Pregnancy outcomes and impact of pregnancy on graft function in women after kidney transplantation.

BACKGROUND: Kidney transplantation facilitates pregnancy in women with end-stage kidney disease; however, the impact of pregnancy on short and longer-term graft function is uncertain. METHODS: Obstetric, fetal, and graft outcomes for pregnancies from a large Australian transplant unit (1976-2015) were reviewed. RESULTS: There were 56 pregnancies in 35 women with mean age at conception 30.4 ± 0.6 years and mean transplant-pregnancy interval 5.5 ± 0.5 years. The live birth rate was 78.9%. Preterm birth (<37 weeks) occurred in 56.5%. Hypertensive disorders affected 76% of women (pre-eclampsia in 30%). Median prepregnancy serum creatinine (SCr) was 100 µmol/L (interquartile range (IQR), 80, 114 µmol/L). One-third had deterioration in graft dysfunction during pregnancy; of these, 63.2% did not return to baseline. At 2 years post-partum, median SCr was 96.4 µmol/L (IQR, 81.5-124.3). Women with prepregnancy SCr > 110 µmol/L had increased risk of pre-eclampsia (OR 4.4; 95% CI 1.2-16.8; P = .03), but not preterm birth (OR 5.4; 95% CI 0.5-53; P = .04) or low birth-weight babies (OR 1.2; 95% CI 0.5-2.9; P = .04). Women with SCr > 140 µmol/L preconception had worst SCr trajectory, including higher rates of graft loss. CONCLUSIONS: Kidney transplantation pregnancies remain at high risk of obstetric complications, particularly pre-eclampsia. Prepregnancy graft function can be used to predict risk of adverse pregnancy outcomes and deterioration in graft function during and after delivery.

External validation of the estimated posttransplant survival score for allocation of deceased donor kidneys in the United States.

The US kidney allocation system adopted in 2013 will allocate the best 20% of deceased donor kidneys (based on the kidney donor risk index [KDRI]) to the 20% of waitlisted patients with the highest estimated posttransplant survival (EPTS). The EPTS has not been externally validated, raising concerns as to its suitability to discriminate between kidney transplant candidates. We examined EPTS using data from the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. We included 4983 adult kidney-only deceased donor transplants over 2000-2011. We constructed three Cox models for patient survival: (i) EPTS alone; (ii) EPTS plus donor age, hypertension and HLA-DR mismatch; and (iii) EPTS plus log(KDRI). All models demonstrated moderately good discrimination, with Harrell's C statistics of 0.67, 0.68 and 0.69, respectively. These results are virtually identical to the internal validation that demonstrated a c-statistic of 0.69. These results provide external validation of the EPTS as a moderately good tool for discriminating posttransplant survival of adult kidney-only transplant recipients.

Dialysis in public and private hospitals in Queensland.

BACKGROUND: Clinical outcomes for patients treated in public and private hospitals may be different. AIM: The aim of the study was to compare the characteristics and outcomes of patients receiving dialysis at public and private hospitals in Queensland. METHODS: Incident adult dialysis patients in Queensland registered with the Australia and New Zealand Dialysis and Transplant Registry between 1999 and 2009 were classified by dialysis modality at either a public or private hospital. Outcomes were dialysis patient characteristics and survival. RESULTS: Three thousand, three hundred and ten patients commenced dialysis in public hospitals, 1939 haemodialysis (HD) and 1371 peritoneal dialysis (PD). Seven hundred and ninety-three patients commenced dialysis in private hospitals, 757 HD and 36 PD. Compared with public HD, private HD patients were older, had more coronary artery disease and less diabetes, and were more likely to live in an urban area. Public HD patients were more likely to be obese and referred late to a nephrologist. Nearly all indigenous patients were managed in public hospitals. Private patients were more likely to have an arteriovenous fistula or graft at first HD (P < 0.001) but not after excluding late referrals (P = 0.09). Public hospitals provided longer HD sessions and more HD hours per week for all age groups except 75+ years. Compared with public hospital HD, patient survival adjusted for multiple variables was comparable for private hospital HD (hazard ratio 1.20 (95% confidence interval 0.98-1.46, P = 0.07)) but worse for public PD (hazard ratio 1.14 (95% confidence interval 1.05-1.24, P = 0.002)). CONCLUSION: Private HD patients are older and less likely to be diabetic than public patients. Patient survival is worse for public PD than public HD.

Effect of type 2 diabetes on mortality risk associated with end-stage kidney disease.

AIMS/HYPOTHESIS: Patients with end-stage kidney disease (ESKD) and patients with diabetes mellitus experience higher mortality rates than the general population. Whether ESKD imparts the same excess in mortality risk for those with diabetes as it does for those without diabetes is unknown. METHODS: Included in the study were all white patients aged > or =25 years with incident ESKD and type 2 diabetes (n = 4,141) or with incident ESKD but without diabetes (n = 13,289) in Australia from 1991 to 2005, and all the individuals aged > or =25 years without ESKD and with type 2 diabetes (n = 909) or without ESKD without diabetes (n = 10,302) enrolled in the AusDiab Study--a nationwide Australian representative cohort--from 1999 to 2005. Excess mortality was analysed in patients with ESKD by diabetes status, using age-, sex- and diabetes-status-specific standardised mortality ratios (SMRs) in the first 8 years after first renal replacement therapy among ANZDATA patients relative to AusDiab participants. RESULTS: The SMRs in patients with ESKD were, in non-diabetic patients and in those with type 2 diabetes, respectively: 14.2 (95% CI 13.9-14.6) and 10.8 (95% CI 10.4-11.2) (p < 0.01); in people aged <60 years, 28.7 (95% CI 27.2-30.4) and 18.6 (95% CI 17.1-20.4) (p < 0.01); in people aged > or =60 years, 12.5 (95% CI 12.1-12.9) vs 9.7 (95% CI 9.3-10.1) (p < 0.01); in men, 11.0 (95% CI 10.7-11.4) vs 8.9 (95% CI 8.4-9.3) (p < 0.01); and in women, 23.4 (95% CI 22.5-24.3) vs 16.2 (95% CI 15.2-17.3) (p < 0.01). CONCLUSIONS/INTERPRETATION: ESKD was associated with a greater relative increase in mortality in the non-diabetic study populations than in the type 2 diabetes population. Excess mortality was greater among younger people and women.

Automated and continuous ambulatory peritoneal dialysis have similar outcomes.

We compared survival and death-censored technique survival in patients on automated peritoneal dialysis (automated dialysis) or on continuous ambulatory peritoneal dialysis. All 4128 patients from the Australia and New Zealand Dialysis and Transplant Registry who started peritoneal dialysis over a 5-year period through March 2004 were included. Times to death and death-censored technique failure were analyzed by Cox proportional hazards models while a conditional risk set model computed technique failure. Compared to patients treated entirely with continuous ambulatory peritoneal dialysis, automated peritoneal dialysis patients were more likely to be young, Caucasian, have marginally lower body mass index, and were less likely to have baseline cardiovascular disease or diabetes. Using univariate and multivariate analysis, our study showed there were no significant differences in patient survival and death-censored technique failure between the two types of peritoneal dialysis modalities.

Associations of hemodialysis dose and session length with mortality risk in Australian and New Zealand patients.

The optimal combination of hemodialysis (HD) dose and session length remains uncertain, and previous studies have not conclusively shown session length to be an important independent determinant of patient mortality. The objective of this study was to examine associations between HD dose and session length with mortality risk using data from the Australian and New Zealand Dialysis and Transplant Registry. Analyses were performed using a prospective inception cohort comprising all incident adult patients treated by thrice-weekly maintenance HD, who commenced renal replacement therapy with HD between 1 April 1997 and 31 March 2004. In all, 6593 patients were identified, of whom 4193 had sufficient data for multivariate analyses. HD dose (single pool fractional clearance of urea, Kt/V) and session length were included in analyses as those recorded 12 months after HD inception to reduce confounding by residual renal function. The outcome examined was patient mortality. Survival analyses included Kaplan-Meier calculations of survival and Cox regression for multivariate analyses. Covariates in Cox models included patient demographics, co-morbid medical conditions at HD inception, and HD operating parameters. After adjustment for covariates and each other, Kt/V of 1.30-1.39 and session length of 4.5-4.9 h were associated with the lowest mortality risk. There was no interaction between HD dose and session length. Thus, the optimal combination for mortality appears to be Kt/V of > or = 1.3 and session length of > or = 4.5 h. These data suggest a randomized controlled trial to test these hypotheses, and support the inclusion of criteria relating to session length in definitions of adequate HD practice.

Health effects of kava use in an eastern Arnhem Land Aboriginal community.

BACKGROUND: Heavy kava use in Aboriginal communities has been linked to various health effects, including anecdotes of sudden cardiac deaths. AIMS: To examine associations between kava use and potential health effects. METHODS: A cross-sectional study was carried out within a kava-using east Arnhem Land Aboriginal community in tropical northern Australia. One-hundred-and-one adults who were current, recent or non-users of kava were enrolled in March 2000. Main outcome measures were physical, anthropometric, biochemical, haematological, immunological and neurocognitive assessments. RESULTS: Kava users more frequently showed a characteristic dermopathy (P<0.001). They had increased levels of gamma-glutamyl transferase and alkaline phosphatase (P<0.001). Lymphocyte counts were significantly lower in kava users (P<0.001). Fibrinogen, plasminogen activator inhibitor-1 and neurocognitive tests were not different between kava use categories. IgE and IgG antibodies were elevated across the whole group, as were C-reactive protein and homocysteine. CONCLUSIONS: Kava use was associated with dermopathy, liver function abnormalities and decreased lymphocytes. If kava continues to be used by Aboriginal populations, monitoring should focus on the health consequences of these findings, including a possible increase in serious infections. The interaction between kava, alcohol and other substances requires further study. Although markers of cardiovascular risk are increased across the population, these were not higher in kava users, and this increase may be linked to the large infectious pathogen burden reflective of the socioeconomic disadvantage seen in many remote Aboriginal communities.

Relationships between homocysteine and related amino acids in chronic hemodialysis patients.

AIMS: Homocysteine (Hcy) has emerged as an important risk factor for atherosclerotic disease. Elevated levels in chronic dialysis patients may contribute to high vascular mortality, but little is known about levels of related amino acids in this group. In an observational study in the clinical setting we sought to document these. METHODS: In 114 hemodialysis patients pre-dialysis total plasma homocysteine, vitamin B12 and red blood cell (RBC) folate concentrations were measured. In a subgroup of patients (n = 42), other plasma amino acids were measured pre- and post-dialysis. All patients were routinely taking oral folic acid supplements (1.2 mg per week). RESULTS: Elevated homocysteine concentrations were found in all patients (geometric mean 33.1 umol/l, range 13.8 - 69.2 umol/l, laboratory reference range (RR) 3-13 umol/l). RBC folate levels were high (1223 +/- 54.5 nmol/l mean +/- SE, RR 300 - 710 nmol/l) and inversely related to pre-dialysis plasma Hcy (r = -0.44, p < 0.001). Hcy levels were not related to vitamin B12 levels. A history of vascular disease was not associated with higher concentrations of Hcy. Hcy clearance on dialysis was substantial (mean Hcy reduction 33 +/- 14%). While plasma methionine levels were normal, serine levels were significantly lower than the reference range (59.3 +/- 2.39 umol/l (mean +/- SE, RR 70 - 195 umol/l)) and directly related to levels of glycine (r = 0.52, p < 0.001). Glycine levels were within normal range. Although overall levels were low, higher serine levels were related to elevated homocysteine (r = 0.42, p < 0.01). Dialytic loss of glycine, serine and methionine was moderate. CONCLUSION: An inverse association between RBC folate and homocysteine levels extended to 3 times the upper limit of normal for folate, suggesting a role for high dose folic acid supplementation in the treatment of renal-failure related hyperhomocysteinemia. Low serine levels are expected as it is primarily synthesized in the kidney. The direct relationship between serine and homocysteine is consistent with the reported lack of effect of serine supplements on high Hcy levels.

Shoulder appearances at MR imaging in long-term dialysis recipients.

PURPOSE: To examine shoulder appearances at magnetic resonance (MR) imaging in long-term dialysis recipients. MATERIALS AND METHODS: Twenty-two chronic dialysis recipients underwent 1.0-T MR imaging with a combination of T1-, T2-, and T2*-weighted sequences. Rotator cuff tendon thickening was graded as present or absent by a musculoskeletal radiologist, who also measured the supraspinatus and subscapularis tendon thicknesses with electronic calipers. The long-axis dimension and location of focal osseous lesions, in addition to their T1, T2, and T2* signal intensities, were noted. RESULTS: Supraspinatus (n = 9) and subscapularis (n = 10) tendon thickening was frequently observed. Six (27%) of the 22 patients had combined thickening of the supraspinatus and subscapularis tendons without substantial involvement of the infraspinatus or teres minor tendons. These patients had undergone dialysis longer (median, 19.2 years; range, 16.3-22.8 years) than had the other patients (median, 11.7 years; range, 5.8-19.3 years; P: =.004). The 29 intraosseous lesions had high, intermediate, and low T2 signal intensity in six (21%), nine (31%), and 14 (48%) instances, respectively. CONCLUSION: Supraspinatus and/or subscapularis tendon thickening is common in chronic dialysis recipients. Bone lesions in such patients are of variable T2 signal intensity and usually subchondral or adjacent to the greater tuberosity.

Physical and biochemical predictors of death in an Australian aboriginal cohort.

1. Predictors of natural and cardiovascular death were examined in a cohort from a remote Australian Aboriginal community with high mortality rates. The cohort was marked by high prevalences of diabetes (17%), hypertension (19% diastolic blood pressure (BP) > 90 mmHg), obesity (16% body mass index (BMI) > 30), albuminuria (26% albumin/creatinine ratio (ACR) > or = 34 g/mol) and renal failure (26% calculated glomerular filtration rate < 80 mL/min). 2. Relationships between baseline characteristics and subsequent mortality were examined using multivariate techniques. 3. Albuminuria, diabetes and hypertension (but not smoking dyslipidaemia or obesity) were all markers for increased risk of natural and especially of cardiovascular death. Age- and sex-adjusted relative risk [95% CI] of natural deaths were 4.3 [1.9-9.5] for overt albuminuria (ACR > or = 34, 3.2 (range 1.6-6.5) for diastolic BP > or = 100 and 3.7 (range 1.5-8.9) for diabetes. 4. The relative risk associated with albuminuria was independent of diabetes and hypertension. Albuminuria was more common than either diabetes or hypertension and represents a target for intervention to reduce not only progression to renal disease, but also overall mortality.

Quinine-induced hemolytic uremic syndrome.

Although quinine use is very common, hemolytic uremic syndrome (HUS) following exposure to quinine is only a recently reported phenomenon, with the first description published in 1991. Previous reports have concentrated on the nature of the hematological process and in particular characterization of the quinine-induced antibodies involved. We present a case of HUS with a clear temporal and immunological relationship to quinine which demonstrates the pathognomonic renal features of HUS. An indirect antiglobulin test with the patient's serum agglutinated red blood cells only in the presence of quinine. Renal biopsy features included glomerular and arteriolar endothelial swelling, capillary loop thrombi, mesangiolysis, segmental sclerosis and segmental ischemia. Early empiric treatment with plasma exchange and corticosteroids was instituted and this resulted in recovery of renal function to normal.

A clinical comparison of non-traumatic methods of treating dental caries.

Over a period of 18 months the following non-traumatic methods of treating dental caries in deciduous teeth were compared: application of stannous fluoride (SnF2); application of SnF2 and silver diamine fluoride (SDF); application of SnF2, SDF, minimal cavity preparation and use of composite resin; minimal cavity preparation and composite resin only; no treatment. Caries progressed in only 5 per cent of the SDF/SnF2 group and 11 per cent of the composite resin group. The results indicate that it may be possible to treat carious lesions in a non-traumatic way using minimally prepared cavities and composite resin. This could significantly alter the restorative care of deciduous molars and it may be reasonable to speculate that the technique could also have important implications for use in the permanent dentition.

The distribution of caries on different tooth surfaces at varying levels of caries--a compilation of data from 18 previous studies.

The aim of this study was to examine the distribution of caries on different tooth surfaces, at varying levels of dental caries, in adolescent populations. Using data obtained from published reports, the relationship between reported mean surface-type caries scores were plotted against the total mean DFS and showed a good "closeness of fit." Mathematical expressions for the relationships were computed. A new "working rule" has been postulated from the data which states that: "As caries prevalence falls, the least susceptible sites (proximal and smooth surfaces) reduce by the greatest proportion, while the most susceptible sites (occlusal) reduce by the smallest proportion." This is true regardless of the presence of fluorides. This study questions the widely held view that fluorides have a special effect on proximal and smooth surface caries. The relationships between total DMFS/DFS and tooth surfaces affected could be useful to determine which preventive agent to use for a given caries prevalence level.

Factors affecting the precision of bone mineral measurements. Part 1: Review of experimentally derived results obtained from single photon absorptiometry.

An evaluation of the factors which influence the precision of bone mineral measurements using single photon absorptiometry (SPA) is presented. This incorporates several techniques which have been developed over the past few years to improve the reliability of such measurements. As such, the figures obtained should provide an objective and up-to-date basis for critical comparison with other modalities such as quantitative computerized tomography (QCT), dual photon absorptiometry (DPA) using Gd-153, and quantitative digital radiography (QDR). Under optimum conditions, a precision of 0.3% was achievable for in vitro phantom measurements. Under realistic working conditions, however, a precision of 1.0% for phantoms and 1.4% for clinical studies was found to be more typical for bone mineral content (BMC) measurements. Derived parameters such as bone mineral density (BMD) were generally less reliable, with a precision of 4.7%. It is unlikely that these values can be improved upon substantially with current SPA technology.

Factors affecting the precision of bone mineral measurements. Part 2: Some statistical notes relating to photon counting statistics and rates of bone loss.

This paper discusses some statistical aspects of absorptiometric bone mineral measurements. In particular, the contribution of photon counting statistics to overall precision is estimated, and methods available for carrying out statistical comparisons of bone loss and determining their precision are reviewed. The use of replicate measurements as a means of improving measurement precision is also discussed.