PTH assays in dialysis patients: Practical considerations.

Parathyroid hormone (PTH) 1-84 is the main biologically active hormone produced by the parathyroid cells. Circulating PTH molecules include the whole PTH 1-84 along with amino (N) and carboxyl (C) terminal fragments. While PTH is the best available noninvasive biomarker to assess bone turnover in dialysis patients, the biological roles of individual circulating PTH fragments are still not completely known. The understanding that there is an enormous variation in the target specificity of currently available PTH assays for different circulating forms of PTH has led to the evolution of assays from first to second then third generation. With a reduction in kidney function, there is a preferential increase in circulating C fragments and non-PTH 1-84 forms, resulting in a decrease in the ratio of PTH 1-84/non-PTH 1-84. However, there are also substantial differences in between-assay measurements, with several fold variations in results. Targets based on multiples of the upper limit of normal (ULN) should be used rather than PTH ranges using absolute iPTH values. To date, the second-generation PTH remains the most widely used assay. Current guidelines recommend following iPTH trends rather than absolute values. Herein, we highlight problems and challenges in PTH assays/measurements and their interpretations in dialysis patients.

Long-term outcomes and management considerations after parathyroidectomy in the dialysis patient.

Parathyroidectomy (PTX) remains an important intervention for dialysis patients with poorly controlled secondary hyperparathyroidism (SHPT), though there are only retrospective and observational data that show a mortality benefit to this procedure. Potential consequences that we seek to avoid after PTX include persistent or recurrent hyperparathyroidism, and parathyroid insufficiency. There is considerable subjectivity in defining and diagnosing these conditions, given that we poorly understand the optimal PTH targets (particularly post PTX) needed to maintain bone and vascular health. While lowering PTH after PTX decreases bone turnover, long-term changes in bone activity have been poorly explored. High turnover bone disease, usually present at the time a PTX is considered, often swings to a state of low turnover in the setting of sufficiently low PTH levels. It remains unclear if all low bone turnover equate with disease. However, such changes in bone turnover appear to predispose to vascular calcification, with positive calcium balance after PTX being a potential contributor. We know little of how the post-PTX state resets calcium balance, how calcium and VDRA requirements change or what kind of adjustments are needed to avoid calcium loading. The current consensus cautions against excessive reduction of PTH although there is insufficient evidence-based guidance regarding the management of chronic kidney disease - mineral bone disease (CKD-MBD) parameters in the post-PTX state. This article aims to compile existing research, provide an overview of current practice with regard to PTX and post-PTX chronic management. It highlights gaps and controversies and aims to re-orient the focus to clinically relevant contemporary priorities in CKD-MBD management after PTX.

Kidney recovery in patients discharged to an acute rehabilitation facility with acute kidney injury requiring hemodialysis
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BACKGROUND: Patients with acute kidney injury requiring renal replacement therapy (AKI-RRT) are at risk of adverse outcomes. Little is known about the incidence of AKI-RRT recovery following hospital discharge. We examine AKI-RRT recovery in hospital survivors discharged to a long-term acute care hospital (LTACH) with need of hemodialysis (HD) for AKI. MATERIALS AND METHODS: Single-center, retrospective cohort study of patients who were hospitalized (08/2015 - 04/2018), suffered from AKI-RRT, and were discharged to an affiliated LTACH with need for HD. Kidney recovery was defined as the patient being alive and no longer requiring HD. RESULTS: 41 patients were included. Mean (SD) age was 61.3 (9.7) years, 63.4% were male, and 90.2% white. At the time of discharge from LTACH, 27 (65.8%) patients had survived and had recovered kidney function (kidney recovery group), 7 had been discharged on HD, and 7 had died (no kidney recovery group, n = 14, 34.2%). In adjusted models, the presence of anemia was associated with a 91% decreased odds of kidney recovery at LTACH discharge. Each additional HD session during LTACH stay had an 18% decreased odds of kidney recovery at LTACH discharge, and each episode of intradialytic hypotension had a 20% decreased odds of kidney recovery at the end of the observation period (median follow-up of 19.0 months). CONCLUSION: Almost 2/3 of AKI-RRT patients discharged to an affiliated LTACH with ongoing HD need recovered kidney function. Anemia and the number of HD sessions and intradialytic hypotension episodes were associated with kidney recovery. Future studies should focus on developing risk-stratification tools for kidney recovery and determining best practices to promote recovery in this susceptible population.

Parathyroidectomy-A last resort for hyperparathyroidism in dialysis patients.

Despite advancements in the medical management of secondary hyperparathyroidism, parathyroidectomy is still necessarily in some patients. However, patients' selection, optimal surgical intervention and long-term outcome are still not well-defined and very challenging for the practicing nephrologists. In this manuscript we will attempt to answer several questions related to parathyroidectomy in dialysis patients. We will discuss the indications, the appropriate parathyroidectomy surgical techniques and current guidelines for parathyroidectomy. We will also discuss short- and long-term outcome and analyze the pros and cons of the procedure. It is readily apparent that the performance of parathyroidectomy in dialysis patients should be highly individualized.

Urinary calcium excretion and bone turnover in osteoporotic patients
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INTRODUCTION: It is well documented that patients with osteoporosis (OP) have high incidence of hypercalciuria (HC). However, the mechanism of HC in patients with OP is not well established. It is thought to be the result of high bone turnover (HBT) with excessive bone resorption. OP also frequently presents with low bone turnover (LBT). At this time, it is not clear whether OP with LBT is also associated with hypercalciuria. PURPOSE: The purpose of this study is to evaluate urinary calcium excretion in osteoporotic patients with HBT and LBT. MATERIALS AND METHODS: This is a retrospective study of 132 patients with osteoporosis who underwent bone biopsy at the University of Kentucky between January 2010 and December 2012. Based on bone biopsy results, patients were divided into HBT or LBT groups. Demographic data, medical history, bone mineral density, serum creatinine, calcium, phosphorus, estimated glomerular filtration rate (eGFR), filtered calcium load, fractional excretion of calcium and phosphorus, 25-hydroxy vitamin D levels, and 24-hour urinary calcium excretion and creatinine were obtained from the patients' medical records. Also, intact parathyroid hormone (iPTH), serum osteocalcin, bone-specific alkaline phosphatase, N-telopeptide of type I collagen, and urine pyridinium levels were measured. RESULTS: Hypercalciuria was present in approximately half of the patients in both the HBT and LBT groups. Patients with HBT OP were significantly younger than those with LBT OP (p = 0.013). There was no difference between HBT and LBT patients in 24-hour urinary calcium excretion, serum creatinine, calcium, phosphorus, eGFR, filtered calcium load, and fractional excretion of phosphorus. Mean values of serum osteocalcin and serum N-telopeptide of type I collagen were significantly lower in the LBT compared to the HBT group (p = 0.000 and 0.0152, respectively). There was a significant correlation between filtered calcium load and urinary calcium excretion in HBT patients but not in patients with LBT. Fractional excretion of calcium significantly correlated with urinary calcium excretion in both groups. There was no correlation between kidney function and 24-hour urinary calcium excretion. There was no correlation between dual-emission X-ray absorptiometry T-scores and 24-hour urinary calcium excretion. CONCLUSION: HC is frequently present in patients with OP regardless of the underlying bone turnover status. This may suggest the presence of a bone-derived renal calcium regulating factor(s). Further studies are needed to understand the exact mechanism and the potential consequences of HC in OP patients.
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Idiopathic Membranous Nephropathy: Diagnostic and Therapeutic Challenges.

BACKGROUND: In adults, membranous nephropathy (MN) is a major cause of nephrotic syndrome. While a majority of cases of MN are idiopathic, secondary forms can be seen in the setting of autoimmune disease, neoplasia, infection, and after being exposed to certain therapeutic agents. Both human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections could cause MN. However, the effect of coexisting HIV and HCV infection on the spectrum and progression of kidney disease as well as the effect of MN treatment on HIV and HCV infection are not well known. METHODS: In this study, we describe a patient with hemophilia A and acquired HIV and HCV infections, a patient who developed severe nephrotic syndrome and for whom renal biopsy showed MN. RESULTS: Patient responded well to adrenocorticotropic hormone gel without adversely affecting HIV or HCV infections. CONCLUSION: Adrenocorticotropic hormone gel might be useful in the management of complex cases of idiopathic MN.

Thrombotic microangiopathy in systemic lupus erythematosus: efficacy of eculizumab.

Thrombotic microangiopathy (TMA) is a severe disorder with poor outcomes. The cause is unknown for many patients, although TMA is associated with connective tissue disorders, including systemic lupus erythematosus (SLE). While uncommon, TMA is one of the most serious complications of SLE and in many cases may be resistant to therapy. We report a patient with SLE complicated by TMA that was refractory to standard therapy but responded well to eculizumab, with continued remission after 1 year of follow-up. Eculizumab might be useful in the management of resistant cases of TMA caused by SLE.

Fibrillary glomerulonephritis masquerading as rapidly progressive glomerulonephritis with pseudo-linear glomerular basement membrane staining.

Fibrillary glomerulonephritis (FGN) is a rare disorder with poor renal prognosis. It is a heterogeneous disease associated with significant risk of end-stage renal disease (ESRD). Its etiology and pathogenesis have not been clearly identified. We report a case of a patient presenting with hypertensive crisis, nephrotic range proteinuria, and rapidly progressive glomerulonephritis (RPGN). The kidney biopsy demonstrates crescentic GN on light microscopy (LM) and strong pseudo-linear/globular glomerular basement membrane (GBM) staining for immunoglobulin G on immunofluorescence (IF), suggestive of anti-GBM disease. However, circulating anti-GBM antibodies were negative. Electron microscopy (EM) revealed fibrillary deposits in the GBM, confirming the diagnosis of FGN. Review of the literature revealed very few reported similar cases. It appears that severe hypertension and heavy proteinuria, while uncommon in anti-GBM disease, are consistent findings in RPGN form of FGN.

Kidney Recovery in Patients With Acute Kidney Injury Treated in Outpatient Hemodialysis or Rehabilitation Facilities.

RATIONALE & OBJECTIVE: Since January 2017, patients with acute kidney injury requiring dialysis (AKI-D) can be discharged to outpatient dialysis centers for continued hemodialysis (HD) support. We aimed to examine the rate of kidney recovery, time to recovery, and hospitalization-related clinical parameters associated with kidney recovery in patients with AKI-D. STUDY DESIGN: Single-center prospective cohort study. SETTING & PARTICIPANTS: 111 adult patients who were admitted to the University of Kentucky Hospital, experienced AKI-D, and were discharged with need of outpatient HD. EXPOSURE: Hospitalization-related clinical parameters were evaluated. OUTCOME: Kidney recovery as a composite of being alive and no longer requiring HD or other form of kidney replacement therapy. ANALYTICAL APPROACH: Discrete-time survival analysis and logistic regression were used to determine adjusted probabilities of kidney recovery at prespecified time points and to evaluate clinical parameters associated with recovery. RESULTS: 45 (41%) patients recovered kidney function, 25 (55.5%) within the first 30 days following discharge, 16 (35.5%) within 30 to 60 days, and 4 (9%) within 60 to 90 days. Adjusted probabilities of recovery were 36.7%, 27.4%, and 6.3%, respectively. Of the remaining patients, 49 (44%) developed kidney failure requiring chronic kidney replacement therapy and 17 (15%) died or went to hospice. Patients who did not recover kidney function were older, had more comorbid conditions, had lower estimated glomerular filtration rates at baseline, and received more blood transfusions during hospitalization when compared with those who recovered kidney function. LIMITATIONS: Selection bias given that patients included in the study were all eligible for AKI management with outpatient HD as part of Medicare/Medicaid services. CONCLUSIONS: At least one-third of AKI-D survivors discharged from an acute care hospital dependent on HD recovered kidney function within the first 90 days of discharge, more commonly in the first 30 days postdischarge. Future studies should elucidate clinical parameters that can inform risk classification and interventions to promote kidney recovery in this vulnerable and growing population.

A Survey Study of Self-Rated Patients' Knowledge About AKI in a Post-Discharge AKI Clinic.

BACKGROUND: Survivors of acute kidney injury (AKI) are at risk of adverse outcomes. Post-discharge nephrology care may improve patients' AKI knowledge and prevent post-AKI complications. OBJECTIVE: The purpose of this study was to examine patients' awareness about their AKI diagnosis and self-rated knowledge and severity of AKI before and after their first post-discharge AKI Clinic encounter. DESIGN: We conducted a pre- and post-survey study among AKI survivors who attended a post-discharge AKI Clinic. SETTING: AKI Clinic at the University of Kentucky Medical Center (October 2016 to December 2017). Education about AKI was based on transformative learning theory and provided through printed materials and interdisciplinary interactions between patients/caregivers and nurses, pharmacists, and nephrologists. PATIENTS: A total of 104 patients completed the survey and were included in the analysis. MEASUREMENTS: Three survey questions were administered before and after the first AKI Clinic encounter: Question 1 (yes-no) for awareness, and questions 2 and 3 (Likert scale, 1 = lowest to 5 = highest) for self-rated knowledge and severity of AKI. METHODS: Two mixed-model analysis of variance (ANOVA) was used for between-group (AKI severity) and within-group (pre- and post-encounter) comparisons. Logistic regression was used to examine parameters associated with the within-group change in self-perceived knowledge. RESULTS: Twenty-two out of 104 (21%) patients were not aware of their AKI diagnosis before the clinic encounter. Patients' self-ratings of their AKI knowledge significantly increased after the first AKI Clinic encounter (mean ± SEM: pre-visit = 1.94 ± 0.12 to post-visit = 3.88 ± 0.09, P = .001), even after adjustment for age, gender, Kidney Disease Improving Global Outcomes (KDIGO) severity stage, or poverty level. Patients with AKI stage 3 self-rated their AKI as more severe than patients with AKI stage 1 or 2. LIMITATIONS: Our study population may not be representative of the general AKI survivor population. Administered surveys are subject to response-shift bias. CONCLUSIONS: Patients' self-perceived knowledge about AKI significantly increased following the first post-discharge AKI Clinic encounter that included interdisciplinary education. This is the first survey study examining self-perceived AKI knowledge in AKI survivors. Further examination of AKI literacy in survivors of AKI and its effect on post-AKI outcomes is needed. TRIAL REGISTRATION: Not applicable.

CONTEXTE: Les survivants d'un épisode d'insuffisance rénale aiguë (IRA) risquent de souffrir de pathologies associées. Un suivi en néphrologie après la sortie de l'hôpital pourrait accroître les connaissances des patients sur la maladie et prévenir les complications. OBJECTIF: L'étude était bipartite : i) savoir si les patients connaissaient leur diagnostic; ii) mesurer, par auto-évaluation, les connaissances des patients sur l'IRA et sur sa gravité, avant et après une consultation dans une clinique d'IRA. TYPE D'ÉTUDE: Un sondage mené auprès de survivants d'un épisode d'IRA, avant et après une consultation en clinique d'IRA suivant leur congé de l'hôpital. CADRE: La clinique d'IRA du centre médical de l'université du Kentucky (d'octobre 2016 à décembre 2017). L'information fournie suivait la théorie de l'apprentissage transformationnel et était transmise sous forme de documents imprimés et d'interactions interdisciplinaires entre les patients/fournisseurs de soins et les infirmières, les pharmaciens et les néphrologues. PARTICIPANTS: L'étude porte sur 104 patients ayant complété le sondage. MESURES: Trois questions ont été posées aux patients avant et après une première consultation à la clinique. Une question portait sur leur connaissance du diagnostic (oui -non) et deux autres auto-évaluaient leurs connaissances sur l'IRA et sa gravité (échelle de Likert, de 1 [plus faible] à 5 [plus élevé]). MÉTHODOLOGIE: Deux modèles mixtes d'analyse de variance ont été employés pour établir des comparaisons inter-groupes (gravité de l'IRA) et intra-groupes (pré et post-consultation). Une régression logistique a été utilisée pour analyser les paramètres associés aux changements du niveau auto-évalué des connaissances dans un même groupe. RÉSULTATS: Des 104 patients inclus à l'étude, 22 (21 %) ignoraient leur diagnostic d'IRA avant la consultation. L'auto-évaluation des connaissances a augmenté après la première consultation (moyenne ± SEM : 1,94 ± 0,12 [pré-visite]; 3,88 ± 0,09 [post-visite], p=0,001) et ce, même après les ajustements en regard de l'âge et du sexe du patient, du stade de la maladie selon le KDIGO (Kidney Disease Improving Global Outcomes) ou du niveau de revenus. Les patients atteints d'une IRA de stade 3 ont davantage surévalué la gravité de leur maladie que les patients de stades 1 ou 2. LIMITES: La population étudiée pourrait ne pas être représentative de la population générale des survivants d'un épisode d'IRA. Les sondages sont sujets aux biais liés aux changements de réponses. CONCLUSION: L'auto-évaluation des connaissances a augmenté significativement après une première consultation à la clinique d'IRA lorsque celle-ci incluait de l'information interdisciplinaire. Il s'agit de la première étude portant sur l'auto-évaluation des connaissances de survivants d'un épisode d'IRA. Il est nécessaire d'examiner davantage la littératie de l'IRA chez les survivants de la maladie et ses effets sur les pathologies qui en découlent.

Value of Intraoperative Parathyroid Hormone Assay during Parathyroidectomy in Dialysis and Renal Transplant Patients with Secondary and Tertiary Hyperparathyroidism.

BACKGROUND: In dialysis and renal transplant patients with secondary and tertiary hyperparathyroidism (HPT), the value of intraoperative parathyroid hormone (ioPTH) during parathyroidectomy (PTX) and its association with long-term PTH levels are unknown. The present study aims at evaluating the relationship of ioPTH with long-term PTH levels post-PTX in dialysis and renal transplant patients in a single-center study. METHODS: The ioPTH was measured in 57 dialysis patients (33 females and 24 males) and 18 renal transplant recipients (12 males and 6 females) who underwent PTX from 2005 to 2015 for refractory HPT. Near-total PTX was performed in 56 patients and total PTX with autotransplantation in 20 patients. The PTH monitoring included 3 samples: pre-intubation, 10- and 20-min (pre-ioPTH, 10-ioPTH, and 20-ioPTH) post parathyroid gland excision. Patients were followed up for up to 5 years. RESULTS: In the dialysis group, the median (25th-75th percentile) pre-, 10-, and 20-ioPTH levels were 1,447 pg/mL (938-2,176), 143 pg/mL (78-244) and 112 pg/mL (59-153) respectively. In the renal transplant group, pre-, 10-, and 20-ioPTH levels were 273 pg/mL (180-403), 42 pg/mL (25-72), and 34 pg/mL (23-45) respectively. All patients in the transplant group had a functional kidney transplant at the time of PTX with a median serum creatinine of 1.3 mg/dL (1.2-1.7) and estimated glomerular filtration rate of 55 mL/min (40-60). The median time between renal transplant and PTX surgeries was 22 months (7-81). The last median follow-up PTH level was 66 pg/mL (15-201) in the dialysis group and 54 pg/mL (17-72) in the transplant group (p = 0.438). The mean time for last PTH post-PTX was 2.3 ± 2.0 years. In both groups, there was no significant difference between 20-ioPTH and any-time post-PTX PTH levels (p = 0.6 and p = 0.9). Nineteen patients (25%) were readmitted within 90 days because of hypocalcemia. One patient in the dialysis group was readmitted for post-PTX hematoma evacuation. No patient required repeat PTX because of recurrent HPT that was refractory to medical therapy. Only one dialysis patient required repeat PTX because the first procedure failed. CONCLUSIONS: The 20-ioPTH is a good indicator of long-term PTH levels in dialysis and renal transplant patients. Hypocalcemia is a common complication, particularly in dialysis patients, and it is the main reason for readmission after PTX. Hypoparathyroidism is a potential concern after PTX in dialysis patients.

Outcome of Patients With Small Vessel Vasculitis After Renal Transplantation: National Database Analysis.

BACKGROUND: Small vessel vasculitis commonly affects the kidney and can progress to end-stage renal disease. The goal of this study is to compare outcomes of patients who received a renal transplant as a result of small vessel vasculitis (group A) with those who received kidney transplants because of other causes (group B). METHODS: This is a retrospective analysis of United Network for Organ Sharing registry data for adult primary kidney transplants from January 2000 to December 2014. Group A patients (N = 2196) were compared with a group B (N = 6588); groups were case matched for age, race, sex, donor type, and year of transplant in a 1:3 ratio. RESULTS: Renal and patient survivals were better in the group A (P < 0.001). New-onset diabetes after transplant developed in 8.3% of the group A and 11.3% of group B (P < 0.001). Seventeen (0.8%) patients in group A developed recurrent disease. Of these, 7 patients had graft failure, 3 of which were due to disease recurrence. Group A patients had significantly higher risk of developing posttransplant solid organ malignancies (11.3% vs 9.3%, P = 0.006) and lymphoproliferative disorder (1.3% vs 0.8%, P = 0.026). Independent predictors of graft failure and patient mortality were recipients' morbid obesity, diabetes, age, and dialysis duration (hazard ratio of 1.7, 1.4, 1.1/10 years, and 1.1/year for graft failure, and 1.7, 1.7, 1.6/10 years and 1.1/year for patient mortality, respectively). CONCLUSIONS: Renal transplantation in patients with has favorable long-term graft and patient outcomes with a low disease recurrence rate. However, they may have a higher risk of developing posttransplant malignancies.

Achieved Blood Pressure and Outcomes in the Secondary Prevention of Small Subcortical Strokes Trial.

UNLABELLED: Studies suggest a J-shaped association between blood pressure and cardiovascular events in the setting of intensive systolic blood pressure control; whether there is a similar association with stroke remains less well established. The Secondary Prevention of Small Subcortical Strokes was a randomized trial to evaluate higher (130-149 mm Hg) versus lower (<130 mm Hg) systolic blood pressure targets in participants with recent lacunar infarcts. We evaluated the association of mean achieved blood pressure, 6 months after randomization, and recurrent stroke, major vascular events, and all-cause mortality. After a mean follow up of 3.7 years, there was a J-shaped association between achieved blood pressure and outcomes; the lowest risk was at ≈124 and 67 mm Hg systolic and diastolic blood pressure, respectively. For example, above a systolic blood pressure of 124 mm Hg, 1 standard deviation higher (11.1 mm Hg) was associated with increased mortality (adjusted hazard ratio: 1.9; 95% confidence interval: 1.4, 2.7), whereas below this level, this relationship was inverted (0.29; 0.10, 0.79), P<0.001 for interaction. Above a diastolic blood pressure of 67 mm Hg, a 1 standard deviation higher (8.2 mm Hg) was associated with an increased risk of stroke (2.2; 1.4, 3.6), whereas below this level, the association was in the opposite direction (0.34; 0.13, 0.89), P=0.02 for interaction. The lowest risk of all events occurred at a nadir of ≈120 to 128 mm Hg systolic blood pressure and 65 to 70 mm Hg diastolic blood pressure. Future studies should evaluate the impact of excessive blood pressure reduction, especially in older populations with preexisting vascular disease. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059306.

Impact of Professional Student Mentored Research Fellowship on Medical Education and Academic Medicine Career Path.

CONTEXT: This study explores the long-term impact of the Professional Student Mentored Research Fellowship (PSMRF) program at the University of Kentucky College of Medicine (UKCOM) on medical students' research productivity and career paths. METHODS: Demographic characteristics, academic profiles, number of publications and residency placements from 2007 to 2012 were used to assess 119 PSMRF graduates against a comparison cohort of 898 UKCOM (non-PSMRF) students. RESULTS: PSMRF students had higher MCAT scores at admission (31.5 ± 0.6 vs. 30.6 ± 0.2, p = 0.007) and achieved higher USMLE Step 1 scores (228 ± 4.2 vs. 223 ± 1.5, p = 0.03) than comparison group. PSMRF students were more likely to publish PubMed-indexed papers (36.7% vs. 17.9%, p < 0.0001), achieve AOA status (19.3% vs. 8.5%, p = 0.0002) and match to top 25 US News and World Report residency programs (23.4% vs. 12.1%, p = 0.008). A greater proportion of PSMRF fellows matched to top tier competitive specialties (23% vs. 14.2%, p = 0.07), however this difference was not statistically significant. CONCLUSIONS: The PSMRF program shows a significant increase in enrollment, as well as positive associations with indicators of success in medical school and subsequent quality of residency program.

Depressive symptoms and dietary adherence in patients with end-stage renal disease.

Depressive symptoms may be associated with fluid and dietary non adherence which could lead to poorer outcomes. The purpose of this study was to examine the relationship between depressive symptoms and fluid and dietary adherence in 100 patients with end-stage renal disease (ESRD) receiving haemodialysis. A descriptive, cross-sectional design with a convenience sample of 100 patients with ESRD receiving maintenance haemodialysis completed instruments that measured self-reported depressive symptoms and perceived fluid and dietary adherence. Demographic and clinical data and objective indicators of fluid and diet adherence were extracted from medical records. As many as two-third of these subjects exhibited depressive symptoms and half were non adherent to fluid and diet prescriptions. After controlling for known covariates, patients determined to have moderate to severe depressive symptoms were more likely to report non adherence to fluid and diet restrictions. Depressive symptoms in patients with ESRD are common and may contribute to dietary and fluid non adherence. Early identification and appropriate interventions may potentially lead to improvement in adherence of these patients.

Response to cyclosporine A in a patient with pure red cell aplasia due to antierythropoietin-alpha antibodies.

Reported cases of pure red cell aplasia (PRCA) from the administration of erythropoietin (EPO)-alpha molecule in the United States are rare, and the optimal treatment is still unknown. We present a patient with end-stage renal disease (ESRD) who became hyporesponsive and later unresponsive to EPO-alpha treatment a few months after initiation of hemodialysis. A comprehensive anemia examination was negative while the patient became transfusion dependent. The diagnosis of EPO-alpha-induced PRCA was confirmed by bone marrow biopsy, by undetectable serum EPO levels following the administration of a large dose of EPO-alpha, and by documenting the presence of EPO-neutralizing antibodies. Administration of cyclosporine A in addition to prednisone enabled the patient to become transfusion and EPO independent. This case further documents the possible occurrence of PRCA with EPO-alpha administration in the United States and reaffirms the potential beneficial effect of cyclosporine A.

Positive effect of dietary soy in ESRD patients with systemic inflammation--correlation between blood levels of the soy isoflavones and the acute-phase reactants.

BACKGROUND: Inflammation is commonly associated with malnutrition and cardiovascular disease in end-stage renal failure patients. Anti-inflammatory properties of the isoflavones, a micronutrient component of soy, have been reported in several experimental models and disease conditions, but never in renal failure. We hypothesized that dietary soy isoflavones correct laboratory evidence of systemic inflammation in haemodialysis (HD) patients with underlying high blood levels of C-reactive protein (CRP). METHODS: End-stage renal disease patients on chronic HD, with elevated CRP (>10.0 mg/l) were enrolled in this pilot study. The subjects were double-blind randomly distributed with 2 : 1 ratio to receive isoflavone-containing soy-based nutritional supplements (soy group) or isoflavone-free milk protein (control group) for 8 weeks. Serum isoflavone, inflammatory markers and nutrition markers were assessed at baseline and at the end of the treatment. RESULTS: Thirty-two subjects were enrolled. Fifteen subjects in the soy group and 10 in the control group completed the study; five dropouts were due to acute illness and two due to food intolerance. After intervention, blood isoflavone levels were 5- to 10-fold higher in the soy group than in the control group [e.g. median genistein (25-75th percentile): 337.9 (175.5-1007) nM in the soy group vs 41.4 (22.9-100.4) nM in the control group; P < 0.001]. However, the isoflavone levels ranged widely in the soy group (e.g. genistein: 33-1868 nM) and, depending on the individual compound, four to seven subjects had end-of-treatment levels that were not different from baseline. Variation from baseline of the individual serum isoflavone levels (Delta-isoflavone) and CRP displayed a strong inverse correlation in the soy group (R = -0.599, P < 0.02). In addition, Delta-isoflavone correlated positively with the variation of albumin (R = 0.522, P = 0.05) and insulin-like growth factor-1 (R = 0.518, P < 0.05). Group levels of CRP were not statistically different after intervention although a trend towards lower levels was noted in the soy group [18.2 (12.7-29.1) mg/l at baseline vs 9.7 (5.2-20.7) mg/l at week 8; NS] but not in the control group [20.6 (9.2-38.5) vs 17.6 (9.1-40.7) mg/l]. CONCLUSION: These data suggest the possibility of beneficial effects of isoflavone-rich soy foods on the inflammatory and nutritional status of HD patients with underlying systemic inflammation.

Bone biopsy: indications, techniques, and complications.

Bone biopsy is the gold standard for diagnosing the type and severity of renal osteodystrophy (ROD) in end-stage renal disease (ESRD) patients. In this article we review the indications, techniques, and complications of this minimally invasive procedure. The importance of careful preparation is emphasized.

Differences in bone turnover and intact PTH levels between African American and Caucasian patients with end-stage renal disease.

BACKGROUND: Evidence derived from healthy subjects suggests that African Americans have higher serum parathyroid hormone (PTH) levels and decreased bone responsiveness to PTH than Caucasians. African American patients with end-stage renal disease (ESRD) also have higher serum PTH than Caucasians. Studies that correlate intact PTH (iPTH) levels with bone turnover in ESRD patients were performed in a predominantly Caucasian population. METHODS: In this study, serum iPTH and bone histomorphometric data were analyzed for racial differences in 76 ESRD patients (Caucasian = 48, African Americans = 28). Bone turnover was determined by histomorphometric measurement of activation frequency in all patients. RESULTS: Age, duration of dialysis, and calcium and phosphorus levels were similar between the two groups. iPTH levels (pg/mL; mean +/- SE) were significantly higher in the African American group (534 +/- 79 vs. 270 +/- 46, P < 0.01). Also, alkaline phosphatase levels (IU/L) were significantly higher in the African American group (162 +/- 31 vs. 144 +/- 43, P < 0.01). Correlations between PTH levels and activation frequency were r = 0.60, P < 0.01 in Caucasians and r = 0.22, P = NS in African Americans. The mean PTH level in African American patients with histologic findings of low bone turnover was 460 +/- 115 vs. 168 +/- 41 in Caucasian patients with similar bone turnover (P < 0.01). In patients with low bone turnover, African Americans had significantly higher osteoid volume and thickness, number of osteoblasts and osteoclasts, erosion surface, peritrabecular fibrosis, and single-label surface than Caucasians. However, erosion depth, bone formation rate per osteoblast and mineralization apposition rate were similar between the two groups. CONCLUSION: There is no correlation between iPTH and bone turnover in African Americans with ESRD. A substantial number of African American patients with low bone turnover have very high serum PTH levels. Bone histomorphometric results reveal differences in remodeling dynamics and responses to PTH between African American and Caucasian patients. Further studies utilizing newer PTH measurement assays are needed to better delineate the correlation between PTH and bone turnover in the various racial groups.