Calciphylaxis in a patient with systemic lupus erythematosus without renal insufficiency or hyperparathyroidism

Calciphylaxis is a frequent entity in patients with chronic renal failure of diverse etiology. The main pathogenic mechanism of calciphylaxis is impairment of either calcium and phosphate metabolism or plasma levels of parathyroid hormone. There are communications of patients with normal renal function, and in some cases with chronic inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus (SLE) and antiphospholipid syndrome. We report a patient with SLE and no renal failure or hyperparathyroidism who developed severe calciphylaxis.     

Successful Treatment of Lung Calciphylaxis With Sodium Thiosulfate in a Patient With Sickle Cell Disease: A Case Report

Calciphylaxis is a small vessel vasculopathy, characterized by medial wall calcification that develops in a few patients with chronic renal failure. The prognosis of skin calciphylaxis has improved considerably since the introduction of sodium thiosulfate (STS), but it remains unclear whether this therapy is effective against organ lesions related to calciphylaxis. Pulmonary calciphylaxis is a usually fatal medical condition that may occur in association with skin involvement in patients with end-stage renal disease.We report here the case of a 49-year-old woman homozygous sickle cell disease patient on chronic hemodialysis with biopsy-proven systemic calciphylaxis involving the lungs and skin. On admission, ulcerative skin lesions on the lower limbs and bilateral pulmonary infiltrates on chest computerized tomography scan were the main clinical and radiological findings. Skin and bronchial biopsies demonstrated calciphylaxis lesions. The intravenous administration of STS in association with cinacalcet for 8 consecutive months led to a clear improvement in skin lesions and thoracic lesions on chest computerized tomography scan.This case suggests for the first time that organ lesions related to calciphylaxis, and particularly lung injury, are potentially reversible. This improvement probably resulted from the combination of 3 interventions (more frequent dialysis, cinacalcet, and STS), rather than the administration of STS alone.     

Mineral metabolism and bone abnormalities in children with chronic renal failure

Abnormalities in mineral metabolism and changes in skeletal histology may contribute to growth impairment in children with chronic renal failure. Hyperphosphatemia, hypocalcemia, metabolic acidosis, alterations in vitamin D and IGF synthesis and parathyroid gland dysfunction play significant roles in the development of secondary hyperparathyroidism and subsequently, bone disease in renal failure. The recent KDIGO conference has made recommendations to consider this as a systemic disorder (chronic kidney disease-mineral bone disorder) and to standardize bone histomorphometry to include bone turnover, mineralization and volume (TMV). The use of DXA to assess bone mass is controversial in children with chronic renal failure. Questions arise regarding the accuracy of bone measurements and difficulty in data interpretation especially in children with renal failure who are not only growth retarded but often have pubertal delay and osteosclerosis. The validity and feasibility of new modalities of skeletal imaging which can detect changes in both trabecular and cortical bone are currently being investigated in children. The management of mineral abnormalities and bone disease in chronic renal failure is multifactorial. To manage hyperphosphatemia, dietary phosphate restriction accompanied by intake of calcium-free and metal-free phosphate binding agents are widely utilized. Vitamin D analogs remain the primary therapy for secondary hyperparathyroidism, although the use of the less hypercalcemic agents is preferred due to concerns of calciphylaxis and vascular calcification. Future clinical studies are needed to evaluate the long-term effects of calcimimetic agents and bisphosphonate therapy in children with chronic renal failure.     

Bone disease in chronic renal failure and its modern therapy

Renal bone disease is one of the most serious complications of chronic renal failure. Secondary hyperparathyreosis is decisive for its pathogenesis. Current prevention and treatment emphasises pathogenetic and clinical interrelationships between bone tissue involvement and cardiovascular complications (CKD-MBD, bone and venous involvement associated with chronic renal disease). The treatment should first correct hyperphosphatemia and, subsequently, hyperreactivity of parathyroid glands through vitamin D receptor (VDR) and calcium receptor (CaR) modulation. Three groups of drugs play a fundamental role here (GIT phosphate binders, calcimimetics and vitamin D receptor activators). Certain other therapeutic approaches are used in some specific situations such as, among others, refractory hyperparathyreosis or calciphylaxis.     

Calciphylaxis: a pseudo-vasculitis syndrome

OBJECTIVES: To report a case of fatal calciphylaxis, an uncommon condition affecting patients with chronic renal disease and calcium metabolism abnormalities, that can mimic vasculitis. METHODS: We reviewed the English literature using the Medline and Embase databases and keywords "calciphylaxis" and "calcific uremic arteriolopathy." RESULTS: A patient with end-stage renal disease and no known calcium metabolism abnormalities presented with intractable lower extremity ulcers and skin findings suggestive of small-vessel disease of the upper extremities. Biopsy of the lesions showed classic calciphylaxis without evidence of vasculitis. The patient died shortly after an above-the-knee amputation. CONCLUSION: Calciphylaxis needs to be considered in the differential diagnosis of vasculitis. Skin biopsy soon after presentation is imperative for diagnosis and to avoid potentially harmful treatments such as corticosteroids and immunosuppressive medications.     

Mysterious calciphylaxis: wounds with eschar--to debride or not to debride?

Calciphylaxis is a confusing disease process that affects people with end-stage renal disease. The prognosis of this increasingly common condition is poor and mortality rates range from 60% to 80% related to wound infection, sepsis, and organ failure. Its presenting sign is skin necrosis related to calcification of the arteriole microvasculature. The disease is painful and debilitating, particularly due to the necrotic wounds. Aggressive wound care to prevent infection is vital when eschar does not protect the wound and drainage is present, but debridement is contraindicated for wounds covered with dry, noninfected eschars. The decision to debride is based on the patient's total clinical picture. Patients with calciphylaxis have poor healing potential due to ischemia and comorbidity factors such as diabetes mellitus, peripheral vascular disease, and obesity. The goal of care is prevention of infection and pain management. Some of the sensitizers and challengers responsible for the chemical imbalance leading to the arteriole calcification, as well as risk factors and clinical manifestations of calciphylaxis, are reviewed. A discussion of treatment focuses on wound care of stable necrotic ulcers and a case report illustrating the progression of calciphylaxis is presented.     

Atypical presentation of calciphylaxis in a patient with renal failure: successful treatment with unfractionated heparin

Calciphylaxis is a rare but serious complication in patients with end-stage renal failure. The condition is associated with high morbidity and mortality. The exact pathogenesis of calciphylaxis and the optimal treatment are still not known. A disturbance of coagulation seems to be relevant in the pathogenesis, and anticoagulation therapy seems to be a rational therapy. Reported herein is a case of calciphylaxis developed in a renal failure patient receiving peritoneal dialysis who was successfully treated with intravenous unfractionated heparin.     

Intestinal ischemia and peripheral gangrene in a patient with chronic renal failure

Gastrointestinal complications are common in patients with renal failure and result in significant morbidity and mortality. Systemic calciphylaxis is an uncommon complication of renal failure, characterized by disseminated intravascular calcification and associated with progressive vascular compromise. We describe the case of a 63-year-old woman who presented with abdominal pain, elevated transaminases, and skin manifestations consistent with a vasculitic process. Hand films and skin biopsies showed extensive vascular calcification, and a computerized tomography scan confirmed colonic perforation and disseminated visceral vascular calcification. Histologic analysis of the resected skin and colonic tissues revealed extensive ischemic damage and mural calcification of medium to large vessels. Gastrointestinal involvement has been reported in only 3 prior cases of calciphylaxis; consequently, gastroenterologists are often unaware of this disease entity and may fail to recognize it, even in patients with the classical presentation. Prompt diagnosis is crucial, as parathyroidectomy may result in clinical improvement in up to two thirds of patients who present with elevated parathyroid hormone levels.     

Calciphylaxis: a rare differential diagnosis of systemic vasculitis

INTRODUCTION: Calciphylaxis is a rare phenomenon of medium- and small-vessel calcifications leading to cutaneous necrosis mimicking vasculitis. CASE REPORT: A 75 year-old-woman with chronic renal insufficiency was admitted for extensive cutaneous necrosis of the limb. Diagnosis of vasculitis was made, but inspite of corticosteroid therapy, the condition of the patient was worsening. After cutaneous biopsy, the diagnosis of calciphylaxis was established. CONCLUSION: Calciphylaxis must be suspected in cases of cutaneous necrosis occurring in a patient with chronic renal failure. Treatment requires rapid normalization of phosphocalcic balance. It is a condition with high mortality.     

Heparin-induced thrombocytopenia complicating hemodialysis

Hemodialysis complicated by heparin-induced thrombocytopenia (HIT) is a rare event requiring anticoagulation with direct-thrombin inhibitors. Contaminant calcific uremic arteriolopathy (calciphylaxis) further complicates this situation due to the possibility that warfarin anticoagulation may exacerbate skin necrosis. The authors report a patient with renal failure and calciphylaxis who developed HIT after starting hemodialysis. She was successfully treated with Argatroban.     

Calciphylaxis from Nonuremic Causes: A Systematic Review

Background and objectives: Calciphylaxis, or calcific uremic arteriolopathy, is a well-described entity in end-stage kidney disease and renal transplant patients; however, little systematic information is available on calciphylaxis from nonuremic causes. This systematic review was designed to characterize etiologies, clinical features, laboratory abnormalities, and prognosis of nonuremic calciphylaxis.Design, setting, participants, & measurements: A systematic review of literature for case reports and case series of nonuremic calciphylaxis was performed. Cases included met the operational definition of nonuremic calciphylaxis–histopathologic diagnosis of calciphylaxis in the absence of end-stage kidney disease, renal transplantation, or acute kidney injury requiring renal replacement therapy.Results: We found 36 cases (75% women, 63% Caucasian, aged 15 to 82 yr) of nonuremic calciphylaxis. Primary hyperparathyroidism, malignancy, alcoholic liver disease, and connective tissue disease were the most common reported causes. Preceding corticosteroid use was reported for 61% patients. Protein C and S deficiencies were seen in 11% of patients. Skin lesions were morphologically similar to calcific uremic arteriolopathy. Mortality rate was 52%, with sepsis being the leading cause of death.Conclusion: Calciphylaxis should be considered while evaluating skin lesions in patients with predisposing conditions even in the absence of end-stage kidney disease and renal transplantation. Nonuremic calciphylaxis is reported most often in white women. Mineral abnormalities that are invoked as potential causes in calcific uremic arteriolopathy are often absent, suggesting that heterogeneous mechanisms may contribute to its pathogenesis. Nonuremic calciphylaxis is associated with high mortality, and there is no known effective treatment.Calciphylaxis, or calcific uremic arteriolopathy (CUA), is a rare but well-described entity in end-stage kidney disease (ESKD) and in renal transplant patients. Prevalence of CUA has been reported as 4% in hemodialysis patients (1), and the incidence of this disorder may be increasing in patients with ESKD (2). The reasons for the increasing incidence of CUA are unclear. Although abnormal bone and mineral metabolism, hyperparathyroidism, and vitamin D therapy are often assumed to contribute to CUA, the mechanisms of disease are poorly understood; therefore, therapeutic strategies are of unproven benefit, and mortality remains high.Calciphylaxis has also been reported in patients without ESKD; however, little systematic information is available on calciphylaxis from nonuremic causes. We performed a systematic review of calciphylaxis from nonuremic causes (NUC) to characterize the etiologies, clinical features, laboratory abnormalities, and prognosis of NUC. Detailed exploration of the clinical features of NUC could help inform further understanding of CUA.     

Abnormalities of endothelial function in patients with predialysis renal failure

BACKGROUND: Endothelial dysfunction plays an important role in the development of atherosclerotic vascular disease, which is the leading cause of mortality in patients with chronic renal failure. OBJECTIVE: To examine the relation between predialysis renal failure and endothelial function. DESIGN: Two groups were studied: 80 patients with non-diabetic chronic renal failure and 26 healthy controls, with similar age and sex distributions. Two indices of endothelial function were assessed: high resolution ultrasonography to measure flow mediated endothelium dependent dilatation of the brachial artery following reactive hyperaemia, and plasma concentration of von Willebrand factor. Endothelium independent dilatation was also assessed following sublingual glyceryl trinitrate. The patients were divided into those with and without overt atherosclerotic vascular disease. RESULTS: Although patients with chronic renal failure had significantly impaired endothelium dependent dilatation compared with controls (median (interquartile range), 2.6% (0.7% to 4.8%) v 6.5% (4.8% to 8.3%); p < 0.001) and increased von Willebrand factor (254 (207 to 294) v 106 (87 to 138) iu/dl; p < 0.001), there was no difference between renal failure patients with and without atherosclerotic vascular disease. Within the chronic renal failure group, endothelium dependent dilatation and von Willebrand factor were similar in patients in the upper and lower quartiles of glomerular filtration rate (2.7% (0.7% to 6.7%) v 2.8% (1.1% to 5.0%); and 255 (205 to 291) v 254 (209 to 292) iu/dl, respectively). Endothelium independent dilatation did not differ between the renal failure or control groups and was also similar in patients with renal failure irrespective of the degree of renal failure or the presence of atherosclerotic vascular disease. CONCLUSIONS: Endothelial function is abnormal in chronic renal failure, even in patients with mild renal insufficiency and those without atherosclerotic vascular disease, suggesting that uraemia may directly promote the development of atherosclerosis early in the progression of chronic renal failure.     

Kalzium-Phosphat- und Knochenstoffwechsel

Renal osteodystrophy reflects a network of highly complex cellular components, and regulatory molecules, such as locally acting mediators including those revealing osteogenic, osteoclastic, calcifying and anti-calcification properties, which also interfere with cytokines. At present calcium phosphate metabolism due to chronic renal failure much more concerns problems of heterotopic calcification resulting in an increased cardiovascular morbidity and mortality, and accelerated arteriosclerosis (e.g. by transdifferentiation of vascular smooth muscles cells) than instability of bone structures. The most dangerous complication resulting from disturbed calcium phosphate metabolism is calciphylaxis. In this article the parameters considered standard are analyzed for their applicability to determination of bony metabolism.     

Role of hypertension on the progression of renal disease in man

The effects of hypertension on the course of early chronic renal failure were evaluated in 233 patients with renal disease of diverse etiology, followed for 12-166 months (mean 51.35) on protein-restricted diet. On entry, 174 patients (74.6%) were hypertensive and 59 (25.4%) were normotensive. Serum creatinine levels rose from 2.40 +/- 1.11 to 4.84 +/- 3.26 mg/dl in the overall population. Deterioration of renal function was more evident in hypertensives (percent increase in serum creatinine 112.8, monthly increase 0.053 mg/dl) than in normotensives (percent increase 70.9, monthly increase 0.032 mg/dl). This difference, however, was not statistically significant. Progression of renal failure was significantly faster in hypertensive than in normotensive patients in the groups of polycystic kidney disease and chronic renal failure of unknown etiology. The actuarial renal survival probability at 72 months was 77% in normotensives and 47% in hypertensives. Among the 84 patients (36.1%) who had a fast deterioration of renal failure, 71 (84.5%) were hypertensive. In conclusion, hypertension seems to play an important role in worsening the prognosis of patients with renal parenchymal disease and early chronic renal failure. It is still difficult to separate the exact role of hypertension from the constellation of pathogenetic factors (such as the underlying renal disease, the magnitude and duration of proteinuria, the inadequate dietary contents of protein and phosphate) which may affect the progression of chronic renal disease in man.     

Systemic lupus erythematosus and calciphylaxis

Calciphylaxis, a rare condition seen in association with endstage renal disease, is characterized by the appearance of painful, indurated plaques, ecchymosis, ulceration, and eschar formation. We describe a patient with systemic lupus erythematosus, endstage renal disease, and skin lesions first diagnosed as lupus profundus with vasculitis. Further investigation confirmed the diagnosis of extensive calciphylaxis.     

Effect of race on expression of acquired immunodeficiency syndrome-associated nephropathy

The prevalence of renal disease associated with the acquired immunodeficiency syndrome (AIDS) is unknown, but appears to vary in different regions. Centers in New York, NY, and Miami, Fla, have reported patients with renal disease complicating AIDS. These populations have included large proportions of black patients and intravenous drug abusers. Reports from San Francisco, Calif, have suggested the prevalence of renal disease complicating AIDS is low, but the population was composed primarily of white patients, with a low proportion of drug abusers. The George Washington University Medical Center was the site of treatment for 31.4% of the patients with AIDS in Washington, DC. This population was split roughly evenly between black and white patients. A retrospective survey of patients with both AIDS and renal disease revealed approximately two thirds of the patients were black, reflecting the demographics of the population with AIDS; 11% of patients had intravenous drug abuse as a risk factor for the development of AIDS; and 74% had acute renal failure. Of these patients, approximately equal proportions were black and white. Twenty-six percent of the population had chronic renal failure, but the overwhelming proportion were black. There were no differences between proportions of patients in age, sex, race, or risk factors in patients with acute renal failure and chronic renal failure, but there was a significant difference in the proportions of black and white patients with chronic renal failure. The reason for these differences is unknown, but differences in host responses to viral proteins, physiologic adaptations, or socioeconomic factors in these populations may play an important role in mediating the expression of renal disease in individual patients.     

Role of secondary hyperparathyroidism and liver function in hyperamylasemia in chronic renal failure

Elevated values of pancreatic-type amylase activity in serum were found in 59% of patients with liver cirrhosis not complicated with renal failure, in 67% of patients with chronic renal failure not complicated with hepatopathy and in 95% of patients with chronic renal failure complicated with hepatopathy. In all the three groups, a significant positive correlation was found between the pancreatic-type amylase and intestinal isoenzyme of serum alkaline phosphatase which is an asialoglycoprotein. However, in pancreatitis a prevalence of an increase in pancreatic-type amylase with respect to intestinal alkaline phosphatase was found. A multivariate analysis showed that in chronic renal failure not complicated with hepatopathy, and in chronic renal failure complicated with chronic liver disease, the changes in calcium homeostasis and also the liver disorder, respectively, contribute significantly to the above-normal values for pancreatic-type amylase.     

Acute renal failure in hospitalized patients with HIV: risk factors and impact on in-hospital mortality

BACKGROUND: Kidney disease is an increasingly important complication of HIV. OBJECTIVES: To examine the incidence and predictors of acute renal failure before and after the introduction of HAART, and the impact of acute renal failure on in-hospital mortality in the post-HAART era. METHODS: Adults hospitalized in acute care hospitals in New York State during 1995 (pre-HAART) or 2003 (post-HAART) were identified from the state Planning and Research Cooperative System database. HIV status was defined by primary or secondary diagnosis code. The impact of HIV and HAART on the incidence of acute renal failure and mortality, and the impact of acute renal failure on mortality, was assessed using chi analysis and multivariate regression. RESULTS: There were 52,580 HIV-infected patients discharged from hospital in 1995 and 25,114 in 2003. Compared with uninfected patients, HIV-infected patients had an increased incidence of acute renal failure in both the pre-HAART [adjusted odds ratio (OR), 4.62; 95% confidence interval (CI), 4.30-4.95] and post-HAART eras (adjusted OR, 2.82; 95% CI, 2.66-2.99). In the post-HAART cohort, acute renal failure was associated with traditional predictors such as age, diabetes mellitus, and chronic kidney disease, as well as acute or chronic liver failure or hepatitis coinfection (P < 0.001 for all comparisons). Acute renal failure was associated with mortality among HIV-infected patients in the post-HAART era (OR, 5.83; 95% CI, 5.11-6.65). CONCLUSIONS: Acute renal failure remains common among hospitalized patients with HIV and is associated with chronic kidney disease, liver disease, and increased mortality.     

Gastric mucosal prostaglandin E2 levels in gastric non-ulcer and ulcer patients with chronic renal failure or without renal disease, and in healthy subjects

Investigations were carried out as to whether a disturbance in the formation of cytoprotective prostaglandin (PG) E2 in gastric mucosa is implicated in chronic renal failure. PGE2-like immunoactivity in gastric mucosal specimens was measured in individuals with chronic renal failure (creatine clearance less than 10 ml/min), in individuals without any renal disease, presenting either gastric ulceration or not, as well as in healthy subjects. Regardless of the group of patients, compared to normal mucosa a significant decrease in PGE2-like immunoactivity (about 50-70%) was found in mucosa from atrophic gastritis but not from superficial gastritis. Whenever patients of the control group or patients with kidney disease suffered from ulcers, PGE2-like immunoactivity showed a decrease of about 60-70% in the non-ulcerated mucosa compared to that of non-ulcer subjects. Moreover, ulcer patients showed the same frequency of gastritis and similar mucosal PGE2-like immunoactivity in their non-ulcerated mucosa. Furthermore, compared to the tissue from the ulcer edge, independent of the presence of renal disease, a relative deficiency of PGE2-like immunoactivity of about 50-60% was detected in the non-ulcerated mucosa of ulcer patients. We therefore conclude that chronic renal failure probably has no impact on PGE2 formation in the gastric mucosa. All told, relative mucosal PGE2 deficiency in gastric ulcer disease seems not to be correlated with chronic renal failure.     

Quantifying a Rare Disease in Administrative Data: The Example of Calciphylaxis

BACKGROUND

Calciphylaxis, a rare disease seen in chronic dialysis patients, is associated with significant morbidity and mortality. As is the case with other rare diseases, the precise epidemiology of calciphylaxis remains unknown. Absence of a unique International Classification of Diseases (ICD) code impedes its identification in large administrative databases such as the United States Renal Data System (USRDS) and hinders patient-oriented research. This study was designed to develop an algorithm to accurately identify cases of calciphylaxis and to examine its incidence and mortality.

DESIGN, PARTICIPANTS, AND MAIN MEASURES

Along with many other diagnoses, calciphylaxis is included in ICD-9 code 275.49, Other Disorders of Calcium Metabolism. Since calciphylaxis is the only disorder listed under this code that requires a skin biopsy for diagnosis, we theorized that simultaneous application of code 275.49 and skin biopsy procedure codes would accurately identify calciphylaxis cases. This novel algorithm was developed using the Partners Research Patient Data Registry (RPDR) (n?=?11,451 chronic hemodialysis patients over study period January 2002 to December 2011) using natural language processing and review of medical and pathology records (the gold-standard strategy). We then applied this algorithm to the USRDS to investigate calciphylaxis incidence and mortality.

KEY RESULTS

Comparison of our novel research strategy against the gold standard yielded: sensitivity 89.2 %, specificity 99.9 %, positive likelihood ratio 3,382.3, negative likelihood ratio 0.11, and area under the curve 0.96. Application of the algorithm to the USRDS identified 649 incident calciphylaxis cases over the study period. Although calciphylaxis is rare, its incidence has been increasing, with a major inflection point during 2006–2007, which corresponded with specific addition of calciphylaxis under code 275.49 in October 2006. Calciphylaxis incidence continued to rise even after limiting the study period to 2007 onwards (from 3.7 to 5.7 per 10,000 chronic hemodialysis patients; r?=?0.91, p?=?0.02). Mortality rates among calciphylaxis patients were noted to be 2.5–3 times higher than average mortality rates for chronic hemodialysis patients.

CONCLUSIONS

By developing and successfully applying a novel algorithm, we observed a significant increase in calciphylaxis incidence. Because calciphylaxis is associated with extremely high mortality, our study provides valuable information for future patient-oriented calciphylaxis research, and also serves as a template for investigating other rare diseases.