Hyperparathyroidism caused by distant pulmonary lesions and parathyromatosis after ethanol injection/parathyroidectomy for secondary hyperparathyroidism

Secondary hyperparathyroidism (SHPT) treatment includes parathyroidectomy and percutaneous ethanol injection therapy (PEIT), which are invasive procedures. The condition in which benign hyperfunctioning parathyroid tissue is distributed throughout the neck and mediastinum is termed parathyromatosis. Here, we present the case of a 51‐year‐old woman who began hemodialysis in 1986 due to chronic kidney disease of unknown etiology and developed SHPT in 1999. She underwent 6 rounds of PEIT followed by total a parathyroidectomy with partial forearm autotransplantation. Between 2011 and 2013, surgeons removed several nodules from her pulmonary and cervical regions and the transplanted masses from her forearm; all showed hyperplasia but exhibited no histological evidence of malignancy. Damage to the parathyroid capsule after repeated PEITs may cause local cervical recurrence and pulmonary lesions, although distant lesions are extremely rare in SHPT. This case is of interest due to the possible association between PEIT and parathyromatosis and distal lesions.     

Use of 3‐hour daily hemodialysis and paricalcitol in patients with severe secondary hyperparathyroidism: A case series

Patients with poor metabolic control receiving conventional hemodialysis are at risk for developing severe secondary hyperparathyroidism. We postulated that daily hemodialysis may be effective at controlling parathyroid hormone (PTH) in the setting of severe secondary hyperparathyroidism by improving the control of hyperphosphatemia and allowing increased use of vitamin D analogs. We present 5 patients with severe secondary hyperparathyroidism (median iPTH=1783 pg/mL) who were treated with 3‐hour daily hemodialysis (3 hours × 6 times a week). Daily hemodialysis, at 1 year, was associated with a 70.4% reduction in median PTH (1783 pg/mL [interquartile range: 1321–1983]–472 pg/mL [334, 704], P<0.001). Additionally, there was an increase in paricalcitol dose from 0 mcg/d to 10.8 (2.00, 11.7) mcg/d, a 39% reduction in calcium × phosphorus product (80.3 ± 26.8–48.9 ± 14.0, P<0.01), a 52% reduction in serum phosphorus (9.90 ± 2.34–4.75 ± 0.79 mg/dL, P<0.0001), and a 17.6% increase in serum calcium (8.18 ± 2.04–9.62 ± 0.93 mg/dL, P<0.01). Three‐hour daily hemodialysis with the use of high‐dose paricalcitol is associated with improved control of severe secondary hyperparathyroidism.     

Facial disfigurement due to osteitis fibrosa cystica or brown tumor from secondary hyperparathyroidism in patients on dialysis: A systematic review and an illustrative case report

Osteitis fibrosa cystica (OFC) is the most frequent type of osseous change in renal osteodystrophy affecting the majority of dialysis patients. Brown tumors are a severe form of OFC. The involvement of the craniofacial skeleton causing facial disfigurement in patients on dialysis appears to be limited to case reports. After searching PubMed, we performed a systematic review of 127 cases with a severe form of OFC resulting in a facial disfigurement to understand possible determinants for this condition. We found that since the first published case in 1974, and after a peak in 1996, there appears to be an increase in published reported cases. Only 27.6% of these cases were published in nephrology journals. The most common region for reported cases was North America. Mean age of these patients was 31.2 years with a mean dialysis duration of 7 years. Almost 67% were women, and almost all were on hemodialysis. The disease tended to most commonly localize to the maxilla (73.2%) and mandible (57.5%). As part of the treatment, 59% of patients had a parathyroidectomy. More than one‐third (35.4%) had symptomatic improvement at follow‐up. Mean follow‐up was 1.6 years. Clinicians should be aware of this clinical presentation of a severe form of OFC and/or brown tumors. Timely diagnosis and intervention may help to prevent or decrease destructive bone changes and reduce negative psychological consequences of facial disfigurement.     

Regression of brown tumor of the maxilla in a patient with secondary hyperparathyroidism after a parathyroidectomy

Brown tumors or osteoclastomas are erosive bony lesions arising as a complication of hyperparathyroidism. In patients with end‐stage renal disease, brown tumors are uncommon skeletal manifestations that are usually seen in severe forms of secondary hyperparathyroidism. Initial treatment involves the correction of hyperparathyroidism, which usually leads to regression of the tumors. We report a case of brown tumors of the maxilla in a 24‐year‐old female referred to us by a local hospital, where she had been on regular hemodialysis for >10 years. After a complete biochemical and radiological workup, she underwent a total parathyroidectomy, which subsequently resulted in significant regression of her tumor.     

Cervical tumoral calcinosis with secondary hyperparathyroidism in a chronic hemodialysis patient

Tumoral calcinosis is an uncommon and severe complication of chronic renal failure. It is generally associated with the presence of a high‐serum calcium‐and‐phosphorus product. We report here a case of a patient on maintenance hemodialysis who presented with progressively increasing, solitary, tumor‐like swelling over the nape of the neck. A 50‐year‐old female on thrice weekly maintenance hemodialysis for the last 3 years presented with a small swelling over the nape of the neck that had been progressively increasing over the last 1 year to cricket ball size. The patient was investigated and diagnosed as having tumoral calcinosis. The metastatic calcification occurring in the patient was most likely related to high calcium × phosphate product with coexistent secondary hyperparathyroidism possibly aggravated by vitamin D therapy. The patient was treated with withdrawal of vitamin D therapy, strict control of serum phosphate levels with noncalcemic phosphate binders, and subtotal parathyroidectomy. The neck swelling started decreasing in size after 2 months of parathyroidectomy and there was marked clinical improvement with drop in serum parathormone levels, over a period of 6 months. After 2 years of parathyroidectomy, the neck swelling again started increasing in size with increase in serum parathormone levels. The patient was treated with cinacalcet and the neck swelling gradually decreased in size along with control of serum parathormone and phosphate levels.     

Effect of pharmacological suppression of secondary hyperparathyroidism on cardiovascular hemodynamics in predialysis CKD patients: A preliminary observation

Cardiovascular events are the principal cause of mortality in patients with chronic kidney disease (CKD). Secondary hyperparathyroidism (SHPT), a common complication of CKD, contributes to cardiac dysfunction. This study is an attempt to demonstrate the effects of parathyroid hormone suppression with oral calcitriol on cardiovascular hemodynamics. Twenty predialysis CKD patients with SHPT were given calcitriol therapy for 12 weeks. Ten similar patients received placebo. Echocardiographic assessment of cardiac function was performed at baseline and after 12 weeks of treatment. Calcitriol therapy effectively suppressed SHPT. Baseline left ventricular (LV) end diastolic diameter and LV end systolic diameter were 4.86+/-0.48 and 2.86+/-0.33 cm, and the mean FS was 41.02+/-4.79%. Left ventricular end systolic and end diastolic volumes were normal (42.30+/-9.07 and 91.40+/-19.68 mL). The ejection fraction was slightly reduced (53.54+/-3.57%). Pretreatment Doppler indices including E velocity (0.816+/-0.087 m/s), A velocity (0.696+/-0.089 m/s), and E/A ratio (1.193+/-0.210) were significantly impaired. After 12 weeks of calcitriol therapy, there was no significant change in the LV dimensions or ejection fraction, but there was a significant improvement in the diastolic parameters, namely the A velocity (0.680+/-0.084) and E/A ratio (1.238+/-0.180). Secondary hyperparathyroidism is an important factor in the pathogenesis of cardiovascular complications in CKD. There is evidence to support that correction of hyperparathyroidism can improve the systolic dysfunction seen in advanced kidney disease. This study shows that diastolic dysfunction seen in predialysis CKD patients may also be possibly improved with calcitriol therapy.     

Switch from calcitriol to paricalcitol in secondary hyperparathyroidism of hemodialysis patients: Responsiveness is related to parathyroid gland size

Paricalcitol is more effective than calcitriol in hemodialysis patients (HD) with secondary hyperparathyroidism (SHPT), but it is not effective in some of them. We have investigated the relationship between paricalcitol responsiveness and parathyroid gland (PTG) size. Thirty HD with SHPT treated previously with calcitriol for at least 6 months were switched to paricalcitol (1:4 conversion ratio). Parathyroid gland number and size (maximum longitudinal diameter [MLD] of largest PTG) was measured by ultrasonography. Patients were divided into 2 groups: group A (MLD ≤9.0 mm [17 HD]); and group B (MLD >9.0 mm [13 HD]). They were defined responder if both the last 2 monthly determinations of inhibit parathyroid hormone (iPTH) were within the target (<300 pg/mL) according to National Kidney Foundation Kidney Disease Outcomes Quality Initiative recommendations. Twenty‐six and 20 HD completed 6‐month and 12‐month paricalcitol therapy, respectively. After 6 months of paricalcitol treatment, 23.5% HD of group A and 7.7% of group B were responders. At 12 months, 41.2 % of group A and 7.7% of group B were responders. Throughout paricalcitol therapy, serum calcium and phosphorus concentrations slightly increased in all HD but more significantly in group B. The baseline iPTH and MLD of the largest PTG were significantly correlated with final iPTH levels. Paricalcitol is more effective than calcitriol in SHPT, but the responsiveness to paricalcitol and hypercalcemia are related to PTG size. The measurement of MLD by ultrasonography may be useful for predicting responsiveness to paricalcitol, avoiding an unnecessary and expensive therapy.     

Efficacy and safety of Cinacalcet on secondary hyperparathyroidism in Chinese chronic kidney disease patients receiving hemodialysis

Introduction Secondary hyperparathyroidism (SHPT) develops in patients with chronic renal failure. Cinacalcet hydrochloride has been used successfully in U.S., Europe, and Japan in the treatment of SHPT, while maintaining serum levels of calcium and phosphorus. The efficacy and safety profile of Cinacalcet treatment vs. conventional treatments has been of great interest in clinical practice. In this recent phase III study conducted in China, efficacy and safety of a calcimimetic agent, Cinacalcet (Kyowa Hakko Kirin Co., Ltd.), were assessed for SHPT treatment in stable chronic renal disease patients on hemodialysis. Methods In this double‐blind, multicenter, placebo‐controlled, randomized phase III study, 238 subjects were enrolled in 12 centers and randomly divided into a Cinacalcet group and a placebo group. The percentage of patients achieving a serum parathyroid hormone (PTH) level ≤250 pg/mL was the primary efficacy end point. Serum calcium and phosphorus levels were measured. Adverse events and serious adverse events were recorded, and causal analysis performed. Findings In primary analysis, 25.4% of the Cinacalcet group and 3.5% of the placebo group achieved the primary end point (PTH ≤250 pg/mL). Calcium and phosphorus levels and calcium–phosphorus product were lower in the Cinacalcet group compared with the placebo group. Eleven serious adverse events were reported and considered to be not related to study drugs. Mild to moderate hypocalcemia and reduced calcium levels were reported and considered to be Cinacalcet related. Discussion This phase III study demonstrated that Cinacalcet is effective and well tolerated in treating SHPT in Chinese chronic kidney disease patients on hemodialysis, and in a patient population with much higher baseline PTH levels.     

Early,Frequent, and Efficient Hemodialysis: A New Trend or Déjà Vu From the 1970s?

After more than a quarter century of dialysis, two factors are still present in dialysis treatment of chronic renal failure patients: inadequacy of technology (the artificial kidney acts as an artificial glomerulus) and inadequate use of technology in terms of dialysis initiation and frequency. This paper presents the results of two less unphysiological dialysis programs, introduced in Bologna at the beginning of the 1960s, which proved their clinical value and are now becoming trendy, at the end of this century. Features of these programs are twofold: (1) daily dialysis, which aims at making treatment more biologically suited to the patient; its validity relies on lower intra- and interdialytic osmotic fluctuations; (2) early dialysis, which aims at making the patient more biologically suited to the treatment. After more than 25 years it is evident that this treatment has fulfilled its original expectations versus late dialysis. There is a 40% improvement in survival, a 35% decrease in morbidity, and a 24% improvement in the cost/benefit ratio. This report is based on a retrospective analysis of our overall experience and clinical results of chronic hemodialysis carried out in 224 patients on early dialysis and 1210 patients on late dialysis in Bologna from 1967 to 1997. Based on this experience, the following should be regarded as particularly important indications for early dialysis: adequate dialysis facilities; symptomatic patients despite renal creatinine clearances between 15 and 20 mL/min; patients unable to comply with dietary measures; children, to allow for adequate development; patients with diabetes mellitus; candidates for renal transplantation.     

Severe jaw enlargement associated with uremic hyperparathyroidism

Marked enlargement of the jaws is a rare complication of renal osteodystrophy. This report describes a localized enlargement of the mandible due to a brown tumor in a patient undergoing chronic hemodialysis. Literature on jaw involvement in secondary hyperparathyroidism is reviewed.     

Sternal instability in a hemodialysis patient with secondary hyperparathyroidism

A 77‐year‐old man, 11 years under chronic hemodialysis treatment for chronic renal failure of unknown origin, presented with anterior chest pain, dyspnea with paradoxical breathing, and sternal instability after a simple fall from a standing height. Patient underwent three‐vessel coronary artery bypass grafting 31 months ago. Computed tomography with three‐dimensional volume rendering showed sternal nonunion with a great gap between the two halves of the sternum and at least one fracture in the left half of the sternum. A successful surgical repair followed. Patient suffered from severe secondary hyperparathyroidism for many years. Despite treatment with sevelamer, paricalcitol and cinacalcet, intact parathyroid hormone was 1682 pg/mL. During the last 5 years, serum intact parathyroid hormone remained steadily above 1000 pg/mL. Patient refused parathyroidectomy in the past. We assume that long‐lasting severe hyperparathyroidism contributed to this rare and life‐threatening complication of median sternotomy in our patient, due to the detrimental effect of hyperparathyroidism on bone metabolism and its association with increased incidence of bone fractures and defect in bone fracture healing.     

Physical examination: How to examine the arm with arteriovenous fistula

Physical examination has demonstrated its effectiveness in identifying complications of arteriovenous fistula (AVF). It should be initiated at the stage prior to the construction of the AVF and continue in its accomplishment, maturation, and subsequent use in the treatment of hemodialysis. Nurses should incorporate the physical examination in their practices, in order to preserve the vascular net of patients and assist in the recognition of complications of AVF. It is intended to describe aspects of the physical examination that enable the identification of the AVF complications including: infection, accessory veins, venous stenosis, steal syndrome, high‐output cardiac failure, and venous hypertension.     

Digital clubbing as an unusual complication associated with severe secondary hyperparathyroidism: report of two cases

Digital clubbing due to secondary hyperparathyroidism has been described as an unusual complication among patients with chronic kidney disease undergoing maintenance hemodialysis therapy. Although the pathogenesis of digital clubbing is unknown, certain growth factors such as platelet-derived growth factor and hepatocyte growth factor have been associated with this clinical syndrome. Two patients of our renal unit population presented this unique clinical feature bilaterally, among the other clinical findings of severe secondary hyperparathyroidism. Both patients were subjected to parathyroidectomy. Histological examination revealed diffuse hyperplasia of parathyroid glands. Despite the improvement of clinical symptoms and laboratory findings of secondary hyperparathyroism after parathyroidectomy, digital clubbing remained unchanged.     

Self-reported symptoms in patients on hemodialysis with moderate to severe secondary hyperparathyroidism receiving combined therapy with cinacalcet and low-dose vitamin D sterols

Patients with secondary hyperparathyroidism experience a variety of clinical symptoms which may adversely affect physical and mental function. As part of a multicenter, open-label clinical trial, subjects completed a questionnaire that included the Medical Outcomes Study Short Form-36 and 14 kidney disease-related symptoms at multiple time points during the study. Out of the 567 subjects who received at least one dose of cinacalcet, 528 to 535 (93.8-94.4%) completed all or portions of the questionnaire at baseline. The median bioactive parathyroid hormone (PTH) was 294 pg/mL (10%, 90% range, 172-655 pg/mL). Following treatment with cinacalcet and low-dose vitamin D sterols, subjects reported significant improvement in the frequency of pain in muscles, joints and bones, stiff joints, dry skin, itchy skin, excessive thirst, and trouble with memory. At end of the efficacy assessment phase (Weeks 16 to 22), the magnitude of improvement was the greatest in joint pain, bone pain, dry skin, and excessive thirst (>5 on a 0-100 scale; P < 0.001). There were no clinically or statistically significant changes in any of the Short Form-36 subscales or in the physical or mental health composite scores. Among patients on hemodialysis with moderate to severe secondary hyperparathyroidism, treatment with cinacalcet and low-dose vitamin D sterols results in significant improvement in pain in the muscles, joints and bones, joint stiffness, dry and itchy skin, excessive thirst, and trouble with memory.     

Left atrial volume index as a predictor of ventricle repolarization abnormalities in adult dialyzed patients

This study was performed to investigate the relationship between left atrium (LA) volume index (LAVI) and left ventricle electrical activity presumably repolarization in end‐stage renal disease patients. Study group was consisted of 120 dialyzed patients divided into two subgroups: 57 (age 50.7 ± 7.1) were on continuous ambulatory peritoneal dialysis (CAPD) and 73 (age 51.6 ± 7.6) were hemodialyzed (HD). All patients were undergoing three‐dimensional vectorcardiographic (VCG) monitoring to assess parameters concerning T vector: QRS‐T angle, Tel, and Taz. Standard echocardiography was performed to assess: LA_max, LA_short, LA_long. LAVI was calculated due to formula: LAVI = (π/6X [LA_max × LA_short × LA_long])/m². LAVI in HD as well as in CAPD patients was significantly higher compared with controls (respectively: 36.29 ± 10.92; 36.41 ± 11.06; 20.64 ± 6.77 mL/m²). The calculated cutoff value of LAVI was 36.32 mL/m². In HD patients, the strong correlations between LAVI and QRS‐T angle and Tel were determined (respectively: r = 0.407, P < 0.001 and r = 0.359, P = 0.006). Similarly in CAPD group were significant associations between LAVI and QRS‐T angle and Tel (respectively: r = 0.423, P < 0.001 and r = 0.374, P = 0.004). The QRS‐T angle, Tel and Taz are independently and markedly associated with LAVI in both HD and CAPD patients. LAVI and VCG indices are higher in both HD and CAPD patients. Correlation between QRS‐T angle and LAVI may reflect unfavorable influence on the electrical activity of the heart in dialyzed patients with left ventricle diastolic dysfunction. LAVI cutoff value is useful biomarker for stratification of ventricle repolarization disturbances in those patients.     

Outcome among patients with acute renal failure needing continuous renal replacement therapy: A single center study

Outcome of acute renal failure (ARF) and use of continuous renal replacement therapy (CRRT) have shown a consistently high mortality. (1) Evaluate the short-term patient survival. (2) Evaluate dialysis-free survival. (3) Evaluate risk factors associated with overall survival and the continued need for intermittent dialysis. We identified adults (≥18 years) needing CRRT, treated in the critical care units of Froedtert Medical and Lutheran Hospital from January 1, 2003 till December 31, 2005. Patients were divided into two major groups needing CRRT, end stage renal disease (ESRD) (chronic dialysis) and non-ESRD with ARF. Continuous renal replacement therapy was performed with an average of 2 L replacement fluid exchanges/h. Sigma stat software was used for analysis. Comparison was done for noncontinuous variables by chi-square and t test for categorical and continuous variables, respectively. A total of 110 (ESRD 24/non-ESRD 86) patients received CRRT during study period. Over all in-hospital mortality among non-ESRD patients was 63% vs. 46% for ESRD. Among non-ESRD patients who survived, 47% needed intermittent hemodialysis on intensive care unit discharge and 28% continued to need hemodialysis at last follow-up. Among non-ESRD patients alive at discharge, those who were dialysis dependent on last follow-up were older (64.5) than those who did not require dialysis on last follow-up (58.4) P=0.347. Non-ESRD patients who died were in the hospital for an average of 17.5 days compared with 29 days for those who were discharged from the hospital. Patients with ARF needing CRRT have high in-hospital mortality. A significant percentage of patients remained dialysis dependant on last follow-up.     

L carnitine in hemodialysis patients

Carnitine, 3-hydroxy-4-trimethylaminobutyrate, a small, water soluble molecule that is essential for mitochondrial fatty acid oxidation, is significantly reduced in hemodialysis patients. Uremia-induced carnitine deficiency, which is magnified by dialysis, is associated with symptoms or clinical problems such as anemia hyporesponsive to erythropoietin, cardiovascular diseases, and muscle weakness. This review examines studies dealing with the different clinical aspects of chronic renal failure patients in which carnitine deficiency may play a role and has also examined the studies, which have evaluated the effect of carnitine deficiency treatment. The reports reviewed in this study, including those more recent from our laboratory, have provided data suggesting that chronic renal failure and particularly hemodialysis patients can benefit from carnitine treatment in particular for renal anemia, insulin sensitivity, and protein catabolism. On the other hand, the heterogeneous clinical response to carnitine therapy in dialysis patients, reported by other studies, and the lack of large-scale randomized trials are the rationale for the reluctance regarding a widespread use of carnitine supplements in dialysis patients. Well-designed randomized clinical trials are therefore required to fully address the potentially important carnitine treatment in dialysis patients.