, were considered censured. Survival was defined as the period from insertion to failure or censure date, and reported using Kaplan Meier analysis. RESULTS: 192 patients with a total of 208 TWH catheters (4,845.3 catheter months) were analyzed. Our overall 1- and 3-year catheter survival rates were identical at 0.9182. Our catheter complication rates (expressed as number of catheter months per event) were 31.3 for peritonitis, 42.9 for exit site infection, 72.3 for obstruction, 538.4 for malfunction, and 969.1 for catheter leak. Our findings were similar to those reported in the literature for TWH and other peritoneal catheters.

Predictive factors of low HCO3- levels in peritoneal dialysis patients.

BACKGROUND: Metabolic acidosis is a major metabolic abnormality in end-stage renal disease (ESRD) and alkali is provided with dialysis treatment to patients on chronic peritoneal dialysis (CPD) to keep their acid-base balance within normal serum HCO3- levels. METHODS AND RESULTS: We examined the levels of venous serum HCO3- in 163 patients on CPD and the predictive factors for HCO3- levels low enough to indicate metabolic acidosis. The mean value for HCO3- was 26+/-2.4 mmol/l and for anion gap was 13.1+/-3.1 mEq/l. A serum bicarbonate concentration of less than 24 mmol/l, compatible with metabolic acidosis, was observed in 13.5% of the patients. In a multivariate analysis HCO3- levels were directly correlated with older age and use of CaCO3- as phosphate binders, and inversely associated with serum potassium, the use of sevelamer and low lactate dialysis solutions. Higher serum urea levels, the use of low lactate solutions and sevelamer instead of CaCO3 were significantly predictive factors for HCO3- levels < 24 mmol/l. CONCLUSIONS: Venous HCO3- and anion gap values were within the normal ranges in stable CPD patients. In 13.5% of them, however, chronic metabolic acidosis was observed based on venous HCO3- levels < 24 mmol/l. Dietary protein intake, the use of sevelamer and low (35 mmol/l) concentration of lactate in dialysis solutions are important predictive factors for chronic metabolic acidosis in these patients.

Effect of valsartan versus lisinopril on peritoneal sclerosis in rats.

BACKGROUND: Peritoneal sclerosis (PS) is one of the most serious causes of failure in long-term peritoneal dialysis. Angiotensin II is known to promote fibrosis and inflammation in various tissues. We previously showed that ACE inhibitors (ACEIs) have beneficial effects on hypertonic PD solutions (3.86% PD) induced peritoneal alterations. The aim of this study is to compare the effects of an ACEI and a receptor blocker on peritoneal alterations induced by hypertonic PD solutions in rats. METHODS: Forty-three non-uremic rats were divided into four groups: group I (Sham) rats received no treatment (n=11), group II received hypertonic (3.86%, 10 ml/day) PD solution (n = 10) and groups III and IV received hypertonic PD solution (10 ml/day) plus 640 mg/L valsartan (n=11) and 100 mg/L lisinopril in drinking water (n = 11). After four weeks, a one-hour peritoneal equilibration test (PET) was performed with 3.86% PD solution. Dialysate-to-plasma urea ratio (D/P urea), glucose reabsorption (D 1 /D 0 glucose), ultrafiltration volume (UF), dialysate protein, TGFbeta 1 and VEGF levels were determined. RESULTS: Administration of valsartan or lisinopril resulted in preserved UF (8+/-0.8 and 6.7+/-0.7 vs 4.9+/-0.8 mL), D1/D0 glucose (0.69+/-0.05 and 0.62+/-0.05 vs 0.56+/-0.04) and peritoneal thickness (19.4+/-2.9 and 28.5+/-5.2 vs 53+/-3 microm), respectively. Both higher level of TGF beta 1 (206+/-40 vs 474+/-120 pg/mL, p<0.05), and VEGF in dialysate effluent (4+/-0.4 vs 7.9+/-3 pg/mL, p>0.05), was determined in the dextrose group. Both cytokines are partially inhibited by valsartan or lisinopril (p >0.05) CONCLUSION: Exposure to hypertonic glucose solution resulted in alterations in peritoneal transport manifested by a rapid dissipation of the glucose gradient and resultant impaired UF response. Administration of valsartan or lisinopril led to attenuation of these alterations. We suggest that the equal protection of the peritoneal membrane from the effects of hypertonic glucose was achieved by receptor blockers and ACE inhibitors.

Atorvastatin improves peritoneal sclerosis induced by hypertonic PD solution in rats.

BACKGROUND: Peritoneal sclerosis is a complication of peritoneal dialysis and results in ultrafiltration failure. It is related to chronic peritoneal injury due to dialysis solution content and recurrent peritonitis. Statins have anti-inflammatory properties which may be of value in modulating responses to injury. We evaluated the capacity of atorvastatin to modify peritoneal alterations secondary to hypertonic glucose. METHODS: Thirty-two non-uremic rats were divided into three groups: group I (Sham) rats received no treatment (n=11), group II received hypertonic (3.86%, 10 ml/day) PD solution (n=10) and group III received hypertonic PD solution (10 ml/day) plus 80 mg/L atorvastatin in drinking water (n=11). After four weeks, a one-hour peritoneal equilibration test (PET) was performed with 3.86% PD solution. Dialysate-to-plasma urea ratio (D/P urea), glucose reabsorption (D 1 /D 0 glucose), ultrafiltration volume (UF), dialysate protein, TGF-beta 1 and VEGF levels were determined. RESULTS: Administration of atorvastatin resulted in preserved UF (4.9+/-0.8 vs 7.5+/-0.6 mL, p <0.01), protein loss (2.2+/-0.2 vs 2.1+/-0.1 g/L, p >0.05), and peritoneal thickness (53+/-3 vs 26+/-4 microm, p <0.01). D 1 /D 0 glucose was significantly reduced in the dextrose group (0.70+/-0.02 vs 0.56+/-0.04, p <0.01). Both higher levels of TGF-ss 1 (206+/-40 vs 474+/-120 pg/mL, p<0.05), and VEGF in dialysate effluent (4+/-0.4 vs 7.9+/-3 pg/mL, p>0.05), was determined in the dextrose group. CONCLUSION: Exposure to hypertonic glucose solution resulted in alterations in peritoneal transport manifested by a rapid dissipation of the glucose gradient and resultant impaired UF response. Administration of atorvastatin led to prevention of these alterations. We suggest that the anti-inflammatory properties of statins are useful in providing protection of the peritoneal membrane from the effects of hypertonic glucose.