Worsening of soft tissue calcifications in a hemodialysis patient following parathyroidectomy

Hemodialysis patients with soft tissue calcifications present unique challenges to nephrologists who play an integral role in their long‐term management. Although disorders of soft tissue calcification are rare in the general population, calciphylaxis and tumoral calcinosis are encountered in up to 4% of the end‐stage renal disease population. Although they are both associated with the deposition of calcium in the soft tissue, they are distinct entities that differ markedly in respect to their clinical presentation, morbidity, and mortality. It is therefore exceedingly important that the nephrologist be aware of these disorders, be able to recognize them, and be able to differentiate them from each other to diagnose and treat patients appropriately. To achieve this it is necessary that the nephrologist be familiar with the diagnostic tools and the treatment modalities that are available. A case of a patient with soft tissue calcifications is presented followed by an overview of these disorders including a comparison of the clinical, laboratory, radiologic, and histologic findings, as well as treatment.     

Coronary and aortic calcifications in patients new to dialysis

Background: Vascular calcification has been associated with all cause and cardiovascular mortality in patients with end‐stage kidney disease (ESRD). Whether vascular calcification is present in persons with advanced chronic kidney disease starting dialysis or develops in patients on dialysis is unknown. The purpose of this study was to examine the prevalence of vascular and coronary calcification in patients new to hemodialysis. Methods: A total of 129 subjects new to dialysis were evaluated using electron beam computed tomography. The primary outcome was the presence and extent of coronary artery, aortic, and valvular calcification. Results: Forty‐three percent of subjects had no significant coronary artery calcification (total score ≤ 30) and 27% had no detectable aortic calcification. Thirty‐four percent had coronary artery scores that placed them above the 90th percentile for age and sex. Coronary artery calcification was significantly associated with a history of coronary artery disease and atherosclerotic vascular disease (ASVD) whereas aortic calcification was significantly associated with ASVD. Age (p < 0.0001), pulse pressure (p = 0.004), diabetes mellitus (p = 0.009), and a history of smoking (p = 0.026) were independently associated with the extent of coronary artery calcification. Age (p < 0.0001) and pulse pressure (p = 0.0003) were independently associated with the extent of aortic calcification. Conclusions: A large fraction of patients new to hemodialysis had no evidence of coronary artery or aortic calcification. Coupled with the extensive vascular calcification reported by others in prevalent dialysis patients these findings suggest that dialysis‐specific factors contribute to calcific vascular disease in ESRD.     

Hemodialysis‐associated soft tissue amyloidomas of the chest and abdominal wall

Amyloidoma is a highly unusual presentation of amyloidosis in tumoral or nodular form. Isolated soft tissue amyloidomas in individuals with end‐stage renal disease on chronic hemodialysis is exceedingly rare, particularly in the era of advanced dialysis technologies. We report the case of a 55‐year‐old male with end‐stage renal disease due to autosomal‐dominant polycystic kidney disease, on HD for over 30 years, who was found to have soft‐tissue, dialysis‐related (β₂‐microglobulin) amyloidomas (DRA). He presented with painful, palpable masses within the thoracic and abdominal walls. Serum β₂‐microglobulin level was only mildly elevated at 24.9 mg/L. Biopsy confirmed amyloidosis with positivity for Congo Red staining and apple‐green birefringence under polarized light. Amyloid subtyping with immunohistochemistry showed positive β₂‐microglobulin staining within the deposits. Conservative therapy involving pain management and close monitoring resulted in eventual improvement in symptoms and thus proved to be a viable option for treatment.     

Metastatic pulmonary calcification in a dialysis patient: case report and a review

A 19-year-old male presented with chest pain and dyspnea. He was anephric following nephrectomy for focal segmental glomerulosclerosis, had a subsequent failed transplant, and had been dialysis dependent for 3 years. Workup revealed hyperparathyroidism and an abnormal chest X-ray and computed tomography scan, significant for massive extra-skeletal pulmonary calcification. A markedly abnormal Technitium99 methylene diphosphonate (Tc99m-MDP) bone scan confirmed the clinical suspicion of metastatic pulmonary calcification. Metastatic pulmonary calcification (MPC) is common, occurring in 60% to 80% of dialysis patients on autopsy and bone scan series. It may lead to impaired oxygenation and restrictive lung disease. Typically, the calcium crystal is whitlockite rather than hydroxyapatite, which occurs in vascular calcification. Four major predisposing factors may contribute to MPC in dialysis patients. First, chronic acidosis leaches calcium from bone. Second, intermittent alkalosis favors deposition of calcium salts. Third, hyperparathyroidism tends to cause bone resorption and intracellular hypercalcemia. Finally, low glomerular filtration rate can cause hyperphosphatemia and an elevated calcium-phosphorus product. There may be other factors. Some authors suggest that the incidence of MPC in recent years may be lower due to improved dialysis techniques. The diagnosis is confirmed by biopsy, but can be suspected by typical findings on a Tc99m-MDP bone scan. Therapy is limited to ensuring adequate dialysis, correcting calcium-phosphorus product, and hyperparathyroidism; discontinuing vitamin D analogues may help. Conflicting reports show that transplantation may either improve or worsen the situation. MPC should be considered in dialysis patients who have characteristic abnormal chest radiography and/or pulmonary symptoms.     

A rare case of Actinomyces skin and soft tissue infection in an end‐stage kidney disease patient with a review of the literature

End‐stage kidney disease (ESKD) patients are a commonly overlooked immunocompromised population that places them at risk for rare infections. We describe the case of a 78‐year‐old man with a history of ESKD managed with thrice weekly in‐center hemodialysis who had a prolonged episode of left elbow pain and drainage and was eventually found to have a skin and soft tissue infection from Actinomyces radingae. We review the bacteriology of Actinomyces spp. and the experiences of other providers who have treated actinomycosis in individuals with ESKD. The anatomic sites and demographics of these individuals are heterogeneous, but they all generally require a long antibiotic course with a beta‐lactam and portend to a good prognosis. High index of suspicion is needed to identify rare and atypical infections in the ESKD population.     

Calculation of the clearance requirements for the development of a hemodialysis‐based wearable artificial kidney

Wearable artificial kidney (WAK) has been considered an alternative to standard hemodialysis (HD) for many years. Although various novel WAK systems have been recently developed for use in clinical applications, the target performance or standard dose of dialysis has not yet been determined. To calculate the appropriate clearance for a HD‐based WAK system for the treatment of patients with end‐stage renal disease with various dialysis conditions, a classic variable–volume two‐compartment kinetic model was used to simulate an anuric patient with variable target time‐averaged creatinine concentration (TAC), daily water intake volume, daily dialysis pause time, and patient body weight. A 70‐kg anuric patient with a HD‐based WAK system operating for 24 h required dialysis clearances of creatinine of at least 100, 50, and 25 mL/min to achieve TACs of 1.0, 2.0, and 4.0 mg/dL, respectively. The daily water intake volume did not affect the clearance required for dialysis under various conditions. As the pause time per day for the dialysis increased, higher dialysis clearances were required to maintain the target TAC. The present study provided theoretical dialysis doses for an HD‐based WAK system to achieve various target TACs through relevant mathematical kinetic modeling. The theoretical results may contribute to the determination of the technical specifications required for the development of a WAK system.     

Restless leg syndrome presenting as chronic severe limb pain in a dialysis patient

“Chronic pain” is a commonly reported symptom among hemodialysis patients. Despite its high prevalence and the poor health-related quality of life associated with it, chronic pain remains an ineffectively assessed and managed entity in dialysis patients. We report a case of a 55-year-old gentleman on maintenance hemodialysis who presented with 3 months history of “excruciating flitting and fleeting type” of pain largely involving both lower limbs and occasionally neck, shoulder, chest, and upper limbs. The pain was so intolerable that it even triggered suicidal intentions in the patient. Common causes of chronic pain in dialysis patients were considered, but the initial history and clinical examination remained elusive. The patient was empirically started on oral analgesics, benzodiazepines, calcitriol, and levocarnitine supplementation but had no significant effect on his symptoms. A comprehensive repeat clinical history revealed the nocturnal periodicity of symptoms, specific aggravation of pain with inactivity, and its temporary relief with movement. This helped us narrow down the diagnosis to restless leg syndrome (RLS) amidst the myriad causes of chronic pain in dialysis patients. The “constant urge to move the legs” which is the defining characteristic of RLS was inconspicuous in our patient and excruciating pain was the predominant manifestation. This atypical presentation of RLS with agonizing pain involving multiple sites of the body led to a delay in the diagnosis and initiation of appropriate therapeutic measures. The patient had a dramatic response to therapy with dopamine agonists and withdrawal of the drug led to reappearance of his symptoms which further confirmed the diagnosis of RLS. RLS should be considered in the evaluation of chronic pain in dialysis patients and renal health care providers should familiarize themselves with the varied atypical, forme fruste manifestations of RLS to avoid diagnostic delay of this disabling but treatable condition.     

Pruritus: Is there a grain of salty truth?

Hemodialysis patients characteristically suffer from a range of unpleasant symptoms. Uremic pruritus effects close to half of the chronic kidney disease population, reducing quality of life and associated with increased mortality. Its pathophysiology though is poorly understood; currently deployed therapeutic approaches are ineffective. Excessive levels of skin and soft tissue sodium accumulate in dialysis patients, producing a range of biological consequences, including inflammation. We report an index case of a hemodialysis patient with debilitating pruritus and extreme levels of tissue sodium, measured with Sodium-23 magnetic resonance imaging. Both the tissue sodium loading and pruritus responded fully to initiation of expanded hemodialysis therapy with a recently introduced medium cutoff dialysis membrane-based dialyzer.     

Risk factors for progression of aortic arch calcification in patients on maintenance hemodialysis and peritoneal dialysis

Vascular calcification is accelerated during dialysis and is known to be an important risk factor for cardiovascular disease. Progression of aortic arch calcification (AoAC) can be simply estimated with an AoAC score (AoACS) using plain chest radiography. The objective of this study was to evaluate risk factors for AoAC progression. The enrolled subjects were 125 newly treated hemodialysis patients and 59 peritoneal dialysis patients. In the patients who had undergone chest radiography before initial dialysis therapy and every year, we estimated AoACS and then divided the patients into two groups based on the presence or absence of AoAC progression. We also compared the baseline clinical and biochemical profiles in the two groups. Eighty‐five (46.2%) were men (mean age, 58.6 ± 12.7 years). Seventy‐six patients (41.3%) had AoAC before initial dialysis, with a mean AoACS of 13.0 ± 20.4%. The mean duration of follow‐up was 2.7 ± 1.0 years. Half of the patients (50%) had progressive AoAC. Age >65 years (p = 0.003), dialysis duration (p = 0.004), diabetes (p = 0.015), and the presence of AoAC at baseline (p = 0.001) were related to AoAC progression. No significant association was found between AoAC progression and the baseline clinical parameters, including gender, obesity, hypertension, and dialysis modality. In a multivariate analysis, dialysis duration (p = 0.003) and the presence of AoAC at baseline (p < 0.001) were independent risk factors for AoAC progression in patients undergoing dialysis. The duration of dialysis and the presence of AoAC before initial dialysis were significantly related to the progression of AoAC in these patients. The results suggest that patients should be carefully managed from the predialysis stage to prevent AoAC progression and to reduce cardiovascular morbidity.     

Integration of clinical and imaging data to predict death in hemodialysis patients

In a prior publication, we demonstrated that a model integrating clinical and simple imaging data predicted the presence and severity of coronary artery calcification in prevalent hemodialysis patients. Herein we report the ability of the same model to predict all‐cause death. We assessed all‐cause mortality in 141 consecutive maintenance hemodialysis patients from two dialysis centers followed for a median of 79 months from enrollment. Patients were risk stratified according to a simple cardiovascular calcification index (CCI) that included patient's age, dialysis vintage, calcification of the cardiac valves, and abdominal aorta. The mean patients’ age was 55 ± 14 years. Abdominal aorta calcification was present in 57% of the patients, and 44% and 38% had aortic and mitral valve calcification, respectively. During follow‐up, 75 deaths (93 deaths per 1000 person‐years) were recorded. The CCI was linearly associated with risk of death, such that the unadjusted hazard risk (HR) increased by 12% for each point increase in CCI (P < 0.001). Further adjustments for age, sex, study center, diabetes mellitus, history of cardiovascular disease, hypertension, congestive heart failure, left ventricular hypertrophy, systolic, and diastolic blood pressure did not substantially change the strength of this association (HR 1.10; 95%CI: 1.00–1.21; P = 0.03). The CCI is a simple clinical model that can be used to risk stratify maintenance hemodialysis patients.     

Utility of 18 F‐FDG PET/CT scan to diagnose the etiology of fever of unknown origin in patients on dialysis

Introduction: Studies on fever of unknown origin (FUO) in patients of chronic kidney disease and end stage renal disease patients on dialysis were not many. In this study, we used 18 F‐FDG PET/CT scan whole body survey for detection of hidden infection, in patients on dialysis, labelled as FUO. Methods: In this retrospective study, 20 patients of end stage renal disease on dialysis were investigated for the cause of FUO using 18F‐FDG PET/CT scan. All these patients satisfied the definition of FUO as defined by Petersdorf and Beeson. Any focal abnormal site of increased FDG concentration detected by PET/CT, either a solitary or multiple lesions was documented and at least one of the detected abnormal sites of radio tracer concentration was further examined for histopathology. Findings: All patients were on renal replacement therapy. Of these, 18 were on hemodialysis and two were on peritoneal dialysis. 18F‐FDG PET/CT scan showed metabolically active lesions in 15 patients and metabolically quiescent in five patients. After 18F‐FDG PET/CT scan all, but one patient had a change in treatment for fever. Anti‐tuberculous treatment was given in 15 patients, antibiotics in four patients and anti‐malaria treatment in one patient. Discussion: The present study is first study of 18F‐FDG PET/CT scan in patients of end stage renal disease on dialysis with FUO. The study showed that the 18 F FDG PET/CT scan may present an opportunity to attain the diagnosis in end stage renal disease patients on dialysis with FUO.     

Monckeberg's calciphylaxis with necrosis of the glans penis: a case presentation

Monckeberg's calcific sclerosis of the media of the small-sized and medium-sized arteries is a well described and potentially life-threatening condition seen almost exclusively in patients with end-stage renal disease (ESRD) and with hyperparathyroidism. Penile gangrene resulting from this entity is associated with a mortality as high as 64%. A 65-year-old man with ESRD on dialysis for 6 years was referred to Harborview Medical Center with severe penile pain and partial necrosis of his glans penis, which progressed despite medical management. The patient had previously undergone amputations on all four extremities. After intraoperative biopsies of the proximal corpora cavernosa and spongiosum demonstrated viable tissue, he underwent partial penectomy. Pathologic evaluation revealed calciphylaxis within the media of the penile vessels. Two months later the patient had persistent wound-healing issues with intractable pain and thus underwent a complete penectomy with ultimate resolution of his severe pain.     

Poor correlation between coronary artery calcification and obstructive coronary artery disease in an end-stage renal disease patient

Vascular calcification is highly prevalent and often severe in patients with chronic kidney disease. Arterial calcification in patients with chronic kidney disease can result from the deposition of mineral along the intimal layer of arteries in conjunction with atheromatous plaques or from calcium deposition in the medial wall of arteries, also known as Monckeberg's sclerosis. Whether coronary artery calcium scores as measured by electron beam computed tomography correlate with occlusive atherosclerotic disease in the dialysis population is uncertain. Here we report a case of an asymptomatic patient with diabetes mellitus and end-stage renal disease undergoing maintenance hemodialysis, who was found to have extremely elevated coronary artery calcium scores on electron beam computed tomography, but varied degrees of atherosclerotic plaque in her coronary arteries on coronary angiography. This suggests that in addition to the calcification anticipated in a remodeled intima, a proportion of the calcification is also likely to be in the arterial media. Thus, this case demonstrates that even an extremely high coronary calcium score may not be a satisfactory surrogate marker for obstructive atherosclerosis in elderly diabetic dialysis patients.     

Spontaneous perirenal hemorrhage in hemodialysis patient treated with selective embolization: A case series and review of the literature

Introduction: Spontaneous perirenal hemorrhage (SPH) or Wunderlich syndrome, is a rare but potentially life‐threatening condition. It is characterized by an unexpected bleeding in the kidneys and usually presents as an abdominal pain. Angiography and more recently selective renal arterial embolization are emerging as effective modalities for the diagnosis and treatment of SPH. In this article, we report a total of three cases of SPH in hemodialysis (HD) patients. Methods: This is the experience of diagnosis and treatment of SPH in HD patients. Findings: All three were female, between 37 and 54 years of age and were undergoing HD for end stage renal disease (ESRD). Two of patients presented with left flank or abdominal pain after termination of HD therapy, while the third patient presented with left abdominal pain during the dialysis session. All patients received anti‐coagulation therapy for HD, but no abnormal levels of coagulation index were found. These patients were diagnosed using CT and two of them were diagnosed with acquired cystic kidney disease (ACKD). Selective renal arterial embolization was performed in the case of active bleeding. Discussion: We are aware that HD patients have elevated risk of bleeding related complications, additionally the presence of an acute abdominal pain increases the suspicion of SPH as a possible cause. ACKD can be considered one of the possible risk factors for SPH in long‐term HD patients. Interventional treatment for kidney injury is useful and safe for active bleeding in most cases.     

Transient mediastinal mass from fluid overload

Mediastinal masses incidentally discovered on chest imaging often suggest underlying malignancy such as lymphoma or metastatic cancer. However, the radiographic appearance of mediastinal edema can mimic a mediastinal mass in the context of acute fluid overload. We describe the case of a 75 year old woman known for end‐stage renal disease on hemodialysis who presented with acute pulmonary edema in the context of a Non ST‐Elevation Myocardial Infarction. Chest CT imaging showed pulmonary edema, pleural effusions, and a middle mediastinum soft‐tissue mass of 4.2 × 2.5cm. Malignancy was initially suspected, however given the clinical context of fluid overload and absence of other signs of malignancy, the possibility of the mass representing soft‐tissue edema was raised. Therefore, the patient's fluid overload was treated with a progressive reduction in the dry weight used for dialysis and a repeat chest CT was obtained 8 weeks later once the patient was euvolemic. The repeat CT showed complete resolution of the mediastinal mass. Fluid overload can manifest in many different ways on chest imaging. Mediastinal masses lead to concerns about a potentially malignant process and often prompt further evaluation with invasive procedures that carry significant risks. In the appropriate clinical context, it is important to consider the possibility of mediastinal edema presenting as a mass on chest imaging. Under such circumstances, it is more prudent to correct the fluid overload and repeat chest imaging before undertaking invasive diagnostic procedures with the potential to cause harm.     

Coronary artery calcification in Korean patients with incident dialysis

Introduction: Patients with chronic kidney disease have an extremely high risk of developing cardiovascular disease (CVD). In patients with end‐stage renal disease (ESRD), coronary artery calcification (CAC) is associated with increased mortality from CVD. Methods: The present study aimed to investigate the risk factors for CAC in Korean patients with incident dialysis. Data on 423 patients with ESRD who started dialysis therapy between December 2012 and March 2014 were obtained from 10 university‐affiliated hospitals. CAC was identified by using noncontrast‐enhanced cardiac multidetector computed tomography. The CAC score was calculated according to the Agatston score, with CAC‐positive subjects defined by an Agatston score >0. Findings: Patients' mean age was 55.6 ± 14.6 years, and 64.1% were men. The CAC‐positive rate was 63.8% (270 of 423). Results of univariate analyses showed significant differences in age, sex, etiology of ESRD and comorbid conditions according to the CAC score. However, results of multiple regression analysis showed that only a higher age was significantly associated with the CAC score. Receiver operating characteristic curves showed that the sensitivity and specificity of L‐spine radiography for diagnosing CAC were 56% and 91%, respectively, for diagnosing CAC (area under the curve, 0.735). Discussion: CAC was frequent in patients with incident dialysis, and multiple regression analysis showed that only age was significantly associated with the CAC score. In addition, L‐spine radiography could be a helpful modality for diagnosing CAC in patients with incident dialysis.     

Kienböck's disease associated with radiocephalic fistula formation in a patient with end‐stage renal disease

Kienböck's disease, which consists of osteonecrosis and collapse of the lunate bone, causes chronic pain and dysfunction of the wrist. Patients on hemodialysis are occasionally present with wrist pain, but Kienböck's disease is rarely reported in dialysis patients. This case study describes Kienböck's disease in a patient with end‐stage renal disease on hemodialysis. A 39‐year‐old male with a 1‐year history of hemodialysis presented with left wrist pain that increased progressively over 6 months. The patient had no history of trauma or any other risk factors known to be associated with Kienböck's disease. Physical examination of the wrist at the site of the arteriovenous fistula showed swelling and tenderness with decreased range of motion. Radiographic examination showed articular collapse and fracture of the body of lunate consistent with stage IIIb Kienböck's disease. An intercarpal arthrodesis with autogenous bone graft was performed.     

Inflammation as a cause of malnutrition, atherosclerotic cardiovascular disease, and poor outcome in hemodialysis patients

Cardiovascular disease (CVD) remains the major cause of morbidity and mortality in end‐stage renal disease (ESRD) patients treated by hemodialysis (HD). Although traditional risk factors are common in dialysis patients, they may not alone be sufficient to account for the unacceptable high prevalence of CVD in this patient group. Recent evidence demonstrates that chronic inflammation, a nontraditional risk factor that is commonly observed in HD patients, may cause malnutrition and progressive atherosclerotic CVD by several pathogenetic mechanisms. The cause(s) of inflammation in HD patients is multifactorial and includes both dialysis‐related (such as graft and fistula infections, bioincompatibility, impure dialysate, and back‐filtration) and dialysis‐unrelated factors. Although inflammation may reflect underlying CVD, an acute‐phase reaction may also be a direct cause of vascular injury. Available data suggest that proinflammatory cytokines play a central role in the genesis of both malnutrition and CVD in ESRD. Thus, it could be speculated that suppression of the vicious cycle of malnutrition, inflammation, and atherosclerosis (MIA syndrome) would improve survival in dialysis patients. As there is not yet any recognized, or even proposed, targeted treatment for ESRD patients with chronic inflammation; it would be of considerable interest to study the long‐term effect of various anti‐inflammatory treatment strategies on nutritional and cardiovascular status as well as outcome in these patients.