Monica Beaulieu

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.

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.

Regional Implementation of Creatinine Measurement Standardization

Because patients may receive care at multiple locations within a geographic area, serum creatinine measurements must be standardized across laboratories to enable comparisons of reported estimated glomerular filtration rate (eGFR). The results of a successful creatinine standardization program designed to minimize the contribution of laboratory error to the reporting of eGFR are reported; 107 laboratories, which tested creatinine on 124 analyzers from six different manufacturers, voluntarily participated. Each laboratory received a correction factor to apply to its creatinine measurements to standardize them to the isotope dilution mass spectrometry reference method. The adjusted values were then used to calculate eGFR using the Modification of Diet in Renal Disease (MDRD) equation. The standardization program reduced the average total error in the measurement of creatinine from 23.9 to 8.7% and the average analytical bias from 16.5 to 2.7%. Implementing this program on a larger scale could reduce the rate of incorrect classification of stage 3 chronic kidney disease by 84%.

Proliferative glomerulonephritis with monoclonal IgG deposits secondary to chronic lymphocytic leukemia. Report of two cases

Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) is a recently described entity that is only rarely associated with a hematological or lymphoproliferative malignancy. We describe the cases of two men with preexisting chronic lymphocytic leukemia (CLL) who developed endocapillary proliferative glomerulonephritis with nonorganized monoclonal IgG(1) deposits. One biopsy also showed CLL infiltration of the cortex. Both patients were treated with rituximab in addition to cyclophosphamide in one case and fludarabine in the other with significant improvement of their renal disease and CLL. This report provides additional evidence to support the use of rituximab in the therapy of CLL-associated PGNMID.

Analysis of Multidisciplinary Care Models and Interface With Primary Care in Management of Chronic Kidney Disease

Public policy efforts and education have led to an increased appreciation of the prevalence of chronic kidney disease (CKD) in general outpatient populations. The complexity of the care of individuals with established CKD has led to the development of multidisciplinary care models, which have been shown to improve the clinical outcomes of those with CKD. The interface between specialty and primary care in various systems remains necessary and desired, albeit a continuing challenge. This overview reviews various models of specialty care for CKD patients, including those that emphasize multidisciplinary team approaches, and highlight the essential role(s) of primary care physicians. Importantly, there is a need for improved definition of CKD populations and individuals, review and refinement of proposed care pathways, and the need to define essential elements of care for the patient. Models of care often are not subject to the same rigor that other interventions applied to this population are; nonetheless, we offer here a framework for establishing and evaluating care models for the CKD populations at various stages of disease and with various comorbidities.

Prevalence and incidence of hepatitis C virus in hemodialysis patients in British Columbia: Follow-up after a possible breach in hemodialysis machines

BACKGROUND A possible breach of the transducer protector in specific dialysis machines was reported in June 2004 in British Columbia (BC), which led to testing of hemodialysis patients for hepatitis C virus (HCV), hepatitis B virus (HBV) and HIV. This testing provided an opportunity to examine HCV incidence, prevalence and coinfection with HBV and HIV, and to compare anti-HCV and HCV polymerase chain reaction (PCR). METHODS The results of hemodialysis patients who were dialyzed on the implicated machines (65% of BC dialysis patients), and tested for HCV, HBV and HIV, between June 1, 2004, and December 31, 2004, were reviewed and compared with available previous results. RESULTS Of 1286 hemodialysis patients with anti-HCV and/or HCV-PCR testing, 69 (5.4%) tested positive. Two HCV genotype 4 seroconversions were identified. HCV incidence rate on dialysis was 78.8 cases per 100,000 person-years. Younger age, history of renal transplant and past HBV infection were associated with HCV infection. No occult infection was identified using HCV-PCR. INTERPRETATION Hemodialysis patients had three times the HCV prevalence rate of the general BC population, and more than 20 times the incident rate of the general Canadian population. One of the two seroconversions occurred before the testing campaign; the patient was likely infected during hemodialysis in South Asia. The other was plausibly a late seroconversion following renal transplant in South Asia. Nosocomial transmission cannot be ruled out because both patients were dialyzed in the same centre. Baseline and annual anti-HCV testing is recommended. HCV-PCR should be considered at baseline for persons with HCV risk factors, and for returning travellers who received dialysis in HCV-endemic countries to identify HCV infection occurring outside the hemodialysis unit.

Diabetes, kidney disease and cardiovascular disease patients. Assessing care of complex patients using outpatient testing and visits: additional metrics by which to evaluate health care system functioning

BACKGROUND The triad of cardiovascular disease (CVD), chronic kidney disease (CKD) and diabetes mellitus (DM) share many fundamental disease pathways. Patients with these conditions contribute excessively to health care costs. Opportunities for system redesign require metrics by which to evaluate the impact. METHODS Using a provincial comprehensive set of administrative billing databases (outpatient visits, laboratory tests, pharmacy and hospital inpatient services), we itemized the prevalence of each and combination of conditions, resource utilization associated with each condition and combinations, using ICD 9-10 billing codes and standard definitions. Three consecutive years (2003-2005) were used to establish stability of findings. RESULTS CKD, CVD and DM diagnoses are found in 422 124 persons within a province of 4.3 million individuals (10%); 1.7% had all three conditions. The median age of each cohort varied significantly between those with multiple conditions (67-79 years) versus those with single condition (56-72 years). The median number of physician visits was 26 per patient year. Duplicate testing accounted for expenditures of

The need for improved uptake of the KDIGO glomerulonephritis guidelines into clinical practice in Canada: a survey of nephrologists

3 million/annum; 7.55% of patients accounted for 34.4% of duplicate tests. Those with DM or CKD had similar use of medications, physician visits and hospital days. Those with all conditions (CVD-CKD-DM) had a median of 6 in-hospital days/year. A significant proportion were not on ACE/ARB or statin medications (30 and 45%, respectively). CONCLUSION Patients with chronic, complex conditions consume a large number of outpatient and inpatient resources. Documenting these allows identification of a set of metrics by which to design and measure health care system redesign initiatives. Potential targets to benchmark in designing more effective systems have been identified.

Randomized Controlled Trial for the Effect of Vitamin D Supplementation on Vascular Stiffness in CKD

Background The lack of glomerulonephritis (GN) guidelines has historically contributed to substantial variability in the treatment of GN. We hypothesize that there are barriers to GN guideline implementation leading to incomplete translation of the 2012 KDIGO GN guidelines into patient care, and that current practice patterns deviate from guideline recommendations. Methods Adult nephrologists in Canada (N = 390) were surveyed using a web-based tool. The survey of 40 questions captured physician demographics, self-reported GN case load, treatment approaches and barriers to guideline implementation. Results The response rate was 44%. Physicians report seeing six (IQR 4,10) new cases of idiopathic GN every 6 months. The majority treat ANCA GN according to guidelines, but 9–37% treat nephrotic focal segmental glomerulosclerosis or membranous nephropathy with non-recommended immunosuppression and 6–9% do not treat with any immunotherapy, whereas 26% treat subnephrotic disease with immunosuppression. The majority indicated that standardized care tools would improve patient care, but they were only available to 25–44%. Patient education tools and nursing support are unavailable to 87 and 67%, respectively; insurance coverage for immune therapies is poorly accessible to 84%, yet 86% feel this would improve care and 96% of physicians support comparing their practice with benchmarks from provincial GN registries. Conclusions We show that 2 years after the publication of the KDIGO GN guidelines, 15–46% of Canadian nephrologists report treatment strategies not in keeping with guideline recommendations. We identify barriers to guideline implementation and widespread physician support for initiatives that address these barriers to improve patient care.

An overview of the British Columbia Glomerulonephritis network and registry: integrating knowledge generation and translation within a single framework

BACKGROUND AND OBJECTIVES Vitamin D is implicated in vascular health in CKD. This study compared placebo, calcifediol, and calcitriol treatment with changes in vascular stiffness, BP, proteinuria, mineral metabolism parameters, C-reactive protein, and fibroblast growth factor 23 in patients with stable CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We conducted a double-blind, randomized controlled trial in out-patient CKD clinics in Vancouver, Canada, from February of 2011 to August of 2014, enrolling 119 patients with an eGFR of 15-45 ml/min per 1.73 m2. Change in pulse wave velocity (PWV) was measured after 6 months of treatment with a fixed dose of oral calcifediol (5000 IU 25-hydroxyvitamin D3), calcitriol (0.5 µg 1,25-dihydroxyvitamin D3), or placebo, thrice weekly. RESULTS Eighty-seven participants were evaluated. Mean age was 66 years, 71% were men, 40% were diabetic, and mean baseline PWV was 11.5 m/s (SD=3.9 m/s). After 6 months, the PWV decreased in the calcifediol group (mean change, -1.1; 95% confidence interval [95% CI], -2.2 to 0.1 m/s), remained unchanged in the calcitriol group (mean change, 0.2; 95% CI, -0.9 to 1.4 m/s), and increased in the placebo group (mean change, 1.1; 95% CI, -0.1 to 2.2 m/s). The overall P value for between-arm changes was 0.03. Absolute PWV change was significantly different between groups (P=0.04): the combined vitamin D treatment group saw decreased PWV (mean change, -0.4; 95% CI, -1.2 to 0.4 m/s) whereas the placebo group saw increased PWV (mean change, +1.1; 95% CI, -0.1 to 2.2 m/s). The treatment group demonstrated significantly decreased serum parathyroid hormone (mean difference, -0.5; 95% CI, -0.7 to -0.3 ln[pg/ml]; P<0.001) and increased calcium (mean difference, 0.4; 95% CI, -0.1 to 0.7 mg/dl; P=0.02). In observational analysis, participants in the highest 25-hydroxyvitamin D tertile at trial end had significant decreases in PWV (mean change, -1.0; 95% CI, -2.0 to 0.0 m/s) compared with the middle and lowest tertiles (P<0.01). Side effects were minor and rare. CONCLUSIONS Six months of supplemental vitamin D analogs at fixed doses may achieve a reduction of PWV in patients with advanced CKD. Because the treatment effect was attenuated when baseline PWV was included as a covariate, these findings should be replicated in larger populations and further studied.