Association Between Implementation Of Novel Therapies And Improved Survival In Patients Starting Hemodialysis: The Swedish Renal Registry 2006-2015.

BACKGROUND: The recent years have witnessed significant therapeutic advances for patients on hemodialysis. We evaluated temporal changes in treatments practices and survival rates among incident hemodialysis patients. METHODS: Observational study of patients initiating hemodialysis in Sweden 2006-2015. Trends of hemodialysis-related practices, medications, and routine laboratory biomarkers were evaluated. The incidence of death and major cardiovascular events (MACE) across calendar years were compared against the age-sex-matched general population. Via Cox regression, we explored whether adjustment for implementation of therapeutic advances modified observed survival and MACE risks. RESULTS: Among 6,612 patients, age and sex were similar, but the burden of co-morbidities increased over time. The proportion of patients receiving treatment by hemodiafiltration, >3 sessions/week, lower ultrafiltration rate, and working fistulas increased progressively, as did use of non-calcium phosphate binders, cinacalcet, and vitamin D3. The standardized 1-year mortality decreased from 13.2% in 2006/07 to 11.1% in 2014/15. The risk of death decreased by 6% (HR 0.94, 95% CI 0.90-0.99) every two years, and the risk of MACE by 4% (HR 0.96; 0.92-1.00). Adjustment for changes in treatment characteristics abrogated these associations (HR 1.00; 0.92-1.09 for death and 1.00; 0.94-1.06 for MACE). Compared with the general population, the risk of death declined from 6 times higher 2006/2007 [standardized incidence rate ratio, sIRR 6.0 (5.3-6.9)], to 5.6 higher 2014/15 [sIRR 5.57 (4.8-6.4)]. CONCLUSIONS: Gradual implementation of therapeutic advances over the last decade was associated with a parallel reduction in short-term risk of death and MACE among hemodialysis patients.

Prostate cancer in kidney transplant recipients - a nationwide register study.

OBJECTIVE: To investigate whether post-transplantation immunosuppression negatively affects prostate cancer outcomes in male kidney transplant recipients. PATIENTS AND METHODS: We used the Swedish Renal Register and the National Prostate Cancer Register to identify all kidney transplantation recipients diagnosed with prostate cancer in Sweden 1998-2016. After linking these registers with Prostate Cancer Database Sweden (PCBaSe), a case-control study was designed to compare time period and risk category-specific probabilities of a prostate cancer diagnosis amongst kidney transplantation recipients versus the male general population. The registers did not include information about the specific immunosuppression agent used in all transplantation recipients. Data from PCBaSe were used to compare prostate cancer characteristics at diagnosis and survival for patients with prostate cancer with versus without a kidney transplant. Propensity score matching, Cox regression analysis and Fisher's exact test were used and 95% confidence intervals (CIs) calculated. RESULTS: Almost half of the 133 kidney transplantation recipients were transplanted before the mid-1990s, when PSA testing became common. The transplant recipients were not more likely than age-matched control men to be diagnosed with any (odds ratio [OR] 0.84, 95% CI 0.70-0.99) or high-risk or metastatic prostate cancer (OR 0.84, 95% CI 0.62-1.13). None of the ORs for the different categories of prostate cancer increased with time since transplantation. Cancer characteristics at the time of diagnosis and cancer-specific survival were similar amongst transplant recipients and the control group of 665 men diagnosed with prostate cancer without a kidney transplant. CONCLUSIONS: This Swedish nationwide, register-based study gave no indication that immunosuppression after kidney transplantation increases the risk of prostate cancer or adversely affects prostate cancer outcomes. The study suggests that men with untreated low-grade prostate cancer can be accepted for transplantation.

Cardiovascular and Cerebrovascular Events After Parathyroidectomy in Patients on Renal Replacement Therapy.

BACKGROUND: A majority of patients with end-stage renal disease suffer from secondary hyperparathyroidism, which is associated with osteoporosis and cardiovascular disease. Parathyroidectomy (PTX) is often necessary despite medical treatment. However, the effect of PTX on cardio- and cerebrovascular events (CVE) remains unclear. Data on the effect of PTX from population-based studies are scarce. Some studies have shown decreased incidence of CVE after PTX. The aim of this study was to evaluate the effect of PTX on risk of CVE in patients on renal replacement therapy. METHODS: We performed a nested case-control study within the Swedish Renal Registry (SRR) by matching PTX patients on dialysis or with functioning renal allograft with up to five non-PTX controls for age, sex and underlying renal disease. To calculate time to CVE, i.e., myocardial infarct, stroke and transient ischemic attack, control patients were assigned the calendar date (d) of the PTX of the case patient. Crude and adjusted proportional hazards regressions with random effect (frailty) were used to calculate hazard ratios for CVE. RESULTS: The study cohort included 20,056 patients in the SRR between 1991 and 2009. Among these, 579 patients had undergone PTX, 423 during dialysis and 156 during time with functioning renal allograft. These patients were matched with 1234 dialysis and 736 transplanted non-PTX patients. The adjusted hazard ratio (HR) with 95% confidence interval (CI) of CVE after PTX was 1.24 (1.03-1.49) for dialysis patients compared with non-PTX patients. Corresponding results for patients with renal allograft at d were HR (95% CI) 0.53 (0.34-0.84). CONCLUSIONS: PTX patients on dialysis at d had a higher risk of CVE than patients without PTX. Patients with renal allograft at d on the other had a lower risk after PTX than patients without PTX.

Total versus subtotal parathyroidectomy for secondary hyperparathyroidism.

BACKGROUND: It remains unclear whether total or subtotal parathyroidectomy for secondary hyperparathyroidism yields the best outcomes. We investigated mortality, cardiovascular events, hip fracture, and recurrent parathyroidectomy after total versus subtotal parathyroidectomy in patients on renal replacement therapy. METHODS: Using the Swedish Renal Registry, the surgical registry for thyroid and parathyroid surgery, and the National Inpatient Registry, we identified patients who underwent parathyroidectomy between 1991 and 2013. We calculated the risk of outcome after total versus subtotal parathyroidectomy using COX's regression, adjusting for age, sex, cause of renal disease, time with a functioning graft before and after parathyroidectomy, Charlson comorbidity index, year of surgery, prevalent cardiovascular disease, time on dialysis, renal transplantation at parathyroidectomy, and treatment with calcimimetics before parathyroidectomy. RESULTS: There were 824 patients who underwent parathyroidectomy, 388 total and 436 subtotal. There was no difference in mortality or risk of incident hip fracture between groups. Comparing the subtotal with the total parathyroidectomy, the adjusted hazard ratio (95% confidence interval) for cardiovascular events was 0.43 (0.25-0.72) and for recurrent parathyroidectomy 3.33 (1.33-8.32). CONCLUSION: There was a higher risk of cardiovascular events in patients after total parathyroidectomy compared with subtotal parathyroidectomy, but a lower risk of recurrent parathyroidectomy.

Effects of Kidney Transplantation on Labor Market Outcomes in Sweden.

BACKGROUND: Kidney transplantation is considered a superior treatment for end-stage renal disease compared with dialysis although little is known about the wider effects, especially on labor market outcomes. The objective is to estimate the treatment effect of kidney transplantation compared with dialysis on labor market outcomes, controlling for the nonrandom selection into treatment. METHODS: The average treatment effect is estimated using an inverse-probability weighting regression adjustment approach on all patients in renal replacement therapy 1995 to 2012. RESULTS: Kidney transplantation is associated with a treatment advantage over dialysis on employment, labor force participation, early retirement, and labor income. The probability of being employed 1 year after treatment is 21 (95% confidence interval, 16-25) percentage points higher for transplantation. The positive effect increases to 38 (95% confidence interval, 30-46) percentage points after 5 years, mainly due to worsening outcomes on dialysis. The effect on labor income is mainly mediated through employment probability. The productivity gains of transplantation compared to dialysis amounts to &OV0556;33 000 over 5 years. CONCLUSIONS: Transplantation is superior to dialysis in terms of potential to return to work as well as in terms of labor income and risk of early retirement, after controlling for treatment selection. This positive effect increases over time after transplantation.

Do kidney transplantations save money? A study using a before-after design and multiple register-based data from Sweden.

BACKGROUND: The health care costs of kidney transplantation and dialysis are generally unknown. This study estimates the Swedish health care costs of kidney transplantation and dialysis over 10 years from a health care perspective. METHOD: A before-after design was used, in which the patients served as their own controls. Health care costs the year before transplantation were assumed to continue in the absence of a transplant and the cost savings was therefore calculated as the difference between the expected costs and the actual costs during the 10-year follow-up period. Factors associated with the size of the cost savings were studied using ordinary least-squares regression. RESULTS: Altogether 66-79% of the expected health care costs over 10 years were avoided through kidney transplantation, resulting in a cost savings of €380 000 (2012 price-year) per patient. Savings were the highest for successful transplantations, but on average the treatment was cost-saving also for patients who returned to dialysis. No gender or age differences could be found, with the exception of a higher cost of transplantation for children and a generally higher cost for younger compared with older patients on dialysis. A negative association was also found between age at the time of transplantation and the size of the cost savings for the younger part of the sample. CONCLUSION: Kidney transplantations have led to substantial cost savings for the Swedish health care system. An increase in donated kidneys has the potential to further reduce the cost of renal replacement therapy.

The effect of parathyroidectomy on patient survival in secondary hyperparathyroidism.

BACKGROUND: Secondary hyperparathyroidism is a common condition in patients with end-stage renal disease and is associated with osteoporosis and cardiovascular disease. Despite improved medical treatment, parathyroidectomy (PTX) is still necessary for many patients on renal replacement therapy. The aim of this study was to evaluate the effect of PTX on patient survival. METHODS: A nested index-referent study was performed within the Swedish Renal Registry (SRR). Patients on maintenance dialysis and transplantation at the time of PTX were analysed separately. The PTX patients in each of these strata were matched for age, sex and underlying renal diseases with up to five referent patients who had not undergone PTX. To calculate survival time and hazard ratios, indexes and referents were assigned the calendar date (d) of the PTX of the index patient. The risk of death after PTX was calculated using crude and adjusted Cox proportional hazards regressions. RESULTS: There were 20 056 patients in the SRR between 1991 and 2009. Of these, 579 (423 on dialysis and 156 with a renal transplant at d) incident patients with PTX were matched with 1234/892 non-PTX patients. The adjusted relative risk of death was a hazard ratio (HR) of 0.80 [95% confidence interval (CI) 0.65-0.99] for dialysis patients at d who had undergone PTX compared with matched patients who had not. Corresponding results for the patients with a renal allograft at d were an HR of 1.10 (95% CI 0.71-1.70). CONCLUSIONS: PTX was associated with improved survival in patients on maintenance dialysis but not in patients with renal allograft.

Temporal trends and risk factors for parathyroidectomy in the Swedish dialysis and transplant population - a nationwide, population-based study 1991 - 2009.

BACKGROUND: Many patients on renal replacement therapy (RRT) require parathyroidectomy (PTX). Trends and current rates of PTX on a national level are not known. Furthermore, it is not completely clear which factors influence rates of PTX. Thus, our aim was to investigate the incidence, regional distribution and factors associated with PTX as well as possible temporal changes, in the Swedish RRT population. METHODS: From the Swedish Renal Registry we extracted data on 20 015 patients on RRT between 1991 and 2009. In these, 679 incident PTX (3.4%) were identified by linkage with the National Inpatient Registry, and the Scandinavian Quality Registry for Thyroid Parathyroid and Adrenal Surgery. Poisson models were used to estimate rates per calendar year, adjusted for risk factors such as gender, age, time with renal transplant, and underlying cause of renal disease. RESULTS: The PTX rate was 8.8/1 000 person-years. There was a significant increase 2001-2004 after which the rate fell, as compared with year 2000. Female gender, non-diabetic cause of renal disease and age between 40-55 were all associated with an increased frequency of PTX. CONCLUSION: The rise in PTX rates after year 2000 might reflect increasing awareness of the potential benefits of PTX. The introduction of calcimimetics and paricalcitol might explain the decreased rate after 2005.

Glomerular filtration rate-estimating equations for patients with advanced chronic kidney disease.

BACKGROUND: Renal function is often estimated using one of several glomerular filtration rate (GFR) estimating equations. However, there is no consensus which estimating equation performs best in patients with advanced renal failure. METHODS: We compared the performance of five different estimated GFR (eGFR) equations [Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease (CKD) Epidemiology collaboration (CKD-EPI) and Mayo Clinic and Lund-Malmö] with measured GFR (plasma iohexol clearance) in 2098 referred CKD patients with mGFR <30 mL/min/1.73 m(2). RESULTS: There were 398 patients with an mGFR ≤ 10 mL/min/1.73 m(2), 1974 with a measured GFR (mGFR) 11-20 mL/min/1.73 m(2) and 749 patients with mGFR 21-30 mL/min/1.73 m(2). Across the entire range, the median bias of eGFR was lowest for the Lund-Malmö equation (0.7 mL/min/1.73 m(2)), followed by the CKD-EPI (1.2 mL/min/1.73 m(2)), the MDRD (1.6 mL/min/1.73 m(2)), Mayo Clinic equation (1.7 mL/min/1.73 m(2)) and Cockcroft-Gault equation (4.6 mL/min/1.73 m(2)). The best accuracy within 30% of mGFR was also for Lund-Malmö (76%), while it was similar for CKD-EPI, MDRD and Mayo (65-67%). The Cockcroft-Gault had the worst accuracy of only ∼54%.The median bias was stable across mGFR categories, while the accuracy within 30% of mGFR became worse with decreasing mGFR. All equations performed best among patients with hereditary kidney diseases and tubulointerstitial disease. Accuracy was generally worse for patients >65 years of age and for those with diabetic nephropathy. CONCLUSIONS: In patients with advanced renal failure, the GFR-estimating equations show reasonably good performance on the population level. On the individual patient level, they are inaccurate, especially in elderly patients and those with diabetic nephropathy.

The increase in renal replacement therapy (RRT) incidence has come to an end in Sweden-analysis of variations by region over the period 1991-2010.

BACKGROUND: Renal replacement therapy (RRT) incidence has increased significantly in Sweden during the past decades. This study analyses variations in time and regional trends in RRT incidence in Sweden, adjusted for age and gender, focusing on the impact change in incidence during the last decade. METHODS: Using data from the Swedish Renal Registry (SRR) (21 counties in Sweden, total population 9 million), we identified all incident subjects starting RRT from 1991 through 2010. Only individuals alive following 90 days of RRT start were included. Gender- and age-specific standardized RRT incidences on an annual and regional basis were calculated, and differences between counties and variations over time were examined. We compared the overall age and gender-adjusted RRT incidence rates for Sweden by calendar year. Furthermore, we also calculated the age and gender-adjusted RRT incidence in each county during two time periods (1991-1999 versus 2000-2010). RESULTS: There were 20 172 new subjects treated with RRT between January 1991 and December 2010. The most common cause of end-stage renal disease (ESRD) was diabetes (24%) and hypertension/renal vascular disease (19%), followed by glomerulonephritis (16%). Sixty-four percent of new patients were male; the median age when commencing RRT was 66 years (10-90 percentiles; 39-80). The overall standardized RRT incidence reached its peak in 2000, and slowly decreased thereafter. A decrease in RRT incidence was observed over the study period in eight regions. The standardized RRT incidence varied between the different counties, from 0.82 to 1.19. CONCLUSIONS: Adjusted for demographic changes in the population, an overall decrease in RRT incidence was observed from the year 2000 onwards-suggesting that the previously reported steady increase in RRT incidence is coming to an end in Sweden. Noteworthy differences were found between counties and in 8 out of 21 counties, a decreased incidence of RRT was found. Further studies need to identify the factors that contribute to this decrease.

Increased risk of end-stage renal disease in individuals with coeliac disease.

OBJECTIVE: The prevalence of end-stage renal disease (ESRD) is increasing worldwide. Although increased levels of coeliac disease (CD) autoantibodies are often seen in renal disease, the importance of biopsy-verified CD for the risk of future ESRD is unclear. The aim of this study was therefore to investigate the risk of future ESRD in individuals with CD. METHODS: This was a population-based prospective cohort study. 29,050 individuals with CD (Marsh III) were identified through small-intestinal biopsy reports obtained between July 1969 and February 2008 in Sweden's 28 pathology departments. ESRD was defined as the need for renal dialysis or renal transplant in accordance with the international classification of disease and procedure codes in Swedish patient registers. Using Cox regression, the risk of ESRD in individuals with CD compared with age- and sex-matched reference individuals was estimated. RESULTS: During follow-up, 90 individuals with CD developed ESRD (expected count 31). This corresponded to a HR for ESRD of 2.87 (95% CI 2.22 to 3.71, p<0.001). Adjusting for diabetes mellitus had only a marginal effect on the risk estimate (HR 2.52, 95% CI 1.92 to 3.31). Excluding individuals with any urinary/renal disorder before study entry, the HR for ESRD in CD was 2.47 (95% CI 1.80 to 3.40). When restricting the outcome measure to ESRD confirmed by independent data from the Swedish Renal Registry (SRR), the risk estimate increased to 3.20 (95% CI 2.39 to 4.28). CONCLUSION: This study indicates that individuals with biopsy-verified CD suffer increased risk of subsequent ESRD.

Interdialytic weight gain and ultrafiltration rate in hemodialysis: lessons about fluid adherence from a national registry of clinical practice.

Excessive interdialytic weight gain (IWG) and ultrafiltration rates (UFR) above 10 mL/h/kg body weight imply higher morbidity and mortality. This study aimed to estimate the prevalence of high fluid consumers, describe UFR patterns, and describe patient characteristics associated with IWG and UFR. The Swedish Dialysis DataBase and The Swedish Renal Registry of Active Treatment of Uremia were used as data sources. Data were analyzed from patients aged >/=18 on regular treatment with hemodialysis (HD) and registered during 2002 to 2006. Interdialytic weight gain and dialytic UFR were examined in annual cohorts and the records were based on 9693 HD sessions in 4498 patients. Differences in proportions were analyzed with the chi-square test and differences in means were tested using the ANOVA or the t test. About 30% of the patients had IWG that exceed 3.5% of dry body weight and 5% had IWG >/=5.7%. The volume removed during HD was >10 mL/h/kg for 15% to 23% of the patients, and this rate increased during the first dialytic year. Patient characteristics associated with fluid overload were younger age, lower body mass index, longer dialytic vintage, and high blood pressure. By studying IWG and dialytic UFR as quality indicators, it is shown that there is a potential for continuing improvement in the care of patients in HD settings, i.e., to enhanced adherence to fluid restriction or alternatively to extend the frequency of dialysis for all patients, e.g., by providing daily treatment.

Mortality among hemodialysis patients in Europe, Japan, and the United States: case-mix effects.

BACKGROUND: The Dialysis Outcomes and Practice Patterns Study is well suited to identify case-mix effects, given its extensive data set. The data set was used to examine the influence of case-mix variables on mortality and the extent to which these variables account for differences in mortality across regions, as well as the prevalence and incidence of hepatitis B and hepatitis C. METHODS: Demographic and comorbid disease features were determined for 8,615 patients internationally; mortality was recorded for this cohort, plus replacement patients (total n = 16,720), from 1996 to 2002. Mortality was associated with increasing age, nonblack race, coronary artery disease, congestive heart failure, other cardiac disease, diabetes mellitus, peripheral vascular disease, cerebrovascular disease, absence of hypertension, lung disease, cancer, human immunodeficiency virus infection, gastrointestinal bleeding, neurologic disease, psychiatric disease, cellulitis/gangrene, hepatitis C, and smoking. RESULTS: US patients were slightly older than those in Europe or Japan and had the highest prevalence of diabetes, coronary artery disease, congestive heart failure, peripheral vascular disease, and cerebrovascular disease. CONCLUSION: Upon adjusting for case-mix to assess mortality across facilities, it was found that regional differences in mortality (highest in the United States and lowest in Japan) and differences across facilities within nations remain after such corrections. It is likely that practice patterns account for some of this variation. Prevalence of hepatitis B virus (HBV) across facilities increased as the number of dialyzing patients per facility increased; risk of HBV seroconversion decreased among facilities using protocols for treatment of patients with HBV infection. Greater employment of staff with at least 2 years of formal nursing training was associated with lower prevalence of hepatitis C virus infection and lower seroconversion risk.