Does Surgeon Volume Impact Morbidity Following Parathyroidectomy? A Study of 16,140 Parathyroidectomies from the UK Registry of Endocrine and Thyroid Surgery (UKRETS) Database.

BACKGROUND: Outcomes in endocrine surgery have been shown to improve with surgeon volume. We aimed to study the effect of surgeon volume on morbidity following parathyroidectomy. METHODS: UKRETS data from 2004 to 2019 was studied. Parathyroidectomies for primary hyperparathyroidism with complete data were included. Exclusion criteria were age <18 or >80 years; surgeons contributing <10 cases overall; and length of stay >28 days. Multivariable analysis was performed. Primary outcome was persistent hypercalcaemia; secondary outcomes were haemorrhage, length of stay, need for re-admission, post-operative hypocalcaemia, and need for calcium/vitamin D supplements to maintain eucalcaemia at 6 months. RESULTS: 153 surgeons undertook mean 22.5 (median 17, range 2-115) parathyroidectomies/year. Persistent hypercalcaemia affected 4.8% (776/16140) overall; 5.7% (71/1242) in surgeons undertaking < 10 cases/year; 5.1% (3339/6617) for 10-30 cases/year; 5.0% (270/5397) for 30-50 cases; and 3.3% (96/2884) for >50 cases/year. High-volume (>50 parathyroidectomies/year) surgeons operated 23.4% (809/3464) of negative localisation cases compared to 16.4% (2074/12676) of positive localisation cases. Persistent hypercalcaemia was almost twice as common in image negative (7.9%) compared to image-positive (4%) cases. Persistent hypercalcaemia was significantly more likely to occur in the low volume (<10 parathyroidectomies/year) group than high volume (>50 parathyroidectomies/year), regardless of image positivity (p = 0.0006). Surgeon volume significantly reduced persistent hypercalcaemia on multivariable analysis (OR = 0.878, 95%CI 0.842-0.914, p < 0.001), along with age, sex, and positive localisation. BNE and re-operation significantly increased persistent hypercalcaemia. Post-operative hypocalcaemia occurred in 3.2% (509/16040) and was reduced with increasing surgeon volume (OR = 0.951, 95%CI 0.910-0.993, p < 0.001). Haemorrhage and length of stay were not significantly associated with surgeon volume. CONCLUSION: The incidence of persistent hypercalcaemia, post-operative hypocalcaemia, and persistent hypoparathyroidism decreased with increasing surgeon volume. The relative reduction in persistent hypercalcaemia with surgeon volume was similar in image negative and positive groups, but the absolute reduction was higher in image negative cases. Restricting image negative parathyroidectomy to high-volume surgeons could be considered.

Incidence of Post-denosumab Rebound Hypercalcaemia in Bony-Metastatic Breast Cancer.

Denosumab reduces incidence of skeletal related events in patients with bony-metastatic breast cancer, however cessation is associated with a rebound phenomenon which, rarely, has been associated with hypercalcaemia. We aimed to identify the incidence of post-denosumab cessation rebound hypercalcaemia amongst patients with breast cancer-related bony metastases. We performed a single-centre retrospective cohort analysis to determine the incident of rebound hypercalcaemia amongst patients treated with antiresorptive agents for bony metastatic breast cancer between 2016-2020. 22,320 outpatient encounters were reviewed, which identified 97 patients with bonymetastatic disease treated with antiresorptive therapy. Of the 21 patients who had denosumab ceased, six (28.6%) developed hypercalcaemia. Interval between last denosumab dose and onset of hypercalcaemia was a median 7.5 (range 2-13) months. There was a significant difference in both denosumab treatment duration as well as total treatment dose exposure between patients who developed hypercalcaemia post-denosumab cessation (median 41 months, 40 doses) and those who remained normocalcaemic (median 10 months, 5 doses), p = 0.009. In our study, hypercalcaemia occurred between two and thirteen months after denosumab cessation. Greater denosumab treatment duration as well as total denosumab dose exposure was associated with higher risk of hypercalcaemia after denosumab cessation. Hormonal therapy or previous bisphosphonate treatment was not seen to impact upon development of hypercalcaemia. Rebound hypercalcaemia is a rare but important diagnosis to consider in patients experiencing hypercalcaemia after denosumab cessation.

Independent effects of secondary hyperparathyroidism and hyperphosphataemia on chronic kidney disease progression and cardiovascular events: an analysis from the NEFRONA cohort.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is a complication of chronic kidney disease (CKD) and is associated with changes in calcium and phosphate. These related changes have been associated with increased cardiovascular mortality and CKD progression. It is not clear whether negative outcomes linked to SHPT are confounded by such factors. The present study was designed to assess the possible independent effects of SHPT [defined as patients with excessive parathyroid hormone (PTH) levels or on treatment with PTH-reducing agents] on the risk of CKD progression and cardiovascular event (CVE) incidence in CKD patients, as well as whether hypercalcaemia and/or hyperphosphataemia act as effect modifiers. METHODS: The study enrolled 2445 CKD patients without previous CVE from the National Observatory of Atherosclerosis in Nephrology (NEFRONA) cohort (Stage 3, 950; Stage 4, 612; Stage 5, 195; on dialysis, 688). Multivariate logistic and Fine and Gray regression analysis were used to determine the risk of patients suffering CKD progression or a CVE. RESULTS: The prevalence of SHPT in the cohort was 65.6% (CKD Stage 3, 54.7%; CKD Stage 4, 74.7%; CKD Stage 5, 71.4%; on dialysis, 68.6%). After 2 years, 301 patients presented CKD progression. During 4 years of follow-up, 203 CVEs were registered. Patients with SHPT showed a higher adjusted risk for CKD progression and CVE. Furthermore, hyperphosphataemia was shown to be an independent risk factor in both outcomes and did not modify SHPT effect. No significant interactions were detected between the presence of SHPT and hypercalcaemia or hyperphosphataemia. CONCLUSIONS: We conclude that SHPT and hyperphosphataemia are independently associated with CKD progression and the incidence of CVE in CKD patients.

Predictors of Mortality in Hypercalcemia of Advanced Chronic Liver Disease.

OBJECTIVE: Hypercalcemia is sometimes observed in patients with cirrhosis, but very little is known about the epidemiology in patients with hypercalcemia of chronic liver disease (HCLD) or how its presence may modulate the overall mortality risk. We assessed the associations between the clinical and laboratory characteristics of patients with HCLD with 90-day mortality. METHODS: A systematic search of the medical records at our institution over a 10-year period was performed to retrospectively identify subjects with HCLD during inpatient admission. Univariate and multivariable regression analyses were performed to detect the risk factors for all-cause 90-day mortality. RESULTS: Thirty-eight subjects with HCLD were identified using stringent inclusion and exclusion criteria to exclude individuals with other secondary causes of hypercalcemia. A total of 35 subjects had 90-day vital status available, which revealed 40% mortality. The model for end-stage liver disease sodium score and duration of inpatient hypercalcemia were positively associated with mortality with respective odds ratios of 1.23 (95% CI, 1.06-3.23) and 1.24 (95% CI, 1.04-1.49) in a univariate regression model and 1.30 (95% CI, 1.04-1.62) and 1.33 (95% CI, 1.04-1.71) in a multivariable regression model. The admission and peak serum calcium levels were not associated with mortality. Only 6 subjects received bisphosphonates or calcitonin during their admission, limiting our ability to assess the impact of treatment on outcomes. CONCLUSION: In patients admitted to the hospital with HCLD, the duration of hypercalcemia was positively associated with 90-day mortality, providing a potential interventional target to reduce mortality in this high-risk population. Studies to validate the utility of treating hypercalcemia are required.

Prevalence, causes and associated mortality of hypercalcaemia in modern hospital care.

BACKGROUND: Studies examining hypercalcaemia in inpatients were largely published over 20 years ago, and it is likely the epidemiology of hypercalcaemia has changed related to increased lifespan and changes in the prevalence of the underlying causes such as malignancy. AIM: To explore the epidemiology of hypercalcaemia in a modern tertiary hospital setting in Australia and evaluate the risk of mortality associated with hypercalcaemia. METHODS: A retrospective study was performed in all inpatients with elevated blood calcium levels admitted from July 2013 to June 2018. ICD coding data identified primary diagnoses and mortality. Electronic medical records were reviewed in n = 292 patients admitted across 12 months from January to December 2017, to determine the causes of hypercalcaemia. RESULTS: Hypercalcaemia occurred in 1819 admissions (0.93% of all hospital admissions), during the 5-year period. The admission primary diagnoses were: malignancy (20% of cases), cardiovascular disease (17%) and gastrointestinal disease (11%). The top causes of hypercalcaemia among the 292 cases where electronic records were reviewed were malignancy (26%), primary hyperparathyroidism (25%) and hyperparathyroidism in the setting of chronic kidney disease (12%). Mortality occurred in 17% of these admissions. Non-survivors had significantly higher calcium levels, phosphate and white cell count, and had lower haemoglobin and albumin levels. CONCLUSION: Hypercalcaemia occurred in ~1% of admissions with main causes being malignancy and primary hyperparathyroidism, similar to historical studies. Hypercalcaemia in hospitalised patients is associated with high mortality and higher levels may be a marker for more severe underlying disease.

Severe hypercalcemia requiring acute hemodialysis: A retrospective cohort study with increased incidence during the Covid-19 pandemic.

BACKGROUND: The Covid-19 pandemic has had dramatic consequences on the progression of numerous pathologies, especially neoplastic ones. The orientation of hospital activities toward the care of patients with SARS-Cov2 infection has caused significant delays in the diagnosis and therapy of many other pathologies. What about severe hypercalcemia? The aim of this work was to determine the clinical and biological presentation, etiologies, mortality, and the impact of the Covid-19 pandemic on severe hypercalcemia. MATERIAL AND METHODS: we conducted a retrospective study for 84 months (September 2014 to September 2021) at the Nephrology Unit in University Hospital Mohammed VI, Oujda, Morocco. Included were all adult patients diagnosed with severe hypercalcemia (defined as corrected total serum calcium of >3.5 mmol/l or > 14.0 mg/dl) and who had benefited from one or more hemodialysis sessions. RESULTS: 66 episodes of severe hypercalcemia occurred in 64 patients. The mean age was 57 ± 15 years and 57.6% were female. The mean corrected serum calcium at admission was 16.9 ± 2.1 mg/dl and 33.3% had more than 18.0 mg/dl. Malignancies represented 80.4% of all etiologies. Acute kidney injury was observed in 69.7%. The delta drop in serum calcium 48 h after initiation of medical treatment was 4.64 ± 1.63 mg /dl. Mortality was noted in 14% of all cases. Electrocardiographic abnormalities were observed in 58.3%, 87.5% and 85.7%, respectively, in group 1 (14.0-16.0 mg/dl), group 2 (16.1-18.0 mg/dl), and group 3 (> 18.0 mg/dl) (p = 0.04). The mean serum potassium value was 5.1 ± 1.3, 4.0 ± 1.0, and 3.7 ± 0.7 respectively, in group 1 (14.0-16.0 mg/dl), group 2 (16.1-18.0 mg/dl), and group 3 (> 18.0 mg/dl) (p < 0.001). Newly diagnosed neoplasia, severe hypercalcemia (> 16.0 mg/dl), and mortality have been observed in 15.4% vs. 23.7% (p = 0.31), 25% vs. 50% (p = 0.03), and 35.7% vs. 52.6% (p = 0.13) respectively, in patients before and during the Covid-19 pandemic. CONCLUSIONS: The Covid-19 pandemic caused an increase in both the incidence and severity of hypercalcemia and the hemodialysis practiced in this context remains efficient and safe.

Plasma Ionized Calcium and Risk of Cardiovascular Disease: 106 774 Individuals from the Copenhagen General Population Study.

BACKGROUND: Circulating total calcium or albumin-adjusted calcium is a risk factor for cardiovascular disease. As the biologically active ionized calcium is a physiologically more relevant measure and its association with cardiovascular disease is poorly understood, we tested the hypothesis that high plasma ionized calcium is associated with higher risk of myocardial infarction and ischemic stroke in individuals in the general population. METHODS: We included 106 774 individuals from the Copenhagen General Population Study, and defined hypocalcemia and hypercalcemia by the lowest and highest 2.5 percentiles, respectively, using the central 95% reference interval. Information on myocardial infarction and ischemic stroke was from registries and risks calculated using Cox regression and Fine and Gray competing-risks regression. RESULTS: During a median follow-up of 9.2 years, 4932 individuals received a diagnosis of either myocardial infarction or ischemic stroke. Hypercalcemia was associated with subdistribution hazard ratios of 1.67 (95%CI: 1.05-2.67) for myocardial infarction, 1.28 (0.81-2.02) for ischemic stroke, and of 1.54 (1.10-2.15) for the combined endpoint compared to individuals with plasma ionized calcium within the reference interval; hypocalcemia was not associated with cardiovascular disease. In models using plasma ionized calcium as a continuous variable, the associations were nonlinear; above the median, each 0.1 mmol/L higher plasma ionized calcium was associated with a hazard ratio of 1.31(1.02-1.68) for myocardial infarction, 1.21 (0.95-1.54) for ischemic stroke, and of 1.28 (1.08-1.53) for the combined endpoint. CONCLUSIONS: High plasma ionized calcium is associated with higher risk of myocardial infarction and ischemic stroke compared to plasma ionized calcium within the reference interval.

ECHOCARDIOGRAPHIC FINDINGS IN PATIENTS WITH NORMOCALCEMIC PRIMARY HYPERPARATHYROIDISM COMPARED WITH FINDINGS IN HYPERCALCEMIC PRIMARY HYPERPARATHYROID PATIENTS AND CONTROL SUBJECTS.

OBJECTIVE: There are no data regarding echocardiographic parameters in patients with normocalcemic primary hyperparathyroidism (NCPHPT). We compared the echocardiographic findings in postmenopausal women with NCPHPT with those in patients with hypercalcemic primary hyperparathyroidism (PHPT) and controls. METHODS: Seventeen consecutive Caucasian postmenopausal women with NCPHPT were compared with 20 women with hypercalcemic PHPT and 20 controls. Obesity, diabetes, kidney failure, and previous cardiovascular diseases were considered exclusion criteria. Each patient underwent biochemical evaluation, bone mineral density scan, and echocardiographic measurements. Patients with parathyroid disorders underwent kidney ultrasound evaluation. RESULTS: Patients with PHPT had significantly higher mean total serum calcium, ionized calcium, 24-hour urinary calcium, and parathyroid hormone and lower mean phosphorus levels compared with those in the controls (all P < .05). The only differences between patients with NCPHPT and PHPT were significantly lower mean total serum calcium, ionized calcium, and 24-hour urinary calcium and higher phosphorus levels in patients with NCPHPT (all P < .05). The only biochemical difference between patients with NCPHPT and the controls was a higher level of mean parathyroid hormone in patients with NCPHPT. There were no differences in cardiovascular risk factors between patients with NCPHPT and PHPT and the controls. Hypertension was the most frequent cardiovascular risk factor, diagnosed in 65% of patients with PHPT. This high prevalence was not statistically significant compared with that observed in patients with NCPHPT (59%) and in the controls (30%). Echocardiography parameters were not different between patients with NCPHPT and PHPT and the controls when subdivided according to the presence of hypertension (ANOVA followed by Bonferroni correction). CONCLUSION: In a population with a low cardiovascular risk, we found no differences in cardiovascular risk factors and echocardiographic parameters between patients with NCPHPT and PHPT and the controls.

Misclassification of calcium status in end-stage kidney disease using albumin-adjusted calcium levels.

BACKGROUND: Albumin-adjusted calcium remains widely used in clinical practice with guidelines for chronic kidney disease (CKD) mineral bone disorder recommending the use of serum calcium for monitoring. This is despite ionized calcium being the biologically active fraction. This study aimed to investigate the ability of total calcium and albumin-adjusted calcium to correctly assign calcium status in stage 5/5D CKD across non-dialysis, haemodialysis and peritoneal dialysis patients. METHODS: Over a 6-months, 352 paired serum and ionized calcium samples were collected from stage 5 (n = 58) and 5D (n = 294, 196 haemodialysis, 98 peritoneal dialysis) CKD patients in a tertiary-hospital setting. Albumin-adjusted calcium was calculated using the modified-Payne formula. Ionized calcium was the reference standard. The agreement between the two methods in assigning calcium status was assessed using Cohen's weighted kappa (κ) statistic. RESULTS: Albumin-adjusted calcium was a poor predictor of calcium status compared to ionized calcium in stage 5/5D CKD (observed agreement 0.42, weighted κ 0.20, 95% CI 0.15-0.26). Dialysis dependence was associated with worse agreement (observed agreement 0.38, weighted κ 0.14, 95% CI 0.09-0.19). Total calcium was more reliable, however, remained inaccurate. Calcium status was not more accurately classified in those with higher albumin levels ≥30 g/L (observed agreement 0.47, weighted κ 0.23, 95% CI 0.10-0.36). CONCLUSION: Total calcium provides better approximation of calcium status than albumin-adjusted calcium in stage 5/5D CKD. Albumin-adjusted calcium tends to 'overcorrect' serum calcium upward. Clinicians should use ionized calcium where accurate measure of calcium is indicated, with total calcium used as the next best option where resources are limited.

Hypercalcemia in the nephrology department patients - incidence, etiology and impact on renal function.

Hypercalcemia (HCM) is predominantly caused by primary hyperparathyroidism (PHPT) or malignancy. It's incidence varies from 0.17% to 4.74%. Its numerous manifestations include renal symptoms. AIM: The aim of the study was to assess the incidence and etiology of hypercalcemia in patients hospitalized at the Department of Nephrology of the Warsaw Military Institute, as well as to evaluate its impact on renal function. MATERIALS AND METHODS: In this cross-sectional study patients admitted to the Nephrology Department of the Warsaw Military Institute between January 2017 and December 2018 were retrospectively screened for presence of HCM, defined as total calcium level or corrected calcium level in case of hypoalbuminemia >10.2 mg/dl, measured at least twice. Each patient's medical history as well as other laboratory findings were subsequently analyzed in order to establish the etiology of hypercalcemia. RESULTS: Among 3062 hospitalisations (1993 patients) at The Department, 96 patients had elevated calcium level of which 36 were identified as hypercalcemic (1,81%). Median calcium level was 11.9 mg/dl (IQR: 11.25-13.46) with 22.24 mg/dl being the maximum observed value. Malignancy and drugs having hypercalcemizing effect were the most common etiologies identified, both being found in 9 cases (25%). Other causes of HCM included sarcoidosis, multiple myeloma (analyzed separately from other malignancies), PHPT and hypercalcemic hypocalciuria. In 7 cases HCM etiology could not be established, it therefore remained idiopathic. Acute kidney injury (AKI) developed in 20 patients (56%), in this group serum calcium levels were significantly higher than in non-AKI patients (median: 12.85 mg/dl (IQR:11.82-14.65) vs 11.25 mg/dl (IQR:10.75-11.93); p=0.0039). Additionally, chronic kidney disease (CKD) patients presented significantly lower calcium values than non-CKD patients (median: 11.47 mg/dl (IQR: 10.8-12.6) vs 13.01 mg/dl (IQR:11.9-16.08; p=0.0131). CONCLUSIONS: Hypercalcemia is a rare disorder among Nephrology Department patients, which primary etiology is malignancy and medications having hypercalcemizing effect. Kidney injury is dependent on the severity of hypercalcemia.

Calcium-Alkali Syndrome Associated with Hypoparathyroidism Following Total Thyroidectomy.

BACKGROUND: Patients with permanent postsurgical hypoparathyroidism, a complication of total thyroidectomy, often require high calcium supplementation with vitamin D to maintain serum calcium levels. The epidemiology of calcium-alkali syndrome (CAS) in patients with hypoparathyroidism after total thyroidectomy remains unclear. This study aimed to investigate the incidence of hypercalcemia, renal impairment, metabolic alkalosis, and CAS in patients treated for presumed hypoparathyroidism after total thyroidectomy. METHODS: Twenty-seven patients with neck cancers who underwent total thyroidectomy without parathyroid autotransplantation between January 2010 and October 2013 at our hospital were consecutively included. All patients received calcium lactate and alfacalcidol for postsurgical hypocalcemia. We defined hypercalcemia as a corrected serum calcium level (cCa) ≥10.5 mg/dL, metabolic alkalosis as a difference in serum sodium and serum chloride ([sNa-sCl]) ≥39 mEq/L, and renal impairment as a ≥50% increase in serum creatine and/or ≥35% decrease in estimated glomerular filtration rate (eGFR) compared to baseline. RESULTS: cCa peaked (11.1 ± 1.5 mg/dL) at a median of 326 days (interquartile range 78-869) after surgery. At peak cCa, [sNa-sCl] was significantly higher (p < 0.01), and eGFR was significantly lower (p < 0.01) than that at baseline. Fifteen patients (55.6%) had hypercalcemia, 19 (70.3%) had alkalosis, 12 (44.4%) had renal impairment, and 9 (33.3%) had CAS. Patients with CAS (mean age 67.1 ± 10.8 years) were older than those without CAS (56.7 ± 13.6 years, p = 0.06). The mean dose of alfacalcidol in the CAS group (3.1 ± 1.2 µg/day) was significantly larger than that in the non-CAS group (2.1 ± 1.0 µg/day, p = 0.03). CONCLUSIONS: This retrospective study reveals the high incidence of CAS in patients with hypoparathyroidism after total thyroidectomy. Furthermore, these findings suggest that the serum calcium level, acid-base balance, and renal function should be closely monitored in patients with postsurgical hypoparathyroidism who receive large doses of active vitamin D.

Hypercalcemia at diagnosis of diffuse large B-cell lymphoma is not uncommon and is associated with high-risk features and a short diagnosis-to-treatment interval.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive type of non-Hodgkin lymphoma. The prevalence of hypercalcemia in this neoplasm and its prognostic significance is unclear. We retrospectively evaluated the prevalence of hypercalcemia at diagnosis of DLBCL and explored associations of hypercalcemia with clinical factors and outcome. Outcome was assessed using event-free survival at 24 months (EFS24). A total of 305 patients (248 de novo DLBCL and 57 transformed indolent lymphomas) diagnosed between 2006 and 2018 in Reims were analyzed. The prevalence of calcemia >10.5 mg/dL at diagnosis of de novo DLBCL and transformed indolent lymphomas was 23% and 26%, respectively. Hypercalcemia in de novo DLBCL was strongly associated with high-risk features, especially with International Prognostic Index (IPI) components, but also with B symptoms, ß2-microglobulin, hemoglobin, and albumin levels. The diagnosis-to-treatment interval was significantly shorter for hypercalcemic patients (P = .001). These associations with adverse prognostic factors translated into lower rates of EFS24 (HR = 1.66; 95% CI, 1.08-2.54) and shorter PFS (P = .0059) and OS (P = .0003) for patients with lymphoma-related hypercalcemia but not independently of IPI parameters. These data suggest that hypercalcemia is rather a biomarker of the underlying biological aggressiveness of DLBCL.

Influence of common clinical variables on intraoperative parathyroid hormone monitoring during surgery for primary hyperparathyroidism.

BACKGROUND: Intraoperative monitoring of parathyroid hormone (IOPTH) is a reliable method of predicting the cure of primary hyperparathyroidism (PHPT). The aim of this study is to assess whether common clinical variables (CCV) frequently encountered in patients with PHPT may affect the magnitude of PTH drop or the likelihood of patients meeting the intraoperative cure criterion. DESIGN: Patients who were surgically cured from PHPT caused by single gland disease (SGD) and had full IOPTH protocol (4 measurements) were stratified according to age, gland weight, renal function, vitamin D status and severity of hypercalcemia. The percentage of IOPTH drop and the frequency of patients who had true positive IOPTH test results were compared among groups. RESULTS: 762 patients had surgery for PHPT, of whom 746 were (98%) cured. Of these 746 patients, 511 who had SGD and a full IOPTH protocol were included in this study. The median IOPTH drop was significantly higher among younger patients, those with severe hypercalcaemia at 5, 10, 15 min after gland excision, giant glands (at 5-min only), patients with vitamin D deficiency (at 10, 15 min), and those with normal renal function (at 15 min only). The likelihood of the patients meeting the intraoperative cure criterion was not significantly affected among the groups except in patients with mild hypercalcaemia, who were significantly less likely to have 50% IOPTH drop than those with severe hypercalcaemia at all time points. The frequency of mildly hypercalcaemic patients who met cure criterion was significantly improved by extending measurement to 15 min. CONCLUSIONS: IOPTH monitoring has the ability to mitigate the variability of IOPTH kinetics associated with most clinical variables. Mildly hypercalcemic patients in particular may benefit from waiting for 15-min measurement before any surgical decision is made.

Prevalence of renal dysfunction among HIV infected patients receiving Tenofovir at Mulago: a cross-sectional study.

BACKGROUND: There is an increasing burden of non-communicable disease globally. Tenofovir disoproxil fumarate (TDF) is the most commonly prescribed antiretroviral drug globally. Studies show that patients receiving TDF are more prone to renal dysfunction at some point in time during treatment. Evaluation of kidney function is not routinely done in most HIV public clinics. Identification of renal dysfunction is key in resource constrained settings because managing patients with end stage renal disease is costly. METHOD: This was a cross-sectional study conducted at an outpatient clinic in 2018 involving patients on TDF for at least 6 months who were 18 years or older. Patients with documented kidney disease and pregnancy were excluded. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-Epi formula. Renal dysfunction was defined as any of the following; either eGFR< 60 mL/min/1.73m2,or proteinuria of ≥2+ on urine dipstick, glycosuria with normal blood glucose. Electrolyte abnormalities were also documented. RESULTS: We enrolled 278 participants. One hundred sixty nine (60.8%) were females, majority 234(84.2%) were < 50 years old, 205 (73.74%) were in WHO stage 1, most participants 271(97.5%) in addition to TDF were receiving lamivudine/efavirenz. The median age was 37(IQR 29-45) years; median duration on ART was 36 (IQR 24-60) months. The prevalence of renal dysfunction was 2.52% (7/278). Most noted electrolyte abnormality was hypocalcaemia (15.44%). CONCLUSIONS: The prevalence of renal dysfunction was low though some participants had hypocalcaemia. Screening for kidney disease should be done in symptomatic HIV infected patients on TDF.

Impact of Perinatal Primary Hyperparathyroidism on Maternal and Fetal and Neonatal Outcomes: Retrospective Case Series.

OBJECTIVE: We sought to describe the maternal, fetal, and neonatal outcomes of primary hyperparathyroidism in a contemporary setting through a retrospective case series conducted in a tertiary referral centre focused on women diagnosed with primary hyperparathyroidism prior to conception, in the antepartum period, or within 6 weeks postpartum. METHODS: A retrospective chart review was conducted and data were abstracted to case report forms. Summary statistics are reported. RESULTS: From 2000 to 2017, 19 women (23 pregnancies) with primary hyperparathyroidism were identified. Most women (79%) were symptomatic at presentation, though often with non-specific manifestations. While 14% of pregnancies involved maternal/obstetric complications, fetal/neonatal complications were observed in 45%. Mild hypercalcemia was identified in 57% of women, with accompanying hypophosphatemia and hypomagnesemia in 46% and 36% of women, respectively. Surgical intervention was performed for 89% women, and no complications were encountered. Normal calcium levels achieved through treatment before conception did not fully eliminate adverse outcomes. CONCLUSION: Rates of perinatal complications in our series are more reassuring than the ubiquitously quoted rates from small and dated studies. The diagnosis of primary hyperparathyroidism may be easily missed during pregnancy, owing to its non-specific presentation. A high index of suspicion and measurement of ionized calcium levels is encouraged, especially for patients with excessive nausea and vomiting, nephrolithiasis, atypical presentations of hypertensive disorders, or isolated polyhydramnios. Mild degrees of calcium derangement do not preclude adverse perinatal outcomes. Surgery appears to be safe, even in the third trimester. The attenuated rate of complications noted in our series may have been the result of the high proportion of surgery, though this will require verification via meta-analysis or future prospective work.

[Multiple myeloma in old people : Practical skills for geriatricians and general practitioners]. / Multiples Myelom bei Älteren : Praxiswissen für Geriater und Allgemeinmediziner.

Multiple myeloma is an age-associated disease. In aged and multimorbid patients the diagnosis could be delayed due to the diversity of symptoms of this disease. Key diagnostic steps are the detection of an M protein as a surrogate of clonal plasma cell proliferation and evaluation of the CRAB criteria (hypercalcemia, renal insufficiency, anemia, bone lesions). The individual prognosis and vulnerability to treatment complications can be assessed by use of validated scores. Following the introduction of many new drugs, vulnerable aged patients with multiple myeloma can also be very effectively treated with modern (partially chemotherapy-free) combination treatment and additional supportive care. Successful management of aged and multimorbid patients with multiple myeloma is not the sole task of the treating hemato-oncologist but also mostly requires the inclusion of general practitioners and geriatricians.

Prevalence and predictors of early hypercalcemia after kidney transplantation: a nested case-control study within a cohort of 100 patients.

BACKGROUND: Hypercalcemia (HC) after kidney transplantation (KTx) can deteriorate both graft and patient survival. However, HC as a clinical condition and its clinical significance after KTx remain unknown. We evaluated the prevalence and risk factors of early HC after KTx. METHODS: We performed a nested case-control study using a cohort of 100 KTx patients. KTx patients were divided into the HC and normocalcemia (NC) groups based on the baseline serum-corrected calcium (cCa) levels (≥ 10.5 and < 10.5 mg/dL) within 1 year after KTx. RESULTS: Overall, the median value of maximum serum cCa level within 1 year after KTx was 10.1 (9.1-13.8) mg/dL. Of the 100 KTx patients within the cohort, 31 patients (31.0%) were classified as the HC group. The maximum serum cCa level was reached significantly earlier in the HC group compared with the NC group (2 vs. 4 months, p = 0.024). In univariate analysis, the risk factors of early HC after KTx were dialysis duration ≥ 10 years, serum cCa level the day before KTx, and cinacalcet administration before KTx. Among these risk factors, serum cCa level the day before KTx and cinacalcet administration before KTx were identified as significant independent risk factors of early HC after KTx in multivariate analysis. CONCLUSIONS: One-third of the KTx patients presented early HC within 1 year after KTx. Early HC after KTx resulted from persistent hyperparathyroidism. Therapeutic strategies to manage HC after KTx must be established.

Subcutaneous fat necrosis of the newborn and associated hypercalcemia: A systematic review of the literature.

Subcutaneous fat necrosis of the newborn is an uncommon disorder, and although usually benign, associated hypercalcemia can lead to complications such as failure to thrive and renal failure. Many sources suggest screening for hypercalcemia for 6 months following resolution of skin lesions, but little data are available to support this recommendation. This study examines existing published literature to better guide practitioners regarding screening evaluations of asymptomatic patients with subcutaneous fat necrosis. A systematic review of the literature was conducted using a PubMed English literature search. Data from case reports and case series were collected regarding the presence of hypercalcemia and associated complications, birth history, and age of onset/resolution of skin lesions and laboratory abnormalities. Approximately half (51%) of infants reported had hypercalcemia. Most (77%) developed detectable hypercalcemia within 30 days of skin lesion onset, and 95% developed detectable hypercalcemia within 60 days of skin lesion onset. Hypercalcemia was detected in only 4% of patients > 70 days following onset of skin lesions. Seventy-six percent had resolution of hypercalcemia within 4 weeks of detection. Hypercalcemia was more prevalent in full-term vs pre-term infants (P-value = 0.054), and higher birthweight was significantly associated with an increased risk of developing hypercalcemia (P-value = 0.022). Although gestational age trended toward significance, the only statistically significant clinical feature predicting the development of hypercalcemia was higher birthweight. Current recommendations for laboratory monitoring are not evidence-based, and this study provides interim data to guide practitioners until prospective, randomized controlled trials are conducted.

Mineral disorders in pediatric pre-emptive kidney transplantation.

BACKGROUND: Pre-emptive kidney transplantation (PEKT) is beneficial for patients, improves graft survival and minimizes the complications associated with chronic kidney disease. Reports on pediatric PEKT, however, are limited, and little is known about the parathyroid hormone (PTH) abnormalities and calcium-phosphorus disorders (CPD) in this condition. This study was the first to report on mineral disorders in pediatric PEKT patients during a 1 year period. METHODS: We conducted a comparative examination of the abnormalities in calcium, phosphorus, calcium-phosphorus products and PTH before and 1 year after living donor kidney transplantation in PEKT and non-PEKT patients. RESULTS: Thirty-one patients were included. The patients were divided into two groups: PEKT (n = 11; 5 months in CKD stage 4-5) and non-PEKT (n = 20; 31.5 months in dialysis). Mean age at transplantation was 9.4 ± 5.0 years. Hypercalcemia and hyperphosphatemia were observed before and after transplantation in the PEKT and non-PEKT groups, and >15% of patients in each group had bone disorder and ectopic calcification associated with mineral disorder. Mineral disorder was present for approximately 3 months after transplantation in both treatment groups. CONCLUSIONS: No significant differences in PTH or CPD were noted between PEKT and non-PEKT groups; moreover, normalization of abnormal values did not differ between the PEKT and non-PEKT groups. Compared with non-PEKT, PEKT did not improve the course of mineral metabolism disorders. Mineral and bone disorder treatment was likely insufficiently provided to pediatric PEKT patients. To obtain the maximum advantage of PEKT, calcium and phosphorus levels should be strictly controlled before kidney transplantation.

The Effect of Short-Term Vitamin D Supplementation on Calcium Status in Vitamin D Insufficient Renal Transplant Recipients at Risk of Hypercalcemia.

OBJECTIVE: Vitamin D insufficiency is highly prevalent among renal transplant recipients and in observational studies is associated with adverse outcomes. Hypercalcemia, usually due to persistent hyperparathyroidism, also commonly occurs in this population and often coexists with vitamin D insufficiency. However, concern that vitamin D supplementation might exacerbate the pre-existing hypercalcemia often leads clinicians to avoid vitamin D supplementation in such patients. This feasibility study aimed to quantify the effect on serum calcium of short-term low-dose cholecalciferol supplementation in a group of renal transplant recipients with a recent history of serum calcium levels >10 mg/dL. DESIGN: A 2-week, single arm, open-label trial. SETTING: Renal transplant follow-up clinic in an Irish University Hospital. SUBJECTS: Eighteen vitamin D-insufficient adult patients with a functioning renal allograft (estimated glomerular filtration rate > 30 mL/minute/1.73 m2) and a recent history of serum calcium >10 mg/dL. INTERVENTION: Two weeks of treatment with 1,000 IU cholecalciferol/day. MAIN OUTCOME MEASURE: Change in ionized calcium and urine calcium:creatinine ratio at follow-up compared with baseline. RESULTS: Mean (standard deviation [SD]) baseline 25 (OH) vitamin D (25 (OH) D) concentration was 15.9 (5.97) ng/mL and mean (SD) baseline serum calcium was 10.50 (0.6) mg/dL. Following the 2-week intervention, median (interquartile range [IQR]) change in serum calcium from baseline was -0.08 (-3.6 to 0.08) mg/dL, P = .3. Mean (SD) ionized calcium decreased from 5.24 (0.32) mg/dL at baseline to 5.16 (0.28) mg/dL, P = .05. Median (IQR) change in the urinary calcium:creatinine ratio was 0.001 (-0.026 to 0.299) mg/mg, P = .88. Median (IQR) change in 25 (OH) D was 3.6 (2.9-6.2) ng/mL, P < .05. CONCLUSIONS: In vitamin D-insufficient renal transplant recipients at risk of hypercalcemia, low-dose short-term oral cholecalciferol supplementation improves 25 (OH) D concentrations without exacerbating hypercalcemia or increasing the urinary calcium:creatinine ratio.