Lee Er

Variability and Risk Factors for Kidney Disease Progression and Death Following Attainment of Stage 4 CKD in a Referred Cohort

BACKGROUND The outcomes of patients referred to nephrologists are not well described in large cohorts. The objectives of this analysis are to describe the predictors of rapid progression of kidney disease and death in patients followed up by nephrologists. STUDY DESIGN Retrospective study. SETTING & PARTICIPANTS A cohort derived from all patients registered in the provincial database was formed that included all patients with index estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73 m(2), at least 3 subsequent eGFR values, and 4 months of follow-up between January 2000 and January 2004. PREDICTORS Variables used to predict outcomes included baseline eGFR, duration of follow-up before eGFR less than 30 mL/min/1.73 m(2), age, sex, ethnicity, presence of diabetes, blood pressure, level of proteinuria, hemoglobin level, phosphate level, calcium level, parathyroid hormone level, and use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, erythropoiesis-stimulating agents, and vitamin D. OUTCOMES Key outcomes of interest were death, dialysis therapy start, or loss of GFR greater than 5 mL/min/1.73 m(2)/y. RESULTS 4,231 patients met inclusion criteria. Mean age was 67 years. Median follow-up was 31 months. During the first 2 years of follow-up, 24% started dialysis therapy, 1% received a transplant, 7% died, and 1% was lost to follow-up. Statistically significant variables associated with more rapid kidney disease progression differ from those that predict death. Younger age, male sex, higher eGFR, higher systolic and diastolic blood pressure, lower hemoglobin level, higher phosphorus and parathyroid hormone levels, and greater proteinuria are associated with more rapid kidney disease progression, and use of angiotensin-converting enzymes/angiotensin receptor blockers are protective. Older age, lower diastolic blood pressure, lower hemoglobin level, and higher phosphorous and parathyroid hormone levels are associated with death, whereas vitamin D use is protective. LIMITATIONS Results cannot be generalized to unreferred patients with eGFR less than 30 mL/min/1.73 m(2). CONCLUSION The clinical course of patients with chronic kidney disease stage 4 is variable. Targeted therapy aimed at modifiable risk factors needs to be evaluated to determine benefits of this approach.

A comparison of the predictive performance of different methods of kidney function estimation in a well-characterized HIV-infected population.

Background: Glomerular filtration rate (GFR) estimation equations have never been validated in the HIV population. This pilot study aimed to compare all currently available methods of kidney function assessment with nuclear GFR in HIV-infected adults. Methods: Patients underwent GFR measurement with 99mTc-diethylenetriaminepentaacetic acid (Tc-99m Pentetate), and measured values were compared with results of creatinine-based estimation equations [abbreviated 4-variable Modification of Diet in Renal Disease (MDRD) formula and Cockcroft-Gault (CG) formulae], 24-hour urine creatinine clearance and estimated cystatin C GFR. Results: Twenty-seven HIV-infected adults were studied. Most were male and Caucasian, with a mean age of 52 years. Median CD4 was 290 cells/mm3, 70% of patients had HIV RNA <50 copies/ml and all were receiving highly active antiretroviral therapy (median 5 drugs). Median Tc-99m Pentetate-GFR was 91 ml/min/1.73 m2. Despite greater bias and similar accuracy, the MDRD formula was more precise than the CG formula, regardless of whether CG estimations were corrected for ideal body weight or body surface area. Relative accuracy within 30% of nuclear GFR was greater for the MDRD formula than for all other methods. The performance of 24-hour urine creatinine clearance was similar to that of the MDRD formula for patients with GFR <90 ml/min/1.73 m2, although it performed less well at higher GFR. The performance of cystatin C GFR was inferior to that of all the creatinine-based methods. Conclusions: While no method of kidney function estimation performed highly, both 24-hour urine creatinine clearance and the MDRD formula performed with a level of precision and accuracy sufficient for clinical decision making. Our findings support the preferential use of the MDRD formula in the treated HIV population and suggest that there are no HIV-specific factors that limit equation applicability. Larger validation studies are needed to confirm our findings and allow generalization to the HIV population at large.

Elevated osteoprotegerin is associated with all-cause mortality in CKD stage 4 and 5 patients in addition to vascular calcification

BACKGROUND Cardiovascular disease is the leading cause of death in the chronic kidney disease (CKD) population. The mechanisms of vascular damage are not fully understood. The objective of this study was to prospectively investigate the importance of novel mediators of vascular damage, in conjunction with vascular calcification (VC), on survival. METHODS A total of 134 subjects [60 haemodialysis (HD), 28 peritoneal dialysis (PD) and 46 CKD stage 4] were studied. All survivors completed 40 months of follow-up. VC was measured using multi-slice spiral CT of the superficial femoral artery. Circulating osteoprotegerin (OPG), Fetuin-A and high sensitivity C-reactive protein (hs-CRP) were measured in addition to standard clinical biochemical analysis. RESULTS After a 40-month follow-up, 31 patients had died (27 men and 4 women). Of 31 subjects, 31 had evidence of significant VC. The majority of deaths were in the HD group (48%), 36% were PD subjects and 16% were CKD subjects. The outcome of interest was survival at the end of follow-up. Multivariate logistical regression analysis revealed male gender [OR 8.06 (1.34-48.450) P = 0.02], OPG >25 pmol/L [OR 5.31(1.35-20.88) P = 0.02] and hypoalbuminaemia [OR 0.26 (0.12-0.56) P < 0.01], were associated with increased odds of death. CONCLUSION We have previously reported that VC and low albumin predict death in CKD stages 4 and 5 over a 2-year follow-up period. These data show that OPG, independent of CRP, is also associated with a negative outcome. The mechanisms remain to be elucidated; however, it is likely that they are associated with vascular damage through mechanisms in addition to VC.

Responsiveness of FGF-23 and mineral metabolism to altered dietary phosphate intake in chronic kidney disease (CKD): results of a randomized trial

BACKGROUND High fibroblast growth factor-23 (FGF-23) levels are associated with adverse outcomes. We studied the responsiveness of FGF-23 and mineral metabolism to altered dietary phosphate intake in chronic kidney disease (CKD) and healthy control patients. METHODS Thirty patients were enrolled: 18 normophosphatemic CKD subjects and 12 healthy controls. The study duration was 21 days with three 7-day dietary interventions; a high phosphate (HP, 2000 mg/day), low phosphate (750 mg/day) and low phosphate plus phosphate binder (aluminum hydroxide, 500 mg thrice daily with meals), with comparable macronutrient content, administered in random sequence. Baseline and weekly fasting morning measurements of FGF-23, serum phosphate (sPO(4)), 1,25-hydroxyvitamin D (1,25 D) and 24-h urinary calcium (uCa) and phosphate (uPO(4)) were collected. RESULTS FGF-23 levels were higher in subjects versus controls (72 pg/mL versus 30 pg/mL) at baseline, while sPO(4) remained in the normal range throughout the study. The absolute changes of uPO(4) and uCa for CKD and controls vary according to diet. The absolute changes of FGF-23 and sPO(4) suggest that the effect of the diets might also depend on the CKD status (P-values interaction effect = 0.08 and 0.07, respectively); nonetheless, these changes are evident as a function of dietary interventions, irrespective of CKD status (P-values diet effect = 0.006 and <0.001, respectively). CONCLUSIONS FGF-23 levels appear to be responsive to changes in diet in both CKD patients and controls. Further studies are required to determine whether lowering dietary phosphate and thus FGF-23 levels are of long-term benefit in CKD patients, irrespective of sPO(4) levels.

Exploration of Association of 1,25-OH2D3 with Augmentation Index, a Composite Measure of Arterial Stiffness

BACKGROUND AND OBJECTIVES Abnormalities in mineral metabolism [calcium, phosphate, and immunoreactive parathyroid hormone (PTH)] and vitamin D have been linked to increases in central arterial stiffness. Central arterial stiffness can be measured using noninvasive technologies, including augmentation index (AIx), a composite measure of arterial stiffness. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS In 131 outpatients identified from individual cardiac or kidney disease clinics, we examined conventional demographic and laboratory risk factors, vitamin D levels (1,25-OH2D3 and 25-OHD3), and markers of inflammation or endothelial function [C-reactive peptide (hsCRP), matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9), and IL-6] in relationship to AIx. RESULTS The median eGFR was significantly different between clinics (range 25-81 ml/min). Subjects with higher phosphate or MMP-9 levels were found to have a higher AIx (P = 0.02 and 0.07, respectively). Lower 1,25-OH2D3 levels or reduced eGFR were associated with higher AIx (P = 0.002 and 0.005, respectively). The associations between 1,25-OH2D3 and phosphate levels and AIx were observed for values within the normal range. No association was noted for calcium, iPTH, 25-OHD3, or hsCRP and AIx. Adjusting for potential confounders [eGFR, calcium, phosphate, and (log) iPTH] the association of lower 1,25-OH2D3 with AIx remained statistically significant. CONCLUSION This exploratory study demonstrates a significant association between AIx and 1,25-OH2D3 in a diverse group with cardiac, kidney disease, or both. These increasing understanding of the role of vitamin D in vascular health lends a context to these findings and raises questions as to additional modifiable risk factors in complex patients. Further studies are required.

CKD Following Kidney Transplantation in Children and Adolescents

BACKGROUND There is under-recognition of comorbid conditions associated with chronic kidney disease (CKD) in children and adolescents after successful renal transplantation. STUDY DESIGN Retrospective cross-sectional. SETTING & PARTICIPANTS Children and adolescents aged 1 to 20 years with kidney disease in a transplant (n = 45) and native-kidney-disease cohort (n = 102) matched for CKD stages. CKD stages were assigned using glomerular filtration rate measured by means of nuclear medicine studies. A single pediatric nephrology group cared for all patients. PREDICTOR History of kidney transplantation. OUTCOMES Complications of CKD (anemia, hypertension, acidosis, and bone mineral metabolism). RESULTS The transplant (38% CKD stages 1 to 2, 62% CKD stages 3 to 5) and native-kidney (55% CKD stages 1 to 2, 45% CKD stages 3 to 5) cohorts were similar in demographic and baseline profiles; 68% of transplant recipients had 2 or more complications compared with 29% of native-kidney patients. After adjusting for baseline variables, the odds of having anemia was greater in transplant recipients (odds ratio, 9.7; 95% confidence interval, 3.9 to 24.6) at all CKD stages. The odds of having hypertension was particularly greater (odds ratio, 12.9; 95% confidence interval, 3.4 to 49.4) in transplant recipients with stages 1 to 2 CKD. No significant differences in bone mineral metabolism or acidosis were seen between groups. LIMITATIONS Retrospective cross-sectional design limits availability of data; lack of consistent protocols introduces treatment bias among physicians. CONCLUSIONS Children with CKD after transplantation appear to have greater odds of having anemia and hypertension than those with CKD in native kidneys. We suggest that increased awareness and attention to these 2 modifiable risk factors for CKD and cardiovascular disease may improve outcomes after transplantation.

Implementing a home haemodialysis programme without adversely affecting a peritoneal dialysis programme

BACKGROUND As the population with stage 5 CKD grows, the associated costs of providing dialysis care increase. Due to the high costs of these therapies, home haemodialysis is enjoying a renaissance in many jurisdictions. However, concerns persist as to whether home haemodialysis programmes grow at the expense of other home therapies such as peritoneal dialysis. This study attempts to look at the impact of a new home haemodialysis programme on an existing peritoneal dialysis programme in the province of British Columbia. METHODS Using the provincial renal database in British Columbia (PROMIS), all patients receiving dialysis were tracked over the years preceding the implementation of a home haemodialysis programme and following its implementation. Rate of growth by specific dialysis modality (hospital haemodialysis, community haemodialysis, home haemodialysis, and peritoneal dialysis) were tracked. RESULTS When comparing the provincial growth rates in the peritoneal dialysis programme, using the 4 years before and following the introduction of the home haemodialysis programme, they were unchanged both annually (7.84% versus 7.34%) and overall (25.27% versus 23.62%). The growth within the home haemodialysis programme appears to have come from the community haemodialysis programme (annual growth rate 12.28% versus 5.87%) and in-hospital haemodialysis (annual growth rate 4.61% versus 1.3%). Incident rates of dialysis were similar both prior to and following the introduction of the home haemodialysis programme.Finally, only 6.4% of the total patients entering the home haemodialysis programme had discontinued peritoneal dialysis within the 6 months preceding home haemodialysis training, indicating a low frequency of movement from peritoneal dialysis to home haemodialysis. CONCLUSIONS Successful implementation of a home haemodialysis programme can be done at a provincial level without having an adverse impact on the growth rate of existing peritoneal dialysis programmes.

Coronary artery calcification scores in patients with chronic kidney disease prior to dialysis: reliability as a trial outcome measure

BACKGROUND Coronary artery calcification (CAC) is prevalent in patients with chronic kidney disease (CKD). Data on the reliability and validity of high-resolution computerized tomography (HRCT) in patients with CKD is lacking. The purpose of this study was to evaluate the inter- and intra-reviewer agreement and inter-scan reproducibility of CACS measurement with HRCT in a cohort of patients with CKD prior to dialysis, and to compare the change in CACS at 30 minutes to the change in CACS over 1 year. METHODS Thirty-three patients with CKD not yet on dialysis underwent an HRCT scan at baseline and 1 year to assess for CAC and CAC progression. Two radiologists independently reviewed films and each radiologist re-reviewed a randomly selected subset of films they had previously viewed, to assess for inter-reviewer and intra-reviewer reliability, respectively. Patients underwent a repeat scan within 30 min of the first baseline scan to assess for inter-scan reproducibility. RESULTS At baseline, eight patients (24%) had no CAC. Of the 25 patients (76%) with CAC, 10 (40%) had severe calcification. Intra-reviewer agreement was 83%. Inter-reviewer agreement ranged between 77 and 94%. Six (27%) of the patients with >30 baseline CACS had >15% change in CACS following repositioning. Four of these patients had an increase in CACS with position change [18% (95% CI: 5-40%)]. Of the 21 patients who underwent a follow-up scan at 1 year, 7 (33%) demonstrated CACS progression. CONCLUSIONS There is significant imprecision in HRCT-derived CACS in CKD patients. This suggests a need for standardization of methods of CACS measurement with HRCT.

EVALUATION OF A 12-MONTH PILOT OF LONG-TERM AND TEMPORARY ASSISTED PERITONEAL DIALYSIS

♦ Background: Peritoneal dialysis (PD) is challenging for patients with functional limitations, and assisted PD can support these patients, but previous reports of assisted PD have not examined the role of temporary assisted PD and had difficulty identifying adequate comparator cohorts. ♦ Methods: Peritoneal Dialysis Assist (PDA), a 12-month pilot of long-term and temporary assisted PD was completed in multiple PD centers in British Columbia, Canada. Continuous cycler PD (CCPD) patients were identified for PDA by standardized criteria, and service could be long-term or temporary/respite. The PDA program provided daily assistance with cycler dismantle and setup, but patients remained responsible for cycler connections and treatment decisions. Outcomes were compared against both the general CCPD population and patients who met PDA criteria but were not enrolled (PDA-eligible). ♦ Results: Fifty-three PDA patients had an 88% 1-year death- and transplant-censored technique survival that was similar to the general CCPD cohort (84%) and PDA-eligible cohort (86%). The PDA cohort had lower peritonitis rates (0.18 episodes/patient-year vs 0.22 and 0.36, respectively), but higher hospitalization (55% vs 34% and 35%, respectively). Long-term PDA cost approximately CDN

Variability of Hepatitis B Testing in British Columbian ESRD Patients: The Case to Focus on Implementation of Guidelines

15,000/year in addition to existing dialysis costs. A total of 8/11 respite PDA patients (73%) returned to self-care PD after a median PDA use of 29 days, which costs