Denis Ouimet

Long-term bone loss in kidney transplant recipients: a cross-sectional and longitudinal study

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, P < 0.001 and R = 0.29, P < 0.05, 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 (P < 0.05), larger cumulative prednisone dose (P < 0.05), 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% (P < 0.001). 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 (P < 0.01). 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.

Dialysate Leaks in Peritoneal Dialysis

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 (≤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.

Renal Replacement in End-Stage Renal Disease Patients over 75 Years Old

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.

Lithium poisoning treated by high-performance continuous arteriovenous and venovenous hemodiafiltration

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.

Solute clearances with high dialysate flow rates and glucose absorption from the dialysate in continuous arteriovenous hemodialysis.

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.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduced Hepatic Synthesis of Calcidiol in Uremia

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 (P < 0.002). 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.

Successful Treatment of Encapsulating Peritoneal Sclerosis With Immunosuppressive Therapy

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.

High Dialysate Flow Rate Continuous Arteriovenous Hemodialysis: A New Approach for the Treatment of Acute Renal Failure and Tumor Lysis Syndrome

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-m2 hollow-fiber polyacrylonitrile dialyzer (Multiflow 60; Hospal, St-Léonard, Québec, 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 x 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 KCl 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Atheroembolic Renal Failure Requiring Dialysis: Potential for Renal Recovery?

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.

Continuous ambulatory peritoneal dialysis for patients with severe left ventricular systolic dysfunction and end-stage renal disease

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.