Prolonged immunosuppression does not improve risk of sensitization or likelihood of retransplantation after kidney transplant graft failure.

The optimum approach towards immunosuppression withdrawal following kidney transplant failure is unclear. Prolonged weaning may be associated with reduced sensitization, less graft nephrectomy and greater likelihood of retransplantation, but conversely increased risk of infection, malignancy and death. We conducted a single-centre retrospective analysis of patients experiencing graft failure between 2007 and 2017, comparing rates of sensitization, retransplantation, nephrectomy, infection, malignancy and death between patients who had immunosuppression weaned over <90 vs. 90-180 vs. >180 days. Patient survival after immunosuppression withdrawal over <90 vs. 90-180 vs. >180 days was 73.3%, 72.1% and 80.4%, respectively (P = 0.35), with no differences in cPRA (80.06 vs. 81.21 vs. 85.42, P = 0.66) or retransplantation rate [24/31 (77.4%) vs. 21/35 (60.0%) vs. 22/36 (61.1%), P = 0.13]. There was significantly less nephrectomy after late immunosuppression cessation [10/42 (23.8%) vs. 7/42 (16.7%) vs. 3/43 (7.0%), P = 0.01] but no differences in infections or malignancy. On competing risk regression (death as competing risk) controlling for cofactors including age, nephrectomy and rejection, prolonged immunosuppression did not predict likelihood of retransplantation (SHR 1.000, P = 0.88). Prolonged immunosuppression withdrawal does not reduce sensitization or improve retransplantation rates but is associated with less nephrectomy. Immunosuppression withdrawal should be tailored to individual circumstances after graft failure.

The potential role of antibodies against minor blood group antigens in renal transplantation.

Blood group antigens are red blood cell (RBC) surface markers comprising specific carbohydrate moieties attached to the glycolipids and glycoproteins within the membrane. In addition to the major ABO blood group antigens, at least 35 minor blood group antigens have been defined to date. These antigens have immunogenic potential and may cause a transfusion reaction. There is evidence for renal expression of antigens from the Kidd, MNS, Duffy and Lewis groups and therefore the potential for antibodies directed against these antigens to cross-react in a transplanted kidney. In individuals lacking a specific RBC antigen, antibodies may develop after de novo exposure to that antigen, in addition to the potential presence of pre-existing innate antibodies. Relatively little attention has been paid to non-ABO system antibodies, with most reports in the literature focusing on transfusion reactions rather than on any putative role in allograft rejection. Here, we review each of these antigens in the context of renal transplantation and what limited evidence there is on how such immunological risk may be assessed and managed.

De novo or early conversion to everolimus and long-term cancer outcomes in kidney transplant recipients: A trial-based linkage study.

Choice of immunosuppression may modify the risk of cancer after kidney transplantation, however, long-term data are lacking. Using the Australian and New Zealand Dialysis and Transplant Registry, we compared the 9-year risk of incident cancer, non-melanoma skin cancer (NMSC), and death attributed to cancer among participants from Australia and New Zealand in four randomized-controlled trials which compared de novo or early switch to an everolimus-containing regimen with calcineurin-inhibitor-based triple therapy. An adjusted Cox-model with random effects was used to determine such risks. Two hundred seventy-nine patients (192 everolimus, 87 control) were followed for a median of 9 years (IQR 6.7, 11.2). Compared with control, everolimus use was not associated with a reduction in the risk of incident cancer, NMSC, or cancer-related death (unadjusted HR [95% CI] 0.86 [0.49-1.48], 0.58 [0.30-1.12], and 1.18 [0.32-4.38], respectively). Subgroup analyses showed a 56% reduction for NMSC in patients randomized to everolimus + reduced-dose calcineurin-inhibitor versus control (unadjusted HR 0.44 [0.21-0.92]), which remained significant after adjusting for age, gender and smoking (adjusted HR 0.45 [0.21-0.96]). Although de novo or early switch to everolimus did not alter the 9-year risk of incident cancer or cancer-related death, everolimus with reduced-dose calcineurin-inhibitor strategy may reduce the long-term risk of NMSC.

Deterioration of Cortical Bone Microarchitecture: Critical Component of Renal Osteodystrophy Evaluation.

BACKGROUND: Cortical bone is a significant determinant of bone strength and its deterioration contributes to bone fragility. Thin cortices and increased cortical porosity have been noted in patients with chronic kidney disease (CKD), but the "Turnover Mineralization Volume" classification of renal osteodystrophy does not emphasize cortical bone as a key parameter. We aimed to assess trabecular and cortical bone microarchitecture by histomorphometry and micro-CT in patients with CKD G5 and 5D (dialysis). METHODS: Transiliac bone biopsies were performed in 14 patients undergoing kidney transplantation (n = 12) and parathyroidectomy (n = 2). Structural parameters were analysed by histomorphometry and micro-CT including trabecular bone volume, thickness (TbTh), number (TbN) and separation and cortical thickness (CtTh) and porosity (CtPo). Indices of bone remodelling and mineralisation were obtained and relationships to bone biomarkers examined. Associations were determined by Spearman's or Pearson's rank correlation coefficients. RESULTS: By micro-CT, trabecular parameters were within normal ranges in most patients, but all patients showed very low CtTh (127 ± 44 µm) and high CtPo (60.3 ± 22.5%). CtPo was inversely related to TbN (r = -0.56; p = 0.03) by micro-CT and to TbTh (r = -0.60; p = 0.024) by histomorphometry and correlated to parathyroid hormone values (r = 0.62; p = 0.021). By histomorphometry, bone turnover was high in 50%, low in 21% and normal in 29%, while 36% showed abnormal patterns of mineralization. Significant positive associations were observed between osteoblast surface, osteoclast surface, mineralization surface and bone turnover markers. CONCLUSIONS: Deterioration of cortical -microarchitecture despite predominantly normal trabecular parameters reinforces the importance of comprehensive cortical evaluation in patients with CKD.

Changes in bone microarchitecture following kidney transplantation-Beyond bone mineral density.

Bone disease in kidney transplant recipients (KTRs) is characterized by bone mineral density (BMD) loss but bone microarchitecture changes are poorly defined. In this prospective cohort study, we evaluated bone microarchitecture using non-invasive imaging modalities; high-resolution magnetic resonance imaging (MRI), peripheral quantitative computed tomography (pQCT), dual energy X-ray absorptiometry (DXA), and the trabecular bone score (TBS) following kidney transplantation. Eleven KTRs (48.3 ± 11.2 years) underwent MRI (tibia), pQCT (radius) and DXA at baseline and 12 months post-transplantation. Transiliac bone biopsies, performed at transplantation, showed 70% of patients with high/normal bone turnover. Compared with baseline, 12-month MRI showed deterioration in indices of trabecular network integrity-surface to curve ratio (S/C; -15%, P = 0.03) and erosion index (EI; +19%, P = 0.01). However, cortical area increased (+10.3%, P = 0.04), with a non-significant increase in cortical thickness (CtTh; +7.8%, P = 0.06). At 12 months, parathyroid hormone values (median 10.7 pmol/L) correlated with improved S/C (r = 0.75, P = 0.009) and EI (r = -0.71, P = 0.01) while osteocalcin correlated with CtTh (r = 0.72, P = 0.02) and area (r = 0.70, P = 0.02). TBS decreased from baseline (-5.1%, P = 0.01) with no significant changes in BMD or pQCT. These findings highlight a post-transplant deterioration in trabecular bone quality detected by MRI and TBS, independent of changes in BMD, underlining the potential utility of these modalities in evaluating bone microarchitecture in KTRs.

Emerging role of high-resolution imaging in the detection of renal osteodystrophy.

The term renal osteodystrophy refers to changes in bone morphology induced by chronic kidney disease (CKD) and represents the skeletal component of the entity 'chronic kidney disease - mineral and bone disorder'. Changes in turnover, mineralization, mass and microarchitecture impair bone quality, compromising strength and increasing susceptibility to fractures. Fractures are more common in CKD compared with the general population and result in increased morbidity and mortality. Screening for fracture risk and management of renal osteodystrophy are hindered by the complex, and still only partially understood, pathophysiology and the inadequacy of currently available diagnostic methods. Bone densitometry and bone turnover markers, although potentially helpful, have significant limitations in patients with CKD, and the 'gold standard' test of bone biopsy is infrequently performed in routine clinical practice. However, recent advances in high-resolution bone microarchitecture imaging may offer greater potential for quantification and assessment of bone structure and strength and, when used in conjunction with serum biomarkers, may allow non-invasive testing for a diagnostic virtual bone biopsy.

Impact of cinacalcet pre-transplantation on mineral metabolism in renal transplant recipients.

AIM: Cinacalcet is effective in reducing parathyroid hormone (PTH) in patients on dialysis. Reports of biochemical profiles and other clinical outcomes in patients discontinuing cinacalcet at time of renal transplantation are limited. METHODS: A retrospective study assessing markers of mineral metabolism, graft and patient outcomes in renal transplant recipients to determine differences in patients discontinuing cinacalcet (C+) compared with patients not treated with cinacalcet (C-) at time of transplantation. To allow for differences between groups in pre-transplant biochemical parameters, we also analysed a matched cohort of C- with C+ recipients (2:1), matched for age, calcium and PTH levels at transplantation. RESULTS: Five hundred thirty-two recipients (460 C-, 72 C+), transplanted January 2006-December 2012, were analysed, mean age 48.0 ± 12.7 years and 64.3% were men. At a median 42.9 months follow up, there were 10 deaths (1.9%), 56 allograft loss (10.6%) and 5 parathyroidectomies post-transplant (0.8%). Median PTH immediately pre-transplant was higher in C+ versus C- (50.7(25.4-75.2) versus 28.3(13.9-49.7) pmol/L, P < 0.001). Twelve-month post-transplant PTH was reduced but higher in C+ (11.7(6.9-21.2) vs 7.2(4.6-11.2) pmol/L, P < 0.001). Mean calcium was higher for C+ versus C- at 12 months (2.50 ± 0.19 vs 2.43 ± 0.17 mmol/L, P < 0.001), with differences to 4 years post-transplant. No difference was seen in renal function, graft loss, post-transplant parathyroidectomy rate and mortality. In the matched cohort (144 C- vs 72 C+), similar findings were also seen. CONCLUSION: Differences in mineral metabolism post-transplant are seen with cinacalcet pre-transplant compared with no cinacalcet. Transplant recipients discontinuing cinacalcet had higher post-transplant PTH and calcium although the clinical significance is unclear.

Outcomes of extended-hours hemodialysis performed predominantly at home.

BACKGROUND: Recent evidence suggests that increased frequency and/or duration of dialysis are associated with improved outcomes. We aimed to describe the outcomes associated with patients starting extended-hours hemodialysis and assess for risk factors for these outcomes. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: Patients were from 6 Australian centers offering extended-hours hemodialysis. Cases were patients who started treatment for 24 hours per week or longer at any time. OUTCOMES: All-cause mortality, technique failure (withdrawal from extended-hours hemodialysis therapy), and access-related events. MEASUREMENTS: Baseline patient characteristics (sex, primary cause of end-stage kidney disease, age, ethnicity, diabetes, and cannulation technique), presence of a vascular access-related event, and dialysis frequency. RESULTS: 286 patients receiving extended-hours hemodialysis were identified, most of whom performed home (96%) or nocturnal (77%) hemodialysis. Most patients performed alternate-daily dialysis (52%). Patient survival rates using an intention-to-treat approach at 1, 3, and 5 years were 98%, 92%, and 83%, respectively. Of 24 deaths overall, cardiac death (n = 7) and sepsis (n = 5) were the leading causes. Technique survival rates at 1, 3, and 5 years were 90%, 77%, and 68%, respectively. Access event-free rates at the same times were 80%, 68%, and 61%, respectively. Access events significantly predicted death (HR, 2.85; 95% CI, 1.14-7.15) and technique failure (HR, 3.76; 95% CI, 1.93-7.35). Patients with glomerulonephritis had a reduced risk of technique failure (HR, 0.31; 95% CI, 0.14-0.69). Higher dialysis frequency was associated with elevated risk of developing an access event (HR per dialysis session, 1.56; 95% CI, 1.03-2.36). LIMITATIONS: Selection bias, lack of a comparator group. CONCLUSIONS: Extended-hours hemodialysis is associated with excellent survival rates and is an effective treatment option for a select group of patients. The major treatment-associated adverse events were related to complications of vascular access, particularly infection. The risk of developing vascular access complications may be increased in extended-hours hemodialysis, which may negatively affect long-term outcomes.

Perspective - the issues surrounding ESKD and dialysis in the elderly and those with co-morbidities.

There is a disproportionate increase in the number of elderly patients, many with multiple co-morbidities, commencing dialysis. Predictors of survival for elderly patients on dialysis include age, comorbidity score, malnutrition, poor functional status and late referral. Patients with high co morbidity scores may not gain a survival advantage with dialysis vs a non dialysis pathway. Late referral and lack of dialysis access are independent predictors of mortality in elderly patients commencing dialysis. Hospital free survival may be similar in dialysis and non-dialysis treated groups We have little data on those choosing not to start dialysis in terms of numbers, clinical course and survival. Most available data is not from an Australian or New Zealand source. The effects on quality of life of different management pathways on patients, carers and staff still need to be addressed.

Dialysis modality preference of patients with CKD and family caregivers: a discrete-choice study.

BACKGROUND: Dialysis modality preferences of patients with chronic kidney disease (CKD) and family caregivers are important, yet rarely quantified. STUDY DESIGN: Prospective, unlabeled, discrete-choice experiment with random-parameter logit analysis. SETTING & PARTICIPANTS: Adults with stages 3-5 CKD and caregivers educated about dialysis treatment options from 8 Australian renal clinics. PREDICTORS: Preferences for and trade-offs between the dialysis treatment attributes of life expectancy, number of hospital visits per week, ability to travel, hours per treatment, treatment time of day, subsidized transport service, and flexibility of treatment schedule. OUTCOMES & MEASUREMENTS: Results presented as ORs for preferring home-based or in-center dialysis to conservative care. RESULTS: 105 predialysis patients and 73 family caregivers completed the study. Median patient age was 63 years, and mean estimated glomerular filtration rate was 18.1 (range, 6-34) mL/min/1.73 m(2). Median caregiver age was 61 years. Home-based dialysis (either peritoneal or home hemodialysis) was chosen by patients in 65% of choice sets; in-center dialysis, in 35%; and conservative care, in 10%. For caregivers, this was 72%, 25%, and 3%, respectively. Both patients and caregivers preferred longer rather than shorter hours of dialysis (ORs of 2.02 [95% CI, 1.51-2.70] and 2.67 [95% CI, 1.85-3.85] for patients and caregivers, respectively), but were less likely to choose nocturnal than daytime dialysis (ORs of 0.07 [95% CI, 0.01-0.75] and 0.03 [95% CI, 0.01-0.20]). Patients were willing to forgo 23 (95% CI, 19-27) months of life expectancy with home-based dialysis to decrease their travel restrictions. For caregivers, this was 17 (95% CI, 16-18) patient-months. LIMITATIONS: Data were limited to stated preferences rather than actual choice of dialysis modality. CONCLUSIONS: Our study suggests that it is rare for caregivers to prefer conservative nondialytic care for family members with CKD. Home-based dialysis modalities that enable patients and their family members to travel with minimal restriction would be strongly aligned with the preferences of both parties.

Factors influencing patient choice of dialysis versus conservative care to treat end-stage kidney disease.

BACKGROUND: For every patient with chronic kidney disease who undergoes renal-replacement therapy, there is one patient who undergoes conservative management of their disease. We aimed to determine the most important characteristics of dialysis and the trade-offs patients were willing to make in choosing dialysis instead of conservative care. METHODS: We conducted a discrete choice experiment involving adults with stage 3-5 chronic kidney disease from eight renal clinics in Australia. We assessed the influence of treatment characteristics (life expectancy, number of visits to the hospital per week, ability to travel, time spent undergoing dialysis [i.e., time spent attached to a dialysis machine per treatment, measured in hours], time of day at which treatment occurred, availability of subsidized transport and flexibility of the treatment schedule) on patients' preferences for dialysis versus conservative care. RESULTS: Of 151 patients invited to participate, 105 completed our survey. Patients were more likely to choose dialysis than conservative care if dialysis involved an increased average life expectancy (odds ratio [OR] 1.84, 95% confidence interval [CI] 1.57-2.15), if they were able to dialyse during the day or evening rather than during the day only (OR 8.95, 95% CI 4.46-17.97), and if subsidized transport was available (OR 1.55, 95% CI 1.24-1.95). Patients were less likely to choose dialysis over conservative care if an increase in the number of visits to hospital was required (OR 0.70, 95% CI 0.56-0.88) and if there were more restrictions on their ability to travel (OR=0.47, 95%CI 0.36-0.61). Patients were willing to forgo 7 months of life expectancy to reduce the number of required visits to hospital and 15 months of life expectancy to increase their ability to travel. INTERPRETATION: Patients approaching end-stage kidney disease are willing to trade considerable life expectancy to reduce the burden and restrictions imposed by dialysis.

New onset diabetes after kidney transplantation in autosomal dominant polycystic kidney disease: a retrospective cohort study.

BACKGROUND: New onset diabetes after transplantation (NODAT) is a common adverse outcome of organ transplantation that increases the risk of cardiovascular disease, infection and graft rejection. In kidney transplantation, apart from traditional risk factors, autosomal dominant polycystic kidney disease (ADPKD) has also been reported by several authors as a predisposing factor to the development of NODAT, but any rationale for an association between ADPKD and NODAT is unclear. We examined the cumulative incidence of NODAT in or own transplant population comparing ADPKD patients with non-ADPKD controls. METHODS: A retrospective cohort study to determine the cumulative incidence of patients developing NODAT (defined by World Health Organization-based criteria and/or use of hypoglycaemic medication) was conducted in 79 patients with ADPKD (79 transplants) and 423 non-ADPKD controls (426 transplants) selected from 613 sequential transplant recipients over 8 years. Patients with pre-existing diabetes as a primary disease or comorbidity and/or with minimal follow up or early graft loss/death were excluded. RESULTS: Of the 502 patients (505 transplants) studied, 86 (17.0%) developed NODAT. There was no significant difference in the cumulative incidence of NODAT in the ADPKD (16.5%; CI 13.6-20.7%) compared with the non-ADPKD (17.1%; CI 8.3-24.6%) control group. Of the 13 patients in the ADPKD group with NODAT, three required treatment with insulin with or without oral hypoglycaemic agents. Among the 73 NODAT patients in the non-ADPKD group, eight received insulin with or without oral hypoglycaemics. Furthermore, of the patients that did develop NODAT, there was no difference in the time to its development in patients with and without ADPKD. CONCLUSION: There was no evidence of an increased incidence of NODAT in ADPKD kidney transplant recipients.

Transition from a renal paediatric clinic to an adult clinic: Perspectives of adolescents and young adults, parents and health professionals.

The management of chronic kidney disease is complex. With disease management being the responsibility of parents in the paediatric renal clinic, the responsibility is gradually shifted to adolescents and young adults during the transition to adult care. This multi-perspective qualitative study aimed to explore the experiences of adolescents and young adults, their parents and health professionals to gain an insight into transitional care. Focussing on the transition process and transfer to adult care, 18 adolescents and young adults and eight mothers participated in individual semi-structured interviews. Additionally, three focus groups were conducted with 20 multidisciplinary health professionals. Data were transcribed verbatim and analysed thematically. Similar responses from adolescents and young adults and mothers included the reluctance to leave the paediatric health service. Mothers found the transition to adult care more challenging than the adolescents and young adults. While health professionals acknowledged that engaging adolescents and young adults in their own care was challenging, they believed parents had an important role in facilitating their child's independence. This study highlights that health professionals in both paediatric and adult health services need to work collaboratively. However, importantly, health professionals need to be mindful that parents require an equal amount of engagement as adolescents and young adults, if not more, to mitigate parental barriers in achieving a successful transfer.

Successful Implementation of an Increased Viral Risk Donor Waiting List for Preconsented Kidney Transplant Candidates in Victoria, Australia.

Increased viral risk donors (IVRDs) with increased risk behaviors for blood-borne virus infection and negative nucleic acid testing have a low absolute risk of "window period" infection. Utilization and allocation of IVRD organs differ between jurisdictions. METHODS: We examined the characteristics and utilization of deceased donor IVRD kidneys and recipient outcomes within a 2-y period (July 31, 2018-July 31, 2020) postimplementation of a new opt-in allocation pathway for preconsented recipients in Victoria, Australia. RESULTS: Fifty-six kidneys from 31 IVRDs were utilized, comprising 13% of donors. Preconsent rate to accept IVRD kidneys increased to 41% of the waitlist in the 2 y postimplementation, and IVRDs having no kidneys utilized reduced to 0%. Compared with non-IVRD kidneys, kidney offer declines >10 per donor were less likely from IVRDs (3% vs 19%; P < 0.05). IVRDs were younger (median age 36 [IQR 30-44] vs 51 [35-60] y; P < 0.0001), with lower kidney donor profile index (25% [13-40%] vs 57% [29-75%]; P < 0.0001), and less hypertension (0% vs 22%; P < 0.01). Estimated glomerular filtration rate 3 mo post-transplant was superior (P < 0.01). Injecting drug use (61%) was the most common increased risk behavior. 29% of IVRDs were hepatitis C antibody positive but nucleic acid testing negative. No active infection was detected in any recipient post-transplant. CONCLUSIONS: The described opt-in system permits efficient allocation and utilization of kidneys from IVRDs, with superior quality and graft function. Education is crucial to facilitate informed consent and equity of access to this donor pool.

Residual kidney function in nocturnal vs conventional haemodialysis patients: a prospective observational study.

BACKGROUND: Residual kidney function (RKF) provides substantial volume and solute clearance even after dialysis initiation. Preservation of RKF is associated with improved outcomes including mortality in patients on both peritoneal and haemodialysis (HD). Factors predicting RKF loss are unclear, including HD modality. Nocturnal haemodialysis (NHD) may result in less aggressive fluid and solute shifts, however, retrospective data suggests frequent NHD may accelerate RKF decline. The aim of the study was to determine if decline in RKF differs between patients undergoing conventional haemodialysis (CHD) versus NHD. METHODS: A prospective observational study of incident HD patients was undertaken comparing patients undertaking CHD (4-5 h, 3 days/week) and NHD (8 h, 3-5 nights/week). Change in RKF was measured by urea and creatinine clearance (48-h interdialytic urine collection) and glomerular filtration rate (GFR) (Cr51-EDTA nuclear scan) at initiation of dialysis (baseline) and 12 months. RESULTS: A total of 18 incident HD patients were recruited (8 CHD, 10 NHD). Three patients withdrew after baseline (n = 15). Baseline RKF was similar between groups with mean nuclear GFR of 13.3 ± 4.1 mL/min in the CHD cohort vs 13.5 ± 4.6 mL/min in the NHD group (p = 0.89). Baseline urine volume was 2399 ± 950 mLs and 2794 ± 1662 mLs in the CHD and NHD, respectively (p = 0.57). Nuclear GFR declined from time 0 to 12 months to 9.3 ± 2.5 mL/min and 10.4 ± 4.3 mL/min in the CHD and NHD, respectively (p = 0.52). There was a significant decline in 48-h urine volume over 12 months with a mean volume of 1943 ± 1087.0 mLs in the CHD compared to 601.7 ± 315.3 mLs in the NHD (p = 0.01). No significant difference was found in other measures of RKF between groups over 12 months. CONCLUSION: This small prospective cohort study found that the loss of residual urine volume was greater in the NHD vs the CHD cohort but there was no difference in other measures of RKF.

Bone microarchitecture in patients undergoing parathyroidectomy for management of secondary hyperparathyroidism.

BACKGROUND: Secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) leads to complex bone disease, affecting both trabecular and cortical bone, and increased fracture risk. Optimal assessment of bone in patients with CKD is yet to be determined. High-resolution magnetic resonance imaging (MRI) can provide three-dimensional assessment of bone microarchitecture, as well as determination of mechanical strength with finite element analysis (FEA). METHODS: We conducted a single-centre, cross-sectional study to determine bone microarchitecture with MRI in CKD patients with SHPT undergoing parathyroidectomy. Within two weeks of surgery, MRI was performed at the distal tibia and biochemical markers of SHPT (parathyroid hormone [PTH] and alkaline phosphatase [ALP]) were collected. Trabecular and cortical topological parameters as well as bone mechanical competence using FEA were assessed. Correlation of MRI findings of bone was made with biochemical markers. RESULTS: Twenty patients with CKD (15 male, 5 female) underwent MRI at the time of parathyroidectomy (16 on dialysis, 3 with functioning kidney transplant, one pre-dialysis with CKD stage 5). Median PTH at the time of surgery was 138.5 pmol/L [39.6-186.7 pmol/L]. MRI parameters in patients were consistent with trabecular deterioration, with erosion index (EI) 1.01 ±â€¯0.3, and trabecular bone volume (BV/TV) 10.8 ±â€¯2.9%, as well as poor trabecular network integrity with surface-to-curve ratio (S/C) 5.4 ±â€¯2.3. There was also evidence of reduced cortical thickness, with CTh 2.698 ±â€¯0.630 mm, and FEA demonstrated overall poor bone mechanical strength with mean elastic modulus of 2.07 ±â€¯0.44. CONCLUSION: Patients with severe SHPT requiring parathyroidectomy have evidence of significant changes in bone microarchitecture with trabecular deterioration, low trabecular and cortical bone volume, and reduced mechanical competence of bone.

Propagation and culture of renal fibroblasts.

In this chapter we describe a reliable and reproducible method for the selective propagation and culture of renal fibroblasts derived from explantation of renal cortical tissue in vitro. The chapter outlines how primary renal interstitial fibroblasts are derived from explants grown in medium supplemented with foetal calf serum. The subculture of confluent cells and their ultimate characterisation as fibroblasts through immunohistochemical and immunocytochemical techniques are described in detail.

The advantages and disadvantages of home hemodialysis.

In Australia, 12% of the hemodialysis population dialyze at home. Until recently, the majority of these patients dialyzed for similar hours to those in satellite dialysis. However, in the past 5 years there has been a new departure such that in many centers the concept of home hemodialysis is now synonymous with extended hours dialysis. Registry data supports the concept that increased frequency and duration of dialysis may result in improved patient survival and a reduction in cardiovascular risk profile. It is hoped, therefore, that the long recognized survival benefit observed in home hemodialysis patients may be further augmented by the swing to extended hours dialysis in this patient population. In addition to the physiological benefits of extended hours home dialysis, there are clear quality of life, social, and economic advantages associated with dialyzing at home. There are however a number of perceived disadvantages to home hemodialysis including the application and time commitment required for training, the potential for relationship strain or "burnout," and reluctance to "hospitalize" the home. Overall, however, in this new era of extended hours dialysis, the advantages both physiological and lifestyle of home hemodialysis far outweigh the disadvantages.

Magnetic resonance imaging based assessment of bone microstructure as a non-invasive alternative to histomorphometry in patients with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) adversely affects bone microarchitecture and increases fracture risk. Historically, bone biopsy has been the 'gold standard' for evaluating renal bone disease but is invasive and infrequently performed. High-resolution magnetic resonance imaging (MRI) quantifies bone microarchitecture noninvasively. In patients with CKD, it has not been compared with results derived from bone biopsy or with imaging using dual energy X-ray absorptiometry (DXA). METHODS: Fourteen patients with end-stage kidney disease (ESKD) underwent MRI at the distal tibia, bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA; hip and spine) and transiliac bone biopsies with histomorphometry and microcomputed tomography (micro-CT). All patients had biomarkers of mineral metabolism. Associations were determined by Spearman's or Pearson's rank correlation coefficients. RESULTS: MRI indices of trabecular network integrity, surface to curve ratio (S/C) and erosion index (EI), correlated to histomorphometric trabecular bone volume (S/C r = 0.85, p = 0.0003; EI r = -0.82, p = 0.001), separation (S/C r = -0.58, p = 0.039; EI r = 0.79, p = 0.0012) and thickness (S/C, r = 0.65, p = 0.017). MRI EI and trabecular thickness (TbTh) also correlated to micro-CT trabecular separation (EI r = 0.63, p = 0.02; TbTh r = -0.60, p = 0.02). Significant correlations were observed between histomorphometric mineralization and turnover indices and various MRI parameters. MRI-derived trabecular parameters were also significantly related to femoral neck BMD. CONCLUSIONS: This study highlights the heterogeneity of bone microarchitecture at differing skeletal sites. MRI demonstrates significant, relevant associations to important bone biopsy and DXA indices and warrants further investigation to assess its potential to non-invasively evaluate changes in bone structure and quality over time.