Fiix-prothrombin time monitoring improves warfarin anticoagulation outcome in atrial fibrillation: a systematic review of randomized trials comparing Fiix-warfarin or direct oral anticoagulants to standard PT-warfarin.

BACKGROUND: Monitoring warfarin with Fiix-prothrombin time (Fiix-PT), which is only affected by coagulation factors II and X, stabilizes anticoagulation and reduces thromboembolism compared to PT/INR monitoring. We compared outcome in nonvalvular atrial fibrillation (NVAF) patients treated with Fiix-warfarin, direct oral anticoagulants (DOACs), or PT-warfarin. METHODS: A systematic efficacy and safety assessment by retrieving data from the Fiix trial and the four major phase III DOAC trials in NVAF. Prespecified outcomes included stroke and systemic embolism (SSE), SSE and myocardial infarction (MI), major bleeding (MB), composite major vascular events (SSEMI and MB; CMVE), and deaths. We calculated relative risk, 95% CI, and 95% confidence limits (CL) for each outcome and performed meta-analysis using fixed- and random-effects modeling. RESULTS: There were 613 and 628 observation years with Fiix-warfarin and PT-warfarin in the Fiix trial, and 70 628 and 57 962 with DOACs and PT-warfarin in DOAC trials. Populations were comparable although death rates were lower in the Fiix trial. Compared to pooled PT-warfarin, Fiix-warfarin reduced SSE (RR 0.54;95% CI 0.26-1.10/95% CL <1.00), SSEMI (0.51;0.26-0.99/<0.90), MB (RR 0.63;0.37-1.07/<0.99), and CMVE (RR 0.66;0.43-1.00/<0.94). Vascular death was lower (RR 0.13;0.04-0.47/<0.42). Compared to pooled DOACs, Fiix-warfarin consistently had lower point estimates for the RR for efficacy and safety, but only significant for lower death rates (vascular death RR 0.14;0.04-0.49/<0.43). Meta-analysis comparing Fiix-warfarin and DOACs with PT-warfarin consistently found Fiix-warfarin to have the lowest point estimates for efficacy. CONCLUSION: Monitoring warfarin with Fiix-PT reduces risk of vascular events in NVAF patients as much as DOACs. Warfarin monitored with Fiix-PT is an improved anticoagulant.

Plasma 25-hydroxyvitamin D2 and D3 levels and incidence of postoperative atrial fibrillation.

Low circulating levels of total 25-hydroxyvitamin D (25(OH)D) have been associated with an increased risk of adverse effects after cardiac surgery. The metabolites, 25(OH)D2 and 25(OH)D3, provide a good index of vitamin D status. In this study, we examined the association between preoperative plasma levels of total 25(OH)D, 25(OH)D2 and 25(OH)D3 and the risk of postoperative atrial fibrillation (POAF) following open heart surgery. The levels of plasma 25(OH)D2 and 25(OH)D3 in 118 patients, who underwent coronary artery bypass grafting and/or valvular surgery, were measured immediately prior to surgery and on postoperative day 3 by liquid chromatography-tandem mass spectrometry. Patients who developed POAF had higher median plasma levels of 25(OH)D2 than those who remained in sinus rhythm (SR) (P = 0·003), but no significant difference was noted in levels of 25(OH)D3 or total 25(OH)D between the two groups (P > 0·05). By univariate analysis, patients with total 25(OH)D and 25(OH)D2 levels above the median had higher frequency of POAF (P < 0·05) and the incidence of POAF increased significantly with each higher quartile of preoperative plasma levels of 25(OH)D2 (P = 0·001), an association that was independent of confounding factors. In both the SR and POAF groups, the median plasma levels of 25(OH)D2, 25(OH)D3 and total 25(OH)D were lower (P < 0·05) on the third postoperative day compared with preoperatively. Our findings demonstrate that higher plasma levels of 25(OH)D2 are associated with increased risk of POAF, while this is not the case for 25(OH)D3 or total 25(OH)D. The reason for these discrepant results is not clear but warrants further study.

U-shaped relationship between tissue docosahexaenoic acid and atrial fibrillation following cardiac surgery.

BACKGROUND/OBJECTIVES: Randomised controlled trials (RCTs) evaluating the effect of fish oil supplementation on postoperative atrial fibrillation (POAF) following cardiac surgery have produced mixed results. In this study, we examined relationships between levels of red blood cell (RBC) n-3 long-chain polyunsaturated fatty acids (LC-PUFAs) and the incidence of POAF. SUBJECTS/METHODS: We used combined data (n=355) from RCTs conducted in Australia and Iceland. The primary end point was defined as POAF lasting >10 min in the first 6 days following surgery. The odds ratios (ORs) for POAF were compared between quintiles of preoperative RBC n-3 LC-PUFA levels by multivariable logistic regression. RESULTS: Subjects with RBC docosahexaenoic acid (DHA) in the fourth quintile, comprising a RBC DHA range of 7.0-7.9%, had the lowest incidence of POAF. Subjects in the lowest and highest quintiles had significantly higher risk of developing POAF compared with those in the fourth quintile (OR=2.36: 95% CI; 1.07-5.24 and OR=2.45: 95% CI; 1.16-5.17, respectively). There was no association between RBC eicosapentaenoic acid levels and POAF incidence. CONCLUSIONS: The results suggest a 'U-shaped' relationship between RBC DHA levels and POAF incidence. The possibility of increased risk of POAF at high levels of DHA suggests an upper limit for n-3 LC-PUFAs in certain conditions.

Inflammatory response following heart surgery and association with n-3 and n-6 long-chain polyunsaturated fatty acids in plasma and red blood cell membrane lipids.

BACKGROUND: Open heart surgery is associated with a systemic inflammatory response. The n-3 long-chain polyunsaturated fatty acids (LC-PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and the n-6 LC-PUFA arachidonic acid (AA) may contribute to modulation of the inflammatory response. OBJECTIVE: We investigated whether the preoperative levels of EPA, DHA and AA in plasma phospholipids (PL) and red blood cell (RBC) membrane lipids in patients (n=168) undergoing open heart surgery were associated with changes in the plasma concentration of selected inflammatory mediators in the immediate postoperative period. RESULTS AND CONCLUSIONS: The postoperative concentration of TNF-ß was lower (P<0.05) and those of hs-CRP, IL-6, IL-8, IL-18 and IL-10 higher (P<0.05) than the respective preoperative concentrations. We observed that the preoperative levels of EPA and AA in plasma PL and RBC membrane lipids were associated with changes in the concentration of pro-inflammatory and anti-inflammatory mediators, suggesting a complex role in the postoperative inflammatory process.

Acute kidney injury in intensive care units according to RIFLE classification: a population-based study.

INTRODUCTION: Recent studies of the incidence of acute kidney injury (AKI) are largely based on estimated baseline serum creatinine values. The aim of this study was to more accurately determine the incidence of AKI using the RIFLE criteria for intensive care unit (ICU) patients of a whole population. MATERIALS AND METHODS: All adult patients admitted to the ICUs of Landspitali - The National University Hospital of Iceland in 2007 (n = 1026) were studied with meticulous search for baseline creatinine. The underlying risk factors and contributing causes for AKI were defined, and survival and ratio of end-stage renal failure evaluated. RESULTS: A measured baseline creatinine value was found for all but two patients with AKI. The incidence of AKI according to RIFLE criteria was 21.7% [95% confidence interval (CI): 19.0-24.1%], with 7.1% (95 CI: 5.6-8.9%), 6.8% (95 CI: 5.3-8.5%) and 7.8% (95 CI: 6.2-9.6%) in the risk, injury and failure subgroups. Using estimated baseline creatinine overestimated the incidence of AKI by 3.5%. The sensitivity and specificity of the RIFLE criteria using estimated baseline creatinine were 76% and 95%. Renal replacement therapy was required for 17% of the AKI patients. One year survival of AKI patients was 51%, but only 2.5% of patients surviving 90 days required chronic renal replacement therapy. CONCLUSIONS: The incidence of AKI in the ICU was lower than previously published, perhaps due to overestimation of AKI using estimated baseline creatinine or bias from tertiary referrals. AKI patients have high mortality, but the survivors have a low incidence of end-stage renal failure.

Factors associated with elevated or blunted PTH response in vitamin D insufficient adults.

OBJECTIVES: The purpose of this study was to examine factors associated with high or low parathyroid hormone (PTH) levels in relationship to vitamin D insufficiency. DESIGN: This was a cross-sectional study consisting of 516 healthy men and women, aged 30-85, all Caucasians with vitamin D insufficiency [serum 25(OH)D<45 nmol L(-1)]. The group was divided into quartiles by PTH levels and the highest and lowest quartiles were compared with regard to various factors likely to affect calcium metabolism. We used stepwise multivariable logistic regression to determine the independent association between PTH levels and other variables for men and women separately. RESULTS: We found that men in the lowest PTH quartile were significantly younger, had less energy intake, lower body mass index (BMI) and better kidney function compared with the highest PTH quartile. They had also higher ionized calcium, insulin-like growth factor (IGF1) and testosterone and were more likely to smoke. Women within the lowest PTH quartile were younger, had lower BMI and magnesium values and higher IGF1 levels and were more likely to smoke. Stepwise multivariate regression showed that IGF1, testosterone and BMI were significantly associated with PTH in men (R(2)=0.472) but smoking, BMI and kidney function in women (R(2)=0.362). CONCLUSIONS: Our results indicate that during vitamin D insufficiency, factors other than calcium and vitamin D may modify PTH response. These factors may be different between sexes and we have identified novel factors, IGF1 and testosterone in men which may be compensatory in nature and confirmed previous factors such as smoking, BMI and kidney function in women.

AHI1 mutations cause both retinal dystrophy and renal cystic disease in Joubert syndrome.

BACKGROUND: Joubert syndrome (JS) is an autosomal recessive disorder characterised by hypotonia, ataxia, mental retardation, altered respiratory pattern, abnormal eye movements, and a brain malformation known as the molar tooth sign (MTS) on cranial MRI. Four genetic loci have been mapped, with two genes identified (AHI1 and NPHP1). METHODS: We screened a cohort of 117 JS subjects for AHI1 mutations by a combination of haplotype analysis and sequencing of the gene, and for the homozygous NPHP1 deletion by sequencing and marker analysis. RESULTS: We identified a total of 15 novel AHI1 mutations in 13 families, including nonsense, missense, splice site, and insertion mutations, with some clustering in the WD40 domains. Eight families were consanguineous, but no single founder mutation was apparent. In addition to the MTS, retinal dystrophy was present in 11 of 12 informative families; however, no subjects exhibited variable features of JS such as polydactyly, encephalocele, colobomas, or liver fibrosis. In contrast to previous reports, we identified two families with affected siblings who developed renal disease consistent with nephronophthisis (NPH) in their 20s. In addition, two individuals with classic NPH were found to have homozygous NPHP1 deletions. CONCLUSIONS: Overall, 11% of subjects had AHI1 mutations, while approximately 2% had the NPHP1 deletion, representing a total of less than 15% in a large JS cohort. Some preliminary genotype-phenotype correlations are possible, notably the association of renal impairment, specifically NPH, in those with NPHP1 deletions. Subjects with AHI1 mutations may be at risk of developing both retinal dystrophy and progressive kidney disease.

Unchanged incidence of diabetic nephropathy in Type 1 diabetes: a nation-wide study in Iceland.

AIMS: Diabetic nephropathy is an uncommon cause of end-stage renal disease in Iceland in contrast to most industrialized countries. The aim of this study was to examine the incidence of diabetic nephropathy in Iceland. METHODS: All patients diagnosed with Type 1 diabetes in Iceland before 1992 were studied retrospectively. Patients diagnosed before age 30, who were insulin dependent from the onset, were defined as having Type 1 diabetes. Diabetic nephropathy was defined as persistent proteinuria measured with a dipstick test (Albustix) on three consecutive clinic visits at least 2 months apart. Patients were followed to the end of year 1998, to their last recorded outpatient visit, or until death. The cumulative incidence of diabetic nephropathy was calculated with the Kaplan-Meier method and presented according to the duration of diabetes divided into 5-year intervals. RESULTS: A total of 343 patients with Type 1 diabetes were identified. The mean follow-up period was 20.2 +/- 11.4 (mean +/- sd) years. Only 9.3% of patients were lost to follow-up. Sixty-five patients developed diabetic nephropathy. The cumulative incidence was 22.6% at 20 years and levelled off at 40.3% after approximately 35 years of diabetes duration. No significant changes in cumulative incidence were observed over time. Mean glycated haemoglobin was 8.4% in patients with proteinuria and 7.8% in a group of patients without proteinuria that was matched for age, gender and duration of diabetes (P = 0.04). CONCLUSIONS: The cumulative incidence of diabetic nephropathy in Iceland is comparable with previously reported cumulative incidence rates and has remained unchanged. Glycaemic control was significantly better in patients without proteinuria.

Comparison of transposed brachiobasilic fistulas to upper arm grafts and brachiocephalic fistulas.

BACKGROUND: Renewed interest in transposed brachiobasilic fistulas has occurred since the release of the National Kidney Foundation-Dialysis Outcomes Quality Initiative (NKF-DOQI) guidelines because it is an alternative method to achieve an upper arm fistula in patients who cannot achieve a functional brachiocephalic fistula. The objective of this study was to compare outcomes among transposed brachiobasilic fistulas, upper arm grafts, and brachiocephalic fistulas. METHODS: A cohort of patients with upper arm accesses was retrospectively identified. Access outcomes were determined from medical records and contact with physicians, dialysis providers, and patients. Primary outcome was thrombosis-free survival. Secondary outcomes were primary failure, time to use, risk of catheter-related bacteremia, need for intervention, incidence of access-related complications, cumulative, and functional patency. Group differences in age, sex, race, diabetes, peripheral vascular disease, and number of previous accesses were adjusted for in the analysis where appropriate. RESULTS: Transposed brachiobasilic fistulas, upper arm grafts, and brachiocephalic fistulas were compared in 59, 82, and 56 patients, respectively. Compared with transposed brachiobasilic fistulas, upper arm grafts were more likely to thrombose with an adjusted relative risk (RR) of 2.6 (95% CI, 1.3 to 5.3) excluding primary failures and 1.6 (95% CI, 1.0 to 2.7) when accounting for the lower risk of primary failure for grafts. Transposed brachiobasilic fistulas also required less intervention (0.7 vs. 2.4 per access-year, P < 0.01) and were less likely to become infected (0 vs. 13%, P < 0.05) than grafts. Mature brachiocephalic fistulas were less likely to fail (RR 0.3, 95% CI, 0.1 to 1.0) and showed a trend for less thrombosis (RR 0.3, 0.1 to 1.1) than mature brachiobasilic fistulas. There was no significant difference in cumulative patency (failure-free survival) among the three types of access if primary failure was included at the median follow-up of 594 days. Transposed brachiobasilic fistulas provided catheter-free access one month sooner than brachiocephalic fistulas and one month later than upper arm grafts. CONCLUSIONS: Transposed brachiobasilic fistulas provide cumulative patency equivalent to upper arm grafts and brachiocephalic fistulas. They are less likely to thrombose and become infected than upper arm grafts. Compared with brachiocephalic fistula, they are more likely to mature but are at increased risk of thrombosis after maturation. Transposed brachiobasilic fistulas should be considered before placing an upper arm graft for patients that cannot achieve a functional brachiocephalic fistula.

[Calcaneal ultrasound as a screening test for osteoporosis.].

INTRODUCTION: Dual energy X-ray absorptiometry (DEXA) has been the cornerstone in the diagnosis of osteoporosis. Quantitative ultrasound (QUS) of calcaneus is easy to perform and cheaper than DEXA but prior studies have shown a limited correlation and agreement between the two tests. The purpose of this study was to assess calcaneal ultrasound as a screening test for osteoporosis. MATERIAL AND METHODS: Two-hundred-ninety-seven 70-years-old Icelandic women underwent a DEXA measurement of lumbar spine, left hip and whole body as well as QUS of left calcaneus. We assessed the correlation and agreement between the two tests and searched for the optimal cut-off point in QUS for the diagnosis of osteoporosis from sensitivity and specificity calculations and ROC curves. We also examined correlation between DEXA or QUS and anthropometric or biochemical measurements of bone markers. Finally, we compared the women who had sustained a fracture to those who had not with regard to DEXA and QUS. RESULTS: The correlation between DEXA at different sites and QUS ranged form 0.40 to 0.57 (Spearman's correlation coefficient) with the best correlation for left hip DEXA. The best sensitivity/specificity relationship of QUS in diagnosis of osteoporosis (WHO criteria) at the hip, was found for QUS T-score of -2.5; sensitivity 91.7%, specificity 49.0%, positive predictive value 25.8% and negative predictive value of 96.8%. Kappa-statistic showed a marginal agreement between the two tests (k=0.25, p<0.01). The correlation was generally stronger between DEXA and serum biochemical markers of bone turnover or weight than between QUS and these parameters but was in the same direction. Mean hip bone density and QUS results were lower in the group of women with history of fractures than the others, 0.731+/-0.112 g/cm(2) vs. 0.779+/-0.130 g/cm(2) (T-score -1.18+/-1.18 vs. -1.61+/-1.20, p=0.001) and T-score -3.12+/-0.94 vs. -2.40+/-1.22 (p=0.0001) for QUS. CONCLUSIONS: Even though QUS is not a good test for diagnosing osteoporosis as defined by WHO criteria, it is a reasonable screening test with good sensitivity and fair specificity when using T-score of -2.5 as the cut-off point.

Comparison of treatments for mild secondary hyperparathyroidism in hemodialysis patients. Durham Renal Osteodystrophy Study Group.

UNLABELLED: Comparison of treatments for mild secondary hyperparathyroidism in hemodialysis patients. BACKGROUND: In the management of patients with mild secondary hyperparathyroidism, it is not known whether calcium supplementation alone is sufficient to correct abnormalities in bone and mineral metabolism or if calcitriol is needed in either physiologic oral or intravenous pharmacologic doses. METHODS: This was a 40-week prospective nonmasked trial of 52 patients [parathyroid hormone (PTH) 150 to 600 pg/mL] who were randomized to receive escalating doses of either calcium carbonate (CaCO3) alone (calcium group, N = 11), daily oral calcitriol (oral group, N = 20), or intermittent intravenous calcitriol (IV group, N = 21). The groups were compared with regard to changes in serum intact PTH, serum bone-specific alkaline phosphatase (BAP), incidence of hypercalcemia (>10.5 mg/dL), and hyperphosphatemia (>6.5 mg/dL). RESULTS: PTH levels decreased in all groups (P < 0.01, paired t-test). In the calcium group, PTH (mean +/- SEM) decreased from 325 +/- 46.2 to 160 +/- 44.5 pg/mL. In the oral group, it decreased from 265 +/- 26.4 to 125 +/- 23.7 pg/mL, and in the IV group, it decreased from 240 +/- 27.7 to 65 +/- 10.0 pg/mL. Upon analysis of covariance, controlling for the initial PTH level, we found no differences in the PTH response between the groups (P > 0.10). In contrast, the BAP concentration increased from 20.7 +/- 7.6 to 27.5 +/- 7.0 microg/L in the calcium group (P = 0.17), decreased from 20. 6 +/- 3.9 to 17.8 +/- 4.5 microg/L in the oral group (P = 0.26), and from 19.1 +/- 2.6 to 10.6 +/- 1.1 microg/L in the IV group (P = 0. 007). Serum calcium increased significantly in all groups from 8.4 +/- 0.25 to 9.0 +/- 0.28, 8.5 +/- 0.16 to 9.2 +/- 0.27, and 8.7 +/- 0.16 to 9.4 +/- 0.18 mg/dL in the calcium, oral, and IV groups, respectively (P = NS difference between groups). Serum phosphorus was significantly lower in the calcium group throughout the study (P = 0.02). Hypercalcemic episodes were 2.0 +/- 0.8, 3.0 +/- 0.6, and 3. 4 +/- 0.6 per patient-year (P > 0.10), and hyperphosphatemic episodes were 0.9 +/- 0.56, 4.2 +/- 0.79 and 4.9 +/- 0.84 in the calcium, oral, and IV groups, respectively (P < 0.01). CONCLUSION: In mild secondary hyperparathyroidism, all three strategies are effective. High-dose CaCO3 alone may be sufficient to control PTH with a favorable side-effect profile, but calcitriol appears to have additional suppressive effects on bone that are greater following the intravenous route of administration and may increase the risk of adynamic bone disease.

Association of plasma levels of human immunodeficiency virus type 1 RNA and oropharyngeal Candida colonization.

The pathophysiology of oropharyngeal candidiasis in patients infected with human immunodeficiency virus (HIV) type 1 is poorly understood. Association between oropharyngeal yeast carriage and various clinical factors in HIV-1-infected patients was studied in 83 patients with no clinical evidence of thrush and no recent antifungal use. Of the clinical factors measured, the only correlate of yeast colonization was with plasma HIV-1 RNA levels (P=.001), whereas the correlation with CD4 cell count was poor (P=.36). By multivariable regression modeling, plasma HIV-1 RNA was the only parameter that correlated with the extent of colonization with Candida infection (P=.003). These data indicate that the presence and amount of asymptomatic oropharyngeal yeast carriage in persons with HIV-1 infection is more significantly correlated with plasma HIV-1 RNA levels than with CD4 cell count. Further studies on the effect of HIV-1 on oropharyngeal yeast colonization, infection, and local immunity are warranted.

Role of urine and serum protein electrophoresis in evaluation of nephrotic-range proteinuria.

The usefulness of routine serum protein electrophoresis (SPEP) and urine protein electrophoresis (UPEP) screening in the evaluation of proteinuria is not known. The data on the clinical utility of these tests in 165 male patients with proteinuria greater than 3 g/d of protein who were screened for the presence of an M-spike are presented. Two hundred fifty-four studies were performed (SPEP, 155; UPEP 99) in these 165 patients. Twenty-four studies (9.8%) were positive for an M-spike (15 serum; 9 urine samples) in 19 patients (11.5%). Fourteen patients (8.5%) had an M-spike in either serum or urine, five patients (3%) in both studies. Two of these 19 patients were diagnosed with myeloma and 1 patient was diagnosed with primary amyloidosis. The other 16 patients were diagnosed with monoclonal gammopathy of unknown significance (MGUS). The group with a positive M-spike was significantly older (mean +/- SEM, 65 +/- 2 years; range, 39 to 78 years v 58 +/- 1 years; range, 25 to 84 years; P = 0.03), had a lower incidence of coexistent diabetes (21.1% v 61.6%; P = 0. 01), and a lower serum albumin level (3.2 v 3.6 g/dL; P = 0.05). Using a multivariable logistic regression model, the presence of an M band was positively correlated with age (odds ratio [OR], 1.056; 95% confidence interval [CI], 1.006 to 1.108) and negatively correlated for serum albumin level (OR, 0.386; 95% CI, 0.184 to 0. 810), hematocrit (OR, 0.923; 95% CI, 0.852 to 1.001), and the presence of diabetes mellitus (OR, 0.128; 95% CI, 0.038 to 0.434). In summary, routine SPEP and UPEP screening in patients with proteinuria greater than 3 g/d of protein detected an M-spike in 11. 5% and myeloma in 1.2% of the patients. The cost per case of myeloma or MGUS discovered was $1,192.

[Secondary hyperparathyroidism in patients with renal failure.].

In renal failure, several factors lead to parathyroid gland overactivity, manifested by hypersecretion of parathyroid hormnone (PTH) and glanudal hyperplasia eventually leading to monoclonal expansion of glandular cells in severe cases. Main factors contributing to this secondary hyperparathyoidism are increased end-organ resistance to PTH, low serum calcium and high serum phosphate concentrations and decreased production of 1,25-dihydroxyvitamin D3 by the kidneys. Treatment is directed towards correction of these underlying disturbances in meneral metabolism, however, such maneuvers are not always successful in controlling parathyroid gland activity. Functional disturbances within the parathyroid glands e.g., decrements in vitamin D or calcium sensing receptor number or function and/or increased cell mass have been implicated in therapeutic resistance. This article discusses the role of such functional derangements and details the results of a recent study demonstrating the importance of gland mass in this context.

Predictors of short-term changes in serum intact parathyroid hormone levels in hemodialysis patients: role of phosphorus, calcium, and gender.

Several factors have been identified as important in the pathogenesis of secondary hyperparathyroidism in end-stage renal disease, including serum calcium, phosphorus, and calcitriol. To examine the independent effects of key factors, we prospectively studied 52 new hemodialysis patients with mild secondary hyperparathyroidism (PTH, 110-670 pg/mL) treated with a standardized regimen of calcium supplements, phosphorus binders, and no vitamin D derivatives. We used simple and multivariable linear regression analysis to examine the relationship between changes in PTH (deltaPTH) levels observed over a 4-week period and various biochemical and demographic variables. By simple linear regression we found that changes in serum phosphorus (r2 = 0.31; beta = 41.6; P = 0.0001), initial phosphorus concentration (r2 = 0.15; beta = 33.4; P = 0.005), initial PTH level (r2 = 0.29; beta = 0.58; P = 0.0001), changes in serum calcium (r2 = 0.12; beta = -74.0; P = 0.01), and gender (r2 = 0.07; beta = 76.1; P = 0.05) were significantly associated with deltaPTH. However, upon multivariable regression analysis, only the changes in phosphorus (partial r2 = 0.31; beta = 37.0; P = 0.0001), initial PTH level (partial r2 = 0.23; beta = 0.50; P = 0.0001), and gender (partial r2 = 0.05; beta = 63.1; P = 0.02) remained significantly associated with deltaPTH. Neither the serum concentration of 1,25-dihydroxyvitamin D3, bicarbonate, aluminum, or albumin nor changes in the serum bicarbonate concentration, the presence of diabetes, KT/V, or age were significantly associated with the deltaPTH. Our findings are consistent with independent effects of phosphorus and gender on parathyroid gland function in patients with dialysis-dependent renal failure through mechanisms that remain to be defined.

Non-suppressible parathyroid hormone secretion is related to gland size in uremic secondary hyperparathyroidism.

To determine the relative importance of parathyroid gland enlargement and alterations in calcium sensing (set-point changes) in the pathogenesis of uremic secondary hyperparathyroidism (2 degrees HPT), we investigated the relationship between estimates of parathyroid gland size and calcium-mediated parathyroid hormone (PTH) suppression in 19 normocalcemic 2 degrees HPT patients on chronic maintenance hemodialysis. We compared our results to calcium-mediated PTH suppression in 12 normal volunteers, 12 patients with familial benign hypocalciuric hypercalcemia (FBHH), a disorder of abnormal calcium sensing, and 9 subjects with primary hyperparathyroidism (1 degree HPT), which is characterized by both calcium set-point abnormalities and parathyroid gland enlargement. We found that the 2 degrees HPT group displayed a distinctive pattern of calcium-mediated PTH suppression characterized by a failure to normally suppress PTH at supraphysiologic ionized calcium concentrations, similar to 1 degree HPT, but without the rightward shift of the calcium-PTH suppression curve that characterizes calcium sensing abnormalities in FBHH and 1 degree HPT. In the patients with 2 degrees HPT, hypercalcemic suppression resulted in an ending PTH (as a percent of baseline) that was significantly higher (39.8 +/- 4.47%), and a slope of the calcium-PTH suppression curve that was significantly less negative (-4.8 +/- 0.53), compared to respective values of 19.4 +/- 1.81% (P = 0.0009) and -9.0 +/- 1.02 (P = 0.001) in normals and 19.1 +/- 2.49% (P = 0.001) and -9.6 +/- 1.11 (P = 0.0006) in FBHH. Values of ending PTH and slope in 2 degrees HPT patients, however, were similar to those found in 1 degree HPT (49.8 +/- 6.35%, P = 0.21 and -4.5 +/- 0.74, P = 0.72). The ionized calcium concentration required to attain half maximal PTH suppression (EC50) in 2 degrees HPT (1.20 +/- 0.02 mmol/liter) was not significantly different from normals (1.25 +/- 0.01 mmol/liter, P = 0.12) but was significantly less than in 1 degree HPT (1.52 +/- 0.02 mmol/liter, P < 0.0001) and in FBHH (1.44 +/- 0.02 mmol/liter, P < 0.0001). More importantly, we found a significant linear correlation between the natural logarithm of gland size and ending PTH suppression (r = 0.71, P < 0.001) and slope of the calcium-PTH curve (r = 0.67, P = 0.002) in 2 degrees HPT. Thus, calcium non-suppressible PTH secretion in 2 degrees HPT does not represent a simple set-point error, but rather correlates with the degree of parathyroid gland enlargement.

Medullary sponge kidney associated with congenital hemihypertrophy.

Medullary sponge kidney is a developmental disorder characterized by ectatic and cystic malformation of the collecting ducts and tubules. Clinical manifestations include urinary tract infections, renal stones, and hematuria. It can be associated with other developmental disorders. A case of medullary sponge kidney associated with congenital hemihypertrophy, complicated by nephrocalcinosis and nephrolithiasis, is reported here.

Calcitriol administration in end-stage renal disease: intravenous or oral?

1,25-Dihydroxyvitamin D deficiency plays an important role in the pathogenesis of secondary hyperparathyroidism, and adequate replacement of this hormone is considered essential to normalize parathyroid gland function and restore bone homeostasis in patients with advanced renal failure. Although initial uncontrolled clinical trials suggested the superiority of intravenous calcitriol treatment, more recent controlled investigations show that different routes (oral versus intravenous), frequency (daily versus intermittent), and dosing (physiological versus pharmacological) of calcitriol administration are clinically equivalent. Overall, the response to calcitriol treatment depends more on the severity of secondary hyperparathyroidism and the presence of confounding variables, such as hyperphosphatemia and acquired abnormalities of parathyroid cell function, than the method of calcitriol administration.

[Peritonitis associated with peritoneal dialysis.].

Continuous ambulatory peritoneal dialysis (CAPD) is now a recognised treatment for end stage renal disease. An estimated number of 27.000 patients was being treated by CAPD world-wide in the year 1985. The most important complication is infection, peritonitis. The CAPD program started in Iceland in April 1985 at the dialysis department of the National University Hospital. The aim of this study was to estimate the incidence of infection associated with peritoneal dialysis during the first five years. All positive cultures of peritoneal dialysates from the Department of Bacteriology, and the hospital records of patients on CAPD, during the time period 12.04.1985 to 12.04.1990, were studied retrospectively. CAPD was considered started as soon as the peritoneal catheter had been inserted. Peritonitis was considered to be present when the white blood cell count was > 100/ul or there were clinical signs of infection together with a positive culture from the dialysate. During the study period 27 patients were treated by CAPD for 609.6 treatment months. Peritonitis was diagnosed 83 times in 18 of these patients, giving an incidence of 1.63/treatment year. The most common cause was Staphylococcus aureus, which was isolated 35 times (42%). Other causative organisms were: 17 coagulase negative staphylococci (21%), three Gram negative rods (4%), one yeasts and three mixed cultures. In 12 (14%) of the peritonitis episodes, no organisms were isolated. Admission to hospital was considered necessary in 74% of the episodes. One patient died of peritonitis. Studies have demonstrated various infection rates (0.23-6.3 infections/year), but has usually been between 0.8 and 1.2 infections/year. It is of interest to note that the most common causative organism in this study was S. aureus, as opposed to coagulase negative staphylococci, that have normally been the most prevalent. S. aureus usually causes tunnel infections, that are difficult to clear, without removing the catheter. This study demonstrates an above average prevalence of infection, which should prompt a reevaluation of the current management protocols.