Patiromer utilization in patients with advanced chronic kidney disease under nephrology care in Germany.

Background: Hyperkalemia (HK) is a frequent condition in patients with chronic kidney disease (CKD) that is associated with high morbidity and mortality. Patiromer has recently been introduced as a potassium binder. Data on patiromer use in patients with CKD in the real-world setting in Europe are lacking. We describe time to discontinuation and changes in serum potassium levels among German CKD stage 3-5 patients starting patiromer. Methods: Duration of patiromer use was estimated by Kaplan-Meier curve, starting at patiromer initiation and censoring for death, dialysis, transplant or loss to follow-up. Serum potassium levels and renin-angiotensin-aldosterone system inhibitor (RAASi) use are described at baseline and during follow-up, restricted to patients remaining on patiromer. Results: We identified 140 patiromer users within our analysis sample [81% CKD stage 4/5, 83% receiving RAASi, and median K+ 5.7 (5.4, 6.3) mmol/L]. Thirty percent of patiromer users had prior history of polystyrene sulfonate use. Overall, 95% of patiromer users stayed on treatment past 1 month, with 53% continuing for over a year. Mean serum potassium levels decreased after patiromer initiation and remained stable under treatment during follow-up (up to 180 days). Among these patients, 73%-82% used RAASis during the time periods before and after patiromer initiation, with no obvious trend indicating discontinuation. Conclusion: Real-world evidence of patiromer use in Germany shows that, in line with what has been observed in clinical trials, patients on patiromer have a reduction in serum potassium when used long-term. Moreover, most patients on patiromer do not discontinue treatment prior to 1 year after initiation.

Economic burden of secondary hyperparathyroidism in Germany: a matched comparison.

PURPOSE: Secondary hyperparathyroidism (SHPT) of renal origin is a progressive complication in chronic kidney disease (CKD) and is associated with serious osseous and non-osseous complications, CKD progression, and economic burden for healthcare systems worldwide. We aimed at assessing characteristics, healthcare resource utilization, and costs of incident SHPT patients in CKD stage 3 (CKD3) and 4 (CKD4), using administrative claims data. METHODS: German claims data were used to identify CKD3 and CKD4 patients, who were stratified by the occurrence of incident SHPT. Patients with SHPT were matched 1:1 to non-SHPT patients with the same CKD stage using propensity scores. Matched groups were compared during a 2-year follow-up period. RESULTS: Overall, 1156 CKD3 and 517 CKD4 incident SHPT patients and their respective matches were identified. Mean number of all-cause hospitalizations were significantly higher among SHPT patients (2.7 vs. 2.0 in CKD3, 2.8 vs. 1.5 in CKD4) during follow-up. Similarly, the mean number of outpatient encounters was significantly higher among the SHPT cohorts (95.0 vs. 64.3 in CKD3, 101.4 vs. 49.8 in CKD4). SHPT patients progressed to CKD5 more often (6.1% vs. 1.2% from CKD3, 26.7% vs. 2.9% from CKD4, both P < 0.01) resulting in a higher proportion of dialysis (6.1% vs. 1.3% in CKD3, 22.1% vs. 3.7% in CKD4, both P < 0.01). Consequently, average all-cause healthcare costs significantly increased per patient (€19,477 vs. €15,115 in CKD3, €25,921 vs. €12,265 in CKD4). CONCLUSIONS: Patients with CKD3&4 and incident SHPT of renal origin presented with significantly higher healthcare resource utilization and costs, as well as increased disease progression compared to non-SHPT patients.

Cyclosporine A-Induced Conchal Hyperplasia with Nasal Obstruction in a Patient with Membranous Nephropathy.

BACKGROUND The immunomodulatory and pharmacokinetic effects of cyclosporine A are used to treat diverse disease entities in different medical fields, including organ transplantation and/or autoimmune diseases. It is also applied in patients with nephrotic range proteinuria as an adjunct to steroids and supportive antihypertensive/antiproteinuric medications. Cyclosporine has a small therapeutic window and is dosed with respect to the underlying disease entity and severity via trough level adaptations. Among its most frequent adverse effects are hypertension, nephrotoxicity, neurotoxicity, and electrolyte disturbances. Hypertrichosis and gingival hyperplasia are obvious and widely recognized adverse effects. CASE REPORT We report on a 66-year-old woman who was treated with cyclosporine A for primary membranous nephropathy. During treatment with cyclosporine, she developed hirsutism and gingival hyperplasia. Later, she reported having impaired nasal breathing and dyspnea on mild physical exercise. Clinical, rhinoscopic, and radiological evaluations showed marked conchal hyperplasia as a potential cause of her symptoms. An extensive medical work-up did not show evidence of allergic, immunologic, or other drug adverse effects, suggesting cyclosporine-induced hyperplasia of the turbinates as a hypothetical causative factor. Dose reductions did not lead to resolution of symptoms but resulted in increasing proteinuria. Therefore, cyclosporine was stopped, and the patient was treated with rituximab. Thereafter, hirsutism and gingival and conchal hyperplasia gradually regressed over 2-4 months, showing complete resolution of conchal hyperplasia on computed-tomography follow-up after 6 months. CONCLUSIONS Cyclosporine can not only result in gingival hyperplasia but also in hyperplasia of the turbinates leading to impaired nasal breathing and shortness of breath on exertion. An extensive search for many other known causes of conchal swelling is warranted to finally suggest an adverse effect of cyclosporine. Discontinuation of cyclosporine resulted in complete remission of conchal hyperplasia as well as other adverse effects.

Effect of Third and Fourth mRNA-Based Booster Vaccinations on SARS-CoV-2 Neutralizing Antibody Titer Formation, Risk Factors for Non-Response, and Outcome after SARS-CoV-2 Omicron Breakthrough Infections in Patients on Chronic Hemodialysis: A Prospective Multicenter Cohort Study.

The aim of this study is to determine the effect of repeated vaccinations on neutralizing SARS-CoV-2 IgG antibody titers, evaluate risk factors for immunological non-response, and to report breakthrough infections in chronic hemodialysis patients. METHODS: A prospective, multi-center cohort study in 163 chronic hemodialysis patients was conducted. Antibody titers were measured three months after second, third, and fourth (10 pts) booster vaccinations. SARS-CoV-2 neutralizing antibody titers in BAU/mL and % inhibition were divided into three categories (<216, 216-433, >433 and <33, 33-66, and >66%). Somers's test, paired t-test, and univariable and multivariable logistic regression analysis were applied to evaluate differences in antibody levels and search for risk factors for vaccination failure defined as neutralizing titers <50% and/or need for repeated booster vaccinations. Furthermore, we report on a case series to describe characteristics of patients after four vaccinations (n = 10) and breakthrough infections (n = 20). RESULTS: Third dose boosters resulted in higher proportions of patients with neutralizing antibody levels >66% as compared to after the second dose (64.7% after second dose vs. 88.9% after third dose, p = 0.003), as well as in a respective increase in neutralizing titer levels in % from 68 ± 33% to 89 ± 24 (p <0.001). The proportion of patients with IgG-titers below 216 BAU/mL decreased from 38.6 to 10.5% (p ≤ 0.001). Age (p = 0.004, OR 1.066, 95% CI 1.020-1.114) and presence of immunosuppressive medications (p = 0.002, OR 8.267, 95% CI 2.206-30.975) were identified as major risk factors for vaccination failure. Repeated booster vaccinations ≥4 times were effective in 8 out of 10 former low-responders (80%) without any side effects or safety concerns. Breakthrough infections showed a clinically mild course but were associated with prolonged viral shedding on PCR-testing ranging 7-29 (mean 13) days. CONCLUSIONS: Third and fourth mRNA-based booster vaccinations resulted in higher and longer lasting SARS-CoV-2 antibody levels as compared to after two dosages. The presence of immunosuppressive medication and repeat vaccinations are major potentially modifiable measures to increase antibody levels in non-or low-responders. Breakthrough infections with SARS-CoV-2 Omicron were associated with prolonged viral shedding but clinically mild disease courses.

A Rare Cause of Left Shoulder Pain in a Peritoneal Dialysis Patient.

BACKGROUND Non-specific pain of connective tissues and joints is one of the most frequently expressed patient concerns in everyday practice. The most common cause is osteo-degenerative changes in the cartilage and/or joint system. Metastatic calcification is a rare and initially often overlooked cause of persistent, therapy-resistant pain of connective tissues and joint apparatus in end-stage renal disease (ESRD) patients on dialysis therapy. These calcifications are induced by persistent hyperphosphatemia/hyperparathyroidism and can occur in various organs, including joints, tendons, heart valves, soft tissues, and blood vessels. CASE REPORT We report on a 46-year-old male patient with ESRD due to cANCA-associated systemic vasculitis. The patient evolved unfavorably to end-stage renal failure and started continuous ambulatory peritoneal dialysis (CAPD). Four years after initiation of CAPD, the patient reported having painful motion of the left shoulder, and symptomatic physiotherapy and non-steroidal-anti-inflammatory-drugs (NSAIDs) were prescribed. An X-ray examination of the left shoulder showed severe periarticular calcifications. Repeated nutritional counselling was offered, and intensive phosphate-binder therapy was administered, resulting in a reduction in phosphate levels from 2.10 mmol at the time of diagnosis to 1.26 mmol/l 16 months later. Radiological reevaluation showed a near complete resolution of the periarticular calcifications. CONCLUSIONS Metastatic calcifications may arise in ESRD patients despite only moderately elevated blood phosphate levels. Intensive measures to reduce the phosphate load to normal levels should be implemented and can lead to almost complete resolution of ectopic calcifications in affected patients.

Evolution of SARS-CoV-2-Neutralizing Antibodies after Two Standard Dose Vaccinations, Risk Factors for Non-Response and Effect of a Third Dose Booster Vaccination in Non-Responders on Hemodialysis: A Prospective Multi-Centre Cohort Study.

The aim of this investigation was to determine the effect of SARS-Cov-2 vaccination in hemodialysis patients, search for risk factors for non- or low-response, and to measure the effect of a third booster vaccination in non- or low-responders. Methods SARS-CoV-2 IgG antibodies and the virus-neutralizing capacity were measured 4-5 weeks after a full standard vaccination in 95 chronic hemodialysis patients and 60 controls. IgG titers > 30 AU/mL served to classify participants as responders. Multivariable binary logistic regression analysis was used to search for risk factors of reduced vaccination success. Patients with vaccination failure were offered a third booster dosage. Results 82.1% of the patient cohort as compared to 98.3% of the healthy control group were able to mount SARS-CoV-2 titers above 30 AU/mL after two standard vaccine doses. Mean IgG antibody titers were lower in hemodialysis patients than controls (78 ± 35 vs. 90 ± 20 AU/mL, p = 0.002). Multivariable binary logistic regression analysis showed age and immunosuppressive medication as major risk factors for vaccination failure with a decreased probability of successful vaccination of -6.1% (95% CI -1.2 to -10.9) per increase in age of one year and -87.4% (95% CI -98.0 to -21.5) in patients on immunosuppressive therapy (crude odds ratio for vaccination failure for immunosuppressive therapy 6.4). Ten out of 17 patients with non-response to vaccination were offered a third dose. Booster vaccination after the second dose induced an increase in effective antibody titers of >30 AU/mL in seven out of ten patients 4-5 weeks later (70%). Conclusion Standard SARS-CoV-2 vaccination schemes are highly effective in mounting protective neutralizing IgG antibodies in chronic hemodialysis patients. Nevertheless, response to vaccination is diminished as compared to a healthy control group. Major risk factors for vaccination failure are older age and immunosuppressive therapy. In non- or low-responders to standard vaccination a third booster vaccination was able to induce effective antibody titers in about 70% of patients, indicating that a third booster vaccination might be preferable to decreasing immunosuppressive therapy.

Hashimoto's Thyroiditis-Associated Acute Renal Failure and Pitfalls of eGFR Interpretation in Thyroid Diseases.

The authors describe a patient with severe hypothyroidism due to Hashimoto's thyroiditis and describe the pitfalls of estimated glomerular filtration rate interpretation in such cases. LEARNING POINTS: Manifest hypothyroidism can lead to a functional reduction in glomerular filtration rates (GFRs).Restoration of a normal thyroid stimulating hormone (TSH) will also restore kidney function.Cystatin C-based GFR formulas will overestimate renal filtration rates in cases of hypothyroidism and underestimate GFRs in cases of hyperthyroidism.

Effect of recipient-donor sex and weight mismatch on graft survival after deceased donor renal transplantation.

This study evaluated the combined effect of recipient-to-donor weight and sex mismatch after deceased-donor renal transplantation in a German transplant cohort and the evolution of recipient-to-donor weight difference over a 13-year observation period. The association of absolute weight and sex difference with graft failure was explored in an outpatient cohort of deceased-donor transplant recipients who underwent kidney transplantation between 2000 and 2012. Graft failure was defined as repeated need for dialysis or death with a functioning graft. Recipient and donor sex pairings were classified as sex concordant (MDMR/FDFR) or discordant (MDFR/FDMR). These classes were further stratified into four groups according to recipient-to-donor weight mismatch ≥10 kg (recipient > donor) or <10 kg (recipient < donor). Multivariable Cox proportional hazards models were applied to evaluate the time to graft loss adjusting for donor, immunologic, surgical, organizational, and recipient predictors. Sex-concordant transplant pairings <10 kg weight difference served as the reference group. Among 826 transplant recipients, 154 developed graft failure (18.6%). Median graft survival time was 3.9 years; first quartile (0.2-1.2), second quartile (1.2-2.9), third quartile (2.9-5.8), and fourth quartile (5.8-12.4). After multivariable adjustment, the highest relative hazard for graft failure was observed for sex-discordant transplant pairings with a ≥10 kg weight difference between recipient and donor (compared to the reference group MDMR/FDFR with weight difference <10 kg, MDMR/FDFR with weight difference ≥10 kg, hazard ratio 1.86, 95% confidence interval 1.07-3.32-p = 0.029; MDFR/FDMR with weight difference <10 kg, hazard ratio 1.14, 95% confidence interval 0.78-1.68-p = 0.507, and MDFR/FDMR with weight difference ≥10 kg, hazard ratio 2.00, 95% confidence interval 1.15-3.48-p = 0.014). A recipient-to-donor weight mismatch of ≥10 kg was associated with an increased risk of graft loss or recipient death with a functioning graft. Concurrent sex discordance seemed to enhance this effect as indicated by an increase in the hazard ratio. We detected no significant tendency for increasing recipient-to-donor weight differences from 2000 to 2012.

[Digital Nephrology]. / Digitale Nephrologie.

Clinical Nephrology faces considerable structural challenges. Digitization can be a critical catalyst to better address the needs of patients and their healthcare providers with new system solutions. Improved communication is the key driver. Through health-related mobile applications, big data and machine learning, as well as natural language processing, treatment processes can be rethought and redesigned.

HbA1c levels at 90 days after renal transplantation in non-diabetic recipients predict de novo pre-diabetes and diabetes at 1 and 3 years after transplantation.

PURPOSE: Pre-diabetes, a risk factor for post-transplant diabetes mellitus (PTDM), represents an early therapeutic target for prevention of PTDM. We evaluated glucose metabolism post-transplantation and the ability to predict pre-diabetes and PTDM from haemoglobin A1c (HbA1c) levels at 90 days, at 1 year, and at 3 years in long-term post-transplantation follow-up. METHODS: HbA1c levels were measured in 71 non-diabetic deceased-donor transplant recipients at four time points (during transplantation, 90-days post-transplantation, 1-year post-transplantion, and at the final post-transplantation follow-up visit 2.71 ± 1.26 years after transplantation). The predictive power of HbA1c levels at 90 days post-transplantation was determined by calculating the sensitivity, specificity, false-positive rates, and false-negative rates. A multivariate logistic regression analysis was performed to determine risk factors for pre-diabetes and PTDM at 1-year post-transplantation and at the last follow-up visit (2.71 ± 1.26 years after renal transplantation). RESULTS: HbA1c values ≥ 5.7% were seen in 79% of patients at 90 days post-transplant, in 83% at 1 year, and in 69% of patients on follow-up. HbA1c cut-off levels of < 5.7% or ≥ 5.7% showed the highest predictive sensitivity for pathological HbA1c levels (≥ 5.7%) at 1 year post-transplantation (0.83) and at last follow-up (0.86), whereas cut-off levels of < 6.2% or .≥ 6.2% showed the highest specificity (0.97 and 1.00, respectively). The HbA1c level at 90 days was a risk factor for disturbed glucose-metabolism at 1 year (p = 0.000) and at the final follow-up (p = 0.031). CONCLUSION: HbA1c levels at 90 days post-transplantation are predictive of disturbed glucose metabolism at 1 year and on long-term follow-up and may serve as predictive tools for early therapeutic interventions to prevent PTDM.

Impact of monocyte-macrophage inhibition by ibandronate on graft function and survival after kidney transplantation: a single-centre follow-up study over 15 years.

BACKGROUND: The aim of this study was to evaluate the effect of ibandronate administration on long-term graft function and graft survival after successful renal transplantation. METHODS: Seventy-two renal transplant recipients (36 patients each in the treatment and control group) were included and followed over a 15-year period. Data on graft function and death-censored transplant outcome were recorded at 1, 5, 10, and 15 years. RESULTS: Death-censored Kaplan-Meier analysis showed significantly improved graft survival of the treatment group (p = 0.026), whereas Cox regression analysis showed that ibandronate was positively associated with improved transplant survival (p = 0.028, hazard ratio 0.24, 95% confidence interval 0.07-0.86). Although general linear modelling did not indicate that ibandronate had a significant effect on transplant function (calculated using the estimated glomerular filtration rate according to Chronic Kidney Disease Epidemiology Collaboration equation) over the entire 15-year period (p = 0.650), there was a tendency towards improved graft function 1-year post-transplantion (p = 0.056). CONCLUSIONS: Ibandronate treatment within the first year of transplantation resulted in a trend towards better graft function within the first few year post-transplant, and was associated with increased transplant survival at long-term follow-up.

Effect of Prediabetes on Allograft Survival and Evolution of New-Onset Diabetes After Transplant in Deceased-Donor Kidney Transplant Recipients During Long-Term Follow-Up.

OBJECTIVES: This study investigated the effect of prediabetes in long-term deceased-donor renal transplant recipients regarding graft survival, graft function, and evolution of new-onset diabetes after transplant compared with a control group of graft recipients with normal glucose tolerance test results. MATERIALS AND METHODS: This was a follow-up trial of 187 deceased-donor renal transplant recipients. Based on oral glucose tolerance test results, the cohort was divided into groups A and B, comprising individuals with normal glucose metabolism (n = 130, 69.9%) and individuals with prediabetes (n = 56, 30.1%). Data are shown as means ± standard errors. RESULTS: Both groups showed similar total transplant survival (116.8 ± 5.4 vs 114.5 ± 7.4 mo; P = .742) and transplant survival measured since oral glucose tolerance test (58.5 ± 1.4 vs 59.5 ± 1.9 mo; P = .990, Mantel-Cox P = .943). Univariate and multivariate Cox regression analyses showed no association of prediabetes with graft loss. Transplant function changes were similar between cohorts (-3 ± 1 vs -5 ± 2 mL/min/1.73 m2 body surface area, using the Chronic Kidney Disease Epidemiology Collaboration formula; P = .538). At 5-year follow-up, recipients with prediabetes had higher hemoglobin A1c than controls (5.99% ± 0.10% vs 5.67% ± 0.04%; P = .002). Prediabetes was associated with a 4.5-fold increased hazard of new-onset diabetes after transplant (P = .021). CONCLUSIONS: Prediabetes was associated with a 4.5-fold higher hazard ratio for new-onset diabetes after transplant but not with reduced graft function or survival.

Long-Term Effect of Renal Transplantation and Aging on Hemoglobin A1C Levels: A Case-Control Study in 191 Non-Diabetic Deceased Donor Renal Transplant Recipients.

BACKGROUND: Reduced renal function in patients with chronic kidney disease is linked to insulin resistance; and impairments in glucose homeostasis, as measured by HbA1c levels, are related to cardiovascular events. Recently, aging has been reported to affect HbA1c levels over time in non-diabetic individuals. The objective of this study was to investigate the association between renal function and aging in non-diabetic deceased-donor renal transplant recipients. MATERIAL AND METHODS: A total of 191 patients were analyzed (mean age 50.6±12.2 years, dialysis vintage 6.5±3.1 years, 53.4% male patients). HbA1-c levels were measured on the day of transplantation and on follow-up. The mean follow-up time was 4.9±3.1 years. RESULTS: Renal transplantation resulted in an increase in eGFR of 38.6±18.9 mL/min/1.73 m2 as compared to baseline levels on dialysis and the mean eGFR on follow-up was 45.5±18.9 mL/min/1.73 m2. HbA1c levels increased significantly from the day of transplantation to the last follow-up (5.3±0.4% to 5.6±0.4%, p<0.0001). Correlation analysis demonstrated non-significant associations between the change in HbA1c levels and the parameters of age and renal transplant function. CONCLUSIONS: In conclusion, we observed a significant increase in HbA1c levels over a 5-year post-transplant follow-up period in non-diabetic deceased-donor renal transplant recipients. In contrast to the non-diabetic general population, the increase in HbA1c observed in this cohort was greater but not associated with aging.

Effects of Different 1-34 Parathyroid Hormone Dosages on Fibroblast Growth Factor-23 Secretion in Human Bone Marrow Cells following Osteogenic Differentiation.

The importance of fibroblast growth factor (FGF)-23 as part of a hormonal bone-kidney-axis has been well established. Lately, FGF-23 has been suggested as an independent risk factor of death in patients on chronic hemodialysis. Hyperparathyroidism is a common feature of advanced kidney failure or end-stage renal disease. The independent effect of elevated parathyroid hormone (PTH) levels on FGF-23 secretion is still a matter of debate and has not yet been studied in an in vitro model of human bone marrow cells (BMC) during osteogenic differentiation. BMC from three different donors were cultivated for 4 weeks in cell cultures devoid of vitamin D either without 1-34 PTH or with PTH concentrations of 10 or 100 pmol/L, respectively. After 28 days, protein expression of the cells was determined by immunocytochemical staining, whereas real time-polymerase chain reaction served to analyze gene expression of several osteoblastic (osteocalcin, RANKL, Runx-2 and ostase) and osteoclastic markers (RANK, TRAP-5b). The concentrations of FGF-23, ostase and TRAP-5b were determined by ELISA at weeks 2, 3 and 4. We found a basal expression of FGF-23 with no increase in FGF-23 secretion after stimulation with 10 pmol/L 1-34 PTH. Stimulation with 100 pmol/L PTH resulted in an increase in FGF-23 expression (14.1±3.6 pg/mL with no PTH, 13.7±4.0 pg/mL with 10 pmol/L, P=0.84 and 17.6±3.4 pg/mL with 100 pmol/L, P=0.047). These results suggest a vitamin D and PTH-independent FGF-23 expression in human BMC after osteogenic stimulation. As only higher PTH levels stimulated FGF-23 expression, a threshold level might be hypothesized.

Vitamin D and cinacalcet administration pre-transplantation predict hypercalcaemic hyperparathyroidism post-transplantation: a case-control study of 355 deceased-donor renal transplant recipients over 3 years.

BACKGROUND: The effects of pre-transplantation medication for secondary hyperparathyroidism on post-transplantation parathyroid hormone (PTH) and calcium levels have not yet been conclusively determined. Therefore, this study sought to determine the level of off-label use of cinacalcet and to determine predictors of its administration during the long-term follow-up of a cohort of individuals who received deceased-donor renal transplants. Furthermore, safety considerations concerning the off-label use of cinacalcet are addressed. METHODS: This was a case-control study of 355 stable renal transplant recipients. The patient cohort was divided into two groups. Transplant group A comprised patients who did not receive cinacalcet treatment, and transplant group B comprised patients who received cinacalcet treatment during follow-up after renal transplantation. The characteristics of the patients were evaluated to determine predictors of cinacalcet use after successful renal transplantation. RESULTS: Compared with the control individuals (n = 300), the cinacalcet-treated individuals (n = 55) had significantly higher PTH levels at 4 weeks post-transplantation (20.3 ± 1.6 versus 40.7 ± 4.0 pmol/L, p = 0.0000) when they were drug naive. At 3.2 years post-transplantation, cinacalcet-treated patients showed higher PTH (26.2 ± 2.3 versus 18.4 ± 2.3 pmol/L, p = 0.0000), higher calcium (2.42 ± 0.03 versus 2.33 ± 0.01 mmol/L, p = 0.0045) and lower phosphate (0.95 ± 0.04 versus 1.06 ± 0.17 mmol/L, p = 0.0021) levels. Individuals in the verum group were more likely to receive cinacalcet therapy (45.5% versus 14.3%, p = 0.0000), and they had higher pill burdens for the treatment of hyperparathyroidism (1.40 ± 0.08 versus 0.72 ± 0.03 pills per patient, p = 0.0000) whilst they were on the waiting list for transplantation. Regression analysis confirmed the associations between hypercalcaemic hyperparathyroidism and PTH levels at 4 weeks post-transplantation (p = 0.0001), cinacalcet use (p = 0.0000) and the preoperative total pill burden (p = 0.0000). Renal function was the same in both groups. CONCLUSIONS: Parathyroid gland dysfunction pre-transplantation translates into clinically relevant hyperparathyroidism post-transplantation, despite patients being administered more intensive treatment whilst on dialysis. PTH levels at 4 weeks post-transplantation might serve as a marker for the occurrence of hypercalcaemic hyperparathyroidism during follow-up.

Prevalence and risk factors of pre-diabetes after renal transplantation: a single-centre cohort study in 200 consecutive patients.

BACKGROUND: After renal transplantation, patients are prone to develop impairments in glucose metabolism. In 2005, the American Diabetes Association published new guidelines on the diagnosis of pre-diabetes [plasma glucose levels from 100 to 125 mg/dL fasting or from 140 to 199 mg/dL 2 h after an oral glucose tolerance test (OGTT)]. This study sought to evaluate the prevalence and the potentially associated factors of pre-diabetes in a cohort of renal transplant patients on maintenance immunosuppressive medication. Furthermore, the diagnostic value of HbA1-c measurements in predicting pre-diabetes in transplant patients is undetermined. METHODS: Two hundred consecutive renal transplant patients of our outpatient transplant clinic were evaluated using a standard OGTT. On the day of testing, multiple factors presumably associated with pre-diabetes were assessed via a standardized questionnaire: daily steroid dosage, triglyceride levels, cholesterol levels, estimated glomerular filtration rate (eGFR) [abbreviated Modification of Diet in Renal Disease (MDRD) formula], systolic and diastolic blood pressure, pulse pressure, age, gender, body mass index (BMI), BMI <>30 and <>25, number of renal transplants, number of rejection episodes prior to testing, source of renal transplant, cause of renal failure and medications as related to the prescription of cyclosporine, tacrolimus, mycophenolate mophetil, angiotensin-converting enzyme inhibitors, AT1-blockers, statins, ß-blockers and thiazide diuretics. Patients diagnosed with pre-diabetes were compared to subjects with normal test results. Fishers exact test and the Wilcoxon rank-sum test were applied to compare the two study populations, whereas multivariate logistic regression was used to seek potential risk factors as related to other covariates. Risk ratios (RRs) to develop pre-diabetes were calculated for significant variables. RESULTS: Ten patients had results indicative of post-transplant diabetes whereas data sets of three other patients were incomplete and were thus not included in the analysis. From the remaining 187 patients, 130 (69.5%) displayed normal test results whereas 57 (30.5%) had results indicative of pre-diabetes. On multivariate regression analysis, patients with pre-diabetes were significantly older {55.3 ± 12.1 versus 47.7 ± 12.6 years, P = 0.0007, RRs per 5 years increase 1.28 [95% confidence interval (95% CI) 1.11-1.47]}, had more rejection episodes [0.26 ± 0.48 versus 0.12 ± 0.37, P = 0.0024, RRs per rejection episode 3.99 (95% CI 1.63-9.77)] and showed lower diastolic blood pressure readings [77 ± 10 mmHg versus 81 ± 10 mmHg, P = 0.0362, RR per 5 mmHg decrease 1.14 (95% CI 1.04-1.49)]. CONCLUSIONS: There is a high incidence of latent pre-diabetes among renal transplant recipients. Increasing age, rejection episodes and lower diastolic blood pressure proved to be associated with pre-diabetes. In contrast to post-transplant diabetes, tacrolimus use and HbA1-c levels were not prognostic of pre-diabetes.

Rationale for prostaglandin I2 in bone marrow oedema--from theory to application.

INTRODUCTION: Bone marrow oedema (BME) and avascular osteonecrosis (AVN) are disorders of unclear origin. Although there are numerous operative and non-operative treatments for AVN, pain management in patients with AVN remains challenging. Prostaglandins play an important role in inflammatory responses and cell differentiation. It is thought that prostaglandin I2 ([PGI2] or synonoma prostacyclin) and its analogues promote bone regeneration on a cellular or systemic level. The purpose of this study was to assess the curative and symptomatic efficacy of the prostacyclin analogue iloprost in BME and AVN patients. METHOD: We are reporting on 50 patients (117 bones) affected by BME/AVN who were treated with iloprost. Pain levels before, during and 3 and 6 months after iloprost application were evaluated by a visual analogue scale (VAS). The short form(SF)-36 health survey served to judge general health status before and after treatment. Harris Hip Score (HHS) and Knee Society Score (KSS) were performed as functional scores and MRI and X-rays before and 3 and 6 months after iloprost application served as objective parameters for morphological changes of the affected bones. RESULTS: We found a significant improvement in pain, functional and radiological outcome in BME and early AVN stages after iloprost application, whereas patients with advanced AVN stages did not benefit from iloprost infusions. Mean pain level decreased from 5.26 (day 0) to 1.63 (6 months) and both HHS and KSS increased during follow-up. Moreover, the SF-36 increased from 353.2 (day 0) to 560.5 points (6 months). We found a significant decrease in BME on MRI scans after iloprost application. CONCLUSIONS: In addition to other drugs, iloprost may be an alternative substance which should be considered in the treatment of BME/AVN-associated pain.

Post-transplant distal limb syndrome: clinical diagnosis and long-term outcome in 37 renal transplant recipients.

After the introduction of steroid sparing immunosuppressive protocols, osteonecrosis of the hip has become a rare entity in renal transplantation. Instead, an elusive bilateral pain syndrome of the distal extremities has gained more clinical attention. Because of the typical presentation, it is sometimes referred to as 'post-transplant distal limb syndrome' (PTDLS). The syndrome typically manifests during the first year after transplantation and may lead to significant morbidity because of pain induced immobilization. On MRI-scans, a characteristic bilateral patchy osteoedema can be demonstrated. The etiology of PTDLS has not been determined definitely so far. Over the last 8 years, we have seen the syndrome in 37 out of 639 renal transplant patients (5.8%). There was no association to steroid-medication, age, gender, PTH levels or delayed graft function. As an important finding, we saw a significant rise in alkaline phosphatase from 160 +/- 54 to 271 +/- 108 U/l (P = 0.001) and calcium from 2.46 +/- 0.18 to 2.58 +/- 0.18 mmol/l (P = 0.013) preceding the onset of pain by several weeks. Mean duration of clinical symptoms was 5.1 +/- 3.1 months; however, all patients experienced remission without signs of chronic damage on long-term follow up.