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Encapsulating peritoneal sclerosis is a rare, but potentially lethal, complication of peritoneal dialysis. Treatment of patients with encapsulating peritoneal sclerosis is controversial. Conservative treatment carries a poor outcome, and immunosuppressive drugs are now used frequently. Most commonly, these immunosuppressive regimens include steroids with or without azathioprine or cyclosporine. Mycophenolate mofetil is a reversible DNA synthesis inhibitor that frequently replaces azathioprine in renal transplantation because of its improved immunosuppressive potency and better side-effect profile. We report 3 cases of encapsulating peritoneal sclerosis in continuous ambulatory peritoneal dialysis patients for which an association of prednisone and mycophenolate mofetil significantly modified the evolution of the disease. All 3 patients showed significant improvement within a month and are still alive more than 2 years after the diagnosis of encapsulating peritoneal sclerosis. None experienced a relapse or abdominal symptoms, and body weights are stable. This is the first report of 3 cases of successful treatment of patients with encapsulating peritoneal sclerosis with prednisone and mycophenolate mofetil.

Secondary hyperparathyroidism develops early in patients with chronic kidney disease (CKD). Clinical guidelines from the National Kidney Foundation-Kidney/Disease Outcomes Quality Initiative emphasize the need to control parathyroid hormone (PTH), calcium, and phosphorus levels in patients with CKD not receiving dialysis to reduce poor outcomes. This phase 2 study evaluated the effects of the oral calcimimetic cinacalcet hydrochloride in patients with CKD not on dialysis therapy.A randomized, double-blind, placebo-controlled, 18-week study enrolled adults with an estimated glomerular filtration rate of 15 to 50 mL/min/1.73 m2 (0.25 to 0.83 mL/s/1.73 m2) and an intact PTH (iPTH) level greater than 130 pg/mL (ng/L). Cinacalcet (or placebo) was titrated from 30 to 180 mg once daily to obtain a 30% or greater reduction in iPTH levels from baseline.Baseline mean iPTH levels were 243 pg/mL (ng/L) in the cinacalcet group (n = 27) and 236 pg/mL (ng/L) in the control group (n = 27). At baseline, 28% of subjects were being administered vitamin D sterols and 43% were being administered phosphate binders or calcium supplements. The addition of cinacalcet significantly decreased iPTH concentrations compared with controls during the efficacy-assessment phase: 56% versus 19% of subjects achieved a 30% or greater reduction in iPTH levels (P = 0.006), and mean iPTH levels decreased by 32% in the cinacalcet group, but increased by 6% in the control group (P0.001). Mean serum calcium and phosphorus levels remained within normal range throughout the study. Cinacalcet generally was well tolerated; the most frequent adverse events were gastrointestinal.This preliminary study provides evidence that cinacalcet is efficacious for the treatment of secondary hyperparathyroidism in subjects with CKD not receiving dialysis.

The saphenous partial ligation (SPL) model is a new, easily performed, rodent model of neuropathic pain that consists of a unilateral partial injury to the saphenous nerve. The present study describes behavioral, pharmacological and molecular properties of this model. Starting between 3 and 5 days after surgery, depending on the modality tested, animals developed clear behaviors indicative of neuropathic pain such as cold and mechanical allodynia, and thermal and mechanical hyperalgesia compared with naive and sham animals. These pain behaviors were still present at 1 month. Signs of allodynia also extended to the sciatic nerve territory. No evidence of autotomy or bodyweight loss was observed. Cold and mechanical allodynia but not thermal and mechanical hyperalgesia was reversed by morphine (4 mg/kg i.p.). The cannabinoid receptor agonist WIN 55,212-2 (5 mg/kg i.p.) improved signs of allodynia and hyperalgesia tested except for mechanical hyperalgesia. Gabapentin (50 mg/kg i.p.) was effective against cold and mechanical allodynia but not hyperalgesia. Finally, amitriptyline (10 mg/kg i.p.) failed to reverse allodynia and hyperalgesia and its administration even led to hyperesthesia. Neurobiological studies looking at the expression of μ opioid receptor (MOR), cannabinoid CB 1 and CB 2 receptors showed a significant increase for all three receptors in ipsilateral paw skin, L3–L4 dorsal root ganglia and spinal cord of neuropathic rats compared with naive and sham animals. These changes in MOR, CB 1 and CB 2 receptor expression are compatible with what is observed in other neuropathic pain models and may explain the analgesia produced by morphine and WIN 55,212-2 administrations. In conclusion, we have shown that the SPL is an adequate model that will provide a new tool for clarifying peripheral mechanisms of neuropathic pain in an exclusive sensory nerve.

Inflammation reduces activity and expression of hepatic cytochrome P450 (P450) and therefore diminishes drug biotransformation. This study aimed to identify the serum mediators triggered by a viral infection and an aseptic inflammation that downregulate P450 isoforms. Incubation of hepatocytes with serum from rabbits with a turpentine-induced inflammation or humans with a viral infection decreased the amount of cytochrome 1A1 (CYP1A1), 1A2 and 3A6 mRNA and apoproteins. By serum fractionation and immuno-neutralization, we showed that in the aseptic inflammation, interleukin-6 and, to a lesser degree, interleukin-1beta are involved in the downregulation of all three isoforms. In serum from humans with a viral infection, interleukin-1beta, interleukin-6, interferon-gamma and tumour necrosis factor-alpha contribute to the downregulation of P450 isoforms. CYP1A1 and 1A2 are regulated by serum mediators at the transcriptional level, while the expression of CYP3A6 appears to be under the control of pre- and posttranscriptional mechanisms.

Background: Over the last decade, the age of dialysis patients has been increasing steadily in several units in Canada. Our main objective was to assess prevalence, co-morbidity and outcome of ESRD patients over 75 years old at the beginning of dialysis treatment in our center. As a group, they were compared to younger dialysis patients treated simultaneously. Methods: In the last 5 years, all cases beginning dialysis in our institution who were above 75 years of age were reviewed, as well as cases aged between 50 and 60 years who started dialysis during the same period. Between January 1996 and December 2000, among a total of 429 new chronic dialysis patients, 67 ESRD patients over 75 years (15.6%) and 66 patients between 50 and 60 years (15.4%) began dialysis treatment. Results – Primary and Secondary: Diabetes was present in 37% of elderly and in 56% of the younger patients. Younger patients had been referred earlier to our nephrologists than the older ones (42 vs. 27%). Elderly were more frequently treated by hemodialysis than peritoneal dialysis (81 vs. 19%) when compared to their younger counterparts (65 vs. 35%). Long-term catheters for hemodialysis were used more often in elderly patients. No renal transplantation were performed in older patients while 7 younger patients received a renal graft. Survival rates after 1 and 3 years were, respectively, 93 and 74% for patients between 50 and 60 years, whereas it decreased to 80 and 45% for those over 75 years (p = 0.002). More than 50% of patients older than 75 years died within 2 years after starting dialysis; their mean survival was 31 months; patients starting dialysis between 50 and 60 years survived on the average 44 months during the study period. According to the multivariate logistic regression model, risk factors for increased mortality in the older group were: number of hospitalization days during the past 3 months (OR 34.8, 95% CI 8.3–145.7, p < 0.001) and lower weight (OR 16.6, 95% CI 2.0–139.0, p = 0.001). Conclusion: We may conclude that, in our hands, life expectancy of patients who began dialysis above 75 years is significantly shorter than for patients for whom dialysis is initiated between age 50 and 60 years, especially if they have a low weight, lose weight and/or require hospitalization.

Our objectives were to review the characteristics of patients who developed atheroembolic renal disease requiring dialysis as well as their renal function recovery and survival rates.All cases of atheroembolic disease with renal failure severe enough to require dialysis were reviewed from January 1984 to December 2000 in two centers. The diagnosis of atheroemboli was based on clinical presentation and/or biopsy. Acute renal failure was defined as a serum creatinine200 micromol/l if normal at baseline or doubling from baseline if chronic renal failure, whereas renal function recovery was the ability to discontinue renal replacement therapy foror=3 months.Forty-three cases were identified (37 males and 6 females; mean age 67 +/- 5 years); the average time to acute renal failure and to diagnosis was similar at 36 days. The majority of patients had at least one precipitating factor identified (58% coronary angiography, 26% angiography, 16% vascular surgery, 2% anticoagulation); 1 had a spontaneous presentation whereas 7 had more than one factor. More than 90% had underlying hypertension and chronic renal dysfunction with a baseline creatinine of 195 +/- 81 micromol/l, approximately 80% had coronary artery disease, 80% were smokers, 60% had a history of abdominal aorta aneurysm,50% presented with intermittent claudication, and 56% were anticoagulated at the time of the event. Most patients were nonoliguric (80%), had increased hypertension (71%), blue toes (67%), livedo reticularis (52%), whereas abdominal pain and central nervous system symptoms were present in 33 and 7% of the cases, respectively. Eosinophilia was found in 88%, while hypocomplementemia was present in less than 15%. When compared to the 12 patients with recovery of renal function (after a mean delay of 409 +/- 336 days), the 31 patients who did not recover function presented with more severe intermittent claudication and underlying chronic renal dysfunction (p0.05). Indeed, the only variable found to unfavorably influence renal function recovery was the presence of intermittent claudication. Patients were mainly treated by intermittent hemodialysis except for 5 (2 on CRRT and 3 on peritoneal dialysis). Renal function recovery was associated with a higher chance of survival; 33% of patients died in the first year after diagnosis.Atheroembolic renal disease carries a high mortality rate reflective of the extensive cardiovascular disease of affected patients; nevertheless, the potential for renal function recovery appears greater than for other vascular causes of renal failure.

Dialysate leakage represents a major noninfectious complication of peritoneal dialysis (PD). An exit-site leak refers to the appearance of any moisture around the PD catheter identified as dialysate; however, the spectrum of dialysate leaks also includes any dialysate loss from the peritoneal cavity other than via the lumen of the catheter. The incidence of dialysate leakage is somewhat more than 5% in continuous ambulatory peritoneal dialysis (CAPD) patients, but this percentage probably underestimates the number of early leaks. The incidence of hydrothorax or pleural leak as a complication of PD remains unclear. Factors identified as potentially related to dialysate leakage are those related to the technique of PD catheter insertion, the way PD is initiated, and weakness of the abdominal wall. The pediatric literature tends to favor Tenckhoff catheters over other catheters as being superior with respect to dialysate leakage, but no consensus on catheter choice exists for adults in this regard. An association has been found between early leaks (< or =30 days) and immediate CAPD initiation and perhaps median catheter insertion. Risk factors contributing to abdominal weakness appear to predispose mostly to late leaks; one or more of them can generally be identified in the majority of patients. Early leakage most often manifests as a pericatheter leak. Late leaks may present more subtly with subcutaneous swelling and edema, weight gain, peripheral or genital edema, and apparent ultrafiltration failure. Dyspnea is the first clinical clue to the diagnosis of a pleural leak. Late leaks tend to develop during the first year of CAPD. The most widely used approach to determine the exact site of the leakage is with computed tomography after infusion of 2 L of dialysis fluid containing radiocontrast material. Treatments for dialysate leaks include surgical repair, temporary transfer to hemodialysis, lower dialysate volumes, and PD with a cycler. Recent recommendation propose a standard approach to the treatment of early and late dialysate leaks: 1-2 weeks of rest from CAPD, and surgery if recurrence. Surgical repair has been strongly suggested for leakage causing genital swelling. Delaying CAPD for 14 days after catheter insertion may prevent early leakage. Initiating CAPD with low dialysate volume has also been recommended as a good practice measure. Although peritonitis and exit-site infections are the most frequent causes of technical failure in peritoneal dialysis (PD), dialysate leaks represent one of the major noninfectious complications of PD. In some instances, dialysate leakage may lead to discontinuation of the technique (1). Despite its importance, the incidence, risk factors, management, and outcome of dialysate leakage are poorly characterized in the literature. We will review the limited available information on this topic in the next few sections.

Chronic renal failure (CRF) is associated with a decrease in drug metabolism. The mechanism remains poorly understood. The present study investigated the repercussions of CRF on liver cytochrome P450 (CYP450). Three groups of rats were defined: control, control paired-fed, and CRF. Total CYP450 activity, protein expression of several CYP450 isoforms as well as their mRNA, and the in vitro N-demethylation of erythromycin were assessed in liver microsomes. The regulation of liver CYP450 by dexamethasone and phenobarbital was assessed in CRF rats. Compared with control and control paired-fed rats, creatinine clearance was reduced by 60% (P:0.01) in CRF rats. Weight was reduced by 30% (P:0.01) in control paired-fed and CRF rats, compared with control animals. There was no difference in the CYP450 parameters between control and control paired-fed. Compared with control paired-fed rats, total CYP450 was reduced by 47% (P:0.001) in CRF rats. Protein expression of CYP2C11, CYP3A1, and CYP3A2 were considerably reduced (40%, P:0.001) in rats with CRF. The levels of CYP1A2, CYP2C6, CYP2D, and CYP2E1 were the same in the three groups. Northern blot analysis revealed a marked downregulation in gene expression of CYP2C11, 3A1, and 3A2 in CRF rats. Although liver CYP450 was reduced in CRF, its induction by dexamethasone and phenobarbital was present. N-demethylation of erythromycin was decreased by 50% in CRF rats compared with control (P:0.001). In conclusion, CRF in rats is associated with a decrease in liver cytochrome P450 activity (mainly in CYP2C11, CYP3A1, and 3A2), secondary to reduced gene expression.

Objectives: To determine the serum status in folate, pyridoxal-5′-phosphate (the active moiety of pyridoxine), cobalamin, and total homocysteine of chronic dialysis patients not routinely supplemented with B-complex vitamins and to evaluate induced intradialytic losses during high-efficiency hemodialysis. Design: A cross-sectional study. Setting: A university medical center providing tertiary care. Patients: Thirty-six chronic dialysis patients (23 men and 13 women, mean age 57 ± 13 years) treated since 3.8 ± 2.2 years by hemodialysis and not supplemented with hydrosoluble vitamins. Methods: Thrice-weekly hemodialysis was performed using CT-190G (Baxter, IL) or F-20 (Hospal, St-Leonard, Canada) reused dialyzers with a mean blood flow rate of 371 ± 40 mL/min, a dialysate flow rate of 500 mL/min, and a mean session time of 3.7 ± 0.4 hours. Prehemodialysis serum vitamin B 12 and homocysteine, and predialysis and postdialysis serum folate, pyridoxal-5′-phosphate, and urea were measured. Blood-side folate and pyridoxal-5′-phosphate clearances were calculated. Results: Predialysis serum total homocysteine was above normal in all patients, with values ranging from 14.4 to 158.0 μmol/L (mean 40.2 ± 29.6 μmol/L, median 33.5 μmol/L). Whereas the majority, 21 patients, had evidence of coronary, cerebrovascular, and/or peripheral vascular diseases, there was no difference in total homocysteine in patients with or without vascular disease (respectively, 40.8 ± 37.0 μmol/L v 39.4 ± 15.1 μmol/L, P = NS). Predialysis serum concentrations of pyridoxal-5′-phosphate were reduced in 20 patients (56%) and were in the lower normal range for 14 patients. Predialysis and postdialysis serum folate concentrations were 12.4 ± 6.1 nmol/L and 8.6 ± 3.6 nmol/L, whereas predialysis and postdialysis serum pyridoxal-5′-phosphate concentrations were 11.1 ± 7.5 nmol/L and 8.0 ± 5.9 nmol/L. Percent reduction ratios were 68.4% ± 6.6% for urea, 26.3% ± 16.0% for folates, and 27.9% ± 14.2% for pyridoxal-5′-phosphate. Blood-side clearances reached 134.7 ± 22.2 mL/min for folates and 54.4 ± 38.2 mL/min for pyridoxal-5′-phosphate. There was no significant difference in predialysis serum folate and pyridoxal-5′-phosphate in patients with or without evidence of vascular disease. Conclusion: This study confirms that: (1) total serum homocysteine levels are very high in chronic hemodialysis patients not supplemented with B-complex vitamins; (2) folate is significantly cleared or lost during high-efficiency hemodialysis; and (3) pyridoxal-5′-phosphate, the active moiety of pyridoxine, is depleted in most chronic hemodialysis patients without supplementation and that high-efficiency hemodialysis contributes to its depletion.

poisoning They infused 95% ethanol at the dialysate inlet tubing of the dialyser at a constant rate of 40 ml/min. They added phosphate in the base concentrate of the dialys

Although ammonium acid urate (AAU) stones are endemic in Asia, pure AAU calculi have almost disappeared from industrialized countries and clinical pathophysiologic relevance of sporadic stones containing AAU crystals is currently unknown. We reviewed 1,396 crystallographic stone analyses performed in our institution over a 10-year period. Prevalence of stones containing AAU crystals and predominantly AAU stones were 3.1% and 0.2%, respectively. In more than two thirds of cases, AAU crystals represented less than 10% of stone crystal composition. No pure AAU stone was found. According to crystalline predominance, 42%, 35%, and 12% of these calculi were uric acid, infectious, and calcium oxalate stones, respectively. AAU crystals were detected as discrete intercrystalline or peripheral deposits in 74.4% of stones. In only one calculus was AAU crystals detected in the nucleus. The hospital charts of 37 patients who presented with 43 calculi containing AAU crystals were also reviewed. The mean age was 53.1 +/- 16.6 years. Fifty-seven percent of calculi were upper urinary tract stones and 43% were bladder stones. Upper urinary tract calculi were more frequently uric acid stones, followed by infectious and calcium oxalate stones. Lower urinary tract calculi were more frequently infectious stones, followed by uric acid stones. Upper urinary tract stones were passed spontaneously in 13 patients and removed surgically in nine patients. Nine of these subjects were idiopathic recurrent stone formers who had passed other calculi with no trace of AAU crystal. Fifty-seven percent of lower urinary tract stones were associated with documented bladder dysfunction. In conclusion, although AAU-containing urolithiases are occasionally seen in our population, predominantly or primarily AAU stones are exceptional. AAU crystal formation usually appears as a minor and secondary phenomenon of no primary pathophysiologic relevance in stone formation.

Organ transplantation is associated with an early bone loss that subsequently increases the risk of osteopenia and bone fractures. It is not known whether bone loss continues in long-term survivors, but persistent bone demineralization could further jeopardize an already diminished bone mass. To better define long-term bone status of kidney transplant recipients (KTR), we conducted cross-sectional and longitudinal evaluations of bone mineral density (BMD) in 70 KTR with a mean posttransplantation time of 8.1 years. BMD was determined by dual-energy X-ray absorptiometry and was repeated in 55 of the patients after a mean follow-up period of 22 +/- 5 months. Lumbar and femoral osteopenia, defined as a BMD lower than 2 standard deviations from mean value of sex- and age-matched controls, was present in 28.6% and 10.5% of patients, respectively. There was a significant negative correlation between cumulative prednisone dose and adjusted lumbar as well as femoral BMD (R = 0.45, P0.001 and R = 0.29, P0.05, respectively). Five patients had a vertebral BMD below a fracture threshold of 0.777 g/cm2. Vertebral fractures (VF) were found in four men and were associated with higher prednisone dosage (P0.05), larger cumulative prednisone dose (P0.05), and significantly lower BMD values. According to World Health Organization recent criteria for women, prevalences of lumbar and femoral osteopenia and lumbar and femoral osteoporosis in female patients reach 75%, 65%, 33%, and 10%, respectively. The longitudinal part of the study showed a persistent pathological lumbar demineralization process. Over the study period, BMD, expressed as a percentage of that of controls, decreased from 89 +/- 14% to 86 +/- 14% (P0.001). Annual change of bone mass was -1.7 +/- 2.8% per year. Accelerated vertebral bone loss (defined as a decrease of BMD, expressed as a percentage of that of controls, of more than 1% per year) was present in 56% of patients and was associated with higher prednisone dosage (P0.01). In conclusion, although VF are relatively infrequent in long-term survivors of renal transplantation, osteopenia is a frequent finding, and a substantial proportion of women present lumbar osteoporosis. An ongoing demineralization process of the spine is also demonstrated and probably contributes to long-term spinal osteoporosis incidence. Prednisone dosage remains the most constantly isolated risk factor.

Intermittent hemodialysis is considered the modality of choice when enhanced lithium removal is indicated. However, postdialysis rebound in serum lithium concentration is frequently observed after the dialysis sessions and results from incomplete intracellular removal. Continuous renal replacement therapy could provide a more gradual and complete lithium removal since it is performed over longer time periods, thus avoiding rebound following therapy. Seven patients presenting with symptomatic lithium intoxication were treated by continuous renal replacement therapy (continuous arteriovenous and venovenous hemodiafiltration [CAVHDF and CVVHDF]). For CAVHDF, the dialysate flow rate was increased to 4 L/hr to optimize solute clearances. Five intoxicated patients (four acute and one chronic) were treated by high dialysate flow rate (HDFR) (4 L/hr) CAVHDF and two patients with chronic poisoning were treated by CVVHDF, one with a dialysate flow rate of 1 L/hr and one with a dialysate flow rate of 2 L/hr. Serum lithium concentrations for the four acute poisoning cases were 4.0, 4.6, 4.4, and 3.2 mEq/L, at initiation of HDFR CAVHDF, and decreased respectively to 1.2, 0.8, 1.2, and 1.1 mEq/L after 15, 19, 35, and 21 hours of treatment. No lithium rebound was observed over 24 to 36 hours following CAVHDF. For the three chronic intoxication cases, serum lithium concentrations dropped from 1.7, 2.2, and 3.8 mEq/L to 0.7, 0.17, and 0.4 mEq/L, respectively, after 18, 42, and 44 hours of HDFR CAVHDF or CVVHDF. The chronic case treated for only 18 hours presented a slight rebound in lithium level (0.3 mEq/L), whereas no significant rebound was observed for the two other cases treated for longer periods. Mean +/- SEM dialyser urea, lithium, and creatinine clearance during HDFR CAVHDF were 50.5 +/- 5.0, 41.4 +/- 4.6, and 37.6 +/- 3.7 mL/min, respectively (number of measurements = 41). Dialyser lithium clearance during CVVHDF was 48.4 +/- 1.4 mL/min (n = 10) and 61.9 +/- 2.3 mL/min (n = 7), with dialysate flow rates of 1 and 2 L/hr, respectively. Mean dialyzer lithium removal for the seven cases was 106.4 mEq, while mean renal lithium removal was 21.5 mEq during the same period. We conclude that HDFR CAVHDF and CVVHDF are effective alternatives to intermittent hemodialysis for treatment of lithium poisoning. They provide excellent lithium clearances (60 to 85 L/d); in addition, because of their continuous nature, they prevent posttherapy lithium rebound by allowing a more gradual and complete removal from intracellular compartments, and they may be particularly useful in chronic poisoning in which intracellular lithium accumulation is more extensive.

The site where furosemide is metabolized and the location where probenecid reduces furosemide metabolism remain poorly defined. The liver appears to play a minor role, and there is indirect evidence suggesting that the kidneys could be responsible for the metabolism of furosemide. To assess the role of the kidneys in the metabolism of furosemide, its intravenous kinetics have been studied in control and anephric rabbits, after the ligation of the renal pedicles. Two additional groups of rabbits, control and anephric, have received probenecid before the administration of furosemide. In the control group, the total clearance of furosemide was 18.65 +/- 1.01 mL/ min per kg; urinary and metabolic clearances of furosemide were 7.95 +/- 0.65 and 10.70 +/- 1.11 mL/min per kg, respectively. In anephric rabbits, total clearance was reduced by 85% to 2.69 +/- 0.26 mL/min per kg (P < 0.001), secondary to the abolition of furosemide renal excretion and to the reduction in metabolic clearance from 10.70 +/- 1.11 to 2.69 +/- 0.26 mL/min per kg (P < 0.001). The pretreatment with probenecid reduced the total clearance of furosemide by 80%, to 3.62 +/- 0.24 mL/min per kg (P < 0.001), because of a reduction of 90 and 75% in urinary and metabolic clearances, respectively. The administration of probenecid to anephric rabbits did not reduce further the metabolic clearance. It is concluded that the kidneys are responsible for 85% of furosemide total clearance, either via excretion (43%) or biotransformation (42%), and that probenecid inhibits both processes.

To characterize the urinary kinetics of AVP, and the influence of regional blood flow on the metabolic degradation of AVP, multiple doses of AVP were administered to conscious rabbits. AVP systemic clearance (ClT) was not influenced by changes in dose, in spite of a decrease in AVP urinary clearance following the highest dose. Hepatic blood flow was inversely associated with AVP concentrations, and despite a decrease in hepatic plasma flow of 37% (p < 0.05), following the high dose of AVP, ClT remained unchanged. These results indicate that AVP plasma kinetics are first order and plasma flow independent, and urinary kinetics are zero order.

To better define the survival and quality of life of patients with major left ventricular systolic dysfunction and end-stage renal disease treated by continuous ambulatory peritoneal dialysis (CAPD), we reviewed all cases who started CAPD between May 1984 and March 1993 who had an isotopic left ventricular ejection fraction (LVEF) < or = 35%. Seventeen patients (12 men and five women with a mean age of 51.6 +/- 14.9 years) met the inclusion criteria. Mean isotopic LVEF before initiation of CAPD was 24.8% +/- 8.2%. All patients were symptomatic from congestive heart failure. Thirteen patients were classified as New York Heart Association grade III or IV. Continuous ambulatory peritoneal dialysis was associated with a significant improvement of isotopic LVEF, of functional status, and of blood pressure control. In 10 patients with a second measurement on CAPD, LVEF increased from a mean value of 23.2% +/- 9.1% to a mean value of 30.3% +/- 8.1% (P < 0.01). This represents a 30% increase of LVEF. After 6 months on CAPD, 94% of patients were classified as New York Heart Association grade I or II. Actuarial survival rates were 94%, 80%, and 64% at 12, 18, and 24 months, respectively. The mean duration of CAPD was 24 +/- 17 months. These results suggest that current CAPD treatment is an elective modality of treatment in patients with concomitant heart and renal failure.

classic pathway C3 convertases are powerful amplifiers that are regulated by a family of complement binding proteins that function by disassembling the convertases or by facilitating their proteolytic cleavage in collaboration with the serine protease factor I. Through complement control protein modules (also known as short consensus repeats), membrane regulators, such as membrane-cofactor protein, inhibit complement on host tissue, while soluble inhibitors, such as factor H, mainly prevent phase activation. In familial DHUS caused by mutations in factor H or in the membranecofactor protein, it is thought that reduced expression or activity favours activation on vascular surfaces after an endothelial injury. The findings of Richards et al and Noris and colleagues have potential clinical implications. First, the phenotypes of carriers of the mutation in the membrane-cofactor protein are highly variable within families, ranging from early onset HUS and end-stage renal failure to an apparently normal life. This situation is similar to factor H kindreds, and strengthens the hypothesis that environmental and genetic modifiers, including initial endothelial injury, are also involved. Additionally, serum C3 levels seem unreliable in the prediction of carrier status, and perhaps the serum ratio of C3d (an inactivated metabolite of C3b) to C3 is a more accurate proxy. Second, the outcome of renal transplantation in families with the mutation in the membrane-cofactor protein seems to be more favourable than in factor H kindreds, because recurrence was not seen in 3 affected relatives. Since the transplanted tissue harbours wild-type membrane-cofactor protein, it should provide “protection” because of its expression on endothelial cells. Thus better genetic counselling will be possible in familial HUS, including for living-related kidney donation. Third, although DHUS is rare, identification of susceptibility genes will indicate potential targets for drug or gene therapy that could be used for the more frequent DHUS. Finally, the molecular basis of DHUS remains to be identified for more than half the cases. So stay tuned for more genes to come.

Renal function recovery (RFR) is a rare event in patients with end-stage renal disease (ESRD). Although some predictive factors have been described, there are still unresolved questions. We have analyzed the Canadian Organ Replacement Register data for the 1981 to 1989 period to assess the incidence and factors predictive of RFR in a large ESRD population as well as the outcome after recovery. Renal function recovery was defined as the interruption of renal replacement therapy (RRT) for more than 3 months. Patients on RRT for ≤45 days were excluded. Of 14,318 registered ESRD patients, 342 (2.4%) experienced RFR after 8.9 ± 0.5 months of RRT (mean ± SEM); 52.3% of the recoveries occurred within 6 months of initiating RRT, while 23.7% were only observed after 12 months or more. By Cox regression, patients within the following diagnostic groups had a significantly higher rate of RFR than those with primary glomerulonephritis, who are considered to comprise the reference group: myeloma (relative rate [RR] = 6.00; P P P P P = 0.004) and diabetic patients (RR = 0.56; P = 0.024) had a lower rate of RFR than those with glomerulonephritis. Men younger than 45 years had a lower rate of RFR than older men and women of all ages ( P P = 0.043). By actuarial analysis, only 43% of patients with RFR were estimated to return to dialysis within 78 months. By Cox regression, among cases of RFR, diabetic patients had a higher rate (RR = 2.32; P = 0.012) and patients with vascular/hypertensive disease had a lower rate (RR = 0.55; P = 0.048) of relapse than those with glomerulonephritis; on the other hand, women experiencing RFR had a lower risk of returning to dialysis than men (RR = 0.68; P = 0.044). Our study outlines predictive factors for RFR in an ESRD population and defines renal outcome after recovery. This may have implications for the planning of RRT (for example, early renal transplantation), especially in young women with vascular/hypertensive disease in whom a lasting RFR is not a rare event.

Background Activated vitamin D is the mainstay of treatment for secondary hyperparathyroidism (SHPT) in chronic hemodialysis patients. However, the optimal route of administration is still debated. The aim of our study was to compare efficacy of oral vs intravenous (IV) administration of alfacalcidol in hemodialysis. A secondary objective was to determine the cost-effectiveness advantage of oral administration. Methods Eighty-eight chronic hemodialysis patients receiving IV alfacalcidol three times a week were included in the study. All were switched to the same dose of alfacalcidol given orally three times a week during the hemodialysis session. A budget impact analysis was performed. Results Mean patient age was 64 years old and 43% were males. The mean alfacalcidol dose administered was 2.1 μg three times a week. After three months, serum parathormone (PTH) levels decreased from 80 to 59 pmol/L (p = 0.001) and total serum calcium levels increased from 2.34 to 2.40 mmol/L (p = 0.002). After six months, total serum calcium levels were still significantly higher. Alfacalcidol dosage was significantly decreased during study period; the mean reduction was 0.44 μg per dose. Finally, oral administration was associated with an annual cost reduction of 197 678$CAN and an annual nursing time reduction of 25 days. Conclusion Our findings support that switching IV to oral administration of alfacalcidol during hemodialysis sessions may lead to a similar control of SHPT with lower doses of activated vitamin D. This is a good strategy for optimizing compliance and may allow a dose reduction because of a greater efficacy to suppress PTH. Oral administration also has significant cost-effectiveness advantages.

Background Discordance between dialysis registry and death certificate reported death has been demonstrated. Since cause of death is measured using registry data in dialysis patients and death certificate data in the general population, comparisons of cause of death proportions between dialysis patients and the general population may be biased. Our aim was to compare the proportion of deaths attributed to cardiovascular disease (CVD), malignancy, and infections between patients receiving dialysis and the general population using death certificates for both, and to quantify the magnitude of discrepancy between registry and death certificate estimates in dialysis patients. Methods A retrospective cohort study of 5858 patients initiating maintenance dialysis between 2001 and 2007 was conducted. Cause of death was obtained from both registry and death certificate data for dialysis patients, and from death certificate data for the general population. Results Compared to the general population, use of death certificate data in dialysis patients resulted in smaller differences in the proportion of deaths attributed to CVD or infection than that from the registry. In the general population, the proportion of deaths due to CVD is 29.3% for men and 28.2% for women, and the proportion of deaths due to infection is 3.3% for men and 3.6% for women. For men, the proportion of deaths in dialysis patients due to CVD using registry data is 41.5%, compared with a proportion of 32.1% using death certificate data. Similarly for women, the proportion of deaths due to CVD using registry data is 35.2% and that using death certificate data 24.3%. The proportion of deaths due to infection in dialysis patients follows the same pattern: for men, the proportion of deaths due to infection using registry data is 9.9% and that from death certificate data at 5.0%; while for women the proportions are 11.6% and 4.8%, respectively. Conclusions While absolute cause-specific mortality rates did differ, evaluation of causes of death using death certificate in dialysis patients in Quebec revealed that they do not have substantially different proportion of death due to CVD or infections than the general population. Infections appeared to be a frequent complication leading to death, suggesting that infections are an important target to consider for reducing mortality in dialysis populations.