Suboptimal dialysis initiation is associated with comorbidities and uraemia progression rate but not with estimated glomerular filtration rate.

BACKGROUND: Despite early referral of uraemic patients to nephrological care, suboptimal dialysis initiation (SDI) remains a common problem associated with increased morbimortality. We hypothesized that SDI is related to pre-dialysis care. METHODS: In the 'Peridialysis' study, time and reasons for dialysis initiation (DI), clinical and biochemical data and centre characteristics were registered during the pre- and peri-dialytic period for 1583 end-stage kidney disease patients starting dialysis over a 3-year period at 15 nephrology departments in the Nordic and Baltic countries to identify factors associated with SDI. RESULTS: SDI occurred in 42%. Risk factors for SDI were late referral, cachexia, comorbidity (particularly cardiovascular), hypoalbuminaemia and rapid uraemia progression. Patients with polycystic renal disease had a lower incidence of SDI. High urea and C-reactive protein levels, acidosis and other electrolyte disorders were markers of SDI, independently of estimated glomerular filtration rate (eGFR). SDI patients had higher eGFR than non-SDI patients during the pre-dialysis period, but lower eGFR at DI. eGFR as such did not predict SDI. Patients with comorbidities had higher eGFR at DI. Centre practice and policy did not associate with the incidence of SDI. CONCLUSIONS: SDI occurred in 42% of all DIs. SDI was associated with hypoalbuminaemia, comorbidity and rate of eGFR loss, but not with the degree of renal failure as assessed by eGFR.

Twelve months of exercise training did not halt abdominal aortic calcification in patients with CKD - a sub-study of RENEXC-a randomized controlled trial.

BACKGROUND: Arteriosclerosis is prevalent in patients with chronic kidney disease (CKD). Our aims were to investigate (1) the effects of 12 months of either balance- or strength- both in combination with endurance training on abdominal aortic calcification (AAC); on some lipids and calcific- and inflammatory markers; and (2) the relationships between the change in AAC score and these markers in non-dialysis dependent patients with CKD stages 3 to 5. METHODS: One hundred twelve patients (mean age 67 ± 13 years), who completed 12 months of exercise training; comprising either balance- or strength training, both in combination with endurance training; with a measured glomerular filtration rate (mGFR) 22.6 ± 8 mL/min/1.73m2, were included in this study. AAC was evaluated with lateral lumbar X-ray using the scoring system described by Kauppila. Plasma fetuin-A, fibroblast growth factor 23 (FGF23) and interleukin 6 (IL6) were measured with Enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: After 12 months of exercise training, the AAC score increased significantly in both groups; mGFR and lipoprotein (a) decreased significantly in both groups; parathyroid hormone (PTH) and 1,25(OH)2D3 increased significantly only in the strength group; fetuin-A increased significantly only in the balance group. Plasma triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, FGF23, phosphate, calcium, IL6, C-reactive protein (CRP), albumin were unchanged. The increase in AAC score was positively related to ageing and the levels of baseline triglycerides and lipoprotein (a). CONCLUSIONS: Exercise training did not prevent the progression of AAC; it might have contributed to the reduced levels of lipoprotein (a) and unchanged levels of calcific- and inflammatory markers in these patients with non-dialysis dependent CKD. Hypertriglyceridemia, high levels of lipoprotein (a) and ageing emerged as longitudinal predictors of vascular calcification in these patients. TRIAL REGISTRATION: NCT02041156 at www.ClinicalTrials.gov. Date of registration: January 20, 2014. Retrospectively registered.

The treatment of renal hyperparathyroidism.

Renal hyperparathyroidism (rHPT) is a complex and challenging disorder. It develops early in the course of renal failure and is associated with increased risks of fractures, cardiovascular disease and death. It is treated medically, but when medical therapy cannot control the hyperparathyroidism, surgical parathyroidectomy is an option. In this review, we summarize the pathophysiology, diagnosis, and medical treatment; we describe the effects of renal transplantation; and discuss the indications and strategies in parathyroidectomy for rHPT. Renal hyperparathyroidism develops early in renal failure, mainly as a consequence of lower levels of vitamin D, hypocalcemia, diminished excretion of phosphate and inability to activate vitamin D. Treatment consists of supplying vitamin D and reducing phosphate intake. In later stages calcimimetics might be added. RHPT refractory to medical treatment can be managed surgically with parathyroidectomy. Risks of surgery are small but not negligible. Parathyroidectomy should likely not be too radical, especially if the patient is a candidate for future renal transplantation. Subtotal or total parathyroidectomy with autotransplantation are recognized surgical options. Renal transplantation improves rHPT but does not cure it.

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.

Improved long-term survival with home hemodialysis compared with institutional hemodialysis and peritoneal dialysis: a matched cohort study.

BACKGROUND: The survival rate for dialysis patients is poor. Previous studies have shown improved survival with home hemodialysis (HHD), but this could be due to patient selection, since HHD patients tend to be younger and healthier. The aim of the present study is to analyse the long-term effects of HHD on patient survival and on subsequent renal transplantation, compared with institutional hemodialysis (IHD) and peritoneal dialysis (PD), taking age and comorbidity into account. METHODS: Patients starting HHD as initial renal replacement therapy (RRT) were matched with patients on IHD or PD, according to gender, age, Charlson Comorbidity Index and start date of RRT, using the Swedish Renal Registry from 1991 to 2012. Survival analyses were performed as intention-to-treat (disregarding changes in RRT) and per-protocol (as on initial RRT). RESULTS: A total of 152 patients with HHD as initial RRT were matched with 608 IHD and 456 PD patients, respectively. Median survival was longer for HHD in intention-to-treat analyses: 18.5 years compared with 11.9 for IHD (p <  0.001) and 15.0 for PD (p = 0.002). The difference remained significant in per-protocol analyses omitting the contribution of subsequent transplantation. Patients on HHD were more likely to receive a renal transplant compared with IHD and PD, although treatment modality did not affect subsequent graft survival (p > 0.05). CONCLUSION: HHD as initial RRT showed improved long-term patient survival compared with IHD and PD. This survival advantage persisted after matching and adjusting for a higher transplantation rate. Dialysis modality had no impact on subsequent graft survival.

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.

Relationships between abdominal aortic calcification, glomerular filtration rate, and cardiovascular risk factors in patients with non-dialysis dependent chronic kidney disease
.

BACKGROUND: Abdominal aortic calcification (AAC) is an established risk factor for cardiovascular events in patients with chronic kidney disease (CKD). We hypothesized that AAC is associated with a decline in glomerular filtration rate (GFR) as well as with some other cardiovascular risk factors. MATERIALS AND METHODS: This is a cross-sectional analysis of baseline data from a randomized controlled clinical trial (RENEXC). A total of 151 patients (aged 66 ± 14 years) with an average measured GFR (mGFR) of 22.5 ± 8.2 mL/min/1.73m2, not on renal replacement therapy, irrespective of number of comorbidities, were included. GFR was measured with iohexol clearance and estimated using cystatin C- and creatinine-based equations (eGFR). AAC was evaluated with lateral lumbar X-ray using the scoring system described by Kauppila. All patients underwent laboratory analyses, 24-hour ambulatory blood pressure monitoring, and standard echocardiography. Multiple linear regression analyses controlling for sex, age, cardiovascular comorbidities, and hypertension were performed. RESULTS: The prevalence of AAC in this group of patients was 73%, and 47% had severe calcification (AAC score ≥ 7). More men (76%) had AAC than women (69%). AAC score was associated with mGFR (p = 0.03), eGFR (p = 0.006), plasma albumin (p = 0.006), plasma phosphate (p = 0.01), pulse pressure (p = 0.004), left ventricular mass (LVM) (p = 0.02), left atrial volume (LAV; p < 0.001), and left atrial volume index (LAVI; p = 0.001). CONCLUSION: AAC was highly prevalent in CKD. The degree of calcification in the abdominal aorta was strongly associated with a decline in GFR, a decrease in plasma albumin, an increase in plasma phosphate, an increase in pulse pressure, and cardiac structural changes, such as an increase in LVM, LAV, and LAVI.
.

Why do physicians prescribe dialysis? A prospective questionnaire study.

INTRODUCTION: The incidence of unplanned dialysis initiation (DI) with consequent increased comorbidity, mortality and reduced modality choice remains high, but the optimal timing of dialysis initiation (DI) remains controversial, and there is a lack of studies of specific reasons for DI. We investigated why and when physicians prescribe dialysis and hypothesized that physician motivation for DI is an independent factor which may have clinical consequences. METHODS: In the Peridialysis study, an ongoing multicenter prospective study assessing the causes and timing of DI and consequences of unplanned dialysis, physicians in 11 hospitals were asked to describe their primary, secondary and further reasons for prescribing DI. The stated reasons for DI were analyzed in relation to clinical and biochemical data at DI, and characteristics of physicians. RESULTS: In 446 patients (median age 67 years; 38% females; diabetes 25.6%), DI was prescribed by 84 doctors who stated 23 different primary reasons for DI. The primary indication was clinical in 63% and biochemical in 37%; 23% started for life-threatening conditions. Reduced renal function accounted for only 19% of primary reasons for DI but was a primary or contributing reason in 69%. The eGFR at DI was 7.2 ±3.4 ml/min/1.73 m2, but varied according to comorbidity and cause of DI. Patients with cachexia, anorexia and pulmonary stasis (34% with heart failure) had the highest eGFR (8.2-9.8 ml/min/1.73 m2), and those with edema, "low GFR", and acidosis, the lowest (4.6-6.1 ml/min/1.73 m2). Patients with multiple comorbidity including diabetes started at a high eGFR (8.7 ml/min/1.73 m2). Physician experience played a role in dialysis prescription. Non-specialists were more likely to prescribe dialysis for life-threatening conditions, while older and more experienced physicians were more likely to start dialysis for clinical reasons, and at a lower eGFR. Female doctors started dialysis at a higher eGFR than males (8.0 vs. 7.1 ml/min/1.73 m2). CONCLUSIONS: DI was prescribed mainly based on clinical reasons in accordance with current recommendations while low renal function accounted for only 19% of primary reasons for DI. There are considerable differences in physicians´ stated motivations for DI, related to their age, clinical experience and interpretation of biochemical variables. These differences may be an independent factor in the clinical treatment of patients, with consequences for the risk of unplanned DI.

The Effect of Parathyroidectomy on Risk of Hip Fracture in Secondary Hyperparathyroidism.

BACKGROUND: Secondary hyperparathyroidism increases the risk for fractures. Despite improvement in medical therapy, surgical parathyroidectomy (PTX) often becomes necessary, but its effect on risk of fractures is not clear. Our aim was to study the effect of parathyroidectomy on the risk of hip fractures in patients on dialysis or with a functioning renal graft at time of parathyroidectomy. DESIGN: In a cohort of 20,056 patients on dialysis or with functioning renal allograft, we identified 590 patients who underwent parathyroidectomy between 1991 and 2009. Of these, 579 were matched with 1970 non-PTX patients on age, sex, cause of renal disease and functioning renal allograft or not at the time of PTX or at the corresponding time for non-PTX patients (t). We calculated the risk for hip fracture after PTX using crude and adjusted Cox proportional hazards regressions, adjusting for time in renal replacement therapy before t, time with functioning renal allograft before and after t, comorbidity at t and a hip fracture before t. RESULTS: The adjusted hazard ratio (95% confidence interval) for hip fracture was 0.40 (0.18-0.88) for PTX patients, compared to non-PTX patients. When analyses were performed separately for sex, only women had a lower risk of hip fracture after PTX compared to non-PTX patients. The risk of hip fracture after PTX was similar in patients with or without functioning renal allograft at time for PTX. CONCLUSION: Parathyroidectomy is associated with a lower risk of hip fracture in female patients with secondary hyperparathyroidism.

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.

Normalization of hemoglobin level in patients with chronic kidney disease and anemia.

BACKGROUND: Whether correction of anemia in patients with stage 3 or 4 chronic kidney disease improves cardiovascular outcomes is not established. METHODS: We randomly assigned 603 patients with an estimated glomerular filtration rate (GFR) of 15.0 to 35.0 ml per minute per 1.73 m2 of body-surface area and mild-to-moderate anemia (hemoglobin level, 11.0 to 12.5 g per deciliter) to a target hemoglobin value in the normal range (13.0 to 15.0 g per deciliter, group 1) or the subnormal range (10.5 to 11.5 g per deciliter, group 2). Subcutaneous erythropoietin (epoetin beta) was initiated at randomization (group 1) or only after the hemoglobin level fell below 10.5 g per deciliter (group 2). The primary end point was a composite of eight cardiovascular events; secondary end points included left ventricular mass index, quality-of-life scores, and the progression of chronic kidney disease. RESULTS: During the 3-year study, complete correction of anemia did not affect the likelihood of a first cardiovascular event (58 events in group 1 vs. 47 events in group 2; hazard ratio, 0.78; 95% confidence interval, 0.53 to 1.14; P=0.20). Left ventricular mass index remained stable in both groups. The mean estimated GFR was 24.9 ml per minute in group 1 and 24.2 ml per minute in group 2 at baseline and decreased by 3.6 and 3.1 ml per minute per year, respectively (P=0.40). Dialysis was required in more patients in group 1 than in group 2 (127 vs. 111, P=0.03). General health and physical function improved significantly (P=0.003 and P<0.001, respectively, in group 1, as compared with group 2). There was no significant difference in the combined incidence of adverse events between the two groups, but hypertensive episodes and headaches were more prevalent in group 1. CONCLUSIONS: In patients with chronic kidney disease, early complete correction of anemia does not reduce the risk of cardiovascular events. (ClinicalTrials.gov number, NCT00321919 [ClinicalTrials.gov].).