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Residual renal function and diuresis preservation are associated with improved volume control and lower mortality in peritoneal dialysis (PD). Loop diuretics are used to maintain diuresis, although their optimal dosage remains unclear. This study aimed to compare the pharmacodynamics of a 250-mg and a 500-mg dose of oral furosemide in PD patients. 12 patients with a diuresis > 100 mL per day were randomized in a crossover pattern to successively receive an oral dose of 250 mg and 500 mg of furosemide. Twelve-hour natriuresis and diuresis were measured before and after each furosemide dose. Fractional excretion of sodium (FENa) and absolute sodium excretion increased after each dose, although these rises were not statistically significantly different (5.8% (250 mg) vs. 6.9% (500 mg), p = 0.57 for FENa and 42.6 mmol/12h (250 mg) vs. 70.8 mmol/12h (500 mg), p = 0.07 for absolute sodium excretion). Urinary volume was significantly increased after the 500-mg dose, whilst the difference did not reach statistical significance after the 250-mg dose. Furthermore, the higher dose was associated with a greater increase in diuresis than the lower dose (226 mL (250 mg) vs. 522 mL (500 mg), p = 0.04). Furosemide could be used at oral single doses reaching 500 mg in PD patients requiring greater volume control.

The optimal vitamin D3 therapy for the treatment of secondary hyperparathyroidism (SHPT) in chronic hemodialysis patients is still controversial. Recent studies suggest that uremia in end-stage renal disease is associated with enzymatic hepatic dysfunction altering 25-hydroxylation of vitamin D3. The goal of our study was to compare the efficacy of calcitriol, the fully hydroxylated active form of vitamin D3, to alfacalcidol which needs 25-hydroxylation to be effective, for the treatment of SHPT in chronic hemodialysis patients. We retrospectively reviewed 45 chronic hemodialysis patients who were switched from oral alfacalcidol to oral calcitriol for the treatment of SHPT. Parathyroid hormone (PTH), serum calcium and serum phosphorus levels were compared pre- and post-conversion using paired Student’s t tests. The mean dose of active vitamin D3 decreased from 3.50 mcg/week at baseline to 2.86 mcg (P

It is a fact that recurrence of urinary stones is a common medical problem. One of the key factors used in determining the risk of urinary stone-formation is the urine relative saturation in the major constituents of lithiasis. Nomograms were developed in the 1970's to estimate the relative saturation of urine. We present here easy-to-use mathematical equations derived from these nomograms. These equations can be integrated directly in the LIS of any laboratories, and can be used as a tool in the treatment and prevention of recurrent stone-formation.

Hyperphosphatemia and metabolic acidosis are frequently encountered in advanced chronic kidney disease (CKD) patients. Correction of metabolic acidosis in patients with advanced CKD leads to a decrease in the progression of renal impairment and improves nutritional outcomes. Lanthanum carbonate is used for control of hyperphosphatemia. This study evaluated the effect of lanthanum carbonate on metabolic acidosis in CKD IV-V patients and in patients on dialysis.Retrospective data of patients in whom lanthanum carbonate therapy was initiated were collected from 2009 to 2013 in a single dialysis center. Of the 79 patients in whom lanthanum carbonate was introduced, 51 patients were included in the analysis. Of the 51 patients, 39 patients received chronic hemodialysis, two patients received peritoneal dialysis therapy, and 10 patients had stage IV-V CKD not on dialysis. The primary outcome was the serum bicarbonate change after the introduction of lanthanum carbonate.There was a significant increase in mean serum bicarbonate concentration of 2.79 mmol/L (p ≤ 0.001) compared to baseline. The increase remained in the CKD IV-V patients (2.50 mmol/L, p = 0.005) and in the patients on dialysis (2.81 mmol/L, p0.001). Serum bicarbonate remained higher (p0.05) than baseline up to 6 months after lanthanum carbonate introduction.In this study, lanthanum carbonate introduction increased serum bicarbonate concentration in a small sample of CKD IV-V patients and in patients on dialysis. Further studies are needed to confirm this effect and investigate whether the correction of metabolic acidosis by using lanthanum carbonate in CKD IV-V patients can improve clinical outcomes.

Background and objectives Peritoneal dialysis (PD) is associated with an increased risk of infection-related hospitalization (IRH) compared with hemodialysis. The objective of this study was to compare mortality and overall readmission after an IRH between PD and hemodialysis. Design, setting, participants, & measurements This propensity score–matched retrospective cohort study assessed patients undergoing long-term dialysis patients, derived from the Canadian Organ Replacement Register and Regie de l’assurance maladie du Quebec, who had at least one IRH between January 2001 and December 2007. Patients were followed until death, kidney transplantation, or end of the study period. To estimate the probability of receiving PD versus hemodialysis, propensity scores were obtained using multivariable logistic regression. Mortality and overall readmission risks after the initial IRH were compared using a Cox survival model. Results A total of 354 pairs of patients who had at least one IRH were matched for propensity score. During follow-up (median, 1.25 years), 138 hemodialysis patients (24.7/100 patient-years; 95% confidence interval [95% CI], 20.7 to 29.1) and 130 PD patients (21.2/100 patient-years; 95% CI, 17.7 to 25.1) died; 265 hemodialysis patients (144.6/100 patient-years; 95% CI, 127.7 to 163.1) and 299 PD patients (173.2/100 patient-years; 95% CI, 154.1 to 194.0) were readmitted for any cause; and 121 hemodialysis patients (29.7/100 patient-years; 95% CI, 24.7 to 35.5) and 168 PD patients (44.7/100 patient-years; 95% CI, 38.2 to 52.0) were readmitted for an infection. Compared with hemodialysis, PD was not associated with a different mortality risk after an IRH (hazard ratio [HR], 0.87; 95% CI, 0.69 to 1.11). PD was associated with a higher risk of infection-related overall readmission compared with hemodialysis (HR, 1.44; 95% CI, 1.14 to 1.81), but not with the risk of all-cause overall readmission (HR, 1.15; 95% CI, 0.98 to 1.36). Conclusions PD was not associated with higher mortality or all-cause overall readmission following an IRH compared with hemodialysis, but PD patients were at higher risk of infection-related overall readmission after IRH. IRHs are associated with significant mortality and overall readmissions. Evaluation of strategies to reduce infections in both hemodialysis and PD recipients are needed to improve patient care and outcomes.

Objectives.The primary objective of this study is to evaluate the use of cinacalcet in the management of hyperparathyroidism in kidney transplant recipients. The secondary objective is to identify baseline factors that predict cinacalcet use after transplantation.Methods.In this single-center retrospective study, we conducted a chart review of all patients having been transplanted from 2003 to 2012 and having received cinacalcet up to kidney transplantation and/or thereafter.Results.Twenty-seven patients were included with a mean follow-up of2.9±2.4years. Twenty-one were already taking cinacalcet at the time of transplantation. Cinacalcet was stopped within the first month in 12 of these patients of which 7 had to restart therapy. The main reason for restarting cinacalcet was hypercalcemia. Length of treatment was23±26months. There were only 3 cases of mild hypocalcemia. There was no statistically significant association between baseline factors and cinacalcet status a year later.Conclusions.Discontinuing cinacalcet within the first month of kidney transplantation often leads to hypercalcemia. Cinacalcet appears to be an effective treatment of hypercalcemic hyperparathyroidism in kidney transplant recipients. Further studies are needed to evaluate safety and long-term benefits.

Background Patients suffering from chronic kidney disease are at greater risk of developing infection than the normal population, and infections are the second cause of mortality after cardiovascular complications in this population. Some reports suggest that the intake of active vitamin D might be beneficial to prevent infections. Therefore, we aimed to determine if the oral intake of vitamin D receptor activator (VDRA) is associated with a lower risk of infection-related hospitalization (IRH) among incident chronic hemodialysis patients. Methods We conducted a nested case–control study in a cohort of 4933 patients initiating chronic hemodialysis between 1 January 2001 and 31 December 2007 in Quebec, Canada, using administrative databases. We identified cases of hospital admission indicating an infection as main diagnosis on the hospital's discharge sheet. Up to 10 controls were randomly selected for each case. Association between oral VDRA use and risk of IRH was estimated using conditional logistic regression. Results We identified 1136 cases of IRH and 10 396 controls during the study period. The intake of VDRA was not associated with the risk of being hospitalized due to an infection (odds ratio [OR], 1.07; 95% confidence interval [CI], 0.95–1.20). Using the prior 6-month cumulative dose of VDRA, we also found that a cumulative VDRA dose of less than 45 mcg (OR, 1.05; 95%CI, 0.92–1.19) or greater than 45 mcg (OR, 1.15; 95%CI, 0.96–1.36) was not associated with the IRH risk. Conclusions The oral intake of VDRA was not associated with the risk of IRH in incident hemodialysis patients. Copyright © 2014 John Wiley & Sons, Ltd.

Aortic dissection is often misdiagnosed, especially among young patients, and it is associated with a high mortality rate. We present here a case of fatal acute aortic dissection in a young man who was misdiagnosed with pericarditis. We reviewed the literature of acute aortic dissection in young people and we focused particularly on clinical presentations, outcomes and investigations of aortic dissection. We report a case of a 33-year-old man with a history of uncontrolled hypertension with acute pleuretic chest pain who was transferred to our hospital for suspected pulmonary embolism and died of acute hemorragic pericardial effusion from an ascendant aortic dissection. We should never rule out aortic dissection off our differential diagnosis on the sole basis of a patient's young age.

Calcidiol insufficiency is highly prevalent in chronic kidney disease (CKD), but the reasons for this are incompletely understood. CKD associates with a decrease in liver cytochrome P450 (CYP450) enzymes, and specific CYP450 isoforms mediate vitamin D(3) C-25-hydroxylation, which forms calcidiol. Abnormal levels of parathyroid hormone (PTH), which also modulates liver CYP450, could also contribute to the decrease in liver CYP450 associated with CKD. Here, we evaluated the effects of PTH and uremia on liver CYP450 isoforms involved in calcidiol synthesis in rats. Uremic rats had 52% lower concentrations of serum calcidiol than control rats (P0.002). Compared with controls, uremic rats produced 71% less calcidiol and 48% less calcitriol after the administration of vitamin D(3) or 1alpha-hydroxyvitamin D(3), respectively, suggesting impaired C-25-hydroxylation of vitamin D(3). Furthermore, uremia associated with a reduction of liver CYP2C11, 2J3, 3A2, and 27A1. Parathyroidectomy prevented the uremia-associated decreases in calcidiol and liver CYP450 isoforms. In conclusion, these data suggest that uremia decreases calcidiol synthesis secondary to a PTH-mediated reduction in liver CYP450 isoforms.

Calcidiol insufficiency is highly prevalent in chronic kidney disease (CKD) and osteoporotic patients. We assessed and compared calcidiol levels in these two groups from the same geographical area to differentiate environmental factors from characteristics related to CKD.We measured calcidiol levels in 160 predialysis (group 1) and 53 osteoporotic (group 2) patients from a single center. Calcidiol insufficiency was defined as a level between 37.5 and 75 nmol/l and calcidiol deficiency was defined as a level below 37.5 nmol/l.In group 1, mean glomerular filtration rate (GFR), calcidiol, and parathyroid hormone (PTH) levels were 18.3 +/- 4.7 ml/min, 38.7 +/- 15.1 nmol/l, and 21.9 +/- 19.1 pmol/l. Calcidiol insufficiency and deficiency were present in 98.7% of patients. There was an inverse correlation between calcidiol and PTH levels (r = -0.25; P = 0.001). In group 2, mean GFR, calcidiol levels, and PTH levels were 68.6 +/- 17.6 ml/min, 73.8 +/- 27.1 nmol/l, and 4.23 +/- 1.83 pmol/l, respectively. Calcidiol insufficiency and deficiency were present in 50.9% of patients. There was an inverse correlation between calcidiol and PTH levels (r =-0.44; P = 0.02).In our predialysis population, calcidiol insufficiency and deficiency are present in almost every patient, being more common than previously reported. It is also more frequent than in a similar osteoporotic population, suggesting a cause unrelated to environmental factors. Interestingly, there is a significant inverse correlation between calcidiol and parathyroid levels in both populations. Further studies are needed to enable understanding of the mechanisms underlying calcidiol insufficiency.

Aims: 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. Methods: 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 creatinine >200 µmol/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 for ≧3 months. Results: 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 µmol/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 (p < 0.05). 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. Conclusion: 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.

The aim of our study was to evaluate the efficacy and bioavailibility of a commonly used oral furosemide dose (500 mg) compared to a 250 mg intravenous (IV) dose in PD patients with significant residual renal function (urine volume > 100 mL). We also evaluated the immediate blood pressure effect in these patients. The data were obtained from a study we performed for the homologation of a 500-mg dose of furosemide by Health Canada.

Summary Objective To describe the clinical and microbiological features associated with fungal peritonitis in peritoneal dialysis (PD) patients at Hopital Maisonneuve-Rosemont, from August 1996 to July 2006. Methods Cases were retrieved from the microbiology laboratory culture registry. Antifungal susceptibility was determined by the Clinical and Laboratory Standards Institute M27A3 method. Results Among 288 PD patients (total follow-up of 7258 patient-months), nine were found with fungal peritonitis. Candida spp were identified in all of them, with a majority of non-albicans Candida species. Resistance to fluconazole, itraconazole, or voriconazole was as frequent as potential resistance to amphotericin B. No isolate was resistant to caspofungin and one was resistant to micafungin. Prior bacterial peritonitis was frequent (67%). All patients had their PD catheter removed and all of them survived. Conclusions In our institution, fungal peritonitis in PD patients is rare. All cases were caused by Candida species. Variable susceptibility patterns were observed, which may influence the initial empirical antifungal therapy and underscore the importance of individual speciation and susceptibility testing of invasive Candida isolates.

Combined heart-kidney transplant has become an alternative for heart transplant candidates with significant chronic kidney disease. However, it is not clear which patients will benefit most from such intervention, and in whom cardiac transplant alone will be sufficient to restore adequate renal function. We report the case of a man with ischemic cardiomyopathy and chronic kidney disease who was wait-listed for heart-kidney transplant after acute decompensated heart failure and renal failure requiring hemodialysis. Because of unexpected circumstances, the kidney transplant was cancelled, and only a heart transplant was performed. Nonetheless, the kidney function rapidly improved beyond the levels before hospitalization and remains stable months after transplant. This case illustrates the difficulties in assessing the reversibility of kidney damage in the context of heart failure requiring transplant. This issue is primordial to improve selection of patients who will benefit most from combined heart-kidney transplant in a context of scarce organ allocation resources.

A family-based study of metabolic phenotypes in calcium urolithiasis.BackgroundA family history increases the risk of kidney stone passage independent of dietary risk factors. However, the metabolic basis for familial aggregation of urolithiasis is unknown.MethodsWe evaluated metabolic risk factors in families with at least two sibs with a history of calcium stones. Sibs underwent outpatient evaluations simultaneously, including 24-hour urine collection and oral calcium loading. Phenotypes were compared between affected and unaffected sibs from the same sibship.ResultsEighty-three sibships comprising 388 sibs (212 affected sibs, 114 males and 98 females, and 176 unaffected sibs, 68 males and 108 females) from 71 families were analyzed. Daily urine calcium excretion was higher in affected compared with unaffected sibs (0.64 ± 0.33 vs. 0.50 ± 0.22 mmol Ca2+/mmol creatinine, respectively, P < 10­5). This corresponded to absolute values of 7.4 ± 3.9 and 5.1 ± 2.3 mmol Ca2+/day, respectively, for affected and unaffected males, and 5.4 ± 2.6 and 4.2 ± 1.9 mmol Ca2+/day, respectively, for affected and unaffected female sibs. When analyzed by tertile of onset age of stone passage, the differences in urine calcium were only significant in the first two tertiles (with onset age of stone passage

Thirty-eight intensive care unit (ICU) patients (26 men and 12 women with a mean age of 57.0 +/- 16.6 years) with acute renal failure (ARF) treated by venovenous continuous renal replacement therapy (CRRT) were evaluated while in relatively steady metabolic control. Twenty-seven were undergoing continuous venovenous hemodialysis, nine were undergoing continuous venovenous hemodiafiltration, and two were undergoing continuous venovenous hemofiltration. Periods of analysis varied between 24 and 408 hours (mean duration, 82.7 +/- 70.6 hours; median, 72 hours). Their mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score within 24 hours of admission to the ICU was 21.3 +/- 6.3 and survival rate was 31.6%. Urea nitrogen and creatinine concentrations were determined every 6 to 12 hours in both serum (Cun and Cc, respectively) and effluent (spent dialysate and/or ultrafiltrate). The mean effluent rate was 1,472 +/- 580 mL/h and blood flow rate, 166 +/- 32 mL/min. Urine was collected daily for urea nitrogen and creatinine measurement. Urea nitrogen appearance rate (UnA) and creatinine production rate (Pc), calculated from urea nitrogen (UnMR) and creatinine mass removal (CMR) from both the effluent and the urine, using Garred mass balance equations and the Forbes-Bruining formula, allowed normalized protein catabolic rate (nPCR) and estimates of lean body mass (LBM) to be derived. Creatinine metabolic degradation rate (Dc), estimated by the Mitch formula, was included in the calculation. The lowest body weight recorded during the study period was considered as dry weight (BW). The creatinine index (CI) was also obtained. For each parameter, the results are presented as mean, median, and range values: UnMRe (from effluent), 13.6 +/- 7.2, 12.5, 1.6 to 32.6 mg/min; UnMRu (from urine), 0.13 +/- 0.40, 0, 0 to 2.30 mg/min; UnA, 13.6 +/- 7.0, 12.5, 3.8 to 32.1 mg/min; nPCR, 1.75 +/- 0.82, 1.60, 0.61 to 4.23 g/kg/d; CMRe (from effluent), 942.0 +/- 362.3, 918.0, 211.2 to 1,641.6 mg/d; CMRu (from urine), 44.4 +/- 138.8, 0, 0 to 698.5 mg/d; Dc, 94.6 +/- 49.9, 81.9, 31.0 to 294.1 mg/d; Pc total, 1,067.1 +/- 409.7, 1,053.7, 261.5 to 1,988.2 mg/d; LBM, 38.3 +/- 11.9, 37.9, 15.0 to 65.0 kg; LBM/BW ratio, 49.5% +/- 14.0%, 50.3%, 22.5% to 86.0%; and CI, 13.7 +/- 4.7, 14.2, 4.1 to 25.8 mg/kg/d. When Pc was estimated from the Cockcroft-Gault equations (as Pc'), the mean value for Pc and Pc' was similar (1,067.1 +/- 409.7 v 1,284.9 +/- 484.1 mg/d), but there were relatively large differences for the majority of cases. A positive correlation was observed between UnA and Pc (R = 0.42). Serum albumin and LBM/BW correlated poorly (R = 0.20). Outcome was weakly related to UnA and to nPCR (R = 0.29 and R = 0.31, respectively). Urea nitrogen appearance appears widely variable in critically ill ARF patients. This simple approach can provide useful information for an easy estimate of net protein catabolism in critically ill patients with ARF undergoing CRRT.

Patients suffering from chronic kidney disease are at greater risk of developing infection than the normal population, and infections are the second cause of mortality after cardiovascular complications in this population. Some reports suggest that the intake of active vitamin D might be beneficial to prevent infections. Therefore, we aimed to determine if the oral intake of vitamin D receptor activator (VDRA) is associated with a lower risk of infection-related hospitalization (IRH) among incident chronic hemodialysis patients.We conducted a nested case-control study in a cohort of 4933 patients initiating chronic hemodialysis between 1 January 2001 and 31 December 2007 in Quebec, Canada, using administrative databases. We identified cases of hospital admission indicating an infection as main diagnosis on the hospital's discharge sheet. Up to 10 controls were randomly selected for each case. Association between oral VDRA use and risk of IRH was estimated using conditional logistic regression.We identified 1136 cases of IRH and 10396 controls during the study period. The intake of VDRA was not associated with the risk of being hospitalized due to an infection (odds ratio [OR], 1.07; 95% confidence interval [CI], 0.95-1.20). Using the prior 6-month cumulative dose of VDRA, we also found that a cumulative VDRA dose of less than 45 mcg (OR, 1.05; 95%CI, 0.92-1.19) or greater than 45 mcg (OR, 1.15; 95%CI, 0.96-1.36) was not associated with the IRH risk.The oral intake of VDRA was not associated with the risk of IRH in incident hemodialysis patients.

A continuous dialysis technique such as continuous arteriovenous hemodialysis (CAVHD) could be an interesting alternative to frequent intermittent hemodialysis to treat acute renal failure (ARF) secondary to tumor lysis syndrome (TLS). However, because of massive release of intracellular solutes in TLS, CAVHD clearances need to be increased to treat this syndrome. Continuous arteriovenous hemodialysis using a high dialysate flow rate at 4 L/hr was assessed in TLS and ARF associated with severe hyperphosphatemia. A 0.6-m 2 hollow-fiber polyacrylonitrile dialyzer (Multiflow 60; Hospal, St-Leonard, Quebec, Canada) was used. Blood urea nitrogen and serum creatinine levels decreased, respectively, from 102.5 to 27.2 mg/dL and from 3.1 to 1.8 mg/dL during the 36 hours of treatment. Serum urate concentration was normal at the beginning of treatment (4.5 mg/dL) and decreased to 2.1 mg/dl by the end of CAVHD. Serum phosphorus decreased from 16.7 to 4.4 mg/dL after the 36 hours of treatment. The calcium × phosphorus product decreased from 111.1 to 42.1 by 28 hours and remained under 50 thereafter. Serum potassium was easily controlled with the addition of 2.5 mEq/L of KCI in dialysate and replacement solutions. No rebound increases in phosphorus or potassium were noted after cessation of therapy. Continuous arteriovenous hemodialysis clearances of urea, creatinine, phosphorus, and urate were measured at 2-hour intervals for the first 24 hours and at 4-hour intervals for the remaining 12 hours. They were 53.0 ± 2.3 mL/min, 43.7 ± 2.2 mL/min, 40.4 ± 1.9 mL/min, and 39.3 ± 1.9 mL/min (n =15), respectively. The 24-hour CAVHD clearance of urea was 76 L, which is equivalent to 8.5 hours of conventional hemodialysis. Extraction of phosphorus and potassium with CAVHD was, respectively, 8.28 g and 188.5 mEq for 36 hours. In conclusion, CAVHD optimized by high dialysate flow rate becomes a powerful purifying technique for the treatment of ARF and TLS. It provides excellent continuous clearances of small molecular weight solutes, resulting in a rapid and sustained control of serum urate, potassium, and calcium × phosphorus product, avoiding the potentially deleterious rebound effects seen after hemodialysis.

To the Editor, It is with great interest that we read the manuscript entitled ‘‘Predictors of Bone Mineral Density Improvement in Patients Undergoing Parathyroidectomy for Primary Hyperparathyroidism’’ [1]. In that study, several factors have been identified as predictors of bone mineral density (BMD) improvement following parathyroidectomy (PTX) in primary hyperparathyroidism (PHPT). Unfortunately, no firm conclusion could be drawn about vitamin D levels mainly because no follow-up vitamin D levels were available [1]. However, vitamin D status probably plays an important role in the improvement of BMD in these patients. It has been known for several years that PHPT is associated with vitamin D deficiency (25OHD) [2]. Although the mechanism is still poorly understood, several mechanisms have been proposed: increased conversion of 25OHD to 1.25OHD or inactivation of 25OHD [2]. However, recent data suggest that PTH itself could inhibit liver hydroxylation of vitamin D2 or D3 by decreasing key cytochrome P450 isoforms [3]. Moreover, PTX done in the setting of secondary HPT (SHPT) (as seen in renal failure) restores the ability of the liver to hydroxylate vitamin D [3]. In PHPT, very few studies have evaluated the effect of PTX on 25OHD levels [4]. We reviewed nine cases of PHPT where vitamin D measurements were available preand post-PTX and in whom no vitamin D supplementation was administered. As shown in Table 1, following PTX, there was an increase in 25OHD and a decrease in 1.25OHD. Thus, PTX in PHPT could restore vitamin D by a mechanism probably similar to SHPT. Although the impact of restoring vitamin D levels in PHPT by PTX on BMD has not been studied directly, recent data clearly suggest that the administration of cholecalciferol in PHPT is accompanied by an improvement of BMD [5]. C. Lamarche D. Ouimet V. Pichette Department of Nephrology, Maisonneuve-Rosemont Hospital, Montreal, Canada e-mail: caroline.lamarche.1@umontreal.ca

We determined whether genetic variation at 3 loci coding for putative crystallization inhibitors is linked to calcium urolithiasis.We studied a cohort of 64 French-Canadian sibships including multiple recurrent calcium stone formers, comprising 154 independent pairs of siblings with at least 1 stone episode. Physical and meiotic mapping of the genes coding for osteopontin and uromodulin (Tamm-Horsfall protein) as well as the osteocalcin related gene (ORG or putative nephrocalcin) was performed and microsatellite markers were identified. We used nonparametric linkage analysis in the whole affected sib pair cohort as well as in affected pairs without hypercalciuria, that is concordant for 24-hour urine calcium excretion in the first quartile (mean plus or minus standard deviation 0.053 +/- 0.020 mmol./kg. or 3.4 +/- 1.3 mmol. daily), and in the first and second quartiles (mean 0.064 +/- 0.027 mmol./kg. or 4.9 +/- 2.1 mmol. daily, respectively).Lod scores were less than 0.3 for all 3 loci using these affection statuses. Further analysis enabled the exclusion of uromodulin at (relative risk or lambda = 3.9 and 2.5), osteopontin (lambda = 2.7 and 1.6) and ORG (lambda = 5.5 and 3.7) for affected sib pairs concordant for urine calcium excretion in the lowest and 2 lowest quartiles, respectively.Loci encoding 3 crystallization inhibitors are unlikely to be major genes involved in calcium stone formation in our population.

One hundred one continuous ambulatory peritoneal dialysis (CAPD) patients from a single North American center were analyzed in a retrospective and cross-over study for peritonitis rates using a standard system (Travenol System II) or a Y-shaped disconnect-disinfectant system (Travenol O-set). Twenty-one of 34 patients using the standard set (group I) had 53 episodes of peritonitis in 508 patient-months or one episode per 9.6 patient-months. Nine of 17 patients switching from the standard to the disconnect-disinfectant system (group II) experienced 22 episodes of peritonitis in 275 patient-months or one episode per 12.5 patient-months on the standard set, while six patients had 10 episodes of peritonitis in 275 patient-months or one episode per 27.5 patient-months on the disconnect-disinfectant system ( P P v group I). Exit-site infections (ESI) occurred in 35.3% of patients using the standard set versus 34.3% of those using the O-set. The presence of an ESI was not associated with a higher risk of peritonitis, but modified the bacteriological profile of subsequent peritonitis episodes in patients using the O-set, favoring the organisms isolated from the exit site. Decreases in peritonitis rates with the O-set were due to a reduction of peritonitis episodes secondary to most bacterial agents and not only to skin organisms. Diabetics using intraperitoneal insulin had similar peritonitis and ESI rates as nondiabetics. We conclude that, compared with a standard system, the O-set, a Y-shaped system with disinfectant, is associated with a twofold to threefold reduction in peritonitis rates. The presence of an ESI is not associated with a significantly higher peritonitis rate subsequently.

The purpose of this study was to determine the effects of high inlet dialysate flow rates (IDFR) on the clearances of urea and creatinine and to measure the absorption of glucose through the dialyzer in continuous arteriovenous hemodialysis (CAVHD). Ten anuric acute renal failure patients in the intensive care unit were studied. Increasing the IDFR from 0 to 33.3 mL/min (0 to 2 L/h) produced linear increments in the clearances of urea and creatinine, whereas further increases in the IDFR from 33.3 to 66.7 mL/min (2 to 4 L/h) produced less important, but still significant, increases in the clearances. At 66.7 mL/min, the clearances for urea and creatinine were 48.5 ± 3.4 and 42.2 ± 2.5 mL/min, respectively. Using a dialysate with a glucose concentration of 25.3 mmol/L (0.5 g/dL), the net transfer of glucose through the dialyzer did not change significantly, from 16.7 to 66.7 mL/min of IDFR. Increasing the inlet dialysate glucose concentration from 25.3 to 75.8, 126.3, and 214.6 mmol/L (0.5 to 1.5, 2.5, and 4.25 g/dL) at a fixed IDFR of 16.7 mL/min produced linear increments in the net glucose transferred to the patient, from 0.12 ± 0.02 to 0.67 ± 0.05, 1.25 ± 0.06 and 2.30 ± 0.14 mmol/min, respectively (21.4, 121.0, 225.7, and 414.5 mg/min). No significant changes in the ultrafiltration and plasma flow rates through the dialyzer were recorded at these different IDFR or inlet dialysate glucose concentrations. Ten patients were treated for 4 days or more with 16.7 mL/min (1 L/h) IDFR CAVHD with excellent control over kidney function parameters. We conclude that CAVHD with an IDFR of 16.7 mL/min is generally sufficient to control uremia, as it yields urea clearances of 35 L/d, equivalent to 4 hours of conventional hemodialysis. Since 60% of the glucose is absorbed through the dialyzer, intradialytic parenteral nutrition can be achieved with dialysate solutions containing glucose concentrations of 75.8 and 126.3 mmol/L (1.5 and 2.5 g/dL) yielding 2,900 to 5,500 kJ/d (700 to 1,300 kcal/24 h). High IDFR of 66.7 mL/min provide daily urea clearances of 70 L, equivalent to 8 hours of daily conventional hemodialysis. Potential new applications of such high IDFR CAVHD include lithium and methanol intoxications, as well as hyperkalemia, hyperuricemia, hyperphosphatemia, and hypercalcemia.

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.

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.

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.

Evaluation of the calcium-sensing receptor gene in idiopathic probably a polygenic trait (3) associated with increased hypercalciuria and calcium nephrolithiasis. urine calcium excretion (idiopathic hypercalciuria (IH)) Background. Calcium urolithiasis is in part genetically de- in up to 40% of stone formers. The genetic basis of IH termined and associated with idiopathic hypercalciuria. is largely unknown. Methods. We have used a candidate gene approach to deter- The calcium-sensing receptor (CaR) is a candidate mine whether the calcium-sensing receptor (CaR) gene is linked to idiopathic hypercalciuria and calcium urolithiasis in gene for IH. This G-protein-coupled receptor is ex- a cohort of French Canadian sibships with multiple affected pressed in parathyroid glands and kidneys and is a key members (64 sibships from 55 pedigrees yielding 359 affected regulator of parathyroid hormone (PTH) secretion and sibling pairs with $1 stone episode). renal tubular calcium reabsorption according to extracel- Results. Using nonparametric linkage analysis with various lular calcium concentration (7). In the parathyroid gland, intragenic and flanking markers, we showed that the CaR gene could be excluded as a major gene for hypercalciuric stone the CaR induces inhibition of PTH secretion upon bind- formation. We excluded the CaR (lod score ,22) at ls values ing of calcium. In the kidney, the CaR is highly expressed of 1.5, 1.68, and 2.6 for sib pairs concordant for at least one in multiple nephron segments, including medullar and stone passage, at least two stone passages, and at least one stone cortical thick ascending limbs, proximal and distal convo- passage and calciuria above the 75th percentile, respectively. luted tubules, and inner medullary collecting duct (8), Quantitative trait linkage analyses did not suggest that the CaR gene was linked to biochemical markers of idiopathic where it regulates renal tubular calcium reabsorption. hypercalciuria. In addition, the CaR is involved in urine concentration Conclusions. This study shows that genetic variants of the and dilution, as it inhibits the action of vasopressin to CaR gene are not associated with idiopathic hypercalciuria and balance the need for excreting calcium and conserving calcium nephrolithiasis in this population of French Canadians. water (9). Genetic variation at the CaR locus is linked to urine calcium excretion in rare monogenic traits, in- cluding familial benign hypercalcemia, neonatal severe The passage of a kidney stone (nephrolithiasis) is a hyperparathyroidism, and an autosomal dominant form common event that will affect 5 to 15% of the North of hypocalcemia (10-13). American population. In the United States, complica- We present the results of a sib-pair linkage analysis tions related to nephrolithiasis represent 1% of all hospi- of the CaR locus in a large group of French Canadian talizations and have an important economic impact (1). sibships. We tested this locus for linkage to calcium stone The most common type of nephrolithiasis is composed formation and quantitative phenotypes relevant to cal- of calcium, either as an oxalate or phosphate salt alone, cium metabolism. or as a combination of both. Familial aggregation studies suggest that genetic factors underlie stone formation (2-6). A positive family history is a strong risk factor METHODS (6), and the passage or formation of calcium stones is Pedigrees and phenotyping All families in the study were of French Canadian descent and were recruited from several specialized

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

Calcium is the principal crystalline constituent in up to 80% of kidney stones. Epidemiologic studies have suggested that genetic predisposition plays a major role in the etiology of this condition. This study evaluates by a candidate-gene approach whether the vitamin D receptor (VDR) locus on chromosome 12q12-14 is implicated in idiopathic hypercalciuria and calcium nephrolithiasis in a cohort of 47 French Canadian pedigrees. These comprised 54 sibships with a total of 303 pairs of siblings concordant for > or =1 stone episode. Evidence is provided for linkage to nephrolithiasis with microsatellite marker D12S339 (near the VDR locus, P = 0.01), as well as with flanking markers (D12S1663: P = 0.03 and D12S368: P = 0.01). Inclusion of unaffected sibs in the analyses also supported evidence for linkage. Quantitative trait linkage analysis of urinary calcium excretion yielded linkage to some, but not all, markers. This appears to be the first study to suggest linkage for idiopathic calcium stone formation.

Calcium urolithiasis is often associated with increased intestinal absorption and urine excretion of calcium, and has been suggested to result from increased vitamin D production. The role of the enzyme 1 alpha-hydroxylase, the rate-limiting step in active vitamin D production, was evaluated in 36 families, including 28 sibships with at least a pair of affected sibs, using qualitative and quantitative trait linkage analyses. Sibs with a verified calcium urolithiasis passage (n = 117) had higher 24-h calciuria (P = 0.03), oxaluria (P = 0.02), fasting and postcalcium loading urine calcium/creatinine (Ca/cr) ratios (P = 0.008 and P = 0.002, respectively), and serum 1,25(OH)2 vitamin D levels (P = 0.02) compared with nonstone-forming sibs (n = 120). Markers from a 9-centiMorgan interval encompassing the VDD1 locus on chromosome 12q13-14 (putative 1 alpha-hydroxylase) were analyzed in 28 sibships (146 sib pairs) of single and recurrent stone formers and in 14 sibships (65 sib pairs) with recurrent-only (> or = 3 episodes) stone-forming sibs. Two-point and multipoint analyses did not reveal excess in alleles shared among affected sibs at the VDD1 locus. Linkage of stone formation to the VDD1 locus could be excluded, respectively, with a lambda d of 2.0 (single and recurrent stone formers) and 3.25 (recurrent stone formers). Quantitative trait analyses revealed no evidence for linkage to 24-h calciuria and oxaluria, serum 1,25(OH)2 vitamin D levels, and Ca/cr ratios. This study shows absence of linkage of the putative 1 alpha-hydroxylase locus to calcium stone formation or to quantitative traits associated with idiopathic hypercalciuria. In addition, there is coaggregation of calciuric and oxaluric phenotypes with stone formation.

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.

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.

Hyperhomocysteinemia in hemodialysis patients: Effects of 12-month supplementation with hydrosoluble vitamins.BackgroundHigh-efficiency hemodialysis may induce a deficiency in hydrosoluble vitamins. Supplementation with B-complex vitamins has been shown to lower serum homocysteine concentrations in several groups, but relatively few studies have concerned hemodialysis patients. Our objectives were to determine the status in B-complex vitamins in a large cohort of unsupplemented hemodialysis patients and to assess the effects of supplementation with hydrosoluble vitamins on serum homocysteine over one year.MethodsSerum total homocysteine (tHcy), vitamin B12, folate, pyridoxal-5′-phosphate (P-5′-P; the active moiety of vitamin B6), as well as red blood cell folate concentrations, were measured in 168 chronic dialysis patients on three times weekly high-efficiency hemodialysis and not supplemented with hydrosoluble vitamins. Their methylenetetrahydrofolate reductase C677T (MTHFR) genotypes were also determined (homozygotes TT, heterozygotes CT, without mutation CC). All involved patients were then supplemented with hydrosoluble vitamins (once daily by mouth, DiaVite®; R&D Laboratories, Minneapolis, MN, USA), and half of them were randomized to receive in addition 10 mg intravenously of folic acid posthemodialysis (30 mg intravenously per week). Serum tHcy was monitored after 6 and 12 months of supplementation in the 140 and 128 patients available for follow-up.ResultsAt baseline, serum and red blood cell folate concentrations were within normal limits in all patients except for two with borderline serum folate (mean values of 21 ± 8 and 1195 ± 454 nmol/L), whereas serum vitamin B12 and P-5′-P were below normal in 11 and 65 patients, respectively (mean values of 327 ± 215 pmol/L and 19 ± 16 nmol/L for the 168 patients). Initial tHcy levels were increased in all patients (mean 33.3 ± 16.6 for a normal below 11.8 ± 1.5 μmol/L); tHcy significantly decreased to 23.5 ± 7.6 μmol/L after six months (P < 0.0001 vs. baseline) and to 21.7 ± 6.1 μmol/L after 12 months (P < 0.0001 vs. baseline) for the entire group, but was normalized in only four patients at 12 months. After six months, the mean reduction in tHcy was slightly but significantly greater for patients receiving intravenous folic acid (12.2 ± 18.5 μmol/L) compared with patients not receiving it (8.3 ± 9.8 μmol/L, P < 0.05). However, at 12 months, no difference between both subgroups persisted. When considering the different genotypes, tHcy at baseline tended to be higher for TT than CT and CC (39.8 ± 30.9 vs. 31.4 ± 10.5 vs. 31.6 ± 11.8 μmol/L) and decreased to respective values of 21.1 ± 6.9 versus 21.4 ± 6.1 versus 22.2 ± 5.9 μmol/L at 12 months. The impact of the addition of folic acid to DiaVite® appeared particularly significant in TT patients at six months.Conclusions(1) Hyperhomocysteinemia was present in 100% of our hemodialysis patients. (2) Nearly 40% of our unsupplemented hemodialysis patients were deficient in vitamin B6. (3) Supplementation with DiaVite® has resulted in significant tHcy reductions for all three genotypes. (4) The impact of the proposed supplementation protocol was found after six months and was maintained, but did not increase further after 12 months of the same regimen. (5) The addition of intravenous folic acid has been associated with a more pronounced decrease in tHcy in TT patients.

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.