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N Ahsan

Publications and source records attributed to N Ahsan.

At least 19 recordsLinked to original sources
PubMed2006

Continued influence of preoperative renal function on outcome of orthotopic liver transplant (OLTX) in the US: where will MELD lead us?

Renal function is a component of the Model for End Stage Liver Disease (MELD), We queried the 1999-2004 OPTN/UNOS database to determine whether preoperative renal function remained an important determinant of survival in primary deceased donor liver transplant alone patients (DDLTA) or primary combined kidney liver transplant patients (KLTX). We examined preoperative creatinine, renal replacement therapy (RRT), incidence of KLTX, and patient survival in the 34 months before and after introduction of MELD and performed a multivariate Cox regression analysis of time to death. Preoperative renal function is an independent predictor of survival in DDLTA but not in KLTX. When compared to DDLTA with a preoperative serum creatinine of 0-0.99 mg/dL, patients with serum creatinine from 1-1.99 mg/dL, >2.0 mg/dL, those requiring RRT, and those receiving KLTX had a relative risk of death following transplant of 1.11, 1.58, 1.77, and 1.44 respectively. KLTX requiring RRT had better survival than DDLTA requiring RRT. Since introduction of MELD, KLTX, preoperative creatinine, and number of patients requiring preoperative RRT have increased. Despite this, patient survival following orthotopic liver transplant (OLTX) in the 34 months after introduction of MELD is not different than prior to introduction of MELD.

Adolescent↗
PubMed2004

Genetic basis of heterosis and inbreeding depression in rice (Oryza sativa L.).

The genetic basis of heterosis was studied through mid-parent, standard variety and better parent for 11 quantitative traits in 17 parental lines and their 10 selected hybrids in rice (Oryza sativa L.). The characters were plant height, days to flag leaf initiation, days to first panicle initiation, days to 100% flowering, panicle length, flag leaf length, days to maturity, number of fertile spikelet/panicle, number of effective tillers/hill, grain yield/10-hill, and 1000-grain weight. In general the hybrids performed significantly better than the respective parents. Significant heterosis was observed for most of the studied characters. Among the 10 hybrids, four hybrids viz., 17Ax45R, 25Ax37R, 27Ax39R, 31Ax47R, and 35Ax47R showed highest heterosis in 10-hill grain yield/10-hill. Inbreeding depression of F2 progeny was also studied for 11 characters of 10 hybrids. Both positive and negative inbreeding depression were found in many crosses for the studied characters, but none was found significant. Selection of good parents was found to be the most important for developing high yielding hybrid rice varieties.

Hybrid Vigor↗
PubMed2003

Induction immunotherapy with IL-2Ra monoclonal antibody in kidney transplantation.

The development of new immunosuppressive agents is designed to reduce the incidence and severity of early acute post-transplant rejection. One potential target for more specific immunosuppressive therapy with monoclonal antibodies is the high affinity a chain of interleukin-2 receptors (IL-2Ra). Clinical investigation of murine IL-2Ra monoclonal antibodies (IL-2Ra mAb) in renal transplantation has indicated that a complete blockade of IL-2Ra during the critical first post-transplant months allows effective immunoprophylaxis, especially in the early post-transplant period. Efficacy of these agents, however, is hampered by their short disposition half-lives in humans and their immunogenicity in the form of neutralizing human antimouse antibodies. These inherent problems can be partially overcome by chi-meric, hyper-chimeric (humanized) products and multiple dose regimens. Both IL-2Ra mAbs: daclizumab (humanized) and basiliximab (chimeric) currently approved for clinical use have been found to reduce the frequency of acute rejections in renal transplant recipients without an apparent increase in short-term toxicities. In most transplant centers where these agents are utilized, they are being routinely administered as induction immunoprophylaxis in recommended multiple dose regimens to recipients of solid organ transplants. Others have restricted their use to certain high-risk patients such as those undergoing multi-organ transplantation, recipients with high panel-reactive antibodies, African-Americans, patients at risk for developing delayed graft function (DGF), and children. Recently some investigators have successfully administered these antibodies co-administered with newer immunosuppressive agents in limited dose protocols thus developing cost effective and simplified regimens. Therefore, in the absence of a favorable long-term efficacy, it is likely that these agents will be administered in limited dose protocols along with one of the modulators of IL-2, i.e. calcineurin inhibitors (CNI), to a selected group of patients in whom additional immunosuppression in the early post-transplantation period is desirable.

Adult↗
PubMed2001

Randomized trial of tacrolimus plus mycophenolate mofetil or azathioprine versus cyclosporine oral solution (modified) plus mycophenolate mofetil after cadaveric kidney transplantation: results at 2 years.

BACKGROUND: A previous report described the 1-year results of a prospective, randomized trial designed to investigate the optimal combination of immunosuppressants in kidney transplantation. Recipients of first cadaveric kidney allografts were treated with tacrolimus+mycophenolate mofetil (MMF), cyclosporine oral solution (modified) (CsA)+MMF, or tacrolimus+azathioprine (AZA). Results at 1 year revealed that optimal efficacy and safety were achieved with a regimen containing tacrolimus+MMF. The present report describes results at 2 years. METHODS: Two hundred twenty-three recipients of first cadaveric kidney allografts were randomized to receive tacrolimus+MMF, CsA+MMF, or tacrolimus+AZA. All regimens contained corticosteroids, and antibody induction was used only in patients who experienced delayed graft function. Patients were followed up for 2 years. RESULTS: The results at 2 years corroborate and extend the findings of the previous report. Patients randomized to either treatment arm containing tacrolimus experienced improved kidney function. New-onset insulin dependence remained in four, three, and four patients in the tacrolimus+MMF, CsA+MMF, and tacrolimus+AZA treatment arms, respectively. Furthermore, patients with delayed graft function/acute tubular necrosis who were treated with tacrolimus+MMF experienced a 23% increase in allograft survival compared with patients receiving CsA+MMF (P=0.06). Patients randomized to tacrolimus+MMF received significantly lower doses of MMF compared with those administered CsA+MMF. CONCLUSIONS: All three immunosuppressive regi-mens provided excellent safety and efficacy. How-ever, the best results overall were achieved with tacrolimus+MMF. The combination may provide particular benefit to kidney allograft recipients who develop delayed graft function/acute tubular necrosis. Renal function at 2 years was better in the tacrolimus treatment groups compared with the CsA group.

Administration, Oral↗
PubMed2001

Lipid formulations of polyene antifungal drugs and attenuation of associated nephrotoxicity.

Amphotericin B is an effective broad-spectrum antifungal agent, but various side effects, especially nephrotoxicity, have restricted its use. Recently, lipid formulations of amphotericin B have been developed in order to reduce its toxic side effects. Clinical trials, although in the early stages, suggest promising results, and that some of these lipid formulations are potent and less toxic, even at higher doses. We summarize herein the existing information about newer lipid formulations of polyene antifungal drugs, which could attenuate associated nephrotoxicity.

Amphotericin B↗
PubMed2001

Myoglobinuria: evaluation of methods in the clinical diagnosis acute renal failure.

Patients with red--brown urine which may be a sign of myoglobinuria, can develop acute renal failure. We assayed serum creatinine, blood urea nitrogen (BUN) and creatine kinase activity in a total of 33 patients of equal groups, A (automobile accident), B (trauma) and C (undergoing rhabdomyolysis). In addition we tested 132 urine samples for the presence of myoglobin using a dipstick assay. Only five patients in group A showed any sign of myoglobinuria with increased creatine kinase activity upto 7 times the normal value but their serum creatinine level and BUN were within the normal range. In contrast, all 22 patients in group B and C showed myoglobinuria and above normal concentrations of serum creatinine and BUN, with significantly increased (p < 0.0001) creatine kinase activity upto 150 times the normal range. Four of the most seriously ill patients in group C developed acute renal failure. Supplementation of routine determinations of serum creatinine and BUN and serum creatine kinase activity with a rapid test for myoglobinuria provides an extra indication of impending renal dysfunction. It may be beneficial in the emergency management of these patients.

Acute Kidney Injury↗
PubMed2000

Expression of angiotensin II type I receptor on erythroid progenitors of patients with post transplant erythrocytosis.

BACKGROUND: The pathogenesis of posttransplant erythrocytosis (PTE) has been elusive. Angiotensin converting enzyme inhibitors (ACEI) are efficacious in lowering the hematocrit of patients with PTE and angiotensin II (AII) type I receptors (AT1R) were recently detected on red blood cell precursors, burst-forming unit-erythroid- (BFU-E) derived cells. The purpose of this study was to determine whether there is increased expression of the AT1R on BFU-E-derived cells of patients with PTE, which might contribute to the pathogenesis of PTE. METHODS: Twelve healthy volunteers and 25 transplant recipients (13 patients with and 12 without PTE) were studied. BFU-E from peripheral blood were cultured in methylcellulose and BFU-E-derived colonies were harvested on day 10. Western blotting was used to detect AT1R and erythropoietin receptor (EpoR) expression. Intracellular free calcium in response to AII and erythropoietin (Epo) was measured with digital video imaging. RESULTS: There were no differences between transplant patients, with and without PTE, with respect to weight, age, sex, blood pressure, serum creatinine, circulating renin, angiotensin II, and Epo levels. Hematocrit, red blood cell number, BFU-E-derived colony number,and size were significantly increased in PTE compared with other two groups. AT1R expression was increased by 44% on the erythroid progenitors of PTE versus non posttransplant erythrocytosis patients and by 32% in PTE patients versus normal volunteers. AT1R expression correlated significantly with the hematocrit in PTE (Spearman r=0.68, P=0.01). In contrast, EpoR expression was equivalent in all groups. The AT1R was functional since a significant increase in [Ca(i)] was observed in Fura-2 loaded day 10 cells when stimulated with AII (182%, P<0.0001). CONCLUSION: An increase in AT1R density was observed in erythroid precursors of transplant patients with PTE compared to those without PTE and normal volunteers, and the level of AT1R expression in PTE correlated significantly with the hematocrit. In contrast, EpoR expression was not different in PTE compared with non posttransplant erythrocytosis or normal controls. This study supports a role for the AT1 receptor signaling pathway in the pathogenesis of PTE.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Randomized trial of tacrolimus (Prograf) in combination with azathioprine or mycophenolate mofetil versus cyclosporine (Neoral) with mycophenolate mofetil after cadaveric kidney transplantation.

BACKGROUND: Our clinical trial was designed to investigate the optimal combination of immunosuppressants for renal transplantation. METHODS: A randomized three-arm, parallel group, open label, prospective study was performed at 15 North American centers to compare three immunosuppressive regimens: tacrolimus + azathioprine (AZA) versus cyclosporine (Neoral) + mycophenolate mofetil (MMF) versus tacrolimus + MMF. All patients were first cadaveric kidney transplants receiving the same maintenance corticosteroid regimen. Only patients with delayed graft function (32%) received antilymphocyte induction. A total of 223 patients were randomized, transplanted, and followed for 1 year. RESULTS: There were no significant differences in baseline demography between the three treatment groups. At 1 year the results are as follows: acute rejection 17% (95% confidence interval 9%, 26%) in tacrolimus + AZA; 20% (confidence interval 11%, 29%) in cyclosporine + MMF; and 15% (confidence interval 7%, 24%) in tacrolimus + MMF. The incidence of steroid resistant rejection requiring antilymphocyte therapy was 12% in the tacrolimus + AZA group, 11% in the cyclosporine + MMF group, and 4% in the tacrolimus + MMF group. There were no significant differences in overall patient or graft survival. Tacrolimus-treated patients had a lower incidence of hyperlipidemia through 6 months posttransplant. The incidence of posttransplant diabetes mellitus requiring insulin was 14% in the tacrolimus + AZA group, 7% in the cyclosporine + MMF and 7% in the tacrolimus + MMF groups. CONCLUSIONS: All regimens yielded similar acute rejection rates and graft survival, but the tacrolimus + MMF regimen was associated with the lowest rate of steroid resistant rejection requiring antilymphocyte therapy.

Adult↗
PubMed2000

Laparoscopic-assisted renal biopsy: an alternative to open approach.

An open renal biopsy frequently is performed when the conventional percutaneous approach is contraindicated. Although many of the surgical procedures, previously performed by a traditional open technique, are now successfully accomplished by laparoscopic technique, there remains a paucity of reports on laparoscopic kidney biopsy. We describe the use of laparoscopic technique in performing native kidney biopsy in three patients and review the potential safety and accuracy of this approach. To date, laparoscopic-assisted renal biopsy has been reported in six patients. The average length of stay in our small series was 1.3 days, and there were no major or catastrophic complications. Adequate numbers of glomeruli for confirmation of microscopic diagnosis were obtained in all cases. The review of literature, in addition to our encouraging preliminary results of a small group of patients, shows a possible role of laparoscopic-assisted renal biopsy in place of an open renal biopsy.

Aged↗
PubMed2000

Heat shock protein 47 in renal scarring.

Heat shock protein 47 (HSP47) is a collagen-binding protein, thought to play an essential mechanistic role in the assembly and processing of procollagens. HSP47 is increasingly being implicated in the pathogenesis of several human and experimental fibrotic diseases. HSP47 could mediate increased accumulation of collagens in the fibrotic mass, possibly by regulating increased assembly of procollagens. Therefore, modulation of HSP47 might be a valuable tool for manipulation of some fibrotic diseases, including renal scarring

Cicatrix↗
PubMed2000

Infusion of total dose iron versus oral iron supplementation in ambulatory peritoneal dialysis patients: a prospective, cross-over trial.

The efficacy of intermittent, small doses of intravenous iron in hemodialysis patients is well established. But poor peripheral vascular access and frequency of therapy preclude acceptability of this method in peritoneal dialysis (PD) patients. Therefore, despite its marginal efficacy, oral iron remains the common method of iron supplementation in these patients. This prospective, cross-over trial compares infusion of total dose iron (ITDI) and oral iron supplementation in outpatient PD patients. Eleven stable CAPD patients with an hematocrit (Hct) of less than 33%, or a transferrin saturation (TSAT) of less than 30%, or both, were entered into the study. The study design included an oral phase [4 months, ferrous sulfate 325 mg (195 mg elemental iron), three times daily], a "wash-out" phase (1 month, no iron supplementation), and an ITDI phase [4 months, single infusion over 4 hours of 1 g iron dextran mixed in 1/2 normal saline]. Laboratory parameters were monitored monthly, and subcutaneous recombinant human erythropoietin (rHuEPO) doses were adjusted monthly to maintain a hematocrit above 33%. Patients with hyperparathyroidism, aluminum toxicity, and weekly Kt/V below 1.8 were excluded. Nine patients [8 Caucasians, 1 African American; causes of end-stage renal disease (ESRD): hypertension (4 cases), diabetes (3 cases), glomerulonephritis (1 case), and polycystic kidney disease (1 case); mean age: 43.3 +/- 2 years; mean weight: 73.0 +/- 4 kg; duration of ESRD: 28 +/- 13 months] completed the 9-month study. During the oral phase, TSAT rapidly decreased and a higher dose of rHuEPO failed to maintain Hct, a pattern sustained during the "wash-out" phase. During the ITDI phase, TSAT significantly increased and improvement in Hct resulted in a significant lowering of rHuEPO doses. The ITDI therapy was well tolerated. We conclude that ITDI is the preferred method of iron supplementation in outpatient PD patients.

Administration, Oral↗
PubMed1999

Prednisone withdrawal in kidney transplant recipients on cyclosporine and mycophenolate mofetil--a prospective randomized study. Steroid Withdrawal Study Group.

BACKGROUND: Prospective randomized trials have shown a reduced rate of acute rejection (AR) in mycophenolate mofetil-treated kidney transplant recipients. We hypothesized that this increased protection from AR could allow successful prednisone (P) withdrawal in cyclosporine/mycophenolate mofetil/P-treated recipients. METHODS: A multicenter, prospective, randomized, double-blind trial of P withdrawal at 3 months post-transplant was initiated. Entry criteria were: primary transplant, adult, no AR by 90 days, mycophenolate mofetil dose > or =2 g/day, cyclosporine dose = 5-15 mg/kg/ day, P dose = 10-15 mg/day. Study participants were randomized to have P tapered over 8 weeks (beginning at 3 months posttransplant) to 0 vs. 10 mg/day. Prestudy power analysis determined 500 recipients should be randomized for 80% statistical power to test equivalence of the primary endpoint, AR, or treatment failure at 1 year posttransplant. By design, the study was to be stopped if interim data precluded reaching equivalence. An established data safety monitoring board monitored the study. RESULTS: After 266 patients were enrolled, the patient enrollment was stopped (after safety monitoring board review) because of excess rejection in the P withdrawal group. The Kaplan-Meier estimate of the cumulative incidence of rejection or treatment failure within 1 year posttransplant (+/-95% confidence interval) for the maintenance group was 9.8% (4.4%; treatment failure, 14.9%); for the withdrawal group, 30.8% (21.0%; 39.3%). Treatment differences in the distribution of time to event were highly significant (P = 0.0007). Of note, risk was higher in blacks (39.6%) versus nonblacks (16.0%) (P<0.001). At 1 year post-transplant, there was no difference between groups in patient or graft survival. For the patients with functioning grafts at 6 months posttransplant, withdrawal patients had lower cholesterol (P = 0.0005), had higher creatinine (P = 0.03), and were less likely to use antihypertensives (P = 0.001). These differences persist to 1 yr posttransplant. CONCLUSIONS: We conclude that for recipients on cyclosporine/mycophenolate mofetil/P with no AR at 90 days, the chance of developing subsequent AR is small; if P is tapered and withdrawn, the risk increases (but the majority remain free of acute and chronic rejection). After withdrawal, the risk of AR is different for blacks versus nonblacks. Withdrawal patients had a lower cholesterol level and less need for antihypertensives.

Adolescent↗
PubMed1999

New strategies using 'low-dose' mycophenolate mofetil to reduce acute rejection in patients following kidney transplantation.

CONTEXT: Tacrolimus, microemulsion cyclosporine (Neoral), and mycophenolate mofetil (MMF) at 2 and 3 grams daily have demonstrated superior immunosuppressive properties in several recent clinical trials involving solid-organ transplants. An effective immunosuppression may be maintained with lower doses of MMF administered with either tacrolimus or microemulsion cyclosporine. OBJECTIVE: To compare tacrolimus plus "low-dose" MMF-based immunosuppressive regimen (TMBIR) with Neoral plus "low-dose" MMF-based immunosuppressive regimens (NMBIR) among kidney transplant recipients. DESIGN: Prospective, randomized study. PATIENTS: 53 consecutive adult recipients of kidney transplant. Both groups (TMBIR and NMBIR) were equally matched on demographic characteristics. INTERVENTIONS: Participants were randomized to receive orally either tacrolimus (0.08 mg/kg twice daily) (n = 27) or Neoral (4 mg/kg twice daily) (n = 26). Both regimens were started before surgery and continued when allograft demonstrated no postoperative acute tubular necrosis. Both groups received similar "low-dose" MMF (500 mg twice daily) and prednisone (2 mg/kg/day to taper off after 1 year). Switch from tacrolimus to Neoral or vice versa was allowed after refractory rejection or serious adverse events. MAIN OUTCOME MEASURE: Acute rejection and patient and graft survival 1 year following kidney transplant. RESULTS: One-year patient survival rates were 88.9% for the TMBIR group and 100% for the NMBIR group; 1-year graft survival rates were 88.9% for the TMBIR group and 96.1% for the NMBIR group. No significant differences were found in the incidence of biopsy-confirmed acute rejection (14.8% TMBIR vs 23% NMBIR). Steroid-resistant rejections requiring cytolytic antibody therapy were higher in the NMBIR group (50% vs 25%). Three patients crossed over from NMBIR to TMBIR for refractory rejections and 1 patient crossed over from TMBIR to NMBIR for new onset seizure. Three episodes of cytomegalovirus infection were observed in the TMBIR group. Other adverse events were similar in both groups. CONCLUSIONS: Both tacrolimus and microemulsion cyclosporine combined with "low-dose" MMF and corticosteroids provide effective immunosuppression and have similar adverse events in kidney transplant recipients.

Acute Disease↗
PubMed1998

Peloisis hepatis due to Bartonella henselae in transplantation: a hemato-hepato-renal syndrome.

BACKGROUND: Bacillary peliosis hepatis is an uncommon but well recognized disease due to disseminated Bartonella infections occurring predominantly in immunocompromised individuals infected with human immunodeficiency virus, type 1. A similar condition in the absence of Bartonella infection when described in organ transplant patients was felt to be secondary to azathioprine and/or cyclosporine. METHODS: Herein, we report the first case of bacillary peliosis hepatis due to systemic Bartonella henselae infection in a patient after kidney transplant. The patient presented with severe anemia, persistent thrombocytopenia, and hepato-renal syndrome. DNA-based polymerase chain reactions (PCR), which allowed direct detection of both B henselae and quintana DNA in patient's peripheral blood and liver tissue, were used. Indirect immunofluorescence assay for Bartonella serology was performed on peripheral blood. RESULTS: Histopathology of the liver biopsy demonstrated peliosis hepatis. Indirect immunofluorescence assay for Bartonella serology was positive, and B henselae DNA was identified by PCR in the peripheral blood and liver tissue. Treatment with a 3-month course of oral erythromycin resulted in an excellent clinical response. CONCLUSIONS: The present case suggests that although various anti-rejection therapies and opportunistic infections are associated with hepatic and renal dysfunction along with bone marrow suppression, the diagnostic evaluation in this situation should include liver biopsy and a careful search for evidence of systemic Bartonella infection, e.g., exposure to cats, Bartonella serology, and Bartonella DNA by PCR. A reduction in immunosuppression and prolonged therapy with antibiotics such as erythromycin will often result in early recovery.

Adult↗
PubMed1998

Immunohistochemical study of actin binding protein (p55) in the human kidney.

BACKGROUND: In clinical transplantation, "passenger" dendritic cells (DCs) in the allograft have been thought to induce allograft rejection. However, the presence of DCs in the normal human kidney is controversial. Most reports have relied on the examination of MHC class I and II antigen expression in combination with DC morphology for identification of DCs. METHODS: The distribution of the p55 antigen (fascin), which is selectively expressed by human blood and lymphoid DCs, was investigated by immunohistochemistry. RESULTS: Our study demonstrates that p55-positive DCs are absent from the normal human kidney and CD1a- and S100-positive cells are absent or very rare. Furthermore, HLA-DR and factor VIII-related antigen show almost complete colocalization in capillaries. In contrast, all 16 kidney biopsies from patients with inflammatory processes demonstrated p55-positive DCs in the cellular infiltrates. CONCLUSIONS: These results suggest that DCs are not present or are very rare in normal renal tissues but may migrate into the renal interstitium with inflammatory changes.

Adult↗
PubMed1998

In vivo and in vitro modulation of immune stimulatory capacity of primary dendritic cells by adenovirus-mediated gene transduction.

Dendritic cells (DCs) are potent antigen-presenting cells which are key leukocytes in the initiation of cell-mediated organ graft rejection, antiviral immunity, and antitumor responses. In this study we demonstrate that genetic modification of primary human and mouse DCs by adenoviral gene transfer is an effective means of induction and modulation of antigen presentation by DCs. An adenovirus vector (AdLacZ) was used to express an intracellular model antigen beta-galactosidase (beta-gal) in DCs. Our results show that 30-40% of precursor dendritic cells (PDCs) derived from human umbilical cord blood and circulating mature blood DCs express high levels beta-galactosidase (beta-gal) after infection with AdLacZ with no cytopathic effect observed. In vitro, AdLacZ transduced PDCs and DCs demonstrated a 10- to 20-fold higher mixed lymphocyte reaction (MLR) stimulatory capacity as compared to that of monocytes. In vivo, immunization with AdLacZ transduced mouse DCs resulted in more potent cytotoxic T lymphocyte (CTL) responses against the predicted H-2 restricted beta-gal epitope as compared to CTL responses obtained by beta-gal peptide pulsed DCs. Modulations of the MLR stimulatory capacity of DCs were examined by expression of mouse B7 and CTLA-4Ig. The results show that expression of mouse B7 by a recombinant adenoviral vector (Ad7) significantly enhances the MLR stimulatory capacity of human DCs. In contrast, expression of CTLA-4Ig (AdCTLA-4Ig) reduces the MLR stimulatory capacity of the transduced cells. We conclude that recombinant adenovirus can readily be used for genetic modulation DC-induced immune responses in vivo and in vitro. DCs targeted for induction of specific antigen responses or for modulation of the immune stimulatory capacity may have a potential use in the control of transplantation rejection or viral infections.

Adenoviridae↗
PubMed1998

Pyrazinoylguanidine in end-stage renal disease: a prospective, placebo-controlled pilot study.

Cardiovascular disease is the leading cause of mortality in end-stage renal disease (ESRD) patients receiving dialysis. In these patients, hypertriglyceridemia appears to increase the risk of accelerated atherosclerosis. The present placebo-controlled study evaluated prospectively lipid-lowering effects of pyrazinoylguanidine (PZG) in 6 ESRD patients undergoing maintenance hemodialysis. The design of the study entailed a placebo phase of 1 week followed by 3 weeks of PZG, 400 mg three times a day. Compared to placebo, PZG reduced serum triglycerides (PZG vs. placebo 370 +/- 171 vs. 414 +/- 182 mg/dl; p = 0.01). PZG also tended to decrease total cholesterol. In addition, PZG selectively lowered blood glucose in hyperglycemic patients. PZG was well tolerated; it did not interfere with hemodynamic parameters or alter liver function tests, nutritional parameters or dialysis clearance.

Administration, Oral↗