ABSTRACT
BACKGROUND: Immune-mediated necrotizing myopathy (IMNM) is a newly identified subgroup of idiopathic inflammatory myopathies. It is defined as a rare and severe disease, with symmetrical and proximal muscle weakness and a characteristic histology. An autoimmune aspect of IMNM is suggested by its association with autoantibodies directed against signal recognition particle (SRP) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in the majority of patients. Statin use is strongly associated with anti-HMGCR-positive IMNM. The pathophysiological mechanisms of this disease are still poorly understood, and as a result, no therapeutic strategy has been validated to date. OBJECTIVE: The aim of this article is to provide an overview of the current knowledge about epidemiology, clinical features, and pathophysiology of IMNM, as well as treatment strategies. RESULTS AND CONCLUSION: IMNM is a subject of widespread interest, with quick and meaningful advances being made. In recent years, huge progress has been made in terms of diagnosis and patient management. However, the understanding of pathophysiological mechanisms and treatment strategies still requires further investigation.
Subject(s)
Autoimmune Diseases/diagnosis , Autoimmune Diseases/drug therapy , Myositis/diagnosis , Myositis/drug therapy , Autoimmune Diseases/epidemiology , Evidence-Based Medicine , Germany/epidemiology , Humans , Immunosuppressive Agents/therapeutic use , Myositis/epidemiology , Prevalence , Rare Diseases/diagnosis , Rare Diseases/epidemiology , Rare Diseases/therapy , Treatment OutcomeABSTRACT
BACKGROUND: Secondary hyperparathyroidism (SHPT) is a relevant problem in patients undergoing dialysis, and cinacalcet hydrochloride seems to be the best option for controlling it. After kidney transplantation (KTx), moderate to severe SHPT may persist and cause hypercalcemia and hypophosphatemia, among other deleterious effects. The number of patients receiving cinacalcet before KTx is increasing. OBJECTIVE: To evaluate the evolution of calcemia, phosphatemia, and intact parathyroid hormone (iPTH) after KTx in patients with SHPT receiving cinacalcet on dialysis. PATIENTS AND METHODS: The study included 19 patients (15 men and 4 women; mean [SD] age, 52 [13] years) undergoing dialysis and receiving cinacalcet before KTx. Mean duration of dialysis before KTx was 33 (25) months, and cinacalcet dose was 45 (15) mg/d. Creatinine, calcium, phosphorus, alkaline phosphatase, and iPTH concentrations were evaluated at baseline (day of surgery), at 15 days after surgery, and then monthly for 6 months. In all patients, cinacalcet therapy was discontinued on the day of surgery. RESULTS: After the first month post-KTx, mean (SD) serum creatinine concentration was 1.6 (0.4) mg/dL and remained stable during follow-up. Calcium and phosphorus concentrations were normal in 13 patients after KTx; however, in 6 patients, hypercalcemia (calcium concentration, 11 [1.3] mg/dL) or hypophosphatemia (phosphorus concentration, 1.7 [0.6] mg/dL) developed, with iPTH concentration of 557 (400) pg/mL and alkaline phosphatase concentration of 307 (114) IU/mL. Treatment with cinacalcet resulted in correction of calcium and phosphorus concentrations (10.1 [0.4] mg/dL and 1.7 [0.7] mg/dL, respectively). Patients in whom hypercalcemia or hypophosphatemia developed were receiving cinacalcet, 60 mg/d or more, during dialysis therapy. Patients who received cinacalcet, 30 mg/d, before KTx did not exhibit hypercalcemia or hypophosphatemia after KTx. CONCLUSION: In patients with HPT undergoing dialysis and receiving cinacalcet, 60 mg/d or more, this drug therapy should be continued after KTx to avert development of hypercalcemia or hypophosphatemia.
Subject(s)
Hyperparathyroidism, Secondary/drug therapy , Kidney Transplantation/physiology , Naphthalenes/therapeutic use , Renal Replacement Therapy/adverse effects , Adult , Aged , Alkaline Phosphatase/blood , Calcium/blood , Cinacalcet , Creatinine/blood , Female , Humans , Hypercalcemia/drug therapy , Hypercalcemia/etiology , Hyperparathyroidism, Secondary/epidemiology , Hyperparathyroidism, Secondary/etiology , Hypophosphatemia/drug therapy , Hypophosphatemia/etiology , Hypophosphatemia/prevention & control , Incidence , Kidney Transplantation/adverse effects , Male , Middle Aged , Prospective Studies , Time Factors , Treatment OutcomeABSTRACT
Persistent hyperparathyroidism is the most frequent cause of hypercalcemia after renal transplantation, namely, hypercalcemia is observed in about 10% of patients at 1 year. This prospective study evaluated the effect of cinacalcet, a second-generation calcimimetic, on serum calcium and parathyroid hormone (PTH) blood levels among recipients with hypercalcemia due to persistent hyperparathyroidism. Thirteen renal transplanted patients (10 women and 3 men) were included based upon: a total serum calcium >10.5 mg/dL; intact PTH (iPTH) blood levels >65 pg/mL; graft function >6 months, and stable maintenance immunosuppressive therapy. After inclusion, patients initially received 30 mg of cinacalcet once daily. The mean time of initiation was 64 +/- 7 months after transplantation. The follow-up was 6 months. The median dose of cinacalcet was 30 mg/d (5 patients received 60 mg/d). During the study period, renal function remained stable. Serum calcium levels decreased significantly from 11.7 +/- 0.39 to 10.35 +/- 0.8 mg/dL (P < .001). Serum phosphate levels increased from 2.82 +/- 0.34 mg/dL to 3.2 +/- 0.41 mg/dL (P < .05). The mean iPTH levels significantly decreased from 308 +/- 120 to 210 +/- 80 pg/mL (P < .05). There were no significant change in 25-hydroxyvitamin D3 blood levels (from 17.7 +/- 9 to 17.4 +/- 6 ng/mL), but the 1,25-dihydroxyvitamin D3 blood levels decreased from 53.8 +/- 18.2 to 32.6 +/- 9.2 pg/mL (P < .01). There were no significant changes in blood levels of alkaline phosphatase, magnesium, bicarbonate, calciuria, phosphaturia, and immunosuppressive drugs. Cinacalcet was well tolerated in all patients except one who had gastrointestinal discomfort. In summary, cinacalcet corrected hypercalcemia and improved phosphatemia in patients with persistent hyperparathyroidism after transplantation with no negative effects on renal function.
Subject(s)
Hypercalcemia/prevention & control , Hyperparathyroidism, Secondary/drug therapy , Kidney Failure, Chronic/complications , Kidney Transplantation/adverse effects , Naphthalenes/therapeutic use , Adult , Cinacalcet , Female , Humans , Hypercalcemia/etiology , Male , Middle Aged , Patient Selection , Prospective StudiesABSTRACT
We report a case of renal cell carcinoma that had manifested as massive retroperitoneal hemorrhage in the second trimester of pregnancy. The diagnosis was made on the basis of the clinical and ultrasound findings. The patient was submitted to unilateral nephrectomy at 27 wk of gestation and she delivered by cesarean section at 35 wk gestation. Both mother and infant are well 1 year postoperatively.
Subject(s)
Carcinoma, Renal Cell/diagnosis , Hemorrhage/diagnosis , Kidney Neoplasms/diagnosis , Pregnancy Complications, Neoplastic/diagnosis , Adult , Carcinoma, Renal Cell/complications , Carcinoma, Renal Cell/surgery , Diagnosis, Differential , Female , Hemorrhage/etiology , Hemorrhage/surgery , Humans , Kidney Neoplasms/complications , Kidney Neoplasms/surgery , Nephrectomy , Pregnancy , Pregnancy Complications, Neoplastic/surgery , Retroperitoneal SpaceABSTRACT
We studied the behaviour of 56 clinical isolates of Pseudomonas aeruginosa strains against the following beta-lactam antibiotics: cefotaxime, cefoperazone, cefsulodin, lamoxactam, Ro 13-9904, azlocillin, mezlocillin and ticarcillin. Twenty-six strains were resistant to gentamicin and 30 to gentamicin and/or carbenicillin. The MICs were measured by the serial dilution test on solid agar. Cefsulodin was the most active cephalosporin against carbenicillin-resistant strains (MIC greater than or equal to 128 mg/l); it inhibited 56.6% of these strains at a concentration of 8 mg/l. Azlocillin was the most active penicillin, inhibiting 79.96% of the same strains at a concentration of 64 mg/l. Cefsulodin was the most active cephalosporin against the gentamicin-resistant group of Pseudomonas aeruginosa strains (MIC greater than or equal to 8 mg/l) which were sensitive to carbenicillin (MIC less than or equal to 64 mg/l). It inhibited 100% of the strains at a concentration of 4 mg/l. All of the penicillins studied inhibited all of the strains in this group. The required concentrations were the following: 16 mg/l for azlocillin, 32 mg/l for mezlocillin and 64 mg/l for ticarcillin.