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Biomedical subjects

G B Appel

Publications and source records attributed to G B Appel.

At least 37 records · Page 2Linked to original sources
PubMed1995

Progressive renal insufficiency following cardiac transplantation: cyclosporine, lipids, and hypertension.

The increasing success of cardiac transplantation has been attributed to the availability of potent immunosuppressive agents, including cyclosporine. With improved graft and patient survival, the incidence of chronic renal insufficiency has increased. We reviewed the medical records of patients who had undergone orthotopic cardiac transplantation and had been followed for at least 3 years posttransplantation to determine the risk factors at initial evaluation and in the early posttransplantation period for subsequent renal insufficiency. We followed 80 adult patients over a mean period of 4.7 years: 39 patients had a serum creatinine > or = 2.4 mg/dL at last follow-up (renal insufficiency or RI group); 41 patients had a serum creatinine < or = 1.7 mg/dL at last follow-up (controls). RI patients tended to be older and had a lower mean glomerular filtration rate (GFR) at initial evaluation. There were no differences in race, gender, or previous history of hypertension between the two groups. Although both groups experienced an improvement in GFR at transplantation and a subsequent decline in GFR by 6 months posttransplantation, the RI group achieved a lower peak GFR at transplantation and a far lower mean GFR at the 6-month analysis. Only the RI group showed a continued decline in GFR. The RI group had more severe hypertension and required a significantly greater number of antihypertensive medications. The RI group had a higher mean total cholesterol at 6 months, but this difference was not sustained. They also had higher triglyceride levels and lower high-density lipoprotein (HDL) levels; there was no difference in low-density lipoprotein (LDL) levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Renal transplantation in anticardiolipin antibody-positive lupus erythematosus patients.

Up to 44% of patients with systemic lupus erythematosus have antiphospholipid antibodies, which in some patients have been associated with thrombocytopenia, in vitro coagulation abnormalities, and a thrombotic tendency. Patients with lupus nephritis who reach end-stage renal disease may continue to have anticardiolipin antibodies (ACL-Ab) at the time of renal transplantation despite a lack of clinical or serologic activity of systemic lupus. The risk of thrombotic and other complications has not been previously reported in these patients. To evaluate the effect of ACL-Ab on the course of renal transplantation, the clinical course of eight ACL-Ab-positive lupus patients transplanted in the period from January 1990 to June 1992 were compared with five ACL-Ab-negative lupus patients transplanted during the same period. All patients had lupus nephritis as the cause of renal failure. There were four thrombotic episodes in the patients who were ACL-Ab-positive but none in the control group. Neither of the two groups differed in the number of rejection episodes, the rate of graft loss, or renal function at last follow-up. Patients with systemic lupus erythematosus who are ACL-Ab-positive can be successfully transplanted. However, these patients require attention to possible thrombotic events with a potential role for prophylactic anticoagulation.

Adult↗
PubMed1994

The course and treatment of lupus nephritis.

Renal involvement by systemic lupus is variable; some patients have minimal clinical and histologic involvement, whereas others have fulminant renal failure and severe proliferative renal lesions on biopsy. The World Health Organization (WHO) classification has greatly aided in the study of lupus nephritis. This classification defines six major patterns of renal involvement, each with characteristic clinical correlates and a typical course and prognosis. Transformations from one pattern of lupus nephritis to another may occur, and there may also be prominent involvement of the tubulointerstitial compartment and vasculature. Treatment of the renal lesions may be directed at the individual class of lupus nephritis. Thus patients with mesangial involvement (WHO Class II) do not require therapy directed at their kidney lesions. Many patients with biopsies showing focal proliferative disease (WHO Class III) and all patients whose biopsies show diffuse proliferative lesions (WHO Class IV) require vigorous treatment, which has included high-dose daily and alternate-day corticosteroids, azathioprine, i.v. pulse methylprednisolone, plasmapheresis, total lymphoid irradiation, cyclosporine, and oral and i.v. cyclophosphamide. Controlled trials have yielded reasonable evidence for the safety and efficacy of some treatments, whereas others have been used only in uncontrolled studies. When used judiciously, such vigorous therapy can improve the renal survival of patients with severe lupus nephritis.

Azathioprine↗
PubMed1994

Influence of oral felodipine on serum cyclosporine concentrations.

Hypertension and nephrotoxicity are frequent in renal transplant patients treated with cyclosporine. Calcium-channel blockers, because of their vasodilatory effects on the renal afferent arteriole, may be the anti-hypertensive agents of choice in this population. Unfortunately, many calcium channel blockers inhibit the clearance of cyclosporine, resulting in elevated blood levels, and worsening nephrotoxicity. Thirteen hypertensive renal transplant patients, on stable cyclosporine doses and with stable cyclosporine blood levels, had felodipine added to their antihypertensive regimens. The effect on cyclosporine level was measured. Mean trough serum cyclosporine concentration increased slightly, from 122.8 +/- 51.8 ng/ml to 143.1 +/- 81.9 ng/ml with chronic felodipine administration (p = NS). Mean systolic and diastolic pressures both fell significantly, by approximately 10 mmHg (systolic from 161 +/- 14 to 152 +/- 13 mmHg; diastolic from 100 +/- 6 to 90 +/- 7 mmHg). Serum creatinine remained unchanged. Four patients eventually discontinued felodipine. There was no significant change in their mean trough serum cyclosporine concentration when felodipine was discontinued. Thus, felodipine is an effective anti-hypertensive medication in cyclosporine-treated renal transplant recipients, without significant effect on cyclosporine blood levels, or adverse effect on allograft function.

Administration, Oral↗
PubMed1994

Intravenous pulse cyclophosphamide treatment of severe lupus nephritis: a prospective five-year study.

Despite its widespread use, there are only a few published studies of the use of intravenous high dose pulse cyclophosphamide in systemic lupus nephritis. There are few data about the long-term efficacy and safety of this form of therapy. This study evaluates the clinical efficacy, toxicity, and effects on renal morphology of this regimen in patients with severe lupus nephritis followed prospectively over a five-year period. Twenty consecutive patients with severe active lupus nephritis were enrolled in a treatment regimen of six monthly intravenous pulses of cyclophosphamide (0.5 to 1 g/m2) together with high dose corticosteroid therapy which was rapidly tapered. Efficacy was assessed by improvement or stabilization of clinical, serologic and renal functional parameters. Repeat renal biopsies were performed in 15 patients. Potential toxicity related to therapy was documented. Over the first six months of treatment, this regimen resulted in improvement of clinical activity, lupus serology, stabilization of renal function and decreased proteinuria in 19/20 patients. Nephrotic syndrome remitted in 8/10 patients by one year. Over five years of follow-up, there were five treatment failures defined as a doubling of serum creatinine over baseline. At five years, 3 patients required renal replacement therapy. Elevated plasma creatinine at time of first biopsy, degree of proteinuria, histologic activity and chronicity were not statistically correlated with treatment failure. Patients who failed to respond to this treatment were, however, more likely to have diffuse proliferative lupus nephritis (WHO Class IV) lesions on initial biopsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Cyclosporine treatment of lupus membranous nephropathy.

Few studies describe the treatment of membranous nephropathy associated with systemic lupus erythematosus. Although cyclosporine-A has been used to treat patients with the nephrotic syndrome and also with systemic lupus, only a few of these patients have had lupus membranous nephropathy. In this pilot study, we assessed the safety and efficacy of cyclosporine in ten nephrotic patients with either pure membranous lupus nephropathy (seven patients) or membranous lupus nephropathy with superimposed mild proliferative lesions (three patients). Cyclosporine (4-6 mg/kg/day) alone (2 patients), or in conjunction with low dose corticosteroids (8 patients) was given for a period of up to 43 months. Six patients achieved a nadir proteinuria of less than 1 gram daily, two patients decreased urinary protein excretion to 1-2 grams daily, and the remaining two patients continued to excrete over 2 grams of protein daily. All patients experienced symptomatic improvement of their nephrotic syndrome and serum creatinine was not significantly increased at the end of the study period. Three patients with superimposed mild proliferative lesions experienced renal and systemic lupus flares while on treatment requiring additional immunosuppressive therapy. Side-effects were minor except for transient rises in serum creatinine in one patient and a case of drug-related hepatitis possibly caused by cyclosporine. Repeat renal biopsies in five patients revealed a decrease in the lupus activity index and a rise in the chronicity index. There was an increase in the stage of the membranous nephropathy on these repeat biopsies, but a reduction in the number of fresh deposits.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

The nephrotic syndrome, lipids, and risk factors for cardiovascular disease.

The hyperlipidemia associated with the nephrotic syndrome is well characterized. There is, however, a paucity of data in humans on the risk factors for atherosclerotic heart disease and the role of hyperlipidemia on the risk of progression of renal disease in this population. In our study, we retrospectively evaluated a large uniform population of patients (mean creatinine, 1.78 mg/dL; mean 24-hour proteinuria, 7.1 g) with idiopathic nephrotic syndrome for the presence of risk factors for coronary artery disease. One hundred patients with either focal segmental glomerulosclerosis (n = 56) or membranous nephropathy (n = 44) were assessed for the following cardiovascular risk factors: male sex or postmenopausal female, hyperlipidemia, hypertension, smoking history, and left ventricular hypertrophy. Sixty-six percent of the patients were either male or postmenopausal females; 35% were smokers. Hypertension and left ventricular hypertrophy were present in 53% and 13% of patients, respectively. Eighty-seven percent, 53%, and 25% of patients had a total cholesterol of more than 200 mg/dL, more than 300 mg/dL, and more than 400 mg/dL, respectively. Low-density lipoprotein cholesterol was greater than 130 mg/dL and greater than 160 mg/dL in 77.2% and 64.9% of patients, respectively. Virtually all patients (99%) had at least one risk factor for cardiovascular disease; over two thirds (68%) had two risk factors and over one quarter (26%) had three risk factors. In comparing the group that progressed to renal failure with the groups that did not, the initial mean serum cholesterol was lower in the group that progressed (292 mg/dL v 388 mg/dL, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Cyclosporine: nephrotoxic effects and guidelines for safe use in patients with rheumatoid arthritis.

Renal abnormalities occur frequently in patients with rheumatoid arthritis; they may be complications of the rheumatoid disease process itself (amyloidosis) or may result from various therapies including gold compounds, D-penicillamine, analgesics such as aspirin or phenacetin used long term, and nonsteroidal anti-inflammatory drugs. Cyclosporine, a highly effective immunosuppressive agent currently under investigation as a treatment for RA, is also known to produce renal dysfunction. Some forms of functional and structural tubular changes appear readily reversible. Others associated with renal vasculopathy and interstitial fibrosis can lead to irreversible nephrotoxicity. A clear understanding of the pharmacology, drug interactions, and types of renal side effects encountered with cyclosporine can lead to a reduction of adverse renal reactions. Similarly, an understanding of which patients are at high risk for renal dysfunction can lead to safer and more efficacious use of this potent immunosuppressive agent.

Arthritis, Rheumatoid↗
PubMed1992

Increased concentration of plasma cholesteryl ester transfer protein in nephrotic syndrome: role in dyslipidemia.

Hyperlipidemia is a prominent feature of the nephrotic syndrome. Lipoprotein abnormalities include increased very low and low density lipoprotein (VLDL and LDL) cholesterol and variable reductions in high density lipoprotein (HDL) cholesterol. We hypothesized that plasma cholesteryl ester transfer protein (CETP), which influences the distribution of cholesteryl esters among the lipoproteins, might contribute to lipoprotein abnormalities in nephrotic syndrome. Plasma CETP, apolipoprotein and lipoprotein concentrations were measured in 14 consecutive untreated and 7 treated nephrotic patients, 5 patients with primary hypertriglyceridemia, and 18 normolipidemic controls. Patients with nephrotic syndrome displayed increased plasma concentrations of apoB, VLDL, and LDL cholesterol. The VLDL was enriched with cholesteryl ester (CE), shown by a CE/triglyceride (TG) ratio approximately twice that in normolipidemic or hypertriglyceridemic controls (P < 0.001). Plasma CETP concentration was increased in patients with untreated nephrotic syndrome compared to controls (3.6 vs. 2.3 mg/l, P < 0.001), and was positively correlated with the CE concentration in VLDL (r = 0.69, P = 0.004) and with plasma apoB concentration (r = 0.68, P = 0.007). Treatment with corticosteroids resulted in normalization of plasma CETP and of the CE/TG ratio in VLDL. An inverse correlation between plasma CETP and HDL cholesterol was observed in hypertriglyceridemic nephrotic syndrome patients (r = -0.67, P = 0.03). The dyslipidemia of nephrotic syndrome includes increased levels of apoB-lipoproteins and VLDL that are unusually enriched in CE and likely to be atherogenic. Increased plasma CETP probably plays a significant role in the enrichment of VLDL with CE, and may also contribute to increased concentrations of apoB-lipoproteins and decreased HDL cholesterol in some patients.

Adult↗
PubMed1992

Intravenous "pulse" cyclophosphamide therapy of crescentic glomerulonephritis.

Pulse steroids and monthly intravenous cyclophosphamide with a rapid steroid taper were used to treat seven patients with crescentic glomerulonephritis. Despite major impairment of renal function, all patients had a marked improvement in GFR by six months and improvement in proteinuria occurred in six of the seven patients. Two patients were able to discontinue dialysis. The doses of steroids and cyclophosphamide used were less than in comparable studies and side-effects of therapy were minimal. Repeat renal biopsies at over one year demonstrated marked glomerulosclerosis despite relatively stable renal function. Histologic analysis of total glomerular involvement indices on serial biopsies suggested no recruitment of new glomeruli into the crescenteric process once treatment had been initiated. Thus, intravenous pulse cyclophosphamide with pulse steroid therapy appears to be a safe and effective initial therapy for some patients with RPGN. Significant glomerulosclerosis on repeat biopsies suggests that glomerulosclerosis may be predetermined by the initial degree of irreversible glomerular damage and that the long-term course of the disease remains guarded.

Adult↗
PubMed1990

Aminoglycoside nephrotoxicity.

The high incidence of associated nephrotoxicity represents an important concern in the use of aminoglycoside antibiotics, which have been implicated as one of the primary causes of drug-induced acute renal failure. Several factors, including the underlying health of the patient, criteria used to define nephrotoxicity, and the specific aminoglycoside administered, may contribute to the nephrotoxic potential of these agents. The development of aminoglycoside-induced nephrotoxicity is a complex problem. These drugs appear to be only minimally metabolized within the body and undergo nearly exclusive renal excretion, primarily by glomerular filtration. Ultimately, reabsorption and accumulation within the kidney results in proximal tubular cell damage; several possible mechanisms have been proposed, both for the development of such cell damage and for its subsequent role in the evolution of nephrotoxicity. The pathology and the clinical pattern of aminoglycoside-induced kidney damage have been extensively studied in animal models and in humans. Although the data often conflict, many of these studies have attempted to identify some of the factors associated with a higher risk for aminoglycoside nephrotoxicity. Of the factors generally agreed upon to influence risk, correction of volume depletion and diminished renal perfusion, as well as dose adjustment for level of renal function, have been identified as critical measures for prevention of renal damage by aminoglycosides. Recent studies have indicated that newer agents, such as third-generation cephalosporins and aztreonam, often may be as therapeutic and cost-effective as the aminoglycosides without the nephrotoxicity associated with the latter agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1990

Lipid-lowering agents in proteinuric diseases.

Hyperlipidemia is common in patients with glomerular proteinuria. It may contribute to atherosclerotic complications and accelerate glomerular damage. Early trials of the fibric acid derivative clofibrate led to a myositis syndrome causing many nephrologists to abandon attempts at treatment of nephrotic hyperlipidemia. Recent trials with lipid-lowering medications have been successful without major side effects. The bile acid sequestrants colestipol and cholestyramine bind bile acids in the gut and deplete the hepatic cholesterol pool, thus inducing LDL hepatocyte receptors. Recent studies showed a reduction of total cholesterol of 8-20% and LDL cholesterol of 19-31% without significant changes in HDL cholesterol. Probucol has reduced total cholesterol 23-30% and LDL cholesterol 23-25% in nephrotic patients. Although HDL cholesterol was reduced, the LDL/HDL ratio remains favorably changed. The fibric acid derivative gemfibrozil inhibits adipose lipolysis and enhances lipoprotein lipase activity thus decreasing LDL synthesis and increasing its removal. It caused a large decrease in triglycerides with a 13-15% decrease in total and LDL cholesterol in a recent trial. HDL cholesterol increased 18%. The HMG-CoA reductase inhibitors inhibit the rate-limiting step in cholesterol biosynthesis hence inducing an increase in LDL receptors on hepatocytes. Trials have shown decreases of 18-36% in total cholesterol and 18-47% in LDL cholesterol, while HDL cholesterol was either increased or unchanged. The use of lipid-lowering agents of several classes has been effective in ameliorating the progression of glomerular damage in a number of different models of glomerulosclerosis. Nevertheless, so far in humans lipid lowering drugs have not been established to have an effect on either the degree of proteinuria or the progression of glomerulosclerosis.

Animals↗
PubMed1990

Anti-cardiolipin antibody and renal disease: a report three cases.

Anti-cardiolipin antibodies have been linked to recurrent arterial and venous thrombosis in multiple organs. We present a biopsy-documented report of thrombotic renal disease apparently attributable to circulating anti-cardiolipin antibodies. One patient had primary anti-cardiolipin syndrome, one had mild SLE, and the third had a mild lupus-like syndrome. All three patients had a clinical course dominated by repeated multi-organ system thrombosis. Renal biopsy disclosed thrombosis at the level of the glomerular capillaries, arterioles, and interlobular arteries--similar to that described in other thrombotic microangiopathies. Renal thrombosis was not associated with active endocapillary proliferative lupus nephritis, suggesting a mechanism independent of subendothelial immune deposit injury. Renal presentation was variable, ranging from asymptomatic mild proteinuria to nephrotic-range proteinuria, renal insufficiency, and hypertension.

Adult↗