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Biomedical subjects

Mark A Perazella

Publications and source records attributed to Mark A Perazella.

At least 37 records · Page 2Linked to original sources
PubMed2004

The renin-angiotensin-aldosterone system and the kidney: effects on kidney disease.

The renin-angiotensin-aldosterone system regulates renal vasomotor activity, maintains optimal salt and water homeostasis, and controls tissue growth in the kidney. However, pathologic consequences can result from overactivity of this cascade, involving it in the pathophysiology of kidney disease. An activated renin-angiotensin-aldosterone system promotes both systemic and glomerular capillary hypertension, which can induce hemodynamic injury to the vascular endothelium and glomerulus. In addition, direct profibrotic and proinflammatory actions of angiotensin II and aldosterone may also promote kidney damage. The majority of the untoward effects associated with angiotensin II appear to be mediated through its binding to the angiotensin II type 1 receptor. Aldosterone can also induce renal injury by binding to its receptor in the kidney. An understanding of this system is important to appreciate that inhibitors of this cascade can reduce the progression of chronic kidney disease in proteinuric disease states. Pharmacologic agents that can interfere with this cascade include angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone receptor antagonists. This paper will provide an overview of the renin-angiotensin system, review its role in kidney disease, examine the renal effects of inhibition of this cascade in experimental animal models, and review clinical studies utilizing renin-angiotensin-aldosterone inhibitors in patients with diabetic and nondiabetic nephropathies.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

Intradialytic administration of amphotericin B: clinical observations on efficacy and safety.

BACKGROUND: Amphotericin B is used commonly to treat fungal infections. Unfortunately, little information exists regarding the use of intravenous amphotericin B in patients with end-stage renal disease (ESRD). METHODS: We retrospectively reviewed the clinical course of patients receiving amphotericin B during hemodialysis (HD). Twenty-five episodes of systemic fungal infection occurring in 24 patients with ESRD treated with parenteral amphotericin B administered during HD were noted. Patients received a maintenance dose of 0.5 to 1.0 mg/kg amphotericin B intravenously thrice weekly during HD sessions. Twenty-three patients received either 500 or 1000 mg of amphotericin B, whereas 1 patient with AIDS received a total of 6,500 mg. RESULTS: Intradialytic hypotension developed in 27.7% of HD sessions during treatment with amphotericin B compared with 28.8% of 20 HD sessions evaluated before initiation of amphotericin B therapy. Four patients exhibited a temperature rise greater than 38.8 degrees C during drug infusion (1 episode per patient). Increases in heart rate and ventricular ectopy were rare. Serum potassium concentrations as well as Kt/V and urea reduction ratio did not change significantly. All patients (except the patient with AIDS) resolved their respective fungal infections. CONCLUSIONS: Intradialytic administration of amphotericin B was generally well tolerated. Our observations suggest that amphotericin B is effective and safe for outpatient intradialytic therapy when administered according to protocol.

Adolescent↗
PubMed2004

A review of chronic lead intoxication: an unrecognized cause of chronic kidney disease.

Chronic lead nephropathy occurs as a result of years of lead exposure. This disease has been prevalent throughout human history. It is important that primary care providers and internists recognize this disorder because it can contribute to progressive loss of kidney function. Diagnosis is made by a thorough history in combination with physical examination. A history of lead intoxication often requires knowledge of the various sources of lead exposure. Laboratory tests, many previously known and some newly described, are available to further support this diagnosis. Therapy to reduce lead burden may be useful when employed early in the disease; new data sheds more light on which patients should be treated and when such patients should undergo chelation therapy. In particular, treatment with calcium EDTA chelation may benefit certain patients with chronic kidney disease by slowing the progression to end-stage renal disease.

Animals↗
PubMed2004

Can dual blockade of the renin-angiotensin system reduce progression of kidney disease beyond monotherapy?

It is well-accepted that therapies directed at the renin-angiotensin system (RAS) reduce the progression of chronic kidney disease. Angiotensin-converting enzyme (ACE) inhibitors and the angiotensin receptor blockers (ARBs) are currently available to interrupt this cascade. Their positive actions result from better blood pressure control, a reduction in glomerular capillary pressure and a decrease in proteinuria. Blockade of the RAS may also reduce renal scarring by blunting direct pro-fibrotic effects of angiotensin II and aldosterone. Although these drugs successfully reduce urinary protein excretion and improve renal survival, a significant number of patients continue to progress to end stage renal disease. It is possible, however, that dual blockade of the RAS with an ACE inhibitor and an ARB might offer further benefit beyond using either agent alone. Optimally, the goal should be to completely halt the progression of kidney disease. With these concepts in mind, this paper will review the RAS and its effects on the kidney. The efficacy and safety of dual RAS blockade in proteinuric renal diseases will be examined. Finally, recommendations for utilising combined therapy with ACE inhibitors and ARBs will be provided.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

Acute interstitial nephritis associated with atazanavir, a new protease inhibitor.

Atazanavir is a new human immunodeficiency virus 1 protease inhibitor that has a favorable side-effect profile and is available in once-daily dosing. We report the case of a young man with human immunodeficiency virus infection who developed acute renal failure after therapy with this drug. Renal biopsy showed acute interstitial nephritis. This is the first report of acute interstitial nephritis from atazanavir.

Acute Disease↗
PubMed2003

Vascular access surveillance: evaluation of combining dynamic venous pressure and vascular access blood flow measurements.

BACKGROUND/AIMS: Vascular access thrombosis is one of the most morbid problems encountered by hemodialysis patients. Surveillance protocols utilizing venous pressure (Vp) and vascular access blood flow (VABF) measurements have been employed to preserve vascular access. We undertook a study to evaluate combined dynamic Vp and VABF measurements in the identification of vascular access impairment. We also assessed the effect of preventive repair on thrombosis rates in impaired vascular accesses identified by surveillance. METHODS: Eighty-six chronic hemodialysis patients with a functioning vascular access were enrolled into the surveillance protocol. All vascular accesses with greater than 50% of monthly Vp readings >120 mm Hg or VABF <500 ml/min in arteriovenous fistulas (AVFs) and VABF <650 ml/min in arteriovenous grafts (AVGs), or a decrease in VABF >25% compared to the highest previously measured value, were considered positive. Stenosis >50% on fistulography or a thrombotic event were defined as a 'vascular access impairment episode' while a stenosis <50% or the absence of a thrombotic event was defined as 'no vascular access impairment episode'. Thrombosis rates and intervention rates were calculated per access year at risk. RESULTS: The sensitivity and specificity of the combined surveillance protocol for AVFs were 73.3 and 91%, respectively. In AVGs, they were 68.8 and 87.5%, respectively. The rate of thrombotic events was lower in patients who underwent early repair. The addition of dynamic Vp did not reduce the thrombosis rate any further than surveillance based on VABF alone. CONCLUSION: Combined monitoring for surveillance of AVFs improved sensitivity but had little benefit in AVGs over VABF monitoring alone. Raising VABF cutoff levels might increase and improve identification of vascular access risk for thrombosis, but at the expense of lower specificity.

Arteriovenous Shunt, Surgical↗
PubMed2003

Drug-induced renal failure: update on new medications and unique mechanisms of nephrotoxicity.

Medications cause renal failure through a variety of mechanisms. Hemodynamic renal failure may result from drugs that reduce renal prostaglandins and hence renal blood flow and glomerular filtration rate. A relatively new group of drugs with this potential is the cyclooxygenase-2 selective inhibitors. Direct renal tubular toxicity has also been described with a number of new medications with unique effects on the epithelial cells of the kidney. These include the antiviral agents cidofovir, adefovir, and tenofovir as well as the bisphosphonate pamidronate. Additionally, crystal deposition in the kidney may promote the development of renal failure. Several different drugs have been described to induce crystal nephropathy, including the antiparasitic drug sulfadiazine, the antiviral agent acyclovir, and the protease inhibitor indinavir. Finally, an unusual form of renal failure characterized by swollen, vacuolated proximal tubular cells can develop from hyperosmolar substances. Agents recently described to induce an "osmotic nephrosis" include intravenous immunoglobulin and the plasma expander hydroxyethyl starch.

Animals↗
PubMed2003

The renin-angiotensin-aldosterone system: cardiorenal effects and implications for renal and cardiovascular disease states.

The renin-angiotensin-aldosterone system (RAAS) plays an integral role in maintaining vascular tone, optimal salt and water homeostasis, and cardiac function in humans. However, it has been recognized in recent years that pathologic consequences may also result from overactivity of the RAAS. Clinical disease states such as renal artery stenosis, hypertension, diabetic and nondiabetic nephropathies, left ventricular hypertrophy, coronary atherosclerosis, myocardial infarction, and congestive heart failure (CHF) are examples. Part of the adverse cardiorenal effects of the RAAS may be related to the prominent role that this system plays in the activation of the sympathetic nervous system, the dysregulation of endothelial function and progression of atherosclerosis, as well as inhibition of the fibrinolytic system. Also, direct profibrotic actions of angiotensin II and aldosterone in the kidney and heart promote end organ injury. Current basic science and clinical research supports the use of inhibitors of the RAAS, including angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone antagonists in treating hypertension, improving diabetic nephropathy and other forms of chronic kidney disease, preventing or ameliorating CHF, and optimizing prognosis after myocardial infarction.

Cardiovascular Diseases↗
PubMed2003

Addition of sertraline to other therapies to reduce dialysis-associated hypotension.

Sertraline has shown promise in the treatment of dialysis-associated hypotension (DAH) in a limited number of end-stage renal disease patients. We undertook a study to evaluate the effect of adding sertraline to other therapies for patients with documented DAH. We also measured the effect of sertraline on intradialytic haemodynamics. We used the ultrasound dilution technique (HD01 monitor) to measure cardiac output (CO), central blood volume (CBV) and peripheral vascular resistance (PVR) in these patients. The study was performed in two phases. Phase 1 was a control, while the second phase consisted of treatment with sertraline (50 mg/day). Cardiac output and central blood volume were measured 30 min following the initiation of dialysis and 30 min prior to the termination of dialysis. Blood pressure (BP) was monitored during haemodynamic measurements and throughout dialysis. Eighteen patients with documented DAH completed the study. Cardiac output, CBV and PVR were no different in the sertraline phase as compared with the control phase. The declines in systolic BP, diastolic BP and mean arterial pressures from pre-haemodialysis (HD) to lowest intradialytic and pre-HD to post-HD were not significantly different for the sertraline phase versus the control phase. In conclusion, it appears that sertraline has no additive effect on intradialytic haemodynamics to improve blood pressure in patients with DAH who are under therapy (with sodium modelling, cool dialysate and midodrine).

Adult↗
PubMed2003

Efficacy and safety of midodrine in the treatment of dialysis-associated hypotension.

Dialysis-associated hypotension is a morbid problem in haemodialysis patients. Employment of midodrine at the start of dialysis has reduced the severity and frequency of hypotensive episodes in these patients. Through selective alpha(1)-adrenergic receptor-binding, desglymidodrine, the active metabolite of midodrine, raises blood pressure by enhancing venous and arterial tone. This medication has been demonstrated to be effective and safe in the acute and chronic treatment of haemodialysis-associated hypotension in end stage renal disease patients.

Animals↗
PubMed2002

Hemodynamics in patients with intradialytic hypotension treated with cool dialysate or midodrine.

Cool dialysate and midodrine have been used successfully to treat intradialytic hypotension (IDH) in the end-stage renal disease population. However, the exact mechanisms by which these interventions improve hemodynamic stability are not well known. We undertook a study to evaluate the effect of these modalities on intradialytic hemodynamics in patients with documented dialysis-associated hypotension. We used the ultrasound dilution technique to measure cardiac output (CO), central blood volume (CBV), and peripheral vascular resistance (PVR) in these patients. The study was performed in two phases. Phase 1 consisted of control (1A) and cool dialysate (1B) studies, whereas phase 2 consisted of control (2A) and midodrine (2B) studies. CO, CBV, and PVR were measured 30 minutes after the initiation of hemodialysis (HD) and 30 minutes before the termination of HD using the HD01 monitor. Blood pressure was measured pre-HD and post-HD. Fourteen patients with documented IDH completed the study. CO and CBV were significantly more preserved in the cool dialysate and midodrine phases compared with control phases. PVR increased in all phases of the study. Declines in mean arterial pressures from pre-HD to post-HD were less with cool dialysate versus control and midodrine versus control. Ultrafiltration volumes were not significantly different between phases. Cool dialysate and midodrine appear to improve intradialytic hemodynamics in patients with dialysis-associated hypotension, mainly through the preservation of CBV and CO, rather than significantly elevating PVR.

Adrenergic alpha-Agonists↗
PubMed2002

Pamidronate-associated nephrotoxicity in a patient with Langerhans's histiocytosis.

Pamidronate is used frequently to treat malignancy-associated hypercalcemia and osteolytic lesions. This widely used bisphosphonate has been noted to cause nephrotoxicity in patients with multiple myeloma and metastatic breast cancer. We encountered a patient with Langerhans's histiocytosis who developed nephrotic syndrome and renal failure after pamidronate therapy. We describe the clinical and renal biopsy findings in this patient.

Anti-Inflammatory Agents↗
PubMed2002

Observations on HIV-associated renal disease in the era of highly active antiretroviral therapy.

BACKGROUND: Renal disease in patients infected with HIV has evolved to include several lesions, including HIV-associated nephropathy (HIV-AN), which can promote progressive loss of renal function. Although angiotensin-converting enzyme inhibitors and corticosteroids are beneficial in selected patients, the effect of highly active antiretroviral therapy (HAART) on renal function is currently being explored. METHODS: We undertook a retrospective study to determine the types of renal lesions present in patients infected with HIV with renal insufficiency and/or proteinuria during the era of HAART availability and the effect of HAART on renal outcomes in these patients. Patients with HIV infection referred to the renal clinic from July 1996 through December 2000 were evaluated. Patient characteristics and data were collected including CD4 count, viral load, serum creatinine, blood pressure, proteinuria, renal ultrasound, and biopsy results, and treatment with HAART. Study endpoints were doubling of serum creatinine, initiation of dialysis, or death. RESULTS: Twenty-three patients met study criteria, 13 received HAART, and 10 did not. Baseline characteristics were similar except for renal function parameters, viral loads, and CD4 counts. A variety of lesions were noted on 12 renal biopsies. A clinical diagnosis of HIV-AN was made in the other 11 patients. Only 2 patients receiving HAART before renal evaluation were noted to have HIV-AN. In the HAART group, none of the patients, including those with HIV-AN, developed a doubling of serum creatinine. In the non-HAART group, all patients manifested a doubling of serum creatinine, 2 patients died, and 8 patients required dialysis. CONCLUSIONS: A variety of renal lesions are noted in patients infected with HIV during the HAART era. Patients who received HAART maintained stable renal function, whereas patients who did not required dialysis therapy or died with advanced renal failure. It seems that HAART may improve renal outcomes in patients with HIV and renal disease.

AIDS-Associated Nephropathy↗
PubMed2002

Rapid communication: acute renal failure associated with tenofovir: evidence of drug-induced nephrotoxicity.

Drug-induced renal failure is a relatively common event in patients infected with HIV. This group of patients receives a number of potentially nephrotoxic medications for a variety of illnesses. The acyclic nucleoside phosphonates cidofovir and adefovir are antivirals that possess significant nephrotoxicity. Interestingly, tenofovir disoproxil fumurate (DF) is structurally similar to these 2 agents, yet seems to be less nephrotoxic based on a few published studies in HIV patients with intact renal function. We present a case in which acute renal failure developed after therapy with tenofovir DF in a patient with HIV and stable chronic kidney disease.

Acute Kidney Injury↗
PubMed2002

COX-2 selective inhibitors: analysis of the renal effects.

COX-2 selective inhibitors provide analgesia and blunt inflammation while also sparing the gastrointestinal tract from classic NSAID toxicity. Therapeutic effects are thought to result from inhibition of the inflammatory COX-2 isoform. Organ sparing is considered the result of preservation of homeostatic COX-1 enzyme function. Similar roles of the COX isoforms in the kidney would reduce NSAID-associated nephrotoxicity. However, human kidney tissue expresses COX-2 enzyme, suggesting a role for this isoform in maintenance of physiological renal processes. Available clinical data on the renal effects of COX-2 selective inhibitors in humans also demonstrate nephrotoxic potential.

Acute Kidney Injury↗
PubMed2002

Chronic kidney disease: a new approach to an old problem.

Chronic kidney disease (CKD) is a growing health problem in the United States. Recognition of this chronic condition is crucial to facilitate the employment of measures that can slow progression to end-stage renal disease and reduce associated disease states. Furthermore, a system to classify stages of CKD is worthwhile to permit a logical approach to therapy in these patients. We herein review and summarize clinical practice guidelines put forward by the National Kidney Foundation Working Group to aid physicians in the diagnosis and management of CKD.

Adult↗