Calcific mitral stenosis in the hemodialysis patient

The dialysis patient is prone to elevations in the calcium phosphorus product and hyperparathyroidism, which contributes to valvular and vascular calcification. We present the case of a young lady on chronic dialysis that developed mitral calcification complicated by severe mitral stenosis, caseous calcification and retinal embolization. She subsequently required mitral valve replacement.     

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.     

Testicular angina during hemodialysis: An unusual complication of ultrafiltration

During hemodialysis, the development of hypotension or symptoms suggestive of ischemia is used as a surrogate marker for the establishment of dry weight. These symptoms manifest commonly as muscle cramps, chest pain or abdominal pain. Hemodialysis patients are also prone to vascular calcification which may be medial or intimal. We report the case of a 68‐year‐old male who developed testicular pain while attempting to establish dry weight. Computerized tomography scan of his abdomen showed extensive vascular calcification. The end result in this case was bilateral orchiectomy. Histopathology revealed hyperplastic arteriolosclerosis with intimal calcification contributing to ischemia.     

Treatment of severe metastatic calcification in hemodialysis patients

Soft tissue and vascular calcifications are commonly present in uremic patients secondary to disturbances in calcium and phosphate balance and secondary to hyperparathyroidism. We report a uremic patient who developed uncontrolled hyperparathyroidism rapidly within 6 months after commencing hemodialysis (HD) therapy, with clinical presentations of tumoral calcinosis, calciphylaxis, and myocardial calcifications. After treatment with a low-calcium dialysate, non–calcium-containing phosphate binders, and parathyroidectomy, a dramatic resolution of soft tissue calcification was achieved. However, there was relatively little change in the vascular and other visceral calcifications over the 3-month observation period. This case highlights an unusual and rapid development of tertiary hyperparathyroidism, the importance of tight calcium/phosphate control in uremic patients, the potential hazards of a high calcium concentration dialysate, and the dangers of the overzealous use of active vitamin D therapy in HD patients with uncontrolled hyperparathyroidism.     

Clinical epidemiology of parathyroidectomy in hemodialysis patients: the USRDS waves 1, 3, and 4 study

Despite advances in the medical management of secondary hyperparathyroidism, parathyroidectomy remains necessary in some end-stage renal disease patients. Observational studies may help with the design of intervention trials. We linked the retrospective Waves 1, 3, and 4 Dialysis Morbidity and Mortality Study datasets to Medicare claims data to identify incident parathyroidectomy in 10,588 Medicare patients receiving hemodialysis in the United States on December 31, 1993. The mean age was 60.0 years, and the mean follow-up 3.6 years. De novo parathyroidectomy incidence was 14.2/1000 patient-years. Considered as quintiles (Q), higher levels of standard bone metabolism variables were associated (p<0.0001) with parathyroidectomy stepwise, such that adjusted hazards ratios (AHR) for Q5 (vs. Q1) were, for calcium (>10.3 mg/dL), 5.09 (3.64-7.10); for phosphorus (>7.5 mg/dL), 2.92 (2.06-4.15); for calcium-phosphorus product (>71 mg2/dL2), 3.32 (2.27-4.85); and for parathyroid hormone (PTH; >480 pg/mL), 13.81 (7.47-25.55). Other antecedent associations included younger age, lower hemoglobin, and longer dialysis vintage, while transplantation, as a time-dependent covariate, was associated with lower hazards ratios. Using interval Poisson analysis, parathyroidectomy was associated with higher mortality risk ratios in the first year, and progressively lower risk ratios subsequently. Demographic variables may modify the risk of parathyroidectomy. Younger patients on long-term hemodialysis may be at a special risk. Parathyroidectomy risk increases stepwise with alterations in bone metabolism variables, suggesting that a single-threshold management approach may not be ideal.     

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.     

Long-term effects of magnesium carbonate on coronary artery calcification and bone mineral density in hemodialysis patients: A pilot study

Observational data suggest that elevated magnesium levels in dialysis patients may prevent vascular calcification and in vitro magnesium can prevent hydroxyapatite crystal growth. However, the effects of magnesium on vascular calcification and bone mineral density have not been studied prospectively. Seven chronic hemodialysis patients participated in this open label, prospective pilot study to evaluate the effects of a magnesium-based phosphate binder on coronary artery calcification (CAC) scores and vertebral bone mineral density (V-BMD) in patients with baseline CAC scores >30. Magnesium carbonate/calcium carbonate (elemental Mg: 86 mg/elemental Ca 100 mg) was administered as the principal phosphate binder for a period of 18 months and changes in CAC and V-BMD were measured at baseline, 6, 12, and 18 months. Serum magnesium levels averaged 2.2±0.4 mEq/L (range: 1.3–3.9 mEq/L). Phosphorus levels (4.5±0.6 mg/dL) were well controlled throughout the 18 months study. Electron beam computed tomography results demonstrated a small not statically significant increase in absolute CAC scores, no significant change in median percent change, and a small none significant change in V-BMD. Magnesium may have a favorable effect on CAC. The long-term effect on bone mineral density remains unclear. Larger studies are needed to confirm these findings.     

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.     

Hyperphosphatemia among end‐stage renal disease patients in developing countries: A forgotten issue?

The prevalence of hyperphosphatemia and increased calcium-phosphorus product has never been evaluated in a large multicenter study in a developing country. Our aim is to study the prevalence of hyperphosphatemia in 38 HD centers in Egypt (as an example of a developing country) and to correlate it with different co-morbid conditions and the patient's demographic data. This is a cross-sectional study conducted on 1005 chronic kidney disease stage 5 patients (CKD-stage 5) on HD for a period of more than 1 year in 38 dialysis centers in Egypt. All patients were receiving calcium-based salts as a phosphate binder. Hyperphosphatemia and increased calcium-phosphorus product were evaluated and correlated with different parameters including age, sex, knowledge by diet parameters, HD session duration, the frequency of HD per week, the type of dialysis membrane, the surface area of the dialyzer, dialyzer phosphorus clearance (phosphorus KoA), and the type of dialysate. Other co-morbid medical conditions and evidence of IHD were also investigated. Hyperphosphatemia was present in 69.1% of cases and a high calcium-phosphorus product was present in 30.2%. A higher calcium-phosphorus product was found among males. 83.2% of those with a poor knowledge by diet parameters had hyperphosphatemia compared with 67.6% in patients with a satisfactory knowledge by diet parameters. 72.3% of patients using a membrane with low-to-medium clearance had hyperphosphatemia, compared with 67.2% using a membrane with a high clearance. Seventy-two percent of patients with IHD were hyperphosphatemic compared with 67.6% of the non-ischemic patients. Hyperphosphatemia is a major problem in dialysis patients in developing countries, reflecting differences from developed countries regarding dietary habits, ethnic factors, dialysis quality, types of dialysis membranes, as well as economic factors hampering the use of the more expensive phosphate binders. Extended dialysis hours may be a good alternative solution in developing countries.     

Malnutrition‐inflammation‐coronary calcification in pediatric patients receiving chronic hemodialysis

Malnutrition, inflammation, and renal osteodystrophy parameters with resultant coronary calcification (CC) are associated with increased cardiovascular mortality in adults. Previous pediatric studies demonstrated CC in children but none assessed for an association between inflammation, malnutrition, renal osteodystrophy, and CC. To assess CC, ultrafast computerized tomogram was obtained for 16 pediatric patients (6 females; median age 17.2 years; range 9.1–21.2 years) receiving hemodialysis for ≥2 months. Inflammation was assessed by serum IL‐6, IL‐8, and C‐reactive protein levels on the day of the computerized tomogram scan; nutrition parameters included serum albumin, cholesterol, the body mass index standard deviation score, and normalized protein catabolic rate. Renal osteodystrophy parameters included time‐averaged serum calcium, phosphorus, total PTH, and calcitriol/calcium dose. Patients received hemodialysis thrice‐weekly; mean single pool Kt/V 1.48±0.13; and mean normalized protein catabolic rate 1.27±0.17 g/kg/day. Five of 16 patients had CC. Patients with CC were older (19.1±2.1 vs. 15.4±3.1 months; P=0.03), had longer dialysis vintage (49.4±15.3 vs. 17.2±10.5 months, P=0.0002), lower serum cholesterol (122±17.7 vs. 160.4±10.6 mg/dL, P=0.02), and higher phosphorus (9.05±1.2 vs. 6.1±0.96 mg/dL, P=0.0001). Mean serum albumin and normalized protein catabolic rate did not differ for patients with CC. All patients had elevated IL‐6 and IL‐8 levels compared with healthy norms; the mean IL‐6, IL‐8, and C‐reactive protein levels were not different in patients with CC. Coronary calcification was prevalent in older children receiving maintenance hemodialysis with a longer dialysis vintage. Worse renal osteodystrophy control and malnutrition (low cholesterol) may contribute to CC development.     

Simple evaluation of aortic arch calcification by chest radiography in hemodialysis patients

Vascular calcification is associated with a poor prognosis in dialysis patients. It can be assessed with computed tomography but simple inoffice techniques may provide useful information. We compared the results obtained with a simple noninvasive technique with those obtained using multidetector computed tomography for aortic arch calcification volume (AoACV) in chronic hemodialysis (HD) patients. The enrolled study subjects were 63 (32 men and 31 women) maintenance HD patients. Calcification of the aortic arch was semiquantitatively estimated with a AoAC score (AoACS) on plain chest radiology. The AoACV was increased, with a mean value of 6.6 ranging from 0% to 36.5%. The coefficient of intraobserver variation was less than 2.5%. Aortic arch calcification score was highly correlated with AoACV (r=0.635, P<0.001). Multiple regression analysis showed age (F value=12.62, P<0.001) and pulse pressure (F value=4.54, P=0.037) to be significant independent determinants of AoACS. In conclusion, a simple measurement of AoACS may be useful for inoffice imaging to choose a therapeutic regimen in HD patients.     

Vascular calcification: Inducers and inhibitors

Unlike the traditional beliefs, there are mounting evidences suggesting that ectopic mineral depositions, including vascular calcification are mostly active processes, many times resembling that of the bone mineralization. Numbers of agents are involved in the differentiation of certain subpopulation of smooth muscle cells (SMCs) into the osteoblast-like entity, and the activation and initiation of extracellular matrix ossification process. On the other hand, there are factors as well, that prevent such differentiation and ectopic calcium phosphate formation. In normal physiological environments, activities of such procalcific and anticalcific regulatory factors are in harmony, prohibiting abnormal calcification from occurring. However, in certain pathophysiological conditions, such as atherosclerosis, chronic kidney disease (CKD), and diabetes, such balances are altered, resulting in abnormal ectopic mineral deposition. Understanding the factors that regulate the formation and inhibition of ectopic mineral formation would be beneficial in the development of tissue engineering strategies for prevention and/or treatment of such soft-tissue calcification. Current review focuses on the factors that seem to be clinically relevant and/or could be useful in developing future tissue regeneration strategies. Clinical utilities and implications of such factors are also discussed.     

A study on sensitivity correction factor of gamma camera in whole body bone image

The aim of this study was to calculate a reasonable correction factor that could be corrected when the sensitivity of each gamma camera is measured and a whole body bone scan is performed as a follow-up examination. Seven pieces of equipment were used to analyse the sensitivity measurements of each gamma camera based on the source sensitivity measurement method recommended by the IAEA. These were BRIGHTVIEW, PRECEDENCE, ECAM, ECAM signature, ECAM Plus, SYMBIA T2 and INFINIA. The ^99mTc line source for the sensitivity measurement was generated in 4–7 kcps, which are the common values in a whole body bone scan. All the cameras were equipped with a low-energy and high-resolution parallel multi-hole collimator and set at a window width and photo peak of 15% and 140 keV, respectively. After placing the ^99mTc source as closely as possible to the collimator, the count was measured for 60 and 120 seconds to calculate correction factor. To determine if the correction factor calculated using the ^99mTc line source could be applied to a whole body bone scan of a real patient, a whole body bone scan was performed on 27 patients before applying the correction factor for comparative analysis. According to the experimental results using the ^99mTc line source, the gamma camera sensitivity was the highest for ECAM plus, followed in order by the gamma cameras, ECAM signature, SYMBIA T2, ECAM, BRIGHTVIEW, INFINIA and PRECEDENCE. When the results were used to calculate the correction factor based on the ECAM gamma camera, which had a medium-degree of sensitivity, the respective correction factors were 1·07, 1·05, 1·03, 1·00, 0·90, 0·83 and 0·72. The correction factors calculated based on the experiment using a ^99mTc line source were similar to those calculated based on the whole body bone scan. Clinical application of correction factor for measured sensitivity enables estimation of factor correction depending on difference in equipment when image is read, which improves accuracy and reliability of examination, and is expected to be used especially for continuous follow-up examination.     

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.     

Dialysate calcium and calcium/phosphate balance in hemodialysis

The changing pattern of pharmaceutical use in dialysis patients has resulted in several alterations to dialysate calcium concentration over the past 40 years. Non‐calcium–containing phosphate binders and calcimimetics are the most recent examples of drugs that influence the overall calcium balance in dialysis patients. Renal osteodystrophy, vascular disease, and mortality are believed to be linked in patients with chronic kidney disease (CKD), although to date most of the evidence is based only on statistical associations. The precise pathophysiology of vascular calcification in end‐stage renal disease is unknown, but risk factors include age, hypertension, time on dialysis, and, most significantly, abnormalities in calcium and phosphate balance. Prospective studies are required before “cause and effect” can be established with certainty, but it is an active metabolic process with inhibitors and promoters. Serum calcium levels are clearly influenced by dialysate calcium and may therefore play an important role in influencing vascular calcification. Clinical management of hyperphosphatemia is being made easier by the introduction of potent non‐calcium–based oral phosphate binders such as lanthanum carbonate. Short‐term and long‐term studies have demonstrated its efficacy and safety. Vitamin D analogs have been a disappointment in the control of serum parathyroid hormone (PTH) levels, but evidence is emerging that vitamin D has other important metabolic effects apart from this, and may confer survival advantages to patients with CKD. Calcimimetics such as cinacalcet enable much more effective and precise control of PTH levels, but at the cost of a major financial burden. While it is unreasonable to expect that any one of these recent pharmacological developments will be a panacea, they provide researchers with the tools to begin to examine the complex interplay between calcium, phosphate, vitamin D, and PTH, such that further progress is fortunately inevitable.     

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.     

Treatment of a soft tissue calcification in a patient receiving peritoneal dialysis

Chronic Kidney Disease patients suffer from Mineral and Bone Disorder (CKD‐MBD) leading to increased vascular and soft‐tissue calcification. The prevalence of soft tissue calcification in dialysis patients is not well described, and most cases describe such calcifications in hemodialysis patients. We describe a case of a massive soft tissue calcification in the right gluteal region in a peritoneal dialysis patient. The patient had severe pain and were disabled. The treatment was converted to an intensive hemodialysis regimen with a minimal calcium load and high dose of cinacalcet. During the treatment, the calcification diminished rapidly from a diameter of 26.6 to 2.9 cm, and the patient symptoms were relieved, leaving the patient with no pain or restriction in mobilization.