Early determinants of atherosclerosis in paediatric systemic lupus erythematosus.

OBJECTIVES: To assess traditional and non-traditional cardiovascular risk factors and to determine the prevalence and correlates of early vascular markers of atherosclerosis in paediatric systemic lupus erythematosus (pSLE). METHODS: Fifty-four adolescents with pSLE had cardiovascular risk factor assessment, disease activity and vascular testing including carotid intima-media thickness (CIMT), flow-mediated dilatation (FMD), arterial stiffness measures, and myocardial perfusion studies. RESULTS: The traditional risk factors of hypertension, elevated triglycerides, apolipoprotein B, haemoglobin A1c and insulin levels and non-traditional risk factors of elevated homocysteine and fibrinogen were present (all p<0.001). Some arterial stiffness measures, central pulse wave velocity and characteristic impedance were elevated (p<0.001), but CIMT, FMD and myocardial perfusion were normal. Cumulative prednisone dose correlated with total cholesterol (r=0.5790, p<0.001) and elevated LDL-C (r=0.4488, p=0.0012). Hydroxychloroquine treatment correlated negatively with total cholesterol (r=-0.4867, p=0.0002), LDL-C (r=-0.4805, p=0.0002) and apolipoprotein B (r=-0.4443, p=0.0011). In multivariate analysis LDL-C correlated with cumulative prednisone dose and negatively with hydroxychloroquine treatment (R2=0.40, p<0.001). CONCLUSIONS: An increased burden of traditional and non-traditional risk factors and early evidence of insulin resistance and increased central arterial stiffness were present in paediatric SLE. Disease-specific and therapy-related factors are likely modifying these cardiovascular risk profiles warranting prospective longitudinal studies.

Improved parathyroid hormone control by cinacalcet is associated with reduction in darbepoetin requirement in patients with end-stage renal disease.

BACKGROUND: Uncontrolled hy-per-parathyroidism causes bone marrow fibrosis, leading to erythropoietin (EPO) resistance. Medical treatment with cinacalcet is effective in reducing plasma parathyroid hormone (PTH) levels, but its effect on darbepoetin dosing is unknown. METHODS AND AIMS: We conducted a retrospective cohort study of 40 end-stage renal disease (ESRD) patients (age: 55 ± 14; mean ± SD; 21:male) who had at least 12 months of cinacalcet therapy. The distribution of renal replacement therapies were: 14 peritoneal dialysis, 18 conventional hemodialysis and 8 nocturnal hemodialysis. Standard dialysis related biochemical indices and medications used were recorded. The primary objective of the study was to ascertain the difference in darbepoetin responsiveness before and after 12 months of cinacalcet therapy. Our secondary objective was to determine if there was a relationship between the changes in PTH and darbepoetin requirement. RESULTS: Overall, PTH levels decreased from 197.5 (151.8; 249.2) to 66.1 (41.2; 136.5) (median (25th;75th percentile)) pmol/l; p < 0.001. Cinacalcet dose increased from 30.0 ± 6 to 63 ± 25 mg/day, p < 0.05. Hemoglobin remained unchanged (116 ± 13 to 116 ± 13 g/l), while darbepoetin requirement decreased from 40 (20; 60) to 24 (19; 59) µg/week, p = 0.02. The remainder of the dialysis-related biochemistry (electrolytes, calcium, phosphate, iron status) and vitamin D use remained unchanged. A reduction in PTH level of greater than 30% was experienced by 82.5% (33/40) of our cohort. Among the responders, the fall in PTH and reduction darbepoetin requirement were related (R = -0.48, p = 0.004). CONCLUSIONS: Reduction of PTH by cinacalcet is associated with a decrease in darbepoetin requirement. The interface between bone and bone marrow in uremia represents a critical step in red blood cell production which merits further investigation.

The higher risk of death on peritoneal dialysis in the United States is not explained by background general population mortality: the CANUSA study revisited.

The CANUSA investigators reported a near doubling of the risk of death in peritoneal dialysis patients treated at U.S. sites compared to Canadian centers. Recently, evidence has suggested that background mortality rates in the general population might be responsible for differences in death rates on dialysis. The objective of this study was to determine if differences in background mortality in the general population were responsible for the increased risk of death observed in American patients in the CANUSA study. The CANUSA study was a prospective cohort study of 680 consecutive peritoneal dialysis patients at 14 centers in the U.S. and Canada. Extensive baseline data were available for all patients. The expected mortality rate of an individual of the same age, sex, and country of residence was determined at the time of enrollment in the CANUSA study. Cox proportional hazards models were used to determine if background mortality rates were responsible for the observed differences in survival between the two countries. Background mortality rate in the general population was associated with an increased risk of death on peritoneal dialysis, but after adjustment for other baseline factors, it was no longer significant. The adjusted, relative hazard of dying in the U.S. compared to Canada was unchanged after further adjusting for background mortality rate in statistical models (HR = 1.93; 95% confidence interval: 1.13 - 3.28). In conclusion, the increased risk of mortality in U.S. patients enrolled in the CANUSA study was not explained by differences in the background mortality rate in the general population.

Acute renal failure in paediatric systemic lupus erythematosus: treatment and outcome.

OBJECTIVE: To determine the outcome of paediatric SLE (pSLE) patients with nephritis who developed acute renal failure (ARF). Efficacy and safety of treatment regimens were compared. METHODS: A total of 249 pSLE patients were diagnosed and prospectively followed at a single centre between July 1973 and July 2003; 127 children (51%) had lupus nephritis. ARF was defined as serum creatinine of > 250 micromol/l or > 75% above baseline. Standardized assessments included clinical data and medications, laboratory testing, disease activity and damage scores were obtained. Subsequent renal flares were documented. PRIMARY OUTCOME: renal function at last follow-up. SECONDARY OUTCOMES: treatment efficacy and safety. AZA- and cyclophosphamide (CYCLO)-treated patients were compared. Propensity score methods were applied to balance covariates. An intention to treat approach was chosen. RESULTS: The ARF study cohort included 50 patients; 13 boys and 37 girls with a median age of 13.2 yrs at diagnosis and a mean follow-up of 45 months. Renal histology: Class III nephritis in 16; Class IV in 34. Dialysis requirement and disease activity were similar in both groups. TREATMENT: AZA in 33 patients, CYCLO in 9 and corticosteroids only in 8. OUTCOME: no statistically significant or clinically relevant differences were found for any of the outcome measures including last serum creatinine, time to renal flare, overall renal survival, disease activity over time, disease damage, mean annual corticosteroid dose and rate of infection. CONCLUSION: The treatment of renal failure in this pSLE cohort was associated with an excellent outcome. AZA and CYCLO were equally efficacious.

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

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

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

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

Examination of transepithelial exchange of water and solute in the rat renal pelvis.

Severance of the ureter beyond the renal papilla causes a fall in urinary osmolality, which suggests that exchange of water or solute between urine and renal parenchyma normally occurs in the intact renal pelvis. We examined water and solute flux in the renal pelvis with micropuncture and microcatheterization techniques. Four groups of antidiuretic rats were studied. Group I (n = 17) underwent micropuncture through the intact contracting ureter. Urine samples were obtained at the papillary tip, and in the pelvis beside the base of the extrarenal papilla. Urinary osmolality at the base, 880 +/- 97 mosmol/kg H2O (mean +/- SE), was less than that at the tip, 1,425 +/- 104 mosmol/kg H2O (P less than 0.005). In group II (n = 24), samples were analyzed for inulin and osmolality. In 15 rats (group IIA), comparison was made between base and tip samples. In the other nine animals (group IIB), comparisons were made among base, tip, and bladder samples and urea was also measured. In group II (A and B combined) urine-to-plasma (U/P) osmolality was lower at the base, 4.31 +/- 0.27, than at the tip, 6.08 +/- 0.23 (P less than 0.001), and U/P inulin was lower at the base, 192 +/- 25, than at the tip, 306 +/- 16 (P less than 0.001). In group IIB, the bladder urine had a lower U/P osmolality, 5.27 +/- 0.25, than the tip, 6.01 +/- 0.31 (P less than 0.02). The U/P urea was 59 +/- 10.6 (base), 98 +/- 9.4 (tip) (base vs. tip, P less than 0.05), and 81 +/- 6.5 (bladder, P less than 0.005, compared with tip). In group III (n = 8), samples were obtained by microcatheter from the fornices, the deepest intrarenal extensions of the pelvis, and compared with samples at the tip. Urinary osmolality was lower in the fornix, 646 +/- 106 mosmol/kg H2O, than at the tip, 1,296 +/- 99 mosmol/kg H2O (P less than 0.001). Similarly, U/P inulin was lower in the fornix, 48 +/- 14, than at the tip, 128 +/- 12 (P less than 0.001). The lower U/P inulin in the pelvic urine is the result of either the addition of fluid to the pelvis, or the backleak of inulin across the epithelium lining the pelvis. To verify that the pelvic epithelium was impermeable to inulin, in group IVA (n = 4) the left renal pelvis was superfused with a solution of chemical inulin. Cumulative absorption of inulin from the left kidney was 0.15 +/- 0.08% of that superfused. Using [14C]inulin in group IVB (n= 3), similar results were obtained (0.05 +/- 0.02%). These findings indicate that in the renal pelvis, fluid is added to urine after it emerges from the collecting ducts. We suggest that reflux of hyperosmotic urine over the renal papilla creates a transepithelial gradient for the flux of water into the pelvis. A model that incorporates diffusive and convective forces for water and solute transport is proposed to account for these findings.

Reverse epidemiology in peritoneal dialysis patients: the Canadian experience and review of the literature.

High Body Mass Index (BMI) has been associated with improved survival of End-Stage Renal Disease (ESRD) patients on chronic hemodialysis (HD); however, studies on the relationship of BMI with survival in Peritoneal Dialysis (PD) patients have yielded conflicting results. The purpose of this study was to evaluate the impact of BMI on survival of Canadian ESRD patients on PD, correcting for their age, sex, race, diabetes mellitus, and arterial hypertension. In an intent to treat study, we reviewed data of the Canadian Organ Replacement Register (CORR), of incident patients, starting PD between 1994 and 1998 and followed up from their initial PD treatment to the end of 2003. Patients were censored at loss to follow up, transplantation, and the end of the observation period. Cox regression (multivariate) analysis was performed and adjustments were made for age, gender, race, primary renal disease and BMI. During these years, 4054 patients commenced PD, 1742 (43%) of them were females and 1471 (36.3%) were diabetics. The majority were Caucasians (n=3058, 75.4%); 120 (3%) belonged to the First Nations, 137 (3.4%) were black, and the rest (739 pts-18.2%) belonged to various other ethnicities. Based on quartiles of the BMI distribution, 1130 patients (28%) had a BMI < 18.5 kg/m(2); 1163 (28.7%), 18.5-24.9 kg/m(2); 1214 (30%), 25-29.9 kg/m(2); 547 (13.5%) > 30 kg/m(2). Intent to treat Cox regression analysis showed that being underweight was a strong risk factor for death. Specifically, a BMI less than 18.5 was associated with a death hazard ratio (HR) 1.3, (CI: 1.1-1.6). On the contrary, BMI > 30 was not associated with worse survival than those with normal BMI (HR = 1.009, CI = 0.89-1.14). High-BMI patients should not be discouraged from PD just because of their size.

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

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

A multicenter study of noncompliance with continuous ambulatory peritoneal dialysis exchanges in US and Canadian patients.

Recent evidence suggested that noncompliance (NC) with continuous ambulatory peritoneal dialysis (CAPD) exchanges may be more common in US than in Canadian dialysis centers. This issue was investigated using a questionnaire-based method in 656 CAPD patients at 14 centers in the United States and Canada. NC was defined as missing more than one exchange per week or more than two exchanges per month. Patients were ensured of the confidentiality of their individual results. Mean patient age was 56 +/- 16 years, 52% were women, and 39% had diabetes. The overall admitted rate of NC was 13%, with a rate of 18% in the United States and 7% in Canada (P < 0.001). NC was more common in younger patients (P < 0.0001), those without diabetes (P < 0.001), and employed patients (P < 0.05). It was also more common in black and Hispanic than in Asian and white patients (P < 0.001). NC was more common in patients prescribed more than four exchanges daily (P < 0.0001) but was not affected by dwell volume. On multiple regression analysis, the independent predictors of NC, in order of importance, were being prescribed more than four exchanges per day, black race, being employed, younger age, and not having diabetes. Being treated in a US unit did not quite achieve significance as a multivariate independent predictor. These findings suggest that NC is not uncommon in CAPD patients and is more frequent in US than in Canadian patients. However, country of residence is less powerful as a predictor of NC than a variety of other demographic and prescription factors.

Management of minimal lesion glomerulonephritis: evidence-based recommendations.

The treatment of idiopathic minimal lesion disease in children has been extensively studied in randomized controlled trials, however, there is less information available for adults. This article summarizes evidence-based recommendations for management. The first attack should be treated with prednisone or prednisolone at 60 mg/m2 per day (up to a maximum of 80 mg/day) for four to six weeks, followed by 40 mg/m2 of prednisone every other day for another four to six weeks (grade A). Relapse should be treated with 60 mg/m2/day of prednisone (up to 80 mg/day) only until the urine becomes protein free for three days, and then an alternate day regimen of 40 mg/m2 should be used for another month (grade A). Patients with frequently relapsing disease will have a significant reduction in relapse frequency after eight weeks of an alkylating agent (grade A). Less rigorous studies have suggested benefit with long-term, alternate-day corticosteroid (grade D) or the antihelminthic agent levamisole (grade D). For patients with steroid-dependent disease, an 8- or 12-week course with cyclophosphamide can induce remission (grade D). In true steroid-resistant disease, observational studies have suggested that a course of cyclosporine may sometimes induce remission or restore steroid responsiveness (grade D). Large retrospective studies in adults suggest that therapeutic response is slower than in children, but adults experience fewer relapses and more prolonged remission.

Resolution of hyperparathyroidism associated with immunosuppressive therapy.

A patient maintained on continuous ambulatory peritoneal dialysis with severe hyperparathyroidism received a cadaver renal transplant. In the weeks following the transplant there was dramatic biochemical resolution of parathyroid hyperfunction associated with intensive immunosuppressive therapy, but without sustained return of function of the transplant kidney. Tertiary hyperparathyroidism often resolves slowly with successful renal transplantation. There are no previous reports of spontaneous resolution of hyperparathyroidism as demonstrated by this patient. Possible mechanisms, including the role of cytolytic antirejection therapy, are discussed.

Deterioration in renal function associated with fibrate therapy.

BACKGROUND: Fibric acid derivatives (fibrates) are commonly used for the treatment of hyperlipidemia. A side-effect of these medications that is not well recognized is deterioration in renal function during therapy. This study reviewed a series of patients who showed such a deterioration. METHODS: The design was a retrospective chart review. Data extracted included creatinine, urea, cyclosporine levels, medical history, and medications. Charts were examined for other potential reasons for a change in creatinine. RESULTS: There were a total of 10 patients. All were males between the ages of 37 and 71. All had a history of renal insufficiency. Six had received a renal transplant and, of these, 5 were on cyclosporine. Reasons for underlying renal impairment included diabetes, hypertension, nephrosclerosis, and renal disease of unknown etiology. Most patients had risk factors for or the presence of vascular disease. The mean pre-treatment creatinine was 182 +/- 14 micromol/l (2.1 +/- 0.2 mg/dl) (mean +/- SE), compared to a peak creatinine on the medication of 247 +/- 16 micromol/l (2.8 +/- 0.2 mg/dl) (p < 0.001). The post-medication mean was 183 +/- 13 (2.1 +/- 0.1 mg/dl) (p < 0.001 vs maximum creatinine). Urea values also increased with therapy and decreased following discontinuation of the fibrate. Cyclosporine levels did not change with treatment. All recorded creatine kinase values were within the normal range. CONCLUSIONS: A group of 10 men showed a reversible deterioration in renal function while being treated with a fibrate for hyperlipidemia. The mechanism involved in the deterioration in renal function is not clear. The most plausible mechanism is one based on renal hemodynamics, given the rapid and complete reversibility that was noted and the finding that most patients had risk factors for vascular disease. If patients with pre-existing renal dysfunction are to receive a trial of fibrate therapy, this should be done with caution and

A unique renal lesion in common variable immunodeficiency.

This article reports the case of a 33-year-old woman with common variable immunodeficiency (CVI) who developed renal failure 17 years after diagnosis and initiation of treatment with monthly IVIG. A renal biopsy revealed mesangial and paramesangial immune complex deposition and interstitial granulomatous infiltration. Renal function improved with oral corticosteroids, but did not return to normal. Decreasing the dose of IVIG had no effect on renal function. Immune dysfunction can be associated with both granulomatous disease and immune complex glomerulonephritis, or the latter may be related to chronic infection or immunoglobulin use. This is the first report of concomitant glomerular-tubulointerstitial lesions in this immunodeficiency syndrome. Renal function should be closely followed in patients with CVI.

IgA nephritis in HIV-positive patients: a new HIV-associated nephropathy?

Four HIV-positive patients were shown to have IgA-associated nephritis on biopsy, including one with anaphylactoid purpura. Three were homosexuals, while the fourth acquired the infection from his mother. All had hematuria, a variable degree of proteinuria and renal disease with a benign course. Serologic studies showed elevated levels of IgA as well as IgA immune complexes and rheumatoid factor. IgA antibodies to multiple HIV antigens were detected by Western blot. Pathologic studies showed tubuloreticular inclusions in endothelial cells and nuclear bodies in interstitial cells in all cases. HIV antigens were not detected in kidney biopsies by monoclonal antibodies nor was HIV viral genome demonstrated by in situ hybridization. The possibility that this represents a unique type of IgA-associated HIV nephropathy is discussed.

Long-term continuous ambulatory peritoneal dialysis in diabetics.

Of 147 diabetic patients with end-stage renal disease who were treated in our CAPD program between 1978 and 1991, 6 men and 1 woman (5 had type II and 2 type I diabetes) with a mean age of 54 (range 21-70) years have been on CAPD for more than five years (mean: 76 mos, range: 65-109 mos) and on peritoneal dialysis (IPD+CAPD) for an average of 85 (range: 67-118) mos. They had a variety of comorbid conditions at the start of CAPD: Retinopathy (5/7), blindness (3/7), hypertension (5/7), peripheral neuropathy (7/7), peripheral vascular disease (3/7), congestive heart failure (3/7), myocardial infarction (1/7), ischemic heart disease (2/7). Two were smokers and five over the age of 65. Peritonitis rate was 1 episode/11.4 pt mos, exit-site infection 1/76.4 pt mos and average hospitalization rate 32.8 days/patient/year. Hypertension was well-controlled with discontinuation of all medications; after initiation of CAPD two of them remained without medications throughout the study but in the rest, medications had to be restarted. As assessed by HbA1c, blood glucose control improved with IP administration of insulin. Residual renal function progressively decreased. None of them developed severe hyperparathyroidism. Peripheral neuropathy remained stable in four and deteriorated in two. Total protein, albumin, cholesterol and triglycerides decreased during the last two years indicating a degree of malnutrition. Our experience with these seven patients suggests that diabetic patients, even the aged and those with many comorbid conditions and complications, can survive for long periods on CAPD.

The rationale and ultimate limitations of urea kinetic modelling in the estimation of nutritional status.

OBJECTIVE: This paper reviews protein flux and amino acid metabolism and the potential inaccuracies inherent in using urea kinetics as an estimate of these processes, particularly in the patient undergoing peritoneal dialysis. The problems of extrapolating these estimates back to the whole patient are examined, addressing assumptions about neutral nitrogen balance, and the difficult issue of normalizing urea-derived indices to body size. CONCLUSIONS: Urea kinetics can be a helpful tool for assessing nutritional indices, but there are many caveats and many pitfalls that must be kept in mind to avoid being lulled into a false sense of confidence by the comfort of numbers.

The role of Na,K-ATPase inhibitors in hypertension and end-stage renal disease.

OBJECTIVE: To review the role of Na,K-ATPase inhibitors in the pathogenesis of essential hypertension and hypertension associated with end-stage renal disease. DATA SOURCES: MEDLINE search, 1966 to 1997. RESULTS: There is a suggestive physiologic and epidemiologic relationship between Na,K-ATPase inhibition and hypertension. However, clearance data cannot support the hypothesis that differential metabolism of this family of compounds explains the improved hypertensive control seen in patients on peritoneal dialysis compared to those on hemodialysis. CONCLUSIONS: As a result of the complex methodologies involved, it is unclear whether Na,K-ATPase inhibitors play a significant role in the hypertension of end-stage renal disease in general and peritoneal dialysis in particular.

The pharmacokinetics of intraperitoneal erythropoietin administered undiluted or diluted in dialysate.

OBJECTIVE: To compare the bioavailability of intraperitoneal erythropoietin (EPO) administered undiluted versus diluted in 2 L of dialysis fluid. DESIGN: Group 1 patients received one dose of EPO, 400 U/kg BW given with vehicle only. This dwelled for 8 hours after which 2 L of dialysate were infused. Group 2 patients received the same dose of EPO diluted in 2 L of dialysate which dwelled for 8 hours. Both groups resumed their CAPD regimen after the first 8 hours. Blood levels of EPO were measured for 24 hours in both groups. SETTING: The Home Peritoneal Dialysis Unit, Toronto Hospital, Western Division. PATIENTS: The participants were on CAPD for at least three months, free of peritonitis, and had no abnormalities of peritoneal transport. Three patients took part in both arms of the study, and there were 6 patients altogether in each group. RESULTS: When EPO was administered undiluted, there was a greater than ninefold increase in bioavailability of the hormone as measured by the area under the curve (AUC), compared to when the same dose was diluted in 2 L of dialysis fluid. CONCLUSIONS: The previous studies that reported low bioavailability of intraperitoneal EPO used the hormone diluted in dialysate. The current findings suggest that if EPO is given in the dry peritoneal cavity, the bioavailability is greatly improved and may be clinically effective. Intraperitoneal instillation may prove to be an alternative route for EPO in the peritoneal dialysis patient unable or unwilling to receive subcutaneous injections. We are currently studying the effectiveness of undiluted intraperitoneal EPO in CAPD patients.