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.

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.

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.

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.

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.

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.

Structural changes in silicon rubber peritoneal dialysis catheters in patients using mupirocin at the exit site.

Structural damage to polyurethane PD (peritoneal dialysis) catheters in patients using mupirocin ointment is widely appreciated, but damage to silicon rubber PD catheters is less well described. Ten catheters (6.6%) out of 152 were found to have structural alterations such as opacification, ballooning, thinning, and rupture. The duration of PD in these 10 patients ranged from 23 months to 80 months (mean duration 51.1 months). The frequency of mupirocin application varied from daily (2 cases) to 2-3 times per week (7 cases). In eight catheters opacification occurred at the exit site whereas one catheter showed opacification midway between the exit site and the titanium adaptor. One catheter showed opacification, ballooning, and thinning at the exit site ruptured in the form of two slit-like openings. In conclusion, various structural changes such as opacification, ballooning or thinning were seen in 6.6% of silicon rubber PD catheters in patients using mupirocin at the exit site. Although the mechanism remains elusive, mupirocin or the antiseptic solution alone or in combination may be contributory. We believe that this is an under-reported complication and encourage other health care givers to incorporate a search for such changes during clinic visits.

Renal cell carcinoma in peritoneal dialysis patients.

Renal cell carcinoma is a rare but serious complication in ESRD patients. In these patients the incidence of renal cell carcinoma (RCC) is 20-40 times higher than in the general population. We performed a retrospective study to measure the incidence rate, prevalence, characteristics and survival among our peritoneal dialysis (PD) patients diagnosed with renal cell carcinoma. The study was carried out among 607 patients who were on the PD program from January 1997 to June 2002. RCC was detected in eight patients (four males and four females) with mean age of 52.1 +/- 10.6 years. Among these eight patients four were new cases that were diagnosed before the patients were started on dialysis (three in native kidneys and one in a transplanted kidney). In the other four patients the RCC was diagnosed after they had been on dialysis for 33-204 months (mean 60.75 +/- 50.48). We found an incidence rate of 1.3 per 1000 patients per year and a prevalence of 1.3%. Six of the eight patients had renal cysts. Tumor size was less than 7 cm in seven patients and in the other patient it was 8.5 cm. Seven of eight patients were alive at the time of study with a survival time ranging from 3-138 months (mean 122.25 +/- 88.2) months. In one patient, the RCC metastasised to the scalp, and, in two other patients, the tumors subsequently involved the second kidney. A cardiovascular complication was the cause of one death. Two patients received a renal transplant 36 and 66 months after diagnosis. We conclude that despite the low rate of metastases and mortality in our study, regular ultrasonography should be added to the follow-up of PD patients. Renal transplantation can be considered in these ESRD patients with RCC; however, close follow-up for metastases is recommended.

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.