Richard D. Swartz

Nephrogenic fibrosing dermopathy: a novel cutaneous fibrosing disorder in patients with renal failure

BACKGROUND Nephrogenic fibrosing dermopathy is a newly recognized cutaneous fibrosing disorder marked by the acute onset of induration involving the upper and lower limbs in patients with acute or chronic renal failure. The etiology, pathogenesis, associated clinical conditions (other than renal failure), and ultimate course have not been defined in the few cases studied. Presently, there is no effective treatment, and the condition persists in most patients. METHODS Clinical and histopathologic data on 13 patients from our institution with the diagnosis of nephrogenic fibrosing dermopathy were reviewed. Several clinical and laboratory parameters were examined to see if any were consistently associated with the disease. Biopsy specimens were analyzed to determine if there was a pattern to the evolution of fibrosis in these patients. RESULTS All 13 patients had renal failure before disease onset: 8 were undergoing chronic hemodialysis, 2 were undergoing chronic peritoneal dialysis, and 3 with acute renal failure had never undergone dialysis before the development of dermopathy. Most patients had other serious underlying medical conditions. Many patients were taking erythropoietin, cyclosporine, or both before the onset of disease. In transplant patients, no histocompatibility antigens were found to be associated with the disease. There were various laboratory abnormalities, but none were consistently associated with the condition. In skin biopsy specimens taken 7 to 180 days after disease onset, there were histopathologic changes suggestive of a tissue reaction to injury, as well as the development of smooth muscle actin-positive myofibroblasts. CONCLUSION Nephrogenic fibrosing dermopathy is a novel cutaneous fibrosing disorder that is distinguished from other sclerosing or fibrosing skin disorders by distinctive clinical and histopathologic findings occurring in the setting of renal failure. There were no additional clinical risk factors or laboratory findings common to the 13 patients studied, other than renal failure. The resemblance to a tissue injury reaction and the presence of myofibroblasts in the tissue specimens suggest that fibrogenic cytokines may be involved in the evolution of the disease.

Renal failure following major angiography

Acute renal failure following angiography with contrast agents is known to occur, but the circumstances and frequency of its occurrence are not well described. A retrospective review of consecutive angiographic procedures performed over a six month interval revealed a 12 per cent incidence of renal failure following angiography. The degree of failure was severe in approximately 30 per cent of these cases and was associated with a significant mortality even though renal function usually recovered. The occurrence of renal failure was associated with the presence of renal insufficiency, impaired liver function, diabetes mellitus, hypoalbuminemia and proteinuria at the time of angiography to a statistically significant level. Furthermore, combinations of these factors, particularly preexisting combined renal insufficiency and impaired liver function, were associated with an increased incidence of acute renal failure. It is concluded that angiography poses a significant hazard to patients with underlying medical problems, particularly those involving the excretory routes of the contrast agent.

Comparing continuous hemofiltration with hemodialysis in patients with severe acute renal failure.

Continuous venovenous hemofiltration (CVVH) or CVVH with additional diffusive dialysis (CVVH-D) has theoretical advantages in treating severe acute renal failure (ARF), but no prospective clinical trials or restrospective comparison studies have clearly shown its superiority over intermittent hemodialysis (HD). To evaluate this question, all 349 adult patients with ARF receiving renal replacement therapy (RRT) at our medical center during 1995 and 1996 were analyzed using multivariate Cox proportional hazards methods. Initial univariate analysis showed the odds of death when receiving initial CVVH to be more than twice those when receiving initial HD (risk for death, 2.03; P < 0.01). Progressive exclusion of patients in whom the RRT modality might not be open to choice and the risk for death was very high (systolic blood pressure < 90 mm Hg; total bilirubin level > 15 mg/dL; or total RRT < 48 hours) for total RRT left 227 patients in whom the risk for death was 1.09 (95% confidence interval [CI], 0.67 to 1.80; P = 0.72) for initial CVVH, virtually equivalent to the risk for initial HD. Comorbid indicators significantly associated with death or failure to recover renal function included: older age; medical rather than surgical diagnosis; preexisting infection or trauma and liver disease as primary diagnoses; and abnormal bilirubin level or vital signs at initiation of RRT. These results show that the high crude mortality rate of patients undergoing CVVH was related to severity of illness and not the treatment choice itself. With the addition of more inclusive comorbidity data and a broader spectrum of interim outcomes, this type of analysis is a practical alternative to what would almost assuredly be a cumbersome and costly prospective, controlled trial comparing traditional HD with CVVH.

Nephrogenic Systemic Fibrosis: A Report of 29 Cases

OBJECTIVE The purpose of this study was to determine the incidence of nephrogenic systemic fibrosis and its relation to renal failure and the administration of gadolinium-based contrast material at an academic medical center. MATERIALS AND METHODS A dermatopathology database was searched to identify patients in whom nephrogenic systemic fibrosis was diagnosed. The medical records of these patients were reviewed. Renal function concurrent with any administration of gadolinium-based contrast material was assessed, as was patient outcome. A database of patients undergoing long-term dialysis was reviewed separately to determine how many had received gadolinium and the frequency of nephrogenic systemic fibrosis among these patients. RESULTS Twenty-nine patients were found to have had nephrogenic systemic fibrosis between November 15, 1999, and December 31, 2006. It was known that gadolinium-based contrast material had been administered to 25 of these patients before diagnosis. All 29 patients had compromised renal function (27 had chronic renal failure, and two had acute renal failure). Determination of the temporal relation between gadolinium-based contrast administration and symptom onset often was difficult. Only eight patients had severe morbidity. Nephrogenic systemic fibrosis developed in 12 (2.9%) of 414 patients undergoing long-term dialysis who received gadolinium-based contrast material. CONCLUSION We confirm the strong association between nephrogenic systemic fibrosis and gadolinium-based contrast administration. Although the use of high doses of gadolinium and the occurrence of chronic renal failure have been implicated in other reports, several of our patients received standard doses of gadolinium, and two had transient acute renal failure before diagnosis. Most patients had mild or moderate symptoms. Nephrogenic systemic fibrosis developed in 2.9% of patients undergoing long-term dialysis who received gadolinium-based contrast material but in none of the long-term dialysis patients who did not receive gadolinium-based contrast material.

Severe acetaminophen toxicity in a patient receiving isoniazid

A woman who was being treated with isoniazid developed life-threatening hepatic and renal toxicity after ingesting not more than 11.5 g of acetaminophen. We believe the toxicity may have resulted f...

Hemorrhage during High-Risk Hemodialysis Using Controlled Heparinization

The risk of worsening or commencement of bleeding in high-risk patients requiring hemodialysis has not been established. The present study of 300 dialyses in 51 patients with prospectively assessed increased risk for bleeding describes a method for limiting heparin administration by using the thrombin clotting time to assess heparin sensitivity before dialysis and to monitor heparin levels during dialysis. The procedure prevented clotting in the extracorporeal device and limited bleeding complications to 5% of cases overall. Patients with a higher risk for hemorrhage had a higher incidence of bleeding complication (26%), a larger fall in hematocrit, and more frequent requirement for blood replacement. We conclude that although hemodialysis poses a risk for actively bleeding patients, patients at risk but without active bleeding can be dialyzed with strict control of heparin administration.

Idiopathic Retroperitoneal Fibrosis: A Review of the Pathogenesis and Approaches to Treatment

Idiopathic retroperitoneal fibrosis (IRPF) is an increasingly recognized syndrome. The development of inflammation and fibrosis in the retroperitoneum most often results in a periaortic mass on computed tomography or magnetic resonance imaging that causes pain and constitutional symptoms. Its organ involvement results in urinary tract obstruction, bowel dysfunction, and venous compression with leg swelling, or thrombosis. The syndrome appears autoimmune in nature, but has no specific immunologic markers. However, nonspecific inflammatory indicators, such as sedimentation rate and C-reactive protein level, reflect disease activity and therapeutic response. Retroperitoneal fibrosis also can arise secondary to inflammatory, infectious, or malignant disease in retroperitoneal organs, in which case treatment is directed at the primary process. However, in patients with IRPF, initial treatment of the local mechanical complications must be followed by medical therapy with corticosteroids or, more recently, the addition of steroid-sparing agents. Although there are no controlled therapeutic trials, a number of reports with as few as 3 or as many as 28 cases describe sustained and effective steroid-sparing treatment with cyclophosphamide, azathioprine or colchicine, or such newer agents as mycophenolate mofetil or tamoxifen. Overall, IRPF responds to corticosteroid therapy initially but recurs without prolonged treatment. Sustained remission can be attained with steroid-sparing treatment. Kidney function can be preserved, and local organ dysfunction can remit for periods of 10 years or more. Although not randomized or controlled, the evidence convincingly supports a combination of initial surgical or urological intervention, along with early corticosteroid therapy for up to 6 months followed by either mycophenolate or tamoxifen for 1 to 3 years. What was previously believed to be an uncommon and challenging syndrome can be treated successfully when recognized by its characteristic presentation.

Chronic Peritoneal Dialysis: Mechanical and Infectious Complications

The present report summarizes the mechanical and infectious complications attributable to the devices and procedures used for chronic peritoneal dialysis (PD), comparing the type and frequency of such complications in contemporaneous groups of patients undergoing continuous ambulatory PD (CAPD) or intermittent PD (IPD). Mechanical complications related directly to the catheter and its placement proved to be equally frequent during CAPD and IPD. On the other hand, mechanical complications related to increased intraperitoneal pressure were more frequent during CAPD. In most instances mechanical complication can be managed without permanent interruption of chronic PD. Peritonitis occurs more frequently during CAPD (1.6 episodes per patient-year) than during IPD (0.4 episodes per patient-year), with a tendency to more frequent peritonitis among diabetics, children, patients with white blood cell abnormalities, patients with catheter cuff or tunnel inflammation, and during the 1st month of treatment. Medical therapy eradicates peritonitis and allows continuation of chronic PD with retention of the catheter in more than 90% of episodes, although special problems may be encountered with fungal, pseudomonal, and some coagulase-positive staphylococcal infections.

Intraleukocytic sequestration as a cause of persistent Staphylococcus aureus peritonitis in continuous ambulatory peritoneal dialysis

Peritonitis caused by Staphylococcus aureus in four patients undergoing continuous ambulatory peritoneal dialysis failed to respond to, or relapsed immediately after cessation of, intraperitoneal antibiotic therapy with vancomycin or cephalothin and tobramycin. Sequestration of viable staphylococci within polymorphonuclear leukocytes in the peritoneal fluid was suspected for two reasons: (1) staphylococci could still be grown after treatment of the dialysate cell fraction with lysostaphin, a procedure that kills only extracellular staphylococci, and (2) diminished polymorphonuclear leukocyte bactericidal activity was demonstrated in peritoneal dialysis effluent. Addition of rifampin, which readily penetrates polymorphonuclear leukocytes, to the treatment regimen of all patients led to prompt resolution of peritonitis without relapse.

Microcytic Anemia in Dialysis Patients: Reversible Marker of Aluminum Toxicity

Improvement of microcytic anemia after deferoxamine treatment is described in eight long-term dialysis patients with high serum aluminum concentration and other clinical signs of aluminum toxicity. Hematocrit increase of 3 to 19 vol% was associated with correction of microcytosis, significant reduction in abnormal levels of free erythrocyte protoporphyrins, and amelioration of the bone-related symptoms and neurologic signs of aluminum intoxication. Increase in hematocrit, reversal of microcytosis, and reduction in protoporphyrin levels all correlated with the aluminum burden as indicated by the pretreatment serum aluminum levels and by the peak serum aluminum levels during mobilization with deferoxamine. Furthermore, deferoxamine resulted in marked improvement in anemia despite significant reduction in serum ferritin levels. This reversal of microcytosis with deferoxamine provides objective evidence verifying the toxicity of aluminum, and suggests that microcytosis may be an easily detected marker for both clinical diagnosis as well as response to treatment in some cases of aluminum intoxication.