A comparison of the calcium-free phosphate binder sevelamer hydrochloride with calcium acetate in the treatment of hyperphosphatemia in hemodialysis patients.

Current phosphate binders used in hemodialysis patients include calcium-based binders that result in frequent hypercalcemia and aluminum-based binders that result in total body aluminum accumulation over time. This investigation describes the use of a calcium- and aluminum-free phosphate-binding polymer in hemodialysis patients and compares it with a standard calcium-based phosphate binder. An open-label, randomized, crossover study was performed to evaluate the safety and effectiveness of sevelamer hydrochloride in controlling hyperphosphatemia in hemodialysis patients. After a 2-week phosphate binder washout period, stable hemodialysis patients were administered either sevelamer or calcium acetate, and the dosages were titrated upward to achieve improved phosphate control over an 8-week period. After a 2-week washout period, patients crossed over to the alternate agent for 8 weeks. Eighty-four patients from eight centers participated in the study. There was a similar decrease in serum phosphate values over the course of the study with both sevelamer (-2.0 +/- 2.3 mg/dL) and calcium acetate (-2.1 +/- 1.9 mg/dL). Twenty-two percent of patients developed a serum calcium greater than 11.0 mg/dL while receiving calcium acetate, versus 5% of patients receiving sevelamer (P < 0.01). The incidence of hypercalcemia for sevelamer was not different from the incidence of hypercalcemia during the washout period. Patients treated with sevelamer also sustained a 24% mean decrease in serum low-density lipoprotein cholesterol levels. Sevelamer was effective in controlling hyperphosphatemia without resulting in an increase in the incidence of hypercalcemia seen with calcium acetate. This agent appears quite effective in the treatment of hyperphosphatemia in hemodialysis patients, and its usage may be advantageous in the treatment of dialysis patients.

Catastrophic secondary antiphospholipid syndrome with concomitant antithrombin III deficiency.

The association between thrombotic events and primary or secondary antiphospholipid/anticardiolipin syndrome is now well recognized. A spectrum of renal involvement ranging from glomerular thrombosis to renal infarction has been described. A case of systemic lupus erythematosus with immunoglobulin G and M antiphospholipid/anticardiolipin antibodies is reported. The patient developed catastrophic thrombosis in multiple organs, and glomerular thrombosis was documented by renal biopsy. The patient had an acquired antithrombin III deficiency, and the combination of secondary antiphospholipid syndrome with accompanying antithrombin III deficiency predisposed to thrombosis. Several mechanisms by which antiphospholipid/anticardiolipin antibodies cause thrombosis have been proposed and are briefly reviewed.

Pancreatitis in patients with end-stage renal disease.

In a population of 716 patients with end-stage renal disease (ESRD), 46 patients (6.4%) were identified as having pancreatitis. Pancreatitis was significantly more common in those with alcohol abuse, systemic lupus erythematosus (SLE), and polycystic kidney disease. It was not significantly associated with hyperlipidemia, biliary tract disease, or hypercalcemia. Acute pancreatitis occurring before the patient developed ESRD was mainly alcohol-related and did not appear to be a significant risk factor for future episodes of pancreatitis during dialysis. Chronic calcific pancreatitis diagnosed before ESRD was almost invariably due to alcohol abuse, and tended to be a marker for recurrent acute exacerbation after development of ESRD, whether alcohol consumption continued or not. Pancreatitis occurring for the first time after ESRD in patients on dialysis was generally benign, and was usually accompanied by an uneventful recovery and few recurrent episodes. However, a significant elevation of the calcium x phosphate product was observed in these patients, occurring in about half the patients without any known precipitating factor. After kidney transplantation, the development of pancreatitis was associated with higher morbidity and mortality. Chronic calcific pancreatitis diagnosed after ESRD occurred only in patients with SLE; reported here for the first time, it may be a manifestation of long-standing disease, chronic steroid therapy, or both.

A case study of a recent decline in the dialysis fatality rate.

Geoffrey Berlyne, whom we honor in this Festschrift, has contributed much to the modern understanding of diseases of the kidney, and of the clinical and metabolic disorders that occur in acute and chronic renal failure. The Festschrift highlights the many areas of his contributions. It is important to note that underlying them all is astute clinical observation, incisive analysis and reasoning, a breadth of approach, experimentation that facilitated understanding of the relevant clinical issues, and an unusual clarity of exposition in the literature. As author, editor, and teacher, Geoffrey Berlyne has brought this clarity of approach to a generation in nephrology. The following analysis of clinical data from a working dialysis unit, rendering care to a predominantly underprivileged patient population, is presented in the hope that it throws light on everyday problems in nephrology in a manner similar to that in which Geoffrey has guided the nephrology community.

Continuous quality improvement in chronic disease: a computerized medical record enables description of a severity index to evaluate outcomes in end-stage renal disease.

We have previously derived an index, based on retrospective data, for mortality in patients with end-stage renal disease (ESRD) treated by dialysis and transplantation. We used this index to calculate probability of death and rates of hospitalization, two measures of severity of illness, for 436 patients enrolled in our ESRD program after the original index was derived. Applied when ESRD treatment was initiated, it predicted future mortality and hospitalization rates. We then analyzed clinical characteristics, including variables in the predictive model, in all 718 patients enrolled in 3-year cohorts from 1976 to 1989. Over time, there was trend toward enrolling patients with a higher likelihood of dying, ie, more severely ill. The severity index facilitated description of the patients and their changing characteristics over time, and proved useful in comparing the degree of illness in different population groups.

Protein S deficiency and skin necrosis associated with continuous ambulatory peritoneal dialysis.

Skin necrosis associated with protein C deficiency has recently been reported to occur in hemodialysis patients. The clinical presentation and course of this syndrome appears indistinguishable from skin necrosis (purpura fulminans) seen in other settings with inherited or acquired deficiency of the naturally occurring anticoagulant proteins, protein C and S. Patients on maintenance hemodialysis may have low levels of these factors. However, patients on peritoneal dialysis have normal or elevated levels of these proteins despite documented peritoneal losses. We report two patients in whom the occurrence of protein S deficiency and subsequent skin necrosis can be related to demonstrated peritoneal dialysis-associated losses. We suggest that these losses may become critical under appropriate conditions and suggest caution in peritoneal dialysis patients requiring warfarin therapy.

Diffuse proliferative lupus nephritis: long-term observations in patients treated with ancrod.

Twenty-two patients with histologically demonstrated diffuse proliferative lupus nephritis (DPLN) and glomerular thrombosis received a 14-day course of ancrod, followed in most by nitrogen mustard (mechlorethamine hydrochloride) 0.4 mg/kg. Many were referred when renal function was deteriorating despite large doses of prednisone. The patients had severe disease; there was a high degree of glomerular sclerosis; the median serum creatinine was 137 mumol/l, the diastolic blood pressure 101 mm Hg. Reported previously was a short-term improvement in renal function, blood pressure, and renal histology. Reported here is the long-term follow-up on all 22 patients for an average of 58 months. Three died of causes other than renal failure. Eleven developed end-stage renal disease an average of 27 months after ancrod treatment. The other 8 are alive with no deterioration of renal function after an average of 70 months. This outcome seems satisfactory when disease severity is taken into consideration. Factors present at treatment start that might be associated with subsequent renal function deterioration were: prior prolonged prednisone treatment, extensive glomerular sclerosis, high plasma alpha 2-antiplasmin and possibly triglycerides. During the follow-up period after completion of treatment, later relapses of SLE and DPLN appeared to be an important predictor of deterioration of renal function.

Pain referred to teeth as the sole discomfort in undiagnosed mediastinal lymphoma: report of case.

The role of routine medical examination in dental diagnosis is described in a report of case involving a young, seemingly healthy patient whose only symptom, pain in the mandibular left molars, proved a manifestation of a malignant mediastinal lymphoma.

Fibrinolysis in glomerulonephritis treated with ancrod: renal functional, immunologic and histopathologic effects.

The effects of a 14-day course of ancrod on fibrinolysis, renal function and structure, and immunologic findings are reported in 37 patients with glomerulonephritis. Patients were divided into two groups. In the first, the level of fibrin degradation products within 48 h was relatively low (less than 1 mg/ml). In these patients there was a linear relationship between changes in levels of fibrin degradation products and fibrinogen, suggesting that fibrin degradation products derived from ancrod-cleaved-fibrinogen in the circulating pool; in most, level of plasma alpha 2-antiplasmin before treatment was elevated. In the second, the level of fibrin degradation products within 48 h was high (greater than 1 mg/ml). Compared with the change in fibrinogen, a disproportionate increase in levels of fibrin degradation products suggested that a significant amount derived from sources other than plasmin digested ancrod-cleaved-fibrinogen, thus reflecting effective fibrinolysis, perhaps also in tissues; in most, the level of plasma alpha 2-antiplasmin was normal before treatment. In those with initial high levels of fibrin degradation products, higher levels persisted throughout treatment, changes in other fibrinolysis components were greater, and plasminogen activator inhibitor levels became normal. In patients with initial high but not with initial low response in fibrin degradation products renal function improved within 24 to 48 h and continued to improve thereafter; there was an immediate but temporary increase in proteinuria. Microvascular thrombosis decreased significantly, indicating effective removal of fibrin from glomeruli. The relation of early fibrinolysis to changes in immunologic and histopathologic findings was analyzed in patients with lupus nephritis. With ancrod, there was an increase toward normal of serum C3 and C4, a decrease in serum Igs, gamma globulin and anti-dsDNA antibody and in glomerular C3 and Ig deposits, suggesting that ancrod had favorable effects on immunologic factors. There were no clinical differences in patients with initial high and low responses, but the relationship of microvascular and inflammatory indexes before treatment differed. Initial renal biopsies and those after treatment were carried out on average 28 days apart. Inflammatory and microvascular indexes and glomerular thrombi decreased in patients with initial high levels of fibrin degradation products; fibrosclerosis index and glomerular sclerosis increased in patients with initial low levels of fibrin degradation products. Fibrinolysis expressed as the 48 h (fibrin degradation products/fibrinogen) ratio, correlated inversely with change in fibrosclerosis index and glomerular sclerosis in the whole group, and especially in those with initial high levels of fibrin degradation products.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of first and subsequent use of hemodialyzers on patient well-being: the rise and fall of a syndrome associated with new dialyzer use.

In a single large dialysis unit in which dialyzers are routinely subjected to multiple use, the incidence rates of intradialytic symptoms during first use and reuse were compared. Dialyses administered during two periods were analyzed: During the first (26,592 treatments), dialyzers were processed by a manual method before both first and subsequent use. During the second (12,395 treatments), dialyzers were processed by an automated machine method before first and subsequent use. During the first (manual processing) period, 12 symptoms were found to occur more frequently during first use than during reuse. The most striking findings related to chest pain (2.8 times more frequent with first use), back pain (6 times), and concurrent chest and back pain (42 times). Thus, a "first-use syndrome" characterized by chest and back pain was clearly evident. During the second (machine processing) period, the previously noted increased symptom incidence during first use was no longer present. In particular, the incidence of chest pain and back pain was no longer greater during first use than during reuse. Our results suggest that subjecting dialyzers to an automated reuse processing system before first use can markedly diminish the incidence of first-use syndrome.

Fibrinolysis in health and disease: abnormal levels of plasminogen activator, plasminogen activator inhibitor, and protein C in thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is characterized by widespread occluding and persistent microthrombotic lesions. Evidence for both endothelial damage and primary platelet aggregation as possible pathogenetic mechanisms has been produced. Persistence of microthrombi has not been explained satisfactorily. In patients with TTP we studied plasma fibrinolysis and protein C. Tissue plasminogen activator (t-PA) activity levels, measured functionally, were low or unmeasurable in 11 of 12 patients; t-PA antigen levels, measured immunochemically, were normal in all six observed. The level of potent inhibitor of plasminogen activation directed against both t-PA and urokinase was elevated significantly in all 12, whereas the alpha 2-antiplasmin level was elevated in only two. Protein C antigen levels were low in three of six patients observed. Fibrinolysis levels in patients in remission did not differ from those in patients with acute disease. Plasma exchange resulted in temporary reversal of the abnormalities, but achievement of clinical remission was not associated with permanent normalization of fibrinolysis. Inasmuch as all 12 patients had severely depressed fibrinolytic mechanisms it is possible that a defect in the fibrin-clearing system permits thrombus formation to occur and proceed in an unchallenged fashion, thereby contributing to the complex events leading to arterial ischemia in vital organs.

Effect of first and subsequent use of hemodialyzers on patient well-being. Analysis of the incidence of symptoms and events and description of a syndrome associated with new dialyzer use.

To determine the effect of multiple dialyzer use on intradialytic symptoms, data from 26,592 successive dialyses on 147 patients were analyzed. Over the 26-month period of study 4,933 new dialyzers were used. All symptoms, considered together, occurred 1.3 times more frequently during the initial than during the subsequent use of the dialyzer. No symptom occurred more frequently in the second or subsequent use of the dialyzer. Concurrent chest and back pain were 41 times more frequent when the dialyzer was used for the first time. A syndrome associated with the first use of the dialyzer is described.