|Year : 2015 | Volume
| Issue : 2 | Page : 344-348
|Multiple sites of calciphylaxis in a patient with chronic renal failure
Ramy Magdy Hanna1, Joseph Riad Nabil2, Eduardo A Lopez3, Dalila B Corry1, James Wilson1
1 Department of Medicine, Olive-View UCLA Medical Center; Division of Nephrology, David Geffen School of Medicine, Ronald Regan UCLA Medical Center, Los Angeles, CA, USA
2 Division of Nephrology, David Geffen School of Medicine, Ronald Regan UCLA Medical Center, Los Angeles, USA
3 Department of Medicine, Olive-View UCLA Medical Center, Los Angeles, CA, USA
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|Date of Web Publication||3-Mar-2015|
| Abstract|| |
Calciphylaxis has seldom been reported in patients with acute renal failure or in pre-dialysis patients. It also has been reported at lower calcium phosphorous products and in patients with adynamic bone disease. We report a pre-hemodialysis (HD) patient with acute renal failure and biopsy-proven calciphylaxis involving multiple cutaneous sites with calcification of the perineal area resulting in dry gangrene of the penis that necessitated a partial penectomy. The patient had elevated serum calcium, phosphorous and parathyroid hormone level of 612 pg/mL. The same patient suffered subsequently from a calcium embolus that occluded his left ophthalmic artery and resulted in left eye blindness. Calciphylaxis is a devastating phenomenon and physicians should have a high clinical suspicion for it in HD patients as well as in patients with late stages of chronic kidney disease.
|How to cite this article:|
Hanna RM, Nabil JR, Lopez EA, Corry DB, Wilson J. Multiple sites of calciphylaxis in a patient with chronic renal failure. Saudi J Kidney Dis Transpl 2015;26:344-8
|How to cite this URL:|
Hanna RM, Nabil JR, Lopez EA, Corry DB, Wilson J. Multiple sites of calciphylaxis in a patient with chronic renal failure. Saudi J Kidney Dis Transpl [serial online] 2015 [cited 2020 May 30];26:344-8. Available from: http://www.sjkdt.org/text.asp?2015/26/2/344/152506
| Introduction|| |
Calciphylaxis was once thought to be solely secondary to the precipitation of calcium phosphate crystals in patients with hypercalcemia or hyperphosphatemia. ,,,,, It is now known to be a process of ossification of the arteriolar media muscle layer and is heavily dependent on the expression of the fibroblast growth factor-23 (FGF-23). 
The incidence of calciphylaxis is about 1% for the hemodialysis (HD) and peritoneal dialysis (PD) patients from 2004 to 2006. ,, It is unusual for chronic kidney disease (CKD) patients who have not yet been started on chronic dialysis. However, it has been reported in patients with secondary hyperparathyroidism,  malignancy  or rheumatoid arthritis and no renal dysfunction,  in patients with no known parathyroid disease, renal impairment or malignancy  and in neonates who concomitantly received infusion of ceftriaxone and intravenous calcium-containing solutions. 
The pathophysiology of calciphylaxis is not fully understood. , Clinically, the presentation of calciphylaxis is variable, such as extensive painful distal ulcers that are prone to infection,  rhabdomyolysis,  intravascular calciphylaxis mimicking endocarditis,  temporal arteritis,  pulmonary calcifications  and inflammatory breast cancer.  In general, calciphylaxis presents as an extremely painful violacious plaque. 
Penile calciphylaxis has been reported previously, and this is a urologic emergency as untreated penile calciphylaxis can lead to wet or dry gangrene of the affected site with a mortality rate of 64%. 
Calciphylaxis is typically prevented by avoiding administration of excess calcium and excess active vitamin D, ,, reducing phosphate levels with non-calcium-based phosphate binders and bisphosphoantes (in patients with an adequate glomerular filtration rate) ,, or the use of cinacalcet , or lanthanum carbonate.  Multiple-agent approaches in conjunction with veno-venous HD have been reported to have efficacy in some case reports. ,, Sodium thiosulfate decreases the effects of reactive oxygen species that inhibit Fetuin A, a new approach to the treatment of calciphylaxis, , and hyperbaric oxygen was found to also be helpful.  Finally, hypercoagulability has also been postulated to be a factor in calciphylaxis. 
| Case Report|| |
A 64-year-old Caucasian male presented to our emergency department (ED) on 17 January 2006 complaining of two weeks of severe abdominal pain, three days of anuria and occasional confusion. His past medical history was significant for hypertension on multiple medications, diabetes mellitus on oral medications, congestive heart failure (CHF) with an ejection fraction (EF) of 10-15% and stage III CKD. A review of his records showed multiple admissions for pneumonia, CHF exacerbations and physician notes on dietary non-compliance and occasional medication non-compliance.
His serum creatinine increased acutely from 1.7-1.8 mg/dL from September 2005 [estimated glomerular filtration rate (eGFR) of 38 stage III] to 9.3 mg/dL (an eGFR of 6). The patient denied having any past surgeries or present or past use of alcohol or drugs and his family history was unremarkable. The patient's home medication regimen included Carvedilol 12.5 mg PO BID, Aspirin 325 mg PO Qday, Simvastatin 20 mg PO QHS, Furosemide 80 mg PO QAM and 40 mg PO QPM, Digoxin 0.125 mg PO Qday, Benazepril 40 mg PO Qday and Glipizide 5 mg PO Qday.
The physical exam in the Emergency Department disclosed temperature 35.3°C, blood pressure 138/63 mm Hg, pulse 85 bpm, respirations 16/min and O 2 saturation initially 100% on 2 L O 2 via a nasal cannula. The patient was noted to be alert and oriented times three, but somnolent and falling asleep frequently during the physical exam and medical interview. His pupils were equal, round and reactive to light and accommodation. His oropharynx was noted to be clear and he had no lymphadenopathy. His lungs were initially noted to be clear and his cardiovascular exam was without murmurs, rubs or gallops. His abdominal exam was mainly notable for abdominal distension and ascites, bowel sounds were present and the abdomen was not tender to palpation. The genitourinary exam, however, revealed a well-demarcated 1 cm round violaceous patch at the tip of the glans penis. A Foley catheter was passed through the urethra and a post-void residual (PVR) of 800 mL of urine was obtained. Several necrotic papules were noted on the patient's bilateral lower extremities that were similar to this patch, and severe xerosis of the lower extremities was also noted.
The laboratory investigations showed sodium of 149 mmol/L, potassium of 7.4 mmol/L, Cl of 116 mmol/L, bicarbonate of 10 mmol/L, anion gap of 23 (anion gap corrected for serum albumin of 2.5 was 27.75), blood urea nitrogen of 178 mg/dL, creatinine of 9.3, eGFR of 6 mL/min, glucose of 115 mg/dL, corrected calcium for albumin of 10.2 mg/dL, phosphorous of 13.5 mg/dL and magnesium of 2.8 mg/dL. The calcium phosphorous double product was 121.5 mg 2 /dL 2 . Liver function tests were unremarkable, but albumin was 2.5 mg/dL. His white blood count was14.8 K/μL, hemoglobin was 8.7 g/dL and MCV was 91. There were no reports of shistocytes on the peripheral smear and the coagulation profile was within normal limits.
The urinalysis was unremarkable and the patient's chest X-ray showed cardiomegaly, pulmonary vascular cephalization, old granulomatous calcification and a left pleural effusion.
A renal ultrasound was performed and showed multiple punctuate renal calcifications, perihepatic ascites and a right pleural effusion. The patient's kidneys were of normal size, with the right kidney measuring 10 cm and the left kidney measuring 10.9 cm, but both were abnormally echogenic, consistent with CKD. His testicular ultrasound was performed and showed multiple calcifications in both testes, consistent with microliths.
The patient's human immunodeficiency virus status was checked and was negative. His serological workup, including anti-nuclear antibody, anti-neutrophil cytoplasmic antibody, and hepatitis serologies were all negative. The patient's serum protein electrophoresis and urine protein electrophoresis were negative for monoclonal bands. The parathyroid hormone level was very high at 612, likely due to renal osteodystrophy and secondary hyper-parathyroidism. A sestamibi scan of the parathyroid glands was performed to exclude primary hyperparathyroidism, and showed no evidence of increased uptake in the parathyroid glands.
The punch biopsy of the patient's left lower extremity papular lesions showed calcinosis and the patient's penile biopsy showed gangrene and acute necrotizing inflammation as well as calciphylaxis at the margins. A kidney biopsy showed acute tubular necrosis (ATN) and diabetic glomerulosclerosis without evidence of calciphylaxis.
During his stay in the Emergency Department, the patient became acutely short of breath and had to be intubated and was sent to the Intensive Care Unit for mechanical ventilation. His blood gases test at that time showed a pH of 7.22, a PaO 2 of 26, a PCO 2 of 28 and a bicarbonate level of 11 mmol/L. He was treated for pneumonia and his penile ulcer. Because of the patient's compromised renal function and his severe hyperphosphatemia, hyperkalemia, acidosis and volume overload, a Quinton catheter was placed in his right internal jugular vein and HD was initiated to correct the electrolyte abnormalities and remove fluid. The patient continued to improve. The Foley's catheter relieved the patient's obstruction and his creatinine continued to decrease, his electrolyte abnormalities resolved and his volume status improved. He was extubated on hospital Day 3 and continued to do well. A tunneled HD permacath catheter was placed during this admission. He was evaluated by the urology team who diagnosed him with dry gangrene of the glans penis secondary to calciphylaxis. The gangrenous penile lesion was treated with IV zosyn as an inpatient and PO levaquin as an outpatient.
The patient was scheduled for a partial pencetomy as an outpatient, which was done 5 weeks post-discharge on 7 March 2006. He was eventually discharged with three times a week HD.
He was followed at his local dialysis center when he re-presented to our center with sudden onset of left eye blindness on April 2006. A magnetic resonance imaging/magnetic resonance angiography (MRA) of the brain demonstrated multiple lacunar infarcts but no acute infarct. It did, however, show inflammatory changes in the patient's left optic nerve, consistent with optic nerve ischemia/inflammation. The patient's MRA showed multiple areas of narrowing in the patient's bilateral ACA and MCA arteries and none of the ophthalmic arteries was visualized on the MRA. After an extensive vasculitis workup, which was negative, the neurological consultants felt that a calcium embolus likely resulted in the patient's left optic nerve ischemia/inflammation.
| Discussion|| |
Our patient had sudden onset of calciphylaxis at many sites during his episode of acute on chronic renal failure. It is possible that hypovolemia from diuresis or from a low flow state precipitated his ATN that resulted in fulminant acute renal failure and eventual calciphylaxis. It is also possible that the penile calciphylaxis resulted in a distal urethral obstruction causing a post-renal renal failure, which resulted in the further deterioration of his renal function.
Although his PVR was very high, the absence of hydronephrosis on ultrasound renders the theory of a distal urethral obstruction less tenable, unless it was a very acute obstructive picture that did not have time to cause hydronephrosis. It is very likely that the cause of this acute episode was multifactorial. The patient's treatment centered around immediate HD and reversal of the hyperphoshpatemia and reduction the calcium phosphorous product. Furosemide and non-calcium-based phosphate binders (Sevelamer) were also used to correct the electrolyte abnormalities and maintain normal calcium and phosphate levels.
The patient had multiple sites of calciphylaxis, including the skin of his lower extremities and his glans penis. The management of this patient consisted of addressing his electrolyte abnormalities immediately and infection control with antibiotics, given the fact that his calciphylaxis had caused only dry gangrene. Had he developed wet gangrene or skin necrosis, he would have needed immediate debridement.  The extent of calciphylaxis was rather severe and calcifications were noted grossly in the skin and in the perineum and microliths were noted in the kidneys and testicles. His subsequent embolic calcium stroke was catastrophic and probably resulted from intravascular calcification. Chronic calciphylaxis caused by hyperphosphatemia can also be more insidious and probably has a role to play in the cardiovascular morbidity and mortality as well as many adverse outcomes in CRF patients.  Accordingly, it is crucial to maintain calcium and phosphorous homeostasis to prevent both acute and chronic complications for CKD patients.
Conflict of interest: None declared.
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Dr. Ramy Magdy Hanna
Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA 91342
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